Nov-Dec 2002
Synthesis and Spectral Properties of 2-methylthio-3H-7-[(o-; m- and
p-substituted)phenoxy]-4-(p-substituted-phenyl)-[1,5]benzodiazepines
1323
General Procedure for the Synthesis of the 2-Methylthio-3H-7-
[(o-; m- and p-substituted)phenoxy]-4-(p-substituted-phenyl)-
[1,5]benzodiazepines IV,1-11.
7-(p-Methylphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (4).
This compound was obtained as orange semisolid in 94% yield; ir
(chloroform): n C=N 1596, CH -S 1317, C-N 1261 and 1238, C-O
A mixture of 0.007 mole of 2,3-Dihydro-4-[(p-R2)phenyl]-7-
[(o-; m- and p-R1)phenoxy]-1H-[1,5]benzodiazepine-2-thiones
III, 0.021 mole of sodium hydride in 100 ml of dry ortho-
xylene was heat at reflux for one hour. After the reaction mix-
ture was cooled at room temperature, 0.021 mole of methyl
iodide was subsequently added dropwise over a few minutes
and the reflux was continued for four additional hours. The
reaction mixture was cooled to room temperature, filtered and
the organic solution was dried with sodium sulphate, filtered
and evaporated in vacuo to yield a semisolid; the compounds
IV, with 83-98% yield.
3
1
1192 and 1083 cm-1; H nmr (deuteriochloroform): d 2.33 (s, 3H,
C4'-CH3), 2.39 (s, 3H, C4''-CH3), 2.44 (s, 3H, S-CH3), 3.40 (bs, 2H,
3-H), 6.94 (dd, 1H, J = 1.5, 8.7 Hz, 8-H), 6.97 and 7.14 (AA'BB', 4H,
J = 8.4 Hz, phenyl protons of "C" ring), 7.02 (d, 1H, J = 2.7 Hz, 6-H),
7.25 and 7.93 (AA'BB', 4H, J = 8.1 Hz, phenyl protons of "D" ring),
7.35 (d, 1H, J = 8.7 Hz, 9-H); ms: m/z 386 (M)+, 388 [M+2]+.
Anal. Calcd. for: C24H22N2OS: C, 74.58; H, 5.73; N, 7.25.
Found: C, 74.68; H, 5.64; N, 7.31.
7-(o-Methoxyphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (5).
4-(p-Methylphenyl)-2-methylthio-3H-7-phenoxy-[1,5]benzodi-
azepine (1).
This compound was obtained as orange semisolid in 95%
yield; ir (chloroform): n C=N 1591, CH3-S 1315, C-N 1262 and
1254, C-O 1182 and 1041 cm-1; 1H nmr (deuteriochloroform): d
2.39 (s, 3H, C4''-CH3), 2.44 (s, 3H, S-CH3), 3.40 (bs, 2H, 3-H),
3.84 (s, 3H, C2'-OCH3), 6.92 (dd, 1H, J = 1.8, 7.8 Hz, 8-H), 6.98
(d, 1H, J = 2.7 Hz, 6-H), 7.04 (dd, 1H, J = 1.8, 8.7 Hz, 6'-H), 7.09
(dd, 1H, J = 1.5, 7.2 Hz, 3'-H), 7.11 (dt, 1H, J = 1.5, 7.3 Hz, 4'-H),
7.14 (dt, 1H, J = 1.8, 7.2 Hz, 5'-H), 7.24 and 7.92 (AA'BB', 4H, J
= 8.4 Hz, phenyl protons of "D" ring), 7.34 (d, 1H, J = 9.3 Hz, 9-
H); ms: m/z 402 (M)+, 404 [M+2]+.
This compound was obtained as orange semisolid in 98%
yield; ir (chloroform): n C=N 1592, CH3-S 1317, C-N 1261 and
1240, C-O 1186 and 1090 cm-1; 1H nmr (deuteriochloroform): d
2.40 (s, 3H, C4''-CH3), 2.45 (s, 3H, S-CH3), 3.40 (bs, 2H, 3-H),
6.97 (dd, 1H, J = 2.7, 8.7 Hz, 8-H), 7.07 (d, 1H, J = 3.3 Hz, 6-H),
7.08 (dd, 1H, J = 1.8, 7.2 Hz, 2'-H), 7.08 (dd, 1H, J = 1.8, 7.2 Hz,
6'-H), 7.11 (dt, 1H, J = 0.9, 7.4 Hz, 4'-H), 7.26 and 7.94
(AA'BB', 4H, J = 8.1 Hz, phenyl protons of "D" ring), 7.34 (dd,
1H, J = 1.8, 7.5 Hz, 3'-H), 7.34 (dd, 1H, J = 1.8, 7.5 Hz, 5'-H),
7.37 (d, 1H, J = 9.0 Hz, 9-H); ms: m/z 372 (M)+, 374 [M+2]+.
Anal. Calcd. for: C23H20N2OS: C, 74.16; H, 5.41; N, 7.52.
Found: C, 74.22; H, 5.50; N, 7.41.
Anal. Calcd. for: C24H22N2O2S: C, 71.61; H, 5.51; N, 6.96.
Found: C, 71.50; H, 5.62 ; N, 6.91.
7-(m-Methoxyphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (6).
This compound was obtained as orange semisolid in 83%
yield; ir (chloroform): n C=N 1590, CH3-S 1315, C-N 1263 and
1260, C-O 1178 and 1042 cm-1; 1H nmr (deuteriochloroform): d
2.40 (s, 3H, C4''-CH3), 2.45 (s, 3H, S-CH3), 3.40 (bs, 2H, 3-H),
3.78 (s, 3H, C3'-OCH3), 6.64 (d, 1H, J = 2.1 Hz, 2'-H), 6.64 (dd,
1H, J = 1.8, 8.4 Hz, 4'-H), 6.67 (dd, 1H, J = 1.8, 8.4 Hz, 6'-H),
6.97 (dd, 1H, J = 2.7, 8.7 Hz, 8-H), 7.09 (d, 1H, J = 2.4 Hz, 6-H),
7.23 (t, 1H, J = 8.1 Hz, 5'-H), 7.26 and 7.95 (AA'BB', 4H, J = 8.4
Hz, phenyl protons of "D" ring), 7.37 (d, 1H, J = 9.0 Hz, 9-H);
ms: m/z 402 (M)+, 404 [M+2]+.
7-(o-Methylphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (2).
This compound was obtained as orange semisolid in 91%
yield; ir (chloroform): n C=N 1593, CH3-S 1317, C-N 1256 and
1236, C-O 1183 and 1082 cm-1; 1H nmr (deuteriochloroform): d
2.27 (s, 3H, C2'-CH3), 2.40 (s, 3H, C4''-CH3), 2.45 (s, 3H,
S-CH3), 3.40 (bs, 2H, 3-H), 6.92 (dd, 1H, J = 2.7, 7.2 Hz, 8-H),
6.93 (d, 1H, J = 3.0 Hz, 6-H), 6.99 (dd, 1H, J = 1.5, 8.1 Hz, 6'-H),
7.08 (dd, 1H, J = 1.6, 8.1 Hz, 3'-H), 7.08 (dt, 1H, J = 1.5, 7.5 Hz,
4'-H), 7.18 (dt, 1H, J = 2.1, 8.1 Hz, 5'-H), 7.25 and 7.93 (AA'BB',
4H, J = 8.7 Hz, phenyl protons of "D" ring), 7.35 (d, 1H, J = 9.3
Hz, 9-H); ms: m/z 386 (M)+, 388 [M+2]+.
Anal. Calcd. for: C24H22N2O2S: C, 71.61; H, 5.51; N, 6.96.
Found: C, 71.72; H, 5.45; N, 6.88.
7-(p-Methoxyphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (7).
Anal. Calcd. for: C24H22N2OS: C, 74.58; H, 5.73; N, 7.25.
Found: C, 74.45; H, 5.80; N, 7.35.
This compound was obtained as orange semisolid in 94%
yield; ir (chloroform): n C=N 1597, CH3-S 1317, C-N 1258 and
1250, C-O 1175 and 1037 cm-1; 1H nmr (deuteriochloroform): d
2.39 (s, 3H, C4''-CH3), 2.44 (s, 3H, S-CH3), 3.40 (bs, 2H, 3-H),
3.80 (s, 3H, C4'-OCH3), 6.89 and 7.04 (AA'BB', 4H, J = 9.0 Hz,
phenyl protons of "C" ring), 6.93 (dd, 1H, J = 2.7, 9.0 Hz, 8-H),
6.97 (d, 1H, J = 2.1 Hz, 6-H), 7.25 and 7.93 (AA'BB', 4H, J = 8.4
Hz, phenyl protons of "D" ring), 7.34 (d, 1H, J = 9.0 Hz, 9-H);
ms: m/z 402 (M)+, 404 [M+2]+.
7-(m-Methylphenoxy)-4-(p-methylphenyl)-2-methylthio-3H-
[1,5]benzodiazepine (3).
This compound was obtained as orange semisolid in 89% yield;
ir (chloroform): n C=N 1599, CH3-S 1313, C-N 1257 and 1240,
C-O 1186 and 1080 cm-1; 1H nmr (deuteriochloroform): d 2.33 (s,
3H, C3'-CH3), 2.39 (s, 3H, C4''-CH3), 2.45 (s, 3H, S-CH3), 3.40
(bs, 2H, 3-H), 6.90 (d, 1H, J = 2.0, Hz, 2'-H), 6.90 (dd, 1H, J = 1.8,
8.4 Hz, 4'-H), 6.93 (dd, 1H, J = 1.9, 8.1 Hz, 6'-H), 6.96 (dd, 1H,
J= 2.5, 8.5 Hz, 8-H), 7.06 (d, 1H, J = 3.0 Hz, 6-H), 7.25 (t, 1H, J=
9.0 Hz, 5'-H), 7.26 and 7.94 (AA'BB', 4H, J = 8.0 Hz, phenyl pro-
tons of "D" ring), 7.37 (d, 1H, J = 8.5 Hz, 9-H); ms: m/z 386 (M)+,
388 [M+2]+.
Anal. Calcd. for: C24H22N2O2S: C, 71.61; H, 5.51; N, 6.96.
Found: C, 71.56; H, 5.61; N, 7.03.
4-(p-Methoxyphenyl)-2-methylthio-3H-7-phenoxy-[1,5]benzo-
diazepine (8).
Anal. Calcd. for: C24H22N2OS: C, 74.58; H, 5.73; N, 7.25.
Found: C, 74.66; H, 5.82; N, 8.32.
This compound was obtained as orange semisolid in 87%
yield; ir (chloroform): n C=N 1590, CH3-S 1316, C-N 1254 and