Microwave promoted facile synthesis of methyl and ethyl carboxylates

Article abstract of DOI:10.1081/SCC-120005431

Microwave irradiation of carboxylic acids with trialkyl orthoacetate in solvent-free conditions afforded an efficient method for alkylation of carboxylic acids to corresponding alkyl carboxylates.

Full text of DOI:10.1081/SCC-120005431

This article was downloaded by: [Michigan State University]
On: 28 January 2015, At: 09:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
MICROWAVE PROMOTED FACILE SYNTHESIS OF METHYL
AND ETHYL CARBOXYLATES
a
a
a
Jong Chan Lee , In-Goul Song & Jin Young Park
a
Department of Chemistry , Chung-Ang University , Seoul, 156–756, Korea
Published online: 18 Oct 2011.
To cite this article: Jong Chan Lee , In-Goul Song & Jin Young Park (2002) MICROWAVE PROMOTED FACILE SYNTHESIS OF
METHYL AND ETHYL CARBOXYLATES, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:14, 2209-2213, DOI: 10.1081/SCC-120005431
To link to this article: http://dx.doi.org/10.1081/SCC-120005431
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS
Vol. 32, No. 14, pp. 2209–2213, 2002
MICROWAVE PROMOTED FACILE
SYNTHESIS OF METHYL AND ETHYL
CARBOXYLATES
Jong Chan Lee,* In-GoulSong, and Jin Young Park
Department of Chemistry, Chung-Ang University,
Seoul 156–756, Korea
ABSTRACT
Microwave irradiation of carboxylic acids with trialkyl
orthoacetate in solvent-free conditions afforded an efficient
method for alkylation of carboxylic acids to corresponding
alkyl carboxylates.
Key Words: Alkyl carboxylates; Carboxylic acids; Esterifi-
cation; Microwave heating
Wide variety of esterification methods for carboxylic acids have been
[1]
reported. Most of the commonly used methods are either condensation of
carboxylic acids with alcohols under acidic conditions or reaction of car-
[
2]
boxylic acids with alkyl halides under basic conditions. Microwave assisted
organic synthesis have gained popularity due to their enhanced reaction rates,
[
3]
improved selectivity, and ease of manipulation. In recent years, a number of
methods for the preparation of carboxylic esters from carboxylic acids were
reported utilizing microwave irradiation conditions. These include the alky-
[
4]
lation of potassium benzoate with n-octyl bromide, reaction of aromatic
*
Corresponding author. E-mail: jclee@cau.ac.kr
209
2
DOI: 10.1081/SCC-120005431
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

2
210
LEE, SONG, AND PARK
carboxylic acids with long-chain alkyl halides under phase transfer catalytic
[5]
conditions, esterification of 2,4,6-trimethylbenzoic acid with 2-propanol in
[6]
sealed tube, acid catalyzed esterification of acetic acid with isopentyl alco-
[7]
hol in closed system, and acid catalyzed reaction of benzoic acid with etha-
[
8]
nol in a continuous tubular flow reactor. However, these methods are
limited to the use of either alkylating agents with high boiling points or
closed reaction systems with acidic or basic reaction conditions.
Among others, methyl and ethyl carboxylates constitute the most
common of the carboxylate esters because of their case of preparations,
simple structures, and low molecular weights. Esterification of carboxylic
[9]
[10]
acids with alcohol
or alkyl halides
can be easily achieved in
conventional reaction conditions. However, preparation of methyl or ethyl
carboxylates from carboxylic acids under open vessel solvent-free microwave
conditions has not been reported due to the problems associated with low-
boiling nature of corresponding alcohols or alkyl halides. Therefore, we have
sought to develop a facile and general route for the preparation of methyl or
ethyl carboxylates from carboxylic acids with particular interests in the
microwave irradiation technique without using any solvents, solid supports
or catalysts. Preparation of ethyl carboxylates from the reaction of carboxylic
ꢀ
acids with triethyl orthoacetate (TEOA) in toluene at 110 C has been briefly
reported.
[11]
Trialkyl orthoacetates have considerably high boiling points
which is suitable for the application to the solvent-free microwave irradiation
technique. We have, therefore, attempted the use of trialkyl orthoacetates as
alkylation reagents for the esterification of carboxylic acids under solvent-
free microwave irradiation conditions.
We now wish to report a facile and efficient method for the conversion
of carboxylic acids to corresponding methyl and ethyl carboxylates under
microwave irradiation in solvent-free and neutral reaction conditions.
Microwave irradiation to the mixture of carboxylic acids and trialkyl
orthoacetate (3.0 equiv.) for 2–5 min cleanly afforded corresponding alkyl
carboxylates. As shown in the Table 1, a variety of aromatic, aliphatic, and
heteroaromatic carboxylic acids undergo efficient esterification to afford
high yields of alkyl carboxylates. By the comparison with conventional
[
11]
heating conditions (Entries 9, 11, 12, and 14),
the yields obtained in
this method are always superior and reaction times are dramatically reduced
from 24 h to less than 5 min.

MICROWAVE IRRADIATION OF CARBOXYLIC ACIDS
2211
Table 1. Trialkylorthoacetate Mediated Synthesis of Alkyl Carboxylates
a
a
Yield (%)
Yield (%)
Entry
Product
R ¼ M e R¼ Et Entry
Product
R ¼ M e R¼ Et
85 84
1
77
84
10
b
b
2
3
97
94
11
97 98(89)
b
94(81) 95(92)
92
95
12
4
5
92
99
98
95
13
14
CH ðCH Þ -
75
80
3
2 4
COOR
b
96(68) 95(89)
b
RCOOðCH Þ -
2
4
COOR
6
97
98
15
92
91
7
8
9
92
95
98
92
16
17
90
98
94
87
87
93
b
88 (77) 86 (81) 18
b
a
b
Isolated yield; Yields in parenthesis are obtained from conventional heating in
ꢀ
toluene at 100 C for 24 h (Ref. [11]).
There are few methods that dealt with chemoselective esterification of
[
12]
phenolic carboxylic acids.
To investigate the efficiency of this method
for chemoselective esterification, selective esterification of various phenolic
carboxylic acids were investigated. The examples (Entries 15–18) shown in
Table 1, exhibited high chemoselectivities in favor of more acidic carboxylic
acid groups.

2
212
LEE, SONG, AND PARK
In summary, we have demonstrated that the microwave promoted
esterification of carboxylic acids is efficiently and rapidly accomplished.
We believe this protocol provide a useful alternative to known conventional
esterification methods.
EXPERIMENTAL SECTION
1
H NMR spectra were recorded on a varian 2000 (300 MHz) spectrom-
eter. IR spectra were recorded with a Jasco FT/IR 5300 spectrophotometer.
Merck silica gel (230–400 mesh A.S.T.M.) was employed for flash column
chromatography. All esterification products exhibited spectral data consis-
tent with assigned structure.
GeneralProcedure
A mixture of carboxylic acid (5.0 mmol) and trialkyl orthoacetate
15.0 mmol) in an open test tube was heated in a domestic microwave
(
oven at full power (600 W) for 2–5 min at 1 min intervals. After cooling,
the reaction mixture was extracted with ethyl acetate (2 ꢁ 30 mL). The
combined extracts were washed with water (2 ꢁ 25 mL) and dried over
MgSO . Evaporation of the solvent provided the crude product of high
4
chemical purity. Further purification of the crude product by short
column chromatography using ethyl acetate : hexane (1 : 1) as eluent gave
pure alkyl carboxylate.
REFERENCES
1
2
. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis;
John Wiley & Sons: New York, 1999; Chapter 5.
. Mulzer, J. In Comprehensive Organic Synthesis, Trost, B.M.; Fleming, I.,
Heathcock, C.W. Eds., Pergamon Press: New York; 1991, vol. 6,
pp. 324–337.
3. (a) Galema, S.A. Chem. Soc. Rev. 1997, 26, 233; (b) Deshayes, S.;
Liagre, M.; Loupy, A.; Luche, J.-L.; Petit, A. Tetrahedron 1999, 55,
10851; (c) Varma, R. S. Green Chemistry 1999, 43.
4. Barry, J.; Bram, G.; Decodts, G.; Loupy, A.; Orange, C.; Petit, A.;
Sansoulet, J. Synthesis 1985, 40.

MICROWAVE IRRADIATION OF CARBOXYLIC ACIDS
2213
5. (a) Loupy, A.; Sansoulet, J.; Pedoussaut, M. J. Org. Chem. 1986, 51,
740; (b) Loupy, A.; Pigeon, P.; Ramdani, M. Tetrahedron 1996, 52,
6705.
6
7
. Raner, K.D.; Strauss, C.R. J. Org. Chem. 1992, 57, 6231.
. Kabza, K.G.; Chapados, B.R.; Gestwicki, J.E.; McGrath, J.L. J. Org.
Chem. 2000, 65, 1210.
8. Pipus, G.; Plazl, I.; Koloini, T. Chem. Engineering Journal 2000,
76, 239.
9. Examples: (a) Brook, M.A.; Chan, T.H. Synthesis 1983, 201; (b)
Hendrickson, J.B.; Schwartzman, S.M. Tetrahedron Lett. 1975, 277.
1
0. Examples: (a) Karanewsky, D.S.; Malley, M.F.; Gougoutas, J.Z. J.
Org. Chem. 1991, 56, 3744; (b) Sato, T.; Otera, J.; Nozaki, H. J.
Org. Chem. 1992, 57, 2166.
1
1
1. Trujillo, J.I.; Gopalan, A.S. Tetrahedron Lett. 1993, 34, 7355.
2. (a) Lee, J.C.; Choi, Y. Synth. Comm. 1998, 28, 2021; (b) Riegle, J.;
Maddox, M.L.; Harrison, I.T. J. Med. Chem. 1974, 17, 377.
Received in Japan June 4, 2001