1210 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Eissa
(384.82): C, 62.42; H, 4.45; N, 7.28%. Found: C, 62.00; H,
4.50; N, 7.32%.
3.31, 5.11 (d, 2H, 2 methine proton), 6.96-7.95 (m, 9H, ArH),
10.62 (s, 1H, OH exchangeable). Anal calcd for C19H14N3O3Cl
(367.79): C, 62.05; H, 3.84; N, 11.42%. Found: C, 62.09; H,
3.87; N, 11.45%.
General procedure of formation of diazepine derivatives
(4a,b-10a,b)
A solution of Michael adducts 2b-h (0.005 mol) in
n-butanol (30 mL) was treated with hydrazines, namely (hy-
drazine hydrate and phenyl hydrazine) (0.005 mol), and the
solution refluxed for 4 h. The solid product formed after con-
centration and cooling was crystallized from an appropriate
solvent to give (4a,b-10a,b).
3-(4-Chlorophenyl)-9,10,10-trimethyl-4,5,6,7,8,9-hexahy-
dro-1H-6,9-methano-benzo[c][1,2]diazepine-5-carboxylic
acid (6a)
(59% yield) yellow crystals, m.p. 240-242 °C. IR:
3420-3250 (OH, NH) and 1685 cm-1 (C=O of acid); Anal
calcd for C20H23N2O2Cl (358.87): C, 66.94; H, 6.46; N,
7.81%. Found: C, 66.97; H, 6.50; N, 7.84%.
6-Acetyl-3-(4-chlorophenyl)-7-methyl-4,5-dihydro-1H-
[1,2]diazepine-5-carboxylic acid (4a)
3-(4-Chlorophenyl)-9,10,10-trimethyl-1-phenyl-4,5,6,7,8,9-
hexahydro-1H-6,9-methanobenzo[c][1,2]diazepine-5-car-
boxylic acid (6b)
(62% yield) pale yellow crystals, m.p. 220-224 °C. IR:
3390-3200 (OH, NH) and 1695-1670 cm-1 (C=O of acid and
ketone); 1H NMR (CDCl3) d: 1.71 (s, 3H, CH3), 1.5, 1.7 (d,
2H, CH2 of the ring), 2.30 (s, 3H, COCH3), 3.00 (t, 1H, CH-
COOH), 7.00 (s, 1H, NH), 7.29-7.62 (m, 4H, ArH) and 11.00
(s, 1H, OH exchangeable). Anal calcd for C15H15ClN2O3
(306.74): C, 58.73; H, 4.93; N, 9.13%. Found: C, 58.51; H,
5.59; N, 9.11%.
(68% yield) pale yellow crystals, m.p. 180-182 °C. IR:
3400 (OH) and 1683 cm-1 (C=O of acid); MS: m/z (%) M+-2 =
332 (25). Anal calcd for C26H27N2O2Cl (334.97): C, 71.80; H,
6.26; N, 6.44%. Found: C, 71.84; H, 6.30; N, 6.47%.
3-(4-Chlorophenyl)-4,5,6,7,8,9-hexahydro-1H-benzo[c][1,2]-
diazepine-5-carboxylic acid (7a)
6-Acetyl-3-(4-chlorophenyl)-7-methyl-1-phenyl-4,5-dihy-
dro-1H-[1,2]diazepine-5-carboxylic acid (4b)
(63% yield) pale yellow crystals, m.p. 157-159 °C. IR:
3405-3230 (OH, NH) and 1690 cm-1 (C=O of acid); Anal
calcd for C16H17N2O2Cl (304.78): C, 63.05; H, 5.62; N,
9.19%. Found: C, 63.08; H, 5.65; N, 9.22%.
(66% yield) reddish yellow crystals, m.p. 192-194 °C.
IR: 3395 (OH) and 1684-1663 cm-1 (C=O of acid and ketone);
1H NMR (CDCl3) d: 1.70 (s, 3H, CH3), 1.4, 1.7 (d, 2H, CH2 of
the ring), 2.30 (s, 3H, COCH3), 3.01 (t, 1H, CH-COOH),
6.46-7.62 (m, 9H, ArH) and 11.00 (s, 1H, OH exchangeable).
MS: m/z (%) M++1 = 383 (32). Anal calcd for C21H19 ClN2O3
(382.84): C, 65.88; H, 5.00; N, 7.23%. Found: C, 65.59; H,
5.54; N, 7.33%.
3-(4-Chlorophenyl)-1-phenyl-4,5,6,7,8,9-hexahydro-1H-
benzo[c][1,2]diazepine-5-carboxylic acid (7b)
(60% yield) yellow crystals, m.p. 141-143 °C. IR: 3420
1
(OH) and 1682 cm-1 (C=O of acid); H NMR (DMSO) d:
2.21-3.81 (m, 8H, 4 CH2), 3.31 (t, 1H, CH), 4.96 (d, 2H,
CH2), 7.02-8.13 (m, 9H, ArH), 10.26 (s, 1H, OH exchange-
able). Anal calcd for C22H21N2O2Cl (380.88): C, 69.38; H,
5.56; N, 7.35%. Found: C, 69.41; H, 5.59; N, 7.38%.
3-(4-Chlorophenyl)-6-cyano-7-oxo-4,5,6,7-tetrahydro-1H-
[1,2]diazepine-5-carboxylic acid (5a)
(85% yield) white yellow crystals, m.p. 178-180 °C.
IR: 3410-3320 (OH, NH), 2240 (C=N) and 1680-1665 cm-1
(C=O of acid, ketone and amide); Anal calcd for C13H10N3O3Cl
(291.70): C, 53.53; H, 3.46; N, 14.41%. Found: C, 53.57; H,
3,49; N, 14.45%.
3-(4-Chlorophenyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydro-1H-
[1,2]diazepine-5-carboxylic acid (8a)
(66% yield) pale yellow crystals, m.p. 230-232 °C. IR:
3390-3180 (OH, NH), and 1690-1675 cm-1 (C=O of acid and
amide); Anal calcd for C18H15N2O3Cl (342.78): C, 63.07; H,
4.41; N, 8.17%. Found: C, 63.11; H, 4.44; N, 8.21%.
3-(4-Chlorophenyl)-6-cyano-7-oxo-1-phenyl-4,5,6,7-tetra-
hydro-1H-[1,2]diazepine-5-carboxylic acid (5b)
(60% yield) pale yellow crystals, m.p. 160-162 °C. IR:
3420 (OH), 2230 (C=N) and 1680-1665 cm-1 (C=O of acid,
3-(4-Chlorophenyl)-7-oxo-1,6-diphenyl-4,5,6,7-tetrahydro-
1H-[1,2]diazepine-5-carboxylic acid (8b)
1
ketone and amide); H NMR (CDCl3) d: 4.11 (d, 2H, CH2),
(72% yield) yellow crystals, m.p. 199-201 °C. IR: 3392