1
886
Sahar Said El-Sakka et al.
2
.14 (3H, s, CH ), 3.29–3.45 (2H, m, CH -CH), 3.80 C, 65.12; H, 5.18; N, 15.99. Found: C, 65.33; H,
3
2
−1
(
(
(
3H, s, OCH ), 4.34–4.39 (1H, m, CH-CH ), 7.03–7.80 5.16; N, 16.11; IR (KBr, ν, cm ): 3349 (NH), 1601
3
2
1
3H, m, Ar-H), 8.76, 9.00 (2H, 2s, NH); MS (m/z, 278 (C=N) or (C=C); H-NMR (DMSO-d , δ ppm): 2.19
6
+
20%)) (M ).
(3H, s, CH ), 3.24 (2H, s, CH ), 3.89 (3H, s, OCH ),
.75–7.85 (8H, m, Ar-H); MS (m/z, 350 (1.3%)) (M ).
3
2
3
+
6
2
.8b 2-anilino-4-hydroxy-5-[2-(4-methoxy-3-methyl-
2
.9b 1,4-dihydro-3-[4-methoxy-3-methylphenyl]-6-(4-
phenyl)-2-oxoethyl]-1,3-thiazole (9b): From butanol,
M.p. 210 C. Anal. Calcd. for C H N O S (354.42):
C, 64.39; H, 5.12; N, 7.90. Found: C, 64.40; H, 5.00;
◦
toludino)-1,3-thiazolo[4,5-c]pyridazine (10b): From
ethanol, M.p. 240–242 C. Anal. Calcd. for C H N OS
19
18
2
3
◦
20 20
4
−1
(364.46): C, 65.91; H, 5.53; N, 15.37. Found: C, 66.05;
N, 8.03; IR (KBr, ν, cm ): 3260 (NH), 1664 (C=O);
−1
1
H, 5.76; N, 15.29; IR (KBr, ν, cm ): 3342 (NH), 1603
H-NMR (DMSO-d , δ ppm): 2.11 (3H, s, CH ), 3.29–
6
3
1
(
2
C=N) or (C=C). ); H-NMR (DMSO-d , δ ppm):
3.64 (2H, m, CH -CH), 3.86 (3H, s, OCH ), 4.40–4.50
6
2
3
.16, 2.19 (6H, 2s, 2CH -Ar), 3.33 (2H, s, CH ), 3.80
(H, m, CH-CH ), 6.96–7.89 (8H, m, Ar-H), 11.15 (H,
3
2
2
+
(3H, s, OCH ), 6.93–7.89 (7H, m, Ar-H), 8.96 (H,
s, NH); MS (m/z, 354 (42%)) (M ).
3
s, NH), 13.1 (H, s, NH); MS (m/z, 363 (14.7%))
+
(M - H).
2.8c 4-hydroxy-5-[2-(4-methoxy-3-methylphenyl)-2-
oxoethyl]-2-(4-toludino)-1,3-thiazole (9c): From butanol,
◦
2.9c 6-(4-chloroanilino)-1,4-dihydro-3-[4-methoxy-3-
methylphenyl]-1,3-thiazolo[4,5-c]pyridazine (10c): From
M.p. 225 C. Anal. Calcd. for C H N O S (368.45):
20
20
2
3
C, 65.20; H, 5.47; N, 7.60. Found: C, 65.51; H, 5.63;
◦
−1
butanol, M.p. 256–258 C. Anal. Calcd. for C H
19
17
N, 7.91; IR (KBr, ν, cm ): 3181 (NH), 1684 (C=O);
1
ClN OS (384.88): C, 59.29; H, 4.45; N, 14.56. Found:
4
H-NMR (DMSO-d , δ ppm): 2.11, 2.26 (6H, 2s,
6
−1
C, 59.00; H, 4.56; N, 14.48; IR (KBr, ν, cm ): 3331
2
CH -Ar.), 3.28–3.55 (2H, m, CH -CH), 3.86 (3H, s,
3
2
1
(
NH), 1601 (C=N) or (C=C); H-NMR (DMSO-
OCH ), 4.44–4.48 (H, m, CH-CH ), 6.88–7.89 (7H, m,
3
2
+
d , δ ppm): 2.16 (3H, s, CH ), 3.30 (2H, s, CH ),
6
3
2
Ar-H), 11.08 (1H, s, NH); MS (m/z, 368 (98%)) (M ).
3
.80 (3H, s, OCH ), 6.93–7.55 (7H, m, Ar-H), 9.2
3
(
H, s, NH), 13.2 (H, s, NH); MS (m/z, 384 (4.5%))
+
2
.8d 2-(4-chloroanilino)-4-hydroxy-5-[2-(4-methoxy- (M ).
3
-methylphenyl)-2-oxoethyl]-1,3-thiazole (9d): From
◦
acetic acid, M.p. 228 C. Anal. Calcd. for C H ClN
19
17
2
2
.10 Synthesis of 1,4-dihydro-3-[4-methoxy-3-methyl-
O S (388.45): C, 58.69; H, 4.41; N, 7.20. Found: C,
3
−1
phenyl]-1-phenyl-6-(4-toludino)-1,3-thiazolo[4,5-c]
pyridazine (11)
5
9.06; H, 4.92; N, 6.97; IR (KBr, ν, cm ): 3173 (NH),
1
1667 (C=O); H-NMR (DMSO-d , δ ppm): 2.17 (3H,
6
s, CH ), 3.28–3.67(2H, m, CH -CH), 3.86 (3H, s,
3
2
A mixture of 4-hydroxy-5-[2-(4-methoxy-3-methyl-
phenyl)-2-oxoethyl]-2-(4-toludino)-1,3-thiazole (9b)
(0.005 mol) and phenylhydrazine hydrochloride (0.006
mol) in pyridine (5 mL) was heated under reflux for 6
hrs. the solid separated after evaporation of the most of
OCH ), 4.40–4.60 (H, m, CH-CH ), 6.91–7.98 (7H, m,
3
2
+
Ar-H), 11.32 (H, s, NH); MS (m/z, 388 (62%)) (M ),
90 (27%) (M +2).
+
3
2
.9 General procedure for the synthesis of 6-arylamino-1, the solvent and cooling, was washed by benzene and
4
-dihydro-3-[4-methoxy-3-methylphenyl]-1,3-thiazolo
crystallized from the proper solvent to give (11) with
◦
[4,5-c]pyridazines (10a-c)
M.p. 316 C. Anal. Calcd. for C26
H
24
N
4
OS (440.56); C,
7
0.88; H, 5.49; N, 12.72; Found: C, 71.32; H, 5.42;
−1
To a solution of the thiazoles (9b-d) (0.01 mol) in
ethanol (20 mL); hydrazine hydrate 80% (0.015 mol)
was added and the reaction mixture was refluxed for
N, 12.66; IR (KBr, ν, cm ): 3018 (CH-Ar), 2839–
1
0
2918 (CH aliph.), 1620 (C=C); H-NMR (DMSO-d ,
6
δ ppm): 2.23 and 2.25 (6H, 2s, 2CH - Ar), 2.36 (2H, s,
3
6
h. The solid that separated after cooling was crystal-
CH ), 3.89 (3H, s, OCH ), 7.20–8.03 (12H, m, Ar- H)
2
3
+
lized from suitable solvent to give the corresponding
thiazolopyridazine (10a-c).
9.23 (H, s, NH); MS (m/z, 440 (10%)) (M ).
2.11 Synthesis of acetyl derivatives of thiazoles (12a-d)
2.9a 6-anilino-1,4-dihydro-3-[4-methoxy-3-methylphenyl]
-
1,3-thiazolo[4,5-c]pyridazine (10a): From ethanol, A solution of thiazoles (9a-d) (1 gm) in acetic
◦
M.p. 290 C. Anal. Calcd. for C H N OS (350.43): anhydride (5 mL) was refluxed for 4 h. The solid
19
18
4