An efficient and simple procedure for preparation of esters and anhydrides from acid chlorides in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) under solvent-free conditions

Article abstract of DOI:10.1081/SCC-120001504

A manipulatively one-pot and rapid method for the synthesis of aliphatic and aromatic ester and anhydride from acid chloride and alcohol or potassium salt of carboxylic acid under solvent-free conditions is reported. The reaction has been carried out in excellent yield and short reaction time in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) under solvent-free conditions.

Full text of DOI:10.1081/SCC-120001504

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AN EFFICIENT AND SIMPLE PROCEDURE FOR
PREPARATION OF ESTERS AND ANHYDRIDES
FROM ACID CHLORIDES IN THE PRESENCE OF 1,4-
DIAZABICYCLO[2.2.2]OCTANE (DABCO) UNDER
SOLVENT-FREE CONDITIONS
A. R. Hajipour & Gh. Mazloumi a
a Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of
Technology, Isfahan, IR, 84156, Iran
Published online: 21 Aug 2006.
To cite this article: A. R. Hajipour & Gh. Mazloumi (2002): AN EFFICIENT AND SIMPLE PROCEDURE FOR PREPARATION OF
ESTERS AND ANHYDRIDES FROM ACID CHLORIDES IN THE PRESENCE OF 1,4-DIAZABICYCLO[2.2.2]OCTANE (DABCO) UNDER
SOLVENT-FREE CONDITIONS, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 32:1, 23-30
To link to this article: http://dx.doi.org/10.1081/SCC-120001504
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SYNTHETIC COMMUNICATIONS, 32(1), 23–30 (2002)
AN EFFICIENT AND SIMPLE
PROCEDURE FOR PREPARATION OF
ESTERS AND ANHYDRIDES FROM ACID
CHLORIDES IN THE PRESENCE OF 1,4-
DIAZABICYCLO[2.2.2]OCTANE (DABCO)
UNDER SOLVENT-FREE CONDITIONS
A. R. Hajipour* and Gh. Mazloumi
Pharmaceutical Research Laboratory,
College of Chemistry, Isfahan
University of Technology, Isfahan, 84156, IR, Iran
ABSTRACT
A manipulatively one-pot and rapid method for the synthesis
of aliphatic and aromatic ester and anhydride from acid
chloride and alcohol or potassium salt of carboxylic acid
under solvent-free conditions is reported. The reaction has
been carried out in excellent yield and short reaction time in
the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) under
solvent-free conditions.
*Corresponding author. E-mail: haji@cc.iut.ac.ir
23
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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24
HAJIPOUR AND MAZLOUMI
The protection of hydroxyl group of alcohols and phenols by formation
of esters is of great importance in synthetic organic chemistry.1 Although
several methods employ transesterification method,2 the esterification of
alcohols and phenols is routinely carried out by acid anhydride or acid
chloride in the presence of tertiary amines such as triethylamine and pyri-
dine.3 4-(Dimethylamino)pyridine(DMAP) as a much more efficient catalyst
for acylation of tertiary alcohols is particularly noteworthy.4 Tributyl-
phosphine has been used as a similar catalyst for protection of alcohols.5
Recently, iodine was reported to be a useful catalyst for esterification of
alcohols.6 In addition to the above catalysts, protonic acid such as p-toluene-
sulfonic acid,7 Lewis acids such as zinc chloride,8 cobalt chloride9 and scan-
dium trifluromethansulfonate10 were also applied to catalyze the protection
of alcohols and phenols. More recently chlorotrimethylsilane,11 lithium
chloride12 and ferric perchlorate13 have been used for acetylation of alcohols.
Each of the above methods has its merit and some shortcomings. There is still
a great demand for acid catalysts to generate esters under mild conditions and
environmentally friendly process. Monmorillonite K-10 and KSF14 were
applied as solid catalysts for protection of hydroxyl group of alcohols and
phenols to obtain relatively better results.
Heterogeneous reaction that are facilitated by supported reagents on
various solid inorganic surfaces have received attention in recent years.15–17
The advantage of these methods over conventional homogenous reactions
is that they provide greater selectivity, enhanced reaction rates, cleaner
products and manipulative simplicity. In connection with our ongoing
program to develop environmentally benign methods using solid supports,18
herein we wish to report an extremely convenient method for esterification
of different acid chloride with different alcohols and phenols in the presence
of DABCO under solvent-free conditions (Scheme 1).
Scheme 1.
The process in its entirety involves a simple mixing of acid chloride
and alcohols in the presence of DABCO in a mortar and grinding
the mixture for the time specified in the Table 1 at room temperature.

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ESTERS AND ANHYDRIDES FROM ACID CHLORIDES
25
Table 1. Preparation of Esters
Reaction
Yield
bp/mmHg or
M.P. ꢀC (Lit.)2–14
Entry
R1
R2
Time (min) (%)a
1
2
3
4
5
CH3
CH3
CH3
CH3
CH3
CH3
2
4
4
8
5
10
92
95
95
97
95
90
75/760 (75)
CH3CH2
CH3(CH2)2
C6H5
4-MeOC6H4
2-NO2C6H4
cyclohexyl
s-butyl
179–183/760 (179–181)
126–128/760 (126–127)
93–95/20 (196/760)
31–32 (32)
6CH
7
8
39–40 (40–41)
3
CH3
CH3
CH3
690 0 (117732/)76
5
10
4
95
89
95
114/760 (112)
46–47 (47–48)
98/760 (98)
9
1-naphthyl
CH3CH2
CH3(CH2)8 CH3CH2
10
11
12
13
14
15
164-NO
17
18
19
CH3CH2
685 0 (224452/)76
8
8
10
10
10
10
10
10
C6H5
C6H5
C6H5
4-BrC6H4
CH3
98
90
95
93
94
98
98
92
197–198/760 (199)
265–267/760 (262)
67–69 (68–70)
80 (81)
95 (96)
55 (57)
(CH3)2CH
C6H5
CH3
2C6H4 CH3
4-NO2C6H4 CH3CH2
3-NO2C6H4 CH3CH2
4-NO2C6H4 CH3
49 (47)
59 (79)
aIsolated yield after simple extraction.
To the best of our knowledge this methodology for preparation of
esters under solid phase conditions has not been reported in literature.
This method is very fast and purification of product is very easy (Scheme 1).
1
The esters have been identified by H NMR analyze by comparing
with authentic compounds the results of these efforts are presented in
Table 1. the desired product was usually isolated in excellent yield (Table 1).
As shown in Table 1, a series of acid chlorides were reacted with alcohols
and phenols in the presence of DABCO under solvent-free conditions.
Primary and secondary alcohols and phenol could be easily reacted with
different acid chlorides at room temperature. No selective esterification
between primary, secondary alcohol and phenol was observed. The tertiary
alcohols remained unchanged even the reaction mixture was heated at 70ꢀC
for 2 h. These results indicated that DABCO was not efficient reagent for
esterification of tertiary alcohols. It is noteworthy that DABCO could
recovered easily by filtration and washing with NaOH 10% and extraction
with CH2Cl2 and could be reused again without significant decrease in its
activity.

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HAJIPOUR AND MAZLOUMI
Acid anhydrides are among the most important class of reagents used
in organic synthesis. They are the preferred reactive acid derivatives for
the preparation of amides, esters and peptides.19 Further, the use of acid
anhydrides does not require any acid scavengers unlike in the case of acid
chloride.
We also have used this method for the synthesis of various symmetrical
and unsymmetrical anhydrides. This method involves the reaction of
potassium salt of various carboxylic acids with different acid chlorides in the
presence of DABCO at room temperature under solvent-free conditions
(Scheme 2 and Table 2). The potassium salts were prepared by dissolving the
respective carboxylic acids in methanol at room temperature (rt.), adding
Scheme 2.
Table 2. Preparation of Acid Anhydrides
Reaction
Time (min)
Yield
(%)a
M.P. ꢀC
Entry
R1
C6H5
p-ClC6H4
p-MeC6H4
p-NO2C6H4
m-MeOC6H4
C6H5
p-ClC6H4
C6H5
p-NO2C6H4
CH3
p-ClC6H4
CH3
p-MeC6H4
CH3
p-NO2C6H4
m-MeOC6H4
CH3
R2
C6H5
p-ClC6H4
p-MeC6H4
p-NO2C6H4
m-MeOC6H4
p-ClC6H4
C6H5
p-NO2C6H4
C6H5
p-ClC6H4
CH3
(Lit.)20–25
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
698
7
5
8
5
694
690
8
5
7
698
8
10
697
4
43 (42–43)
98 195–96(195)
9694–95 (95)
93
188–190 (189)
65–67 (67)
99
8–7730–)75 (6
8–7730–)75 (6
99
136–138 (131)
136–138 (131)
197–98 (196–97)
99
95
19–79–79)8 (196
9694–95 (94–95)
92
184–85 (183–85)
99
94
98
p-MeC6H4
CH3
p-NO2C6H4
CH3
CH3
94–95 (94–95)
184–85 (183–85)
65–67 (63–66)
65–67 (63–66)
10
10
m-MeOC6H4
aIsolated yield after simple extraction.

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ESTERS AND ANHYDRIDES FROM ACID CHLORIDES
27
methanolic-KOH (1:1) to the reaction mixture and stirring the reaction
mixture at rt. for 30 min. followed by filtration. This is a rapid and very
convenient method for the synthesis of both symmetric as well as unsymme-
trical acid anhydrides in excellent yields with high purity. By this method
a variety of acid anhydrides such as aliphatic–aromatic, aliphatic–
aliphatic and aromatic–aliphatic acid anhydride types can be readily
prepared in short reaction time at room temperature under solvent-free
conditions (Table 2).
We believe that the effect of DABCO is to react with acid chloride
to produce 1-aza-acyl-4-azoniabycyclo[2.2.2]ocatane chloride. This salt then
reacts with alcohol or potassium salt of carboxylic acid to produce
corresponding ester or anhydride, the probably mechanism is shown in
Scheme 3.
Scheme 3.
The Structure of intermediate (i.e. 1-aza-p-nitrobenzyl-4-azoniabi-
cyclo[2.2.2]ocatane chloride that obtained in this work showed two very
strong and sharp bands in the region 1800–1715 cmÀ1 due to symmetric
and asymmetric carbonyl stretching vibrations, characteristic of this
intermediate.
In conclusion a simple and efficient method for synthesis of esters and
acid anhydrides under solvent-free conditions at room temperature has been
developed. This method should allow a more rapid and complete screening
of substituent effects on protection of alcohols than the method which
has previously been reported. This work also is a rapid and very convenient
method for the synthesis of both symmetric as well as unsymmetric
acid anhydride in excellent yields with high purity. By this method a
variety of acid anhydrides such as aliphatic–aromatic, aliphatic–aliphatic
and aromatic–aliphatic acid anhydride type can be readily prepared
in short reaction time. This methodology is superior from point of view
of yield, short reaction time and the easier work-up than the reported
methods.

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HAJIPOUR AND MAZLOUMI
EXPERIMENTAL
General
All products were identified by spectroscopic data (IR, NMR) and
melting or boiling point by comparing with authentic compounds.2–14,20–25
The structure of all the anhydrides that obtained in this work showed two
very strong and sharp absorption bands in the region 1800–1720 cmÀ1, due to
symmetric and asymmetric carbonyl stretching vibrations, characteristic of
acid anhydrides. All mps. were taken on a Gallenkamp melting apparatus
1
and are uncorrected. H NMR spectra were recorded on a Varian EM-390
NMR Spectrometer operating at 90 MHz. The spectra were measured in CCl4
and CDCl3 relative to TMS (0.00 ppm). IR spectra were recorded on a
Shimadzu 435 IR spectrophotometer. Spectra of solids were performed
using KBr pellets.
General Procedure
After a mortar was charged with acid chloride (1 mmol), DABCO
(0.11 g, 1 mmol), the mixture was ground with a pestle for 1 min until the
reaction mixture solidified. Then alcohol (1 mmol) or potassium salts of
carboxylic acid (1 mmol) was added to the mixture. The reaction mixture
was ground for the time specified in Table 1 and 2. Then the reaction
mixture was poured into a mixture of ether (20 ml) and H2O (5 ml). The
ethereal layer was dried (CaCl2), and evaporated to dryness using a rotary
evaporator to give the pure product.
ACKNOWLEDGMENTS
Financial support of this work by the Graduate School (IUT) and the
research Affairs Division of Isfahan University of Technology (IUT) is
acknowledged.
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Received in Japan October 31, 2000

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