Z. M. Nofal, E. A. Soliman, S. S. Abd El-Karim, M. I. El-Zahar,
A. M. Srour, S. Sethumadhavan, and T. J. Maher
Vol 000
cooled, poured onto ice/cold water, and acidified by hydrochloric
acid. The formed precipitate was filtered, dried, and recrystallized
from ethanol to produce 12.
(s, 1H, thiazole proton), 8.46 (s, 2H, 2(NH)); MS, m/z (%): 425
[M+] (11), 77 [C6H5] (100); Anal. Calcd for C20H23N7S2
(425.57): C, 56.44; H, 5.45; N, 23.04. Found: C, 56.13; H,
5.67; N, 22.84.
Yield 86%, mp 210–212ꢂC. IR (KBr, cmꢀ1): 1698, 1620 (2
N2-(3-Chlorophenyl)-N5-(4-(1-methyl-1H-benzo[d]imidazol-2-
1
(C═O), thiazindione); H NMR (DMSO d6, d ppm): 2.17 (s, 4H,
yl)thiazol-2-yl)-6H-1,3,4-thiadiazine-2,5-diamine (14d).
Yield
2(CH2-thiazindione)), 4.17 (s, 3H, N–CH3), 7.24, 7.60 (m, m, 4H,
benzimidazole protons), 7.92 (s, 1H, thiazole proton); MS, m/z
(%): 344 [M+] (5.6), 230 [C11H10N4S] (100); Anal. Calcd for
C15H12N4O2S2 (344.41): C, 52.31; H, 3.51; N, 16.27. Found: C,
52.86; H, 3.54; N, 16.21.
2-Amino-4,5-dihydro-1-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)
76%, mp 191–193ꢂC; IR (KBr, cmꢀ1): 3231, 3188 (2NH); 1H
NMR (DMSO d6, d ppm): 4.26 (s, 3H, N–CH3), 4.21 (s, 2H, CH2-
thiadiazine protons ), 7.22–7.79 (m, 8H, Ar–H, benzimidazole
protons), 7.76 (s, 1H, thiazole proton), 8.99 (s, 2H, 2(NH)); MS, m/
z (%): 453, 455 [M+] (24, 8), 61 [CH3NS] (100); Anal. Calcd for
C20H16ClN7S2 (453.97): C, 52.91; H, 3.55; N, 21.60. Found: C,
53.10; H, 3.78; N, 21.23.
thiazol-2-yl)-5-oxo-1H-pyrrole-3-carbonitrile (13).
A mixture
of compound 6 (0.61 g, 2 mmol) and malononitrile (0.13mL,
2 mmol) in sodium ethoxide (Na, 0.23g, 10mmol in 20mL
ethanol) was refluxed for 10h. Upon cooling, the reaction mixture
was poured onto ice/cold water and acidified by hydrochloric
acid. The formed precipitate was filtered, dried, and recrystallized
from ethanol to produce 13
2-(Substituted)-N-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)
thiazol-2-yl)acetamide (15a–c).
General method.
A
mixture of compound (0.92 g, 3 mmol) and appropriate
6
secondary amines, namely dimethylamine, diethanolamine, and/or
piperidine (3 mmol) in ethanol (20 mL) containing few drops of
triethylamine was refluxed for 8 h. Upon cooling, the reaction
mixture was poured onto ice/cold water, the formed precipitate
was filtered, dried, and recrystallized from ethanol to produce
15a–c, respectively.
2-(Dimethylamino)-N-(4-(1-methyl-1H-benzo[d]imidazol-2-
yl)thiazol-2-yl)acetamide (15a). Yield 58%, mp 260–262ꢂC; IR
(KBr, cmꢀ1): 3372 (NH), 1698 (CO); 1H NMR (DMSO d6, d ppm):
2.89 (s, 6H, N–(CH3)2), 4.28 (s, 3H, N–CH3), 4.37 (s, 2H, COCH2),
7.54, 7.79 (m, m, 4H, benzimidazole protons), 7.80 (s, 1H, thiazole
proton), 8.74 (s, 1H, NH); MS, m/z (%): 315 [M+] (8), 58 [C3H8N]
(100); Anal. Calcd for C15H17N5OS (315.39): C, 57.12; H, 5.43; N,
22.21. Found: C, 57.03; H, 5.22; N, 22.13.
Yield 54%, mp 188–190ꢂC. IR (KBr, cmꢀ1): 3340 (NH2),
2198 (CN), 1687 (CO); 1H NMR (DMSO d6, d ppm): 2.16
(s, 2H, CH2-pyrrole protons), 4.12 (s, 3H, CH3), 7.22,
7.60 (m, m, 4H, benzimidazole protons), 7.85 (s, 1H, thiazole
proton), and at 12.35 (s, 2H, NH2); MS, m/z (%): 335 [M-1]
(14), 44 [C3H8] (100); Anal. Calcd for C16H12N6OS
(336.37): C, 57.13; H, 3.60; N, 24.98. Found: C, 56.94; H,
3.51; N, 24.73.
N5-(4-(1-Methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)-6H-
1,3,4-oxadiazine-2,5-diamine (14a), N5-(4-(1-methyl-1H-benzo
[d]imidazol-2-yl)thiazol-2-yl)-6H-1,3,4-thiadiazine-2,5-diamine
(14b), and N2 substituted-N5-(4-(1-methyl-1H-benzo[d]imidazol-
2-yl)thiazol-2-yl)6H-1,3,4-thiadiazine-2,5-diamine (14c,d).
General method. A mixture of compound 6 (0.61 g, 2 mmol)
and different semi and/or thiosemicarbazides, namely semicarbazide
hydrochloride, thiosemicarbazide, cyclohexylthiosemicarbazide,
and/or 3-chlorophenylthiosemicarbazide (2 mmol) in ethanol
(30 mL) was refluxed for 6–8 h. The crystals obtained after cooling
was filtered, dried, washed with petroleum ether 40–60, and
recrystallized from ethanol to produce 14a–d, respectively.
N5-(4-(1-Methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)-6H-
1,3,4-oxadiazine-2,5-diamine (14a). Yield 62%, mp 208–210ꢂC;
2-(Bis(2-hydroxyethyl)amino)-N-(4-(1-methyl-1H-benzo[d]
imidazol-2-yl)thiazol-2-yl)acetamide (15b).
Yield 60%, mp
178–180ꢂC; IR (KBr, cmꢀ1): 3299 (OH), 3144 (NH), 1687 (CO);
MS, m/z (%): 376 [M+1] (5), 230 [C11H10N4S] (100); Anal. Calcd
for C17H21N5O3S (375.45): C, 54.38; H, 5.64; N, 18.65. Found:
C, 54.65; H, 5.41; N, 18.30.
2-(piperidine-1-yl)-N-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)
thiazol-2-yl)acetamide (15c). Yield 55%, mp 210–212ꢂC; IR
(KBr, cmꢀ1): 3354 (NH), 1680 (CO); 1H NMR (DMSO d6,
d ppm): 1.19–1.25 (m, 10H, piperidine protons), 4.17 (s, 3H,
N–CH3), 4.19 (s, 2H, COCH2), 7.23, 7.60 (m, m, 4H,
benzimidazole protons), 7.84 (s, 1H, thiazole proton), 8.40 (s, 1H,
NH); MS, m/z (%): 357 [M + 2] (22%), 149 [C8H11N3] (100);
Anal. Calcd for C18H21N5OS (355.46): C, 60.82; H, 5.95; N,
19.70. Found: C, 60.66; H, 5.65; N, 19.23.
N-(4-(1-Methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)-2-
thiocyanatoacetamide (16). A mixture of compound 6 (0.61 g, 2
mmol) and potassium thiocyanate (0.20 g, 2 mmol) in absolute
ethanol (30 mL) was refluxed for 4 h. The formed precipitate was
filtered, dried and recrystallized from ethanol to produce 16.
1
IR (KBr, cmꢀ1): 3428, 3291 (NH2, NH); H NMR (DMSO d6, d
ppm): 3.65 (s, 2H, CH2-oxadiazine protons), 4.14 (s, 3H, CH3),
7.20, 7.64 (m, m, 4H, benzimidazole protons), 7.81 (s, 1H,
thiazole proton), and at 9.21, 12.35 (s, 3H, (NH, NH2)); MS, m/z
(%): 327 [M+] (85.5%), 91 [C2H7N2S] (100); Anal. Calcd for
C14H13N7OS (327.36): C, 51.36; H, 4.00; N, 29.95. Found: C,
51.12; H, 3.88; N, 29.71.
N5-(4-(1-Methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)-6H-
1,3,4-thiadiazine-2,5-diamine (14b). Yield 48%, mp 150–152ꢂC;
1
IR (KBr, cmꢀ1): 3376, 3237 (NH2, NH); H NMR (DMSO d6, d
Yield 72%, mp 224–226ꢂC; IR (KBr, cmꢀ1): 3391 (NH), 2218
(CN), 1653 (CO); 1H NMR (DMSO d6, d ppm): 4.22 (s, 3H, N–
CH3), 4.48 (s, 2H, COCH2), 7.36, 7.70 (m, m, 4H, benzimidazole
protons), 7.72 (s, 1H, thiazole proton), and at 8.16 (s, 1H, NH);
Anal. Calcd for C14H11N5OS2 (329.40): C, 51.05; H, 3.37; N,
ppm): 4.01 (s, 2H, CH2-thiadiazine protons), 4.19 (s, 3H, CH3),
7.18, 7.59 (m, m, 4H, benzimidazole protons), 7.79 (s, 1H,
thiazole proton), and at 8.29, 11.34 (s, 3H, (NH, NH2)) MS, m/z
(%): 344 [M+1] (3), 130.9 [C8H7N2] (100); Anal. Calcd for
C14H13N7S2 (343.43): C, 48.96; H, 3.82; N, 28.55. Found: C,
48.84; H, 3.77; N, 28.40.
21.26. Found: C, 50.84; H, 3.10; N, 21.54.
N2-Cyclohexyl-N5-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)
2-Imino-3-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)
thiazol-2-yl)6H-1,3,4-thiadiazine-2,5-diamine (14c).
Yield
thiazolidin-4-one (17).
A mixture of compound 16 (0.33 g,
1
64%, mp 140–142ꢂC; IR (KBr, cmꢀ1): 3440, 3214 (2 NH); H
NMR (DMSO d6, d ppm): 1.10–1.80 (m, 11H, cyclohexyl
protons), 4.26 (s, 3H, N–CH3), 4.48 (s, 2H, CH2-thiadiazine
protons ), 7.52, 7.78 (m, m, 4H, benzimidazole protons), 7.89
1 mmol) in ethanol (20 mL) containing pyridine (5mL) was
refluxed for 10h. Upon cooling, the reaction mixture was poured
onto ice/cold water. The formed precipitate was filtered, dried,
and recrystallized form ethanol to produce 17.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet