Dabco/SOCl2, mild, and convenient reagent for the preparation of symmetrical carboxylic acid anhydrides

Article abstract of DOI:10.1080/713744563

Various types of carboxylic acids undergo rapid dehydration with 1,4-diazabicyclo[2.2.2]octane, dabco / thionyl chloride, under mild reaction conditions to afford symmetrical acid anhydrides in high isolated yields.

Full text of DOI:10.1080/713744563

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Phosphorus, Sulfur, and Silicon and the Related
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Dabco/SOCl 2 , Mild, and Convenient Reagent for the
Preparation of Symmetrical Carboxylic Acid Anhydrides
Foad Kazemi a & Ali Reza Kiasat a
a Shahid Chamran University , Ahvaz, Iran
Published online: 27 Oct 2010.
To cite this article: Foad Kazemi & Ali Reza Kiasat (2003) Dabco/SOCl 2 , Mild, and Convenient Reagent for the Preparation of
Symmetrical Carboxylic Acid Anhydrides, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:10, 2287-2291, DOI:
10.1080/713744563
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Phosphorus, Sulfur, and Silicon, 178:2287–2291, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390234902
DABCO/SOCl2, MILD, AND CONVENIENT REAGENT
FOR THE PREPARATION OF SYMMETRICAL
CARBOXYLIC ACID ANHYDRIDES
Foad Kazemi and Ali Reza Kiasat
Shahid Chamran University, Ahvaz, Iran
(Received March 25, 2003)
Various types of carboxylic acids undergo rapid dehydration with 1,4-
diazabicyclo[2.2.2]octane, dabco/thionyl chloride, under mild reaction
conditions to afford symmetrical acid anhydrides in high isolated
yields.
Keywords: Carboxylic acid; symmetrical anhydrides; thionyl chloride;
dabco
Carboxylic acid anhydrides are among the most important class of
reagents used in organic synthesis.1,2 They are frequently the preferred
reactive acid derivative for preparation of esters, amides, and peptides.2
Availability of symmetrical acid anhydrides is quite important for many
transacylation applications because their acylation precludes the for-
mation of by-products due to attack at the second acyl carbonyl group
of unsymmetrical anhydrides.2,3
Generally, carboxylic acid anhydrides are prepared by reacting
sodium, potassium, and especially thallium salts of carboxylic acids
with powerful acylating agents, such as acid chlorides3,4 or acid anhy-
drides,3,5 or reacting carboxylic acids with dehydrative coupling agents
such as thionyl chloride,6 ketene,7 phosgene,8 phosphorus pentoxide,9
dicyclohexylcarbodiimide,10 N,N-carbonyldimidazole,7 isocyanate,11
ethoxyacetylene,7 bromotriphenylphosphonium bromide,12 N-phenyl-
phosphoramidochloridate,12 diphenylphosphorochloridate,12 bis (tri-
chloromethyl) carbonate,8 or trichloroacetonitrile/PPh3.3 However,
many of these methods met with some limitations, including low yields,
laborious procedures, expensive or not readily accessible reagents, un-
stable or special reagents, harsh reaction conditions, necessary pres-
ence of a phase transfer catalyst, or tedious work-up. Consequently,
Address correspondence to Foad Kazemi, Chemistry Department, College of Science,
Shahid Chamran University, Ahvaz, Iran.
2287

2288
F. Kazemi and A. R. Kiasat
it seems that there is a still great demand for new and efficient
methods. In our development of new methods for functional group
transformation,13 we especially are interested in developing the ap-
plication of modified form of thionyl chloride in organic synthesis.13h−j
In this line, very recently, we have found that aldoximes undergo rapid
dehydration using Na2SO3/SOCl2,14j and dabco/SOCl213i under mild re-
action conditions to afford the corresponding nitriles. Now we report on
conditions whereby various types of symmetrical anhydride can be con-
veniently synthesized from the corresponding carboxylic acids under
mild nonaqueous reaction conditions by dabco/thionyl chloride.
RESULTS AND DISCUSSION
The reagent was prepared easily in essentially quantitative yield as
a white solid by the reaction of thionyl chloride with stiochiometric
amount of dabco in dichloromethane at 0◦C. Since this white complex
was sensitive to moisture, it was used directly in its crude form sus-
pended in anhydrous dichloromethane. The obtained reagent can be
used efficiently as dehydrative coupling agent for synthesis of symmet-
rical anhydride from the carboxylic acids. The plausible mechanism
for the successful application of this reagent as dehydrating agent in
symmetrical anhydride synthesis is as follows. At first, (I) is proba-
bly formed; this kind of mechanism has been proposed in the reaction
of thionyl chloride and polyvinylpyrrolidone,13h N-methyl pyrolidone,14
or N,N-dimethylformamide.15 Representative carboxylic acids were
treated with (I) in CH2Cl2 at room temperature. The reaction proceeded,
probably via O-substituted carboxylic acid (II), which turns to symmet-
rical carboxylic anhydride with the nucleophilic addition of carboxylic
acid followed by elimination of sulfur dioxide as shown in Scheme 1.
Several controlled reactions were carried out in order to establish the
optimal reaction conditions. It revealed that simple stirring of benzoic
acid (1 equiv.) and 3 equiv. of dabco/SOCl2 (1:1) in CH2Cl2 effected the
formation of benzoic anhydride in 80% isolated yield within 45 min.
The procedure turned out to be general for a range of structurally
diverse carboxylic acids. Aliphatic and aromatic carboxylic acids were
dehydrated easily and afforded the corresponding anhydrides in high
isolated yields. The scope and generality of this process is illustrated
with several examples and the results are summarized in Table I. The
structure of all the products were settled from their analytical and

Carboxylic Acid Anhydrides
2289
TABLE I Conversion of Carboxylic Acids to Anhydrides Using Dabco Thionyl
Chloride
Entry
Substrate
Product
Time (min)
Yield (%)
1
2
CH3(CH2)3CO2H
CH3(CH2)16CO2H
(CH3(CH2)3CO2)2O
(CH3(CH2)16CO2)2O
35
40
80
85
3
4
5
6
45
45
45
45
80
75
85
75
7
50
82
8
9
50
60
87
80
aMolar ratio of reagent to substrate was 3:1 and performed at rt.
bYields refer to pure isolated products.
cProducts were characterized by comparison of their physical data, IR, and NMR
spectra with known samples.
SCHEME 1

2290
F. Kazemi and A. R. Kiasat
1
spectral (IR, H NMR) data and by direct comparison with authentic
samples.
It is noteworthy that no evidence for the formation of carboxylic acid
chlorides as by-product of the reaction was observed and the products
were obtained in pure form after aqueous basic work-up without further
purification. It was found that the yield of reaction products in the
absence of dabco was very low.
The reaction of phthalic acid as a dicarboxylic acid compound pro-
ceeded under the same reaction conditions to afford the expected cyclic
anhydride, phthalic anhydride in 80% isolated yield.
Compared to some previously reported reagents with major or mi-
nor drawbacks, several noteworthy features of this system are appar-
ent. These are the easy work-up procedure, availability of the reagent,
operational simplicities, and use of inexpensive reagent.
CONCLUSION
We believe this procedure using dabco/SOCl2 presents a useful and
convenient alternative to the existing methods for dehydration coupling
of carboxylic acids. Further application of this dehydrative system in
organic synthesis are currently under investigation.
EXPERIMENTAL
General
IR spectra were recorded on a Shimadzo 450 spectrophotometer;
1
and HNMR spectra in CDCl3 on a Bruker Avance DPX instrument
(250 MHz). Carboxylic acids, dabco, and thionyl chloride were pur-
chased from Fluka and Merck. Products were characterized by compar-
ison of their physical data, IR and 1H NMR spectra with authentic sam-
ples. The purity determination of the products and reaction monitoring
were accomplished by TLC on silica gel polygram SILG/UV 254 plates.
General Procedure for the Preparation of Dabco/Thionyl
Chloride Complex and Its Application in Conversion
of Carboxylic Acid to Anhydrides
To a stirred solution of dabco (3 mmol, 0.336 g) in anhydrous CH2Cl2
(3 ml) at 0◦C freshly distilled thionyl chloride was added slowly (3 mmol,
0.357 g) to give a white precipitate. The reaction mixture was stirred for

Carboxylic Acid Anhydrides
2291
about 5 min to effect the complete reaction of thionyl chloride and dabco.
To the reaction mixture, carboxylic acid (1 mmol) was slowly added and
stirred at room temperature for 30–50 min. Progress of the reaction was
monitored by TLC. On completion of the reaction, the reaction mixture
was basified with a dilute solution of NaHCO3 (10%) and extracted with
CH2Cl2 (15 ml). The organic layer was dried over anhydrous sodium
sulfate and the solvent evaporated under reduced pressure to afford
the TLC and 1HNMR pure products in 75–90% isolated yields.
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