A convenient synthesis of 2-amino-1,3-selenazoles using ionic liquids and microwave irradiation

Article abstract of DOI:10.1080/10426507.2010.527557

A simple and environmentally benign synthesis of 2-amino-1,3-selenazoles by microwave irradiation using 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF₄) ionic liquid (IL) is described. Acyl halides, phenacyl halides, and-bromo-keto est

Full text of DOI:10.1080/10426507.2010.527557

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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A Convenient Synthesis of 2-Amino-1,3-
selenazoles Using Ionic Liquid and
Microwave Irradiation
Mohanbabu Maradolla a & G. V. P. Chandramouli a
a Department of Chemistry, National Institute of Technology,
Warangal, India
Version of record first published: 11 Aug 2011
To cite this article: Mohanbabu Maradolla & G. V. P. Chandramouli (2011): A Convenient Synthesis of
2-Amino-1,3- selenazoles Using Ionic Liquid and Microwave Irradiation, Phosphorus, Sulfur, and Silicon
and the Related Elements, 186:8, 1650-1654
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Phosphorus, Sulfur, and Silicon, 186:1650–1654, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.527557
A CONVENIENT SYNTHESIS OF 2-AMINO-1,3-
SELENAZOLES USING IONIC LIQUID
AND MICROWAVE IRRADIATION
Mohanbabu Maradolla and G. V. P. Chandramouli
Department of Chemistry, National Institute of Technology, Warangal, India
GRAPHICAL ABSTRACT
NH2
Se
O
N
R1
([Bmim]BF4)
MW
Se
R1
R
+
H2N
NH2
R
Br
2
1
3
Abstract A simple and environmentally benign synthesis of 2-amino-1,3-selenazoles by mi-
crowave irradiation using 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) ionic
liquid (IL) is described. Acyl halides, phenacyl halides, and α-bromo-β-keto esters easily un-
dergo condensation with selenourea in ([Bmim]BF4) by microwave irradiation to afford the
desired products of good purity in excellent yields. The ionic liquid can be easily recovered and
reused at least 10 times without losing its activity. The duration of the reaction ranges from
4–6 min.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords [Bmim]BF4; microwave irradiation; selenazoles; selenourea
INTRODUCTION
Selenium, an essential biological trace element, is an integral part of several enzymes,
and its use as a nutritional supplement has been popularized recently due to its potential role
as an antioxidant in low concentrations and as an anticancer agent in high concentrations.1
It has also been observed that a number of diseases result from selenium deficiency.2 The
pharmacological properties and therapeutic applications of substituted selenazoles made
us enthusiastic about synthesizing a series of 2-amino-1,3-selenazole derivatives using
microwave irradiation. The methodology is of particular interest for us, as the ionic liquid
(IL) used acts as a solvent and catalyst in the present investigation.
Received 22 July 2010; accepted 23 September 2010.
The authors are thankful to the Director, NIT, Warangal for providing facilities and financial support.
Address correspondence to G. V. P. Chandramouli, Department of Chemistry, National Institute of Technol-
ogy, Warangal-506 004, India. E-mail: gvpc 2000@yahoo.co.in
1650

SYNTHESIS OF 2-AMINO-1,3-SELENAZOLES USING IL
1651
Room temperature ILs have been the subject of considerable interest as new, non-
volatile, and environmentally friendly alternatives to conventional organic solvents. They
contain large organic cations and a variety of anions.3–6 Ionic liquids are compatible with
several organic transformations,7–9 and they readily immobilize several catalysts in their
native form10,11 or supported catalysts.12 They have been found to alter the outcome of
chemical reactions in a dramatic fashion,13 thus forming a new paradigm in organic syn-
thesis. ILs have also been used in the synthesis of heterocycles such as isoxazoles.14
RESULTS AND DISCUSSION
A good number of methods for the synthesis of selenazoles have been reported using
starting materials such as selenourea and aracylbromides.15 Some of the reported meth-
ods of the synthesis of selenazoles describe the use of cyanomethyl-1-piperidinoseleno
carboimidate hydrochloride,16 selenourea,17 1,4-benzenedicarboselenamide,18 or seleno-
carboxylic amides19 as starting materials. The other procedures mainly start with selenaza-
dienes,20 phenylselenourea,21 lithium hexamethyldisilazide (LHMDS),22 selenoamides,23
or selenoformamide.24,25
However, some of the reported methods require a prolonged reaction time and use
of toxic solvents. The increasing attention during the last two decades for environmental
protection has led both modern academic and industrial groups to develop green chemi-
cal processes with maximum yield and minimum cost. Moreover, selenourea is air- and
light-sensitive,26 and there is a need to develop a mild and eco-friendly methodology
for synthesizing this high value compound. As a part of our program, which aimed at
the development of synthetic methedologies27 by eliminating flammable, toxic, or car-
cinogenic organic solvents, we employed 1-butyl-3-methylimidazolium tetrafluoroborate
([Bmim]BF4) ionic liquid as a green chemical solvent. The IL plays the dual role of sol-
vent and catalyst. The rapid use of microwave activation as a nonconventional energy
source in organic chemistry has also helped us in devising the above synthetic route.
Numerous organic reactions such as acylation and alkylation reactions, aromatic and nucle-
ophilic substitutions, condensations, cycloadditions, protection and deprotection reactions,
esterifications and transesterifications, heterocyclizations, rearrangements, organometallic
reactions, oxidations, and reductions assisted by microwave heating have been widely
described.28 A synthetic strategy using [Bmim]BF4 ionic liquid and microwave irradia-
tion collectively was found to be a successful and efficient method for the synthesis of
2-amino-1,3-selenazoles. In general, the reaction was carried out by keeping the mixture
of α-bromocarbonyl compound, selenourea, and [Bmim]BF4 in a microwave oven for
few minutes. Selenazoles were obtained in quantitative yields. The yields of selenazoles
produced from aromatic α-bromoketones (phenacyl bromides) were comparatively higher
than those obtained from aliphatic α-bromoketones. Similarly a better yield was observed
when α-bromoethylacetoacetate reacted with selenourea. These reactions proceed smoothly
without the formation of byproducts or rearranged products.
The compounds 3a–3j (Scheme 1) registered an IR absorption band for N-H stretching
in the range of 3446–3360 cm−1. The 1H NMR signal for the characteristic proton at position
4 for these selenazoles was observed in the region of δ 7.11–7.55. 13C NMR signals for the
three carbon atoms of the selenazole framework are observed in the regions of δ 108–115 for
C4, δ 140–150 for C5, and δ 155–165 for C2 carbons, respectively. All the final compounds
were characterized by elemental analysis, IR, 1H NMR, 13C NMR, and mass spectrometry.
The data of some of the known compounds were compared with the reported data.29,30

1652
M. MARADOLLA AND G. V. P. CHANDRAMOULI
NH2
Se
O
N
R1
([Bmim]BF4)
Se
R
+
H2N
NH2
R
MW
Br
R1
2
1
3
R
R1
H
H
H
H
H
H
H
H
3(a) C6H5
(b) 4-CH3-C6H4
(c) 4-CH3OC6H4
(d) 4-Cl-C6H4
(e) 4-Br-C6H4
(f) 4-I-C6H4
(g) 4-NO2-C6H4
(h) (CH)3C
(i) C6H5
C6H5
(j ) CH3
COOC2H5
Scheme 1 Synthesis of 2-amino-1,3-selenazoles by starting from α-bromocarbonyl compounds and selenourea
using [Bmim]BF4 ionic liquid and microwave irradiation.
The catalyst was easily recovered by washing the reaction mixture with distilled water and
was directly reused for the next turn after evaporation of water under reduced pressure.
The recycled catalyst was reused 10 times to catalyze the model reaction affording the
corresponding selenazoles in good yields. When ([Bmim]BF4) IL was reused 11 times or
more, the yields were decreased by 15–20% (Table 1).
Table 1 Synthesis of 2-amino-1,3-selenazoles by starting from α-bromocarbonyl compounds and selenourea
Producta
R
R1
Time (min)
Yield (%)b
Mp (◦C)
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5
H
H
H
H
H
H
H
H
4
5
6
4
4
6
6
4
6
4
95
96
96
97
95
95
98
96
96
95
130–132
165–167
172–173
156–158
130–132
188–190
248–250
58–60
4-CH3- C6H4
4-CH3OC6H4
4-Cl- C6H4
4-Br- C6H4
4-I- C6H4
4-NO2- C6H4
(CH3)3C
C6H5
CH3
C6H5
COOC2H5
198–200
162–164
3j
aAll of the products were identified by mp, 1H NMR, IR, 13C NMR, and mass spectrometry and were compared
with the reported data.29,30
bIsolated yields after purification.

SYNTHESIS OF 2-AMINO-1,3-SELENAZOLES USING IL
1653
CONCLUSION
In conclusion, we describe a practical and efficient procedure for the preparation
of 2-amino-1,3-selenazoles through microwave irradiation by using ([Bmim]BF4) ionic
liquid as the catalyst. This is a fast reaction which could be completed within a duration of
4–6 min.
EXPERIMENTAL
Melting points were measured in open capillary on Buchi melting point B-540 ap-
paratus and were uncorrected. IR spectra were recorded on ATI MATT-SON RS-1 FTIR
spectrometer using KBr pellets. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded in DMSO-d6 and CDCl3 on a Bruker Avance 300 instrument with the TMS at
δ 0.00 ppm as an internal standard. Mass spectra (EI-MS) were taken on Perkin Elmer
(SCIEX API- 2000, ESI) at 12.5 eV. Microwave KMIC-1.5KW (Korean Microwave Instru-
ment Co.) was used to carry out the reactions. CHNS analysis was carried out on Carlo Erba
EA 1108 automatic elemental analyzer. The progress of the reactions was monitored, and
the purity of the compounds was checked by TLC. The chemicals, reagents, and solvents
used were of commercial grade and were used without further purification unless otherwise
stated.
Synthesis of 2-Amino-1,3-selenazoles: General Procedure
A mixture of α-bromocarbonyl compound (1 mmol) and selenourea (1.2 mmol)
was dissolved in 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) (2 mL) in a
stoppered RB flask, which was placed in a beaker containing water and kept in a microwave
oven. The flask was irradiated at 1.5 kW for 1 min, and then the oven was opened, and
the hot water contained in the beaker was changed. After 1 min of resting time, another
1 min of irradiation was applied followed by 1 min of resting and the water was changed
repeatedly 3–4 times. After ensuring the completion of the reaction by TLC, the reaction
mixture was poured into water (10 mL), the product was extracted using ethyl acetate (3
× 10 mL), and the extract was separated. The organic layer was dried over anhydrous
Na2SO4, and the solvent was removed under reduced pressure. The resulting product was
further purified by column chromatography on silica gel using ethylacetate:hexane (20:80)
as eluent. The aqueous layer consisting of the ionic liquid ([Bmim]BF4) was subjected to
distillation (80 ◦C at 10 mmHg) for 2 h. Water was removed leaving behind the ionic liquid
([Bmim]BF4). The ionic liquid can be reused 10 times for the remaining reactions. The
characterization data are given in the Supplemental Materials (available online) and is in
accord with those in Refs. 29 and 30.
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