Synthesis of Aryloxyacetic Acids, Esters, and Hydrazides Assisted by Microwave Irradiation

Article abstract of DOI:10.1081/SCC-120027275

Under microwave irradiation on clay a series of transformations of a number of phenols into their aryloxyacetic acids 3 and then their methyl esters 4 and hydrazides 5 has been achieved efficiently in good yields.

Full text of DOI:10.1081/SCC-120027275

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Synthesis of Aryloxyacetic Acids, Esters, and
Hydrazides Assisted by Microwave Irradiation
a
a
a
Hamida M. Abdel Hamid , El Sayed Ramadan , Mohamed Hagar & El Sayed H. El
a
Ashry
a
Department of Chemistry, Faculty of Science, Alexandria University, Elhoria Street,
Alexandria, Egypt
Version of record first published: 16 Aug 2006.
To cite this article: Hamida M. Abdel Hamid , El Sayed Ramadan , Mohamed Hagar & El Sayed H. El Ashry (2004):
Synthesis of Aryloxyacetic Acids, Esters, and Hydrazides Assisted by Microwave Irradiation, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:3, 377-382
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 3, pp. 377–382, 2004
Synthesis of Aryloxyacetic Acids,
Esters, and Hydrazides Assisted
by Microwave Irradiation
Hamida M. Abdel Hamid, El Sayed Ramadan,
*
Mohamed Hagar, and El Sayed H. El Ashry
Department of Chemistry, Faculty of Science, Alexandria University,
Alexandria, Egypt
ABSTRACT
Under microwave irradiation on clay a series of transformations of a
number of phenols into their aryloxyacetic acids 3 and then their methyl
esters 4 and hydrazides 5 has been achieved efficiently in good yields.
Key Words: Microwave irradiation; Aryloxyacetic acids; Esters;
Hydrazides.
Much interest has been devoted for using the microwave in accelerating
the proceeding of organic reactions.
[1–5]
Such unconventional reaction
*
Correspondence: El Sayed H. El Ashry, Department of Chemistry, Faculty of Science,
Alexandria University, Elhoria Street, Alexandria, Egypt; Fax: þ20-3-4271360;
E-mail: eelashry60@link.net or eelashry60@hotmail.com.
3
77
DOI: 10.1081/SCC-120027275
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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3
78
Hamid et al.
conditions have several environmental and economical impacts, such as
saving energy and time, as well as avoiding the use of sometimes expensive
and/or toxic solvents. Moreover, it requires shorter reaction-time and ease of
[6–8]
work-up after reaction. Also the synthesis can be done in dry media.
The aryloxyacetic acid derivatives have a wide range of biological effects.
Thus, some of them are effective in inducing calluses from differentiated
[
9–11]
tissues and organs of plants.
[
Others are used as a post-emergence,
to control terrestrial and aquatic broad-leaved weeds
12,13]
selective herbicide
in some plants. Moreover, they have been investigated as chemotherapeutic
agents for lowering triglycerides than serum cholestrols as well as possess
[14–18]
favourable hyperlipidaemic activity in rats.
The conventional method
for the synthesis of aryloxyacetic acids can be carried out by heating the
preformed sodium salts of phenolic compounds and chloroacetic acid fol-
[
19]
lowed by acidification.
using microwave irradiation.
Recently, we have initiated a program in our laboratory for using the
Such reaction was also achieved in solution by
[
20]
[21]
microwave irradiation in organic synthesis. Continuing our interest in the
synthesis of aryloxyacetic acid derivatives, we report herein efficient
synthesis of aryloxyacetic acids and their methyl esters as well as hydrazides
[22,23]
(
Sch. 1) utilizing microwave irradiation and bentonite as a support.
Scheme 1. Synthesis of aryloxyacetic acids 3, esters 4 and hydrazides 5.

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Synthesis of Aryloxyacetic Acids
379
The synthesis of aryloxyacetic acids 3 can be done in a one pot by
irradiating in a microwave oven, for five minutes, a paste of the phenolic
compound 1, chloroacetic acid (2) and sodium hydroxide as reactants
supported on bentonite using the least amount of water. This method could be
applied for the synthesis of o-methyl, p-methyl, p-bromo and p-chloro-
phenoxyacetic acids. However, the p-nitrophenoxyacetic acid could not be
prepared under such conditions. This can be explained in term of the strong 2I
and 2M effects of the nitro group which decrease the nucleophilic character of
the oxygen atom of the aryloxide ion in order to displace the chlorine atom in
chloroacetic acid. In order to overcome that problem, sodium carbonate was
used instead of sodium hydroxide under the same reaction conditions, which
readily led to the formation of p-nitrophenoxyacetic acid (3f). The
[
24]
literature
indicated that 3f was prepared in low yield when in the classical
method sodium hydroxide was incorporated whereas with using sodium
carbonate the yield was improved. Thus, a better chance for the aryloxide ion,
as a nucleophile, could occur rather than formation of the expected quinoide
structure.
The methyl esters of the aryloxyacetic acids 4 were readily prepared by
microwave irradiation of the corresponding acids and methyl alcohol in the
presence of catalytic amount of concentrated sulfuric acid. The use of bento-
nite as a support improved the yield of the methyl esters. Also microwave was
found to be efficient for the synthesis of the corresponding hydrazides 5 by the
irradiation of methyl esters 4 with hydrazine hydrate. The results are
summarized in Table 1.
In conclusion, the use of microwave irradiation is an easy, clean, quick
and safe tool for the synthesis of aryloxyacetic acids, esters and hydrazides in
good yields. This method is also attractive to be used for combinatorial
synthesis of a library of such type of compounds.
EXPERIMENTAL
General Methods
Melting points were determined with a Mel-Temp apparatus and are
uncorrected. TLC was performed on Baker-Flex silica gel 1B-F plates using
ethyl acetate and ethyl acetate : Petroleum ether (1 : 2) as developing solvents;
the spots were detected by their characteristic color and by UV light
absorption. Irradiation was done in a domestic microwave oven EM-230M
(
800 watt output power).

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3
80
Hamid et al.
Table 1. Yield and mp data for aryloxyacetic acids 3, esters 4 and hydrazides 5.
Cpd
No.
0
R
R
Yield%
Mp 8C
Lit mp 8C
Aryloxyacetic acids
[
25]
3a
3b
3c
3d
3e
3f
H
Cl
H
H
66
76
78
80
94
65
98–99
98–99
[
[
[
[
26]
151–152
153–154
134–135
152–153
184–186
151–152
153–154
135–136
151–152
27]
28]
29]
Br
H
Me
H
H
Me
H
[
24]
NO2
187
a
Methyl aryloxyacetates
4
4
4
4
4
4
a
b
c
d
e
f
H
Cl
Br
Me
H
H
H
86
90
99
87
95
77
[
30]
35–37
46–47
39
49.5
[
31]
H
H
Me
H
[
32]
NO
2
95–97
99
Aryloxyacetic acid hydrazides
[
[
33]
33]
5
5
5
5
5
5
a
b
c
d
e
f
H
Cl
H
H
99
99
92
95
95
90
104–106
157–158
171–172
135–136
118–119
185–186
108
158
Br
H
[
[
[
33]
33]
34]
Me
H
H
136
121
187
Me
H
NO2
a
Method b: In bentonite: 4a (98%), 4d (98%) and 4f (93%).
General Procedure
Aryloxyacetic acids (3a–e). A mixture of the phenolic compounds 1a–f
0.02 mol) and sodium hydroxide (0.07 mol) in water (8 ml) was treated with
(
chloroacetic acid (0.03 mol) and bentonite (2.0 g). The reaction mixture was
irradiated in the microwave oven for 5 min. The product was extracted from
the paste in the least amount of water, filtered and then acidified with sulfuric
acid. It was recrystallized from hot water to give 3a–e. When p-nitrophenol
(
1f) was subjected to the same reaction conditions as above, it was recovered
unchanged.
p-Nitrophenoxyacetic acid (3f). A mixture of p-nitrophenol (0.02 mol)
and sodium carbonate (0.07 mol) in water (8 ml) was treated with chloroacetic

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Synthesis of Aryloxyacetic Acids
381
acid (0.03 mol) and bentonite (2.0 g). The reaction mixture was irradiated as
above for 5 min and then processed as above to give 3f.
General Procedure
Methyl aryloxyacetates (4a–f). (a) A mixture of the aryloxyacetic acids
a–f (0.002 mol), methyl alcohol (5 ml) and concentrated sulfuric acid (0.5–
3
ml)was irradiated by microwave for 2 min. The mixture was neutralized with
sodium bicarbonate solution. The products were extracted with CHCl to give
3
4a, 4d and 4e as syrups, and 4b, 4c and 4f as crystals that were recrystallized
from methanol.
(
b) A mixture of the aryloxyacetic acids 3a, 3d and 3f (0.002 mol),
bentonite (0.25 g), methyl alcohol (5 ml) and concentrated sulfuric acid
(0.5 ml) was irradiated by microwave for 2 min. The mixture was cooled,
filtered and processed as above to give 4a, 4d and 4f.
General Procedure
Aryloxyacetic acid hydrazides (5a–f). A solution of the methyl ester
4
a–f (0.001 mol) in methyl alcohol (5 ml) was treated with hydrazine hydrate
0.01 mol) and then irradiated by microwave for l min. The product was
recrystallized from ethanol.
(
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Received in the UK May 14, 2003

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