Rapid and high-yield synthesis of aryloxyacetates under microwave irradiation and phase-transfer catalysis conditions

Article abstract of DOI:10.1081/SCC-200063928

A series of methyl aryloxyacetates (3a-3f) have been synthesized by the reaction of substituted phenol with methyl chloroacetate under the conditions of microwave irradiation and phase-transfer catalysis. By the optimization of the reaction conditions, we developed a good method for the preparation of methyl aryloxyacetates, which have the advantages of high yields, short reaction times, ease of workup, and simple operation. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200063928

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Rapid and High‐Yield Synthesis
of Aryloxyacetates Under
Microwave Irradiation and
Phase‐Transfer Catalysis
Conditions
a
a
a
Tai‐Bao Wei , Hong Liu , Man‐Lin Li & You‐Ming
a
Zhang
a
Department of Chemistry, Gansu Key Laboratory
of Polymer Materials, Northwest Normal University,
Lanzhou, China
Version of record first published: 15 Aug 2006.
To cite this article: Tai‐Bao Wei , Hong Liu , Man‐Lin Li & You‐Ming Zhang (2005):
Rapid and High‐Yield Synthesis of Aryloxyacetates Under Microwave Irradiation and
Phase‐Transfer Catalysis Conditions, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 35:13, 1759-1764
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Synthetic Communications , 35: 1759–1764, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200063928
Rapid and High-Yield Synthesis of
Aryloxyacetates Under Microwave
Irradiation and Phase-Transfer
Catalysis Conditions
Tai-Bao Wei, Hong Liu, Man-Lin Li, and You-Ming Zhang
Department of Chemistry, Gansu Key Laboratory of Polymer Materials,
Northwest Normal University, Lanzhou, China
Abstract: A series of methyl aryloxyacetates (3a–3f) have been synthesized by the
reaction of substituted phenol with methyl chloroacetate under the conditions of
microwave irradiation and phase-transfer catalysis. By the optimization of the
reaction conditions, we developed a good method for the preparation of methyl
aryloxyacetates, which have the advantages of high yields, short reaction times, ease
of workup, and simple operation.
Keywords: Methyl aryloxyacetates, microwave, phase-transfer catalyst
INTRODUCTION
The derivatives of aryloxyacetic acids constitute a class of compounds for both
[
1–5]
[6–10]
biological activity
show antituberculotic activities.
and plant growth regulators.
Some are found to
Some are used as a postemergent,
to control some terrestrial and aquatic broad-leaved
[
11]
[12]
selective herbicide
weeds. For instance, several aryloxyacetic acids are in the herbicides market
with common names such as 2,4-D, MCPA, and 2,4,5-T. Many organic
esters of the aryloxyacetic acids are also used as herbicides. The esters of
2
,4-D, such as methyl, ethyl, propyl, isopropyl, butyl, amyl, iso-octyl, and
Received in Japan March 14, 2005
Address correspondence to You-Ming Zhang, Department of Chemistry, Gansu
Key Laboratory of Polymer Materials, Northwest Normal University, Lanzhou,
Gansu, 730070, China. Fax: þ086 931 7971216; E-mail: zhangnwnu@126.com
1
759

1760
T.-B. Wei et al.
propylene glycol butyl esters, have all been used as selective weed killers in the
presence of cereal crops. Aryloxyacetic acid derivatives have been also inves-
tigated as chemotherapeutic agents for lowering triglycerides lower than serum
[13]
cholesterols. They also possess favorable hyperlipidaemic activity.
addition, they are important intermediates in many reactions.
In
[14,15]
By far, the most common synthesis of aryloxyacetic acid esters is accom-
plished by heating the acid with an excess of the appropriate alcohol in the
[
2,5]
presence of an acid catalyst.
reaction through the nucleophilic displacement of an aryloxide ion on methyl
The esters are also prepared by the Williamson
[
11,12]
haloacetate or ethyl haloacetate.
Recently, Lacan and coworkers have
reported that substituted phenols react with ethyl bromoacetate in the
presence of potassium carbonate in anhydrous DMF (dimethyl formamide)
[
16]
to give the corresponding esters.
However, conventional methods have
the disadvantages of long reaction times, low yields, inconvenient of
workup, and no benefit for environment.
In recent years, the use of microwave technology in organic synthesis
has received considerable attention. This technology can increase the purity
of the resulting products, enhance the chemical yield, and shorten the
[
17]
reaction time.
Moreover, phase-transfer catalysis, with the advantages of
simple experimental operations, mild reaction conditions, and inexpensive
and environmentally benign reagents, has established its significance in
organic synthesis as one of the most useful methods for the acceleration
[
18]
of heterogeneous reactions.
interest in microwave and phase-transfer catalysis promotion of organic
In our previous work, we have had an
[19,20]
synthesis.
In view of these facts and as a part of our work on the synthesis and
biological activity of aryloxyacetic acid derivatives, herein we report a
convenient and high-yield method for the rapid synthesis of methyl aryloxya-
cetates under the conditions of microwave irradiation and phase-transfer
catalysis. It was found that methyl aryloxyacetates could be prepared in
high yields within several minutes (Scheme 1).
In searching for the best reaction conditions, we carried out a series of
experiments. We first followed the Husain’s classical method, which needed
p-nitrophenol and methyl chloroaceate to reflux in acetone with potassium
[6c]
carbonate for 15 h to produce methyl p-nitrophenoxyacetate.
It gives
methyl p-nitrophenoxyacetate in a low yield of 40%. To shorten reaction
times and increase the yield of methyl aryloxyacetate, we carried out the
reaction under the conditions shown in Scheme 1, and a satisfactory result
Scheme 1.

Synthesis of Aryloxyacetates
1761
was obtained. The reaction time was reduced to 4 min, and p-nitrophenoxya-
cetate was obtained in a good yield of 95%.
Because the solvent had a great effect on the reaction, we investigated
various solvents. As different solvents were employed under the same
reaction conditions shown in Scheme 1, different results were obtained as
summarized in Table 1. No reaction took place in the polar protonic
solvents, H O, C H OH (entries 1 and 2), whereas good to excellent yields
2
2 5
were achieved in strongly polar nonprotonic solvents, CH CN, DMF, and
3
DMSO (entries 4, 5 and 6). From these data, we conclude that DMF is the
appropriate solvent for this reaction.
For the purpose of evaluating the catalytic effect on this reaction, another
series of experiments was carried out. Using p-nitrophenol as an example and
under the same reaction conditions shown in Scheme 1, we first examined the
catalysis effect of PTC (phase-transfer catalyst). With the enhancement of
the ion exchange between the inorganic salt and the organic solution, PTC
efficiently catalyzed this solid–liquid diphase reaction and the result is
summarized in Table 2. From the result it was found that PEG-600 was the
best catalyst for this reaction. Next, we evaluated the catalysis effect of
KI. The experiment results indicated that 3e was produced in 95% yield
when KI was added. However, the yield of 3e was only 71% without
addition of KI.
Moreover, to investigate the combination effects of microwave irradiation
and PTC on this reaction, using p-nitrophenol as an example, a series of experi-
ments were also carried out. As shown in Table 3, the combination of
microwave and PTC enhanced the reaction efficiency and yields.
In conclusion, a good method is found for the preparation of methyl
aryloxyacetate under the condition of microwave irradiation and phase-
transfer catalyst. The method possesses the advantages of speed, high
yield, cleanliness, and ease of workup over the reported methods, and the
catalyst PEG-600 is inexpensive, relatively nontoxic, highly stable, easily
available.
Table 1. Effect of solvent on the yield of compound 3
a
a
b
Yieldof 3a
(%)
Yield of 3e
(%)
Yield of 3f
(%)
Entry
Solvent
1
2
3
4
5
6
H
2
O
C H OH
—
—
13
35
93
62
—
—
29
81
95
79
—
—
15
40
95
87
2
5
CH
COCH
3 3
CH
DMF
3
CN
DMSO
a
Isolated yields.
b
Yield of dimethyl 1,4-phenylenedioxyacetate.

1762
T.-B. Wei et al.
Table 2. Effect of phase-transfer catalysits on the yield of compound 3e
a
Yield (%)
Entry
Phase-transfer catalysts
1
2
3
4
None
PEG-400
68
90
95
86
PEG-600
Tetrabutylammonium Iodide
a
Isolated yields.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
Microwave irradiation was carried out with a WP 750B commercial
microwave oven at 2450 MHz.
General Procedure
Phenol (5 mmol), methyl chloroacetate (5 mmol), K CO (5 mmol), KI
2
3
(
1 mmol), DMF (1 mL), and PEG-600 (0.5 mmol) were placed in a dried
round-bottomed flask, and the mixture was irradiated by microwave
200 W) for 4 min. When the reaction completed as monitored by TLC, the
(
mixture was cooled to room temperature and then added to ethanol (10 mL)
with constant stirring. Inorganic salts were removed by filtration, and the
filtrate was heated and added in water to recrystallize 3b, 3c, 3d, 3e, and 3f
as crystals and 3a as syrup. The pure product was obtained by recrystallization
from ethanol and the yields of 3 were shown in Table 4.
Preparation of p-nitrophenoxyacetate under condition A. p-Nitrophenol,
(5 mmol), methyl chloroacetate (5 mmol), K CO (5 mmol), and DMF
2 3
(15 ml) were placed in a dried round-bottomed flask. The mixture was
heated at 808C for 2.5 h with vigorous stirring and then cooled to room
Table 3. Combination effects of microwave irradiation and phase-transfer catalysts
on the yield of compound 3e
a
Yield of 3e (%)
Entry
Reaction conditions
Time
b
1
2
3
4
K CO , KI, DMF
2.5 h
2.5 h
4 min
4 min
60
86
68
95
2
2
2
3
c
K
K
CO
CO
3
, KI, PEG-600, DMF
, KI, DMF, MW
3
K CO , KI, PEG-600, DMF, MW
2
3
a
Isolated yields.
Condition A.
b
c
Condition B.

Synthesis of Aryloxyacetates
1763
Table 4. Methyl aryloxyacetates prepared
a
Yield (%)
Entry
R
Product
Mp8C
Lit. Mp8C
b
1
2
3
4
5
6
H
4-Cl
3a
3b
3c
3d
3e
3f
93
96
96
93
95
[
[
21]
22]
36–38
54–56
64–66
96–98
96–98
39
58
2-NO
2
[
22]
3-NO2
4-NO2
Hydroquinone
66.5
[
22]
99
99–100
c
c
[23]
[22]
95
a
Isolated yields.
b
c
3
a was obtained in oil liquid; Bp and Lit Bp of 3a were 244–2468C and 2458C.
Yield of dimethyl 1,4-phenyl lenedioxyacetate.
temperature. The mixture was poured into water (50 mL) and extracted with
CHCl , The extract was evaporated to leave the crude product and the pure
product was obtained by recrystallization from ethanol.
3
Preparation of p-nitrophenoxyacetate under condition B. p-Nitrophenol
(5 mmol), methyl chloroacetate (5mmol), K CO (5 mmol), DMF (15 ml), and
2 3
PEG-600 (0.5mmol) were place in a dried round-bottomed flask. The mixture
was heated at 808C for 2.5 h with vigorous stirring and processed as
previously described to give product 3f.
ACKNOWLEDGMENT
This work was supported by Natural Science Foundation (No. 20371040) of
China, the Natural Science Foundation (No. 031-A21-004, 3ZS041-A25-
007) of Gansu province, and the Foundation (No. 02-18) of Northwest
Normal University, which are gratefully acknowledged.
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