Synthesis and X-ray characterization of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives

Article abstract of DOI:10.1002/jhet.678

A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles via Mannich reaction of imidazo[2,1- b][1,3,4]thiadiazoles with morpholine and formaldehyde were synthesized. Structures of all the newly synthesized compounds are well supported by spectr

Full text of DOI:10.1002/jhet.678

102
Synthesis and X-Ray Characterization of 2,5,6-Trisubstituted
Imidazo[2,1-b][1,3,4]thiadiazole Derivatives
Vol 49
Yu-Xia Da,a,b Ji-Hua Zhu,a,b Zhang Zhang,a,b Xiao-Dong Jia,a,b
Cai-Xia Yang,a,b and Zheng-Jun Quana,b
*
aKey Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, College
of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070,
People’s Republic of China
bGansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu 730070, People’s Republic of China
*E-mail: quanzj@nwnu.edu.cn
Received March 26, 2010
DOI 10.1002/jhet.678
Published online 12 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles via Mannich reaction of imidazo[2,1-
b][1,3,4]thiadiazoles with morpholine and formaldehyde were synthesized. Structures of all the newly
synthesized compounds are well supported by spectral data such as IR, NMR, Mass, and Elemental
analysis. Compound 3a has been confirmed by X-ray diffraction studies.
J. Heterocyclic Chem., 49, 102 (2012).
INTRODUCTION
1,3,4-thiadiazole derivatives [14], we herein wish to
report an expeditious, one-pot method for the prepara-
tion of a series of new 2,5,6-trisubstituted imidazo[2,1-
b][1,3,4]thiadiazoles via Mannich reaction of imidazo
[2,1-b][1,3,4]thiadiazole (2) with morpholine and form-
aldehyde (Scheme 1).
Imidazo[2,1-b]-1,3,4-thiadiazole derivatives have been
of interest to the medicinal chemists for many years
because of their anticancer [1], antitubercular [2], anti-
bacterial [3], antifungal [4], analgesic [5], and antisecre-
tory [6] activities. Moreover, much interest has also
been focused on the anti-inflammatory [7], cardiotonic
[8], diuretic [9], herbicidal [10] activities displayed by
compounds incorporating this heterocyclic system.
Because the imidazo[2,1-b]-1,3,4-thiadiazole system is
similar in part to Levamisole, a well-known immunomo-
dulator [11], the possibility of reducing the harmful
effects of the cytotoxic agents on the immune system
also appears to be very attractive.
RESULTS AND DISCUSSION
Synthesis. The synthesis of imidazo[2,1-b][1,3,4]thia-
diazole is reported many years ago [16]. In this article,
the synthesis of the basic nucleus imidazo[2,1-
b][1,3,4]thiadiazole is brought about by the condensation
of 2-amino-1,3,4-thiadiazole (1) with a-bromoarylketone
under microwave irradiation in ethanol [14], Mannich
reaction of imidazo[2,1-b][1,3,4]thiadiazole (2) with
morpholine and formaldehyde in methanol in the pres-
ence of acetic acid yielded corresponding products (3).
Generally, 5-(morpholin-4-ylmethyl)-6-arylimidazo[2,1-
b][1,3,4]thiadiazoles could be prepared in good yields
via Mannich reaction of 2-(aryloxymethyl)-6-phenylimi-
dazo[2,1-b][1,3,4]thiadiazoles with morpholine and
formaldehyde. In fact, when using 2-benzofuranyl-6-ary-
limidazo[2,1-b]-1,3,4-thiadiazoles (2k–m) as substrates,
lower yields of products 3k–m resulted.
Biheterocycles containing benzofuran, pyridine, thia-
diazoles, and chromone rings have been found to exhibit
antimicrobial, psychotropic, and anti-inflammatory activ-
ities [12]. It has been envisaged that these two active
pharmacophores, if linked together would generate novel
molecular templates which are likely to exhibit interest-
ing biological properties in animal models. For example,
it has been shown that some of methylene bridged ben-
zofuranylimidazo[2,1-b][1,3,4]thiadiazoles can increase
both analgesic and anti-inflammatory activities [13].
Recently, we have reported the synthesis of some 2-
aryloxymethylene-6-arylimidazoimidazo[2,1-b]-1,3,4-thia-
diazole under microwave irradiation [14]. In continua-
tion of our interest on biologically active compounds
such as benzofuran derivatives [15], imidazo[2,1-b]-
Spectroscopic characterization. The formation of
Mannich bases imidazothiadiazole derivatives (3) were
1
confirmed by the absence of imidazole proton in the H
NMR spectra. A singlet and two triplets were observed
C
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Imidazo[2,1-b][1,3,4]thiadiazole Derivatives
103
Scheme 1
cetophenone (5 mmol) dissolved in ethanol (10 mL) was
stirred at refluxing for 24 h. Completion of the reaction was
monitored by TLC using ethyl acetate, acetone, and petroleum
ether (1:1:2) as eluent. The solution was concentrated, and the
residue was recrystallized from DMF-EtOH to give compounds
2k–m.
2k: m.p. 240–242ꢀC, yield: 75%. IR (KBr) m: 3108, 1622
1
cmꢁ1. H NMR (400 MHz, DMSO-d6) d ¼ 7.32 (d, 1H, J ¼
8.0 Hz, Ar-H), 7.35 (t, 1H, J ¼ 8.0 Hz, Ar-H), 7.44 (d, 2H, J
¼ 8.0 Hz, Ar-H), 7.55 (t, 1H, J ¼ 8.0 Hz, Ar-H), 7.66–7.74
(m, 5H, Ph-H), 8.10 (s, 1H, imidazole). Anal. Calcd. For
C18H11N3OS: C, 68.12; H, 3.49; N, 13.24. Found: C, 67.97; H,
3.42; N, 13.17. MS (FAB) m/z: 317 (Mþ).
2l: m.p. 242–244ꢀC, yield: 70%. IR (KBr) m: 3100, 1623
cmꢁ1
.
1H NMR (400 MHz, DMSO-d6) d ¼ 7.35 (t, 1H, J ¼
around d 4.00, d 2.30, and d 3.70, which were assigned
to methylene protons and morpholine protons, respec-
tively. Formation of Mannich bases was further con-
firmed by their 13C NMR and mass spectra. The single
crystal X-ray crystallography of product 3a also con-
firmed the structures of obtained products (Fig. 1,
CCDC Deposit no. 644233).
8.0 Hz, Ar-H), 7.46 (d, 1H, J ¼ 8.0 Hz, Ar-H), 7.55 (t, 1H, J
¼ 8.0 Hz, Ar-H), 7.61 (d, 2H, J ¼ 8.0 Hz, Ar-H), 7.69 (d, 1H,
J ¼ 8.0 Hz, Ar-H), 7.72 (t, 1H, J ¼ 7.2 Hz, Ar-H), 7.73–7.75
(m, 2H, Ar-H), 8.08 (s, 1H, imidazole-H). Anal. Calcd. For
C18H10ClN3OS: C, 61.45; H, 2.87; N, 11.94. Found: C, 61.62;
H, 2.93; N, 11.84. MS (FAB) m/z: 351 (Mþ).
2m: m.p. 268–270ꢀC, yield: 79%. IR (KBr) m: 3076, 1612
cmꢁ1. H NMR (400 MHz, DMSO-d6) d ¼ 7.36 (d, 1H, J ¼
1
Molecular and crystal structure of 2-phenyloxy-
methyl-5-(morpholin-4-ylmethyl)-6-phenylimidazo[2,1-b]
[1,3,4]thiadiazole 3a. Compound 3a crystallized in the
centrosymetric space group P21/c with one molecule per
asymmetric unit. The ORTEP view of the molecule 3a
with the atomic numbering scheme is given in Figure 1.
In conclusion, 2,5,6-trisubstituted imidazo[2,1-b]
[1,3,4]thiadiazole derivatives via Mannich reaction of
imidazo[2,1-b][1,3,4]thiadiazole (2) with morpholine
and formaldehyde were synthesized. A new crystal 2-
phenyloxymethyl-5-(morpholin-4-ylmethyl)-6-phenylimi-
dazo[2,1-b][1,3,4]thiadiazole has been obtained by slow
evaporation of ethanol. Detailed crystal structure analysis
has been performed to identify the molecular arrange-
ment. Spectral analyses have also been carried out.
8.0 Hz, Ar-H), 7.50 (d, 2H, J ¼ 8.0 Hz, Ar-H), 7.55 (d, 1H, J
¼ 7.2 Hz, Ar-H), 7.64 (s, 1H, Ar-H), 7.67–7.69 (m, 2H, Ar-
H), 7.71–7.74 (m, 2H, Ar-H), 8.07 (s, 1H, imidazole-H). Anal.
Calcd. For C18H10BrN3OS: C, 65.69; H, 5.75; N, 13.32.
Found: C, 65.52; H, 5.81; N, 13.24. MS (FAB) m/z: 395 (Mþ).
General procedure for the preparation of 2,5,6-trisubsti-
tuted imidazo[2,1-b][1,3,4]thiadiazoles (3a–m). A mixture of
2-aryloxymethyl-6-arylimidazo[2,1-b][1,3,4]-thiadiazole (2a–
m) (1 mmol), morpholine (1.2 mmol), formalin (1 mL), and
acetic acid (1 mL) in methanol (10 mL) was refluxed for 8 h.
The resulting mixture was cooled to room temperature and
concentrated. The resulting crystals were collected by filtration
and recrystallized from ethanol to give the products (3a–m).
3a: m.p. 130–132ꢀC, Yield 82%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.53 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.69 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.90 (s, 2H, CH2), 5.36 (s, 2H,
CH2O), 7.00–7.05 (m, 3H, Ar-H), 7.30–7.34 (m, 3H, Ar-H),
7.43 (d, J ¼ 7.6 Hz, 2H, Ar-H), 7.95 (t, 2H, J ¼ 7.2 Hz, Ar-
H). 13C NMR (100 MHz, CDCl3) d ¼ 160.60, 157.19, 145.02,
143.85, 134.41, 129.71, 128.43, 127.62, 127.40, 122.35,
119.91, 114.91, 66.90, 65.33, 53.05, 51.26. Anal. Calcd. For
C22H22N4O2S: C, 65.00; H, 5.46; N, 13.78. Found: C, 64.82;
H, 5.52; N, 13.65. MS (FAB) m/z: 407 (Mþ1)þ.
EXPERIMENTAL
All reagents were obtained commercially and used without
further purification. Melting points were determined on an XT-
4 electrothermal micromelting point apparatus and uncorrected.
IR spectra were recorded using KBr pellets on a Nicolet
AVATAR 360 FTIR spectrophotometer. NMR spectra were
recorded at 400 (1H) and 100 (13C) MHz, respectively, on a
Varian Mercury plus-400 instrument using CDCl3 and DMSO-
d6 as solvent and TMS as internal standard. Elemental analyses
were performed on a Carlo-Erba 1106 Elemental Analysis
instrument. Mass spectra were recorded on a ZAB-HS spec-
trometer. The single crystal X-ray data collections of com-
pounds 3a was caried out on a Bruker Smart Apex CCD area
detector using a graphite monochromated MoKa radiation (k
ꢀ
˚
¼ 0.71073 A) at 20 C. 2-Aryoxylmethylene-6-arylimidazo[2,1-
b]-1,3,4-thiadiazoles (2a–j) were prepared according to our
previous procedures [14].
General procedure for 2-(2-benzofuranyl)-6-arylimi-
dazo[2,1-b]-1,3,4-thiadiazole (2k–m). A mixture of 2-amino-
5-(2-benzofuranyl)-1,3,4-thiadiazole (5 mmol) and x-bromoa-
Figure 1. ORTEP diagram of compound 3a.
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DOI 10.1002/jhet

104
Y.-X. Da, J.-H. Zhu, Z. Zhang, X.-D. Jia, C.-X. Yang, and Z.-J. Quan
Vol 49
3b: m.p. 120–122ꢀC, Yield 80%. 1H NMR (400 MHz,
Hz, Ar-H). 13C NMR (100 MHz, CDCl3) d ¼ 160.99, 157.33,
145.07, 143.83, 134.48, 129.79, 129.28, 128.49, 127.69,
126.55, 119.94, 115.59, 66.91, 65.64, 53.07, 51.32. Anal.
Calcd. For C22H21ClN4O2S: C, 59.92; H, 4.80; N, 12.71.
Found: C, 60.10; H, 4.87; N, 12.80. MS (FAB) m/z: 440 (Mþ).
3h: m.p. 167–168ꢀC, Yield 85%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.51 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.68 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.90 (s, 2H, CH2), 5.36 (s, 2H,
CH2O), 6.91–7.17 (m, 2H, Ar-H), 7.31–7.35 (m, 2H, Ar-H),
7.42 (d, J ¼ 7.6 Hz, 2H, Ar-H), 7.95 (t, 2H, J ¼ 7.2 Hz, Ar-
H). 13C NMR (100 MHz, CDCl3) d ¼ 160.99, 157.11, 145.15,
143.81, 134.40, 131.41, 129.32, 128.49, 128.19, 128.02,
127.66, 124.86, 119.91, 117.61, 66.92, 65.65, 53.12, 51.40.
Anal. Calcd. For C22H20Cl2N4O2S: C, 55.58; H, 4.24; N,
11.79. Found: C, 55.74; H, 4.29; N, 11.67. MS (FAB) m/z:
475 (Mþ1)þ.
CDCl3) d ¼ 2.30 (s, 3H, CH3), 2.54 (t, J ¼ 4.0 Hz, 4H,
CH2NCH2), 3.69 (t, J ¼ 4.0 Hz, 4H, CH2OCH2), 3.91 (s, 2H,
CH2), 5.35 (s, 2H, CH2O), 6.93–7.10 (m, 4H, Ar-H), 7.33 (t, J
¼ 8.0 Hz, 1H, Ar-H), 7.44 (d, J ¼ 7.6 Hz, 2H, Ar-H), 7.96 (t,
2H, J ¼ 7.2 Hz, Ar-H). 13C NMR (100 MHz, CDCl3) d ¼
160.96, 157.05, 145.15, 143.88, 134.40, 130.19, 129.91,
128.49, 127.69, 126.46, 124.95, 122.45, 119.91, 114.91, 66.92,
65.65, 53.12, 51.38, 12.24. Anal. Calcd. For C23H24N4O2S: C,
65.69; H, 5.75; N, 13.32. Found: C, 65.58; H, 5.81; N, 13.40.
MS (FAB) m/z: 421 (Mþ1)þ.
3c: m.p. 142–144ꢀC, Yield 83%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.31 (s, 3H, CH3), 2.54 (t, J ¼ 4.0 Hz, 4H,
CH2NCH2), 3.69 (t, J ¼ 4.0 Hz, 4H, CH2OCH2), 3.91 (s, 2H,
CH2), 5.35 (s, 2H, CH2O), 6.88–7.15 (m, 4H, Ar-H), 7.35 (t, J
¼ 8.0 Hz, 1H, Ar-H), 7.43 (d, J ¼ 7.6 Hz, 2H, Ar-H), 7.95 (t,
2H, J ¼ 7.2 Hz, Ar-H). 13C NMR (100 MHz, CDCl3) d ¼
160.96, 157.05, 145.15, 143.88, 138.09, 134.40, 129.91,
129.41, 128.49, 127.69, 122.36, 119.89, 113.80, 111.21, 66.92,
65.65, 53.12, 51.38, 21.15. Anal. Calcd. For C23H24N4O2S: C,
65.69; H, 5.75; N, 13.32. Found: C, 65.76; H, 5.67; N, 13.20.
MS (FAB) m/z: 421 (Mþ1)þ.
3i: m.p. 162–164ꢀC, Yield 82%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.52 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.69 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.91 (s, 2H, CH2), 5.36 (s, 2H,
CH2O), 7.33–7.87 (m, 7H, Ar-H), 7.96 (t, 2H, J ¼ 7.2 Hz, Ar-
H). 13C NMR (100 MHz, CDCl3) d ¼ 160.96, 158.01, 149.32,
145.15, 143.88, 134.40, 129.99, 129.41, 128.49, 127.61,
120.36, 119.89, 113.80, 111.13, 66.89, 65.64, 53.22, 51.32.
Anal. Calcd. For C22H21N5O4S: C, 58.52; H, 4.69; N, 15.51.
Found: C, 58.38; H, 4.80; N, 15.39. MS (FAB) m/z: 451 (Mþ).
3j: m.p. 188–189ꢀC, Yield 83%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.54 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.70 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.92 (s, 2H, CH2), 5.36 (s, 2H,
CH2O), 7.27 (d, J ¼ 8.0 Hz, 2H, Ar-H), 7.33 (t, J ¼ 8.0 Hz,
1H, Ar-H), 7.44 (d, 2H, J ¼ 7.6 Hz, Ar-H), 7.95 (t, 2H, J ¼
7.2 Hz, Ar-H), 8.22 (d, 2H, J ¼ 8.0 Hz, Ar-H). 13C NMR
(100 MHz, CDCl3) d ¼ 161.85, 160.79, 145.07, 143.89,
140.66, 134.69, 129.11, 128.52, 127.72, 122.00, 119.94,
114.99, 66.89, 65.66, 53.20, 51.32. Anal. Calcd. For
C22H21N5O4S: C, 58.52; H, 4.69; N, 15.51. Found: C, 58.71;
H, 4.53; N, 15.40. MS (FAB) m/z: 451 (Mþ).
3d: m.p. 152–154ꢀC, Yield 81%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.31 (s, 3H, CH3), 2.54 (t, J ¼ 4.0 Hz, 4H,
CH2NCH2), 3.70 (t, J ¼ 4.0 Hz, 4H, CH2OCH2), 3.92 (s, 2H,
CH2), 5.36 (s, 2H, CH2O), 6.91 (d, J ¼ 8.0 Hz, 2H, Ar-H),
7.12 (d, J ¼ 8.0 Hz, 2H, Ar-H), 7.34 (t, J ¼ 8.0 Hz, 1H, Ar-
H), 7.44 (d, 2H, J ¼ 7.6 Hz, Ar-H), 7.95 (t, 2H, J ¼ 7.2 Hz,
Ar-H). 13C NMR (100 MHz, CDCl3) d ¼ 160.96, 157.36,
145.07, 143.83, 134.49, 131.86, 130.19, 128.49, 127.69,
127.46, 119.94, 114.90, 66.98, 65.64, 53.11, 51.32, 20.51.
Anal. Calcd. For C23H24N4O2S: C, 65.69; H, 5.75; N, 13.32.
Found: C, 65.52; H, 5.81; N, 13.24. MS (FAB) m/z: 421
(Mþ1)þ.
3e: m.p. 118–120ꢀC, Yield 87%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.54 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.71 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.76 (s, 3H, CH3O), 3.92 (s, 2H,
CH2), 5.38 (s, 2H, CH2O), 6.85–7.06 (m, 4H, Ar-H), 7.33 (t, J
¼ 8.0 Hz, 1H, Ar-H), 7.42 (d, 2H, J ¼ 7.6 Hz, Ar-H), 7.96 (t,
2H, J ¼ 7.2 Hz, Ar-H). 13C NMR (100 MHz, CDCl3) d ¼
160.98, 153.36, 150.18, 145.07, 143.83, 134.49, 130.03,
128.49, 127.69, 119.94, 115.41, 115.12, 66.98, 65.64, 53.11,
51.32, 53.86. Anal. Calcd. For C23H24N4O3S: C, 63.28; H,
5.54; N, 12.83. Found: C, 63.13; H, 5.47; N, 12.69. MS (FAB)
m/z: 436 (Mþ).
3k: m.p. 206–208ꢀC, Yield 79%. IR (KBr) m: 2988, 1620,
1
1475, 794 cmꢁ1. H NMR (400 MHz, DMSO-d6) d ¼ 2.49 (t,
J ¼ 4.5 Hz, 4H, CH2NCH2), 3.57 (t, J ¼ 4.5 Hz, 4H,
CH2OCH2), 3.92 (s, 2H, CH2), 7.33 (d, 1H, J ¼ 7.6 Hz, Ar-
H), 7.39 (d, 1H, J ¼ 7.2 Hz, Ar-H), 7.44–7.48 (m, 2H, Ar-H),
7.51 (d, 1H, J ¼ 7.2 Hz, Ar-H), 7.79 (d, 2H, J ¼ 8.6 Hz, Ar-
H), 7.89–7.98 (m, 3H, Ar-H). Anal. Calcd. For C23H20N4O2S:
C, 66.33; H, 4.84; N, 13.45. Found: C, 66.49; H, 4.92; N,
13.60. MS (FAB) m/z: 417 (Mþ1)þ.
3f: m.p. 136–138ꢀC, Yield 80%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.52 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.68 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.92 (s, 2H, CH2), 5.35 (s, 2H,
CH2O), 6.91–7.16 (m, 3H, Ar-H), 7.28 (d, J ¼ 8.0 Hz, H, Ar-
H), 7.36 (d, J ¼ 8.0 Hz, 1H, Ar-H), 7.45 (d, J ¼ 7.6 Hz, 2H,
Ar-H), 7.99 (d, 2H, J ¼ 7.2 Hz, Ar-H). 13C NMR (100 MHz,
CDCl3) d ¼ 160.97, 157.05, 145.15, 143.88, 134.40, 129.91,
129.32, 128.49, 127.69, 127.46, 122.86, 122.45, 119.91,
115.61, 66.92, 65.65, 53.12, 51.38. Anal. Calcd. For
C22H21ClN4O2S: C, 59.92; H, 4.80; N, 12.71. Found: C,
60.07; H, 4.90; N, 12.84. MS (FAB) m/z: 441 (Mþ1)þ.
3g: m.p. 133–134ꢀC, Yield 81%. 1H NMR (400 MHz,
CDCl3) d ¼ 2.53 (t, J ¼ 4.0 Hz, 4H, CH2NCH2), 3.69 (t, J ¼
4.0 Hz, 4H, CH2OCH2), 3.90 (s, 2H, CH2), 5.36 (s, 2H,
CH2O), 6.95 (d, J ¼ 8.0 Hz, 2H, Ar-H), 7.29–7.35 (m, 3H,
Ar-H), 7.43 (d, J ¼ 7.6 Hz, 2H, Ar-H), 7.95 (t, 2H, J ¼ 7.2
3l: m.p. 220–222ꢀC, Yield 73%. IR (KBr) m: 2960, 1612,
1
1450, 748 cmꢁ1. H NMR (400 MHz, DMSO-d6) d ¼ 2.50 (t,
J ¼ 4.5 Hz, 4H, CH2NCH2), 3.59 (t, J ¼ 4.5 Hz, 4H,
CH2OCH2), 3.92 (s, 2H, CH2), 7.31 (d, 1H, J ¼ 7.6 Hz, Ar-
H), 7.41 (d, 1H, J ¼ 7.2 Hz, Ar-H), 7.46 (d, 1H, J ¼ 8.0 Hz,
Ar-H), 7.50 (d, 1H, J ¼ 8.0 Hz, Ar-H), 7.77 (d, 2H, J ¼ 8.0
Hz, Ar-H), 7.86–7.97 (m, 3H, Ar-H). Anal. Calcd. For
C23H19ClN4O2S: C, 61.26; H, 4.25; N, 12.42. Found: C,
61.10; H, 4.18; N, 12.35. MS (FAB) m/z: 451 (Mþ1)þ.
3m: m.p. 210–212ꢀC, Yield 74%. IR (KBr) m: 2928, 1600,
1
1469, 760 cmꢁ1. H NMR (400 MHz, DMSO-d6) d ¼ 2.52 (t,
J ¼ 4.0 Hz, 4H, CH2NCH2), 3.55 (t, J ¼ 4.0 Hz, 4H,
CH2OCH2), 3.90 (s, 2H, CH2), 7.35 (d, 1H, J ¼ 8.0 Hz, Ar-
H), 7.42 (d, 2H, J ¼ 8.0 Hz, Ar-H), 7.49 (d, 1H, J ¼ 7.2 Hz,
Ar-H), 7.52 (d, 1H, J ¼ 7.2 Hz, Ar-H), 7.65 (d, 1H, J ¼ 8.4
Hz, Ar-H), 7.85–7.99 (m, 3H, Ar-H). Anal. Calcd. For
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[5] Khazi, I. A. M.; Mahajanshetti, C. S.; Gadad, A. K.; Tar-
nalli, A. D.; Sultanpur, C. M. Arzneim-Forsch/Drug Res 1996, 46,
949.
C23H19BrN4O2S: C, 55.76; H, 3.87; N, 11.31. Found: C,
55.95; H, 3.97; N, 11.45. MS (FAB) m/z: 495 (Mþ1)þ.
Crystal structure determination of compound 3a. X-ray
quality crystals of the colorless title compound 3a were
obtained by crystallization from EtOH solution. The diffraction
data were collected with a Bruker Smart Apex CCD area de-
tector using a graphite monochromated MoKa radiation (k ¼
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ꢀ
˚
0.71073 A) at 20 C. The data collection and processing were
performed using program SMART and SAINT [17]. The struc-
ture solution, refinement, and geometrical calculations were
carried out through SHELX TL [18]. All hydrogen atoms were
added theoretically. Crystallographic data for the structure
analysis has been deposited at the Cambridge Crystallographic
Data Centre, CCDC No. 644233 for 3a. Copies of these infor-
mation can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: (44)
01223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
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Acknowledgment. The authors thank for the financial support
by the National Nature Science Foundation of China (No.
20902073), the Natural Science Foundation of Gansu Province
(No. 096RJZA116), and the Gansu Key Laboratory of Polymer
Materials.
[13] Jadhav, V. B.; Kulkarni, M. V.; Rasal, V. P.; Biradar, S. S.;
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet