T. M. A. Eldebss, A. M. Farag, and A. Y. M. Shamy
Vol 000
ꢀ
1
1
1
υmax/cm : 1717 and 1674 (2C¼O). H NMR (DMSO-d ):
3425 (NH), 2437 (CꢁN), 1620 (C¼O). H NMR
6
δ 2.69 (s, 3H, CH ), 4.60 (s, 2H, CH ), 7.65–7.01 (m, 4H,
ArH). MS (m/z): 281 (M , 7.2%), 225 (7.19%), 160
17.29.0%). For C H BrN O (281.11): Calcd: C, 47.00;
(DMSO-d ): δ 3.14 (s, 6H, N–(CH ) ), 4.08 (s, 3H, N–
CH ), 7.28 (s, 4CH thiazole), 7.63–7.22 (m, 4H, ArH),
3
2
6
3 2
+
3
(
7.75 (s, 1H, –CH¼), 8.61 (br. s, 1H, NH, D O-
1
1
9
2
2
2
13
H, 3.23; N, 9.97; Br, 28.42. Found: C, 46.67; H, 3.27; N,
.93; Br, 28.93.
-(1-Acetylbenzimidazole-2-yl)-2-aminothiazole (5c). To a
solution of 1-acetyl-2-bromoacetylbenzimidazole (4c)
2.81 g, 10 mmol) in ethanol (20 mL) was added
thiourea (0.76 g, 10 mmol). The mixture was refluxed
for 2 h and then allowed to cool and treated with
ammonium hydroxide solution till pH 9. The formed
product was filtered off, washed with water, dried, and
finally recrystallized from dioxane to afford 4-(1-
acetylbenzimidazole-2-yl)-2-aminothiazole (5c) 1.94 g
exchangeable). C NMR (DMSO-d ):174.33 (C¼O),
6
9
166.05 (C thiazole), 157.53 (N–CH), (142.45, 136.23,
2
4
122.52, 118.80, 110.313) (aromatic carbons), 142.29(C,
imidazole), 139.22 (C thiazole), 114.65 (CꢁN), 85.86
5
(
(C thiazole), 67.77 (C–CꢁN), 40.31 (N–(CH ) ), 14.38
4
3 2
+
(
N–CH ). MS (m/z): 352 (M , 57%), 285 (65%), 188
3
(
100%). For C H N OS (352.41): Calcd: C, 57.94; H,
.58; N, 23.85; S, 9.10. Found: C, 57.87; H, 4.59; N,
17 16 6
4
2
3.92; S, 9.02.
2-Cayno-3-ethoxy-N-(4-(1-methylbbenzimidazol-yl)thiazol-2-
yl)
acrylamide
(8).
To
2-cyano-N-(4-
ꢀ
1
(
75%) yield; mp >300°C. IR (KBr) υmax/cm : 3420
(1-methylbenzimidazole-2-yl)thiazol-2-yl)acetamide(6b)
(0.592 g, 2 mmol) was added triethyl orthoformate (10 mL)
and was refluxed for 2 h. After the reaction was complete,
the reaction mixture allowed to cool to room temperature,
and the precipitated solid was filtered off, washed with
water, and dried and afforded compound (8) 0.57 g (80%
1
and 3263 (NH ), 1593 (C¼O). H NMR (DMSO-d ):
2
6
2
.76 (s, 3H, CH ), 6.29 (br. s, 2H, NH2, D O-
3
2
exchangeable), 7.92–7.11 (m, 4H, ArH), 7.28 (s, 1H,
CH thiazole). MS (m/z): 260 (M , 7%), 258 (M ,
8%), 215 (31%), 160 (41%). For C H N OS
258.30): Calcd: C, 55.80; H, 3.90; N, 21.69; S, 12.41.
Found: C, 55.62; H, 4.00; N, 21.63; S, 12.50.
-Cyano-N-(4-(1-acetylbenzimidazole-2-yl-thiazol-2-yl)
acetamide (6c).
bottomed flask, fitted with air condenser and thermometer,
were placed ethyl cyanoacetate (22.6 g, 200 mmol).
The flask was immersed in an oil bath heated to 145–
0°C and then, 28.6 g of 4-(1-acetylbenzimidazole-2-yl)-
-aminothiazole (5c) was added portionwise over a period
of 1 h. Heating was continued for an additional 15 min;
then, the reaction flask was removed from the oil bath and
left to cool. The formed product was filtered off, washed
several times with ethanol, and dried. Recrystallization
from ethanol afforded the compound 6c 36.36 g (90%
+
2
+
4
1
1
2 10 4
ꢀ
1
(
yield), mp 135–6°C. IR (KBr) υmax/cm : 3248 (NH),
1
2156 (CꢁN), 1682 (C¼O). H NMR (DMSO-d ): δ 1.22
6
2
(t, 3H, CH ), 4.27 (s, 3H, CH ), 4.30 (q, 2H, CH ), 7.77
3
3
2
In a 250-mL three-necked round-
(
s, 1H, 4CH thiazole), 8.46–7.58 (m, 4H, ArH), 8.67 (s,
1
H, O–CH¼), 12.8 (br. s, 1H, NH, D O-exchangeable).
2
+
MS (m/z): 353 (M , 68%), 323 (84%), 282 (91%). For
C H N O S (353.40): Calcd: C, 57.78; H, 4.28; N,
9.82; S, 9.07. Found: C, 57.75; H, 4.35; N, 19.78; S, 9.1.
17 15 5 2
5
2
1
Reaction of 2-cyano-3-ehtoxy-N-(4-(1-methylbenzimidazol-
-yl)thiazol-2-yl) acrylamide with hydroxyl amine, hydrazine,
phenylhydrazine, and thiourea. General procedure. To a
solution of 2-cyano-3-ehtoxy-N-(4-(1-methylbenzimidazol-
-yl)thiazol-2-yl) acrylamide (8) or (7) (0.592 g, 2 mmol)
in ethanol was added an equimolar amount of the
hydroxylamine, hydrazine, phenylhydrazine, or thiourea
(2 mmol), and the reaction mixture was heated for 3 h.
The solid product was collected by filtration, washed with
ethanol, and then crystallized from appropriate solvent to
afford the corresponding products 11, 12, 13, and 16,
2
2
ꢀ
1
Yield), mp 247–8°C. IR (KBr) υmax/cm : 3166 (NH),
1
2
206 (CꢁN), 1743 (C¼O). H NMR (DMSO-d ): δ 2.52
6
(
s, 3H, CO–CH ), 3.47 (s, 2H, CH ), 7.28 (s, 1H, 4CH
3 2
thiazole), 7.77–7.15 (m, 4H, ArH), 12.03 (br. s, 1H, NH,
D O-exchangeable). MS (m/z): 326 (M + 1, 1.82%), 281
22.4%), 207 (39.32%).
+
2
(
respectively.
For C H N O S (325.35): Calcd: C, 55.38; H, 3.41;
15
11
5
2
3-Amino-N-(4-(1-methylbenzimidazol-2-yl)thiazol-2-yl)
N, 21.53; S, 9.84. Found: C, 55.50; H, 3.31; N, 21.61;
S, 9.78.
isoxazole-4-carboxamide (11). Yield: (66%). mp >300°C.
ꢀ
1
IR (KBr) υmax/cm : 3776 and 3418 (NH2), 3047 (NH),
+
2
-Cayno-3-(dimethylamino)-N-(4-(1-ethylbbenzimidazol2yl)
1
2
697 (C¼O). MS (m/z): 340 (M , 34%), 337 (0.18%),
thiazol2-yl) acrylamide (7).
To 2-cyano-N-(4-(1-
methylbenzimidazole-2-yl)thiazol-2-yl) acetamide (6b)
0.592 g, mmol) was added
57 (36%), 213 (40%). For C H N O S (340.36):
1
5 12 6 2
Calcd: C, 52.93; H, 3.55; N, 24.69; S, 9.42. Found: C,
2.95; H, 3.40; N, 24.98; S, 9.30.
(
2
5
dimethylformamide/dimethylacetal (10 mL) with stirring
at room temperature over a period of 2 h. The
precipitated solid product was collected by filtration,
washed with water, dried, and finally recrystallized from
dimethylformamide/ethanol to afford the compound (7)
3
-Amino-N-(4-(1-methylbenzimidazol-2-yl)thiazol-2-yl)-
(1H)-pyrazole-4-carboxamide (12).
>300°C. IR (KBr) υmax/cm : 3850 and 3742 (NH2),
Yield: (76%). mp
ꢀ
1
1
3260 (NH), 3128 (NH), 1648 (C¼O). H NMR (DMSO-
d ): δ 4.15 (s, 3H, N–CH ), 6.90 (br. s, 2H, NH , D O-
6
3
2
2
ꢀ
1
0.60 g (85% Yield), mp 204–5°C. IR (KBr) υmax/cm
:
exchangeable), 7.64–7.07 (m, 4H, ArH), 7.28 (s, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet