Chemoselective acetylation of alcohols, amines, and thiols without catalyst and solvent

Article abstract of DOI:10.1081/SCC-100104824

Microwave induced rapid and selective acetylation of alcohols, amines and thiols with acetic anhydride was carried out under non-catalytic and solvent free conditions.

Full text of DOI:10.1081/SCC-100104824

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CHEMOSELECTIVE ACETYLATION OF ALCOHOLS,
AMINES, AND THIOLS WITHOUT CATALYST AND
SOLVENT
B. P. Bandgar a , S. P. Kasture a & V. T. Kamble a
a School of Chemical Sciences, Swami Ramanand Teerth Marathwada Univ., Organic
Chemistry Res. Lab., Vishnupuri, Nanded, Maharashtra, 431 606, India
Published online: 09 Nov 2006.
To cite this article: B. P. Bandgar , S. P. Kasture & V. T. Kamble (2001): CHEMOSELECTIVE ACETYLATION OF ALCOHOLS,
AMINES, AND THIOLS WITHOUT CATALYST AND SOLVENT, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:15, 2255-2259
To link to this article: http://dx.doi.org/10.1081/SCC-100104824
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SYNTHETIC COMMUNICATIONS, 31(15), 2255–2259 (2001)
CHEMOSELECTIVE ACETYLATION OF
ALCOHOLS, AMINES, AND THIOLS
WITHOUT CATALYST AND SOLVENT
B. P. Bandgar,* S. P. Kasture, and V. T. Kamble
Organic Chemistry Res. Lab., School of Chemical Sciences,
Swami Ramanand Teerth Marathwada Univ., Vishnupuri,
Nanded-431 606, Maharashtra, India
ABSTRACT
Microwave induced rapid and selective acetylation of alco-
hols, amines and thiols with acetic anhydride was carried
out under non-catalytic and solvent free conditions.
Hydroxyl groups are present in a number of compounds of biological
and synthetic interest including nucleosides, carbohydrates, steroids and the
side chain of some amino acids. During oxidation, acylation, halogenation
with phosphorus or hydrogen halides or dehydration reactions of these
compounds, a hydroxyl group must be protected. The protection of hydro-
xyl, amino and thiol groups is of great importance in synthetic organic
chemistry.1 Though several methods are available for transesterification,2
routinely acetylation of alcohols, phenols, amines and thiols is carried out
with acetic anhydride or acetyl chloride in the presence of either acid or base
catalyst.1 The reaction is generally carried out using tertiary amine catalyst
such as triethylamine or pyridine.3 4-(Dimethylamino)pyridine, (DMAP) is
*Corresponding author. Fax: 0091-2462-29245; E-mail: upekam@hotmail.com
2255
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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2256
BANDGAR, KASTURE, AND KAMBLE
known to increase the rate of acetylation when used as co-catalyst.4 Vedejs
et al reported tributylphosphine as less basic catalyst for acetylation of
alcohols.5 Recently, iodine was used as an acetyl transfer catalyst.6 In addi-
tion to the above catalysts, protonic acids such as toluene-p-sulfonic acid,7
Lewis acids such as zinc chloride,8 cobalt chloride9 and scandium trifluoro-
methanesulfonate10 were also applied to catalyse the acylation of alcohols
and phenols. More recently montmorillonite K-10 and KSF,11 expansive
graphite,12 sulfamic acid,13 chlorotrimethylsilane14 and lithium chloride15
were also used as catalysts for this purpose. Each of the above methods
has its merit and shortcomings. These methods are not entirely satisfactory.
Triethylamine and pyridine3 have unpleasant odour and are not so easy to
remove from the reaction mixture. DMAP is expensive and not easily
obtained whereas tributylphosphine is irritant, highly flammable and still
expensive. But to the best of our knowledge, there is no report available in
the literature for acetylation of alcohols, phenols, amines and thiols without
catalyst under solvent-free condition.
There is an increasing interest in the use of environmentally benign
reagents and conditions particularly to solvent-free procedures.16 Micro-
wave heating has been used for a wide variety of applications including the
rapid synthesis of organic compounds.16 Avoiding organic solvent during the
reactions in organic synthesis leads to a clean, efficient and economical tech-
nology: safety is largely increased, working is considerably simplified, cost is
reduced, increased amount of reactants can be used. Reactivities and some-
times selectivities are enhanced. We wish to report herein first non-catalytic
acetylation of alcohols, amines and thiols using microwaves under solvent-
free condition.
As shown in table 1, primary, secondary, benzylic and allylic alcohols,
primary amines and thiols are acetylated with acetic anhydride under non-
catalytic and solvent-free conditions using microwaves. Diols were also
converted into the corresponding diacetates (entries 2,3). It is worth com-
menting that tertiary alcohols give different results or do not undergo
acetylation using acid catalyst.13 But under this non-catalytic condition
using microwaves even tertiary alcohols underwent smooth acetylation
(entries 13, 14). Furthermore, a,b-unsaturated alcohol is also acetylated
without interfering carbon-carbon double bond (entry 4).
Using an alternative heating mode (oil bath) at temperature of 120ꢀC,
the reaction of benzyl alcohol with acetic anhydride could not even proceed
after 7 hours. In order to know whether there is any effect of acetic acid
formed on acetylation or not, attempt was made to carry out acetylation in
the presence of sodium bicarbonate (acid scavenger) and it was observed
that acetylation proceeded equally well in the presence or absence of sodium
bicarbonate. It is important to noteworthy that alcohol (entry 17), amine

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CHEMOSELECTIVE ACETYLATION
2257
Table 1. Acetylation of Alcohols, Amines and Thiols Using Microwaves
Without Solvent
b
aYields are of pure isolated products. Products are characterised by their physi-
cal constants,17 spectral characteristics (IR, 1H NMR) and comparison with
authentic samples.17

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BANDGAR, KASTURE, AND KAMBLE
(entries 18) and thiol (entry 19) were chemoselectively acetylated in the
presence of phenol. Though acetic acid is generated during the reaction,
benzyl alcohols are selectively acetylated without touching other acid sensi-
tive functional groups such as methoxy (entry 7), methylenedioxy (entry 8),
thioacetal (entry 20), acetal (entry 21) and oxime (entry 22). Thus tolerance
of different sensitive functional groups to these reaction conditions depicits
the flexibility and generality of the protocol.
EXPERIMENTAL
Microwave oven (Kelvinator T-37 model) was used with its 100%
power at 2450 MHz.
Typical Procedure
A mixture of 4-methoxybenzyl alcohol (5 mmol) and acetic anhydride
(5 mmol) in a beaker covered with watch glass was irradiated by microwaves
for 10 min. (heating and cooling at the interval of 1 min.). After completion
of the reaction (TLC), the product was extracted with ether (3 Â 15 ml). The
ether layer was washed with 10% NaOH and then dried with anhydrous
sodium sulfate. Removal of the solvent under reduced pressure gave
4-methoxybenzyl acetate in excellent yield (95%).
ACKNOWLEDGMENT
We thank UGC, New Delhi for financial assistance.
REFERENCES
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2259
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Received in Japan July 12, 2000

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