Electrochemical synthesis of α-hydroxycarboxylic acids from acetophenones

Article abstract of DOI:10.1080/00397910500328811

α-Hydroxy carboxylic acids are synthesized in 80-86% isolated yields by electrochemical carboxylation of methyl aryl ketones in the presence of carbon dioxide (1 atm.) using a platinum cathode and a sacrificial magnesium anode at a constant current density of 10 mA/cm². Reversibility of the carbonyl group reduction and generation of anionic radical were shown by cyclic voltammetry. Copyright Taylor & Francis LLC.

Full text of DOI:10.1080/00397910500328811

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Electrochemical Synthesis of
α‐Hydroxycarboxylic Acids From
Acetophenones
a
a
a
S. Khaja Lateef , R. Ramesh Raju , S. Krishna Mohan & S. Jayarama
a
Reddy
a
Electrochemical Research Laboratory, Department of Chemistry , Sri
Venkateswara University , Tirupati, India
Published online: 21 Aug 2006.
To cite this article: S. Khaja Lateef , R. Ramesh Raju , S. Krishna Mohan & S. Jayarama Reddy (2006)
Electrochemical Synthesis of α‐Hydroxycarboxylic Acids From Acetophenones, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:1, 31-36, DOI:
10.1080/00397910500328811
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Synthetic Communications , 36: 31–36, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500328811
Electrochemical Synthesis of
a-Hydroxycarboxylic Acids
From Acetophenones
S. Khaja Lateef, R. Ramesh Raju, S. Krishna Mohan,
and S. Jayarama Reddy
Electrochemical Research Laboratory, Department of Chemistry,
Sri Venkateswara University, Tirupati, India
Abstract: a-Hydroxy carboxylic acids are synthesized in 80–86% isolated yields by
electrochemical carboxylation of methyl aryl ketones in the presence of carbon
dioxide (1 atm.) using a platinum cathode and a sacrificial magnesium anode at a
2
constant current density of 10 mA/cm . Reversibility of the carbonyl group
reduction and generation of anionic radical were shown by cyclic voltammetry.
Keywords: Cyclic voltammetry, electrochemical carboxylation, a-hydroxy carboxylic
acids, methyl aryl ketones, sacrificial anode
INTRODUCTION
a-Hydroxy acids (AHAs) are used extensively in cosmetic dermatology to
cure skin disorders including acne, warts, and psoriasis and to correct
[
1–3]
[4]
Howard et al. reported the possible role of AHAs in
photoaged skin.
photocarcinogenesis. The preparation of AHAs from the corresponding cya-
nohydrins using hydrogen cyanide is unattractive because of the use of
[
5]
[6]
[7]
highly toxic cyanides. Wawzoneck and Hori reported electrochemical
carboxylation of acetophenones in low yields. By using oxalates and
[8]
formates as counterelectrodes, Engels et al.
improved the yields of
Received in India July 18, 2005
Address correspondence to S. Jayarama Reddy, Electrochemical Research Labora-
tory, Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India.
Tel.: þ 91-877-2249962; Fax: þ91-877-2249611; E-mail: profjreddy_s@yahoo.com
31

3
2
S. K. Lateef et al.
electrocarboxylation of acetophenones. Electrochemical synthesis of AHAs
[9]
using a mercury cathode in a divided cell (reported by Ikeda et al. ) in
spite of good yields was not efficient because of the inability of the system
to be developed into a commercially useful process. Also, the use of highly
toxic mercury was environmentally unacceptable, and the use of a divided
[10]
cell substantially increases the cost of production. Later Silvestri et al.
used a sacrificial Al anode in the electrocarboxylation of acetophenones.
[
11,12]
Wagenknecht et al.
on a pilot scale. In electrocarboxylation, magnesium is used as the most
developed the process for the electrocarboxylation
[
13,14]
efficient sacrificial anode,
which solves the problem of cathodic
reaction. The dissolved ions also function as added supporting electrolytes,
and in many cases the magnesium ions play an important role in forming
[
15]
the product during the reaction. To develop a convenient and commercially
useful synthesis, it is desirable to develop a high-yield system with an
undivided cell and a sacrificial anode.
Electrochemical methods are frequently referred to as one of the proto-
In this communication, we
[16]
typical green technologies of the future.
describe the synthesis and mechanism of electrochemical carboxylation of
a-hydroxy acids by employing waste-free technologies such as electrochemi-
cal carboxylation and avoiding the use of toxic reagents such as cyanides.
EXPERIMENTAL
Electrolyses were carried out using Potentiostat (model PS 605). Melting
1
points were determined on Mel-Temp apparatus and are uncorrected. H
NMR were recorded on a Varian EM-360. IR spectra were recorded on a
Perkin-Elmer 1600. Cyclic voltammetric measurements were carried out
with a Metrohm unit 757VA Comptrance. Solvent DMF and MeCN were
distilled by standard Vogel’s procedure and supporting electrolytes, TBAI
and TBAB, were analytical grade. Carbon dioxide used was 99% pure.
Electrochemical Carboxylation
A mixture of acetophenone (1a; 1.16 mL) and TBAI (3.69 g) in DMF (50 mL)
was added into an undivided cell equipped with a platinum cathode and

a-Hydroxycarboxylic Acids Synthesis
33
magnesium anode. Before electrolysis, the O in the system was removed by
2
passing N gas through this solution. The mechanically stirred homogeneous
2
solution was electrolyzed at about 258C at constant current density of 10 mA/
2
cm under a constant pressure (1 atm.) of carbon dioxide until 2 F/mol of elec-
tricity was passed. After electrolysis, the power supply was shut off, and the
solution was transferred to a round-bottom flask. The DMF solvent was
stripped in a rotary evaporator until a viscous residue was obtained. The
residue was stirred well in 50 mL of toluene for about 5 h for removal of
uncorrected starting material. The mixture was filtered, and the solid was
stirred well in 50 mL of 5% aqueous hydrochloric acid for 5 h. The product
was extracted with diethylether (90 mL) and dried over MgSO . Evaporation
4
of solvent afforded 1.41 g of 2-hydroxy-2-phenylpropanoic acid (2a) in 85%
17]
[
yield; mp 113–1148C [lit.
mp 115–1168C]. IR (neat): n ¼ 3485 (OH)
2
1
21 1
cm , 1732 (C 55 O) cm . H NMR (CDCl ): d ¼ 11.34 (bs, 1H, –COOH),
3
9
calcd for C H O (166.18): C, 65.05; H, 6.07. Found: C, 65.14; H, 6.02.
.32 (bs, 1H, OH), 7.11–7.32 (m, 5H, Ar-H), 1.92 (s, 3H, CH ). Anal.
3
9
10 3
2
-Hydroxy-2-(4-hydroxyphenyl)propanoic acid (2b): Yield 83%; mp
21
[
18]
2
18–2208C [lit.
mp 220–2238C]. IR (neat): n ¼ 3481 (OH) cm , 1726
2
1 1
(
C 55 O) cm . H NMR (CDCl ): d ¼ 11.45 (bs, 1H, –COOH), 9.12 (bs,
3
OH), 4.53 (s, 1H, Ar-OH), 7.08–7.23 (m, 4H, Ar-H), 1.91 (s, 3H, CH ).
3
Anal. calcd. for C H O (182.17): C, 59.34; H, 5.53. Found: C, 59.09;
9
10 4
H, 5.61.
2
-Hydroxy-2-(4-methoxyphenyl)propanoic acid (2c): Yield 82%; mp
[
19]
21
mp 146–1478C]. IR (neat): n ¼ 3472 (OH) cm , 1728
1
45–1478C [lit.
2
1 1
(
C 55 O) cm . H NMR (CDCl ): d ¼ 11.48 (bs, 1H, –COOH), 9.25 (bs,
3
1
CH ). Anal. calcd. for C H O (196.20): C, 61.22; H, 6.16. Found: C,
H, OH), 7.01–7.19 (m, 4H, Ar-H), 3.81 (s, 1H, –OCH ), 1.99 (s, 3H,
3
3
10 12 4
6
1.08; H, 6.19.
2
-(4-cyanophenyl)-2-Hydroxypropanoic acid (2d): Yield 85%, mp 196–
[
18]
21
mp 199–2018C]. IR (neat): n ¼ 2234 (CN) cm , 3462 (OH)
1
988C [lit.
2
1
21 1
cm , 1733 (C 55 O) cm . H NMR (CDCl ): d ¼ 11.39 (bs, 1H, –COOH),
3
9
calcd. for C H NO (191.18): C, 62.82; H, 4.74; N, 7.33. Found: C, 62.90;
.27 (bs, 1H, OH), 7.15–7.29 (m, 4H, Ar-H), 1.81 (s, 3H, CH ). Anal.
3
1
0
9
3
H, 4.71; N, 7.18.
-Hydroxy-2-(4-nitrophenyl)propanoic acid (2e): Yield 86%; mp 219–
2
2
1
21
1
2
208C. IR (neat): n ¼ 3468 (OH) cm , 1725 (C 55 O) cm . H NMR
(
CDCl ): d ¼ 11.51 (bs, 1H, –COOH), 9.29 (bs, 1H, OH), 7.24–7.41
3
(
m, 4H, Ar-H), 1.77 (s, 3H, CH ). Anal. calcd for C H NO (211.18): C,
3
9
9
5
5
1.19; H, 4.30; N, 6.63. Found: C, 51.28; H, 4.23; N, 6.59.
2
-Hydroxy-2-thiophene-2-yl-propanoic acid (2f): Yield 80%; mp 108–
21
[
20]
1
108C, [lit.
mp 111–1138C]. IR (neat): n ¼ 3468 (OH) cm , 1724
2
1 1
(
C 55 O) cm . H NMR (CDCl ): d ¼ 11.42 (bs, 1H, –COOH), 9.16 (bs,
3
1
C H O S (172.2): C, 48.82; H, 4.68; N, 27.87. Found: C, 48.79; H, 4.71;
H, OH), 6.51–6.94 (m, 3H, thio H), 1.61 (s, 3H, CH ). Anal. calcd. for
3
7
8 3
N, 27.81.

3
4
S. K. Lateef et al.
a
Table 1. Electrochemical carboxylation of methyl aryl ketones
b
Yields (%)
Supporting
electrolyte
No.
Solvent
2a
2b
2c
2d
2e
2f
1
2
3
4
TBAI
—
DME
84
77
83
75
83
71
82
71
82
71
80
70
85
74
83
74
86
76
84
76
80
72
79
70
MeCN
DMF
MeCN
TBABr
—
a
Electrolysis was carried in the presence of carbon dioxide (1 atm.) with a platinum
2
cathode and magnesium anode at 10 mA/cm .
b
Isolated yields.
RESULTS AND DISCUSSION
Electrochemical carboxylation of methyl aryl ketones, 1a–f readily takes
place to give a-hydroxy carboxylic acids 2a–f as carboxylation products in
80–86% yields. Table 1 shows that yields of 2a–f are quite sensitive to the
reaction media and the reaction conditions. The yields are less in acetonitrile
than DMF because of the lower polarity of acetonitrile. In less polar solvents
such as acetonitrile, the carboxylation product precipitated on the electrodes
during the reaction and caused by-product formation. The major by-product
was pinacol-type dimer.
Cyclic voltammogram of p-Cyanoacetophenone (1d) (Fig. 1) shows a
reduction peak at 21.60 V vs. Ag/AgCl in DMF containing 0.1 M Bu NI at
4
2
.2 V/s at glassy carbon disk electrode (GCDE) of area 0.0706 cm , which
0
Figure 1. Cyclic voltammogram of p-cyanoacetophenone in DMF containing 0.1 M
TBABr at scan rate of 0.2 V/s and Ag/AgCl as reference electrode: (a) absence of CO
and (b) presence of CO2.
2

a-Hydroxycarboxylic Acids Synthesis
35
is due to a reduction of the carbonyl group in a reversible process. Addition of
carbon dioxide to the solution causes an increase in cathodic current, an anodic
shift in peak potential, and elimination of the reverse anodic current. This
indicates a very fast reduction of the anion radical of methyl aryl ketone.
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