Catalyst-free, rapid synthesis of fused bicyclic thiazolo-pyrimidine and pyrimido-thiazine derivatives by a microwave-assisted method

Article abstract of DOI:10.1080/10426500802077564

The present investigation deals with the rapid microwave-assisted synthesis of compounds containing fused bicyclic systems. Dihydropyrimidines obtained via a microwave-assisted Biginelli reaction were treated with dibromo alkanes under microwave condition

Full text of DOI:10.1080/10426500802077564

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Catalyst-Free, Rapid Synthesis
of Fused Bicyclic Thiazolo-
Pyrimidine and Pyrimido-
Thiazine Derivatives by a
Microwave-Assisted Method
Vijay R. Virsodia a , Nikhil R. Vekariya a , Atul T.
Manvar b , Rupesh C. Khunt b , Bhavin R. Marvania b ,
Bharat S. Savalia b & Anamik K. Shah b
a Jubilant Organosys, Noida, India
b Department of Chemistry, Saurashtra University,
Rajkot, India
Published online: 19 Dec 2008.
To cite this article: Vijay R. Virsodia , Nikhil R. Vekariya , Atul T. Manvar , Rupesh
C. Khunt , Bhavin R. Marvania , Bharat S. Savalia & Anamik K. Shah (2008): Catalyst-
Free, Rapid Synthesis of Fused Bicyclic Thiazolo-Pyrimidine and Pyrimido-Thiazine
Derivatives by a Microwave-Assisted Method, Phosphorus, Sulfur, and Silicon and the
Related Elements, 184:1, 34-44
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Phosphorus, Sulfur, and Silicon, 184:34–44, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802077564
Catalyst-Free, Rapid Synthesis of Fused Bicyclic
Thiazolo-Pyrimidine and Pyrimido-Thiazine Derivatives
by a Microwave-Assisted Method
Vijay R. Virsodia,1 Nikhil R. Vekariya,1 Atul T. Manvar,2
Rupesh C. Khunt,2 Bhavin R. Marvania,2 Bharat S.
Savalia,2 and Anamik K. Shah2
1Jubilant Organosys, Noida, India
2Department of Chemistry, Saurashtra University, Rajkot, India
The present investigation deals with the rapid microwave-assisted synthesis of
compounds containing fused bicyclic systems. Dihydropyrimidines obtained via a
microwave-assisted Biginelli reaction were treated with dibromo alkanes under
microwave conditions to yield thiazolo-pyrimidine and pyrimido-thiazine systems.
The usefulness of this method lies in carrying out the reaction without a catalyst
and solvent in a shorter time. The reaction was successfully extended to develop
fused systems from benzimidazole-2-thiol.
Keywords Fused bicyclic systems; MAOS; pyrimido-thiazine; thiazolo-pyrimidine;
without catalyst
INTRODUCTION
The synthesis of dihydropyrimidine derivatives by the Biginelli reac-
tion is not only important because these structural classes are known to
exhibit very interesting pharmacological profiles,1−7 but because vari-
ous fused bicyclic systems can also be developed from this precursor.8
Various modified building blocks, e.g. β-ketoesters, ureas/thioureas, and
aldehydes, are used to synthesize molecules with targeted substitu-
tions on a basic skeleton. A large number of catalysts9−14 are reported
to catalyze the reaction efficiently and to provide higher yields. Differ-
ent methods of synthesis, e.g., microwave-assisted synthesis,15−17 solid
Received 6 December 2007; accepted 25 March 2008.
Authors are grateful to the Department of Chemistry, Saurashtra University, Rajkot
for providing the necessary infrastructural facilities. A.T.M. and R.C.K. are grateful to
the Department of Science and Technology (DST), New Delhi for providing the financial
assistance under the National Facility scheme (Grant no. VI-D&P/188/06-07/TDT).
Address correspondence to Prof. Anamik Shah, Department of Chemistry, Saurashtra
University, Rajkot360 005, Gujarat, India. E-mail: anamik shah@yahoo.com
34

Fused Bicyclic Systems by Microwave-Assisted Method
35
phase synthesis,18 and use of ionic liquids,19 have also been investi-
gated. This reaction may be utilized to its maximum by developing
a rapid method of synthesis of various bicyclic fused systems from
this precursor to produce a library of compounds. C. Oliver Kappe has
been involved with the high speed scaffold decoration of this hetero-
cyclic core, exploring the diversity on at least six points around the
scaffold.20 During the last few years, we have intensively studied the
effects of different modifications to the 1,4-dihydropyridine structural
class on their therapeutic activity.21−26 Very interesting results were
obtained for 1,4-dihydropyridine derivatives with a phenyl carbamoyl
side chain, which inspired us to apply the same modification to aza ana-
logues of 1,4-dihydropyridine, i.e., dihydropyrimidine, and to develop
various bicyclic systems with a phenyl carbamoyl moiety. Recently, we
reported26 the synthesis of dihydropyrimidine derivatives bearing a
phenyl carbamoyl side chain, their anti-tubercular activity, and 3D-
QSAR study. In continuation of our work, this current article reports
a rapid microwave-assisted synthesis of fused bicyclic systems with
aphenyl carbamoyl side chain without the use of a catalyst.
RESULTS AND DISCUSSION
In the conventional method, substituted acetoacetanilide, thiourea, and
aromatic aldehydes were reacted in methanol, and dihydropyrimidines
were obtained in 40–45% yield after a long reaction time (12–15 h).
Earlier the Biginelli reaction was reported under microwave irradia-
tion, but we wished to optimize the reaction conditions for the current
reaction where substituted acetoacetanilides are used as new build-
ing blocks. To check the effect of microwave power, the reactions were
carried out at 200 W and 400 W at 120◦C. The reaction was found to
complete in shorter time at 400 W than at 200 W. At higher temper-
ature (400 W, 140◦C), slightly less or equivalent yields were obtained
after same reaction time. Dihydropyrimidines, thus synthesized, were
used as a precursor to develop fused bicyclic systems.
To develop fused bicyclic systems, dihydropyrimidines were reacted
with dibromo alkanes. In the conventional method, the reaction was
carried out in methanol and dimethylformamide using potassium car-
bonate as a base. By employing methanol as a solvent media, 30–40%
yields were obtained after 5 h of refluxing; while in dimethylformamide,
the reaction proceeded faster and 50–55% yields were obtained after
2–2.5 h of refluxing. In order to get higher yields and shorten reaction
time, the reaction was subjected to microwave irradiation procedure
(Scheme 1). Surprisingly, the reaction was found to proceed without a

36
V. R. Virsodia et al.
SCHEME 1 Catalyst-free microwave-assisted synthesis of thiazolo-
pyrimidine and pyrimido-thiazine derivatives.
catalyst, leading to the formation of final compounds in good yield (81–
93%). Dihydropyrimidine and dibromo ethane were taken in the ratio
of 1:1.5 and irradiated using microwaves. Higher ratios of dihydropy-
rimidine and dibromo ethane did not provide any advantage in terms
of yield and reaction time. Similarly, pyrimido-thiazine–fused systems
were also synthesized efficiently by this method using dibromo propane.
The compounds were characterized by spectral analysis. To expand the
use of these optimized reaction conditions, benzimidazole-2-thiol was
reacted with dibromo alkanes to develop bicyclic fused systems, and
target compounds were synthesized with the advantages of high yield
(80–85%) and shorter reaction time (4–5 min) (Scheme 2). The con-
ventional method requires the use of potassium carbonate as a base
and solvent media, while under microwave the reactions could proceed
without a catalyst and solvent.
EXPERIMENTAL
Materials and Methods
All the chemicals and solvents were purchased from Spectrochem
(Mumbai, India) and used without further purification. 1H NMR spec-
tra were recorded on a Bruker Avance II 400MHz spectrometer in
DMSO d6. Chemical shifts (δ) are given in ppm relative to TMS, cou-
pling constants (J) in Hz. IR spectra were recorded on a Shimadzu
SCHEME 2 Catalyst-free microwave-assisted synthesis of thiazolo-
pyrimidine and pyrimido-thiazine derivatives.

Fused Bicyclic Systems by Microwave-Assisted Method
37
FTIR-8400 using KBr optics. Mass spectra were recorded on Shimadzu
GC-MS, QP2010 by EI method. A microwave synthesizer (Questron
Technologies Corporation, Canada) QPro-M model monomode open-
vessel was used for the synthesis. Elemental analysis of the compounds
was carried out on Elementar Vario EL III Carlo Erba 1108 model.
General Method of Synthesis of N-(substituted phenyl)-7-
methyl-5-(4-substituted phenyl)-2,3-Dihydro-5H-[1,3]thiazolo-
[3,2-a]pyrimidine-6-carboxamide (3a–r)
N-(substituted phenyl)-4-(substituted phenyl)-1,2,3,4-tetrahydro-
6-methyl-2-oxo-pyrimidine-5-carboxamide (0.01 mol) and a dibro-
moalkane (0.015 mol) were taken into the reaction vessel. The reaction
mixture was subjected to microwave irradiation and was monitored
with thin layer chromatography. After completion of the reaction, as
indicated by TLC (ethyl acetate:hexane [3:2]), methanol was added to
the reaction mixture. The crude product obtained was filtered and sub-
jected to silica gel column chromatography (60–100 mesh) to elute the
pure product. A similar procedure was adopted for the synthesis of the
compounds listed in Table I.
General Method of Synthesis of 2,3-Dihydro[1,3]thiazolo-
[3,2-a]benzimidazole (5a–f)
Benzimidazole-2-thiol (0.01 mol) and dibromoalkane (0.015 mol)
were taken into the reaction vessel and subjected to microwave irradia-
tion. The reaction was monitored with thin layer chromatography. After
completion of the reaction, as indicated by TLC (chloroform:methanol
[4:1]), acetone was added to the reaction mixture. Acetone was stripped
off at reduced pressure to leave the crude product. Finally it was puri-
fied by silica gel column chromatography (60–100 mesh) using chloro-
form and methanol as eluents. This process was adopted to synthesize
compounds listed in Table II.
SPECTRAL DATA
N-(4-chlorophenyl)-3,5-dihydro-7-methyl-5-phenyl-2H-thiazolo-
[3,2-a]pyrimidine-6-carboxamide (3a, C20H18ClN3OS)
White solid, mp 153–154◦C; IR (cm−1): 3256 (N H), 3089 (Ar-H), 2914
1
( CH3), 2818 ( CH2), 1673 (C O), 1614 (C C), 1126 (C O); H NMR
(DMSO-d6) δ = 2.23 (3H, s), 3.11 (1H, m), 3.22 (1H, m), 3.42 (1H, m), 3.61
(1H, m), 5.48 (1H, s), 7.16–7.40 (9H, m), 8.16(1H, brs); 13C NMR (DMS-
d6) δ = 183.9, 165.2, 152.9, 138.5, 134.4, 129.8, 129.1, 128.9, 128.5,
127.5, 126.1, 123.4, 63.8, 49.8, 24.5, 20.8; Mass (M/z): 384 (M+). Anal.

38
V. R. Virsodia et al.
TABLE I Effect of Microwave Power on Synthesis of Thiazolo-
Pyrimidine and Pyrimido-Thiazine Derivatives (3a–r)
MW(200 W)
at 140◦C
MW (400 W) MW(400 W)
at 140◦C at 160◦C
Time Yield Time Yield Time Yield
Entry
3a
R1
R2
(min)
(%)
(min)
(%)
(min)
(%)
Ph
5
82
3
87
3
85
3b
3c
3,4-di-OCH3-Ph
3-NO2-Ph
4-OH-Ph
6
5
5
5
6
6
6
6
5
5
6
6
6
5
85
76
80
83
78
76
80
77
84
87
84
87
82
88
4
4
3
3
3
4
3
4
3
3
4
4
4
3
86
89
85
84
84
89
93
81
89
91
85
93
84
92
4
4
3
3
3
4
3
4
5
3
4
4
4
3
85
89
83
84
85
88
90
83
88
92
85
93
84
92
3d
3e
4-OCH3-Ph
2-Cl-Ph
3f
#3g
#3h
#3i
#3j
3k
3l
3-NO2-Ph
4-Cl-Ph
2-OCH3-Ph
Ph
2-OH-Ph
4-N(CH3)2-Ph
2-Cl-Ph
3m
3n
3o
4-NO2-Ph
4-OCH3-Ph
3p
3q
3r
4-N(CH3)2-Ph
2-Cl-Ph
5
5
5
86
85
87
3
3
3
90
88
89
3
3
3
90
89
89
2-OH-Ph
#
n= 2.

Fused Bicyclic Systems by Microwave-Assisted Method
39
TABLE II Effect of Microwave Power on Synthesis of
ThiazoloBbenzimidaole and Thiazino-Benzimidazole Derivatives
(5a–f)
MW (200 W) at
140◦C
MW (400 W) at
140◦C
MW (400 W) at
160◦C
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
Entry
R
5a
H
H
OCH3
OCH3
CH3
CH3
7
7
6
6
7
6
82
86
80
82
78
81
4
4
4
5
5
4
88
86
85
83
82
84
4
4
4
5
5
3
88
85
84
83
84
85
#5b
5c
#5d
5e
#5f
#
n= 2.
Calc.: C, 62.57; H, 4.73; Cl, 9.24; N, 10.95; O, 4.17; S, 8.35%; Anal.
Observed: C, 62.62; H, 4.77, N, 10.91.
N-(4-chlorophenyl)-3,5-dihydro-7-methyl-5-(3-nitrophenyl)-2H-
thiazolo[3,2-a]pyrimidine-6-carboxamide (3c, C20H17ClN4O3S)
White solid, mp 214–214◦C; IR (cm−1): 3174 ( NH, str), 3021
( CH CH), 2926 (Ar-CH,asym), 2845 (Ar-CH,sym), 1675 ( C O), 1532
( C C skeletal vibration), 1270 (C S, str), 1175 (C H IPD), 1083
1
(C O C), 781 (C H, OPD); H NMR (DMSO-d6) δ = 2.17 (3H, s), 3.20
(2H, m), 3.39 (1H , m), 3.68 (1H, m), 5.71 (1H, s), 7.19 (2H, m, J = 2.84,
2.92 Hz), 7.42 (2H, m, J = 2.00, 2.96 Hz), 7.53 (1H, t, J = 7.92, 7.88
Hz), 7.72 (1H, d, J = 7.64 Hz), 8.15 (1H, m), 8.24 (1H, t, J= 1.84 Hz),
8.14 (1H, brs); 13C NMR (DMSO-d6) δ ppm = 183.8, 163.9, 153.5, 148.9,
138.6, 134.7, 134.0, 130.0, 129.5, 129.7, 125.9, 123.8, 123.1, 120.5, 62.8,
49.8, 25.1, 21.5; Mass (M/z): 429 (M+). Anal. Calc.: C, 56.01; H, 4.00; Cl,
8.27; N, 13.06; O, 11.19; S, 7.48%; Anal. Observed: C, 56.05; H, 4,05; N,
13.01%.
N-(4-chlorophenyl)-3,5-dihydro-5-(4-methoxyphenyl)-7-methyl-
2H-thiazolo[3,2-a]pyrimidine-6-carboxamide
(3e, C21H20ClN3O2S)
Yellow solid, mp 160–162◦C; IR (cm−1): 3273 (N H), 3051 (Ar-H), 2924
1
( CH3), 2868 ( CH2), 1662 (C O), 1639 (C C), 1107 (C O); H NMR
(DMSO-d6) δ = 2.25 (3H, s), 2.93 (1H, m), 3.01 (1H, m), 3.23 (1H, m),

40
V. R. Virsodia et al.
3.41 (1H, m), 3.46 (3H, s), 5.39 (1H, s), 7.23 (2H, m), 7.37 (2H, m),
7.53 (1H, t, J = 7.96), 7.76 (1H, d, J = 7.76 Hz), 8.13 (1H, dd, J= 8.12,
2.16 Hz), 8.17 (1H, brs), 8.22 (1H, t, J= 2.11 Hz); 13C NMR (DMSO-d6)
δ = 183.7, 163.7, 159.5, 153.2, 134.8, 130.8, 129.0, 129.5, 129.9, 125.8,
123.2, 114.5, 63.8, 56.8, 49.8, 24.8, 21.1; Mass (M/z): 414 (M+). Anal.
Calc.: C, 60.94; H, 4.87; Cl, 8.57; N, 10.15; O, 7.73; S, 7.75%; Anal.
Observed: C, 60.99; H, 4.92; N, 10.11%.
5-(2-Chlorophenyl)-N-(4-chlorophenyl)-3,5-dihydro-7-methyl-
2H-thiazolo[3,2-a]pyrimidine-6-carboxamide
(3f, C20H17C12N3OS)
White solid, mp 177–178◦C; IR (cm−1): 3284 (N H), 3012 (Ar-H), 2926
1
( CH3), 2878 ( CH2), 1674 (C O), 1637 (C C), 1112 (C O); H NMR
(DMSO-d6) δ = 2.21 (3H, s), 3.14 (1H, m), 3.25 (1H, m), 3.44 (1H, m),
3.61 (1H, m), 7.20–7.34 (8H, m), 8.12 (1H, brs); 13C NMR (DMSO-d6)
δ = 183.8, 163.4, 153.8, 137.8, 134.2, 133.5, 129.8, 129.5, 129.0, 128.9,
127.2, 126.9, 125.7, 123.2, 54.8, 49.9, 24.4, 21.4; Mass (M/z): 418 (M+);
Anal. Calc.: C, 57.42; H, 4.10; Cl, 16.95; N, 10.04; O, 3.82; S, 7.66%;
Anal. Observed: C, 57.48; H, 4.15, N, 10.0%.
N-(4-chlorophenyl)-2,3,4,6-tetrahydro-8-methyl-6-(3-
nitrophenyl)Pyrimido[2,1-b][1,3]thiazine-7-carboxamide
(3g, C21H19ClN4O3S)
Yellow solid, 214–217◦C; IR (cm−1): 3216 ( NH, str), 3015 ( CH CH),
2968 (Ar-CH, asym), 2842 (Ar-CH, sym), 1677 ( C O), 1570 ( C C
skeletal vibration), 1290 (C S, str), 1182 (C H IPD), 1075 (C O C),
1
771 (C H, OPD); H NMR (DMSO-d6) δ = 2.25 (3H, s), 2.19 (1H, m),
2.25 (1H, m), 2.93 (1H, m), 3.02 (1H, m), 3.2 (1H, m), 3.42 (1H, m), 5.39
(1H, s), 7.23 (2H, tt, J= 2.92, 1.96 Hz), 7.37 (2H, m), 7.53 (1H, t, J= 7.88,
7.96 Hz), 7.76 (1H, t, J= 1.32, 6.44 Hz), 8.15 (1H, qt-qt, J= 1.86 Hz),
8.15(brs, 1H), 8.20 (1H, t, J= 1.92 Hz ); 13C NMR (DMSO-d6) δ = 157.9,
163.5, 153.1, 148.6, 139.4, 134.8, 134.2, 130.5, 129.8, 129.5, 125.5, 123.7,
123.2, 119.5, 62.8, 39.7, 25.8, 22.1, 21.4; Mass (M/z): 443 (M+); Anal.
Calc.: C, 58.34; H, 4.43; Cl, 16.40; N, 9.72; O, 3.70; S, 7.42%; Anal.
Observed: C, 58.38; H, 4.47; N, 9.76%.
N,6-bis(4-chlorophenyl)-2,3,4,6-tetrahydro-8-methylpyrimido-
[2,1-b][1,3]thiazine-7-carboxamide (3h, C21H19C12N3OS)
White solid, mp 210–212◦C; IR (cm−1): 3284 ( NH, str), 3012
( CH CH), 2924 (Ar-CH, asym), 2868 (Ar-CH, sym), 1674 ( C O),

Fused Bicyclic Systems by Microwave-Assisted Method
41
1516 ( C C skeletal vibration), 1263 (C S, str), 1190 (C H IPD), 1089
(C O C), 813 (C H, OPD); 1H NMR (DMSO-d6) δ = 2.15 (1H, m), 2.23
(1H, m), 2.23 (1H, m), 2.90 (1H, m), 2.98 (1H, m), 3.21 (1H, m), 3.33
(1H, m), 5.21 (1H, s), 7.07 (1H, s), 7.21–7.24 (2H, tt, J= 2.04, 2.88 Hz),
7.29–7.37 (5H, m), 8.16 (brs, 1H); 13C NMR (DMSO-d6) δ = 163.5, 157.9,
153.8, 136.2, 134.5, 132.9, 130.2, 129.8, 129.2, 128.4, 125.5, 123.1, 63.9,
39.5, 25.2, 22.4, 21.5; Mass (M/z): 432 (M+); Anal. Calc.: C, 58.34; H,
4.43; Cl, 16.40; N, 9.72; O, 3.70; S, 7.42%; Anal. Observed: C, 58.35; H,
4.46; N, 9.76%.
N-(4-chlorophenyl)-2,3,4,6-tetrahydro-6-(2-methoxyphenyl)-8-
methyl pyrimido[2,1-b] [1,3]thiazine-7-carboxamide
(3i, C22H22ClN3O2S)
White solid 222–224◦C; IR (cm−1): 3256 ( NH, str), 3018 ( CH CH),
2965 (Ar-CH, asym), 2829 (Ar-CH, sym), 1668 ( C O), 1570 ( C C
skeletal vibration), 1253 (C S, str),1168 (C H IPD),1072 (C O C),
1
786 (C H, OPD); H NMR (DMSO-d6) δ = 2.10 (3H, m), 2.23 (1H, m),
2.29 (1H, s), 2.82–2.95 (2H, m), 3.20 (1H, m), 3.43 (1H, m), 3.47 (3H,
s), 5.80 (1H, s), 7.66 (1H, dd, J= 1.72, 7.68 Hz), 7.26–7.37 (5H, m), 7.20
(2H, tt, J= 2.92 Hz), 8.14 (1H, brs); 13C NMR (DMSO-d6) δ = 163.5,
158.2, 157.5, 153.2, 134.5, 130.4, 129.5, 129.1, 128.5, 125.6, 123.4, 121.5,
116.8, 114.2, 56.4, 53.9, 39.6, 25.3, 22.3, 21.5; Mass (M/z): 428 (M+);
Anal. Calc.: C, 61.74; H, 5.18; Cl, 8.28; N, 9.82; O, 7.48; S, 7.49%; Anal.
Observed: C, 61.77; H, 5.21; N, 9.79%.
5-(2-chlorophenyl)-N-(4-fluorophenyl)-3,5-dihydro-7-methyl-
2H-thiazolo[3,2-a] pyrimidine-6-carboxamide
(3m, C20H17ClFN3OS)
White solid, mp 196–197◦C; IR (cm−1): 3214 ( NH, str), 3010
( CH CH), 2915 (Ar-CH, asym), 2852 (Ar-CH, sym), 1662 ( C O),
1546 ( C C skeletal vibration), 1274 (C S, str), 1168 (C H IPD), 1075
(C O C), 768 (C H, OPD); 1H NMR (DMSO-d6) δ = 2.17 (3H, s), 3.11
(1H, m), 3.25 (1H, m), 3.35 (1H, m), 3.74 (1H, m), 6.11 (1H, s), 6.92
(2H, tt, J= 3.32, 2.04 Hz), 7.25 (1H, tt, J= 1.64, 2.04 Hz), 7.33 (2H,
qt-qt, J= 1.04, 3.04 Hz), 7.46 (2H, m, J= 2.04, 3.24, 4.92 Hz), 7.60 (1H,
t, J= 7.00 Hz), 8.16 (1H, brs); 13C NMR (DMSO-d6) δ = 183.8, 163.5,
159.2, 153.2, 137.8, 133.6, 131.8, 129.7, 128.9, 128.7, 126.9, 125.5, 123.4,
115.9, 54.7, 49.8, 24.8, 21.2; Mass (M/z): 402 (M+); Anal. Calc.: C, 59.77;
H, 4.26; Cl, 8.82; F, 4.73; N, 10.46; O, 3.98; S, 7.98%; Anal. Observed:
C, 59.80; H, 4.29; N, 10.44%.

42
V. R. Virsodia et al.
3,5-Dihydro-5-(4-methoxyphenyl)-7-methyl-N-(naphthalen-1-
yl)-2H-thiazolo [3,2-a] pyrimidine-6-carboxamide
(3o, C25H23N3O2S)
White solid, mp 234-236◦C; IR (cm−1): 3186 ( NH, str), 3025
( CH CH), 2916 (Ar-CH, asym), 2834 (Ar-CH, sym), 1670 ( C O),
1526 ( C C skeletal vibration), 1276 (C S, str), 1191 (C H IPD),
1
1069 (C O C), 768 (C H, OPD); H NMR (DMSO-d6) δ = 2.31 (3H,
s), 3.10 (1H, m), 3.20(1H, m), 3.44 (1H, m), 3.56 (1H, m), 3.82 (1H, s),
5.44 (1H, s), 7.77 (2H, J= 9.2Hz), 7.38 (1H, d, J= 8.2 Hz), 6.91–7.29
(4H, m, J= 8.76, 7.02 Hz), 7.34–7.43 (4H, m), 8.17 (brs, 1H); 13C NMR
(DMSO-d6) δ = 183.8, 163.5, 159.5, 153.2, 141.0, 134.5, 130.5, 129.2,
128.9, 126.8, 126.0, 125.5, 125.1, 124.8, 121.2, 119.2, 114.6, 109.4, 63.5,
56.2, 49.5, 24.5, 21.4; Mass (M/z): 429 (M+); Anal. Calc.: C, 69.91; H,
5.40; N, 9.78; O, 7.45; S, 7.47%; Anal. Observed: C, 69.95; H, 5.43; N,
9.75%.
5-(2-Chlorophenyl)-3,5-dihydro-7-methyl-N-(naphthalen-1-yl)-
2H-thiazolo [3,2-a] pyrimidine-6-carboxamide
(3q, C24H20ClN3OS)
Yellow solid, mp 162–163◦C; IR (cm−1): 3277 (N H), 3032 (Ar-H), 2947
1
( CH3), 2877 ( CH2), 1681 (C O), 1620 (C C), 1116 (C O); H NMR
(DMSO-d6) δ = 2.36 (3H, s), 3.09 (1H, m), 3.22 (1H, m), 3.40 (1H, m),
3.72 (1H, m), 6.13 (1H, s), 7.16 (1H, s), 7.37 (2H, m), 7.40 (4H, m), 7.64
(2H, dd, J = 8.2, 2.1 Hz), 7.73 (1H, d, J = 7.48 Hz), 7.80 (1H, d, J = 8.2
Hz), 8.19(1H, brs); 13C NMR (DMSO-d6) δ = 183.9, 163.5, 153.0, 140.9,
137.9, 134.5, 133.5, 129.8, 129.0, 128.7, 128.2, 126.9, 126.6, 126.2, 125.5,
125.0, 124.7, 121.4, 119.2, 109.9, 54.8, 49.8, 24.8, 21.4; Mass (M/z): 434
(M+) Anal. Calc.: C, 66.43; H, 4.65; Cl, 8.17; N, 9.68; O, 3.69; S, 7.39%;
Anal. Observed: C, 66.45; H, 4.67; N, 9.66%.
6-Methoxy-2,3-dihydro[1,3]thiazolo[3,2-a]benzimidazole
(5c, C10H10N2OS)
White solid, 190–191◦C; IR (cm−1): 3055 (Ar-H), 2969, 2947, 2850
1
(alkane), 1604, 1583, 1531, 1494 (C C), 1348 (C N), 748 (OOP); H
NMR (DMSO-d6) δ = 3.18 (2H, m), 3.83 (3H, s), 4.10 (2H, m), 6.79 (1H,
dd, J= 2.37, 8.73 Hz), 7.06 (1H, d, J= 8.72 Hz), 7.11 (1H, d, J= 2.36
Hz); 13C NMR (DMSO-d6) δ = 156.4, 152.9, 135.6, 131.8, 116.4, 110.5,
101.4, 57.8, 56.6, 36.3; Mass (M/z): 202 (M+) Anal. Calc.: C, 58.23; H,
4.89; N, 13.58; O, 7.76; S, 15.55%; Anal. Observed: C, 58.25; H, 4.92; N,
13.55%.

Fused Bicyclic Systems by Microwave-Assisted Method
43
7-Methoxy-3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole
(5d, C11H12N2OS)
White solid, mp 205—207◦C; IR (cm−1): 3060 (Ar-H), 2944, 2908, 2859,
2811 (alkane), 1589, 1547, 1486, 1453 (C C), 1330 (C N), 711 (OOP);
1H NMR (DMSO-d6) δ = 2.45 (2H, m), 3.20 (2H, m), 3.84 (3H, s), 4.14
(2H, m), 6.82 (1H, dd, J= 2.26, 8.67 Hz), 7.09 (1H, d, J= 8.68 Hz), 7.12
(1H, d, J= 2.32 Hz); 13C NMR (DMSO) δ ppm = 156.9, 152.9, 135.8,
131.5, 116.9, 110.0, 101.6, 60.2, 50.7, 25.2, 23.7; Mass (M/z): 220 (M+)
Anal. Calc.: C, 59.97; H, 5.49; N, 12.72; O, 7.26; S, 14.56%; Anal. Ob-
served: C, 59.99; H, 5.52; N, 12.69%.
CONCLUSION
A bicyclic fused system can be synthesized efficiently under microwave
irradiation with advantages of high yield and shorter reaction time.
The use of a catalyst or solvent can be eliminated, which enhances
the current method, and we anticipate that it may be used further to
develop a library of differently substituted compounds containing fused
bicyclic systems.
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