Iodine as an extremely powerful catalyst for the acetylation of alcohols under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2004.04.076

Iodine was found to promote quantitative acetylation of alcohols in a very short time with an equimolar amount of acetic anhydride under solvent-free conditions at room temperature.

Full text of DOI:10.1016/j.tetlet.2004.04.076

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4785–4787
Iodine as an extremely powerful catalyst for the acetylation
of alcohols under solvent-free conditions
Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India
Received 11 November 2003; revised 29 March 2004; accepted 8 April 2004
Abstract—Iodine was found to promote quantitative acetylation of alcohols in a very short time with an equimolar amount of acetic
anhydride under solvent-free conditions at room temperature.
Ó 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
Ac O (1.05 eq.)
2
R OH
1
R OAc
I2 (cat.)
Acylation of alcohols is an important and routinely
1
2
utilised transformation in organic synthesis. The most
commonly used reagent combination for this reaction
uses an acid anhydride in the presence of an acid or base
8
5 - 100%
R = alkyl, aryl, benzyl
2
Scheme 1.
catalyst. This process is activated by addition of ter-
3
tiary amines such as triethylamine, pyridine or DMAP.
Tributyl phosphine was subsequently introduced for
convenient procedure for acetylation of alcohols under
solvent-free conditions in the presence of a catalytic
amount of iodine (Scheme 1).
4
acylation of base sensitive substances. Various metal
5
6
7
8
salts such as CoCl
9
2
, ZnCl
10
2
, TiCl
4
–AgClO
4
, Me
3
SiCl,
LiClO , Mg(ClO ) and some metal triflates such as
4
4 2
1
1
12
13
14
Sc(OTf)
3
,
Me
3
SiOTf, In(OTf) and
have been investigated to meet the demand
3
,
Cu(OTf)
2
Initially a systematic study was carried out for catalytic
evaluation of iodine for acetylation of 1-octanol (Table
15
3
Bi(OTf) ,
for more efficient and selective methods. In most of the
cases the catalyst is either less or not effective for sec-
ondary and tertiary alcohols or longer reaction times are
necessary in order to achieve good yields. These draw-
backs are eliminated by the use of Lewis acids but many
of the Lewis acids employed are moisture sensitive and
metal triflates are highly expensive. Recently perchl-
1
). The reaction is very slow in the absence of catalyst.
When the reaction was carried out in dichloromethane it
was not complete in 12 h. Surprisingly, there was an
abrupt change in the rate of acetylation when the reac-
tion was carried out without additional solvent.
Several examples illustrating this novel and rapid
procedure for acetylation of alcohols are presented in
9;10
orates
for this transformation, however, perchlorates are
have been reported to be effective activators
16
4 2
potentially explosive. Moreover, Mg(ClO ) should be
a
10
Table 1. Acetylation of 1-octanol under different conditions
anhydrous in order to obtain good yields. In recent
years, iodine has been used as a Lewis acid catalyst for
Run
Solvent
I
2
(mol %)
Time
Yield (%)
17
various organic transformations. We recently reported
on the effectiveness of iodine in catalysing Mukaiyama
b
1
2
––
CH Cl
(2 mL)
Nil
10
72 h
12 h
42
72
b
2
2
18
aldol reactions. We describe herein an efficient and
3
4
––
––
10
5
1 min
5 min
>99
>99
a
1-Octanol: 1 mmol, T ¼ 25 °C; Ac
Remainder is unreacted octanol.
2
O: 1.05 equiv.
b
E-mail: pphukan@yahoo.com
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.076

4786
P. Phukan / Tetrahedron Letters 45 (2004) 4785–4787
Table 2. The general efficiency of this reaction is evident
from the variety of hydroxy compounds including pri-
mary, secondary, tertiary, benzylic alcohols and phe-
nols, which react in excellent yields within a very short
time, primary alcohols being acetylated within a minute.
In general, this method works well with a 1:1.05 M ratio
acetylated in 10 min in very good yield and functional
groups such as chloro, double bonds and triple bonds
were not affected during the reaction. The rate of acetyl-
ation is comparable to reactions catalysed by TMSOTf
but the major drawback of TMSOTf is that it is mois-
ture sensitive.
12
2
of alcohol to Ac O in the presence of a catalytic amount
of iodine (0.1 M equiv) without solvent. In the case of
menthol (1i) 3.5 equiv of Ac O were used in order to
solubilise the substrate. The tertiary alcohol 1l was
In conclusion, iodine shows very strong catalytic activity
for acetylation of alcohols when the reaction is carried
out without added solvent. Near equimolar amounts of
2
a
Table 2. Acetylation of various alcohols catalysed by iodine
b
c
Entry
Substrate 1
t (min)
Product
2
Yield (%)
OH
OAc
a
1
>99
>99
OH
OAc
b
1
MeO
HO
MeO
c
OH
1
1
OAc
OAc
>99
d
d
OH
AcO
OAc
98
e
f
1
3
98
97
HO
OH
OH
OAc
OAc
g
h
i
7
2
8
96
99
OH
OAc
e
95
HO
AcO
OH
OAc
j
2
2
99
OH
OAc
k
>99
l
OH
10
12
OAc
85
97
OH
OAc
m
CO Me
CO Me
2
2
MeO C
MeO C
2
2
OH
OH
OAc
OAc
n
o
p
1
1
1
>99
>99
>99
OMe
OH
OMe
OAc
a
b
c
Reaction conditions: substrate ¼ 1 mmol, Ac O ¼ 1.05 mmol, iodine ¼ 0.1 mmol, 25 °C.
2
Products were characterised by IR, NMR and MS spectroscopy and matched with literature data.
Isolated yield.
d
e
Ac
Ac
2
O (2.1 equiv) were used.
O (3.5 equiv) were used.
2

P. Phukan / Tetrahedron Letters 45 (2004) 4785–4787
4787
alcohol and Ac O are typically used avoiding waste and
providing very simple experimental and workup proce-
dures.
2
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2
.1. General procedure for acylation
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(
2
1
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(
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1
1
with saturated NaHCO
2 ꢀ 5 mL), dried (Na SO
pure product.
3
solution (2 ꢀ 5 mL), brine
(
2
4
) and concentrated to give the
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