One-pot tandem synthesis of β-trimethylsilyloxy thioesters from thioacids, epoxides, and HMDS catalyzed by silica gel under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2012.667183

A procedure for one-pot preparation of β-trimethylsilyloxy thioesters from epoxides, thioacids, and hexamethyl disilazane (HMDS) in the presence of silica gel under solvent-free condition was developed. The desired silylated products were isolated in good

Full text of DOI:10.1080/00397911.2012.667183

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One-Pot Tandem Synthesis of β-
Trimethylsilyloxy Thioesters from
Thioacids, Epoxides, and HMDS
Catalyzed by Silica Gel Under Solvent-
Free Conditions
Mohammad Abbasi a
a Department of Chemistry, Faculty of Science, Persian Gulf
University, Bushehr, Iran
Version of record first published: 04 Apr 2013.
To cite this article: Mohammad Abbasi (2013): One-Pot Tandem Synthesis of β-Trimethylsilyloxy
Thioesters from Thioacids, Epoxides, and HMDS Catalyzed by Silica Gel Under Solvent-Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:13, 1759-1765
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Synthetic Communications1, 43: 1759–1765, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.667183
ONE-POT TANDEM SYNTHESIS OF
b-TRIMETHYLSILYLOXY THIOESTERS FROM
THIOACIDS, EPOXIDES, AND HMDS CATALYZED BY
SILICA GEL UNDER SOLVENT-FREE CONDITIONS
Mohammad Abbasi
Department of Chemistry, Faculty of Science, Persian Gulf University,
Bushehr, Iran
GRAPHICAL ABSTRACT
Abstract A procedure for one-pot preparation of b-trimethylsilyloxy thioesters from
epoxides, thioacids, and hexamethyl disilazane (HMDS) in the presence of silica gel under
solvent-free condition was developed. The desired silylated products were isolated in good to
excellent yields after silica-gel column chromatography.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Epoxide; hexamethyl disilazane; silica gel; solvent-free; thioacid; thioester
INTRODUCTION
The addition of sulfur nucleophiles to epoxides is a powerful tool for the
synthesis of b-hydroxy organosulfur compounds in organic synthesis. In this regard,
the addition of thioacids to epoxides has been applied for the preparation of
b-hydroxy thioesters in organosulfur synthesis. This reaction is important because
b-hydroxy thioesters are essential intermediates for the preparation of some bioac-
tive molecules.[1] In addition, thioester molecules are recognized as mild acyl transfer
agents[2] and important intermediates in the synthesis of acyl radicals,[3] ketones,[4]
heterocycles,[5] asymmetric aldols,[6] and biologically active compounds[7] in organic
synthesis. On the other hand, because of the ease of thioester linkage hydrolysis,
the addition of thioacids to epoxides provides a simple, mild, and efficient access
to precursors of b-hydroxy mercaptans in organic synthesis.[8] However, the reaction
of thioacids with oxiranes is limited to a few scattered reports in the literature.[9–12]
In this regard, the ring opening of cyclopentene oxides with thioacids in the presence
Received December 20, 2011.
Address correspondence to Mohammad Abbasi, Department of Chemistry, Faculty of Sciences,
Persian Gulf University, Bushehr 75169, Iran. E-mail: abbassi@pgu.ac.ir
1759

1760
M. ABBASI
of alumina,[9] ring opening of an epoxy ring in a steroidal molecule with thioacetic
acid,[10] and addition of potassium ethyl monothiocarbonate to cyclopentene oxide
and 1-butene oxide catalyzed by a Brønsted acid[11] are among the reports dealing
with this important reaction. The regioselective ring opening of structurally diverse
oxiranes with thioacids in water in the presence of b-cyclodextrin[12a] and in the
absence of any catalysts[12b] has been also reported in recent years.
In continuation of our interest in the development of organosulfur synthesis,[13]
we now report a novel and facile method for one-pot preparation of b-trimethylsilyloxy
thioesters from thioacids, epoxides, and hexamethyl disilazane (HMDS) on a silica-gel
surface.
RESULTS AND DISCUSSION
The development of efficient, economical, and environmentally benign proce-
dures for organic reactions has received increased attention in recent years. The
accomplishment of organic reactions under solvent-free conditions is certainly valu-
able from ecological and economical points of view. Meanwhile, solvent-free organic
reactions studies in the past three decades show that many synthetic processes in the
absence of solvents are faster, more efficient, and more convenient.[14] Therefore, we
studied the catalyst-free addition of thioacetic acid (2.1 mmol) to 2-(phenoxymethy-
l)oxirane (2 mmol) as a model reaction under solvent-free conditions at room
temperature. The reaction proceeded sluggishly, and after a prolonged reaction time
(24 h) the starting epoxide was recovered from the reaction mixture in nearly 55%
yield. Silica gel as an ecofriendly compound has been widely used as a heterogeneous,
cheap and mild catalyst in organic synthesis.[15] Hence, we studied the previously
mentioned reaction under similar conditions in the presence of silica gel 60 (70–230
mesh) (200 mg). The addition reaction proceeded cleanly and completed within 2 h,
which after extraction with EtOAc and neutralization with aqueous solution of
NaHCO3 gave the corresponding b-hydroxy thioester (0.443 g) in good purity (as
shown by thin-layer chromatography, TLC). The infrared (IR) spectrum of the crude
product showed a broad peak at 3450 cmꢀ1 (alcoholic OH stretching) and a sharp
peak at 1693 cmꢀ1 (thioesteric C O stretching). However, further purification by
=
column chromatography on silica gel failed because the product was contaminated
with its b-acyloxy mercaptan isomer during the process. The 1H NMR and IR spectra
analysis of the mixture showed the presence of –OH, -SH, esteric, and thioesteric
=
C O functionalities. This isomerization process was a general trend for the reaction
of structurally diverse epoxides and thioacids. A likely pathway for this rearrange-
ment is presented in Scheme 1.
Scheme 1. Proposed pathway for the conversion of b-hydroxy thioester to b-acyloxy mercaptan and vice
versa.

ADDITION OF THIOACIDS TO EPOXIDES
1761
Table 1. One-pot tandem synthesis of b-trimethylsilyloxy thioesters from thioacids, epoxides, and HMDS
catalyzed by SiO2
Entry
1
Epoxide
R’
t (min)
Product
Yield (%)
93
CH3
90 (1)
2
3
4
Ph
CH3
Ph
100 (2)
120 (3)
120 (4)
89
91
90
5
6
CH3
Ph
90 (5)
90 (6)
95
91
7
8
CH3
Ph
60 (7)
70 (8)
84
82
9
10
11
12
CH3
Ph
60 (9)
60 (10)
60 (11)
60 (12)
88
85
86
CH3
Ph
90
(Continued )

1762
M. ABBASI
Table 1. Continued
Entry
13
Epoxide
R’
t (min)
Product
Yield (%)
85
CH3
75 (13)
70 (14)
14
15
Ph
84
85
CH3
60 (15)
70 (16)
16
Ph
83
To eliminate side reactions under the purification process, the hydroxyl
function of b-hydroxy thioester was first protected as b-trimethylsilyloxy thioester.
In this regard, hexamethyldisilazane (HMDS) (2 mmol) was added to the mixture
at the end of the reaction between 2-(phenoxymethyl)oxirane (2 mmol) and thioace-
tic acid (2.1 mmol), and the stirring was continued for another 10–15 min at room
temperature. The corresponding b-trimethylsilyloxy thioester was successfully iso-
lated in 91% yield after silica-gel column chromatography. The scope and generality
of this process is illustrated with respect to various epoxides, thioacetic, and thioben-
zoic acids in Table 1.
As is evident, the ring opening of the terminal epoxides with thioacids was
mostly achieved regioselectively by preferential attack at the less-hindered carbon
atom of the epoxide. 2,3-Epoxypropyl methacrylate (Table 1, entries 13 and 14)
under similar reaction conditions produced selectively the product from the ring-
opening reaction of the epoxide instead of the expected Michael addition reaction.
In conclusion, we have developed a mild, efficient, and convenient procedure
for one-pot synthesis of b-trimethylsilyloxy thioesters from the reaction of thioacids,
epoxides, and HMDS under solvent-free conditions at room temperature. The
process was efficiently catalyzed by a small portion of silica gel, which produces
the corresponding b-trimethylsilyloxy thioesters in good to excellent yields. The b-
trimethylsilyloxy thioesters can be easily deprotected to the corresponding b-hydroxy
thioesters under mild conditions.[15]
EXPERIMENTAL
All yields refer to the pure isolated products. Chemicals were purchased from
different chemical companies. IR spectra were run on a Shimadzu Fourier transform
(FT)–IR 8300 spectrophotometer. 1H NMR and 13C NMR spectra were recorded in

ADDITION OF THIOACIDS TO EPOXIDES
1763
CDCl3 using a Bruker Avance DPX instrument (1H NMR 250 MHz, 13C NMR
62.5 MHz). Chemical shifts are reported in parts per million (d) downfield from tet-
ramathylsilane (TMS). Coupling constants (J) are in hertz. Elemental analyses were
run on a Thermo Finnigan Flash EA-1112 series. Thin-layer chromatography (TLC)
was carried out on silica-gel 254 analytical sheets obtained from Fluka. Column
chromatography was performed on Merck silica gel 60 (70–230 mesh).
General Procedure for One-Pot Preparation of b-Trimethylsilyloxy
Thioesters Using Epoxides, Thioacids, and HMDS at Room
Temperature in the Absence of Solvent
Thioacid (2.1 mmol), epoxide (2 mmol), and silica gel 60 (70–230 mesh)
(200 mg) were added together, and the mixture were stirred magnetically at room
temperature for the appropriate reaction time as indicated in Table 1. The progress
of the reaction was monitored by TLC and gas chromatography (GC). After com-
pletion of the reaction, HMDS (2 mmol) was added, and the resulting mixture was
stirred magnetically for 10–15 min. Then, the crude product was directly purified
by silica-gel chromatography, using petroleum ether=ethyl acetate (20=1) as eluent
to provide the desired product in good to excellent yields (Table 1).
S-f3-Butoxy-2-[(trimethylsilyl)oxy]propylgethanethioate (1)
Colorless oil; 1H NMR (250 MHz, CDCl3) d: 3.79–3.70 (m, 1H), 3.29
(t, J ¼ 6.5 Hz, 2H), 3.22 (d, J ¼ 5.3 Hz, 2H), 2.98 (dd, J ¼ 13.7, 5.2 Hz, 1H), 2.80
(dd, J ¼ 13.7, 6.9 Hz, 1H), 2.19 (s, 3H), 1.47–1.36 (m, 2H), 1.31–1.19 (m, 2H), 0.78
(t, J ¼ 7.3 Hz, 3H), 0.00 (s, 9H); 13C NMR (62.5 MHz, CDCl3) d: 194.8, 73.9, 71.1,
70.7, 33.1, 31.6, 30.2, 19.1, 13.7, 0.0; IR (neat): n (cmꢀ1) ¼ 1695 (C O thioester).
=
Anal. calcd. for (C12H26O3SSi): C, 51.75; H, 9.41; S, 11.51. Found: C, 51.57; H,
9.43; S, 11.39.
S-f3-Butoxy-2-[(trimethylsilyl)oxy]propylgbenzenecarbothioate (2)
Colorless oil; 1H NMR (250 MHz, CDCl3) d: 7.84–7.80 (m, 2H), 7.41–7.35 (m,
1H), 7.29–7.23 (m, 2H), 3.89–3.80 (m, 1H), 3.32–3.27 (m, 4H), 3.18 (dd, J ¼ 13.5,
5.2 Hz, 1H), 3.00 (dd, J ¼ 13.5, 6.8 Hz, 1H), 1.47–1.35 (m, 2H), 1.30–1.15 (m, 2H),
0.76 (t, J ¼ 7.3 Hz, 3H), 0.00 (s, 9H); 13C NMR (62.5 MHz, CDCl3) d: 191.2,
136.9, 133.0, 128.3, 126.9, 73.9, 71.1, 70.4, 33.0, 31.5, 19.0, 13.6, 0.0; IR (neat): n
(cmꢀ1) ¼ 1666 (C O thioester), 1597 (C C aromatic). Anal. calcd. for (C17H28
=
=
O3SSi): C, 59.96; H, 8.29; S, 9.42. Found: C, 59.91; H, 8.46; S, 9.59.
S-f3-Phenoxy-2-[(trimethylsilyl)oxy]propylgethanethioate (3)
Colorless oil; 1H NMR (250 MHz, CDCl3) d: 7.12–7.05 (m, 2H), 6.78–6.68 (m,
3H), 3.98–3.90 (m, 1H), 3.79–3.66 (m, 2H), 3.00 (dd, J ¼ 13.7, 5.5 Hz, 1H), 2.86
(dd, J ¼ 13.7, 6.4 Hz, 1H), 2.14 (s, 3H), 0.00 (s, 9H); 13C NMR (62.5 MHz, CDCl3)

1764
M. ABBASI
d: 194.6, 158.3, 129.2, 120.6, 114.3, 70.6, 69.8, 32.9, 30.2, 0.0; IR (neat): n (cmꢀ1) ¼
=
1695 (C O thioester), 1601 (C C aromatic). Anal. calcd. for (C14H22O3SSi): C,
=
56.34; H, 7.43; S, 10.74. Found: C, 56.42; H, 7.30; S, 10.56.
SUPPLEMENTAL MATERIAL
1H NMR, 13C NMR, and IR spectra and elemental analysis data of all
products are provided as Supplemental Material available online.
ACKNOWLEDGMENT
We gratefully acknowledge the support of this study by the Persian Gulf
University Research Council.
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