A facile synthesis of thiazole-2(3H)-thiones through [hydroxy(tosyloxy) iodo]benzene

Article abstract of DOI:10.1081/SCC-200025631

A one-pot facile synthesis of thiazole-2(3H)-thiones (4) has been achieved by hypervalent iodine oxidation of ketones (1) using [hydroxy (tosyloxy)iodo]benzene, followed by the treatment of the reaction mixture with dithiocarbamate salts (3) The intermediate α-tosyloxy-ketones (2) have also been isolated and converted to the target compounds.

Full text of DOI:10.1081/SCC-200025631

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A Facile Synthesis of
Thiazole‐2(3H)‐thiones
Through
[Hydroxy(tosyloxy)iodo]benzene
Ranjana Aggarwal a , Rashmi Pundeer a , Vinod
Kumar a , Vishwas Chaudhri a , Shiv P. Singh a & Om
Prakash a
a Chemistry Department , Kurukshetra University ,
Kurukshetra, 136119, Haryana, India
Published online: 10 Jan 2011.
To cite this article: Ranjana Aggarwal , Rashmi Pundeer , Vinod Kumar ,
Vishwas Chaudhri , Shiv P. Singh & Om Prakash (2004) A Facile Synthesis of
Thiazole‐2(3H)‐thiones Through [Hydroxy(tosyloxy)iodo]benzene, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:14, 2659-2664, DOI: 10.1081/SCC-200025631
To link to this article: http://dx.doi.org/10.1081/SCC-200025631
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 14, pp. 2659–2664, 2004
A Facile Synthesis of Thiazole-2(3H)-thiones
Through [Hydroxy(tosyloxy)iodo]benzene
Ranjana Aggarwal, Rashmi Pundeer, Vinod Kumar,
Vishwas Chaudhri, Shiv P. Singh,
*
and Om Prakash
Chemistry Department, Kurukshetra University,
Kurukshetra, Haryana, India
ABSTRACT
A one-pot facile synthesis of thiazole-2(3H)-thiones (4) has been
achieved by hypervalent iodine oxidation of ketones (1) using [hydroxy
(tosyloxy)iodo]benzene, followed by the treatment of the reaction
mixture with dithiocarbamate salts (3). The intermediate a-tosyloxy-
ketones (2) have also been isolated and converted to the target
compounds.
*
Correspondence: Om Prakash, Chemistry Department, Kurukshetra University,
Kurukshetra 136119, Haryana, India.
2659
DOI: 10.1080/SCC-200025631
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2660
Aggarwal et al.
INTRODUCTION
The use of [hydroxy(tosyloxy)iodo]benzene (HTIB or Koser’s reagent) in
organic synthesis has been recognized in recent years.[1] One of the most
important reactions of HTIB particularly a-tosyloxylation of carbonyl com-
pounds, was first reported in 1982 by Koser et al.[2] Recent work from our
laboratory has shown that HTIB mediated preparation of a-tosyloxyketones
can offer a superior alternative to the existing synthesis of a variety of hetero-
cycles involving lachrymatric a-haloketones.[3] As an example, the reaction of
a-tosyloxyketones with thioureas or thioamides leading to the formation of a
large number of 2-aminoalkyl/aryl thiazoles not only avoids the use of
a-haloketones but has also provided an one-pot procedure.[4] However, the
reaction of a-tosyloxyketones as a substitute of a-haloketones with dithiocar-
bamate salt for the synthesis of biologically important thiazole-2(3H)-thione is
yet to be explored.[5]
Based on our previous work, the synthesis of 4 could be achieved by two
alternative methods as outlined in Sch. 1. The synthesis of thiazole-2(3H)-
thiones was first attempted in a stepwise manner via the isolation of inter-
mediate a-tosyloxyketones (Method A). The reported a-tosyloxyketones
were treated with dithiocarbamate salt (3a) in ethanol to give 4-aryl-2,3-
dihydro-3H-thiazole-2-thiones (4a–d) in 62–84% yield. The formation
of 4 was confirmed by comparing their mp. with those reported in the
literature.[5–8] Encouraged by the results of stepwise procedure, the one-pot
Scheme 1.

Synthesis of Thiazole-2(3H)-thiones Through HTIB
2661
reaction (Method B) to obtain the title compounds starting from enolizable
ketones was attempted.
The ketones 1 were oxidized with HTIB in acetonitrile followed by treat-
ment with dithiocarbamate (3a) salt afforded 4 in comparable yields.
The generality of this methodology was illustrated by using different
ketones and dithiocarbamate salts namely, 2-acetylthiophene, acetylacetone,
and phenylammonium dithiocarbamate salt. The one-pot procedure with all
the ketones afforded the respective thiazole-2(3H)-thiones in excellent
yields with ammonium and phenylammonium salts (Table 1).
Finally, the hypervalent iodine mediated approach for the synthesis of
title compounds is significant because of a large number of alkyl, aryl andhe-
terocyclylthiazole-2(3H)-thione derivatives would be prepared and avoids the
use of highly toxic, unstable, and lachrymatory a-haloketones.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
1H NMR spectra were recorded on Brucker 300 MHz instrument using TMS
as an internal standard. Dithiocarbamate salts[9,10] and a-tosyloxyketones[2,4d]
were prepared according to literature procedure.
Experimental Procedure
Method A: Synthesis of 4 via Isolation of a-Tosyloxyketone
A suspension of dithiocarbamate salt of ammonia (3a) (1.1 g, 10 mmol) in
ethanol (10 mL) and a-tosyloxyacetophenone (2a) (2.9 g, 10 mmol) in ethanol
(20 mL) were stirred for 1 hr and then refluxed for 5 hr. The excess of solvent
was removed, the solid residue was washed with ethanol, and dissolved in
10% NaOH solution. The solution was neutralized with dil. HCl, solid filtered,
washed with water, and recrystallized from ethanol to give 4a, yield (1.42 g,
74%), mp. 1688C (Lit.[2] mp. 1688C). Other products 4b–d, j–l were syn-
thesized by the same procedure.
In cases 4e–i, the solid residue obtained was purified by recrystallization
from ethanol.
Method B: One-pot Synthesis of the Compounds 4a–l
A mixture of 1a (1.2 g, 10 mmol) in acetonitrile (20 mL) and HTIB
(4.31 g, 11 mmol) was refluxed for 2 hr and concenterated. The residue was

2662
Aggarwal et al.
Table 1. Characterization data of thiazole-2(3H)-thiones (4a–l).
Compound
4a
M.p.
(8C)
Lit. m.p.
(8C)
Yield
(%)b
R
R1
C6H5
R2
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
H
H
H
168
198
211
193
135
247
133
138
155
210
175
166
168[5]
199[5]
214[5]
194[5]
135[6]
250[6]
134[6]
141[6]
74 (67)
82 (74)
76 (71)
76 (65)
85 (77)
72 (65)
69 (62)
75 (69)
80 (72)
4-ClC6H4
4-BrC6H4
4-OMeC6H4
C6H5 C6H5
C6H5 4-ClC6H4
C6H5 4-BrC6H4
C6H5 4-MeC6H4
C6H5 4-OMeC6H4
g
h
i
c
—
j
H
H
H
CH3
COCH3
210–211[7] 73 (66)
k
l
2-Thienyl
4-OCH2CO2
EtC6H4
H
H
177[8]
74 (69)
77 (72)
c
—
a1H NMR (CDCl3 þ DMSO, d): 4a, 6.76 (s, 1H, H-5), 7.35–7.45 (m, 5H, C6H5); 4b,
6.72 (s, 1H, H-5), 7.38–7.47 (m, 4H, C6H4); 4c, 6.87 (s, 1H, H-5), 7.54 (d, J ¼ 8.6 Hz,
2H, H-20,60), 7.74 (d, J ¼ 8.5 Hz, 2H, H-30,50); 4d, 3.85 (s, 3H, OCH3), 6.58 (s, 1H, H-5),
6.97 (d, J ¼ 8.8 Hz, 2H, H-20,60), 7.46 (d, J ¼ 8.7 Hz, 2H, H-30,50); 4e, 6.66 (s, 1H, H-5),
7.09–7.40 (m, 10H, C4-C6H5, N-C6H5); 4f, 6.64 (s, 1H, H-5), 7.37–7.46 (m, 4H,
C4-C6H4), 7.16–7.20 (m, 5H, N-C6H5); 4g, 6.64 (s, 1H, H-5), 7.16–7.36 (m, 5H,
N-C6H5), 7.51 (d, J ¼ 8.3 Hz, 2H, H-20,60), 7.69 (d, J ¼ 8.3 Hz, 2H, H-30,50); 4h, 2.28
(s, 3H, CH3), 6.73 (s, 1H, H-5), 6.96 (d, J ¼ 9.0 Hz, H-30,5), 7.05 (d, J ¼ 9.0 Hz, 2H,
H-20,60), 7.16–7.46 (m, 5H, N-C6H5); 4i, 3.75 (s, 3H, OCH3), 6.57 (s, 1H, H-5),
6.72–7.40 (m, 9H, N-C6H5, C4-C6H5); 4j, 2.39 (s, 3H, C4-CH3), 2.57 (s, 3H, C5-
COCH3); 4k, 6.73 (s, 1H, H-5), 7.12–7.16 (m, 1H, thienyl-4H), 7.56–7.60 (m, 1H,
thienyl-3H), 7.64–7.64 (m, 1H, thienyl-5H); 4l, 1.18–1.25 (t, J ¼ 7.1 Hz, 3H,
–CO2CH2CH3), 4.19–4.26 (q, J ¼ 6.9 Hz, 2H, –CO2CH2), 4.60 (s, 2H, –OCH2),
6.76 (s, 1H, H-5), 6.82–6.87 (m, 2H, H-30,50), 7.37–7.42 (m, 2H, H-20,60).
bYields in parenthesis correspond to Method A.
cElemental analyses (C, H, N) were satisfactory.
dissolved in ethanol (10 mL) and solution of compound 3a (1.1 g, 10 mmol) in
ethanol (10 mL) was introduced. The resultant mixture was heated under
reflux for 5 hr. The solid was processed as described earlier to obtain 4a
(1.35 g, 70%), mp. 1688C (Lit. mp. 1688C).

Synthesis of Thiazole-2(3H)-thiones Through HTIB
2663
ACKNOWLEDGMENT
We are grateful to DRDO (ERIP/ER/0103294/M/01) and UGC,
New Delhi for financial assistance.
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Received January 28, 2004