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Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl
halides when a good leaving group is needed
Three general methods exist for conversion of alcohols to alkyl halides, depending on
the classification of the alcohol and the halogen desired
Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen halides
Sec. 11 -alcohols 1
Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2
Sec. 11 -alcohols 2
Reaction of thionyl chloride to give alkyl chlorides
Often an amine is added to react with HCl formed in the reaction
Sec. 11 -alcohols 3
Tosylates, Mesylates, and Triflates: Leaving Group
Derivatives of Alcohols
The hydroxyl group of an alcohol can be converted to a good leaving
group by conversion to a sulfonate ester
Sec. 11 -alcohols 4
A sulfonate ion (a weak base) is an excellent leaving group
Sec. 11 -alcohols 5
Alcohols by Reduction of Carbonyl Compounds
with LiAlH4 and NaBH4
R-OH
Nucleophile Electrophile
(base) (acid)
Sec. 11 -alcohols 6
Mechanism with LiAlH4 and NaBH4
Electrophile H
(acid) O R C R
O R
+ 3 C R O R
C H C OAlH3 Li R R H C O Al O C H
R R
R R O R
+ R H3O +
R C R
Li H3Al- H
H C OH H
Nucleophile
(base) R a tetra-alkyl aluminate
Electrophile
(acid)
O
H2O
C δ+
R R
+
Na H3B- H
Nucleophile
(base)
Sec. 11 -alcohols 7
Examples Reduction - gain of electrons
or add hydrogens
O 1) LiAlH4/Et2O
2) H3O+
H or
OS = +1 NaBH4/H2O
O
NaBH4/H2O
OS = +3 O
HO OS = +2
O
OS = +2 O 1) LiAlH4/Et2O
2) H3O+
O OS = +3
O
1) LiAlH4/Et2O
2) H3O+
OH
OS = +3
Sec. 11 -alcohols 8
Oxidation of Alcohols Oxidation - loss of electrons
or add oxygens
OS = -1 very hard to
KMnO4 / OH¯ / heat stop oxidation
CH3CH2CH2OH
or
propanol NaCr2O7 / H2SO4
or
H2CrO4 or CrO3 Jones reagent
OH OH
H2CrO4 H2CrO4
acetone acetone
OS = -1
O
CH2Cl2
CH3CH2CH2OH + PCC CH3CH2CH
Cl
stops at aldehyde C
H Cl
H
aprotic solvent
Sec. 11 -alcohols 9
Organometallic Compounds
+
δ δ+
C M - C M C M
Organolithium Compounds
ether Li
Br + 2 Li + LiBr
ether Li + LiBr
Br + 2 Li
Sec. 11 -alcohols 10
Grignard Reagents
Br ether MgBr
+ Mg
ether
Br + Mg MgBr
General Reactions
The actual structure of the Grignard reagents are more complex than the formula
2 RMgX R2Mg + MgX2
Sec. 11 -alcohols 11
Grignard reagents as well as organolithium compounds are very strong
bases. They act as if they have free carbanions. Organolithium
compounds will react as a Bronsted-Lowry base or as a nucleophile.
CH3MgBr + CH3CH2O-H
carbon with a negative charge is a stronger base than an oxygen with a negative charge
C C H +
SN2 O
dilute HCl
Sec. 11 -alcohols 12
Grignard Reagents and Carbonyl Compounds
Step One
Mechanism
nucleophilic attack
R on carbonyl carbon
R MgX + C O
nucleophile ether
R
(base)
electrophile halomagnesium alkoxide
Step Two (acid)
R H
+
R C O H O X
Mg2+ X
H
R
alcohol
δ δ+ δ H HBr
δ+ δ ether
-R1MgBr- + (dilute)
C -O + MgBr2
H
formaldehyde 1° alcohol
R2
δ δ+ δ HCl
δ+ δ ether
-R1MgBr- + (dilute)
C -O + MgBrCl
H
an aldehyde 2° alcohol
R2
δ δ+ δ HCl
δ+ δ ether
-R1MgBr- + (dilute)
C -O + MgBrCl
R3
a ketone
3° alcohol
Sec. 11 -alcohols 14
General Reactions
R2
δ δ+ δ δ+ δ
-R1MgBr- ether
+ C -O
R3O
δ δ+
a ester
-R1MgBr
HCl
(dilute)
3° alcohol
Grignard Reagent add twice because a ketone is created as an intermediate that can
react with the second equivalence of the Grignard Reagent
Sec. 11 -alcohols 15
Sec. 11 -alcohols 16
Sec. 11 -alcohols 17
Examples
Because Grignard reagents are very strong bases they can not be made from
compounds that have acidic hydrogens → -OH, -NH2, -SH, -CO2H, -SO3H etc.
Although we can make acetylenic Grignards through an acid base reaction and
use it to our advantage. δ O
-δ+ OH
CH3MgBr 1)
CH3CH2C CH CH3CH2C CMgBr H
ether
+ CH4(g) 2) H3O+
H3C
O 1) CH CH2Li
H3 C
2) H3O+ OH
Sec. 11 -alcohols 18
Examples
Sometimes a Grignard reaction can be completed with a compound containing an
acidic hydrogen if two equivalents of the reagent is used
O
ether CH3MgBr
CH3MgBr + HOCH2CH2CCH3
2) H3O+
C
Na NH2 1) H3C CH3
CH3CH2C CH
2) NH4Cl, H2O
H
+
H N H
H Cl
H2 / Pd
acid