(Bromodimethyl)sulfonium bromide-mediated thiolysis of epoxides: An easy access to -hydroxy sulfides and benzoxathiepinones in solvent-free conditions

Article abstract of DOI:10.1080/00397910903458595

A mild, rapid and highly regioselective opening of epoxides by mercaptans to bη-hydroxy sulfides and benzoxathiepinones has been achieved in excellent yields, using catalytic amount of (bromodimethyl)sulfonium bromide in solvent free reaction conditions.

Full text of DOI:10.1080/00397910903458595

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(Bromodimethyl)sulfonium
Bromide–Mediated Thiolysis of Epoxides:
An Easy Access to β-Hydroxy Sulfides
and Benzoxathiepinones in Solvent-Free
Conditions
M. Shailaja a , A. Manjula a & B. Vittal Rao a
a Organic Chemistry Division II, Indian Institute of Chemical
Technology , Hyderabad, India
Published online: 09 Nov 2010.
To cite this article: M. Shailaja , A. Manjula & B. Vittal Rao (2010) (Bromodimethyl)sulfonium
Bromide–Mediated Thiolysis of Epoxides: An Easy Access to β-Hydroxy Sulfides and Benzoxathiepinones
in Solvent-Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:24, 3629-3639, DOI: 10.1080/00397910903458595
To link to this article: http://dx.doi.org/10.1080/00397910903458595
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Synthetic Communications1, 40: 3629–3639, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903458595
(BROMODIMETHYL)SULFONIUM BROMIDE–MEDIATED
THIOLYSIS OF EPOXIDES: AN EASY ACCESS TO
b-HYDROXY SULFIDES AND BENZOXATHIEPINONES IN
SOLVENT-FREE CONDITIONS
M. Shailaja, A. Manjula, and B. Vittal Rao
Organic Chemistry Division II, Indian Institute of Chemical Technology,
Hyderabad, India
A mild, rapid and highly regioselective opening of epoxides by mercaptans to b-hydroxy
sulfides and benzoxathiepinones has been achieved in excellent yields, using catalytic
amount of (bromodimethyl)sulfonium bromide in solvent free reaction conditions.
Keywords: (Bromodimethyl)sulfonium bromide; epoxides; b-hydroxy sulfides; solvent-free reactions;
thiols
INTRODUCTION
Development of clean methods in synthetic organic chemistry comprises of a
series of reductions or simplifications of the number of chemicals and steps involved
in the process. Removal of solvent, either from a reaction step or work-up, would be
a significant step toward a green chemical approach. Consequently, the solvent-free
methods constitute an excellent tool for accomplishing environmentally friendly
organic reactions. Solvent free reactions are generally rapid, highly selective and
often high yielding.[1] Our research devoted to the development of new protocols
for synthesis of bioactive molecules and intermediates has been aimed at performing
organic transformations under solvent-free conditions using a versatile catalyst,
(bromodimethyl) sulfonium bromide.[2,3] We have earlier demonstrated the versa-
tility of the catalyst for a-amino phosponates[4] Michael addition with thiols,[5] pro-
tection of amines,[6] Mannich reaction,[7] etc. Furthermore, we now report,
(bromodimethyl)sulfonium bromide as a highly efficient catalyst in thiolysis of epox-
ides in solvent free reaction conditions.
Oxiranes are valuable intermediates[8] in organic synthesis as they can be
subjected to nucleophilic ring opening, with the most common nucleophiles like
alcohols, thiols, or amines,[9,12] leading to 1,2-difunctional compounds with high
Received August 10, 2009.
Presented at the Asian Symposium on Medicinal Plants, Spices and Other Natural Products
(ASOMPS-XIII), Indian Institute of Chemical Technology, Hyderabad, India, November 3–6, 2008.
Address correspondence to B. Vittal Rao, Organic Chemistry Division II, Indian Institute of
Chemical Technology, Hyderabad 500607, India. E-mail: vittalrao@iict.res.in
3629

3630
M. SHAILAJA, A. MANJULA, AND B. VITTAL RAO
degree of chemo and regioselectivty under ideal conditions. Thiolysis of oxirane by
sulfur nucleophiles leads to b-hydroxy thio derivatives[13,15] like b-hydroxy sulfides,
b-hydroxy sulfoxides,[16,17] a-carbonyl vinylsulfides, a-thioketones, which are crucial
synthetic intermediates for pharmaceuticals[18] and natural products[19,20] especially
small molecules like benzothiazepines, benzoxathiazepinones etc. Owing to their sig-
nificance,[21–25] the thiolysis of epoxides has been investigated widely in literature.
The conventional protocols of thiolysis involve use of acid or base,[26,27] Lewis
acids,[28–32] metal salts or doped catalysts (alumina, silica, etc).[33] microwave.[34]
However, only a few practical methods are reported without limitations. The usual
methods available in existing literature for nucleophilic ring opening in acidic and
basic media are neither regio selective, and in the later case, nor chemoselective.[35]
In this context, we disclose herein our results on ring opening of epoxide assisted
by (bromodimethyl)sulfonium bromide with thiols, dithiols and disulfides.[36]
RESULTS AND DISCUSSION
To begin with, the epoxide ring was opened with simple aliphatic and aromatic
thiols in the presence of (bromodimethyl)sulfonium bromide (Scheme 1). Treating
styrene epoxide with thiophenol in the presence of 10 mole percent (bromodimethyl)-
sulfonium bromide at room temperature under solvent free conditions (10 mins.,
Entry 1, (Table 1) provided the corresponding b-hydroxy sulfide in 94% yield.
Further, styrene epoxide was opened with, other both aliphatic and aromatic thiols
(Entries 2–5). In all cases corresponding b-hydroxy sulfides were obtained in excel-
lent yields in a matter of few minutes. The regio chemistry of opening was interest-
ingly an attack of the thiol at benzylic position and only primary alcohol was
produced. This was substantiated by the spectral data and is in congruence with
the literature reports. It is thought that such an attack occurs because the benzylic
ꢀCHꢀ is more prone to nucleophilic attack.
Encouraged by this, we subjected various other epoxides namely, epichlorohy-
drin, tert-butyl 6-oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylate, 4-((oxiran-2-
yloxy)methyl)-9H-carbazole etc., to thiolysis under similar conditions with catalytic
amount of (bromodimethyl)sulfonium bromide (Table 1, Entries 17–20). These ali-
phatic epoxides provided the corresponding b-hydroxy sulfides in very good yield.
The regio selectivity in this case was opposite of the styrene epoxide, since the nucleo-
philic attack on an epoxide is at the least substituted carbon. Consequently, the pro-
duct obtained was a secondary alcohol. This was substantiated by the spectral data.
Scheme 1. Epoxide opening by thiols.

EASY ACCESS TO b-HYDROXY SULFIDES
Table 1. Thiolysis of epoxides
3631
S.no.
1
Epoxide
Thiol
Product
Time (min)
Yield (%)
[33]
10
94
[39]
2
3
7
5
89
[39]
C4H9SH
C5H11SH
C10H21SH
88
[38]
4
5
5
3
92
[40]
90
[37]
6
7
5
2
92
90
95
8
C5H11SH
4
9
C10H21SH
C5H11SH
6
91
86
10
10
11
12
C10H21SH
4
8
93
85
(Continued )

3632
M. SHAILAJA, A. MANJULA, AND B. VITTAL RAO
Table 1. Continued
S.no.
13
Epoxide
Thiol
Product
Time (min)
Yield (%)
88
5
14
3
91
15
16
17
15
88
90
86
6
8
18
19
C10H21SH
13
15
78
87
20
21
5
5
92ꢁ
92ꢁ
Reported compounds are indicated by the references in brackets in the yields column.
ꢁDetermined by HPLC apparatus fitted with a chiralcel OJ-H chiral column (i-prOH=hexane ¼ 1=99;
flow rate 0.8 ml=min; detector ¼ 254 nm).

EASY ACCESS TO b-HYDROXY SULFIDES
3633
Scheme 2. Thiolysis of epoxide by disulfides.
Even chiral epichlorohydrins were examined so as to find out the stereochem-
istry of the products. Both R and S-epichlorohyrins gave corresponding opti-
cally active b-hydroxy sulfides (<99% ee by HPLC) without any racemisation or
inversion.
Opening of styrene epoxide with propane dithiol (Table 1, Entry 12) was also
facile and proceeded to yield 2-phenyl-2-[{3-sulfanylpropyl} sulfanyl]-1-ethanol in
85% yield in just 8 minutes. Epichlorohydrin followed the same pattern (Table 1,
Entry 13). The regiochemistry of opening was similar to that of mono thiols.
It has become clear now that neither the reaction condition nor catalyst system
have any adverse effects like dimerisation or disulphide formation. Enthusiastic
about this positive feature, we wanted to experiment the thiolysis of epoxides with
disulfides as nucleophiles. As anticipated, the reaction did not proceed with disulfide
and styrene epoxide in the presence of 10 mole percent catalyst. However, addition of
ethanol as solvent facilitated the ring opening (Scheme 2). Though the reaction was
sluggish compared with free thiols it proceeded smoothly to provide b-hydroxy sul-
fides in excellent yields, that too, with half the stoichiometry of disulphide to oxirane
(Table 2).
Convinced by these results, we further attempted the thiolysis of epoxides with
substituted bifunctional thiols like p-aminothiophenol, p-bromothiophenol and thio-
salicylic acid to study the chemo selectivity. In case of aminothiophenol, the reaction
Table 2. Thiolysis of epoxides with disulfides
S.no.
1
Epoxide
Disulphide
Productꢁ
Time (h) Yield (%)
2.5
2
92
89
2
3
4
4
3
85
90
ꢁReaction done in solvent (ethanol).

3634
M. SHAILAJA, A. MANJULA, AND B. VITTAL RAO
Scheme 3. Thiolysis of epoxide by thiosalicylic acid.
gave 88% of corresponding b-hydroxy sulfide (Table 1, Entries 14 and 15) with no
trace of other isomer or dimeric compound. Identical results were obtained with
p-bromothiophenol and corresponding b-hydroxy sulfide was obtained in 90% yield
(Table 1, Entry 16).
Thiolysis of styrene epoxides with thiosalicylic acid was interesting (Scheme 3).
Though the ring opening of epoxide was as usual fast, the resulting b-hydroxy sulfide
was found to cyclise to yield benzoxathiepinones at room temperature itself on
increasing the reaction time by a few minutes (Table 3). Literature precedents on this
kind of cyclization revealed that higher temperatures (ꢂ200 ꢃC for 20 h) and more
often solvents (water at 100 ꢃC, 24 h)[26] were needed. Whereas, in our approach
room temperature without any solvent, provided the cyclic benzoxathiepinones, in
a much lesser time compared to known literature methods. However, when epichlor-
ohydrin was the substrate the reaction yielded only the open chain ring opened pro-
duct. IR, NMR, and mass spectral data substantially proved the structure.
Further with a view to establish the efficiency of the catalyst (bromodimethyl)
sulfonium bromide, a comparative study was performed with other two catalysts,
namely, indium cloride, iodine. With indium chloride and iodine, the reaction times
Table 3. Thiolysis of epoxides with thiosalicylic acid
S.no
Epoxide
Thiol
Product
Time (h)
Yield (%)
1
2
93[26]
2
3
3
85
88
2.5

EASY ACCESS TO b-HYDROXY SULFIDES
3635
were longer and took few hours to complete. In both the cases, the reaction has to be
performed in solvent medium only. Whereas with catalytic amount of (bromodi-
methyl)sulfonium bromide the same job could be performed in solvent free
conditions in a matter of few minutes.
The role of the catalyst, (bromodimethyl)sulfonium bromide, could be that of a
Lewis acid, i.e., it coordinates with the epoxide oxygen thereby rendering the ring
carbons susceptible to nucleophilic attack.
To conclude, we have been able to demonstrate that (bromodimethyl) sulfo-
nium bromide efficiently promotes the thiolysis of epoxides resulting in b-hydroxy
sulfides in excellent yields and short reaction times. The protocol could be succes-
sfully extended to disulfides and bifunctional thiols. Further benzoxathiepinones
were produced at room temperature and under solvent free conditions by a one-pot
protocol involving nucleophilic ring opening of 1,2-epoxides by thiosalicylic acid
followed by the ring closure in an efficient and elegant manner.
EXPERIMENTAL[36]
Epoxide Opening with Thiols
A mixture of epoxide (1 mmol), thiol (1 mmol) and (10 mole%) of (bromodi-
methyl)sulfonium bromide was stirred at ambient temperature for an appropriate
time (Table 1). After completion of the reaction, as indicated by TLC, the reaction
mixture was diluted with water and extracted with dicloromethane, dried over anhy-
drous Na2SO4, filtered and concentrated under reduced pressure and purified by
column chromatography to give corresponding b-hydroxy sulphides.
Epoxide Opening with Disulphides
A mixture of epoxide (1 mmol), disulphide (0.5 mmol) dissolved in ethanol
(3 ml) and (bromodimethyl)sulfonium bromide (10 mole%) was added and stirred
at ambient temperature for an appropriate time (Table 2). After completion of the
reaction, as indicated by TLC, the solvent was removed under reduced pressure
and the reaction mixture was worked up as mentioned above. Further, purification
by column chromatography gave corresponding b-hydroxy sulphide.
Epoxide Opening with Thiosalicylic Acid
A mixture of epoxide (1 mmol), thiosalicylic acid (1 mmol) and (10 mole%) of
(bromodimethyl)sulfonium bromide was stirred at ambient temperature for an
appropriate time (Table 3). On monitoring the reaction by TLC it was observed that
styrene epoxide ring was opened in few minutes and on leaving the reaction mixture
to stir at RT for more time ring closure was observed by TLC, whereas in case of
epichlorohydrin, only ring opened product was observed even after 2.5 h. After com-
pletion of the reaction, the reaction mixture was worked up as mentioned above for
thiols and purified by column chromatography to give corresponding product.

3636
M. SHAILAJA, A. MANJULA, AND B. VITTAL RAO
Spectral Data
Since most of the b-hydroxy sulphides could not be detected by ESI-HRMS
probe, only their E I-Mass could be recorded.
2-Phenylthio-2-phenyl 1-ethanol. [Table 1, Entry 1] liquid; IR (neat, cmꢀ1):
3432, 2928, 2855, 1711, 1620, 1121, 769; 1H NMR (200 MHz, CDCl3, d) : 2.31 (br s,
1H), 3.66 (d, 2H, J ¼ 8.3 Hz), 3.60 (dd, 1H, J ¼ 8.3, 13.5 Hz), 7.30–7.15 (m, 10H, Ar).
ESIMS: m=z: 218 [M-2].
1-(Phenylthio) propan-2-ol. [Table 1, Entry6] liquid; IR (neat, cmꢀ1): 3438,
2875,1538,1228, 682; 1H NMR (200 MHz, CDCl3, d): 7.30 (m, 5H, Ar), 3.88 (dd, 2H,
OCH2, J ¼ 5.2, 15.1 Hz), 3.68 (d, 2H, CH2, J ¼ 5.3 Hz), 3.64 (d, 1H, SCH,
J ¼ 5.2 Hz); ESIMS: m=z: 240 [M þ 39]; C13 NMR: 136.12, 133.19, 128.96, 128.74,
128.41, 127.38, 127.16, 62.64, 31.33, 29.00.
2-(3-Mercaptopropylthio)-phenylethanol. [Table 1, Entry 12] Liquid IR
1
(KBr, cmꢀ1): 3449, 2919, 1449, 1099, 759, 699; H NMR (200 MHz, d, CDCl3):
7.2–7.39 (m, 5H, Ar), 5.2 (br, S, OH), 3.8 (dd, 1H, J ¼ 2.45, 3.96 Hz), 3.1 (dd, 1H,
J ¼ 3.96, 5.67 Hz), 2.8 (dd, 1H, J ¼ 2.64, 5.85 Hz), 2.65 (t, 2H, J ¼ 3.9 Hz), 2.4 (t,
2H, J ¼ 3.9 Hz), 2.01 (m, 2H),1.39 (s, 1H, SH). EIMS (m=z): 227[M]þ.
2-(3-Mercaptopropylthio)-1-chloroethanol. [Table 1, Entry 13] Solid, M.
1
p. 70–72ꢃC; IR (KBr, cmꢀ1): 3404, 2923,1598,1348,1176. H NMR (200 MHz, d,
CDCl3): 5.38 (m, 1H), 4.91 (d, 1H, J ¼ 5.14 Hz), 4.41 (d, 1H, J ¼ 5.1 HZ), 3.88 (t,
1H, J ¼ 5.1 Hz), 3.61 (d, 1H, J ¼ 5.1 Hz), 2.79 (t, 2H, J ¼ 6.2 Hz), 2.69 (t, 1H,
J ¼ 6.2 Hz), 2.45 (t, 2H, J ¼ 6.2 Hz), 2.15 (m, 2H), 1.59 (S, 1H, SH); EIMS (m=z):
199 [M-1]þ; CHN Analysis calcd.-C: 35.89, H: 6.52, S: 32.94; Found: C; 35.75, H:
6.50, S: 32.60.
1-(4-Aminophenylthio)-3-chloropropan-2-ol. [Table 1, Entry 15] Solid, M.
1
p. 110–112ꢃc; IR (KBr, cmꢀ1): 3426, 3329, 2867, 1575, 1078. H NMR (200MHz, d,
CDCl3): 7.36 (d, 2H, J ¼ 8.1 Hz), 6.7 (d, 2H, J ¼ 7.7 Hz), 5.3 (bs S, 2H, NH2), 4.07
(Br S, 1H, OH), 3.76 (m, 1H), 3.59 (d, 1H, J ¼ 5.6 Hz), 3.52 (d, 1H, J ¼ 5.6 Hz), 2.96
(dd, 1H, J ¼ 4.7, 13.5 Hz), 2.82 (dd, 1H, J ¼ 7.3, 13.5 Hz). EIMS (m=z): 216[M-1]þ.
t-Butyl 3-hydroxy-4-(phenylthio) pyrrolidine-1-carboxylate. [Table 1, Entry
1
17] Solid, M.p. 49–51 ꢃC; IR (neat, cmꢀ1): 3429, 2975, 1699, 1161, 738, 688. H
NMR (200 MHz, d, CDCl3): 7.49 (d, 2H, Ar, J ¼ 6.70 Hz), 7.33–7.20 (m, 2H, Ar),
4.5 (m, 2H), 4.8 (S, 1H, OH), 4.24 (2t, 2H, J ¼ 3.77 Hz), 3.84 (d, 1H, CH2,
J ¼ 4.532 HZ), 3.62 (d, 1H, J ¼ 3.7 Hz), 3.26 (d, 1H, J ¼ 12.0 Hz), 1.38 (S, 9H);
ESIMS: m=z: 296[M]þ; CHN Analysis calcd.-C: 60.91, H: 7.16, N: 4.76, S: 10.88;
Found: C: 60.88, H: 7.10, N: 4.72, S: 10.83.
t-Butyl 3-(decylthio)-4-hydroxypyrrolidine-1-carboxylate. [Table 1, Entry
1
18] liquid IR (neat, cmꢀ1): 3350, 2924, 1707, 1162, 722. H NMR (200 MHz, d,
CDCl3): 4.8 (S, 1H, OH), 4.24 (2 t, 4H, J ¼ 3.77 Hz), 3.62–3.8 (m, 1H), 3.6 (d, 1H,
J ¼ 5.2 Hz), 3.26 (dd, 1H, J ¼ 3.7, 9.0 Hz), 1.65 (m, 2H), 1.45 (m, 16H), 1.38 (S,
9H), 0.85 (t, 3H, J ¼ 3.7 Hz). EIMS: m=z: 356 [M-3]þ; CHN Analysis calcd.-C:
63.46, H: 10.36, N.3.89, S: 8.91; Found: C; 63.40, H: 10.32, N: 3.85, S: 8.86.

EASY ACCESS TO b-HYDROXY SULFIDES
3637
1-(9H-Carbazol-5-yloxy)-3-(phenylthio)propan-2-ol. [Table 1, Entry 19]
1
liquid IR (neat, cmꢀ1): 3405, 2925, 1574, 1437, 735; H NMR (200MHz, CDCl3 þ
DMSO d): 8.12 (d, 1H, ArH, J ¼ 6.79Hz), 7.44–7.47 (d, 1H, ArH, J¼ 6.79 Hz),
7.2–7.4 (m, 5H, ArH), 7.18–7.35 (m, ArH, 3H), 6.62–6.65 (d, 1H, ArH, J ¼ 8.3 Hz)
4.42–4.22 (br m, 2H, OH&CHOH), 3.82–3.65 (2dd, 2H, J ¼ 5.2, 10.5 Hz), 2.95 (t, 2H,
J ¼ 3.0 Hz), 2.85 (t, 2H, J ¼ 3.0 Hz). CHN Analysis calcd-C: 72.17, H: 5.48, N.4.00, S:
9.77; Found: C; 71.92, H: 5.42, N: 3.95, S: 9.71. ESIMS: m=z: 348 [M-1]þ.
(S)-1-Chloro-3-(phenylthio)propan-2-olꢁ. [Table 1, Entry 20] liquid [a]D ¼
ꢀ9.3(c 1,CHCl3); IR (neat, cmꢀ1): 3434, 2925, 1580, 1438, 740; 1H NMR
(200 MHz, CDCl3, d): 7.07 (d, 1H, Ar, J ¼ 8.3 Hz), 6.97 (d, 1H, Ar, J ¼ 8.3 Hz),
6.91–6.80 (m, 3H, Ar) 3.5 (m, 1H), 3.25 (d, 2H, J ¼ 5.2 Hz), 2.76 (dd,1H, J ¼ 6.0,
14.3 Hz), 2.64 (dd, 1H, J ¼ 6.7, 13.5 Hz), 2.17 (d, 1H, Ar, J ¼ 5.2 Hz); EIMS: m=z:
202[M]þ; C13 NMR: 133.05, 129.5, 129.0, 127.38, 126.4, 69.2, 46.3, and 37.5.
(R)-1-Chloro-3-(phenylthio)propan-2-olꢁ. [Table 1, Entry 21] liquid
1
[a]D ¼ þ9.5 (c1, CHCl3); IR (neat, cmꢀ1): 3419, 2922, 1580, 1436, 740. H NMR
(200 MHz, CDCl3, d): 7.42 (d, 1H, Ar, J ¼ 7.5 Hz), 7.33 (d, 1H, Ar, J ¼ 7.5 Hz),
7.26–7.14 (m, 3H, Ar) 3.8 (m, 1H), 3.62 (d, 2H, J ¼ 5.2 Hz), 3.18 (dd, 1H, J ¼ 6.0,
14.3 Hz), 3.05 (dd, 1H, J ¼ 6.7, 13.5 Hz), 2.15 (d, 1H, Ar, J ¼ 5.2 Hz); EIMS: m=z:
202 [M]þ; C13 NMR: 134.05, 129.8, 129.0, 127.38, 127.5, 69.2, 47.3, and 37.9.
ꢁDetermined by HPLC apparatus fitted with a chiralcel OJ-H chiral
column(iPrOH= hexane ¼ 1=99; flow rate 0.8 ml=min; detector ¼ 254 nm).
2,3-Dihydro-2-phenylbenzo[e][1,4]-oxathiepin-5-one. [Table 3, Entry 1]
1
Solid, M.p. 58–60 ꢃC; IR (neat, cmꢀ1): 3434, 2924, 1711, 1246, 757, 698. H NMR
(200 MHz, CDCl3, d): 7.35 (m, 9H, Ar), 5.02 (t, 1H, J ¼ 5.8 Hz), 3.89 (dd, 2H,
J ¼ 7.3, 13.9 HZ). C13 NMR; 164.83, 144.54, 133.30, 131.11, 127.50, 77.32, 66.31.
ESIMS: m=z: 257[M þ 2].
2-(3-Chloro-2-hydroxypropylthio)benzoic acid. [Table 3, Entry 3] Solid,
1
M.p. 282–285 ꢃC; IR (neat, cmꢀ1): 3000, 2861, 1680, 1415, 1291, 738; H NMR
(200 MHz,CDCl3 þ DMSO,d): 8.06 (d, 1H, Ar, J ¼ 6.9 Hz), 7.41 (t, 1H, Ar,
J ¼ 6.1 Hz), 7.22 (t, 1H, Ar, J ¼ 6.1 Hz), 3.9 (t, 1H, J ¼ 5.3 Hz), 3.63 (t, 1H,
J ¼ 7.6 Hz), 3.50 (d, 2H, J ¼ 3.8 Hz), 3.09 (dd, 2H, J ¼ 5.3, 9.9 Hz), 2.56 (m, 1H);
EIMS (m=z): 247[M]þ.
ACKNOWLEDGMENTS
The authors thank Director, IICT for facilities, and M. S. thanks CSIR for the
financial support.
REFERENCES
1. Tanaka, K.; Toda, F. Foreword. In Solvent-Free Organic Synthesis; Wiley-VCH:
Weinheim, Germany, 2003.
2. Olah, G. A.; Vankar, Y. D.; Arvanghi, M. Synthetic methods and reactions. Conversion
of epoxides and enamines into a–haloketones with halodimethyl sulfonium halides. Tetra-
hedron Lett. 1979, 38, 3653–3656.

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M. SHAILAJA, A. MANJULA, AND B. VITTAL RAO
3. Das, B.; Holla, H.; Srinivas, Y. Efficient (bromodimethyl)sulfonium bromide mediated
synthesis of benzimidazoles. Tetrahedron Lett. 2007, 48, 61–64.
4. Vittal Rao, B.; Sucheta, K. (Bromodimethyl)sulfonium bromide: An inexpensive reagent
for the solvent–free, one pot synthesis of a-amino phophonates. Tetrahedron Lett. 2005,
46, 1209–1210.
5. Shailaja, M.; Manjula, A.; Vittal Rao, B. (Bromodimethyl) sulfonium bromide mediated
Michael addition of thiols to a,b-unsaturated ketones. J. Sulfur Chem. 2007, 28, 31–38.
6. Shailaja, M.; Manjula, A.; Vittal Rao, B. (Bromodimethyl) sulfonium bromide mediated
rapid and facile protection of amines. Org. Chem. Ind. J. 2006, 2, 5.
7. Shailaja, M.; Manjula, A.; Vittal Rao, B. Three component one pot synthesis of b-Amino
ketones mediated by (Bromodimethyl) sulfonium Bromide postet presented at
RRTSONPC-08, S. V. University, Thirupathi, India, February 25–26, 2008.
8. Lidy, W.; Sundermeyer, W. Spattungsreaktionen des trimethylsilylcyanids Durch Epoxide
Carbonsaurechloride, chorokohlensaureester und Sulfenylchloride. Tetrahedron Lett.
1973, 14, 1449–1450.
9. Mullis, J. C.; Weber, W. P. Regiospecificity of reactions of epoxides and oxetanes with
trimethyl silylcyanide. J. Org. Chem. 1983, 47, 2873–2875.
10. Blandy, C.; Choukroun, T. L.; Gervias, D. Gold(III) chloride promoted addition of
=
=
electron-rich heteroaromatic compounds to the C C and C O bonds of enals. Tetra-
hedron Lett. 1983, 47, 2871–2873.
11. Sinou, D.; Emziane, M. Overture regioselective depoxydes par Me3SiN3 catalysee par Ti
[oiPr]4.. Tetrahedron Lett. 1986, 27, 6423–6432.
12. Kesavan, V.; Daniele, B. D.; Begue, J. P. Highly Diastereoselective dihydroxylation of
Cis – Substituted sulfonyl vinyl oxiranes. Tetrahedron Lett. 2000, 41, 2871–2874.
13. Devan, N.; Sridhar, P. R.; Prabhu, R. K.; Chandrasekaran, S. Tetrathiomolybdate
assisted epoxide ring opening with masked thiolates and selenoates: Multistep reactionsin
one pot. J. Org. Chem. 2002, 67, 9417–9420.
14. Posner, G. H.; Rogers, D. Z. Organic reactions at alumina surfaces mild and selective
opening of epoxides by alcohols, thiols, benzeneselenol, amines and acetic acid. J. Am.
Chem. Soc. 1977, 99, 8208–8214.
15. Chini, M.; Crotti, E.; Giovani, E.; Macchia, F.; Pineschi, M. Ytterbium triflate and high
pressure mediated ring opening of epoxides. Synlett. 1992, 303–308.
16. Meguro, M.; Asao, N.; Yamamoto. Ytterbium triflate and high pressure-mediated ring
opening of epoxides with amines. J. Chem. Soc. Perkin Trans.1 1994, 2597–2601.
17. Cote, V.; Di Furia, F.; Licini, G.; Modena, G.; Valle, G. Enantioselective oxidation of b-
hydroxyl thioethers. Synthesis of optically active alcohols and epoxides. Tetrahedron
Assymmetry 1991, 2, 257–276.
18. Su, W.; Chen, J.; Wu, H.; Jin, C. A general and efficient method for the selective synthesis
of b-hydroxy sulfides and b-hydroxy sulfoxides catalyzed by gallium(III) triflate. J. Org.
Chem. 2007, 72, 4524–4527.
19. Gabbi, C.; Ghelfi, F.; Grandi, R. The preparation of b-hydroxyl sulfoxides. Synth. Com-
mun. 1997, 27, 2857–2863.
20. Luly, J. R.; Soderquist, N. Yi. H.; Stein, J.; Perun, T. J.; Plattner, J. J. New inhibitors of
human rennin that contain novel Leu-Val replacements. J. Med. Chem. 1987, 30, 1609–1616.
21. Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, C.; Mioskowski, B.; Hammarstro, S. S.
Stereospecific total synthesis of a slow reacting substance of anaphylaxis, Leukotriene
C-1. J. Am. Chem. Soc. 1980, 102, 3663–3670.
22. Corey, E. J.; Clark, D. A.; Goto, G. Total synthesis of slow reacting substances (SRS)
Leukotriene C-2(11-trans-leukotreiene c) (3) and Leukotriene D (4). Tetrahedron Lett.
1980, 21, 3143–3146.

EASY ACCESS TO b-HYDROXY SULFIDES
3639
23. Piper, G. M.; Siebeneich, W. Temocapril, an angiotensin converting enzyme inhibitor,
protects against diabetes-induced endothelial dysfunction. Eur. J. Phamacol. 2000, 403,
129–132.
24. Lesuisse, D.; Deprez, P.; Albert, E.; Duc, T. T.; Sortais, B.; Gofflo, D.; Jean-Baptiste, V.;
Marquette, J. P.; Schoot, B.; Sarubbi, E.; Lange, G.; Broto, P.; Mandine, E. Discovery of
thiazepinone Lignds for Src SH2; From non-specific to specific binding. Bioorg. Med.
Chem. Lett. 2001, 11, 2127–2131.
25. Ambliard, M.; Daffix, I.; Bedos, P.; Berge, G.; Pruneau, D.; Paquetr, J. L.; Luccarini, J.
M.; Belichard, P.; Dodey, P.; Martinez, J. Design and synthesis of potent Bradykinin
agonists containing a benzothiazepine moiety. J. Med. Chem. 1999, 42, 4185–4192.
26. Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vacaro, L. One pot synthesis benzo [e]
1,4-oxathiepin-5-one under solvent free condition via self – promoted thiolysis of 1,2–
epoxides. J. Org. Chem. 2004, 69, 8780–8785 (references cited therein).
27. Corbelli, F.; Monetti, F.; Tafi, A.; Nacci, V.; Botta, M. Diitiazem-like calcium entry
blockers: A Hypothesis of the receptors-binding site based on a comparative molecular
field analysis model. J. Med. Chem. 1997, 40, 125–131.
28. Peach, M. E. In The Chemistry of the Thiol Group; S. Patai (Ed.); John Wiley & Sons: New
York, 1974; Part 3, p. 771.
29. Chini, M.; Crotti, E.; Giovani, E.; Macchia, F.; Pineschi, M. Stereo and regioselective
metl salt-promoted Ring Opening of 1,2-epoxides with thiols in acetonitrile. Synlett.
1992, 303–305 (and references cited therein).
30. Vougioukas, A. E.; Kagan, H. B. Oxirane ring opening Reactions with thiols Catalyzed by
lanthanide complexes. Tetrahedron Lett. 1987, 28, 6065–6068.
31. Iqbal, J.; Padey, A.; Shukla, A.; Srivastava, R. R.; Tripathi, S. Cobalt mediated regiose-
lective ring opening of oxiranes with benzenethiol: A mechanistic study. Tetrahedron 1990,
28, 6423–6432.
32. Matti, A. K.; Battacharyya, P. Polyethylene glycol (PEG)4000 catalysed regioselective
nucleophilic ring opening of oxiranes-Anew and convenient synthesis of b-hydroxyl sul-
fone and b-hydroxyl sulfide. Tetrahedron 1994, 50, 10483–10490.
33. Lida, T.; Yamamoto, N.; Sasai, H.; Shibasaki, M. New asymmetric reactions using a gal-
lium complex: A highly enantioselective ring opening of epoxides with thiols catalyzed by
a gallium ꢄ lithium ꢄ bis(binaphthoxide) complex. J. Am. Chem. Soc. 1997, 119, 4783–4784.
34. Mukherjee, C.; Gour Hari, M.; Anup Kumar, M. Regioselective ring opening of epoxides
with thiols in water. ARKIVOC 2008, 11, 46–55.
35. Guindon, Y.; Young, R. N.; Frenette, R. Synthesis of b-trimethylsilyloxythioethers and b-
hydroxy thioethers. Synth. Commun. 1981, 11, 391–398.
36. De Pomar, J. C. J.; Soderquist, J. A. Regio and stereospecific synthesis of (o-TIPS) –
protected 2-hydroxyl alky lmercaptans from epoxides and trisopropylsilanethiol.
Tetrahedron Lett. 1998, 39, 4409–4412.
37. Buchanan, J. B.; Sable, H. Z.; Thyagarajan, B. S. (Ed.), In Selective Organic Transforma-
tions; Wiley-Interscience: New York, Vol. 2, 1972.
38. Vivek, P.; Kaushik, M. P. CSF-Celite catalyzed region- and chemoselective SN2 type ring
opening of epoxide with thiol. Catal. Commun. 2004, 5, 515–518.
39. Aziz, N.; Saidi, M. R. LiClO4 ꢄ 3H2O promoted highly regioselective ring-opening of epox-
ide with thiols under neutral conditions. Catal. Commun. 2006, 7, 224–227.
40. Yadav, J. S.; Reddy, B. V. S.; Gakul, B. Incl3-catalyzed highly regioselective ring opening
of epoxides with thiols. Chem. Lett. 2002, 906–907.