Efficient synthesis of-Hydroxy sulfides and-Hydroxy sulfoxides catalyzed by Cu/MgO under solvent-free conditions

Article abstract of DOI:10.1080/00397910903219500

Regio-, stereo-, and chemoselective ring opening of epoxides with thiols using Cu/MgO as a heterogeneous catalyst has efficiently been carried out to produce the corresponding β-hydroxy sulfides in excellent yields at room temperature under solvent-free c

Full text of DOI:10.1080/00397910903219500

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Efficient Synthesis of β-Hydroxy Sulfides
and β-Hydroxy Sulfoxides Catalyzed by
Cu/MgO Under Solvent-Free Conditions
Biswanath Das a , Penagaluri Balasubramanyam a , Maddeboina
Krishnaiah a , Boyapati Veeranjaneyulu a & Dega Sudhakar a
a Organic Chemistry Division I , Indian Institute of Chemical
Technology , Hyderabad, India
Published online: 17 Jun 2010.
To cite this article: Biswanath Das , Penagaluri Balasubramanyam , Maddeboina Krishnaiah , Boyapati
Veeranjaneyulu & Dega Sudhakar (2010) Efficient Synthesis of β-Hydroxy Sulfides and β-Hydroxy
Sulfoxides Catalyzed by Cu/MgO Under Solvent-Free Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:14, 2113-2121,
DOI: 10.1080/00397910903219500
To link to this article: http://dx.doi.org/10.1080/00397910903219500
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Synthetic Communications1, 40: 2113–2121, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219500
EFFICIENT SYNTHESIS OF b-HYDROXY SULFIDES AND
b-HYDROXY SULFOXIDES CATALYZED BY Cu/MgO
UNDER SOLVENT-FREE CONDITIONS
Biswanath Das, Penagaluri Balasubramanyam,
Maddeboina Krishnaiah, Boyapati Veeranjaneyulu,
and Dega Sudhakar
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Regio-, stereo-, and chemoselective ring opening of epoxides with thiols using Cu/MgO as a
heterogeneous catalyst has efficiently been carried out to produce the corresponding
b-hydroxy sulfides in excellent yields at room temperature under solvent-free conditions.
The treatment of the epoxides with thiols and 50% aqueous H2O2 in the presence of the
same catalyst at room temperature affords the b-hydroxy sulfoxides in excellent yields.
Keywords: Cu=MgO; epoxide; H2O2; b-hydroxy sulfide; b-hydroxy sulfoxide; thiol
INTRODUCTION
b-Hydroxy sulfides are important intermediates for the synthesis of pharma-
ceuticals and natural products.[1–3] The ring opening of epoxides with thiols is a
straightforward route to b-hydroxy sulfides. The conversion usually takes place in
the presence of a promoter such as alumina,[4] silica gel,[5] resin,[6] or a common=
complex Lewis acid.[7–13] However, harsh reaction conditions, long reaction times,
poor yields, and use of an expensive catalyst are drawbacks in many of the
methods. Here we report an efficient method for the preparation of b-hydroxy
sulfides by ring opening of epoxides with thiols in the presence of Cu=MgO as a
heterogeneous catalyst. The method has also been extended for the preparation of
b-hydroxy sulfoxides using the same catalyst.
RESULTS AND DISCUSSION
In continuation of our work[14–16] on the development of useful synthetic
methodologies, we have observed that the ring opening of epoxides with thiols can
be carried out efficiently using Cu=MgO as a catalyst at room temperature (Scheme 1).
Received April 28, 2009.
Part 170 in the series ‘‘Studies on Novel Synthetic Methodologies.’’
Address correspondence to Biswanath Das, Organic Chemistry Division I, Indian Institute of
Chemical Technology, Hyderabad, India. E-mail: biswanathdas@yahoo.com
2113

2114
B. DAS ET AL.
Scheme 1. Synthesis of b-hydroxy sulfides from epoxides using Cu=MgO.
A series of epoxides was converted into the corresponding b-hydroxy sulfides
on treatment with different thiols following this procedure (Table 1). The conversion
was complete within 20–30 min. The products were formed in excellent yields
(82–95%). 2-Phenyl, 2-alkyl, and bicyclic epoxides undewent the conversion
smoothly. Both aromatic and aliphatic thiols afforded the products with equal ease.
The formation of b-hydroxy sulfides from epoxides took place with high regio-,
stereo-, and chemoselectivity. 2-Phenyl epoxide formed the products by attack of the
thiols mainly at the benzylic position, and 2-alkyl epoxides furnished the products by
1
attack at the terminal position. The H NMR spectra of the crude products showed
the formation of only 3 from 2-alkyl epoxides and the formation of 4 (along with a
minor amount of 3) from styrene oxide.
The ring opening of a bicyclic epoxide with a thiol occurred with anti selectivity
1
to form the product with trans configuration. In the H NMR spectrum of the pro-
duct, the coupling constants of the ring protons adjacent to the ꢀOH and ꢀSR1
groups support this stereochemical assigment. For example, the J values of these
two protons for 3n (Table 1) are 9.5, 9.0, and 4.2 Hz and 9.2, 9.0, and 4.0 Hz, suggest-
ing the trans configuration of the compound.
The present conversion is also chemoselective, because an epoxide opened with
a thiol containing a hydroxyl group afforded only the sulfide (not a thiol) (Table 1,
entries d, e, and r), indicating that the hydroxyl group did not attack the epoxide ring.
The work has been extended to the one-pot preparation of b-hydroxy sulfox-
ides, which are also important intermediates in organic synthesis for the preparation
of natural products.[17–19] There are only a limited number of methods for one-pot
conversion of epoxides into b-hydroxy sulfoxides.[20,13] These compounds can be
prepared by treatment of epoxides with thiols and 50% aqueous H2O2 in the presence
of the same catalyst (Cu=MgO) at room temperature (Scheme 2).
Various epoxides were reacted with different thiols following this method to
form a series of b-hydroxy sulfoxides (Table 2). The conversion was complete within
70 min in water medium, and the products were formed in excellent yields. All alkyl
epoxides afforded only one regioisomer formed by attack of the thiols at the terminal
position followed by oxidation. The bicyclic cyclohexene oxide furnished the trans
product (Table 2, entry j). Two diastereomers (82:18) of this product was separated
by column chromotography. However, the diastereomers of the other products
could not be separated. Both aromatic and aliphatic thiols were applied for the prep-
aration of b-hydroxy sulfoxides. Here also a thiol containing a hydroxyl group
afforded only a b-hydroxy sulfoxide. No sulfone could be detected.
The catalyst, Cu=MgO,[21,22] works under heterogeneous conditions. It can
conveniently be handled and removed from the reaction mixture. It is inexpensive
and can easily be prepared from the readily available Cu(NO3)2 and Mg(NO3)2
following the coprecipitation method. The catalytic activity of Cu=MgO in organic

2115

2116

SYNTHESIS OF b-HYDROXY SULFIDES AND b-HYDROXY SULFOXIDES
2117
Scheme 2. Synthesis of b-hydroxy sulfoxides from epoxides using Cu=MgO.
synthesis has not yet been properly explored. Here this catalyst has been found to be
highly effective for the preparation of b-hydroxy sulfides and b-hydroxy sulfoxides.
In absence of this catalyst, the present conversion afforded the products with poor
yields after longer reaction time.
CONCLUSION
In conclusion, we have developed efficient, mild, and selective methods for
organic solvent–free, high-yielding synthesis of b-hydroxy sulfides and b-hydroxy
sulfoxides using very small quantities of an ecofriendly heterogeneous catalyst,
Cu=MgO, for the first time.
EXPERIMENTAL
General Procedure for the Synthesis of b-Hydroxy Sulfides
Cu=MgO (5 mg) was added to a mixture of an epoxide (2 mmol) and a thiophe-
nol (2 mmol). The mixture was stirred at room temperature, and the reaction was
monitored by thin-layer chromatography (TLC). After completion, the reaction mix-
ture was diluted with EtOAc (10 mL) and filtered to remove the catalyst. The filtrate
was concentrated, and the residue was subjected to column chromatography (silica
gel, hexane–EtOAc) to obtain pure b-hydroxy sulfide.
General Procedure for the Synthesis of b-Hydroxy Sulfoxides
Cu=MgO (5 mg) was added to a mixture of an epoxide (2 mmol) and a thiophe-
nol (2 mmol). The mixture was stirred at room temperature. After completion of the
ring-opening reaction (monitered by TLC), 50% aqueous H2O2 (4 mL) was added at
0 ꢁC over 5 min. The reaction mixture was stirred continuously at room temperature.
At the end of the reaction, excess H2O2 was destroyed by addition of saturated aque-
ous Na2SO3 solution. The mixture was extracted with EtOAc (3 ꢂ 10 mL), and the
total extract was dried over Na2SO4 and concentrated. The residue was purified
by column chromotography (silica gel, hexane–EtOAc) to isolate pure b-hydroxy
sulfoxide.
Spectral Data for Unknown Compounds
The spectral (1H NMR and MS) and analytical data of the unknown products
are given below.

2118
B. DAS ET AL.
Table 2. Synthesis of b-hydroxy sulfoxides catalyzed by Cu=MgOa
Isolated
yield
(%)
Entry
Epoxide
Thiol
Product (5)
a
91
89
b
c
90
d
e
85
87
f
85
91
g
h
89
(Continued )

SYNTHESIS OF b-HYDROXY SULFIDES AND b-HYDROXY SULFOXIDES
Table 2. Continued
2119
Isolated
yield
(%)
Entry
Epoxide
Thiol
Product (5)
i
91
j
82b
aThe structures of the products were established from their spectral (1H NMR and MS) data.
bDiastereomeric (82:18) mixture determined by 1H NMR analysis.
Compound 3d. 1H NMR (200 MHz, CDCl3): d 7.09 (2H, d, J ¼ 8.0 Hz), 6.80
(2H, d, J ¼ 8.0 HZ), 4.10 (1H, m), 3.99–3.92 (2H, m), 3.84 (1H, m), 3.72 (1H, m),
3.56–349 (2H, m), 3.34 (3H, s), 2.89–2.70 (6H, m); ESIMS: m=z 309 [M þ Na]þ.
Compound 3g. 1H NMR (200 MHz, CDCl3): d 7.30 (2H, d, J ¼ 8.0 Hz), 7.09
(2H, d, J ¼ 8.0 Hz), 3.82 (1H, m), 3.64 (2H, d, J ¼ 4.0 Hz), 3.15–2.93 (2H, m), 2.66
(1H, brs), 2.32 (3H, s); ESIMS: m=z 241, 239 [M þ Na]þ.
Compound 3n. 1H NMR (200 MHz, CDCl3): d 7.39 (2H, d, J ¼ 8.0 Hz), 7.27
(2H, d, J ¼ 8.0 Hz), 3.28 (1H, ddd, J ¼ 9.5, 9.0, 4.2 Hz), 2.78 (1H, brs), 2.70 (1H, ddd,
J ¼ 9.2, 9.0, 4.0 Hz), 2.20–2.01 (2H, m), 1.80–1.61 (2H, m), 1.38–1.16 (4H, m);
ESIMS: m=z 267, 265 [M þ Na]þ.
Compound 4b. 1H NMR (200 MHz, CDCl3): d 7.31–7.14 (7H, m), 7.01 (2H,
d, J ¼ 8.0 Hz), 4.19 (1H, t, J ¼ 7.0 Hz), 3.82 (2H, d, J ¼ 7.0 Hz), 2.31 (3H, s); ESIMS:
m=z 267 [M þ Na]þ.
Compound 5d. 1H NMR (200 MHz, CDCl3): d 7.32–7.15 (2H, m), 6.97–6.83
(3H, m), 5.77 (1H, brs), 5.30 (1H, brs), 4.48 (1H, m), 4.05–3.87 (4H, m), 3.57–3.40
(2H, m), 3.31–3.11 (2H, m); ESIMS: m=z 267 [M þ Na]þ.
Compound 5f. 1H NMR (200 MHz, CDCl3): d 7.81 (2H, d, J ¼ 8.0 Hz), 7.39
(2H, d, J ¼ 8.0 Hz), 4.26 (1H, m), 3.42 (1H, brs), 3.21–3.01 (2H, m), 2.49 (3H, s), 1.22
(3H, d, J ¼ 7.0 Hz); ESIMS: m=z 221 [M þ Na]þ.
Compound 5j (major diastereomer). 1H NMR (200 MHz, CDCl3): d 7.68
(2H, d, J ¼ 8.0 Hz), 7.52 (2H, d, J ¼ 8.0 Hz), 4.69 (1H, brs), 4.02 (1H, ddd, J ¼ 9.5,
9.0, 4.2 Hz), 2.62 (1H, ddd, J ¼ 9.5, 9.0, 4.5 Hz), 2.20–2.01 (2H, m), 1.81–1.60 (2H,
m), 1.50–1.09 (4H, m); ESIMS: m=z 283, 281 [M þ Na]þ.

2120
B. DAS ET AL.
Compound 5j (minor diastereomer). 1H NMR (200 MHz, CDCl3): d
7.58–7.47 (4H, brs), 3.85 (1H, ddd, J ¼ 9.5, 9.0, 4.0 Hz), 3.31 (1H, brs), 2.51 (1H,
ddd, J ¼ 9.2, 9.0, 4.0 Hz), 2.17–1.91 (2H, m), 1.89–1.62 (2H, m), 1.49–1.10 (4H,
m); ESIMS: m=z 283, 281 [M þ Na]þ.
ACKNOWLEDGMENTS
The authors thank the Council of Scientific and Industrial Research and the
University Grants Commission, New Delhi, for financial assistance.
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