A simple and convenient one-pot synthesis of fatty acid esters from hindered alcohols using N,N-dimethylchloro-sulfitemethaniminium chloride as dehydrating agent

Article abstract of DOI:10.1081/SCC-120006474

N,N-Dimethylchlorosulfitemethaniminium chloride (SOCl₂-DMF) has been found to be an efficient reagent for one-pot synthesis of esters from equimolar amounts of fatty acids and hindered alcohols under mild conditions.

Full text of DOI:10.1081/SCC-120006474

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A SIMPLE AND CONVENIENT ONE-POT SYNTHESIS
OF FATTY ACID ESTERS FROM HINDERED ALCOHOLS
USING N,N-DIMETHYLCHLORO-SULFITEMETHANIMINIUM
CHLORIDE AS DEHYDRATING AGENT
Savita Kaul a , Ajay Kumar a , Bir Sain b & A. K. Gupta a
a Indian Institute of Petroleum , Dehradun, 248 005, India
b Indian Institute of Petroleum , Dehradun, 248 005, India
Published online: 18 Oct 2011.
To cite this article: Savita Kaul , Ajay Kumar , Bir Sain & A. K. Gupta (2002) A SIMPLE AND CONVENIENT ONE-POT SYNTHESIS
OF FATTY ACID ESTERS FROM HINDERED ALCOHOLS USING N,N-DIMETHYLCHLORO-SULFITEMETHANIMINIUM CHLORIDE AS
DEHYDRATING AGENT, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 32:18, 2885-2891, DOI: 10.1081/SCC-120006474
To link to this article: http://dx.doi.org/10.1081/SCC-120006474
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 18, pp. 2885–2891, 2002
A SIMPLE AND CONVENIENT ONE-POT
SYNTHESIS OF FATTY ACID ESTERS
FROM HINDERED ALCOHOLS USING
N,N-DIMETHYLCHLORO-
SULFITEMETHANIMINIUM CHLORIDE
AS DEHYDRATING AGENT
*
Savita Kaul, Ajay Kumar, Bir Sain, and A. K. Gupta
Indian Institute of Petroleum, Dehradun-248 005, India
ABSTRACT
N,N-Dimethylchlorosulfitemethaniminium chloride (SOCl2-
DMF) has been found to be an efficient reagent for one-pot
synthesis of esters from equimolar amounts of fatty acids and
hindered alcohols under mild conditions.
Key Words: Fatty acid esters; Hindered alcohols; N,N-
Dimethylchlorosulfitemethaniminium chloride
Esterification of alcohols is an important transformation in organic
synthesis[1] and a variety of methods have been developed to accomplish it.[2]
The classical acid catalyzed esterification methods are of little value for the
preparation of esters from sterically hindered alcohols.[3] Acid anhydrides
without any catalyst[4] and in the presence of catalysts like N,N-dimethyl-
aminopyridine (DMAP),[5] cobalt (II) chloride,[6,7] magnesium bromide with
*Corresponding author. E-mail: birsain@iip.res.in
2885
DOI: 10.1081/SCC-120006474
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2886
KAUL ET AL.
tertiary amines,[8] scandium triflate,[9] trimethylsilyl triflate,[10] indium
triflate[11] and bismuth triflate[12] have been extensively used for esterifica-
tion of hindered alcohols. However, acid anhydride method has limitation
for its application in case of acids like fatty acids which do not yield anhy-
drides easily. Another approach for facile esterification of sterically hindered
alcohols has been the use of various type of dehydrating reagents which
activates carboxyl group.[1] In this context the use of reagents like
N-alkyl-2-halopyridinium salts with trialkylamines,[13] di(2-pyridyl) carbon-
ate with DMAP,[14,15] 2-thiopyridyl chloroformate with tertiary amines[16]
and O,O0-di(2-pyridyl) thiocarbonate with DMAP[17–19] has been reported
in the literature.
N,N-Dimethylchlorosulfitemethaniminium chloride, a versatile dehy-
drating agent is easily prepared from dimethylformamide and thionyl chlo-
ride and has been used for carboxyl group activation in various synthetic
transformations.[20–23] However, the literature search indicate that the
potential of this reagent for esterification of hindered alcohols has not
been exploited.
In connection with one of our ongoing projects we needed a variety of
fatty acid esters of hindered alcohols and these could not be prepared by
conventional acid catalysed esterification methods. In search of a simple and
convenient method we focused our attention on N,N-dimethylchlorosulfite-
methaniminium chloride (SOCl2-DMF) (1) due to its easy preparation from
readily available reagents, and now report a direct and efficient one-pot
procedure for the preparation of esters (5) from fatty acids (2) and hindered
alcohols (4) using SOCl2-DMF (1) as dehydrating agent (Scheme 1).
Scheme 1.

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N,N-DIMETHYLCHLOROSULFITEMETHANIMINIUM CHLORIDE
2887
A variety of hindered primary alcohols (polyols) like dipentaerythritol
(Table 1, Entry 1), 1,1,1-trihydroxymethylethane (Table 1, Entry 3),
pentaerythritol (Table 1, Entry 5), 2,2-diethyl-1,3-propanediol) (Table 1,
Entry 10) and 2-methyl-2-propyl-1,3-propanediol (Table 1, Entry 14) were
esterified with C6–C12 fatty acid to give esters in almost quantitative yields
with all CH2OH groups being converted into esters. These results are pre-
sented in Table 1.
Similarly a number of different types of hindered secondary alcohols
like endoborneol (Table 2, Entry 1), isoborneol (Table 2, Entry 3), 4-tert-
butylcyclohexanol (Table 2, Entry 5) were esterified with C6–C8 fatty acids
to yield corresponding esters in excellent yields. These results are presented
in Table 2.
The protocol developed consist of adding equimolar quantities of
N,N-dimethylchlorosulfitemethaniminium chloride to a suspension of fatty
acid in dichloromethane, stirring the mixture for about 15 min, then addition
of equivalent quantities of alcohol followed by addition of excess pyridine,
stirring the mixture at room temperature for six hours and usual work-up.
The reaction proceed through the formation of activated carboxylic
acid species (3) which react with the hindered alcohols (4) to give carboxylic
esters (5). As the reactions were conducted at room temperature there is no
possibility for the formation of carboxylic acid chlorides.[20]
In conclusion, easy preparation of N,N-dimethylchlorosulfitemethani-
minium chloride from readily available and low cost reagents, mild reaction
conditions, wide applicability make this method to be simple and convenient
for one-pot synthesis of esters from fatty acids and hindered alcohols.
EXPERIMENTAL
N,N-Dimethylchlorosulfitemethaniminium chloride was prepared
from dimethylformamide and thionyl chloride following the procedure
reported by C. Palomo et al.[20]
A typical procedure for the preparation of ester from fatty acid and
hindered alcohol is as follows: To a solution of hexanoic acid (4.64 g,
40 mmol) in anhydrous dichloromethane (75 mL) was added freshly prepared
N,N-dimethylchlorosulfitemethaniminiumchloride (9.6 g, 50 mmol)at0–5ꢀC.
After stirring the mixture at this temperature for 15 min, pentaerythritol
(1.36 g, 10 mmol) was added followed by drop wise addition of anhydrous
pyridine (12.1 mL, 0.15 mol) in dichloromethane (30 mL). The resulting mix-
ture was stirred at room temperature for 6 h, washed with water (3 ꢁ 50 mL),
organic layer separated and dried over anhydrous sodium sulphate.
Evaporation of the solvent gave pure ester (5.17 g, 98%). Similarly, other

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2888
KAUL ET AL.
Table 1. Esterification of Hindered Primary Alcohols (Polyols) with Fatty
Acids Using N,N-Dimethylchlorosulfitemethaniminium Chloride
Entry
1
Alcohol (Polyol)
Fatty Acid
Yield (%)a
94
CH3-(CH2)6COOH
2
3
C
3-(CH2)8COOH
93
96
H
H
CH3-(CH2)4COOH
4
5
C
3-(CH2)6COOH
96
98
CH3-(CH2)4COOH
6
7
8
9
C
C
C
C
3-(CH2)6COOH
3-(CH2)8COOH
3-(CH2)10COOH
3-(CH2)3-
97
96
96
98
H
H
H
H
CH-(C2H5)COOH
10
CH3-(CH2)4COOH
96
11
12
13
14
CH3-(CH2)6COOH
CH3-(CH2)8COOH
CH3-(CH2)10COOH
CH3-(CH2)4COOH
95
96
96
96
15
16
17
18
CH3-(CH2)6COOH
CH3-(CH2)8COOH
CH3-(CH2)10COOH
CH3-(CH2)3-
98
96
97
98
CH(C2H5)COOH
aIsolated yields.

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N,N-DIMETHYLCHLOROSULFITEMETHANIMINIUM CHLORIDE
2889
Table 2. Esterification of Hindered Secondary Alcohols with
Fatty Acids Using N,N-Dimethylchlorosulfitemethaniminium
Chloride
Entry
1
Alcohol
Fatty Acid
Yield (%)a
96
CH3(CH2)4COOH
2
3
C 3(CH2)6COOH
CH3(CH2)4COOH
93 H
97
4
5
C 3(CH2)6COOH
CH3(CH2)4COOH
99 H
97
6
7
C 3(CH2)6COOH
CH3(CH2)4COOH
99 H
97
8
97
9
10
C 3(CH2)6COOH
CH3(CH2)4COOH
97 H
98
11
97
aIsolated yields.

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2890
KAUL ET AL.
esters were prepared and their yields obtained are shown in Tables 1 and 2.
The products were identified by comparing their physical and spectral data
with those of authentic compounds reported in the literature.
ACKNOWLEDGMENT
We are thankful to Director, Indian Institute of Petroleum, Dehradun
for his kind permission to publish these results.
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Received in the UK August 6, 2001