DS KythuatSXDP t1 W

B y t
K thut
sn xut dc phm

Tp I
K thut sn xut thuc bng phng php
tng hp ha dc v chit xut dc liu
Sch o to dc s i hc
M s: .20.Z.09
Ch bin: PGS.TS. T Minh Kong

Nh xut bn y hc
H ni - 2007
2

Ch o bin son
V Khoa hc & o to, B Y t

Ch bin:
PGS.TS. T Minh Kong

Nhng ngi bin son:

ThS. Nguyn Vn Hn
KS. Nguyn Vit Hng
TS. Nguyn nh Luyn
PGS.TS. Hu Ngh

Hiu nh:
KS. Nguyn Vit Hng

Tham gia t chc bn tho:
TS. Nguyn Mnh Pha
ThS. Ph Vn Thm

Bn quyn thuc B Y t (V Khoa hc & o to)

3

Li gii thiu

Thc hin mt s iu ca Lut Gio dc, B Gio dc v o to v B
Y t ban hnh chng trnh khung o to i tng l Dc s i hc Cao
ng iu dng. B Y t t chc bin son ti liu dy hc cc mn c s,
chuyn mn v c bn chuyn ngnh theo chng trnh trn nhm tng bc
xy dng b sch chun v chuyn mn m bo cht lng o to nhn
lc y t.
Sch K thut sn xut dc phm c bin son da trn chng
trnh gio dc cao ng iu dng ca Trng i hc iu dng Nam nh
trn c s chng trnh khung c ph duyt. Sch c ThS. Trng
Tun Anh, mt nh gio giu kinh nghim v tm huyt vi cng tc o to
bin son theo phng chm: Kin thc c bn, h thng; ni dung chnh xc,
khoa hc, cp nht cc tin b khoa hc, k thut hin i v thc tin Vit
Nam.
Sch K thut sn xut dc phm c Hi ng chuyn mn
thm nh sch v ti liu dy hc chuyn ngnh C nhn iu dng v
Cao ng iu dng ca B Y t thm nh vo nm 2006. B Y t quyt
nh ban hnh l ti liu dy hc t chun chuyn mn ca ngnh y t
trong giai on 2006-2010. Trong qu trnh s dng, sch phi c chnh l,
b sung v cp nht.
B Y t xin chn thnh cm n ThS. Trng Tun Anh, cng tc ti B
mn iu dng thn kinh tm thn Trng i hc iu dng Nam nh
ginh nhiu cng sc hon thnh cun sch ny, cm n TS. inh ng
Ho, PGS.TS. Ng ng Thc c, phn bin cun sch c hon
chnh, kp thi phc v cho cng tc o to nhn lc y t.
V ln u xut bn, chng ti mong nhn c kin ng gp ca
ng nghip, cc bn sinh vin v cc c gi ln xut bn sau c hon
thin hn.

V Khoa hc v o to
B Y t
4
5

Li ni u

Cun gio trnh "K thut sn xut dc phm" c bin son
ging cho sinh vin Dc h i hc vo hc k 8 c xut bn ln th
nht nm 2001, gm 2 tp. Theo chng trnh c, thi lng ging dy mn
hc ny l qu t so vi nhng kin thc chung ca Dc s i hc. c bit
trong tnh hnh hin nay, sau khi c ngh quyt ca B Chnh tr (NQ-46/BCT-
2005) v pht trin nn Cng nghip Dc ca t nc trong tnh hnh mi,
phi u tin pht trin cng nghip sn xut nguyn liu lm thuc, trong
ch trng Cng nghip Ha dc v Cng ngh Sinh hc. Ban chng trnh
nh trng quyt nh tng thm mt n v hc trnh cho hc phn "Sn xut
thuc bng Cng ngh sinh hc".
B mn bin son li xut bn cun gio trnh mi gm 3 tp. C
ba tp u c tn chung ca gio trnh: K thut sn xut dc phm.
Gio trnh c bin son theo hai ni dung:
1. K thut sn xut cc nguyn liu lm thuc.
2. K thut sn xut cc dng thuc thnh phm.
Trong :
Ni dung th nht gm 2 tp l:
* Tp 1. K thut sn xut thuc bng phng php tng hp ha dc
v chit xut dc liu.
* Tp 2. K thut sn xut thuc bng phng php sinh tng hp.
Ni dung th hai gm 1 tp l:
* Tp 3. K thut sn xut cc dng thuc.
So vi ln xut bn trc, cc tc gi bin son c gng cht lc nhng
kin thc ch yu nht cung cp cho ngi hc hiu c ngnh khoa hc
va hp dn va quan trng ny. Tuy nhin, vi ni dung phong ph, a dng
v thi lng hn ch nn khng th i su hn c. V vy cun gio trnh
khng trnh khi nhng thiu st. Cc tc gi mong nhn c s gp ca
c gi chnh sa cho ln xut bn sau c hon chnh hn. Xin chn
thnh cm n.

B mn Cng nghip Dc
Trng i hc Dc H Ni
6
7
Mc lc

Li gii thiu 3
Li ni u 5
Phn I. K thut tng hp ha dc 11
Chng 1. Mt s kin thc chung v cng nghip ho dc 11
1. i cng TS. Nguyn nh Luyn 11
2. c im ca cng nghip ho dc 12
3. Phng php nghin cu sn xut thuc mi 14
4. Ngun nguyn liu ca cng nghip ho dc 17
Chng 2. Nitro ho 24
2. C ch phn ng nitro ho 24
3. Tc nhn nitro ho 26
4. Cc yu t nh hng n phn ng 27
5. Cch tin hnh phn ng 28
6. Nitrozo ha 29
7. Thit b phn ng v an ton lao ng 29
8. Mt s v d 29
Chng 3. Sulfo ha 32
2. C ch phn ng 33
3. Tc nhn sulfo ha 34
4. iu kin ca qu trnh sulfo ha 37
5. Kh nng ng dng ca phn ng 38
7. Tch cc acid sulfonic t hn hp phn ng 40
8. Mt s v d 40
Chng 4. Halogen ha 42
2. C ch phn ng 43
8
3. Tc nhn halogen ha 45
4. Mt s v d 47
Chng 5. Alkyl ha 49
2. Cc tc nhn alkyl ha 50
3. Cc loi alkyl ha 51
4. Cc yu t nh hng n qu trnh alkyl ha 53
6. Mt s v d 54
Chng 6. Acyl ha 56
2. Tc nhn acyl ho 58
3. C ch phn ng 59
4. Mt s yu t cn ch trong qu trnh acyl ho 60
5. Mt s v d 61
Chng 7. Ester ho 63
2. C ch phn ng 65
3. Cc yu t nh hng n qu trnh ester ho 66
4. Cc phng php chuyn dch cn bng cho phn ng ester ho 69
5. Mt s v d 70
Chng 8. Phn ng thu phn 72
2. C ch ca phn ng thu phn 72
3. Cc tc nhn thu phn 73
4. Cc phn ng thu phn v c ch phn ng 74
5. Thit b ca phn ng thu phn 80
6. K thut an ton lao ng 81
7. Mt s v d 81
Chng 9. Oxy ho 83
9
2. C ch phn ng oxy ho 84
3. Cc tc nhn oxy ho 86
4. Cc phn ng oxy ho 89
5. Thit b ca phn ng oxy ho 92
6. K thut an ton trong qu trnh oxy ha 92
7. Mt s v d 92
Chng 10. Kh ho 95
2. Tc nhn kh ho 96
3. ng dng ca phn ng kh ho 104
4. Hydro phn 109
5. Mt s v d 109
Chng 11. Diazo ho 112
2. c im ca mui diazoni 113
3. C ch ca phn ng diazo ho 113
4. Cc yu t nh hng n qu trnh diazo ho 115
5. Nguyn tc tin hnh diazo ho 116
6. Cc phn ng ca mui diazoni 117
7. Thit b v an ton lao ng 119
8. V d 120
Chng 12. Phn ng ngng t 121
2. Cc loi phn ng ngng t 122
Chng 13. Phn ng chuyn v 128
2. C ch phn ng chuyn v anion -1,2 129
3. Cc loi phn ng chuyn v 129
Phn II. K thut chit xut dc liu 145
Chng 14. Mt s kin thc c bn v chit xut dc liu 145
1. Nguyn liu chit xut KS. Nguyn Vit Hng 146
2. Mt s qu trnh xy ra trong chit xut dc liu 148
10
3. Nhng yu t nh hng n qu trnh chit xut dc liu 151
4. Cc phng php chit xut 157
5. Thit b chit xut 161
Chng 15. Mt s qu trnh thng gp giai on tinh ch 177
1. Lng KS. Nguyn Vit Hng 177
2. Lc 181
3. Kt tinh 187
4. Hp ph 192
Chng 16. K thut sn xut mt s nguyn liu di dng cao thuc 199
1. Khi nim cao thuc ThS. Nguyn Vn Hn 199
2. Phn loi cao thuc 200
3. K thut iu ch 200
4. Cc ch tiu cht lng cao thuc 206
5. Bo qun, ghi nhn 206
6. Mt s v d cao thuc 207
Chng 17. Chit xut alcaloid 208
1. i cng v alcaloid PGS. TS. Hu Ngh 208
2. Tnh cht chung ca alcaloid 209
3. Cc phng php chung chit alcaloid 210
4. Cc phng php tch alcaloid di dng tinh khit 213
5. Chit xut mt s alcaloid 215
Chng 18. Chit xut cc hot cht c ngun gc t nhin khc 242
PGS. TS. Hu Ngh
1. Chit xut artemisinin v acid artemisinic t cy thanh hao hoa vng 242
2. Chit xut rutin t hoa ho 249
Ti liu tham kho 251

11
Phn I. K thut tng hp ho dc
Chng 1
Mt s Kin thc chung
v cng nghip ho dc
Mc tiu
Sau khi hc xong chng ny, sinh vin phi trnh by c:
1. Bn c im ca cng nghip Ho dc.
2. Ni dung ca phng php nghin cu sn xut thuc mi trong k
thut tng hp Ho dc.
3. Cc ngun nguyn liu v c v hu c ca cng nghip Ho dc.
1. i cng
K thut tng hp Ho dc hnh thnh v pht trin da trn c s ca
K thut tng hp Hu c. Ngy nay n tr thnh mt ngnh khoa hc
ring bit vi mt tim nng v cng to ln. Mt mt do nhu cu iu tr ngy
cng tng, mt khc do li ch v kinh t rt ln thc y cc hng Dc
phm ln trn th gii u t mnh m vo lnh vc ny.
Hin nay, do s cnh tranh khc lit trn th trng, nn c quyn
trong sn xut mt sn phm thuc cng tr nn rt quan trng i vi s tn
ti ca mt hng Dc phm. Chnh v vy, vic sn xut ra nguyn liu lm
thuc vi gi r v nghin cu tm kim thuc mi l hai nhim v chnh ca
ngnh Cng nghip Ho dc hin nay.
Cc cht hu c dng lm thuc thng c phn t lng khng ln
(khng qu 500 n v C) v c cu trc kh phc tp, nhiu cht d b phn
hu bi nh sng, nhit v m. Chng c iu ch bng nhiu phn
ng ho hc khc nhau. Chnh v vy, cc nh nghin cu, cc dc s v k
s lm vic trong lnh vc ny phi c s am hiu su sc v cc qu trnh ho
hc c bn (nitro ho, sulfo ho, halogen ho, oxy ho, kh ho...) hoc nhng
qu trnh ho hc c bit khc. Phi c s hiu bit c bn v cc nhm thuc
v phng php tng hp chng. Ngoi ra cn phi c kin thc v thit b,
12
vt liu ch to thit b dng trong cng nghip Ho dc v vn n mn
thit b... trnh a tp cht vo thuc.
K thut tng hp Ho dc l mn hc nhm p ng nhng yu cu
trn, ni dung gm hai phn chnh:
A. Cc qu trnh ho hc c bn ca k thut tng hp Ho dc.
B. K thut tng hp Ho dc.
Phn cc qu trnh ho hc c bn gii thiu cc phn ng c s dng
nhiu trong tng hp Hu c, Ho dc. Cc phn ng ny c k thut
ho vi vic s dng cc tc nhn v iu kin phn ng ti u thu c
cc sn phm mong mun t tiu chun. Phn K thut tng hp Ho dc
gii thiu cc phng php tng hp cc nhm thuc c th nh: Thuc h
nhit gim au, Thuc st rt, Thuc cha l, Thuc tr giun sn...
V s gi ging trong i hc c hn, nn phn B c trnh by trong
gio trnh Cao hc ca chuyn ngnh Cng ngh Dc phm v Bo ch.
2. c im ca Cng nghip Ho Dc
Tuy l mt trong nhng ngnh ca cng nghip ha hc, nhng mc ch
ca cng nghip Ha dc l sn xut ra cc hot cht nhm iu tr bnh cho
ngi. Cho nn n c nhng c im ring, rt cn ch trong qu trnh t
chc v pht trin sn xut.
c im quan trng nht l cht lng thnh phm phi t tiu
chun Dc in quc gia
Mc ch s dng thuc l iu tr bnh, thuc khng ch c a
vo c th bng ng ung m cn bng ng tim, t hoc phn phi trc
tip qua da... C ngha l c nhiu con ng a thuc trc tip vo mu ca
mt c th bnh. Do hot cht dng lm thuc phi tinh khit, khng c
cha tp cht hay bt k mt tc nhn no bt li cho sc kho.
T yu cu trn, trc khi xut xng, thnh phm phi c kim
nghim rt cht ch v mt ha hc v sinh hc theo cc tiu chun ca Dc
in. Vic qui nh hm lng tp cht c trong thuc ht sc cht ch nhm
trnh cc tc dng c hi do tch lu khi s dng di ngy, loi nhng tp
cht khc khng th pht hin c trong sn xut, trnh nhng tng k
khng gii thch c khi bo ch hoc ko di tui th ca thuc...
c im ny i hi nh my Ha dc phi t cc yu cu sau:
Phi m bo cc tiu chun v v sinh cng nghip. Ngi lao ng
phi c hiu bit v nguyn tc v sinh v v trng trong sn xut.
Thit b sn xut phi chng n mn tt khng a thm tp cht
vo thuc.
13
Nguyn liu dng cho sn xut phi c cht lng cao, r ngun gc
loi nhng tp cht khng pht hin c trong sn xut. Cng v
l do ny m hin nay khuynh hng: "Cng nghip Ha Dc t sn
xut ly sn phm trung gian" ngy cng pht trin.
Do s phc tp ca phn t thuc v yu cu tinh khit cao ca
sn phm, nn cc quy trnh sn xut Ho dc thng gm nhiu
giai on bin i ho hc v l hc. nng cao hiu sut v trnh
tht thot, cn phi s dng nhng quy trnh lin tc v t ng ho.
Thnh phm ca cng nghip Ho dc nhiu loi l thuc c, cc
thuc khng t tiu chun cht lng th khng th xut xng m
phi hu hoc x l thu hi nguyn liu. V vy, vic ng gi
thnh phm v lu kho phi c thc hin nghim tc theo ng
th tc v yu cu k thut. Vt liu ng gi v quy cch nhn bao
b u phi tun theo quy nh.
Tm li, mt nh my Ho dc cn t tiu chun GMP cho mt nh
my sn xut nguyn liu lm thuc.
V mt khi lng v gi tr
Khi lng ca sn xut Ho dc so vi cc ngnh cng nghip khc
thng khng ln v vi mi loi thuc cng khc xa nhau.
C loi ch cn vi kg l p ng cho nhu cu iu tr trong c nc,
nhng c loi phi cn ti hng trm, hng ngn tn. Trong gi thnh ca
chng rt chnh lch nhau v gi tr kinh t cng rt khc nhau. V vy, trc
khi a mt mt hng vo sn xut phi nghin cu rt k c k thut ln
hiu qu kinh t m bo sn xut n nh v c hiu qu cao.
Mt khc, mun cho thnh phm khng qu t, cng nghip Ho dc
phi trit khai thc d phm ca nhiu ngnh khc. Cn phi hp tc rng
ri vi nhiu ngnh nh cng nghip ho hc, phm nhum, cht do, thuc
n, luyn kim, khai thc qung, lm nghip, chn nui, giy, thc phm, ...
nhm s dng lin hon cc nguyn liu.
Khng nhng thnh phm nhiu loi l thuc c m nhiu nguyn
ph liu dng trong sn xut Ho dc l nhng cht c, nhiu qu
trnh phn ng v tinh ch s dng cc loi dung mi d chy n.
Nhiu dung mi to hn hp n vi khng kh. trnh chy n, khng
c dng khng kh nn chuyn vn cc dung mi d chy n, m phi
dng kh tr hoc bm vn chuyn.
Vic tip xc vi ho cht v dung mi c nh hng khng tt n sc
kho con ngi, gy nn nhiu bnh ngh nghip mn tnh. V vy phi
nghim tc tun theo nhng qui nh v an ton lao ng. Phi c hiu bit
su v chuyn mn, c tnh k lut v tinh thn trch nhim cao trong sn
xut.
14
Rt nhiu qui trnh sn xut thuc l nhng tng hp tinh vi, s
dng nguyn liu t v him, thit b t ng phc tp.
V vy i ng cn b v cng nhn ca cng nghip Ha dc phi c
trnh cao, thnh tho v chuyn nghip ha. c bit nhng ngi ph
trch tng dy chuyn sn xut phi c o to tt, m bo hiu qu ca
sn xut v cht lng thnh phm. Vic t chc, v qun l sn xut phi
thng xuyn nng cao, ci tin v hp l ho.
3. Phng php nghin cu sn xut thuc mi
S i hi thng xuyn ca iu tr bnh c tc dng thc y mnh m
vic nghin cu sn xut cc thuc mi. i vi mi quc gia, y l vn v
cng quan trng trong chin lc bo v sc kho con ngi. Hin nay, vic
nghin cu a mt thuc mi vo sn xut thng c hai xu hng:
3.1. Nghin cu tm kim hp cht mi dng lm thuc
Trn c s nhng pht minh ca cc nh khoa hc thuc nhiu lnh vc
khc nhau nh sinh hc, dc l... v nhng hp cht t nhin c tc dng
sinh hc, cc nh ho hc xc nh cu trc phn t v tng hp ra hp cht
ny cng nhng dn xut mi ca n. Kt qu s c mt lot cc hp cht mi
cho cc nh sinh hc, dc l... tin hnh th tc dng sinh hc, dc l nhm
chn ra nhng hp cht p ng yu cu iu tr. Con ng ny rt kh, v
trong hng trm thm ch hng ngn hp cht iu ch c c th ch mt
hoc vi cht c la chn iu tr.
3.2. Nghin cu xy dng qui trnh sn xut m
Nhim v ch yu y l tm phng php tng hp mi, trn c s
xy dng mt quy trnh mi tin li hn, kinh t hn sn xut cc hp cht
c s dng trong iu tr. Xu hng nghin cu ny thng c thc
hin nhng trng hp sau:
Cc phng php tng hp hoc quy trnh sn xut c lc hu,
khng kinh t, khng c kh nng sn xut quy m cng nghip.
n nay nh s pht trin ca cng ngh tng hp hu c, c kh
nng thay i bng mt phng php tng hp mi hin i hn,
kinh t hn.
Cc hp cht chit xut t t nhin c hot tnh sinh hc cao, hin
ang c dng lm thuc, nhng do ngun nguyn liu t nhin cn
kit, khng p ng nhu cu iu tr cho nn cn phi nghin cu
phng php tng hp, bn tng hp.
Do nguyn nhn khng mua c bn quyn sng ch, do phi
nghin cu tm mt phng php khc sn xut dc cht bit
(Hin nay, i vi cc nc ang pht trin c th mua li nhng
15
bng pht minh ht bn quyn tit kim chi ph nghin cu v
rt ngn thi gian a mt thuc ang c s dng vo sn xut).
Vic a mt thuc mi vo sn xut bt k theo xu hng no cng
gm nhng bc sau:
+ Nghin cu tng hp qui m phng th nghim: R (Research).
+ Nghin cu trin khai quy m pilot: D (Development).
+ Nghin cu sn xut quy m cng nghip: P (Production).
3.3. Nghin cu tng hp qui m phng th nghim
u tin cn tra cu, thu thp ti liu cng y cng tt v hp
cht cn nghin cu tng hp nh: phng php tng hp, phng
php xc nh cu trc, cc hng s ho l, phng php kim
nghim, tc dng sinh hc ...
Trn c s ti liu tra cu c, phn tch chn lc nhng ni dung
ph hp vi iu kin phng th nghim, iu kin sn xut trong
nc. Sau tin hnh th nghim qui m nh kho st nhng
yu t nh hng ti hiu sut to thnh sn phm (tc nhn phn
ng, xc tc, dung mi, nhit , t l mol cc cht tham gia phn
ng, nng , thi gian phn ng...), kho st phng php x l sau
phn ng, phng php tinh ch, kh nng thu hi d phm, phng
php xc nh cu trc, n nh ca qui trnh, ...
Sau khi c sn phm tinh khit, tin hnh th hot tnh sinh hc
(in vitro, in vivo), th tc dng dc l, c tnh trn ng vt th
nghim, th tin lm sng v lm sng.
Xy dng quy trnh iu ch hot cht t tiu chun dc dng
(theo tiu chun ngnh hoc tiu chun Dc in).
Ni dung quy trnh phng th nghim:
Trn c s cc kt qu nghin cu, vit thnh quy trnh phng th
nghim cc nh chuyn mn da vo thc hin nghin cu trin khai
qui m pilot. Mt qui trnh phng th nghim tng hp Ho dc thng gm
nhng ni dung sau:
1. Tn ti: cn ghi r tn ti, cc bc phn ng, cc cht trung
gian mi hoc sn phm mi c to thnh.
2. Tn sn phm: cn vit tn khoa hc theo ti liu v tn gi c s
dng trong nh my hoc x nghip.
3. Cc hng s ho hc, vt l: cn nu cng thc cu to, cng thc
nguyn, phn t lng, mu sc, dng tinh th, im chy, si ca
16
sn phm. Ring ho tan cn nu k cc loi dung mi v lng
cht c th ho tan cc nhit khc nhau. Cc iu cn bit v
bn vng, iu kin bo qun ca sn phm v cc s liu lin quan
v tc dng sinh hc.
4. Yu cu v cht lng sn phm: cn a ra cc yu cu ca ti liu
tham kho v kt qu bn thn t c v cc ch tiu cht lng ca
sn phm nh mu sc, mi v, cc tnh cht vt l... V d im chy
ti liu ghi l l30
o
C, nhng phn ng tip theo ch cn im chy
l25
o
C l t yu cu th trong qui trnh cng ghi im chy ny.
5. Lch s tm tt ca sn phm: cc phng php sn xut, ni sn
xut, ngi pht minh v thi gian lm ra sn phm.
6. Cc phng trnh phn ng iu ch, phn t lng, t l mol thc
dng, im si, im chy v mt s tnh cht ca cc cht tham gia
phn ng...
7. Qui trnh tm tt: ch ghi qui trnh mt cch tm tt v cc im cn
ch .
8. Lit k tn nguyn liu, ph liu cn thit cho qui trnh, ghi r yu
cu v cht lng v s lng.
9. Qui trnh chi tit: m t chi tit cch tin hnh, lit k cc thit b,
nu chi tit cc s liu cc nh chuyn mn bit cch thc hin th
nghim.
10. An ton v bo h lao ng: cn ghi r cc im cn ch v an ton
lao ng trong qu trnh tin hnh th nghim.
11. Mt s kinh nghim khi thc hin th nghim: cn ghi li nhng kinh
nghim c nhn trong qu trnh tin hnh th nghim ngoi nhng
m t trong qui trnh chi tit.
12. Ch tiu nguyn liu ph liu: cn phi tnh ton ch tiu nguyn
liu, ph liu, dung mi cn thit cho mt kg sn phm.
13. Cc ti liu tham kho: cn trch dn cc ti liu tham kho lin
quan n ti thu thp c.
14. Thi gian, a im, h tn nhng ngi tham gia tin hnh ti
nghin cu v ch k (c ghi r h tn) ngi vit qui trnh.
3.4. Nghin cu trin khai qui m pilot
Nhim v chnh ca giai on ny l gii quyt cc vn k thut khi
"to ho" quy trnh v ti u ho cc iu kin th nghim. c bit lu n
cc vn ny sinh khi m rng qui m th nghim nh an ton trong sn
xut, cht lng sn phm, hiu qu kinh t... trnh nhng sai phm
17
khng thy c qui m phng th nghim. Cn nghin cu gii quyt cc
vn c th sau:
Vn dung mi: tm cch thay th cc dung mi d chy n, c hi
bng cc dung mi an ton hn, thay cc dung mi t tin bng cc
dung mi r hn.
Vn phng thc np liu: ti u ho cch thc np liu cho ph
hp vi tng thit b v ton b dy chuyn sn xut.
Vn lin tc ho qu trnh: nghin cu thay cc cng on sn
xut gin on thnh mt qu trnh lin tc.
Vn phn lp v tinh ch sn phm: nghin cu phng php
phn lp v tinh ch sn phm thch hp cho qui m sn xut ln.
V theo di im kt thc phn ng.
V vn phng php thao tc, gia nhit.
Vn thit b: cc yu cu v vt liu lm thit b v cc loi thit b
cn s dng.
Vn thu hi, x l dung mi v sn phm ph.
Vn nh mc nguyn liu vt t, thi gian cho mt qui trnh sn
xut.
3.5. Xy dng qui trnh sn xut qui m cng nghip
T nhng kt qu nghin cu trn, tng kt vit thnh qui trnh k
thut qui m sn xut cng nghip. Qui trnh ny bao gm cc giai on sn
xut rt c th. Mi giai on c cc thao tc k thut to ra sn phm
trung gian hoc thnh phm. C th ho nh mc vt t nguyn liu, nng
lng, thi gian sn xut, la chn v b tr thit b, phng php x l, thu
hi dung mi v sn phm ph... Vi qui trnh chi tit ny ngi cng nhn c
th sn xut ra cc sn phm theo ng yu cu.
4. Ngun nguyn liu ca cng nghip ho dc
Cng nghip Ho dc sn xut ra tt c cc loi nguyn liu cho cng
nghip Bo ch dc phm nh: hot cht, cc cht ph tr, cc t dc v cc
loi dung mi... V vy ngun nguyn liu ca cng nghip Ho dc rt rng
ri, bao gm khong sn, thc vt, ng vt, hay sn phm tng hp ho hc.
4.1. Cc nguyn liu v c
Cc khong sn:
L ngun nguyn liu ch yu sn xut cc ho dc v c.
18
T nc bin c th sn xut cc mui v c nh: NaBr, KBr, NaI, KI,
NaCl, KCl. Rong bin l ngun sn xut iod ng k v cng l
ngun thc n b sung iod cho c th.
T nc t (nc ci sau khi phi nng kt tinh mui n t nc bin)
c th iu ch c cc mui magnesi dng trong ngnh dc nh
MgSO
4
.7H
2
O lm thuc ty, thuc nhun trng. Ngoi ra cc mui
magnesi carbonat nh MgCO
3
, Mg(HCO
3
)
2
, 3MgCO
3
.Mg(OH)
2
.3H
2
O
dng lm thuc nhun trng, chng toan mu v lm t dc.
T qung Pyrolusit c th iu ch KMnO
4
dng lm thuc st trng.
T qung Barytin (c cha khong 90 - 98% BaSO
4
)

c th tinh ch
c BaSO
4
dc dng dng lm cht cn quang chp d dy, ng
tiu ho.
T qung Dolomi (cha carbonat kp ca magnesi v calci) c s
dng sn xut mui magnesi lm t dc.
T thch cao (CaSO
4
.2H
2
O) khi nung 120 - 130
o
C mt nc to
thnh CaSO
4
.1/2H
2
O dng lm bt b.
Vit Nam, qung Barytin c Tuyn Quang v Bc Giang (hm lng
BaSO
4
khong 98%), qung Pyrolusit Cao Bng (hm lng MnO
2
trn 43%),
qung Dolomi Thanh Ho, Vnh Phc. Chng ta khai thc sn xut
cc ho cht v c phc v cho y t v cc ngnh khc.
Cc acid v kim v c:
Cc acid v kim v c (H
2
SO
4,
, HNO
3
, HCl, NaOH, KOH, NH
4
OH...) l
nguyn liu khng th thiu c ca cng nghip Ho dc.
Acid sulfuric sn xut t qung Pyrit (FeS
2
). Acid clorosulfuric iu ch
t Cl
2
v acid sulfuric, c s dng trong sn xut cc sulfamid. Acid
sulfuric, oleum v acid clorosulfuric c sn xut Cng ty ho cht Lm
Thao t qung Pyrit (FeS
2
).
Acid hydrocloric c sn xut bng phn ng ca kh Cl
2
vi H
2
(Cl
2
thu
c khi in phn mui n). Natri hydroxyd l d phm khi in phn mui
n NaCl. nc ta acid hydrocloric v NaOH dung dch c sn xut ti
Nh my ho cht Vit Tr.
Amoni hydroxyd, acid nitric c sn xut ti Cng ty ho cht, phn
m Bc Giang.
Than v du m:
Cc hp cht thu c t than v du m l ngun nguyn liu quan
trng nht ca cng nghip ho cht ni chung v cng nghip Ho dc ni
19
ring. Hu ht ho cht c bn ca cng nghip tng hp ho hc v cng
nghip Ha dc l sn phm ca hai ngnh cng nghip chng ct than v
chng ct du m.
Nguyn liu t than :
Xut pht t nhu cu cn c than cc luyn kim, cng nghip chng
ct than bt u t th k XVI (1584). Sn phm chnh lc l than
cc luyn kim. Ti cui th k XVIII, nn cng nghip ny sn xut c
kh thp sng, s dng rng ri cho ti th k th XIX. Sau nh s pht
trin ca cng nghip in lc, cc kh thu c khi chng ct than c
chuyn sang dng lm nhin liu cho cc ngnh cng nghip v un nu trong
gia nh. ng thi sn phm ca chng ct than c x l to ra
nhng nguyn liu ho cht cho cc ngnh cng nghip ho hc (Hnh 1.1).

H O CH
2
CH
2
N(C
2
H
5
)
2
C C l
4
ClCH
2
CH
2
O H
C H C l
3
( H
2
,

C H
4
,

C O ,

C
2
H
4
, C
2
H
2
, C O
2
,

N
2
...)
Cc
Nc
amoniac
Nha
Gudrng
Kh kh
ngng t
Than
CCl
2
=CCl
2
C C l
4
ClCH
2
CH
2
O H
C H C l
3
( H
2
,

C H
4
,

C O ,

C
2
H
4
, C
2
H
2
, C O
2
,

N
2
...)
Cc
Nc
amoniac
Nha
Gudrng
Kh kh
ngng t
Than
CCl
2 2
C C l
4
ClCH
2
CH
2
O H
C l C H
2
C H
2
C l C H C l
3
( H
2
,

C H
4
,

C O ,

C
2
H
4
, C
2
H
2
, C O
2
,

N
2
...)
Cc
Nc
amoniac
Nha
Gudrng
Kh kh
ngng t
Than
CCl
2
Pavatrin Thuc ho
creozot
Dictyl
phtalat
Phenol
Phtalein
Phtalazol
Cresyla
st trng
Aspirin
dn xut
salicylat
Sulfamid Xylocain Anestesin
Novocain
DDS
tr
phong
v dn xut
Vitamin PP
Coramin
Rimifon
phtalic salicylic nilit
xilen toluen benzen
Quinolin picolin
Nitro
Anhydrit Acid
Acet- Nitro Cloro
picolin
Fluoren Creozot Naphtalin
Crezol
Phenol
Anilin Xylen Toluen Benzen Base pyridin
Du
Antracenic
Du nng
Creozot
Du trung
bnh phenolic
B - re
Du nh
" Naphta"
- -
tr ho
-
Pavatrin Thuc ho
creozot
Dictyl
Phenol
Phtalein
Phtalazol
Cresyla
st trng
Aspirin
dn xut
salicylat
Novocain
DDS Vitamin PP
Coramin
Rimifon
xilen toluen benzen
Quinolin picolin
Nitro
Anhydrit Acid
Acet- Nitro Cloro
picolin
Crezol
Phenol
Anilin Xylen Toluen Benzen
Du
Antracenic
Du nng
Creozot
Du trung
bnh phenolic
B - re
Du nh
" Naphta"
- -
tr ho
-
Pavatrin Thuc ho
creozot
Dietyl-
Phenol
Phtalein
Phtalazol
Cresyla
st trng
Aspirin
dn xut
salicylat
Novocain
DDS Vitamin PP
Coramin
Rimifon
xilen toluen benzen
Quinolin picolin
Nitro
Anhydrit Acid
Aceta- Nitro Cloro
picolin
Crezol
Phenol
Anilin Xylen Toluen Benzen
Du
Antracenic
Du nng
Creozot
Du trung
bnh phenolic
B - re
Du nh
" Naphta"
- -
tr ho
-
Hnh 1.1. S tm tt sn phm chng ct than v kh nng s dng
ca chng trong cng nghip Ho dc
20
Khi chng ct khan than trong ni kn ta c 3 phn:
Phn kh.
Phn lng gm nha gurng v nc amoniac.
Phn cn rn l than cc luyn kim.
T 1 tn than, khi chng khan trong ni kn c th thu c 230-250 m
3

kh kh ngng t; 65-70 kg nc amoniac (x l ly c 12 kg amoni sulfat
dng lm phn bn); 60-65 kg nha gurng; 600-700 kg than cc dng luyn
kim (theo Dupont).
T 1 tn than (theo Jukelson) c th thu c:
Benzen: 3,5 kg Naphtalin: 2,00 kg
Toluen: 1,5 kg Quinolin: 0,01 kg
Xilen: 0,7 kg Antracen: 0,15 kg
Phenol: 0,07 kg Carbazol: 0,02 kg
Cresol: 0,1 kg Pyridin: 0,02 kg
Phn kh kh ngng t, tnh theo th tch c khong trn 50% H
2
; 20-
32% CH
4
; 5-8% CO, 0,5-2,2% ethan ...
Nguyn liu t du m:
T du m qua x l, nh cng ngh Ho du cung cp cho cng
nghip ho cht (trong c cng nghip Ho dc) rt nhiu loi nguyn liu
c bn.
Du m th cha nhiu loi hydrocarbon nh: parafin, cycloparafin v
cc hydrocarbon thm. Du ca mi m c thnh phn ho hc khc nhau.
Ti nguyn du m Vit Nam rt phong ph. Tr lng cha c nh
gi y , song theo c tnh ca mt s chuyn gia, c th ti hng t tn.
s dng du m vo cc ngnh cng nghip khc nhau, ngi ta phi
ch bin bng cch chng ct trong cc nh my lc du.
Hnh 1.2, 1.3, 1.4, 1.5 tm tt mt s sn phm chnh t qu trnh chng
ct du m v mt s qu trnh tng hp hu c t sn phm ca cng ngh
Ho du.

21

Cht lm tng
ch s octan
trong xng du
v lm dung mi
Lm dung mi v nguyn
liu tng hp ho hc
Lm nguyn liu tng hp
ho hc
Lm nguyn liu tng hp
ho hc
Lm nguyn liu tng hp
ho hc
Lm dung mi
lm nguyn liu tng hp
ho hc
Lm dung mi
v nguyn liu
tng hp ho hc
t - Amyl methyl ether (TAME)
Ethyl t -Buthyl ether (ETBE)
Methyl t - Buthylether (MTBE)
naftalen
alkylbenzen
benzen
alkylacetylen
acetylen
isopenten
isobuten
isohexan
isobutan
isopropan
butylen
propylen
ethylen
cyclohexan
cyclopentan
hexan
pentan
butan
propan
ethan
methan
Ether
Aromatic
Isoparafin
isoolefin
Olefin
Cycloparafin
Parafin
Du
th
Cc
acetylen

Hnh 1.2. Nhng sn phm chnh ca qu trnh chng ct du m

lm nguyn liu
tng hp hu c
lm nguyn liu
tng hp hu c
lm nguyn liu tng hp
lm dung mi
Lm dung mi v nguyn
liu tng hp ho
oxy ho
NH
3
O
2
+
nitro ho
Methan
C H
4
C + H
2
CH CH
CO + H
2
H COOH
C H
2
O
C H
3
OH
H C N
C H
3
NO
2
C C l
4
C H C l
3
C H
2
C l
C H
3
C l
clo ho 2

Hnh 1.3. Tng hp cc nguyn liu hu c t kh metan
22
ClCH
2
CH
2
Cl
Ethylen
CH
2
CH
2
CH
3
CH
2
OH
CH
2
CH
2
O
ClCH
2
CH
2
OH
CH
3
CH
2
Cl
C
6
H
5
C
2
H
5
CH
3
CH
2
CHO
CH
3
CH
2
COOH
CH
3
CH
2
NH
2
Ho cht
trung gian
Cht trung gian cho
ho dc, ho hc
Ho cht trung gian
Dung mi v ho cht
trung gian
Nguyn liu cho cao
phn t
Cht gy t
CHCl CH
2

Hnh 1.4. Tng hp cc nguyn liu hu c t kh ethylen

SO
3
H
Benzen
clo ho
sulfo ho
nitro ho
C H
2
CH
2
O
C l
N O
2
C H
2
CH
2
OH
NaOH
P, t cao
o
OH
O H
NaOH
300 C
o
OH
Fe/HCl
NH
2
CH
2
CH
2
I
Paracetamol
aspirin
sulfamid,
Mebendazol
Praziquantel
Hydroxyl ho
H
2
O
2
/HSO
3
F

Hnh 1.5. Tng hp cc nguyn liu hu c t benzen
Trong ngun nguyn liu du m, ngoi cc sn phm t cng nghip
Ho du nh k trn, cn phi k ti thnh phn th hai l kh ng hnh.
Thnh phn ca kh ng hnh v kh thin nhin ch yu l methan v ng
ng, y cng l ngun nguyn liu qu. Ngoi vic s dng lm cht t,
cn l nguyn liu cho cc nh my phn m, sn xut methanol, ethylen ...
23
4.2. Cc nguyn liu ng vt v thc vt
Nguyn liu ng vt:
Mt s ph tng, dch c th hay dch o thi ca ng vt c th c
s dng sn xut ra thuc. V d: t tuyn tu sn xut c insulin, nc
tiu nga ging l nguyn liu sn xut foliculin, t tuyn thng thn chit
c adrenalin, cc acid mt l ngun sn xut mt s steroid, t phi b c
th sn xut heparin, t tuyn gip ln sn xut c thyroxin...
Nguyn liu thc vt:
iu kin kh hu nhit i to cho nc ta mt ngun dc liu phong
ph. Nhiu hot cht dng lm thuc c sn xut qui m cng nghip
da trn ngun nguyn liu ny nh codein, vincamin, strychnin, rutin,
berberin, rotundin, cc dn cht artemisinin...
Ngnh cng nghip Ho dc nc ta hin nay cha pht trin. S hiu
bit v ngun nguyn liu ca ngnh ny gip chng ta nh hng nghin
cu v sn xut. T c th t to ra mt s nguyn liu cho ngnh cng
nghip Dc dn i vo qu o pht trin.
T lng gi
1. Trnh by v phn tch 4 c im ca cng nghip ho dc.
2. Vic nghin cu, sn xut thuc mi hin nay thng theo nhng xu
hng no? Nu ni dung ca nhng xu hng .
3. Nu cc giai on cn thit thc hin a 1 thuc mi vo sn
xut.
4. Trnh by cc ngun nghin liu ca cng nghip ho dc.
24
Chng 2
Nitro ho
Mc tiu
1. Khi nim v c ch phn ng nitro ho.
2. Cc tc nhn ca qu trnh nitro ho.
3. Cc yu t nh hng n phn ng nitro ho.
4. Cc v d ng dng ca phn ng nitro ho.
1. i cng
Nitro ho l qu trnh ho hc nhm thay th mt hoc nhiu nguyn t
hydro ca hp cht hu c bng mt hay nhiu nhm nitro (-NO
2
).
Phng trnh phn ng nh sau:
R-H + HNO
3
R-NO
2
+ H
2
O
Nitro ho l phn ng to lin kt C-NO
2
. Cc ester ca acid nitric vi
alcol (hp cht cha lin kt O-NO
2
) khng c xt n trong chng ny.
Cc hp cht nitro thng l cht lng hay tinh th mu vng hoc nu,
mi hc c bit. Dn cht nitro c s dng lm dung mi, thuc th, thuc
n. L trung gian quan trng trong nhiu qu trnh tng hp thuc v cc cht
hu c. Trong thc t cng c mt s loi thuc cha nhm -NO
2
nh
cloramphenicol, furaxilin...
2. C ch phn ng nitro ho
Phn ng nitro ho c th xy ra theo 2 kiu c ch: Th i in t (S
E
)
v th gc t do (S
R
), ph thuc bn cht cc cht c nitro ho v iu kin
phn ng.
2.1. Th i in t (Electrophilic Substitution)
Khi nitro ho nhng hp cht thm bng hn hp sulfo-nitric thng xy
ra theo c ch th i in t (S
E
). Phn ng thc hin pha lng v nhit
25
khng cao. Ion nitroni NO
2
+
l tc nhn i in t, c to thnh theo
phng trnh sau:
HNO
3
+ 2H
2
SO
4
NO
2
+
+ 2HSO
4
-
+ H
3
O
+
Sau ion nitroni NO
2
+
tn cng vo nhn thm theo c ch th i in
t chung. Phn ng nitro ho xy ra theo hai giai on, trong giai on to
phc (sigma) l giai on chm, quyt nh tc phn ng.

H
2
SO
4
l xc tc to ion nitroni v to ra mi trng acid mnh
ngn cn s phn ly ca HNO
3
thnh H
+
v NO
3
. Khi nng H
2
SO
4
gim th
tc phn ng nitro ho cng gim theo.
V d:
Khi nitro ho benzen 25
0
C, nu nng acid sulfuric nh hn 80% th
phn ng xy ra khng ng k. Nu nng acid sulfuric l 80-90% th tc
phn ng tng ln 1000 ln.
Nhm th c sn trn nhn nh hng ng k n phn ng nitro
ho theo qui lut:
Nhm th loi 1 lm tng qu trnh nitro ho v nh hng nhm
-NO
2
vo v tr ortho v para.
Nhm th loi 2 lm gim qu trnh nitro ho v nh hng nhm
-NO
2
vo v tr meta.
2.2. Th gc t do (Radical Substitution)
Khi nitro ho cc hp cht hydrocarbon no mch thng, ngi ta thng
dng tc nhn l acid nitric long (30%-40%). Phn ng thc hin th kh,
nhit cao (300-500
0
C) v xy ra theo c ch th gc t do:

H O N O 2 +
OH NO2
R H
+
N O 2
+
HNO2 R
R
+ H N O 3
RNO2
+
OH
R H
+
O H R
+
H2O
R
+
H N O 3 ROH
+
NO2
R
+
N O 2 RNO2
R
+
O H ROH
O H
+
N O 2 HO NO2
R
+
R R R

+ NO
2
+

H NO
2
+
NO
2
+ H
+
26
Ngoi sn phm chnh, cn thu c 1 hn hp cc sn phm ph gm
alcol, hydrocarbon v 1 vi sn phm oxy ho t hydrocarbon.
3. Tc nhn nitro ho
3.1. Acid nitric (HNO
3
)
Dng tinh khit l cht lng trong, mi hc mnh, t
0
nc
= -41,6
0
C, t
0
s
=
85,3
0
C, d =1,502. un si hay lu ngoi nh sng b phn hu:
4HNO
3
4NO
2
+ 2H
2
O + O
2
Trong cng nghip thng gp cc loi nng 65-68% (d=1,42), 95%
(d =1,49, bc khi). Loi nng cao c th ng trong bnh thu tinh, snh
hoc nhm. Loi nng thp c th ng trong bnh thu tinh, snh hoc
thp khng g. Trnh nh sng.
Acid nitric l tc nhn nitro ho yu v b pha long bi nc to thnh
trong phn ng. Mt khc, do c tnh oxy ho mnh, nn to nhiu tp cht l
sn phm oxy ho cc hydrocarbon tham gia phn ng. Lng acid nitric dng
cho phn ng nitro ho khong 1,5-2 ln so vi l thuyt.
3.2. Hn hp sulfo-nitric (H
2
SO
4
+ HNO
3
+ H
2
O)
khc phc nhng nhc im ca acid nitric, trong cng nghip ngi
ta dng hn hp ca acid nitric v sulfuric (hn hp sulfo-nitric). Cation
nitroni NO
2
+
c to thnh theo phng trnh:
HNO
3
+ H
2
SO
4
2
NO
2
+ HSO
4
+ H
3
O 2

T l hn hp H
2
SO
4
: HNO
3
: H
2
O ph thuc bn cht ca cc hp cht
c nitro ha:
Vi cc hp cht thm c kh nng phn ng cao (phenol, phenol-
ether) ch cn dng dung dch HNO
3
40%.
Cc hp cht thm c kh nng phn ng trung bnh (phn ln c
nhm th loi 1, tr dn cht halogen) th nitro ho 1 mol, cn 1,5
mol HNO
3
68% v 2,2 mol H
2
SO
4
98%.
Cc hp cht thm c kh nng phn ng thp (cc cht c nhm th
loi 2) th nitro ho 1 mol, cn 2,3 mol HNO
3
95-100% (d =1,49-1,5)
v 2,6 mol H
2
SO
4
98%.
Trong cng nghip ngi ta thng pha sn hn hp sulfo-nitric c nng
nh sau:
27
+ HNO
3
: 88% (loi 60-65 %, d=1,4)
+ H
2
SO
4
: 9,5% (loi monohydrat hay oleum 20 %)
+ H
2
O: 2,5 %
T l trn c th pha long thm tu . Mt khc, n c th ng c
trong bnh thp thng, d vn chuyn.
u im ca loi tc nhn ny l:
Tc dng nitro ho mnh hn HNO

3
.

Gim tc dng oxy ho ca HNO
3
khi dng nng cao.
Trnh to thnh dn cht polynitro.
3.3. Mui nitrat v acid sulfuric
y l tc nhn c s dng khi cn nitro ho trong mi trng khan
nc, thng c s dng iu ch cc dn cht polynitro.
2NaNO
3
+ H
2
SO
4
2HNO
3
+ Na
2
SO
4
3.4. Acylnitrat (AcONO
2
)
L tc nhn nitro ho mnh, dng nitro ho cc cht d b phn hu
bi nc hoc acid v c. Tc nhn ny khng cha acid v c, sn phm ph
ca phn ng l acid acetic.
(CH
3
CO)
2
O + HNO
3
CH
3
COONO
2
+ CH
3
COOH
+ CH
3
COONO
2
NO
2
+ CH
3
COOH

Khi dng tc nhn ny nitro ho cc amin thm, ng thi vi qu trnh
nitro ho nhm amin cng c bo v.

4. Cc yu t nh hng n phn ng
4.1. nh hng ca nhit
Nitro ho l qu trnh to nhit mnh. Lng nhit ny bao gm nhit
phn ng v nhit pha long acid sulfuric bi nc to thnh trong phn ng.
NH
2
NHCOCH
3
NO
2
Ac
2
O/HNO
3

28
Tc v hiu sut phn ng ph thuc nhiu vo nhit . Nhit ti
u ca phn ng ph thuc vo bn cht cc cht c nitro ha (thng bin
i t -10
0
C n 500
0
C). Vi cc hydrocarbon no mch thng, thng tin
hnh 170-500
0
C (phn ng theo c ch gc t do). Cn khi nitro ho cc
hydrocarbon thm, th lng th tin hnh nhit thp hn (-10 n 170
0
C).
Nhit cao sinh ra nhiu tp cht do phn ng oxy ho, v vy b phn trao
i nhit ca thit b nitro ho phi hiu qu trnh hin tng qu nhit.
4.2. Tc dng ca khuy trn
Phn ng nitro ha thng l d pha: pha hu c (cc cht cn nitro ho)
v pha acid (tc nhn nitro ho). V vy cn phi khuy trn mnh tng
tip xc v trnh qu nhit cc b.
4.3. Dung lng kh nc
Trong qu trnh nitro ho, nc c to ra lm gim nng acid
sulfuric. Phn ng s t ti cn bng khi nng acid gim ti mt gii hn
nht nh. Mi cht khc nhau gi tr gii hn cng khc nhau. i lng
c trng cho gi tr gii hn ca mi cht c gi l dung lng kh nc
ca cht . Dung lng kh nc (D.L.K.N.) c tnh theo cng thc sau:
% H
2
SO
4
a vo phn ng
% H
2
O ban u
+
%
H
2
O do phn ng sinh ra
D.L.K.N. =

Bit c D.L.K.N. ca mi cht c th tnh c lng acid sulfuric cn
dng pha hn hp sulfo-nitric khi nitro ha cht . V d D.L.K.N ca mt
s hp cht hu c nh sau: nitrobenzen: 7,4; clorobenzen: 4,4; benzen: 3,5;
toluen: 2,4; naphtalen: 2,0.
5. Cch tin hnh phn ng
Nitro ho cc hp cht thm tin hnh pha lng theo nguyn tc sau:
Cht cn nitro ha c lm lnh xung di 10
0
C. Va khuy, va nh
git tc nhn nitro ha vo vi tc sao cho nhit phn ng khng vt
qu 10
0
C. Cc hp cht c kh nng phn ng cao th khuy thm 30 pht
nhit phng, cc cht kh nng phn ng trung bnh th khuy thm 2-3
gi, cc cht kh nng phn ng km th 3-5 gi. Trng hp cn thit c th
lm nng phn ng kt thc.
hn hp phn ng vo nc , khuy k. Nu sn phm l cht rn
th lc, ra li vi nc, sau kt tinh li trong dung mi thch hp. Nu sn
phm th lng th chit hn hp phn ng vi ether hoc dicloromethan, ra
dch chit, lm khan v ct loi dung mi. Sn phm c tinh ch bng ct
phn on.
29
Vi cc hp cht mch thng th qu trnh nitro ha thng tin hnh
pha hi, nhit cao, trong thit b lin tc. Sau hn hp phn ng c
ngng t, phn lp v ra li bng nc. Trung ha bng dung dch natri
bicarbonat, lm khan v cui cng l ct phn on.
6. Nitrozo ha
Nitrozo ha l qu trnh a nhm -NO vo hp cht hu c. y l
phn ng gia hp cht thm c cha nhm th hot ha nhn mnh (-OH,
-NR
2
...) vi acid nitr. Nitrozo ho cng l phn ng th i in t, tc nhn i
in t l ion nitrozoni NO
+
. Phn ng tin hnh nhit thp (<10
0
C).
2NaNO
2
+ H
2
SO
4
HNO
2
+ Na
2
SO
4
HNO
2
+ H
2
SO
4
NO
+
+ H
2
O + HSO
4

X= -OH, -NR
2

Sn phm nitrozo ho thng l ng phn para.
7. Thit b phn ng v an ton lao ng
Cc thit b dng cho phn ng nitro ho cn m bo cc yu cu v
khuy trn v trao i nhit. y l phn ng to nhit mnh nn ngoi v
lm lnh, cn thit c b phn trao i nhit bn trong nh ng xon hoc ng
hnh tr m bo hiu qu lm lnh. Cnh khuy thng l dng tuc bin
vi tc 300-400 vng/pht. Vt liu ch to thit b c th dng thp khng
g, thp trng men chu acid, thu tinh...
Phn ng nitro ho d gy tai nn nu lm lnh khng tt. Khi hn hp
nitro ho c th pht ra ngoi gy bng acid. Trng hp t ngt mt in,
my khuy khng lm vic phi lp tc ngng phn ng v lm lnh cc b
bng nc . Cc polinitro l nhng cht d gy n nn khi ct tinh ch sn
phm phi ht sc ch phng chy n. Khi x l hn hp sau phn ng, c
tip xc vi acid c v kim, cn mang dng c bo h lao ng y .
8. Mt s v d
8.1. Sn xut nitrobenzen bng phng php lin tc
Nitrobenzen c s dng lm dung mi v cht trung gian trong nhiu
phn ng tng hp ho hc. N c iu ch bng cch nitro ho benzen theo
phng php gin on pha lng hoc phng php lin tc pha hi.

X H X NO
+
N O
+
+
H S O
4
+ H
2
S O
4
30
Phng php lin tc c tin hnh theo s sau:

c
)
O
O
U
U
U
U
1
2
3
4
5
6
7
8
9
10
Nitrobenzen

1,2. Bnh ong.
3. Ct nitro ho.
4. Sinh hn.
5,7. Bnh tch.
6. B phn ct.
8. Ct ct.
9. Bm.
10. Bnh ho hi.
Hnh 2.1. S thit b iu ch nitrobenzen theo phng php lin tc
Acid nitric 61% t bnh ong 1 c ho hi trong thit b s 10 ri a
vo thp nitro ho 3. Ti y, phn ng vi benzen (c a xung t bnh
ong 2). Hn hp phn ng khong 72-78
0
C c a xung bnh 6, tch ly 1
phn benzen a li phn ng. Sau hn hp phn ng tip tc c dn
vo ct ct 8. Ct ly hn hp acid v benzen cn li (118
0
C) a li phn ng
v thu sn phm nitrobenzen khng bay hi (im si 208
0
C).
8.2. Tng hp thuc h nhit, gim au paracetamol
Paracetamol l thuc h nhit gim au, c tng hp t phenol. Qu
trnh iu ch gm nhng giai on sau:
Nitro ho phenol bng hn hp sulfo-nitric thu c hn hp hai ng
phn o-nitro-phenol v p-nitro-phenol. Tch ring hai ng phn ny
bng phng php ct ko hi nc.
Kh ho p-nitro-phenol bng Fe/HCl hoc Na
2
S/NaOH thu c
p-amino-phenol.
Acyl ho p-amino-phenol bng Ac
2
O c paracetamol.
S phn ng nh sau:
31

T lng gi
1. Th no l qu trnh nitro ho? C ch phn ng nitro ho gm my
loi, iu kin v ni dung ca mi loi c ch l g?
2. C bao nhiu loi tc nhn ca qu trnh nitro ho? K tn v trnh
by ni dung ca mi loi ?
3. C nhng yu t no nh hng n phn ng nitro ho? Ni dung
nh hng ca chng l g?
4. Trnh by nguyn tc chung ca cch tin hnh cc phn ng nitro ho.
5. Nitrozo ho thng xy ra vi nhng nhm hp cht no? Tc nhn
ca chng l g?
6. Hy nu nhng iu cn c bit ch v an ton lao ng trong qu
trnh thc hin phn ng nitro ho?
7. Trnh by phng php sn xut nitrobenzen v phng php tng
hp paracetamol trong cng nghip?
OH OH
NO
2
OH
NO
2
OH
NO
2
OH
NH
2
OH
NHCOCH
3
+
HNO
3
/H
2
SO
4
Na
2
S/H
2
O
Ac
2
O/AcOH
32
Chng 3
Sulfo ha
Mc tiu
1. Khi nim v c ch phn ng sulfo ho.
2. Cc tc nhn ca qu trnh sulfo ho.
3. iu kin ca phn ng sulfo ho.
4. Phm vi ng dng, cch tin hnh phn ng v phn lp sn phm
ca qu trnh sulfo ho.
5. Cc v d ng dng ca phn ng sulfo ho.
1. i cng
Sulfo ha l mt qu trnh ha hc a nhm sulfonyl (-SO
3
H) vo mt
hp cht hu c.
R-H R-SO
3
H
Chng ny ch nghin cu phn ng a nhm sulfonyl vo hp cht
hu c mt cch trc tip bng phn ng th hoc phn ng cng. Sulfo ha l
qu trnh to lin kt C-S. Cn phn bit vi cc qu trnh sulfat ho (nhm
-SO
3
H gn vi oxy) hoc sulfamic ho (nhm -SO
3
H gn vi nit). V d:

C H
3
C H
2
S O
3
H C H
3
CH
2
OSO
3
H CH
3
C O N H S O
3
H
Acid ethyl sulfonic
Ethyl sulfat Acid ethyl sulfamic

Danh php ha hc mt s nhm hp cht hu c cha lu hunh:
R-SO
2
H : acid sulfinic (acid alkyl sulfinic)
R-SO
3
H : acid sulfonic (acid alkyl sulfonic)
R-SH : mecaptan (alkyl mecaptan)
R
2
SO : sulfoxit (dialkyl sulfoxit)
R
2
SO
2
: sulfon (dialkyl sulfon)
R-SR : thioether (dialkyl thioether).
33
SO
2
RHN NHR
Cc hp cht sulfonic c ng dng rt rng ri. Trong dc phm, vic
a nhm sulfonyl vo phn t thuc lm tng ha tan ca n trong nc,
thun tin cho vic bo ch cc dng thuc c hiu lc nhanh. V d B.A.L
(2,3-dimecapto-propanol) chng ng c thy ngn, asen l dng thuc tim
trong du. Nu chuyn thnh sulfonat natri (unithiol), c th pha dung dch
nc tim.
CH
2
CH CH
2
OH
SH SH

CH
2
CH CH
2
SO
3
Na
SH SH

(B.A.L.-thuc tim/du) (Unithiol)
a nhm SO
3
H vo phn t thuc cn l bin php lm gim c tnh
ca thuc. V d nhm thuc tr lao, phong: diamin-diphenylsulfon (DDS) rt
t tan v rt c, khi chuyn thnh cc dn cht sulfonat l Promin, Sunfetron,
Baludon, th d tan hn v t c hn.

R Tn thuc
-H D.D.S
CH (CHOH)
4
CH
2
OH
SO
3
Na

Promin
CH CH
2
CH
SO
3
Na
C
6
H
5
SO
3
Na

Sunfetron
CH CH
3
SO
3
Na

Baludon
Trong tng hp ha hc: Cc hp cht sulfonic c tnh phn ng mnh, c
th thay th bng nhng nhm khc nh -OH, -H, -NH
2
, -Cl, -NO
2
, -SH, -CN, ...
Cc alkyl ester ca sulfonat l nhng tc nhn alkyl ha tt (v d: methyl,
ethyl ca benzen sulfonat hoc p-toluen-sulfonat).
Trong k ngh x phng, sulfonat ca cc hp cht mch thng c s
carbon cao c dng lm cht din hot b mt.
2. C ch phn ng
Cng tng t nh qu trnh nitro ho, sulfo ho c th xy ra theo c
ch th i in t (S
E
) hoc th gc t do (S
R
), ph thuc vo bn cht cc cht
c sulfo ho, tc nhn v iu kin phn ng.
34
2.1. Phn ng th i in t (Electrophilic Substitution)
Xy ra khi sulfo ha cc hp cht thm vi tc nhn l acid sulfuric.
Tc nhn i in t l SO
3
c sinh ra theo phng trnh sau:
H
2
SO
4 H
3
O
+ HSO
4
+ SO
3
2

Tc nhn SO
3
tn cng vo nhn thm to thnh phc dng lng cc.
Sau c s chuyn v ca proton to thnh dn cht sulfonic:

2.2. Phn ng th gc t do (Radical Substitution)
Khi sulfo ho cc hydrocarbon no, mch thng nhit cao, xc tc nh
sng v tc nhn l hn hp kh SO
2
v Cl
2
.
Cl
2
as
2 Cl
Cl + RH R + HCl
R + SO
2 R
RSO
2
+
Cl
2
SO
2
R SO
2
Cl R + Cl

3. Tc nhn sulfo ha
3.1. Trioxyd lu hunh (SO
3
) v cc phc hp ca n
3.1.1. Trioxyd lu hunh (SO
3
)
SO
3
tn ti nhiu dng. Dng monome th hi, dng l trime ca
SO
3
th lng (nng chy 16,8
0
C), dng l polime ca SO
3
th rn (nng
chy 32,5
0
C); dng l polime ca SO
3
th rn c nhit nng chy cao
hn (62,3
0
C).

(n>n)
Dng hay c s dng trong cng nghip. Dng v t c s dng
do kh thao tc. Dng ny khi chng ct thu c khong 90% trime (dng )
+ SO
3
H
SO
3
SO
3
H
+

O S
O
O
S
O
S
O
S
O
O
O
O
O
O O
S
O
O
O O S
O
O
O S
O
O
n
( m on om e ) (trime)
(polyme)
35
v 10% SO
3
monome. SO
3
monome trong khng kh, nhit thng sau
vi gi s chuyn sang dng v . ngn cn qu trnh chuyn dng k
trn ngi ta cho thm xc tc l bor trioxyd, bor, lu hunh hoc phospho.
SO
3
l tc nhn sulfo ha mnh, gim tc phn ng v ngn cn
cc phn ng ph (than ha, sulfo ho nhiu ln), thng phi pha long n
vi dung mi nh SO
2
, CCl
4
hoc dicloromethan.
3.1.2. Cc phc hp ca SO
3

a. Cc dng hydrat ca SO
3

SO
3
to vi nc thnh nhiu dng hydrat. Trong cc dng hay c s
dng sulfo ho l acid pirosulfuric, acid sulfuric v acid sulfuric monohydrat.

Acid sulfuric monohydrat
SO
3
.H
2
O
Acid sulfuric
Acid pirosulfuric
S
O
OH
OH
HO
HO
S
O
O OH
OH
S
O O
O
S
O O
OH
OH
H
2
S O
4
.H
2
O
S O
3
H
2
O
2 1

Ngoi ra, lu hunh trioxyd cn tn ti di cc dng phc hp vi 3 v 5
phn t nc. iu ny l gii ti sao acid sulfuric rt ho nc:

SO
3
.3H
2
O SO
3
.5H
2
O
(H
2
SO
4
.2H
2
O) (H
2
SO
4
.4H
2
O)
trihydrat pentahydrat
74,1% H
2
SO
4
, c = 26,7
0
C 57,6% H
2
SO
4
, c = 25
0
C

nhit thp, cc dng
hydrat trn bn vng. B phn
hy nhit cao (450
0
C th
phn hy hon ton thnh nc
v SO
3
).
Oleum l dung dch ca
SO
3
trong acid sulfuric 100%.
Trong thc t, cc qu trnh
sulfo ha thng dng oleum.
Hai loi oleum hay dng c nng
20% v 65%. Cc nng
khc d b kt tinh nhit
thp, gy kh khn cho thao tc
trong qu trnh sulfo ha.
-
-
-
-
-
-
-
-
+ + + + +
20
40
0
60 80
100 % SO
3
40 20
t
0
C
0
( )
H
2
SO
4
Hnh 3.1. S ph thuc gia nhit nng chy
ca cc dng SO
3
hydrat vo nng ca n
36
Hin tng ny c gii thch bng biu hnh 3.1.
b. Cc phc hu c ca SO
3

Nguyn t lu hunh trong phn t SO
3
c kh nng nhn in t. Do
n d to phc vi mt s hp cht hu c c i in t t do.
Cc phc ca SO
3
vi dioxan, thioxan, pyridin v amin bc 3 hay c s
dng. Chng c dng sulfo ha nhng hp cht hu c d b ph hy bi
acid hoc hn ch tc ca phn ng sulfo ha.
N
R1
N R
2
R
3
O O
O S
S O SO
3
SO
3
SO
3
SO
3
SO
3
SO
3
O O SO
3
SO
3

3.1.3. Cc acid halogen sulfuric
Acid clorosulfuric l tc nhn quan trng nht ca nhm ny. Acid
fluorosulfuric v t nn ch dng trong cc trng hp c bit. Dng acid
clorosulfuric sulfocloro ha khng cn nhit cao, sn phm tinh khit
hn khi dng acid sulfuric hoc oleum. Acid clorosulfuric c dng nhiu
trong sn xut cc sulfamid.

A r H C l SO
3
H ArSO
2
OH HCl
ArSO
2
Cl H
2
SO
4
+ +
A r S O
2
O H + ClSO
3
H
+
A r H +
ClSO
3
H
2
ArSO
2
Cl + H
2
SO
4
+ HCl

3.1.4. Acid sulfamic (NH
2
-SO
3
H)
Acid sulfamic c acid mnh nh H
2
SO
4
. Trong sulfo ha hoc sulfat
ho, n tc dng nh phc hp amin SO
3
, nhng khc vi phc amin SO
3
l
n dng c trong mi trng khan nc v nhit cao. Thng dng
sulfo ho cc hp cht thm khng no (stirol) v phenol.
C
6
H
5
-CH= CH
2
+ NH
2
-SO
3
H C
6
H
5
CH = CH-SO
3
H + NH
3

37
3.2. Cc dn cht ca SO
2

3.2.1. Cc mui sulfit, bisulfit
Dng iu ch cc sulfonat ca hydrocarbon mch thng t dn cht
halogen tng ng (phn ng Strecker). Phn ng xy ra theo c ch th i
nhn.
R-X + Na
2
SO
3
R-SO
3
Na + NaX
Cc dn cht halogen thm ch tc dng c vi mui sulfit hoc bisulfit
nu trn nhn thm c nhm NO
2
v tr ortho hoc para.
3.2.2. Sulfonyl clorid (SO
2
Cl
2
)
sulfo-cloro ha cc alkan, cycloalkan, arakan, ngi ta dng SO
2
Cl
2
c
mt base yu (pyridin).
3.2.3. Hn hp kh SO
2
v Cl
2

Dng hn hp kh SO
2
v Cl
2
sulfocloro ho cc parafin. Phn ng xy
ra theo c ch gc t do di tc dng ca nh sng.
4. iu kin ca qu trnh sulfo ha
Phn ng sulfo ha l phn ng thun nghch:
Ar-H + H
2
SO
4

Ar-SO
3
H + H
2
O
chuyn cn bng v pha phi thng dng lng H
2
SO
4
(tnh ra nng
SO
3
) tha khong 2-5 ln.
Trong qu trnh phn ng, nng H
2
SO
4
gim dn do b tiu th to
nhm -SO
3
H v b pha long bi nc to thnh. Tc phn ng cng gim
dn v n mt gii hn no th ngng. Ngi ta gi gii hn nng H
2
SO
4

m phn ng sulfo ha khng xy ra na l pisulfo ha (-sulfo ha). Gi
tr ph thuc vo nguyn liu em sulfo ha v nhit thc hin phn ng.
Pisulfo ha c biu th bng nng ca SO
3
trong hn hp phn ng.
V d: -sulfo ha benzen nhit 60
0
C l 66,4.
-sulfo ha naphtalen l 56 ( 60
0
C) v 52 ( 160
0
C).
-sulfo ha benzen l 66,4 c ngha l khi nng SO
3
trong hn hp
phn ng gim xung 64,4% (tnh ra nng H
2
SO
4
l 66,4 : 0,8164 = 81,3%)
th khng th to ra sn phm benzen sulfonic na.
Khi bit gi tr -sulfo ha ca mt cht mt nhit no ta c th
tnh c lng SO
3
phn ng c thc hin hon ton. Trong thc t,
lng H
2
SO
4
cn thit sulfo ha 1 kmol hp cht hu c c tnh nh sau:
38

=
a
X
) 100 ( 80

Trong : X: s kg H
2
SO
4
cn tnh.
a: nng ban u ca SO
3
trong tc nhn sulfo ha.
: gi tr sulfo ha ca cht hu c nguyn liu.
(H
2
SO
4
100% c nng SO
3
l 81,64%)
T cng thc trn ta thy cht no c gi tr -sulfo ho nh th cng d
phn ng.
5. Kh nng ng dng ca phn ng
5.1. Sulfo ha cc hp cht mch thng
Cc hydrocarbon no mch thng khi sulfo ha vi H
2
SO
4
to ra nhiu tp
do cc phn ng oxy ho v ng phn ho. Do trong cng nghip ngi ta
thng dng tc nhn SO
2
Cl
2
th kh theo c ch th gc (S
R
).
Nhiu dn cht sulfonic ca hp cht mch thng c iu ch t cc
halogenid tng ng ca n bng phn ng Strecker (nung alkyl halogenid vi
mui natri hoc amoni sulfit).
R-X + Na
2
SO
3
R.SO
2
ONa + NaX
R-X + (NH
4
)
2
SO
3
RSO
2
ONH
4
+ NH
4
X
X = halogenid
Cc olefin khi tc dng vi acid sulfuric to thnh alkylsulfat theo c ch
cng hp Marconyikov:
R CH CH
2
+ H
2
SO
4
R CH CH
3
OSO
3
H

Acid hu c mch thng d dng sulfo ho vi oleum to ra acid -sulfo-
carboxylic.
R CH
2
COOH + SO
3 R CH COOH
SO
3
H

Vi acid clorosulfonic cng to ra acid -sulfo-carboxylic.
R CH
2
COOH + ClSO
2
OH R CH COOH
SO
3
H

39
5.2. Sulfo ha cc hp cht thm
Khc vi cc hp cht mch thng, cc hp cht thm d sulfo ha hn
nhiu. Ch cn nhit thp v nng acid sulfuric khong 65-100% cng c
th sulfo ha c. Phn ng xy ra theo c ch i in t.
Benzen c sulfo ha vi H
2
SO
4
98% 80
0
C cho acid benzen
sulfonic. Nu tip tc sulfo ho 220
0
C cho dn xut disulfonic v
300
0
C cho trisulfonic.

Naphtalen khi sulfo ha vi H
2
SO
4
nhit khc nhau th cng cho
cc sn phm khc nhau.

6.1. Sulfo ha cc hp cht thm
Thng thng cht phn ng c ha tan trong cc dung mi thch hp
(cloroform hoc tetraclorocarbon). Sau va khuy, va cho tc nhn sulfo
ha (theo tnh ton) vo khi phn ng vi vn tc sao cho gi c phn ng
nhit cn thit (t -10
0
C n 150
0
C tu cht tham gia phn ng). Sau khi
phn ng kt thc, lm ngui v va khuy va t t hn hp phn ng
vo nc . Khuy k v tin hnh tch sn phm t khi phn ng.
6.2. Sulfo ha cc hp cht mch thng
Thng c thc hin th kh, nhit cao, tc nhn l hn hp
SO
2
+ Cl
2
. Khi phn ng khi ra khi thp sulfo ha c ngng t. Sau ,
dch ngng t c cho t t vo nc v phn lp.

S O
3
H SO
3
H
SO
3
H
S O
3
H
S O
3
H HSO
3
H
2
SO
4
/80
0
C
300
0
C
H
2
SO
4
/220
0
C

S O
3
H
S O
3
H SO
3
H
S O
3
H
+ H
2
SO
4
160
0
C
40
0

C
9 6
4 15
85
%
%
% %
40
7. Tch cc acid sulfonic t hn hp phn ng
7.1. Tch bng mui n
Mui kim ca acid sulfonic tan tt trong nc nhng li t tan trong
dung dch mui. Do c th dng mui n to dung dch bo ha y
sulfonat kim ra khi dung dch ca n.
7.2. Tch bng cch to mui vi kim loi kim th
Da trn kh nng ha tan khc nhau ca mui sulfonat vi kim loi
kim th.
V d: Khi trung ha vi nc vi trong, ng phn naphtalen-2-sulfonat
calci tch ra khi dung dch v kh nng ha tan ca n km ng phn
naphtalen-1-sulfonat calci.
7.3. Tch bng nc
Mt s acid sulfonic a vng t tan trong nc. V vy khi hn hp
phn ng ca chng vo nc , chng c tch ra. Lc v thu sn phm.
8. Mt s v d
8.1. iu ch acid benzensulfonic
Benzen c phn ng vi acid sulfuric 100% trong thit b sulfo ha
(1). Acid benzensulfonic to thnh c chit bng nc hoc dung dch NaOH
trong thit b chit (2). Benzen cha phn ng c lm khan trong thit b (3)
v c a tr li phn ng.
Kh SO
3
c dn vo thit b sulfo ho m bo nng H
2
SO
4
lun
t 100%.
H
2
SO
4
100%
SO
3
Benzen
Nc hoc dd xt
Acid benzensulfonic
1
2
3

Hnh 3.2. S thit b iu ch acid benzensulfonic theo phng php lin tc
41
8.2. Sn xut cc thuc sulfamid
Acyl ha anilin thu c acetanilid. Acetanilid tc dng vi acid
clorosulfuric thu c p-acetylamino-benzen-sulfonyl clorid. Phn ng ca
sulfonyl clorid vi amin tng ng to ra dn xut sulfonamid. Cui cng l
thy phn loi nhm acetyl thu c sulfamid tng ng. Phng trnh cc
giai on phn ng nh sau:

NH2
A c N H S O
2
Cl
AcNH S O 2 Cl
A c N H H
H
2
NR' +
CS O 3 H
+
SO
2
NHR'
SO
2
NHR'
SO
2
NHR'
A c N H
AcNH
AcNH
N H
2
+
( C H
3
C O )
2
O
-
hay OH
H

t lng gi
1. Qu trnh sulfo ho l g? Mc ch ca n?
2. C ch phn ng sulfo ho gm my loi, iu kin v ni dung ca
mi loi c ch ?
3. Tc nhn ca qu trnh sulfo ho gm c nhng loi no? Hy trnh
by chi tit ni dung ca mi loi ?
4. Trnh by hiu bit ca anh (ch) v iu kin ca qu trnh sulfo
ha? Phn ng sulfo ho thng c ng dng trong cc nhm hp
cht no?
5. Trnh by phng php chung tin hnh cc phn ng sulfo ho.
6. Hy nu cc phng php ch yu dng tch cc acid sulfonic t
hn hp phn ng sulfo ho?
7. Trnh by phng php sn xut acid benzensulfonic v phng php
chung tng hp cc sulfamid?

42
Chng 4
Halogen ha
Mc tiu
1. Khi nim v c ch phn ng halogen ho.
2. Cc tc nhn ca qu trnh halogen ho.
3. Cc v d ng dng ca phn ng halogen ho.
1. i cng
Halogen ha l qu trnh ha hc nhm a 1 hay nhiu nguyn t
halogen vo hp cht hu c. Ty bn cht halogen m ngi ta gi qu trnh
ny l fluoro ha, cloro ha, bromo ha hoc iodo ha.
a halogen vo phn t hu c nhm cc mc ch sau:
To hp cht trung gian c tnh phn ng cao cho cc qu trnh tng
hp ho hc. T dn cht halogen, c th thay th bng cc nhm
-OH, -OR, -CN, -NH
2
to nn hp cht mi. Mt s dn cht
halogen c dng lm tc nhn alkyl ho (CH
3
I, C
2
H
5
Br), tc nhn
acyl ho (R-COCl).
To ra cc hp cht c tnh ng dng cao hn. Nhiu dn cht
halogen hu c c dng lm dung mi (dicloromethan, cloroform,
tetraclorocarbon...).
Nhiu ho dc l hp cht cha halogen (thuc st trng CHI
3
,
thuc ho CHBr
3
, thuc cn quang cha iod Urokon, thuc li tiu
clorthiazid ...). Cc dn cht cha fluor c u im l bm chc vo
h enzym ca c th. Do nhiu thuc cha fluor c thi gian bn
thi di v tc dng mnh (thuc st rt mefloquin, cc quinolon
khng khun peflacin, ciprofloxacin).
Qu trnh to dn xut halogen c th dng cc phng php sau:
1. Th hydro hay nhm nguyn t khc bng halogen.
2. Cng hp halogen vo lin kt kp ca phn t hu c.
43
2. C ch phn ng
2.1. Halogen ho theo c ch ion
Thng xy ra nhit thp (150-200
0
C) vi xc tc l cc cht to ion
(acid, base, mui kim loi).
2.1.1. Th i in t (Electrophilic Substitution)
Phn ng ny c th thay th mt hay nhiu nguyn t H ca nhn thm
bng mt hoc nhiu nguyn t halogen. Xc tc cho qu trnh l acid Lewis
(FeCl
3
, AlCl
3
):

2.1.2. Cng hp i in t (Electrophilic Addition)
Phn ng cng hp ca halogen, acid hydro-halogenid v acid
hypohalogenid vo olefin nhit thp v trnh tc dng ca nh sng xy ra
theo c ch cng hp i in t. Xc tc acid Lewis (FeCl
3
, AlCl
3
) c tc dng
lm phn cc halogen v acid hydro-halogenid, to ra tc nhn i in t.
CH
2
CH
2
+ Br
2 C C
Br
H
H
H
H
+ Br
CH
2
CH
2
Br Br

Phn ng cng HX vo olefin khng i xng tun theo nguyn l
Markonyikov:
CH CH
2
CH
3
+ HBr
CH
3
CH CH
3
Br
CH CH
3
CH
3
Br

Nu c nhm ht in t mnh lin kt vi olefin th sn phm cng hp
ngc vi nguyn l Markonyikov:
Br
+
CH CH
2
CF
3
CH
2
CH
2
CF
3 HBr
CH
2
Br CH
2
CF
3

Cl
2
+
F e C l
3 Cl
+
+ (FeCl
4
)
-
C l
Cl H
Cl
C l
+
C l
+
+
H
+
H
+
-
H
+
+
(F e C l
4
)
-
HCl
+ FeCl
3
44
2.1.3. Th i nhn (Nucleophilic Substitution)
Khi cc alcol tc dng vi cc acid hydro-halogenid:
R-OH + HX R-X + H
2
O
Phn ng xy ra qua ba giai on v c gii thch nh sau:
H-X H
+
+ X
-
RBr
+
-
Br
+
R
H
2
O
+
+
R
R O H
H
+
H
+
ROH

2.2. Halogen ho theo c ch gc
Phn ng halogen ha xy ra theo c ch gc t do khi c tc dng ca
nh sng, nhit cao hoc xc tc to gc t do (peroxyd).
2.2.1. Phn ng th gc hydrocarbon no mch thng
Phn ng th H cc hp cht parafin hoc H trn mch nhnh cc hp
cht thm nhit cao, xc tc nh sng. Qu trnh xy ra qua ba giai on:
To gc t do: Di tc dng ca nh sng hay nhit cao (300
0
C).
Cl
2
Cl
2

Gc t do tham gia phn ng vi hydrocarbon to chui phn ng dy
chuyn:
Cl
2
R CH
2
R CH
2
Cl Cl
+
+
Cl R CH
3
+ + HCl
R CH
2

Cc gc t do phn ng vi nhau, kt thc qu trnh:
Cl
2
R CH
2
CH
2
R
R CH
2
2
+ R CH
2
Cl
R CH
2
Cl
Cl
+ Cl

45
2.2.2. Phn ng cng hp halogen vo hydrocarbon thm
Di tc dng ca nh sng, clor v brom c th cng hp vo nhn thm
theo c ch gc t do:
Cl
Cl
Cl
Cl
Cl
Cl
Cl +
Cl
Cl
Cl
2
Cl
Cl
Cl 2 Cl
2
as

2.2.3. Phn ng cng hp halogen vo olefin
Phn ng cng hp halogen phn t vo olefin di tc dng ca nh
sng thng xy ra theo c ch gc t do.
Trong s cc hydro-halogenid th ch HBr di tc dng ca peroxyd cng
hp vo olefin theo c ch gc t do. Cn HCl v HF do nng lng lin kt
H-X ln, kh c kh nng tch thnh gc t do tham gia phn ng ny.
+
CH CH
2
CH
3
H
2
O
2
HBr
CH
3
CH
2
Br CH
2

3. Tc nhn halogen ha
3.1. Cc halogen phn t
Clor l kh mu vng lc, d=2,49, ho lng -34,5
0
C. Trong cng
nghip clor c s dng kh ph bin, thng c ng trong bnh
thp di dng lng. Clor phn t c s dng clor ha cc hp
cht thm theo c ch th i in t. N cng c dng clor ha
cc hp cht hydrocarbon no bng phn ng th gc vi xc tc l
nh sng v nhit cao. Ngoi ra cn dng cng hp vo cc lin
kt kp. Clor l mt kh rt c.
Brom l cht lng mu nu sm, d bay hi, d=3,1, si 59
0
C. C th
ng trong bnh thu tinh. Dng halogen ho ging nh clor.
Iod l tinh th mu tm sm, nng chy 113
0
C, t khi c s dng
v kh nng phn ng km.
Fluor l kh mu lc, ho lng -188
0
C. N hu nh khng th s
dng c fluor ha trc tip v phn ng qu mnh lit. Hp cht
fluor phi iu ch bng phng php gin tip (qua mui diazoni
hoc dng phn ng thay th halogen).
46
3.2. Cc acid hydro-halogenid
Gm HCl, HBr, HI v HF. Thng dng cng hp vo cc lin kt kp
ca hydrocarbon khng no theo c ch phn ng cng hp, hoc th nhm -OH
alcol bng halogen theo c ch th i nhn.
3.3. Cc hipohalogenid v mui ca chng
Cc hp cht ny l HOCl, NaOCl. Cng hp vi ethylen to
ethylenclorhydrin l nguyn liu quan trng tng hp metronidazol.
CH
2
= CH
2
+ HOCl HO-CH
2
-CH
2
-Cl
c bit khi cho phenol tc dng vi NaOCl th ch to thnh ng phn
ortho:

Mt ng dng kh quan trng ca NaOCl l clor ha cc sulfamid
iu ch cc cht st trng (cloramin T).

3.4. Cc clorid acid v c
Nhm ny c SOCl
2
, SO
2
Cl
2
, COCl
2
, PCl
3
, POCl
3
, PCl
5
. Chng tn ti
dng rn hoc lng, rt nhy cm vi nc. Thng c dng iu ch
clorid acid t cc acid carboxylic tng ng.
3.5. Cc mui ca halogen vi kim loi kim
Nhm ny gm NaF, NaCl, NaBr, NaI. Thng c dng chuyn ha
cc sulfon ester, cc mui hydroclorat ca amin thnh dn xut halogen:
R O SO
3
H + NaF
RF
+ NaHSO
4
R NH
2
.HCl + NaF RF + NaCl + NH
3

hoc thay th clor thnh iod.
OH + NaOCl OH
Cl
+ NaOH
SO
2
NH
2
R
+ NaOCl SO
2
NNaCl
R
47
CH
2
CH CH
2
Cl OH Cl
+ 2NaI 2NaCl CH
2
CH CH
2
I OH I
+

3.6. Cc tc nhn halogen ha khc
l S
2
Cl
2
, SbF
3
, N-brom-succinimid. S
2
Cl
2
c ng dng trong cng
nghip sn xut tetraclorid carbon:
CS
2
+ 2S
2
Cl
2
CCl
4
+ 6S
Vi SbF
3
ngi ta c th iu ch c cc dn xut fluor t cc dn xut
clor tng ng:
CF
3
CCl
3
SbCl
3
+
130C
SbF
3
+
o

4. Mt s v d
4.1. Clor ho toluen
Tu xc tc v iu kin phn ng, c th to thnh cc sn phm khc
nhau. Clor ho nhit si ca toluen, vi tc dng ca nh sng, phn ng
xy ra th hi theo c ch gc t do. Sn phm l benzylclorid, benzyliden-
clorid v benzylidinclorid.
CH
3
Cl
2
/as
t
0
CH
2
Cl
Cl
2
/as
t
0
CHCl
2
Cl
2
/as
t
0
CCl
3

Cn nu clor ho nhit phng vi xc tc l FeCl
3
th thu c sn
phm l cc dn xut clor th trn nhn.
CH
3 CH
3
Cl
Cl
2
FeCl
3
+
CH
3
Cl

4.2. iu ch cht cn quang Urokon
Urokon c s dng khi chp cn quang ng mt. N c iu ch
t N-acetyl-meta-amino-benzoic theo phng trnh sau:
48
CH
3
COOH
+
COOH
I I
I
NHCOCH
3
COOH
NHCOCH
3
ICl 3

t lng gi
1. Th no l qu trnh halogen ho? Mc ch ca qu trnh ny l g?
2. C ch phn ng halogen ho c phn lm my nhm? iu kin
xy ra v cc v d ca mi loi c ch?
3. Trnh by cc loi tc nhn ca qu trnh halogen ho?
4. Nu cc v d ng dng ca qu trnh halogen ho trong tng hp hu
c v ho dc.

49
Chng 5
Alkyl ha
Mc tiu
1. Khi nim v cc tc nhn ca qu trnh alkyl ho.
2. Cc loi phn ng alkyl ho.
3. Cc yu t nh hng n phn ng alkyl ho.
4. Cc v d ng dng ca phn ng alkyl ho.
1. i cng
Alkyl ha l qu trnh thay th mt hoc nhiu nguyn t hydro ca hp
cht hu c bng mt hoc nhiu nhm alkyl.
Nhm alkyl c th lin kt trc tip vi carbon, oxy, nit, hoc lu
hunh, tng ng ta c cc qu trnh C-alkyl ha, O-alkyl ha, N-alkyl ha
hoc S-alkyl ha.
C-alkyl ha:
Mc ch ko di mch carbon ca phn t hu c. V d trong tng
hp cc dn cht ester ca acid malonic lm trung gian cho tng hp cc thuc
chng ng kinh nhm barbituric.

O-alkyl ha:
Alkyl ha cn thu c cc ether, cn alkyl ho acid carboxylic thu c
cc ester tng ng.
R-OH + ROH R-OR + H
2
O ether
R-ONa + RX R-OR + NaX
H
2
C
COOC
2
H
5
COOC
2
H
5
NaOC
2
H
5
NaCH
COOC
2
H
5
COOC
2
H
5
RX
R CH
COOC
2
H
5
COOC
2
H
5
50
R-COOH + ROH R-COOR + H
2
O ester
R-COONa + R-X R-COOR + NaX

N-alkyl ha:
Sn phm ca phn ng l cc amin.

S-alkyl ha:
Sn phm ca phn ng l thioether.
R-X + NaSH R-SH R-S-R
Qu trnh alkyl ha c s dng nhiu trong k thut tng hp ha
dc. Nhiu thuc quan trng l sn phm ca qu trnh alkyl ha (codein,
antipyrin, analgin...)
2. Cc tc nhn alkyl ha
2.1. Cc alcol (R-OH)
Methanol v ethanol l nhng tc nhn alkyl ha quan trng. Hu nh
trong mi trng hp alkyl ha, phi s dng acid v c lm xc tc.
Alcol thng dng alkyl ha cc amin hoc alcol khc. Sn phm l
cc amin hoc ether.
2.2. Cc alkyl halogenid (R-X)
Cc alkyl halogenid mch carbon ngn (C=1-3) l cht lng c si
thp. Tc nhn hay dng l methyl halogen v ethyl halogen. Alkyl halogenid
c s dng alkyl ha cc amin.
2.3. Cc arakyl halogenid (Ar-(CH
2
)
n
X)
Benzyl clorid hoc benzyl bromid c s dng nhiu. N thng c dng
bo v nhm -OH ca ng hoc cellulose trong ha hc cc hydratcarbon.
2.4. Cc ester ca acid v c cha oxy
Gm cc dialkyl sulfat, alkyl nitrat, alkyl phosphat, dialkyl carbonat.
Tc nhn c s dng nhiu nht l dimethyl sulfat. N c th alkyl ha
nhm -OH phenol trong mi trng kim, nc, nc-alcol, thm ch c trong
mi trng acid. Cc alkyl nitrat rt t khi c s dng v d gy n.
R NH
2
+ R'X RNHR'
R'X
R N
R'
R'
R'X
R NR'
3
X
51
2.5. Cc ester ca acid sulfonic
Cc ester hu c ca acid sulfonic thm c ngha trong thc t. Vic s
dng n ging vi dialkyl-sulfat. Nhm tc nhn ny thng c dng
alkyl ha nhm -OH phenol hoc -NH amin. Mt s tc nhn in hnh l
methyl-benzensulfonat, benzyl-benzensulfonat hoc methyl, benzyl ester ca
acid p-toluen sulfonic.
2.6. Cc mui amino bc 4
Trong phenyl-trimethyl-amoni clorid l tc nhn hay c s dng.
Tc nhn ny methyl ha chn lc nhm -OH phenol trong mi trng kim.
V th n c s dng methyl ha morphin thnh codein.
2.7. Cc tc nhn alkyl ha khc
Cc epoxyd: c s dng iu ch cc polyether-alcol, cht c tc
dng lm gim sc cng b mt.

Cc hp cht c kim: Hp cht c magnesi dng iu ch cc ether
hn tp.
C
2
H
5
MgCl + ClCH
2
OCH
3
C
2
H
5
CH
2
OCH
3
+ MgCl
2
3. Cc loi alkyl ha
3.1. C-alkyl ha
C-alkyl ha thng l phn ng alkyl ho cc hp cht cha nhm
methylen hot ng. l cc hp cht c nguyn t hydro gn cc nhm ht
in t mnh (V d: ester malonat, ester ca acid cyanacetic, malon dinitrin,
acetoacetat ethyl).
Tc nhn alkyl ha c s dng y l alkyl halogenid, dialkyl sulfat,
alkyl sulfonat, i khi l alkyl nitrat, epoxyd, arakyl halogenid.

NC-CH
2
-COOR + B
NC-CH-COOR + BH

R CH
2
OH
CH
2
CH
2
O
RCH
2
OCH
2
CH
2
OH
CH
2
CH
2
O
RCH
2
OCH
2
CH
2
OCH
2
CH
2
OH
RX + HC
CN
COOR'
RCH
CN
COOR'
+ X
52
Xc tc cho phn ng l cc base (alcolat kim loi, Na-hydrid, cc kim
loi Na hoc K). Dung mi thng l alcol, mt s trng hp c th dng
ether hoc benzen.
3.2. O-alkyl ha
Gm cc phn ng alkyl ho nhm -OH alcol hoc phenol, sn phm l
cc ether. Ring alkyl ha nhm -OH ca acid carboxylic s c nghin cu
trong chng ester ha.
Cc ether c iu ch bng ba phng php sau:
Loi nc t hai phn t alcol:
ROH + R'OH
H
2
SO
4
/
140
0
C
ROR' + H
2
O

Tc dng ca natri alcolat vi alkyl halogenid (phn ng Williamson):
R-ONa + RX R-OR + NaX
(X = -Br, -Cl, -I)
Cng hp ca alcol vi olefin:
+ R'OH R CH CH
2
H
2
SO
4
R CH CH
3
OR'

Cc phenol-ether c iu ch ging vi ether mch thng. Tc nhn
alkyl ho thng dng l alkyl-halogenid, dialkyl sulfat hoc alkyl-
toluensulfonat trong mi trng kim (natri alcolat).
3.3. N-alkyl ha
Khi alkyl ha amin bc nht hoc amoniac vi alkyl halogenid, c th
thu c mt hn hp amin bc cao hn hoc mui amin bc 4.
RX + NH
3 RNH
3
X
HX
-
+ HX
RNH
2
RNH
2 R
2
NH
RX RX
R
3
N
RX
R
4
NX

Nu dng tc nhn l alcol th qu trnh dng li amin bc 3.
Mun to amin bc hai, cn phi bo v mt nguyn t hydro ca amin
bng phn ng acyl ho, sau mi alkyl ha v cui cng thy phn nhm
bo v.
53
R NH
2
ClSO3H
R NHSO
3
H
R'X
R NSO
3
H
R'
HOH
R NH
R'

Gn y, nh s dng nhm alcolat lm tc nhn alkyl ho, hiu sut
phn ng cao hn v khng ln tp cht dialkyl ho.
(C
2
H
5
O)
3
Al + ArNH
2
3
ArN
H
C
2
H
5
+ Al(OH)
3
3

3.4. S-alkyl ha
S-alkyl ha thng l phn ng gia hp cht mecaptan vi alkyl-
halogenid, sn phm l cc thioether.
SH R + R'X
OH
S R R' + HX

4. Cc yu t nh hng n qu trnh alkyl ha
4.1. Nhit
Khi dng tc nhn alkyl ha l alcol (methanol, ethanol) hoc alkyl-
halogenid th phn ng cn c thc hin nhit cao hn so vi alkyl
sulfat. Alkyl ha pha hi th i hi nhit ln ti 400
0
C. Vi cc amin
thm, khi nhit tng nhm alkyl c xu hng chuyn vo nhn.
4.2. p sut
Hu ht cc phn ng alkyl ho khng lm gim s phn t v thng
tin hnh pha lng, v vy khng cn p sut. Tuy nhin tng tc phn
ng, i khi phi thc hin phn ng nhit cao.
i vi cc tc nhn c nhit si thp hoc cn dung mi ho tan
cc cht tham gia phn ng th cn thit tin hnh phn ng trong ni chu
p sut (autoclav).
4.3. T l mol cc cht phn ng
Vic s dng tha tc nhn alkyl ho nh hng n mc alkyl ho
sn phm, c bit l alkyl-halogenid v dialkyl-sulfat. C th loi c nh
hng ny bng cch s dng alcol l tc nhn yu hn.
Vi cc amin vic la chn t l mol ban u c ngha quyt nh n t
l to thnh cc bc amin trong sn phm.
54
Phn ng alkyl ha pha lng c tin hnh bng phng php gin
on hoc lin tc, cn pha hi th lun c thc hin bng phng php
lin tc.
5.1. Phng php gin on
i vi cc cht d phn ng, khng cn thc hin nhit cao, phn
ng ta nhit nhiu nn cn lm lnh. Cht alkyl ha c ha tan trong
dung mi thch hp, thm xc tc, sau nng nhit v cho dn tc nhn
alkyl ha vo. Khng ch nhit cn thit trong sut thi gian phn
ng. Sau khi kt thc, lm lnh, hn hp phn ng vo nc , tch
pha hu c, ra li vi nc. Lm khan v ct phn on thu sn phm p
sut gim.
i vi cc cht kh phn ng th cho nguyn liu, tc nhn v xc tc
vo ni phn ng (autoclav). un n nhit cn thit v duy tr cho ti lc
phn ng hon thnh. Kt thc phn ng, ct loi nguyn liu tha v x l
hn hp phn ng nh trng hp trn.
5.2. Phng php lin tc
Tin hnh trong thit b chu p lc hnh thp. Cht cn alkyl ha, tc
nhn v xc tc c ha hi v dn lin tc vo thit b phn ng. Tnh ton
duy tr thi gian cho hn hp phn ng nhit cn thit. Sn phm
ly ra khi thp phn ng mt cch lin tc, c ngng t v x l nh trong
trng hp gin on.
6. Mt s v d
6.1. Sn xut thuc gy ng diethyl barbituric (Veronal)
Qu trnh tng hp Veronal gm hai giai on:
Giai on 1: Tng hp diethyl malonat diethyl ester bng phn ng
alkyl ho diethyl malonat vi ethylbromid, xc tc natri alcolat trong mi
trng alcol.
Giai on 2: Ngng t diethyl malonat diethyl ester vi ur to thnh
diethyl barbituric (Veronal).

55
S phn ng nh sau:

6.2. Sn xut thuc gim ho, gim au codein bng phng php alkyl
ho morphin
Codein c bn tng hp t morphin bng phng php methyl ho vi
tc nhn l mt mui amoni bc bn (phenyl trimethyl amoni hydroxyd). u
im ca tc nhn ny l ch methyl ho nhm -OH phenol v khng to mui
amoni bc bn vi nit bc ba ca phn t morphin nn cho hiu sut cao.
HO
HO
N CH
3
O + C
6
H
5
N CH
3
CH
3
CH
3
OH
CH
3
O
HO
N CH
3
O

t lng gi
1. Th no l qu trnh alkyl ho? Cch phn loi v mc ch ca qu
trnh alkyl ho?
2. Tc nhn ca qu trnh alkyl ho gm c nhng loi no? Trnh by
tnh cht v cch dng ca mi loi ?
3. Nu nhng yu t nh hng n phn ng alkyl ho?
4. Trnh by cc phng php tin hnh phn ng alkyl ho.
5. Trnh by phng php tng hp Veronal v phng php sn xut
codein trong cng nghip?

H
2
C
C O O C
2
H
5
C O O C
2
H
5
1.NaOC 2 H 5
2. C2H5B r
C
2
H
5
CH
COOC
2
H
5
COOC
2
H
5
1.NaOC2H5
2. C2H5Br
C
COOC
2
H
5
COOC
2
H
5
H
5
C
2
H
5
C
2
+ C O
H
2
N
H
2
N
-2C
2
H
5
OH
C N H
C
N H C
C
H
5
C
2
H
5
C
2
O
O
O
(C
2
H
5
)
2
C
C O O C
2
H
5
C O O C
2
H
5
56
Chng 6
Acyl ha
Mc tiu
1. Khi nim v phn loi phn ng acyl ho.
2. Cc tc nhn ca qu trnh acyl ho.
3. C ch phn ng v cc yu t nh hng n qu trnh acyl ho.
4. Cc v d ng dng ca phn ng acyl ho.
1. i cng
1.1. nh ngha
Acyl ha l qu trnh thay th nguyn t hydro ca hp cht hu c bng
nhm acyl (RCO-).

Acyl l gc cn li khi loi i nhm -OH t acid v c c oxy, acid carboxylic
hoc acid sulfonic. Cc nhm acyl quan trng c nu trong bng 6.1.
Bng 6.1. Cc nhm acyl quan trng
Tn acid xut x Cng thc nhm acyl
Acid carboxylic R-CO-
Acid sulfonic R-SO
2
-
Bn ester ca acid carbonic R-OCO-
Acid carbamic R-NH-CO-
Trong R l mch thng hoc nhn thm.
nh
2 nhcoch
3
+
ch
3
cooh + H
2
O
57
Chng ny ch nghin cu phn ng acyl ho ca cc nhm acyl c
to thnh t acid hu c.
Qu trnh acyl ho c dng vo cc mc ch sau:
To ra hp cht vi nhng tnh cht mi. V d: Khi acyl ho anilin
thu c acetanilid l thuc h nhit, t c hn anilin nhiu ln. Ur
khi acyl ho vi cc dn cht ca acid malonic to thnh nhiu thuc
ng v chng ng kinh nhm barbituric
To nhm bo v cho mt qu trnh tng hp ho hc. V d: Trong
tng hp cc sulfamid, trc khi lm phn ng sulfocloro ho anilin,
ngi ta phi bo v nhm amin bng cch acetyl ho.
To hp cht trung gian trong qu trnh tng hp ho hc. V d:
Amid ca homoveratrilamin vi cc acid carboxylic khc nhau l
trung gian tng hp nhn isoquinolin trong tng hp cc thuc
papaverin, emetin.
1.2. Phn loi phn ng acyl ha
Nhm acyl (RCO-) c th thay th H trong cc lin kt -OH, -NH, -SH
hoc -CH, tng ng ta c cc loi phn ng O-acyl ha, N-acyl ha, S-acyl
ha, hoc C-acyl ho.
O-acyl ho: L qu trnh acyl ho nhm -OH ca alcol, phenol, enol
hoc acid carboxylic. Sn phm l cc ester hoc anhydrid acid.
ROH + RCOX ROCOR + HX
2RCOOH (RCO)
2
O + H
2
O
N-acyl ho: L qu trnh acyl ho amoniac hoc cc amin hu c (bc
nht, bc hai), sn phm ca phn ng l cc amid.
R-NH
2
+ RCOX RNHCOR + HX
S-acyl ho: l qu trnh acyl ho nhm -SH ca thioalcol hoc
thiophenol. Sn phm ca phn ng l thioester.
R-SH + R COX RSCOR + HX
C-acyl ho: L qu trnh thay th hydro ca nhng hp cht hu c
cha hydro hot ng.
H
2
C(COOR)
2
+ NaOC
2
H
5
NaCH(COOR)
2
NaCH(COOR)
2
+ CH
3
COCl CH
3
COCH(COOR)
2

58
2. Tc nhn acyl ho
Tc nhn acyl ho c cng thc chung nh sau:
Trong X c th l:
OH: acid carboxylic
OR: ester
NH
2
: amid
OCOR: anhydrid
X: halogenid acid.
Sau y l mt s tc nhn acyl ho hay gp:
2.1. Cc acid carboxylic
Thng dng acyl ho amin v alcol. Acid carboxylic khng c kh
nng acyl ho phenol. Sn phm l cc amid hoc ester. Cc acid hay c s
dng l acid formic, acid acetic. Acyl ho alcol l phn ng thun nghch, v
vy nng cao hiu sut phn ng cn c bin php loi nc ra khi khi
phn ng. Acyl ho vi tc nhn acid thng c tin hnh nhit cao
(khong 200
0
C).
2.2. Cc ester
Cc ester khng phi l tc nhn acyl ho mnh. Nhng n c s dng
trong nhiu trng hp, c bit l nhng ester c nhm ht in t mnh
trong phn t. V d clorocarbonat ethyl l mt tc nhn c s dng rng
ri a nhm ethyl carbonat vo phn t hu c.
Ester c dng trong cc trng hp O
, N
, C-acyl ho. Tuy nhin,

trong cng nghip ngi ta t dng ester lm tc nhn N-acyl ho, tr
trng hp iu ch formamid v dimethyl formamid. Acid formic khng c
dng anhydrid hoc clorid acid tng ng, nn ch c th s dng dng acid
hoc ester ca n.
NH
3
+ HCOOCH
3
HCONH
2
+ CH
3
OH
2.3. Cc amid
Cc amid l nhng tc nhn acyl ho yu nn t khi c s dng. Hai
tc nhn hay s dng hn l formamid (HCONH
2
) v carbamid (H
2
NCONH
2
).
Carbamid c dng acyl ho alcol thnh uretan:
C
2
H
5
OH + H
2
NCONH
2
.HNO
3
C
2
H
5
OCONH
2
+ NH
4
NO
3

r c
o
x
59
2.4. Cc anhydrid acid
Anhydrid acid l tc nhn acyl ho mnh, c th acyl ho c amin,
alcol v phenol. Khng to ra nc trong qu trnh phn ng. Tc nhn hay
c s dng l anhydrid acetic. N t b thu phn trong nc nn c th acyl
ho trong mi trng nc hoc mi trng kim.
Nu tc nhn l anhydrid hn tp (anhydrid ca 2 acid khc nhau) th
nhm acyl no hot ho hn s th vo phn t cn acyl ho.
Xc tc cho phn ng acyl ho thng l cc amin bc ba (trietylamin,
pyridin, 4-dimethyl-amino-pyridin).
2.5. Cc halogenid acid
Halogenid acid l tc nhn acyl ho rt mnh, trong cc clorid acid
c s dng nhiu nht. Halogenid acid thng l nhng cht lng, d b
phn hu bi nc. Qu trnh acyl ho to ra HX, v vy ngi ta thng phi
dng cc base hu c nh pyridin, triethylamin, quinolin, diethylanilinlm
cht hp th. Vi cc clorid acid t b thu phn bi nc (clorid acid ca acid
thm, sulfonyl clorid) th c th acyl ho trong dung dch kim 10-20% hoc
carbonat kim.
Cc tc nhn in hnh ca nhm ny l acetyl clorid, benzoyl clorid,
photgen, benzensulfo clorid
Halogenid acid c th acyl ho cc nhm -OH, -NH
2
:
ROH + RCOX R-OCOR + HX
RNH
2
+ RCOX R-NHCOR + HX
2.6. Xeten
Xeten (CH
2
= CO) l tc nhn acyl ho mnh nht, c s dng rng
ri trong cng nghip. N c s dng acyl ho cc nhm -OH alcol, -NH
amin, -OH acid. L tc nhn acyl ho chn lc nhm -NH amin, v nhit
thng n phn ng mnh vi -NH ca amin m khng phn ng vi -OH
ca alcol.
3. C ch phn ng
Lin kt C-X c th b ct theo 3 kiu:
o
x
+
r c
o
x +
r c
r + x c
o

60
Tng ng ta c cc loi c ch sau:
3.1. Acyl ho theo c ch gc
Di tc dng ca tc nhn peroxyd, gc acyl to thnh v tham gia
vo cc phn ng theo c ch gc t do.

c h
3
c h
2
c h
2
c o c h
3
c h
3
c h =c h
2
O C
3
H C
+
+
H C C
3
O C H
peroxid
c h
3
c h o

3.2. Acyl ho theo c ch i in t
Nhm acyl d b phn cc do i in t lch v pha nguyn t oxy c
m in ln hn. Nu X l nhm ht in t mnh th tc nhn ny cng d b
phn li thnh cation acyli (RCO
+
). Nguyn t C ca nhm acyl mang in tch
dng nn l tc nhn i in t.
C ch phn ng c th vit nh sau:
RCOX RCO + X
R'OH
RCOOR' + HX
RCOX + R'OH R C X
OH
OR'
RCOOR' + HX

3.3. Acyl ho theo c ch i nhn
Trong thc t rt t gp qu trnh acyl ho xy ra theo c ch ny. Bi v
kh nng to anion acyli (RCO
-
) l rt kh. Cc aldehyd trong mi trng
kim mnh to thnh hp cht dimer l mt trng hp c bit:

4. Mt s yu t cn ch trong qu trnh acyl ho
4.1. Xc tc
Xc tc cho qu trnh acyl ho c th l base hoc acid.
+
C H
O
CN
Ph C
O
C N
Ph
H
P hC H O
C
OH
CN
Ph C O
H
P h
P hC H O CN
C CH Ph
O
Ph
OH
61
Acyl ho alcol hoc amin bng tc nhn halogenid hoc anhydrid acid th
xc tc l cc amin bc ba nh triethylamin, pyridin, quinolin, 4-dimethyl-
amino-pyridin, mt s trng hp c th dng carbonat kim hoc kim.
Acyl ho alcol bng acid carboxylic (ester ho) th xc tc l acid sulfuric.
4.2. Dung mi
Dung mi thng l cc cht tham gia phn ng (cc alcol hoc amin)
hoc chnh tc nhn acyl ho. Trng hp cc cht tham gia phn ng khng
ho tan tc nhn acyl ho th dng mt dung mi tr tan thch hp (benzen,
toluen, clorobenzen, cloroform, tetraclorocarbon, dicloromethan...).
4.3. Nhit
Acyl ho l qu trnh to nhit. Tuy nhin giai on u cn cung cp
nhit cho phn ng. Sau c th phi lm lnh loi bt nhit phn ng.
Giai on cui cn cung nhit li phn ng kt thc. Tu cc cht tham gia
phn ng v tc nhn m nhit phn ng khc nhau. V d vi tc nhn l
acid carboxylic, khi acyl ho alcol cn tin hnh 200
o
C, acyl ho amin 120-
140
0
C. Tc nhn halogenid acid ch cn nhit di 50
0
C.
5. Mt s v d
5.1. iu ch thuc h nhit gim au aspirin
Cho acid salicylic tc dng vi anhydrid acetic, xc tc l acid sulfuric
c nhit 80-90
0
C trong thi gian 30-45 pht. ngui, lc thu tinh th.
Ra bng nc v sy thu sn phm.

5.2. Bn tng hp thuc st rt artesunat
Acyl ho dihydroartemisinin bng anhydrid succinic vi xc tc l cc
amin bc ba nh pyridin, triethylamin hoc 4-dimethylamino-pyridin.

O
O
C
H
H
C
OCOCH
2
CH
2
COOH
H
3
C
O
O
O
O
O
O
O
CH
3

H
H
CH
3

OH
H
3
C
O
O
+

COOH
OH
+ (CH
3
CO)
2
O
COOH
OCOCH
3
+ CH
3
COOH
62
5.3. iu ch acetanilid
NH
2
+ CH
3
COOH
NHCOCH
3
+ H
2
O

Anilin v acid acetic c cho vo bnh phn ng 1 (Hnh 6.1), nng
nhit ln 140
0
C v gi trong 8-10 gi. Trong qu trnh phn ng, nc to
thnh c ct ra lin tc. Sau , khi phn ng c x l vi nc thu
tinh th sn phm. Ra li bng nc, lc v sy.
Anilin
AcOH
1
2
3
4
5 6
H
2
O
Nc
H
2
O
AcOH
H
2
O

Hnh 6.1. S thit b iu ch acetanilid
1. Bnh phn ng, 2. Ct tch, 3. Sinh hn, 4. Ni kt ta, 5. My vy li tm, 6. T sy
T lng gi
1. Trnh by nh ngha qu trnh acyl ho? Cch phn loi v mc ch
ca qu trnh acyl ho?
2. Trnh by cng thc chung v cc loi tc nhn ca qu trnh acyl ho?
3. C ch phn ng acyl ho v mt s yu t cn ch trong qu trnh
thc hin phn ng acyl ho?
4. Trnh by phng php tng hp aspirin, artesunat v acetanilid.
63
Chng 7
Ester ho
Mc tiu
1. Khi nim v phn ng ester ho v cc phng php iu ch ester.
2. C ch ca phn ng ester ho.
3. Cc yu t nh hng n qu trnh ester ho v phng php chuyn
dch cn bng cho phn ng ester ho.
4. Cc v d ng dng ca phn ng ester ho.
1. i cng
Qu trnh to hp cht ester bng phn ng gia acid carboxylic vi
alcol, xc tc acid v c c gi l qu trnh ester ha.
Ester ha l phn ng thun nghch, phng trnh nh sau:
R COOH
+ R'OH RCOOR' + H
2
O

C nhiu phng php iu ch ester, trong gio trnh ny chng ti chia cc
phng php lm ba nhm: acyl ho, alkyl ho v phng php oxy ho kh.
1.1. iu ch ester bng phng php acyl ho
Phn ng ester ho (esterification):
R-COOH + R-OH R-COOR + H
2
O
Phn ng ru phn (alcoholysis):
C
2
H
5
OH +
NH
2
COOCH
2
CH
2
N(C
2
H
5
)
2
HOCH
2
CH
2
N(C
2
H
5
)
2
+
NH
2
COOC
2
H
5

64
Phn ng acid phn (acidolysis):

CH
3
COOCH=CH
2
+ C
11
H
23
COOH C
11
H
23
COOCH=CH
2
+ CH
3
COOH
(Acid laurinic) (Vinyl laurinat)
Phn ng chuyn i ester:

HCOOC(CH
3
)
3
+ R-COOCH
3
R-COOC(CH
3
)
3
+ HCOOCH
3
Phn ng ca anhydrid vi alcol hoc phenol:
(CH
3
CO)
2
O + R-OH CH
3
COOR + CH
3
COOH
(CH
3
CO)
2
O + Ar-OH CH
3
COOAr + CH
3
COOH
Phn ng gia halogenid acid vi alcol hoc alcolat:
Cl-CO-Cl + C
2
H
5
OH ClCOOC
2
H
5
+ HCl
Phn ng gia amid vi alcol:
R-CONH
2
+ R-OH R-COOR + NH
3

1.2. iu ch ester bng phng php alkyl ho
Phn ng gia mui carboxylat vi alkyl halogenid hoc arakyl
halogenid:
CH
3
COONa + C
2
H
5
Br CH
3
COOC
2
H
5
+ NaBr
CH
3
COONa + Cl-CH
2
-C
6
H
5
CH
3
COOCH
2
-C
6
H
5
+ NaCl
Phn ng alkyl ho nhm OH ca acid bng epoxyd:
H
2
C
O
CH
2
+ CH
3
COOH OH CH
2
CH
2
O CO CH
3

Phn ng cng hp vo ni i C=C ca acid v c v hu c:
CH
2
=CH
2
+ H
2
SO
4
CH
3
CH
2
-OSO
2
OH
CH
2
=CH
2
+ CH
3
COOH CH
3
COOCH
2
CH
3

65
1.3. iu ch ester bng phng php oxy ho-kh
Phn ng Canizzaro (benzaldehyd trong mi trng kim c):
C
6
H
5
CHO
2
OH
C
6
H
5
CH
2
O CO C
6
H
5

Phn ng Tischenko (aldehyd/nhm -alcolat):
2CH
3
CHO CH
3
COOC
2
H
5

Phn ng gia carbon-monoxyd vi alcol trong alcolat kim loi
nhit v p sut ln:
R-OH + CO HCOOR
Sn phm ester ho c s dng rng ri trong cc lnh vc sau:
Trong dc phm, dng lm thuc (aspirin, novocain, diethylphthalat,
artesunat...)
Lm cht trung gian trong tng hp ho hu c v ho dc.
Trong ho m phm, cc ester dng lm hng liu.
Lm dung mi (ethylacetat, butylacetat...).
2. C ch phn ng
Phn ng ester ho kinh in l phn ng to ester gia acid carboxylic
v alcol. y l phn ng thun nghch, xc tc l acid v c.
Phn t nc to thnh trong phn ng ester ha c th theo 2 cch:

H
2
O
+
OR' R CO
+ R' H O
R C
O
O H
R' H O +
R C
O
O H
H

Kt qu ca nhiu cng trnh nghin cu chng minh rng bc carbon
trong phn t alcol quyt nh phn t nc loi ra theo kiu no. Trong thc
t c hai kiu c ch tng ng vi hai trng hp sau:
2.1. Ester ho vi alcol bc 1 v bc 2
Di tc dng ca acid v c, qu trnh ester ho c th xy ra theo c
ch n phn t hoc lng phn t:
66

Hoc:
ch
nh
R C OH
OH
O
H
R'
R C
O H
OH
+
H
+
R C
O
OH
nh
nh
R'OH
nh
ch
R C
OH
O R'
nh
nh
R C
O
OR'
+ H
_
H
2
O

C hai trng hp u ly nhm -OH ca acid carboxylic to thnh
phn t nc.
2.2. Ester ho vi alcol bc 3
Trng hp ny phn t nc c to thnh t nhm -OH ca alcol. C
ch phn ng nh sau:

3. Cc yu t nh hng n qu trnh ester ho
3.1. Xc tc
Xc tc c tc dng y nhanh qu trnh ester ho. Cc xc tc hay dng
l acid proton mnh nh: sulfuric, hydrocloric, sulfonic, percloric, phosphoric.
Ngoi ra cn s dng mt s acid Lewis khc (BF
3
, ZnCl
2
, SnCl
4
, SiF
4
, FeCl
3
).
R C
O
OH
+ H
+
R C
O
OH
R C
O
OH
H
R C
O
+ H
2
O
R C
O
+ O R
H
R C
O
OR
H
R C
O
OR
+ H
+
nh
nh
ch
nh
nh
ch
nh
ch

C O H C H
3
C H
3
C H
3
+ H
+
C OH C H
3
CH
3
C H
C CH
3
C H
3
C H
3 H
3
+ H
2
O
R C O O H n h
c h
n h
n h
ch
nh
R
O
O H
C ( C H
3
)
3
R
O
OC(CH
3
)
3
+ H
+
n h
n h
C C
67
Gn y ngi ta dng cc cht trao i ion lm xc tc thay cho acid.
Vi xc tc loi ny qu trnh x l sau phn ng s n gin v c th s
dng li xc tc.
Xc tc khng nh hng n cn bng ca phn ng.
3.2. Dung mi
Dung mi ca qu trnh ester ho thng l cc alcol tham gia phn ng
c dng qu tha. Nu acid carboxylic khng tan trong alcol th cn mt
dung mi tr tan thch hp (aceton, benzen, toluen, cloroform, dicloromethan...)
3.3. Nhit
Cng nh nhiu phn ng khc, nhit c tc dng lm tng tc phn
ng ester ho. Vic tng nhit ca phn ng ch n si ca alcol, nu
mun nng nhit ln cao hn th phi dng thit b chu p sut.
3.4. iu kin cn bng ca phn ng
3.4.1. Hng s cn bng ca phn ng ester ho
Ester ho l phn ng thun nghch. Mi phn ng c th c mt hng
s cn bng ring. Hng s cn bng c tnh theo cng thc sau:
K =
ester . nc
acid alcol

Gi tr K cng ln th kh nng chuyn ho thnh ester cng cao. Cng
thc ny cho php tnh c nng ca ester to thnh trong phn ng nu
s dng qu tha mt trong hai thnh phn tham gia phn ng.
3.4.2. nh hng ca cu trc alcol ti vn tc ester ho v nng
ester ti im cn bng
Th nghim ca Mencsutkin (1897) khi ester ho cc alcol vi acid acetic
c th hin bng 6.2.

68
Bng 6.2. Tc dng ca cc alcol khc nhau n vn tc ester ho
Khi lng ester to thnh
[%mol]
S TT Tn alcol
Sau 1 gi
im cn bng
K
1 Methanol 55.59 69,59 5,24
2 Ethanol 46,95 66,57 3,96
3 Propanol 46,92 66,85 4,07
4 Buthanol 46,85 67,30 4,24
5 Allyl alcol 35,72 59,41 2,18
6 Benzyl alcol 38,64 60,75 2,39
7 Izopropanol 26,53 60,52 2,35
8 Methyl, ethyl carbinol 22,59 59,28 2,12
9 Diethyl carbinol 16,93 58,66 2,01
10 Diallyl carbinol 10,31 50,12 1,01
11 Menthol 15,29 61,49 2,55
12 Trimethyl carbinol 1,43 6,59 0,0049
13 Dimethyl propyl carbinol 2,15 0,83 0,00007
14 Phenol 1,45 8,64 0,0089
15 Thimol 0,55 9,46 0,0192
Kt qu cho thy methanol c vn tc phn ng ln nht v nng
ester ti im cn bng cng cao nht. Cc alcol bc nht, cc alcol no c vn
tc phn ng v h s cn bng cao hn cc alcol bc hai hoc cc alcol khng
no tng ng. Cc alcol bc ba c vn tc ester ho b nht. Tm li, alcol cng
phn nhnh v mch nhnh cng gn nhm -OH th vn tc ester ho cng
gim, nng ester ti im cn bng cng thp.
3.4.3. nh hng cu trc ca acid ti vn tc ester ho v nng
ester ti im cn bng
Cng tng t nh cc alcol, Mencsutkin kho st kh nng ester ho
ca mt s acid c cu trc khc nhau vi alcol isopropylic 150
0
C (Bng 6.3).
Kt qu cho thy nh hng ca mch carbon khng nh trong trng hp
ca alcol. Tc ester ho v gi tr nng ester ti im cn bng khng t
l theo s phn nhnh ca mch carbon.

Bng 6.3. Tc dng ca cc acid khc nhau n vn tc ester ho
69
Khi lng ester to thnh
[%mol]
S TT Tn alcol
Sau 1 gi im cn bng
K
1 Formic 61,69 64,23 3,22
2 Acetic 44,36 67,38 4,27
3 Propionic 41,18 68,70 4,82
4 n-Butyric 33,25 69,52 5,20
5 Isobutyric 29,03 69,51 5,20
6 Methyl, ethyl acetic 21,50 73,73 7,88
7 Trimethyl acetic 8,28 72,65 7,06
8 Dimethyl, ethyl acetic 3,45 74,15 8,23
9 Phenyl acetic 48,82 73,87 7,99
10 Phenyl propionic 40,26 72,02 7,60
11 Benzoic 8,62 72,57 7,00
12 p-Toluenic 6,64 76,52 10,62
4. Cc phng php chuyn dch cn bng cho phn ng
ester ho
C hai phng php chuyn dch cn bng lm tng hiu sut ca qu
trnh ester ho:
1. Tng nng mt trong hai cht tham gia phn ng (acid hoc alcol).
Vn ny thc hin n gin v thng dng alcol tha nhiu ln.
2. Loi khi phn ng mt trong hai cht to thnh. Trng hp ny
c thc hin bi hai bin php sau y:
Loi nc ra khi phn ng:
Nu c acid ln alcol dng trong phn ng ester ho u l nhng
cht c si cao th loi nc bng cch ct ko lin tc, c th sc
kh tr vo tng tc loi nc.
Nu acid c si cao, alcol c si thp hn nc th dng alcol
tha nhiu ln, ct loi nc v alcol lin tc trong qu trnh phn
ng.
Thm mt dung mi to hn hp si ng ph ba cu t (nc-
alcol-dung mi) c nhit si thp hn nhit si ca nc v ct
loi chng ra khi hn hp phn ng. Hn hp hi c ngng t,
70
tch loi pha nc, pha hu c cha alcol c dn tr li bnh phn
ng. Cc dung mi hay dng l benzen, toluen, cloroform,
dicloroethan, tetraclorocarbon.
Loi ester ra khi phn ng:
C hai phng php sau:
Nu ester to thnh c si thp nht trong hn hp phn ng th
lin tc ct thu ester trong qu trnh phn ng.
Nu ester to hn hp ng ph hai hoc ba cu t vi cc cht tham
gia phn ng, th hn hp hi ct ra c ngng t tch ly ester.
Pha nc acid c dn tr li khi phn ng.
5. Mt s v d
5.1. iu ch diethylphthalat
Hi lu anhydrid phthalic v ethanol tha (3-5 ln) vi xc tc l acid
sulfuric c trong hai gi. Phn ng xy ra qua hai giai on: giai on u
ethanol cng hp vo anhydrid phthalic to thnh monoester. Sau ester
ho monoester ny thnh diethyphthalat.
Kt thc phn ng, ct thu hi alcol tha. Ra ester bng nc, sau
trung ho vi dung dch natri carbonat loi acid xc tc. Ra li bng nc
n trung tnh, lm khan v ct phn on thu ester tinh khit.
S cc giai on phn ng nh sau:
COOC
2
H
5
COOC
2
H
5
+
H
2
SO
4
C
2
H
5
OH
COOC
2
H
5
COOH
C
2
H
5
OH +
C
O
C
O
O

5.2. iu ch methyl salicylat
Hi lu hn hp acid salicylic v methanol (tha gp 10 ln) trong 10 gi
vi xc tc l acid sulfuric c. Phn ng kt thc, ct loi methanol v ra
hn hp phn ng vi nc nhiu ln. Sau trung ho vi dung dch natri
hydrocarbonat n trung tnh. Ra li bng nc, lm khan v ct phn on
thu methyl salicylat tinh khit.

COOH
OH
COOCH
3
OH
+ CH
3
OH
H
2
SO
4
+
H
2
O
71

T lng gi
1. Qu trnh ester ho c hiu nh th no? Mc ch ca n?
2. iu ch ester gm c nhng phng php no? Vit phng trnh
phn ng mi loi ?
3. Trnh by c ch phn ng ester ho?
4. Nu cc yu t nh hng n qu trnh ester ho v cc phng
php chuyn dch cn bng nng cao hiu sut ca qu trnh ester
ho.
5. Trnh by phng php sn xut diethylphthalat v methyl salicylat.
72
Chng 8
Phn ng thu phn
Mc tiu
1. Khi nim v phn ng thu phn v cc loi tc nhn thu phn.
2. Cc loi phn ng thu phn v c ch ca n.
3. Mt s v d v phn ng thu phn.
1. i cng
Thu phn l qu trnh phn hu mt hp cht no bng nc to
ra hai hp cht mi. Trong cc thnh phn ca phn t nc u tham gia
vo cu to hai hp cht mi ny.
V d: Phn ng thu phn ester:

Xc tc cho phn ng thu phn l cc acid, kim v enzym. Chng ny
khng cp n phn ng thu phn xc tc enzym.
Thng thng thu phn xc tc acid l phn ng thun nghch, cn
thu phn xc tc kim l phn ng khng thun nghch.
2. C ch ca phn ng thu phn
Thu phn l phn ng th i nhn (S
N
), tc nhn i nhn l nc. Xc
tc cho phn ng l acid hoc base.
Vi cc nhm hp cht khc nhau v xc tc khc nhau, phn ng thu
phn cng xy ra vi c ch khc nhau. V vy, i vi tng nhm hp cht c
th s c c ch phn ng ring.

R COOR' + H
2
O R COOH + R'OH
73
3. Cc tc nhn thu phn
3.1. Thu phn bng nc
Phn ng thu phn bng nc c th khng cn xc tc. Nhit ca
phn ng ph thuc bn cht cc cht cn thu phn. Nhiu trng hp, phn
ng thu phn s sinh ra acid hoc base, cc cht ny s xc tc cho qu trnh
thu phn tip theo. Cn c vo , ngi ta chia phn ng lm hai loi:
3.1.1. Thu phn vi s to thnh sn phm ph l base
Thu phn cc hp cht c kim c th xy ra mt cch mnh lit ngay
nhit thp. V d: diethyl km 0
0
C phn ng mnh lit vi nc:

Cc hp cht Grignard cng phn ng mnh lit vi nc ngay nhit
thp.
C
2
H
5
MgBr + H
2
O C
2
H
6
+ Mg(OH)Br
Cc alcolat cng d thu phn vi nc to ra alcol v hydroxyd. Phn
ng ny khng c mc ch iu ch, m ch phn hu alcolat to thnh
trong mt qu trnh ho hc.
Al(OC
2
H
5
)
3
+ 3H
2
O Al(OH)
3
+ 3C
2
H
5
OH
3.1.2. Thu phn vi s to thnh sn phm ph l acid
Cc halogenid acid, anhydrid v ester phn ng vi nc to thnh cc
acid tng ng.
Cc clorid acid v c (POCl
3
, HOSO
2
Cl, PCl
5
) v clorid acid ca cc acid
carboxylic c mch carbon ngn phn ng v cng mnh lit vi nc. Clorid
acetic phn ng vi nc mnh n mc c th gy n.
Cc anhydrid acid v c (v d SO
3
, P
2
O
5
) cng phn ng mnh lit vi
nc to ra acid tng ng. Anhydrid acetic lc vi nc cng thu phn
thnh acid acetic.
Cc ester ca cc acid v c, c bit l cc bn ester (v d: alkyl hydro
sulfat) thu phn trong nc mt cch d dng. Ngc li, ester ca acid hu
c thu phn vi nc rt chm (tr methyl formiat).
3.2. Thu phn vi xc tc acid hoc kim
3.2.1. Xc tc acid
Acid lm tng tc thu phn ca nhiu loi hp cht: ester, nitril,
amid. Xc tc acid dng trong nhng trng hp khi thu phn vi nc phn
ng khng chy hay khng s dng c xc tc kim.
Zn(C
2
H
5
)
2
+ H
2
O
2
2C
2
H
6
+ Zn(OH)
2
74
Thng s dng acid sulfuric v hydrocloric. Hot lc xc tc ca acid
sulfuric km acid hydrocloric, nhng n c s dng nhiu hn bi v t gy
n mn hn acid hydrocloric. Acid sulfuric c s dng khi thu phn du
m, cellulose v khi ng ho tinh bt.
Ngoi ra cn s dng acid phosphoric, acid percloric, poliphosphoric v
cht trao i cation.
3.2.2. Xc tc kim
u im: Tc thu phn ln hn xc tc acid, phn ng khng thun
nghch, khng s n mn thit b nh trng hp acid.
Thng s dng NaOH, KOH hoc Ca(OH)
2
. Trong trng hp cn mi
trng kim nh c th dng carbonat kim hay Ba(OH)
2
.
Lng kim s dng trong tng phn ng cng khc nhau: ch xc
tc, dng theo ng lng hoc dng qu tha.
Nng kim cng thay i tu loi phn ng. Thng thng hay dng
nng 5-20% trong nc (tr phn ng nung kim).
3.3. Phn ng nung kim
c tin hnh trong kim nung chy c cha 5-10% nc 200-350
0
C.
Phn ng ny c s dng sn xut phenol quy m cng nghip. Phng
trnh phn ng tng qut nh sau:
ArSO
3
H + 3 NaOH ArONa + Na
2
SO
3
+ H
2
O
Phn ng xy ra theo c ch S
N
2
:
Ngi ta thng s dng NaOH, KOH hoc hn hp NaOH+KOH c
chy thp hn trong phn ng nung kim.
4. Cc phn ng thu phn v c ch phn ng
4.1. Thu phn cc alkyl v aryl halogenid
Thu phn cc hp cht alkyl, aryl halogenid thu c cc dn xut alcol
hoc phenol tng ng.
ONa
H
SO
3
Na
H
ONa
S ONa
O
O
S ONa
O
O
ONa
75
Cc dn cht halogen phn ng vi nc khng c xc tc l phn ng
thun nghch:
R-X + H
2
O R-OH + HX
V phn ng vi nc qu chm (c bit chm l cc aryl-halogenid) nn
qu trnh thu phn thng tin hnh trong mi trng kim. Phn ng ny
c ngha trong cng nghip tng hp nhiu nguyn liu quan trng nh: alcol
amylic, alcol allylic, alcol benzylic, glycol, phenol v dn cht...t cc
halogenid tng ng.
C ch phn ng:
C th xy ra 2 trng hp ph thuc vo bc ca carbon trong alkyl-
halogenid:
Th i nhn nh phn t (S
N
2
):
Thng xy ra vi alkyl-halogenid bc 1 v bc 2. C ch nh sau:

Sn phm c cu hnh khng gian ngc vi cu hnh ban u.
Th i nhn n phn t (SN1):
Xy ra vi alkyl-halogenid bc 3. C ch ca phn ng nh sau:

Thu phn cc aryl-halogenid thng xy ra theo c ch nh phn t.
4.2. Thu phn cc dn xut ca acid carboxylic
Phn ng ny c ngha thc t trong cng nghip thu phn cc ester,
amid, anhydrid v clorid acid. Phn ng xy ra d dng khi in tch dng
ring phn ca nguyn t carbon trn nhm carbonyl cng ln. Nu nhm
th gn vi nhm carbonyl ht in t cng mnh th kh nng phn ng
cng cao.
Kh nng phn ng ca cc nhm chc c sp xp theo th t sau:
C
O
NHR
C
O
OR
C
O
OCOR
C
O
Cl
<
<
<

OH +
C
H H
CH
3
X
C
H H
CH
3
X HO C
H H
CH
3
HO
ch
nh
+ X
CH
3
CH
3
CH
3
C X
X
CH
3
CH
3
CH
3
C
OH
nh
ch
CH
3
CH
3
CH
3
C OH + X
76
Xc tc acid lm tng s phn cc ca nhm carbonyl, do cng lm
tng kh nng th i nhn.
C O + H
+
C OH C OH

Cc dn xut c kh nng thu phn yu (ester, amid), s thu phn s
d dng hn nu c ion OH
-
xc tc.
4.2.1. Thu phn cc ester
Thu phn cc ester c th s dng xc tc acid hoc kim.
Trng hp dng xc tc acid th phn ng l thun nghch, tng t
chiu nghch ca phn ng ester ho.
Qu trnh thu phn c th xy ra theo hai hng sau y:

1. Ct lin kt Acyl-oxy(Ac)
2. Ct lin kt Alkyl-oxy (Al)

Tng ng ta c 8 trng hp khc nhau c th hin bng 8.1.
(A: xc tc acid, B: xc tc base, cc s 1, 2 ch bc ca phn ng)
Bng 8.1. Cc kh nng ca phn ng ester ho v thu phn
Phn ng Kh nng xy ra phn ng
A
Ac
2
Thu phn ester v ester ho alcol bc nht v bc hai
A
Ac
1
Thu phn ester v ester ho cc acid c cn tr khng gian
A
Al
2
n nay cha gp
A
Al
1
Thu phn ester v ester ho alcol bc ba
B
Ac
2
Thu phn cc ester bng base
B
Ac
1
n nay cha gp
B
Al
2

B
Al
1
Thu phn cc ester ca alcol bc ba, tu iu kin phn ng m xy
ra theo c ch n hoc lng phn t
C ch ct acyl (Ac):
Thu phn ester v ester ho cc dn xut ca acid carboxylic theo c
ch A
Ac
2
c biu din nh sau:
R C
O
O R'

2
1
77
R C O
X
H
+
nh
ch
R C OH
X
R'OH ch
ch
C OH R
X
O R' H
nh
ch
(
-
HX)
C OH R
O R'
H
+
C R O
OR'
I II
III
IV

Trong : R = alkyl, aryl
Nu: R = alkyl, X = OH: Ester ho
R = alkyl , X = OR: Alcol phn
R = H , X = Cl , OCOR, NH
2
, OR: Thu phn
Giai on to hp cht trung gian II l giai on chm, quyt nh tc
phn ng.
C ch A
Ac
1
:
Di tc dng xc tc acid mnh, ion acyli (II) hnh thnh, y l bc
quyt nh vn tc phn ng:
R C O
X
H
+
nh
nh
R C OH
X
HX ch
nh
C O R
nh
ch
(
C O R
O R' H
H
+
C R O
OR'
I II
III
IV
- +
ROH)

C ch B
Ac
2
:
y l loi phn ng khng thun nghch. C ch nh sau:
R C O
X
+ OH
- ch
nh
R C O
X
OH
R C
O
OH
+ X
-
RCOO
-
+ H
+
nh
ch

C ch phn ng thu phn trong mi trng trung tnh cng tng t
nh c ch B
Ac
2
nhng l qu trnh thun nghch:
R C O
X
+
ch
nh
R C O
X
OH
2
R C OH
X
OH
+ HX
O
H
H
-
H
+
nh
ch
RCOOH

C ch ct alkyl (Al):
Khi thu phn ester ca cc alcol bc ba (v d: t-butyl alcol), xc tc
acid hoc base u ct lin kt alkyl-oxy. C ch A
Al
1
c minh ha nh sau:
78
olefin
ch
nh
R'OH
H
+
-
R' OH
2
H
2
O + R'
+
R'
+
+
R C
O
OH
R C
OH
+
OR'
R C
O
OR'

R l nhm y in t mnh v d dng c tch ra. Carbocation R
+
c
th to vi nc thnh alcol mi hoc loi H
+
to thnh olefin.
4.2.2. Thu phn cc halogenid acid
Khi thu phn cc halogenid acid ta c acid carboxylic v HX:
R C
O
Cl
+ H
2
O RCOOH
+
HCl

Kh nng phn ng ph thuc vo tc nhn i nhn v cu trc ca
phn t halogenid acid.
C R
O
Cl
C R
Cl
O
(

Vi cc clorid acid, nguyn t clor ht in t mnh lm in tch dng
ring phn ca carbon ln, nn n d thu phn hn acid carboxylic tng ng.
Phn ng thu phn thng xy ra theo c ch B
Ac
2
.
4.2.3. Thu phn cc anhydrid
Sn phm thu phn l cc acid:
(RCO)
2
O + H
2
O 2RCOOH
Kh nng thu phn yu hn cc clorid acid, nhng mnh hn cc dn
xut khc ca acid. Phn ng thu phn c tng cng vi xc tc acid hoc
base. Thng xy ra theo c ch nh phn t.
Trong cng nghip vic thu phn anhydrid khng c ngha thc tin
nhiu. Tuy nhin n cng c ng dng trong sn xut acid phthalic, acid
cinamic v acid acetic bng t cc anhydrid tng ng.
79
4.2.4. Thu phn nitril v amid
Qu trnh thu phn gm hai giai on, giai on 1 l hydrat ha, giai
on 2 l thu phn. Xc tc l acid hoc base.
RCN 1
.
+ H
2
O
RCONH
2
2
.
RCONH
2
+ H
2
O
RCOOH
+ NH
3

Phn ng c ngha quan trng trong vic iu ch cc amid v acid t
cc nitril tng ng.
Thu phn amid thnh acid c ng dng trong vic bo v cc amin
(nhm amin thng c bo v bng cch amid ho).
4.3. Thu phn cc ether, acetal, cetal
Phng trnh phn ng thy phn tng qut c vit nh sau:
ROR' + H
2
O
H
+
ROH
+ R'OH
R CH
OR
1
OR
2
H
+
R
1
OH + R
2
OH + R CH
OH
OH
R CH
O
H
+ H
2
O

C hai phn ng u xy ra theo c ch th i nhn lng phn t (S
N
2
).
C ch c gii thch theo s di y:

R
1
C H
2
O C H R
3
X
H
+
R
1
C H
2
O CH R
3
X
H
H
2
O
ch
RCH
2
OH + CH
OH
2
X
R
3
- H
+
R
3
C H X
O H
Trong : X=OH (bn acetal)
X= OR (acetal)
X= H (ether)
Trng hp thu phn m vng epoxyd xc tc acid hoc base cng l
phn ng S
N
2
. Sn phm glycol to ra thng l ng phn trans.
C C
O
H
+
C C
O
H
2
O
O C
C
H
H
OH
H
C HO
C OH
+ H
+

80
Trong cng nghip qu trnh ny c ng dng iu ch glycol t
olefin v bo v nhm oxo thng qua trung gian acetal v bn acetal.
4.4. Thu phn cc hp cht cha lin kt carbon-carbon phn cc
Khi trn hai carbon c nhng nhm ht in t mnh to nn s phn
cc ca phn t. Do in tch dng ring phn trn C ca nhm carbonyl
ln. V d:
Cl
Cl
Cl
C C
O
X
+ H
2
O
OH
-
CHCl
3
+ HO C
O
X

X: -OH, -H, -alkyl
Phn ng ny c ng dng sn xut cloroform trong cng nghip.
Xc tc thng l kim, t khi thc hin mi trng trung tnh hay xc
tc acid.
4.5. Thu phn cc amin
Cc amin thng t b thu phn. Nhng cc hp cht c cu trc enamin
th d thu phn vi xc tc acid to thnh enol.
C C NR
2
HOH
C C OH
+ HNR
2

Cc amin thm c th thu phn nu v tr para ca n c nhm ht in
t mnh. V d: iu ch dimethylamin tinh khit, ngi ta s dng
phng php sau:
N(CH
3
)
2
N O
OH
-
OH N O + HN(CH
3
)
2

5. Thit b ca phn ng thu phn
Thit b ca phn ng thu phn ph thuc vo nguyn liu cn thu phn:
Nguyn liu d thu phn th c th s dng cc thit b h hoc kn,
c my khuy, hai v c th lm lnh hoc un nng.
Nguyn liu kh thu phn th dng thit b chu p sut.
Thu phn xc tc kim, c th dng thit b bng st hoc thp.
Thu phn bng acid H
2
SO
4
dng thit b bng st silic bc ch, gn
y ngi ta dng thp chu acid.
81
Thu phn bng acid HCl gy n mn ln. Nu nng HCl long, c
th dng thit b ch to bng hp kim niken hoc hp kim ng
(phospho-ng ; nhm-ng ; mangan-ng ). Cc thit b lm
bng cao su, nha, thu tinh cng c th c s dng. i vi kh
HCl th s dng c thit b bng st v ngay nhit cao cng b
n mn rt thp.
Ngoi ra cc loi thit b kim loi c lt nha cng hay c s dng vo
mc ch thu phn.
6. K thut an ton lao ng
Cn ch n vn n mn thit b v phng nhng nguy him v
acid, base. trnh dung dch acid hoc base bn vo mt, lc thao tc cn
eo knh hoc mt n bo h lao ng. Cn i ng, mc o chong, eo gng
tay trnh acid hoc base bn vo ngi, vo chn tay.
7. Mt s v d
7.1. iu ch sulfanylamid
Phn ng thu phn 4-(acetyl-amino)-benzensulfonamid loi nhm
acetyl l giai on cui cng trong qu trnh iu ch sulfanylamid.
CH
3
CONH SO
2
NH
2
NH
2
SO
2
NH
2
OH
-
+ CH
3
COOH

Trong cng nghip thng hay s dng thu phn kim v nhm
sulfonamid tan tt trong kim long.
Hi lu 4-(acetyl-amino)-benzensulfonamid vi 5-10 phn dung dch
NaOH 8-10% trong vi gi. Lm lnh, acid ha bng HCl c n pH=3-5.
lnh, sulfanylamid s kt tinh. Lc, ra bng nc v sy thu sn phm.
7.2. Cc phng php iu ch phenol
7.2.1. Phng php nung kim
Nung chy mui natri benzen sulfonat trong NaOH c cha 10% nc
300-320
0
C theo phn ng sau:
C
6
H
5
SO
3
Na + 2NaOH C
6
H
5
OH + Na
2
SO
3
+ H
2
O
7.2.2. Thu phn clorobenzen (phng php ca Dow)
Nguyn tc ca phng php l thu phn clorobenzen trong dung dch
NaOH 360
0
C. T benzen, qu trnh phn ng nh sau:
82

C
6
H
6

+
C l
2
F e C l
3
80
0
C
C
6
H
5
C l
+
H Cl
C
6
H
5
C l + 2N aO H
360
0
C
240
ba r
C
6
H
5
O N a +
N aC l +
H
2
O
C
6
H
5
O N a + H C l
C
6
H
5
O H +
N a C l

7.2.3. Thu phn clorobenzen theo phng php ca Raschig
iu ch phenol t clorobenzen pha hi. Phn ng c tin hnh theo
hai giai on:
C
6
H
6
+ 1 / 2 O
2
+ HCl
xt
C
6
H
5
Cl + H
2
O
C
6
H
5
Cl + H
2
O
Ca(PO
4
)
2
500
o
C
C
6
H
5
OH + HCl

7.2.4. Phng php Hock
CH
3
COCH
3
+ C
6
H
5
OH
H
+
C
6
H
5
COOH
CH
3
CH
3
O
2
CH
3
C
6
H
5
CH
CH
3 AlCl
3
CH
3
CH CH
2
+ C
6
H
6

Phng php ny ngoi phenol cn thu c aceton l dung mi c s
dng nhiu. Do y l mt phng php kinh t.
T lng gi
1. Khi nim v phn ng thu phn v cc loi tc nhn thu phn?
2. Trnh by c ch phn ng thu phn cc loi hp cht khc nhau?
3. Thit b ca phn ng thu phn c th s dng nhng loi no? Nu
cc nguyn liu ch to chng?
4. Trnh by phng php thu phn loi nhm acetyl trong tng hp
cc sulfamid v cc phng php sn xut phenol?

83
Chng 9
Oxy ho
Mc tiu
1. Khi nim v phn ng oxy ho v cc loi c ch ca chng.
2. Cc tc nhn oxy ho.
3. Cc loi phn ng oxy ho.
4. Mt s v d v phn ng oxy ho.
1. i cng
Trong ho v c v in ho hc chng ta bit, oxy ho v kh ho l
hai qu trnh ng thi xy ra, c gi chung l qu trnh oxy ho-kh.
V d:
HgCl
2
+ SnCl
2
Hg + SnCl
4

Hg
2+
+ 2e Hg
0

Sn
2+
- 2e Sn
4+
Trong phn ng ny thu ngn l cht b kh cn thic l cht b oxy
ho. S lng in t do cht b oxy ho cho i bng s lng nhng in t
cht b kh nhn vo.
Tuy nhin trong ho hc hu c, khi nim cho v nhn in t khng
c s dng rng ri nh trong ho hc v c. Bi v trong cc phn ng hu
c rt kh o c s chuyn dch in t. Mt khc cc lin kt trong ho
hu c l lin kt cng ho tr, t c kh nng chuyn thnh lin kt ion. Do
trong ho hu c ngi ta nh ngha phn ng oxy ho nh sau:
Oxy ho l phn ng lm tng oxy ho ca nguyn t hoc phn t
tham gia phn ng.
oxy ho ca mt hp cht hay mt nguyn t no tng ln c th
hin 3 yu t:
Tng s nguyn t oxy trong phn t.
84
Gim s nguyn t hydro ca phn t.
Gim s in t trong nguyn t hoc phn t.
V d:
CH
3
CHO + H
2
O
2
CH
3
COOH + H
2
O
HCOOH + C
6
H
5
CH CH
2
CO
2
+ C
6
H
5
CH
2
CH
3
Cu + Ag Cu + Ag

Trong ba v d trn, cc nguyn liu u tin l cht b oxy ho cn
nguyn liu th hai l cht b kh. Cng c th gi nguyn liu u tin l tc
nhn kh v nguyn liu th hai l tc nhn oxy ho.
2. C ch phn ng oxy ho
Tu tc nhn v mi trng, phn ng oxy ha xy ra theo nhng c ch
khc nhau. Sau y l mt s loi c ch thng gp:
2.1. C ch phn ng t oxy ha
C ch ny nhm gii thch cc hin tng t oxy ho trong mi trng
sng ca chng ta. l s phn hu ca cc hp cht hu c nh oxy khng
kh.
Di tc dng ca nh sng, nhit hoc tc nhn to gc t do, cc
phn t hu c b kch thch v to thnh cc gc t do. Sau cc gc t do
ny phn ng vi oxy khng kh theo phn ng dy chuyn:

R H
h

R H
R H
R
+
H
R
+
O
2
R O O
R O O + R H
R O O H +
R O O
+
R
R R O O R
R O O H +
O H
R O O R
2
R O
R O
R O
Alcol; Hp cht Carbonyl ; Acid

85
2.2. C ch oxy ho c xc tc
Phn ng oxy ho xc tc c chia thnh hai loi: oxy ho xc tc ng
th v oxy ho xc tc d th. Oxy ho xc tc ng th thng thc hin th
lng, cn oxy ho xc tc d th th thc hin th hi-rn hoc lng-rn.
Trng hp oxy ho xc tc ng th, ngun tc nhn oxy v xc tc l
cc ion kim loi u ho tan trong cht lng v tham gia phn ng.
Phn ng xy ra theo c ch gc t do:
RH + Me
3+
R
+ Me
2+
+ H
+
R

+ O
2
ROO

ROO
+ RH ROOH + R

ROOH + Me
3+
ROO
+ Me
2+
+ H
+

ROOH + Me
2+
RO
+ Me
3+
+ OH

ROO
+ RO
Sn phm oxy ho
Oxy ho xc tc d th c phn thnh hai nhm: Xc tc kim loi v
xc tc oxyd kim loi. C ch ca qu trnh ny n nay vn cha c chng
minh.
Trong s cc xc tc kim loi th bc v ng c s dng nhiu. Oxyd
kim loi th V
2
O
5
l quan trng nht. Xc tc ny ng vai tr nh mt cht
vn chuyn oxy.
2.3. C ch oxy ho bng tc nhn ho hc
Da vo tc nhn oxy ha, c ch phn ng oxy ho bng tc nhn ho
hc c th phn thnh hai nhm:
C ch oxy ha ca cc hp cht ca kim loi c ho tr thay i.
C ch oxy ha ca cc hp cht cha oxy hot ng (cc peroxyd).
2.3.1. C ch phn ng ca cc hp cht ca kim loi c ho tr thay i
V d: Phn ng oxy ho alcol thnh aldehyd bng acid cromic:
R CH
2
OH + H
2
CrO
4
R CH
2
O Cr
O
O
OH
+ H
2
O
R C O Cr
O
O
OH
H
H
HOH
R CHO + H
3
O + HCrO
3
(1)
(2)

86
Vi nhng alcol c cu trc t cn tr khng gian th qu trnh to ester
(1) nhanh. Qu trnh quyt nh vn tc phn ng l qu trnh phn hu ester
(2). Trn c s kim tra qu trnh phn ng, ngi ta cho rng lc phn hu
ester khng to ra Cr
V
m l Cr
IV
, ion ny b Cr
VI
oxy ho thnh Cr
V
. Sau
Cr
V
oxy ho mt phn t alcol mi v n b kh thnh Cr
III
.
Cr
VI
+ R-CH
2
OH R-CHO + 2H
+
+ Cr
IV
Cr
VI
+ Cr
IV
2Cr
V
R-CH
2
OH + Cr
V
R-CHO + 2H
+
+ Cr
III
T v d trn chng ta thy rng, trong qu trnh oxy ho s to ra nhiu
loi ion c ion ho khc nhau, chng u tham gia vo qu trnh oxy ho.
Cho nn khi s dng tc nhn ny, t khi nhn c mt sn phm ng nht
m thng l mt hn hp gm nhiu cht.
2.3.2. C ch phn ng ca cc hp cht cha oxy hot ng
V d oxy ho olefin bng peroxyd. Qu trnh oxy ha xy ra qua phc
trung gian nh s sau:
+
C
C
O
H
O
O C
R
O
+
C
C
C
C
H
O
O
R C
O
C
O
R
HO

Hp cht pecarboxylic tn cng vo ni i ca olefin pha t c cn tr
khng gian hn.
3. Cc tc nhn oxy ho
Tc nhn oxy ho l nhng hp cht c th nhng oxy, loi hydro hoc
in t ca cc phn t khc lm tng oxy ho ca chng.
Ngi ta phn cc tc nhn oxy ho thnh ba nhm sau:
Khng kh v kh oxy.
Cc hp cht cha oxy hot ng.
Cc hp cht ca cc kim loi c ho tr thay i.
3.1. Khng kh v kh oxy
Thnh phn khng kh c 21% oxy, do c th dng lm tc nhn oxy
ha. Trc khi s dng, khng kh cn phi c lm sch. Qu trnh lm
sch gm hai giai on:
Lc tp cht c hc bng cch nn khng kh qua mt phin lc kh.
87
Loi cc tp cht th hi trnh ng c xc tc (bng cch cho
khng kh qua ct cha than hot tnh).
Trong cng nghip, ngi ta sn xut v s dng kh oxy sch (hm
lng oxy 94-96%). Oxy c cha trong bnh p lc di dng lng.
Phn ng oxy ho bng kh oxy thng c tin hnh trong mi trng
nc trnh chy n. Ch nhng hp cht c kh nng phn ng km mi
tin hnh trong dung mi hu c.
C khng kh ln kh oxy u to hn hp n vi cc hp cht hu c, do
cn nghin cu cn thn gii hn n trc khi s dng. Cc thit b oxy ho
cn lp thm mt a n m bo an ton.
3.2. Cc hp cht cha oxy hot ng
Tc nhn ny gm hai nhm hp cht: nhm peroxyd (cc hp cht cha
lin kt -O-O-), nhm hypoclorid v dn cht (cha nhm chc -O-Cl).
3.2.1. Nhm peroxyd
L nhng hp cht v c hay hu c c to thnh t hydrogen peroxyd
(H
2
O
2
), trong mt hoc c hai nguyn t hydro c thay bng nguyn t
hoc nhm nguyn t v c hoc hu c. Nhm ny gm cc tc nhn sau:
Hydrogen peroxyd (H
2
O
2
):
Trn th trng c cc loi nng 30%, 70% hoc 100%. Loi nng
30% trong nc khng bn vng, nn thng phi cho thm ur hoc cht to
phc tng bn vng ca dung dch. Loi 70% hoc 100% l cht lng
snh, khng mu, phn ng mnh vi cc hp cht hu c.
Cc peroxyd v c:
Hydro ca H
2
O
2
c tnh acid, c th thay th bng kim loi. Cc peroxyd
kim loi (K-, Na-, Ba-peroxyd) cng l nhng tc nhn oxy ho tt.
Persulfuric (H
2
SO
5
) l tc nhn oxy ho quan trng trong s cc peracid
v c. Phng php iu ch n gin nht l cho H
2
SO
4
phn ng vi H
2
O
2
.
H
2
SO
5
l cht khng mu, nng chy 45
0
C. Ngi ta s dng tc nhn ny
oxy ho cc ceton thnh ester.
Cc peroxyd hu c:
Cc tc nhn in hnh ca nhm ny l acid percarboxylic. Gm c: acid
peracetic, trifluor-peracetic, perbenzoic, monoperphthalic.
Trong phn t ca chng cha nhm chc peracid, cu trc nh sau:

C O
O
OH
88
Peracid c s carbon thp l cht lng (peracetic), cc peracid c s
carbon ln hn l cht rn.
Phn ng oxy ho vi tc nhn peroxyd c tin hnh trong dung mi l
dn cht halogen hu c, nhit 0-10
0
C.
3.2.2. Nhm hypoclorid
Gm cc dng mui Ca(OCl)
2
, NaOCl, KOCl. Cc mui ny gp m d b
phn hu, cn bo qun trong ti nha hoc l kn.
Trong mi trng acid, n phn hu v gii phng Cl
2
. Khi oxy ho olefin
cn ch ti sn phm ph do phn ng cng hp vi Cl
2
hoc HOCl.
3.3. Cc hp cht ca kim loi c ho tr thay i
Cc tc nhn thng s dng l hp cht ca crom (Cr
VI
) v mangan
(Mn
VII
).
3.3.1. Cc hp cht crom
Nhm tc nhn ny gm anhydrid cromic (CrO
3
), natri v kali dicromat
(Na
2
Cr
2
O
7
, K
2
Cr
2
O
7
). Phn ng oxy ho tin hnh trong mi trng acid, trong
qu trnh phn ng Cr (III) c to thnh.
Anhydrid cromic (CrO
3
): Dng tinh th mu hng, trong khng kh
ht m to thnh acid cromic. Oxy ho cc hp cht hu c mt cch
mnh lit theo phng trnh sau:
2CrO
3
Cr
2
O
3
+ 3O
Phn ng oxy ho tin hnh trong dung mi hu c (benzen,
dicloromethan, ether) hoc trong acid acetic bng. Thi gian gn
y, ngi ta thng s dng phc [(pyridin)
2
CrO
3
] v tin hnh
phn ng trong pyridin hoc cc dung mi clor hu c v n ho tan
tt trong cc dung mi ny.
Kali hoc natri dicromat: Dng tinh th mu vng cam. Trong mi
trng acid n gii phng oxy nguyn t theo phn ng sau:
K
2
Cr
2
O
7
+ 4H
2
SO
4
K
2
SO
4
+ Cr
2
(SO
4
)
3
+ 3O + H
2
O
Tc nhn ny khng mnh nh CrO
3
, thng s dng trong mi
trng acid (sulfuric hoc acetic).
3.3.2. Cc hp cht mangan
Trong cc hp cht ca mangan, c hai loi thng c s dng lm tc
nhn oxy ha l kali hoc natri permanganat v dioxyd mangan.
89
Cc permanganat l tinh th mu tm. Natri permanganat d ht m
v chy nc nn kali permanganat c dng nhiu hn. Hp cht
ny c th oxy ho trong mi trng acid, trung tnh hoc kim:
2KMnO
4
+ 3H
2
SO
4
2MnSO
4
+ K
2
SO
4
+ 5O + 3H
2
O
2KMnO
4
+ H
2
O 2MnO
2
+ KOH + 3O
Phn ng trong mi trng trung tnh to ra KOH, nn cn thm
MgSO
4
hoc phng kh CO
2
vo gi cho pH khng chuyn sang
kim.
MgSO
4
+ KOH MgO + K
2
SO
4
D phm ca phn ng l mangan dioxyd, d dng lc b hoc tinh
ch li lm tc nhn oxy ho.
Dung mi phn ng thng l benzen hoc dn xut clor hu c.
Ngoi ra cn c th s dng aceton, acid acetic v pyridin. Nu dng
dung dch nc cn thm cht ho tan chuyn pha l terc-butanol
hoc acid acetic.
Mangan dioxyd (MnO
2
) l tc nhn oxy ho yu hn permanganat.
Trong cng nghip, c th s dng thng MnO
2
t nhin. Vi nhng
phn ng cn MnO
2
cht lng cao hn th c th nhit phn mangan
oxalat hoc mangan carbonat. MnO
2
c cht lng tt nht l loi
c kh ho t permanganat.
Tc nhn MnO
2
trong phn ng oxy ha dng huyn ph. Cht cn
oxy ho c th ho tan trong cc dung mi nh nc, acid acetic,
CCl
4
, CHCl
3
, CH
2
Cl
2
, benzen, tetrahydrofuran, isopropanol,
ethylacetat, ether, pyridin, acetonitril.
4. Cc phn ng oxy ho
Trong k thut tng hp Ho dc, qu trnh oxy ho cc alcol, hp cht
carbonyl, amin, oxy ho bin i khung cc hp cht a vng hoc dehydrogen
hol nhng phn ng quan trng v c s dng nhiu. Do chng ta s
nghin cu tng loi qu trnh ny.
4.1. Oxy ho alcol
Cc alcol bc nht v bc hai khi oxy ho vi oxy khng kh th hi, xc
tc bc hoc ng to thnh hp cht carbonyl. Trng hp xc tc bc th
nhit phn ng 550-600
0
C, xc tc ng hoc hp kim ca ng, nhit
phn ng l 350-500
0
C.
90
Xc tc kim loi thng c hot ho trn cht mang, khi xc tc
c hot ha hn v thi gian s dng di hn.
Oxy ho alcol c ni kp v tr , , xc tc ng thu c hp cht
carbonyl tng ng m khng nh hng n ni i.
Oxy ho ethanol bng oxy khng kh, xc tc bc, trc ht to ra
aldehyd acetic, sau oxy ho tip thnh acid acetic. Ngoi bc, c th dng
ng, niken, coban, st v cc oxyd ca chng.
Cc alcol bc mt v bc hai b oxy ha bi Cr(VI) to thnh hp cht
carbonyl. Aldehyd to thnh b oxy ha tip trong nc n acid carboxylic.
4.2. Oxy ho hp cht carbonyl
Oxy ho aldehyd acetic th lng vi oxy khng kh, xc tc coban
hoc mangan-acetat (nhit 50-70
0
C, p sut 5-8 bar) to thnh
acid acetic.
Oxy ho cc aldehyd vi oxy, xc tc ng trong mi trng amoniac
to thnh nitril:
R C
O
H
NH
3
R C
NH
H
O
2
/Cu
R CN

Cc ceton b oxy ho bi hp cht Cr(VI) thnh hn hp ca hai acid:
R-C=O Cr
VI
R-COOH + R-COOH
CH
2
R
4.3. Oxy ho cc hp cht thm
Cc hp cht thm b oxy ho c th lng v hi vi oxy khng kh, xc
tc l V
2
O
5
. Vi cc hp cht thm c mch nhnh, nu phn ng tin hnh
pha lng, mi trng acid (H
2
SO
4
hoc CH
3
COOH), sn phm to thnh cha
nhm carbonyl v tr .
Ar-CH
2
-CH
3
V
2
O
5
/O
2
Ar-CO-CH
3
Vi tc nhn kali permanganat, t -picolin thu c acid isonicotinic l
nguyn liu tng hp isoniazid:
N
CH
3
KMnO
4
N
COOH

91
Vic oxy ho nhn thm kh khn hn, iu kin phn ng mnh lit
hn. Phn ng c tin hnh 350-450
0
C vi oxy khng kh, xc tc V
2
O
5
s
ph v nhn thm, to thnh anhydrid dicarboxylic.
O
O
O
O
O
OH
OH
O
O
H
H
O
O
O
2
/V
2
O
5
350-450 C
0 0

T naphtalen thu c anhydrid phthalic l nguyn liu tng hp
diethyl-phthalat:
CO
O
CO
V
2
O
5
/O
2

T -nitro-naphtalen thu c sn phm chnh l phthalimid:
NO
2
V2O5/O2
CO
CO
NH
CO
CO
O
+
41-48%
8-13%

T antraxen to thnh antraquinon:
O
O
V
2
O
5
/O
2

4.4. Dehydro ho
Dehydro ho l qu trnh loi hydro khi phn t hu c. Trong cng
nghip tng hp ho hc, qu trnh dehydro ho c s dng iu ch cc
olefin, acetylen, hp cht carbonyl hoc nitril. Trong cng nghip Ho dc n
thng c s dng thm ho cc hp cht vng.
Dehydro ho l qu trnh thu nhit, v vy nhit ca phn ng lun
cao (> 250
0
C).
Tt c xc tc cho phn ng hydro ho u s dng lm xc tc cho phn
ng dehydro ho.
Phn ng thng c thc hin trong cc dung mi c nhit si cao
nh decalin, tetralin.
92
5. Thit b ca phn ng oxy ho
Phn ng oxy ho th kh, xc tc d th c tin hnh mt cch lin
tc trong ct phn ng cha xc tc. H thng ct phn ng c hai v lm
lnh hoc un nng. Cht ti nhit thng dng l DIFIL (diphenyl metan).
Phn ng oxy ho xc tc pha lng c thc hin trong thp phn
ng. Thp ny gm 8-12 on, mi on c th un nng hoc lm ngui mt
cch c lp. Bn trong xp y cc vng Raschig nhm lm tng kh nng
tip xc gia cc cht tham gia phn ng.
Oxy ho bng tc nhn ho hc thng c tin hnh trong ni phn
ng hai v, c my khuy. H thng trao i nhit phi hiu qu v an ton v
c th phi un nng v lm lnh nhiu ln.
Oxy ho l phn ng to nhit mnh. Do thit b cn lm lnh mt
cch hiu qu. Ngi ta thng ch to thit b c th tch nh tin gia
nhit v loi nhit.
6. K thut an ton trong qu trnh oxy ha
Oxy ho l phn ng to nhit mnh, nhng cn cung nhit cho giai
on khi ng. Sau phi lm lnh tt khng ch c nhit phn
ng. Do thit b phn ng phi m bo trao i nhit hiu qu, mt khc
cn tnh ton tc np nguyn liu hp l trnh hin tng qu nhit, d
gy n.
Cc cht hu c, cc dung mi v tc nhn oxy ho c th to vi oxy
hoc khng kh thnh hn hp n. V vy cn nghin cu k t l gii hn gy
n ca hn hp cc thnh phn trn phng.
Peroxyd l cc cht d gy n. Do cn trnh nng qu ln ca n
trong thit b phn ng. Vi cc phn ng c to thnh peroxyd, khi tinh ch
sn phm khng c ct qu kit trnh n.
7. Mt s v d
7.1. iu ch anhydrid phthalic
Anhydrid phthalic l nguyn liu quan trng ca cng nghip nha (cht
lm mm ho nha). N cng l nguyn liu sn xut acid benzoic nguyn
cht. Trong cng nghip dc phm n c s dng iu ch diethylphthalat.
Anhydrid phthalic c iu ch bng cch oxy ho naphtalen vi oxy
khng kh th hi, xc tc l V
2
O
5
.
93
CO
O
CO
400 - 250
V
2
O
5
/O
2
C

Naphtalen c lm nng ln 180-200
0
C, trn vi khng kh thnh hn
hp hi. Hn hp hi ny c thi cng khng kh vo thit b phn ng. Qu
trnh oxy ho c tin hnh mt cch lin tc trong thit b cha xc tc.
Hiu sut qu trnh oxy ho t 75%.
7.2. iu ch acid acetic bng cch oxy ho aldehyd acetic
Acid acetic l nguyn liu quan trng ca nhiu ngnh cng nghip ho
hc v thc phm. N c iu ch bng cch oxy ho aldehyd acetic vi oxy
khng kh, xc tc l mangan acetat. Lng xc tc s dng trong phn ng
l 0,1%. Acid acetic c to thnh qua trung gian peracetic theo phng
trnh sau:
CH
3
-CHO + O
2
CH
3
-COOOH
CH
3
-COOOH + CH
3
-CHO 2CH
3
COOH
Phn ng tin hnh nhit 60
0
C, p sut 4-5 bar v duy tr thi gian
12-14 gi. Sn phm thu c c hm lng acid acetic 96%.
7.3. iu ch formaldehyd t methanol
Formaldehyd c iu ch bng cch dehydrogen ho hoc oxy ho
methanol theo phng trnh sau:
CH
3
-OH CH
2
O + H
2

CH
3
-OH + O
2
CH
2
O + H
2
O
Trong thc t, ngi ta thng oxy ho methanol vi oxy hoc khng kh,
xc tc bc. Nhit khi ng cho phn ng l 400-450
0
C, sau do phn
ng to nhit nn tng ln 550-600
0
C. C th duy tr nhit cho phn ng
bng tc cp hn hp methanol v khng kh vo thit b oxy ho (theo t l
1:1). Sn phm thu c c nng formaldehyd 35-37% trong nc.

94
Methanol thu hi
Formalin
Nc
Nc
Kh thi
5
6
7
9
8
Methanol
3
1
4
2
Khng kh
u

Hnh 9.1. S thit b phn ng iu ch formaldehyd t methanol
1. Bung trn v ho hi, 2. Bung xc tc,
3. Bnh ong methanol, 4. B phn hp th, 5.7. Sinh hn,
6. Bnh ra kh, 8. B phn tch kh, 9. Bnh cha sn phm ph
T lng gi
1. Qu trnh oxy ho trong ho hc hu c c hiu nh th no?
2. Trnh by cc loi c ch ca phn ng oxy ho?
3. Nu cc loi tc nhn c s dng cho phn ng oxy ho trong tng
hp hu c v ho dc.
4. Trnh by cc phn ng oxy ho cc nhm hp cht quan trng v
phng php dehydro ho.
5. Nu cc thit b ca phn ng oxy ho v k thut an ton trong vic
thc hin cc qu trnh oxy ho.
6. Trnh by phng php sn xut anhydid phthalic, acid acetic v
formaldehyd.
95
Chng 10
Kh ho
Mc tiu
1. Khi nim v cc loi tc nhn ca phn ng kh ho.
2. Cc loi c ch ca phn ng kh ho.
2. Cc loi phn ng kh ho.
3. Mt s v d v phn ng kh ho.
1. i cng
chng oxy ho, chng ti trnh by mt s khi nim v qu trnh
oxy ho kh trong ho v c v in ho hc. Khi nim kh ho c hiu l
qu trnh nhn thm in t ca mt nguyn t hoc ion no .
Trong ho hc hu c, ngi ta gi kh ho l qu trnh lm gim oxy
ho ca cht em kh. Trong hp cht hu c ly thm nguyn t hydro,
loi khi n cc d t (thng l oxy) hoc nhn thm in t.
Qu trnh phn t hu c nhn hydro l phn ng cng hp. Qu trnh
loi d t ra khi phn t hu c l qu trnh hydro phn (hydrogenolysis).
y l qu trnh ph hu lin kt gia carbon v d t bng hydro m sn
phm ph thng l H
2
O, NH
3
,
Mc ch ca qu trnh kh ho l iu ch cc hydrocarbon no t hp
cht hydrocarbon khng no tng ng, t nhng hp cht c oxy ho cao
thnh cc cht c oxy ho thp hn. Trong cng nghip Ho dc, quan
trng nht l qu trnh kh cc nitro thnh amin. Nhiu amin thm l hp
cht trung gian c s dng tng hp cc nhm thuc khc nhau (nhm
sulfamid, nhm thuc h nhit).
Phn ng kh ho khng c mt c ch chung m mi loi tc nhn kh
ho c c ch phn ng ring. Khi nghin cu v tc nhn kh ho, chng ta
s nghin cu c ch ca chng.
96
2. Tc nhn kh ho
Tc nhn kh ho c nhiu loi khc nhau, chng c chia thnh ba
nhm chnh sau:
Tc nhn kh ho ho hc.
Tc nhn l hydro phn t vi xc tc.
Tc nhn kh ho in ho.
Trong 3 tc nhn kh trn, hin nay kh bng in ho rt t c s dng
trong tng hp Ho dc, v vy chng ti khng trnh by trong chng ny.
2.1. Tc nhn kh ho hc
Gm c cc tc nhn sau:
1. Kim loi (Fe, Zn, Sn) trong mi trng acid, kim.
2. Hn hng kim loi (cc hn hng Na, Al, Mg, Sn, Zn).
3. Kim loi kim trong alcol.
4. Kim loi v amoniac.
5. Kim loi v amin hu c.
6. Cc hydrid kim loi (LiAlH
4
, NaBH
4
).
7. Hydrazin N
2
H
4
.
8. Cc hp cht ca lu hunh.
2.1.1. Kim loi trong mi trng acid, kim
Phng php ny ch yu c s dng kh ho cc hp cht nitro
hoc nitrozo thnh amin. St v thic ch s dng trong mi trng acid, cn
km s dng c trong acid v kim.
St trong mi trng acid:
Phn ng kh ho ca Fe trong mi trng acid hydrocloric (phn ng
Bechamp) c ngha thc t ln nht. y l phng php quan trng iu
ch cc amin thm trong cng nghip.
Trc y ngi ta cho rng phn ng kh ho bng st trong acid xy
ra theo phng trnh sau:
ArNO
2
+ 3Fe + 6H
+
ArNH
2
+ 3Fe
2+
+ 2H
2
O
Tuy nhin trong thc t, lng acid HCl ch cn 2% cng phn ng
thc hin. N ch ng vai tr nh mt cht xc tc cho phn ng. Nghin cu
v phn ng ny, Bechamp ngh phng trnh phn ng nh sau:
97
4ArNO
2
+ 9Fe + 4H
2
O
100 C
0
4ArNH
2
+ 3Fe
3
O
4
Phn ng t hiu qu tt nht khi s dng bt gang xm. Bt gang ny
giu graphit, gin, d nghin thnh bt mn. N khng ng nht nn to
nhiu cp pin in ho tham gia qu trnh kh.
Mt s mui trung tnh cng xc tc cho phn ng kh ho do lm tng
dn in ca dung dch (FeCl
2
, FeSO
4
, FeCl
3
, CaCl
2
, MgCl
2
...).
Thic trong mi trng acid:
Ngoi hp cht nitro, tc nhn ny cn kh c nhiu loi hp cht
khc. Nhng v gi thnh cao nn vic s dng thic lm tc nhn kh trong
cng nghip cn hn ch. Phn ng kh c tin hnh bng cch hi lu cht
cn kh trong dung dch nc-acid hydrocloric. Sau va cho t t bt thic
v acid hydrocloric c vo khi phn ng vi t l 0,4-1 nguyn t gam
thic/1 nguyn t gam hydro; 2,1 mol HCl/1 nguyn t gam thic.
Km trong mi trng acid:
y cng l tc nhn kh c gi thnh cao, tuy nhin vic s dng bt
km lm tc nhn kh ha ph bin hn thic. Lng km cn thit cho phn
ng kh ho c dng vi t l nh sau: 1-1,1 mol km/1 mol cht cn kh,
lng acid l 2,5 mol /1 mol km.
Cc acid thng dng cho qu trnh kh l HCl, H
2
SO
4
, acid acetic. Nu
cht cn kh khng tan trong hn hp nc-acid, c th dng dung mi nc-
cn, acid acetic, dioxan...lm mi trng kh ha.
Tc nhn ny c th kh c lin kt kp carbon, cc dn cht quinon,
epoxy, nitro, halogen
Km trong mi trng kim:
Ch yu c dng kh cc hp cht nitro. Mt mol hp cht nitro
kh thnh hydrazo-benzen cn 3-3,4 mol bt km. Lng kim ch cn 5-10%
theo tnh ton v qu trnh thy phn natri-zincat s ti sinh ra kim:
2ArNO
2
+ 5Zn + 10NaOH Ar-NH-NH-Ar + 5Zn(ONa)
2
+ 4H
2
O
Zn(ONa)
2
+ 2H
2
O Zn(OH)
2
+ 2NaOH
2.1.2. Hn hng kim loi
Hn hng natri cha ti a 5% natri kim loi. iu ch bng cch cho t
t 30-50 phn thu ngn vo natri kim loi trong bu kh N
2
. Nghin ngay
thnh bt lc hn hng cn ang nng.
Phn ng kh c tin hnh bng cch ho tan hoc to huyn ph
cht cn kh trong nc, cn hoc ether. Sau va khuy va cho dn hn
hng vo khi phn ng v gi nhit khong 25
0
C.
98
Cc hn hng kim loi c th bo qun trong chai nt kn, nhng tt
nht l nn iu ch ngay trc khi tin hnh phn ng.
Hn hng natri c s dng hydro phn lin kt C-N ca mui
amoni bc 4, lin kt C-O, dimer ho kh cc acrylnitril, acrylester. Hn hng
magnesi c th dime ho kh cc aldehyd v ceton.
2.1.3. Kim loi kim trong alcol
Thng s dng natri kim loi trong cc alcol c 2-5 carbon. Phn ng
gii phng kh hydro nn phi rt cn thn. Na kim loi c dng di dng
ht nh tng tc phn ng v trnh nguy him.
Phn ng kh c tin hnh nh sau: Va khuy va cho t t natri
kim loi vo dung dch ca cht cn kh trong alcol tuyt i. C th iu
chnh tc phn ng bng lng natri cho vo v lm lnh. Nu tc phn
ng gim th c th lm nng. Cn gi cho phn ng tuyt i khan nc. Kt
thc phn ng, nu cn natri d th thm alcol phn hu.
Natri kim loi trong alcol c s dng kh cc ester, aldehyd v
ceton thnh alcol; nitril thnh amin. Ngoi ra c th kh cc oxim, nhn thm
v cc d vng. Trong ho hc cc hp cht hydratcarbon, phng php ny
c s dng loi nhm bo v benzyl.
2.1.4. Kim loi v amoniac
Hin nay, kim loi v amoniac l mt trong nhng tc nhn quan trng
nht v hay c s dng nht kh cc hp cht c cn tr khng gian ln,
m tc nhn kh ho khc khng tc dng.
Ngi ta thng dng lithi hoc natri (t dng kali hoc calci) trong
amoniac lng. Qu trnh kh ho c tin hnh bng cch cho t t kim loi
vo dung dch ca cht cn kh trong amoniac v dung mi (nu cn) nhit
si ca amoniac (-33,4
0
C).
Tc nhn ny c th hydro phn cc lin kt C-O, C-S, C-halogen, kh
ho olefin thnh parafin, acetylen thnh olefin, ester thnh alcol, naphtalen
v dn cht thnh 1,4-dihydro-naphtalen v dn cht tng ng.
2.1.5. Kim loi v amin
Hu nh ch s dng lithi kim loi, ch mt vi trng hp dng natri.
Cc amin hu c hay dng ethylamin v ethylendiamin.
Phn ng kh ho c tin hnh nhit phng hoc nhit si ca
amin.
99
Kim loi v amin c th kh olefin thnh parafin, acetylen thnh olefin,
parafin, aldehyd v ceton thnh alcol, nitril thnh amin, nitro thnh amin,
benzen th thnh hn hp cyclohexen v cyclohexan tng ng, naphtalen
thnh cc ng phn decalin...
2.1.6. Cc hydrid kim loi
Lithium aluminium hydrid (LiAlH
4
) v natri boronhydrid (NaBH
4
) l cc
tc nhn kh c s dng nhiu trong cng nghip. C hai u l cht rn,
tng i bn vng nn d thao tc.
C ch phn ng kh ho nhm carbonyl nh sau:
C O
H M
C O
H M
M=LiAlH
3
; NaBH
3

Tng t nh trn, ton b cc anion hydrid khc u tham gia phn
ng to phc alcolat:
Li [AlH
4
] + 4
Li [Al(OCH)
4
]
Na [BH]
4
+
C O 4
C O 4 Na [B(OCH)
4
]

Thu phn cc phc alcolat cho alcol tng ng:
Li [Al(OCH)
4
] + H
2
O
4 CH OH + LiOH + Al(OH)
3
4
Na [B(OCH)
4
] + H
2
O
4 CH OH + NaOH + B(OH)
3
4

Phn ng kh ho vi LiAlH
4
tin hnh trong dung mi dietylether,
tetrahydrofuran khan. N c th kh aldehyd, ceton, epoxyd, acid carboxylic,
ester thnh alcol; amid, nitril, nitro thnh amin; dn cht halogen thnh
hydrocarbon.
NaBH
4
l cht kh nh, c th kh trong mi trng nc, alcol,
tetrahydrofuran, ether... NaBH
4
kh chn lc aldehyd, ceton v halogenid
acid. Khi c hot ho bng cc clorid kim loi (AlCl
3
, ZnCl
2
, MgCl
2
...) n c
th kh acid, ester, anhydrid thnh alcol; amid, nitro, nitril thnh amin; C-
halogen thnh C-H.
100
2.1.7. Hydrazin (NH
2
-NH
2
)
Hydrazin l tc nhn kh ha mnh. N c th kh hp cht carbonyl
thnh hydrocarbon (phn ng Wolff-Kishner):
R CO R
1
NH
2
NH
2
KOH
R
C N N
H
R
1
R CH
2
R
1
+ N
2
H
2
O

Hu ht cc phn ng kh ha u dng hydrazin-hydrat, t dng
hydrazin khan, mc d kh nng kh ha ca hydrazin khan tt hn. Phn
ng thng tin hnh nhit cao (150-250
0
C), nn phi thc hin trong ni
chu p sut hoc dng dung mi c nhit si cao (ethylen-glycol, diethylen-
glycol, triethanol-amin).
2.1.8. Cc hp cht ca lu hunh
Natri sulfid (Na
2
S):
Thng dng loi k thut, hm lng 60-65%. Dng tinh th ngm 9
phn t nc, d ht m. Natri sulfid c th kh ho nhm nitro v nitrozo
thnh amin.
Trong tng hp paracetamol, ngi ta dng tc nhn kh ho ny
kh para nitro-phenol hoc para nitrozo-phenol thnh cc amin tng ng:
HO-C
6
H
4
-NO
2
+ Na
2
S.9H
2
O HO-C
6
H
4
-NH
2
+ NaOH + Na
2
S
2
O
3

HO-C
6
H
4
-NO + Na
2
S.9H
2
O HO-C
6
H
4
-NH
2
+ NaOH + Na
2
S
2
O
3

Trong mi trng kim, kh ho hp cht nitro l qu trnh phc tp,
qua nhiu hp cht trung gian nh: nitrozo, hydroxylamin, azoxy benzen, azo
benzen, hydrazo-benzen v cui cng thnh amin:
Ar NO
2 Ar NO
[H] [H]
Ar NHOH
Ar NH
2
[H]
Ar NO Ar NHOH Ar N N Ar
O
+
Ar NH NH Ar
[H]
[H]
Ar N N Ar

Nu kh ho 0
0
C th ch to thnh hydroxylamin, cn khi un nng th
thu c amin.
im c bit l Na
2
S c tc dng kh ho chn lc, vi dn xut
polinitro n ch kh nhm nitro v tr para so vi nhm th:
101

C H
3
N O
2
N O
2
CH
3
NO
2
NH
2
N a
2
S

Natri disulfid (Na
2
S
2
):
Kh bng natri disulfid khng to ra NaOH, nn cc polisulfid c chn
cho cc phn ng khng chu c kim mnh nh dng Na
2
S. Cc
polisulfid (Na
2
S
2
, Na
2
S
5
) c tc thy phn km Na
2
S vi ln, phn ng
kh ha cng nh nhng hn.
Cc tc nhn ny cng c dng kh cc nitro thm thnh amin:
Ar-NO
2
+ Na
2
S
2
+ H
2
O Ar-NH
2
+ Na
2
S
2
O
3

Ar-NO
2
+ Na
2
S
5
+ H
2
O Ar-NH
2
+ Na
2
S
2
O
3
+ 3S
Trong cc polisulfid, thng dng Na
2
S
2
v n khng gii phng S nn
khng gy tr ngi cho vic phn lp sn phm.
Natri sulfit v natri bisulfit (Na
2
SO
3
v NaHSO
3
):
Cc tc nhn ny tn ti dng tinh th khng mu hoc mu trng, d
b oxy ha thnh sulfat nn cn bo qun trong l kn, trnh tip xc lu vi
khng kh.
c dng kh cc dn cht nitro thnh amin:
Ar-NO
2
+ Na
2
SO
3
+ H
2
O Ar-NH
2
+ Na
2
SO
4
+ H
2
O
Cn ch khi dng tc nhn bisulfid, thnh phm amin s phn ng vi
n ta ra acid sulfamic.
Ar-NH
2
+ NaHSO
4
Ar-NH-SO
3
Na + H
2
O
2.2. Kh ha bng hydro phn t vi xc tc
iu kin thng, hydro phn t t c kh nng phn ng. Khi tip xc
vi xc tc, hydro c hot ha v c kh nng tham gia phn ng. V vy
phn ng hydro ho bao gi cng cn xc tc.
hot ho ca cc cht xc tc c th hin bng lng hydro hp
ph trn mt n v khi lng.
Hydro ho xc tc c th xy ra hai trng hp: ng th v d th.
Trng hp hydro ho xc tc d th c ng dng nhiu trong cng nghip.
102
2.2.1. Cc xc tc cho phn ng
Xc tc c th s dng ring hoc a ln mt cht mang. S dng cht
mang khng ch tit kim, m cht mang cn nh hng n hot tnh,
chn lc, tui th, nhy cm vi nhit v cc cht gy c xc tc...
Cc cht mang c din tch b mt nh gm thy tinh, oxyd nhm, bt,
bauxit. Loi c b mt ln gm caolanh, titan dioxyd, than hot, silicagel...
Thng thng c khong 5% cht xc tc c a ln cht mang. Ngoi
ra ngi ta c th thm cht lm tng hot tnh xc tc (promotor) hoc cht
c ch xc tc (inhibitor).
a. Cc xc tc kim loi
Niken (Ni):
L xc tc s dng ph bin nht, c th s dng mt mnh hoc a ln
cht mang.
Ni-Raney (niken xng) c dng nhiu v hot ha rt tt ca n.
Ni-Raney c iu ch nh sau:
Nung hn hp nhm v niken (t l 1:1) n 1200-1500
0
C thnh hp kim,
lm ngui v tn nh. Sau dng dung dch NaOH ho tan ht nhm trong
bt hp kim va iu ch c. Niken cn li dng bt ti xp. Ra nc
nhiu ln n ht kim. Ra li bng alcol v bo qun trong alcol tuyt i.
Trong qu trnh iu ch xc tc, kh hydro c gii phng, ch phng
chy n.
Mt gam xc tc ny c th hp ph 25-150 cm
3
kh hydro. Khi kh,
Ni-Raney t bc chy trong khng kh.
Xc tc Ni-Raney c th dng hydro ho cc alken, alcol, ceton, nitril
v cc hp cht thm.
Xc tc niken hoc niken trn cht mang (dng bt hoc ht), hot lc
thng thp hn Ni-Raney. Do phn ng hydro ho thng phi tin hnh
nhit cao hn.
ng (Cu):
Bt ng c s dng lm xc tc kh cc hp cht nitro thm thnh
amin (xc tc ny khng nh hng nhn thm).
C th s dng mt mnh hoc cng cht mang. iu ch bng cch kh
ho ng oxyd, hydroxyd hoc carbonat base vi kh hydro 150-300
0
C.
Hn hp Cu-Cromit l xc tc c gi tr thc t ln. Xc tc ny c th
hydro ho cc ester v amid. Cu-Cromit l hn hp dng bt mn ca ng kim
loi, CuO, CuCr
2
O
4
v Cu
2
Cr
2
O
4
. Phn ng hydro ho c tin hnh iu
kin p sut, nhit trn 100
0
C.
103
Cc kim loi qu:
Xc tc nhm ny gm c: platin, palladi, rutheni v rhodi. V gi thnh
cao nn thng trn vi cht mang (t st, silicagel, than hot...). Xc tc
cha khong 3-10% kim loi.
Platin xc tc hydro ho nhiu loi nhm chc mt cch d dng (tr
acid caboxylic, amid v ester). Platin oxyd, platin clorid cng c s
dng lm xc tc hydro ho.
Xc tc palladi v hot tnh cng ging nh platin nhng tnh chn
lc tt hn v c th thay i tu cch iu ch. C th s dng
kh ho hu ht cc nhm chc, nhng hot tnh yu hn platin khi
dng kh ceton mch thng v nhn thm. Phn ng hydro ho
thng tin hnh p sut thng.
Cc xc tc rutheni v rhodi khng tham gia qu trnh hydro phn,
nn khng s n ct loi nhm hydroxy hoc amin trn nhn thm.
Duy nht rutheni c th xc tc kh ho acid carboxylic. N c u im
l khng b c bi lu hunh.
b. Cc hp cht phi kim loi
Cc oxyd-kim loi (km, crom, vanadi) hoc sulfid-kim loi (molypden,
st, coban, niken) v boron-kim loi (st, niken, bc, crom...) t khi s dng
lm xc tc cho phn ng hydro ho.
Cc sulfid-kim loi khng b nhim c vi lu hunh v cc hp cht
ca lu hunh. Do c th s dng hydro ho hay hydro phn cc hp cht
cha lu hunh.
2.2.2. Cc yu t nh hng n phn ng hydro ho
Nhit :
Cng nh cc phn ng ho hc khc, khi nhit tng th tc phn
ng hydro ho cng tng, nhng phn ng khng mong mun dehydro ho
cng xut hin. Mt khc, nhit tng lm gim tnh chn lc ca xc tc.
Trong thc t cn phi tm mt nhit thch hp thp nht phn
ng c th thc hin c.
Thng thng, vi xc tc l cc kim loi qu (Pt, Pd), Ni-Raney phn
ng tin hnh t nhit phng n 150
0
C; vi Ni, Cu nhit t 150-
250
0
C. Cc kim loi khc v oxyd kim loi t 250-400
0
C.
p sut:
p sut lm tng tc phn ng, nh hng n cn bng ca phn
ng v tnh chn lc ca xc tc. C th nh sau:
104
+ Tng p sut phn ng l tng nng ca cht tham gia phn
ng, do lm tng tc phn ng.
+ p sut tng, cn bng phn ng chuyn v bn phi.
+ p sut tng lm gim tnh chn lc ca xc tc. V d: xc tc Ni-
Raney p sut kh quyn hydro ho acetylen thnh olefin. Khi
tng p sut ln 3 bar th ch thu c parafin.
2.2.3. K thut an ton trong phn ng hydro ho xc tc
Hydro l cht kh nh nht, n d b r r qua nhng ch m cc kh khc
khng th qua c. Do phi ch cn thn cc ch ni, h thng ng
dn, cc van.
Hydro to hn hp n vi khng kh khong nng rt rng (4,1-
74,2%). V vy trc khi dn kh hydro vo thit b phn ng, phi ui ht
khng kh trong thit b bng kh tr nhiu ln.
3. ng dng ca Phn ng Kh ho
3.1. Kh ho lin kt carbon-carbon khng no
Kh ho olefin:
C th kh ho lin kt C=C vi natri kim loi trong alcol, natri kim loi
trong amin, hydro ho xc tc (Pd, Pt, Ni-Raney) nhit phng v p sut
kh quyn. Mch carbon cng di, nhiu mch nhnh cng kh kh. Cis-olefin
d hydro ho hn trans-olefin.
Qu trnh kh ho ni i to ra ng phn khng gian. V d khi hydro
ho acid dimethyl-maleic, xc tc paladi trn cht mang than hot (Pd/C) hoc
niken to thnh dimethyl succinic vi ng phn mezo chim 86% v racemic
l 14%:
COOH
C
H
3
C
C
H
3
C COOH
H
2
/ Pd/C
CH
3
CH
3
COOH
C
C
COOH
H
H
H
CH
3
COOH
C
C
COOH
H
H
3
C
+
(mezo 86
%) (racemic 14 %)

Khng ch xc tc m dung mi v mi trng phn ng cng nh hng
n t l cc ng phn.
Kh ho acetylen:
Acetylen c th hydro ho d dng thnh parafin, cng c th kh chn
lc thnh olefin bng tc nhn ho hc hay hydro ho xc tc.
105
V d: Hydro ho acetylen thnh ethan vi xc tc Ni-Raney. Nhng khi
xc tc l Ni hoc Pd trn cht mang t st th sn phm ch yu l etylen.
Hydro ho lin kt CC cui mch carbon d hn gia mch.
Khi hydro ho ni ba thnh olefin th thu c hn hp cis-trans. V d:

Hydro ho nhn thm:
Kh ho nhn thm kh hn cc hp cht khng no mch thng. Bng
tc nhn kh ho hc khng th no ho ton b nhn thm. Kh ho benzen
bng natri trong amoniac to sn phm chnh l cyclohexa-1,4-dien. Sn
phm ph cyclohexa-1,3-dien sau b kh nhanh thnh cyclohexen.

Nhm ht in t trn nhn lm tng kh nng kh ho, nhm y in
t th ngc li lm gim kh nng ny.
Hydro ho xc tc benzen v dn cht thu c cyclohexan v cc dn
cht tng ng. Phn ng cn p sut v nhit cao. Tuy nhin, nhit
khng c vt qu gii hn, v khi phn ng dehydro ho ng thi xy ra.
Cc aldehyd, ceton, amin thm, nu mun hydro ho nhn thm cn bo
v nhm carbonyl (to hydrazon hoc base-schiff). Sau khi hydro ho th thu
phn loi cc nhm bo v.
Cc hp cht thm a vng d hydro ho hn benzen. Kh nng phn
ng theo th t sau: benzen < naphtalen < phenantren.
3.2. Kh ho hp cht nitro
y l phng php quan trng nht iu ch cc amin, c bit l
cc amin thm bc nht. Tu tc nhn v mi trng kh, c th thu c sn
phm c mc kh ho khc nhau.
3.2.1. Kh ho vi Fe trong mi trng acid
Phn ng kh hp cht nitro thnh amino trong mi trng nc-acid
(phn ng Bechamp) xy ra theo c ch nh sau:
C
C
H R
H R'
C
C
R
R'
C
C
R H
H R'
106
Trong mi trng acid, nhm nitro ly hai in t ca st, ng thi ly
thm hai proton v loi i mt phn t nc to thnh nitrozo:
R N
O
O
+ H
+
R N
OH
O
R N O
-
H
2
O
+ H
+
2
e

Sau cng tng t, t nitrozo to ra hydroxylamin:
R N O
R NH OH
+ 2H
+
2
e

Cui cng l kh ho hydroxylamin thnh amin:
R NH OH R NH O
H
H
H
+
2
e
-
H
2
O
R NH
H
+
R NH
2

Phn ng xy ra ba pha: pha hu c (hp cht nitro), st v nc acid.
Do tc phn ng ph thuc rt ln vo kch thc bt st v tc
khuy trn. i vi cc cht kh ho tan trong nc, cn s dng thm dung
mi tr tan (ethanol, methanol).
3.2.2. Kh ho vi kim loi (Fe, Zn) trong mi trng kim
Ch yu dng kim loi km, mc d km c gi thnh t hn. Qu trnh
kh ho xy ra nh sau:
Trc ht nitro b kh thnh nitrozo, sau thnh hydroxylamin.
2
Ar NO
2
+ Zn
NaOH
Ar NO + ZnO
2
Ar NO + Zn + H
2
O
NaOH
Ar NHOH + ZnO

Di tc dng ca mi trng kim, nitrozo phn ng vi hydroxylamin
to ra azoxy benzen:
Ar NO +
H
2
O
NaOH
Ar NHOH + Ar N N Ar
O

Sau azoxy benzen b kh thnh azo (Ar-N=N-Ar) v hydrazobenzen
(Ar-NH-NH-Ar).
Hydrazobenzen c dng sn xut cc dn cht diamin-diphenyl
bng phn ng chuyn v trong mi trng acid:
NH NH
H
H
2
N NH
2

107
3.2.3. Kh ho bng cc hp cht ca lu hunh
Cc cht kh lu hunh (sulfid, disulfid, hydrosulfid) c th kh hp
cht nitro thnh amin. Natri v amoni sulfid c s dng kh chn lc cc
hp cht polinitro thnh cc dn xut amin-nitro. V d, vi mt ng lng
cht kh Na
2
S c th kh ho m-dinitrobenzen thnh m-nitro-anilin:
NO
2
NO
2
Na
2
S
NH
2
NO
2

Nu dng tha Na
2
S th n s kh tt c cc nhm -NO
2
thnh -NH
2
.
Cc sulfid cn c dng kh ho cc hp cht nitro-phenol, halogen-
nitrobenzen, nitro-azobenzen v iu ch amino-antraquinon.
3.2.4. Kh ho bng hydro phn t c xc tc
y l phng php ph bin nht iu ch cc amin trong cng
nghip. Phng php ny to ra anilin c tinh khit cao hn v loi c
nhng kh khn khi s dng phng php Bechamp. Hydro ho nitrobenzen
c th tin hnh c pha hi ln pha lng, xc tc l niken v ng.
Khi hydro ho nitrobenzen trong acid sulfuric xc tc Pt hoc Co, c mt
molipden-sulfid to thnh N-phenyl-hydroxylamin, trong mi trng acid
sulfuric cht ny chuyn v thnh p-aminophenol. y l nguyn liu tng hp
paracetamol:

NO2
[H ]
NHOH
H
2
SO
4
NH2
OH

Hydro ho cc hp cht nitro thng thc hin p sut kh quyn, nhit
150-300
0
C.
3.3. Kh ho cc aldehyd v ceton
Tu tc nhn v iu kin kh c th thu c alcol, kh v dimer ha
thnh pinacol hoc kh ti hydrocarbon.
Kh aldehyd thnh alcol c th s dng hn hng natri, hn hng nhm
hay kim loi trong amoniac. Ceton mch thng vi kim loi kim trong alcol
c th kh thnh alcol bc hai.
108
Tc nhn kh nhm carbonyl c hiu nht l hydrid kim loi. LiAlH
4
l
cht kh mnh, ngoi nhm C=O ca hp cht carbonyl n cn kh c
nhiu nhm chc khc. NaBH
4
l cht kh nh nhng, n c th kh chn lc
nhm C=O thnh alcol.
V d: Kh ho ceton trong mi trng kim hoc trung tnh vi hn
hng (nhm hoc magnesi), sn phm l pinacol:
CH
3
C
CH
3
O +
CH
3
C
CH
3
O
Mg/Hg
C C HO
CH
3
CH
3
OH
CH
3
CH
3

Cc aldehyd thm c th hydro ho thnh alcol tng ng vi xc tc l
Ni-Raney nhit phng v p sut kh quyn.
3.4. Kh ho acid carboxylic, ester, amid
Kh ho acid carboxylic thnh alcol thng dng cc hydrid kim loi
(LiAlH
4
, NaBH
4
) hoc alcoxyhydrid kim loi [LiAlH(t.BuO)
3
]. Trong hay dng
nht l LiAlH
4
trong tetrahydrofuran hoc ether. Acid carboxylic rt t tan trong
cc dung mi trn, nn tt nht l chuyn thnh ester trc khi kh ho.
Trong cng nghip, kh acid carboxylic thnh alcol, ngi ta thng
dng phng php hydro ho vi xc tc Cu-Cromid 250-400
0
C, p sut 200-
300 bar. kh ho chn lc cc ester, hay dng LiAlH
4
hot ho vi AlCl
3
.
Tc nhn LiAlH
4
-AlCl
3
ch kh nhm ester thnh alcol, khng nh hng n
cc nhm halogen, nitro hoc ni kp trong phn t cht cn kh.
Hydro ho cc ester d dng hn hydro ho cc acid carboxylic (xc tc
Cu-Cromit).
V d: Hydro ho ester ca acid adipic, xc tc Cu-Cromit, 250
0
C, p
sut 120-200 bar, thu c 1,6-hexandiol vi hiu sut 85-90%:
EtOOC-(CH
2
)
4
-COOEt HOCH
2
-(CH
2
)
4
-CH
2
OH
C th kh ho cc amid, lactam thnh amin tng ng hoc amid thnh
aldehyd, sau thnh alcol bc nht bng hydrid kim loi (LiAlH
4
).
3.5. Kh ho cc hp cht cha nit khng no
Nhm hp cht cha nit khng no gm nhiu loi: nitril, izonitril,
hydrazon, oxim, imin, azoxy, azo. Trong vic kh ho nhm nitril thnh
amin c ngha thc t nht.
Tc nhn kh nitril thch hp l hydro phn t v hydrid kim loi (LiAlH
4
).
Hydro ho nitril vi xc tc, thu c hn hp amin bc mt v bc hai:
109
R-CN
H
2
R-CH=NH
H
2
R-CH
2
-NH
2

R-CH=NH + R-CH
2
-NH
2
RCH
2
NH-CH-R R-CH
2
-N=CH-R+NH
3

H
2

R-CH
2
-NH-CH
2
-R
C th hn ch phn ng to thnh amin bc hai bng cch hydro ho
trong amoniac.
Trong cng nghip dc phm, kh ho nitril thnh amin bng LiAlH
4

hoc B
2
H
6
c s dng nhiu.
4. Hydro phn
Hydro phn l phn ng ct cc lin kt carbon-carbon, carbon-oxy,
carbon-nit v carbon-halogen nh tc dng ca hydro. Phn ng c th thc
hin bng tc nhn kh ho hc hoc hydro ho xc tc.
Cc tc nhn kh ho hc hay s dng l kim loi kim-alcol, kim loi-
amoniac, LiAlH
4
. Cc xc tc hydro ho gm Pd, Ni-Raney.
Hydro phn lin kt C-C t gp trong thc t. Hydro phn C-O gp khi
kh ho cc ester, alcol, ether, epoxyd, acetal.
Cc alcol khi hydro phn thng dng tc nhn LiAlH
4
-AlCl
3
.
Vi cc ether thng kh ct lin kt carbon-oxy.
Hydro phn cc benzyl-ether trong ho hc hydrat carbon nhm loi
nhm bo v benzyl c th dng cc tc nhn: natri trong alcol, hn hp
LiAlH
4
-AlCl
3
hoc hydro ho vi xc tc palladi.
Hydro phn lin kt C-X d hay kh ph thuc bn cht ca halogen, cu
trc ca phn t v tc nhn s dng. Alkyl halogenid c kh nng phn ng
yu hn benzyl-, aryl-, allyl-, v vinyl-halogenid. Tc nhn hay dng l kim
loi-amoniac. Ngoi ra, c th hydro phn lin kt carbon-halogen bng phn
ng hydro ho vi xc tc Pd.
5. Mt s v d
5.1. iu ch anilin
Anilin l nguyn liu quan trng ca cng ngh phm mu v tng hp
Ha dc. Nhiu thuc c tng hp t nguyn liu ny nh: Sulfamid,
khng histamin, thuc tr giun sn...Trc y anilin c sn xut theo
phng php Bechamp. Hin nay, trong cng nghip n c sn xut bng
con ng hydro ha nitro-benzen.
110
Phng trnh phn ng:
C
6
H
5
-NO
2
+ 3H
2
C
6
H
5
NH
2
+ 2H
2
O
Nitrobenzen c ho hi ri dn vo ct phn ng cha xc tc ng-
amonium-nitrat. Kh hydro c dn vo cng chiu vi hi nitrobenzen. Phn
ng c thc hin 200
0
C.
Hn hp hi sau phn ng c ngng t, yn cho tch pha. Pha trn
l nc cha 4% anilin ho tan trong nitrobenzen, chit thu hi a li
phn ng. Pha di l anilin c cha 0,5% nitrobenzen v 5% nc, ct phn
on thu anilin.
C 1 kg xc tc ng-amonium-nitrat c th s dng iu ch c
khong 1500 kg anilin.
5.2. Sn xut sorbit t glucose
Sorbit l hp cht trung gian trong qu trnh tng hp vitamin C. Qu
trnh tm tt nh sau:

d-Sorbit d-Glucose
H
2
/ Ni [O]
l-Sorbose
Aceton
Diaceton-sorbose
O
2
/ N a O H
Diaceton-2-ceto-l-gulonic acid
enol ha
Vitamin C

Phng trnh kh ho glucose thnh sorbit:
CH
2
OH
CH
C
C
CH
C
HO
HO
OH
HO
O
H
H
H
H
2
/
Ni-Raney
CH
2
OH
CH
C
C
CH
HO
HO
OH
HO
H
H
CH
2
OH

Cch tin hnh hydro ho nh sau:
Thit b phn ng l autoclav bng thp, c hai v, my khuy m neo,
van thot kh, ng nhit k
Dung dch glucose nng 50-55% c cho vo autoclav, iu chnh n
pH = 8,3-8,4. Tip cho Ni-Raney va iu ch (khong 5% so vi trng
lng glucose) vo ni phn ng. ui ht khng kh trong ni v nn kh H
2

(hm lng 99,5%) vo n khi p sut t 80 at. Cho hi nng vo v ni v
a nhit ln 135
0
C. Lun gi p sut trong ni l 80 at bng cch b sung
111
H
2
. Thi gian phn ng khong 40-60 pht. Ngng un nng v lm lnh v
ni n nhit 75-80
0
C. M van cho thot H
2
tha, gim p sut cn 5 at.
y khi phn ng ra ngoi qua phin lc. Thu hi cht xc tc v bo qun
di lp nc ct. Dung dch sorbit c a qua ct trao i ion Wolfatit
loi Fe, Cu, Ni... Sau ct chn khng 650 mmHg n khi ch cn m
5%. Cn c ho tan trong cn 96
0
78
0
C. Kt tinh (khuy) 18-20
0
C. Lc
ly tinh th, ra bng cn, sy kh 35-40
0
C.
T lng gi
1. Khi nim v mc ch ca qu trnh kh ho trong ho hc hu c v
tng hp ho dc.
2. Trnh by cc loi tc nhn ca phn ng kh ho v c ch kh ca
chng.
3. Nu cc phn ng kh ho v phng php hydro phn cc nhm hp
cht c bn.
4. Trnh by phng php sn xut anilin t nitrobenzen v sorbit t
glucose.

112
Chng 11
Diazo ho
Mc tiu
1. Khi nim v phn ng diazo ho v cc c im ca mui diazoni.
2. Cc thuyt v c ch ca phn ng diazo ho.
3. Cc yu t nh hng n qu trnh diazo ho v nguyn tc tin hnh
phn ng.
4. Cc phn ng ca mui diazoni.
1. i cng
Diazo ho l qu trnh ho hc to hp cht diazo (-N
+
N) t amin thm
bc nht v acid nitr. Phng trnh phn ng nh sau:
Ar-NH
2
+ NaNO
2
+ 2HX Ar [N
+
N] X
-
+ 2H
2
O + NaX
Trong : Ar: aryl
X: -Cl, -Br, -NO
2
, -HSO
4
(ty loi acid s dng).
Phn ng ny c P.Griss pht hin vo nm 1858. Cu to ca cation
diazoni l s tc dng tng h ca hai dng sau y:
Ar-N
(+)
N Ar-N=N
(+)
Qu trnh diazo ho c ngha quan trng trong tng hp Ha dc v n
to ra hp cht c kh nng phn ng cao. N l qu trnh ho hc trung gian
chuyn nhm -NH
2
ca amin thm thnh cc nhm -H, -OH, -Cl, -I, -Br, -F,
-CN, -NO
2
, -SH, -AsO
3
H
2

Diazo ho l phn ng ch yu c dng trong cng nghip sn xut cc
phm mu azoic. Hng nm ngi ta sn xut hng trm ngn tn phm mu
azoic t cc hp cht diazo. Qu trnh diazo ho cng l mt trong nhng qu
trnh c s dng nhiu nht trong tng hp hu c, ho dc.
113
2. c im ca mui diazoni
Mui diazoni c cc c im sau:
Tn ti dng bt t tan trong nc.
L hp cht khng bn, c tnh phn ng rt mnh (dng bt kh c
th gy n do phn hu gii phng N
2
). Cn bo qun di lp nc
acid. Thng lm xong th em dng lun do khng bo qun c lu.
Di tc dng ca nhit , m mui diazoni phn hu thnh phenol:
[Ar-N
(+)
N]Cl
-
+ H
2
O Ar-OH + N
2
+ HCl
Trong mi trng kim mui diazoni chuyn thnh diazotat hai
dng syn v anti:
Ar N N OH + NaOH
Ar N
N NaO
Ar N
N ONa
+ + H
2
O

Syn-diazotat km bn hn, d b thu phn. Dng ny c dng trong
phn ng ngng t, s dng trong cng ngh phm nhum. nhit 100-
105
0
C syn-diazotat chuyn thnh dng anti-diazotat l hp cht bn vng,
khng tham gia phn ng ngng t.
3. C ch ca phn ng diazo ho
C nhiu tc gi a ra gi thit v c ch phn ng diazo ho, ng
ch l nhng c ch sau:
Bamberger (1894):
Tc gi ny cho rng phn ng diazo ho thc cht l qu trnh nitrozo
ha N-amin bng acid nitr c proton ha.
Tc nhn nitrozo ha khi diazo ho trong acid hydrocloric gm c:
nitrozil-clorid, dinitrogen-trioxyd. Chng c to thnh t nitrozo-acidium
theo cc phn ng sau:
HO-NO + H
(+)
H
2
O
(+)
-NO
H
2
O
(+)
-NO + Cl
(-)
ON-Cl + H
2
O
H
2
O
(+)
-NO + NO
2
(-)
ON-NO
2
+ H
2
O
Cc tc nhn ny u c th to thnh cation nitrozil (NO
(+)
) tham gia
phn ng vi thnh phn amin theo c ch i in t.
S qu trnh phn ng diazo ha c trnh by hnh 11.1:
114
Ar N N
_
H
2
O
2 pH<
Ar NH
2 Ar NH
2
NO
2
Cl
NO Cl
NO NO
2
Ar NH
2
NO
H
2
O NO
H
HO NO
Cl
(Nitroso-arylamin)
Ar NH NO
_
H
(Nitrosamin)
Ar N N OH
Ar N N X
(Diazoni salt)
(Diazoni hydroxyd)
Ch
nh
HX

Hnh 11.1. S qu trnh phn ng diazo ho
Ingold (1958):
Khi nghin cu ng hc ca phn ng diazo ha, tc gi cho rng phn
ng ny cng bt u bng s proton ha acid nitr. Sau nitrozo ha amin
bng phn ng th i in t ca ion nitrozo-acidium hoc nitrozil. y l giai
on chm quyt nh tc phn ng. Tip theo l ng phn ha hp cht
nitrozo v loi nhm -OH ca diazo hydroxyd trong mi trng acid, to thnh
mui diazo:
HO N O
+ H H
2
O N O N O
+ H
2
O

Ar N NO
H
H
H
Ar N N
H
O Ar N
H
H
+ N O
ch
Ar N N OH
-
H
-
Ar N N
+ H
2
O

115
4. Cc yu t nh hng n qu trnh diazo ho
4.1. nh hng ca pH mi trng
Phn ng diazo ho bao gi cng thc hin trong mi trng acid. Mi
trng ti u diazo ho thng pH =1-3.
Acid trong phn ng diazo ho gi vai tr quan trng v:
Ho tan amin di dng mui tham gia phn ng.
Gii phng HNO
2
t natri nitrit cung cp cho phn ng.
Hn ch phn ng ngng t gia mui diazoni vi amin t do to
thnh hp cht diazo-amin khng tan (phn ng t ngng t ny ch
xy ra trong mi trng acid yu v trung tnh).
Ar N N Cl + H
2
N Ar Ar N N Ar + HCl

Mi trng acid lm tng bn vng ca mui diazoni.
Trong nhng trng hp khng th dng nng acid v c qu ln th
phi dng phng php diazo ho ngc: Lm lnh hn hp amin-natri
nitrit trc, sau cho dn hn hp ny vo dung dch HCl lm lnh. Nh
vy trong mi trng phn ng khng tn ti amin t do, phn ng t ngng
t s khng xy ra.
4.2. nh hng ca nng nguyn liu
Thng s dng nng amin trong phn ng t 0,2-2,0N. Nng
long lm phn ng xy ra chm, nng c s kh khng ch nhit phn
ng, v y l phn ng to nhit mnh.
Lng NaNO
2
thng s dng khng cn tha. V nu tha s lm gim
bn ca mui diazoni v gy ra phn ng ph (oxy ho hay a thm nhm
nitro vo sn phm). Kt thc phn ng nu lng acid nitr cn tha cn
phi phn hu bng ur hoc acid sulfamic.
O C
NH
2
NH
2
+ HNO
2
CO
2
+ N
2
+ H
2
O
3 2 2
O
2
S
OH
NH
2
+ HNO
2
H
2
SO
4
+ N
2
+ H
2
O

116
4.3. nh hng ca nhit
Trong phn ng diazo ho, nhit l yu t quyt nh n hiu sut
sn phm. Thng thng phn ng tin hnh nhit khong 0-5
0
C. nhit
ny HNO
2
t b phn hu, mt khc mui diazoni cng bn vng hn. V
nh chng ta bit, diazoni l hp cht khng bn, rt d b phn hu bi
nhit v mi trng. Rt t trng hp diazo ho nhit cao hn 15
0
C.
m bo nhit thp, ngi ta phi lm lnh bng cch cho nc
trc tip vo hn hp phn ng, mt khc phi duy tr lm lnh bn ngoi
lin tc.
4.4. nh hng ca cu trc phn t amin
Cc nhm th trn nhn c nh hng mnh n tnh base, tan ca
amin thm. Do c nh hng n vic thc hin phn ng diazo ho. Cc
amin thm c nhm ht in t trn nhn rt kh diazo ha.
Cc diamin thm khi diazo ho khng xy ra ng thi v nhm diazo to
thnh ht in t, gy kh khn cho vic diazo ho nhm amin th hai.
Cc ng phn ortho-diamin khi diazo ho to ra sn phm ng vng do
phn ng t ngng t:
NH
2
NH
2
N
2
Cl
NH
2
N
N
N
H
HNO
2 HCl

Mun trnh hin tng t ngng t phi bo v mt nhm amin bng
cch acyl ho trc khi tin hnh diazo ho.
5. Nguyn tc tin hnh diazo ho
Qu trnh diazo ho c tin hnh theo trnh t sau:
Trc ht cho nc vo ni phn ng, tip cho acid v c, ri n
amin. Khuy cho tan ht, cho nc trc tip vo lm lnh khi
phn ng n 0
0
C.
Sau , va khuy va cho dn dung dch natri nitrit vo (thng
dng dung dch 30-35%) sao cho nhit < 5
0
C. Khi cho c 2/3
lng natri nitrit, phi lun kim tra pH ca phn ng (pH=1-3)
v lng NaNO
2
tha. Phn ng kt thc khi mu th c phn ng
dng tnh vi giy tm tinh bt ln KI. Hn hp c lc, dch lc
c dng ngay cho phn ng tip theo.
117
6. Cc phn ng ca mui diazoni
Cc mui diazoni c kh nng phn ng rt ln. N c dng lm trung
gian trong sn xut Ha dc v nhiu ngnh ha hc khc. Cc phn ng ca
mui diazoni c chia thnh hai nhm:
6.1. Cc phn ng c gii phng nit
6.1.1. Thu phn nhm diazoni thnh -OH
Phn ng thy phn to ra phenol thc hin trong mi trng acid, xc
tc l CuSO
4
, Cu
2
Cl
2
:
[Ar-N
(+)
N] SO
4
H
(-)
+ H
2
O Ar-OH + N
2
+ H
2
SO
4

6.1.2. Th nhm diazoni bng nhm -OR v H
Mui diazoni tc dng vi alcol nhit trn 5
0
C, qu trnh phn ng ng
thi xy ra theo hai hng: To ra alcoxybenzen v kh diazo thnh benzen:
[Ar-N
(+)
N]SO
4
H
(-)
+ R-CH
2
OH Ar-OCH
2
R + N
2
+ H
2
SO
4
[Ar-N
(+)
N]SO
4
H
(-)
+ R-CH
2
OH Ar-H + N
2
+ H
2
SO
4
+ R-CHO
Phn ng theo hng no ph thuc vo nhm th trn thm ca hp
cht diazo v ln ca gc R trong alcol. Cc alcol n gin th kh nng to
dn cht alcoxy cng cao.
Phn ng ny c ngha quan trng trong vic nh hng cc nhm th.
V d iu ch 1,3,5 tribromobenzen:

N H
2 NH
2
Br
Br
Br
3B r
2
B r
Br
Br

6.1.3. Th nhm diazoni bng halogen v nitril
y l phng php iu ch cc dn xut iod v fluor thm.
+
KI Ar I N
2
KHSO
4
+ +
H
2
O/t
0

Ar N N SO
4
H
Ar N N BF
4 Ar F N
2
BF
3
+ +
t
0

118
Phn ng th diazoni bng -Cl, -Br hoc -CN thu c hiu sut cao nu
c xc tc Cu
2
Cl
2
, Cu
2
Br
2
, hoc Cu
2
(CN)
2
tng ng (phn ng Sandmeyer).
Ar Br N
2
+
Br Ar N N
Cu
2
Br
2
/ t
0

Ar CN N
2
+
CN Ar N N
Cu
2
(CN)
2
/ t
0

Phn ng ny c ngha khi mun a halogen vo nhn thm ti cc v
tr m khng th halogen ho trc tip c.
6.1.4. Th nhm diazo bng -NO
2
, -SH, AsO
3
H
2

Khi mun a nhm nitro vo v tr cn thit m khng th nitro ho
trc tip c (v d iu ch para-dinitrobenzen t meta-nitroanilin), ngi
ta dng phng php qua trung gian diazo:
/Cu/H
2
O
Ar N N BF
4
Ar NO
2
N
2
NaBF
4
+ +
t
0
+ NaNO
2

Phn ng th nhm -SH v iu ch cc hp cht hu c cha asen t
mui diazo theo cc phng trnh sau:
Ar SH +
Cl Ar N N
t
0
+ KSH N
2
+ KCl
Ar N N SO
4
H + Na
3
AsO
3
t
0
Ar AsO
3
Na + N
2
+ Na
2
SO
4

Cc hp cht hu c cha asen trc y c dng tr l, giang mai nh
Stovason, CarbasonHin nay do c tnh mnh nn khng cn c s dng.
6.2. Cc phn ng khng gii phng nit
6.2.1. Phn ng kh to arylhydrazin
Kh ho nhm diazoni vi tc nhn kh SnCl
2
trong acid HCl to thnh
hydrazin.
Ar NH NH
2
.
Cl Ar N N + SnCl
2
+
HCl
HCl SnCl
4

Trong cng nghip, ngi ta thng dng phng php ca E. Fischer (1877):
Ar N N SO
3
Na

Cl Ar N N
HCl/H
2
O
Na
2
SO
4 Zn/H
2
O
Ar NH NH SO
3
Na
Ar NH NH
2
.HCl

119
Phenylhydrazin l nguyn liu sn xut thuc h nhit gim au nhm
pyrazolon.
6.2.2. Phn ng ngng t
Phn ng gia mui diazoni vi amin thm hay phenol to thnh hp
cht azoic:
Ar N N X + Y Ar N N Y + H
2
O
X=Cl; Br; SO
4
H
Y=OH, NH
2
, NHR, NR
2

Phn ng ny thuc loi th i in t S
E
. S ngng t thng xy ra
v tr para so vi nhm amin hoc -OH.
Phn ng ngng t vi cc dn cht ca phenol pH = 7-9, vi cc dn
cht amin pH = 4-7.
Phn ng ny dng iu ch cc p-aminophenol hoc p-diamin thm
khi kh ho dn cht azobenzen:
N N C
6
H
5
NH
2 X
+
H
2
N X
X=OH,NH
2
,N(CH
3
)
2

7. Thit b v an ton lao ng
V cc ion kim loi xc tc cho qu trnh phn hu mui diazoni, nn ngi
ta khng ch to thit b phn ng bng kim loi hoc hp kim, m thng lm
bng g. Thit b phn ng l nhng thng g, cnh khuy cng lm bng g
hoc bng nha. Nu lm bng kim loi th c bc bng cht do.
Mui diazoni thng rt nhy cm vi nh sng, cho nn qu trnh sn
xut cn trnh tc dng ca nh sng (cc knh ca s nh xng phi qut
bng sn , cc qu trnh lc ht trnh nh sng, ...)
Phn ng diazo ho thng gii phng NO, NO
2
l nhng kh rt c.
Ni sn xut phi c h thng thng kh tt, phi hp th ht kh gii phng
trnh ng c cho ngi lm vic. Phi c phng tin bo h lao ng
v mt n phng c.

120
8. V d
Tng hp thuc h nhit gim au phenazol:
Phenazon c tng hp theo phng php ca Knorr:
Ngng t acetoacetat ethyl vi phenylhydrazin thu c dn cht
pyrazolon. Sau methyl ha hp cht ny vi methyl-iodid hoc dimethyl-
sulfat thu c phenazon.
Nguyn liu phenylhydrazin c iu ch t anilin qua trung gian diazo
theo s phn ng sau:
C
6
H
5
NH
2
C
6
H
5
N N Cl
-
+ NaNO
2
/ HCl
C
6
H
5
NH NH
2
NaHSO
3
Na
2
SO
3

N
N
O
C
6
H
5
C H
3
H
N
N
O
C
6
H
5
CH
3
CH
3
c (CH 3 ) 3 SO4 ho
( Ph e na zo n)
O
C
O C
2
H
5
O
C H
3
+
C
6
H
5
NH
NH
2
N
N O
C
6
H
5
CH
3
C 2 H5O H + H2O
( ) -
CH3 I

T lng gi
1. Khi nim v phn ng diazo ho v c im ca mui diazoni?
2. C ch phn ng diazo ho?
3. Nu cc yu t nh hng n qu trnh diazo ho v nguyn tc tin
hnh qu trnh diazo ho.
4. Trnh by cc phn ng in hnh ca mui diazo?
5. Nu cc loi vt liu c th s dng lm thit b cho phn ng diazo
ho v cc ch v an ton lao ng trong sn xut.
121
Chng 12
Phn ng ngng t
Mc tiu
1. Khi nim v phn ng ngng t.
2. Cc loi phn ng ngng t v v d ng dng trong tng hp Ha dc.
1. i cng
Phn ng ngng t l phn ng to nn hp cht mi bng cch loi ra
t mt hay nhiu hp cht ban u cc nguyn t hot ng hoc cc nhm
chc di dng cc sn phm ph nh H
2
O, HCl, C
2
H
5
OH, NH
3
... Nh vy
chng gm rt nhiu cc loi phn ng khc nhau nh alkyl ho, acyl ho,
ester hoTrong K thut tng hp Ho dc, thu hp li khi nim trn
v lm r hn mc ch ca qu trnh ngng t, ngi ta a ra nh ngha
v phn ng ngng t nh sau:
Phn ng ngng t l phn ng to ra lin kt mi gia hai nguyn t
carbon hoc to ra hp cht d vng t hai carbon khng cnh nhau trong
cng mt phn t hoc t hai phn t khc nhau.
Nh vy, qu trnh ngng t bao gi cng lm cho b khung carbon ca
phn t tr nn phc tp hn hoc to ra mt d vng. Cc qu trnh to lin
kt C-O, C-N, C-S, m khng to d vng th khng c coi l phn ng
ngng t.
Tuy nhin, phn ng to base Shif t aldehyd v ceton do tnh cht c
bit nhy v s ng dng nhiu trong tng hp Ho dc m ngi ta vn coi
y l phn ng ngng t.
Nhiu phn ng ngng t cn s dng tc nhn thc hin qu trnh.
Cc tc nhn ny c lc ng vai tr nh cht xc tc cho phn ng, c lc l
mt cht kha hoc loi cc sn phm ph to thnh. Trong thc t ngi
ta thng dng cc tc nhn sau:
Tc nhn loi nc: H
2
SO
4
, HCl, P
2
O
5
, POCl
3
, kali hoc natri-acetat,
SnCl
4
.
122

Tc nhn loi HCl: AlCl
3
, ZnCl
2
, pyridin, Na
2
CO
3
, NaOH, hn hng
Na.
Tc nhn loi alcol: Na kim loi, natri-acetat , natri-ethylat.
Tc nhn loi NH
3
: ZnCl
2
, acid proton.
Qu trnh ngng t xy ra trong cng 1 phn t c gi l ngng t ni
phn t, hoc gia cc phn t vi nhau ta c ngng t ngoi phn t.
Ngng t l phn ng rt quan trng trong tng hp cc thuc Ha dc
v trong tng hp nhiu hp cht trung gian ca Ha hc hu c. Phn ng
ny c ng dng nhiu tng hp nhn pyrazolon ca thuc h nhit
anagin; nhn imidazol ca cc thuc metronidazol, tinidazol; nhn quinolin v
isoquinolin ca cc thuc st rt, l v chng co tht, ...
2. Cc loi phn ng ngng t
Da vo cc sn phm ph to thnh trong phn ng, ngi ta phn loi
qu trnh ngng t nh sau:
Ngng t loi nc
Ngng t loi HCl
Ngng t loi alcol
Ngng t loi NH
3

2.1. Ngng t loi nc
2.1.1. Cc phn ng in hnh
a. Phn ng gia aldehyd, ceton vi amin to base Shif
y l phn ng c trng ca nhm carbonyl. Phn ng ny c th s
dng bo v hoc phn lp cc aldehyd v ceton trong cc qu trnh tng
hp ha hc. Phng trnh phn ng nh sau:
Z= R , Ar, NHCONH
2
, NHCSNH
2
, NHPh
xt= acid proton
C N Z
H
2
O
C
OH
NHZ
xt
NH
2
Z + C O
-

b. Phn ng ca nhm carbonyl vi nhm methylen linh ng
Phn ng gm 2 giai on: cng hp v ngng t alcol. c dng ni
di mch carbon ca cc hp cht hu c.
123

C O
+ H
2
C
X
Z
x t
C
OH
CH
Z
X
H2O
C C
X
Z
-
X,Z = COO R , C N , C O
Xc tc
= natri al c ol a t

Trong tng hp Ha dc, qu trnh ngng t to acid cinamic, cinemal
(phn ng Perkin) c ng dng nhiu:
C
6
H
5
CHO + Ac
2
O
NaOC
2
H
5
-
H
2
O
C
6
H
5
CH CH COOH + AcOH + H
2
O
C
6
H
5
CHO + CH
3
CHO C
6
H
5
CH CH CHO (Cinemal)

c. Ngng t formaldehyd vi phenol to thnh nha bakelit
Phn ng ngng t phenol v formaldehyd c s dng trong cng ngh
sn xut nha bakelit. y l loi cht do c s dng rng ri ch to
nhiu vt dng phc v i sng v cht cch in.
OH
+ HCHO
OH
CH
2
OH
OH
CH
2
OH
+
OH
CH
2
HO
CH
2
OH
CH
2

d. Tng hp quinolin v dn cht bng phn ng ng vng Skraupp
Nhn quinolin v dn cht 8-oxyquinolin l cc nguyn liu quan trng
tng hp cc thuc st rt v thuc cha l.
Phn ng to d vng quinolin c thc hin t anilin v acrolein theo
phng php ng vng Skraupp qua hai giai on: u tin l phn ng ca
anilin vi acrolein, sau l ngng t loi nc vi tc nhn l acid sulfuric
thu c dn cht 1,2-dihydroquinolin.

124
S phn ng nh sau:
NH
2
N
CHO
CH
CH
2
C
N
O
H
H
H
H
-
H
2
O
+
H
2
SO
4

Dehydro ha 1,2-dihydroquinolin thu c quinolin tng ng.
8- oxyquinolin cng c tng hp tng t phng php trn, t ortho
amino-phenol v acrolein.
2.1.2. Mt s v d
Sn xut phenolphthalein:

CO
O
C
O H
OH
H
O H
H
2
S O
4

CO
O
C
OH
O H
c

Ho tan anhydrid phthalic trong H
2
SO
4
, thm 3 ln phenol v un 10-12
h 115-120
0
C. khi phn ng vo nc si v un n ht mi phenol.
ngui, phenolphthalein kt ta lng xung y. Gn b nc, ho tan cn
trong kim long v kt ta li phenolphthalein bng acid acetic pH=7. Lc
thu tinh th v kt tinh li trong cn.
Sn xut fluoretxein:
CO
O
C
O
H
OH
OH
H
HO
OH
C
HO O O
COOH
+
2
H
2
O

Anhydrid phthalic tn nh, trn vi resocin v un khan 195-200
o
C.
Hn hp chy lng ri ho rn li. ngui, ho tan cn trong NaOH 2%. Kt
ta bng cch trung ho vi H
2
SO
4
long. Sn phm kt tinh dng tinh th
mnh mu . Lc v sy.
125
Fluoretxein l cht ch th mu trong ho phn tch v l cht trung gian
trong sn xut thuc Mecurocrom.
2.2. Ngng t loi HCl
y l phn ng ngng t quan trng v n to nhiu hp cht trung
gian cho cng ngh tng hp ho hc. in hnh cho ngng t loi ny l phn
ng Friedel-Craft:
H
C Cl
O
Ar(R)
xt
C Ar(R)
O
+ HCl
+

Xc tc cho phn ng l cc acid Lewis: AlCl
3
, ZnCl
2
, FeCl
3
.
Phn ng Friedel-Craft xy ra theo c ch S
E
. Xc tc acid ng vai tr
to ra tc nhn i in t:
RCOCl + AlCl
3 RCO AlCl
4
RCO AlCl
4
+ ArH
H
COR AlCl
4
COR
+ HCl + AlCl
3

V d: Tng hp acridon l khung c bn ca nhm thuc st rt nhn
acridin (Quinacrin).
xt
+ HCl
N
H
COCl
H
N
O
H

2.3. Ngng t loi alcol
Trong tng hp ho hc, ngng t loi ny t c s dng hn so vi hai
loi trn. Tuy nhin n cng c s dng trong tng hp mt s ceton vng.
c bit l ng dng ca n trong tng hp cc thuc nhn pyrazolon v
cc quinolon khng khun.
V d:
Tng hp nguyn liu cho cc thuc h nhit nhn pyrazolon:
126
CH
3
CH CH
OH C
OC
2
H
5
O
C
6
H
5
H
N
NH
H
_
H
2
O,
_
C
2
H
5
OH
HN
N
O
H
3
C
C
6
H
5

Phn ng to thnh nhn pyrazolon l qu trnh ngng t va loi nc,
va loi alcol.
Tng hp cc quinolon khng khun:
Phng php chung l ngng t arylamin vi ethoxymethylen-malonat
diethyl thnh anilinomethylen-malonat-diethyl. Sau un diester-ethylic
250
0
C ngng t ni phn t to thnh quinolon.
NH
2
C
C
COOEt EtOOC
EtO H
+
N
C
COOEt
O
EtO
H
N
COOEt
O
H

3.4. Ngng t loi NH
3

Ngng t loi ny c s dng trong mt s trng hp sau:
Tng hp indol (E. Fisher):
un nng phenyl hydrazon vi mt tc nhn ngng t thch hp (ZnCl
2
)
to Indol v gii phng NH
3
. Nhn indol c trong nhiu dc phm quan trng
hin ang c s dng iu tr nh cc dn cht ca vincamin, reserpin...
Phn ng tng hp xy ra theo s sau:
NH NH
2
O
CH
CH
2
R
NH N
CH
CH
2
R
NH NH
R CH
CH
NH N
CH
CH R
H
+
/ ZnCl
2
H H
NH
2
C H
CH
NH
R
C R
CH
NH
2
NH
2
-NH
3
N
R
H

127
Tng hp nhn pyrazolon:
Ngng t aceto-acetylamid vi phenylhydrazin to nhn pyrazolon theo
phng php ny hiu sut tt hn so vi phng php loi alcol trnh by
trn.
CH
3
CO
CH
2
CONH
2
+ NH
2
NH Ar
N
N O
Ar
CH
3
+ NH
3
+ H
2
O

T lng gi
1. Khi nim v phn ng ngng t v cc tc nhn ca n?
2. Cc phn ng ngng t v ng dng ca n trong tng hp mt s
hp cht c bn?
128
Chng 13
Phn ng chuyn v
Mc tiu
1. Khi nim v cch phn loi phn ng chuyn v.
2. C ch ca phn ng chuyn v.
3. Ni dung ca cc phn ng chuyn v.
1. i cng
Phn ng chuyn v l phn ng xy ra, khi trong phn t c mt nhm
th c chuyn t v tr ny sang v tr khc di tc dng ca mt tc nhn
ho hc. V d:
A B
Y
A B
Y

Trong , Y l nhm di c, A l im khi u, B l ch ca chuyn v. A
v B c th l carbon, nit hoc oxy.
Phn ng chuyn v ph bin nht l chuyn v t mt nguyn t sang
nguyn t cnh n, hay cn gi l chuyn v-1,2. Trong thc t t gp cc
chuyn v -1,3; -1,4; -1,5; -1,6 ...
Nu nhm di c Y mang theo c i in t, ta c chuyn v anion. Nu Y
khng mang theo in t, ta c chuyn v cation. Cn nu Y mang theo ch mt
in t, ta c chuyn v gc.
Phn ng chuyn v quan trng nht v c s dng nhiu trong cng
nghip tng hp Ho dc l chuyn v anion-1,2.
C nhiu cch phn loi phn ng chuyn v: Ngoi cch phn loi theo
v tr v tnh cht ca nhm di c Y (nh trnh by trn), ngi ta cn
phn loi theo cu to ca b khung carbon (c cc chuyn v trong cc hp
cht no, cha no v chuyn v trong cc hp cht thm).
Thng thng vic phn loi hay da vo bn cht ca im khi u (A)
v im cui (B). Theo cch ny, ta c cc loi chuyn v sau:
129
Chuyn v t C n C,
Chuyn v t C n N,
Chuyn v t C n O,
Chuyn v t N n C,
Chuyn v t O n C.
2. C ch phn ng chuyn v anion -1,2
C ch phn ng chuyn v anion-1,2 v c bn gn ging nhau, c th
c chia lm ba bc:
Bc 1: Di tc dng ca tc nhn ho hc, mt nhm th tch ra mang
theo i in t t do, hnh thnh trng thi in t b su trn nguyn t B.
V vy chuyn v ny cn c gi l chuyn v in t b su.
Bc 2: Anion Y va c tch ra lun di chuyn gn A v B bng mt
lin kt ha hc tm thi (Y to vi A v B mt lin kt vng ba cnh).
Bc 3: Nguyn t B loi mt proton to thnh carbanion, carbanion
ny c th to lin kt vi carbon bn cnh dn n chuyn v tch loi hoc
1 tc nhn i nhn Nu
(-)
gn vi nguyn t A, ta c chuyn v thay th.
C ch ca qu trnh chuyn v anion -1,2 c th hin qua s sau:

C C
R
1
OH
H
C C
R
1
H
H
_
H
2
O
C C
R
1
H
C C
H
R
1
H
_
C C
R
1
C C
R
1
C C
H
R
1
Nu
N u
(Chuyn v tch loi)
( Chuyn v thay th)

3. Cc loi phn ng chuyn v
3.1. Chuyn v -1,2 t carbon n carbon
3.1.1. Chuyn v Wagner-Meerwein (G. Wagner-1899, Meerwein -1910)
S phn ng nh sau:

130
C R
2
R
1
R
3
H
+
C R
2
R
1
R
3
R
4
R
5
OH C C
R
5
R
4
~ R1
OH
C R
2
R
3
OH R
1
R
5
R
4
C
C R
2
R
1
R
3
R
4
OH CH
H
+
C R
2
R
1
R
3
CH
R
4
OH
-
H
C C
R
1
R
4
R
2
R
3

Xc tc cho phn ng l acid proton hoc acid Lewis.
Phn ng chuyn v ny gn ging chuyn v pinacolic. Tuy nhin theo
xu hng phn u nhm th cho hai carbon cnh nhau, chuyn v pinacolic th
ngc li. V vy ngi ta cn gi chuyn v ny l chuyn v ngc pinacolic.
Nu thay alcol bng dn xut halogen hoc amin cng c th thc hin
c phn ng chuyn v ny. Khi , phn ng mang tn chuyn v
Demjanov. Vi cc dn cht halogen dng xc tc l Ag
2
O, cn vi amin xc
tc l acid nitr:
C CH R
2
R
1
R
3
Cl
R
4
Ag
2
O
C CH R
2
R
1
R
3
R
4
OH
C CH R
2
OH
R
3
R
4
R
1
C CH R
2
R
1
R
3
NH
2
R
4
HNO
2
N
2
-
-H
2
O
C CH R
2
R
1
R
3
R
4
OH
C CH R
2
OH
R
3
R
4
R
1

Cc chuyn v kiu Wagner-Meerwein c th s dng m rng hoc
thu hp cc hp cht vng.
V d:
131

O
H
C H 2 OH
H
+
- H
2
O
O
H
CH2
~
O
- H
+
O
Dihydro pyran

N H2
HNO
2
-
N
2
-
H
2
O
~
CH2
H
-
H
+
OH
C H 2
C H 2 HO

HO H
CH3
H 3 C
H 3 C
H
+
-
H
2
O
CH3
H 3C
H
3
C
~
H
2
C
C H 3
CH3
Bocneol
Camphen

Cc iu kin ca phn ng:
Chuyn v Wagner-Meerwein ca cc dn cht halogen c tin hnh
trong cc dung mi khng proton (v d nitrometan hoc SO
2
lng), xc tc cho
qu trnh dehalogen ha l cc acid Lewis nh SnCl
4
, HgCl
2
.
Vi cc alcol th xc tc l cc tc nhn dehydrat ha (H
2
SO
4
hoc Al
2
O
3

nhit cao).
Chuyn v Demijanov cc amin c tin hnh trong dung dch nc c
pH = 3-7. Lng NaNO
2
s dng tha khong 50%.
3.1.2. Chuyn v pinacolic (R.Fittig -1860)
Cc pinalcol di tc dng xc tc ca acid mnh s loi i mt phn t
nc, ng thi mt nhm alkyl di c sang carbon bn cnh to thnh ceton.

C C R
2
R
1
O H
R
4
O H
R
3
H
+
-
H2O
C C R
2
OH
R
4
R
3
R
1
~R1
C C R
2
OH
R
3
R
1
R
4
-
H
+
C C R
2
O
R
3
R
1
R
4
(pinacolon)

132
Nhm OH c tch ra carbon mang nhiu nhm th c tc dng lm
bn vng cation carbeni hn. Cc nhm th ny c sp xp theo th t sau:
H < alkyl < aryl
Trn c s chuyn v pinacolic, M.Tiffeneau thc hin chuyn v ca cc
hp cht , -aminoalcol vi acid nitr. Phn ng ny dng m rng cc
ceton vng v c gi l chuyn v Tiffeneau:
C
O
(CH
2
)n
H
+
-
CH OH 1 + (CH
2
)n
(CH
2
)n C
CH
2
OH
H
2
O - N
2
-
HNO
2
LiAlH
4
2
.
1
.HCN
C
CH
2
NH
2
OH
(CH
2
)n
CO (CH
2
)n
+1

Chuyn v pinacolic c tin hnh trong dung dch acid sulfuric 10-20%.
Phn ng Tiffeneau thng c tin hnh trong cc iu kin ging nh
phn ng chuyn v Demjanov.
3.1.3. Chuyn v Favorskij (A.E.Favorskij -1913)
Cc -halogen ceton di tc dng ca cc base mnh to thnh cc ester.

C C R
1
Br
R
2
R
3
O
OR ;
~
R
3
C C R
2
R
1
R
3
OR
O

C ch phn ng c gii thch nh sau:
C C R
1
Br
R
2
R
3
O
~R
3
C C R
2
R
1
R
3
O
OR
C C R
2
R
1
R
3
O
OR
C C R
2
R
1
R
3
O
OR

Cc base thng dng l natri-alcolat, c th dng natri-amid, natri-
hydroxyd (trng hp ny sn phm thu c l amid hoc acid).
Chuyn v Favorskij c s dng lm gim s carbon ca cc ceton
vng. N c ng dng nhiu trong ho hc terpen v steroid:
133

Br
O
NaNH
2
;
~
CONH
2
1-brom-8-oxo-
norcamfan
bicyclo-[3,3,0]-octan-7
carboxylamid

C H
3
C O O
CH
3
CH
3
O
Br
NaOCH
3
~
CH
3
COO
CH
3
CH
3
C O O C H
3
17-brom-homoandrostan-17a-on

Phn ng ny phn ln c thc hin trong dung mi tr. Lng base
s dng thng l ng lng, c ha tan hoc to huyn ph trong ether.
Nhit phn ng t -20
0
C n 30
0
C.
3.1.4. Tng hp Arndt-Eistert v chuyn v Wolff
Cc diazoceton di tc dng ca nhit, xc tc bc oxyd chuyn v thnh
xeten. Cht ny phn ng vi tc nhn i nhn trong mi trng phn ng,
to ra dn xut ca acid carboxylic c mch carbon tng ln 1 C.

R C
O
C l
+ CH
2
N
2 R C
O
CH N N
-
N
2
Ag2O
R C C H
O
C a r be n
R C H C O
X e t en
R CH
2
CO O H
R CH
2
CO O R
R CH
2
C O N H
2
(RCH
2
CO N H R ' )
H
2
O
R O H
N H
3
(N H
2
R ' )

V cha chng minh c s tn ti ca hp cht carben. Do c ch c
th gii thch nh sau:
R C CH N N
O
R
1
OH
R
1
O C CH
2
R
O
N N R
1
O C CH
2
O
R
- N
2
Ag
2
O

134
Tng hp Arndt-Eister:
L phn ng tng hp ester c s carbon tng ln 1 C t clorid acid v
diazometan. Tc nhn i nhn s dng trong phn ng ny l alcol, nn sn
phm thu c l mt ester:
R
1
C
O
Cl
+ CH
2
N N R
1
C
O
CH N N
-
HCl
O C CH R
1
ROH, Ag
2
O
-
N
2
RO C CH
2
R
1
O

Tng hp Arndt-Eister rt ngn phng php iu ch acid carboxylic
v dn cht c mch carbon tng ln 1 C t cc clorid acid tng ng.
Nu thay clorid acid bng mt ceton trong phn ng chuyn v kiu Wolff
vi diazoalkan, s thu c ceton khc c mch carbon tng ln mt:
R
1
C
O
R
2
+
R
1
C CH
O
R
2
N N
Ag
2
O
- N
2
RO C CH
2
O
R
2
N N CH
2 N N CH
2
R
1
C CH
2
R
2
O

Phn ng ny s dng c hiu qu m rng mch cc ceton vng:

O C H
2
N N
C y c l oh e x a n on
O
CH
2
N N
Ag
2
O
-
N
2
O
CH
2
O
Cy c l oh e pt a n on ( s u be r on )

Nh t t dung dch clorid acid trong benzen khan vo dung dch lm
lnh ca diazometan trong ether, benzen hay dioxan. Sau khi HCl ngng gii
phng th yn hn hp 10-12 gi nhit phng, thu c dung dch cha
diazoceton. Nu iu ch acid, th 60-70
0
C nh t t dung dch ca
diazoceton trong dioxan vo dung dch ca AgNO
3
trong nc c cha natri
thiosulfat hoc vo huyn ph ca Ag
2
O trong dung dch natri thiosulfat.
135
Nu iu ch ester th cho t t huyn ph trong alcol ca Ag
2
O vo
dung dch ca diazoceton trong alcol tuyt i.
Nu iu ch amid th nh git amoniac vo dung dch alcol ca
diazoceton v huyn ph Ag
2
O hoc nh t t dung dch AgNO
3
trong amoniac
c vo dung dch diazoceton trong alcol nng.
Lng xc tc s dng trong phn ng t vi phn trm n 20-25%.
ng dng ca phn ng:
y l phng php ni di mch carbon ca cc acid hu c:
V d:
COCl
NO
2
N
2
CH
2
COCHN
2
NO
2
Ag
2
O
- N
2
CH
2
COOH
NO
2

C th s dng cho c lacton v acid carboxylic cha no:
O
COOH C
2
H
5
O
Arndt - Eistert
O
CH
2
COOH C
2
H
5
O
CH
3
CH
2
COOH
Arndt Eistert -
CH
3
CH
2
CH
2
COOH

Trong tng hp papaverin, phn ng Arndt-Eister c ng dng tng
hp trung gian amid:
MeO
MeO
NH
2
+
N N CH CO
OMe
OMe
MeO
MeO
NH
CH
2
OMe
OMe
O

3.1.5. Chuyn v benzylic (J.Liebig-1838)
Chuyn v ca cc , -aryl-diceton di tc dng ca kim c cho sn
phm l acid 1,1-diaryl -1-hydroxy-acetic.
136
C C Ar
2
Ar
1
O O
OH
-
C C Ar
2
Ar
1
O
HO
O
~ Ar
1
C C Ar
2
HO
O O
Ar
1
~
H
+
C C Ar
2
O
O OH
Ar
1

Trong phn ng trn nu Ar
1
, Ar
2
l C
6
H
5
- th sn phm l acid benzylic.
Cht ny l nguyn liu quan trng trong tng hp thuc chng ng kinh
phenyltoin.
3.1.6. Chuyn v kiu Fritsch (P.Fritsch -1894)
Di tc dng ca kim mnh (alcolat, amid ca kim loi kim), cc hp
cht 1,1-diaryl-2-brom-ethylen chuyn v thnh 1,2-diaryl-acethylen.

Phn ng c th xy ra theo hai c ch sau:
C ch carben:

A r
2
C C A r
1
O R
-
C C
A r
1
A r
2
H
B r
B r
-
-
H
C C
A r
1
A r
2
Ca r be n

C ch y-ko:

3.2. Chuyn v -1,2 t carbon n nit
3.2.1. Phn ng thoi phn amid kiu Hofmann (Hofmann-1881)
Cc amid di tc dng ca hypohalogenid, thoi phn to thnh amin
bc nht:

(X=Cl, Br)
C C
Ar
1
Ar
2
H
Br
OR
-
ROH
Ar
1
C C Ar
2
C C
Ar
1
Ar
2
Br
H -
C C
Ar
1
Ar
2
H
Br
Ar
2
C C Ar
1
R C
O
NH
2
NaOX
R C
O
NHX
R
1
O
-
H
R C
O
N X
-
X
R C
O
N
~
R
O C N R
nitren
R
1
OH
O C
OR
1
NHR
H
2
O/OH
R
1
OH + RNH
2
+ CO
2
137
y l phng php iu ch cc amin bc nht tinh khit t amid.
iu kin ca phn ng:
Tc nhn to N-halogenid l NaOBr, NaOCl. Cn tnh ton lng
halogen tha 10%, lng kim NaOH gp 4-5 ln.
Nhit phn ng 70-80
0
C.
ng dng ca phn ng:
Phn ng thoi phn Hofmann c s dng iu ch cc amin bc
nht c mch carbon gim mt C t cc amid tng ng.
V d: iu ch --diamin c mch carbon ngn i hai carbon t cc
amid tng ng:

Khi thoi phn diethyl-malonic-diamid, thu c diethylhydantoin.

Trong cng nghip, phng php ny c s dng sn xut acid
antranilic t phthalimid.

3.2.2. Phn ng chuyn v Curtius (T.Curtus-1894)
Khi un azit ca acid carboxylic (R-CON
3
) trong dung mi tr, n s loi
N
2
to thnh nitren, sau chuyn v thnh isocianat.
CH
2
CH
2
CH
2
CH
2
CONH
2
CONH
2
Adipin diamid
KOBr
CH
2
CH
2
CH
2
CH
2
NH
2
NH
2
1
,
4
- diaminobutan
C
C
2
H
5
C
2
H
5
CONH
2
CONH
2
NaOCl
NH
N
O
C
2
H
5
C
2
H
5
H
O
NH
O
O
NaOCl
COONa
NH
2
O C N R
R
~
R C
O
N
R C
O
N N N
138
Isocyanat c th phn lp ring t hn hp phn ng trong dung mi tr.
Nhng n d phn ng vi cc tc nhn i nhn cho sn phm cng hp:
Vi nc to amid th, sau thu phn thnh amin bc nht:

Vi alcol to ra uretan:

Vi amin bc nht hoc bc hai, to thnh carbamid:

3.2.3. Chuyn v Beckman (E. Beckman-1886)
Aldoxim hoc cetoxim di tc dng ca acid Lewis hoc tc nhn loi
nc chuyn v thnh amid hoc amid th:

(R1,R2 = H, alkyl , aryl )
C ch phn ng:
Phn ng Beckman l phn ng chuyn v -1,2 loi i nhn. Qu trnh
ny c th do proton hoc acid Lewis lm xc tc.
Vi proton:

Vi acid Lewis:

O C N R + H
2
O
R NH
2
+ CO
2
O C N R 2 + H
2
O
R NH CONHR
H
+
/H
2
O
2 R NH
2
+ CO
2
R N C O
+ R
1
OH
RNH CO OR
1
R N C O + R
1
NH
2 RNH CO NHR
1
R N C O +
R
1
NHR
2
RNH CO NR
1
R
2
C N
R
1
R
2
OH
-
OH
C N
R
1
R
2
~
R
2
R
1
C N R
2
H
2
O
O
C
H H
R
1
N R
2
~
H
-
H
R
1
C NHR
2
O
C N
R
1
R
2
OH
H
+
C N
R
1
R
2
OH
2
oxoni ion
C N
R
1
R
2
nitroni ion
C N
R
1
R
2
C N
R
1
R
2
OH
+ BF
3
+ BF
3
OH
139
Theo Chapman, trong mi trng alcol th khng to ra amid m l
iminoester, di tc dng ca mi trng acid n chuyn v thnh amid th
hai ln, cn trong mi trng nc th iminoester thy phn thnh amid th
mt ln.

ng dng ca phn ng:
ng dng quan trng nht l chuyn v ca cycloalkan-oxim thnh
lactam c vng rng hn mt cnh:

Chuyn v Beckman cn c ngha quan trng trong ha hc cc steroid,
c bit trong tng hp cc thuc khung steroid:
CH
3
COO
C
CH
3
N OH
HO
NH
2
TsCl/Pyridin
87%

3- -acetoxy-4-pregnen-20-on-oxim 17-amino-
4
-androsten-3- -ol

CH
3
COO
N OH
NH
HO
O
p.AcNHC
6
H
4
SO
2
Cl/Pyridin
73%
3--acetoxy-4-androsten-17-on-oxim
-13-amino-13,17-secoandrosten-17-lactam
3- -hydroxy-
4
-

C
R
1
R
2
N OH
- OH
-
~
R
1
R
2
C N R
1
ROH
- H
R
2
C
OR
NR
1
~
H
2
O
R
2
C
O
N
R
1
R
R
2
C
O
NHR
1

N OH
H
2
SO
4
SO
3
O N
H
C y c l opentanon ox i m
Valerolactam
N O H
C y c l oheptanon ox i m
H
2
SO
4
SO
3
N
O
H
Caprolactam
140
3.2.4. Chuyn v Schmidt (R.F.Schmidt-1924)
Di tc dng ca xc tc acid, sn phm cng hp ca azoimid (HN
3
) vi
aldehit hoc ceton chuyn v to thnh amid th (hoc amid khng th).

Cc phn ng ph:
Nu tha HN
3
th n s phn ng vi ion iminocarbeni cho dn xut tetrazol:

Phn ng ph ny c ng dng iu ch thuc tr tim Cardiazol, s
phn ng nh sau:

3.3. Chuyn v -1,2 t carbon n oxy
3.3.1. Chuyn v Baeyer-Villiger (A.Baeyer,V.Villiger-1899-1990)
Ceton tc dng vi cc peroxyd (hydrogen-peroxyd, acid percarboxylic)
chuyn v thnh cc ester:

R
1
C N R
2
+ HN
3
R
1
C N R
2
HN N N
- H
N
N
N
N
R
1
R
2
C
R
1
R
2
O + R O OH C O OR R
2
R
1
OH
- OR
C O R
2
R
1
OH
~
R
1
C OR
1
R
2
OH
- H
C OR
1
R
2
O

( T etr a c or )
cardi a z ol
HN
3
N
O H
N N N
N O H
O
H N
3
H
2 S O
4
H N
3
H
2
S O
4
N N N
~
- N
2
H
2
O
NH
O
N
N
N
N
pe n t a m e t ylen
im i n oc a c beni ion

C
R
1
R
2
N
N N
C N
R
1
R
2
N i t r oni i on
C
R
1
N
R
2
Iminocarbeni
OH
C
R
1
O
N H R
2
141
Phn ng cho hiu sut tt vi cc ceton mch thng nu t nht R
1
l
nhm alkyl bc hai. Phn ng cng d thc hin khi mch carbon lin kt vi
carbon cha nhm carbonyl cng phn nhnh, c bit cc ceton thm cho
hiu sut phn ng tt hn.
Cc cycloalkanon cho hiu sut tt v sn phm l lacton c vng ln hn
mt cnh. y l ng dng quan trng nht ca phn ng chuyn v ny:

Cng c th coi chuyn v Baeyer-Villiger l phng php oxy ha chn
lc. V iu kin phn ng nh nhng v tnh chn lc cao, nn ngy cng c
s dng rng ri.
Cc iu kin phn ng:
Tc nhn ca chuyn v Baeyer-Villiger thng c s dng ln hn
mt ng lng, chng gm cc peroxyd nh H
2
O
2
, H
2
SO
5
, acid
perbenzoic, acid perphthalic, acid peracetic, acid pertrifloacetic.
Nu cc peracid mnh th khng cn xc tc, nhng nu s dng
hydrogenperoxyd hoc percarboxylic th cn xc tc. Cc xc tc hay
s dng l acid sulfuric, HF, acid percloric hoc p-toluensulfonic vi
lng 1-5%.
Tin hnh phn ng nhit phng, thi gian phn ng thay i t
20-30 pht hoc mt vi ngy. Khng c lm nng v d gy n,
mt khc nhit s thc y qu trnh t phn hy ca tc nhn.
ng dng ca phn ng:
Phn ng thng c s dng xc nh cu trc ca cc ceton c
cu to phc tp.
V hiu sut phn ng tng i tt v tnh chn lc cao, nn c s
dng chuyn ha mt s ceton thnh ester quy m cng nghip,
c bit l trong iu ch cc hp cht thin nhin.
quy m cng nghip, ngi ta sn xut c caprolactam t
cyclohexanon nh chuyn v ny:

(CH
2
)n C O
RCOOOH
(CH
2
)n
CO
O
142
Phn ng Baeyer-Villiger c ng dng trong tng hp
prostaglandin: Tng hp hp cht trung gian 3-carboxymethyl-4-
benzyloxymethyl-hydroxy-penten-1-en (3) t 7-syn-benzyloxymethyl-
norborn-2-en-5-on (1) theo s sau:

X l (1) vi acid perbenzoic chuyn v thnh lacton (2), sau thy
phn (2) thu c sn phm mong mun (3).
3.3.2. Chuyn v ca hydroperoxyd
Cc dn cht hydroperoxyd ca alcol bc ba cha ti thiu mt nhm
aryl, di tc dng ca xc tc acid chuyn v thnh O-aryl ca bn acetal,
cht ny phn hu thnh ceton v phenol.
Phn ng ny c gi l tng hp Hock. y l c s ca phng php
iu ch phenol v aceton qua trung gian cumol-peroxyd:
O
H PhCH
2
OCH
2
ArCO
3
H
O
H PhCH
2
OCH
2
O
1
.
OH
-
2
.
H
+
OH
CH
2
COOH
CH
2
OCH
2
Ph
1
2
3
C
Ar
R
1
O OH
R
2
H
+
- H
2
O
C
Ar
R
1
O
R
2
C
R
1
OAr
R
2
H
2
O
H
+
C
R
1
R
2
OH
OAr
H
+
C
R
1
O
R
2
+ HOAr
+ CH
3
CH CH
2
AlCl
3
CH
CH
3
CH
3
O
2
CH
CH
3
CH
3
OOH
H
+
OH
+ CH
3
C CH
3
O
143
3.4. Chuyn v -1,2 t nit n carbon
Chuyn v Stevens (T.S.Steven-1928).
Cc mui amin bc bn di tc dng ca cc base mnh (phenyl-lithi,
natri-amid, natri-alcolat), chuyn v to thnh amin bc ba:
Phn ng ny l chuyn v cation-1,2, rt t gp.
Chuyn v Stevens khng ch c ngha l thuyt, m ngy cng c nhiu
ng dng thc t.
V d: Chuyn v dimethyl-(1-phenylethyl)-(2-oxo-2-phenylethyl)-
amonium bromid thnh 2-dimethylamino-1,3-diphenyl-butan-1-on vi hiu
sut trn 95%.
Ngi ta cn s dng phn ng ny m rng hoc thu hp cc hp
cht vng:
3.5. Chuyn v -1,2 t oxy n carbon
Chuyn v Wittig (G.Wittig-1942)
Di tc dng ca phenyl-lithi, mt s ether c th chuyn v theo c ch
cation 1,2 ging chuyn v Stevens, to thnh alcol bc ba:
Hin nay, chuyn v Wittig cn t c ng dng trong tng hp Ho hc.
N CH R
2
R
1
R
3
R
4
R
5
B
-
-
H
+
N C R
2
R
1
R
3
R
4
R
5
~ R
1
N
R
2
R
3
C R
4
R
1
R
5
N
CH
3
Ph
N
CH
3
Ph
PhCOCH
2
N
CH
Me
Me
Me Ph
~
Ph
CHCH
3 PhCO CH
CH Me Ph
N(CH
3
)
2
Br
+

144

T lng gi
1. Nu khi nim v phn ng chuyn v v cc cch phn loi chng?
2. C ch ca phn ng chuyn v anion -1,2 gm nhng bc c bn
no? Nu ni dung cc bc v vit s ca chng?
3. Trnh by c ch, iu kin v ng dng ca cc phn ng chuyn v -
1,2 t C n C, t C n N, t C n O, t N n C v t O n C.

O CH
R
2
R
3
R
1
B
O C R
1
R
2
R
3
~
R
1
C R
2
O
R
1
R
3
H
+
C R
2
HO
R
1
R
3
145
Phn II. K thut chit xut dc liu
Chng 14
Mt s kin thc c bn
v chit xut dc liu
Mc tiu
1. i tng ca chit xut dc liu.
2. Mt s qu trnh xy ra trong chit xut dc liu.
3. Nhng yu t nh hng n qu trnh chit xut dc liu.
4. Mt s phng php chit xut thng gp.
5. Mt s thit b chit xut hay dng trong ngnh Dc.
TM QUAN TRNG CA CHIT XUT DC LIU
T thi xa xa, loi ngi bit dng cy c cha bnh. Tri qua
hng ngn nm lch s, cc cy thuc c pht hin ngy cng nhiu hn, cc
phng php ch bin cng phong ph hn, cc kinh nghim dng cy thuc
cha bnh c tch lu dn trong nhn dn, ri c truyn t i ny
sang i khc. Cho n tn ngy nay, phng php cha bnh c truyn vn
c k tha v pht huy mnh, c nhng ng gp to ln v c o trong
vic cha bnh cho con ngi.
Tuy nhin, loi thuc thang phi mt thi gian sc thuc, khi lng
cng knh, kh bo qun, hm lng hot cht trong dc liu thp nn
thng phi ung nhiu cho mi ln s dng, t iu tr thng phi ko di.
Mt s loi thuc c sn xut t dch chit ca dc liu, hoc t dc liu
kh tn bt (cao thuc, cn thuc, sir, tr ti lc, ch tan, hoc nhng ch
phm thuc mi) th tin dng hn v d bo qun hn. Tuy vy, cc loi
thuc ny vn phi ph thuc vo dc liu, m dc liu li khng n nh.
Do , cht lng cng nh thnh phn ca thuc s kh ng u qui m
sn xut cng nghip. Cc tiu chun kim nghim thuc loi ny cng
cha c y . V vy, hiu qu iu tr cng nh c tnh ca thuc s
146
khng c n nh. khc phc nhng nhc im ny, sau khi ly dch
chit t dc liu, ngi ta tm cch tinh ch, loi b cc tp cht, phn lp
tch ring mt hoc mt s hot cht tinh khit.
So vi thuc ng y, thuc phn lp t dc liu c mt s u im:
Thnh phn r rng, hm lng chnh xc, khi lng gn nh, cch dng
thun tin, bo qun d dng, thi gian bo qun lu, c phng php kim
nghim r rng.
Tuy nhin, tc dng cha bnh, hiu qu iu tr, c tnh ca thuc
phn lp t dc liu c th c thay i so vi thuc i t dc liu (cha phn
lp hot cht).
Thc t, c nhng thuc ch c sn xut bng phng php chit xut
dc liu khi cng nghip ho dc cha tng hp c, hoc c th tng hp
c nhng gi thnh li qu cao, hoc tc dng iu tr ca thuc tng hp
cha th thay th c thuc c ngun gc dc liu. V d: morphin, quinin,
strychnin, berberin, ...
Chit xut dc liu tch hot cht tinh khit, c tc dng to ngun
nguyn liu cung cp cho qu trnh bn tng hp mt s thuc mi nhm lm
tng u im cho thuc: tng tc dng iu tr ca thuc, hoc gim bt
nhng tc dng khng mong mun ca thuc, hoc to ra nhng tc dng
mi. Chng hn, t l cy thanh cao hoa vng, ngi ta phn lp ra
artemisinin, sau ngi ta li bn tng hp ra artesunat, arteether,... Cc
dn cht ny cng c dng iu tr st rt nhng cho hiu qu iu tr
cao hn. T v cy canhkina ngi ta phn lp ra quinin, sau li bn tng
hp ra quinidin. Quinidin cng c tc dng dit k sinh trng st rt nh
quinin nhng tc dng km hn nn c dng ch yu cha bnh lon
nhp tim. Diosgenin (phn lp t nhiu loi thuc chi Dioscorea, h C nu -
Dioscoreaceae), c dng lm nguyn liu bn tng hp ra nhiu loi
thuc steroid quan trng.
i vi ngnh dc Vit Nam, chit xut dc liu c tm quan trng c
bit. Vit Nam ta c kh hu nhit i, m kh cao, din tch rng rt rng,
li c c mt s vng ni cao v cao nguyn, do h thc vt rt phong ph
v a dng. V vy, nc ta c nhiu iu kin t trng trt v khai thc
dc liu trong nc, chnh l iu kin thun li pht trin cng nghip
chit xut dc liu.
Trong nhng nm gn y, xu hng Vit Nam cng nh trn th gii,
con ngi ngy cng thch nhng thuc c ngun gc t dc liu, do cng
nghip chit xut dc liu cng ngy li cng c vai tr quan trng, v c kh
nng s tr thnh th mnh ca ngnh dc Vit Nam.
1. Nguyn liu chit xut
Nguyn liu dng chit xut c th l nhng b phn ca ng vt,
thc vt, khong vt hoc vi sinh vt. Trong phm vi ca ti liu ny, chng
147
ta ch nghin cu dc liu l thc vt. Thc vt dng chit xut bao gm
cc b phn ca cy, l nhng b phn c thnh phn phc tp, khng r
rng v km n nh, hm lng hot cht hay thay i v ph thuc vo rt
nhiu yu t: ging, loi, kh hu, t ai, iu kin trng trt, b phn dng,
giai on sinh trng, thi k thu hi... v cch bo qun.
B phn dng chit ca cy c th l: hoa, qu, ht, thn, l, r, v,
nha, phn trn mt t, ... hoc ton cy. Di y l mt s v d c th:
Hoa:
N hoa ho: dng chit rutin, hm lng kh cao (20-28% Thi
Bnh).
N hoa inh hng: ct tinh du (15-20%), cha eugenol (78-95%).
Hoa bi: ct tinh du, cha nerolidol (40%), farnesol (18%), ...
Qu:
Qu thuc phin chit cc alcaloid: morphin, codein, papaverin,...
(0,2-0,3% alcaloid ton phn trong qu kh). C th chit bng qu
ti cha chch nha.
Qu i hi: ct tinh du hi (8-9%), cha anethol (85-90%).
Qu hi ni: ct tinh du (1,5%), thnh phn ch yu l safrol
(77,5%).
Ht:
Ht m tin, loi Strychnos nux vomica l. dng chit strychnin (1%).
Ht sng d hoa vng: chit mt s glycosid tim, c cha divaricosid, ...
Ht thng thin: chit thevetin (l hn hp ca thevetin A v thevetin
B).
Thn:
Thn v r cy vng ng: dng chit berberin (l,5-3%).
Thn r cy hong ng: dng chit palmatin (3%).
Thn g long no: ct tinh du (4,4%), c cha camphor (64,l%).
L:
L da cn: dng chit cc alcaloid c tc dng tr bnh ung th
nh vinblastin (0,005-0,015%) v vincristin (0,003-0,005%).
L cy thanh cao hoa vng: dng chit artemisinin (1%).
L trc o: chit neriolin (oleanrin), c 0,08-0,15% trong l kh.
148
R:
R c bnh vi: dng chit rotundin (0,2 - 3,55%).
R ba gc: cha reserpin, ajmalin (0,9-2,2% alcaloid ton phn Vit
Nam).
R cy dy mt: chit rotenon (4-8%), dng duc c, dit cn trng.
V:
V (thn, cnh, r) ca cy canhkina: dng chit quinin (3 - 5%).
V thn mc hoa trng (0,22-4,2% alcaloid ton phn): chit conesin.
V thn cy hong b: chit berberin (3% loi xuyn hong b).
Phn trn mt t (thn, cnh mang l v hoa):
Cy c l x: cha solasodin (1,4% l), bn tng hp cc thuc
steroid.
Cy hng nhu trng: ct tinh du (1,1%), cha eugenol (60-70%).
Cy bc h : ct tinh du (0,5%), thnh phn chnh l menthol
(>70%).
2. Mt s qu trnh xy ra trong chit xut dc liu
Khi dc liu v dung mi tip xc vi nhau, lc u dung mi thm vo
dc liu, sau nhng cht tan trong t bo dc liu ho tan vo dung mi,
ri c khuch tn ra ngoi t bo. Trong chit xut dc liu s xy ra mt
s qu trnh sau: khuch tn, thm thu, thm tch, ...
2.1. Qu trnh khuch tn
Khi nim chung:
Qu trnh di chuyn vt cht t pha ny sang pha khc khi hai pha tip xc
trc tip vi nhau gi l qu trnh khuch tn (hay l qu trnh chuyn khi).
Qu trnh tch cht ho tan trong dc liu bng dung mi chnh l qu
trnh chit xut dc liu. y dc liu l pha rn, dung mi l pha lng.
Khi hai pha chuyn ng tip xc vi nhau, do s cn tr ca pha ny i
vi pha kia, ngha l do ma st gia chng m trn b mt phn chia pha to
thnh lp mng. trong lp mng lun lun c ch chuyn ng dng, cn
gia nhn ca dng th c th c chuyn ng xoy. c trng di chuyn vt
cht trong mng v trong nhn ca dng c khc nhau.
Trong lp mng, qu trnh di chuyn vt cht c bn l nh s tip xc
gia cc phn t v s tc dng tng h gia chng, do qu trnh khuch
tn qua mng c gi l qu trnh khuch tn phn t.
149
Trong nhn ca dng, qu trnh di chuyn vt cht nh vo s xo trn
cc phn t ca dng, v th gi l khuch tn i lu.
Qu trnh khuch tn trong lp mng xy ra rt chm so vi qu trnh
khuch tn trong nhn ca dng, do mc d lp mng rt mng nhng n
vn c gi tr quyt nh i vi qu trnh khuch tn. Vn tc khuch tn
chung ph thuc nhiu vo vn tc khuch tn trong mng.
2.1.1. Khuch tn phn t
Khuch tn phn t xy ra trong lp mng hay trong mi trng ng
yn. ng lc ca qu trnh khuch tn l graien nng theo hng x, tc
l s bin i nng trn mt n v ng i.
Vn tc khuch tn: L lng vt cht i qua mt n v b mt trong
mt n v thi gian. Theo nh lut Fick, vn tc khuch tn t l vi graien
nng .
Ta c:

dx
dC
D
Fd
dG
=
Trong :
Fd
dG
: vn tc khuch tn.
D : h s t l, gi l h s khuch tn.
Du (-) c ngha l nng gim theo hng khuch tn.
dx
dC
: graien nng .
Gii phng trnh trn, ta tnh c lng vt cht khuch tn:
dx
dc
D.F.. G =
Trong :
G : lng vt cht khuch tn, [kg]
F : b mt khuch tn, vung gc vi hng khuch tn, [m
2
]
: thi gian khuch tn, [h]
C : nng cht tan, [kg/m
3
]
x : chiu di qung ng khuch tn, [m]
H s khuch tn phn t l lng vt cht i qua mt n v b mt,
trong mt n v thi gian, khi nng vt cht gim i mt n v trn mt
150
n v chiu di theo hng khuch tn. H s khuch tn ca mt cht c
trng cho tnh cht khuch tn ca cht trong mt mi trng no y.
Cng thc tnh h s khuch tn phn t theo Einstein:
6r
1
N
RT
D =
Trong :
R : hng s kh.
T : nhit tuyt i.
N : hng s Avogaro.
: nht ca cht lng.
r : bn knh ca phn t khuch tn.
ng dng:
Trong qu trnh chit xut dc liu, c trng ca qu trnh khuch
tn qua mng t bo chnh l khuch tn phn t.
Da vo biu thc ca nh lut Fick, ta thy rng nhng yu t c
nh hng n qu trnh chit xut l: mn ca dc liu, thi
gian chit xut, nhit chit xut, dung mi chit, khuy trn, kch
thc ca phn t khuch tn.
2.1.2. Khuch tn i lu
Trong chit xut dc liu, qu trnh khuch tn ca cht tan trong dung
mi c c trng ch yu bng khuch tn i lu.
Khuch tn trong mi trng cht lng chuyn ng c m t bng
phng trnh vi phn ca khuch tn i lu.
Vit di dng rt gn:
C D (vgrad)C
t
C
2
= +

Vit theo cc trc to :
2
2
2
2
2
2
z
C
y
C
x
C
D
z
C
y
C
x
C
t
C
z y x

Phng trnh khuch tn i lu rt phc tp. Tu tng trng hp c
th m ngi ta gii phng trnh p dng cho nhng trng hp ring.
Trong phm vi ca ti liu ny, chng ta khng cn i su nghin cu.
151
2.2. Qu trnh thm thu
Khi nim: Qu trnh thm thu l qu trnh khuch tn gia hai pha
lng qua mt mng c tnh cht bn thm, c ngha l mng ch cho dung
mi i qua m khng cho cht tan i qua. Mng gi l mng bn thm. Do
p lc thm thu ca cc phn t cht tan, dung mi s c thm t pha
lng c nng cht tan thp hn sang pha lng c nng cao hn, cho n
khi p lc thu tnh cn bng vi p lc thm thu.
ng dng: Trong t bo dc liu cht nguyn sinh c tnh cht bn
thm, v vy khi dc liu cn ti, do tc dng ca cht nguyn sinh m ch
c dung mi c thm vo t bo lm cho dc liu b trng n, cn cht tan
trong t bo th khng khuch tn ra ngoi c. Do trong chit xut, ngi
ta phi tm cch ph hu cht nguyn sinh bng nhit hoc bng cn thc
hin qu trnh chit xut.
2.3. Qu trnh thm tch
Khi nim: Qu trnh thm tch l qu trnh khuch tn gia hai pha
lng qua mt mng c tnh cht thm tch, c ngha l mng khng ch cho
dung mi i qua m cn cho c cht tan i qua, nhng ch cho qua nhng cht
c phn t nh.
ng dng: Mng t bo dc liu c tnh cht ca mt mng thm tch,
do khi chit xut nu mng t bo cn nguyn vn th ch c cht tan l
phn t nh v ion (phn ln l hot cht) khuch tn qua c mng t bo;
cn cc cht c phn t ln (thng l cht keo, cht tp, ...) th khng qua
c mng t bo nn khng b chit vo dch chit. Nh vy, c th coi mng
t bo nh mt mng lc c tnh chn lc. y chnh l u im ca mng t
bo i vi qu trnh chit xut. Do trong qu trnh chit xut, khng nn
xay dc liu qu mn; v khi mng t bo b ph v, tnh chn lc ca
mng t bo khng cn, dch chit s ln nhiu tp, gy kh khn cho qu
trnh tinh ch.
3. Nhng yu t nh hng n qu trnh chit xut
dc liu
3.1. Nhng yu t thuc v thnh phn, cu to ca dc liu
3.1.1. Mng t bo dc liu
Mng t bo dc liu c nh hng nhiu n qu trnh khuch tn. Khi
cn sng, l ni xy ra qu trnh trao i cht c tnh cht chn lc. Khi
cht, l ni xy ra cc hin tng khuch tn, thm thu, thm tch, ...
Mng t bo c cu to khng n nh, c th b thay i tnh cht vt l v
thnh phn ho hc p ng vi nhng chc phn sinh l c bit m n
152
m nhim (ho g, ho khong, ph sp, ...). Nhng s thay i ny c th
xy ra tng phn hoc ton phn mng t bo v thng thay i nhiu
thc vt gi.
i vi thc vt cn non hay mng mm nh c cy, hoa l, thnh
phn ca mng t bo ch yu l cellulose. Cellulose c tnh cht
khng tan trong nc v khng tan trong cc dung mi khc, bn
vng nhit cao, c tnh mm do n hi. i vi dc liu loi
ny, dung mi d thm vo dc liu, do ch cn xay th dc liu.
Nu xay mn, d ko theo nhiu tp vo dch chit.
i vi dc liu gi, rn chc nh ht, g, r, v thn... th mng
t bo tr nn dy v c th xy ra nhng bin i sau:
+ Mng t bo c th b ho bn, ho cutin, hoc c th b ph thm mt
lp sp,... l nhng cht c bn cht lipid, c tnh cht khng thm
nc v kh, do dung mi kh thm vo dc liu.
+ Mng t bo c th b ho g, ho khong, b ph thm lp dioxyd silic
hoc calci carbonat, mng t bo tr nn dy, rn chc, nn dung mi
kh thm vo dc liu.
+ Mng t bo c th b ph thm lp cht nhy. Cht nhy tan c
trong nc, nhng khi ht nc n b trng n v tr nn nht, lm
bt kn cc ng mao qun trn mng t bo, gy cn tr s thm ca
dung mi, cn tr qu trnh khuch tn.
Do vi nhng dc liu gi, rn chc, nn xay nh dc liu, to
iu kin cho dung mi d thm t dc liu, cht tan d khuch tn vo
dung mi.
3.1.2. Cht nguyn sinh
Cht nguyn sinh c thnh phn ho hc rt phc tp v khng n nh.
Cht nguyn sinh c tnh nht, tnh n hi, khng tan trong nc, khng
mu v khng bn i vi nhit. nhit 50 - 60
0
C, chng b mt hot tnh
sinh hc (tr trng hp nhng ht kh, qu kh, cht nguyn sinh c th
chu c ti 80 - 105
0
C). C th ni cht nguyn sinh l mt mi trng d th
phc tp, c th coi l mt h keo nhiu pha, to thnh t nhng hp cht
cao phn t, phn tn trong mi trng nc (v d: git du, git m, ht tinh
bt, ht tinh th ...).
Cht nguyn sinh c tnh cht bn thm, c ngha l ch thm i vi dung
mi m khng cho cht tan i qua. Do chit c cc cht tan trong t
bo, ngi ta phi tm cch ph hu cht nguyn sinh bng cch lm ng vn
chng bng nhit (sy hoc phi kh) hoc bng cn (hi hoc cn nng).
153
3.1.3. Mt s tp cht c th c trong dc liu
l sn phm ca cc qu trnh trao i cht, l cht d tr hoc cht
thi ca cy. Cc cht ny thng gy cn tr hoc cng c khi c tc dng
thun li cho qu trnh chit xut. Di y l mt s v d:
i vi nhng dc liu cha nhiu pectin, gm hoc cht nhy:
l nhng cht tan c trong nc, v khi tan trong nc th b
trng n, to dung dch keo, lm tng nht, gy cn tr cho qu trnh
chit xut. C th loi cc cht ny bng cch cho kt ta trong cn cao .
i vi nhng dc liu cha nhiu tinh bt:
Tinh bt c tnh cht khng tan trong nc lnh, nhng nhit cao
tinh bt b h ho, lm tng nht ca dung dch, gy cn tr cho qu trnh
chit xut. Do i vi nhng dc liu loi ny, khng nn xay dc liu
qu mn, trnh gii phng ra nhiu tinh bt v khng nn chit nhit cao
trnh b h ho.
i vi nhng dc liu cha cht bo, du m, tinh du, sp, nha:
l nhng cht khng tan trong nc v thng tan trong cc dung
mi khng phn cc. Nu dng dung mi chit l nc, cc cht ny s lm
dung mi kh thm vo dc liu, gy cn tr qu trnh chit xut, do cn
phi loi chng i bng cc dung mi thch hp trc khi chit. Nu dng
dung mi khng phn cc chit, dch chit s ln nhiu tp, nhng tp ny
s b loi i trong giai on tinh ch.
i vi nhng dc liu cha enzym:
Enzym c bn cht l protein, nhit 60-70
0
C enzym b mt hot
tnh, cn nhit lnh enzym ch b ngng hot ng, sau nu nng n
nhit thch hp th enzym li c phc hi. Tu tng trng hp c th
m enzym c th gy cn tr hoc cng c khi li to iu kin thun li cho
qu trnh chit xut. V d: glycosid trong cy bao gm hai phn l phn
ng v phn khng ng. Di tc dng ca enzym vn c sn trong dc
liu, gp iu kin thun li (m, m), glycosid s b thu phn, mch ng
s b ct mt phn hoc ton phn, lm thay i phn cc ca glycosid, lm
cho glycosid t tan trong nc hn. C trng hp ngi ta cn glycosid th
cp ( b ct bt mt phn ng), lc ngi ta s to iu kin cho enzym
hot ng bng cch v nt, ct nh dc liu, dc liu thnh ng v to
nhit thch hp (30-40
0
C). Cng c trng hp ngi ta cn glycosid s cp
(cha b thu phn), khi ngi ta li phi dit enzym trnh cho glycosid
khi b thu phn.
C ba phng php dit enzym:
+ PP nhit t: nhng dc liu vo lng si (nc si hoc cn si).
+ PP nhit m: cho dc liu qua hi m (hi nc si hay hi cn si).
+ PP nhit kh: cho dc liu qua lung khng kh nng.
154
3.2. Nhng yu t thuc v dung mi
Mt s yu t ca dung mi c nh hng n qu trnh chit xut l:
phn cc, nht, sc cng b mt.
3.2.1. phn cc ca dung mi
Ni chung dung mi t phn cc th d ho tan cc cht khng phn cc
v kh ho tan cc cht c nhiu nhm phn cc. Ngc li, dung mi phn
cc mnh th d ho tan cc cht c nhiu nhm phn cc v kh ho tan cc
cht t phn cc.
Da vo phn cc ca dung mi ngi ta phn loi nh sau:
+ Dung mi khng phn cc: ether du ho, xng, hexan, heptan,
benzen, toluen
+ Dung mi phn cc yu v va: chloroform, diclorethan, aceton,
ethylacetat ...
+ Dung mi phn cc mnh: nc, glycerin, cc loi cn c mch
carbon ngn (methanol, ethanol, isopropanol...).
3.2.2. nht, sc cng b mt ca dung mi
Ni chung, dung mi c nht cng thp hoc c sc cng b mt cng
nh th dung mi cng d thm vo dc liu, to iu kin thun li cho qu
trnh chit xut v ngc li.
Di y l nht () v sc cng b mt () ca mt s dung mi
thng gp nhit phng 20
o
C (xp theo th t tng dn).

Dung mi (cp) Dung mi (dyn/cm)
Hexan 0,31 Hexan 1,11
Aceton 0,32 Ethanol 22,03
Chloroform 0,57 Propanol 22,90
Methanol 0,60 Methanol 22,99
Benzen 0,65 Aceton 23,70
Dicloetan 0,89 Chloroform 27,70
Nc 1,00 Benzen 28,87
Ethanol 1,20 Dicloethan 32,20
Propanol 2,23

Nc 72,75

155
3.3. Nhng yu t thuc v k thut
l nhng yu t c th thay i c bng cc bin php k thut
khc nhau, nhm to ra nhng iu kin thun li cho qu trnh chit xut.
c th l nhng yu t: nhit , thi gian, mn ca dc liu, khuy
trn, siu m ...
3.3.1. Nhit chit xut
Theo cng thc tnh h s khuch tn ca Einstein, khi nhit tng th
h s khuch tn cng tng, do theo nh lut Fick, lng cht khuch tn
cng tng ln. Hn na, khi nhit tng th nht ca dung mi gim, do
s to iu kin thun li cho qu trnh chit xut. Tuy nhin, khi nhit
tng s gy bt li cho qu trnh chit xut trong mt s trng hp sau:
i vi nhng hp cht km bn nhit cao: nhit tng cao s
gy ph hu mt s hot cht nh vitamin, glycosid, alcaloid ...
i vi tp: khi nhit tng, khng ch tan ca hot cht tng
m tan ca tp cng ng thi tng theo, dch chit s b ln nhiu
tp. Nht l i vi mt s tp nh gm, cht nhy ... khi nhit
tng s b trng n; tinh bt b h ho, nht ca dch chit s b
tng, gy kh khn cho qu trnh chit xut, tinh ch.
i vi dung mi d bay hi c nhit si thp: khi tng nhit th
dung mi d b hao ht, khi thit b phi kn v phi c b phn
hi lu dung mi.
i vi mt s cht c bit c qu trnh ho tan to nhit: khi nhit
tng, tan ca chng li b gim. Do tng tan th cn
phi lm gim nhit .
T nhng phn tch trn ta thy tu tng trng hp c th m cn la
chn nhit sao cho ph hp (tu thuc vo cc yu t nh dc liu, dung
mi, phng php chit xut ...).
3.3.2. Thi gian chit xut
Khi bt u chit, cc cht c phn t lng nh (thng l hot cht) s
c ho tan v khuch tn vo dung mi trc, sau mi n cc cht c
phn t lng ln (thng l tp nh nha, keo...). Do , nu thi gian chit
ngn s khng chit c ht hot cht trong dc liu; nhng nu thi gian
chit di qu, dch chit s b ln nhiu tp, gy bt li cho qu trnh tinh ch
v bo qun. Tm li, cn phi la chn thi gian chit xut sao cho ph hp
vi thnh phn dc liu, dung mi, phng php chit xut ...
3.3.3. mn ca dc liu
Khi kch thc dc liu th qu, dung mi s kh thm t dc liu,
hot cht kh c chit vo dung mi. Khi mn dc liu tng ln, b mt
156
tip xc gia dc liu v dung mi tng ln; theo nh lut Fick, lng cht
khuch tn vo dung mi tng ln, do thi gian chit xut s nhanh hn.
Tuy nhin trong thc t, nu xay dc liu qu mn s gy ra mt s bt
li cho qu trnh chit xut nh sau:
Khi ngm dc liu vo dung mi, bt dc liu b dnh bt vo nhau,
to thnh dng bt nho, vn cc. Do s kh khuy trn gia dc
liu v dung mi, qu trnh chit xut xy ra b chm li. Mt khc,
v bt dc liu b dnh bt vo nhau nn khi rt dch chit, dch chit
b chy chm hoc khng chy c (gi l hin tng tc thit b).
Khi bt dc liu qu mn, nhiu t bo thc vt b ph hu, dch
chit b ln nhiu tp; gy kh khn cho qu trnh tinh ch, bo
qun.
T nhng phn tch trn ta thy cn phi la chn mn ca dc
liu sao cho thch hp, tu thuc vo tng trng hp hp c th, tu
thuc vo dc liu, dung mi, phng php chit xut ... V d:
+ i vi dc liu mng manh nh hoa l, cy c ... hoc i vi nhng
dc liu cha nhiu cht nhy, cht nha, cht keo ... th khng nn
xay dc liu qu mn m ch nn xay th dc liu. i vi nhng
dc liu gi, dc liu rn chc nh ht, r, thn g ... cn phi
xay mn hn.
+ i vi trng hp dng loi dung mi d ho tan nhiu tp, nn
trnh xay dc liu qu mn.
+ i vi trng hp chit xut nhit cao, cng nn trnh xay dc
liu qu mn trnh a nhiu tp vo dch chit.
3.3.4. Khuy trn
Khi dung mi tip xc vi dc liu, dung mi s thm vo dc liu, ho
tan cht tan, cht tan s khuch tn t dc liu vo dung mi qua mng t
bo. Sau mt thi gian khuch tn, nng cht tan trong t bo gim dn,
nng cht tan trong lp dung mi tng dn, chnh lch nng gia trong
v ngoi t bo gim dn, tc qu trnh khuch tn cng gim dn, n mt
lc no s xy ra qu trnh cn bng ng gia hai pha. Nh vy, nu
khng c khuy trn, qu trnh khuch tn s xy ra rt chm. Theo nh lut
Fick, chnh lch nng gia hai pha l ng lc ca qu trnh khuch tn.
Do mun tng cng qu trnh khuch tn, cn phi to ra chnh lch nng
bng cch di chuyn lp dch chit pha st mng t bo (ni c nng
cao hn) ra pha xa hn v di chuyn lp dung mi pha xa (ni c nng
thp hn) n st mng t bo. iu ny c thc hin bng cch khuy
trn. Nh vy bng cch khuy trn, ngi ta tng cng c tc
khuch tn.
157
Tu tng trng hp c th m ngi ta chn loi cu to cnh khuy v
tc khuy sao cho ph hp. V d:
Nu dc liu l hoa l mng manh, ch cn chn tc khuy nh,
khng nn khuy mnh trnh cho dc liu khi b dp nt gy
vn, trnh a nhiu tp vo dch chit.
Nu dc liu cng chc nh ht, r, thn, g... cn phi chn loi
cnh khuy kho, tc khuy mnh.
3.3.5. Siu m
Nng lng ca siu m c tc dng lm tng mnh tnh thm thu v
khuch tn nh nhng tc dng ca siu m nh sau:
Lm tng din tch tip xc gia hai pha bng cch phn tn chng
thnh nhng ht nh.
Ph v mt phn mng t bo.
Tng cng s xo trn ca hn hp.
C tc dng lm nng ti ch.
Phng php siu m c nhiu u im lm tng cng qu trnh chit
xut. Tuy nhin, phng php ny mi ch c nghin cu trong phng th
nghim m cha c p dng trong sn xut.
Ngoi nhng yu t k trn, cn nhiu yu t khc cng gy nh hng
n qu trnh chit xut. V d: p sut, pH mi trng, chn ng c hc,
dng in cao p
4. Cc phng php chit xut
4.1. Phn loi
C nhiu cch phn loi, da vo nhng yu t khc nhau.
Da vo nhit , c cc phng php chit sau:
Chit nng.
Chit ngui ( nhit thng).
Da vo ch lm vic c cc phng php chit sau:
Gin on.
Bn lin tc.
Lin tc.
Da vo chiu chuyn ng tng h gia hai pha, c cc phng php:
Ngc dng.
158
Xui dng.
Cho dng.
Da vo p sut lm vic, c cc phng php chit :
p sut thng (p sut kh quyn).
p sut gim (p sut chn khng).
p sut cao (lm vic c p lc).
Da vo trng thi lm vic ca hai pha, c cc phng php chit sau:
Ngm.
Ngm kit.
Da vo nhng bin php k thut c bit
C th lm rt ngn c thi gian chit bng cc phng php chit sau:
Phng php siu m.
Phng php to dng xoy.
Phng php mch nhp...
4.2. Mt s phng php chit xut
Khi chit xut, qu trnh chit xut xy ra ch yu hai khu vc: bn
trong nguyn liu v gia cc lp dung mi. Trong , qu trnh xy ra bn
trong nguyn liu c nh hng quyt nh v ph thuc vo bn cht nguyn
liu (cu trc, tnh cht l ho...). Cc phng php chit xut thng ch tc
ng n cc yu t bn ngoi, nhm t c hiu qu chit xut cao trong
thi gian ngn i vi mi loi nguyn liu. Di y l mt s phng php
thng gp.
4.2.1. Phng php chit xut gin on
a. Phng php ngm
Phng php ngm l phng php n gin nht v c t thi c
xa.
Tin hnh:
Sau khi chun b dc liu, ngi ta dung mi cho ngp dc liu
trong bnh chit xut, sau mt thi gian ngm nht nh (qui nh ring cho
tng loi dc liu), rt ly dch chit (lc hoc gn) v ra dc liu bng mt
lng dung mi thch hp. tng cng hiu qu chit xut, c th tin hnh
khuy trn bng cnh khuy hoc rt dch chit di ri li ln trn
(tun hon cng bc dung mi).
159
C nhiu cch ngm: C th ngm tnh hoc ngm ng, ngm nng hoc
ngm lnh, ngm mt ln hoc nhiu ln (cn gi l ngm phn on hay
ngm nhiu m).
u im:
y l phng php n gin nht, d thc hin, thit b n gin, r tin.
Nhc im:
Nhc im chung ca phng php chit xut gin on: nng sut
thp, thao tc th cng (giai on tho b v np liu).
Nu ch chit mt ln th khng chit kit c hot cht trong dc
liu.
Nu chit nhiu ln th dch chit long, tn dung mi, tn thi gian
chit.
b. Phng php ngm kit
Tin hnh:
Sau khi chun b dc liu, ngm dc liu vo dung mi trong bnh
ngm kit. Sau mt khong thi gian xc nh (tu tng loi dc liu), rt
nh git dch chit pha di, ng thi b sung thm dung mi pha trn
bng cch cho dung mi chy rt chm v lin tc qua lp dc liu nm yn
(khng c khuy trn). Lp dung mi trong bnh chit thng c ngp
b mt dc liu khong 3 - 4 cm.
Ngm kit n gin: L phng php ngm kit lun s dng dung
mi mi chit n kit hot cht trong dc liu.
Ngm kit phn on (ti ngm kit): L phng php ngm kit c
s dng dch chit long chit m mi (dc liu mi) hoc chit
cc m c mc chit kit khc nhau.
u im:
Dc liu c chit kit.
Tit kim c dung mi (ti ngm kit).
Nhc im:
C nhc im chung ca phng php chit xut gin on: nng
sut thp, lao ng th cng.
Cch tin hnh phc tp hn so vi phng php ngm.
Tn dung mi (ngm kit n gin).
4.2.2. Phng php chit xut bn lin tc
(Cn gi l phng php chit xut nhiu bc, phng php chit ngc
dng tng i hay phng php chit ngc dng gin on).
160
S (xem hnh 14.3a)
Phng php ny c s dng mt h thng thit b gm nhiu bnh chit
khc nhau, c th mc thnh mt dy t 4-16 bnh chit ni tip nhau. y,
qu trnh coi nh l ngc chiu tng i v thc t dc liu khng chuyn
ng.
Tin hnh:
Lc u, dc liu v dung mi c np vo trong tt c cc thit b,
dc liu c ngm vo dung mi trong mt khong thi gian xc nh (tu
thuc vo dc liu v dung mi). Lc ny dc liu v dung mi u khng
chuyn ng. Sau dch chit c chuyn tun t t thit b ny sang thit
b khc. H thng t hp kn cc bnh chit ny cho php ng ngt mt cch
c chu k mt trong nhng thit b ra khi h thng tun hon, cho php tho
b dc liu bnh c chit kit ri np dc liu mi. Sau , thit b
ny li c a vo h thng tun hon v dch chit m c nht c dn
qua n m dch chit ny va i qua tt c cc thit b cn li. Tip theo, li
ng ngt mt thit b k tip m trc dung mi mi va c dn qua. S
thit b cng nhiu th qu trnh xy ra cng gn vi qu trnh lin tc.
y, b dc liu trc khi ra khi h thng thit b s c tip xc
vi dung mi mi nn dc liu s c chit kit. Dch chit trc khi ra khi
h thng s c tip xc vi dc liu mi nn dch chit thu c s m c
nht. Nh vy c th ni qu trnh xy ra theo nguyn tc: "dung mi mi tip
xc vi dc liu c v dc liu mi tip xc vi dung mi c". Trong phng
php ny, qu trnh xy ra gn vi qu trnh ngc chiu, do phng php
ny cn c gi l phng php chit ngc chiu tng i.
u im (so vi phng php chit gin on)
Dch chit m c.
Dc liu c chit kit.
Nhc im:
H thng thit b cng knh, chim nhiu din tch lp t.
Vn hnh phc tp.
Thao tc th cng.
Khng t ng ho qu trnh c.
4.2.3. Phng php chit xut lin tc
Tin hnh:
Phng php ny c thc hin trong nhng thit b lm vic lin tc.
y dc liu v dung mi lin tc c a vo v chuyn ng ngc chiu
nhau trong thit b. Dc liu di chuyn c trong thit b l nh nhng c
161
cu vn chuyn chuyn dng khc nhau. Dch chit trc khi ra khi thit b
c tip xc vi dc liu mi nn dch chit thu c m c. B dc liu
trc khi ra khi thit b c tip xc vi dung mi mi nn b dc liu c
chit kit.
So vi phng php chit gin on th phng php chit lin tc c
nhng u nhc im sau:
u im:
Nng sut lm vic cao, tit kim thi gian chit.
Khng phi lao ng th cng (tho b, np liu).
Dch chit thu c m c.
Dc liu c chit kit.
Dung mi t tn km.
C th t ng ho, c gii ho c qu trnh.
Nhc im:
Thit b c cu to phc tp, t tin.
Vn hnh phc tp.
5. Thit b chit xut
Phn loi
cc thit b chit xut lm vic c hiu qu, p ng c yu cu ca
nhng qu trnh cng ngh cao hin nay (cng sut ln vi chi ph ch to kim
loi thp, chit kit c hot cht trong khong thi gian ngn, ...), cn phi
m bo qu trnh xy ra iu kin gn nh ngc dng m tr lc thu lc
li phi nh, cng nh t l lng pha lng so vi pha rn phi nh (ngha l
tn t dung mi), tng tr lc khuch tn trong v ngoi cng phi nh.
Nguyn liu chit xut rt phong ph v hnh dng, cu trc, tnh
cht vt l (khi lng ring, xp, n hi, tr lc khuch tn, ...) nn
cc qu trnh chit xut xy ra cng khc nhau, do thit b chit xut cng
rt a dng v cu to.
phn loi cc thit b chit xut, c rt nhiu cch. Tu theo cc yu
t khc nhau ngi ta c th phn loi nh sau:
Theo ch lm vic, c cc loi thit b:
Gin on
Bn lin tc
Lin tc
162
Theo chiu chuyn ng tng h gia hai pha rn lng, c cc loi:
Xui chiu
Ngc chiu
Loi hn hp (va xui chiu, va ngc chiu)
Theo kiu chuyn ng tun hon ca dung mi, c cc loi thit b:
Tun hon n
Tun hon kp
Loi ti
Theo p sut, c cc loi thit b lm vic :
p sut thng
p sut chn khng
p sut cao
Theo cu to, c nhiu cch phn loi v khng thng nht:
Theo hnh dng ca thn thit b, c cc thit b:
+ Kiu thp
+ Kiu bung (hp)
Theo cu to v tnh cht ca b phn vn chuyn, c cc loi thit b:
+ C b phn vn chuyn bng:
kiu tm
vt ti
bng ti
bng chuyn xch
gu ti
+ Loi quay
Theo v tr lp t thit b, c cc loi thit b:
+ Thng ng
+ Nm ngang
+ Nm nghing
Theo trng thi pha rn c cc loi thit b vi:
Pha rn ng yn
Pha rn chuyn ng
Pha rn l lng (thit b tng si)
163
Tm li:
C rt nhiu kiu phn loi thit b chit xut. Cch phn loi nh trn
tuy c a ra c c im no ca qu trnh hay thit b chit xut,
nhng nhng cch phn loi khng a ra c hon ton c trng chnh
ca qu trnh hay thit b. Thng thng, ngi ta hay t tn cho thit b
theo cu to hay theo ch lm vic ca thit b. V d: Thit b kiu thp,
thit b kiu quay, thit b kiu tng si, thit b c ti dung mi, thit b loi
nghing c b phn vn chuyn bng vt ti
Mt s thit b chit xut c th
5.1. Thit b chit xut gin on
Cc thit b chit xut gin on thng c dng bung (dng hp), gm:
Thit b c khuy bng: c hc, thu lc, hoc thu c kt hp.
Thit b c lp vt liu ng yn: c tun hon hoc khng tun hon
dung mi.
5.1.1. Thit b chit xut gin on
loi c khuy trn
S thit b: Hnh 14.1.
Cu to:
Thit b chit xut kiu hp c
dng hnh ng tr, c y phng hoc
y nn, c ch to bng thp khng
g hoc thp c trng men hoc trng
mt hay mt vi lp vt liu chng n
mn.
5.1.2. Thit b chit xut gin on
loi c lp vt liu ng yn
S thit b: Hnh 14.2.
Cu to:
Thng l thit b loi ng, phn chnh ca thit b c dng hnh tr,
mt u hoc c hai u c dng hnh nn ct. u trn dng np liu, y
di dng tho b. Thng c m c hc c bit hoc m thu lc lp
y v nh cho kn kht. Li lc thng c lp pha trn ca y di.
Hnh 14.1. Thit b chit xut
kiu hp c khuy.
1. y gi c khoan l (li lc)
2. Cnh khuy.
164
u nhc im chung ca thit b chit
xut gin on:
u im:
+ Thit b n gin, d ch to,
chim t din tch lp t.
+ D vn hnh, d sa cha.
Nhc im:
+ Thit b lm vic gin on, nng
sut thp.
+ Lao ng th cng (giai on np
liu, tho b).
+ Qu trnh khng t ng ho
c.

5.2.2. Thit b chit xut bn lin tc
S h thng thit b:Hnh 14.3a, 14.3b, 14.3c.

Hnh 14.3a. H thng thit b chit xut bn lin tc
(Lc bt u, thit b s 1 l thit b u)
Hnh 14.2. Thit b chit c li
lc hnh nn ct pha di

1. Np 3. Li chnh
2. Li b sung 4. Thn thit b.
165

Hnh 14.3b. Thit b s 1 ang tho b v dung mi

Hnh 14.3c. Thit b s 2 l thit b u, thit b s 1 l thit b cui.
166
Cu to:
H thng bao gm mt dy cc thit b lm vic gin on c lp ni
tip nhau. Mt dy c th bao gm t 4-16 thit b.
Nguyn l lm vic:
Trc tin tt c cc thit b u c np dc liu v dung mi, dc
liu c ngm vo dung mi trong mt khong thi gian xc nh. Sau ,
khi t c m c, t thit b cui dch chit c a vo bnh
cha, ng thi dung mi s c lin tc a vo tun t t thit b u n
thit b cui (Hnh 14.3a). Cho n khi dc liu trong thit b s 1 c chit
kit th thit b s 1 s c tho dung mi v b, ri li c np dc liu
mi vo (Hnh 14.3b). Tip theo thit b s 1 s tr thnh thit b cui v thit
b s 2 s tr thnh thit b u (Hnh 14.3c).
Ti thit b s 2, sau khi dc liu c chit kit th dung mi v b s
c tho ra, ri dc liu mi li c np vo. Lc ny thit b s 2 li tr
thnh thit b cui, cn thit b s 3 li tr thnh thit b u, Qu trnh c
tip tc nh th cho n khi kt thc (ht dc liu).
u nhc im ca h thng thit b:
u im: Lp nguyn liu trong thit b t u n cui qu trnh
khng b nghin nt, do cht lng dch chit tt, ch thu
ng tt.
Nhc im:
+ H thng thit b cng knh, tn din tch lp t, tn kim loi ch
to.
+ Lao ng th cng, kh vn hnh qu trnh.
+ Khng c gii ho, khng t ng ho qu trnh c.
5.3. Thit b chit xut lin tc
u nhc im chung (so vi thit b gin on v bn lin tc)
u im:
+ Loi b c lao ng chn tay (tho b, np liu).
+ C th t ng ho, to thit b thnh mt th thng nht c nng
sut cao.
+ Lm tng h s chuyn khi.
Nhc im: Do dung mi v vt rn c khuy trn theo chiu dc,
nn trt t vt rn b ph hu, do qu trnh chuyn khi xy ra
khng ng u.
167
Di y l mt s thit b chit xut lin tc thng gp:
Thit b chit kiu thp ng
Ni chung, thit b chit xut lin tc thng c s dng l thit b
kiu thp. C th c loi thp mt ct, thp hai ct, thp ba ct hoc thp
nhiu ct.
5.3.1. Thp chit loi mt ct
S :

1. V thn thp
2. Trc quay
3. Tm truyn ti
4. Tm hm c nh
5. Li phn phi
Hnh 14.4a. Thp mt ct c b phn vn chuyn loi tm
Cu to:
Thp c hnh tr, tit din thp l hnh trn. hnh 14.4a, cc cnh
dng tm (3) c gn theo hnh xon c trn trc rng thng ng (2); cc
cnh hm c nh gn trn thn thit b, khong gia cc tm (3), c tc
dng lm cn tr s quay ca pha rn cng vi trc quay. hnh 14.4b, b
phn vn chuyn ca thp l trc vt, trong khong khng gian gia cc cnh
hnh xon c l cc cnh hm, c gn c nh vo thn thit b.
Nguyn l lm vic:
Pha rn c a vo thp t di ln nh mt bm chuyn dng, dung
mi c a t trn xung, hai pha chuyn ng ngc chiu. Ch lm
vic lin tc. B pha rn c a ra khi thp pha trn, dch chit c lc
qua li (5) pha di, ri c a i tinh ch tip. Qu trnh chuyn khi
xy ra rt mnh lit phn gia ca thp, cc ht rn l lng t do trong
168
pha lng. gn nh v y thp, cc ht rn b p st v pha li phn phi
hoc v pha b phn tho liu. y cng qu trnh chuyn khi b gim
i nhiu ln. S phn b gi tr ca h s chuyn khi c th hin trn s
hnh 14.5 v c th c gii thch nh sau:

Hnh 14.4b. Thp c b phn
vn chuyn bng trc vt
Hnh 14.5. S bin i HSCK theo
chiu di ca thp loi mt ct

phn di thp, lp vt rn b nn cht do tho dch chit ra khi thp,
do lm xu i ch thu ng khi dch chit chy vng qua ht rn. H s
chuyn khi nh.
phn gia thp, ch thu ng ca qu trnh thng l ti u nht.
y, hn hp hai pha rn lng c khuy trn tt bng b phn vn chuyn
v c phn phi u theo tit din ca thp, m iu ny khng th thc
hin c phn di ca thp. Gi tr ca h s chuyn khi vng ny t
c gi tr cc i.
phn trn ca thp, ni m nhng ht rn b nghin nt nht, b dnh
bt vo nhau, hnh thnh cc cc vn m dng cht lng khng len c vo
bn trong, hin tng c gi l hin tng "trt". Hin tng tng t
cng xy ra khi hai pha rn-lng tc dng tng h vi nhau qu mnh lit.
Ti trng ring vng ny tng, lp rn b nn cht, lm gim b mt hot
ng ca pha rn, lm xu i ch thu ng ca qu trnh chit xut. H s
chuyn khi vng ny b gim.
169
u nhc im:
u im: u im chung ca loi thp mt ct l:
+ Qu trnh xy ra trong thp l lin tc v ngc chiu.
+ Ton pha rn c trn ln trong pha lng, do din tch tip xc
pha ln.
+ Thit b gn, chim t din tch lp t, tn t kim loi ch to.
+ Tt c khong khng gian trong thit b u c s dng hu ch.
Nhc im: Khi chit xut, cn phi xay nh pha rn. Tuy nhin
trong thp chit xut c trc vt; khi vn chuyn, pha rn ng thi
b nghin vn thm, do lm xu i ch thu ng ca qu trnh.
5.3.2. Thp hai ct c b phn vn chuyn bng xch truyn ti (thp
ch U y trn)
S : Hnh 14.6

Hnh 14.6. Thit b chit hai ct c b phn vn chuyn bng xch
1. on un cong;
2. Ct ng;
3. Con ln xch;
4. Khung
5. Tang trng dn ng
170
Cu to:
Phn di ca thp c on 1 l on chuyn tip c un trn gc.
Ton b tit din ca thp u l hnh vung. Bn trong thp, xch chuyn
ng c nh cc con ln. Trn xch, c theo mt on nht nh (0,5-0,6 m),
ngi ta gn c nh nhng khung hnh vung, m trn c cng cc bng
ti. Bng ti chuyn ng c nh ng c in, qua c cu truyn ng l
tang trng 5.
Nguyn l lm vic:
y hai pha cng chuyn ng ngc chiu. Ch lm vic lin tc.
Dc liu c phn b gia cc khung, do khi chuyn ng chng khng b
bin dng, y l u im ln ca thp loi ny. ct np liu ng, iu kin
ca qu trnh chuyn khi c bit thun li, bi v lp dc liu trn khung
c phn b mt cch ng u. Tuy nhin, khi chuyn ng qua on thp
un cong, dc liu b o trn tng i bi cc khung, do to kh nng
cho dung mi i trn lp dc liu. ct chit xut, lng dc liu cn lu li
trn khung b gim i v b phn b mt cch khng ng u. B dc liu
trc khi ra khi thp c ra bng lng dung mi mi vo. Dch chit trc
khi ra khi thp tip xc vi dc liu mi vo nn dch chit cng m c.
u nhc im:
Ngoi nhng u nhc im chung ca thit b chit lin tc, loi thp
ny cn c nhng c im sau:
u im: Dc liu khng b nghin nt, do cht lng dch chit tt.
Nhc im: c liu phn phi trong thp khng u, cu to thit
b kh phc tp.
5.3.3. Thp chit ba ct c b phn vn chuyn bng vt ti (thp ch
U y vung)
S : Hnh 14.7.
Cu to:
Thp c ba ct nh hnh v. C ba ct u c vt xon. Vt xon (4) ca ct tip
liu v vt xon (5) ca ct chit xut u c treo nh trc da trn cc
chn. Phn trn ca ct tip liu c li hnh tr (6) tch dch chit ra khi
pha rn khi i ra khi thp. Thp chit xut kiu ny c s dng ph bin
trong cng nghip dc, cng nghip ho hc v cng nghip thc phm.
171

Hnh 14.7. Thp chit 3 ct
1. Ct tip liu; 2. Ct nm ngang;
3. Ct chit xut; 4,5. Vt ti; 6.Li phn phi
Hnh 14.8. S bin i h s chuyn
khi theo chiu di ca thp ba ct c
b phn vn chuyn bng vt xon.

Nguyn l lm vic:
Nguyn liu c a vo ct tip liu, b c tho ra phn trn ca
ct chit xut. Hai pha chuyn ng ngc chiu, lin tc. Dung mi c a
vo phn u ca ct chit xut, dch chit c ly ra phn trn ca ct
tip liu. Cng qu trnh chuyn khi theo chiu di thit b c s thay i
ln (Hnh 14.8) v c c im sau:
+ ct tip liu: H s chuyn khi (HSCK) gim
+ ct nm ngang: HSCK c tng ln mt cht
+ ct chit xut: Lc u HSCK gim khng nhiu, sau tng ln
t ngt.
u nhc im:
u im:
+ Cu to n gin, chim t din tch lp t, tn t kim loi ch to.
+ Ton b th tch thit b u c s dng mt cch hu hiu.
+ D bo dng, d sa cha.
H (m)
172
Nhc im: Dc liu b nghin nt mnh, mt vi dng (c bit l
tho dc) b p li, gy vn cc, lm gim b mt tip xc pha. Dc
liu cn b xon cht vo trc vt, cng lm gim b mt tip xc pha,
lm xu i ch thu ng ca qu trnh. Do dch chit b ln
tp, h s chuyn khi b gim.
Thit b chit kiu nghing
5.3.4. Thit b chit lin tc loi nghing, c hai vt xon
S : Hnh 14.9

Hnh 14.9: Thit b chit xut loi nghing, c hai vt ti
Cu to:
Thit b c t nghing to thnh hnh lng mng, c v bc bn ngoi
gia nhit bng hi. Trong thn c t hai trc vt quay vo nhau, to thnh
hnh ti tit din ngang. Trc vt c da trn mt lot gi , t u
n theo chiu di ca thit b. Cc vt ca gung xon c lng ci n vo
ci kia mt cch khng hon ton, nhm ngn nga cc ht b quay cng
gung xon. Pha trc ca u di ca thnh thit b c t li, li ny
cng vi thnh thit b to thnh mt khoang, dng tch dch chit. Li
1,2. Trc ca vt ti;
3. Cnh vt
173
lc c lm sch nh tc dng quay ca li co. Pha trn phn u ca
thit b c t phu tip liu. Gung xon quay c l nh hai b phn truyn
ng c bit, c t da vo thnh u di v u trn ca thit b.
Bnh xe cng vi gu mc c dng tho b rn ra khi u trn ca thit
b. Dung mi c a vo thit b nh c ng quay c bit, c vi phun vo
u trn thit b, phun ln trn vt xon v tr cao nht. im c bit ch
yu v cu to ca thit b ny l n c chia thnh nm on ging nhau,
m ch ni ca n c t trn trc.
Nguyn l lm vic:
Thit b ny c kh nng
vn chuyn vt liu theo dc trc,
ging nh m hnh loi thp. S
bin i h s chuyn khi dc
theo chiu di ca thit b loi hai
vt ti c qui lut ring bit ca
n, c lin quan ti cu to c
bit ca loi thit b ny. S bin
i ny c th hin trn s
hnh 14.10.
c trng chuyn ng ca
hai pha rn lng trong mi on
ca thit b v ch ni ca cc
on, ni xy ra qu trnh chuyn
khi mnh lit, c s khc bit
ng k. Cng chuyn khi t cc i ch gn vi ch gin on ca vt
ti. H s chuyn khi t gi tr nh nht phn gia mi on ca thit b,
ni m nhng ht rn c khuy trn km mnh nht. Vic gim cng
chuyn khi phn cui thit b, cng vi nhng yu t, c lin quan n s
thay i tnh cht vt liu rn, nht l vic ph hu thm nhng ht rn gy
ra do khuy trn mnh ti nhng ch ni cc on ca thit b, dn n lm
xu i ch thu ng ca qu trnh chit xut.
u nhc im:
u im:
+ Cu to tng i n gin.
+ D vn hnh, d sa cha.
Nhc im:
+ Vt rn b nghin nt mnh, do cht lng dch chit km
+ Kh to c ch nhit cn thit (nht l i vi thp c kch
thc ln).

Hnh 14.10. S bin i HSCK theo
chiu di thp nghing, c hai vt xon
174
5.3.5. Thit b chit kiu ti
S : Hnh 14.11.

Hnh 14.11. Thit b chit kiu ti c bng ti nm ngang
1. V; 2. Boongke; 3. a xch; 4. Bng ti;
5. Phu hng; 6. Bm; 7. Vi phun (ng ti).
Cu to:
Theo nguyn tc cu to, thit b dng ti c chia thnh loi bng ti,
gu ti v vt ti. y do phm vi hn ch ca gio trnh, chng ta ch
nghin cu thit b chit kiu ti c bng ti nm ngang.
Thit b c v thp (1). Bn trong v, ngi ta t bng chuyn (4), m
tm ti c gn cht vo hai ci xch - truyn ng c nh s chuyn ng
ca a xch (3). Bng ti c g cng v trn ngi ta t loi tm c c l.
Nguyn l lm vic:
a dc liu vo thp qua boongke (2), dc liu dch chuyn c nh
chiu cao lp dc liu l 0,6-1,2 m theo phng thng ng, pha trn ca
bng ti. Pha trn ca lp dc liu ngi ta t nhng vi phun 7 (ng ti),
m bo phn phi u dung mi ln trn lp dc liu. Pha di bng ti
ngi ta t nhng phu hng (5), v dch chit sau khi chy qua lp dc
liu s chy vo phu. S phu bng s bc chit xut. T mi mt phu, cht
lng s chy vo mt bm ly tm tng ng, bm s y cht lng vo mi
vi phun nht nh. Khi cht lng thng hng khng phi ln trn on
m di n c tp trung li, m hng ln trn on k bn (ln cn) -
175
c t theo hng ngc vi chiu chuyn ng ca bng ti, do m bo
s chuyn cht lng t bc ny sang bc khc theo nguyn tc ngc dng.
Lp dc liu nm trn bng ti c chiu dy khng ln v khng b bin dng.
Qu trnh trong thit b xy ra theo mt s phc tp: dng chy trn mi
on, thc t qu trnh c khuy trn hon ton v l ngc chiu khi
chuyn t on ny sang on khc.
u nhc im:
u im:
+ Dc liu t b bin dng, cht lng dch chit tt.
+ Dc liu c ti u dung mi, b mt tip xc pha tt.
Nhc im:
+ Cu to thit b phc tp
+ Tn kim loi ch to
+ Khng s dng ht th tch thit b
+ Kh vn hnh, kh sa cha

Tm li:
Thit b chit xut rt a dng v cu to l do nguyn liu chit c
nhiu loi khc nhau. V d: i vi loi nguyn liu d b ph hu trong qu
trnh chit th nn dng thit b dng ti. i vi loi nguyn liu d b dnh
bt, vn cc th nn s dng thp chit loi nhiu ct hoc loi c hai vt xon.
Cn ch l khng c mt loi cu to thit b no li p ng c y
cc yu cu k thut i vi thit b l:
+ m bo c ch chy ngc dng vi tr lc khuch tn ngoi
nh khi nguyn liu c kch thc mn.
+ Tn t lng kim loi ch to thit b.
+ Chim t din tch lp t thit b.
+ Cu to thit b n gin, d ch to.
+ D vn hnh, d bo dng, d sa cha.
T lng gi
1. Nu tm quan trng ca chit xut dc liu.
2. K ra nhng nguyn liu ca chit xut dc liu.
176
3. Th no l qu trnh khuch tn phn t, qu trnh thm thu, qu
trnh thm tch.
4. Trnh by nh lut Fick. Nu ng dng ca nh lut Fick.
5. Phn tch nhng yu t nh hng n qu trnh chit xut dc liu.
6. M t cc phng php chit xut: gin on, bn lin tc, lin tc
(khi nim, s , cch tin hnh, u nhc im).
7. So snh gia hai phng php chit xut vi nhau (nu ln nhng
im ging nhau v khc nhau).
Gin on v lin tc.
Gin on v bn lin tc.
Bn lin tc v lin tc.
8. Phn loi thit b chit xut.
9. Trnh by thit b chit xut bn lin tc (s , cu to, nguyn l
lm vic, u nhc im).
10. Trnh by thp chit xut loi mt ct (s , cu to, nguyn l lm
vic, u nhc im).
11. Trnh by thp chit xut loi hai ct (thp ch U trn) (s , cu
to, nguyn l lm vic, u nhc im).
12. Trnh by thp chit xut loi ba ct (thp ch U vung) (s , cu
to, nguyn l lm vic, u nhc im).
13. Trnh by thit b chit lin tc kiu nghing, loi c hai vt xon (s
, cu to, nguyn l lm vic, u nhc im).
14. So snh gia hai thit b chit xut lin tc vi nhau (nu ln nhng
im ging nhau, khc nhau v cu to, ch lm vic, chiu chuyn
ng ca hai pha v v nhng im c trng cho thit b).
177
Chng 15
Mt s qu trnh thng gp
giai on tinh ch
Mc tiu
1. Mt s khi nim c bn v lng, lc, kt tinh, hp ph.
2. S lng ca mt ht n chic v s lng ca khi ht.
3. Nhng yu t c nh hng n qu trnh lc.
4. Qu trnh hnh thnh tinh th.
5. Cc trng hp hp ph trn b mt vt rn - dung dch.
1. Lng
1.1. Khi nim
Trong chit xut dc liu, nhiu qu trnh sn xut to ra nhng hn
hp khng ng nht, cn phi tch ra. H khng ng nht l hn hp cc
cht cc trng thi khc nhau, thng gp l huyn ph (lng - rn) hoc
nh tng (lng - lng).
Chng hn khi chit strychnin t ht m tin bng dung mi hu c l
du ha, ta thu c dch chit l cc alcaloid tan trong dung mi hu c.
thu hi li dung mi hu c, ta cn phi chuyn cc alcaloid dng base sang
dng mui tan trong nc bng cch cho thm dung dch acid vo dch chit.
Khi ta s thu c mt h gm hai pha lng - lng (h nh tng) khng
tan ln vo nhau l pha nc v pha dung mi hu c. lng mt thi gian
nht nh, pha dung mi nh hn s ni ln trn, pha nc nng hn s lng
xung pha di. Gia hai pha s xut hin b mt phn chia pha. Bng cch
gn ta s tch c hai pha lng ra khi nhau. Lc ny ta s thu c pha
nc l mui ca cc alcaloid tan trong nc. Cho dung dch kim vo, cc
alcaloid ton phn s c tch di dng ta, khi s to thnh h hai pha
rn - lng (huyn ph). lng mt thi gian pha rn nng hn s lng xung
pha di, bng cch gn ta cng s tch c hai pha ra khi nhau.
178
Lng huyn ph l qu trnh tch ht rn trong huyn ph nh trng lc
ca ht. Thng huyn ph th th d lng, di tc dng ca trng lc, ht
rn trong huyn ph s lng xung y to thnh lp b, phn nc trong
trn s c tch ra bng cch gn hoc cho chy ra bng cch ht xi phng
hoc cho chy trn qua g ra ngoi.
Khi huyn ph qu long cc ht rn s lng ring l v khng nh
hng ln nhau, khi ta s c qu trnh lng n chic.
1.2. S lng ca mt ht ring l (lng n chic)
1.2.1. Tc lng
n gin ta xt h huyn ph th, ht rn c kh nng lng di tc
dng ca lc trng trng. Gi thit ht rn s lng trong mi trng lng
tnh, ht rn c dng hnh cu, kch thc v khi lng khng i trong qu
trnh lng.
Ta bit mt ht rn s lng c trong huyn ph do lc trng trng
khi khi lng ring ca ht ln hn khi lng ring ca huyn ph.
Xt cc lc tc dng vo ht rn khi lng, ta c s :

P : Trng lc ca ht
S
1
: Lc ma st
S
2
: Lc y Acsimet
R : Lc cn ca mi trng lng.

Hnh 15.1. S lng trong mi trng lng
Ta c: R = S
1
+ S
2

Nu R > P, lc cn ln hn trng lc, ht rn s l lng trong pha
lng.
Nu P > R, trng lc ln hn lc cn, ht rn s chuyn ng xung
pha di c gia tc a vi lc P - R. Theo nh lut Newton: P - R = m.a
Trong : m: khi lng ht rn
a: gia tc chuyn ng ca ht rn.
Khi sc cn cht lng tng ln th hiu s P - R gim xung, do gia tc
a cng b gim. Sau khi lng mt thi gian th lc P v R tr nn bng nhau,
do : a = 0. Ti thi im m ht rn bt u chuyn ng vi tc khng
i th tc gi l tc lng, k hiu l w
0

179
Nh vy, iu kin xy ra qu trnh lng l: P R. Lc u, trong mt
khong thi gian rt ngn, ht rn s c chuyn ng chm dn u, ri sau
s lng vi tc khng i l tc lng w
0
.
Nu P = R = S
1
+ S
2

Theo nh lut Stockes, khi ht rn ri xung di tc dng ca lc ht
trong cht lng hoc kh th lc ma st S
1
t l vi tc lng, ngha l:
S
1
= 3d w
0
, [N]
Trong : d: ng knh ca ht rn, m
W: tc lng, m/s
: nht ng lc ca mi trng, Ns/m
2
Lc y Archimedes S
2
s l: S
2
= V
2
g, [N].
Trong : V : th tch ca cc ht rn, m
3

S
2
: khi lng ring ca cht lng, kg/m
3
Lc ht P chnh l trng lng ca cc ht rn: P = V
1
g, [N]
Trong :
1
: khi lng ring ca ht rn, kg/m
3

V : th tch ca ht rn, m
3

Ta coi ht rn l hnh cu, do : V = [ ]
3
3
,
6
m
d

Thay cc gi tr ca S
1
, S
2
, vo cng thc P = S
1
+ S
2
, ta c:
V
1
g = 3dw
0
+ V
2
g Vg(
1
-
2
) = 3dw
0
.
Thay gi tr ca V vo cng thc trn ta c phng trnh:
( ) =
0 2 1
3
d 3
6
g d

( )

=
18
g d
2 1
2
0
, [m/s]
Nh vy, tc lng ca cc ht rn c dng hnh cu vi kch thc b
trong mi trng lng tnh t l vi bnh phng ng knh ca n v hiu s
t trng ca ht rn vi mi trng v t l nghch vi nht ca mi trng.
lm tng tc lng ca ht rn, ta cng c th lm gim nht ca
mi trng cht lng bng cch un nng u huyn ph theo tt c chiu cao
ca thit b lng. V khi un nng u huyn ph s khng to ra dng cht
lng i lu lm cn tr s lng ca ht rn.
180
1.2.2. Nng sut thit b lng
a huyn ph vo mt b lng, cho ng yn. Sau mt thi gian, di
tc dng ca trng lc cc ht rn s lng xung di y to thnh lp b,
cn cht lng trong c ly ra ngoi pha trn.

Hnh 15.2. S qu trnh lng
Tc lng l w
0
, tc l sau mt n v thi gian lng
l
th ht rn s i
c mt qung ng l h, ta c: h = w
0
l
, [m].
Th tch ca lng lng trong thu c trong mt n v thi gian l:

l
l 0
l
0
F hF
V
= , [m
3
/h]
V
o
= w
0
F, [m
3
/h]
T cng thc trn ta thy rng: Nng sut ca b lng t l vi din tch
lng v tc lng m khng ph thuc vo chiu cao ca b lng. Nh vy b
lng c nng sut cao l b lng c din tch lng ln. Tuy nhin chiu cao lng
cng phi ln ngn nga khng cho b b nc trong ko theo ra ngoi.
1.3. S lng ca khi ht (lng tp th)
Khi nng huyn ph tng th s lng ca cc ht khng cn t do na
m c s cn tr ln nhau, gi l s lng ca khi ht. Qu trnh lng ca
khi ht trong b lng xy ra phc tp hn qu trnh lng ca ht n chic
khi huyn ph cn long. i vi huyn ph m c, lp cc ht lng to vi
lp nc trong mt b mt phn cch. Vn tc lng b mt phn cch biu
th cho vn tc lng ca khi ht w. Vn tc lng ph thuc vo s tc ng
tng h gia cc ht, tnh cht vt l ca ht rn v lng. Kch thc v hnh
dng ht cng nh hng n qu trnh lng.
Chiu cao lng ph thuc vo nng huyn ph v thi gian lng. Mi
quan h ny c biu th bng th gi l th ng cong lng. Trn
th a) ng cong 2 tng ng vi huyn ph m c hn, c nghing t
hn so vi ng cong 1. iu ny l do c nh hng ca s va chm gia cc
ht v lp b y b lng.
l
: thi gian lng, h
F: b mt lng, m
2

h: chiu cao ca lp cht lng trong, m
w
0
: tc lng ca ht, m/s
V
0
: nng sut b lng, l lng nc trong
thu c trong mt n v thi gian, m
3
/h.
181

Hnh 15.3. ng cong lng
a) Lp b dy, b) Lp b mng.
Qu trnh lng xy ra trong b lng c hnh thnh cc khu vc khc
nhau. Nghin cu mi quan h gia chiu cao lng v thi gian lng, ngi ta
xy dng c ng cong H = f(t) tng ng vi cc khu vc trong b lng.

Hnh 15.4. Nghin cu s lng cho lp b dy
1. Vng nc trong, 2. Vng huyn ph, 3. Vng nn, 4. Vng b rn.
Ni chung phng php lng n gin, thit b r tin, d thc hin. Tuy
nhin c nhng trng hp nh huyn ph long, cc ht rn c kch thc
nh hoc cc ht nh l lng khng th lng c hoc rt kh lng th khi
ngi ta phi tch cc ht rn ra khi pha lng bng phng php lc. Hn
na dng phng php lc th c th tch mt cch nhanh hn v trit hn
so vi phng php lng.
2. Lc
2.1. Khi nim
Sau giai on chit xut ta thu c dch chit. giai on tinh ch,
thu c hot cht tinh khit, thng ta thng phi thc hin qu trnh kt
tinh. Sau khi kt tinh xong, tch ring cc tinh th ca hot cht ra khi
dung dch nc ci, ngi ta phi tin hnh qu trnh lc. Chng hn trong
qu trnh sn xut quinin sulfat t v cy canhkina, sau khi thc hin phn
182
ng to mui quinin sulfat basic ti pH = 6,5, kt tinh ri em lc. Sau khi
lc ta thu c tinh th l quinin sulfat basic, cn nc ci c cha mui sulfat
ca cc alcaloid khc b loi i.
Lc l qu trnh phn ring 2 pha rn - lng (huyn ph) ra khi nhau
bng cch cho hn hp i qua lp vt ngn xp. Mt pha (cc ht rn) s c
gi li mt pha ca b mt vt ngn, cn pha kia (nc trong) s i qua b
mt vt ngn.
lp nc trong c th i qua c vt ngn th cn phi c chnh lch
p sut gia trn v di b mt vt ngn khc phc c tr lc ca vt
ngn (lc u ch c tr lc ca vt ngn, v sau c c tr lc ca b). Nh vy
huyn ph cn phi c p sut d so vi p sut di b mt vt ngn.
Phn loi cc phng php lc:
Da vo p sut c ba loi:
+ Lc do p sut thu tnh (to bi chiu cao ct cht lng trn vt ngn).
+ Lc p lc (to bi bm).
+ Lc chn khng (to bi ht chn khng).
Da vo cu to ca lp vt ngn: rt a dng v phong ph.
+ Dng ht: n gin c th l , si, ct, than, ...
+ Dng si: si t nhn to, si bng, ay, gai, ...
+ Dng tm: nh li kim loi, ...
+ Vt liu xp: c th l loi s xp, thu tinh xp,
+ Mng lc: ngy nay k thut lc pht trin trnh cao, c
nhng loi vt ngn hin i nh mng siu lc, c th lc c c
vi khun,
Phn loi b, da vo cu to v c tnh ca b c hai loi:
B khng nn c: Gm cc ht khng b bin dng (ch yu l cc
ht tinh th) phn b to thnh cc khe h c kch thc khng i
khi thay i p sut. Lng nc nm trong b khng thay i khi p
sut thay i t 0,7 4at.
B nn c: Gm cc ht b bin dng (ch yu l nhng cht v
nh hnh). Khi tng p sut cht lng ln t t, th tch b b gim,
ng knh ng mao qun b thu hp, cn tc lc cht lng s tng
khng t l vi s tng p sut, ngha l tc lc tng chm hn so
vi s tng p sut v n mt lc no nu c tip tc tng p
sut ln na th s khng c li cho qu trnh lc.
Khi lc, theo l thuyt nhng ht rn c kch thc ln hn l lc (l mao
qun ca vt ngn) s b gi li trn b mt vt ngn, cn nhng ht c kch
183
thc b hn s chui qua l lc. Tuy nhin, thc t cng khng hn nh vy,
ch c mt s ht c kch thc b hn l chui qua l lc, cn mt s ht tuy c
kch thc b hn l lc nhng vn khng chui qua c l lc. S d nh vy
l do tnh cht bc cu ca cc ht qua ca l nn cc l mao qun s b b dn
li. Khi lp b trn b mt vt ngn dy ln th tr lc cng tng, n mt lc
no ton b mao qun s b lp kn v nc trong s khng i qua vt ngn
c, do ngi ta phi tm cch ly b ra mt cch lin tc hoc gin on,
i khi cn phi ra b mt vt ngn.
Phng trnh lc
Tc lc l lng nc trong thu c trong mt n v thi gian i vi
mt n v din tch b mt lc.
Ta c:

=
Fd
dV
C ,
s m
m
2
3

Trong :
C : tc lc, m
3
/m
2
s
F : din tch b mt lc, m
2

V : th tch nc lc, m
3

: thi gian lc, s
n gin tnh ton, y ta gi thit l lp b c to bi tp hp
ht v hnh thnh cc ng mao qun thng, song song theo hng ca dng
chy v c chiu di c nh. Nc trong chy qua cc ng mao qun ch
chy dng.
Lng nc trong c tnh theo phng trnh ca Hagen-Poiseuille:

l 8
pF r n
V
4

= , [m
3
].
Trong :
N: s ng mao qun trong 1 m
2
b mt lc. - thi gian lc, s;
R: bn knh ng mao qun, m. F - b mt lc, m
2
;
p: hiu s p sut hai pha vt ngn, N/m
2
: nht nc lc, Ns/m
2
;
l - chiu di ng mao qun, m
Phng trnh trn ch c tnh s b lng nc trong i qua lp b c
nh. Thc t trong qu trnh lc, chiu dy lp b c thay i v ph thuc
vo thi gian lc, do thc t phng trnh lc rt phc tp, ph thuc vo
nhiu yu t, y ta khng i su nghin cu.
Hnh 15.5. S qu trnh lc
184
2.2. Nhng yu t nh hng n qu trnh lc
Nhng i lng quan trng ca qu trnh lc l: nng sut lc, tch
nc, m ca b. Nhng yu t c bn c nh hng trc tip n qu trnh
lc gm:
Huyn ph: khi lng, kch thc, b mt, dng, tnh v phn
tn ca ht trong huyn ph; nhit , nht, tnh in ly ca lng,
trng lng ring ca nc trong v b.
Vch lc (gm vt ngn v b): th tch, kch thc, chiu di mao
qun, dng mao qun, tr lc ca vch lc.
Mt s yu t khc: chnh lch p sut hai u vch lc, vn tc dng
chy qua vch lc, tnh cht ca b, ch chy ca dng cht lng.
Nhng yu t trn c lp vi nhau, nhng c quan h v nh hng ln
nhau. Di y nu ln nh hng ca mt s yu t.
2.2.1. nh hng ca lp b
Vn tc ca nc trong t l thun vi ng lc v t l nghch vi tr
lc. Tr lc ca vch ngn thng rt nh so vi tr lc ca lp b, nn tr
lc chung ca qu trnh lc ph thuc ch yu vo tr lc ca lp b. V vy,
s hnh thnh lp b v xp ca lp b c vai tr rt quan trng i vi
qu trnh lc. Lp b cng mng v xp cng ln th kh nng chy qua
ca cht lng cng nhanh. Do , lp b cn th tch t do v s lng mao
qun ln.
Hnh 15.6 th hin s tng ca tr
lc theo chiu dy ca lp b trong qu
trnh lc huyn ph cha bi than vi
kch thc ht 0,5 m.
Trn hnh ta thy tr lc tng
nhanh khi mi bt u hnh thnh lp
b, khi n mt dy no th tr
lc s tng chm li v tuyn tnh vi
chiu dy. Do cho qu trnh lc
c tt, cho dng cht lng chy qua
c d dng th lp b cn phi c tr
lc nh, tng ng vi lp b c chiu
dy v cu to thch hp.
2.2.2. nh hng ca kch thc ht rn trong lp b
Lng cht lng chy qua lp b ph thuc vo kch thc ca mao qun
nn cng b nh hng bi kch thc ca tng ht ring l. Ht nh s to ra
mao qun nh, nn tr lc s ln v dng cht lng i qua s kh khn.

Hnh 15.6. Quan h gia tr lc v
chiu dy ca lp b
185
Thc t, cc ht trong lp b c kch thc khng ng u. Cc ht ln
s to thnh nhng mao qun c ng knh ln, cn cc ht dng cu b hn
s d chui vo mao qun ln lm chon mt th tch t do. V do kch thc
cc ht ln nh khc nhau nn d to kh nng bc cu, do khi kch thc
ht khng ng u th tr lc lp b cng ln. Lp b gm cc ht ln s to
thnh mng mao qun c kch thc ln v dng cht lng chy qua s d
dng hn. Lp b c nhng ht nh s c tng din tch b mt ln hn so vi
lp b ca nhng ht ln, cn m th c phn b u khp cc b mt ca
ht. Ni chung lp b m c nhng ht ln th qu trnh lc s thun li hn.
2.2.3. nh hng ca b mt ht, dng ht v tnh ca ht
B mt ca ht c nh hng n cu to ca lp b. B mt ht g gh
s to iu kin thun li cho hin tng bc cu, to kh nng tt cho s to
m. Dng ht v tch ca ht cng nh hng n s hnh thnh lp b.
Hnh dng ht rt a dng, c th l hnh a din, hnh trn, dng si
hay dng tm. Th trng ht c th l cng hay mm, c th l n hi hoc
do. B c th l tp hp nhng ht rn c cu to a dng. Cc ht a din
(nhiu gc cnh) d bc cu hn cc ht trn, kh nng tip xc nhau ca
chng nhiu hn. Cc ht hnh a din v cc ht di khi i qua mao qun d
gy tc hn so vi cc ht hnh trn. Nht l nhng ht c dng tm, do chng
xp ln nhau v to ra lp b c rt t mao qun cho cht lng i qua. Cc ht
c tnh n hi hoc tnh do cao cng d lp kn cc mao qun, hn ch hin
tng bc cu, c bit l p sut cao hay chn khng cao. Vic lc cc
loi huyn ph c cha loi b ny rt kh khn, thc t ngi ta p dng
phng php lc c bit, nh lc p lc nh v c s dng cht tr lc.
2.2.4. nh hng ca dng chy
Huyn ph cha cc ht rn dng a din v dng thanh ni chung c
tr lc dng chy thp, nht l nu cc thanh c xp theo hng ca dng.
Trong nhiu trng hp khi tc dng chy mnh th s c mt lng ln cc
thanh n vch ngn, lm bt kn cc mao qun, lm cho tr lc lc tng
nhanh. Nu vn tc dng b th s c mt lng nh cc ht c cnh di n
vch ngn v bc ngang qua mao qun, do s to ra hin tng bc cu hp
l v lp b hnh thnh xp hn.
2.2.5. nh hng ca chnh lch p sut
chnh p hai pha vch lc nh hng n dng chy ca nc
trong. Theo l thuyt, tc dng chy ca nc trong qua mao qun t l vi
p lc. p lc thay i lm nh hng n cc yu t khc trong qu trnh lc.
Lc p sut thu tnh s to ra c lp lc xp nht. Lc chn khng c
chnh p ln s to ra lp b dy.
186
Lc c p lc thng c vng lm vic vi khong p sut d t 1 1,5
at. Nu lc p sut cao, p sut d c th n 35at hoc ln hn, lm lp b
b nn mnh v mt kh nng xp, nn vn tc lc gim (Hnh 15.7) v cc ht
rn (b) b nn mnh lm mt kh nng bc cu, thm ch cc cu c lp
cng c th b b gy.
Gii hn nn ca p sut lp b c tnh n hi th nh hn so vi lp
b c ht tinh th dng cng. p sut cng tng th tr lc lp b cng ln. B
cng c nn cht th m ca b cng gim (b cng kh) (Hnh 15.8).

Nh vy, c lp b tr lc b nht cn lc p sut thu tnh, cn
mun b kh hn th phi lc p sut cao, nn vic chn p sut lc l do yu
cu c th ca thc t.
2.2.6. nh hng ca nng huyn ph
Nng cc ht rn trong huyn ph cng ln, cc hn rn cng gn
nhau v tip xc vi nhau cng thng xuyn hn, s lm gim s cn tr ln
nhau v lm ng nht qung ng lng. Huyn ph c chuyn ng theo
nhiu hng khc nhau trn b mt lp b, nn cc ht rn c gi li
mt cch ln xn to thnh lp t nhin, nc trong i qua d dng hn so
vi cc lp sp xp u n, v cc mao qun c to thnh do tnh bc cu
ca cc ht nhiu hn.
Khi c cng chiu dy lp b, nu huyn ph c nng ln hn th b s
kh hn (Hnh 15.9).
Khi nng huyn ph tng th lng b thu c trong mt n v thi
gian trn mt n v din tch b mt lc (nng sut lc) cng s tng theo
(Hnh 15.10).

Hnh 15.8. Quan h gia p sut
vi tr lc v m

Hnh 15.7. Quan h gia p sut v vn tc
187

2.2.7. nh hng ca nhit
Nhit ca huyn ph c
nh hng n nht huyn
ph, do c nh hng n tc
chy ca nc trong qua lp
b. Khi nhit huyn ph
tng ln th nht huyn ph
s gim xung v tc nc
trong s tng ln. V d: nhit
huyn ph tng t 10
0
C n
40
0
C th vn tc lc c th tng
ln gp i. Tuy nhin, thc t
cn c nhiu nguyn nhn khc
c nh hng n qu trnh lc
nh nh hng ca vch lc,
nng sut lc,. do khi tng
nhit th vn tc lc s tng
khng ln lm. Quan h gia
nhit vi nng sut lc v vi
m ca b c th hin hnh 15.11.
3. Kt tinh
3.1. Khi nim
Khi tinh ch, loi tp to ra hot cht tinh khit, ngi ta thng p
dng phng php kt tinh. Chng hn trong qu trnh sn xut strychnin t
ht m tin, tch brucin ra khi strychnin, ngi ta phi to mui nitrat

Hnh 15.9. Quan h gia m
v nng

Hnh 15.10. Quan h gia nng sut lc
v nng

Hnh 15.11. Nng sut v m b ph thuc
vo nhit huyn ph
188
sao cho mui strychnin nitrat d kt tinh hn s c kt tinh, cn mui
brucin nitrat s b tan ra trong nc ci. Sau lc loi nc ci, s thu c
strychnin tinh khit.
Kt tinh l qu trnh tch cht rn ho tan trong dung dch di dng
tinh th. Tinh th l vt rn ng nht c hnh dng khc nhau, gii hn bi
cc mt phng. Tinh th gm c cc phn t nc gi l tinh th ngm nc
(tinh th hydrat). Tu theo iu kin thc hin qu trnh m tinh th c th
ngm s phn t nc khc nhau.
3.1.1. ho tan
ho tan ca mt cht l lng ti a cht tan c trong mt n
v dung mi mt nhit nht nh. ho tan c th tnh bng g/l, g/kg,
phn khi lng ho tan ca mt cht ph thuc vo bn cht ho hc
ca cht , ph thuc vo tnh cht v nhit ca dung mi. i vi a s
cc cht, khi nhit tng th ho tan tng, khi gi l ho tan "dng".
Nhng cng c t trng hp khi nhit tng th ho tan li gim, khi
gi l ho tan "m".
Kt tinh cc cht ho tan trong dung dch da vo ho tan hn ch
ca cht rn. ho tan ca vt cht thng c xc nh bng thc nghim
v c biu din bng ng cong th hin s ph thuc gia ho tan v
nhit . i vi a s cht th ng cong l mt ng cong u n
(Hnh 15.12).
i vi nhng cht to thnh tinh th ngm nc th ng cong c im
gy (Hnh 15.13).
Khi ho tan cng c th gim khi tng nhit (on 4a-4-4b, hnh
15.14). Vn xc nh ho tan ca cht tan nhit nht nh c gi tr
thc t ln nhng cho n nay khng c cng thc no m bo chnh xc
tnh ton m tu theo tng trng hp c th m ngi ta vn dng nhng s
liu thc nghim bit.

Hnh 15.12. Quan h gia nng
bo ha v nhit

Hnh 15.13. ha tan ca tinh th ngm nc
189
ng ho tan ca mt s cht mui v c ph thuc vo nhit c
biu din trn hnh 15.14.

- ng 1-1: ng vi KNO
3

- ng 2-2: ng vi KCl
- ng 3-3: ng vi NaCl
- on 4a-4: ng vi Na
2
SO
4
.10H
2
O
- on 4-4b: ng vi Na
2
SO
4
.

Hnh 15.14. ng ho tan ca cc mui
ng 1-1 (KNO
3
): ho tan tng nhanh khi nhit tng.
ng 2-2 (KCl): ho tan tng chm khi nhit tng.
ng 3-3 (NaCl): ho tan tng khng ng k khi nhit tng.
ng 4a-4-4b ca mui sulfat natri:
+ on 4a-4 (Na
2
SO
4
.10H
2
O): ho tan tng, gi l "ho tan dng".
+ on 4-4b (Na
2
SO
4
khng ngm nc): ho tan gim-"ho tan m".
3.1.2. Cc trng thi ca dung dch
c th tin hnh c qu trnh kt tinh, ngi ta phi to ra trng
thi qu bo ho ca dung dch. Trng thi qu bo ho ca dung dch thng
khng bn, cht ho tan tha s tch ra khi dung dch kt tinh, khi
dung dch s d chuyn v trng thi bo ho.
Dung dch bo ho mt nhit nht nh l dung dch c cha lng
cht ho tan ln nht nhit . Trong dung dch bo ho th tinh th v
190
dung dch trng thi cn bng ng, c ngha l trong mt n v thi gian
c c bao nhiu tinh th mi c to thnh th cng c by nhiu tinh th b
tan vo trong dung dch.
Cc trng thi ca dung dch c biu din bng biu gi l biu
trng thi ca dung dch. Cc loi dung dch khc nhau c th hin bng
nhng biu trng thi khc nhau, th hin trn hnh 15.15 di y.

a) b) c)
Hnh 15.15. Biu trng thi ca cc loi dung dch
Trong :
+ Hnh a - biu trng thi ca dung dch mui KNO
3
.

+ Hnh b -

biu trng thi ca dung dch mui KCl.
+ Hnh c - biu trng thi ca dung dch mui NaCl.
Trn mi biu :
Vng A - vng qu bo ho, nm pha trn ng 2-2, l vng khng
n nh.
Vng C - vng cha bo ho, nm di ng 1-1.
Vng B - vng hn hp, nm gia ng 1-1 v ng 2-2. Gii hn
ca vng hn hp ph thuc vo nhit ca dung dch, vo tc
lm lnh hay bay hi, vo s khuy trn dung dch,
Tu theo tng trng hp c th m ngi ta p dng nhng phng
php kt tinh sau sao cho ph hp:
Trng hp a:
i vi nhng dung dch c tan tng nhanh khi tng nhit , v d
dung dch mui KNO
3
. Khi nhit gim t t
2
n t
1
, dung dch chuyn t
trng thi bo ho sang trng thi qu bo ho, nng dung dch s bin i
t C
0
n C
x
, sau pha rn s tch ra, dung dch s li tr v trng thi bo
ho v nng dung dch s b gim t C
x
n C
0
. kt tinh loi dung dch
191
ny thng ngi ta tin hnh lm lnh dung dch, v khong chnh lch nhit
nh nn dung dch d chuyn nhanh v trng thi qu bo ho thun tin
cho qu trnh kt tinh.
Trng hp b:
i vi nhng dung dch c tan tng chm khi tng nhit , v d
dung dch mui KCl. chuyn dung dch ny vo vng qu bo ha (t im
n im) th cn phi gim mt khong nhit ln. Do kt tinh loi
dung dch ny cn cho bay hi mt phn dung mi.
Trng hp c:
i vi nhng dung dch c ho tan thay i khng ng k theo nhit
, v d dung dch NaCl. kt tinh loi mui ny ngi ta cn thc hin
qu trnh c c.
3.2. Qu trnh hnh thnh tinh th
S to thnh tinh th bao gm hai giai on: giai on to mm tinh th
v giai on pht trin mm tinh th thnh tinh th hon chnh.
3.2.1. Qu trnh to mm
Mm tinh th (cn gi l tm kt tinh) c t hnh thnh khi dung dch
trng thi qu bo ho do dung dch c lm lnh hoc cho bc hi mt
phn dung mi. Theo quan im hin i, cc ion (phn t) cht tan khi va
chm vi nhau th lin kt li vi nhau to thnh mm.
Tc to mm ph thuc vo rt nhiu yu t: bn cht ca cht tan v
dung mi, mc qu bo ho ca dung dch, nhit , phng php khuy
trn, nng cc tp cht,
Thi gian to mm c th rt nhanh (t vi giy) cho n rt chm (c
th vi thng). S lng mm to thnh c nh hng n kch thc ca tinh
th. Khi s mm to thnh t th tinh th s ln v ngc li khi s mm to
thnh nhiu th tinh th s nh.
cho qu trnh to mm c d dng, ngi ta cho thm vo dung
dch mt t tinh th ca cht tan hoc tinh th ca cht khc nhng c cng
cu trc tinh th ging cht tan trong dung dch. Cht cho thm gi l cht
"tr mm". Bin php ny c bit cn thit i vi nhng dung dch kh to
mm, k c khi dung dch c qu bo ho rt ln.
to iu kin thun li cho qu trnh to mm cn c nhiu bin php
khc nhau: thay i nhit , tng cng khuy trn, tng cng nhng tc
ng c hc bn ngoi (rung, lc, va p,). nhm ca b mt thit b kt
tinh v vt liu lm cnh khuy cng nh hng n qu trnh to mm.
192
3.2.2. Qu trnh ln ln ca tinh th
Tinh th pht trin v kch thc v t ti gi tr ti hn ca mm.
Tinh th c nng lng b mt ln ln n ht (hp th) cc cht tan trong
dung dch. Tinh th ln ln ng thi theo tt c cc mt ca n. Tu theo
iu kin kt tinh m vn tc ln ln ca cc mt tinh th c khc nhau. Tinh
th ca mt cht c th c kch thc khc nhau. Mi mt dng tinh th ch
bn mt khong p sut v nhit nht nh. S bin dng ca tinh th c
km theo s to nhit hoc thu nhit.
Theo thuyt khuch tn th
cht ho tan bt u khuch tn
t trong lng dung dch, xuyn
qua lp bin (c chuyn ng
dng v nm st b mt tinh th)
ri sau dnh vo tinh th.
Chiu dy ca lp bin ph thuc
vo tc khuy trn dung dch.
Nu dung dch khng khuy trn
th b dy lp bin 20 150
m. Nu c khuy trn mnh th
0.
Trong thc t, qu trnh
ln ln ca mm thng xy ra
chm hn nhiu so vi qu trnh
ho tan. Tc kt tinh thay i
theo thi gian c th hin trn hnh 15.16.
S thay i tc kt tinh ph thuc vo mc qu bo ho. Lc bt
u, tc kt tinh bng 0 ( giai on to mm), ri t ti gi tr cc i,
sau li gim dn n gi tr 0.
4. Hp ph
4.1. Khi nim
Hp ph l mt hin tng b mt, l s tch t cht trn b mt
phn chia pha (kh - rn, lng - rn, kh - lng, lng - lng). Cht c b mt,
trn xy ra s hp ph c gi l cht hp ph, cn cht c tch t trn
b mt gi l cht b hp ph. Trng hp cht ny c th xuyn qua lp b
mt v i vo trong lng th tch ca mt cht khc, c gi l s hp th.
Ngc vi s hp ph, s i ra ca cht b hp ph khi lp b mt c gi l
s gii hp ph (kh hp ph). Khi s hp ph t ti trng thi cn bng th
tc hp ph bng tc gii hp ph.

Hnh 15.16. S thay i tc kt tinh
theo thi gian
1. Khi qu bo ha ln,
2. Khi qu bo ha nh.
193
Qu trnh hp ph c c trng bng mt s i lng nh sau:
hp ph a: Biu th lng cht b hp ph trn mt n v khi
lng ca cht hp ph, thng c biu din bng n v mol/g.
i lng : Ch lng cht b hp ph trn mt n v b mt ca
cht hp ph, thng c biu din bng n v mol/m
2
.
B mt ring: Din tch b mt tng ng vi 1 g cht hp ph, n
v l m
2
.
Cht hp ph cng mnh th b mt ca n cng pht trin. Nhng cht
rn xp c cu trc l rng c b mt ring rt pht trin, c th t ti hng
nghn m
2
/g nh than hot tnh, silicagel
Qu trnh hp ph c phn thnh hai loi tu theo bn cht ca lc
tng tc gia cht b hp ph v cht hp ph: hp ph vt l v hp ph
ho hc. Hp ph vt l xy ra do lc ht gia cc phn t, lc ht
Vanderwaals (c tng tc yu). Cn hp ph ho hc xy ra do lc lin kt
ho hc, c tng tc mnh.
Hp ph vt l l qu trnh thun nghch, chiu ngc ca s hp ph l
s kh hp ph. Hp ph vt l km theo hiu ng nhit nh, cc cht b
hp ph d b kh hp ph. Qu trnh tun theo nguyn 1 v chuyn dch cn
bng ca Le Chtelier.
Khc vi hp ph vt l, trong hp ph ho hc, cc phn t ca cht b
hp ph lin kt vi cht hp ph bi cc lc ho hc bn vng to thnh
nhng hp cht ho hc b mt mi. V d: s hp ph xy trn b mt kim
loi l hp ph ho hc. Hp ph ho hc c hiu ng nhit ln. Cht b hp
ph kh b kh hp ph.
Trong lnh vc hp ph ng k l nhng thuyt hp ph, nhng phng
trnh hp ph ca Langmuir, Freundlich, Polanyi, Gibbbs, Brunauer, Dubinin, ...
Da vo trng thi ca cht b hp ph v cht hp ph, ngi ta phn
ra nhng trng hp hp ph sau:
Hp ph trn b mt vt rn - kh.
Hp ph trn b mt dung dch - kh.
Hp ph trn b mt cht rn - dung dch.
Khi sn xut thuc bng phng php chit xut t dc liu, giai on
tinh ch, lm sch dung dch khi cc cht bn, cht mu ngi ta thng
dng than hot ty mu, chnh l qu trnh hp ph cht tan (cht
mu) t dung dch ln b mt vt rn (than hot). y ta ch nghin cu
trng hp hp ph trn b mt cht rn - dung dch.
194
4.2. Hp ph trn b mt rn - dung dch
S hp ph trn b mt rn - dung dch ni chung tng t nh s hp
ph trn b mt rn - kh. Tuy nhin y cc phn t ca dung mi c nh
hng ln n qu trnh hp ph.
Chng ta phn bit hai trng hp: hp ph cht khng in li v hp ph
cht in li, khi c s hp ph chn lc ca mt trong cc ion t dung dch.
4.2.1. Hp ph phn t t dung dch
Lng cht b hp ph bi 1 g cht hp ph rn c tnh theo cng thc:
a =
1000 .
m
V ) C C (
0

Trong :
a : hp ph, mol/g
C
o
, C: nng ban u v nng cn bng ca cht b hp ph, mol/l
V : th tch dung dch, l
m : khi lng cht hp ph, g.
i vi dung dch long c th p dng phng trnh hp ph ng nhit
ca Langmuir v Freundlich cho s hp ph phn t kh, trong p sut
c thay bng nng .
T phng trnh hp ph ca Langmuir, ta c:
a =
KC 1
C . K . a
max
+

Trong :
C : nng cn bng ca dung dch.
a : hp ph.
a
max
: hp ph cc i, tng ng vi ton b b mt hot ng ca
cht hp ph b che ph, c ngha l tng ng vi = 1
l phn b mt b che ph bi lp hp ph.
hp ph ng vi che ph no s l: a = a
max
.
K - hng s cn bng, ph thuc vo bn cht ca cht hp ph v cht
b hp ph, l mt hm ca nhit .
T phng trnh hp ph ca Freundlich, ta c:
a = .C
1/n

195
Phng trnh Freundlich p dng tt cho vng c nng trung bnh.
Trong :
, 1/n: hng s thc nghim.
V tr s bng hp ph khi nng bng 1.
Khi hp ph trn b mt rn t dung dch, thng th 1/n = 0,1 0,5.
Khi 1/n=0 a=, khi hp ph t gi tr cc i khng i.
Khi 1/n=1 a=C, hp ph t l thun tuyn tnh vi nng
dung dch.
Di y s xt nhng yu t nh hng n s hp ph t dung dch.
nh hng ca dung mi
Cc phn t dung mi l i th cnh tranh vi cc phn t cht tan
trong qu trnh hp ph. Nu dung mi b hp ph km hn trn cht hp
ph cho th cht tan s c hp ph tt hn. Nhng cht hot ng b
mt c sc cng b mt nh hn sc cng b mt ca dung mi s b hp ph
mnh hn trn b mt rn. Chnh v vy s hp ph t dung dch nc thng
mnh hn nhiu so vi s hp ph t cc dung dch vi dung mi l
cacbuahydro, ru v cc cht lng hu c khc c sc cng b mt nh hn so
vi nc. C th ni rng nu cht tan ho tan tt trong mt dung mi no
th s hp ph trong mi trng s yu v ngc li. Trn c s cng c
th rt ra c s lin h gia kh nng hp ph vi hng s in mi cng
nh sc cng b mt ca mi trng trong xy ra s hp ph.
nh hng ca tnh cht cht hp ph v cht b hp ph
Nhng cht hp ph phn cc (silicagel, t st, ...) hp ph tt cc cht
phn cc, nhng cht hp ph khng phn cc (than) hp ph tt cc cht
khng phn cc. Rehbinder a ra quy tc v s ph thuc ca hp ph
vo phn cc ca cc cht trong h. Theo quy tc ny, mt cht C no c
th b hp ph trn b mt phn chia hai pha A v B khi hng s in mi ca
n c gi tr trung gian gia hng s in mi ca A v ca B, ngha l:
A
>
C
>
B
hay l
A
<
C
<
B

i vi nhng cht hot ng b mt m phn t c hai phn (phn phn
cc v phn khng phn cc) th khi b hp ph trn b mt phn chia pha s
c s nh hng phn t nh sau: phn phn cc hng v pha phn cc,
phn khng phn cc hng v pha khng phn cc.

196

Hnh 15.19. S s nh hng cc phn t cht hot ng b mt
trn b mt phn chia hai pha bn cht khc nhau
Cu trc xp vi cc mao qun ca cht hp ph cng nh hng n s
hp ph bi v s hp ph xy ra ch yu l trn b mt cc mao qun. i vi
cc phn t nh c kh nng i su vo cc mao qun th khi xp ca cht
hp ph tng, hp ph tng. i vi cht hp ph c mao qun hp, khi
kch thc phn t cht b hp ph tng th hp ph gim.
4.2.2. Hp ph ion
y chng ta ch xt s hp ph ion t cc dung dch trong nc. Cc
ion b hp ph trn nhng b mt cu to t nhng phn t phn cc hoc t
nhng ion. Cho nn, hp ph ion cn mang tn l hp ph phn cc.
Nhng phn b mt vi din tch nht nh hp ph t dung dch nhng
ion c in tch tri du. Lc cc ion tri du vi cc ion b hp ph di
tc dng ca lc ht tnh in s cng vi nhng ion b hp ph to ra mt
lp in tch kp.
i vi nhng ion c cng in tch, kh nng b hp ph tng theo bn
knh ion. iu ny c gii thch bi s tng phn cc ca ion v bi s
gim hydrat ho m lp v hydrat ho cng mng th tng tc in cng
tng. V d, chng ta c nhng dy sau theo chiu tng kh nng b hp ph:
Li
+
< Na
+
< K
+
< Rb
+
< Cs
+

Mg
2+
< Ca
2+
< Sr
2+
< Ba
2+

Cl
-
< Br
-
< NO
3
-
< I
-
< NCS
-

in tch ion cng ln th tng tc in cng mnh v kh nng b hp
ph cng ln. V d: K
+
<< Ca
2+
<< Al
3+
<< Th
4+

Bn cht b mt cht hp ph c nh hng c bit n s hp ph
chn lc t dung dch. B mt rn thng hp ph chn lc t dung dch
nhng ion c trong thnh phn ca n hoc hp ph chn lc t dung dch
nhng ion c kh nng to thnh vi nhng ion c trong thnh phn ca n
nhng hp cht t tan. V d: Tinh th AgI hp ph ion I
-
t dung dch KI hoc
ion Cl
-
t dung dch NaCl. iu ny c gii thch bi s xy dng cc cu trc
Nc Benzen
Than Silicagel
Phn phn cc
Phn khng phn cc
197
tinh th bng nhng lin kt bn vng vi b mt cht rn. Than c kh nng
gi cht nhng gc carbuahydro ca cc cht hu c, cn oxyd v hydroxyd ca
nhm v st th c kh nng lin kt cht nhng nhm c cha oxy.
4.2.3. Hp ph trao i
Nu nh mt cht in li b hp ph trn b mt cht hp ph th khi
cht hp ph tip xc vi mt cht in li khc s xy ra s trao i ion gia
lp in tch kp ca n vi mi trng. Cht hp ph ly t dung dch mt
lng xc nh nhng ion no v ng thi trao i vo trong dung dch
mt lng tng ng cc ion in tch cng du. l s hp ph trao i.
S trao i ion khng nhng xy ra trn b mt cht hp ph m cn c
th xy ra nhng lp nm su bn trong n nu dung dch c th ti c.
Cht hp ph c th c bn cht acid hoc bn cht base. Cht hp ph acid
c kh nng hp ph trao i cation c gi l cationit. Cht hp ph base c
kh nng hp ph trao i anion gi l l anionit. S trao i ion c m t
theo s sau:
Cationit
-
H
+
+ Na
+
+ Cl
-
Cationit
-
Na
+
+ H
+
+ Cl
-

Anionit
+
OH
-
+ Na
+
+ Cl
-
Anionit
+
Cl
-
+ Na
+
+ OH
-
Tn ti c nhng cht hp ph lng tnh c kh nng trao i cation
trong nhng iu kin nht nh v trao i anion trong nhng iu kin
khc. Nhng cht trao i ion (ionit) c th l alumosilicat (nh permutit
Na
2
O.Al
2
O
3
.3SiO
2
.2H
2
O), than c hot ho bi hydro hoc bi oxy hay
nhng cht nha tng hp c bit (cc polyme).
Hp ph trao i ion c ng dng trong vic lm mm nc cng; tch
cc nguyn t, c bit l cc nguyn t him v cc sn phm phng x;
iu ch cc ha cht tinh khit,...
T lng gi
1. Trnh by qu trnh lng, lc, kt tinh, hp ph.
2. Trnh by s lng ca mt ht n l.
3. Trnh by s lng ca khi ht.
4. Phn loi cc phng php lc.
5. Phn loi cc kiu b.
6. Tnh s b lng nc trong thu c sau qu trnh lc.
198
7. Phn tch nhng yu t c nh hng n qu trnh lc.
8. nh ngha ho tan ca mt cht.
9. Trnh by cc trng thi ca dung dch.
10. Qu trnh to mm v qu trnh ln ln ca tinh th xy ra nh th no?
11. Trnh by mt s i lng c bn c trng cho qu trnh hp ph:
hp ph a, i lng , b mt ring.
12. Phn loi qu trnh hp ph da vo bn cht ca lc tng tc gia
cht b hp ph v cht hp ph.
13. Th no l hp ph vt l v hp ph ho hc?
14. Phn bit gia hp ph vt l v hp ph ho hc?
15. Phn tch nhng yu t c nh hng n s hp ph trn b mt vt
rn t dung dch.
16. Trnh by qu trnh hp ph ion t cc dung dch trong nc.
17. Trnh by qu trnh hp ph trao i ion.
199
Chng 16
K thut sn xut mt s nguyn liu
di dng cao thuc
Mc tiu
1. Khi nim, k thut iu ch v cc ch tiu cht lng chnh ca cao thuc.
2. Mt s v d cao thuc.
1. Khi nim cao thuc
Nhng ch phm iu ch bng cch chit xut dc liu mt kch
thc tiu phn nht nh vi dung mi chit thch hp c gi chung l cao
thuc. l nhng ch phm c th cht lng (cao lng, cn thuc), bn rn
(cao mm) hay rn (cao kh).
Nu dung mi chit xut l ethanol v dch chit thu c khng qua
giai on bc hi dung mi, ch phm thu c gi l cn thuc.
Cao thuc c th l dng bo ch hon chnh, c s dng trc tip
(thuc sc, thuc hm, cao lng) nhng thng thng, l nhng sn phm
trung gian dng bo ch cc dng thuc khc (v d sir, vin trn, vin nn,
vin nang).
Cao thuc thng c loi bt mt phn tp cht trong qu trnh iu
ch. T l hot cht trong cao thuc thng cao hn t l hot cht trong dc
liu. Ring cao lng th t l hot cht c th bng t l hot cht c trong dc
liu.
Dc liu iu ch cao thuc c th l dc liu thc vt hay ng vt,
cn ti hoc sy kh, c chia nh n kch thc thch hp.
Dung mi chit xut phi l nhng dung mi khng c hi, v thng
khng loi ht dung mi khi cao thuc. Nu cao thuc phi loi ht dung mi
(v d cao kh), hoc sau khi x l dch chit ch cn li dung mi khng c,
th c th u tin yu t chn lc v kinh t ca hn hp dung mi s dng.
Dung mi nc v hn hp ethanol - nc c s dng ph bin nht trong
iu ch cao thuc, c bit khi cao thuc yu cu tan c trong nc.
200
Cc dch chit v cao thnh phm thng cha nhiu vi sinh vt nhim
t nguyn liu ban u (vi khun, nm mc, nm men), nht l khi n c
iu ch nhit thp bo v hot cht. Bn thn cao thuc cng l mi
trng dinh dng thun li cho vi sinh vt pht trin. V vy cn ch s
dng cc bin php thch hp gim bt vi sinh vt v bo qun cao thuc.
Ngoi ra cao thuc c th cha nhng t dc thch hp nhm mc ch
tng tnh ng nht, iu chnh th cht, iu chnh hm lng hay bo qun.
2. Phn loi cao thuc
Theo th cht, cao thuc c chia lm 3 loi:
Cao lng: C th cht lng hi snh, thng qui c 1 ml cao lng
tng ng vi 1 g dc liu dng iu ch cao thuc.
Cao c: C th cht c qunh hoc do, s khng dnh tay nhit
thng, nhng chy lng thnh khi dch c hoc nht khi un
nng. Cao c c iu ch bng cch c c ko di v cn thn cc
dch chit dc liu. T l dung mi cn li trong cao thng khng
qu 20%. Do c n nh km v d nhim vi sinh vt nn phn ln
cao c nay c thay bng cao kh.
Cao kh: L khi kh hay bt kh, rt d ht m. Hm m (hoc mt
khi lng do lm kh) khng qu 5%. Ngoi l mt s cao kh (hm
m di 5%) nhng c th cht do, v d khi cao cha nhiu hp
cht thn du, hoc cao c t l ln cc thnh phn thn nc to ra
hn hp eutectic. Khi lnh, khi do rn li v c th nghin c.
Dc in Chu u cn phn bit mt s loi cao nh sau:
Cao qui nh hm lng (quantified extracts): L cao c iu chnh
hm lng cc thnh phn n mt gii hn nht nh.
Cao chun ho (standardised extracts): L cao c iu chnh hm
lng cc thnh phn c hot tnh iu tr bit n mt gii hn
nht nh.
Ngoi ra, c th phn loi cao thuc theo dung mi chit xut (cao
nc, cao cn, cao ete), theo phng php chit xut (thuc sc, thuc
hm) hay theo trng thi dc liu em chit xut (cao dc liu ti,
cao dc liu kh).
3. K thut iu ch
Qu trnh iu ch cao thuc thng bao gm nhng giai on sau:
Chun b dc liu, dung mi.
Chit xut hot cht.
201
Loi bt tp cht.
C c, sy kh.
iu chnh hm lng hot cht
Hon chnh ch phm.
3.1. Chun b dc liu, dung mi
Dc liu phi t tiu chun qui nh. m bo cht lng cao thuc
cn lu nhng vn sau:
B phn dng c ph hp theo qui nh.
T l tp cht trong dc liu.
Mc nhim vi sinh vt.
Gii hn cht dit cn trng, cht bo qun.
Gii hn tro sulfat, kim loi nng.
Dc liu thng c sy kh v chia nh ti mn thch hp. Mc
chia nh dc liu ph thuc vo cu trc vt l ca dc liu, kh nng
khuch tn ca dung mi, t l dung mi s dng v thi gian qui nh
chit kit dc liu. V d nu cn chit kit nhanh hot cht trong dc liu
c cu trc rn chc, dc liu phi c nghin mn. Dc liu mm, xp
v d thm dung mi c th c chit dng bt th. Tu theo b phn dng,
mc chia nh c th p dng nh sau:
L, hoa, cy tho: tn nh (4 mm)
Thn g, v cy, r: tn nh (2,8 mm)
Qu v ht: tn nh (2 mm)
Dc liu cha alcaloid: tn mn (0,7 mm)
Mt s dc liu c bit c th phi dit men hoc loi cht bo. Cc bt
dc liu khc nhau c th c trn ln trc khi chit.
Dung mi iu ch cao thuc thng l nc, ethanol, ete ethylic. C
th dng hn hp ethanol - nc hoc ethanol - ete. Nc l dung mi thng
dng v r tin, nhng c nhc im ho tan nhiu tp cht, cao kh bo
qun. Ethanol ho tan c nhiu loi hot cht, ho tan t tp cht nn c
dng rng ri hn, cao thuc d bo qun hn. Ete t dng v t tin v d
chy n. Dng ete trong trng hp hot cht ch tan trong ete, hoc dng
loi tp cht du, m, sp trong dch chit.
tng tan ca hot cht, c th acid ho hoc kim ho dung mi
bng acid hydrocloric, acid acetic, amoniac, natri hydroxyd. iu ch cao c,
cao kh nn dng dung mi d thu hi v ti s dng c.
202
Dung mi chit xut phi t tiu chun Dc in qui nh. Nc dng
chit xut phi l nc tinh khit t tiu chun Dc in hoc nc ung c.
3.2. Chit xut hot cht
Tu theo bn cht ca dc liu v dung mi, tiu chun cht lng
thnh phm cng nh iu kin trang thit b v qui m sn xut, c th s
dng cc phng php: ngm, ngm kit, chit xut ngc dng hay cc
phng php thch hp khc.
Nu dung mi l nc thng dng phng php ngm phn on (ngm
lnh, hm, hm, sc), t khi dng phng php ngm kit. Lng nc thng
gp 8-12 ln lng dc liu. Dung mi l ethanol, ete thng p dng phng
php ngm kit. La chn cn tu theo thnh phn ca dc liu. Dc liu
cha hot cht d tan trong nc dng ethanol 30
o
-60
o
; dc liu cha
alcaloid, glycosid dng ethanol 70
o
; dc liu cha tinh du, nha thm dng
ethanol 80
o
-90
0
; dc liu c hot cht d b thu phn dng ethanol 90
o
-95
o
.
Lng dung mi thng dng gp 6 ln lng dc liu.
3.2.1. Phng php ngm lnh
Cho dc liu chia nh ti mn thch hp (thng l bt th) v
dung mi vo mt bnh kn nhit phng. Ngm trong thi gian xc
nh; thnh thong c khuy trn hoc lc. Sau gn, p b ly dch chit.
lng 2-4 ngy ni mt loi tp cht l lng. Gn, lc ly dch trong. C th
ngm n gin hoc ngm phn on.
Ngm n gin: ngm mt ln vi ton b lng dung mi.
Ngm phn on: chia dung mi ra nhiu phn ri ngm lm nhiu
ln. Sau mi ln ngm, gn ly dch chit, p b, li cho dung mi
mi vo ngm v lm tip nh trn. Cui cng tp trung cc dch
chit li. Cng lng dung mi, ngm phn on rt c nhiu hot
cht hn ngm n gin.
Phng php ngm lnh dng cho cc dc liu cha hot cht d tan
hoc d b phn hu nhit cao.
3.2.2. Phng php ngm nh git (ngm kit)
Ngm nh git l phng php chit xut bng cch cho dung mi chy
rt chm qua khi dc liu ng trong mt dng c c bit gi l bnh ngm
kit. Qu trnh chit xut khng c khuy trn.
Nguyn tc ca phng php:
Khi cho dung mi vo bt dc liu, do trng lc dung mi chy xung
cc khe h. Trong thi gian dung mi c gi li v tip xc vi dc liu,
hot cht c ho tan. Sau thm dung mi mi ln mt khi dc liu, lp
203
dung mi ny ngm vo trong khi dc liu v y dch chit (lp dung mi
c ho tan dc cht) ra ngoi. Lp dung mi mi tip tc ho tan hot
cht cn trong t bo dc liu. Qu trnh tip din cho n khi khng thm
dung mi na. Nh vy c liu lun c tip xc vi dung mi mi nn c
th chit kit hot cht.
Ngm nh git bao gm cc giai on sau:
Chun b dc liu:
Dc liu cn phi kh v c chia nh n mn thch hp. Cng nh
trong phng php ngm, cn hn ch ti a t l bt mn khi chia nh dc
liu. Dc liu qu mn d ln vo dch chit v d gy tc bnh chit.
Lm m dc liu:
Mc ch ca giai on ny dc liu kh ht dung mi v trng n
hon ton trc khi c chuyn vo bnh chit. Nu dc liu khng c
lm m v trng n hon ton, chng s tip tc trng n trong bnh chit,
to ra khi nn chc cn tr dung mi thm qua. Hn na nu dc liu khng
c lm m t trc, khi chuyn vo bnh chit s kh ui ht khng kh ra
khi dc liu, to ra cc khong trng lm cn tr dc liu tip xc vi dung
mi, gim hiu sut chit xut.
Trong mt dng c thch hp, trn dc liu vi mt lng dung mi cho
va m. Lng dung mi lm m tu theo kh nng ht dung mi v
trng n ca bt dc liu, thng 50 - 100% lng dc liu em chit.
Trn u dc liu vi dung mi, y kn yn khong 2 - 4 gi sau ry
qua ry c kch thc mt ry to bt ti u. Cng c th lm m dc
liu ngay trong bnh ngm kit nu dc liu t trng n v bnh chit c
thit k thch hp.
Ngm trung gian:
Cho t t bt dc liu lm m vo bnh tng lp mt, nn nh nhng
v san bng mt trn khi bt. Cho dc liu khng u s to ra cc knh,
dung mi chy theo cc knh m khng thm u qua ton b khi bt. t
mt tm giy lc v cc vt ln trn, mc ch dung mi phn b u v
trnh xo trn dc liu. Sau m van di y bnh, thm dung mi n
khi khng kh thot ra ht v dch chit bt u chy ra. Kho van li v
thm tip dung mi cho ngp dc liu, ngm trong khong 24 gi hoc lu
hn tu loi dc liu.
Rt dch chit:
M kho cho dch chit chy tng git vo bnh hng. Ch thng
xuyn thm dung mi ngp mt dc liu 2 - 3 cm. Tc rt dch chit
ph thuc vo khi lng v tnh cht dc liu s dng. Rt dch qu nhanh
s khng chit kit hot cht; rt dch qu chm, thi gian chit ko di v
hao ph dung mi do bay hi. Vi m chit 1000 g dc liu, tc rt dch
chm khong 1 ml/pht, trung bnh 1 - 3 ml/pht v nhanh l 5 ml/pht.
204
Phng php ngm kit thng c dng chit xut dc liu c hot
cht c mnh. Dung mi chit thng l cn hoc ete. Dc liu cha nhiu
cht keo, tinh bt, cht nhy khng nn p dng phng php ngm kit vi
dung mi c nc. Phng php c u im tn t dung mi v chit kit c
hot cht.
Ngm kit phn on:
Phng php ngm kit nh trn c gi l ngm kit n gin, trong
lun s dng dung mi mi chit n kit hot cht. Phng php ngm
kit phn on c s dng dch chit long chit dc liu mi.
Dc liu c chia ra nhiu bnh, lng u nhau hoc nh dn (v d
1000 g dc liu chia lm ba bnh 500 g, 300 g, 200 g). Tin hnh chit xut
nh ni trn, nhng dch chit ln th nht ca bnh I (bng 80% lng
dc liu) ring; dch chit ln sau dng lm m v chit phn dc liu
bnh II. Dch chit ln th nht ca bnh II bng lng dc liu trong bnh
ring; dch chit ln sau ca bnh II li dng lm dung mi chit xut bnh III,
tip tc nh trn cho n ht.
Phng php ny c u im tn t dung mi v thu c dch chit m
c, nhng nhc im l khng chit kit hot cht.
3.3. Loi bt tp cht
Khi chit bng dung mi nc hay ethanol, dch chit thng cha nhiu
tp cht. Cn phi loi tp cht v chng thng d phn hu nh hng n
cht lng cao thuc. Cao s khng n nh, c mi l, khi ho cao vo nc,
dung dch s khng trong. Trng hp iu ch cao c, cao kh, nu hm
lng hot cht cha qui nh cng c th phi tin hnh loi bt tp cht.
Phng php loi tp ph thuc vo bn cht tp cht c trong dch
chit, tc l ph thuc vo bn cht dc liu, loi dung mi v phng php
chit. Tuy nhin c mt s phng php chung nh sau:
Loi tp cht tan trong nc (thng l protein, gm, cht nhy, pectin,
tinh bt)
Phng php dng nhit: c c dch chit cn 1/2 - 1/4 th tch ban
u, lng ch mt sau gn lc. Nu dch chit cn vn c, c
th thm bt giy lc nghin nh hoc bt talc vo nc chit, un si
v lc. Cch ny c th loi c protein, cht nhy v cc cht khc
d b ng vn do nhit.
Phng php dng ethanol: c dch chit n khi t t l khong 2
kg nguyn liu/1 lt nc chit, thm 2-3 ln th tch ethanol 95
o
,
khuy trn u, lng ch mt sau gn lc. Ct thu hi ethanol
ri c c n th tch qui nh. Phng php ny c th loi c
cht nhy, albumin, gm.
205
Phng php iu chnh pH: dch chit c c c iu chnh n
pH 12, phn ln cc hot cht v tp cht s ta, khi cho acid vo
c pH = 5 - 6 th mt s hot cht tan tr li cn hu ht cc tp
cht khng tan. Phng php ny thng p dng i vi dch chit
cha hot cht flavonoid, alcaloid.
Loi tp cht tan trong ethanol (nha, cht bo).
C c dch chit h thp cn, nha v cht bo s kt ta.
loi chng trit hn, c th pha long gp i bng nc (hoc
nc acid nu hot cht l alcaloid), hoc thm 2% bt talc hp
ph tp cht v to iu kin cho n kt ta.
Dng parafin: dch chit c c c cn li 1/2 - 1/4 th tch ban u,
thm parafin vo dch chit nng, khuy k v ngui. Vt lp
parafin ho tan tp cht.
Ngoi ra, c th dng ether chit cht bo v nha ra khi dch
chit nc.
3.4. C c v sy kh
iu ch cao thuc, thng phi tin hnh bc hi dung mi. Vi cao
lng th c c dch chit n t l qui nh (1 ml cao lng tng ng vi 1 g
dc liu). Khi chit bng phng php ngc dng hay ngm kit, trnh
tc ng ca nhit nn ring phn dch chit u m c (phn ny cha
lng ln hot cht chit c). Sau c c cc phn dch chit tip theo ri
phi hp vi dch chit u.
iu ch cao c, c dch chit n m khng qu 20%. Trng hp
ch cao kh, tip tc sy kh n m khng qu 5%.
C th dng nhiu thit b c, sy khc nhau, nhng tt nht l tin
hnh p sut gim v nhit sao cho s phn hu hot cht l ti thiu
(thng khng qu 60
0
C). Trnh c hoc sy ko di nhit cao.
3.5. Xc nh v iu chnh t l hot cht
i vi cao thuc c qui nh hm lng, sau khi iu ch phi nh
lng hot cht, nu cha t phi iu chnh cao c t l hot cht ng
qui nh.
Trng hp cao lng c t l hot cht thp hn quy nh, th tin hnh
c tip loi bt dung mi. Nu hm lng hot cht cao hn quy nh, c
th pha long bng dung mi thch hp.
Cao c v cao kh c hm lng hot cht thp hn qui nh, phi c
tip dung mi hoc loi bt tp cht. Nu cao hn qui nh c th dng cc t
dc n tr nh dextrin, lactose, tinh bt hay b dc liu nghin mn. Lng
t dc n tnh theo cng thc sau:
206
x =
( )
T
b
a R
100

Trong :
a : lng hot cht (g) c trong cao
b: hm lng hot cht qui nh (%)
R: hm m cho php (%)
T: khi lng cn kh ca tng lng cao (g)
x: khi lng t dc n cn thm (g)
m bo tnh ng nht khi thm t dc n, c th tin hnh nh sau:
C dch chit n th cao mm. Cn v xc nh t l cn kh v hm
lng hot cht. T tnh c lng t dc n cn dng. Sau khi
thm t dc n, cao mm c lm kh n khi t hm m
mong mun.
Trng hp cao kh t hm m qui nh, c th thm t dc n
bng cch nghin cng vi cao kh.
Ngoi ra iu chnh hm lng hot cht trong cao thuc c th thc
hin bng cch phi hp cc m cao c hm lng hot cht khc nhau.
3.6. Hon chnh ch phm
Cao lng ung c th thm cc cht iu hng v nh sir n,
menthol, tinh du, vanilin...
Thm cc cht bo qun chng nm mc nh: acid boric, acid benzoic,
natri benzoat, nipagin, nipasol. Vic thm cc cht bo qun vo cao
thng c thc hin cui giai on c c.
4. Cc ch tiu cht lng cao thuc
Cm quan: cao thuc phi c th cht, mu sc, ng nht theo
qui nh; c mi, v ca dc liu tng ng
tan: cao lng phi tan hon ton trong dung mi dng iu
ch cao.
Mt khi lng do lm kh: thng thng cao c khng qu 20%, cao
kh khng qu 5%.
Cc ch tiu khc: nhim khun, gii hn thuc bo v thc vt,
kim loi nng, cht bo qun, nh tnh, nh lng.
5. Bo qun, ghi nhn
Bo qun cao thuc trong bao b kn, trnh nh sng, ni kh ro,
thong mt, nhit t thay i. Ni dung nhn cn ch r loi cao (lng, c,
207
kh); tn dc liu dng; trng thi dc liu (ti hay kh); t l cao so vi
dc liu; tn v lng t dc thm vo ( pha long, n nh, bo qun);
loi dung mi s dng v hm lng hot cht (nu c).
6. Mt s v d cao thuc
Bng 16.1. Mt s cao thuc thng gp
Tn cao thuc Dc liu
Dung mi v
phng php
chit xut
Hm lng
Cao lng canhkina
(DVNI tp 1)
V canhkina
Nc acid,
ngm kit
3,5% alcaloid ton phn
Cao kh benladon
(DVNI tp 1)
L benladon
Ethanol 70
o
,
ngm kit
1,4-1,5% alcaloid ton phn
tnh theo hyoscyamin
Cao c actis
(DVNIII)
L actis 2,5% cynarin
Cao ch mu (DVNIII)
Hng ph, ch
mu, ngi cu
Nc, sc
Cao kh l benladon
chun ho (BP 2003)
L benladon Ethanol 70
o

0,95-1,05% alcaloid ton
phn tnh theo hyoscyamin
Cao lng ipeca chun
ho (BP 2003)
R ipeca Ethanol 70
o

1,9-2,1% alcaloid ton phn
tnh theo emetin
Cao lng cam tho
chun ho (BP 2003)
R cam tho Ethanol 70
o
3,0-5,0% acid glycyrrhizic
Cao kh l keo chun
ho (BP 2003)
L cy keo
Ethanol 50
o
-
80
o

5,5-8,0% hydroxyanthracen
glycosid, tnh theo sennosid B
Cao kh l hi chun
ho (Ph Eur 1997)
Nha l l hi Nc
19-21% hydroxyanthracen
tnh theo barbaloin
T lng gi
1. Trnh by khi nim cao thuc. Phn bit cc loi cao lng, cao c,
cao kh, cao qui nh hm lng hot cht v cao chun ho.
2. Nu nhng yu cu ca dung mi dng iu ch cao thuc.
3. Trnh by k thut iu ch cao thuc.
4. Nu cc ch tiu cht lng chnh ca cao thuc.
5. Nu mt s v d cao thuc: nguyn liu, dung mi v phng php
iu ch.
208
Chng 17
Chit xut Alcaloid
Mc tiu
1. Cc tnh cht l ha ch yu ca cc alcaloid.
2. Cc phng php chung chit v tch cc alcaloid.
3. S qui trnh sn xut v m t qui trnh sn xut mt s alcaloid:
quinin, strychnin, atropin, berberin, palmatin, rotundin v cc alcaloid
thuc phin.
1. i cng v alcaloid
1.1. nh ngha
Alcaloid l mt cht hu c c cha nit a s c nhn vng, c phn ng
kim, thng gp trong thc vt v i khi trong ng vt, thng c dc lc
tnh mnh v c, cho kt ta v phn ng mu vi mt s thuc th gi l
thuc th ca alcaloid.
1.2. Phn b
Alcaloid thng cha trong cc b phn ca cy nh hoa, l, r, ht, v.
i khi trong cng mt cy th b phn ny rt giu alcaloid b phn khc li
khng c.
Lng alcaloid v t l thnh phn cc alcaloid trong cy c th thay i
ty theo ma thu hi, tui ca cy, iu kin kh hu, th nhng...
Trong mt cy thng cha cc alcaloid c cu trc ho hc gn ging
nhau. c bit trong mt s cy c cha ti vi chc alcaloid nh cy thuc
phin, cy canhkina.
Cc alcaloid trong cy tn ti di dng mui vi cc acid hu c nh
acid succinic, acid oxalic, acid malic, acid meconic.
T l phn trm cc alcaloid trong cc b phn ca cy c th rt cao t
10 n 15% hoc rt thp vi phn nghn, thm ch vi phn vn.
209
Thm thc vt vng nhit i thng c nhiu cy c cha alcaloid vi
hm lng cao.
2. Tnh cht chung ca alcaloid
Alcaloid thng c cu trc phc tp gm c C, H, N, v O, trong nit
thng nm trong mch vng (d vng c nit) v mang li tnh kim cho n.
Chng c mt s tnh cht l ho chnh sau.
2.1. Tnh cht l hc
Th trng:
Alcaloid thng l cc cht c trng lng phn t cao, thng th rn
nhit thng. Cc alcaloid th rn thng l cc alcaloid khng bay hi,
cc alcaloid bay hi thng th lng. Cc alcaloid th rn thng l cc
cht d kt tinh v c chy xc nh. Mt s alcaloid khng o c chy
do n b ph hu nhit thp hn chy. Cc alcaloid dng lng nhit
thng thng khng c oxy trong phn t (nicotin, spartein). Cc alcaloid
th lng di dng t do nhng khi to mui vi acid th n c th chuyn
sang th rn (spartein th lng nhng spartein sulfat th rn). Tuy nhin
c mt vi ngoi l mt s alcaloid c oxy trong phn t nhng vn th lng
nh arecolin (C
18
H
15
ON
2
), pilocarpin (C
11
H
16
O
2
N
2
).
Mu sc
a s cc alcaloid thng khng mu hoc mu trng (cc alcaloid c nit
bc 3), mt s c mu vng (cc alcaloid l cc hydroxyd amoni bc 4). Ngoi ra
c mt s alcaloid dng base khng mu nhng mui ca n vi acid li c
mu (VD sanguinarin base khng mu nhng mui ca n c mu ).
Mi v
Alcaloid thng c v ng.
Nng sut quay cc
Do cu trc ca phn t alcaloid phc tp c cha carbon bt i nn c
tc dng vo nh sng phn cc. Thng alcaloid t nhin c tc dng quay
mt phng nh sng phn cc sang tri (t tuyn). Mt s alcaloid tn ti trong
thc vt di dng ng lng cc ng phn t v hu ta c dng racemic.
tan:
Alcaloid thng khng tan trong nc, tr mt s trng thi lng nh
nicotin d tan trong nc. Alcaloid tan tt trong cc dung mi hu c nh cn,
benzen, toluen, diclomethan. Ngc li, mui ca n vi cc acid hu c v v
c d tan trong nc v mt s dung mi hu c phn cc v khng tan trong
dung mi hu c khng phn cc. Cc dung mi hu c phn cc mnh nh
ethanol v methanol thng ho tan c alcaloid dng mui v dng base.
210
2.2. Ha tnh
Tnh kim:
Alcaloid c nit ho tr 3, c tnh kim tng t nh NH
3
tc dng vi
acid to mui.

Mui hydroclorid
+ HCl
. HCl Alc N
N
Alc

Alcaloid c nit ha tr 5 to mui vi acid loi nc:

Alc
Alc
+ HCl
Mui clorid
N OH N Cl
+

H
2
O

Cc mui thng vng bn hn alcaloid base v trng thi mui chng
kh bin thnh ng phn h bin. Mt khc, di dng mui vi acid chng
tan rt tt trong nc nn chng thng c dng lm thuc. bn vng
ca cc mui ca alcaloid i vi s thy phn ph thuc vo tnh kim mnh
yu khc nhau ca cc alcaloid v bn cht ca acid m n kt hp vi. Tr
alcaloid nhm xanthin, a s cc alcaloid c gi tr pK nh hn 7.
Alcaloid l cc base yu nn chng d dng b cc base mnh v trung
bnh nh NaOH, Ca(OH)
2
, Na
2
CO
3
, NaHCO
3
, NH
4
OH y ra khi mui ca
chng vi acid to alcaloid base.
Tnh cht ny ca alcaloid c ng dng trong chit xut alcaloid t
dc liu.
3. Cc phng php chung chit alcaloid
Trong nguyn liu thc vt ngoi alcaloid cn c v s cc cht khc nh
protein, nha, tanin, terpenoid, glycosid, sp.... Chit xut cc alcaloid l tch
chng ra khi dc liu di dng tinh khit, khng ln cc tp cht ho hc
khc nhau c cha trong dc liu.
Da vo cc tnh cht chung ca alcaloid ngi ta a ra 2 phng php
chung chit tch cc alcaloid ra khi nguyn liu thc vt.
3.1. Phng php chit alcaloid di dng base bng dung mi hu c
khng phn cc (Hnh 17.1)
u im:
Hiu sut chit cc hot cht t dc liu cao do dch chit rt ra sch,
d tinh ch loi cc tp i km theo. Cc dung mi hu c khng phn cc
thng l cc dung mi c kh nng chit chn lc i vi alcaloid dng base.
Nhc im:
Dung mi hu c thng l cc dung mi t tin. Khi s dng cc dung
mi ny chit i hi cc thit b phc tp u t cho thit b ln.
211
Phng php tin hnh gm cc giai on sau:
Giai on 1: Chun b nguyn liu
tng kh nng chit ta phi chia nh dc liu trc khi chit nhm
lm tng b mt tip xc gia hai pha rn v lng y nhanh qu trnh
khuch tn. Tuy nhin nu ta chia nh dc liu qu dung mi s kh chuyn
ng qua khi dc liu v ta rt kh thu c dch chit, do tu thuc vo
tng loi dc liu ta c th xay nh khc nhau va m bo y nhanh
qu trnh khuch tn va d dng trong rt dch chit.
Kim ho v lm trng n nguyn liu bng dung dch kim (thng
dng Ca(OH)
2
, NH
4
OH, Na
2
CO
3
... ) chuyn alcaloid trong nguyn liu sang
dng base.
Giai on 2: Chit
S dng cc dung mi chit l cc dung mi hu c khng phn cc (cc
dung mi khng ho ln vi nc).
Giai on 3: Tinh ch
Tinh ch thu cc alcaloid bng cch chuyn dng mui vi acid v chuyn
dng base bng kim v phn chia chng gia hai pha dung mi hu c khng
phn cc v nc loi cc tp cht khng phi l alcaloid.

Dd kim

Bt dc liu
Dm hu c

Thit b chit xut
Acid long

Tp cht/dm hu c
Mui alc/nc acid

Dm hu c
Tp cht/nc acid
Alc base/dm hu c
Nc thi

Dm hu c Ct thu hi dung mi

Alcaloid base tinh khit
Hnh 17.1. S chit alcaloid di dng base bng dung mi hu c
212
ng dng:
Hin nay hu ht cc alcaloid c sn xut trong nc cng nh trn
th gii s dng phng php ny. Mt khc phng php ny khi s dng
chit cc dc liu c nhiu cht nhy c trng n cao, trnh c s
trng n qu mc ca dc liu v s ho tan cht nhy vo dung mi gy
kh khn cho rt dch chit v tinh ch.
3.2. Phng php chit alcaloid di dng mui bng dung mi nc,
nc acid hoc cn (ethanol, methanol)
u im:
Dung mi r tin, d kim.
Thit b chit xut n gin, u t t.
Nhc im:
Dch chit rt ra ln nhiu tp cht, kh tinh ch do mt mt nhiu
trong khu tinh ch lm cho hiu sut chit thp.
i vi cc dc liu cha nhiu cht nhy, vic s dng nc lm dung
mi chit gp kh khn trong khu rt dch chit.
Phng php tin hnh gm cc giai on sau:
Chun b nguyn liu:
Nguyn liu thc vt c xay th, sau c lm m cho trng n
bng nc.
Tin hnh chit:
S dng dung mi l nc chit alcaloid di dng mui t nhin hoc
mui vi acid v c, hoc dung mi l cn ethylic hoc methylic chit alcaloid
c di dng mui v base.
Tinh ch:
Trong trng hp chit bng nc, alcaloid base c gii phng t dch
chit bng cch thm kim sau c chit bng mt dung mi hu c khng
ha tan trong nc. Tip tc tinh ch bng cch bc hi dung mi v kt tinh
li trong dung mi hu c hoc chuyn sang dng mui kt tinh li.
Trong trng hp chit bng cn, dch chit cn c c c, thm acid v
loi cc tp cht bng cch chit bng dung mi hu c khng phn cc, thm
kim chuyn alcaloid sang dng base ri chit alcaloid bng mt dung mi
hu c. Bc hi dung mi hu c ri kt tinh alcaloid hoc chuyn sang dng
mui kt tinh li.
i vi cc alcaloid kh tch c th s dng phng php sc k hp ph
hoc phng php trao i ion.
213
4. Cc phng php tch alcaloid di dng tinh khit
4.1. Thng hoa
Thng hoa c th thc hin trc tip trn dc liu nh tch caffein t
ch hoc c th s dng tch v tinh ch cc hp cht c trong dch chit
th.
Cc thit b hin i cho php s dng p sut gim v kim sot c
nhit trong qu trnh thng hoa.
4.2. Ct
Ct phn on thng c s dng tch cc hp phn trong mt hn
hp cc cht d bay hi. Trong ha thc vt n c s dng rng ri trong
phn lp cc hp phn ca tinh du. Tuy nhin kh c th s dng phng
php ny tch cc hp phn ph trong hn hp tinh du di dng tinh
khit. phn lp tinh du v acid hydrocyanic v mt s alcaloid th lng nh
spartein, nicotin t thc vt thng s dng phng php ct li cun hi nc.
4.3. Gii phng phn on
Mt s nhm cc hp cht t nhin c th gii phng phn on t mt
hn hp. C th ly v d mt hn hp mui alcaloid trong dung dch nc nu
thm t t va tng phn kim lc u cc base yu nht s c gii
phng ra di dng base t do. Tng dn kim ln s ln lt gii phng
cc base c tnh kim mnh dn. Mi ln thm kim vo ta lc hn hp vi
dung mi hu c ta s thu c mt lot cc phn on base. C th dng
phng php ny tch cc acid hu c c th ho tan trong dung mi khng
trn ln nc. Nu ta c mt hn hp mui cc acid hu c ta c th gii phng
phn on cc acid bng cch thm dn cc acid v c.
4.4. Kt tinh phn on
y l mt phng php phn lp c s dng nhiu trc y v
hin nay vn c gi tr trong vic tch cc hn hp kh tch. Phng php ny
s dng tan khc nhau ca mt hp phn ca mt hn hp cn tch trong
mt dung mi hoc hn hp dung mi nht nh. Ngi ta thng s dng cc
dn xut ca cc hp phn cn tch thay i tan ca n (v d mui
picrat ca cc alcaloid, asazon ca ng).
4.5. Sc k hp ph
Trong cc trng hp khc nhau tch v phn lp cc hp cht t thc
vt, k thut sc k l mt trong nhng k thut c s dng nhiu nht.
ty mu v lm trong dung dch ta s dng than hot, cc tp cht mu s b
hp ph bi than hot v sau khi lc ta s thu c mt dung dch khng mu.
214
Tt c cc cht rn khi c phn chia nh u c kh nng hp ph t
nhiu cc cht khc trn b mt ca n v ngc li tt c cc cht u c th
b hp ph t dung dch cc mc khc nhau. Hin tng hp ph chn lc
l nguyn l c bn ca sc k. Qu trnh c bn ca sc k c th c m t
da trn th nghim ca Tswett nh sau:
Dch chit ether du ho (40-60
O
C) ca l cy ti c cho qua mt ct
thu tinh thng ng trong c cha bt calci carbonat. Cc sc t trong ct b
hp ph vo cht nhi ct v s tch trong qu trnh chy qua ct. Cc sc t
hp ph mnh hn nh xanthophyl v clorophyl s tp trung thnh cc bng
mu c trng r rt gn nh ct trong khi cc sc t c hp ph km hn
nh cc caroten tp trung cc bng thp hn pha di.
Thng vic tch hon ton cc thnh phn thnh cc bng r rt khng
xy ra giai on hp ph u tin m trong giai on ny cc bng cn tp
trung gn nhau phn nh ct. Tip tc trin khai ct bng dung mi tinh
khit, cc cht b hp ph s di chuyn dn xung pha di v cc bng c
tch ra xa nhau hn. Trong nhiu trng hp qu trnh c tin hnh hiu
qu hn nh s dng dung mi trin khai khc m cc cht t b hp ph t n
hn. V d nu ether du ha c cha mt t alcol c cho thng qua ct trong
th nghim c m t trn th cc bng s tch ra xa nhau hn v s chy
qua ct nhanh hn so vi khi ch dng ether-du ha trin khai. Khi ta cho
dung mi tip tc chy qua ct bng thp hn trong ct s chy ti y v bin
mt, sc t s thu c dch chy ra y ct. Qu trnh ny gi l qu trnh
gii hp ph (elution), dung dch c gi l dung dch gii hp ph
(eluate). Cc cht d dng hp ph t cc dung mi khng phn cc nh ether
du ha, benzen thng d dng gii hp ph bng cc dung mi phn cc
nh alcol, nc, piridin... Mt vi cc hp cht b hp ph pH nht nh s
c gii hp ph mt pH khc.
Cc cht khc nhau thng c dng lm cht hp ph l: nhm oxyd,
silicagel, magnesi oxyd, kaolin, calci carbonat, than hot v cc loi ng.
Sucrose dng bt c Tswett s dng tch cc chlorophyl A v B.
Khi ta tin hnh sc k cc cht khng mu, cc bng ca cc cht b
hp ph khng th trng thy c. Trong mt s trng hp c th s dng
n t ngoi xc nh cc vng pht quang di nh sng t ngoi hoc c
th chia sc ph ra nhiu phn nh ring bit v gii hp ph hoc chit tng
phn nh ring r. i khi ngi ta thu dch gii hp ph ca ton b ct
thnh cc phn ring bit ri tin hnh phn tch ring cc phn ring bit .
Dng c tin hnh sc k hp ph rt n gin ch gm mt ct bng
thu tinh trong nhi cht hp ph.
Sc k hp ph thng c s dng trong phn lp v tinh ch cc
vitamin, hormon, mt s cc alcaloid, cc glycosid tim, antraquinon...

215
5. Chit xut mt s alcaloid
5.1. Sn xut alcaloid h C
5.1.1. i cng
H c l mt h ln gm khong 1200 cy, c loi dng n, c loi c
dng trong k ngh, c loi dng lm thuc. Cc loi c cha rt nhiu
alcaloid ta c th chia chng ra thnh 3 nhm chnh:
Nhm alcaloid khng c oxy:
Gm c 5 alcaloid pyrolidin, nicotelin, anabazin, nicotyrin, nicotin.
Nicotin l mt alcaloid ca nhiu loi thuc l, v c t l thp nht thay
i t 0,6-0,8%.
L mt alcaloid lng snh nh du, c cho tim v no. Dng tng hp
acid nicotinic ch to vitamin PP. Ngoi ra c th dng dit su b ph hoi
cy ci.
N
N
H
N
CH
3
N
N
N
H
Nornikotin
Nikotin Anabazin

Nhm alcaloid c oxy:
Gm 7 alcaloid: atropin, hyoscyamin, pseudo hyoscyamin, atropamin,
benladonin, methelsidin, scopolamin.
Nhm ny rt quan trng v c nhiu alcaloid dng lm thuc.
Atropin, hyoscyamin, scopolamin l 3 alcaloid quan trng. C 3 alcaloid
ny u c khung tropan, atropin v hyoscyamin l este ca 1 alcol c bit l
tropanol v acid tropic cn scopolamin l este ca scopinol v acid tropic.
N
CH
3
N
CH
3
OH
N
CH
3
OH
O Mt phng i xng
Tropan Tropanol
Scopinol

216
Acid phenyl 2, ol 3 propionic
(1) (2) (3)
HOOC CH CH
2
OH
C
6
H
5

HOOC C CH
2
C
6
H
5

Atropin Tropanol R + Acid tropic R

.
Hyoscyamin L (tri)
Tropanol R + Acid tropic L (-)

Atropin, Hyoscyamin
N
CH
3
O C
O
CH CH
2
OH
C
6
H
5
+
CH CH
2
OH
C
6
H
5
HO OC H
N
CH
3
O
H
2
O +

Scopolamin
Scopinol + Acid tropic L (-)

Scopolamin
N
CH
3
O
O
H HO OC CH CH
2
OH
C
6
H
5
+
N
CH
3
O OC
O
CH CH
2
OH
C
6
H
5
H
2
O
+

Trong y hc scopolamin dng dng hydrobromid
Nhm alcaloid-glycosid:
Solanin l mt alcaloid-glycosid, n c nhiu tnh cht tng t nh
saponin. em thu phn solanin ta thu c 1 phn alcaloid v 3 phn ng:
C
6
H
12
O
6
+ + +
C
6
H
12
O
5 C
6
H
12
O
6
C
27
H
43
ON C
45
H
73
O
15
N

Solanidin
Solanidin ch gp trong mt s cy thuc loi Solanum c th trong mm
khoai ty, n kh c nn khi n khoai ty mc mm phi khot b ht
mm. Trc y solanin c s dng lm thuc tr su.
5.1.2. Tnh cht ca nhm alcaloid c nhn tropan
L tnh:
Trng thi: u trng thi rn ti nhit thng, u kt tinh c, tt
c u kt tinh khng ngm nc tr scopolamin kt tinh vi 1 phn t nc.
Acid Tropic
Apotropic
217
tan: t tan trong nc (scopolamin d tan hn), d tan trong cn v
trong cloroform.
chy: Hyoscyamin 108,5
0
C
Atropin 115
0
C - 117
0
C
Scopolamin 59
0
C
Nng sut quay cc: Tr atropin l racemic cn li l t tuyn.
Ha tnh:
Ha tnh ca amin bc ba: V c amin bc ba nn mang li tnh kim cho
phn t, lm phenolphtalein, lm xanh giy qu v to mui vi cc acid.
Ha chc ca oxy (ester): C th thu phn cho tropanol v acid tropic.
N
CH
3
OH
N
CH
3
O C
O
CH CH
2
C
6
H
5
OH
HOH
HOOC CH CH
2
C
6
H
5
OH
+

Nu thu phn 130
0
C vi nc, phn ng yu, khng hon ton. Nu s
dng HNO
3
c, nhit thng th xy ra t t. Nu dng NaOH v un
si phn ng mnh.
ng phn ha: Hyoscyamin em t trong chn khng 110
0
C hoc ha
tan trong cn cha 10% NaOH, hoc un si vi cn 2-3 ngy vi ng sinh hn
ngc th s bin thnh atropin.
Atropin em ha tan vo H
2
SO
4
c v dung dch ny vo nc th
atropin mt 1 phn t nc thnh atropamin.
N
CH
3
O C
O
C CH
2
C
6
H
5
N
CH
3
O C
O
CH CH
2
C
6
H
5
OH
H
2
O

5.1.3. Dc lc tnh
Atropin v hyoscyamin u c tc dng c ch h thn kinh ph giao cm.
Lm gin ng t.
Khng bi tit, km hm s hot ng ca cc tuyn nc bt, m hi,
tuyn ty mt.
218
Tng nhp tim.
Gim co git, lm t lit cc c trn.
Gim h hp.
Hyoscyamin c tc dng nh atropin nhng c hn, lm gin ng
t mnh hn. Chng c dng trong khoa cha mt, au d dy, tr
tim, gim co git.
Hyoscin (scopolamin) c tc dng an thn mnh gy ng, gy m.
Mui hydrobromid ca n c dng phi hp vi morphin (gy ng),
cloroform gy m).
5.1.4. Ngun gc thin nhin
Nhng alcaloid k trn c trong nhiu loi cy thuc h C nh
hyoscyamin c nhiu trong cy hyoscyamus, v trong cy Atropa benladona.
Ngoi ra, cn c trong mt s loi C khc nhng vi t l thp hn. Trong l
Atropa benladona c t 0,2-1,2%, r t 0,45- 0,85%, hoa t 0,5-0,65% v ht
khong 0,8% alcaloid, ch yu l hyoscyamin. Trong Atropa benladona
hyoscyamin l alcaloid ch yu nhng v di tc dng ca nhit d bin
thnh dng racemic tc l atropin, v vy trc y ngi ta tng thnh
phn ch yu ca Atropa benladona l atropin.
Atropa benladona mc nhiu Nam u, Ty v Bc Phi. c trng
nhiu nc nh Lin X, Anh, Php, n , Vit Nam cha tm thy loi ny.
Scopolamin l alcaloid ch yu ca cy C c dc (Datura metel) vi t
l khong 0,24%. Trong Datura metel ngoi scopolamin cn c mt t
hyoscyamin. Loi cy ny mc hoang Vit Nam, Lo, Campuchia. Ngoi ra
cn c Trung Quc, n , Malaysia...
Nhn dn ta thng dng l kh thi nh ht hay xng cha hen.
Trong khng chin C c dc hon ton thay th cho Atropa benladona
thy kt qu tt.
Dng dng: Cn thuc 1/10 (ngi ln 0,5-3 g, tr em 0,1 g)
Sir c 50g cn trong 1 lt (10-60 g cho ngi ln, tr em mi tui 2 g).
5.1.5. Phng php sn xut
a. Sn xut hyoscyamin sulfat
Chit hyoscyamin:
R benladon c tn thnh bt, em chit ngc dng trong 4 bnh. Mi
bnh 450 kg bt v khong 1000 lt methanol, sau 2 gi rt dch chit ra.
Ct thu hi methanol: dch chit rt ra c ct thu hi methanol n
cn 1/5 th tch thu c dng cao lng.
219
Tinh ch: C 200 kg cao cho thm vo 200 kg diclomethan 400 lt nc v
1,5 lt HCl c, khuy mnh trong 80 pht cho alcaloid chuyn sang dng
hidroclorid tan trong nc. Chuyn hn hp dung dch hydroclorid alcaloid v
diclomethan vo thit b phn ly. yn 1 m diclomethan s lng xung,
mang theo mt s tp cht v cht mu.
Gn ly pha nc. C 200 kg dung dch cho 200 kg diclomethan v 2 lt
amoniac m my khuy 15 pht. phn lp, gn ly pha dung mi hu c.
Chuyn dng mui-base nhiu ln, sau pha dung mi hu c c ct thu
hi dung mi. Dch c m c nhit phng 24 gi hyoscyamin s kt
tinh, lc thu c hyoscyamin th.
Sn xut hyoscyamin sulfat:
Hyoscyamin th ha tan trong methanol khan nhit phng v lc
qua than hot lnh.
Dung dch ny c lm lnh n -5
0
C v trung ha vi mt dung dch
lnh H
2
SO
4
trong methanol.
iu chnh pH dung dch bng H
2
SO
4
(th bng giy qu).
Dung dch trung tnh c x l vi than hot lnh v bc hi di
chn khng ti nhit thp. Hyoscyamin sulfat s kt tinh t cn sau khi
thm vo aceton v yn. Nu nguyn liu tch ra ging nh du, thm vo
1 t methanol th kt tinh thc hin d dng hn. Kt tinh li nu thy cn
thit hoc x l vi than hot trong dung dch methanol lnh (dung dch
10%) nh trn.
b. Sn xut atropin sulfat
Sn xut atropin:
Tinh ch: Ho tan hyoscyamin th trong methanol thnh dung dch 10%,
thm vo 1-2% than hot, un si, lc ra than bng 1 lng nh methanol
nng. Dung dch thu c dng racemic ha thnh atropin.
Racemic ha: Dung dch trn c un si c sinh hn ngc vi 1-2%
(trng lng) phenol trong 36 gi, th hot tnh quang hc xem hyoscyamin
chuyn ht thnh atropin cha, nu cha ht th phi lm thm 1 thi gian na
(cch th: ly khong 2 g alcaloid lc k vi dung dch 50 ml HCl 1N, lc qua
than hot, th hot tnh quang hc phi khng c, nu c tc l racemic ho cha
tt). Phi ch rng nguyn liu th y ch c khong 75% hyoscyamin.
Dung dch nng atropin li c x l vi than hot. Dch lc c bc
hi di p sut gim (62,5 mmHg) cho n khi thu c dung dch m c
snh nh sir, thm vo dung dch m c ny khi n cn nng ng lng
th tch aceton, atropin s kt tinh lc ly tinh th, ra tinh th bng aceton
loi ht cht mu. Ti ra khay v sy.
220
Atropin ny dng lm nguyn liu iu ch atropin sulfat cha t
atropin tinh khit ha hc.
Tinh ch chuyn dng atropin sulfat:
12 kg atropin th c ha tan trong 50 lt methanol khan, lc nng vi
82g than hot, ra than bng 4 lt methanol nng.
Dch lc yn trong bnh thp khng g dung tch 100 lt. Dung dch
ny c lm lnh bng nc v mui hay dung dch nc mui t t lnh
(ch trnh lm bn nc mui vo dung dch atropin) v khuy tt bng que
khuy thy tinh hoc thp khng g. Duy tr nhit -5
0
C.
iu ch dung dch H
2
SO
4
:
Dung dch ny phi c iu ch trc khi dng khong 12 gi, tt nht
l d tr gn im ng c. Phng php iu ch dung dch ny nh sau:
Nh t t 1050 ml H
2
SO
4
c vo 8-9 lt methanol lnh v khuy cn
thn. Phi duy tr dung dch ti nhit .
To mui atropin sulfat:
Nh t t dung dch H
2
SO
4
ny vo trong dung dch atropin cho n khi
hn hp phn ng chuyn giy qu xanh sang mu hng nh l c.
Tip tc khuy dung dch trong 80 pht. Phi duy tr nhit phn ng
ti -5
0
C (mt khong 6 gi).
Kt tinh atropin sulfat:
Dung dch atropin sulfat c x l vi 80 g than hot nhit 50-60
0
C
v lc. Dung dch lc em bc hi p sut thng n khi cn 1/2 th tch.
Sau bc hi ti p sut gim n sir, thm vo 800 ml methanol v
khuy. Sau thm vo 5 lt aceton v khuy u. Atropin sulfat kt tinh.
Lm lnh trong nhiu gi. Lc, bnh lc c ra k vi aceton cho n khi
ht mu. Ti ra khay v sy.
Atropin thu c nh vy thng trng; khng c tc dng quang hc v
c im chy ng.
c. Sn xut scopolamin hydrobromid
Chit xut scopolamin t Datura metel (phn chit c thc hin nh mc
chit hyoscyamin).
Mt s tc gi khuyn nn dng Na
2
CO
3
hay NaHCO
3
kim ha trc,
nh vy c th loi tr c s ph hy lin kt oxy trong scopinol v ng
thi c th gim n mc ti thiu qu trnh racemic ha thnh atroscin.
Chuyn dng scopolamin hydrobromid
221
Scopolamin th ha tan trong 3 phn th tch aceton, dung dch c lm
lnh tt. Thm vo dung dch m c HBr 48% trong nc cho n khi
phn ng acid nh, th bng giy qu (ch lm lnh tt). Thm vo 1 lng
aceton, lnh qua m, scopolamin hydrobromid s kt tinh vi 1 phn t
nc. Lc ra bng alcol, sy ti nhit phng. Nc m cha c scopolamin
v atroscin hydrobromid. Nu tip tc bc hi ti p sut gim thu thm c
scopolamin hydrobromid.
Qu trnh iu ch scopolamin t Datura metel c th tm tt theo s
hnh 17.2.
Bt dc liu Methanol

Dch chit Thu hi p sut gim
Tetraclorua carbon
Cn sir HCl long

Tetraclorua carbon thu hi dd nc acid NH
4
OH v CHCl
3

Nc b i
dd cloroform HCl long

CHCl
3
thu hi
Dung dch nc acid NH4OH v diclorometan

Nc b i
dd diclorometan HCl long

Diclorometan thu hi
dd nc acid NH
4
OH v ether isopropyl

Nc b i
dd alc.trong
ether isopropyl
Na
2
SO
4
khan

Lc ct p sut
gim

lnh, kt tinh
Lc, sy kh

Hnh 17.2. iu ch scopolamon t Datura metel
222
5.2. Sn xut cc alcaloid ca thuc phin
5.2.1. i cng
Cy thuc phin cn c tn l A ph dung, A phin ...
Tn La tinh: Papaver somniferum L, h Papaveraceae.
Cy thuc phin c trng nhiu nht ti Chu : Th Nh K, Irc, n
, Trung Quc, Nht Bn, Vit Nam (H Giang, Lai Chu, Sn La ...); ti
Chu u: Nam T, Bungari, Hy Lp, Lin X....
Qu thuc phin (Anh tc xc) c gn ht cc alcaloid ca thuc phin
nhng t l thp 0,06 - 0,26%. c dng lm thuc du au, thuc ng nh,
thuc cha ho, t, l, au bng...
Ht c khong 25% du (p lnh), 45% du (p nng); ht dng n
nh vng; du dng n, ch thuc xoa bp, thuc m, thuc cao...
Nha thuc phin c dng di nhiu hnh thc cha bnh: thuc
ng, thuc gim au, thuc iu ha thn kinh, a chy, l...
Trong nha thuc phin c khong 30 alcaloid; ni chung chng tn ti
di dng meconat tc l t hp vi acid meconic.
O
O
HOOC
OH
COOH

(Acid 3 - hydroxy pyron dioic 2 - 6)

Trong 30 alcaloid c 7 alcaloid quan trng l:
Phenantren
7,5% 0,3 ng kho Thebain
7% 0,3 ng kho Codein
21% 6 ng kho Morphin

uinolin Benzylisoq
0,7% 0,1 ng kho Narcein
13% 1,4 ng kho Narcotin
0,008% ng kho Laudanozin
4,5% 0,1 ng kho Papaverin

223
5.2.2. Cu trc
Khung

Ho chc
Ha chc amin bc 3: nit ni lin 3 ha tr, hoc c 1 ha tr t do, ha
tr ny lun lun nh vi nhm methyl.
Cc ha chc oxy: alcol, phenol, ether ni (ether ni l 2 ha chc ca
phenol hay alcol trong cng 1 phn t phn ng vi nhau cho ether), ether
ngoi, lacton, acid, ceton nhng c bit khng c ester.
5.2.3. Tnh cht
L tnh
Hnh th: c, kt tinh c ti nhit thng.
tan: kh tan trong nc, ring codein d tan hn, tan t trong cn
50
0
. Cc mui t nhin ca alcaloid thuc phin u c th tan trong
nc tr narcotin.
Nng sut quay cc: tr papaverin v narcein khng c carbon bt
i cn cc alcaloid khc u c kh nng quay cc.
Ha tnh
Ha tnh nit: tt c u c 1 nit bc 3, l nhng base yu c th y
ra khi mui ca chng vi acid bng Na
2
CO
3
, NaHCO
3
, kt hp vi
acid to mui.
Ha tnh ca oxy: nhm hydroxy ca phenol v alcol c th ester ha
v cho dn xut cha bnh rt qu, nhm -OH phenol lm cho
morphin c th tan trong hydroxyd ca kim loi kim v kim th.
5.2.4. Dc lc tnh v cng dng
Nhm 1 gm c morphin, codein, narcein tc dng vo h thn kinh
trung ng, lm t lit cm gic, nht l cm gic au n, alcaloid cn gy
ng mnh vi mc khc nhau tu theo tng alcaloid. Morphin gim au
gy ng mnh, c dng trong nhng trng hp au nhiu nh: ung th,
cn au si mt, si thn, chng au tht tim ...
Codein v narcein gim au, gy ng nh, tc dng vo trung tm cm
gic ho nn c dng lm thuc ho.
N
N
Phenantren Benzylisoquinolin

224
Nhm morphin:
Alcaloid chnh l morphin chim khong 5-15%, monometylether ca n
l codein c trong nha thuc phin khong 0,9-6,5%. Ngi ta nhn thy
trong nha thuc phin t l morphin cao th t l codein thp v ngc li t
l morphin thp th t l codein cao. Trong ngnh dc dng khi lng rt t
morphin, cn khong 80-90% chuyn ha thnh codein (bng phng php
methyl ha nhng alcaloid cn li gn nh khng c s dng lm thuc),
ring thebain c th dng tng hp codein.
Nhm benzylisoquinolin:
Quan trng nht l papaverin cn cc alcaloid khc khng c tc dng
cha bnh. Papaverin lm gim co git, tc dng thng ln c trn, c dng
iu tr cc cn au d dy, chng nn, ho v co git, a chy tr con.
Narcotin gy co tht nh, lm du ho, trc y dng lm thuc cha ho.
Hin nay c dng lm nguyn liu tng hp kotarnin.

- CH3 R
- H R Morphin:
Codein :
R O
H O
H
N C H 3
O
H

CH
3
O
CH
3
O
H
N CH
3
O
H
Thebain

CH
3
O
CH
3
O
N
OCH
3
OCH
3 Papaverin

CH
3
O
CH
3
O
N C H
3
O R
O C H
3
6
7
3
'
4
'
Laudanosin R

- CH
3

N
R
C H
3
O
C O
O C H
3
O C H
3
O
O
R
R OH
OCH
3
-
- Noscapin:
Narcotolin:

5.2.5. Sn xut cc alcaloid thuc phin
Qu trnh tch cc alcaloid ca thuc phin bng cch chit vi nc
nng chit ngc dng). Dch chit m c chuyn sang dng alcaloid base
bng amoniac.
225
Qu trnh tch cc alcaloid ca thuc phin rt phc tp, qu trnh
c gii thiu trong hnh 17.3.

Hnh 17.3. Qu trnh tch cc alcaloid ca thuc phin
nha thuc phin
Chit bng nc trong my chn khng
Dung dch m c + mt th tch cn
loi cc cht protein, carbua, nha
+ NH
4
OH 25%
S c ta morphin v narcotin khng tan trong cn, nc
Ta
morphin v narcotin
+ Acid acetic
Dch lc (cn, nc, amoni)
papaverin, thebain, codein
+ benzen
(Morphin l mt kim mnh hn to
thnh mui, cn narcotin l kim yu
hn mui ca n d b thy phn nn
tch thnh ta dng base)
Dung dch trong benzen
(papaverin, thebain, codein)
+ Acid acetic
(Dung dch benzen lc vi acid
acetic 5%, codein v thebain l
kim mnh hn to thnh mui, cn
papaverin li trong benzen).
Ta
Narcotin
Dch lc (Morphin)
+ NH
4
OH
Morphin base
(Morphin base thu c t
tinh khit 86% ri chuyn
sang mui chlohydrat, kt
tinh li trong nc v ty
mu bng than hot).
Dung dch nc acid
(thebain, codein)
+ NH
4
OH
Dung dch
benzen
Papaverin
Tinh khit qua
mui oxalat
Dung dch
Codein
Ta
Thebain
Tinh khit
qua mui
tartric
Chit bng
benzen, tinh
khit qua mui
ca acid sulfuric
226
Phng php sn xut morphin hydroclorid:

Hnh 17.4. S quy trnh tch morphin hydrat t thuc phin
Theo s hnh 17.4, t nha thuc phin chng ta mi tch c
morphin, cn cc alcaloid khc cha thu hi c.
Ta
(Morphin v Narcotin)
Dung dch
(Morphin sulfat)
Natri hydrosulfit
Ta
(Morphin base)
Dung dch
Morphin hydroclorid k
Morphin hydroclorid 3H
2
O
Dung dch
Dung dch c
(d = 1,16-1,2)
B
Nc cn (thu hi)
(Thebain)
Ta (thu hi)
(Narcotin)
Nc ci (thu hi)
Nc ci (thu hi)
Ta
Sy ng gi
Natri hydrosulfit
227
Ngoi ra morphin cn c iu ch bng phng php trao i ion t v
qu thuc phin cha chch nha, vi t l 0,5-0,9% morphin. S quy trnh
c m t hnh 17.5.

Hnh 17.5. Chit morphin bng phng php trao i ion (theo Demina - 1963)
5.3. Sn xut alcaloid c nhn berberic
5.3.1. i cng
Trong nhm ny c 3 alcaloid chnh l berberin, palmatin, rotundin.
Berberin c nhiu trong trong cy vng ng (Coscinium usitatum) vi t l
khong 1-3%, ngoi cn c trong cy hong b (Phellodendron amurence Rupr)
vi t l khong 1,6% v cy hong lin gai (Berberis wallichiana) 11%. Cc
cy ny u c nhiu Trung Quc v Vit Nam. Palmatin c nhiu trong cy
hong ng thuc 2 loi: Fibraurea recisa Pierre v Fibraurea tinctoria Lour
h Phng k (Menispermaceae) vi t l 1-8% .
Tch Morphin base
MORPHIN
228
L-tetrahydropalmatin (rotundin) c nhiu trong c bnh vi Stephania
japonica v Stephania rotunda, h Phng k.
C 3 alcaloid ny c cng 1 khung isoquinolin

Palmatin
N
O CH
3
O CH
3
OH
O
O
CH
3
CH
3
Berberin
N
O
O
O
O
CH
3
CH
3
H
2
C
OH

N
O C H
3
O C H
3
O
O
CH
3
CH
3
L - tetrahydropalmatin

5.3.2. Tnh cht
L tnh
Hnh th: L cc alcaloid th rn, khng mi, v ng, t tan trong
nc, tan trong dung mi hu c.
Berberin v palmatin c mu vng. Rotundin c mu trng.
Nng sut quay cc: Berberin v palmatin khng c C bt i khng
c ng phn quang hc, cn rotundin t tuyn do c C bt i.
Ha tnh
Ha tnh ca N:
N ca berberin v palmatin l hydroxyd amoni bc 4 em tnh kim cho
phn t. C th cho mui clorid vi HCl

Alc N OH H C l +
+ N Cl Alc H
2
O

L - tetrahydropalmatin c amin 3 cho mui hydroclorid:

Alc HC l + N] [Alc N HCl

229
Ha tnh ca oxy:
C ha chc ete c th thu phn cho alcol, ring OH trong hydroxyd
amoni bc 4: N khng vng bn, trong mi trng kim d h bin m vng,
cho chc aldehyd gi l berberinal hay palmatinal tng ng.
CH
3
CH
3
O
O
OH
-
CH
3
CH
3
N
+
O
O
O
O
N
CH
3
CH
3
CHO
Palmatin (vng)
Palmatinal ()

Mch kp:
Berberin v palmatin c th mt mch kp ti nhn gia cho cc
hydro alcaloid khng mu.
Ly palmatin mu vng ti em kh vi hn hp Zn+H
2
SO
4
s thu c
bt v nh hnh trng c chy l 215
0
C l DL - tetrahydro palmatin sulfat,
cho tc dng vi amoniac thu c DL - tetrahydro palmatin base, kt tinh
trng, chy 140-147
0
C.
Tri li L - tetrahydro palmatin trng em oxy ha bng iod s chuyn
thnh palmatin mu vng.
Cng dng
Berberin c tc dng khng sinh cha l, gn y pht hin c
tnh cht chng ung th.
Palmatin trc y dng lm thuc cha mt (v cho l c tc dng
khng sinh) hin nay dng lm nguyn liu iu ch DL - tetrahydro
palmatin.
L - tetrahydro palmatin c tc dng an thn gy ng.
5.3.3. Sn xut berberin, palmatin, rotundin
a. Sn xut berberin v palmatin
Phng php sn xut berberin hay palmatin rt ging nhau, ch khc l
chng thc hin trn cc nguyn liu hon ton khc nhau m thi.
C hai alcaloid u c th chit bng nc v bng nc acid (acetic,
sulfuric) hoc bng cn.
Nu chit bng nc hay bng acid long nn thc hin trong my chit
bng g, dch chit thu c cho tc dng trc tip vi HCl (hoc H
2
SO
4
) tha
ta s thu c mui clorid (hay sulfat) kt tinh.
230
Nu chit bng cn, dch chit bc hi, cn ho tan vi nc m ri thm
HCl (hoc H
2
SO
4
) ta cng thu c mui clorid (hay sulfat).
Sn xut palmatin
S tng qut: Hnh 17.6.

Bt thn r hong ng Cn 80
o

Ct

Cn 80
o
Dch chit

Cn H
2
O m
HCl c

Palmatin clorid Cn + than hot

Palmatin clorid (Tinh ch)

Sy 60
o
C

Co v ngoi

ng gi
Hnh 17.6. S quy trnh sn xut palmatin clorid t thn r hong ng
M t quy trnh sn xut:
+ Chun b nguyn liu: Thn r hong ng xay th. Lm m, cho
n bng cn 80
0
, np vo thit b chit.
+ Chit: Chit bng phng php chit ngc dng gin on vi
dung mi l cn 80
0
, thi gian chit l 12 gi, chit 4 ln. Dch chit
ln 1 rt ra em x l thu palmatin. Cc dch chit ln 2, 3, 4 dng
lm dung mi chit cc m sau.
+ Tinh ch: Dch chit ln 1 rt ra c chit thu hi cn. Cn cn li
thm nc nng v HCl thu c ta palmatin clorid. Sau khi loi
b nc ci palmatin clorid c ha tan trong cn 90
0
, ty mu
bng than hot. Lc b than hot. Dch lc 24 gi cho kt tinh
palmatin clorid. Lc ly tinh th, ra tinh th bng cn 90
0
.
231
+ Sy: Ly c khi tinh th trong phu lc ra hong kh cn. Sy
nhit 60
0
C cho n kh. Sau khi sy xong phn ngoi ca khi
tinh th s ng mu . Co ht lp ngoi mu (lp ny kt tinh
li trong cn ta c palmatin vng). Phn palmatin mu vng sau
khi sy xong c lm ti v ng gi.
Sn xut berberin:
S tng qut: Hnh 17.7.

Thn r vng ng
Xay
Bt th vng ng Dd H
2
SO
4
0,4%
B Dc liu Ngm 24 gi
Dch chit NaCl
Nc ci Khuy tan ht, 24 gi, vy
Berberin clorid th Dd HCl 0,4%
Ra, vy
Berberin clorid th Cn 96
o
, than hot
B than hot Ho tan nng, ty mu, lc
Dch lc cn
Nc ci kt tinh, vy
Berberin clorid
Sy, ng gi
Berberin clorid dc dng
Hnh 17.7. S quy trnh sn xut berberin clorid t thn r vng ng
M t quy trnh sn xut:
+ Chun b nguyn liu: Thn r vng ng cht thnh lt mng,
phi kh, xay th. (c th chit bng nguyn liu ti nhng s ko
theo nhiu tp cht, kh tinh ch hn).
+ Chit: Dc liu xay th c np vo thit b chit chu acid. Dng
dung dch H
2
SO
4
0,4% trong nc lm dung mi chit. T l dung
mi/nguyn liu l 5/1. Chit bng phng php ngm nhit
phng trong 24 gi.
+ Tinh ch: Ta berberin clorid: Dch chit rt ra thng cha c
khuy, thm NaCl vi t l 3%-4% so vi lng dch chit, khuy
232
mnh cho tan ht NaCl. yn 24 gi cho berberin kt ta ht.
Ra ta bng dung dch HCl 0,4% loi tp cht, sau ra ta
bng nc cho ht phn ng acid.
+ Kt tinh trong cn: Ha tan nng berberin clorid th trong cn 96
0

vi t l berberin/cn l 1/5. Thm than hot, un hi lu 10 pht.
Lc b than hot, dch lc cn kt tinh trong 12-24 gi. Vy ly
tm thu tinh th, ra tinh th bng cn 90
0
.
+ Sy, kim nghim, ng gi: Tinh th berberin c cho bay ht hi
cn ri sy nhit 60
0
C-70
0
C trong 8 gi.
Kim nghim theo tiu chun Dc in Vit Nam.
ng gi trong 2 ln ti polyethylen.
Bo qun ni kh ro, trnh nh sng.
b. Sn xut L- tetrahydropalmatin t c bnh vi
Chit xut L - tetrapalmatin di dng base bng dung mi hu c
Alcaloid ton phn: C bnh vi phi kh tn nh, kim ha vi
amoniac 10%. Chit vi cloroform. Gn ly dch chit ri c c v
thm vo dch c H
2
SO
4
10% s c mui sulfat ca alcaloid. Li
kim ha sulfat alcaloid bng amoniac pH=8 ri chit alcaloid base
bng cloroform. C chn khng ta c alcaloid ton phn.
Tch L - tetrahydropalmatin: Alcaloid trn ha tan vo H
2
SO
4
1%.
Thm Na
2
CO
3
n pH=6. L - tetrahydropalmatin s ta xung, lc
ly ta. Nc ci thm Na
2
CO
3
n pH=8 s thu c ta mt s cc
alcaloid khc.
Chit xut L-tetrahydropalmatin t c bnh vi di dng mui bng nc
(Hnh 17.8).
C bnh vi ti c bo thnh lt mng chit bng dung dch acid
sulfuric 0,3%. Dch chit rt ra lng trong. Gn phn trong. Phn dch c
c lc qua vi. Dch thu c sau khi gn, lc c ta alcaloid base bng
dung dch Ca(OH)
2
. Lc ly ta alcaloid ton phn. Ta ny c sy cho kh.
Ta alcaloid ton phn kh thu c bng phng php ny c cha t
10% n 30% L-tetrahydropalmatin.
Ta ny c tinh ch bng cch ho tan nng trong cn cao 90
0
-96
0
,
ty mu bng than hot. kt tinh 24 gi ti nhit phng. Lc hoc vy
ly tinh th. Sy nhit 60
0
C-70
0
C thu c L-tetrahydropalmatin tinh
khit.

233
C bnh vi ti
Bo
Lt mng c bnh vi Dd H
2
SO
4
0,3%
Ngm 24 gi
Dch chit Nc vi trong
pH = 9
Lc

L- tetrahydropalmatin th
Sy, phi kh
L- tetrahydropalmatin th kh Cn 96
o
, than hot
Ho tan nng, ty mu, lc nng
Dch lc
kt tinh 24 gi, lc, ra
L- tetrahydropalmatin
Sy 60
o
C
Kim nghim, ng gi
L- tetrahydropalmatin dc dng
Hnh 17.8. S quy trnh chit L tetrahydropalmatin t c bnh vi
5.4. Sn xut cc alcaloid cankina
5.4.1. i cng
C nhiu loi Canhkina: Cinchona succirubra Pavon (Canhkina ),
Cinchona calisaya Wedell (Canhkina vng), Cinchona officinalis L. (Canhkina
xm), Cinchona ledgeriana Moens (Canhkina thm).
Canhkina l cy g cao t l0-25 m. Ngi ta thng dng v chit
quinin, quinidin. C th s dng c v thn, v r, v cnh nhng v thn l
tt nht.
5.4.2. Thnh phn ha hc ca cy canhkina
V canhkina c hm lng alcaloid cao (4-15%). Nguyn liu c s
dng chit quinin, quinidin trong cng nghip c hm lng alcaloid (quinin +
quinidin) t 6% tr ln. Thng ta dng v thn ca Cinchona calsaya Wedell
234
(Canhkina vng), Cinchona ledgeriana Moens (Canhkina thm) v chng c
hm lng alcaloid (quinin+quinidin) kh cao. Alcaloid trong cy canhkina tn
ti 1 phn di dng kt hp rt chc vi tanin catechic mt phn kt hp vi
cc acid hu c trong cy. Ngi ta phn lp c khong 30 alcaloid chia
lm 2 nhm:
Nhm cinchonin: Gm 4 alcaloid quinin, quinidin, cinchonin,
cinchonidin. Quinin, quinidin cng nh cinchonin, cinchonidin l cc
cp ng phn. Cc alcaloid ny l cc alcaloid chim t l cao trong
v cy canhkina.
Nhm cinchonamin: Gm cc alcaloid cinchonamin, cinchophytllin,
quinamin. Cc alcaloid ny chim t l nh trong v cy canhkina.
Cc acid hu c trong v cy canhkina l acid quinic, acid quinotanic.

N
R
HO
H
H
Cinchonidin: R=H
R OCH
3
Quinin:
9
8
7
6
5
4
3
2
1
N
CH CH2
H
Cinchonin: R=H
Quinidin: R OCH
3
9
8
N
CH CH
2
H
N
R
H
H
HO

N
N
CH
2
OH
H
H
H
Cinchonamin

5.4.3. Qui trnh sn xut quinin t v canhkina
a. S qui trnh chit xut: Hnh 17.9.
b. M t qui trnh sn xut
Chun b nguyn liu:
V canhkina cht nh, em phi kh hoc sy kh 50 - 70
0
C em xay
thnh bt kh.
Kim ha:
Bt v canhkina c trn u vi dung dch nc sa vi v dung dch
NaOH 30%, trn k cho ngm u v khi bt tr thnh dng bt nho. Vun
thnh ng ri khong 24 gi. Sau o, trn u lm ti v lm kh trong
khay men.
235

Hnh 17.9. Quy trnh chit xut quinin t v canhkina
dd quinin bisulfat
pht
bo ho
bo ho
bo ho
gi
236
Chit xut:
Nguyn tc chit: C th chit bng phng php ngc dng lin tc
hoc ngc dng gin on tu iu kin thit b cho php.
Nu chit bng phng php ngc dng lin tc th phi tnh ton tc
di chuyn ca dc liu v dung mi ph hp c th chit kit c
quinin trong dc liu.
Nu chit bng phng php ngc dng gin on th phi xc nh s
liu chit, lng dung mi chit cho mt ln v ch rt dch chit mt em x
l thu quinin cn cc dch chit sau c s dng chit cc m tip theo.
Tinh ch:
Acid ha to mui bisulfat tan trong nc ca cc alcaloid:
Cho dung dch H
2
SO
4
3% vo thit b phn ly c khuy ng dch chit
va rt ra. Khuy 10 pht hai pha tip xc tt vi nhau. yn cho
phn lp (cho ti khi hai lp trong li l c). Gn ring dung mi thu
hi dung mi chit cho m sau (x l bng cch kim ha, khuy k,
pH = 6 - 7, lng, gn b cn). Pha nc cha alcaloid tch ra c x l
thu cc alcaloid canhkina.
Kim ha to ta quinin sulfat:
Lp nc acid trn c trung ho bng dung dch Na
2
CO
3
bo ha
nhit cch thu. Va nh t t dung dch kim va khuy k cho n khi
pH = 6,5. ngui cho kt tinh ht (khi ch mui ca quinin kt tinh cn
mui ca cc alcaloid khc tan trong nc ci). Lc ly tinh th quinin sulfat
bng chn khng qua phu Buchner (c th vy li tm ly tinh th). Ht
ht nc ci ri tin hnh ra bng nc ct ngay trn phu lc.
Ra quinin sulfat 3 ln, mi ln bng 1 lng nc sao cho va ngp
tinh th.
Ty mu bng than hot:
ty mu trc tin phi chuyn quinin sulfat basic kh tan trong
nc sang dng quinin bisulfat d ho tan trong nc. Cho quinin sulfat v
mt lng nc va , thm H
2
SO
4
3%, chnh pH = 4, khuy u cho ta tan
ht, nng nhit dung dch ln 90-100
0
C thm than hot khuy 15-20 pht,
lc loi than hot thu dch lc.
To sn phm l quinin sulfat basic:
Dch lc c un nng, va khuy va nh dung dch Na
2
CO
3
vo chnh
pH = 6,5. ngui kt tinh. Lc ly ta ra bng 3 ln bng nc ct. Loi
nc ci. Ht kit. em sy kh 60 - 80
0
C trong khong 2 - 3 gi. Ch
thnh thong o ti ln sy cho nhanh kh.
237
ng gi: Trong l kn, trnh snh sng.
Kim nghim: Theo DVN.
5.5. Sn xut alcaloid m tin
5.5.1. i cng
Cy m tin (Strychnnos nux vomica) l cy g thn ng cao 5-12 m.
Ngoi cy m tin, nc ta cn c mt s loi m tin dy leo thn g khc.
nc ta cy m tin (Strychnos nux vomica) ch mc cc vng ni
pha Nam. Cc loi m tin khc mc hu ht cc tnh vng ni nh Cao Bng,
Lng Sn, Tuyn Quang, Ha Bnh, Bc Giang, Sn La, Ngh An, H Tnh,
Qung Tr...
Nguyn liu ch yu s dng trong chit xut schychnin l ht m tin.
Tuy nhin alcaloid ny cn phn b trong v v mt s loi m tin cn c
trong l.
5.5.2. Thnh phn ha hc
Trong ht m tin (Strychnos nux vomica L) c cha t 2-5% alcaloid,
ch yu l schychnin, brucin, ngoi ra cn c mt s cc alcaloid khc nh
-colubrin, -colubrin, vomicin...

N
H
H
H
H
O
R2
O
N
H
R1

R
1
R
2
H - Strychnin:
Brucin:
R
1
R
2
-O C H
3

colubrin:
colubrin: R
1
H; R
2
O C H
3
-
OC H
3
R
1
- R
2
H ;

R
3
N
O
R
2
O
N
O
CH
3
R
1

R
1
R
2
- O C H
3
R
3
Novaxin:
-H

R1 R2 H -
R3 O H -
Vomixin:

238
5.5.3. Sn xut strychnin sulfat
a. S qui trnh chit xut: Hnh 17.10.
Ht m tin
Sy, xay, cn Sa vi
Bt ht m tin Kim ho, 24 gi
Lm ti, o, hong kh Dung mi
Bt ht m tin kim ho Chit nng
B dc liu Dd H
2
SO
4
3%
Dch chit To mui SO
4
,khuy trn
Dung mi thu hi phn lp, gn
Dd Na
2
CO
3
bo ho
Pha nc acid Kim ho, pH = 11
Nc ci kt ta, lc Dd HNO
3
3%
Ta alcaloid ton phn To mui nitrat pH=4,5
Nc ci
(brucine)

Nc ct
Tinh th strychnin NO
3
Ho tan, cch thu
Than hot
Dd mui strychnin NO
3
Ty mu, khuy 10 pht
B than hot Lc nng Dd Na
2
CO
3
bo ho
Dch lc Kim ho, pH = 11
Nc ci kt tinh, lc Dd H
2
SO
4
3%
Ta strychnin To mui SO
4
, pH = 4,5
Nc ci kt tinh, lc, ht kit
Tinh th strychnin SO
4

Sy, cn, kim nghim, ng gi
Sn phm Strychnin sulfat
Hnh 17.10. S qui trnh chit xut strychnin sulfat t ht m tin

239
b. M t cc giai on sn xut
Chun b nguyn liu:
Ht m tin sau khi chn c loi tt sy kh 60 - 80
0
C em xay thnh
bt th.
Kim ha:
Bt ht m tin c trn u vi dung dch nc sa vi, o k cho n
khi to thnh bt nho. Vun thnh ng ri khong 24 gi. Sau o, trn
u lm ti v lm kh.
Chit xut:
Nguyn tc chit: Chit nng 90-100
o
C. Bng phng php ngc dng
gin on c khuy trn. Dung mi chit l du ho.
Tin hnh chit:
Np bt dc liu kim ha vo thit b chit, dung mi, khuy
trn dung mi tip xc tt vi dc liu. Cp nhit m bo nhit
chit khong 100
0
C. Rt dch chit sau khi chit thi gian qui nh.
Tinh ch:
Acid ha to mui sulfat tan trong nc ca cc alcaloid:
Cho dung dch H
2
SO
4
3% vo thit b phn ly c khuy ng dch chit
va rt ra. Khuy 10 pht hai pha tip xc tt vi nhau. yn cho phn
lp (cho ti khi hai lp trong li l c). Gn ring dung mi, thu hi dung
mi chit cho m sau (x l bng cch kim ha, khuy k, pH = 6-7,
lng, gn b cn. Pha acid tch ra a vo x l tip giai on sau.
Kim ha to ta alcaloid ton phn:
Lp nc acid trn c trung ho bng dung dch Na
2
CO
3
bo ha, n
pH 10-11 alcaloid ton phn s kt ta. Lc ly ta bng phu Buchner (c th
dng my vy thu ta). Ra ta 3 ln, mi ln bng 1 lng nc sao cho
va ngp ta. Loi b nc ci v nc ra.
To mui nitrat ca cc alcaloid (loi brucin):
Nguyn tc loi brucin: To mui nitrat ca cc alcaloid ti pH = 4-4,5.
strychnin nitrat s kt tinh.
Th brucin: Nh 1 git HNO
3
c vo 1 vi ht tinh th, nu c brucin
th s thy xut hin mu hng.
Tin hnh:
Ho ta alcaloid ton phn vo mt lng nc va sao cho va
ngp ta, un trong ni cch thu, va khuy va nh dn dung dch HNO
3

240
vo cho n khi kt ta tan ht v pH = 4 - 4,5 (ch nu pH m vn
cha tan ht kt ta th cho thm nc ct na, nu dung dch b long th
phi c bt to dung dch bo ha). kt tinh qua m s to tinh th
hnh kim, thng kt thnh chm. Lc qua phu Buchner. Ra tinh th 3 ln
bng nc ct lnh.
Ty mu bng than hot:
ty mu trc tin phi ho tan ta vo mt lng nc ct va
un trong ni cch thu khuy u cho tan ht. Sau thm than hot vo,
khuy 10 pht. Lc nng.
To sn phm l strychnin sulfat:
Mun chuyn alcaloid t dng mui ny sang dng mui khc u tin
ta phi chuyn qua dng base.
Chuyn sang dng base: Kim ha dch lc trn bng Na
2
CO
3
bo ho,
va nh va khuy cho n khi ht si bt v pH=10-11. ngui cho kt ta
(khong 30 pht). Lc ly ta base, ra bng nc ct.
Chuyn sang dng mui sulfat: Cho thm vo ta trn mt lng va
nc ct t trn ni cch thu, va khuy va nh dung dch H
2
SO
4
3% vo
v chnh pH = 4 - 4,5. ngui kt tinh qua m. Lc ly tinh th ra bng
nc ct. Sau khi ra ch ht kit nc sy cho nhanh. em sy kh 60
- 70
0
C trong khong 100-150 pht. Ch thnh thong o ti ln sy cho
nhanh kh. Nc ci sau khi lc tp trung thu hi strychnin.
ng gi: Trong l kn, trnh nh sng, dn nhn c bng A, nguyn cht.
Kim nghim: Theo DVN.
T lng gi
1. Nu nh ngha v phn b ca alcaloid trong thc vt.
2. Trnh by tnh cht chung ca alcaloid.
3. Trnh by cc phng php chit alcaloid.
4. Trnh by cc phng php tch alcaloid di dng tinh khit.
5. Cc alcaloid nhm atropin: trnh by cu trc, tnh cht, tc dng
dc l.
6. Trnh by qui trnh chit xut hyoscyamin, atropin, scopolamin.
7. Cc alcaloid chnh ca thuc phin: nu tnh cht, cu trc, tc dng
dc l.
241
8. Trnh by qui trnh chit xut cc alcaloid thuc phin: morphin,
codein.
9. Berberin, palmatin, rotundin: trnh by tnh cht, cu trc, tc dng
dc l.
10. Berberin, palmatin, rotundin: v s qui trnh, m t cc giai on
sn xut.
11. Quinin, quinidin: trnh by tnh cht, cu trc, tc dng dc l.
12. Quinin sulfat: v s qui trnh sn xut v m t cc giai on sn
xut.
13. Strychnin: trnh by cu trc, tc dng dc l.
14. Strychnin sulfat: v s qui trnh sn xut v m t cc giai on
sn xut.

242
Chng 18
Chit xut cc hot cht
c ngun gc t nhin khc
Mc tiu
1. Cc thnh phn ho hc ch yu c trong cy THHV.
2. Cu trc ca artemisinin.
3. Cc tnh cht l ha ch yu ca artemisinin.
4. Cc phng php chit artemisinin t cy THHV.
5. Cu trc ca rutin v cc phng php chit rutin t hoa ho.
1. Chit xut artemisinin v acid artemisinic t cy thanh
hao hoa vng
1.1. i cng v cy thanh hao hoa vng
Chi Artemisia c trn 300 loi v thng c s dng lm gia v, thuc
tr su v l ngun nguyn liu sn xut tinh du. A. vulgaris c s dng
trong y hc c truyn Trung Quc lm thuc iu tr au d dy, nhc u, a
chy, st, thp khp, vim phi... A. absinthium c cha absinthe, mt cht
ma tu c tc dng gy ng v l mt ngun cung cp tinh du s dng trong
xoa bp v au d dy. A. annua, mt cy sng hng nm cc vng c kh
hu n ho c hu nh trn khp lnh th ca Trung quc. M n mc
hoang ch yu dc theo cc sng cc bang New York, New Jersey, Maryland,
Virginia, v Ty Virginia. Tuy nhin, ngi ta cho rng n khng c ngun gc
M. N cng mc hoang Nam T c, Hungari, Bungari, Rumani, Italia,
Php, Ty Ban Nha, Th Nh K, Arhentina v Lin X c.
Cc nghin cu Trung Quc, n , Th Nh K, Australia vi mc
ch nng cao hm lng ca artemisinin trong cy thanh hao hoa vng. Mc
d cy thanh hao hoa vng mc Trung Quc c cng b c hm lng n
0,9% nhng ni chung cy thanh hao hoa vng mc ni khc ch c khong
0,1% artemisinin. Hm lng artemisinin cao nht trong phn l phn ngn
(50 cm t phn ngn tr xung) v thi im trc khi cy ra hoa. V
243
artemisinin c trong cy vi hm lng thp nn ngi ta pht hin cc cy c
hm lng cao v tm cch nng cao hm lng ca n trong cy. Ngoi ra
ngi ta cn tm cch tng hp n, nhng qu trnh tng hp qu phc tp v
khng c kh nng a vo ng dng. Tuy nhin nu ta s dng cc hp phn
khc trong cy thanh hao hoa vng lm nguyn liu bn tng hp artemisinin
th c nhiu trin vng.
1.2. Cc thnh phn ho hc khc trong cy thanh hao hoa vng
Gi tr ca artemisinin lm thuc khng st rt thc y nghin cu
cc thnh phn khc c trong cy thanh hao hoa vng. Artemisiten, c pht
hin ln u tin nh HPLC-EC (Detector in ho) v sau c phn lp
t cy thanh hao hoa vng vi hiu sut rt thp. Sau n c tng hp t
acid artemisinic. Hot tnh chng st rt ca n in-vitro thp hn ca
artemisinin. Ngoi ra ngi ta cn chit xut t cy THHV mt lot cc hp
cht sesquiterpen v cc hp cht hu c khc nh acid artemisinic (Qinghao
acid), Qinghaosu I (arteannuin A), Qinghaosu IV, Qinghaosu V (arteannuin
E), Qinghaosu III (deoxyartemisinin), artemisinilacton (arteannuin F),
artemisiten (dehydroartemisinin), methylether ca acid artemisinic,
arteannuin C, Qinghaosu II (arteannuin B), artemisinin G,
epidesoxyarteannuin B, artemisinol, v acid epoxyartemisinic. Tt c cc
sesquiterpen c phn lp ra t cy THHV u c s lin h mt thit vi
nhau v u c cng mt c trng l s c mt ca b khung cis-decalin
trong phn t ca chng.

Acid artemisinic Desoxyartemisinin
Arteannuin C
C H 2 H O2C
H 3 C
H
CH 3
H
O
O
O
H 3 C
CH3
CH3
H
H
O
H3C
H
C H 3
O
H
O
O
C H 2

Artemisiten Acid epoxyartemisinic Acid artemisinic methylester
O
O
O
O
H 3 C
CH3
H
H
O
CH 2
CH2 HO2C
H3C
H
CH3
H O
H3C
H
C H 3
H
H2C C O O C H 3

244

Artemisinin G Qinghaosu IV Arteannuin E
O
H
C H 3
OH
H3C
O
C H 2
O
O
O
H 3 C
CH3
CH3
H
H
O
H O
O
O
C H 3
CH3
H
H
O
O
O
H 3 C

Arteannuin A
O
O
H
3
C
H
CH
3
H

1.3. Chit xut artemisinin t cy THHV
1.3.1. Cu trc v tnh cht ca artemisinin
Cu trc
O
O
O
O
O
CH
3
H
3
C
H
H H
CH
3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
O
O
O
O
O
CH
3
H
3
C
H
H H
CH
3
1 2
4
5
5a
6
7
8
8a
9
10
12
12a
13
11
3

Hin nay cch nh s theo Merck Index v Chemical Abstract thng
dng hn. Artemisinin l mt sesquiterpenlacton. Phn t artemisinin c 15
nguyn t carbon v 5 nguyn t oxy to h thng 4 vng lin hp A, B, C, D.
Vng A l vng cyclohexan dng gh, vng D l mt delta-lacton v vng B,
C l d vng no cha oxy.
nh s theo h thng vng v
khung carbon theo mt s
tc gi Trung Quc
nh s theo Merck Index v
Chemical Abstract
245
Tnh cht ca artemisinin
Artemisinin l tinh th hnh kim khng mu hoc bt kt tinh trng c
im chy 156-157
0
C (c ti liu vit 153-154
0
C), nng sut quay cc 66,3
0

(C = 1.64, CHCl
3
). Ph hng ngoi c nh hp th 1745 cm
1
(deltalacton) v
772, 831, 881, 1115 cm
-1
(peroxyd). Artemisinin tan nhiu trong etanol,
aceton, cloroform, t tan trong n-hexan, benzen, toluen v hu nh khng tan
trong nc, n d b thy phn v phn hy trong cc dung mi phn cc
nhit cao, tuy nhin trong cc dung mi khng phn cc n kh bn vng.
Artemisinin tinh khit kh bn vng di tc dng ca nhit , n khng
b phn hy nhit chy ca n v cng khng bin i nhit cao hn
chy ca n 50
0
C trong vng 5 pht, v vy c th tinh ch bng phng php
thng hoa. Artemisinin d b phn hy trong mi trng acid, kim.
1.3.2. Mt s phng php c s dng chit artemisinin v acid
artemisinic
Mc du artemisinin c phn lp u tin Trung Quc (c th l
Nam T c) nhng cng b u tin v phng php chit artemisinin trong
phng th nghim li l ca Klayman v cc cng s. L cy thanh hao hoa
vng phi kh c chit vi dung mi petrolether (30-60
0
C). Dch chit c
c c v ho tan li trong cloroform, thm acetonitril vo kt ta cc hp
cht tr trong cy nh ng v sp. Sc k dch c c trn ct silicagel trin
khai bng dung mi cloroform-ethylacetat. Theo di dung dch gii hp ph
ca sc k ct bng sc k lp mng hin mu bng hi iod. Phn dch gii
hp th c hm lng artemisinin cao c th kt tinh t cyclohexan hoc t
cn 50%.
El Feraly v cng s m t k thut chit tch artemisinin quy m
sn xut nh sau: L THHV kh c chit bng hexan. Ch s dng l lm
nguyn liu chit do thn v cnh thanh hao mc d chim n 80% trng
lng ca cy nhng v n khng c artemisinin hoc nu c th vi t l rt
thp. Dch chit c phn b gia hai pha lng khng ng tan c c v
loi b cc tp cht. Giai on trung gian ny ci thin hiu qu ca giai on
tch bng sc k ct.
Vic phn b dch chit hexan c c thc hin bng cch s dng
hexan v acetonitril-nc. C 1 g cn s dng 12 ml hexan v v 4 ml
acetonitril 20% nc. Kt qu ca giai on phn b ny l hu nh ton b
artemisinin chuyn sang pha acetonitril v lng cht rn chuyn sang pha
acetonitril ch bng 32-36% lng cn ban u. Nng cao ca artemisinin
trong mu a vo sc k ct lm tng kh nng tch v tng hiu qu lm
vic ca ct. Trc khi ct loi acetonitril cn loi b nc. Loi b nc c th
thc hin bng phng php thng thng nh ct ng ph vi benzen hoc
cn tuyt i hoc s dng natri sulfat khan. C th s dng mt phng
246
php n gin, hiu qu v r tin loi nc bng cch lm bo ho pha
acetonitril nc bng natri clorid, sau loi b phn nc mui tch ra. Pha
acetonitril c bc hi, thu c cn du mu vng nu c t l artemisinin
giu hn 3 ln c trong dch chit. V pha acetonitril cng giu acid artemisinic
nn c th kt tinh mt phn acid artemisinic. Do c th loi i 10% cht rn
trong pha acetonitril trc khi a vo sc k ct.
Sc k ct c thc hin vi t l cht tan: cht hp ph = 1: 10 cho kt
qu tt nht. Nu khng lm giai on phn chia th t l ny l 1: 44. Hn
hp dung mi chy ct l hexan vi t l ethylacetat t 10 n 20%. Khi chy
sc k ct acid artemisinic s b ra gii ra trc sau l artemisinin, nhng
do acid artemisinic b loi ra phn ln trc nn artemisinin thu c
rt tinh khit.
Qu trnh sc k ct c thc hin nh sau:
Ct sc k c np bng silicagel. Lng silicagel nhi ct ph thuc vo
lng hn hp cha artemisinin a vo tch, theo t l hn hp cha
artemisinin: silicagel = 1:10. Hn hp cha artemisinin c ho tan trong
aceton v luyn vi mt lng silicagel (theo t l hn hp cha artemisinin:
silicagel = 1:1). cho bay hi ht dung mi v np vo phn trn ca ct.
Qu trnh ra gii artemisinin v acid artemisinic t ct c thc hin
qua cc giai on sau:
1. Chy SKC s dng h dung mi ethylacetat: hexan = 10:100 lng
dung dch ra gii rt ra bng mt th tch ct (th tch silicagel trong
ct nhi). Phn dung dch ra gii ny cha acid artemisinic).
2. Tip tc chy SKC bng h dung mi ethylacetat: hexan = 15:100 v
thu lng dung dch ra gii bng 1 th tch ct, trong phn on
u cha acid artemisinic = 0,65 th tch ct v phn on sau cha
artemisinin = 0,35 th tch ct.
3. Tip tc chy SKC bng h dung mi etyl acetat: hexan = 20:100 v rt
ra 1,5 th tch ct dung dch ra gii. Phn ny c cha artemisinin.
Bc hi dung mi cc phn on cha acid artemisinic v artemisinin thu
c acid artemisinic v artemisinin. C th kt tinh li trong cc dung mi khc
nhau thu c sn phm tinh khit.
Ct c th s dng c t nht 2 ln. Trc khi s dng ln tip theo ct
c ra bng 1,5 th tch ethylacetat. Khi s dng ct ln 2, h dung mi
chy phi c gim phn cc, c th l gim lng ethylacetat xung cn
8,13 v 18%. Hn hp ethylacetat/hexan c th s dng li sau khi lm khan
bng Na
2
SO
4
v iu chnh thnh phn ca hn hp.
247
Vit Nam, ngay t nm 1990 nghin cu chit artemisinin. quy
m cng nghip chng ta khng s dng petrol ether c si 30
0
-60
0
C
chit do gi thnh cao v petrol ether kh kim Vit Nam. a s cc c s
chit artemisinin Vit Nam u dng xng cng ngh hoc n-hexan lm
dung mi chit. tng tan ca artemisinin trong dung mi chit c th
thm vo vi phn trm aceton, cn ethylic hay cloroform vo xng cng ngh
hoc n-hexan. Tuy nhin cn ch l khi lm nh vy tan ca artemisinin
tng ln ng k nhng dch chit s ko theo nhiu tp cht khc nh hng
n giai on tinh ch sau ny.
Tinh ch artemisinin
Dch chit sau khi rt ra c ct thu hi dung mi n khi khi lng
cn 1/20 hoc 1/30 dc liu em chit. Cn cn li c th c tinh ch bng 2
phng php sau:
Phng php 1: Chit artemisinin trong cn cn li sau khi ct thu
hi dung mi bng cn 50
0
nng, cn 50
0
nng ch ho tan artemisinin
m khng ho tan sp (tp cht chnh c trong phn cn sau khi ct
thu hi dung mi). ngui artemisinin s kt tinh, kt tinh li
trong cn 96
0
.
Phng php 2: Phn dung dch c c c kt tinh trong 24 gi.
Gn phn nc ci, phn c gm ch yu l sp v tinh th
artemisinin. Loi sp bng nhit v xng nng ta s thu c
artemisinin th. Ho tan trong cn 96
0
, ty mu bng than hot,
ngui kt tinh artemisinin, sy nhit 70-80
0
C.
1.3.3. Phng php chit xut artemisinin c s dng Vit Nam
L THHV c phi kh, xay th v np vo ni chit. C th s dng
dung mi chit l xng cng nghip hoc n- hexan. T l dung mi/nguyn liu
l 5/1, chit nhit 30-50
0
C, thi gian chit 3 gi. Chit 3 ln, dch chit ln
1 v 2 em c thu hi dung mi, dch chiit ln 3 s dng lm dung mi chit
ln 1 m khc. Dch chit 1 c n khi lng dch c c tng vi lng dc
liu em chit. Dch chit 2 c n khi lng dch c c bng 1/5 lng dch c
c ca dch chit 1. Dch c c rt ra c kt tinh t nht 24 gi,
artemisinin s kt tinh ln vi sp. Loi phn dung dch bng cch gn, loi
sp bng nhit v xng nng thu c artemisinin th khng ln sp. C
th kim tra loi sp ht bng cch ho tan artemisinin th trong aceton,
nu dung dch trong l loi ht sp. Artemisinin th loi ht sp c
ho tan trong cn si, thm than hot v un si 20 pht vi sinh hn hi lu,
lc nng loi than hot v kt tinh nhit thng ti thiu 24 gi. Vy
ly tm, ra tinh th bng cn v sy 80
0
C.
248

Hnh 18.1. S chit xut artemisinin t cy THHV
Sp
Than hot
Thu hi DM
Ho tan
Ty mu
Lc loi than
Chit
kt tinh
Ct thu hi DM
Gn
Loi sp
kt tinh
Ly tm
Sy
Xay
L THHV
B TCHV
n-hexan
xng cng nghip
cn 96
0
249
2. Chit xut Rutin t Hoa ho
Hoa he (Sophora japonica Papilionaceae). Cy hoa ho cao t 5-6 m, l kp
hnh lng chim. Vit Nam trng khp ni, dng n hoa he chit rutin.
2.1. Thnh phn ha hc
Hoa he cha t 10-28% rutin, khi thu phn s cho quercetin (C
15
H
10
O
7
),
glucose v rhamnose

Quercetin
Rutin
Rhamnose Glucose
+ +
O HO
OH O
OH
O H
O H
C
6
H
11
O
4
C
6
H
10
O
4
O H
O H
O H O
O H O
O

2.2. Chit xut
C nhiu phng php. Ta c th chit rutin bng nc nng, bng dung
dich kim hoc bng cn.
Chit bng dung dch kim: hoa he gi dp. Ra bng HCl 0,5% ri
ra bng nc cho ht axit. Chit bng dung dch Na
2
CO
3
1% hoc natri
borat 1-3%. Rutin s tan nhiu do c chc phenol trong phn t. Rt dch
chit ra v tip tc chit cho n khi ht Rutin (3-4 ln). Gp cc dch
chit li, dng HCl iu chnh n pH=2 ta c Rutin kt ta. Lc. Tinh
ch: Ra ta bng nc n pH=4-5. Ho tan, kt tinh li trong cn.
Chit bng nc: nc si: 1 lt ho tan 5 g rutin. Nc 20
o
C: 1 lt ha
tan 0,13 g rutin. V vy c th chit rutin t hoa ho bng nc nng sau
ngui rutin s ta nhng phng php ny hiu sut thp.
Chit bng cn: dng cn 90
o
chit. un si cn vi hoa ho trong 2
gi. Rt dch chit, ct thu hi cn. Ta s thu c rutin ta, lm nh
vy vi ln n ht rutin (nu dng Soxchlet chit th tn dung
mi, hiu sut cao). Kt tinh li trong cn, ty mu bng than hot ta c
rutin tinh khit. Phng php chit bng cn cho hiu sut cao, t l
rutin trong hoa ho c th ln n 20-30%.

250
T lng gi
1. Trnh by thnh phn ha hc ca cy thanh hao hoa vng.
2. Trnh by cu trc, tnh cht l, ha ca artemisinin.
3. Trnh by cc phng php chit xut v tinh ch artemisinin t cy
thanh hao hoa vng.
4. Trnh by cu trc ca rutin.
5. Trnh by cc phng php chit xut rutin t hoa ho.
251
ti liu tham kho
1. B mn Bo ch, K thut bo ch v sinh dc hc cc dng thuc,
tp I. Trng H Dc H Ni, 2003.
2. B mn Cng nghip Dc, K thut sn xut dc phm, tp I, Trng
H Dc H Ni, 2001.
3. m Trung Bo, L Quang Ton, K thut bo ch cc dng thuc v
cc ch phm, phn 2, tp IV. Trng H Dc H Ni, 1971.
4. Vn i, Nguyn Bin, Phm Xun Ton, Ngc C..., C s cc
qu trnh v thit b cng ngh ho hc, Tp I, Trng H Bch
khoa, 1999.
5. L Quang Ton, K thut Ho dc, tp 1, Nh xut bn Y hc, 1971.
6. Nguyn Bin, Cc qu trnh, thit b trong cng ngh ho cht v thc
phm, Tp IV, NXB KHKT, 2005.
7. Nguyn Vn n, Nguyn Vit Tu, Phng php nghin cu ho
hc cy thuc. NXB Y hc, 1985.
8. Phm Thanh K, Nguyn Th Tm, Trn Vn Thanh, Bi ging dc
liu, tp II, Trng H Dc H Ni, 2005.
9. Phan nh Chu, C s k thut tng hp Ho dc, Ti liu ging
dy sau i hc, Trng i hc Dc H Ni, 1997.
10. Deak G., Morgos J., Gyurkovics I., Szerves Vegyipari alapfolyamatok,
Muegyetemi Kiado, 1993.
11. Fogassy E., Kadas I., Szabo G. T., Gyogyszerkemiai alapfolyamatok,
Muegyetemi Kiado, 1993.
12. John E. Hoover, Remington's Pharmaceutical Siences, Mack
Publishing Company, 1970.
13. P. H. List and P. C. Schmidt, Phytopharmaceutical Technology, CRC
Press. Inc. 1989.
14. R. H. F. Manske, The alkaloid - Chemistry and Physiology, volume
XIV, Academic Press - New York - London, 1973.
15. Szantay Cs., Elmeleti szerves kemia, Muszaki konyvkiado, Budapest,
1984.

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