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P. Gupta et al. / European Journal of Medicinal Chemistry 39 (2004) 805–814
8.7. 2-Cyclohexyl-1H-4-imidazole carboxylic acid ethyl
ester (2g)
9.3. 2-tert-Butyl-1H-4-imidazole carbohydrazide (3c)
Yield: 91%; m.p. 159–160 °C; 1H NMR (CDCl3): d 8.80
(bs, 1H, NH), 7.56 (s, 1H, 5-H), 3.49 (bs, 2H, NH2), 1.25 (s,
9H, 3 × CH3); APCIMS: m/z 183 (M + 1); Anal. C8H14N4O
(C, H, N).
Yield: 13%; m.p. 151–152 °C; IR (KBr): 1722 cm–1; 1H
NMR (CDCl3): d 7.60 (s, 1H, 5-H), 4.34 (q, 2H, J = 7.2 Hz,
CH2), 2.78 (m, 1H, CH), 1.61 (m, 10H, 5 × CH2), 1.37 (t, 3H,
J = 7.2 Hz, CH3); ESIMS: m/z 223 (M + 1); Anal.
C12H18N2O2 (C, H, N).
9.4. 2,5-Di-tert-butyl-1H-4-imidazole carbohydrazide (3d)
8.8. 2,5-Dicyclohexyl-1H-4-imidazole carboxylic acid ethyl
ester (2h)
Yield: 78%; m.p. 76–78 °C; 1H NMR (CDCl3): d 8.55 (bs,
1H, NH), 3.48 (bs, 2H, NH2), 1.48 (s, 9H, 3 × CH3), 1.25 (s,
9H, 3 × CH3); APCIMS: m/z 239 (M + 1); Anal. C12H24N4O
(C, H, N).
Yield: 10%; m.p. 147–159 °C; IR (KBr): 1703 cm–1; 1H
NMR (CDCl3): d 4.32 (q, 2H, J = 7.2 Hz, CH2), 3.17 (m, 1H,
CH), 2.77 (m, 1H, CH), 1.84 (m, 20H, 10 × CH2), 1.36 (t, 3H,
J = 7.2 Hz, CH3); ESIMS: m/z 305 (M + 1);Anal. C8H28N2O2
(C, H, N).
9.5. 2-Cyclopentyl-1H-4-imidazole carbohydrazide (3e)
Yield: 92%; m.p. 228–230 °C; 1H NMR (CDCl3): d 8.21
(bs, 1H, NH), 7.43 (s, 1H, 5-H), 3.75 (bs, 2H, NH2), 2.75 (m,
1H, CH), 1.81 (m, 8H, 4 × CH2); APCIMS: m/z 195 (M + 1);
Anal. C9H14N4O (C, H, N).
8.9. 2-Adamantan-1-yl-1H-4-imidazole carboxylic acid
ethyl ester (2i)
Yield: 33%; m.p. 218–220 °C; IR (KBr): 1717 cm–1; 1H
NMR (CD3OD): d 7.56 (s, 1H, 5-H), 4.32 (q, 2H, J = 7.2 Hz,
CH2), 1.81 (m, 15H, adamantyl protons), 1.35 (t, 3H,
J = 7.2 Hz, CH3); APCIMS: m/z 275 (M + 1); Anal.
C16H22N2O2 (C, H, N).
9.6. 2,5-Dicyclopentyl-1H-4-imidazole carbohydrazide (3f)
Yield: 93%; m.p. 118–120 °C; 1H NMR (CDCl3): d 8.35
(bs, 1H, NH), 3.95 (bs, 2H, NH2), 2.77 (m, 1H, CH), 2.33 (m,
1H, CH), 1.80 (m, 16H, 8 × CH2);APCIMS: m/z 263 (M + 1);
Anal. C14H22N4O (C, H, N).
8.10. 2,5-Diadamantan-1-yl-1H-4-imidazole carboxylic
acid ethyl ester (2j)
9.7. 2-Cyclohexyl-1H-4-imidazole carbohydrazide (3g)
Yield: 22%; m.p. 164–165 °C: IR (KBr): 1694 cm–1; 1H
NMR (CDCl3): d 4.32 (q, 2H, J = 7.2 Hz, CH2), 1.88 (m,
30H, adamantyl protons), 1.32 (t, 3H, J = 7.2 Hz, CH3);
APCIMS: m/z 409 (M + 1); Anal. C26H36N2O2 (C, H, N).
Yield: 93%; m.p. 82–84 °C; 1H NMR (CDCl3): d 8.25 (bs,
1H, NH), 7.51 (s, 1H, 5-H), 4.01 (bs, 2H, NH2), 2.71 (m, 1H,
CH), 1.61 (m, 10H, 5 × CH2); APCIMS: m/z 209 (M + 1);
Anal. C10H16N4O (C, H, N).
9. General procedure for synthesis of 2-alkyl
and 2,5-dialkyl-1H-4-imidazole carbohydrazides 3(a–j)
9.8. 2,5-Dicyclohexyl-1H-4-imidazole carbohydrazide (3h)
Yield: 93%; m.p. 218–219 °C; 1H NMR (CDCl3): d 8.60
(bs, 1H, NH), 3.92 (bs, 2H, NH2), 3.54 (m, 1H, CH), 2.63 (m,
1H, CH), 1.65 (m, 20H, 10 × CH2); ESIMS: m/z 291 (M + 1);
Anal. C16H26N4O (C, H, N).
To a solution of 2-alkyl or 2,5-dialkyl-1H-4-imidazole
carboxylic acid ethyl ester (2a–j, 1 mmol) in ethanol (2 ml),
hydrazine hydrate (2 ml) was added, and reaction mixture
was heated under reflux for 8 h. The carbohydrazides (3a–j)
were obtained in quantitative yields directly after evapora-
tion of the reaction solution.
9.9. 2-Adamantan-1-yl-1H-4-imidazole carbohydrazide
(3i)
9.1. 2-Isopropyl-1H-4-imidazole carbohydrazide (3a)
Yield: 96%; m.p. 116–117 °C; 1H NMR (CDCl3): d 8.08
(bs, 1H, NH), 7.51 (s, 1H, 5-H), 3.82 (bs, 2H, NH2), 1.94 (m,
15H, adamantyl protons); APCIMS: m/z 261 (M + 1); Anal.
C14H20N4O (C, H, N).
Yield: 92%; m.p. 208–209 °C; 1H NMR (CDCl3): d 8.43
(bs, 1H, NH), 7.49 (s, 1H, 5-H); 3.62 (bs, 2H, NH2), 1.48 (m,
1H, CH), 1.35 (m, 6H, 2 × CH3); APCIMS: m/z 169 (M + 1);
Anal. C7H12N4O (C, H, N).
9.10. 2,5-Diadamantan-1-yl-1H-4-imidazole
carbohydrazide (3j)
9.2. 2,5-Diisopropyl-1H-4-imidazole carbohydrazide (3b)
Yield: 98%; m.p. 144–145 °C; 1H NMR (CDCl3): d 8.59
(bs, 1H, NH), 3.82 (bs, 2H, NH2), 1.93 (m, 30H, adamantyl
protons); ESIMS: m/z 395 (M + 1); Anal. C24H34N4O (C, H,
N).
Yield: 91%; m.p. 108–110 °C; 1H NMR (CDCl3): d 8.95
(bs, 1H, NH), 3.91 (m, 1H, CH), 3.49 (bs, 2H, NH2), 2.96 (m,
1H, CH), 1.32 (m, 6H, 2 × CH3), 1.27 (m, 6H, 2 × CH3);
APCIMS: m/z 211 (M + 1); Anal. C10H18N4O (C, H, N).