Synthesis and bioactivity of a novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

Article abstract of DOI:10.1016/j.cclet.2009.11.008

A novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4- thiadiazoles were synthesized by the condensation of 4-amino-5-[2-(4- chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole with various (un)substituted aromatic acids in the presence of phosphorous oxychloride. These compounds were investigated for their inhibitory activity to E. coli methionine aminopeptidase (EcMetAP1). Some of the tested compounds showed significant inhibitory activity.

Full text of DOI:10.1016/j.cclet.2009.11.008

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 293–296
www.elsevier.com/locate/cclet
Synthesis and bioactivity of a novel series of 3,6-disubstituted
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles
a
b
a
a
Ying Jun Li a, , Li Jun Liu , Kun Jin , Yong Ting Xu , Su Qin Sun
*
a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China
Received 10 July 2009
Abstract
A novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were synthesized by the condensation of 4-amino-5-
[2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole with various (un)substituted aromatic acids in
the presence of phosphorous oxychloride. These compounds were investigated for their inhibitory activity to E. coli methionine
aminopeptidase (EcMetAP1). Some of the tested compounds showed significant inhibitory activity.
# 2009 Ying Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Triazolo-thiadiazoles; Synthesis; Bioactivity
Currently, heterocycles bearing a 1,2,4-triazole or 1,3,4-thiadiazole moiety, represent an interesting class of
compounds possessing a wide spectrum of biological activities such as anti-inflammatory [1], antiviral [2] and
antimicrobial [3] properties. It has also been reported that derivatives of 1,2,4-triazole and 1,3,4-thiadiazole condensed
nucleus systems exert diverse pharmacological activities such as anti-inflammatory [4], antitumor [5], antifungal and
antibacterial [6]. Furthermore, a survey of literature revealed that s-triazolo[3,4-b]-1,3,4-thiadiazole rings, have
received much attention during recent years on account of their prominent utilization as antifungal [7], anti-
inflammatory [8], antiviral, analgesic [9], anthelmintic [10] and antibacterial agents [11].
Meanwhile, the benzimidazole has been an important pharmacophore and privileged structure in medicinal
chemistry. Benzimidazoles exhibit significant activity as potential antitumor agents [12], antimicrobial agents [13],
smooth muscle cell proliferation inhibitors [14], a treatment for intestinal cystitis [15], and in diverse area of chemistry
[16].
Prompted by these observations, as part of our research program aimed at developing new biologically active
nitrogen and sulphur containing heterocycles, we report the synthesis and bioactivity of some new 3,6-disubstiuted-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles containing benzimidazole moiety by incorporating these biologically active
heterocyclic rings. The synthesis entailed the union of two biologically active nuclei, viz, triazole and thiadiazole. All
the newly synthesized compounds were screened for their inhibitory activity to E. coli methionine aminopeptidase
(EcMetAP1).
* Corresponding author.
E-mail address: chemlab.lnnu@163.com (Y.J. Li).
1001-8417/$ – see front matter # 2009 Ying Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.11.008

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Y.J. Li et al. / Chinese Chemical Letters 21 (2010) 293–296
Scheme 1. Synthesis of 3,6 disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles. Reagents and conditions: (a) monochloroacetic acid, NaOH,
reflux, 4 h; (b) o-phenylenediamine, melting, 180 Æ 5 8C, 0.5 h; (c) ethyl chloroacetate, triethylamine, DMF, 80 8C, 8 h; (d) N2H4ÁH2O, EtOH,
reflux, 6 h; (e) CS2, KOH, EtOH, r.t., stir, overnight; (f) N2H4ÁH2O, EtOH, reflux, 7 h; (g) aromatic acid, POCl3, reflux, 7 h.
The synthetic route of the target compounds 7 was shown in Scheme 1. p-Chlorophenol, as the starting material,
was treated with monochloroacetic acid to yield p-chlorophenoxyacetic acid (1), which was reacted with o-
phenylenediamine using a melting method to give the corresponding 2-(4-chlorophenoxymethyl)-1H-benzimidazole
(2), treatment of 2 with ethyl chloroacetate in triethylamine/DMF gave the N-alkylated product, ethyl 2-(4-
chlorophenoxymethyl)-1H-benzimidazole acetate (3). Hydrazine hydrate and the related ester 3 in ethanol were
refluxed for 6 h to give the desired 2-(4-chlorophenoxymethyl)-1H-benzimidazole acetic acid hydrazide (4). The
acetic acid hydrazide 4 was allowed to react with carbondisulfide in the presence of KOH at room temperature to
afford the corresponding potassium dithiocarbazinate 5 which was subsequently converted to the required 4-amino-5-
[2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole (6) through direct hydrazinoly-
sis with hydrazine hydrate in ethanol. The title compounds 7a–q were prepared by condensing 6 with various
Table 1
Inhibitory rate of target compounds 7a–q and L288 against EcMetAP1.
Compounds
Y
Inhibitory rate (%)*
Compounds
Y
Inhibitory rate (%)*
7a
7b
7c
7d
7e
7f
C6H5–
87.26
82.62
15.88
2.03
0
7j
p-ClC6H4–
o-FC6H4–
0
o-CH3C6H4–
m-CH3C6H4–
p-CH3C6H4–
o-CH3OC6H4–
m-CH3OC6H4–
7k
7l
0
m-FC6H4–
p-FC6H4–
47.07
0
7m
7n
7o
m-O2NC6H4–
p-O2NC6H4–
19.94
0
40.00
7g
p-CH3OC6H4–
8.72
7p
0
7h
7i
o-ClC6H4–
m-ClC6H4–
36.69
0
7q
6.88
L288
93.96

Y.J. Li et al. / Chinese Chemical Letters 21 (2010) 293–296
295
(un)substituted aromatic acids in the presence of phosphorous oxychloride. The structures of the target compounds
1
were characterized by IR, H NMR and elemental analysis. The analysis data of compounds 7a–q were shown in
reference [17].
The target compounds 7a–q were screened for their inhibitory activity to EcMetAP1. The results are shown in
Table 1.
In summary, seventeen new 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were synthesized.
Preliminary bioassay indicated that the target compounds 7a and 7b exhibited higher inhibitory activity whose
the inhibitory rate was respectively 87.26% and 82.62% to EcMetAP1, compounds 7f and 7l showed moderate activity.
Acknowledgment
We thank the National Center for Drug Screening for determining bioactivity. This research was supported by the
Education Office of Liaoning Province (No. 2008345).
References
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[11] Z.Y. Zhang, X.W. Sun, C.H. Chu, et al. J. Chin. Chem. Soc. 44 (1997) 535.
[12] W.A. Denny, G.W. Rewcastle, B.C. Baguley, J. Med. Chem. 33 (1990) 814.
[13] T. Fonseca, B. Gigante, T.L. Gilchrist, Tetrahedron 57 (2001) 1793.
[14] H.M. Elokdah, S.Y. Chai, T.L. Sulkowski, U.S. Pat. 5,763,473 (1998).
[15] S. Iyenger, M.A. Nuhlhauser, K.B. Thor, U.S. Pat.13,129 (1996).;
S. Iyenger, M.A. Nuhlhauser, K.B. Thor, International PCT Pat. 33,873 (1997).
[16] C. Stevenson, R. Davies, H. Jeremy, Chem. Res. Toxicol. 12 (1999) 38.
[17] Analytical data: 7a. yield: 50.8%; m.p. 237.9–239.5 8C; IR (KBr) v: 3056, 2928, 2856, 1618, 1598, 1492, 1470, 1444, 1366, 1276, 1238 cmÀ1
;
1H NMR (500 MHz, DMSO-d6): d 7.80 (d, 1H, J = 8.2 Hz, BZM-H), 7.68–7.74 (m, 3H, BZM-H, Ar-H), 7.66 (t, 1H, J = 7.5 Hz, Ar-H), 7.56
(dd, 2H, J1 = 7.9 Hz, J2 = 7.5 Hz, Ar-H), 7.35 (td, 1H, J1 = 7.74 Hz, J2 = 0.9 Hz, BZM-H), 7.27 (td, 1H, J1 = 7.74 Hz, J2 = 0.9 Hz, BZM-H),
7.25 (d, 2H, J = 9.0 Hz, Ar-H), 6.99 (d, 2H, J = 9.0 Hz, Ar-H), 6.14 (s, 2H, NCH2), 5.57 (s, 2H, CH2O); Anal. Calcd. for C24H17ClN6OS: C
60.95, H 3.62, N 17.77; Found: C 60.74, H 3.51, N 17.95. 7b. yield: 40.2%; m.p. 177.0À178.8 8C; IR (KBr) v: 3060, 2948, 2860, 1616, 1596,
1584, 1490, 1470, 1445, 1366, 1288, 1242, 1020 cm–1; 1H NMR (400 MHz, DMSO-d6): d 6.80–7.80 (m, 12H, BZM-H, Ar-H), 6.15 (s, 2H,
NCH2), 5.53 (s, 2H, CH2O), 2.16 (s, 3H, CH3); Anal. Calcd. for C25H19ClN6OS: C 61.66, H 3.93, N 17.26; Found: C 61.38, H 4.13, N 17.51. 7c.
1
yield: 50.7%; m.p. 221.6–222.5 8C; IR (KBr) v: 3056, 2920, 2868, 1616, 1586, 1492, 1464, 1444, 1370, 1282, 1248, 1030 cmÀ1; H NMR
(400 MHz, DMSO-d6): d 7.82 (d, 1H, J = 8.4 Hz, BZM-H), 7.71 (d, 1H, J = 7.6 Hz, BZM-H), 7.40–7.52 (m, 4H, Ar-H), 7.36 (t, 1H, J = 7.6 Hz,
BZM-H), 7.28 (t, 1H, J = 7.6 Hz, BZM-H), 7.23 (d, 2H, J = 8.8 Hz, Ar-H), 6.95 (d, 2H, J = 8.8 Hz, Ar-H), 6.14 (s, 2H, NCH2), 5.56 (s, 2H,
CH2O), 2.38 (s, 3H, CH3); Anal. Calcd. for C25H19ClN6OS: C 61.66, H 3.93, N 17.26; Found: C 61.81, H 3.79, N 17.03. 7d. yield: 50.4%; m.p.
;
242.5–244.4 8C; IR (KBr) v: 3056, 2920, 2872, 1612, 1598, 1584, 1492, 1470, 1444, 1366, 1284, 1238, 1026 cmÀ1 1H NMR (400 MHz,
DMSO-d6): d 7.80 (d, 1H, J = 8.0 Hz, BZM-H), 7.69 (d, 1H, J = 8.4 Hz, BZM-H), 7.59 (d, 2H, J = 8.0 Hz, Ar-H), 7.37 (d, 2H, J = 8.0 Hz, Ar-
H), 7.25–7.35 (m, 2H, BZM-H), 7.25 (d, 2H, J = 8.8 Hz, Ar-H), 7.00 (d, 2H, J = 8.8 Hz, Ar-H), 6.13 (s, 2H, NCH2), 5.57 (s, 2H, CH2O), 2.40 (s,
3H, CH3); Anal. Calcd. for C25H19ClN6OS: C 61.66, H 3.93, N 17.26; Found: C 61.88, H 3.84, N 17.41. 7e. yield: 54.7%; m.p. 257.0–259.0 8C;
IR (KBr) v: 3052, 2940, 2840, 1616, 1600, 1586, 1492, 1464, 1366, 1296, 1240, 1016 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 7.81 (d, 1H,
J = 8.0 Hz, BZM-H), 7.60–7.74 (m, 2H, BZM-H, Ar-H), 7.24–7.40 (m, 4H, BZM-H, Ar-H), 7.22 (d, 2H, J = 8.8 Hz, Ar-H), 7.09 (t, 1H,
J = 7.2 Hz, Ar-H), 6.96 (d, 2H, J = 8.8 Hz, Ar-H), 6.15 (s, 2H, NCH2), 5.57 (s, 2H, CH2O), 4.02 (s, 3H, OCH3); Anal. Calcd. for
C25H19ClN6O2S: C 59.70, H 3.81, N 16.71; Found: C 59.47, H 3.61, N 17.01. 7f. yield: 45.7%; m.p. 228.5–229.5 8C; IR (KBr) v: 3060,
2936, 2836, 1616, 1598, 1584, 1492, 1468, 1434, 1334, 1290, 1234, 1020 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 7.80 (d, 1H, J = 8.0 Hz,
BZM-H), 7.70 (d, 1H, J = 8.0 Hz, BZM-H), 7.48 (dd, 1H, J1 = 7.2 Hz, J2 = 8.4 Hz, Ar-H), 7.34 (t, 1H, J1 = 7.0 Hz, J2 = 7.6 Hz, BZM-H), 7.28
(t, 1H, J = 7.0 Hz, BZM-H), 7.22 (d, 4H, J = 9.2 Hz, Ar-H), 7.14 (s, 1H, Ar-H), 6.95 (d, 2H, J = 9.2 Hz, Ar-H), 6.15 (s, 2H, NCH2), 5.56 (s, 2H,
CH2O), 3.83 (s, 3H, OCH3); Anal. Calcd. for C25H19ClN6O2S: C 59.70, H 3.81, N 16.71; Found: C 59.96, H 4.03, N 16.44. 7g. yield: 55.5%;
m.p. 227.8–229.6 8C; IR (KBr) v: 3056, 2920, 2852, 1608, 1584, 1492, 1470, 1442, 1364, 1260, 1238, 1026 cmÀ1 1H NMR (400 MHz,
;
DMSO-d6): d 7.79 (d, 1H, J = 8.0 Hz, BZM-H), 7.69 (d, 1H, J = 8.0 Hz, BZM-H), 7.64 (d, 2H, J = 8.8 Hz, Ar-H), 7.35 (t, 1H, J1 = 7.2 Hz,
J2 = 7.6 Hz, BZM-H), 7.20–7.30 (m, 3H, BZM-H, Ar-H), 7.09 (d, 2H, J = 8.8 Hz, Ar-H), 7.00 (d, 2H, J = 9.2 Hz, Ar-H), 6.12 (s, 2H, NCH2),

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Y.J. Li et al. / Chinese Chemical Letters 21 (2010) 293–296
5.57 (s, 2H, CH2O), 3.87 (s, 3H, OCH3); Anal. Calcd. for C25H19ClN6O2S: C 59.70, H 3.81, N 16.71; Found: C 59.88, H 3.93, N 16.90. 7h.
1
yield 49.4%; m.p. 202.0–203.8 8C; IR (KBr) v: 3064, 2952, 2868, 1618, 1594, 1492, 1462, 1432, 1368, 1286, 1240, 1026 cmÀ1; H NMR
(400 MHz, DMSO-d6): d 7.78 (d, 1H, J = 8.4 Hz, BZM-H), 7.60–7.74 (m, 4H, BZM-H, Ar-H), 7.51 (t, 1H, J = 8.0 Hz, Ar-H), 7.26 (t, 1H,
J1 = 6.8 Hz, J2 = 7.6 Hz, BZM-H), 7.21 (d, 2H, J = 8.8 Hz, Ar-H), 6.93 (d, 2H, J = 8.8 Hz, Ar-H), 6.16 (s, 2H, NCH2), 5.55 (s, 2H, CH2O);
Anal. Calcd. for C24H16Cl2N6OS: C 56.81, H 3.18, N 16.56; Found: C 56.54, H 3.07, N 16.78. 7i. yield 46.4%; m.p. 248.2–249.4 8C; IR (KBr)
v: 3060, 2924, 2856, 1618, 1598, 1582, 1492, 1460, 1444, 1348, 1282, 1236, 1026 cmÀ1 1H NMR (400 MHz, DMSO-d6): d 7.82 (d, 1H,
;
J = 8.4 Hz, BZM-H), 7.54–7.76 (m, 5H, BZM-H, Ar-H), 7.36 (t, 1H, J = 8.0 Hz, BZM-H), 7.28 (t, 1H, J = 8.0 Hz, BZM-H), 7.20 (d, 2H,
J = 8.8 Hz, Ar-H), 6.91 (d, 2H, J = 8.8 Hz, Ar-H), 6.16 (s, 2H, NCH2), 5.54 (s, 2H, CH2O); Anal. Calcd. for C24H16Cl2N6OS: C 56.81, H 3.18,
N 16.56; Found: C 56.67, H 3.33, N 16.36. 7j. yield: 50.9%; m.p. > 250 8C; IR (KBr) v: 3064, 2936, 2856, 1620, 1596, 1492, 1468, 1444, 1364,
1282, 1236, 1012 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 7.80 (d, 1H, J = 8.4 Hz, BZM-H), 7.70 (d, 3H, J = 8.4 Hz, BZM-H, Ar-H), 7.64 (d,
2H, J = 8.4 Hz, Ar-H), 7.35 (t, 1H, J1 = 7.2 Hz, J2 = 7.6 Hz, BZM-H), 7.27 (t, 1H, J = 7.6 Hz, BZM-H), 7.24 (d, 2H, J = 8.8 Hz, Ar-H), 6.96 (d,
2H, J = 8.8 Hz, Ar-H), 6.14 (s, 2H, NCH2), 5.56 (s, 2H, CH2O); Anal. Calcd. for C24H16Cl2N6OS: C 56.81, H 3.18, N 16.56; Found: C 57.05, H
3.05, N 16.82. 7k. yield: 54.3%; m.p. 222.5–224.5 8C; IR (KBr) v: 3064, 2932, 2860, 1616, 1586, 1492, 1462, 1366, 1288, 1238, 1026 cmÀ1
;
1H NMR (400 MHz, DMSO-d6): d 7.80 (d, 1H, J = 8.0 Hz, BZM-H), 7.60–7.78 (m, 3H, BZM-H, Ar-H), 7.48 (dd, 1H, J1 = 8.4 Hz,
J2 = 11.6 Hz, Ar-H), 7.30–7.42 (m, 2H, BZM-H, Ar-H), 7.27 (t, 1H, J = 7.6 Hz, BZM-H), 7.21 (d, 2H, J = 8.2 Hz, Ar-H), 6.94 (d, 2H,
J = 8.2 Hz, Ar-H), 6.16 (s, 2H, NCH2), 5.56 (s, 2H, CH2O); Anal. Calcd. for C24H16ClFN6OS: C 58.72, H 3.28, N 17.12; Found: C 58.85, H
3.51, N 16.84. 7l. yield: 41.3%; m.p. 238.5–239.5 8C; IR (KBr) v: 3060, 2940, 2872, 1616, 1592, 1492, 1464, 1448, 1348, 1286, 1238,
1026 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 7.81 (d, 1H, J = 7.6 Hz, BZM-H), 7.71 (d, 1H, J = 7.6 Hz, BZM-H), 7.61 (m, 1H, Ar-H), 7.48–
7.56 (m, 2H, Ar-H), 7.46 (d, 1H, J = 8.4 Hz, Ar-H), 7.35 (t, 1H, J = 7.2 Hz, BZM-H), 7.28 (t, 1H, J1 = 7.2 Hz, J2 = 7.6 Hz, BZM-H), 7.21 (d,
2H, J = 8.6 Hz, Ar-H), 6.94 (d, 2H, J = 8.6 Hz, Ar-H), 6.15 (s, 2H, NCH2), 5.55 (s, 2H, CH2O); Anal. Calcd. for C24H16ClFN6OS: C 58.72, H
3.28, N 17.12; Found: C 58.47, H 3.14, N 17.23. 7m. yield: 54.1%; m.p. 248.9–250.6 8C; IR (KBr) v: 3060, 2932, 2868, 1600, 1492, 1470,
1444, 1350, 1276, 1238, 1024 cmÀ1 1H NMR (400 MHz, DMSO-d6): d 7.80 (d, 1H, J = 8.4 Hz, BZM-H), 7.76 (dd, 2H, J1 = 5.2 Hz,
;
J2 = 8.0 Hz, Ar-H), 7.70 (d, 1H, J = 8.0 Hz, BZM-H), 7.42 (t, 2H, J = 8.8 Hz, Ar-H), 7.35 (t, 1H, J1 = 7.2 Hz, J2 = 7.6 Hz, BZM-H), 7.27 (t, 1H,
J = 7.6 Hz, BZM-H), 7.24 (d, 2H, J = 9.0 Hz, Ar-H), 6.96 (d, 2H, J = 9.0 Hz, Ar-H), 6.14 (s, 2H, NCH2), 5.56 (s, 2H, CH2O); Anal. Calcd. for
C
24H16ClFN6OS: C 58.72, H 3.28, N 17.12; Found: C 58.57, H 3.45, N 16.94. 7n. yield: 54.1%; m.p. 245.8–247.4 8C; IR (KBr) v: 3088, 2968,
2860, 1616, 1596, 1582, 1538, 1490, 1462, 1440, 1346, 1284, 1234, 1020 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 8.47 (dd, 1H, J1 = 1.6 Hz,
J2 = 8.0 Hz, Ar-H), 8.36 (s, 1H, Ar-H), 8.12 (d, 1H, J = 8.4 Hz, Ar-H), 7.80–7.90 (m, 2H, BZM-H, Ar-H), 7.71 (d, 1H, J = 8.0 Hz, BZM-H),
7.37 (t, 1H, J = 7.2 Hz, BZM-H), 7.28 (t, 1H, J = 7.2 Hz, BZM-H), 7.15 (d, 2H, J = 8.8 Hz, Ar-H), 6.89 (d, 2H, J = 8.8 Hz, Ar-H), 6.18 (s, 2H,
NCH2), 5.55 (s, 2H, CH2O); Anal. Calcd. for C24H16ClN7O3S: C 55.65, H 3.11, N 18.93; Found: C 55.86, H 3.32, N 18.69. 7o. yield: 60.6%;
m.p. > 250 8C; IR (KBr) v: 3064, 2928, 2860, 1602, 1530, 1492, 1466, 1416, 1348, 1284, 1238, 1020 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d
8.38 (d, 2H, J = 8.4 Hz, Ar-H), 7.94 (d, 2H, J = 8.4 Hz, Ar-H), 7.82 (d, 1H, J = 8.8 Hz, BZM-H), 7.72 (d, 1H, J = 8.0 Hz, BZM-H), 7.37 (t, 1H,
J = 7.6 Hz, BZM-H), 7.28 (t, 1H, J = 7.2 Hz, BZM-H), 7.21 (d, 2H, J = 8.8 Hz, Ar-H), 6.94 (d, 2H, J = 8.8 Hz, Ar-H), 6.17 (s, 2H, NCH2), 5.56
(s, 2H, CH2O); Anal. Calcd. for C24H16ClN7O3S: C 55.65, H 3.11, N 18.93; Found: C 55.49, H 3.01, N 18.79. 7p. yield: 73.2%; m.p. 244.5–
245.8 8C; IR (KBr) v: 3060, 2948, 2864, 1618, 1590, 1492, 1462, 1444, 1336, 1282, 1236, 1020 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 8.85
(s, 1H, Ar-H), 8.81(d, 1H, J = 4.8 Hz, Ar-H), 8.06 (d, 1H, J = 8.0 Hz, Ar-H), 7.81 (d, 1H, J = 8.0 Hz, BZM-H), 7.71 (d, 1H, J = 8.0 Hz, BZM-
H), 7.60 (dd, 1H, J1 = 4.8 Hz, J2 = 8.0 Hz, Ar-H), 7.35 (t, 1H, J1 = 7.2 Hz, J2 = 8.0 Hz, BZM-H), 7.27 (t, 1H, J1 = 7.2 Hz, J2 = 8.0 Hz, BZM-
H), 7.21 (d, 2H, J = 8.4 Hz, Ar-H), 6.94 (d, 2H, J = 8.4 Hz, Ar-H), 6.16 (s, 2H, NCH2), 5.56 (s, 2H, CH2O); Anal. Calcd. for C23H16ClN7OS: C
58.29, H 3.40, N 20.69; Found: C 58.57, H 3.24, N 20.91. 7q. yield: 64.7%, m.p. 247.0–249.0 8C; IR (KBr) v: 3060, 2956, 2868, 1616, 1596,
1492, 1464, 1414, 1364, 1282, 1232, 1018 cmÀ1; 1H NMR (400 MHz, DMSO-d6): d 8.79 (brs, 2H, Ar-H), 7.81 (brs, 1H, BZM-H), 7.71 (brs,
1H, BZM-H), 7.62 (brs, 2H, Ar-H), 7.35 (brs, 1H, BZM-H), 7.27 (brs, 1H, BZM-H), 7.23 (brs, 2H, Ar-H), 6.96 (brs, 2H, Ar-H), 6.17 (s, 2H,
NCH2), 5.56 (s, 2H, CH2O); Anal. Calcd. for C23H16ClN7OS: C 58.29, H 3.40, N 20.69; Found: C 58.48, H 3.62, N 20.50.