Na2CO3/SOCl2: A mild and convenient reagent for the preparation of isopropyl carboxylates

Article abstract of DOI:10.1080/10426500490459812

Na₂CO₃/SOCl₂ has been used for esterification of aliphatic and aromatic acids with isopropanol. This esterification method is compatible with a wide assortment of functional groups.

Full text of DOI:10.1080/10426500490459812

Phosphorus, Sulfur, and Silicon, 179:1187–1191, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490459812
Na2CO3/SOCl2: A MILD AND CONVENIENT
REAGENT FOR THE PREPARATION OF ISOPROPYL
CARBOXYLATES
Foad Kazemi, Ali Reza Kiasat, and Began Mombaini
Shahid Chamran University, Ahvaz, Iran
(Received October 14, 2003; accepted October 16, 2003)
Na2CO3/SOCl2 has been used for esterification of aliphatic and aro-
matic acids with isopropanol. This esterification method is compatible
with a wide assortment of functional groups.
Keywords: Esterification; isopropyl carboxylate; isopropyl ester;
sodium carbonate; thionyl chloride
Esterification is an important and well-established reaction that is
widely used in organic synthesis for various purposes.1−2 A wide vari-
ety of esterification methods for carboxylic acids have been reported.2,3
Most of the commonly used methods are either reaction of carboxylic
acids with alkyl halides under basic conditions or condensation of car-
boxylic acids with alcohols under acidic conditions.2 In addition to ho-
mogeneous acids (sulphuric acid, hydrogen chloride, orthophosphoric
acid, and boric acid), metal salts supported on solid supports are well
known as catalysts for condensation of carboxylic acids with alcohols.4
Other methods also have been suggested recently.5 The disadvantages
of using these catalysts include long reaction time, low yield, expen-
sive reagents, and tedious operation, and are difficult to avoid. Hence,
a need still exists for a convenient, simple, and facile procedure to pre-
pare esters under mild conditions and using readily available reagents.
In continuation of our efforts to explore new methods for functional
group transformation,6 we are especially interested in developing the
application of a modified form of thionyl chloride in organic synthesis.
Along this line, very recently we found that SOCl2 in the presence of
The authors acknowledge the partial support of this work by Shahid Chamran Ahvaz
University Research Council.
Address correspondence to Foad Kazemi, Chemistry Department, College of Science,
Shahid Chamran University, Ahvaz 6137-4-3169, Iran.
1187

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F. Kazemi et al.
6g
polyvinylpyrrolidone,6e 1,4-diazabicyclo[2.2.2]octane,6f and Na2SO3
serve as mild dehydrating agents. In view of the great utility of esters
as valuable intermediates in chemical and pharmaceutical industries,1
it may be worthwhile to explore the versatility of thionyl chloride in
esterification reaction. In 1996, a report by Hosangadi et al.7 outlined
the esterification of aromatic carboxylic acids with some primary alco-
hols such as methanol, ethanol, and n-butanol. Here we describe results
that successfully led to the development of a novel, simple method for
the esterification of aliphatic and aromatic carboxylic acids with iso-
propanol using sodium carbonate/thionyl chloride under mild reaction
conditions.
O
ꢁ
Na2CO3/SOCl2(1:1)
R CO2H
−→ R C O CH(CH3)2
isopropyl alcohol/reflux
The reagent was easily prepared by the reaction of thionyl chlo-
ride with stiochiometric amount of sodium carbonate at room temper-
ature. Initially, in order to establish the optimal reaction conditions,
conversion of benzoic acid to isopropyl benzoate was studied. In order
to achieve a high conversion of the starting carboxylic acid (1 equiv.)
in reasonable time, application of isopropyl alcohol as solvent, reflux
conditions and one equivalent of Na2CO3/SOCl2 were required. Simi-
lar transformations with different starting carboxylic acid in isopropyl
alcohol were carried out. In all cases, the reaction led to a single prod-
uct and the products were obtained in pure form after aqueous basic
work-up without further purification.
The scope and generality of this process is illustrated with several
examples and the results are summarized in Table I Aliphatic and aro-
matic carboxylic acids were easily converted to the corresponding iso-
propyl ester in moderate to high yields. As shown in Table I the yield
of esterification reaction was markedly lowered by introducing strong
electron-donating groups such as hydroxyl or amino groups in ortho
position of the aromatic ring. The structure of all the products were
1
characterized from their analytical and spectral (IR, H NMR) data
and by direct comparison with authentic samples.
The tolerance of various functional groups under the present reac-
tion conditions has been examined by reacting the substrates bearing
OPh, OH, NO2, NH2, and olefinic groups. It was found that the yield of
reaction in the absence of Na2CO3 was very low.
Dicarboxylic acids under the same reaction conditions and with two
equivalents of Na2CO3/SOCl2 were cleanly, easily, and efficiently con-
verted to the corresponding diisopropyl ester in high isolated yields.

Isopropyl Carboxylates
1189
TABLE I Conversion of Carboxylic Acids to Isopropyl Ester Using Na2CO3/
Thionyl Chloridea,b
Entry
Substrate
Product
Yield%c,d
1
2
CH3(CH2)16CO2H
CH3(CH2)16CO2CH(CH3)2
89
89
3
4
88
91
5
6
7
8
HO2C(CH2)4CO2H
HO2C(CH2)2CO2H
HO2CCH CHCO2H
HO2CCH(OH)CH(OH)CO2H (CH3)2HCO2CCH(OH)CH(OH)CO2CH-
(CH3)2
(CH3)2HCO2C(CH2)4CO2CH(CH3)2
(CH3)2HCO2C(CH2)2CO2CH(CH3)2
(CH3)2HCO2CCH CHCO2CH(CH3)2
89
90
91
92
9
10
11
12
89
90
90
22
13
14
89
37
15
83
16
17
89
87
aMolar ratio of substrate to reagent for mono carboxylic acids was 1:1 and for dicar-
boxylic acids was 1:2.
bReactions performed under reflux conditions for 2h.
cYields refer to pure isolated products.
dProducts were characterized by comparsion of their physicial data, IR, NMR spectra
with known samples.

1190
F. Kazemi et al.
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.
In summary, we believe this procedure using Na2CO3/SOCl2 will
present a useful and convenient alternative to the existing methods
for esterification reaction.
EXPERIMENTAL
General
Sodium carbonate and thionyl chloride were purchased from Fluka
Company. Carboxylic acids were purchased from Fluka and Merck.
Products were characterized by comparison of their physical data, IR
and 1H NMR spectra with authentic samples. 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 Conversion of Carboxylic Acid
to Isopropyl Ester with Na2CO3/SOCl2
Fine powdered sodium carbonate (1 mmol, 0.106 g) was mixed with
the freshly distilled thionyl chloride (1 mmol, 0.120 g) in a 25 ml
round-bottomed flask at room temperature. To the resulting powder,
a solution of carboxylic acid (1 mmol) in isopropyl alcohol (5 ml) was
slowly added and stirred under reflux conditions for 2 h. On completion
of the reaction, the reaction mixture was poured into dilute solution
of NaHCO3 (10%) until the pH of the reaction mixture reached 9
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 22–92%
isolated yields.
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Isopropyl Carboxylates
1191
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