Synthesis and spectral determination of new derivatives of 1-[(p-substituted)phenyl]-3a-[(o- and p-substituted)phenyl]-5-chloro-9- methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzodiazepines

Article abstract of DOI:10.1002/jhet.5570440129

(Chemical Equation Presented) A new synthesis to obtain eight novel derivatives of 1-[(p-substituted)phenyl]-3a-[(o- and p-substituted)-phenyl]-5- chloro-9-methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzodiazepines with possible biological and

Full text of DOI:10.1002/jhet.5570440129

Jan-Feb 2007
189
Synthesis and Spectral Determination of New Derivatives
of 1-[(p-Substituted)phenyl]-3a-[(o- and p-substituted)phenyl]-
5-chloro-9-methylthio-10,3a-dihydro-[1,2,4]-
oxadiazolo[2,3-b][1,4]benzodiazepines
Eduardo Cortés* [a][1], Erik Peréz Ramírez [a] and Olivia García-Mellado de Cortés [b]
[a] Instituto de Química [2], Universidad Nacional Autónoma de México. Circuito Exterior, Ciudad
Universitaria, Coyoacán 04510, México, D.F.
[b] F.E.S., Cuautitlán-UNAM, Av. 1° de Mayo s/n, Campo 1, Cuautitlán Izcalli, Edo. de México 5470; México.
Received November 17, 2005
S
CH3
O
H
N
N
1. Lawesson reagent
2. NaH / CH3I
N
Cl
N
Cl
1. Triethylamine
O
R2
N
2. Benzohydroxamoyl
chloride derivates
(N2)
R1
I
IV, 1-8
R1
A new synthesis to obtain eight novel derivatives of 1-[(p-substituted)phenyl]-3a-[(o- and p-substituted)-
phenyl]-5-chloro-9-methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzodiazepines with possible
biological and pharmacological activity as anxiolytics, hypnotics, anticonvulsants in the central nervous
system. The final products were obtained by condensation between 2-methylthio-5-[(o-; p-substituted)-
phenyl]-3H-7-chloro-[1,4]benzodiazepine with benzonitrile oxide generated in situ from benzohydrox-
1
amoyl chloride in triethylamine. The structure of all products was corroborated by ir, H-nmr, 13C-nmr,
with experiments bidimensional and ms in low and high resolution.
J. Heterocyclic Chem., 44, 189 (2007).
INTRODUCTION
III were obtained by following literature methods with
modifications [13-14].
The synthesis of benzodiazepinic derivatives with
heterocyclic rings annelated to the “a”, “c” or “d” side [3-
9] of the heptatomic system has recently attracted the
Compound II was obtained by the reaction of derivates I
with Lawesson's reagent at reflux in anhydrous toluene for two
hours, after this time the reaction mixture was treated with
sodium hydride and methyl iodide at reflux for five hours; the
semisolid residue obtained was purified on a silica gel
chromatography column and elution with hexane-ethyl acetate
(95:5). The derivates II were obtained in a 60-70% yield.
The reaction of compound II, with a slight excess of
benzonitrile oxide generated in situ from benzohydroxamoyl
chloride III, and triethylamine, has been performed at reflux
in chloroform under a nitrogen atmosphere for four hours, the
semisolid obtained of the reaction mixture was purified on a
silica gel chromatography column and elution with hexane-
ethyl acetate (98:2). The oxadiazolo[2,3-b][1,4]benzodiaze-
pines, IV, 1-8 have been obtained in a 20-35% yield, all the
compounds obtained are solid with defined melting points.
The infrared spectra of compounds IV, 1-8 displayed
absorptions at 1602-1608 cm-1 for C=N stretching; at
1361-1368 cm-1 for C-N stretching; at 1072-1096 cm-1 for
C-O stretching and the corresponding absorption for
aromatic and R-substituents.
interest of several researchers. The fusion of
a
heterocyclic system to the benzodiazepine ring appears, in
fact, especially promising for the synthesis of derivates
with greater activity and specificity and they show similar
pharmacological profiles to the benzodiazepines from
which they are obtained [10-12].
RESULTS AND DISCUSSION
We describe in this research report the synthesis of
eight new derivatives and spectral properties of 1-[(p-
substituted)phenyl]-3a-[(o- and p-substituted)phenyl]-5-
chloro-9-methylthio-10,3a-dihydro-[1,2,4]-oxadiazolo-
[2,3-b][1,4]benzodiazepines IV, 1-8 (Figure 1). The
synthesis of these compounds was carried out as shown in
Scheme 1. Compounds I and benzohydroxamoyl chloride
R1
R2
S
CH3
N
1
2
3
4
5
6
7
8
o-Cl
p-Cl
o-F
-Cl
-Cl
-Cl
-Cl
-Br
-Br
-Br
-Br
1
In the H-nmr spectra the presence of three proton
N
Cl
p-F
signals at ꢀ 2.1-2.3 singlet were assigned to the methyl
protons joined to sulfur (S-CH3). The presence of two
proton signals at ꢀ 3.5-3.6 and 3.9-4.2 doublet was
consistent with the methylene protons of C-10. The
presence of three protons signals at ꢀ 6.97-7.93 multiplet
O
R2
o-Cl
p-Cl
o-F
N
R1
IV, 1-8
p-F
Figure 1

190
E. Cortés, E. P. Ramírez and O. García-Mellado de Cortés
Vol 44
was assigned to the aromatic protons of C-4, C-6 and C-7
of the benzodiazepine framework. The other aromatic
protons appear as a multiplet and AA'BB' systems at ꢀ
6.64-7.64 and 7.42-7.65, for phenyl protons of “D” ring;
6.99-7.39 for phenyl protons of “E” ring.
The 13C-nmr spectra of the compounds IV, 1-8 are
given in Table 1, and the signals were confirmed by using
HETCOR; LONG RANGE HETCOR, FLOCK, COSY
and NOESY nmr experiments operating at 300 and 500
MHz.
Scheme 1
N
Cl
C
OH
+
R2
O
S CH3
H
N
S
CH3
N
N
O
1. Lawesson reagent
2. NaH / CH3I
III
N
N
Cl
Cl
N
Cl
R2
N
II
I
IV, 1-8
R1
R1
R1
Table 1
13C nmr Spectral data for compounds IV, 1-8
S
CH3
8
N
7
9
7a
6
5
10
A
B
3b
2''
3a
3''
11
1
N
Cl
5'
4
6'
1''
4''
C
D
O
R2
1'
2'
N
3
E
2
6''
5''
4'
R1
3'
IV, 1-8
Compound
1
2
3
4
5
6
7
8
R1
R2
o-Cl
p-Cl
p-Cl
p-Cl
o-F
p-Cl
p-F
p-Cl
o-Cl
p-Br
p-Cl
p-Br
o-F
p-Br
p-F
p-Br
C-1
C-3a
C-3b
C-4
C-5
C-6
C-7
C-7a
C-9
C-10
C-1'
157.1
102.0
128.1
128.8
130.5
130.3
128.2
145.9
168.4
48.8
156.3
100.8
129.6
126.4
130.5
130.0
126.4
143.2
166.9
48.5
156.0
99.9
156.3
100.9
130.0
126.5
131.0
130.0
126.4
143.3
157.2
102.0
128.2
128.8
130.5
130.3
128.2
145.9
168.4
48.8
156.4
100.8
129.7
126.4
131.0
130.0
126.4
143.2
165.5
48.5
156.1
100.0
129.2
127.8
130.6
130.0
126.6
143.8
166.1
48.2
128.3 (d)
2JC-F=11.7
160.4 (d)
1JC-F=251.5
116.7 (d)
2JC-F=23.0
131.0 (d)
3JC-F=9.2
123.1 (d)
4JC-F=4.5
127.4 (d)
3JC-F=3.2
123.4
156.4
100.9
129.9
126.5
131.0
130.0
126.4
143.3
165.4
48.5
137.0 (d)
4JC-F=3.0
128.1 (d)
3JC-F=8.2
115.0 (d)
2JC-F=21.9
163.0 (d)
1JC-F=247.3
115.0 (d)
2JC-F=21.9
128.1 (d)
3JC-F=8.2
123.3
129.2
127.8
130.6
130.0
126.6
143.8
166.1
48.2
165.4
48.5
137.4
139.7
128.4 (d)
2JC-F=9.0
160.4 (d)
137.0 (d)
4JC-F=3.3
128.1 (d)
3JC-F=8.2
115.0 (d)
2JC-F=21.8
162.9 (d)
1JC-F=246.7
115.0 (d)
2JC-F=21.8
128.1 (d)
3JC-F=8.2
122.8
129.6
129.4
137.5
129.4
129.6
13.3
137.3
139.7
C-2'
C-3'
C-4'
C-5'
C-6'
133.5
130.5
130.0
126.3
131.5
127.5
128.3
134.9
128.3
127.5
133.5
130.2
130.0
126.3
131.5
127.5
128.3
134.8
128.3
127.5
1JC-F=249.1
116.7 (d)
2JC-F=23.0
131.0 (d)
3JC-F=6.9
123.1 (d)
4JC-F=5.8
127.4 (d)
3JC-F=3.7
122.9
C-1"
C-2"
C-3"
C-4"
C-5''
C-6''
S-CH3
123.0
129.7
129.4
137.4
129.4
129.7
13.5
122.7
129.6
129.4
137.5
129.4
129.6
13.3
123.5
132.3
129.8
125.8
129.8
132.3
13.4
123.2
132.5
129.5
125.8
129.5
132.5
13.3
129.5
129.5
137.4
129.5
129.5
13.2
132.4
129.7
125.8
129.7
132.4
13.2
132.6
129.6
125.8
129.6
132.6
13.3
Note: The numbering of the phenyl rings is only for the assignment of the chemical shifts of the carbon in 13C nmr spectra.

Jan-Feb 2007
1-[(p-Substituted)phenyl]-3a-[(o- and p-substituted)phenyl]-5-chloro-9-methylthio-
10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzodiazepines
191
a solution of benzohydroxamoyl chloride derivates III, (1.1 x
10-3 mole) in dichloromethane (5.0 ml) and the reaction mixture
was stirred and heated at reflux for two hours; followed by
cooling to room temperature and the organic mixture was dried
with anhydrous sodium sulphate and evaporated in vacuum to
yield a semisolid. The residual semisolid was purified on a silica
gel chromatography column and elution with hexane-ethyl
acetate (98:2), to yield the compounds IV, 1-8 in a 20-35%.
1-(p-Chlorophenyl)-3a-(o-chlorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzo-
diazepine (1). This compound was obtained as an orange solid
in a 34 % yield, mp 180 ºC; ir (chloroform): ꢁ C=N 1609, C-N
1402 and 1364, S-CH3 1267 and C-O 1094 cm-1; 1H-nmr
(deuterochloroform): ꢀ 2.36 (s, 3H, S-CH3), 3.55 (d, 1H, J =
14.1 Hz, 10-Hb), 4.17 (d, 1H, J = 14.4 Hz, 10-Ha), 7.12 (d, 1H, J
= 8.7 Hz, 7-H), 7.28 (dt, 1H, J = 1.8, 7.6 Hz, 5'-H), 7.31 (dd, 1H,
J = 2.1, 7.5 Hz, 3'-H), 7.32 (dt, 1H, J = 1.8, 7.3 Hz, 4'-H), 7.38
(dd, 1H, J = 2.4, 8.7 Hz, 6'-H), 7.38 (dd, 1H, J = 2.4, 8.4 Hz, 6-
H), 7.42 and 7.60 (AA'BB', 4H, J = 9.0 Hz, phenyl protons of
“D” ring) and 7.81 (d, 1H, J = 2.4 Hz, 4-H). ms: m/z 487 (M+);
489 [M+2]+; 491 [M+4]+; 493 [M+6]+; 495 [M+8]+. Anal.
Calcd. for: C23H16Cl3N3OS: C, 56.51; H, 3.30; N, 8.60. Found:
C, 56.59; H, 3.36; N, 8.50.
The mass spectra of the compounds IV, 1-8 exhibit a
stable molecular ion and the base peak is the [M-(76+R1)]
ion, in all the compounds analyzed. The main
fragmentation was consistent with the assigned structures.
The relative abundance of the main fragmentation in the
compounds IV, 1-8 have some common features and the
proposed fragmentation pathways leading to the
formation of a number of important daughter ions have
been confirmed by the corresponding parent ions spectra
in Collision-Induced Dissociation experiments.
The elemental composition of the molecular ion and the
other principal fragments ion was determined by exact
mass measurements. The most important ion are: M+; [M-
+
+
(76+R1)]+ (base peak); [M-30] ; [M-(133+R2)] ; [M-
+
+
+
(119+R2)] ; [M-(118+R2)] ; [M-(118+ R1+R2)] ; m/z
[130+R2] ; m/z [104+R1]+; m/z [90+R1]+; m/z [76+R1]+;
+
m/z [76+R2]+ and m/z 75.
EXPERIMENTAL
The ir spectra were recorded on a Nicolet Magna TR-750
spectrophotometer. The 1H-nmr spectra were recorded on a
Varian Unity 300 spectrometer operating at 300 MHz and the
1-(p-Chlorophenyl)-3a-(p-chlorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzo-
diazepine (2). This compound was obtained as an orange solid
in a 33% yield, mp 177ºC; ir (chloroform): ꢁ C=N 1602, C-N
1400 and 1382, S-CH3 1205 and C-O 1090 cm-1; 1H-nmr
(deuterochloroform): ꢀ 2.20 (s, 3H, SCH3), 3.57 (d, 1H, J = 12.3
Hz, 10-Hb), 3.85 (d, 1H, J = 12.3 Hz, 10-Ha), 7.00 (d, 1H, J = 8.7
Hz, 7-H), 7.27 and 7.36 (AA'BB', 4H, J = 9.0 Hz, phenyl protons
of “E” ring), 7.38 (dd, 1H, J = 2.4, 8.4 Hz, 6-H), 7.49 and 7.64
(AA'BB', 4H, J = 9.0 Hz, phenyl protons of “D” ring) and 7.92
(d, 1H, J = 2.4 Hz, 4-H). ms: m/z 487 (M+); 489 [M+2]+; 491
13C-nmr spectra were recorded on
a Varian Unity 500
spectrometer operating at 125 MHz in deuterochloroform
solution containing tetramethylsilane as the internal standard with
chemical shifts ꢀ (ppm) expressed downfield from tetramethyl-
silane. The mass spectra were measured on a JEOL JMS-AC505
and JEOL MS-SX 102A high-resolution mass spectrometer with
accurate mass determination of the molecular ion and the
principal fragment ions, using the direct inlet system. The spectra
were recorded by electron impact at an ionization chamber
temperature of 190° and ionizing electron energy of 70 eV.
The compounds I and III were prepared following methods
developed by us, with modification [13-14].
[M+4]+; 493 [M+6]+; 495 [M+8]+.
Anal. Calcd. for:
C23H16Cl3N3OS: C, 56.51; H, 3.30; N, 8.60. Found: C, 56.42; H,
3.23; N, 8.67.
1-(p-Chlorophenyl)-3a-(o-fluorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzo-
diazepine (3). This compound was obtained as an orange solid
in a 20% yield, mp 185ºC; ir (chloroform): ꢁ C=N 1604, C-N
1406 and 1383, S-CH3 1200 and C-O 1095 cm-1; 1H-nmr
(deuterochloroform): ꢀ 2.26 (s, 3H, S-CH3), 3.39 (d, 1H, J =
13.2 Hz, 10-Hb), 3.60 (d, 1H, J = 12.9 Hz, 10-Ha), 6.99 (dd, 1H,
JH-H = 1.3, JH-H = 8.1, JH-F1 = 11.7 Hz, 3'-H), 7.01 (d, 1H, J = 8.4
Hz, 7-H), 7.10 (dt, 1H, JH-H =1.2, JH-H = 7.6 Hz, 5'-H), 7.31 (dt,
1H, JH-H = 1.8, JH-H = 8.1, JH-F2 = 5.2 Hz, 4'-H), 7.36 (dd, 1H, J =
General Procedure for the Synthesis of 7-Chloro-5-[(o-;
p-substituted)phenyl]-3H-2-methylthio-[1,4]benzodiazepines
II. Treatment of compounds [1,4]benzodiazepine-2-one I, (9.0 x
10-3 mole) with (4.5 x 10-3 mole) of Lawesson's reagent at reflux
in anhydrous toluene under nitrogen atmosphere for two hours.
After this time the reaction mixture was treated with sodium
hydride (2.7 x 10-3 mole) and methyl iodide (2.7 x 10-3 mole) and
the reflux under nitrogen atmosphere was continued for five
hours. The reaction mixture was cooled to room temperature,
filtered and the organic solution was dried with anhydrous
sodium sulphate; filtered and evaporated in vacuum to yield a
residual semisolid; and all these derivatives were purified on a
silica gel chromatography column and elution with hexane-ethyl
acetate (95:5) to yield the compounds II in a 60-70%.
General Procedure for the Synthesis 1-[(p-Substituted)-
phenyl]-3a-[(o- and p-substituted)phenyl]-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]benzo-
diazepines IV, 1-8. To a stirred solution of 7-chloro-5-[(o-; p-
substituted)phenyl]-3H-2-methylthio[1,4]benzodiazepines II,
(0.55 x 10-3 mole) in dichloromethane (25.0 ml), a solution of
triethylamine (1.1 x 10-3 mole) in the same solvent (2.0 ml) was
added dropwise over a few minutes. The mixture was kept under
a nitrogen atmosphere at reflux for one hour. Subsequently the
reaction is cooled at room temperature and was added dropwise
2.4, 8.7 Hz, 6-H), 7.47 and 7.63 (AA'BB', 4H, J = 8.7 Hz, phenyl
2
protons of “D” ring), 7.64 (dd, 1H, JH-H = 1.9, JH-H = 7.5, JH-F
=
5.7 Hz, 6'-H) and 7.79 (d, 1H, J = 2.4 Hz, 4-H). ms: m/z 471
(M+); 473 [M+2]+; 475 [M+4]+; 477 [M+6]+. Anal. Calcd. for:
C23H16Cl2FN3OS: C, 58.48; H, 3.41; N, 8.90. Found: C, 58.40;
H, 3.47; N, 8.99.
1-(p-Chlorophenyl)-3a-(p-fluorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzo-
diazepine (4). This compound was obtained as an orange solid
in a 24% yield, mp 205ºC; ir (chloroform): ꢁ C =N 1603, C-N
1406 and 1381, S-CH3 1195 and C-O 1096 cm-1; 1H-nmr
(deuterochloroform): ꢀ 2.17 (s, 3H, S-CH3), 3.56 (d, 1H, J =
12.3 Hz, 10-Hb), 3.85 (d, 1H, J = 12.3 Hz, 10-Ha), 6.97 (d, 1H, J
1
= 8.7 Hz, 7-H), 6.99 (AA'BB', 2H, JH-H = 8.7, JH-F = 12.3 Hz,
phenyl protons, 3'-H and 5'-H of “E” ring), 7.39 (AA'BB', 2H,

192
E. Cortés, E. P. Ramírez and O. García-Mellado de Cortés
Vol 44
2
JH-H = 9.0, JH-F = 5.1 Hz, phenyl protons, 2'-H and 6'-H of “C”
ring), 7.36 (dd, 1H, J = 2.4, 8.4 Hz, 6-H), 7.49 and 7.64
(AA'BB', 4H, J = 8.7 Hz, phenyl protons of “D” ring) and 7.93
(d, 1H, J = 2.4 Hz, 4-H). ms: m/z 471 (M+); 473 [M+2]+; 475
[M+4]+; 477 [M+6]+. Anal. Calcd. for: C23H16Cl2FN3OS: C,
58.48; H, 3.41; N, 8.90. Found: C, 58.56; H, 3.34; N, 8.83.
1-(p-Bromophenyl)-3a-(o-chlorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzodiaze-
pine (5). This compound was obtained as a scarlet solid in a
29% yield, mp 203ºC; ir (chloroform): ꢀ C=N 1608, C-N 1400
solid in a 20% yield, mp 157ºC; ir (chloroform): ꢀ C=N
1604, C-N 1404 and 1381, S-CH3 1240 and C-O 1078 cm-1;
1H-nmr (deuterochloroform): ꢁ 2.17 (s, 3H, S-CH3), 3.55 (d,
1H, J = 12.3 Hz, 10-Hb), 3.84 (d,1H, J = 12.3 Hz, 10-Ha),
6.97 (d, 1H, J = 8.7 Hz, H-7), 6.99 (AA'BB', 2H, JH-H = 8.7,
1
JH-F = 11.7 Hz, phenyl protons 3'-H and 5'-H of “C” ring),
2
7.39 (AA'BB', 2H, JH-H = 9.1, JH-F = 5.1 Hz, phenyl protons
2'-H and 6'-H of “C” ring), 7.39 (dd, 1H, J = 2.4, 8.4 Hz, 6-
H), 7.57 and 7.65 (AA'BB', 4H, J = 8.7 Hz, phenyl protons of
“D” ring) and 7.93 (d, 1H, J = 2.4 Hz, 4-H). ms: m/z 515
(M+); 517 [M+2]+; 519 [M+4]+; 521 [M+6]+. Anal. Calcd.
for: C23H16BrClFN3OS: C, 53.45; H, 3.12; N, 8.13. Found: C,
53.53; H, 3.06; N, 8.04.
and 1363, S-CH3 1195 and C-O 1072 cm-1; H-nmr (deutero-
1
chloroform): ꢁ 2.36 (s, 3H, S-CH3), 3.55 (d, 1H, J = 13.8 Hz, 10-
Hb), 4.17 (d, 1H, J = 14.4 Hz, 10-Ha), 7.12 (d, 1H, J = 8.7 Hz, 7-
H), 7.27 (dt, 1H, J = 1.8, 7.1 Hz, 5'-H), 7.32 (dt, 1H, J = 2.1, 7.3
Hz, 4'-H), 7.33 (dd, 1H, J = 2.1, 7.2 Hz, 3'-H), 7.38 (dd, 1H, J =
2.4, 8.4 Hz, 6-H), 7.43 (dd, 1H, J = 1.8, 7.5 Hz, 6'-H), 7.52 and
7.58 ( AA'BB', 4H, J = 9.0 Hz, phenyl protons of “D” ring) and
7.80 (d, 1H, J = 2.4 Hz, 4-H). ms: m/z 531 (M+); 533 [M+2]+;
535 [M+4]+; 537 [M+6]+ ; 539 [M+8]+. Anal. Calcd. for:
C23H16BrCl2N3OS: C, 51.80; H, 3.02; N, 7.88. Found: C, 51.71;
H, 3.08; N, 7.97.
Acknowledgement. This work was supported by UNAM-
DGAPA project IN-225503. We wish to thank to J. Peréz for
their assistance in the acquisition of the mass spectral data; H.
Rios for the nmr determination and M. Adaya for the ir
determination.
REFERENCES
1-(p-Bromophenyl)-3a-(p-chlorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzodiaze-
pine (6). This compound was obtained as a scarlet solid in a 35%
yield, mp 158ºC; ir (chloroform): ꢀ C=N 1609, C-N 1405 and
[1] Author to whom correspondence should be addressed.
[2] Contribution No. 2639 from Instituto de Química, UNAM.
[3] J. B. Hester, A. D. Rudzik and B. V. Kamdar, J. Med. Chem.,
14, 1078 (1971); K. Meguro, H. Tawada, H. Miyano, Y. Sato and Y.
Kuwada, Chem. Pharm. Bull., 21, 2382 (1973); A. Walser and G.
Zenchoff, J. Med. Chem., 20, 1694 (1977).
[4] A. Gagneux, R. Heckendorn and R. Meier, German Offen.,
2,304,307 (1973); Chem. Abstr., 79, 126535c (1973).
[5] D. L. Coffen, R. I. Fryer, D. A. Katonak and F. Wong, J.
Org. Chem., 40, 894 (1975).
[6] N. W. Gillman, and R. I. Fryer, J. Heterocyclic. Chem., 14,
1171 (1977); R. B. Moffett, G. N. Evenson and P. F. Von Voigtander, J.
Heterocyclic. Chem., 14, 1231 (1977); I. R. Ager, G. W. Danswan, D. R.
Harrison, D. P. Kay, P. D. Kennewell, and J. B. Taylor, J. Med. Chem.,
20, 1035 (1977); G. W. H Cheseman and S. G. Greenberg J.
Heterocyclic. Chem., 16, 241 (1979).
1
1380, S-CH3 1205 and C-O 1077 cm-1; H-nmr (deuterochloro-
form): ꢁ 2.19 (s, 3H, S-CH3), 3.56 (d, 1H, J = 12.3 Hz, 10-Hb),
3.85 (d, 1H, J = 12.6 Hz, 10-Ha), 7.0 (d, 1H, J = 8.4 Hz, 7-H), 7.27
and 7.36 (AA'BB', 4H, J = 9.0 Hz, phenyl protons of “E” ring),
7.38 (dd, 1H, J = 2.4, 8.7 Hz, 6-H), 7.56 and 7.64 (AA'BB', 4H, J
= 8.7 Hz, phenyl protons of “D” ring) and 7.91 (d, 1H, J = 2.4 Hz,
4-H). ms: m/z 531 (M+); 533 [M+2]+; 535 [M+4]+; 537 [M+6]+;
539 [M+8]+. Anal. Calcd. for: C23H16BrCl2N3OS: C, 51.80; H,
3.02; N, 7.88. Found: C, 51.88; H, 3.09; N, 7.81.
1-(p-Bromophenyl)-3a-(o-fluorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzodiaze-
pine (7). This compound was obtained as an orange solid in a
22% yield, mp 175ºC; ir (chloroform): ꢀ C=N 1606, C-N 1404
[7] J. B. Hester, D. J. Duchamp and C. G. Chidester,
Tetrahedron Letters, 1609 (1971).
1
and 1381, S-CH3 1240 and C-O 1078 cm-1; H-nmr (deutero-
[8] R. Madronero and S. Vega, J. Heterocyclic Chem., 15, 1127
(1978); P. C. Wade, B. R. Vogt, B. Toeplitz, M. S. Puar and J. Z. Gougoutas,
J. Org. Chem., 44, 88 (1979); E. Aiello, G. Dattolo, G. Chirrincione, S.
Plecia and G. Daidone, J. Heterocyclic Chem., 16, 209 (1979).
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Zappala, J. Heterocyclic Chem., 27, 371 (1990).
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1159 (1996).
[12] C. B. de Sarro, M. Zappala , S. Grasso, A. Chimirri, C.
Spagnolo and A. de Sarro, Mol. Neuropharmacol., 1, 195 (1992).
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Heterocyclic Chem., 39, 1189 (2002).
[14] K. C. Liu, B.R. Shelton and R. K. Howe, J. Org. Chem., 45,
3916, (1980).
chloroform): ꢁ 2.26 (s, 3H, S-CH3), 3.59 (d, 1H, J = 13.2 Hz, 10-
Hb), 3.93 (d, 1H, J = 12.9 Hz, 10-Ha), 6.84 (dd, 1H, JH-H = 1.5,
1
JH-H = 8.2, JH-F = 11.8 Hz, 3'-H), 7.02 (d, 1H, J = 8.7 Hz, 7-H),
7.10 (dt, 1H, JH-H = 1.2, JH-H = 7.5 Hz, 5'-H), 7.30 (dt, 1H, JH-H
=
2
1.8, JH-H = 8.4, JH-F = 5.4 Hz, 4'-H), 7.36 (dd, 1H, J = 2.3, 8.4
Hz, 6-H), 7.56 and 7.63 (AA'BB', 4H, J = 8.7 Hz, phenyl protons
of “D” ring), 7.63 (dd, 1H, JH-H = 1.8, JH-H = 7.3, JH-F2 = 6.0 Hz,
6'H) and 7.79 (d, 1H, J = 7.79 Hz, 4-H). ms: m/z 515 (M+); 517
[M+2]+; 519 [M+4]+; 521 [M+6]+.
Anal. Calcd. for:
C23H16BrClFN3OS: C, 53.45; H, 3.12; N, 8.13. Found: C, 53.38;
H, 3.17; N, 8.22.
1-(p-Bromophenyl)-3a-(p-fluorophenyl)-5-chloro-9-methyl-
thio-10,3a-dihydro-[1,2,4]-oxadiazolo[2,3-b][1,4]-benzodiaze-
pine (8). This compound was obtained as a scarlet