A new and convenient synthesis of antazoline derivatives

Article abstract of DOI:10.1002/jhet.5570430221

Different N-benzyl anilines were N-alkylated with chloroacetonitrile to give the corresponding nitriles, which were subsequently condensed with ethylenediamine in the presence of thioacetamide to afford the corresponding title antazoline derivatives.

Full text of DOI:10.1002/jhet.5570430221

Mar-Apr 2006
A New and Convenient Synthesis of Antazoline Derivatives
401
∗
P. Dash, D. P. Kudav and J. A. Parihar
Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai-400098, India.
E-mail: japarihar@rediffmail.com
Received July 18, 2005
Different N-benzyl anilines were N-alkylated with chloroacetonitrile to give the corresponding
nitriles, which were subsequently condensed with ethylenediamine in the presence of thioacetamide to
afford the corresponding title antazoline derivatives.
J. Heterocyclic Chem., 43, 401 (2006).
Table 1
Imidazoline derivatives exhibit significant biological and
pharmacological activities including antihypertensive [1,2],
antihyperglycemic [3-7], antidepressive [8], antihypercho-
lesterolemic [9] and anti-inflammatory activities [10]. Due
to these practical applications, we have expended consider-
able effort in the preparation of new imidazoline deriva-
tives. Recently we have reported the synthesis 2-imidazo-
line analogs of phentolamine by the alkylation of dipheny-
lamines with chloroacetonitrile and subsequent cyclisation
of aminonitriles with ethylenediamine in presence of
thioacetamide [11]. Antazoline is a well-known drug of the
imdazoline family having antihistaminic activity [12-13],
ambecidal activity [14] and antiarrhyhmic activity [15].
Earlier synthesis of antazoline starts the cyanomethylation
of the N-benzylaniline with NaCN and formaldehyde
requiring a closed vessel and long reaction period [16]. In
this article we wish to report the synthesis of some novel
antazoline derivatives using alkylation of N-benzylanilines
with chloroacetonitrile as a key step.
Tested alkylation conditions for the reaction of
N-benzylaniline (1a) with ClCH CN.
2
Solvent Base
Additive Temp (°C) Time (h) Yield (%)
HMPA K CO
NaI
NaI
NaI
100
100
100
100
100
0.75
84
51
19
24
64
2
3
KF
5
6
6
3
DMAP
i
Et( Pr) N NaI
2
DMPU K CO
NaI
2
3
have used DMPU as a good and safe alternative for HMPA
for the N-alkylation of less reactive amines. Hence we
thought to investigate the influence of DMPU for the N-
alkylation 1a with chloroacetonitrile. Heating N-benzylani-
line 1a with chloroacetonitrile and NaI in the presence of
K CO in DMPU at 100 °C for 3 h gave 2a in 64% yield
after the column chromatographic purification. The struc-
ture of 2a was ascertained from its elemental analysis and
spectroscopic data. The IR spectrum of 2a displayed C-N
2
3
-
1
1
Towards this end the alkylation of N-benzylaniline 1a
with chloroacetonitrile was undertaken. All our attempts to
stretching at 2255 cm for the CN group and H-NMR
spectrum displayed two 2H singlets for CH -CN and CH -
2
2
carry out the reaction in CH CN, DMF, DMSO and THF as
Ar at δ 4.53 and δ 4.11 respectively thus confirming the
3
H H
reaction solvents using different bases such as K CO , KF,
alkylation of 1a with chloroacetonitrile. These two reaction
conditions (K CO , NaI, HMPA and K CO , NaI, DMPU)
2
3
i
DMAP and Et( Pr) N proved unsuccessful. Although the
2
2
3
2
3
alkylation of 1a with ClCH CN and NaI in presence of KF,
were then utilized for the N-alkylation of other N-benzylani-
lines with chloroacetonitrile to give the corresponding
aminoacetonitriles 2b-h in 80-88% and 61-72% yields
respectively (Scheme 1, Table 2). The aminoacetonitriles
2a-h thus obtained were condensed by refluxing with ethyl-
enediamine in the presence of a catalytic amount of thioac-
etamide for 3 h to afford the corresponding analytically pure
title compounds 3a-h in 75-80% yields (Scheme 1, Table 2).
The structures of 3a-h were ascertained from their elemental
2
i
DMAP, Et( Pr) N in HMPA at 100 °C afforded the corre-
2
sponding nitrile 2a, K CO in HMPA in presence of NaI
2
3
proved be the most effective reaction condition and 2a was
obtained in 84% yield after the column chromatographic
purification (Table 1). This was unlike our earlier observa-
tion [11] wherein the N-alkylation of diphenyl amine with
chloroacetonitrile in the last condition (K CO /NaI/HMPA)
2
3
failed to give any N-alkylated product. Seebach et al. [17]

4
02
P. Dash, D. P. Kudav and J. A. Parihar
Vol. 43
Scheme 1
Reagents and conditions: 1) Chloroacetonitrile, K CO , NaI, HMPA/DMPU, 100∞C. 2) ethylenediamine, thioacetamide, reflux.
2
3
Synthesis of antazoline derivatives.
Table 2
HMPA was also replaced by DMPU, though the yields
obtained in HMPA were slightly better. Nitriles 2a-h were
subsequently condensed with ethylenediamine in the pres-
ence of thioacetamide to afford the corresponding title
compounds 3a-h in good yields.
Synthesized aminoacetonitriles and antazoline derivatives.
a
Compound
R1
R2
R3
R4
Yield / %
b
c
c
c
c
c
c
c
c
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
H
H
H
OCH3
H
H
H
H
H
H
H
OCH3
H
H
84 (64)
87 (71)
81 (61)
85 (67)
88 (72)
84 (68)
82 (66)
80 (65)
b
OCH3
CH3
H
H
H
CH3
Cl
H
OCH3
CH3
H
H
H
CH3
Cl
b
b
EXPERIMENTAL
OCH3
OCH3
OCH3
OCH3
b
OCH3
OCH3
H
b
General Procedure for the Synthesis of Aminoacetonitrile 2a-h.
A mixture of N-benzylaniline (10 mmol) 1a-h, chloroacetoni-
b
b
H
H
H
H
OCH3
H
H
H
77
79
75
77
80
76
79
78
trile (15 mmol), anhyd. K CO (10 mmol) and NaI (10 mmol) in
2
3
3
dry HMPA (caution!)/DMPU (7 cm ) was heated at 100 °C for
5 min/3 h. The reaction mixture was diluted with water and
4
H
OCH3
OCH3
OCH3
OCH3
OCH3
3
extracted with EtOAc (4 × 50 cm ). The combined EtOAc
OCH3
OCH3
H
3
extracts were washed with water (3 × 50 cm ) and then dried
(
anhydrous Na SO ). Evaporation of the solvent gave a brown
g
h
2 4
H
residue which was purified by column chromatography [silica
gel, Hexane:CHCl (50:50)] to afford the corresponding
aminoacetonitrile 2a-h.
3
a
Yield refers to purified product; b Yield obtained with K CO , NaI,
2 3
HMPA; Yield obtained with K CO , NaI, DMPU.
2
3
[
Benzyl(phenyl)amino]acetonitrile (2a).
Pale yellow oil; IR (oil film): ν 2255 (CN) cm ; H-NMR
(CDCl 60 MHz) δ 4.11 (2H, s, Ar-CH ), 4.53 (2H, s, CH -CN),
-
1 1
1
analysis and spectroscopic data. The H-NMR spectrum of
3
,
2
2
6
.54-7.47 (10H, m, Ar-H).
3
3
2
4
e displayed a 4H singlet at δ 3.56 for N-CH -CH -N, two
H 2 2
Anal. Calcd. for C15 H14 N : C, 81.05; H, 6.35; N, 12.60.
H singlets at δ 3.81 and δ 3.86 for two OCH and two
2
H
H
3
Found: C, 80.96; H, 6.39; N, 12.65.
H singlets for CH -C=N and CH -Ar at δ 4.53 and δ
2
2
H
H
13
.15 respectively. The C-NMR spectrum of 3e displayed a
[Benzyl(4-methoxyphenyl)amino]acetonitrile (2b).
signal at δ 166.6 for C=N and MS showed molecular ion
C
-1 1
Pale yellow oil; IR (oil film) ν 2252 (CN) cm ; H-NMR
CDCl3, 60 MHz) δ 3.69 (3H, s, OCH ), 4.01 (2H, s, Ar-CH ),
1
13
peak at m/z = 325. In the H- C gHSQC spectrum of 3e a
signal at δ 50.2 showed correlation with δ 4.53 as well as
(
3
2
C
H
4.42 (2H, s, CH2-CN), 6.66-7.42 (9H, m, Ar-H); MS (EI) m/z
(relative intensity): 252 (M , 10%), 107 (18), 91(100).
Anal. Calcd. for C16 H16 N2 O: C, 76.16; H, 6.39; N, 11.10.
+
δ 3.56 and a signal at δ 55.5 showed correlation with δ
H
C
H
4.15. Based on this, a signal at δ 50.2 was assigned for C-4
C
Found: C, 76.07; H, 6.44; N, 11.14.
and C-5 of imidazoline ring and C-2' and a signal at δ 55.5
C
was assigned for Ar-CH . Use of CS [18] and P S [19]
2
2
2 5
[Benzyl(4-methylphenyl)amino]acetonitrile (2c).
instead of thioacetamide as H S source gives impure com-
2
-1 1
Pale yellow oil; IR (oil film) ν 2257 (CN) cm ; H-NMR
CDCl 60 MHz) δ 2.25 (3H, s, CH ), 4.13 (2H, s, Ar-CH ), 4.49
pound, which requires complicated purification. The yields
of the compounds synthesized are listed in Table 2.
In conclusion, N-benzyl anilines were N-alkylated with
(
(
3
,
3
2
2H, s, CH -CN), 6.50-7.45 (9H, m, Ar-H); MS (EI) m/z (relative
2
+
intensity): 236 (M , 9%), 91 (100).
chloroacetonitrile in presence of K CO and NaI in HMPA
Anal. Calcd. for C16 H16 N : C, 81.32; H, 6.82; N, 11.85.
2
3
2
to give the corresponding nitriles 1a-h. Carcinogenic
Found: C, 81.41; H, 6.78; N, 11.80.

Mar-Apr 2006
A New and Convenient Synthesis of Antazoline Derivatives
403
[
(4-Methoxybenzyl)(phenyl)amino]acetonitrile (2d).
Colourless solid: mp 84 °C; IR (KBr) ν 2251 (CN) cm ; H-
NMR (CDCl 400 MHz) δ 3.80 (3H, s, OCH ), 4.02 (2H, s, Ar-
Anal. Calcd. for C17H19N : C, 76.95; H, 7.22; N, 15.84.
Found: C, 76.88; H, 7.25; N, 15.80.
3
-
1 1
3,
3
Benzyl(4,5-dihydro-1H-imidazol-2-ylmethyl)(4-methoxy-
phenyl)amine (3b)).
CH ), 4.42 (2H, s, CH -CN), 6.88 (2H, d, J = 8.7, H-3 & H-5 of
2
2
Bn group), 6.92-6.98 (3H, m, H-2, H-6 & H-4 of Ph group), 7.23
2H, d, J = 8.7, H-2 & H-6 of Bn group), 7.30 (2H, dd, J = 7.4 &
-1
Colourless solid: mp 107 °C; IR (KBr) ν 3210 (N-H str.) cm ;
(
7
1
H-NMR (CDCl 400 MHz) δ 3.55 (4H, s), 3.73 (3H, s, OCH ),
.1, H-3 & H-5 of Ph group).
3,
3
4
.10 (2H, s, Ar-CH ), 4.56 (2H, s, CH -C=N), 6.78-7.00 (4H, m,
Anal. Calcd. for C16 H N O: C, 76.16; H, 6.39; N, 11.10.
2 2
16
2
Ar-H), 7.22-7.32 (5H, m, Ar-H).
Anal. Calcd. for C H N O: C, 73.19; H, 7.17; N, 14.23.
Found: C, 76.26; H, 6.35; N, 11.06.
1
8 21 3
[
(3,4-Dimethoxybenzyl)(phenyl)amino]acetonitrile (2e).
Found: C, 73.28; H, 7.13; N, 14.20.
-
1
Colourless solid: mp 75-77 °C; IR (KBr) ν 2260 (CN) cm ;
H-NMR (CDCl 60 MHz) δ 3.71 (6H, combined singlet,
Benzyl(4,5-dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)-
amine (3c)).
1
3
,
OCH ), 4.05 (2H, s, Ar-CH ), 4.50 (2H, s, CH -CN), 6.53-7.44
3
2
2
-1
(
8H, m, Ar-H).
Colourless solid: mp 93 °C; IR (KBr) ν 3220 (N-H str.) cm ;
1
Anal Calcd. for C17 H18 N O : C, 72.32; H, 6.43; N, 9.92.
H-NMR (CDCl3, 400 MHz) δ 2.24 (3H, s, CH ), 3.54 (4H, s),
2
2
3
Found: C, 72.23; H, 6.45; N, 9.96.
4.13 (2H, s, Ar-CH ), 4.54 (2H, s, CH -C=N), 6.71 (2H, d, J =
2 2
8
.2, H-2 & H-6 of Ph group), 7.1 (2H, d, J = 8.2, H-3 & H-5 of Ph
[
Phenyl(3,4,5-trimethoxybenzyl)amino]acetonitrile (2f).
group), 7.20-7.31 (5H, m, Ar-H of Bn group); MS (EI) m/z (rela-
tive intensity): 279 (M , 6%), 91 (61), 84 (100).
-
1
1
+
Colourless solid: mp 88 °C; IR (KBr) ν 2256 (CN) cm ; H-
NMR (CDCl 60 MHz) δ 3.69 (9H, combined singlet, OCH ), 4.00
3,
3
Anal. Calcd. for C H N : C, 77.38; H, 7.58; N, 15.04; found:
18 21 3
(2H, s, Ar-CH ), 4.41 (2H, s, CH -CN), 6.65-7.40 (7H, m, Ar-H).
2 2
C, 77.30; H, 7.61; N, 15.09.
Anal. Calcd. for C18 H20 N O : C, 69.21; H, 6.45; N, 8.97.
2
3
(
4,5-Dihydro-1H-imidazol-2-ylmethyl)(4-methoxybenzyl)-
Found: C, 69.29; H, 6.41; N, 8.95.
phenylamine (3d).
[
(4-Methoxybenzyl)(4-methylphenyl)amino]acetonitrile (2g).
-
1 1
Colourless solid: mp 94; IR (KBr) ν 2260 (CN) cm ; H-
Colourless solid: mp 116 °C; IR (KBr) ν 3250 (N-H str.) cm-1;
NMR (CDCl 60 MHz) δ 2.23 (3H, s, CH ), 3.70 (3H, s, OCH ),
4
Ar-H); MS (EI) m/z (relative intensity): 266 (M , 4%), 121 (100),
9
1
3,
3
3
H-NMR (CDCl 500 MHz) δ 3.55 (4H, s), 3.79 (3H, s, OCH ),
3
,
3
.12 (2H, s, Ar-CH ), 4.50 (2H, s, CH -CN), 6.52-7.30 (8H, m,
2 2
4.14 (2H, s, Ar-CH ), 4.53 (2H, s, CH -C=N), 6.78 (1H, t, J =
2 2
+
7
7
.5, H-4 of Ph group), 6.84-6.96 (4H, m, Ar-H), 7.16 (2H, d, J =
.8, H-2 & H-6 of Bn group), 7.23 (2H, t, J = 7.5, H-3 & H-5 of
1 (10).
Anal. Calcd. for C17 H18 N O: C, 76.66; H, 6.81; N, 10.52.
2
Ph group).
Found: C, 76.56; H, 6.85; N, 10.55.
Anal Calcd. for C18H21N O: C, 73.19; H, 7.17; N, 14.23.
3
Found: C, 73.30; H, 7.12; N, 14.20.
[
(4-Chlorophenyl)(4-methoxybenzyl)amino]acetonitrile (2h).
-
1 1
Colourless solid: mp 65 °C; IR (KBr) ν 2258 (CN) cm ; H-
NMR (CDCl 400 MHz) δ 3.81 (3H, s, OCH ), 4.01 (2H, s, Ar-
(4,5-Dihydro-1H-imidazol-2-ylmethyl)(3,4-dimethoxybenzyl)-
phenylamine (3e).
3,
3
CH ), 4.40 (2H, s, CH -CN), 6.88 (2H, d, J = 9.0, H-3 & H-5 of
2
2
Colourless solid: mp 115 °C; IR (KBr) ν 3300 (N-H str.) cm-
Bn group), 6.91 (2H, d, J = 8.9, H-2 & H-6 of Ph group), 7.23
2H, d, J = 9.0, H-2 & H-6 of Bn group), 7.27 (2H, d, J = 8.9, H-
& H-5 of Ph group).
Anal. Calcd. for C16 H15 Cl N O: C, 67.02; H, 5.27; Cl, 12.36;
1; 1
H-NMR (CDCl 500 MHz) δ 3.56 (4H, s), 3.81 (3H, s,
3,
(
3
OCH ), 3.86 (3H, s, OCH ), 4.15 (2H, s, Ar-CH ), 4.53 (2H, s,
3
3
2
CH -C=N), 6.76-6.84 (6H, m, Ar-H), 7.24 (2H, t, J = 7.7, H-3
2
2
13
&
H-5 of Ph group); C-NMR (CDCl 400 MHz): δ 50.2 (C-4,
C-5 of imidazoline ring and C-2'), 55.5 (Ar-CH ), 55.8 (OCH ),
3
,
N, 9.77. Found: C, 67.13; H, 5.23; Cl, 12.33; N, 9.74.
2
3
General Procedure for the Synthesis of Antazoline Derivatives
55.9 (OCH ), 110.3 (CH), 111.3 (CH), 113.2 (C-2, C-6 of
3
3
a-h.
phenyl ring), 118.1 (CH), 119.2 (CH), 129.4 (C-3, C-5 of
phenyl ring), 130.4 (C), 148.2 (C), 148.7, 149.2 (C), 166.6
A mixture of aminoacetonitrile 2a-h (10 mmol), thioacetamide
1 mmol) in ethylenediamine (7 cm ) was refluxed with stirring
+
(
(
C=N); MS (EI) m/z (relative intensity): 325 (M , 8%), 241
65), 150 (48), 82 (100).
3
(
for 3 h. The reaction mixture was diluted with water and
3
Anal. Calcd. for C19H23N3O2: C, 70.13; H, 7.12; N, 12.91.
Found: C, 70.03; H, 7.16; N, 12.95.
extracted with CHCl3 (4 × 50 cm ). The combined CHCl
3
3
extracts were washed with water (3 × 50 cm ) and then dried
anhydrous Na SO ). Evaporation of the solvent followed by trit-
(
2 4
(4,5-Dihydro-1H-imidazol-2-ylmethyl)phenyl(3,4,5-trimethoxy-
benzyl)amine (3f).
uration of the residue obtained with petroleum ether (60:80)
afforded the corresponding analytically pure antazoline deriva-
tives 3a-h which were then further purified by recrystalization
Colourless solid: mp 117 °C; IR (KBr) ν 3220 (N-H str.) cm-
1; 1
H-NMR (CDCl 400 MHz) δ 3.57 (4H, s), 3.78 (6H, s,
with CHCl and hexane.
3,
3
OCH ), 3.82 (3H, s, OCH ), 4.17 (2H, s, Ar-CH ), 4.51 (2H, s,
3
3
2
Benzyl(4,5-dihydro-1H-imidazol-2-ylmethyl)phenylamine (3a).
Colourless solid: mp 120 °C (Lit. [16] mp 120 °C); IR (KBr) ν
CH -C=N), 6.45 (2H, s, H-2 & H-6 of Bn group), 6.79 (3H, m,
2
H-2, H-4 & H-6 of Ph group), 7.22 (2H, t, J = 7.7, H-3 & H-5 of
Ph group).
-
1
1
3
4
215 (N-H str.) cm ; H-NMR (CDCl 60 MHz) δ 3.52 (4H, s),
3,
.00 (2H, s, Ar-CH ), 4.55 (2H, s, CH -C=N), 6.95-7.43 (10H,
Anal. Calcd. for C H N O : C, 67.58; H, 7.09; N, 11.82;
2
2
20 25 3 3
m, Ar-H).
found: C, 67.67; H, 7.06; N, 11.87.

404
P. Dash, D. P. Kudav and J. A. Parihar
Vol. 43
(
4,5-Dihydro-1H-imidazol-2-ylmethyl)(4-methoxybenzyl)(4-
pp 130–153.
2a] P. Blancafort, Drugs of the Future, 3, 592 (1978); [b] M. N.
Serradell and J. Castaner, Drugs of the Future, 6, 470 (1986).
3] X. Wang, F. Rondu, A. Lamouri, R. Dokhan, S. Marc, E.
Touboul, B. Pfeiffer, D. Manechez, P. Renard, B. Guardiola-Lemaitre,
J. J. Godfroid, A. Ktorza and L. Penicaud, J. Pharmacol. Exp. Ther.,
278, 82 (1996).
[
methylphenyl)amine (3g).
-
1
Colourless solid: mp 104 °C; IR (KBr) ν 3230 (N-H str.) cm ;
H-NMR (CDCl3 500 MHz) δ 2.25 (3H, s, CH ), 3.54 (4H, s),
[
1
,
3
3
.78 (3H, s, OCH ), 4.10 (2H, s, Ar-CH ), 4.47 (2H, s, CH -
3 2 2
C=N), 6.74 (2H, d, J = 8.2, H-2 & H-6 of Ph group), 6.84 (2H, d,
J = 8.3, H-3 & H-5 of Bn group), 7.04 (2H, d, J = 8.2, H-3 & H-
5
[
4] F. Rondu, G. Le Bihan, X. Wang, A. Lamouri, E. Touboul,
G. Dive, T. Bellahsene, B. Pfeiffer, P. Renard, B. Guardiola-Lemaitre,
D. Manechez, L. Penicaud, A. Ktorza and J. J. Godfroid, J. Med. Chem.,
of Ph group), 7.15 (2H, d, J = 8.3, H-2 & H-6 of Bn group); MS
+
(EI) m/z (relative intensity): 309 (M , 1%), 121 (40), 84 (100).
4
0, 3793 (1997).
5] A. Pele-Tounian, X. Wang, F. Rondu, A. Lamouri, E.
Anal. Calcd. for C H N O: C, 73.76; H, 7.49; N, 13.58.
1
9 23 3
[
Found: C, 73.66; H, 7.46; N, 13.54.
4-Chlorophenyl)(4,5-dihydro-1H-imidazol-2-ylmethyl)(4-
methoxybenzyl)amine (3h).
Touboul, S. Marc, R. Dokhan, B. Pfeiffer, D. Manechez, P. Renard, B.
Guardiola-Lemaitre, J. J. Godfroid, L. Penicaud and A. Ktorza, Br. J.
Pharmacol., 124, 1591 (1998).
(
[
6] G. Le Bihan, F. Rondu, A. Pele-Tounian, X. Wang, S. Lidy,
-1
Colourless solid: mp 103 °C; IR (KBr) ν 3200 (N-H str.) cm ;
H-NMR (CDCl 400 MHz) δ 3.56 (4H, s), 3.78 (3H, s, OCH ),
E. Touboul, A. Lamouri, G. Dive, J. Huet, B. Pfeiffer, P. Renard, B.
Guardiola-Lemaitre, D. Manechez, L. Penicaud, A. Ktorza and J. J.
Godfroid, J. Med. Chem., 42, 1587 (1999).
1
3,
3
4
8
.12 (2H, s, Ar-CH ), 4.49 (2H, s, CH -C=N), 6.71 (2H, d, J =
2 2
[
7] S. Chan, Clin. Sci., 85, 671 (1993).
[8] E. S. Vizi, Med. Res. Rev., 6, 431 (1986).
9] H. Y. Li, S. Drummond, I. De Lucca and G. A. Boswell,
Tetrahedron, 52, 11153 (1996).
10] M. Ueno, K. Imaizumi, T. Sugita, I. Takata and M.
Takeshita, Int. J. Immunopharmacol., 17, 597 (1995).
11] J. A. Parihar, P. Dash and D. P. Kudav, J. Chem. Res. (S), 220
(2004).
[12] Dj. Sadeghi, Therapie, 22, 191 (1967).
13] V. Nicita-Mauro, Atli Soc. Ital. Cardiol., 29, 194 (1969).
.2, H-2 & H-6 of Ph group), 6.84 (2H, d, J = 8.3, H-3 & H-5 of
1
3
Bn group), 7.09-7.25 (4H, m, Ar-H); C-NMR (CDCl3, 400
MHz): δ = 50.3 (C-4, C-5 of imidazoline ring and C-2'), 55.2 (Ar-
CH ), 55.3 (OCH ), 114.2 (2 CH), 114.4 (2 CH), 122.9 (C),
1
(
[
2
3
[
28.1 (2 CH), 129.1 (2 CH), 129.4 (C), 147.2 (C), 158.9 (C), 167
C=N).
Anal. Calcd. for C H N OCl: C, 65.55; H, 6.11; Cl, 10.75;
[
1
8 20 3
N, 12.74. Found: C, 65.66; H, 6.08; Cl, 10.72; N, 12.70.
[
Acknowledgements.
[14] E. S. M. El-Denshay, A. M. El-Masri, P. M. Scott, J. Egypt.
Med. Ass., 54, 27 (1971).
One of the authors (PD) is thankful to the G. D. Gokhale
Charitable Trust for the financial.
[
15] A. M. Higazi, L. M. El-Ahmadi, M. Ageeb, J. Egypt. Med.
Ass., 54, 376 (1971).
16] H. Isler, H. Schellenberg and E. Urech, U. S. Patent
,505,248; Chem. Abstr., 44, 6889b (1950).
17] E. Juaristi, P. Murer, and D. Seebach, Synthesis, 1243
1993).
[18] J. C. Corbel, P. Uriac, J. Huet, C. A. E. Martin and C.
[
2
REFERENCES AND NOTES
[
(
∗
Current address: GSK Pharmaceuticals Limited, 2nd Pokhran
Road, Thane-400601, India.
1] M. Schorderet, In Pharmacologie: Des Concepts Fonda-
mentaux aux Applications Therapeutiques; Frison-Roche: Paris, 1992;
Advenier, Eur. J. Med. Chem., 30, 3 (1995).
[19] E. E. Korshin, L. I. Sabirova, A. G. Akhadullin and Y. G.
Levin, Y. A. Russian Chem. Bull., 43, 431 (1994).
[