Vol. 30, No. 1 (2018)
Synthesis and Studies of 2-(Arylmethyl)-1-ethyl-1H-benzo[d]imidazol-5-amines 31
tion mixture was heated to 90 °C for 20 h. It was cooled to
0 °C, acidified with 2 N HCl up to pH 2, distilled off the solvent
from it and made alkaline with aqueous NH3 solution up to
pH 8. From which the product was isolated by extraction with
EtOAc (2 × 30 mL). The organic layer was washed with brine
(30 mL), dried (Na2SO4), evaporated under reduced pressure
and the residue was purified by flash column chromatography
over silica gel (100-200 mesh) using a gradient mixture of
1.5 % of methanol + chloroform as eluent to afford 75 % of
N’-allyl-4-nitro-benzene-1,2-diamine (4b) as a whine red
colour gummy material.
-OCH2), 5.6 (S, 1H, -NH, D2O exchangeable), 6.8 (S, 1H, -NH,
D2O exchangeable), 6.6-8.1 (m, 6H, Ar-H); M+.1: 416.
Preparation of 2-(4-chlorophenyl)-N-[2-{(2-(diethyl-
amino)ethyl)amino}-5-nitrophenyl]propanamide (6e): To
a solution of 4b (10 mmol) in dichloromethane was added 4-
chlorophenyl acetic acid (5a) (12 mmol) and EEDQ (10 mmol)
and the resulting mixture was heated to reflux (50 °C) for 24
h. Reaction mass was diluted with dichloromethane (30 mL)
and basify with aqueous NH3 solution pH 8. Dichloromethane
layer was washed with water (25 mL), brine solution (10 mL),
dried over anhydrous sodium sulphate, filtrated and concentrated
to obtain the crude material. The crude material was purified
over silica gel (100-200 mesh) column chromatography using
2 % methanol + CHCl3 as eluent to get 55 % yield of gummy
material 6e.
m.p.: 165-167 °C; IR (KBr pellets): 3459 cm-1 (broad,
-NH group); 1H NMR (400 MHz, CDCl3, TMS): δ 3.8 (d, 2H,
-CH2), 5.1 (t, 2H, -CH=CH), 5.1 (S, 2H, -NH, D2O exchange-
able), 6.2 (S, 1H, -NH, D2O exchangeable), 6.4-7.6 (m, 3H,
Ar-H); M+.1: 193.
Preparation of 2-aryl-N-[2-{(2-(diethylamino)ethyl)-
amino}-5-nitrophenyl]acetamide (6a-d): To a solution of 6a
(10 mmol) in dichloromethane was added 5a-5d (12 mmol)
and EEDQ (10 mmol) and the resulting mixture was heated to
reflux (50 °C) for 24 h. Reaction mass was diluted with dichloro-
methane (30 mL) and basify with aqueous NH3 solution pH 8.
Dichloromethane layer was washed with water (25 mL), brine
solution (10 mL), dried over anhydrous sodium sulphate, filtrated
and concentrated to obtain the crude material. The crude material
was purified over silica gel (100-200 mesh) column chromato-
graphy using 2 % CH3OH + CHCl3 as eluent to get 45-55 %
yield of gummy material 6a-6d.
2-(4-Chlorophenyl)-N-[2-{(2-(diethylamino)ethyl)-
amino}-5-nitrophenyl]acetamide (6a): m.p.: 182-184 °C; IR
(KBr pellets): 3443 cm-1 (broad, -NH group), 1689 cm-1 (broad,
-NH-CO group); 1H NMR (400 MHz, CDCl3, TMS): δ 1.1 (t,
6H, -CH3), 2.7 (q, 4H, -CH2), 2.9 (t, 2H, -CH2), 3.3 (t, 2H,
-CH2), 3.8 (s, 2H, CO-CH2), 5.9 (S, 1H, -NH, D2O
exchangeable), 7.6 (S, 1H, -NH, D2O exchangeable), 6.5-8.2
(m, 7H, Ar-H); M+.1: 405.
m.p.: 175-177 °C; IR (KBr pellets): 3446 cm-1 (broad,
-NH group), 1682 cm-1 (broad, -NH-CO group); 1H NMR (400
MHz, CDCl3, TMS): δ 3.2 (d, 2H, -CH2), 3.9 (s, 2H, -CH2), 5.2
(t, 2H, -CH=CH), 6.9 (S, 1H, -NH, D2O exchangeable), 6.4-
7.6 (m, 7H,Ar-H), 10.1 (S, 1H, -NH, D2O exchangeable); M+.1:
356.
Preparation of 2-(arylmethyl)-1-ethyl-5-nitro-1H-
benzo[d]imidazole 7(a-d): To a solution of 6(a-d) (10 mmol)
in CHCl3 (50 mL) was added PCl5 (20 mmol) and heated to
reflux (80 °C) for 24 h. Reaction mass was cooled to room
temperature and basify with aqueous NH3 solution, Then
CHCl3 layer was separated and washed with water (20 mL),
brine solution (20 mL), dried over anhydrous sodium sulphate
solution, filtrated and concentrated to obtain the crude product
7(a-d).
2-[2-(4-Chlorobenzyl)-5-nitro-1H-benzo[d]imidazol-1-
yl]-N,N-diethylethanamine (7a): m.p.: 200-202 °C; IR (KBr
1
pellets): 3052 cm-1 (stretching, -CH group); H NMR (400
MHz, CDCl3, TMS): δ 0.8 (t, 6H, -CH3), 2.5 (q, 4H, -CH2),
2.7 (t, 2H, -CH2), 4.2 (t, 2H, -CH2), 4.4 (s, 2H,-CH2), 7.2-8.8
(m, 7H, Ar-H); M+.1: 387.
N-[2-{(2-(Diethylamino)ethyl)amino}-5-nitrophenyl]-
2-(4-ethoxyphenyl)acetamide (6b): m.p.: 190-192 °C; IR
(KBr pellets): 3446 cm-1 (broad, -NH group), 1684 cm-1 (broad,
-NH-CO group); 1H NMR (400 MHz, CDCl3, TMS): δ 1.1 (t,
6H, -CH3), 1.5 (t, 3H, -CH3), 2.5 (q, 4H, -CH2), 2.9 (t, 2H,
-CH2), 3.1 (t, 2H, -CH2), 3.7 (s, 2H, CO-CH2), 4.0 (t, 2H,
-OCH2), 5.5 (S, 1H, -NH, D2O exchangeable), 6.8 (S, 1H, -NH,
D2O exchangeable), 6.5-8.2 (m, 7H, Ar-H); M+.1: 415.
2-(4-Chlorophenyl)-N-[2-{(2-(diethylamino)ethyl)-
amino}-5-nitrophenyl]acetamide (6c): m.p.: 195-197 °C; IR
(KBr pellets): 3448 cm-1 (broad, -NH group), 1684 cm-1 (broad,
-NH-CO group); 1H NMR (400 MHz, CDCl3, TMS): δ 1.0 (t,
6H, -CH3), 1.8 (q, 4H, -CH2), 2.5 (d, 3H, -CH3), 2.7 (t, 2H,
-CH2), 3.2 (t, 2H, -CH2), 3.7 (t, 1H, CO-CH), 5.2 (S, 1H, -NH,
D2O exchangeable), 6.8 (S, 1H, -NH, D2O exchangeable), 6.5-
8.1 (m, 7H, Ar-H); M+.1: 419.
2-[2-(4-Ethoxybenzyl)-5-nitro-1H-benzo[d]imidazol-1-
yl]-N,N-diethylethanamine (7b): m.p.: 205-207 °C; IR (KBr
1
pellets): 3042 cm-1 (Stretching, -CH group); H NMR (400
MHz, CDCl3, TMS): δ 0.8 (t, 6H, -CH3), 1.3 (t, 3H, -CH3), 2.4
(q, 4H, -CH2), 2.6 (t, 2H, -CH2), 4.0 (t, 2H, -CH2), 4.1 (t, 2H,
-OCH2), 4.4 (s, 2H, CO-CH2), 6.8-8.8 (m, 7H, Ar-H); M+.1:
415.
2-[2-{1-(4-Chlorophenyl)ethyl}-5-nitro-1H-benzo-
[d]imidazol-1-yl]-N,N-diethylethanamine (7c): m.p.: 208-
210 °C; IR (KBr pellets): 3048 cm-1 (Stretching, -CH group);
1H NMR (400 MHz, CDCl3, TMS): δ 0.8 (t, 6H, -CH3), 1.8 (d,
3H, -CH3), 2.4 (q, 4H, -CH2), 2.6 (t, 1H, -CH), 4.0 (t, 2H, -
CH2), 4.5 (t, 2H, -CH2), 7.1-8.8 (m, 7H, Ar-H); M+.1: 401.
2-[2-{(6-Ethoxypyridin-3-yl)methyl}-5-nitro-1H-
benzo[d]imidazol-1-yl]-N,N-diethylethanamine (7d): m.p.:
203-205 °C; IR (KBr pellets): 3040 cm-1 (Stretching, -CH
group); -NH group); 1H NMR (400 MHz, CDCl3, TMS): δ 0.7
(t, 6H, -CH3), 1.3 (t, 3H, -CH3), 2.4 (q, 4H, -CH2), 2.6 (t, 2H,
-OCH2), 4.2 (t, 4H, -CH2), 4.4 (s, 2H, -CH2), 6.8-8.6 (m, 6H,
Ar-H); M+.1: 398.
N-[2-{(2-(Diethylamino)ethyl)amino}-5-nitrophenyl]-
2-(6-ethoxypyridin-3-yl)acetamide (6d): m.p.: 180-182 °C;
IR (KBr pellets): 3453 cm-1 (broad, -NH group), 1685 cm-1
(broad, -NH-CO group); 1H NMR (400 MHz, CDCl3, TMS):
δ 1.1 (t, 6H, -CH3), 1.4 (t, 3H, -CH3), 2.5 (q, 4H, -CH2), 2.8 (t,
2H, -CH2), 3.2 (t, 2H, -CH2), 3.7 (s, 2H, CO-CH2), 4.1 (t, 2H,
Preparation of 1-allyl-2-(4-chlorobenzyl)-5-nitro-1H-
benzo[d]imidazole (7e): To a solution of 6(a-d) (10 mmol) in