A facile and efficient one-pot synthesis of thiirans by the reaction of benzoxazolyl β-ketosulfides with NaBH4/NaOH

Article abstract of DOI:10.1016/j.tetlet.2007.12.058

Convenient and efficient procedures for thiirans have been developed via a one-pot reaction of benzoxazolyl β-ketosulfides with NaBH₄ and NaOH in MeOH and THF. The reaction is considered to proceed via the spiro intermediate by the ipso-additio

Full text of DOI:10.1016/j.tetlet.2007.12.058

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1166–1168
A facile and efficient one-pot synthesis of thiirans by the reaction
of benzoxazolyl b-ketosulfides with NaBH /NaOH
4
Nobuhiko Yamada, Masayoshi Mizuochi, Masahiro Takeda, Hiroyuki Kawaguchi,
Hiroyuki Morita *
Department of Material Systems Engineering and Life Science, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
Received 11 October 2007; revised 7 December 2007; accepted 11 December 2007
Available online 7 January 2008
Abstract
Convenient and efficient procedures for thiirans have been developed via a one-pot reaction of benzoxazolyl b-ketosulfides with
NaBH and NaOH in MeOH and THF. The reaction is considered to proceed via the spiro intermediate by the ipso-addition of
4
b-hydroxygroup, which is formed by the NaBH
Ó 2007 Elsevier Ltd. All rights reserved.
4
reduction of b-keto group, to 2-position of benzoxazole group.
Keywords: Thiirans; One-pot synthesis; b-Ketosulfides; Benzoxazole
8
Organosulfur compounds are useful and important in
organic synthesis. It is known that thiirans are the simplest
sulfur containing heterocycles, and they are important
building blocks in the field of polymer, pharmaceutical,
ture. To obtain thiirans in good yields without desulfur-
ization, the milder and more efficient reaction conditions
were required. However, we could not find the good result
in the reaction of benzothiazolyl b-hydroxysulfides. After
extensive work using other heterocyclic systems, we have
found a facile and efficient one-pot procedure. Herein, we
report the reactions of benzoxazolyl b-ketosulfides with
NaBH and NaOH in MeOH and THF.
The reactions of b-ketosulfides bearing several hetero-
aromatics, such as benzothiazole, benzoxazole, benzimid-
1
pesticide, and herbicide industries. Many methods for
the preparation of thiirans are reported. The most general
synthetic method is the conversion of oxirans to thiirans
2
3
with several sulfurated reagents such as thiourea, KSCN,
4
4
4
NH CN, and phosphine sulfides. Thiirans are also syn-
4
5
6
thesized from a-haloketones, 2-mercaptoalkanols, alde-
hydes, and ketones. However, some of these methods
7
azole, and 5-(1-phenyl)-1,2,3,4-tetrazole, with NaBH and
4
resulted in low yields, and sometimes required harsh reac-
tion conditions, long reaction time, and the aid of expen-
sive metal catalysts. The formation of polymeric product
is also seen as by product.
Recently, we reported that the thermolysis of benzo-
thiazolyl b-hydroxysulfides afforded the corresponding ole-
fins efficiently. The thermolysis is found to proceed via a
spiro intermediate to afford thiirans, which are successively
decomposed to olefins by desulfurization at high tempera-
NaOH were studied at rt. The results are summarized in
Table 1. In the case of benzothiazolyl b-ketosulfide 1, only
thiiran 5b was obtained in a trace yield with the formation
of the reduction product, namely, benzothiazolyl b-
hydroxysulfides (entry 1) after 30 min. When an excess base
was added and the reaction was continued for prolonged
reaction time, thiiran 5b was not obtained at all, but an
undesired polymerized product was formed, probably via
nucleophilic ring opening reaction of thiiran (Scheme 1).
In contrast, the reaction of benzoxazolyl b-ketosulfide 2b
with NaBH /NaOH was found to proceed very rapidly to
4
*
afford the corresponding thiiran 5b in a high yield as a sole
Corresponding author. Tel.: +81 76 445 6851; fax: +81 76 445 6703.
E-mail address: morita@eng.u-toyama.ac.jp (H. Morita).
product (entry 2). In comparison with benzothiazolyl
0
040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.058

N. Yamada et al. / Tetrahedron Letters 49 (2008) 1166–1168
1167
Table 1
reduction products, namely benzimidazolyl or 5-(1-
phenyl)-1,2,3,4-tetrazolyl b-hydroxysulfides, were formed
quantitatively, instead of 5b (entries 3 and 4). Probably,
in these cases the formation of spiro intermediates by the
ipso addition of b-hydroxy group will be retarded greatly
both electronically and sterically.
Reactions of b-ketosulfides bearing several heteroaromatics 1–4 with base
O
S
NaBH4 (1.0 equiv.), NaOH
S
THF/MeOH (1/1), rt
Ar
5
b
1
-4
To study the scope and limitations, b-ketosulfides bear-
ing benzoxazole having several substituents at a- and/or b-
positions 2a–e were prepared and their reactions under the
same conditions were carried out. The results are summa-
rized in Table 2. All reactions are found to afford the
corresponding thiiran 5a–e in good to excellent yields
within a short time. Interestingly, in the cases of 2c–e,
cis–trans selectivity for the formation of thiirans 5c–e
was observed (entries 3–5). The configuration and ratio
of cis-5c–d and trans-5c–d were determined by comparing
Entry
1
Ar
NaOH (equiv)
Time
Yield (%)
N
S
1.0
1.5
30 min
6 h
Trace
a
1
—
N
b
2
3
2b
3
1.0
2.0
5 min
6 h
88
O
N
c
0
N
H
1
9
Ph
N
with those of the reported H NMR spectra.
In summary, we have found a new and versatile synthetic
c
4
N
N
4
2.0
6 h
0
1
0
procedure for substituted thiirans using benzoxazolyl b-
ketosulfides. A variety of benzoxazolyl b-ketosulfides are
obtained easily from 2-mercaptobenzoxazole and b-halo-
ketones without any toxic and expensive reagents. Namely,
N
a
Complex mixture was obtained.
An isolated yield (not optimized).
Only b-hydroxysulfides were obtained quantitatively.
b
c
the reaction of 2a–e with NaBH and NaOH in MeOH/THF
4
b-hydroxysulfides, the very high reactivity of benzoxazolyl
derivative 2b-1 to provide the corresponding thiiran will be
explained by the more polar nature of N@C bond in benz-
oxazole ring, resulting in the acceleration of the formation
of spiro intermediate 2b-3. The plausible formation path-
way to 5b is illustrated in Scheme 1. First, 2b was reduced
Table 2
Thiiran formation from the reaction of a- and/or b-substituted benzox-
azolyl b-ketosulfides
R1
S
R2
O
NaBH4 (1.0 equiv.)
NaOH (1.0 equiv.)
S
N
O
R1
R2
THF/MeOH (1/1), rt
by NaBH to afford hydroxysulfides 2b-1, and then, the
4
5a-e
2
a-e
ipso addition of hydroxy group to 2-position of benzoxaz-
ole proceeded smoothly by OH catalysis to form spiro
1
2
a
À
Entry
R
R
Time (min) Yield (%) Ratio
b
(cis:trans)
intermediate (2b-2 to 2b-3). Successively, the spiro interme-
diate 2b-3 afforded the corresponding thiiran 5b concert-
edly or via the thiol anion 2b-4. The isolation of 5b is
easily performed by silica gel flash column chromato-
graphy after concentration. In cases of b-ketosulfides 3
and 4 bearing other heteroaryl groups, such as benzimid-
azole and 5-(1-phenyl)-1,2,3,4-tetrazole, the corresponding
1
2
3
4
5
a
H
H
Me
Ph
Ph
2a
5
5
74
88
76
94
90
—
—
2.0:1.0
6.0:1.0
7.0:1.0
2-Nap 2b
Ph
Ph
p-Tol
2c 10
2d 10
2e 10
p-Tol
Isolated yields (not optimized).
Estimated by H NMR.
b
1
O
S
R
R
-
R
HO
O
N
O
N
O
-
OH
N
O
NaBH4
MeOH/THF
S
S
MeOH/THF
2
b-2
2
b (R = 2-Nap)
2b-1
S
R
N
O
H
concertedly
ring opening
OH
+
-
N
O
S
R
5
b
6
O
H
N
S
R
O
S
N
O
R
O
O
2b-3
2b-4
4
Scheme 1. Probable mechanism for the reaction of b-ketosulfide 2b with NaBH /NaOH.

1168
N. Yamada et al. / Tetrahedron Letters 49 (2008) 1166–1168
solution afforded corresponding thiiran 5a–e in high yields
by one-pot procedure. The isolation of thiirans is quite eas-
ily attained without loss by the simple extraction with
4. (a) Bandgar, B. P.; Joshi, N. S.; Kamble, V. T. Tetrahedron Lett.
006, 47, 4775; (b) Sharghi, H.; Nejad, A. Phosphorus, Sulfur Silicon
2
Relat. Elem. 2004, 179, 2297.
5
. Yadav, L. D. S.; Kapoor, R. Synthesis 2002, 16, 2344.
CH Cl , followed by the silica gel flash chromatography.
2
2
6. Takata, T.; Endo, T. Bull. Chem. Soc. Jpn. 1988, 61, 1818.
7
8
. Johnson, C. R.; Tanaka, K. Synthesis 1976, 6, 413.
. Yamada, N.; Mizuochi, M.; Morita, H. Tetrahedron 2007, 63,
References and notes
3
408.
1
2
3
. Dittmer, D. C. In Thiirans and Thiirens in Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Elmsford,
NY, 1984; Vol. 7, pp 132–182.
. (a) Nasser, I.; Habib, F.; Abbas, J. Phosphorus, Sulfur Silicon Relat.
Elem. 2005, 180, 1809; (b) Takata, T.; Endo, T. Bull. Chem. Soc. Jpn.
9. Dybowaski, P.; Skowaronska, A. Synthesis 1997, 10, 1134.
10. A typical thiiran procedure for 5d: To a solution of NaOH
9
(0.50 mmol) and NaBH
was added 2d in 2.0 mL of anhydrous THF with stirring at rt under
. After 10 min, the reaction mixture was quenched by the addition
of water and extracted with 5.0 mL of CH Cl . The organic layer was
washed with brine and water and dried over anhydrous MgSO . The
4
(0.50 mmol) in 2.0 mL of anhydrous MeOH
N
2
1
988, 61, 1818.
. (a) Biswanath, D.; Reddy, V. S.; Krishnaiah, M. Tetrahedron Lett.
006, 47, 8471; (b) Bouda, H.; Borredon, M. E.; Delmas, M.; Gaset,
A. Synth. Commun. 1987, 17, 943.
2
2
4
2
purification was made by flash chromatography on silica gel to afford
thiiran 5d in 90% yield.