J. CHEM. RESEARCH (S), 1998 209
Scheme 2
1
4: mp 218±219 8C; ꢀmax(KBr)/cm 3404, 3292 (NH2); ꢁH (CDCl3)
heterocyclic amines. Thus, when compound 2 was treated
with guanidine, it aorded an excellent yield of a product
which was identi®ed as 5-(benzothiazol-2-yl)-2,4-diamino-
pyrimidine 6 on the basis of its spectral data. Compounds
3±6 are assumed to be formed via addition of the amino
group of hydrazines or guanidine to the activated ethylenic
double bond of 2 followed by cyclization and elimination of
a dimethylamine molecule as depicted in Scheme 1.
5.88 (2 H, br, NH2), 7.29±7.86 (10 H, m, Ar'H); m/z 292 (M )
(Found: C, 65.69; H, 4.02; N, 19.18; S, 10.88%. C16H12N4S requires
C, 65.73; H, 4.13; N, 19.16; S, 10.96%).
5-Amino-4-(benzothiazol-2-yl)isoxazole 3 and 5-(Benzothiazol-2-yl)-
2,4-diaminopyrimidine 6.ÐTo a mixture of the enaminonitrile 2
(0.458 g, 2 mmol) and hydroxylamine hydrochloride or guanidine
nitrate (2.3 mmol) in ethanol (30 ml), anhydrous potassium carbon-
ate (0.552 g, 4 mmol) was added. The resulting mixture was re¯uxed
for 6 h and then allowed to cool to room temperature and diluted
with water (20 ml). The solid product so formed was collected by
®ltration, washed with water and dried. Recrystallization from
DMF aorded the 5-aminoisoxazole 5 and 2,4-diaminopyrimidine
6, respectively. The products are insoluble in the common NMR
solvents. 5: (72% yield); mp >300 8C; ꢀmax(KBr)/cm 3370, 3174
(NH2); m/z 217 (M ) (Found: C, 55.28; H, 3.35; N, 19.26; S, 14.71%.
C10H7N3OS requires C, 55.30; H, 3.23; N, 19.35; S, 14.75%). 6:
(88% yield); mp >300 8C; ꢀmax(KBr)/cm 3371, 3269, 3210, 3118
(2 NH2); m/z 243 (M ) (Found: C, 54.21; H, 3.75; N, 28.84; S,
When enaminonitrile
2 was treated with 5-amino-3-
phenyl-1H-pyrazole in re¯uxing ethanol, in the presence
of piperidine, it aorded a green product identi®ed as
5-amino-6-(benzothiazol-2-yl)-7-phenylpyrazolo[1,5-a]pyrimi-
dine 7 (Scheme 2). The IR spectrum of compound 7 showed
1
1
two characteristic absorption bands at 3385 and 3210 cm
due to the amino group and no bands due to the nitrile
function.
1
In a similar manner, compound 2 reacted with 2-amino-
benzimidazole under the same experimental conditions gave
a red product in good yield. The structure of the obtained
product was assigned as pyrimido[1,2-a]benzimidazole
derivative 8 (Scheme 2). The presence of an amino group in
structure 8 was evidenced by the appearance of two absorp-
13.20%. C11H9N5S requires C, 54.30; H, 3.73; N, 28.79; S, 13.18%).
Reaction of 2 with Heterocyclic Amines.ÐA mixture of the enami-
nonitrile 2 (0.458 g, 2 mmol) and the appropriate heterocyclic amine
(2.2 mmol) in ethanol (30 ml) in the presence of a few drops of
piperidine was re¯uxed for 8 h, then left to cool to room temp. The
precipitated product was ®ltered o, washed with ethanol and dried.
Recrystallization from DMF aorded the corresponding pyrazolo-
[1,5-a]pyrimidine and pyrimido[1,2-a]benzimidazole derivatives 7 and
8, respectively. The products are insoluble in the common NMR
1
tion bands at 3321 and 3100 cm in the IR spectrum of the
reaction product.
1
solvents. 7: (66% yield); mp 268±270 8C; ꢀmax(KBr)/cm 3385, 3210
(NH2); m/z 343 (M ) (Found: C, 66.41; H, 3.77; N, 20.30; S, 9.4%.
C19H13N5S requires C, 66.45; H, 3.82; N, 20.39; S, 9.34%). 8: (58%
Note that the enaminonitrile 2 reacts smoothly with
2-(1H)-benzimidazoleacetonitrile 9 in re¯uxing ethanol in
the presence of a catalytic amount of piperidine to aord
only one isolable product, identi®ed as 3-amino-2-(benzo-
thiazol-2-yl)pyrido[1,2-a]benzimidazole-4-carbonitrile 10. The
IR spectrum of the latter product revealed bands at 3404,
1
yield); mp >300 8C; ꢀmax(KBr)/cm 3321, 3100 (NH2); m/z 317
(M ) (Found: C, 64.27; H, 3.42; N, 22.20; S, 10.24%. C17H11N5S
requires C, 64.34; H, 3.49; N, 22.07; S, 10.16%).
3-Amino-2-(benzothiazol-2-yl)pyrido[1,2-a]benzimidazole-4-carboni-
trile 10.ÐA mixture of the enaminonitrile 2 (0.458 g, 2 mmol) and
(1H)-2-benzimidazoleacetonitrile 9 (0.314 g, 2 mmol) in ethanol
1
3115 and 2218 cm due to the amino and nitrile functions,
respectively.
(30 ml) was heated to re¯ux temperature. To the resulting hot
solution, a catalytic amount of piperidine (0.1 ml) was added and
the re¯ux was continued for 4 h, then allowed to cool to room
temp. The precipitated product was ®ltered o, washed with
ethanol, dried and ®nally recrystallized from DMF to give the
pyrido[1,2-a]benzimidazole derivative 10 in 81% yield (0.55 g);
mp > 300 8C; insoluble in the common NMR solvents; ꢀmax(KBr)/
cm 3404, 3115 (NH2), 2218 (C2N); m/z 341 (M ) (Found: C,
66.79; H, 3.26; N, 20.37; S, 9.40%. C19H11N5S requires C, 66.84;
H, 3.24; N, 20.51; S, 9.39%).
Experimental
2-(Benzothiazol-2-yl)-3-(N,N-dimethylamino)prop-2-enenitrile 2.Ð
A mixture of 2-benzothiazoleacetonitrile 1 (4.04 g, 20 mmol) and
dimethylformamide dimethyl acetal (2.66 ml, 20 mmol) in dry xylene
(30 ml) was re¯uxed for 3 h, then cooled. The orange±yellow precipi-
tated product was ®ltered o, washed with light petroleum and
dried. Recrystallization from toluene gave compound 2 in 96%
1
1
yield (4.39 g); mp 167±168 8C; ꢀmax(KBr)/cm 2189 (C2N); ꢁH
(CDCl3) 3.29 (6 H, s, 2CH3), 7.18±7.77 (4 H, m, Ar'H), 7.98 (1 H,
s, alkenic) (Found: C, 62.68; H, 4.90; N, 18.41; S, 13.87%.
C12H11N3S requires C, 62.86; H, 4.83; N, 18.32; S, 13.98%).
Received, 13th October 1997; Accepted, 15th December 1997
Paper E/7/07362C
Reaction of 2 with Hydrazines.ÐTo a solution of the enamino-
nitrile 2 (0.458 g, 2 mmol) in ethanol (20 ml), hydrazine hydrate
(80%, 0.2 ml) or phenylhydrazine (0.2 ml, 2 mmol) was added. The
reaction mixture was re¯uxed for 4 h, then cooled. The solid pro-
duct so formed was ®ltered o, washed with ethanol and dried.
Recrystallization from dimethylformamide±ethanol aorded bright
yellow needles of the corresponding 5-amino-4-(benzothiazol-2-yl)-
1H-pyrazole 3 and its 1-phenyl derivative 4 in 88% and 83% yields,
References
1 A. M. Farag, J. Chem. Res. (S), 1995, 96.
2 A. M. Farag, K. M. Dawood and Z. E. Kandeel, J. Chem. Res.
(S), 1996, 416.
3 A. M. Farag, K. M. Dawood and Z. E. Kandeel, Tetrahedron,
1996, 52, 7893.
4 A. M. Farag, K. M. Dawood and Z. E. Kandeel, Tetrahedron,
1997, 53, 161.
5 A. M. Farag and K. M. Dawood, Heteroatom Chem., 1997, 8,
45; 129.
1
respectively. 3: mp 230±232 8C; ꢀmax(KBr)/cm 3394, 3284 (NH2,
3112 (NH); ꢁH (DMSO) 6.05 (2 H, br), 7.34±7.86 (4 H, m), 8.02
(1 H, s), 8.77 (br, 1 H) (Found: C, 55.32; H, 3.66; N, 25.87; S,
14.88%. C10H8N4S requires C, 55.54; H, 3.72; N, 25.90; S, 14.82%).