Sodium fluoride as an efficient catalyst for the synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles at ambient temperature

Article abstract of DOI:10.1016/j.cclet.2013.10.001

Sodium fluoride was found to be a simple, mild and efficient catalyst for the synthesis of 2,4-disubstituted 1,3-thiazoles and selenazoles utilizing phenacyl bromides/3-(2-bromoacetyl)-2H-chromen-2-one and thiourea/ phenylthiourea/selenourea in aqueous methanol at ambient temperature. Analytically pure products are formed within 1-3 min in excellent yields.

Full text of DOI:10.1016/j.cclet.2013.10.001

Chinese Chemical Letters 25 (2014) 172–175
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Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Sodium fluoride as an efficient catalyst for the synthesis of 2,4-
disubstituted-1,3-thiazoles and selenazoles at ambient temperature
b
Janardhan Banothu a, Krishnaiah Vaarla a, Rajitha Bavantula a, , Peter A. Crooks
*
a Department of Chemistry, National Institute of Technology, Warangal 506004, India
b Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, AR 72205, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
Sodium fluoride was found to be a simple, mild and efficient catalyst for the synthesis of 2,4-
disubstituted 1,3-thiazoles and selenazoles utilizing phenacyl bromides/3-(2-bromoacetyl)-2H-chro-
men-2-one and thiourea/phenylthiourea/selenourea in aqueous methanol at ambient temperature.
Analytically pure products are formed within 1–3 min in excellent yields.
Received 9 June 2013
Received in revised form 12 September 2013
Accepted 24 September 2013
Available online 9 November 2013
ß 2013 Rajitha Bavantula. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Sodium fluoride
1,3-Thiazoles
Selenazoles
Aqueous methanol
Ambient temperature
1. Introduction
CuPy2Cl2 [17], HMCM-41 [9], and also under different solvent
systems, such as ionic liquid/water [18], PEG-400 [19], glycerin
Thiazole is a core structural motif present in a variety of natural
products, such as vitamin B1 (thiamine) and penicillin. Thiazole
derivatives also exhibit a broad spectrum of medicinal and
biological properties, such as antibacterial, antifungal [1], anti-
inflammatory [2], antiviral [3], antimalarial [4] and anti-HIV
activities [5]. Thiazole analogs have also been reported as ligands
at estrogen receptors [6], neuropeptide Y5 [7], adenosine receptors
[8], and act as inhibitors of human platelet aggregation factor [9],
urokinase [10] and poly (ADP-Ribose) polymerase-1 [11]. Selena-
zoles have been reported to possess antibacterial [12], and
superoxide anion scavenging activity [13], and exhibit cytotoxicity
and DNA fragmentation effects in human HT-1080 fibrosarcoma
cells [14]. The structures of sulfathiazole, meloxicam, and
selenazofurin and their pharmacological activities are given in
Fig. 1.
[20] and water [21]. However, most of these reported methods
suffer from drawbacks, such as harsh reaction conditions,
unsatisfactory yields, longer reaction times and critical isolation
procedures, and use of hazardous and expensive catalysts.
Therefore, to overcome the above limitations we have developed
a simple, mild and highly efficient protocol for the synthesis of
thiazoles and selenazoles utilizing sodium fluoride (NaF) as a
catalyst in aqueous methanol.
2. Experimental
Melting points were recorded on Stuart SMP30 apparatus and
are uncorrected. Analytical thin layer chromatography was
performed on F254 silica-gel precoated sheets using hexane/ethyl
acetate (8:2) as eluent, and visualized with UV light and iodine
vapor. Products were characterized by comparison with authentic
samples, and by spectral data (IR, 1H NMR and mass spectrometry).
IR spectra were recorded on a Perkin-Elmer 100S spectrophotom-
eter using a KBr disk. 1H NMR spectra were recorded on a Bruker
400 MHz spectrometer using DMSO-d6 as solvent and TMS as
internal standard. Elemental analyses were performed on a Carlo
Erba modal EA1108 unit, and the values obtained are within Æ0.4%
of the theoretical values. Mass spectra were recorded on a Jeol JMSD-
300 spectrometer.
In view of the importance of thiazole and selenazole derivatives
in medicinal chemistry, several methods for their synthesis have
been reported utilizing various catalytic systems, such as
ammonium-12-molybdophosphate [15],
b-cyclodextrin [16],
*
Corresponding author.
E-mail addresses: rajitabhargavi@yahoo.com, rajitha_nitw@yahoo.com
(R. Bavantula).
1001-8417/$ – see front matter ß 2013 Rajitha Bavantula. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.10.001

J. Banothu et al. / Chinese Chemical Letters 25 (2014) 172–175
173
O
NH
2
N
O
OH
S
N
O
S
N
H C
O
3
S
N
H
HO
Se
S
N
H
O
N
H C
HO
Selenazofurin (antibacterial)
Fig. 1. Biologically active thiazole and selenazole derivatives.
OH
3
H N
2
O
O
Meloxicam (antiinflammatory)
Sulfathiazole (antibacterial)
X
Table 1
R
O
N
Comparison of the catalytic activity of NaF with other catalysts in the synthesis of 4-
NaF, MeOH:H O (1:1 v/v)
2
R'
Br
(4-chlorophenyl)thiazol-2-amine (4a).
+
H N
R'
2
R
X
r.t., 1-3 min
Entrya
Catalyst (0.02 g)
Time (min)
Yieldb (%)
2
1
3-9
1
2
3
4
5
6
7
8
9
NaF
1
5
99
94
90
88
86
85
82
88
87
KF
R = Aryl/Coumaryl; R' = NH /NH-Ph; X = S/Se
2
CuCl2
AlCl3
SnCl2
BaCl2
PCl5
5
5
Scheme 1. Synthesis of 1,3-thiazoles and 1,3-selenazoles.
10
10
5
2.1. General procedure for the synthesis of 1,3-thiazoles and
CuPy2Cl2
CoPy2Cl2
5
selenazoles (3–9):
5
CuPy2Cl2, Dipyridine copper chloride; CoPy2Cl2, Dipyridine cobalt chloride.
The appropriate phenacylbromide or 3-(2-bromoacetyl)-2H-
chromen-2-one (1 mmol) and either thiourea, phenylthiourea or
selenourea (1 mmol) were dissolved in 2 mL of methanol, water
(2 mL) containing 0.02 g of NaF added and the mixture stirred at
room temperature for the appropriate time. After completion of
a
Reaction conditions: 4-chlorophenacyl bromide (1 mmol), thiourea (1 mmol),
catalyst (0.02 g), methanol:water (1:1 v/v), stirring at ambient temperature.
b
Isolated yields.
Table 2
NaF-catalyzed synthesis of substituted 1,3-thiazoles and 1,3-selenazoles.
Entrya
Product
X
R’
Time (min)
Yieldb (%)
Melting point (8C)
Found
Lit. [Ref.]
1
3a
3b
3c
S
NH2
1
1
2
98
98
97
150–152
134–136
132–134
150–151 [21]
135–136 [21]
132 [16]
S
NH-Ph
NH2
Se
2
3
4a
4b
4c
S
NH2
1
1
1
99
98
97
166–168
145–146
154–156
167–168 [19]
144–146 [19]
157 [16]
S
NH-Ph
NH2
Se
5a
5b
5c
S
NH2
1
1
1
96
98
98
182–184
230–232
177–178
176–177 [23]
–
S
NH-Ph
NH2
Se
132 [16]
4
5
6
6a
6b
6c
S
NH2
3
2
3
93
95
94
204–206
137–138
194–195
206–207 [21]
138–139 [21]
173 [16]
S
NH-Ph
NH2
Se
7a
7b
7c
S
NH2
2
1
2
97
98
98
135–136
102–103
166–168
–
S
NH-Ph
NH2
–
Se
167 [16]
8a
8b
8c
S
NH2
2
1
2
97
97
98
284–286
206–207
269–271
–
S
NH-Ph
NH2
–
Se
250 [16]
7
9a
9b
9c
S
NH2
1
1
1
99
98
98
228–229
188–190
217–218
–
S
NH-Ph
NH2
–
Se
280 [17]
a
Reaction conditions: phenacyl bromide/3-(2-bromoacetyl)-2H-chromen-2-one (1 mmol), thiourea/phenylthiourea/selenourea (1 mmol), methanol:water (1:1 v/v),
stirring at ambient temperature.
b
Isolated yields.

174
J. Banothu et al. / Chinese Chemical Letters 25 (2014) 172–175
NaF
O
X
OH
N
R
R
OH
R
H
_
_
HBr
H O
R
2
N
N
H N
R'
2
H
R'
R'
Br
R'
X
X
X
Br
Scheme 2. Proposed mechanism.
the reaction, 10 mL of water was added and the solid that
separated out was filtered off and washed with water, affording
analytically pure substituted 1,3-thiazoles or 1,3-selenazole
derivatives in excellent yields.
Associated characterization data can be found in Supporting
information.
presence of NaF as a catalyst at ambient temperature. This
methodology offers several advantages over other procedures,
including higher yields, shorter reaction times, easy work-up
procedure, and analytically pure products. We believe that, this
methodology is superior over other reported methods, and may
have industrial utility in the synthesis of substituted 1,3-thiazoles
and 1,3-selenazoles at ambient temperature.
3. Results and discussion
Acknowledgments
In continuation of our studies toward the synthesis of
biologically active molecules [22], we now report the synthesis
of substituted 1,3-thiazoles and 1,3-selenazoles from the reaction
We would like to thank the Director, National Institute of
Technology, Warangal for providing facilities under this RSM
project. The author (BJ) thanks the Ministry of Human Resource
Development for their support, and acknowledges a UGC research
fellowship to KVs.
of
v-bromoacetophenones and 3-(v-bromoacetyl)coumarin with
thiourea, phenylthiourea and selenourea utilizing NaF as catalyst
in 1:1 (v/v) methanol/water at ambient temperature. Under these
conditions excellent yields and rapid reaction times were obtained
(Scheme 1).
Appendix A. Supplementary data
In order to determine optimal conditions, initially, a model
reaction between 4-chlorophenacyl bromide and thiourea was
carried out in methanol by varying the amount of NaF catalyst. A
maximum yield of 92% was obtained with 0.02 g of NaF within
5 min. Increasing amount of NaF led to no change in product yield
or reaction time. Several similar synthetic methodologies have
been reported utilizing water as solvent [21]; hence we carried out
the reaction in 1:1 (v/v) water/methanol utilizing 0.02 g of NaF. To
our surprise, under these conditions the reaction was completed
within 1 min and afforded analytically pure 4-(4-chlorophe-
nyl)thiazol-2-amine (4a) in 99% yield. We also carried out the
reaction in pure water, but these conditions required a longer
reaction time (25 min) for complete conversion. For authenticity,
the structure of 4a was confirmed on the basis of IR, 1H NMR and
mass spectral data and comparison with a literature report [19].
To investigate the unique catalytic activity of NaF, the above
reaction was also carried out utilizing different inorganic and
organometallic catalysts. These results clearly showed that, NaF is
a unique and efficient catalyst for the synthesis of thiazoles at
ambient temperature (Table 1).
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2013.10.001.
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