N.B. Patel et al. / European Journal of Medicinal Chemistry 45 (2010) 4293e4299
4297
exchange), 7.55e7.87 (m, 3H, 3CH) ppm. Anal. Calcd. for C7H6N3ClS:
163e165 ꢂC; IR (KBr): 3449 (NH), 1652 (C]N) cmꢀ1
;
1H NMR
C, 42.11; H, 3.03; N, 17.76; Found: C, 42.07; H, 3.01; N, 18.00%.
(CDCl3) d 2.43 (s, 3H, CH3), 7.90 (s,1H, NH), 9.38 (s,1H, CH), 8.82 (dd,
1H, J ¼ 3.8 Hz, CH), 8.43 (d, 1H, J ¼ 8.5 Hz, CH), 7.51 (t, 1H, CH), 8.35
(d, 2H, J ¼ 8.16 Hz, 2CH), 7.31 (d, 2H, J ¼ 8.16 Hz, 2CH), 7.58 (d, 1H,
J ¼ 7.85 Hz, CH), 8.05 (d, 1H, J ¼ 8.04 Hz, CH), 8.74 (s, 1H, CH); 13C
6.1.2. 2-(3-Pyridyl)-5-(4-methylphenyl)-1,3,4-oxadiazole 5
A mixture of nicotinoyl hydrazide 4 (5 mmol) and 4-methyl-
benzoic acid (5 mmol) in phosphorus oxy chloride (5 ml) was
refluxed on water bath for 9 h. The progress of the reaction was
monitored by TLC using toluene:ethylacetate:methanol (70:20:10)
as mobile phase. After the completion of reaction, it was cooled and
poured onto crushed ice with continuous stirring. The solid mass
separated was neutralized with sodium bicarbonate solution
(10% w/v). The resulting solid thus obtained was collected by
filtration, washed well with cold water, dried and crystallized from
absolute ethanol.
NMR (CDCl3)
d 162.94 (C3-triazole), 162.36 (C5-triazole), 24.37
(CH3), 150.96, 148.83, 146.74, 146.61, 141.77, 134.48, 132.86, 132.60,
132.32, 129.53, 129.31, 124.61, 123.97, 121.98, 110.58, 119.72
(aromatic ring) ppm; MS (m/z): 429 (Mþ); Anal. Calcd. for
C21H15N7O2S: C, 58.73; H, 3.52; N, 22.83; Found: C, 58.69; H, 3.48;
N, 22.87%.
6.1.3.4. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-methyl-1,3-benzo-
thiazol-2-amino)-4H-1,2,4-triazole 6d. Redish brown soꢀli1d (66%), m.
Off-white solid (65%); m.p. 266e270 ꢂC; IR (KBr): 1667 (C]N),1287,
p. 156e158 ꢂC; IR (KBr): 3442 (NH), 1659 (C]N) cm
;
1H NMR
1073 (CeOeC) cmꢀ1; 1H NMR (CDCl3)
d
2.44 (s, 3H, CH3), 9.37 (s, 1H,
(CDCl3) d 2.40 (s, 3H, CH3), 2.33 (s, 3H, CH3), 7.88 (s, 1H, NH), 9.36
CH), 8.81 (dd, 1H, J ¼ 3.48 Hz, CH), 8.44 (d, 1H, J ¼ 8.08 Hz, CH), 7.51 (t,
(s, 1H, CH), 8.82 (dd, 1H, J ¼ 3.4 Hz, CH), 8.43 (d, 1H, J ¼ 8.48 Hz, CH),
7.45 (t, 1H, CH), 8.01 (d, 2H, J ¼ 8.04 Hz, 2CH), 7.58 (d, 2H,
J ¼ 8.38 Hz, 2CH), 7.04e7.48 (m, 3H, benzothiazole-H); 13C NMR
1H, CH), 8.03 (d, 2H, J ¼ 8.16 Hz, 2CH), 7.35 (d, 2H, J ¼ 8.04 Hz, 2CH); 13C
NMR (CDCl3)
d 158.82 (C5-oxadiazole), 157.50 (C2-oxadiazole), 24.96
(CH3),147.5,143.02,138.02,129.42,125.16,125.01,122.29,122.10,115.97
(aromatic ring) ppm; MS (m/z): 237 (Mþ); Anal. Calcd. for C14H11N3O: C,
70.87; H, 4.67; N, 17.71; Found: C, 70.84; H, 4.71; N, 17.68%.
(CDCl3) d 163.01 (C3-triazole), 162.58 (C5-triazole), 24.42 (CH3),
22.91 (CH3), 151.93, 148.85, 146.97, 144.75, 135.28, 135.17, 131.31,
131.15, 129.92, 128.79, 128.52, 124.61, 124.21, 124.02, 121.27, 121.38
(aromatic ring) ppm; MS (m/z): 398 (Mþ); Anal. Calcd. for
C22H18N6S: C, 66.31; H, 4.55; N, 21.09; Found: C, 66.34; H, 4.51;
N, 21.05%.
6.1.3. General procedure for the synthesis of 3-(3-pyridyl)-5-
(4-methylphenyl)-4-(N-substituted-1,3-benzothiazol-2-amino)-
4H-1,2,4-triazole 6aej
A mixture of 2-(3-pyridyl)-5-(4-methylphenyl)-1,3,4-oxadiazole
5 (5 mmol) and substituted 2-hydrazino-1,3-benzothiazole 2aej
(5 mmol) in dry pyridine (10 ml) was refluxed for 18e24 h. The
reaction was monitored by TLC on silica gel using ethyl acetate:
toluene (2.5:7.5). It was then cooled and poured on to crushed ice.
The reaction mass was neutralized by dilute hydrochloric acid and
resulting solid was washed with cold water, dried and crystallized
from absolute ethanol.
6.1.3.5. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-methoxy-1,3-ben-
zothiazol-2-amino)-4H-1,2,4-triazole 6e. Red solid (63%), m.p.
241e243 ꢂC; IR (KBr): 3449 (NH), 1652 (C]N) cmꢀ1 1H NMR
;
(CDCl3) d 2.44 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 7.86 (s, 1H, NH), 9.37
(s, 1H, CH), 8.82 (dd, 1H, J ¼ 4.0 Hz, CH), 8.43 (d, 1H, J ¼ 8.08 Hz, CH),
7.51 (t,1H, CH), 8.05 (d, 2H, J ¼ 8.16 Hz, 2CH), 7.37 (d, 2H, J ¼ 8.16 Hz,
2CH), 6.84e7.28 (m, 3H, benzothiazole-H); 13C NMR (CDCl3)
d
163.38 (C3-triazole), 162.82 (C5-triazole), 24.32 (CH3), 52.69
The other compounds of the series were prepared by similar
procedure.
(OCH3), 152.91, 149.56, 147.83, 147.35,143.02, 134.36, 132.60, 132.44,
131.13, 127.61, 127.42, 124.23, 124.08, 119.15, 113.98, 106.25
(aromatic ring) ppm; MS (m/z): 414 (Mþ); Anal. Calcd. for
C22H18N6OS: C, 63.75; H, 4.38; N, 20.28; Found: C, 63.79; H, 4.42;
N, 20.24%.
6.1.3.1. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-flouro-1,3-benzo-
thiazol-2-amino)-4H-1,2,4-triazole 6a. Pink solid (62%), m.p.
165e167 ꢂC; IR (KBr): 3437 (NH), 1661 (C]N) cmꢀ1 1H NMR
;
(CDCl3)
d
2.42 (s, 3H, CH3), 7.82 (s,1H, NH), 9.36 (s,1H, CH), 8.80 (dd,
6.1.3.6. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-chloro-1,3-benzo-
1H, J ¼ 4.0 Hz, CH), 8.43 (d, 1H, J ¼ 8.35 Hz, CH), 7.49 (t,1H, CH), 8.03
thiazol-2-amino)-4H-1,2,4-triazole 6f. Redish black soliꢀd1(69%), m.p.
(d, 2H, J ¼ 8.16 Hz, 2CH), 7.35 (d, 2H, J ¼ 8.04 Hz, 2CH), 7.06e7.26 (m,
247e249 ꢂC; IR (KBr): 3438 (NH), 1661 (C]N) cm
;
1H NMR
3H, benzothiazole-H); 13C NMR (CDCl3)
d
163.48 (C3-triazole),
(CDCl3) d 2.41 (s, 3H, CH3), 7.85 (s, 1H, NH), 9.36 (s, 1H, CH), 8.48 (dd,
163.35 (C5-triazole), 24.44 (CH3), 152.91, 149.66, 147.94, 145.66,
142.02, 134.42, 132.66, 132.51, 131.12, 129.31, 129.12, 124.85, 124.47,
121.91, 113.66, 109.85 (aromatic ring) ppm; MS (m/z): 402 (Mþ);
Anal. Calcd. for C21H15N6FS: C, 62.67; H, 3.76; N, 20.88; Found:
C, 62.63; H, 3.79; N, 20.91%.
1H, J ¼ 3.8 Hz, CH), 8.43 (d, 1H, J ¼ 8.35 Hz, CH), 7.49 (t,1H, CH), 8.03
(d, 2H, J ¼ 8.20 Hz, 2CH), 7.35 (d, 2H, J ¼ 8.04 Hz, 2CH), 7.59e7.80
(m, 3H, benzothiazole-H); 13C NMR (CDCl3)
d 163.24 (C3-triazole),
162.76 (C5-triazole), 24.38 (CH3), 151.91, 148.97, 146.32, 144.44,
134.08, 131.52, 131.36, 131.05, 127.81, 127.62, 126.85, 125.47, 124.33,
123.84, 121.95,121.52 (aromatic ring) ppm; MS (m/z): 418 (Mþ), 420
(M þ 2); Anal. Calcd. for C21H15N6ClS: C, 60.21; H, 3.61; N, 20.06;
Found: C, 60.25; H, 3.58; N, 20.03%.
6.1.3.2. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-bromo-1,3-benzo-
thiazol-2-amino)-4H-1,2,4-triazole 6b. Light brown soliꢀd1(59%), m.p.
149e151 ꢂC; IR (KBr): 3432 (NH), 1646 (C]N) cm
;
1H NMR
(CDCl3)
d
2.41 (s, 3H, CH3), 7.84 (s, 1H, NH), 9.37 (s, 1H, CH), 8.82 (dd,
6.1.3.7. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-4-methyl-1,3-benzo-
1H, J ¼ 4.0 Hz, CH), 8.43 (d, 1H, J ¼ 8.35 Hz, CH), 7.49 (t,1H, CH), 8.05
thiazol-2-amino)-4H-1,2,4-triazole 6g. Pale yellow solid (61%), m.p.
(d, 2H, J ¼ 8.08 Hz, 2CH), 7.29 (d, 2H, J ¼ 8.16 Hz, 2CH), 7.61e7.76 (m,
159e161 ꢂC; IR (KBr): 3435 (NH), 1660 (C]N) cmꢀ1 1H NMR
;
3H, benzothiazole-H); 13C NMR (CDCl3)
d
163.21 (C3-triazole),
(CDCl3) d 2.39 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.88 (s, 1H, NH), 9.36 (s,
162.69 (C5-triazole), 24.39 (CH3), 151.93, 149.82, 147.69, 145.60,
136.69, 134.28, 131.98, 133.15, 128.83, 129.03, 127.78, 124.49, 124.23,
123.09, 118.99, 111.63 (aromatic ring) ppm; MS (m/z): 463 (Mþ), 465
(M þ 2); Anal. Calcd. for C21H15N6BrS: C, 54.43; H, 3.26; N, 18.14;
Found: C, 54.39; H, 3.22; N, 18.17%.
1H, CH), 8.80 (dd, 1H, J ¼ 3.8 Hz, CH), 8.43 (d, 1H, J ¼ 8.38 Hz, CH),
7.50 (t,1H, CH), 8.04 (d, 2H, J ¼ 8.16 Hz, 2CH), 7.32 (d, 2H, J ¼ 8.12 Hz,
2CH), 7.09e7.28 (m, 3H, benzothiazole-H); 13C NMR (CDCl3)
d
163.18 (C3-triazole), 162.65 (C5-triazole), 24.35 (CH3), 20.49 (CH3),
151.88, 148.93, 146.88, 143.47, 134.11, 132.32, 132.15, 131.07, 129.18,
128.96, 128.82, 127.57, 124.53, 123.97, 122.04, 120.96 (aromatic ring)
ppm; MS (m/z): 398 (Mþ); Anal. Calcd. for C22H18N6S: C, 66.31; H,
4.55; N, 21.09; Found: C, 66.27; H, 4.58; N, 21.12%.
6.1.3.3. 3-(3-Pyridyl)-5-(4-methylphenyl)-4-(N-6-nitro-1,3-benzo-
thiazol-2-amino)-4H-1,2,4-triazole 6c. Yellow solid (63%), m.p.