Diastereoselective synthesis and stereochemistry of (Z)-1-[3-aryl-2- (phenylsulfanyl)-2-oxiranyl]-1-ethanones

Article abstract of DOI:10.1080/10426500490485129

Diastereoselective synthesis of a series of (Z)-1-[3-aryl-2- (phenylsulfanyl)-2-oxiranyl]-1-ethanones was effected from the reaction of (Z)-4-aryl-3-(phenylsulfanyl)-3-buten-2-ones with alkaline hydrogen peroxide in tetrahydrofuran. The stereochemistry of

Full text of DOI:10.1080/10426500490485129

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Phosphorus, Sulfur, and Silicon
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DIASTEREOSELECTIVE
SYNTHESIS AND
STEREOCHEMISTRY OF (Z)-1-[3-
ARYL-2-(PHENYLSULFANYL)-2-
OXIRANYL]-1-ETHANONES
E. Karthikeyan a , S. Perumal a & s. Selvaraj a
a Department of Organic Chemistry, School of
Chemistry, Madurai Kamaraj University , Madurai,
India
Published online: 16 Aug 2010.
To cite this article: E. Karthikeyan , S. Perumal & s. Selvaraj (2004)
DIASTEREOSELECTIVE SYNTHESIS AND STEREOCHEMISTRY OF (Z)-1-[3-ARYL-2-
(PHENYLSULFANYL)-2-OXIRANYL]-1-ETHANONES, Phosphorus, Sulfur, and Silicon and
the Related Elements, 179:11, 2379-2386, DOI: 10.1080/10426500490485129
To link to this article: http://dx.doi.org/10.1080/10426500490485129
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Phosphorus, Sulfur, and Silicon, 179:2379–2386, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485129
DIASTEREOSELECTIVE SYNTHESIS AND
STEREOCHEMISTRY OF (Z)-1-[3-ARYL-2-
(PHENYLSULFANYL)-2-OXIRANYL]-1-ETHANONES
E. Karthikeyan, S. Perumal, and S. Selvaraj
Department of Organic Chemistry, School of Chemistry,
Madurai Kamaraj University, Madurai, India
(Received March 5, 2004; accepted April 28, 2004)
Diastereoselective synthesis of a series of ( Z)-1-[3-aryl-2-(phenylsul-
fanyl)-2-oxiranyl]-1-ethanones was effected from the reaction of ( Z)-4-
aryl-3-(phenylsulfanyl)-3-buten-2-ones with alkaline hydrogen perox-
ide in tetrahydrofuran. The stereochemistry of the oxiranes has been
deduced from two-dimensional NOESY spectrum.
Keywords: 1-[3-aryl-2-(phenylsulfanyl)-2-oxiranyl]-1-ethanones; hyd-
rogen peroxide; NMR; synthesis; stereochemistry; (Z)-4-aryl-3-
(phenylsulfanyl)-3-buten-2-ones
INTRODUCTION
Epoxidation of alkenes is a synthetically important reaction because
epoxides can be transformed into a range of diverse compounds.1 Upon
reaction with alkaline hydrogen peroxide or hydroperoxides, electron-
deficient alkenes such as α, β-unsaturated carbonyl compounds usually
afford a mixture of (E)- and (Z)-oxiranes,2 the yield and the (E)/(Z)-ratio
depending on the nature of substrate, oxidant, and reaction conditions.
For instance, in the epoxidation of (E)-cinnamaldehyde and its deriva-
tives by ROOH (R = H, Et, cumyl, and t-butyl), the (E)/(Z) ratio is found
to vary with the nature of the oxidant.3
S. Perumal thanks the CSIR and DST, New Delhi for major research projects. (S.
Perumal and S. Selvaraj) thank DST for funds under IRHPA program for the purchase
of a high-resolution NMR spectrometer and UGC for a major research project and funds
under the DRS and ASIST programs.
Address correspondence to S. Perumal, Department of Organic Chemistry, School of
Chemistry, Madurai Kamaraj University, Madurai 625 021, India. E-mail: subbu perum@
rediffmail.com
2379

2380
E. Karthikeyan et al.
In our recent study, the epoxidation of a series of E,E-2,2ꢁ-
sulfonylbis1,3-diarylprop-2-en-1-ones with alkaline hydrogen perox-
ide afforded a single diastereomeric bis oxirane, while (E,E)-2,2ꢁ-
thiobis(1,3-diarylprop-2-en-1-ones) afforded (E)- and (Z)-oxiranes in
unequal amounts, the steric interactions in the intermediate enolates
being held responsible for the stereochemistry of the major sulfonylbis
and thiobis oxiranes.4
The present work describes the diastereoselective synthesis of 1-[3-
aryl-2-(phenylsulfanyl)-2-oxiranyl]-1-ethanones 2 from the reaction of
(Z)-4-aryl-3-(phenylsulfanyl)-3-buten-2-ones 1 with alkaline hydrogen
peroxide. These oxiranes and their derivatives such as their β-hydroxy
oxiranes could serve as valuable synthons for the construction of novel
heterocycles. It is also of interest to examine the influence of the rel-
ative sizes and interaction between the functionalities of the trisub-
stituted alkenes, viz. (Z)-4-aryl-3-(phenylsulfanyl)-3-buten-2-ones 1 on
the stereochemical outcome of this reaction.
RESULTS AND DISCUSSION
In the present investigation, the (Z)-4-aryl-3-(phenylsulfanyl)-3-buten-
2-ones 1 employed in the epoxidation were prepared by the condensa-
tion of 1-(phenylsulfanyl)acetone with the appropriate aromatic alde-
hydes in presence of piperidinium acetate in ethanol. The yields of 1
obtained in the present method (Table I) are higher than those reported
earlier by refluxing the starting materials with piperidine in toluene,5
TABLE I Synthesis of 4-Aryl-3-(phenylsulfanyl)-3-buten-2-onesa 1
% Analyses calc.
(found)
Time
Yield
1
X
(Lit. time) (h) (Lit. yield) (%) Mol. formula
C
H
a
b
c
d
e
f
g
h
i
Hb
4 (144)
85 (75)7
84
—
—
4-Cl
6
C16H13ClOS 66.54 (66.49) 4.54 (4.50)
—
C16H13FOS 70.56 (70.61) 4.81 (4.73)
—
4-Meb
4-F
5 (144)
83 (71)7
77
—
6
4-NOb2
2-Cl
3 (15)
89 (85)7
84
—
7
8
9
6
C16H13ClOS 66.54 (66.49) 4.54 (4.56)
2-Me
2-MeO
4-MeOb
83
C17H16OS
C17H16O2S
—
76.08 (76.01) 6.01 (5.94)
71.80 (71.78) 5.67 (5.63)
—
80
815
aMelting points not reported because all the compounds are semisolids except for (e)
m.p. 58◦C (lit.7 56–60◦C).
bKnown compounds.

Phenylsulfanyl Oxiranyl Ethanones
2381
TABLE II 1H and 13C NMR Data of 4-Aryl-3-(phenylsulfanyl)-3-buten-2-ones
1
1
a
1H-NMR [CDCl3/TMS, δ (ppm)]
13C-NMR [CDCl3/TMS, δ (ppm)]
2.33 (s, 3H), 7.14–7.85 (m, 10H), 7.94 27.6, 126.3, 127.7, 128.3, 129.3, 130.1,
(s, 1H)
130.8, 132.2, 134.1, 135.2, 144.2, 198.9
27.3, 126.3, 127.5, 128.3, 129.2, 131.8,
132.4, 132.6, 134.6, 135.7, 42.3, 198.2
21.5, 27.6, 126.2, 127.5, 128.7, 129.1, 129.3,
131.1, 131.4, 135.5, 140.8, 144.9, 199.1
27.6, 115.4, 115.7, 126.5, 127.5, 127.6,
129.0, 129.5, 133.0, 133.2, 135.0, 137.2,
143.2, 198.9
b
c
2.16 (s, 3H), 6.93–7.59 (m, 9H), 7.62
(s, 1H)
2.20 (s, 6H), 6.83–7.68 (m, 9H), 7.84
(s, 1H)
2.34 (s, 3H), 6.87–7.90 (m, 9H), 7.91
(s, 1H)
d
e
f
2.24 (s, 3H), 7.15–8.18 (m, 9H), 7.72
(s, 1H)
2.28 (s, 3H), 7.04–7.86 (m, 9H), 7.98
(s, 1H)
27.8, 123.3, 126.9, 127.2, 128.4, 128.9,
129.5, 130.9, 136.7, 139.3, 147.5, 198.4
27.6, 126.3, 126.6, 127.4, 128.1, 129.4,
129.4, 130.6, 130.7, 132.9, 134.8, 135.9,
140.5, 198.2
g
h
i
2.27 (s, 3H), 2.30 (s, 3H), 7.02–7.74
(m, 9H), 7.98 (s, 1H)
20.1, 27.7, 125.5, 126.3, 127.8, 129.1, 129.3,
129.5, 130.1, 131.6, 133.6, 134.3, 135.5,
143.0, 203.6
27.5, 55.5, 110.4, 119.9, 126.0, 127.5, 129.2,
130.2, 131.5, 132.5, 135.8, 137.1, 140.4,
158.3, 190.4
2.35 (s, 3H), 3.85 (s, 3H), 6.84–8.02
(m, 9H), 8.27 (s, 1H)
2.29 (s, 3H), 3.83 (s, 3H), 6.93–7.79
(m, 9H), 7.94 (s, 1H)
27.6, 55.4, 113.9, 126.1, 127.2, 127.4, 129.0,
129.3, 129.9, 133.3, 145.4, 164.6, 199.2
or in benzene with azeotropic removal of water,6 or in chloroform.7 The
shorter reaction time and the enhanced yield of 1 in the present study
could probably arise from the role of piperidinium acetate functioning
in concert as (1) a base (OAc−) leading to the formation of enolate ion
from the 1-(phenylsulfanyl)acetone, or (2) as an acid (piperidinium ion)
enhancing the electrophilicity of the aldehyde. The NMR spectroscopic
data of the butenones 1 are presented in Table II.
The 1-(phenylsulfanyl)acetone required for the present study, in
turn, was obtained by the reaction of chloroacetone with benzenethiol in
methanol in the absence of any added base in an excellent yield of 95%,
while the literature yields in presence of sodium hydroxide or pyridine
were much lower, 53 and 64%, respectively.8
Epoxidation was affected by reacting 1 with hydrogen peroxide in a
1:1 molar ratio in tetrahydrofuran (THF) in presence of sodium hydrox-
ide at room temperature (Scheme 1). Monitoring the reaction by thin
layer chromatography (TLC) helped in optimizing the reaction time
(Table III). Reactions performed for longer durations led to a mixture
of products, suggesting further reactions of the oxiranes.

2382
E. Karthikeyan et al.
SCHEME 1

Phenylsulfanyl Oxiranyl Ethanones
2383
TABLE III Synthesis of 1-[3-Aryl-2-(phenylsulfanyl)-2-oxiranyl]-
1-ethanonesa 2
% Analyses calc. (found)
Time Yield
2
X
(h)
(%)
Mol. formula
C
H
a
b
c
d
e
f
g
h
i
H
4-Cl
4-Me
4-F
4-NO2
2-Cl
2-Me
2-MeO
4-MeO
39
36
23
19
17
34
25
23
21
67
85
86
79
84
86
87
C16H14O2S
C16H13ClO2S
C17H16O2S
C16H13FO2S
C16H13NO4S
71.08 (71.13) 5.22 (5.13)
63.05 (62.93) 4.30 (4.25)
71.80 (70.91) 5.67 (5.57)
66.65 (66.71) 4.54 (4.50)
60.94 (60.87) 4.16 (4.27)
63.05 (63.13) 4.30 (4.24)
71.80 (71.92) 5.67 (5.60)
C
16H13ClO2S
C17H16O2S
—
—
b
—
—
—
—
—
b
—
aMelting points not reported as all the products are semisolids.
bIn these cases, retro-aldol condensation took place affording the
corresponding benzaldehydes and 1-(phenylsulfanyl)acetone.
All the oxiranes of the present work are hitherto unreported. The
1
analytical data and the H and 13C NMR data are in accordance with
1
the structure of the oxiranes (Table IV). The H NMR spectrum for a
representative example 2a is discussed here. The acetyl methyl and the
methine protons give singlets at 2.23 and 4.28 ppm, respectively. The
aromatic protons of the phenyl rings give a multiplet integrating for 10
protons in the region of 7.27–7.49 ppm. The other oxiranes also showed
similar spectroscopic data supporting their structure.
That the acetyl group and the methine hydrogen in the oxirane 2a are
in a cis relationship is revealed by the presence of a contour correlating
the chemical shifts of these protons in the NOESY spectrum of 2a.
This shows that this oxirane has (Z)-configuration. The predominant
formation of the diastereomer 2a may presumably be rationalized on
the basis that the steric interaction between the 2-phenylsulfanyl group
and the 3-aryl group is likely to be less than that between the acetyl and
the 3-aryl group both in the oxiranes and the corresponding transition
states (Scheme 2).
In the case of 4-(2-methoxyphenyl)-3-(phenylsulfanyl)-3-buten-2-one
1h and 4-(4-methoxyphenyl)-3-(phenylsulfanyl)-3-buten-2-one 1i, the
reaction with alkaline hydrogen peroxide afforded the correspond-
ing aldehydes (2-methoxy- and 4-methoxy-benzaldehydes, respectively)
and 1-(phenylsulfanyl)acetone, presumably via retro-aldol condensa-
tion triggered by the attack of hydroxide ion. In the case of 1h
and 1i, the stronger conjugative interaction between the methoxy
groups with the α,β-unsaturated carbonyl moiety could probably

2384
E. Karthikeyan et al.
SCHEME 2 Mechanism of epoxidation.
raise the energy of activation for the attack of −OOH ion rela-
tive to the attack by −OH, as in −OOH two oxygens with their
lone pairs could be repelled strongly by the electron-rich conjugated
system.

Phenylsulfanyl Oxiranyl Ethanones
2385
TABLE IV The 1H and 13C NMR Data of 1-[3-Aryl-2-(phenylsulfanyl)-
2-oxirany1]-1-ethanones 2
2
a
1H-NMR [CDCl3/TMS, δ (ppm)]
13C-NMR [CDCl3/TMS, δ (ppm)]
2.23 (s, 3H), 4.28 (s, 1H), 7.27–7.49 (m, 26.9, 62.5, 76.3, 127.3, 127.9, 128.0, 129.1,
10H). 129.4, 131.2, 131.3, 132.0, 201.3
2.15 (s, 3H), 4.18 (s, 1H), 7.19–7.41 (m, 26.8, 61.9, 76.2, 128.3, 128.7, 129.0, 129.4,
b
c
9H).
130.5, 130.8, 131.3, 135.07, 200.9
21.3, 26.9, 62.6, 76.4, 127.3, 127.8, 128.8,
128.9, 129.3, 131.2, 131.4, 139.1, 201.4
2.14 (s, 3H), 2.31 (s, 3H), 4.17 (s, 1H),
7.12–7.42 (m, 9H).
d
2.15 (s, 3H), 4.18 (s, 1H), 7.02–7.41 (m, 26.9, 62.0, 76.3, 115.0, 115.3, 127.1, 127.4,
9H).
127.9, 129.0, 129.2, 129.3, 129.4, 130.9,
131.3, 201.1
e
f
2.16 (s, 3H), 4.30 (s, 1H), 7.19–8.20 (m, 26.8, 61.5, 76.0, 123.3, 127.5, 128.3, 129.0,
9H). 129.3, 129.5, 131.7, 139.3, 200.4
2.33 (s, 3H), 4.42 (s, 1H), 7.27–7.56 (m, 27.0, 60.8, 75.6, 126.6, 127.9, 128.8, 128.9,
9H).
129.4, 130.1, 130.8, 130.9, 131.0, 132.9,
200.5
g
2.25 (s, 3H), 2.36 (s, 3H), 4.29 (s, 1H),
7.21–7.51 (m, 9H).
18.8, 26.9, 61.3, 76.0, 125.7, 126.8, 127.4,
127.9, 128.8, 129.0, 129.3, 129.8, 131.0,
131.4, 201.3
EXPERIMENTAL
THF was purified and distilled. Aldehydes were freshly distilled before
use. The 1H and 13C NMR spectra were measured using CDCl3 as sol-
vent in a Bruker (Avance) instrument at 300 and 75 MHz, respectively,
and their chemical shifts referenced to TMS.
Preparation of 1-(Phenylsulfanyl)acetone
To a solution of benzenethiol (10.2 ml, 0.1 mol) in methanol (15 ml)
cooled in an ice bath, a solution of chloroacetone (7.96 ml, 0.1 mol) in
methanol (25 ml) was added dropwise with stirring. After completion
of the addition, the temperature was allowed to rise to 15–20◦C and the
stirring continued overnight at 15–20◦C. Then the reaction mixture was
poured into crushed ice, extracted with ether, organic layer was washed
thoroughly with water, dried over anhydrous sodium sulfate, and the
solvent removed. 1-(Phenylsulfanyl)acetone was obtained as a colorless
crystalline solid (15.8 g, 95%), m.p. 27–28◦C (lit.8 m.p. 25–30◦C).
Synthesis of (Z)-4-Aryl-3-(phenylsulfanyl)-3-buten-
2-ones (1a–i): General Procedure
Benzaldehyde (0.30 ml, 0.003 mol) was added to a solution of
1-(phenylsulfanyl)acetone (0.5 g, 0.003 mol) in ethanol (5 ml), followed

2386
E. Karthikeyan et al.
by 3 drops of piperidine and 2 drops of acetic acid. Then the reaction
mixture was refluxed for 6 h. After the completion of the reaction as
indicated by TLC, the reaction mixture was poured into ice water, ex-
tracted with ether, and the organic layer was washed successively with
sodium bisulfite to remove the unreacted aldehyde. Then the organic
layer was dried over anhydrous sodium sulfate and the solvent removed.
The residue obtained was purified by column chromotography using sil-
ica gel with petroleum ether:ethyl acetate (97:3 v/v) as eluent to give
the pure semisolid product, yield 0.66 g (85%).
Synthesis of (Z)-1-[3-Aryl-2-(phenylsulfanyl)-2-oxiranyl]-
1-ethanones (2a–g): General Procedure
To a solution of (Z)-4-phenyl-3-(phenylsulfanyl)-3-buten-2-one (0.26 g,
0.001 mol) in tetrahydrofuran (10 ml), hydrogen peroxide (1.2 ml, 15%)
was added in one batch followed by a dropwise addition of sodium
hydroxide solution (1 ml, 10%) with stirring. Stirring was continued for
39 h, and the reaction progress was monitored by TLC. After comple-
tion of the reaction, the reaction mixture was dissolved in ether, washed
with water repeatedly, the organic layer dried over anhydrous sodium
sulfate, and the solvent removed. The product was purified using col-
umn chromatography over silica gel with petroleum ether:ethyl acetate
(98:2 v/v) as eluent, yield 0.19 g (67%).
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