Alcohols, Ethers and Phenols

ALCOHOLS, ETHERS AND PHENOLS E M RAO
ALCOHOLS
Physical properties:
Solubility: Alcohols are quite soluble in water as they can form hydrogen bond with water.
But alcohols having equal to or more than 6 carbons per OH group are insoluble in water as they
have predominating hydrophobic (hydrocarbon) chain.
Boiling point: Alcohols have higher boiling points than hydrocarbons of similar molecular
weight due to hydrogen bonding. For a given molecular formula, more the branching lesser is the
boiling point.

0 0
3 2 2 2 3 3 2
0 0
3 2 3 3 3
CH CH CH CH OH 118C CH CH(CH )CH OH 108C
CH CH CH(OH)CH 100 C (CH ) COH 83C

More the number of OH groups more is the boiling point.

0 0
3 2 2 2
CH CH OH 97 C HOCH CH OH 198 C

Methods of preparation:
1. Hydration of alkenes:
Water can be added to alkenes in three different ways. Some alkenes give three different
isomers in the three methods.

CH
3
-CH-CH=CH
2
CH
3
dil. H
2
SO
4
CH
3
CH
3
-C-CH
2
-CH
3
OH
Acid catalysed hydration:
CH
3
-CH-CH=CH
2
CH
3
1.Hg(OAc)
2
/H
2
O
2. NaBH
4
CH
3
CH
3
-CH-CH-CH
3
OH
Oxymercuration-demercuration:
CH
3
-CH-CH=CH
2
CH
3
1. B
2
H
6
;THF
2. H
2
O
2
;OH
-
CH
3
-CH-CH
2
CH
2
OH
CH
3
Hydroboration-oxidation

Acid catalyzed hydration:
Mechanism:
CH
3
-CH=CH
2
H
+
slow
CH
3
-CH-CH
3
+ H
2
O
CH
3
-CH-CH
3
OH
2
+
CH
3
-CH-CH
3
OH
-H
+

Acids that have weakly nucleophilic conjugate bases are used in this reaction e.g. H2SO4, H3PO4
etc. Being weakly nucleophilic, HSO4
-
and H2PO4
-
offer little competition to H2O. In the case of
H2SO4, small amount of ROSO3H may be formed. As soon as formed, it undergoes hydrolysis to
form ROH because HSO4
-
is a very good leaving group.
Reactivity of alkenes towards acid catalyzed hydration: As formation carbocation is the rate
limiting step, the alkene which forms the more stable carbocation will be more reactive.
ALKENE Relative rate of reaction with
H
3
O
+

CH2=CH2 1
CH3-CH=CH2
6
1.6 10
(CH3)2C=CH2
11
2.5 10


Examples:
H
+
OH
H
+
OH
OH
1.
2.
and its enantiomer and its enantiomer
+

Oxymercuration-demercuration:
Mechanism:

(Q)
CH
3
-CH-CH=CH
2
CH
3
Hg(OAc)
2
Hg(OAc)
H
2
O
CH
3
CH
2
-CH-CH-CH
2
-Hg(OAc)
OH
2
+
CH
3
CH
2
-CH-CH-CH
2
- Hg(OAc)
OH
CH
2
-CH-CH-CH
2
-
Hg(OAc)
OH
NaBH
4
CH
3
CH
2
-CH-CH-CH
OH
1.
2. H
2
O as a nucleophile attacks the carbon that can form more stable carbocation (as in the case of cyclic halonium
ion).
(cyclic mercurinium ion)
C
H
CH
3
H
3
C
+
Hg(OAc)
C
H
CH
3
H
3
C
+
CH
3

Cyclic mercurinium ion is similar to cyclic halonium ion. Like in the case of halogenations, there is
no fully fledged carbocation in this reaction too. The net addition of H and OH is syn and anti both
(although oxymercuration is anti addition, demercuration step is a mix of both syn and anti). If H2O
is replaced with any other polar solvent, the product is obtained accordingly.
Examples:

1.Hg(OAc)
2
/H
2
O
2. NaBH
4
OH
1.Hg(OAc)
2
/MeOH
2. NaBH
4
OCH
3
OH 2. NaBH
4
O
1.Hg(OAc)
2
1.
2.
3.

Hydroboration-oxidation:
Diborane in THF exists as the following complex.
O BF
3
+

THF can be replaced by diglyme, CH3OCH2CH2OCH2CH2OCH3.
Mechanism:

CH
2
CH
3
CH
H BH
2
CH
3
CH
2
-CH
2
BH
2
Both H and BH
2
are added from the same side i.e.syn addition
1.
Same reaction repeats until two more alkenes molecules are added. Finally we get tri-
alkyl boride
B
CH
2
CH
2
CH
3
H
3
CH
2
CH
2
C
CH
2
CH
2
CH
3
Tri-alkyl boride

Boron attacks less hindered carbon because of the crowding in trialkyl boride. Trialkyl boride
undergoes oxidation in the second step.
2. H
2
O
2
+OH
-
H-O-O
-
+H
2
O
3. (CH
3
CH
2
CH
2
)
3
B +H-O-O
-
(CH
3
CH
2
CH
2
)
3
B O-OH
B
CH
2
CH
2
CH
3
H
3
CH
2
CH
2
C
CH
2
CH
2
CH
3
O OH
4.
(CH
3
CH
2
CH
2
)
2
B(OCH
2
CH
2
CH
3
)
Step 4 involves migration of alkyl group from boron to oxygen. As is the case
with all migrations, here also it is simultaneous. Steps 3 and 4 repeat two more
times until trialkyl borate is formed. Trialkyl borate undergoes hydrolysis to
give 3 moles of alcohol and H
3
BO
3
.
5. (CH
3
CH
2
CH
2
O)
3
B +OH
-
3 CH
3
CH
2
CH
2
OH +H
3
BO
3

The net addition of H and OH is syn.
Examples:
1.B
2
H
6
;THF
2.H
2
O
2
, OH
-
OH
1.
1.B
2
H
6
;THF
2.H
2
O
2
, OH
-
OH
2.
+
and its enantiomer

EXERCISE I:

1.
OH
1.Hg(OAc)
2
2. NaBH
4

2.
1.B
2
H
6
;THF
2.H
2
O
2
, OH
-

3. H
3
O
+

4.

1.B
2
D
6
;THF
2.H
2
O
2
, OH
-

5.
Et
1.Hg(OAc)
2
/ PhOH
2. NaBH
4

6.
O
CH
3
OH
H
+


2. From the nucleophilic substitution reactions of alkyl halides:

CH
3
CH
2
Br
NaOH
aq. acetone
CH
3
CH
2
OH
(CH
3
)
3
CBr
H
2
O
Acetone
(CH
3
)
3
COH
S
N
2
S
N
1

3. From epoxides: Epoxides are three membered cyclic ethers. They are highly
reactive due to ring strain. Nucleophiles attack epoxides and thereby convert them into alcohols.
O
1.LiAlH
4
2.H
+
CH
3
CH
2
OH
O
1.LiAlH
4
2.H
+
CH
3
CHCH
3
OH

O 2.H
+
CH
3
CH
2
CH
2
OH
O
CH
3
CHCH
2
CH
3
OH
1.CH
3
MgBr/dry ether
2.H
+
1.CH
3
MgBr/dry ether

Mechanism:

O
CH
3
CH
2
OH
H
-
CH
3
CH
2
O
-
H
+

When epoxides undergo attack directly (without first being protonated) by a nucleophile, the
attack occurs at less hindered carbon. But a protonated epoxide undergoes attack by a
nucleophile at more substituted carbon. We will see the details about this later in epoxides.
Epoxides react with LiAlH4, NaBH4, RLi, RMgX and even with R2CuLi.

O
1.(CH
3
)
2
CuLi
2.H
2
O
OH

2. By reduction of carbonyl compounds (aldehydes, ketones, carboxylic acids
and their derivatives):
Alcohols can be prepared by nucleophilic addition reactions of aldehydes and ketones.
They can also be prepared by the nucleophilic acyl substitution reactions of carboxylic acids and
their derivatives. Let us see the mechanism of both the reactions first and then have a look at
different reagents.

O
(H)R
R
Nu
-
O
-
Nu
R R(H)
OH
Nu
R R(H)
H
+
rds
Nucleophilic addition reactions of aldehydes/ketones:

When the nucleophile is H
-
(LiAlH4 or NaBH4) or R
-
(RLi/RMgX), the product will be an alcohol. ,-
unsaturated aldehydes and ketones behave differently toward nucleophile because the
nucleophile may attack the C-C double bond in addition to carbonyl carbon. The reactions of ,-
unsaturated aldehydes and ketones will be discussed in aldehydes and ketones chapter.

O
L
R
Nu
-
O
-
Nu
R L
rds
Nucleophilic acyl substitution reactions of acid chlorides, anhydrides and esters:
O
Nu
R
L - Cl / OR / OCOR


The above mechanism excludes carboxylic acids and amides because the mechanism in their
case is slightly different due to the presence of acidic hydrogen. The mechanism is discussed
later.

Different reagents used for reduction of carbonyl compounds
1. LiAlH4 in
dry ether
followed by
acidification
.
LiAlH4 reduces aldehydes, ketones, carboxylic acids, amides, anhydrides, esters
and acid halides. Alcohols are the products from all the above reductions except
from amides. Amides gove amines with LiAlH4. LiAlH4, being a strong hydride
donor, can only be used in a non-polar solvents like ethers.
1.LiAlH
4
2.H
+
O
H
R
R-CH
2
-OH
1.LiAlH
4
2.H
+
O
R
R
R-CHR-OH

1.LiAlH
4
R-C-Cl
O
R-C-H
O
The aldehyde further gets reduced and ultimately gives alcohol RCH
2
OH.

1.LiAlH
4
O
R-C-H +R'O
-
O
The aldehyde further gets reduced and the ester ultimately gives two alcohols RCH
2
OH
and R'OH.
R-C-OR'

R-C-H
O
The aldehyde further gets reduced and ultimately gives alcohol RCH
2
OH.
O
R-C-OH
H
-
O
R-C-O
-
H
-
O
R-C-O
-
Al
+2
H

1.LiAlH
4
2.H
+
O
R-C-NH
2
R-C-H
NH
R-CH
2
-NH
2
Mechanism:
O
R-C-NH
2
H
-
O
R-C-NH
-
H
-
O
R-C-NH
-
Al
+2
H
imine
H
-
NH
-
R-C-H
H
H
+
R-CH
2
-NH
2

1.LiAlH
4
R-C-H +R'-C-O
-
O
Both the carboxylate ion (R'COO
-
)and the aldehyde (RCHO) further get reduced and the anhydride
ultimately gives two alcohols RCH
2
OH and R'CH
2
OH.
R-C-O-C-R'
O
O O

2. NaBH4 in
C2H5OH
NaBH4 reduces aldehydes, ketones and acid halides only. It does not reduce
esters, anhydrides, amides and carboxylic acids. And the mechanism is similar to
that of LiAlH4. NaBH4, being a very weak hydride donor (due to very high covalent
character of B-H bond), can directly be used in polar solvents.

Organometallic compounds: RLi, RMgX and R2CuLi are the commonly used organometallic
compounds. Out of these, RLi is the strongest R
-
donor and R2CuLi the least. Observe the
following table.

C-M bond Difference in electronegativity Percent ionic character
*

C-Li 2.5-1 =1.5 60
C-Mg 2.5-1.2 =1.3 52
C-Zn 2.5-1.6 =0.9 36
C-Cu 2.5-1.9 =0.6 24

* C M
C
E -E
Percentioniccharacter= 100
E

3. RLi in dry
ether
followed by
acidification
.
Organo lithium compounds can reduce aldehydes, ketones, esters, anhydrides,
acid chlorides into alcohols. They convert carboxylic acids into ketones only. They
do not react with amides (at the most acid-base reaction may happen). Mechanism
of conversion of acid into ketone is given below.
OLi
R-C-OLi
R
H
+
O
R-C-OLi +RH
O
R-C-OH
R
-
R
-
OH
R-C-OH
R
O
R-C-R

4. RMgX in
dry ether
followed by
acidification
.
Grignard reagents convert aldehydes, ketones, acid halides and esters into
alcohols. They do not react with carboxylic acids and amides (at the most acid-
base reaction may happen in both the cases).
5. R2CuLi/
R2Cd
Gilmans reagent (R2CuLi) and R2Cd can only reduce acid chlorides. They do not
react with any other carbonyl compounds including aldehydes and ketones.
or R
2
Cd
O
R-C-Cl
R
2
CuLi
O
R-C-R

6. H2/Ni or
Pt
Catalytic hydrogenation converts aldehydes and ketones into alcohols. It converts
esters into alcohols only under drastic conditions. H2/Ni does not react with
carboxylic acids, amides, acid chlorides and anhydrides. H2 in the presence of
Lindlars catalyst (Pd-BaSO4) converts acid chlorides into aldehydes.

O
H
R
R-CH
2
-OH
O
R
R
R-CHR-OH
H
2
/Ni
H
2
/Ni
O
R'O
R
R-CH
2
-OH +R'OH
H
2
/Ni
O
Cl
R
O
H
R
H
2
Pd-BaSO
4
200
0
C/10 atm

7.B2H6/THF
followed by
hydrolysis
Diborane converts aldehydes, ketones and carboxylic acids into alcohols. The
mechanism of diborane reduction is similar to that of hydroboration oxidation of
alkenes.

O
H
R
R-CH
2
-OH
O
R
R
R-CHR-OH
1. B
2
H
6
/THF
O
HO
R
R-CH
2
-OH
2. NaOH
1. B
2
H
6
/THF
2. NaOH
1. B
2
H
6
/THF
2. NaOH

EXERCISE-II
1. Show how do you prepare n-butyl alcohol using C2H5MgBr?
2.
2.H
+
1.LiAlH
4
/THF
O
A +B

3.
1.CH
3
MgBr/THF O
O
A
2.H
+

4.
1.CH
3
MgBr/THF
O
O
A
2.H
+

5.
2.H
+
1.LiAlH
4
/THF
O-C-CH
3
H
3
CO-C
O O
A +B +C

6.
2.H
+
1.LiAlH
4
/THF
O
O C-OEt
A +B

Chemical reactions of alcohols
1. Conversion of alcohols into alkyl halides
Alcohols have poor leaving group i.e. OH
-
. As result, alcohols do not undergo direct
nucleophilic substitution reactions under normal conditions. But they can be made to undergo
nucleophilic substitution reactions by converting OH
-
into a better leaving group. Reagents like
HCl, PCl3, PCl5 and SOCl2 can convert alcohols into alkyl halides,

ROH +NaCl
No reaction
ROH
NaCl
H
2
SO
4
RCl +H
2
O
ROH +HCl RCl +H
2
O

ROH +NaBr
No reaction
ROH
NaBr
H
2
SO
4
RBr +H
2
O
ROH +HBr RBr +H
2
O

ROH +NaI
No reaction
ROH
NaI
H
2
SO
4
No reaction
ROH +HI RI +H
2
O
ROH
NaI
H
3
PO
4
RI +H
2
O

Note: Protonation makes OH
-
into a better leaving group i.e. H2O. As a result H
+
is necessary in
all the above reactions. H2SO4, being a mild oxidizing agent, oxidizes I
-
to I2. As a result, ROH
cannot be converted into RI with NaI/H2SO4.


I. HX. Observe the following examples.
MECHANISM
R-OH
H
+
R-OH
2
+ X
-
RX +H
2
O
S
N
2 mechanism if the R is primary.
R
+
+H
2
O
R
+
+X
-
RX
S
N
1 if the R is secondary or tertiary.

Some important points:
1. Reactivity of alcohols toward HX 3
0
>2
0
>1
0
.
2. Reactivity of different halides HF <HCl <HBr <HI
2
0
or 1
0
alcohols react with HCl to give very low yield. In order to increase the yield,
a Lewis acid (generally ZnCl2) is added. HCl +ZnCl2 mixture is called as Lucas
reagent. ZnCl2 complexes with the alcohol making OH
-
a better leaving group.

R-OH
ZnCl
2
+
-

II. PCl3 / PBr3 / P +I2
Phosphorous trihalides convert alcohols into alkyl halides. Observe the following
mechanism.

R-OH +
P
Cl Cl
Cl
P Cl
Cl
R-O
H
+
Cl
-
R-Cl +
P
Cl OH
Cl
Second step is S
N
2 mechanism when R is primary or secondary. Phosphorous halides are not used for
3
0
alcohols. P(OH)Cl
2
can convert two more moles of alcohols into RCl.
3 ROH +PCl
3
3 RCl +
P
HO OH
OH
P H
OH
O
OH

III. PCl5:
PCl5 also converts alcohols into alkyl halides and the mechanism is similar to that of PCl3.
But one mole of PCl5 converts only one mole of alcohol into alkyl halide.

ROH +PCl
5
RCl +POCl
3
+HCl

IV. SOCl2 (SNi mechanism)
SOCl2 converts alcohol into alkyl halide. The mechanism of this reaction depends on
presence or absence of a bulky base such as pyridine.

OH
H
R
R
1
+
O
S
Cl Cl
O
H
R
R
1
S
O
Cl +HCl
Substitution Nuceophilic internal,
where nucleophile is part of the
leaving group. Such a front side
attack leads to retention of configuration.
In the absence of pyridine:
In the presence of pyridine:
OH
H
R
R
1
+
O
S
Cl Cl
O
H
R
R
1
S
O
Cl +
N
H
+
Cl
-
A normal SN
2
reaction
which leads to inversion of
configuration.
Cl +SO
2
H
R
R
1
R +SO
2
H
Cl
R
1

SOCl2 readily reacts with a solvent like water giving SO2 and HCl. As a result, a solvent like
ether is taken in the above reaction. HCl gets evaporated in such a solvent and the internal attack
becomes major. A bulky base like pyridine converts HCl into a salt, pyridinium chloride. And as a
result, chloride ion is retained in the solution. Yield of this reaction is very high due to the formation
of a gas SO2.
V. Alkyl tosylates:
Another method is converting alcohol into tosylate by treating it with tosyl chloride (TsCl).

H
3
C S
O
O
Cl
Toluene sulfonyl chloride (TsCl)

ROH +TsCl
pyridine
ROTs +HCl

Mechanism:
H
3
C S
O
O
Cl
ROH
H
3
C S
O
O
OR
H
+
N
H
3
C S
O
O
OR
ROTs

As TsO
-
is a very good leaving group, ROTs undergoes nucleophilic substitution reactions
very easily. Another advantage of ROTs is that it is insoluble in polar media. When the reaction
medium is polar, ROTs gets precipitated and the precipitate can be treated with different
nucleophiles as illustrated below.

ROTs
Cl
-
RCl+TsO
-
ROTs
I
-
RI+TsO
-
ROTs
CN
-
RCN+TsO
-
ROTs
N
3
-
RN
3
+TsO
-
ROTs
CH
3
COO
-
R-O-C-CH
3
+TsO
-
O
ROTs
CH
3
O
-
ROCH
3
+TsO
-

Illustration:1

OH
HBr
PBr
3
A B (i)
OH
HBr
C
PBr
3
D
(ii)

OH
HCl
E
PCl
3
F
G
(iii)
Write the structures of all the unknowns emphasising on stereochemistry whereever appropriate.
SOCl
2

Br
Br
Br
Br
Cl
Cl Cl
A B C D E F G
Answers:
+

2. Fischer esterification and ester hydrolysis:
Alcohols react with carboxylic acids in acidic medium to form esters. The reaction is
reversible and as a result, under suitable conditions, ester can be hydrolysed back to carboxylic
acid and alcohol. Although ester cant be formed in basic medium, it can be hydrolysed in basic
medium which is called saponification.
Mechanism in acidic medium:


R-C-OH +R'H
O
H
+
R-C-OR' +H
2
O
O
R-C-OH
O
H
+
R-C-OH
OH
+
R'OH
rds
R-C-OH
OH
R'OH
+
R-C-OH
OH
R'O
OH
R'O
+
R-C-OR'
OH
+
R-C-OR' +H
+
O
Esterification:
Rate =k
R-C-OH
OH
+
=k k
eq
[RCOOH] [H
+
] [R'OH]
=k' [RCOOH] where k' =k k
eq
[H
+
] [R'OH]
R-C-OH
2

During esterification, alcohol is taken as a solvent to drive the equilibrium in the forward
direction. As solvent is generally taken in excess, its concentration hardly changes. The role of
acid in esterification is catalyst. Its concentration also hardly changes. As a result, acid catalysed
esterification is a pseudo-first order reaction.
R-C-OR' +H
2
O
O
H
+
R-C-OH +R'OH
O
R-C-OR'
O
H
+
R-C-OR'
OH
+
rds
R-C-OR'
OH
HOH
+
R-C-OR'
OH
OH
R-C-OH-R'
OH
OH
+
R-C-OH
OH
+
R-C-OH +H
+
O
Ester Hydrolysis (A
AC
2):
Rate =k
R-C-OR'
OH
+
=k k
eq
[RCOOR'] [H
+
] [H
2
O]
=k' [RCOOR'] where k' =k k
eq
[H
+
] [H
2
O]
HOH
+R'OH

During ester hydrolysis, water is taken as a solvent to drive the equilibrium in the forward
direction. As solvent is generally taken in excess, its concentration hardly changes. The role of
acid in ester hydrolysis is catalyst. Its concentration also hardly changes. As a result, acid
catalysed ester hydrolysis is a pseudo-first order reaction.

Mechanism in basic medium:

R-C-OH
O
R'OH
NaOH
R-C-O
-
O
R'OH
or even R'O
-
No reaction
Partial positive charge on the carbonyl carbon in carboxylate ion is too small to
react even with alkoxide ion. As a result, one can't prepare ester in basic medium.

But ester can be hydrolysed in basic medium which is called as saponification.

Mechanism of ester hydrolysis in basic medium (BAC2):

R-C-OH +R'
-
O
R-C-OR'
O
R-C-OR'
O
-
OH
OH
-
acid base reaction
which is highly favourable
R-C-O
-
+R'H
O
first step is rds.
Rate =k [RCOOR'] [NaOH]

Intramolecular ester formation:
CH
3
-CH-C-OH
OHO
H
+
A
O
O
O
O
CH
3
-CH-CH
2
-C-OH
OH
O
o-hydroxy ester
|-hydroxy ester
CH
3
-CH=CH-C-OH
O
CH
3
-CH-CH
2
-CH
2
-C-OH
OH
O
H
+
A
H
+
A
-hydroxy ester
O
O
Intra molecular esterification is difficult
because of the ring strain. Dehydration
is difficult because the carbocation
at o position is unstable.
Intra molecular esterification is difficult
because of the ring strain. Dehydration
is favorable because of the stability of
the alkene.
Intra molecular esterification is favourable.
a lactone

3. Oxidation of alcohols:

R-CH
2
-OH
Oxidation state
of carbon =-1
[O]
R-C-H
O
Oxidation state
of carbon =+1
[O]
R-C-OH
O
Oxidation state
of carbon =+2

DIFFERENT REAGENTS USED IN THE OXIDATION OF ALCOHOLS:
A. Chromic acid
Chromic acid is prepared by dissolving either chromium (VI) oxide or potassium dichromate in
aqueous sulfuric acid.
2 4
3 2 2 4
2 4 2
2 2 7 2 2 7 2 4
H SO
CrO + H O H CrO
Chromium Chromicacid
(VI)oxide
H SO H O
K Cr O H Cr O 2H CrO
Chromicacid

Chromic acid converts primary alcohols into carboxylic acids, secondary alcohols into ketones. It
does not react with tertiary alcohols. Thus, the prerequisite for the oxidation of an alcohol is at
least one H on the carbon bearing the OH group. A solution of chromic acid

Mechanism of chromic acid oxidation:

OH
H
+ HO-Cr-OH
O
O
fast and
reversible
H
O
O
O-Cr-OH
+H
2
O
H
O
O
O-Cr-OH
H
2
O
slow and rate
determining
O +H
3
O
+
+HCrO
3
-

Chromium (IV) then participates in further oxidations by a similar mechanism and eventually is
transformed to Cr (III) which is green in color.
An aldehyde is oxidized further to carboxylic acid through its hydrate form.
O
H
2
O
+H
3
O
+
+HCrO
3
-
R-C-H
C OH
OH
H
R
An aldehyde
hydrate
O
O
HO-Cr-OH
C
OH
H
R
O
O-Cr-OH
O
RCOOH

We will study about aldehyde hydrates in the aldehyde and ketones chapter.

B. KMnO4: KMnO4 is similar to chromic acid in every respect. It oxidises primary alcohols to
carboxylic acids, secondary alcohols to ketones and does not react with tertiary alcohol. But when
KMnO4 is used in acidic medium at high temperature, the tertiary alcohol may first convert into
alkene and the alkene is further oxidized.

O
C CH
3
OH
CH
3
H
3
C
H
+
/A
KMnO
4
A
CH
3
-C-CH
3
+CO
2

C. PCC, PDC and CrO3/Pyridine/Cold (Collins reagent):

N
H
+
CrO
3
Cl
-
Pyridinium chloro chromate
N
H
+
2
Cr
2
O
7
Pyridinium dichromate

These three reagents convert primary alcohols into aldehydes, secondary alcohols into
ketones and they do not react with tertiary alcohols. PCC oxidations are generally carried out in
aprotic solvents such as CH2Cl2. PCC has no effect on carbon-carbon double bonds

OH
PCC
CH
2
Cl
2
H
O

PCC does not oxidize aldehydes further because the PCC is not used in water but rather in
an organic solvent, CH2Cl2. Without water, the aldehyde cant be in equilibrium with its hydrate.
Recall that only the hydrate of the aldehyde is susceptible to further oxidation not the aldehyde
itself.


C. Cu/350
0
C
Copper at high temperature oxidises primary alcohols into aldehydes, secondary alcohols
into ketones. Tertiary alcohols get dehydrated by copper at 350
0
C.
CH
2
H
3
C
H
3
C
CH
3
CH
2
OH
Cu/350
0
C
CH
3
-C-H
O
CH
3
CHOHCH
3
Cu/350
0
C
CH
3
-C-CH
3
O
C CH
3
CH
3
OH
H
3
C
Cu/350
0
C

D. MnO2
MnO2 oxidises only allyl and benzyl alcohols. If they are primary, aldehydes are the final
products. If they are secondary, ketones are the final products.
OH
MnO
2
H
O
CH
2
OH CHO
MnO
2

Exercise-III:
1.

O
1.CH
3
MgBr
2. H
2
O
A (Mixture of two compounds)
A
H
+
A
B (Mixture of two compounds)
Describe A and B.

2.

C
O
OC
2
H
5
C
2
H
5
O
Diethylcarbonate
1.ex CH
3
MgBr
2. H
2
O
A +B
If both A and B are alcohols, give their structures.

3.

A (C
4
H
8
O
2
)
1.ex CH
3
MgBr
2. H
2
O
B
If A is an ester and B is the only alcohol produced in the reaction, find out the structure

4. Starting with butane, synthesize the following two compounds .
(A) CH3CH2CH2CH2D (B) CH3CHDCH2CH3

5.


O
CH
3
O
HO
O
1.ex CH
3
MgBr
2. H
2
O
OH
HO
O
What is the number of moles of CH
3
MgBr required for the above conversion?

6. Using ethyl bromide as the starting compound, synthesize the following alcohols
in not more than three steps.
(A) 2-Butanol (B) 1-Propanol (C) 1-Butanol

7.

Benzyl methyl ketone
1.LiAlH
4
2.NH
4
Cl
3.PCl
3
4.KO-t-Bu
A
B
1.H
2
/Ni
2. H
+
/A

8.

3-Ethyl-3-pentanol
1. i-PrMgBr
2.
Br

9.
1-Hexen-3-ol
1.NaH
2.
S
O
O
OMe MeO

10.
Ph O
O
1.PhMgCl
2. H
+
1.LiAlH
4
2.H
+

11.
2-Butanol
1.HBr
2. LDA
3.BH
3
/THF
4.H
2
O
2
/OH
-

12.
1.LiAlH
4
2.H
+
O
O
OMe
O
Ph
O
1.NaBH
4
2.H
+
H
2
/Pt

13.


1.LiAlH
4
2.H
+
1.NaBH
4
2.H
+
O
O
1.CH
3
MgBr
2.H
+

14.

1.LiAlH
4
2.H
+
1.NaBH
4
2.H
+
H
N
O
1.H
2
/Pt

15.
1.ex CH
3
MgBr
2. H
2
O
O OH
OH
O
OH OH
OH
O
What is the number of moles of Grignard reagent used in the above reaction?

16.

CO
2
Et O
1.LiAlH
4
2.H
2
O
A +B

If A and B are isomers, what is the relation between them?

POLYHYDROXY COMPOUNDS
Methods of preparation
1. Reaction of Baeyers reagent with alkenes:
Alkenes give vicinal diols with cold alkaline KMnO4 (Baeyers reagent). Both hydroxyl
groups are added from the same side (syn addition).
Examples:

CH
3
H H
3
C
H
cold KMnO
4
CH
3
CH
3
H OH
HO H
CH
3
CH
3
HO H
H OH
+
cold KMnO
4
OH
OH
+
OH
OH
enantiomers
enantiomers
cold KMnO
4 OH
OH
1.
2.
3.

2. Reaction of alkenes with OsO4/H2O; NaHSO3
Alkenes with OsO4/H2O; NaHSO3 give vicinal diols. Similar to the previous case, here also
the hydroxyl groups are added from the same side (syn addition).
3. Reaction of alkenes first with peroxy acetic acid followed by treatment with H
+
or OH
-
.
Alkenes react with peroxy carboxylic acids to give epoxides which then react with H
+
or OH
-

to give vicinal diols. Overall addition of hydroxyl groups is anti.
Examples
CH
3
H H
3
C
H
1. RCOOOH
CH
3
CH
3
H OH
H OH
1.
2. H
+

OH
OH
+
OH
OH
enantiomers
OH
OH
2.
3.
1. RCOOOH
2. H
+
1. RCOOOH
2. H
+
OH
OH
+
enantiomers

Chemical Reactions
1. Pinacol-pinacolone rearrangement
When vicinal diols are treated with H
+
, aldehydes or ketones are obtained.

H
3
C-C-C-CH
3
OOH H
C CH
3
H
3
H
+
H
3
C-C-C-CH
3
O H
C CH
3
H
3
+
H
3
C-C-C-CH
3
OCH
3
H
CH
3
+
+
H
3
C-C-C-CH
3
OCH
3
H
CH
3
H
3
C-C-C-CH
3
O CH
3
CH
3
Pinacol
Pinacolone
Methyl shift

Formation of the first carbocation is the rate determining step. It is surprising, at first
look, that a 3
0
carbocation is getting rearranged. But see the relative stability of the carbocations:
CH
3
-O-CH
2
+
>
Ph-CH
2
+
Ph
2
CH >(CH
3
)
3
C >
+ +

It is often confusing in this reaction as to which group migrates. Whether it depends upon
the migratory aptitude or the stability of the carbocation that is obtained after the migration. It is
found that in some examples the first factor (migratory aptitude) predominates, in other examples,
the second factor (carbocation stability) predominates.

Migratory aptitude
H >Ph >R(3
0
) >R(2
0
) >R(1
0
) >CH3

OCH
3
NO
2
OCH
3
>
>

Phenyl ring migration is an example of intramolecular electrophilic substitution. Presence of an
electron donating group at para position makes benzene ring a better migrating group. Presence of
electron withdrawing group does the opposite. But presence of any group at the ortho group makes
migration of benzene ring difficult because of steric hindrance.
Stereochemistry of rearrangements:
The configuration of the migrating group is retained during migration because the migrating group never
becomes completely free. The configuration of the migratory terminus (the carbon atom to which migration takes
place) is found to be predominantly inverted in some cases and completely inverted in other cases. The
configuration is found to be completely inverted in the case of amino alcohols and cyclic diols. This suggests the
formation of ion pair in the rate determining step.

Ph
HO Ph
H H
3
C
Ph
H
3
C H
Ph
HO Ph
NH
2
H H
3
C
NaNO
2
HCl
N
2
+
O
Ph

Examples:

OH
CH
3
CH
3
OH
H
+
O
CH
3
CH
3
2.
C C CH
3
CH
3
Br
CH
3
OH
H
3
C
AgNO
3
C C CH
3
CH
3
CH
3
O
H
3
C
C C CH
3
CH
3
NH
2
CH
3
OH
H
3
C
NaNO
2
C C CH
3
CH
3
CH
3
O
H
3
C
HCl
3.
4.
C C CH
3
Ph
OH
Ph
OH
Ph
H
+
C C Ph
Ph
Ph O
H
3
C
1.

cold KMnO
4 H
+
CHO
5.
cold KMnO
4
H
+
O
6.
O
+

OH HO
H
+
A
H O
7.


Retropinacol rearrangement
O
O
H
+
OH
O
+
H
2
O
OH
O
OH
tautomerism
OH
OH
tautomerism
O
O
OH
Major
O
H
+
OH
+
OH
+
OH
1.
2.

2. Reaction of vicinal diols with HIO
4
(periodic oxidation)
Vicinal diols are oxidized by HIO4. And in the process HIO4 is reduced to HIO3. If AgNO3 is
added to after the reaction, a white precipitate of AgIO3 is obtained.

C
C
OH
OH
HIO
4
C
C
O
O
I O
O
O
_
C
C
O
O
+ +IO
3
-

Examples
OH
OH
OH
OH
OH
OH
OH
OH
HIO
4
HIO
4
H
O
O
H
H
O
O
H
1.
2.
=
=
OH
OH
HIO
4
No reaction

In chair form, dihedral angle between two equatorial bonds is 60
0
. Dihedral angle between
one equatorial form and one axial form is also 60
0
. As a result, there is no much difference
between the reactivity of cis-1,2-cyclohexanol and its trans isomer. Trans isomer is slightly less

reactive because some of it exists in another conformation in which the two hydroxyl groups are
anti to each other.
OH
OH
OH
OH
OH
HIO
4
H
O
O
H
3
(H
3
C)
3
C
OH
OH
4.
(H
3
C)
3
C
OH
(H
3
C)
3
C
(H
3
C)
3
C
HIO
4
no reaction
C(CH
3
)
3
=
=

C
C
O
OH
HIO
4
C
C
O
O
HO
+
5.

C
C
O
O
HIO
4
C
C
O
O
OH
OH
+
6.

C
C
C
O
OH
HIO
4
OH
C
C
C
O
O
O
O
+
+
7.

CH
2
C
C
OH
HIO
4
OH
8
No reaction

Now it is easily understood that an alternate reagent for O3; Zn/H
+
can be cold alkaline
KMnO4 followed by HIO4. Cold KMnO4 followed by HIO4 is called as Limaeux reagent.

Exercise-IV
C C CH
3
Ph
OH
Ph
OH
Ph
H
+
/A
1.

OH
CH
3
CH
3
OH
2.
H
+
/A

C C CH
3
CH
3
Br
CH
3
OH
H
3
C
AgNO
3
3.

C C CH
3
CH
3
NH
2
CH
3
OH
H
3
C
NaNO
2
HCl
4.

cold KMnO
4
5.
H
+
/A

cold KMnO
4
6.
H
+
/A

O
OH
H
+
7.

O
O
H
3
O
+
8.


O
H
3
O
+
9.

H
+
/A
OH
HO
10.

Exercise-V
1. When one mole of each of the following compounds is treated with HIO4, what will the
products be, and how many moles of HIO4 will be consumed?
(A) CH3CHOHCH2OH (B) CH3CHOHCHO
(C) CH2OHCHOHCH2OCH3 (D) CH2OHCH(OCH3)CH2OH
(E) cis-1,2-Cyclopentanediol (F) CH2OH(CHOH)3CHO
(G) CH2OH(CHOH)3CH2OH
2. Assign the structures to each of the following compounds.

4 3 3
4 2 4
4 2 4
4
4
4 2
4
A+1mol HIO CH COCH +HCHO
B+1mol HIO OHC(CH ) CHO
C+1mol HIO HOOC(CH ) CHO
D+1mol HIO 2HOOC-CHO
E+3mol HIO 2HCOOH+2HCHO
F+3mol HIO 2HCOOH+HCHO+CO
G+5mol HIO 5HCOOH+HCHO

3.

OH
OH
HIO
4
1.LiAlH
4
2.H
2
O
A B

A is pure while B is a mixture. How many isomers does B contain?
4.

HO
OH
ex.Cu/A
H
I
O
4
P
C
C C
H
2 C
l
2
H
+
/
A
e
x
.
C
r
O
3
/
H
+
E
A+B
F
C
D

1.
Exercise-VI
Convert the following.

CH
2
OH
OH
OH

2.


C
6
H
5
OH
C
6
H
5
OH
OH
+its enantiomer
C
6
H
5
OH
OH
+its enantiomer
A
B

3.
O
H
3
C OH
O

4.

Br
CH
3
CHO

5.
H
H
O
O
Without using ozone.

6.
H
O
O

EXERCISE-VII
Write the structures of all the unknowns.
O
O
O
1.AlCl
3
A
Zn-Hg
HCl 2.H
2
O
B
PCl
3
1.AlCl
3
2.H
2
O
Zn-Hg
HCl
Se
A
C
D
E
F
+
1.LAH
2.H
2
O
G
PPA
H
J
I K
N
P
L M O
1
.
L
A
H
2
.H
2O
N
a
B
H4
/
C2
H5
O
H
C
6
H
6
/PPA
C
6
H
6
/PPA
Zn-Hg
HCl
C
6
H
6
/PPA
NaBH
4
/C
2
H
5
OH
C
6
H
6
/PPA
Se/A
Se/A
NaBH
4
/C
2
H
5
OH

Note: PPA stands for polyphosphoric acid, which is a source of H
+
.

ETHERS
Physical properties

Ethers and alcohols have comparable solubility in water as both of them can form hydrogen
bonding with water. But boiling points of ethers are low when compared to those of alcohols as
ethers cant form hydrogen bonds among themselves.
CH3CH2OCH2CH3
Diethyl ether
CH3CH2CH2CH2OH
1-Butanol
Boiling point: 35C 117C
Solubility in water: 7.5 g/100 mL 9 g/100 mL

Methods of preparation
1.Williamsons synthesis:
R-L +RO
-
R-O-R +L
-
L - Cl, Br, I,
OSO
3
CH
3
,

OTs,
N
2
+
etc.

As RO
-
is a strong base, best yields are obtained when R in R-L is CH3 or 1
0
. With 2
0
and
3
0
substrates, RO
-
gives predominantly elimination products.
Examples:
CH
3
CH
2
I
CH
3
ONa
CH
3
OH
CH
3
CH
2
OCH
3
+NaI 1.
CH
3
-O-S-O-CH
3
CH
3
ONa
CH
3
OH
CH
3
OCH
3
+ 2.
O
O
CH
3
-O-S-O-Na
O
O
3. CH
3
CH
2
OH +CH
2
-N
_
+
diazomethane
CH
3
CH
2
O
-
+CH
3
-N N
N
+
CH
3
CH
2
OCH
3
+N
2
4. HO-CH
2
-CH
2
-CH
2
-CH
2
Br
NaOH
O
+NaBr
acid-base
reaction

2. Alkoxymercuration-demercuration:
This method is a slight variation of oxymercuration-demercuration. In oxymercuration-
demercuration, water is taken as solvent in the first step. In alkoxymercuration-demercuration,
alcohol is taken as solvent. Everything else is same. In alkoxymercuration-demercuration, there is
no formation of fully fledged carbocation and as a result there are no rearrangements. But the
addition is according to Markonikovs rule.

Examples:
1. (CH
3
)
2
C=CH
2
1. Hg(OAc)
2
/CH
3
OH
2. NaBH
4
(CH
3
)
2
C-CH
3
OCH
3
2. HO-CH
2
-CH
2
-CH
2
-CH=CH
2
1. Hg(OAc)
2
2. NaBH
4
O
CH
3

3. Intermolecular dehydration of alcohols:
When alcohols are heated at temperatures lower than those required for intra-molecular
dehydration, they give ethers. This method best works for methyl and 1
0
alcohols. 2
0
and 3
0

alcohols give alkenes rather.

CH
3
CH
2
OH
H
+
17O
0
C
CH
2
=CH
2
CH
3
CH
2
OH
H
+
14O
0
C
CH
3
CH
2
OCH
2
CH
3
Elimination
Substitution

Chemical reactions:
Ethers do not contain acidic hydrogen. As a result, they do not react with Na, NaOH or any
other base. As such they do not undergo nucleophilic substitution reactions because RO
-
is not a
good leaving group. But they do undergo nucleophilic substitution reactions under acidic
conditions.
1.Ether cleavage reactions:

R-O-R
dil.H
+
R-O-R
H
+
R-O-R
H
+
H
2
O
ROH +ROH
R
+
+ROH 2 ROH
S
N
1
S
N
2
1. With dil. acids
A

R-O-R R-O-R
H
+
R-O-R
H
+
Br
-
RBr +ROH
R
+
+ROH
S
N
1
S
N
2
conc. HBr
Br
-
RBr +ROH
2. With conc. acids
A

Whether it is SN1 or SN2, depends on the nature of the two alkyl groups. It is
experimentally found that when one of the alkyl groups is 3
0
, benzylic or allylic (or any
other carbon chain that can form stable carbocation), the mechanism follows S
N
1 pathway.
Otherwise it is S
N
2.
Examples:
1. CH
3
CH
2
OCH
3
dil. acid
conc. HBr
CH
3
CH
2
OH +CH
3
OH
CH
3
CH
2
OH +CH
3
Br
ex. HBr
CH
3
CH
2
Br +CH
3
Br
2. CH
3
CHOCH
3
dil. acid
conc. HBr
CH
3
CH(OH)CH
3
+CH
3
OH
CH
3
CH(OH)CH
3
+CH
3
Br
ex. HBr
CH
3
CH(Br)CH
3
+CH
3
Br
CH
3
S
N
2
S
N
2


3. (CH
3
)
3
C-O-CH
3
conc. HI
ex. HI
(CH
3
)
3
C-I +CH
3
OH
(CH
3
)
3
C-I +CH
3
I
S
N
1
4.
O
conc. HI
ex. HI
No reaction
No reaction
5.
O NO
2
conc.HI
OH
I
NO
2
+
ex. HI
OH
I
NO
2
+
ArS
N

O
ex. HI
conc. HI
No reaction
No reaction
6.
7.
O CH=CH
2
dil. H
+
O CH-CH
3
OH
a hemiacetal
OH
+CH
3
CHO
In this example, first water gets added to the double bond as it is highly reactive.
The resultant hemiacetal, being unstable, decomposes.
O CH-CH
3
OH H
+

8. CH
3
-OCH
2
-CH
2
-OCH
3
ex. HI
2CH
3
I +CH
3
CH
2
I
In this example, the two carbon chain is first converted into I-CH
2
-CH
2
-I which,
being unstable, decomposes into ethene. Ethene further reacts with HI.

2.Claisen rearrangement:
When allyl phenyl ethers or allyl vinyl ethers are heated, they undergo rearrangement.
Examples:

O
A
O O
OH
1.

O
O
A
O
OH
O
2.

O
A
O
O
Allyl-vinyl ether
3.

EPOXIDES
Epoxides are three membered cyclic ethers.
O O
Ethylene oxide
(or) oxirane
(or) epoxy ethane
Propylene oxide
(or) 2-methyloxirane
(or) 1,2-epoxypropane

Methods of preparation:
1.Reaction of alkenes with peroxy acids:
Alkenes, when treated with an organic peroxy acids, yield epoxides.

CH
3
H H
H
3
C
RCO
3
H
CH
3
H H
H
3
C
C
O H
O
O R
O
CH
3
H
3
C
+
RCOOH
CH
2
Cl
2


All the bond fissions and bond formations are simultaneous. As a result, there is no scope
for bond rotation in alkene. Consequently, the reaction is stereospecific. Cis alkenes give
cis epoxides and trans alkenes give trans epoxides exclusively.

2. Reactions of halohydrins with bulky bases:
Halohydrins, when treated with bulky bases, yield epoxides. Bulky bases are used to avoid
direct replacement of halogen.
C C
Br
HO
pyridine
O

pyridine
O
H
3
C
H
H
CH
3
CH
3
CH
3
H OH
H Br
(S,R)
(S,S)

Chemical reactions:
Unlike open chain ethers, epoxides are highly reactive toward nucleophiles. This is because
of the ring strain.
O
Nu
-
-
O-CH
2
-CH
2
-Nu
H
+
HO-CH
2
-CH
2
-Nu

In the case of unsymmetrical epoxides, two factors may influence the preferred site of
nucleophilic attack.
1. Magnitude of partial positive charge
2. Steric hindrance.
Which of the two predominates depends on the conditions.
Nucleophile attacks epoxide under two conditions: in acidic medium and in basic medium.
In acidic medium (SN1 like), epoxide is first protonated. Nucleophile attacks in the second
step. Under these conditions, it is invariably the first factor (magnitude of partial positive
charge) which predominates. The nucleophile preferably attacks the carbon which can
stabilize the carbocation better. The important point here is that there is no formation of fully
fledged carbocation and as a result there are no rearrangements.
O
H
+
O
H
+
CH
3
OH
CH
3
-CH-CH
2
OH
OCH
3

In basic medium (SN2 like), the nucleophile directly attacks the epoxide and the protonation
occurs in the second step. Under these conditions, it is invariably the second factor (steric
hindrance) which predominates. The nucleophile preferably attacks the less hindered
carbon.
O
H
+
CH
3
O
-
CH
3
-CH-CH-OCH
3
CH
3
-CH-CH-OCH
3
O
- OH

Examples:

O
1. CN
-
2. H
3
O
+
CH
3
-CH-CH-CN
OH
O
OH
-
CH
3
-CH-CH-OH
OH
18
18
O
H
+
CH
3
-CH-CH-OH
OH
18
18
H
2
O
O
1.AlCl
3
CH
3
-CH-CH-OH
CH
3
2.CH
3
MgBr
3.H
2
O
O
CH
3
-CH-CH-CH
3
OH
1.CH
3
MgBr
2.H
2
O
1.
2.
3.
4.
5.
H
2
O

PHENOLS

Compounds in which a hydroxyl group is bonded to an aromatic ring are called phenols. The
chemical behavior of phenols is different in some respects from that of the alcohols. A corresponding
difference in reactivity was observed in comparing aryl halides, such as bromobenzene, with alkyl
halides, such as butyl bromide and tert-butyl chloride. Thus, nucleophilic substitution and elimination
reactions were common for alkyl halides, but rare with aryl halides. This distinction carries over when
comparing alcohols and phenols, so for all practical purposes substitution and/or elimination of the
phenolic hydroxyl group does not occur.

PHYSICAL PROPERTIES
Phenol is not appreciably soluble in water (8.2 g/ 100 mL of water). But it is quite soluble in aqueous
NaOH because of the soluble salt it forms with NaOH. At the same time it is not soluble in aqueous
NaHCO3.
OH
NaOH
ONa
+H
2
O
OH
NO
2
NaHCO
3 No reaction
OH
NaHCO
3
No reaction


OH
NO
2
NaHCO
3
NO
2
ONa
NO
2
NO
2
+H
2
O +CO
2
OH
NO
2
NaHCO
3
NO
2
ONa
NO
2
NO
2
+H
2
O +CO
2
O
2
N
O
2
N

METHODS OF PREPARATION
1.Dows process:

Cl
NaOH / 350
0
C
High pressure
ONa
+ O +
ONa
Minor products
Major
product

Dows process occurs through benzyne mechanism. The major product is obtained when OH
-

attacks the benzyne. The minor products are obtained when phenoxide ion attacks the benzyne.
2. Alkali fusion of benzene sulfonic acid

SO
3
H
NaOH / 350
0
C
High pressure
ONa
Major
product

Mechanism of this reaction is similar to that of Dows process i.e, benzyne mechanism.
3. Preparation from benzene diazonium chloride
When benzene diazonium chloride is warmed with water, phenol is produced.

NO
2
NH
2 N
2
Cl
OH
H
2
Ni
NaNO
2
HCl
H
2
O
warming

4. Preparation of phenol from p-nitrochlorobenzene
p-Nitrochlorobenzene is first treated with NaOH. Chlorine is replaced with OH in a nucleophilic
aromatic substitution reaction (addition-elimination). Later the unwanted NO2 group can be
removed.

Cl ONa
ONa
OH
NaOH H
2
Ni
NaNO
2
NO
2
NO
2 NH
2
N
2
Cl
OH
HCl
H
3
PO
2

5. Preparation of phenol from cumene hydroperoxide
When cumene hydroperoxide is treated with H3O
+
, phenol and acetone are obtained.

CH
2
=CHCH
3
H
3
PO
4
C CH
3
H
3
C
O-OH
cumene
hydroperoxide
H
+
OH
+CH
3
COCH
3
cumene
O
2

Mechanism

Ph-C-O-OH
CH
3
CH
3
H
+
Ph-C-O-OH
2
CH
3
CH
3
+
CH
3
CH
3
C-OPh
+
CH
3
CH
3
C-OPh H
2
O
+
CH
3
CH
3
C-OPh HO
Hemiacetal
CH
3
CH
3
HO
H
+
C
OPh
+
H
CH
3
COCH
3
+PhOH
H
2
O
rds

Migration and removal of water occurs simultaneously in the rate determining step. Hemiacetals are
unstable in acidic medium and decompose to aldehydes or ketones (hemiacetals and acetals are
discussed in detail in aldehydes and ketones).
Migratory aptitude:
H >Ph >R(3
0
) >R(2
0
) >R(1
0
) >CH3

OCH
3
NO
2
OCH
3
>
>

Phenyl ring migration is an example of intramolecular electrophilic substitution (ipso attack).
Presence of an electron donating group at para position makes benzene ring a better migrating
group. Presence of electron withdrawing group does the opposite. But presence of any group at the
ortho group makes migration of benzene ring difficult because of steric hindrance.
Examples:

p-CH
3
-C
6
H
4
-C
CH
3
Ph
OOH
H
+
p-Cresol +acetophenone 1.
2.
Ph-CH
2
-OOH
H
+
Benzaldehyde


OOH
H
+
O
H
OH
H
H
O
O
O
as a result of hydride migration
as a result of alkyl migration
as a result of alkenyl migration
3.

6. Fries rearrangement
O-C-R
O
OH
C-R
+
OH
C-R
O
O
AlCl
3
Major at low
temperature
Major at high
temperature

The mechanism of Fries rearrangement is similar to that of Friedel-Crafts acylation. It is often
possible to select conditions so that either ortho or para is the major product. High temperature
favors ortho isomer and low temperature favors para product. There is no clarity as to whether the
reaction is intermolecular or intramolecular (whether there is a formation of fully fledged acylium
ion or not).
CHEMICAL REACTIONS OF PHENOL
1. Phenol as an acid:

Phenol +Na
PhONa +H
2
Phenol +NaOH
PhONa +H
2
O


2. Reactions with RX, acid chlorides (RCOCl), and anhydrides (RCOOCOR):
OH
NaOH
O CH
2
CH
2
-Cl
_
OCH
2
CH
3
OH OCCH
3
CH
3
C-Cl
O
O
OH OCCH
3
CH
3
C-O-CCH
3
O
O
O
pyridine
+CH
3
COOH
+HCl
+NaCl

Pyridine (in the case of anhydride) helps converting phenol into phenoxide ion, which is a better
nucleophile. Pyridine is not generally required in the case of acid chloride as it is highly reactive.

3. Reaction of phenol with Br2/H2O

OH
Br
2
H
2
O
OH
Br Br
Br
OH
Br
2
CS
2
OH
Br
Mechanism

OH
OH
+
_ Br-Br
OH
+
Br
tautomerism
OH
Br

Reactions proceeds until all ortho and para positions are substituted. 2,4,6-Tribromophenol is not
soluble in water and is obtained as a white precipitate. In CS2, only monobromination occurs
because of the following reasons:
1. Phenol remains undissociated in CS2. Phenoxide ion is far more reactive than phenol.
2. Heterolytic fission of Br-Br bond is not favorable in non polar media.
3. Introduction of each bromine makes the benzene ring less reactive.
Other compounds, which react with bromine water similar to phenol, are anisole and
aniline.

NH
2 NH
2
Br Br
Br
Br
2
H
2
O
OCH
3 OCH
3
Br Br
Br
Br
2
H
2
O

4. Reimer-Tiemann Reaction
OH
1.CHCl
3
/ KOH
OH
CHO
Major
2.H
+

Mechanism
CHCl
3
+KOH
CCl
2
+KCl +H
2
O

Dichlorocarbene is an electrophile as its central atom has only sextet of electrons. But it is a
weak electrophile due to back bonding and as a result it attacks only highl y activated rings,
eg: phenol, pyrrole, furan etc.
O
CCl
2
O
CCl
2
tautomerism
O
-
CHCl
2
_
_
OH
CHO
hydrolysis
Salicylaldehyde

The reaction is thermodynamically controlled and as a result, more stable product is the major
product.
Some important points regarding Reimer-Tiemann reaction.
1.CHCl3/KOH gives abnormal products with some aromatic compounds. See the example
of pyrrole. Pyrrole, when treated with CHCl3/KOH, gives 3-chrolopyridine as the major product.
In the first step dichlorocarbene undergoes cycloaddition to pyrrole and then the ring expands.
Although there is a loss of aromaticity in the first step, it is regained ultimately.
N
N
H
CHCl
3
KOH
H
Cl
Cl
N
Cl
H
+
N
Cl

N
H
CHCl
3
/ KOH
N
H
CHO
Minor product
Normal Reimer-Tiemann reaction
followed by H
+

2. Aniline, which is otherwise similar to phenol in its properties, does not undergo Reimer-
Tiemann reaction. It gives a different product with CHCl3/KOH. We will discuss this in the
chapter amines.
NH
2
CHCl
3
KOH
NC
Isocyanide
Carbylamine reaction

3. Phenol with CCl4/KOH gives salycilic acid.

CHCl
3
/ KOH
followed by H
+
OH OH
Salicylic acid
COOH

4. Furan reacts with CHCl3/KOH and gives the expected product.

O
CHCl
3
KOH
O CHO
Major product

5. Tropolone (a highly activated aromatic ring) too undergoes Reimer-Tiemann reaction.
CHCl
3
/ KOH
followed by H
+
O
HO
O
HO
OHC
Tropolone

5.Kolbe-Schmitt Reaction (Carboxylation of phenoxide ion)
Carefully observe the following example.
OH
1. NaOH
2.CO
2
OH
COOH
Major product
3.H
3
O
+

RMgX
1.CO
2
2.H
3
O
+
RCOOH
O C O R
_
RCO
O
_
Carboxylation generalised:

O O
COO
tautomerism
O
-
COO
_
OH
COOH
hydrolysis
Salicylic acid
O C O
_
_

The Kolbe-Schmitt reaction is equilibrium controlled and as a result the major product is the more
stable isomer i.e, salicylic acid. Salicylic acid is used in the preparation of acetyl salicylic acid
which is an ingredient of aspirin, an analgesic.
OH
COOH
OCCH
3
COOH
O
CH
3
CCl
O
or
CH
3
COCCH
3
O O acetyl salicylic acid

Summary of the reactions of phenol:
When reactions of phenol are carefully observed, one thing becomes obvious. That is, in some
reactions oxygen is the attacking site and in other reactions it is carbon.

OH
Br
2
/ H
2
O
Reimer
Teimann Reaction
RX / RCOCl /
anhydride
Kolbe's reactio
Carbon attacks
Carbon attacks
Carbon attacks
Oxygen attacks

Why phenol or phenoxide ion behaves differently? This is generally explained on the basis of Hard
and Soft acid-base concept which is beyond the scope of J EE syllabi.
Practical organic chemistry of phenols:
Phenols can be identified by the following reagents:
1. Na: Phenols, like any other compounds having acidic hydrogen, liberate H2 with Na.
Other compounds which liberate H2 with Na are; terminal alkynes, alcohols, carboxylic acids,
sulfonic acids etc.
2. Br2/H2O: Phenols decolorize bromine water and give white precipitate. Other compounds
which also decolorize bromine water are alkenes, alkynes, aniline, anisole, and some aldoses (we
will study about aldoses in Biomolecules).
3. FeCl3: Phenol/substituted phenols give colored (ranging from orange to red) with FeCl3.
In fact all enols (phenol is an enol) give colored compounds with FeCl3. See the following
examples.
O O
O
O

Both the above compounds give colored compounds with FeCl3, as their enols are in appreciable
amounts. Acetone, acetaldehyde etc do not give colored compounds with FeCl3, as enols are in
negligible amounts.
PhOH +FeCl
3 Fe(OPh)
3
a colored compound

Exercise-VIII
1. Show how each of the following ethers is prepared by Williamsons synthesis? If there is any ether
which cant be prepared by Williamsons synthesis, propose an alternate method.
(A)
O
(B)
O
(C)
OMe

(D)
O

(E)
OEt

2. Draw the structural formulas of the major products obtained when each of the following reactions.
(A)
O
1 mol HI
A

(B)
OMe
1 mol HI
A

(C)
O
1 mol HI
A

(D)
OEt
1 mol HI
A

(E)

OCH
3
ex HI
A

(F)
O
1 mol HI
A


(G)

O
2
N O
ex HI
A

(H)
ex HI
A
O
O

(I)
O 1 eq HI PCC
CH
2
Cl
2

(J)
1.PhCO
3
H
2.PhOH,H
+

3. Write the major products for the following reaction.

1.

OH
1. NaOH
2.
Br
3.A

2.
+
2 4
14 12
H /H O HIO
A(C H O) B 2mol Benzaldehyde
A is optically active while B is not. Find the structural formulas of A and B.
4. Write all the unknown reagents in the following sequence of reactions.

Br
Br
OH
OH
O
OH
OMe
OH
C CH
OMe
O
H H
O O
O
1 2
3
4
5
6
7
8
9
10
11
12

Exercise-IX
1.Complete the following equations.

(A) phenol +Br2
0
2
5 C,CS
(B) phenol +conc. H2SO4
0
25 C

(C) phenol +conc. H2SO4
0
100 C
(D) p-cresol +p-toluenesulfonyl chloride
-
OH

(E) phenol +phthalic anhydride
3
AlCl
(F) p-cresol +Br2
2
H O

(G) phenol +C6H5COCl
pyridine
(H) phenol +(C6H5CO)2O
pyridine

(I) phenol +NaOH (J ) product of (I) +CH3OSO2OCH3
(K) product of (I) +CH3I
2. Desribe a simple chemical test for distinguishing following pairs of compounds
a) 4-Chlorophenol and 4-chloro-1-phenylbenzene
b) 4-methylphenol and 2,4,6-trinitrophenol
c) 4-methylphenol and 4-methylbenzoic acid
d) ethyl phenyl ether and 4-ethyl phenol
e) phenyl vinyl ether and ethyl phenyl ether
3. Describe simple chemical tests that would serve to distinguish between;
f) phenol and 0-xylene
g) p-ethylphenol, p-methylanisole, and p-methylbenzyl alcohol
h) 2,5-dimethylphenol, phenylbenzoate, m-toluic acid
i) anisole and 0-toluidine
j) acetylsalicylic acid, ethyl acetylsalicylate, ethyl salicylate, and salicylic acid
k) m-dinitrobenzene, m-nitroaniline, m-nitrobenzoic acid, and m-nitrophenol

4. Describe simple chemical methods for the separation of the compounds of problem 3, parts
a),c),d),and f), recovering each component in essentially pure form.

Exercise-X
Write the major products of the following reactions.
1.
OH
CH=CH
2
H
+

2.
O
Br
CH
3
ONa

3.

O O O
NaOH
MeOH

4.

OH
OH
H
+

5.

COOH HO
O
HOOC
A H
+

6.

O
OH O
1.NaBH
4
2. H
+


EXERCISE-I

1.
O

2.
OH
and its enantiomer

3.
OH
+

4.
D
OH

5.
Et
OPh

6.

O OCH
3

EXERCISE-II
1. n-Butyl alcohol can be prepared by treating C2H5MgBr with ethylene oxide (epoxide)
followed by hydrolysis.
2.
OH OH
&

3.
OH
OH

4.
O
OH

5.
OH
CH
2
OH
+C
2
H
5
OH +CH
3
OH

6.

HO CH
2
OH HO CH
2
OH
+ +C
2
H
5
OH

Answers:
Exercise-III

1.
OH HO
&
A (mixture of diastereomers)

&
B (mixture of enantiomers)

2. (CH3)3COH, 2C2H5OH 3.
C
O
H O-CH
CH
3
CH
3
4. (A) 1.Br2/hv 2.(CH3)3COK/(CH3)3COH 3.HBr/H2O2 4.Mg/THF 5.D2O
(B) 1.Br2/hv 2.Mg/THF 3.D2O
5. 3 6. (A)1.Mg/THF 2.CH3CHO 3. H
+

(B)1.Mg/THF 2.HCHO 3. H
+

O
1.Mg/THF 2. 3.H
+
(C)

7.
CH
2
-CH=CH
2
(A)
CH=CH
2
-CH
2
(B)

8.

9.

CH
2
=CH-CH-CH
2
-CH
2
-CH
3
OCH
3

10.

Ph3COH +CH3CH2CH2CH2OH
PhCH2OH +CH3CH2CH2CH2OH
11. CH3CH2CH2CH2OH

12.

CH
2
OH
OH
HO
HO
OMe
O
O
Ph
O
HO
OMe
O
O
Ph
O

13.
HO
OH
No reaction
HO
OH

14.

H
N
No reaction No reaction

15.

3

16.

HO CH
2
OH HO CH
2
OH
Diastereomers

Exercise-IV
1.
C C CH
3
Ph
Ph
Ph
O

2.
O
CH
3
CH
3
3.
C C CH
3
CH
3
CH
3
O
H
3
C

4.
C C CH
3
CH
3
CH
3
O
H
3
C


5.

CHO
O
&

6.
O

7.

O
O

8.
OH
OH
OH
9.
OH

10. O

Exercise-V
1.
(A) CH3CHO, HCHO,1 (B) CH3CHO, HCOOH,1
(C) HCHO, OHCCH2OCH3,1 (D) No reaction
(E) OHCCH2CH2CH2CH2CHO (F) HCHO,4HCOOH,4
(G) 2HCHO, 3HCOOH, 4
2.
A (CH3)2C(OH)CH2OH B
OH
OH (Cis or trans)
C
O
OH
D HOOC(CHOH)2COOH
E HOCH2(CHOH)2CH2OH F HOCH2COCH(OH)CHO
G OHC(CHOH)4CH2OH
3.
O
O
OH
OH
(A)
(B)
A pair of enantiomers and a meso compound

4.
O
CHO COOH
OH
CHO
OH
(A) (B) HCHO(C)
(D)
CHO
(E) (F)

Exercise-VI
1. 1.HIO4 2.H2/Ni 2. (A) 1.H
+
/A 2. KMnO4/OH
-
/cold
(B) 1.H
+
/A 2.RCO3H/H
+
.
3. 1.CH3MgBr/THF 2. H
+
/A 3. KMnO4/OH
-
/cold
4.CrO3/H
+
.
4. 1.Mg/THF 2.H2O 3.NBS/CCl4 4.H2O
5.PCC/CH2Cl2 (or MnO2)
5. 1.Br2/hv 2.ROH/KOH/ A 3. KMnO4/OH
-
/cold
4.HIO4
6. 1. Br2/hv 2.NaOH 3. CrO3/H
+
4. CH3MgBr/THF
5. H
+
6. H
+
/A 7. O3; Zn/H
+

Exercise-VII

HO
2
C
O
(A)

HO
2
C
(B)

ClOC
(C)

O
(D)

(E)

(F)

(G)
OH
HO
2
C
OH
(H)

O
(I)

(J)
OH
OH

(K)

OH
(L)

(M)

OH
(N)

(O)

(P)

Exercise-VIII
1. (A) Ethyl chloride +Sodium isopropoxide (B) Ethyl chloride +Sodium tertiarybutoxide

(C)
ONa
CH
3
I +

(D)
1.Hg(OAc)
2
/(CH
3
)
3
COH
2.NaBH
4

(E)


ONa
+EtBr

2.
(A) (CH3)3CI +(CH3)2C=CH2 +CH3CH2OH (B)
I
+ +MeOH

(C) Cyclohexanol +Tertiarybutyl iodide +
Isobutene
(D) Cyclohexanol +Ethyl iodide
(E) Phenol +Ethyl iodide (F)
HO
I
HO
+

(G)
I O
2
N + OH

(H) 2 mol CH3CH2I
(I)
I
CHO

(J)
OH
OPh

3.
1.
OH
(Claisen rearrangement)

2.
O
Ph
H
H
Ph
Ph
Ph
H OH
H OH
(A)
(B)

4.
1.
C
CH
3
OH
H
3
C CH CH
3
OCH
3
Pair of enatiomers

2.
C
CH
3
H
3
CO
H
3
C CH CH
3
OH
Configuration is retained

3.
C
CH
3
OH
C
2
H
5
CH
2
CH
3

4.
C
CH
3
OH
C
2
H
5
CH
2
SH

5.
CH(OH)CH
3

6.
C
OH
C-CH
3
+its enantiomer

5.
1. m-CPBA/CH2Cl2 2. CHCNa followed by H2O
3. Baeyers reagent 4. O3 followed by Zn/H
+
5. HIO4 6. One eq TsCl followed by CH3ONa
7. KMnO4 8. H
+
/A (Pinacol-pinacolone rearrangement)
9. HBr 10. NBS/CCl4

11. CH3ONa/CH3OH/ A

Exercise-IX
1.
(A) Para-bromophenol (B) p-Hydroxysulphonic acid
(C) o-Hydroxysulphonic acid
(D)

CH
3
TsO

(E)
O COOH
HO
(F)
OH
Br Br
CH
3
(G)
C OPh
O

(H)
C OPh
O
+CH
3
COOH

(I) Sodium phenoxide (J) Anisole (K) Anisole

2.
a) Na (H2 gas is evolved in the first case)
b) NaHCO3 (CO2 gas is evolved in the second case)
c) NaHCO3 (CO2 gas is evolved in the second case)
d) Na (H2 gas is evolved in the second case)
e) Baeyers reagent or Br2/H2O (Both are decolorised by the first compound)
3.
a) Na (H2 gas is evolved in the first case) or Br2/H2O (decolorised by the first compound)
b) p-ethyl phenol decolorises Br2/H2O. p-methyl benzyl alcohol evolves H2 with Na.
c) 2,5-Dimethyl phenol releases H2 gas with Na. m-Toluic acid evolves CO2 with NaHCO3.
d) o-Toluidine gives offensive smell with CHCl3/KOH (Carbyl amine reaction)
e)
O-C-CH
3
COOH
O
Acetyl salicylic acid
O-C-CH
3
COOC
2
H
5
O
Ethyl acetyl salicylate
OH
COOC
2
H
5
Ethyl acetyl salicylate
OH
COOH
Salicylic acid

First add NaHCO3 to all beakers. 1
st
and 4
th
compounds liberate CO2 gas. Then add Br2/H2O to
those two beakers. Only the fourth compound decolorises Br2/H2O. Add Na to the other two
beakers. Only the third compound liberates H2.
f) m-Nitroaniline gives offensive smell with CHCl3/KOH.
m-Nitrobenzoic acid liberates CO2 gas with NaHCO3.
mNitrophenol gives H2 gas with Na.

4.
a) Aq. NaOH

c)
Mixture
aq.NaHCO
3
aqueous layer
organic layer
COONa
CH
3
H
+
COOH
CH
3
2,5-Dimethylphenol +
Phenyl benzoate
aq.NaOH
aqueous layer
organic layer
ONa
Me
OH
Me
Me
H
+
Me
Phenyl benzoate

d) Aq.HCl
f)
Mixture
aq.NaHCO
3
aqueous layer
organic layer
COONa
H
+
COOH
m-Nitrophenol +
m-Nitroaniline +
m-Dinitrobenzene
aq.NaOH
aqueous layer
organic layer
ONa
OH
H
+
m-Nitroaniline +
m-Dinitrobenzene
NO
2
NO
2
NO
2
NO
aq.HCl
aqueous layer organic layer
NH
3
+
aq.NaOH
NH
2
NO
2
NO
2

Exercise-X
1.
O

2.
O
CH
2
OCH
3

3.
O
H
3
CO
O
OH

4.
O

5.
OH
O
O
+CO
2

6.
O
O

Alcohols, Ethers and Phenols

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Alcohols, Ethers and Phenols

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ALCOHOLS, ETHERS AND PHENOLS E M RAO

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