HTIB-mediated one-pot synthesis of some 2-substituted 4-styrylthiazoles from (E)-4-arylbut-3-en-2-ones

Article abstract of DOI:10.1080/00397911.2011.604815

The reaction of (E)-4-arylbut-3-en-2-ones with [(hydroxy(tosyloxy)iodo] benzene (HTIB) followed by treatment with thioureas, thioamide, and thiobenzamide has offered a one-pot synthesis of 2-substituted 4-styrylthiazoles. Supplemental materials are availa

Full text of DOI:10.1080/00397911.2011.604815

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HTIB-Mediated One-Pot Synthesis of
Some 2-Substituted 4-Styrylthiazoles
from (E)-4-Arylbut-3-en-2-ones
Om Prakash a , Nitya Sharma b & Pooja Ranjan b
a Institute of Pharmaceutical Sciences, Kurukshetra University,
Kurukshetra, India
b Department of Chemistry, Kurukshetra University, Kurukshetra,
India
Accepted author version posted online: 13 Feb 2012.Version of
record first published: 08 Nov 2012.
To cite this article: Om Prakash , Nitya Sharma & Pooja Ranjan (2013): HTIB-Mediated One-
Pot Synthesis of Some 2-Substituted 4-Styrylthiazoles from (E)-4-Arylbut-3-en-2-ones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:4, 582-586
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Synthetic Communications1, 43: 582–586, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.604815
HTIB-MEDIATED ONE-POT SYNTHESIS OF SOME
2-SUBSTITUTED 4-STYRYLTHIAZOLES FROM
(E)-4-ARYLBUT-3-EN-2-ONES
Om Prakash,1 Nitya Sharma,2 and Pooja Ranjan2
1Institute of Pharmaceutical Sciences, Kurukshetra University,
Kurukshetra, India
2Department of Chemistry, Kurukshetra University, Kurukshetra, India
GRAPHICAL ABSTRACT
Abstract The reaction of (E)-4-arylbut-3-en-2-ones with [(hydroxy(tosyloxy)iodo]benzene
(HTIB) followed by treatment with thioureas, thioamide, and thiobenzamide has offered a
one-pot synthesis of 2-substituted 4-styrylthiazoles.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords (E)-4-Arylbut-3-en-2-ones; (E)-4-aryl-1-tosyloxy-but-3-en-2-ones; a-haloketones;
[hydroxy(tosyloxy)iodo]benzene; 4-styrylthiazoles; a-tosyloxyketones
INTRODUCTION
4-Styrylthiazoles 4 are associated with some biological activitities.[1] Recent
studies by Alajarin et al.[2,3] have demonstrated that 4-styrylthiazoles 4 behave as
all-carbon dienes in Diels–Alder reactions with the participation of the formal
C-C double bond of the thiazole ring and the side-chain double bond. The reactions
with N-substituted maleimides, maleic anhydride, and naphthaquinone take place
with a high level of stereocontrol to give the corresponding endo-cycloadducts in
good to excellent yields. These studies have opened new synthetic perspectives for
the functionalization of the thiazole ring. It is also known that 4-styrylthiazoles 4
are important precursors in the synthesis of chiral 2-substituted thiazolecarboxylic
Received March 7, 2011.
Address correspondence to Om Prakash or Nitya Sharma, Kurukshetra University, Kurukshetra
136119, India. E-mail: dromprakash50@rediffmail.com
582

2-SUBSTITUTED 4-STYRYLTHIAZOLES
583
acids, which are building blocks for a number of thiazole-containing natural
products.[4,5]
Synthetic access to these 4-styrylthiazoles 4 was facilitated by Hantzsch thiazole
synthesis involving the reaction between a-halobenzalacetones and thioamides 3.
While initial studies employed a-iodo and a-bromobenzalacetones,[6] the most recent
reports replaced them with a-chlorobenzalacetones.[2,3]
In view of the problems associated with the preparation and handling of a-
haloketones, the development of alternative methodology avoiding the use of a-
haloketones is always desirable. A great deal of research work from our laboratory
and other research groups has emphasized the advantageous use of a-tosyloxyke-
tones, thereby offering a superior alternative to conventional approach involving
a-haloketones.[7–13] In continuation of our interest in developing simple and efficient
procedures for the synthesis of various heterocycles, we report herein a facile
synthesis of 4-styrylthiazoles 4 from (E)-4-arylbut-3-en-2-ones (1) via (E)-4-aryl-1-
tosyloxy-but-3-en-2-ones (2).
We started our work with the preparation of (E)-4-aryl-1-tosyloxy-but-3-en-2-
ones (2) according to the procedure described in our previous study.[14] The resulting
2 was refluxed with equimolar quantities of 3 in EtOH for 2–3 h to give 4-styrylthiazoles
4 (method A) (Scheme 1). Encouraged by the result of stepwise procedure, it was
considered worthwhile to attempt the synthesis of 4 through direct procedure without
isolating (E)-4-aryl-1-tosyloxy-but-3-en-2-ones (2) (Method B) (Scheme 1); thus (E)-4-
arylbut-3-en-2-one 1a was oxidized with [hydroxy(tosyloxy)iodo]benzene (HTIB) in
dichloromethane. Subsequently the residual mass obtained after removal of dichloro-
methane was treated with thiourea to afford 4-styrylthiazole 4a in 86% yield. Other deri-
vatives (4b–4n) were prepared in a similar manner in 80–89% yield. The formation of the
known 4-styrylthiazoles 4a, 4g, and 4k was confirmed by comparing the melting points
with those reported in the literature.[6,15] The new 4-styrylthiazoles 4b–4f and 4h–j were
confirmed on the basis of elemental analysis and spectral data. These results along with
physical data of 4 are summarized in Table 1.
A new facile HTIB method for the synthesis of 4-styrylthiazoles 4 has been
developed. Compared to the previously reported methods, the new one-pot synthesis
Scheme 1.

584
O. PRAKASH, N. SHARMA, AND P. RANJAN
Table 1. Physical data of 2-substituted 4-styrylthiazoles 4
Yield (%)
Compound
Ar
R1
Mp (ꢀC)
157–159c
Method Aa
Method Bb
4a
4b
4c
4d
4e
4f
C6H5
4-CH3C6H4
4-OCH3C6H4
4-BrC6H4
4-ClC6H4
4-FC6H4
C6H5
NH2
NH2
71
67
65
75
74
72
77
75
73
76
68
67
69
65
86
85
82
89
87
83
89
88
87
88
80
83
81
80
113–115
97–99
NH2
NH2
132–134
119–121
189–190
79–81c
NH2
NH2
4g
4h
4i
C6H5 NH
C6H5 NH
C6H5 NH
C6H5 NH
CH3
4-CH3C6H4
4-BrC6H4
4-ClC6H4
C6H5
163–165
135–137
82–84
175–178d (picrates)
79–81
93–95
4j
4k
4l
4-CH3C6H4
C6H5
4-CH3C6H4
CH3
C6H5
C6H5
4m
4n
110–112
aYields of products 4 with regard to 2.
bYields of products 4 with regard to 1.
cLit mpꢀC (4a 160–162, 4g 83, and 4k 177–180).
dYield of product (4a 49%, 4g 64%, and 4k 19%) with regard to iodomethylstyrylketone. To compare the
results of present study with literature procedure, we carried out the synthesis of p-methylliodobenzalace-
tone according to Ref. 6, which on treatment with thioacetamide resulted in the formation of 4l. However,
overall yield of the product 4l was only 10% against 83% obtained from the present study.
is not only manipulatively simpler but also affords much better overall yields than
literature procedure.[6] Finally, the results of the present study further establish the
advantage of HTIB-mediated syntheses of heterocyclic compounds.
EXPERIMENTAL
Melting points were taken in open capillaries and are uncorrected. Infrared
(IR) spectra were recorded on a Perkin-Elmer IR spectrophotometer. The 1H
NMR spectra were recorded on a Brucker 300-MHz instrument. The chemical shifts
were expressed in parts per million (ppm) units downfield from an internal
tetramethylsilane (TMS) standard.
Method B: One-Pot Synthesis of 2-Amino-4-(2-phenylethenyl)thiazole
(4a)
HTIB (11 mmol) was added to a solution of (E)-4-phenylbut-3-en-2-one 1a
(10 mmol) in dichloromethane and the reaction mixture was stirred for 3–4 h. Most
of the dichloromethane was removed by distillation and ethanol was added to it.
Thiourea (10 mmol) was added to the resulting solution and the solution was
refluxed for 2–3 h. Most of the solvent was concentrated in vacuo, and the resulting
residue was basified with a saturated solution of NaHCO3. The solid product thus

2-SUBSTITUTED 4-STYRYLTHIAZOLES
585
obtained was filtered, washed with water, and recrystallized from ethanol to afford
the pure thiazole 4a.
The same experimental procedure was adopted for the synthesis of other
4-styrylthiazole derivatives 4b–4n (Table 1).
ACKNOWLEDGMENT
We are thankful to Kurukshetra University, Kurukshetra, India, for the award
of a university research scholarship to Nitya Sharma and to the Council of Scientific
and Industrial Research, New Delhi, India, for the award of a senior research
fellowship to Pooja Ranjan for carrying out this work. The authors are also thankful
to the Council of Scientific and Industrial Research (CSIR 01(2186)=07=EMR-II) for
financial support.
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