Regiospecific phenyl esterification to some organic acids catalyzed by combined Lewis acids

Article abstract of DOI:10.1080/00397910600773759

A new and efficient method for the preparation of various phenyl esters has been achieved by a simple reaction of an acid with phenol in the presence of anhyd. ZnCl₂ and a catalytic amount of AlCl₃. This combined Lewis acid also catalyzes the selective phenyl esterification to different dioic acids and is very simple and high yielding. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600773759

This article was downloaded by: [Duke University Libraries]
On: 02 December 2012, At: 11:56
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
Regiospecific Phenyl Esterification to Some
Organic Acids Catalyzed by Combined Lewis
Acids
a
a
H. N. Roy & A. H. Al Mamun
a
Department of Chemistry, University of Rajshahi, Rajshahi, Bangladesh
Version of record first published: 16 Feb 2007.
To cite this article: H. N. Roy & A. H. Al Mamun (2006): Regiospecific Phenyl Esterification to Some Organic
Acids Catalyzed by Combined Lewis Acids, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:20, 2975-2981
To link to this article: http://dx.doi.org/10.1080/00397910600773759
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
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.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

w
Synthetic Communications , 36: 2975–2981, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600773759
Regiospecific Phenyl Esterification to Some
Organic Acids Catalyzed by Combined
Lewis Acids
H. N. Roy and A. H. Al Mamun
Department of Chemistry, University of Rajshahi,
Rajshahi, Bangladesh
Abstract: A new and efficient method for the preparation of various phenyl esters has
been achieved by a simple reaction of an acid with phenol in the presence of anhyd.
ZnCl and a catalytic amount of AlCl . This combined Lewis acid also catalyzes the
2
3
selective phenyl esterification to different dioic acids and is very simple and high yielding.
Keywords: Dicarboxylic acid, esterification, mixed Lewis acid catalysts, regiospecific
INTRODUCTION
Phenolic esters of organic acids, especially those of cresols and phenols, are
good flavor compounds because they possess a combination of sweet, floral,
[1]
and fruity odors, which are very desired in food chemistry. Substituted
phenyl esters have wide application in the manufacture of fine chemicals
[
2]
such as insecticides, antioxidant, and photosensitizers.
selective esterification is required in the synthesis of natural products that
Moreover,
[3,4]
contain two or more carboxylic groups.
Fischer esterification, a strong
protic acid in an alcohol solvent, has been used for more than a century to
convert carboxylic acids into their corresponding carboxylate esters, but
strong acid-catalyzed esterification to carboxylic acid, containing double
bonds or other reactive functionalities, often leads to polymeric products in
[5]
addition to ester. Thus, isolation of esters becomes tedious. Phenyl ester
[
6]
formation by acylation
is a well-known procedure, although some
Received in India March 20, 2006
Address correspondence to H. N. Roy, Department of Chemistry, University of
Rajshahi, Rajshahi 6205, Bangladesh. E-mail: hnroy01@yahoo.com
2
975

2
976
H. N. Roy and A. H. Al Mamun
[7]
acylchlorides revert to their mother acid. Many catalytic processes are
available for the alkyl esterification, but phenyl esterification by catalytic
processes is still unusual. The lesser nucleophilicity of the phenol generally
makes the strong acid-catalyzed reaction difficult. Recently, enzymatic
[
8]
phenyl esterification have received success, but they are still few in
numbers and in most cases are reversible and slow. So far, mixed Lewis–
acid catalyzed esterifications are still unavailable for phenyl esterification.
Therefore, we used Lewis acid mixtures for phenyl esterification. Our aim
in using Lewis acid (AlCl ) as a catalyst is to enhance the electrophilicity
3
of carbon in the carboxylic group instead of protic acids, and subsequent
addition of anhyd. ZnCl is intended to dehydrate the reaction mixture.
2
RESULTS AND DISCUSSION
[7c]
Catalytic esterification, especially tin(II) chloride,
of some organic acids
with alcohols has allowed us to develop a new method in phenyl esterification
using AlCl and ZnCl mixed catalyst. Previously, it was done by the addition
3
2
of strong protic acid or tosic acid to a alcohol–acid mixture. However, we
avoided mineral acids for esterification. In the present work, an aliquot of
AlCl was initially added to organic acids to increase the electrophilicity of
3
COOH group. A few minutes later, dry phenol (1 equiv.) was added in
addition to an equivalent amount of anhyd. ZnCl . In a few cases, the
2
reaction mixture was heated at reflux temperature in EtOAc solvent.
Progress and completion of the reaction was monitored by thin-layer chrom-
atography (TLC) in an n-hexane/ethylacetate solvent system (5:1). The top
spot in TLC showed the formation of esters. Quenching of the reaction was
done with dilute hydrochloric acid (1 M) at 08C. Quick silica-gel filtration
furnished the required phenyl esters in good to excellent yields (see
Table 1). All the data are in good agreement with the literature values.
Phenol with organic acids in the presence of AlCl did not bring about any
3
phenyl esters; instead, a Friedel–Crafts product was isolated. In the same
way, as a test case, ZnCl alone did not give any phenyl esters.
2
After achievement of some phenyl esters, regiospecific phenyl esterifica-
tion was carried out using a few dioic acids (entries 13, 14, and 15) by the
same method. At an ice-cold temperature, a 1:1 molar mixture of dioic
acids with phenol directs the phenyl group to the aliphatic part of the
COOH functionality. This is confirmed by the proton magnetic resonance
(
PMR) spectra of phenyl phenyl acetate 12a. Selectivity was good and
phenyl group was directed to the aliphatic part of the COOH functionality
regiospecifically. The same reaction was continued to aliphatic alcohol with
the dioic acids, but in this case regiospecificity has drastically changed and
the alkyl group was found to attach at the aromatic ring-connected COOH
group. Whatever may be the mechanism, the net outcome of this work is to
generate different phenyl esters with excellent yields. From the yield and

Table 1.
Reaction time
(h)
Yield
(%)
1
IR and H NMR
Entry
Acids
Product (esters)
21 1
IR (KBr): 1750 cm ; H NMR (400 MHz, CDCl
1
7
3
):
90
Ad r¼-H7) .. 59–7.51 (m, 5H, Ar-H), 7.39–7.32 (m, 5H,
2
1 1
2
3
4
9
IR (KBr): 1738 cm ; H NMR (400 MHz, CDCl
3
):
83
d ¼ 7.49 (d, 1H, J ¼ 9 Hz, Ar-H), 7.44 (d, 1H,
J ¼ 10 Hz, Ar-H), 7.32–7.22 (m, 5H, Ar-H), 6.95
(
s, 1H, Ar-H). 6.84 (m, 1H, Ar-H), 2.32 (s, 3H, CH
3
)
21 1
IR (KBr): 1748 cm ; H NMR (400 MHz, CDCl
10
9
3
):
85
87
d ¼ 7.58–7.53 (m, 2H, Ar-H), 7.51 (d, 1H, J ¼ 8 Hz,
Ar-H), 7.45–7.41 (m, 5H, Ar-H), 7.25 (d, 1H,
J ¼ 8 Hz, Ar-H), 2.28 (s, 3H, CH
21 1
3
)
3
IR (KBr): 1742 cm ; H NMR (400 MHz, CDCl ):
d ¼ 8.16 (d, 1H, J ¼ 8 Hz, Ar-H), 7.50–7.44 (m, 2H,
Ar-H), 7.33–7.21 (m, 5H, Ar-H), 6.94 (d, 1H,
J ¼ 8 Hz, Ar-H).
(
continued)

Table 1. Continued
Reaction time
(h)
Yield
(%)
1
IR and H NMR
Entry
Acids
Product (esters)
21 1
IR (KBr): 3410, 1733 cm ; H NMR (400 MHz,
CDCl
5
8
83
3
): d ¼ 7.16 (d, 2H, J ¼ 8 Hz, Ar-H), 6.98 (d, 2H,
J ¼ 8 Hz, Ar-H), 6.87–6.77 (m, 5H, Ar-H), 4.05 (s, 1H,
OH).
2
1 1
6
7
10
11
IR (KBr): 2865, 1746 cm ; H NMR (400 MHz,
CDCl
): d ¼ 7.59–7.55 (m, 2H, Ar-H), 7.52 (d, 1H,
J ¼ 8 Hz, Ar-H), 7.38–7.32 (m, 5H, Ar-H), 7.19
d, 1H, J ¼ 8 Hz, Ar-H), 4.25 (s, 1H, OH).
85
80
3
(
21 1
IR (KBr): 1743, 3151 cm ; H NMR (400 MHz,
CDCl ): d ¼ 7.48-7.42 (m, 5H, Ar-H), 7.39 (d, 2H,
3
J ¼ 9 Hz, Ar-H), 7.19 (d, 2H, J ¼ 9 Hz, Ar-H), 3.88 (br
2
s, 2H, NH )
21 1
IR (KBr): 1731 cm ; H NMR (400 MHz, CDCl ):
8
9
12
11
75
88
3
d ¼ 8.03 (dd, 1H, J ¼ 7, 2 Hz), 7.55 (dd, 1H,
J ¼ 7.2 Hz), 7.42 (dd, 1H, J ¼ 7, 2 Hz). 7.28-7.20
(
m, 5H, Ar-H).
21 1
IR (KBr): 1744, 1693 cm ; H NMR (400 MHz,
CDCl ): d ¼ 11.08 (s, 1H, COOH), 7.48–7.45 (m, 5H,
3
Ar-H), 7.43–7.41 (m, 2H, Ar-H), 7.38–7.35 (m, 2H,
Ar-H).

21 1
IR (KBr): 1737 cm ; H NMR (400 MHz, CDCl
1
1
1
1
0
1
2
3
9
9
8
8
3
):
87
80
85
80
d ¼ 7.41–7.37 (m, 2H, Ar-H), 7.23 (d, 1H, J ¼ 15 Hz,
CH), 7.18–7.15 (m, 3H, Ar-H). 6.07 (d, 1H, J ¼ 15 Hz,
21 1
3
CH), 1.93 (s, 3H, CH ).
3
IR (KBr): 1724 cm ; H NMR (400 MHz, CDCl ):
d ¼ 7.92 (d, 1H, J ¼ 16 Hz, CH), 7.60–7.59 (m, 2H,
Ar-H), 7.45–7.42 (m, 5H, Ar-H). 7.29–7.22 (m, 3H,
Ar-H), 6.67 (d, 1H, J ¼ 16 Hz, CH).
2
1 1
IR (KBr): 1749 cm ; H NMR (400 MHz, CDCl ): d
3
¼
7.52–7.39 (m, 5H, Ar-H), 7.19 (d, 2H, J ¼ 8 Hz, Ar-
H), 7.04–7.00 (m, 1H, Ar-H), 6.92 (d, 2H, J ¼ 8 Hz,
21 1
Ar-H), 3.96 (s, 2H, CH ).
2
IR (KBr): 1743, 1693 cm ; H NMR (400 MHz,
CDCl
3
): d ¼11.12 (s, 1H, COOH), 7.52–7.42 (m, 5H,
Ar-H), 7.19 (d, 1H, J ¼ 8 Hz, Ar-H), 7.02 (m, 2H, Ar-
H), 6.92 (d, 1H, J ¼ 8 Hz, Ar-H), 3.96 (s, 2H, CH ).
2
21 1
IR (KBr): 3400, 1751, 1693 cm ; H NMR (400 MHz,
1
4
5
8
9
75
77
CDCl ): d ¼ 11.08 (s, 1H, COOH), 7.48–7.42 (m, 5H,
3
Ar-H), 7.39 (d, 1H, J ¼ 8 Hz, Ar-H), 7.35 (s, 1H,
Ar-H), 7.28 (d, 1H, J ¼ 9 Hz, Ar-H), 4.65 (s, 1H, OH).
21 1
4
.01 (s, 2H, CH ).
2
1
IR (KBr): 1747, 1687 cm ; H NMR (400 MHz,
CDCl
3
): d ¼ 11.13 (s, 1H, COOH). 7.54–7.42 (m, 5H,
Ar-H), 7.19 (d, 1H, J ¼ 8 Hz, Ar-H), 7.02 (s, 1H,
Ar-H), 6.92 (d, 1H, J ¼ 8 Hz, Ar-H), 4.26 (s, 2H, CH
2
),
3
3
.77 (s, 3H, CH ).
[
9–11]
Note: Melting/boiling points were checked from the literature data.

2
980
H. N. Roy and A. H. Al Mamun
Figure 1.
considering the reaction simplicity, we can adopt the present method as a
procedure for phenyl esterification over other existing methodologies (Figure 1).
EXPERIMENTAL
General
The melting points were determined on a capillary melting-point apparatus
and are uncorrected. Infrared spectra were recorded using KBr pellets for
solids and neat for liquids on a FTIR-8400 and a Perkin-Elmer 883 grating
1
13
spectrometer. H NMR and C NMR spectra were taken on an AC Bruker
00-MHz spectrometer in CDCl , containing TMS as the internal standard.
2
3
Mass spectra were taken on Kratos MS 80 system. All J values are given in
Hertz and chemical shifts in d units. EtOAc was simply distilled over
CaCl . Reactions were monitored by TLC, and column chromatography
2
was done on 60–120 mesh E. Merck silica gel.
General Method for the Preparation of Phenyl Esters
To a stirred solution of acid 13 (1 g, 5.5 mmol), anhyd. AlCl (0.01 g,
3
0.20 mmol) was added at ice-cold temperature. Five min later, phenol
(
0.522 g, 5.5 mmol) and anhyd. ZnCl (0.755 g, 5.5 mmol) were added to
2
the reaction mixture, and stirring was continued at 08C for 2 h. The reaction
mixture was additionally stirred at room temperature for about 6 h. Com-
pletion of the reaction was monitored by TLC in n-hexane/EtOAc (5:1)
solvent systems. Reaction mixture was quenched by 1M HCl solution at
ice-cold temperature, and it was extracted by ether (3 Â 25 mL), washed
with water (3 Â 25 mL), and dried over Na SO . Evaporation of the ether
2
4
extract gave crude ester, which upon silica-gel filtration to the same solvent
system, gave compound 13a in 80% yield (1.24 g).
ACKNOWLEDGMENTS
The authors are grateful to the Department of Chemistry, Rajshahi University,
Bangladesh, for the necessary chemicals and to Md. Shahidul Islam, an

Regiospecific Phenyl Esterification
2981
instrument engineer, Bangladesh Council for Scientific and Industrial
1 13
Research (BCSIR), Dhaka, for H NMR and C NMR spectra.
REFERENCES
1
. Burdock, G. A. Fenaroli’s Handbook of Flavour Ingredients, 3rd ed; CRC Press,
994; Vol. 2.
. (a) Maldonado, F. ES 2002544, 1998; (b) Yamada, M.; Naruse, H. EP 853255,
998.
1
2
1
3. Devi, A. R.; Rajaram, S. Indian J. Chem. 2000, 39B, 294.
4. Gallagher, T. P.; Hicks, T. A.; Andrew, P. L.; Martinowton, W. Tetrahedron Lett.
1
994, 35, 289.
. Esther, D.; Laborra, C.; Linaza, A.; Madoz, A.; Issa, A. K. Monatsch Chem. 1989,
43.
. (a) Whiting, D. A. Comprehensive Organic Chemistry; Barton, D., Ollis, W. D.,
Eds.; Pergamon Press: Oxford, 1979; Vol. 1, 734; (b) Hasangadi, B. D.;
Dave, R. H. Tetrahedron Lett. 1995, 37, 6375.
5
6
7
7. (a) Kumar, A. K.; Chattapadhyay, T. K. Tetrahedron Lett. 1987, 28, 3713;
(
(
b) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307;
c) Cho, C. S.; Kim, D. K.; Choi, H.-J.; Kim, T.-J.; Shim, S.-C. Bull. Korean
Chem. Soc. 2002, 23, 539; (d) Gopinath, R.; Patel, B. K. Org. Lett. 2000, 2, 577.
. (a) Karanth, N. G.; Divakar, S. An enzymatic process for the preparation of
phenolic ester. Indian patent 1244/DEL/99, 1999; (b) Suresh Babu, C. V.;
Karanth, N. G.; Divakar, S. Indian J. Chem. 2002, 41B, 1068.
8
9. Ding, Y.; Wu, R.; Lin, Q. Synth. Commun. 2002, 32, 2149.
10. Kang, S. K.; Yamaguchi, T.; Ho, P.-S.; Kim, W.-Y.; Ryu, H.-C. J. Chem. Soc.,
Perkin Trans. 1998, 1, 841.
11. Houston, T. A.; Wilkinson, B. L.; Blanchfield, J. T. Org. Lett. 2004, 6, 679.