Copper acetate-catalyzed, mild, highly efficient, and practical synthesis of thiazoles and aminothiazoles

Article abstract of DOI:10.1080/00397910802654773

A mild and highly efficient synthesis of thiazoles by the condensation of α-bromo ketones with thiourea in the presence of a catalytic amount of copper acetate at room temperature has been described. The method is applicable for a variety of aryl and alkyl α-bromo ketones. The catalyst is inexpensive, and substituted thiazoles are obtained in good yields.

Full text of DOI:10.1080/00397910802654773

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Copper Acetate–Catalyzed,
Mild, Highly Efficient, and
Practical Synthesis of Thiazoles
and Aminothiazoles
a
a
H. M. Meshram , D. Aravind Kumar & B.
a
Ramalinga Vara Prasad
a
Organic Chemistry Division I, Indian Institute of
Chemical Technology, Hyderabad, India
Version of record first published: 01 Jun 2009.
To cite this article: H. M. Meshram , D. Aravind Kumar & B. Ramalinga Vara Prasad
(2009): Copper Acetate–Catalyzed, Mild, Highly Efficient, and Practical Synthesis of
Thiazoles and Aminothiazoles, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 39:13, 2317-2320
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1
Synthetic Communications , 39: 2317–2320, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654773
Copper Acetate–Catalyzed, Mild, Highly
Efficient, and Practical Synthesis of
Thiazoles and Aminothiazoles
H. M. Meshram, D. Aravind Kumar, and B. Ramalinga Vara Prasad
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: A mild and highly efficient synthesis of thiazoles by the condensation of
a-bromo ketones with thiourea in the presence of a catalytic amount of copper
acetate at room temperature has been described. The method is applicable for
a variety of aryl and alkyl a-bromo ketones. The catalyst is inexpensive, and
substituted thiazoles are obtained in good yields.
Keywords: a-Bromo ketones, condensation, copper(II) acetate, thiazoles
Thaizoles have been classically prepared by the condensation of
a-haloketones with thiourea in the presence of bromine or iodine or by the
[1]
reaction of a-thiocyanato carbonyl compounds with amine hydrochloride.
A stoichiometric amount of cyclodextrin was reported to catalyze the synth-
[2]
esis of thiazoles in an aqueous medium. Recently, silica chloride has been
[3]
employed as a heterogeneous catalyst for the syntesis of thiazoles. Another
method reported the use of ammonium 12-molybdophosphate as catalyst
[4]
for the preparation of thiazoles. Most of these methods require a stoichio-
metric amount of activator or catalyst medium. Though these methods are
efficient for the synthesis of thiazoles, they have some drawbacks, including
use of a hazardous and expensive catalyst.
We report the mild and efficient synthesis of thiazoles and ami-
nothiazoles by the condensation of a-halo ketones with thiourea in the
presence of copper acetate.
Received September 8, 2008.
Address correspondence to H. M. Meshram, Organic Division I, Indian Insti-
tute of Chemical Technology, Hyderabad 500 007, India. E-mail: hmmeshram@
yahoo.com
2
317

2318
H. M. Meshram, D. A. Kumar, and B. R. V. Prasad
Table 1. Reaction of phenacyl bromide using different
metal acetates
S. No.
Catalyst
Time (min)
Yield (%)
1
2
3
4
5
Copper acetate
Zinc acetate
Mercury acetate
Lead acetate
Sodium acetate
10
15
18
20
25
95
92
88
82
80
Table 2. Synthesis of thiazoles=aminothiazoles with b-keto bromides catalyzed by
copper (II) acetate in ethanol
a
Time
(min)
Yield
b
(%)
Entry
Substrate
Product
R
1
2
3
R¼CH
R¼Ph
3
10
12
10
90
89
92
R¼NH
2
2
2
4
5
6
R¼CH
R¼Ph
3
5
7
5
92
91
92
R¼NH
7
8
9
R¼CH
R¼Ph
3
5
7
5
90
89
92
R¼NH
10
11
12
R¼CH
R¼Ph
3
12
14
12
90
88
90
R¼NH
2
13
14
15
R¼CH
R¼Ph
3
5
7
5
92
90
91
R¼NH
2
16
17
18
R¼CH
R¼Ph
3
10
12
10
88
86
89
R¼NH
2
a
b
1
All the products were characterized by H NMR, IR, and mass spectroscopy.
Isolated yields after purification.

Thiazole and Aminothiazole Synthesis
2319
To investigate the efficiency of the catalyst, we have examined
various metal acetates. From these results, we observed that copper
acetate was efficient for good conversion of phenacyl halides into
thiazoles in a shorter reaction time than other metal acetates
(
Table 1).
Further, the reaction profile was studied in different solvents in the
presence of copper(II) acetate.
In our investigation, polar solvents such as dimethyl formamide and
ethanol were found to be the choice of solvents for the reaction, whereas
in dichloromethane the reaction was sluggish. It was also noted that the
reaction did not proceed in nonpolar solvents such as hexane or toluene
even after stretching the reaction time (24 h).
To expand the scope of this reaction, a variety of substituted phe-
nacyl halides were employed with thiourea, and results are summarized
in Table 2. Phenacyl bromide and chloride reacted equally with
thiourea and led to good yields of thiazoles. To study the electronic
effects on the reaction, we have examined substrates with electron-
donating and electron-withdrawing groups. It was observed that elec-
tron-withdrawing substituents enhance the rate of reaction whereas
electron-rich substituents suppress the reaction. It is worth mention-
ing that the present procedure is also efficient for aliphatic acyl
bromides.
In conclusion, we have a demonstrated mild, efficient, and high-
yielding procedure for the synthesis of thiazoles and amino thiazoles
by the reaction of a-halo ketones and urea in the presence of copper(II)
acetate.
SPECTRAL DATA FOR SELECTED PRODUCTS
Entry 13
1
H NMR (300 MHz, CDCl , Me Si): d 2.8 (s, 3H), 7.09 (m, 2H), 7.22 (s,
H), 7.86 (m, 2H); IR (KBr): n ¼ 2923, 1603, 1533, 761 cm ; (M þ
3
4
ꢀ1
1
ESIMS): (M þ 1): 194, 178, 95.
Entry 14
1
H NMR (300 MHz, CDCl , Me Si): d 7.13 (m, 2H), 7.4 (s, 1H),
3
4
7
2
9
.99 (m, 2H), 7.45 (m, 3H), 8.05 (m, 2H); IR (KBr): n ¼ 3157,
ꢀ1
925, 1600, 1480, 758 cm ; (M þ ESIMS): (M þ 1): 256, 255, 178,
5, 77.

2320
H. M. Meshram, D. A. Kumar, and B. R. V. Prasad
Entry 15
1
H NMR (200 MHz, CDCl , Me Si): d 5.51 (BS, 2H), 6.55 (s, 1H), 7.03
3
4
ꢀ
1
(
t, 2H), 7.68 (m, 2H); IR (KBr): n ¼ 3425, 2923, 1598, 1505, 744 cm
M þ ESIMS): (M þ Na): 217, 195, 178, 95.
;
(
ACKNOWLEDGMENTS
D. A. and B. R. V. P. thank the Counsil of Scientific and Industrial Res-
earch for the award of a fellowship and J. S. Yadav, director, Indian
Institute of Chemical Technology, for his support and encouragement.
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1
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J. Org. Chem. 1998, 63, 196–200; (b) Rudolp, J. Facile access to N-thiazolyl a-
amino acids from a-bromo ketones and a-amino acids. Tetrahedron 2000, 56,
3161–3165; (c) Schantl, J. G.; Lagoja, I. M. Expedient synthesis of N-
substituted 2-amino thiazoles. Synth. Commun. 1998, 28, 1451–1462.
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2
3
4