Solid state synthesis of 2-aroylbenzo[b]furans, 1,3-thiazoles and 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazoles from α-tosyloxyketones using microwave irradiation

Article abstract of DOI:10.1039/a807563h

The expeditious solventless syntheses of 2-aroylbenzo[e]furans, 1,3-thiazoles and 3-aryl-5,6-dihydroimidazo[2,1-b]-[1,3]thiazoles are described from readily accessible α-tosyloxyketones and mineral oxides in processes that are accelerated by exposure to m

Full text of DOI:10.1039/a807563h

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Solid state synthesis of 2-aroylbenzo[b]furans, 1,3-thiazoles and
3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazoles from á-tosyloxy-
ketones using microwave irradiation†
Rajender S. Varma,* Dalip Kumar and Per J. Liesen
Department of Chemistry and Texas Research Institute for Environmental Studies (TRIES),
Sam Houston State University, Huntsville, TX 77341-2117, USA
Received (in Cambridge) 29th September 1998, Accepted 21st October 1998
The expeditious solventless syntheses of 2-aroylbenzo[b]furans, 1,3-thiazoles and 3-aryl-5,6-dihydroimidazo[2,1-b]-
[1,3]thiazoles are described from readily accessible α-tosyloxyketones and mineral oxides in processes that are
accelerated by exposure to microwaves. The 2-aroylbenzo[b]furans are readily obtained from salicylaldehydes and
α-tosyloxyketones in the presence of solid potassium fluoride doped alumina (KF–Al2O3) whereas montmorillonite
K-10 clay provides 1,3-thiazoles from thioamides and α-tosyloxyketones. Similarly, ethylenethiourea and α-tosyloxy-
ketones provide bridgehead nitrogen heterocycles, 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazoles, in excellent yields
which are not easily obtainable under classical heating conditions.
possibility of upscaling the reactions on a preparative scale.
Introduction
In view of the above mentioned limitations of the reported
The 2-aroylbenzo[b]furans,1 1,3-thiazoles2 and 3-aryl-5,6-di-
methods11–18 and our continued interest in the development
hydroimidazo[2,1-b][1,3]thiazoles3 are important classes of
heterocyclic compounds that are known to possess important
of environmentally benign protocols,10 we now describe a
microwave-accelerated solid state approach for the rapid
biological properties. 2-Aroylbenzo[b]furans, initially reported
assembly of 2-aroylbenzo[b]furans, 1,3-thiazoles and 3-aryl-5,6-
from the flower-heads of Helichrysum arenarium DC,4 form a
dihydroimidazo[2,1-b][1,3]thiazoles.
group of naturally occurring compounds which possesses a
wide range of pharmacological activities.3 In view of their
cyclooxygenase-inhibitory activity, thiazoles find application
in therapy as thromboembolic agents and are of significant
Results and discussion
The key intermediates, α-tosyloxyketones, are important pre-
importance being an integral structural component of vitamin
cursors for the synthesis of a variety of heterocyclic com-
B1 and coenzyme carboxylase.5 The related bridgehead hetero-
pounds.19 Conventionally, the preparation of these tosylated
cyclic compounds, 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thi-
carbonyl derivatives from aryl methyl ketones requires extended
azoles, are known to possess a broad spectrum of anthelmintic
reaction time under refluxing conditions in acetonitrile.20 Here-
and fungicidal activity.3 Generally, synthesis of these hetero-
in, we describe a high yield preparation of α-tosyloxyketones
by simply admixing [hydroxy(tosyloxy)iodo]benzene (HTIB)
cyclic compounds involves utilization of lachrymatory starting
materials and hazardous reagents which requires a longer
with an appropriate aryl methyl ketone followed by MW heat-
reaction time under drastic conditions and which results in the
ing (30 s) in an open vessel. Various electron-donating and
generation of aqueous or organic solvent waste.
electron-withdrawing substituents in the aryl ring influence
neither the reaction time nor the yield of the α-tosylated ketones
(Scheme 1).
Microwave (MW) heating has been used for the rapid syn-
thesis of a variety of compounds6a,7–10 wherein chemical reac-
tions are accelerated because of selective absorption of MW
energy by polar molecules, non-polar molecules being inert to
the MW dielectric loss. Heterogeneous reactions facilitated by
supported reagents on various inorganic surfaces have received
attention in recent years.6 The coupling of MW irradiation with
the use of catalysts or mineral supported reagents, under
solvent-free conditions, provide unique chemical processes with
special attributes such as enhanced reaction rates, higher yields,
greater selectivity and the ease of manipulation.6a,10 In addi-
tion, the limitations of the MW-assisted reactions in solvents,
namely, the development of high pressures and the need for
specialized sealed vessels, are circumvented via this solid state
strategy which enables organic reactions to occur rapidly at
atmospheric pressure.9,10 Consequently, these solvent-free MW-
assisted reactions6a,9,10 have gained popularity as they provide
an opportunity to work with open vessels and an enhanced
Scheme 1
The existing methods for the synthesis of 2-aroylbenzo[b]-
furans normally use lachrymatory α-haloketones,11 N-bromo-
succinimide12 or phase transfer catalysts.13 We have explored a
simplified approach for the rapid formation of 2-aroylbenzo[b]-
furans 3, which involves admixing salicylaldehydes with
α-tosyloxyketones on mineral oxide supports such as basic
alumina or alumina ‘doped’ with potassium fluoride followed
by the exposure to microwaves for 2.5–3.5 min in an unmodified
household microwave oven (Scheme 2). The basic reaction con-
ditions using alumina impregnated with potassium fluoride are
† Presented, in part, as Plenary lectures at the 7th Blue Danube
Symposium on Heterocyclic Chemistry, GL 3, Eger, Hungary, June
7–10, 1998 and the International Conference on Microwave Chemistry,
PL6, Prague, Czech Republic, Sept. 6–11, 1998.
J. Chem. Soc., Perkin Trans. 1, 1998, 4093–4096
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Table 1 Synthesis of 2-aroylbenzo[b]furans (3a–h) from α-tosyloxy-
ketones 1
Table 2 Synthesis of 1,3-thiazole derivatives (5a–h) from α-tosyloxy-
ketones 1
Mp/ЊCb
Mp/ЊCb
Time/
min
Yield
(%)a
Time/
min
Yield
(%)a
Entry
R
R1
Expt.
Ref.
Entry
R
R2
Expt.
Ref.
3a
3b
3c
3d
3e
3f
H
Cl
Me
OMe
H
Cl
Me
OMe
H
H
H
H
Cl
Cl
Cl
Cl
3.0
3.0
2.5
3.5
2.5
2.5
2.5
3.5
94
94
91
89
95
92
96
89
90–91
153–154
95–96
90–9112
5a
5b
5c
5d
5e
5f
H
H
Cl
Cl
Me
Me
OMe
OMe
Cl
OMe
Cl
OMe
Cl
OMe
Cl
3
4
2
4
5
3
3
3.5
90
91
94
96
92
92
90
88
105
100
104–10521
98–992
14521
—
152–15313
95–9614
971b
144
97–98
154c
136–137
184–185
167–168c
136–137c
13815
18517
—
169–170
149–150c
139–140c
169–170c
170–17121
—
3g
3h
5g
5h
—
—
—
OMe
a Yields refer to pure isolated products. b Physical and chemical proper-
ties of all the compounds agreed with the assigned structures. c See
Experimental section.
a Yields refer to pure isolated products. b Physical and chemical proper-
ties of all the compounds agreed with the assigned structures. c See
Experimental section.
Scheme 2
Scheme 4
atives can be further elaborated to interesting thiazole deriv-
atives.
ideally suited for obtaining optimum yields. The generality of
this approach is established by utilising several substituted
salicylaldehydes and α-tosyloxyketones in this reaction which
tolerates a variety of functional groups (Table 1).
A plausible pathway for the formation of 2-aroylbenzo[b]-
furans is the initial formation of an enolate anion under basic
conditions followed by the nucleophilic displacement of the
tosyloxy group and elimination of the water molecule to afford
2-aroyl[b]benzofuran 3.
Thiazoles are conventionally prepared from α-haloketones
and thioamides (or thioureas) via a method pioneered by
Hantzsch.16 In a cumbersome and time consuming preparation
(25 h), King and Hlavacek17 have synthesized 2-aminothiazoles
by replacing α-haloketones with ketones and halogens. Sub-
sequently, other methods18 have been introduced in view of the
pharmacological importance of the thiazole derivatives.5b The
obvious limitations have been the use of strong mineral acids
under drastic reaction conditions. We find that our earlier
described solvent-free approach for the synthesis of 2-aroyl-
benzo[b]furans is equally applicable to thiazoles. The process
simply requires mixing of thioamides with α-tosyloxyketones in
the presence of acidic montmorillonite K-10 clay and brief
exposure of the reaction mixture to 2–5 min of MW irradiation
(Scheme 3). The scope of this reaction is defined by rapid
The mechanistic pathway presumably involves a nucleophilic
displacement of the tosylate group by the sulfur atom onto the
α-carbon of the α-tosyloxyketones followed by intramolecular
nucleophilic attack on the carbonyl carbon and elimination of a
water molecule to afford thiazole derivatives.
The generalisation of this synthetic theme is extended to a
concise preparation of bridgehead thiazoles, 3-aryl-5,6-dihydro-
imidazo[2,1-b][1,3]thiazoles 9. These compounds are normally
difficult to obtain and require a longer heating time in reac-
tions that use α-haloketones18a or α-tosyloxyketones18c under
strongly acidic conditions. Our solventless optimised reaction
conditions for these bridgehead heterocycles merely require a
mixing of α-tosyloxyketones with thioamides in the presence of
montmorillonite K-10 clay. The mixture is then irradiated
in MW for 3 min to afford substituted bridgehead thiazoles
(Scheme 5).
Scheme 5
The contribution of microwaves may not be purely a thermal
one as is borne out by the fact that similar reaction rates are not
attainable at the same bulk temperature in an oil bath. For
example, the reaction of p-methyl-α-tosyloxyacetophenone and
salicylaldehyde in an oil bath at 130 ЊC (the temperature in the
microwave oven reached 130 ЊC after 1.5 min of irradiation)
requires 95 min to deliver the 2-aroylbenzo[b]furan derivative
3c, while the reaction of α-tosyloxyacetophenone and p-chloro-
thiobenzamide at the same temperature (bulk temperature of
130 ЊC) in an oil bath gets completed in 15 min to afford 5a. The
reaction of α-tosyloxyacetophenone with ethylenethiourea,
however, remains incomplete even after heating at 130 ЊC (bulk
temperature) for 24 h. Apparently, there is not a significant
Scheme 3
assembly of several thiazole derivatives starting from various
substituted α-tosyloxyketones and thioamides (Table 2).
In the case of a diketone, exemplified by the reaction of
3-tosyloxypentane-2,4-dione 6, with thioamides 4, the formation
of 5-acetyl-4-methyl-2-aryl-1,3-thiazole derivatives 7, can be
realised in excellent yields (Scheme 4). These 5-acetyl deriv-
4094
J. Chem. Soc., Perkin Trans. 1, 1998, 4093–4096

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difference between the reaction rates using MW irradiation and
alternate heating mode for thiazoles (require 15 min) but it
becomes more distinct in the formation of 2-aroylbenzo[b]-
furans which requires a longer time (95 min). The case of the
corresponding bridgehead heterocycles 9, however, is a special
one where the MW effect really becomes apparent since the
reactions of α-tosyloxyketones with ethylenethioureas are
incomplete in an oil bath. The formation of these heterocyclic
compounds from the reaction intermediates involves the elim-
ination of water molecules which couple very efficiently with
microwaves. Consequently, the MW protocols are responsible
for the faster formation of these heterocycles when compared to
classical heating conditions.
In summary, we have developed efficient and clean syntheses
of 2-aroylbenzo[b]furans, thiazoles and 3-aryl-5,6-dihydroimid-
azo[2,1-b][1,3]thiazoles from readily available α-tosyloxy-
ketones under solvent-free conditions that utilise relatively
benign inorganic oxides as catalysts and clean energy source
microwaves.
dd, J 2.46 and 6.87, 3Ј-H, 5Ј-H), 7.41–7.45 (2H, m, 3-H, 6-H),
7.56 (1H, d, J 8.79, 7-H), 7.69 (1H, d, J 2.82, 4-H), 8.10 (2H,
dd, J 2.46 and 6.87, 2Ј-H, 6Ј-H); δC (CDCl3) 55.63, 113.62,
114.00, 114.47, 122.52, 128.33, 129.56, 132.09, 153.96, 154.12,
163.88, 182.49 (CO).
General procedure for the synthesis of 2,4-disubstituted 1,3-
thiazoles (5a–h)
α-Tosyloxyketone (1 mmol), the appropriate thioamide (1
mmol) and montmorillonite K-10 clay (125 mg) were mixed
thoroughly using a pestle and mortar. The reaction mixture was
transferred into a glass tube and exposed to microwave irradi-
ation in an alumina bath for 2–5 min (intermittently with 1.5
min interval; 130 ЊC). The product was extracted into methyl-
ene chloride (2 × 10 cm3) and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure and
the residue was crystallised from ethanol–hexane to afford the
corresponding 1,3-thiazoles (5a–h).
5d. (Found: C, 63.50; H, 3.72; N, 4.58. Calc. for C16H12ClNOS
requires C, 63.79; H, 3.99; N, 4.65%) δH (CDCl3) 3.87 (3H, s,
OCH3), 6.97 (2H, d, J 8.79, 3Ј-H, 5Ј-H), 7.38 (1H, s, 5-H), 7.40
(2H, d, J 7.98, 3Љ-H, 5Љ-H), 7.91 (2H, d, J 8.52, 2Ј-H, 6Ј-H), 7.97
(2H, d, J 8.64, 2Љ-H, 6Љ-H); δC (CDCl3) 55.43, 112.05, 114.30,
126.40, 127.69, 128.15, 128.86, 132.95, 133.86, 154.67, 161.33,
168.11.
Experimental
Melting points were determined on a Mel-Temp II hot stage
apparatus using a Fluke 51 K/J digital thermometer and are
uncorrected. A Sears Kenmore unmodified household micro-
wave oven (900 W) equipped with a turntable was used for all
experiments. The average bulk temperature at the end of the
reaction was measured by inserting a thermometer in the alu-
mina bath housing the reaction vessel. Microanalyses were per-
formed by Galbraith Laboratories, Inc., Knoxville, TN. The 1H
and 13C NMR spectra were recorded in CDCl3 on a JEOL
5f. (Found: C, 72.40; H, 5.26; N, 4.82. Calc. for C17H15NOS
requires C, 72.60; H, 5.34; N, 4.98%) δH (CDCl3) 2.39 (3H, s,
CH3), 3.87 (3H, s, OCH3), 6.97 (2H, d, J 8.79, 3Љ-H, 5Љ-H), 7.23
(2H, d, J 8.25, 3Ј-H, 5Ј-H), 7.30 (1H, s, 5-H), 7.87 (2H, d,
J 8.22, 2Љ-H, 6Љ-H), 7.97 (2H, d, J 8.52, 2Ј-H, 6Ј-H); δC (CDCl3)
21.30, 55.42, 110.98, 114.22, 126.32, 126.87, 128.08, 129.38,
131.94, 137.89, 156.11, 161.11, 167.61.
Eclipseϩ300 (300 MHz for H NMR and 75 MHz for 13C
NMR) spectrometer using tetramethylsilane as an internal
standard.
1
General procedure for the synthesis of á-tosyloxyketones (1a–d)
5g. (Found: C, 63.58; H, 3.62; N, 4.54. Calc. for C16H12-
ClNOS requires C, 63.79; H, 3.99; N, 4.65%) δH (CDCl3) 3.85
(3H, s, OCH3), 6.97 (2H, d, J 6.87, 3Ј-H, 5Ј-H), 7.35 (1H, s,
5-H), 7.42 (2H, d, J 8.49, 3Љ-H, 5Љ-H), 7.91 (2H, d, J 8.52, 2Ј-H,
6Ј-H), 7.97 (2H, d, J 8.25, 2Љ-H, 6Љ-H); δC (CDCl3) 55.43,
111.19, 114.19, 127.39, 127.82, 129.19, 132.41, 135.93, 156.37,
159.83, 166.39.
A mixture of aryl methyl ketone (1 mmol) and [hydroxy-
(tosyloxy)iodo]benzene (1.2 mmol), taken in a glass tube, was
placed in an alumina bath inside the MW oven and irradiated
for 30 s at 50% power level. After completion of the reaction,
as determined by TLC examination, the crude product was
washed with hexane to afford pure tosyloxymethyl aryl ketone
1a. Yield 96%; mp 91 ЊC (lit.,20 mp 89–91 ЊC); 1b: yield 93%; mp
122 ЊC (lit.,22 119–120 ЊC); 1c: yield 94%; mp 82 ЊC (lit.,22 82–
83 ЊC); 1d: yield 92%; mp 115 ЊC (lit.,22 mp 115–116 ЊC).
5h. (Found: C, 68.38; H, 5.19; N, 4.76. Calc. for C17H15NO2S
requires C, 68.69; H, 5.05; N, 4.71%) δH (CDCl3) 3.85 (3H, s,
OCH3), 3.86 (3H, s, OCH3), 6.86–6.97 (4H, m, 3Ј-H, 5Ј-H,
3Љ-H, 5Љ-H), 7.27 (1H, s, 5-H), 7.89–7.98 (4H, m, 2Ј-H, 6Ј-H,
2Љ-H, 6Љ-H); δC (CDCl3) 55.34, 55.42, 110.04, 114.06, 114.23,
127.72, 128.07, 128.16, 129.88, 155.78, 159.60, 161.11.
General procedure for the synthesis of 2-aroylbenzo[b]furans
(3a–h)
Salicylaldehyde (0.122 mg, 1 mmol), KF–alumina (0.620 g, 2
mmol of KF) and α-tosyloxyketone (1 mmol) were placed in a
glass tube and mixed thoroughly on a vortex mixer. The glass
tube was then placed in an alumina bath inside the MW oven
and irradiated (intermittently at 1.5 min intervals; 130 ЊC) for a
specified time (Table 1). On completion of the reaction, followed
by TLC examination (hexane–EtOAc, 9:1), the product was
extracted into methylene chloride (3 × 10 cm3). The solvent
was then removed under reduced pressure and the residue was
crystallized from ethanol to afford a nearly quantitative yield of
2-aroylbenzo[b]furans (3a–h).
General procedure for the synthesis of 5-acetyl-2-aryl-4-methyl-
1,3-thiazoles (7a–b)
3-Tosyloxypentane-2,4-dione (0.270 mg, 1 mmol), the appropri-
ate thioamide (1 mmol) and montmorillonite K-10 clay (125
mg) were mixed together using a pestle and mortar. The mix-
ture was transferred to a glass tube and exposed to microwave
irradiation in an alumina bath for 3 min (intermittently with 1.5
min interval; 130 ЊC). The product was extracted into methyl-
ene chloride (2 × 10 cm3) and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure and
the residue was crystallised from hexane to afford correspond-
ing 5-acetyl-2-aryl-4-methyl-1,3-thiazoles (7a–b).
3g. (Found: C, 70.85; H, 4.10. Calc. for C16H11ClO2 requires
C, 71.11; H, 4.07%) δH (CDCl3) 2.46 (3H, s, CH3), 7.33 (2H, d,
J 7.71, 3Ј-H, 5Ј-H), 7.42–7.45 (2H, m, 6-H, 3-H), 7.55 (1H,
d, J 8.70, 7Ј-H), 7.68 (1H, d, J 2.19, 4-H), 7.95 (2H, d, J 8.52,
2Ј-H, 6Ј-H); δC (CDCl3) 21.75, 113.63, 114.08, 122.55, 128.28,
129.34, 129.57, 129.69, 150.76, 154.17, 183.72 (CO).
7a. Yield 86%; mp 114 ЊC (Found: C, 57.70; H, 4.14; N, 5.41.
Calc. for C12H10ClNOS requires C, 57.37; H, 3.98; N, 5.58%)
δH (CDCl3) 2.55 (3H, s, 4-CH3), 2.76 (3H, s, COCH3), 7.41 (2H,
d, J 8.22, 3Ј-H, 5Ј-H), 7.89 (2H, d, 2Ј-H, 6Ј-H); δC (CDCl3)
18.49, 30.81, 128.14, 129.42, 131.37, 131.63, 137.34, 159.62,
168.01, 190.43.
3h. (Found: C, 66.82; H, 3.95. Calc. for C16H11ClO3 requires
C, 67.13; H, 3.84%) δH (CDCl3) 3.91 (3H, s, OCH3), 7.02 (2H,
J. Chem. Soc., Perkin Trans. 1, 1998, 4093–4096
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Supported Reagents, Academic Press, San Diego, California, 1987;
(c) G. W. Kabalka and R. M. Pagni, Tetrahedron, 1997, 53, 7999 and
references cited therein; (d) J. H. Clark and D. J. Macquarrie, Chem.
Commun., 1998, 853.
7 For reviews on MW-assisted chemical reactions see (a) R. A.
Abramovich, Org. Prep. Proced. Int., 1991, 23, 683; (b) A. G.
Whittaker and D. M. P. Mingos, J. Microwave Power Electro-
magnetic Energy, 1994, 29, 195; (c) S. Caddick, Tetrahedron, 1995,
51, 10403; (d) R. S. Varma, Green Chem., 1999, in the press.
8 (a) R. Gedye, F. Smith, K. Westway, H. Ali, L. Baldisera, L. Laberge
and J. Rousell, Tetrahedron Lett., 1986, 27, 279; (b) A. K. Bose,
B. K. Banik, N. Lavlinskaia, M. Jayaraman and M. S. Manhas,
Chemtech., 1997, 27, 18.
9 (a) A. Oussaid, L. N. Thach and A. Loupy, Tetrahedron Lett., 1997,
38, 2451; (b) D. Villemin and A. B. Alloum, Synth. Commun., 1991,
21, 63; (c) J. M. Lerestif, L. Toupet, S. Sinbandhit, F. Tonnard,
J. P. Bazureau and J. Hamelin, Tetrahedron, 1997, 53, 6351.
10 For cleavage-deprotection reactions see: (a) R. S. Varma, M. Varma
and A. K. Chatterjee, J. Chem. Soc., Perkin Trans. 1, 1993, 999;
(b) R. S. Varma and R. K. Saini, Tetrahedron Lett., 1997, 38, 2623;
(c) R. S. Varma and H. M. Meshram, Tetrahedron Lett., 1997, 38,
7973; (d) R. S. Varma, R. Dahiya and R. K. Saini, Tetrahedron
Lett., 1997, 38, 8819. For condensation–cyclisation reactions see:
(e) R. S. Varma, R. Dahiya and S. Kumar, Tetrahedron Lett., 1997,
38, 2039; ( f ) R. S. Varma, R. Dahiya and S. Kumar, Tetrahedron
Lett., 1997, 38, 5131; (g) R. S. Varma and R. K. Saini, Synlett, 1997,
857; (h) R. S. Varma, R. K. Saini and D. Kumar, J. Chem. Res. (S),
1998, 348; (i) R. S. Varma and R. Dahiya, J. Org. Chem., 1998,
63, 8038. For oxidation reactions see: (j) R. S. Varma and
R. Dahiya, Tetrahedron Lett., 1997, 38, 2043; (k) R. S. Varma,
R. K. Saini and H. M. Meshram, Tetrahedron Lett., 1997, 38, 6525;
(l) R. S. Varma, R. Dahiya and R. K. Saini, Tetrahedron Lett., 1997,
38, 7029; (m) R. S. Varma, R. Dahiya and R. K. Saini, Tetrahedron
Lett., 1997, 38, 7823; (n) R. S. Varma and R. Dahiya, Tetrahedron
Lett., 1998, 39, 1307; (o) R. S. Varma and R. K. Saini, Tetrahedron
Lett., 1998, 39, 1481; (p) R. S. Varma and K. P. Naicker, Molecules
Online, 1998, 2, 94. For reduction reactions see: (q) R. S. Varma and
R. K. Saini, Tetrahedron Lett., 1997, 38, 4337; (r) R. S. Varma
and R. Dahiya, Tetrahedron, 1998, 54, 6293; (s) R. S. Varma and
K. P. Naicker, Tetrahedron Lett., 1998, 39, 8437.
7b. Yield 89%; mp 88–89 ЊC (Found: C, 63.51; H, 5.45;
N, 5.56. Calc. for C13H13NO2S requires C, 63.16; H, 5.26; N,
5.67%) δH (CDCl3) 2.55 (3H, s, 4-CH3), 2.76 (3H, s, COCH3),
3.86 (3H, s, OCH3), 6.95 (2H, d, J 8.76, 3Ј-H, 5Ј-H), 7.92 (2H,
d, J 8.79, 2Ј-H, 6Ј-H); δC (CDCl3) 18.49, 30.74, 55.47, 114.44,
125.72, 128.56, 130.50, 159.49, 162.12, 169.43, 190.43.
General procedure for the synthesis of 3-aryl-5,6-dihydro-
imidazo[2,1-b][1,3]thiazole (9a–d)
α-Tosyloxyketone (1 mmol), ethylenethiourea (1 mmol) and
montmorillonite K-10 clay (100 mg) were mixed thoroughly
using a pestle and mortar. The mixture was transferred into a
glass tube followed by microwave irradiation in an alumina
bath for 3 min (intermittently). The thiazole salt so obtained
was neutralised by the addition of a dilute solution of sodium
hydroxide. The product was extracted into methylene chloride
(2 × 10 cm3) and dried over anhydrous sodium sulfate. The
solvent was removed under reduced pressure and the residue
was crystallised from benzene–hexane to afford the correspond-
ing 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazole (9a–d).
9a: Yield 85%; mp 111–112 ЊC (lit.,18c 112–113 ЊC); 9b: yield
92%; mp 113–114 ЊC (lit.,18c 113–114 ЊC); 9c: yield 89%; mp 87–
88 ЊC (lit.,18c 85–88 ЊC); 9d: yield 88%; gummy mass.18c
Acknowledgements
We are grateful for financial support to the Texas Advanced
Research Program (ARP) in chemistry (Grant # 003606–023)
and Texas Research Institute for Environmental Studies
(TRIES).
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