Decomposition of sodium trichloroacetate in the presence of quaternary ammonium under microwave irradiation: A convenient one-pot synthesis of α-hydroxy acids in water

Article abstract of DOI:10.1080/00397910600781091

A good yielding phase-transfer-catalyzed procedure for one-pot preparation of α-hydroxy acids from carbonyl compounds and sodium trichloroacetate by in situ addition and hydrolysis under microwave irradiation is described. Decomposition of sodium trichloroacetate is strongly accelerated by the presence of quaternary ammonium. The reaction can be conducted in water. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600781091

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Decomposition of Sodium Trichloroacetate
in the Presence of Quaternary Ammonium
under Microwave Irradiation: A Convenient
One‐Pot Synthesis of α‐Hydroxy Acids in
Water
a
a
a
a
Haitao Yu , Yun Fang , Yongmei Xia & Jing Wu
a
School of Chemical and Material Engineering, Southern Yangtze University,
Wuxi, Jiangsu, China
Published online: 27 Oct 2006.
To cite this article: Haitao Yu , Yun Fang , Yongmei Xia & Jing Wu (2006): Decomposition of Sodium
Trichloroacetate in the Presence of Quaternary Ammonium under Microwave Irradiation: A Convenient
One‐Pot Synthesis of α‐Hydroxy Acids in Water, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:17, 2421-2426
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Synthetic Communications , 36: 2421–2426, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781091
Decomposition of Sodium Trichloroacetate
in the Presence of Quaternary Ammonium
under Microwave Irradiation: A Convenient
One-Pot Synthesis of a-Hydroxy Acids
in Water
Haitao Yu, Yun Fang, Yongmei Xia, and Jing Wu
School of Chemical and Material Engineering, Southern Yangtze
University, Wuxi, Jiangsu, China
Abstract: A good yielding phase-transfer-catalyzed procedure for one-pot preparation
of a-hydroxy acids from carbonyl compounds and sodium trichloroacetate by in situ
addition and hydrolysis under microwave irradiation is described. Decomposition of
sodium trichloroacetate is strongly accelerated by the presence of quaternary
ammonium. The reaction can be conducted in water.
Keywords: a-Hydroxy acid, microwave, phase-transfer catalyst, sodium
trichloroacetate
INTRODUCTION
a-Hydroxy acids could be prepared in good yields by hydrolysis of trichloro-
methyl carbinols. The utility of trichloromethyl carbinols and the lack of sat-
isfactory procedures for the production of a-hydroxy acids prompted us to
investigate improved methods of a-hydroxy acid synthesis. The condensation
of chloroform with aldehydes or ketones under strong basic conditions was a
usual method for synthesis of trichloromethyl carbinols that served as key
[1]
intermediates for synthesis of a-hydroxy acids. However, with highly
Received in Japan December 19, 2005
Address correspondence to Yun Fang, School of Chemical and Material Engineer-
ing, Southern Yangtze University, Wuxi, Jiangsu 214036, China. E-mail: yunfang@
126.com
2
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2
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H. Yu et al.
reactive aldehydes such as nitrobenzaldehydes, the competitive Cannizzaro
[2]
reaction was often a serious problem, and moreover, the adol condensation
induced by strong alkali for the aldehydes containing a-protons could also
[
result in low yields. P. J. Atkins has obtained trichloromethide anion from
3]
[4]
the decomposition of trichloroacetic acid (TCA) in dimethyl sulfoxide.
An additional method has been described for the generation of trichloro-
[5]
methide anions from (trichloromethyl) trimethylsilane or trimethylsilyl
[
6]
trichloroacetate. A mixture of chloroform and aldehyde with no a-protons
in dimethylformamide at 258C to 2108C was treated with a methanolic
solution of potassium hydroxide, which can effectively prevent the
[
3a]
Cannizzaro reaction. E. J. Corey has found that a 1 : 1 mixture of trichloro-
acetic acid and sodium trichloroacetate in dimethylformamide undergoes
rapid decarboxylation at rt to generate the highly nucleophilic trichloromethyl
[
7]
anion. However, compounds of the type have hitherto been prepared only by
procedures that are either more drastic or cumbersome and in absolutely
anhydrous conditions.
Herein, we describe a rapid, simple, and practical procedure for the phase-
transfer (PT) catalytic synthesis of a wide range of a-hydroxy acids by means
of a microwave-assisted addition reaction in one pot. The route involves a con-
venient and efficient formation of trichloromethyl carbinols from carbonyl
compounds and subsequent hydrolysis. The reaction proceeds in the water
system. In experiments, we observed that with the help of a catalytic
quantity of quaternary ammonium, sodium trichloroacetate (NaTCA) could
be easily decarboxylated and react cleanly with carbonyl compounds under
microwave irradiation (MWI), even with highly sensitive aldehydes, to form
the desired trichloromethyl carbinols. Though NaTCA in the polar aprotic
solvent can also undergo rapid decarboxylation to produce a highly nucleophi-
[7,8]
lic and basic carbanion when heated,
a little water dissolved in the solvent
will lead the reaction to failure. However, the treatment of carbonyl
compounds in a nonpolar solvent and NaTCA gave very low yield because
of existing phase interface. The exceptional transformation took place when
a small amount of a tetrabutylammonium bromide (TBAB) was added. Pre-
sumably decomposition of NaTCA is strongly accelerated by the presence
of quaternary ammonium because TBAB facilitates the passage of the
2
TCA anion from the aqueous media into the immiscible organic media and
2
makes the TCA anion naked, to easily result in breakage of the C–C bond.
RESULTS AND DISCUSSION
A study was initiated to evaluate the PT catalysts for the formation of
2
-hydroxy-4-phenyl butanoic acid (HPBA). The results are shown in Table 1.
Investigations of various PT catalysts revealed that dodecylpyridinium
chloride gave the lowest yield (Table 1, entry 3). The best result was
achieved using TBAB, which afforded the a-hydroxy acid in 70% yield

Sodium Trichloroacetate Decomposition
2423
Table 1. Evaluation of the optimum PT catalyst for the synthesis of
a
2
-hydroxy-4-phenyl butanoic acid
PT catalyst (0.2 equiv relative to
b
aldehyde )
Entry
Yield (%)
1
2
3
4
5
Tetrabutylammonium bromide
Tetrabutylammonium chloride
Dodecylpyridinium chloride
Triethylbenzylammonium chloride
Dimethyldodecylbenzylammonium
chloride
70
65
21
68
45
a
The reaction was carried out with aldehyde (14.9 mmol) and NaTCA
22.35 mmol), and subsequent hydrolysis was executed with NaOH
0.119 mol) in a LWMC-205 microwave oven.
(
(
b
After the material was rectified, the purity of hydrocinnamaldehyde
was 99%.
(Table 1, entry 1). It is noteworthy that the purity of the PT catalysts and
aldehydes greatly impact the yield (95% purity 3-phenylpropanal, overall
yield 25%).
After determination of the best PT catalyst, the generality of this one-pot
method was examined, and results are summarized in Table 2. Reactions of
sodium trichloroacetate with the appropriate carbonyl compounds have
provided reasonably good yields. The experimental details exemplify the
simplicity of the procedure and ease of pure product isolation.
The reaction times were optimized by continually monitoring the organic
phase with TLC. In some cases, it was observed that prolonged irradiation and
excessive alkali gave a fuscous polymeric impurity during hydrolysis, thereby
reducing the yields of desired products. Otherwise, our earlier preparation of
HPBA under conventional heating conditions gave a low yield (45%); even an
extended reflux (12 h) did not improve the hydrolysis yield. MWI could appar-
ently shorten the reaction time and result in higher yields of the desired
a-hydroxy acids.
In summary, we have demonstrated a simple, rapid, one-pot procedure for
the preparation of a-hydroxy acids using a microwave procedure. The
decomposition of sodium trichloroacetate in the presence of quaternary
ammonium is a useful synthetic method for introducing the trichloromethyl
group into organic compounds. An advantage of this method is that the inter-
mediate a-trichloromethyl carbinols are not isolated. Additionally, the fact
that products exist in the water phase facilitates a simple isolation of the

2
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H. Yu et al.
Table 2. One-pot synthesis of a-hydroxy acids from the corresponding aldehyde
compounds under microwave irradiation
a
Microwave heating
Conventional heating
Time (h)
Time (min)
addition,
hydrolysis
Yield
c
(%)
addition,
hydrolysis
Yield
c
(%)
Entry
Substrate
1
2
3
4
5
6
7
8
9
Hydrocinnamaldehyde
Cinnamaldehyde
Benzaldehyde
10
10
8
40
40
30
30
30
30
35
40
40
30
70
20
61
63
63
71
80
77
50
56
1.5
2
5
5
4
3
4
4
5
5
5
5
35
12
30
25
36
40
50
45
40
41
1.5
1
b
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
4-Methoxybenzaldehyde
5
8
1.5
1.5
2
8
d
3-Methylbutyraldehyde
d
n-Heptaldehyde
Cyclohexanone
Diphenylketone
6
10
12
10
2
2.5
2.5
1
0
a
b
c
Irradiation in a LWMC-205 microwave oven.
Reaction process at power 30 W with nitrogen protection at all times.
Isolated yield after crystallization.
d
Reaction process at power 50 W at all times.
desired a-hydroxy acids, although hydrolysis reactions produce a few viscous
and fuscous materials. It is very important that the reactions may take place in
the water system to avoid the trouble of anhydrous operations. The research
aimed at studying further the asymmetric synthesis of trichloromethyl
carbinols by the PTC method described in this article to obtain enantiomeric
a-hydroxy acids is currently being pursued and will be reported.
EXPERIMENTAL
The microwave oven used for performing the reactions was a LWMC-205
microwave oven (Nanjing Robiot [Rotatory Optic Biochemical Technology]
1
Co., Ltd.). The identity of the products was confirmed by the H NMR (500
MHz) and FT-IR spectral data.
General Procedure for the Preparation of a-Hydroxy Acids
In an LWMC-205 MW oven, carbonyl compound (10 mmol), sodium tri-
chloroacetate (20 mmol), tetrabutylammonium bromide (2 mmol), water
(
15 mL), and chloroform (10 mL) were added to the 100-mL round-bottom

Sodium Trichloroacetate Decomposition
2425
flask equipped with a glass stir-bar. The mixture was irradiated under 70 W
power for the needed time with vigorous stirring. After cooling, NaOH
powder (80 mmol) was added to the flask, and then refluxed for the needed
time under 100 W power. The reaction mixture was diluted with water (10
mL) and washed with chloroform (2 Â 15 mL). After the aqueous layer was
treated with active charcoal, the filtrate was acidified to pH 1 with HCl (10
M) and turned cloudy. It was extracted with ether (4 Â 25 mL), and
combined organic phases were washed with sat. brine, dried (MgSO ), and
4
concentrated to afford product. After recrystallization with dichloromethane,
a white crystal product was obtained.
2
-Hydroxy-4-phenyl Butanoic Acid
2
1
White needle crystal product, mp 104.6–105.98C. FT-IR (cm ): 3453,
1
3
000–2500, 1719, 1243, 1095, 739, 696. H NMR (500 MHz, CDCl ): d
3
(
ppm) 7.3–7.2 (m, 5H), 4.3 (dd, J ¼ 4.1, 11.9 Hz, 1 H), 2.8 (dd, J ¼ 1.6,
8
H, 6.67. Found: C, 66.91; H, 6.68.
.4 Hz, 2H), 2.2 (m, 1H), 2.0 (m, 1H). Anal. calcd. for C H O : C, 66.67;
10 12 3
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(
c) Reeve, W.; McKee, J. R.; Brown, R.; Lakshmanan, S.; McKee, G. A.
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2
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3
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5
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7
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8
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