Two expedient 'one-pot' methods for synthesis of β-aryl-β- mercaptoketones over anhydrous potassium carbonate or amberlyst-15 catalyst

Article abstract of DOI:10.1007/s12039-013-0513-8

Two expedient one-pot methods have been developed for synthesis of β-aryl-β-mercaptoketones using acetophenones, benzaldehydes and thiols as starting materials. The methods involve microwave irradiation (5min) of 1:1 mixtures of acetophenones and benzaldehydes over neutral alumina supported anhydrous potassium carbonate or amberlyst-15 in the first step, and that is followed by addition of thiol to the resulting material and keeping at room temperature for 1.5 h. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-013-0513-8

c
J. Chem. Sci. Vol. 125, No. 6, November 2013, pp. 1463–1470. ꢀ Indian Academy of Sciences.
Two expedient ‘one-pot’ methods for synthesis
of β-aryl-β-mercaptoketones over anhydrous
potassium carbonate or amberlyst-15 catalyst
CHAYAN GUHA, RINA MONDAL, RAMMOHAN PAL and ASOK K MALLIK∗
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
e-mail: mallikak52@yahoo.co.in
MS received 29 April 2013; revised 24 August 2013; accepted 26 August 2013
Abstract. Two expedient one-pot methods have been developed for synthesis of β-aryl-β-mercaptoketones
using acetophenones, benzaldehydes and thiols as starting materials. The methods involve microwave irradi-
ation (5 min) of 1:1 mixtures of acetophenones and benzaldehydes over neutral alumina supported anhydrous
potassium carbonate or amberlyst-15 in the first step, and that is followed by addition of thiol to the resulting
material and keeping at room temperature for 1.5 h.
Keywords. β-aryl-β-mercaptoketones; anhydrous potassium carbonate; amberlyst-15; chalcones;
thia-Michael addition.
1. Introduction
A domino process usually refers to successive occur-
rence of different reactions in the same reaction vessel
without separation or purification of reactive interme-
diates.33,34 Survey of literature showed a growing trend
in utilization of domino sequential one-pot aldol-thia-
Michael process for synthesis of some important β-
aryl-β-mercaptoketones (1). However, reports on such
processes are very limited.35,36 Herein, we report the
development of two domino sequential one-pot aldol-
thia-Michael processes using inexpensive catalysts such
as anhydrous K2CO3 or amberlyst-15 (a sulphonated
polystyrene resin).
The chemistry of thia-Michael addition is being
explored since a long period1 due to its versatile appli-
cations in biosynthesis2 and for obtaining compounds
having biological activities such as tumour inhibitors,2
γ -secretase inhibitors,3 etc. In order to carry out such
reactions, a good number of methodologies involving
a variety of catalysts or catalytic systems have been
developed so far; the important ones include different
Lewis acids such as CdI2,4 InBr3,5 Zn(ClO4)2.6H2O,6
molecular iodine,7,8 Bi(NO3)3 and VO(OTf)2,10 etc.
9
The process can also be catalysed by organic bases,
both of synthetic and natural origin,11–16 complexes of
different transition metals,17,18 ionic liquids,19–22 solid
supports,23–26 phosphorus doped with other element or
chemical species,27,28 polyethylene glycol,29 porphyrin
rings,30 etc. However, the above mentioned methods
involve some limitations such as use of expensive cata-
lysts, long reaction time, etc. Besides, preparation of
the Michael acceptors needs a separate step in all
cases. These limitations led us to develop a new effi-
cient methodology for a one-pot synthesis of β-aryl-
β-mercaptoketones (1), particularly because of recent
success of our group and also of others in synthesis
of 2,4-diarylthiochromans (2) utilizing them as useful
intermediates (scheme 1).31,32
2. Experimental
Melting points were recorded on a Köfler block and
are uncorrected. Infrared (IR) spectra were recorded
on a Perkin Elmer Fourier Transform Infrared Spec-
1
trophotometer (Spectrum BX II) as KBr pellets. H
and 13C Nuclear Magnetic Resonance (NMR) spec-
tra were obtained in CDCl3 on a Bruker AV-300
(300 MHz) spectrometer using tetramethylsilane as an
internal standard. Mass spectrum was acquired on
a Waters QTOF Micro YA263 Mass Spectrometer.
Analytical samples were dried in vacuo at room
temperature. Microanalytical data were recorded on
two Perkin-Elmer 2400 Series II C, H, N analysers.
An unmodified domestic household microwave oven
(LG, DMO, Model No.-556P, 900 watt) equipped with
inverter technology, which provides a realistic control
∗For correspondence
1463

1464
Chayan Guha et al.
R2
R3
SPh
O
S
R2
R3
i) NaBH4, Dry MeOH, rt, 6-8 h
ii) Amberlyst-15, Dry toluene, 80°C 1.5 h
R1
1
R1
2
Scheme 1. Conversion of β-aryl-β-mercaptoketones (1) to cis-2,4-diarylthiochromans (2).
of the microwave power to the desired level (20–100%) NMR (300 MHz, CDCl3): δ 3.68 (d, 2H, J = 7.2 Hz,
was used for microwave heating. Column chromatogra- -CH2), 5.00 (t, 1H, J = 7.2 Hz, H-2), 7.23–7.34 (m,
phy was performed on silica gel (100–200 mesh) using 5H), 7.37–7.48 (m, 3H), 7.55–7.63 (m, 2H), 7.88–7.91
petroleum ether (60–80◦C) and petroleum ether-ethyl (m, 2H), 8.02–8.07 (m, 1H), 8.17 (t, 1H, J = 2.4 Hz);
acetate mixtures as eluents. Thin layer chromatography Anal. Calcd. for C21H17NO3S (363.43): C, 69.40; H,
was done with silica gel G.
4.71; N, 3.85. Found: C, 69.22; H, 4.93; N, 3.98.
2.2c 3-(4-Nitrophenyl)-1-phenyl-3-phenylsulphanyl-
propan-1-one 1f: Light yellow crystals, IR (KBr)
2.1 General procedure for synthesis
of β-aryl-β-mercaptoketones (1)
υmax
=
1678 (C=O), 1514, 1346, 1228, 984,
825 cm−1; 1H NMR (300 MHz, CDCl3): δ 3.67 (d, 2H,
J = 7.2 Hz, -CH2), 4.97 (t, 1H, J = 7.0 Hz, H-2),
7.23–7.31 (m, 5H), 7.42–7.58 (m, 4H), 7.60–7.87 (m,
1H), 7.89 (dd, 2H, J = 8.1 and 1.2 Hz), 8.08 (d, 2H,
J = 8.7 Hz); Anal. Calcd. for C21H17NO3S (363.43):
C, 69.40; H, 4.71; N, 3.85. Found: C, 69.52; H, 4.63;
N, 4.01.
A mixture of acetophenone (3, 1 mmol) and aromatic
aldehyde (4, 1 mmol) was thoroughly ground over
neutral alumina (4 g) with added anhydrous K2CO3
(1 mmol) or amberlyst-15 (80 mg) and the result-
ing powder was subjected to microwave irradiation
at 540 W for 5 min (120–125◦C). After cooling the
mass to room temperature, thiol (5, 1.3 mmol) was
added and thoroughly mixed and then the mixture was
kept at room temperature for 1.5 h under closed con-
dition. The solid was then washed thoroughly with
dichloromethane and the concentrate of the washings
was subjected to column chromatography over silica gel
using petroleum ether-ethyl acetate mixtures as eluents
to get 1 in pure state.
2.2d
3-(4-N,N-Dimethylphenyl)-1-phenyl-3-phenyl-
sulphanylpropan-1-one 1g: Yellow crystals, IR (KBr)
υmax = 1679 (C=O), 1525, 1360, 1229, 948, 806,
756 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.91 (s, 6H,
-N(CH3)2), 3.48–3.69 (m, 2H, -CH2), 4.93 (dd, 1H,
J = 8.4 and 5.8 Hz, H-2), 6.67 (d, 2H, J = 7.8 Hz),
7.17–7.26 (m, 4H), 7.35 (dd, 2H, J = 7.8 and 1.8 Hz),
7.41 (t, 2H, J = 7.5 Hz), 7.53 (t, 2H, J = 6.9 Hz),
7.86 (d, 2H, J = 7.2 Hz); Anal. Calcd. for C23H23NOS
(361.50): C, 76.42; H, 6.41; N, 3.87. Found: C, 76.18;
H, 6.20; N, 3.91.
The same method was followed for synthesis of 7 and
8 also.
2.2 Analytical and spectral data of some selected
β-aryl-β-mercaptoketones and related compounds
2.2e
3-(3,4-Methylenedioxyphenyl)-1-phenyl-3-phe-
2.2a 3-(4-Methylphenyl)-1-phenyl-3-phenylsulphanyl-
propan-1-one 1b: Colourless crystals, IR (KBr)
υmax = 1668 (C=O), 1597, 1440, 1329, 1233, 1176,
1112, 994, 811, 728 cm−1; 1H NMR (300 MHz,
CDCl3): δ 2.28 (s, 3H, -CH3), 3.50–3.70 (m, 2H,
-CH2), 4.94 (t, 1H, J = 7.0 Hz, H-2), 7.06 (d, 2H,
J = 7.8 Hz), 7.22–7.26 (m, 4H), 7.32–7.35 (m, 2H),
7.42 (t, 2H, J = 7.2 Hz), 7.50–7.59 (m, 2H), 7.87 (d,
2H, J = 7.2 Hz); Anal. Calcd. for C22H20OS (332.46):
C, 79.48; H, 6.06. Found: C, 79.33; H, 6.22.
nylsulphanylpropan-1-one 1h: Colourless crystals, IR
(KBr) υmax = 1678 (C=O), 1596, 1581, 1489, 1255,
1038, 934, 744 cm−1; H NMR (300 MHz, CDCl3): δ
1
3.48–3.67 (m, 2H, -CH2), 4.92 (t, 1H, J = 6.8 Hz, H-
2), 5.89 (s, 2H, -CH2-) 6.65 (d, 1H, J = 7.8 Hz), 6.77
(d, 1H, J = 7.8 Hz), 6.92 (s, 1H) 7.24 (d, 3H, J =
5.4 Hz), 7.35–7.45 (m, 4H), 7.53 (d, 1H, J = 6.6 Hz),
7.88 (d, 2H, J = 7.2 Hz); Anal. Calcd. for C22H18O3S
(362.44): C, 72.90; H, 5.01. Found: C, 72.61; H, 4.82.
2.2b 3-(3-Nitrophenyl)-1-phenyl-3-phenylsulphanyl- 2.2f 3-Phenyl-1-(4-methylphenyl)-3-phenylsulphanyl-
propan-1-one 1e: Light yellow crystals, IR (KBr) propan-1-one 1i: Colourless crystals, IR (KBr)
1
υmax = 1671 (C=O), 1531, 1347, 1224, 987 cm−1; H υmax = 1674 (C=O), 1605, 1440, 1338, 1231, 1180,

Synthesis of β-aryl-β-mercaptoketones
1465
1
976, 812 cm−1; H NMR (300 MHz, CDCl3): δ 2.39 Anal. Calcd. for C23H22O3S (378.48): C, 72.99; H,
(s, 3H, -CH3), 3.56–3.61 (m, 2H, -CH2), 4.94 (dd, 1H, 5.86. Found: C, 72.71; H, 5.74.
J = 7.8 and 6.3 Hz, H-2), 7.17–7.22 (m, 4H), 7.23
(d, 2H, J = 1.8 Hz), 7.26 (s, 2H), 7.30–7.34 (m, 4H),
2.2k 3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-phe-
7.77 (d, 2H, J = 8.1 Hz); Anal. Calcd. for C22H20OS
nylsulphanylpropan-1-one 1n: Colourless crystals, IR
(332.46): C, 79.48; H, 6.06. Found: C, 79.64; H, 6.22.
(KBr) υmax
=
1603 (C=O), 1574, 1492, 1328,
1256, 1176, 1025, 982, 818 cm−1; 1H NMR (300 MHz,
CDCl3): δ 3.51–3.55 (m, 2H, -CH2), 3.85 (s, 3H,
-OCH3), 4.90 (t, 1H, J = 7.0 Hz, H-2), 6.90 (d, 2H,
J = 8.4 Hz), 7.18–7.31 (m, 9H), 7.86 (d, 2H, J =
7.8 Hz); Anal. Calcd. for C22H19ClO2S (382.90): C,
69.01; H, 5.00. Found: C, 69.22; H, 4.83.
2.2g 3-(4-Methoxyphenyl)-1-(4-methylphenyl)-3-phe-
nylsulphanylpropan-1-one 1j: Colourless crystals, IR
(KBr) υmax = 1676 (C=O), 1597, 1460, 1338, 1251,
1
1036, 976, 812 cm−1; H NMR (300 MHz, CDCl3): δ
2.39 (s, 3H, -CH3), 3.52–3.60 (m, 2H, -CH2), 3.75 (s,
3H, -OCH3), 4.92 (dd, 1H, J = 8.3 and 5.8 Hz, H-
2), 6.78 (d, 2H, J = 8.4 Hz), 7.20–7.34 (m, 9H), 7.77
(d, 2H, J = 8.1 Hz); 13C NMR (75 MHz, CDCl3):
21.6, 44.7, 47.7, 55.2, 113.8, 127.4, 128.2, 128.8, 129.3,
132.6, 133.2, 134.3, 134.5, 144.1, 158.7, 196.8; TOF
MS ES+ (M+Na)+: Calcd. 385.1238. Found 385.1237;
Anal. Calcd. for C23H22O2S (362.48): C, 76.21; H, 6.12.
Found: C, 75.98; H, 5.94.
2.2l 3-(4-Chlorophenyl)-1-phenyl-3-(4-methylphenyl-
sulphanyl)propan-1-one 1o: Colourless crystals, IR
(KBr) υmax = 1678 (C=O), 1492, 1325, 1226, 1093,
814 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.30 (s, 3H,
-CH3) 3.50–3.65 (m, 2H, -CH2), 4.83 (t, 1H, J =
7.0 Hz, H-2), 7.04 (d, 2H, J = 7.8 Hz), 7.13–7.26
(m, 6H), 7.43 (t, 2H, J = 7.5 Hz.), 7.55 (br. t, 1H,
J = 7.3 Hz), 7.87 (br. d, 2H, J = 7.2 Hz); 13C NMR
(75 MHz, CDCl3): 21.1, 44.5, 48.1, 128.1, 128.5, 128.7,
129.2, 129.8, 129.9, 132.9, 133.4, 133.7, 136.7, 138.1,
140.0, 196.8; Anal. Calcd. for C22H19ClOS (366.08): C,
72.02; H, 5.22. Found: C, 72.25; H, 5.36.
2.2h
3-(4-Chlorophenyl)-1-(4-methylphenyl)-3-phe-
nylsulphanylpropan-1-one 1k: Colourless crystals, IR
(KBr) υmax = 1656 (C=O), 1564, 1492, 1332, 1184,
1
1012, 988, 817 cm−1; H NMR (300 MHz, CDCl3): δ
2.39 (s, 3H, -CH3), 3.48–3.63 (m, 2H, -CH2), 4.90 (t,
1H, J = 7.1 Hz, H-2), 7.18–7.31 (m, 11H), 7.77 (d, 2H,
J = 8.1 Hz); Anal. Calcd. for C22H19ClOS (366.90): C,
72.02; H, 5.22. Found: C, 72.21; H, 4.98.
2.2m
3-(4-Nitrophenyl)-1-(4-chlorophenyl)-3-(4-
methylphenylsulphanyl)propan-1-one 1p: Colourless
crystals, IR (KBr) υmax = 1686 (C=O), 1514, 1344,
1219, 985, 822 cm−1; H NMR (300 MHz, CDCl3): δ
1
2.30 (s, 3H, -CH3) 3.59–3.62 (m, 2H, -CH2), 4.87 (t,
1H, J = 6.9 Hz, H-2), 7.05 (d, 2H, J = 7.8 Hz),
7.17 (d, 2H, J = 7.8 Hz), 7.26 (s, 1H), 7.42 (t, 3H,
J = 7.5 Hz), 7.83 (d, 2H, J = 8.4 Hz), 8.09 (d, 2H,
J = 8.4 Hz); Anal. Calcd. for C22H18ClNO3S (411.07):
C, 64.15; H, 4.40. Found: C, 63.90; H, 4.31.
2.2i 3-Phenyl-1-(4-methoxyphenyl)-3-phenylsulpha-
nylpropan-1-one 1l: Colourless crystals, IR (KBr)
υmax
=
1670 (C=O), 1601, 1573, 1423, 1338,
1233, 1173, 1024, 984, 845 cm−1; 1H NMR (300 MHz,
CDCl3): δ 3.47–3.65 (m, 2H, -CH2), 3.85 (s, 3H,
-OCH3), 4.95 (dd, 1H, J = 7.8 and 6.0 Hz, H-2), 6.89
(d, 2H, J = 8.7 Hz), 7.15–7.34 (m, 10H), 7.87 (d, 2H,
J = 6.9 Hz); Anal. Calcd. for C22H20ClO2S (348.46):
C, 75.83; H, 5.79. Found: C, 75.91; H, 5.84.
2.2n 3-Phenyl-1-(3-nitrophenyl)-3-phenylsulphanyl-
propan-1-one 1s: Light yellow crystals, IR (KBr)
1
υmax = 1674 (C=O), 1536, 1349, 1236, 987 cm−1; H
NMR (300 MHz, CDCl3): δ 3.57–3.73 (m, 2H, -CH2),
4.94 (t, 1H, J = 7.0 Hz, H-2), 7.21–7.39 (m, 10H),
7.64 (t, 1H, J = 8.0 Hz), 8.18 (dd, 1H, J = 7.8 and
0.9 Hz), 8.38 (dt, 1H, J = 8.1 and 0.9 Hz), 8.67 (s,
1H); Anal. Calcd. for C21H17NO3S (363.43): C, 69.40;
H, 4.71; N, 3.85. Found: C, 69.24; H, 4.95; N, 4.02.
2.2j
3-(4-Methoxyphenyl)-1-(4-methoxyphenyl)-3-
phenylsulphanylpropan-1-one 1m: Colourless crys-
tals, IR (KBr) υmax = 1672 (C=O), 1607, 1515,
1256, 1179, 1030, 822, 733 cm−1; 1H NMR (300 MHz,
CDCl3): δ 3.44–3.62 (m, 2H, -CH2), 3.75 (s, 3H,
-OCH3), 3.84 (s, 3H, -OCH3), 4.94 (dd, 1H, J = 8.1
and 6.0 Hz, H-2), 6.77 (d, 2H, J = 8.7 Hz), 6.89 (d,
2H, J = 8.7 Hz), 7.18–7.35 (m, 7H), 7.85 (d, 2H, 2.2o (E)-1,5-diphenyl-3-(phenylthio)pent-4-en-1-one
J = 8.7 Hz); 13C NMR (75 MHz, CDCl3): 44.4, 47.8, 7: Colourless crystals, mp: 102–104◦C. IR (KBr)
55.2, 55.5, 113.7, 113.8, 127.3, 128.8, 128.9, 129.9, υmax = 1672 (C=O), 1607, 1515, 1256, 1179, 1030,
1
130.4, 132.6, 133.3, 134.6, 158.7, 163.6, 195.6; TOF 822, 733 cm−1. H NMR (300 MHz, CDCl3): δ 3.40–
MS ES+(M+Na)+: Calcd. 401.1187. Found 401.1188; 3.43 (m, 2H, CH2), 4.48 (m, 1H, >CH-S-), 6.16

1466
Chayan Guha et al.
Table 1. Optimization of reaction conditions for generation of chalcone (6a) by
variation of MW power and irradiation time.
Yielda of 6 (%)
Entry
Power (W)
Time (min)
Anh. K2CO3
Amberlyst-15
1
2
3
4
5
6
7
8
180
360
360
360
540
540
540
720
10
3
5
7
3
5
7
3
nil
5
27
43
85
97
97
Nil
Trace
16
30
72
85
85
Reaction mixture charred
aIsolated yield for this and all the subsequent tables
(dd, 1H, J = 15.7 and 8.0 Hz, H-4), 6.30 (d, 1H, benzaldehyde (4a) and thiophenol (5a) was subjected
J = 15.6 Hz, H-5), 7.19–7.33 (m, 8H, Ar-H), 7.44– to microwave irradiation over neutral alumina sup-
7.60 (m, 5H, Ar-H), 7.92–7.94 (m, 2H, ortho-protons ported potassium carbonate or amberlyst-15, instead of
of -COPh) Anal. Calcd. for C23H20OS (344.47): C, the desired compound 1a, the chalcone 6a was formed.
80.19; H, 5.85; Found: C, 80.04; H, 6.02.
The strong characteristic smell of thiophenol obtained
by opening the microwave oven after operation clearly
indicated that failure of the expected reaction was due
to vaporization of thiophenol from the reaction mix-
ture. We, therefore, chose the strategy of generating
chalcones (6) first and then allowing them to react
with thiols in the same pot under a milder condition.
It may be mentioned here that microwave-assisted
Michael reactions over anhydrous K2CO3 are known
in literature.37 The reaction condition for generation
of chalcones (6) by microwave irradiation over neutral
alumina supported anhydrous K2CO3 38,39 or amberlyst-
1540 was freshly optimized in the present study apply-
ing various microwave (MW) powers and irradiation
times (table 1). Screening of different alkali metal car-
bonates and sulphonic acids for their catalytic activities
was also done in this connection (tables 2 and 3). When
MW irradiation was done over only neutral alumina,
formation of only 6a (yield 52%) was observed.
2.2p Diastereomers of 1,3,8,10-tetraaryl-4,7-dithia-
decan-1,10-dione 8: Colourless crystals, melting
range 118–126◦C; 1H NMR (300 MHz, CDCl3): δ
2.40–2.50 (m, 4H, -S-CH2-CH2-S- of the major iso-
mer), 2.60–2.68 (m, ∼1.33H, -S-CH2-CH2-S- of the
minor isomer), 3.45 (d, 4H, J = 6.9 Hz, –CO-CH2-
CH< of the major isomer), 3.51 (d, ∼1H, J = 6.9 Hz,
–CO-CH2-CH< of the minor isomer), 4.46 (br. t, 2H,
J = 6.9 Hz, –CO-CH2-CH< of the major isomer),
4.58 (br. t, ∼0.5 H, J = 6.9 Hz, –CO-CH2-CH< of
the minor isomer), 7.23–7.58 (m, ∼12.5H, Ar-H of
both the isomers), 7.86–7.89 (∼5H, ortho protons
of –COC6H5 of both the isomers).
3. Results and discussion
Our endeavour for synthesis of β-aryl-β-
mercaptoketones (1) started with searching of a suit-
able condition for a three-component reaction. Thus,
when an equimolar mixture of acetophenone (3a),
The results presented in table 1 clearly showed that
irradiation at 540 W for 5 min was the optimum condi-
tion for the reaction. The choice of potassium carbonate
Table 3. Optimization of reaction conditions for genera-
Table 2. Optimization of reaction conditions for genera- tion of 1a by use of different sulphonic acidsa.
tion of 1a by use of different alkali metal carbonatesa.
Entry
Sulphonic acid
Yield (%)
Entry
Metal carbonate
Yield (%)
1
2
3
Amberlyst-15
Camphor sulphonic acid
p-TsOH
82
11
52
1
2
3
Na2CO3
K2CO3
Cs2CO3
81
94
96
aAmount of sulphonic acid = 80 mg/mmol of substrate
aMol ratio of substrate to metal carbonate = 1:1 (yield opti- (yield optimized by use of amberlyst-15); amount of neu-
mized by use of K2CO3); amount of neutral alumina (solid tral alumina (solid support) = 4 g/mmol of substrate (yield
support) = 4 g/mmol of substrate (yield optimized)
optimized)

Synthesis of β-aryl-β-mercaptoketones
1467
SR4
Anhydr. K2CO3
O
O
R4SH (5)
to the same pot
or
R2
R3
R2
R3
COCH3
Amberlyst-15
R2
R3
OHC
rt, 1.5 h
+
MW, 5 min
R1
a: R1 = H
R1
R1
1
6
3
4
a: R2 = R3 = H;
b: R2 = H, R3 = Me
b: R1 = p-Me
c: R1 = p-OMe
d: R1 = p-Cl
c: R2 = H, R3 = OMe; d: R2 = H, R3 = Cl
e: R2 = NO2, R3 = H; f: R2 = H, R3 = NO2
g: R2 = H, R3 = NMe2; h: R2, R3 = -OCH2O-
e: R1 = m-NO2
Scheme 2. Strategy for two-step one-pot synthesis of β-aryl-β-mercaptoketones (1).
over other alkali metal carbonates or amberlyst-15 over at that point indicated the formation of 1a in high
other sulphonic acids was justified by the optimum yield along with a trace amount of 6a. From this mix-
yield and cost effectiveness (tables 2 and 3, respec- ture, pure 1a could be obtained through rapid column
tively).
chromatography.
In the chosen strategy, a reaction mixture using 3a
This protocol was successfully employed for syn-
and 4a as starting materials (1:1 mol ratio) was allowed thesis of 18 other β-aryl-β-mercaptoketones (1b-s) by
to cool to room temperature after microwave irradia- using appropriate combinations of acetophenones (3),
tion over anh. K2CO3 or amberlyst-15 and then thiophe- benzaldehydes (4) and thiols (5) and also for synthe-
nol (5a) (1.3 mol ratio) was added to the same pot and sis of 7 by use of acetophenone (3a) cinnamaldehyde
allowed to stand for 1.5 h (scheme 2). TLC examination and thiophenol (table 4). It is noteworthy that in
Table 4. Results of one-pot synthesis of β-aryl-β-mercaptoketones (1) and a related compound (7)a.
Yield (%)
Anhydr. K2CO3 Amberlyst-15
Melting point (◦C)
[Lit.]
Entry
Product (1/7)
SPh
O
94–96 [96–97]15
1a
1
94
82
SPh
O
1b
Me
2
3
94
90
84
79
72–74
SPh
O
1c
84–86 [87–88]15
OMe
SPh
O
Cl
74–76 [74–75]15
108–110
1d
4
5
95
94
84
83
SPh
O
O
NO2
1e
SPh
1f
NO2
6
7
92
84
80
72
100–102
152–154
O
SPh
NMe2
1g

1468
Chayan Guha et al.
Table 4. (continued)
Yield (%)
Anhydr. K2CO3 Amberlyst-15
Melting point (◦C)
[Lit.]
Entry
Product (1/7)
SPh
O
O
O
1h
8
87
79
66–68
SPh
O
Me
1i
SPh
9
93
88
94
80
78
81
60–62
112–114
90–92
O
Me
OMe
1j
10
11
SPh
O
Me
Cl
1k
SPh
O
MeO
1l
SPh
12
91
80
118–120
O
OMe
MeO
1m
13
14
89
90
78
79
110–112
96–98
SPh
O
1n
MeO
Cl
Me
Cl
S
O
1o
15
83
72
118–120
Me
NO2
Cl
S
O
1p
Cl
16
17
85
88
73
75
126–128
OH
O
S
1q
60–62 [59–62]8

Synthesis of β-aryl-β-mercaptoketones
1469
Table 4. (continued)
Yield (%)
Melting point (◦C)
[Lit.]
Entry
Product (1/7)
Anhydr. K2CO3
Amberlyst-15
OH
O
S
1r
70–72 [69–71]8
OMe
18
82
73
SPh
O
1s
NO2
O
19
20
69
72
55
63
106–108
102–104
SPh
7
aThe 1H NMR spectral features of the product in this case (vide Experimental) led to the elimination of the
alternative structure 7ꢁ.
SPh
O
(E)
7
Cl
Anhydr. K2CO3
SH
or
O
HS
Amberlyst-15
O
O
S
S
to the same pot
rt, 1.5 h
3a + 4d
MW, 5 min
Cl
6d
Cl
8
Scheme 3. Synthesis of 1,3,8,10-tetraaryl-4,7-dithia-decan-1,10-dione (8).
+
δ
δ-
RSH
R
H
Base
(K2CO3)
S
OH
O
6 +
1
SO3H
Ar1
Ar2
Ar2
Ar1
6
Scheme 4. Plausible mechanism of formation of β-aryl-β-mercaptoketones (1).
the latter case, β-position of the intermediate E- the K2CO3-catalysed process, the thiols are activated,
cinnamylideneacetophenone is selectively attacked by while in the amberlyst-15-catalysed process, the α,β-
thiophenol over δ-position.
unsaturated ketones are activated to make the addition
The mentioned methodology was then extended to effective (scheme 4).
the combination of 3a, 4d and ethane-1,2-dithiol (mol
ratio: 1:1:0.6), when a 1:4 (approx.) mixture of the
diastereomers of 8 was obtained in 63% yield. How-
ever, attempted separation of these diastereomers by
column chromatography over silica gel did not meet
with success (scheme 3).
Regarding the mechanistic aspects of the thia-
Michael addition, it may be pointed out that in
4. Conclusion
We have developed a very simple protocol for
rapid, efficient and one-pot synthesis of β-aryl-β-
mercaptoketones by use of tandem reactions on com-
mon inexpensive catalysts such as anhydrous K2CO3

1470
Chayan Guha et al.
and amberlyst-15. Such processes are a matter of cur- 12. Cherkauskas J P and Cohen T 1992 J. Org. Chem.
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2001 Tetrahedron: Asymmetry 12 1923
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Acknowledgements
19. Yadav J S, Reddy B V S and Baishya G 2003 J. Org.
Chem. 68 7098
20. Ranu B C, Dey S S and Hajra A 2003 Tetrahedron 59
2417
Financial assistance from the University of Grants
Commission (UGC)-Center of Advanced Studies and
the Department of Science and Technology-Promotion
of University Research and Scientific Excellence pro-
grammes, of the Department of Chemistry is grate-
fully acknowledged. The authors also acknowledge the
DST-FIST programme to the Department of Chemistry,
Jadavpur University for providing the NMR spectral
data. CG and RM are thankful to UGC, New Delhi for
their Research Fellowships.
21. Ranu B C and Dey S S 2004 Tetrahedron 60 4183
ˇ
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