482 JOURNAL OF CHEMICAL RESEARCH 2007
2-[(4-Ethoxycarbonylphenyl)hydrazono]-3-methyl-7-phenyl-2H-
imidazo[2,1-b][1,3,4]thiadiazine (4Ah): Yellow solid (0.70 g, 70%),
m.p. 240–242°C (EtOH-dioxan). IR: νmax 3386, 1701 cm-1. NMR:
δH 1.30 (t, J = 7 Hz, 3H, CH3), 2.45 (s, 3H, CH3), 4.27 (q, J = 7 Hz,
2H, CH2), 7.26–7.41 (m, 5H, ArH), 7.79 (d, J = 7 Hz, 2H, ArH), 7.88
(d, J = 7 Hz, 2H, ArH), 8.18 (s,1H, ArH), 10.40 (s, 1H, NH). MS: m/z
(%) 406 (M+ + 1, 20), 405 (M+, 76), 189 (11), 187 (100), 174 (37),
149 (74), 121 (39), 103 (82), 91 (29), 77 (19), 73 (44). Anal. Calcd.
for C21H19N5O2S (405.48): C, 62.21; H, 4.72; N, 17.27. Found: C,
62.01; H, 4.55; N, 17.10%.
1H, ArH), 10.89 (s, 1H, NH). MS: m/z (%) 441(M+ + 1, 2), 440 (M+,
8), 186 (20), 122 (12), 116 (19), 105 (100), 103 (33), 91 (15), 76 (34).
Anal. Calcd. for C23H16N6O2S (440.49): C, 62.72; H, 3.66; N, 19.08.
Found: C, 62.97; H, 3.68; N, 19.20%.
2-[(4-Ethoxycarbonylphenyl)hydrazono]-3,7-diphenyl-2H-
imidazo[2,1-b][1,3,4]-thiadiazine (4Bh): Orange solid (0.81 g,
69%), m.p. 180°C (EtOH-dioxan). IR: νmax 3155, 1708 cm-1. NMR:
δH 1.29 (t, J = 7 Hz, 3H, CH3), 4.25 (q, J = 7 Hz, 2H, CH2), 7.26–7.85
(m, 14H, ArH), 8.31 (s, 1H, ArH), 10.57 (s, 1H, NH). MS: m/z (%)
468 (M+ + 1, 9), 467 (M+, 27), 439 (23), 295 (5), 291 (25), 205 (6),
187 (88), 174 (17), 161 (11), 150 (12), 137 (35), 121 (25), 116 (80),
103 (100), 77 (99), 74 (10). Anal. Calcd. for C26H21N5O2S (467.55):
C, 66.79; H, 4.53; N, 14.98. Found: C, 66.64; H, 4.30; N, 14.90%.
2-[(4-Acetylphenyl)hydrazono]-3,7-diphenyl-2H-imidazo[2,1-b]
[1,3,4]thiadiazine (4Bi): Yellow solid (0.76 g, 70%), m.p. 224°C
(EtOH-dioxan). IR: νmax 3220, 1662 cm-1. 1H NMR (DMSO-d6)
δ 2.47 (s, 3H, COCH3), 7.13 (d, J = 8 Hz, 2H, ArH), 7.25-7.86 (m,
10H, ArH), 7.77 (d, J = 8 Hz, 2H, ArH), 8.32 (s, 1H, ArH), 10.59
(s, 1H, NH). MS: m/z (%) 439 (M+ + 2, 6), 438 (M+ + 1, 17), 437
(M+, 53), 409 (12), 290 (24), 245 (19), 244 (32), 211 (12), 187 (100),
173 (21), 147 (29), 129 (13), 119 (61), 116 (56), 105 (33), 103 (86),
91 (37), 77 (67). Anal. Calcd. for C25H19N5OS (437.53): C, 68.63;
H, 4.38; N, 16.01. Found: C, 69.00; H, 4.70; N, 16.40%.
2-[(4-Cyanophenyl)hydrazono]-3,7-diphenyl-2H-imidazo[2,1-b]
[1,3,4]thiadiazine (4Bj): Orange solid (0.77 g, 73%), m.p. 272°C
(dioxan). IR: νmax 3236, 2221 cm-1. NMR: δH 7.15 (d, J = 7 Hz, 2H,
ArH), 7.28–7.76 (m, 10H, ArH), 7.83 (d, J = 7 Hz, 2H, ArH), 8.33 (s,
1H, ArH), 10.65 (s, 1H, NH). MS: m/z (%) 422 (M+ + 2, 6), 421 (M+
+ 1, 18), 420 (M+, 62), 290 (22), 244 (27), 187 (100), 173 (21), 146
(17), 117 (32), 115 (52), 105 (28), 103 (85), 91 (35), 77 (52). Anal.
Calcd. for C24H16N6S (420.50): C, 68.55; H, 3.84; N, 19.99. Found:
C, 68.45; H, 4.12; N, 19.81%.
2-[(4-Acetylphenyl)hydrazono]-3-methyl-7-phenyl-2H-
imidazo[2,1-b][1,3,4]thiadiazine (4Ai): Dark red solid (0.62 g, 66%),
m.p. 268–269°C (EtOH). IR: νmax 3244, 1658 cm-1. NMR: δH 2.46
(s, 3H, CH3), 2.50 (s, 3H, COCH3), 7.26–7.43 (m, 5H, ArH), 7.79 (d,
J = 8 Hz, 2H, ArH), 7.91 (d, J = 8 Hz, 2H, ArH), 8.2 (s, 1H, ArH), 10.40
(s, 1H, NH). MS: m/z (%) 377 (M+ + 2, 10), 376 (M+ + 1, 29), 375
(M+, 100), 256 (11), 228 (15), 187 (61), 183 (17), 174 (18), 147 (14),
119 (42), 103 (31), 77 (15). Anal. Calcd. for C20H17N5OS (375.46): C,
63.98; H, 4.56; N, 18.65. Found: C, 64.21; H, 4.32; N, 18.75%.
2-[(4-Cyanophenylhydrazono]-3-methyl-7-phenyl-2H-
imidazo[2,1-b][1,3,4]thiadiazine (4Aj): Yellow solid (0.63 g,
1
70%), m.p. 260–262°C (EtOH). IR: νmax 3386, 2218 cm-1. H NMR
(DMSO-d6) δ 2.44 (s, 3H, CH3), 7.23–7.44 (m, 5H, ArH), 7.71 (d,
J = 8 Hz, 2H, ArH),, 7.78 (d, J = 8 Hz, 2H, ArH), 8.19 (s, 1H, ArH),
10.46 (s, 1H, NH). MS: m/z (%) 360 (M+ + 2, 7), 359 (M+ + 1, 24),
358 (M+, 100), 187 (65), 177 (26), 147 (18), 142 (12), 116 (37), 103
(67), 90 (39), 77 (10). Anal. Calcd. for C19H14N6S (358.43): C, 63.67;
H, 3.94; N, 23.45. Found: C, 63.54; H, 3.65; N, 23.20%.
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one2-(4-methoxy-
phenyl)hydrazone (4Ba): Dark red solid, (Yield 0.64 g, 60%),
m.p.108–110°C (EtOH). IR: νmax 3140 cm-1. NMR: δH 3.68 (s, 3H,
OCH3), 6.82 (d, J = 9 Hz, 2H, ArH), 7.02 (d, J = 9 Hz, 2H, ArH),
7.27–7.85 (m, 10H, ArH), 8.27 (s, 1H, ArH), 10.08 (s, 1H, NH).
MS: m/z (%) 427 (M+ + 2, 16), 426 (M+ + 1, 20), 425 (M+, 73), 365
(11), 290 (28), 268 (4), 236 (3), 213 (6), 187 (45), 160 (7), 147 (6),
135 (43), 122 (73), 107 (100), 77 (35), 76 (13). Anal. Calcd. for
C24H19N5OS (425.52): C, 67.75; H, 4.50; N, 16.46. Found: C, 67.42;
H, 4.23; N, 16.32%.
Cyclisation of the open-chain intermediates 3Bc and 3Cd
A solution of 3Bc or 3Cd (0.0025 mole) in glacial acetic acid
(30 ml) was refluxed for 5 hours, then poured onto ice with stirring.
The solid that precipitated was filtered off, dried and crystallised from
the ethanol to give the respective 4Bc or 4Cd.
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-(4-methyl-
phenyl)hydrazone (4Bb): Dark red solid (0.66 g, 65%), m.p. 110–
112°C (EtOH). IR: νmax 3218 cm-1. NMR: δH 2.21 (s, 3H, CH3), 6.97
(d, J = 9 Hz, 2H, ArH), 7.02 (d, J = 9 Hz, 2H, ArH), 7.28–7.85 (m,
10H, ArH), 8.28 (s, 1H, ArH), 10.13 (s, 1H, NH). MS: m/z (%) 411
(M+ + 2, 8), 410 (M+ + 1, 21), 409 (M+, 58), 290 (19), 245 (11),
244 (21), 187 (60), 137 (6), 119 (20), 116 (27), 103 (35), 91 (100),
77 (25). Anal. Calcd. for C24H19N5S (409.52): C, 70.39; H, 4.68; N,
17.10. Found: C, 70.34; H, 4.52; N, 17.40%.
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-(4-chloro-
phenyl)hydrazone (4Bd): Yellow solid (0.77 g, 72%), m.p.158–160°C
(EtOH). IR: νmax 3417 cm-1. NMR: δH 7.06–7.55 (m, 10H, ArH), 7.74
(d, J = 9 Hz, 2H, ArH), 7.82 (d, J = 9 Hz, 2H, ArH), 8.30 (s, 1H,
ArH), 10.33 (s, 1H, NH); δC 113.7, 115.3, 118.1, 122.5, 123.5, 125.3,
125.9, 126.1, 126.7, 127.0, 127.7, 128.1, 130.7, 132.8, 137.5, 140.9,
148.5. MS: m/z (%) 432 (M+ + 3, 13) 431 (M+ + 2, 39), 430 (M+ +
1, 33), 429 (M+, 100), 290 (46), 244 (27), 187 (96), 173 (16), 139
(16), 116 (26), 111 (30), 103 (41), 89 (12), 77 (15). Anal. Calcd. for
C23H16ClN5S (429.93): C, 64.26; H, 3.75; N, 16.29. Found: C, 64.42;
H, 3.58; N, 16.13%.
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-phenyl-
hydrazone (4Bc): Yellow solid (0.68 g, 69%), m.p.100°C (EtOH).
IR: νmax 3417 cm-1. NMR: δH 6.48-8.14 (m, 15H, ArH), 8.17 (s, 1H,
ArH), 10.00 (s, 1H, NH). MS: m/z (%) 397 (M+ + 2, 6), 396 (M+
+ 1, 24), 395 (M+, 71), 290 (19), 244 (20), 187 (63), 173 (16), 147
(12), 116 (27), 105 (24),103 (48), 77 (100), 76 (16). Anal. Calcd. for
C23H17N5S (395.49): C, 69.85; H, 4.33; N, 17.71. Found: C, 69.62;
H, 4.35; N, 17.35%.
7-Phenyl-3-(2-thienyl)-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one
2-(4-chlorophenyl)hydrazone (4Cd): Dark red solid (0.65 g, 60%),
m.p.140°C (EtOH). IR: νmax 3150 cm-1. NMR: δH 7.25–7.38 (m, 8H,
ArH), 7.41 (d, J = 7 Hz, 2H, ArH), 7.83 (d, J = 7 Hz, 2H, ArH), 8.32
(s, 1H, ArH), 10.39 (s, 1H, NH). MS: m/z (%) 439 (M+ + 3, 4), 438
(M+ + 2, 5), 437 (M+ + 1, 26), 436 (M+, 17), 269 (13), 250 (15), 178
(100), 174 (11), 139 (23), 116 (49), 113 (11), 103 (37), 99 (21), 89
(18), 77 (16), 76 (18). Anal. Calcd. for C21H14ClN5S2 (435.96): C,
57.86; H, 3.24; N, 16.06. Found: C, 57.52; H, 3.10; N, 15.94%.
Synthesis of 2-acetyl-3-methyl-7-phenyl-2H-imidazo-[2,1-b][1,3,4]
thiadiazine (8)
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-(3-chloro-
phenyl)hydrazone (4Be): Dark red solid (0.73 g, 68%), m.p.120–
122°C (EtOH). IR: νmax 3358 cm-1. NMR: δH 6.92-7.85 (m, 14H,
ArH), 8.32 (s, 1H, ArH), 10.38 (s, 1H, NH). MS: m/z (%) 432 (M+ +
3, 12), 431 (M+ + 2, 39), 430 (M+ + 1, 31), 429 (M+, 74), 290 (31),
272 (19), 244 (22), 187 (100), 173 (16), 147 (12), 139 (11), 116 (28),
111 (25), 103 (42), 89 (15), 77 (19). Anal. Calcd. for C23H16ClN5S
(429.93): C, 64.26; H, 3.75; N, 16.29. Found: C, 64.09; H, 3.58; N,
16.14%.
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-(3-nitro-
phenyl)hydrazone (4Bf): Dark red solid (0.72 g, 65%), m.p.160°C
(EtOH). IR: νmax 3293 cm-1. NMR: δH 7.28–7.91 (m, 14H, ArH),
8.33 (s, 1H, ArH), 10.62 (s, 1H, NH). MS: m/z (%) 442 (M+ + 2, 10),
441(M+ + 1, 35), 440 (M+, 100), 290 (28), 277 (18), 245 (27),
174 (15), 118 (32), 103 (44), 89 (12), 77 (21). Anal. Calcd. for
C23H16N6O2S (440.49): C, 62.72; H, 3.66; N, 19.08. Found: C, 62.53;
H, 3.80; N, 19.00%.
To a solution of 2 (0.96 g, 5 mmole) in ethanol was added an aqueous
solution of potassium hydroxide (0.4 ml, 75%) and the mixture was
warmed for 10 min. at 80°C and then cooled. To the resulting clear
solution was added 3-chloro-2,4-pentanedione (0.6 ml, 5 mmol)
dropwise with stirring. After the addition was complete the mixture
was stirred for a further 18 h at room temperature. Petroleum ether
was added and the mixture was left in a refrigerator over night.
A solid which separated was filtered off and crystallised from
petroleum ether to give pure 8 as a pale yellow solid (0.75 g, 55%),
m.p.128–130°C. IR: νmax 1712 cm-1. NMR: δH 2.26 (s, 3H, CH3),
2.33 (s, 3H, COCH3), 4.99 (s, 1H, CH), 7.35–7.75 (m, 5H, ArH), 8.08
(s,1H, ArH). MS: m/z (%) 272 (M+ + 1, 10), 271 (M+, 49), 228 (100),
201 (34), 188 (77), 116 (97), 102 (93), 89 (56), 76 (76). Anal. Calcd.
for C14H13N3OS (271): C, 61.99; H, 4.80; N, 15.50. Found: C, 62.10;
H, 4.63; N, 15.32%.
Alternative synthesis of 4Ac
3,7-Diphenyl-2H-imidazo[2,1-b][1,3,4]thiadiazin-2-one 2-(4-nitro-
phenyl)hydrazone (4Bg): Orange solid (0.74 g, 67%), m.p. 250–
252°C (EtOH). IR: νmax 3375 cm-1. NMR: δH 7.18 (d, J = 9 Hz, 2H,
ArH), 7.26–7.85 (m, 10H, ArH), 8.12 (d, J = 9 Hz, 2H, ArH), 8.34 (s,
To a solution of 8 (0.68 g, 2.5 mmol) in ethanol (20 ml) was added
sodium acetate trihydrate (0.34 g, 2.5 mmol) and the mixture was
cooled to 0–5°C in an ice-bath. A solution of benzenediazonium
chloride, prepared as usual by diazotising (2.5 mmol) in hydrochloric
PAPER: 07/4686