A Cheap, Simple and Efficient Method for the Preparation of Symmetrical Carboxylic Acid Anhydrides

Article abstract of DOI:10.1055/s-2003-44381

A manipulatively simple and facile one-pot procedure for the synthesis of symmetrical anhydride is reported. Treatment of carboxylic acids with tosyl chloride in K₂CO₃ media under solvent free conditions gives the corresponding anhydrides in good to excellent yields in a short reaction time via carboxylic sulfonic anhydride as the key intermediate.

Full text of DOI:10.1055/s-2003-44381

SHORT PAPER
205
A Cheap, Simple and Efficient Method for the Preparation of Symmetrical
Carboxylic Acid Anhydrides
P
reparation of
o
S
ymmetric
a
a
l
Carboxyli
d
c
Acid Anhydride
s
Kazemi,a Hashem Sharghi,*b Mohammad Ali Nasserib
a
Department of Chemistry, College of Sciences, Chamran University, Ahvaz, I. R. Iran
b
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, I. R. Iran
Fax +98(711)2286008; E-mail: shashem@chem.susc.ac.ir
Received 13 October 2003; revised 25 November 2003
hydride RCO2SO2Ar, which should be a highly reactive
acylating agent.12,13
Abstract: A manipulatively simple and facile one-pot procedure
for the synthesis of symmetrical anhydride is reported. Treatment of
carboxylic acids with tosyl chloride in K2CO3 media under solvent
free conditions gives the corresponding anhydrides in good to ex-
cellent yields in a short reaction time via carboxylic sulfonic anhy-
dride as the key intermediate.
Now we wish to report that, carboxylic acid reacts with to-
syl chloride in K2CO3 media to produce the corresponding
anhydride. The scope and generality of this process is il-
lustrated with several examples and the results are sum-
marized in Table 1. The process in its entirety involves a
simple mixing of carboxylic acid with 0.5 equivalent of
TsCl in the presence of K2CO3 in a mortar and grinding
the mixture for the time specified in Table 1 at room tem-
perature. This method is very fast and purification of
product is very easy. Thus, 1-naphthalenecarboxylic acid
give the best result with 95% isolated yield of 1-naphtha-
lenecarboxylic anhydride in 25 minutes (Table 1). The
structure of all the products were settled from their
analytical and spectral (IR, 1H and 13C NMR) data and by
direct comparison with authentic samples. The proposed
mechanism is shown in Scheme 1.
Key words: anhydrides, tosyl chloride, grinding, carboxylic acid
Carboxylic anhydrides are very important reagents, func-
tioning not only as acylating agents but also as reactive in-
termediates, for preparing many other functional groups
such as ester, amide, and peptide in organic synthesis.1 Es-
pecially, the availability of symmetrical acid anhydride is
quite important for many transacylation applications be-
cause they do not give any by-products due to attack at
second acyl carbonyl group, which is the case when mixed
anhydrides are used.2 Generally carboxylic anhydrides are
prepared by dehydration of carboxylic acids with a pow-
erful acylating or dehydrating agents such as acid chlo-
rides,3 acid anhydrides,4 thionyl chloride,2,5 DCC,6
ketene,7 phosgene,8 chlorosulfonyl isocynate,9 P2O5,10
(trimethylsilyl)ethoxyacetylene,7 and CCl3CN/Ph3P.11
However, these methods have some drawbacks that limit
their applications: toxicity, high cost, low yield, instabili-
ty, high reaction temperature, harsh reaction conditions,
necessary presence of a phase-transfer catalyst or tedious
work-up.11,12
CH3
ArCO2H
K2CO3
O
O
O
--OTs
grinding
Cl
Ar
OTs
-OOCAr
+
Ar
O
Ar
SO2
ArCOO-
Scheme 1
This method was applicable to the preparation of a num-
ber of symmetrical aromatic and some aliphatic anhy-
drides, provided that the anhydrides were not moisture
sensitive. Yield of this method compare favorably with
those of reported procedures which are invariably more
complex for instance, the accepted preparation camphoric
anhydride14 involves more stages and give inferior yields
than the simple procedure of grinding camphoric acid in
the presence of tosyl chloride in K2CO3 media.
On the other hand, aromatic sulfonyl agents such as ben-
zenesulfonyl chloride or N-sulfonyl heterocycles in basic
media have been used for different proposes e.g., Beck-
mann and Lossen rearrangements, dehydration of al-
doximes and primary amides to nitriles, cyclization of a -
hydroxy amide to a sulfonimido ether and esterification,
amidation and dehydration of carboxylic acids.12,13 These
diverse reactions appear to involve two major steps for
each of which there is ample precedent: first the formation
of an O–S bond by replacement of chlorine from the sul-
fonyl halide, and second, the displacement, elimination or
The reaction of phthalic acid as a dicarboxylic acid com-
pound and halobenzoic acid derivatives proceeded under
the same reaction conditions but we could not detect the
formation of the corresponding anhydride by TLC moni-
toring. In the case of 2,6-dichlorobenzoic acid, the related
carboxylic sulfonic anhydrides was produced in 70% iso-
lated yield.
–
migration of the arenesulfonate ion ArSO3 . By analogy,
it would be expected that carboxylic acid would react with
an aromatic sulfonyl halide to form a mixed aromatic an-
In conclusion a simple and efficient method for synthesis
of carboxylic anhydrides under solvent-free conditions at
room temperature has been developed. This work is a
cheap and very convenient method for the synthesis of
SYNTHESIS 2004, No. 2, pp 0205–0207
Advanced online publication: 15.12.2003
DOI: 10.1055/s-2003-44381; Art ID: Z15303SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
3

206
F. Kazemi et al.
SHORT PAPER
Table 1 Conversion of Carboxylic Acids to Anhydrides Using Tosyl Chloride in K2CO3 Media
Entry
1
Acid
Product
Time (min)
25
Yield
(%)a
Mp (°C) (Lit.)
95
142–144 (145)15a
CO2H
O
O
O
O
2
30
92
132–133 (134)15b
CO2H
O
O
O
3
4
20
35
85
85
70–71 (71–72)10
218–220 (221)14
OH
O
O
O
O
CO2H
CO2H
O
O
5
6
30
20
88
90
158–159 (160)15d
72–74 (71–73)8
OCH3
CO2H
OCH3
O
O
OCH3
H3CO
O
OCH3 H3CO
OCH3
CO2H
OCH3
O
O
OCH3
O
7
8
15
40
94
79
65–66 (67)15e
O
O
CO2H
H3CO
O2N
OCH3
H3CO
O2N
O
O
161 (161–63)15c
O
O
CO2H
NO2
9
20
25
90
85
92–94 (95)15c
25–26 (25)15a
O
O
H3C
CO2H
H3C
CH3
O
10
O
O
CO2H
O
11
12
45
25
74
80
189–191 (194)15c
102–104 (104)15d
O
O
O
O2N
CO2H
O2N
NO2
O
O
O
CO2H
a Yields refer to pure isolated products.
with the literature values.8–12,14,15 NMR spectra were recorded in
CDCl3 on a Bruker Advanced Dpx-250 (1H NMR 250 MHz and 13
NMR 62.9 MHz) spectrometer using TMS as internal standard. IR
spectra were recorded on a Perkin-Elmer IR-157G and a Perkin-
Elmer 781 spectrometer. All mps were taken on a Gallenkamp melt-
ing point apparatus. TLC was performed on glass plates coated with
silica gel (silica gel 60 F254, Merck).
carboxylic acid anhydrides in good to excellent yields
with high purity. This methodology is superior to the re-
ported method from the point of view of yield, short reac-
tion time, operational simplicity, straightforward work-up
of the products, and use of inexpensive and easily avail-
able reagents.
C
Symmetrical Carboxylic Acid Anhydrides; General Procedure
Tosyl chloride (5–6 mmol, in 6 portions) and a few drops of EtOAc
or CHCl3 were gradually added to a well ground mixture of carbox-
High purity carboxylic acid, tosyl chloride, and K2CO3 were pur-
chased from Fluka and Merck. The spectroscopic and physical data
of all the anhydrides prepared by our procedure were compared
Synthesis 2004, No. 2, 205–207 © Thieme Stuttgart · New York

SHORT PAPER
Preparation of Symmetrical Carboxylic Acid Anhydrides
207
ylic acid (10 mmol) and K2CO3 (6 g) in a mortar. The mixture was
ground by a pestle for 5 min at r.t., and the progress of the reaction
was monitored by TLC. Addition of a few drops of a solvent such
as EtOAc made the grinding easier with formation of more homog-
enous mixture and consequently a reduction in the reaction time.
After completion of the reaction, CH2Cl2 or CHCl3 (3 × 20 mL) was
added to the contents of the mortar, stirred, filtered and the organic
layer was dried (CaCl2). Evaporation of the solvent afforded a high-
ly pure product, which could be purified further by recrystallization
from a suitable solvent (Table 1). Selected spectral data for some
acid anhydrides prepared are given below.
Acknowledgment
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
References
(1) Ogliaruso, M. A.; Wolfe, J. F. Synthesis of Carboxylic Acids,
Esters and Their Derivatives; Wiley: New York, 1991, 198–
217.
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Yasuda, H.; Tamura, Y. J. Org Chem. 1986, 51, 4150; and
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1-Naphthoic Anhydride
Mp 142–144 °C (Lit.15a mp 145 °C).
IR (KBr): 1709 (C=O), 1770 cm–1 (C=O).
1H NMR (CDCl3): = 7.4–7.6 (m, 6 H), 7.9 (m, 2 H), 8.1 (m, 2 H),
8.4 (m, 2 H), 9.1 (m, 2 H).
13C NMR (CDCl3): = 124.9, 125.2, 126, 126.8, 127.2, 129.3,
132.3, 132.6, 134.4, 136, 163.4.
(+)-Camphoric Anhydride
(8) Remigiusz, K.; Juliatiek, R.; Shahriar, M. J. Org. Chem.
1994, 59, 2913.
Mp 218–220 °C (Lit.14 mp 221 °C).
(9) Keshavamurthy, K. S.; Vankar, Y. D.; Dhar, D. N. Synthesis
1982, 506.
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2003, 1517; and references cited therein.
IR (KBr): 1761 (C=O), 1805 cm–1 (C=O).
1H NMR (CDCl3): = 1.0 (s, 3 H), 1.1 (s, 3 H), 1.28 (s, 3 H), 2.1
(m, 4 H), 2.84 (dd, J = 6.7 Hz, 1 H).
13C NMR (CDCl3): = 14, 20, 21, 25, 33, 44, 54, 55, 170, 173.
(13) Brewster, J. H.; Ciotti, C. J. J. Am. Chem. Soc. 1955, 77,
6214; and references cited therein.
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2002, 32, 1659.
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32, 23.
2,4,6-Trimethylbenzoic Anhydride
Mp 102–104 °C (Lit.15d mp 104 °C).
IR (KBr): 1735 (C=O), 1792 cm–1 (C=O).
1H NMR (CDCl3): = 2.2 (s, 6 H), 2.4 (s, 12 H), 6.9 (s, 4 H).
13C NMR (CDCl3): = 20, 22, 128, 129, 136, 141, 166.
2,6-Dimethoxybenzoic Anhydride
Mp 158–159 °C (Lit.15d mp 160 °C).
IR (KBr): 1749 (C=O), 1807 cm–1 (C=O).
1H NMR (DMSO): = 3.79 (s, 12 H), 6.7 (d, J = 8.4 Hz, 4 H), 7.38
(t, J = 8.4 Hz, 2 H).
13C NMR (DMSO-d6): = 56.4, 104, 110.9, 133, 157.7, 160.7.
Synthesis 2004, No. 2, 205–207 © Thieme Stuttgart · New York