Synthesis and spectral properties of 11-[(o-; and p-substituted)-phenyl]-8-[(o-; m-; p-methoxy)phenylthio]-3,3-dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e] [1,4]diazepin-1-ones

Article abstract of DOI:10.1002/jhet.5570390107

The preparation of twelve novel 2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e] [1,4]diazepin-1-ones which have potentially useful pharmacological properties; by condensation and cyclization between 3-{[4-(o-; m-; p-methoxy)phenylthio]-1,2-phenylenediamine}-5,5-d

Full text of DOI:10.1002/jhet.5570390107

Jan-Feb 2002
Synthesis and Spectral Properties of 11-[(o-; and p-substituted)-
phenyl]-8-[(o-; m-; p-methoxy)phenylthio]-3,3-dimethyl-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones
55
Eduardo Cortés Cortés*[a], [1], Ana María Hernández Sanabria [b],
Olivia García Mellado [b]
[a] Instituto de Química [2], Universidad Nacional Autónoma de México, Circuito Exterior,
Ciudad Universitaria, Coyoacán, 04510, México, D.F.
[b] Facultad de Estudios Superiores Cuautitlán, Av. 1º. de Mayo s/n, Campo 1,
Cuautitlán Izcalli Edo. de México, 54740. México
Received May 8, 2001
The preparation of twelve novel 2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e] [1,4]diazepin-1-ones which
have potentially useful pharmacological properties; by condensation and cyclization between 3-{[4-(o-; m-;
p-methoxy)phenylthio]-1,2-phenylenediamine}-5,5-dimethyl-2-cyclohexenone with (o-; and p-substi-
1
13
tuted)benzaldehyde. The structure of all final products were corroborated by ir, H-nmr, C-nmr and ms.
J. Heterocyclic Chem., 39, 55 (2002).
Scheme 2
A piperidine derivative of the dibenzodiazepine family
is the clozapine that is an atypical antipsychotic agent with
proven efficacy in the management of refractory schizo-
phrenia [3-4]. Currently there is considerable interest in
the synthesis of new benzodiazepines with pharmacologi-
cal activity [5-7]. We have previously reported the synthe-
sis of 2,3-dihydro-2-[o-; and p-substituted)anilinylidene]-
1H-4-(p-methylphenyl)-7-[(o-; and p-methyl)phenoxy]-
1,5-benzodiazepines [8]; 2-[(o-; and p-substituted)-
aminophenyl]-3H-5-[(o-; and p-substituted)phenyl]-7-
chloro-1,4-benzodiazepines [9] and 2-methylthio-7-[(o-;
p-substituted)phenylthio]-1,5-benzodiazepines [10].
As a part of a program directed towards the synthesis
and the spectral property determination of dibenzo-
[b,e][1,4]diazepin-1-ones derivatives. We describe in this
report the synthesis of novel compounds 11-[(o-; and
p-substituted)phenyl]-8-[(o-; m-; p-methoxy)phenylthio]-
3,3-dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e]-
[1,4]diazepin-1-ones IV, 1-12, (Scheme 1) as shown in
Scheme 2.
Treatment of 4-[(o-; m-; p-methoxy)phenylthio]-1,2-
phenylenediamines I with 5,5-dimethyl-1,3-cyclohexane-
dione II at reflux in anhydrous benzene with a Dean-Stark
apparatus were performed for 24 hours to obtain the 3-{[4-
(o-; m-; p-methoxy)phenylthio]-1,2-phenylenediamine}-5,5-
dimethyl-2-cyclohexenone III, which have been obtained in
55-60% yields. A mixture of 0.001 mole of compounds III,
0.001 mole of the corresponding (o-; and p-substituted)ben-
zaldehyde in the presence of a few drops of acetic acid at
reflux in ethanol for 1.5 hours afforded the 11-[(o-; and p-
substituted)phenyl]-8-[(o-; m-; p-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones IV, 1-12 in 45-70% yields.
The infrared spectrum of compounds 1-12, displayed
-1
absorptions at 3410-3412 cm for N-H stretching, at

56
E. Cortés Cortés, A. M. Hernández Sanabria, O. G. Mellado
Vol. 39
-1
6.28-6.80 was assigned to the aromatic protons at C-6, C-7
and C-9 of the dibenzodiazepine framework. The other
aromatic protons appeared as a multiplet and an AA'BB'
system at δ 6.58-7.30 and with the signal for the R-sub-
stituents.
1597-1616 cm for C=O stretching, at 1387-1393 and
-1
1273-1365 cm for C-N stretching, at 1177-1151 and
-1
1028-1094 cm for C-O stretching and the corresponding
absorptions for aromatic and R-substituents.
In the H-nmr spectra the presence of two singlet signals
1
13
at δ 1.01-1.16 were assigned to the methyl protons at C-3.
The presence of a doublet at δ 2.23-2.25 and 2.30-2.32 was
consistent with the methylene protons at C-2. The presence
of a doublet at δ 2.40-2.49 and 2.54-2.62 was consistent
with the methylene protons at C-4. The presence of a dou-
blet at δ 5.83-6.22 was consistent with the methyne proton
at C-11. The presence of a broad proton signal at δ 6.27-
6.59 was consistent with N-H, deuterium oxide exchange-
able. The presence of a three proton multiplet signal at δ
The C-nmr spectra data for compounds 1-12 are given
in Table 1. The signals were confirmed by using HET-
COR, COSY, FLOCK, and NOESY nmr experiments
operating at 300 and 500 MHz.
The mass spectra for compounds 1-12 include ions of m/z
+
+
+
corresponding to molecular ion [M] ; [M-CH ] ; [M-CH ] ;
3
4
+
+
+
+
+
[M-R] ; [M-(HR)] ; [M-(R+CH )] ; [M-47] ; [M-57] ; [M-
4
+
+
+
84] ; [M-85] ; [M-(76+R)] ; m/z 363; 351; 311; 275; 240;
83. The ion at m/z [M-(76+R)] is the base peak; except for
+
Table 1
C NMR Spectral Data for Compounds 1-12
13
Compounds
1
2
3
4
5
6
7
8
9
10
p-OCH
p-Cl
11
p-OCH
o-OCH
12
p-OCH
p-OCH
OCH
R
o-OCH
o-Cl
o-OCH
p-Cl
o-OCH
o-OCH
o-OCH m-OCH m-OCH m-OCH m-OCH p-OCH
p-OCH
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
o-Cl
p-Cl
o-OCH
p-OCH
o-Cl
3
3
C-1
C-2
C-3
C-4
C-4a
C-5a
C-6
C-7
C-8
C-9
C-9a
C-11
193.9
49.7
32.4
193.9
49.7
32.4
193.9
49.7
32.2
194.0
49.7
32.3
193.9
49.7
32.4
193.9
49.6
32.3
193.9
49.7
32.3
194.0
49.7
32.3
193.7
49.7
32.3
193.9
49.7
32.4
193.7
49.8
32.3
193.8
49.7
32.3
46.0
46.3
46.0
46.1
46.1
46.3
46.2
46.0
46.1
46.4
46.4
46.5
154.5
126.0
128.1
127.4
131.6
126.5
139.7
55.7
152.8
125.7
128.3
126.5
131.6
126.4
137.7
57.4
154.6
125.8
127.8
126.7
131.5
126.7
139.1
53.7
153.2
125.9
128.5
126.8
131.8
126.9
138.2
57.4
154.4
125.9
122.2
120.4
131.8
123.7
137.9
55.9
152.7
125.8
123.3
120.3
131.5
123.6
137.4
58.0
156.6
125.2
121.9
119.8
130.1
121.9
139.6
57.7
153.2
126.3
122.4
120.1
131.7
123.7
138.0
57.2
154.4
125.9
123.7
120.4
131.7
122.9
139.7
55.9
152.7
126.0
123.4
120.5
132.0
123.6
142.2
57.5
153.8
126.5
123.5
120.1
131.4
123.2
138.9
55.3
152.4
126.6
123.5
120.4
131.3
123.6
137.9
57.4
C-11a
C-1'
C-2'
C-3'
C-4'
C-5'
C-6'
C-1''
C-2''
C-3''
C-4''
C-5''
C-6''
110.2
138.0
155.6
110.3
126.7
120.6
129.8
133.6
132.1
110.4
126.1
128.5
129.7
28.0
111.4
137.5
156.1
110.5
126.8
121.2
129.0
132.3
128.4
128.5
129.9
128.5
128.4
27.8
110.4
139.1
155.6
110.3
126.5
119.7
129.9
130.3
156.7
110.3
126.4
121.2
127.7
28.0
111.9
138.1
155.8
110.3
126.6
121.2
130.0
131.5
128.2
113.5
158.1
113.5
128.2
27.8
110.1
139.6
114.8
159.9
129.6
129.6
132.8
133.7
132.0
111.5
126.2
128.3
129.6
28.1
111.9
142.1
114.8
159.2
129.6
129.7
133.0
132.4
128.3
128.4
129.8
128.4
128.3
27.7
110.4
139.8
112.7
159.9
129.1
129.9
132.2
133.8
156.6
110.3
126.7
120.5
126.9
28.0
112.1
139.9
114.8
159.9
129.6
129.7
132.7
131.6
128.1
113.6
158.1
128.1
113.6
27.6
109.9
137.9
133.0
114.7
159.1
114.7
133.0
133.6
130.3
114.7
126.6
122.0
129.7
28.0
111.3
137.5
133.0
114.8
159.2
114.8
133.0
132.3
128.4
128.5
129.9
128.5
128.4
27.8
110.5
138.0
132.8
114.7
158.9
114.7
132.8
130.1
156.7
110.2
126.7
119.8
128.0
28.1
111.9
135.9
132.7
114.8
159.1
114.8
132.7
130.1
128.1
113.6
158.2
113.6
128.1
27.8
C-3(CH )
3
28.5
28.8
28.7
28.8
28.5
28.7
28.4
28.8
28.6
28.7
28.9
28.8
C-2'-OCH
C-3'-OCH
56.0
-
55.8
-
55.6
-
55.8
-
-
-
-
-
-
-
-
-
-
-
-
-
3
3
50.1
55.0
55.2
55.2

Jan-Feb 2002
Synthesis and Spectral Properties
57
Table 1 (Continued)
Compounds
1
2
3
4
5
6
7
8
9
10
p-OCH
p-Cl
11
p-OCH
o-OCH
12
p-OCH
p-OCH
3
OCH
R
o-OCH
o-Cl
o-OCH
p-Cl
o-OCH
o-OCH
o-OCH m-OCH m-OCH m-OCH m-OCH p-OCH
p-OCH
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
o-Cl
p-Cl
o-OCH
p-OCH
o-Cl
3
3
C-4'-OCH
C-2''-OCH
C-4''-OCH
-
-
-
-
-
-
-
55.3
-
-
-
-
-
-
-
-
-
-
55.2
-
-
-
55.3
-
-
55.4
-
-
53.7
53.6
-
55.3
-
55.1
3
3
3
55.0
55.0
A mixture of 0.001 mole of 3-{4-[(o-; m-; p-methoxy)phenyl-
11-[(o-methoxy)phenyl]-8-[(m-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo
[b,e][1,4]diazepin-1-ones and 11-[(o-methoxy)phenyl]-8-[(p-
methoxy)phenylthio]- 3,3-dimethyl-2,3,4,5,10,11-hexahy-
dro-1H-dibenzo[b,e][1,4]diazepin-1-ones in which the base
thio]-1,2-phenylenediamine}-5,5-dimethyl-2-cyclohexenone III,
0.001 mole of corresponding (o-; and p-substituted)benzalde-
hyde, 0.5 ml of acetic acid in 5 ml ethanol was heated at reflux
for 1.5 hours. The reaction mixture was cooled to room tempera-
ture and evaporated in vacuo to yield a semisolid. The residual
semisolid was purified by crystallization from hexane-ethyl
acetate to yield compounds IV, 1-12 ( 45-70%).
+
peak corresponds to the fragment ion [M-47] . The mass
spectra of the compounds exhibit a stable molecular ion; and
the main fragmentation was consistent with the assigned
structures. The proposed fragmentation pathways leading to
the formation of a number of important daughter ions have
been confirmed by the corresponding parent ion spectra using
collision-induced dissociation experiments. The elemental
composition of the molecular ion and the principal fragment
ion was determined by mass measurements.
11-[(o-Chloro)phenyl]-8-[(o-methoxy)phenylthio]-3,3-dimethyl-
2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones (1).
This compound was obtained as a yellow solid in 60% yield, mp
110°; ir (chloroform): ν N-H 3412, C=O 1616, C-N 1387 and
-1
1
1273, C-O 1153 and 1066 cm ; H nmr (deuteriochloroform): δ
1.06 and 1.13 (s, 6H, C -CH ), 2.23 (d, 1H, J = 16.5 Hz, 2-H ),
2
3
a
and 2.32 (d, 1H, J = 16.5 Hz, 2-H ), 2.49 (d, 1H, J = 15.9 Hz,
b
4-H ) and 2.62 (d, 1H, J = 15.9 Hz, 4-H ), 3.81 (s, 3H, C -OCH ),
a
b
2'
3
6.22 (d, 1H, J = 6.5 Hz, 11-H), 6.45 (d, 1H, J = 8.1, 6-H), 6.46 (bs,
2H, -NH, deuterium oxide exchangeable), 6.53 (d, 1H, J = 1.8 Hz,
9-H), 6.70 (dt, 1H, J = 2.0, 8.4 Hz, 5'-H), 6.73 (dd, 1H, J = 1.5, 7.8
Hz, 3''-H), 6.76 ( dd, 1H, J = 3.3, 8.1 Hz, 7-H), 6.81 (dd, 1H, J =
1.8, 8.1 Hz, 3'-H), 6.92 (dt, 1H, J = 2.1, 7.5 Hz, 4''-H), 6.92 (dt, 1H,
J = 2.1, 7.8 Hz, 5''-H), 6.93 (dt, 1H, J = 1.5, 7.5 Hz, 4'-H), 7.26 (dd,
1H, J = 1.8, 8.1 Hz, 6''-H), 7.30 (dd, 1H, J = 1.5, 7.5 Hz, 6'-H); ms:
EXPERIMENTAL
The ir spectra were recorded on a Nicolet Magna TR-750 spec-
trophotometer. The H-nmr spectra were recorded on a Varian
Unity 300 spectrometer operating at 300 MHz and the C-nmr
1
13
spectra were recorded on a Varian Unity 500 spectrometer oper-
ating at 125 MHz in deuteriochloroform solution containing
tetramethylsilane as the internal standard with chemical shifts δ
(ppm) expressed downfield from tetramethylsilane. The mass
spectra were measured on a JEOL JMS-AX505 and JEOL MS-
SX 102A high resolution mass spectrometer with accurate mass
determination of the molecular ion and the principal fragments
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.
+
+
+
m/z 490 (M) ; 492 [M+2] ; 494 [M+4] .
Anal. Calcd. for C ClN O S: C, 68.49; H, 5.54; N, 5.70.
H
28 27
2 2
Found: C, 68.40; H, 5.43; N, 5.82.
11-[(p-Chloro)phenyl]-8-[(o-methoxy)phenylthio]-3,3-dimethyl-
2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones (2).
This compound was obtained as an orange solid in 70% yield,
mp 123°; ir (chloroform): ν N-H 3412, C=O 1616, C-N 1392 and
-1
1
1365, C-O 1153 and 1028 cm ; H nmr (deuteriochloroform): δ
1.07 and 1.14 (s, 6H, C -CH ), 2.23 (d, 1H, J = 16.5 Hz, 2-H )
The 4-[(o-; m-; p-methoxy)phenylthio]-1,2-phenylenedi-
amines I was prepared following literature methods with modifi-
cations [11].
2
3
a
and 2.32 (d, 1H, J = 16.5 Hz, 2-H ), 2.42 (d, 1H, J = 15.9 Hz, 4-
b
H ) and 2.60 (d, 1H, J = 15.9 Hz, 4-H ), 3.80 (s, 3H, C -OCH ),
a
b
2'
3
General Procedure for the Synthesis of the 3-{4-[(o-; m-;
p-Methoxy)phenylthio]-1,2-phenylenediamine}-5,5-dimethyl-2-
cyclohexenone III.
5.88 (d, 1H, J = 6.5 Hz, 11-H), 6.42 (d, 1H, J = 8.1, 6-H), 6.50 (d,
1H, J = 2.1 Hz, 9-H), 6.55 (bs, 2H, -NH, deuterium oxide
exchangeable), 6.71 ( dd, 1H, J = 2.3, 7.8 Hz, 7-H), 6.82 (dd, 1H,
J = 1.8, 8.1 Hz, 3'-H), 6.82 (dt, 1H, J = 1.2, 8.4 Hz, 5'-H), 7.00
and 7.11 (AA'BB', 4H, J = 8.6 Hz, phenyl protons of "E" ring),
7.17 (dt, 1H, J = 1.5, 7.3 Hz, 4'-H), 7.17 (dd, 1H, J = 1.5, 7.2 Hz,
A mixture of 0.01 mole of 4-[(o-; m-; p-methoxy)phenylthio]-
1,2-phenylenediamines I, 0.01 mole of 5,5-dimethyl-1,3-cyclo-
hexanedione II in 10 ml of dry benzene was heated at reflux with
a Dean-Stark apparatus for 24 hours. The reaction mixture was
cooled to room temperature and evaporated in vacuo to yield a
semisolid. The residual semisolid was purified on a silica gel
chromatography column and elution with hexane-ethyl acetate
(1:9) to yield the compounds III, with 55-60% yield.
+
+
+
6'-H); ms: m/z 490 (M) ; 492 [M+2] ; 494 [M+4] .
Anal. Calcd. for C ClN O S: C, 68.49; H, 5.54; N, 5.70.
H
28 27
2 2
Found: C, 68.59; H, 5.61; N, 5.62.
11-[(o-Methoxy)phenyl]-8-[(o-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-
1-ones (3).
General Procedure for the Synthesis of the 11-[(o-; and
p-Substituted)phenyl]-8-[(o-; m-; p-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones IV, 1-12.
This compound was obtained as a yellow solid in 60% yield, mp
85°; ir (chloroform): ν N-H 3412, C=O 1616, C-N 1393 and 1273,
-1 1
C-O 1153 and 1028 cm ; H nmr (deuteriochloroform): δ 1.03 and

58
E. Cortés Cortés, A. M. Hernández Sanabria, O. G. Mellado
Vol. 39
1.09 (s, 6H, C -CH ), 2.25 (d, 1H, J = 16.5 Hz, 2-H ) and 2.32 (d,
C -OCH ), 5.86 (d, 1H, J = 5.4 Hz, 11-H), 6.33 (d, 1H, J = 1.5
3' 3
2
3
a
1H, J = 16.5 Hz, 2-H ), 2.42 (d, 1H, J = 16.2 Hz, 4-H ) and 2.56
Hz, 9-H), 6.35 (d, 1H, J = 8.4, 6-H), 6.37 (bs, 2H, -NH, deuterium
oxide exchangeable), 6.68 (dd, 1H, J = 2.4, 7.3 Hz, 7-H), 6.83 (d,
1H, J = 2.1 Hz, 2'-H), 6.84 (dd, 1H, J = 2.1, 7.8 Hz, 4'-H), 6.92
(dd, 1H, J = 1.8, 7.8 Hz, 6'-H), 6.97 and 7.08 (AA'BB', 4H, J =
8.7 Hz, phenyl protons of "E" ring), 7.11 (t, 1H, J = 7.8 Hz, 5'-H);
b
a
(d, 1H, J = 16.2 Hz, 4-H ), 3.78 (s, 3H, C -OCH ), 3.85 (s, 3H,
b
2'
3
C -OCH ), 6.15 (d, 1H, J = 6.5 Hz, 11-H), 6.36 (d, 1H, J = 8.1, 6-
2''
3
H), 6.47 (d, 1H, J = 1.8 Hz, 9-H), 6.59 (bs, 2H, -NH, deuterium
oxide exchangeable), 6.62 (dt, 1H, J = 1.8, 8.1 Hz, 5'-H), 6.64 (dt,
1H, J = 1.8, 7.8 Hz, 4''-H), 6.72 (dd, 1H, J = 1.8, 7.2 Hz, 3''-H), 6.73
(dt, 1H, J = 2.1, 7.8 Hz, 5''-H), 6.77 (dd, 1H, J = 2.7, 8.4 Hz, 7-H),
6.79 ( dd, 1H, J = 1.8, 8.1 Hz, 3'-H), 7.08 (dd, 1H, J = 1.5, 7.4 Hz,
6'-H), 7.08 (dd, 1H, J = 1.8, 8.1 Hz, 6''-H), 7.10 (dt, 1H, J = 1.5, 7.2
+
+
+
ms: m/z 490 (M) ; 492 [M+2] ; 494 [M+4] .
Anal. Calcd. for C ClN O S: C, 68.49; H, 5.54; N, 5.70.
H
28 27
2 2
Found: C, 68.39; H, 5.62; N, 5.81.
11-[(o-Methoxy)phenyl]-8-[(m-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (7).
+
+
Hz, 4'-H); ms: m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
H
29 30
2 3
Found: C, 71.45; H, 6.28; N, 5.70.
This compound was obtained as a dark brown solid in 50%
11-[(p-Methoxy)phenyl]-8-[(o-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (4).
yield, mp 95°; ir (chloroform): ν N-H 3410, C=O 1612, C-N
-1
1
1389 and 1283, C-O 1151 and 1094 cm ; H nmr (deuteri-
ochloroform): δ 1.05 and 1.14 (s, 6H, C -CH ), 2.21 (d, 1H, J =
2
3
This compound was obtained as an orange solid in 55% yield,
16.5 Hz, 2-H ) and 2.32 (d, 1H, J = 16.5 Hz, 2-H ), 2.44 (d,
a
b
mp 117°; ir (chloroform): ν N-H 3412, C=O 1614, C-N 1393 and
1H, J = 15.6 Hz, 4-H ) and 2.58 (d, 2H, J = 15.6 Hz, 4-H ),
a b
-1
1
1288, C-O 1177 and 1028 cm ; H nmr (deuteriochloroform): δ
1.02 and 1.08 (s, 6H, C -CH ), 2.22 (d, 1H, J = 16.5 Hz, 2-H ) and
3.71 (s, 3H, C -OCH ), 3.91 (s, 3H, C -OCH ), 6.19 (d, 1H,
3' 3 2'' 3
J = 5.4 Hz, 11-H), 6.36 (d, 1H, J = 8.1, 6-H), 6.38 (bs, 2H, -NH,
deuterium oxide exchangeable), 6.49 (d, 1H, J = 1.5 Hz, 9-H),
6.63 (dt, 1H, J = 1.8, 7.9 Hz, 5''-H), 6.65 (dt, 1H, J = 1.8, 7.2 Hz,
4''-H), 6.57 ( dd, 1H, J = 2.0, 7.5 Hz, 7-H), 6.75 (d, 1H, J = 2.1
Hz, 2'-H), 6.76 (dd, 1H, J = 1.9, 8.4 Hz, 3''-H), 6.78 (dd, 1H, J =
2.1, 7.8 Hz, 4'-H), 6.90 (dd, 1H, J = 2.1, 7.8 Hz, 6'-H), 7.06 (dd,
1H, J = 1.8, 8.1 Hz, 6''-H), 7.12 (t, 1H, J = 7.8 Hz, 5'-H); ms:
2
3
a
2.30 (d, 1H, J = 16.5 Hz, 2-H ), 2.40 (d, 1H, J = 15.6 Hz, 4-H )
b
a
and 2.54 (d, 1H, J = 15.6 Hz, 4-H ), 3.68 (s, 3H, C -OCH ), 3.82
b
2'
3
(s, 3H, C -OCH ), 5.87 (d, 1H, J = 6.6 Hz, 11-H), 6.42 (d, 1H, J =
4''
3
8.1, 6-H), 6.42 (d, 1H, J = 1.8 Hz, 9-H), 6.48 (bs, 2H, -NH, deu-
terium oxide exchangeable), 6.73 (dt, 1H, J = 1.2, 8.1 Hz, 5'-H),
6.80 ( dd, 1H, J = 2.7, 8.1 Hz, 7-H), 6.80 (dd, 1H, J = 1.8, 8.1 Hz,
3'-H), 6.97 and 7.09 (AA'BB', 4H, J = 8.7 Hz, phenyl protons of
"E" ring), 7.09 (dt, 1H, J = 1.5, 7.2 Hz, 4'-H), 7.10 (dd, 1H, J = 1.5,
+
+
m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
H
29 30
2 3
+
+
7.2 Hz, 6'-H); ms: m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
Found: C, 71.69; H, 6.30; N, 5.70.
H
29 30
2 3
11-[(p-Methoxy)phenyl]-8-[(m-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (8).
Found: C, 71.50; H, 6.29; N, 5.87.
11-[(o-Chloro)phenyl]-8-[(m-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (5).
This compound was obtained as an orange solid in 45% yield,
mp 90°; ir (chloroform): ν N-H 3412, C=O 1612, C-N 1389 and
-1
1
This compound was obtained as an orange solid in 60% yield,
1273, C-O 1175 and 1035 cm ; H nmr (deuteriochloroform): δ
1.01 and 1.13 (s, 6H, C -CH ), 2.24 (d, 1H, J = 16.5 Hz, 2-H )
mp 115°; ir (chloroform): ν N-H 3412, C=O 1616, C-N 1390 and
2
3
a
-1
1
1286, C-O 1153 and 1036 cm ; H nmr (deuteriochloroform): δ
1.11 and 1.14 (s, 6H, C -CH ), 2.21 (d, 1H, J = 16.5 Hz, 2-H )
and 2.31 (d, 1H, J = 16.5 Hz, 2-H ), 2.46 (d, 1H, J = 16.2 Hz, 4-
b
H ) and 2.59 (d, 1H, J = 16.2 Hz, 4-H ), 3.65 (s, 3H, C -OCH ),
2
3
a
a
b
3'
3
and 2.30 (d, 1H, J = 16.5 Hz, 2-H ), 2.46 (d, 1H, J = 15.9 Hz,
3.75 (s, 3H, C -OCH ), 5.83 (d, 1H, J = 5.4 Hz, 11-H), 6.33 (d,
b
4'' 3
4-H ) and 2.59 (d, 1H, J = 15.9 Hz, 4-H ), 3.79 (s, 3H, C -
1H, J = 1.5 Hz, 9-H), 6.34 (d, 1H, J = 8.5, 6-H), 6.35 (bs, 2H, -
NH, deuterium oxide exchangeable), 6.66 and 6.94 (AA'BB', 4H,
J = 8.5 Hz, phenyl protons of "E" ring), 6.66 (dd, 1H, J = 2.0, 7.5
Hz, 7-H), 6.78 (d, 1H, J = 2.5 Hz, 2'-H), 6.84 (dd, 1H, J = 2.0, 7.5
Hz, 4'-H), 7.05 (dd, 1H, J = 2.0, 8.0 Hz, 6'-H), 7.12 (t, 1H, J = 8.0
a
b
3'
OCH ), 6.19 (d, 1H, J = 6.0 Hz, 11-H), 6.34 (d, 1H, J = 1.5 Hz, 9-
3
H), 6.37 (bs, 2H, -NH, deuterium oxide exchangeable), 6.43 (d,
1H, J = 8.4 Hz, 6-H), 6.63 ( dd, 1H, J = 2.7, 7.0 Hz, 7-H), 6.70
(dd, 1H, J = 2.1, 8.2 Hz, 3''-H), 6.78 (dt, 1H, J = 1.8, 7.9 Hz, 5''-
H), 6.79 (d, 1H, J= 2.4 Hz, 2'-H), 6.86 (dd, 1H, J = 2.1, 7.5 Hz, 4'-
H), 6.90 (dt, 1H, J = 1.8, 7.2 Hz, 4''-H), 7.03 (dd, 1H, J = 2.1, 7.7
Hz, 6'-H), 7.11 (t, 1H, J = 7.9 Hz, 5'-H), 7.28 (dd, 1H, J = 1.8, 7.6
+
+
Hz, 5'-H); ms: m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
H
29 30
2 3
Found: C, 71.70; H, 6.10; N, 5.83.
+
+
+
Hz, 6''-H); ms: m/z 490 (M) ; 492 [M+2] ; 494 [M+4] .
Anal. Calcd. for C ClN O S: C, 68.49; H, 5.54; N, 5.70.
11-[(o-Chloro)phenyl]-8-[(p-methoxy)phenylthio]-3,3-dimethyl-
2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (9).
H
28 27
2 2
Found: C, 68.61; H, 5.42; N, 5.60.
This compound was obtained as an orange solid in 51%
11-[(p-Chloro)phenyl]-8-[(m-methoxy)phenylthio]-3,3-dimethyl-
2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones (6).
yield, mp 85°; ir (chloroform): ν N-H 3412, C=O 1616, C-N
-1
1
1389 and 1286, C-O 1174 and 1034 cm ; H nmr (deuteri-
ochloroform): δ 1.05 and 1.12 (s, 6H, C -CH ), 2.21 (d, 1H, J
This compound was obtained as a dark brown solid in 50%
2
3
yield, mp 125°; ir (chloroform): ν N-H 3412, C=O 1616, C-N
= 16.5 Hz, 2-H ) and 2.30 (d, 1H, J = 16.5 Hz, 2-H ), 2.45 (d,
1H, J = 15.9 Hz, 4-H ) and 2.58 (d, 1H, J = 15.9 Hz, 4-H ),
a b
a
b
-1
1
1387 and 1285, C-O 1153 and 1094 cm ; H nmr (deuteriochlo-
roform): δ 1.06 and 1.14 (s, 6H, C -CH ), 2.22 (d, 1H, J = 16.5
3.79 (s, 3H, C -OCH ), 6.19 (d, 1H, J = 3.6 Hz, 11-H), 6.34 (d,
2
3
4'
3
Hz, 2-H ) and 2.32 (d, 1H, J = 16.5 Hz, 2-H ), 2.42 (d, 1H, J =
1H, J = 1.5 Hz, 9-H), 6.37 (bs, 2H, -NH, deuterium oxide
exchangeable), 6.57 (dd, 1H, J = 1.8, 8.3 Hz, 7-H), 6.62 (d, 1H,
a
b
16.2 Hz, 4-H ) and 2.58 (d, 1H, J = 16.2 Hz, 4-H ), 3.80 (s, 3H,
a
b

Jan-Feb 2002
Synthesis and Spectral Properties
59
J = 8.1, 6-H), 6.73 (dt, 1H, J = 1.4, 7.9 Hz, 5''-H), 6.74 (dd, 1H,
J = 1.2, 7.9 Hz, 3''-H), 6.78 and 7.03 (AA'BB', 4H, J = 9.0 Hz,
phenyl protons of "D" ring), 6.89 (dt, 1H, J = 1.2, 7.3 Hz, 4''-
11-[(p- Methoxy)phenyl]-8-[(p-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (12).
+
H), 7.12 (dd, 1H, J = 1.8, 8.7 Hz, 6''-H); ms: m/z 490 (M) ; 492
This compound was obtained as an orange solid in 65% yield,
+
+
[M+2] ; 494 [M+4] .
Anal. Calcd. for C
mp 85°; ir (chloroform): ν N-H 3412, C=O 1614, C-N 1389 and
H
ClN O S: C, 68.49; H, 5.54; N, 5.70.
2 2
28 27
-1 1
1317, C-O 1177 and 1034 cm ; H nmr (deuteriochloroform): δ
1.06 and 1.13 (s, 6H, C -CH ), 2.21 (d, 1H, J = 16.2 Hz, 2-H )
Found: C, 68.39; H, 5.65; N, 5.84.
2
3
a
and 2.31 (d, 1H, J = 16.2 Hz, 2-H ), 2.40 (d, 1H, J = 15.9 Hz,
11-[(p-Chloro)phenyl]-8-[(p-methoxy)phenylthio]-3,3-dimethyl-
2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones (10).
b
4-H ) and 2.59 (d, 1H, J = 15.9 Hz, 4-H ), 3.69 (s, 3H, C -
a
b
4'
OCH ), 3.75 (s, 3H, C -OCH ), 5.84 (d, 1H, J = 3.6 Hz, 11-H),
3
4''
3
This compound was obtained as an orange solid in 53% yield,
6.27 (bs, 2H, -NH, deuterium oxide exchangeable), 6.35 (d, 1H,
J = 8.1, 6-H), 6.36 (d, 1H, J = 1.8 Hz, 9-H), 6.66 ( dd, 1H, J = 1.8,
8.7 Hz, 7-H), 6.66 and 6.93 (AA'BB', 4H, J = 9.0 Hz, phenyl pro-
tons of "E" ring), 6.79 and 7.06 (AA'BB', 4H, J = 8.7 Hz, phenyl
mp 119°; ir (chloroform): ν N-H 3412, C=O 1616, C-N 1389 and
-1
1
1317, C-O 1176 and 1032 cm ; H nmr (deuteriochloroform): δ
1.09 and 1.10 (s, 6H, C -CH ), 2.21 (d, 1H, J = 16.5 Hz, 2-H )
2
3
a
and 2.31 (d, 1H, J = 16.5 Hz, 2-H ), 2.40 (d, 1H, J = 15.6 Hz,
b
+
+
protons of "D" ring); ms: m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
4-H ) and 2.58 (d, 1H, J = 15.6 Hz, 4-H ), 3.80 (s, 3H,
a
b
H
29 30
2 3
C -OCH ), 5.84 (d, 1H, J = 3.6 Hz, 11-H), 6.32 (d, 1H, J = 2.1
4'
3
Found: C, 71.49; H, 6.32; N, 5.82.
Hz, 9-H), 6.36 (d, 1H, J = 8.1, 6-H), 6.43 (bs, 2H, -NH, deuterium
oxide exchangeable), 6.67 ( dd, 1H, J = 1.8, 8.7 Hz, 7-H), 6.84
and 7.08 (AA'BB', 4H, J = 9.0 Hz, phenyl protons of "D" ring),
6.97 and 7.10 (AA'BB', 4H, J = 8.7 Hz, phenyl protons of "E"
Acknowledgement
We wish to thank J. Pérez and L. Velasco for their assistance in
the acquisition of the mass spectral data and H. Rios, B. Quiroz
and I. Chavéz for the nmr determinations; and R. Patiño for the ir
determinations.
+
+
+
ring); ms: m/z 490 (M) ; 492 [M+2] ; 494 [M+4] .
Anal. Calcd. for C ClN O S: C, 68.49; H, 5.54; N, 5.70.
H
28 27
2 2
Found: C, 68.56; H, 5.43; N, 5.78.
11-[(o-Methoxy)phenyl]-8-[(p-methoxy)phenylthio]-3,3-
dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-
diazepin-1-ones (11).
REFERENCES AND NOTES
[1] Author to whom correspondence should be addressed.
[2] Contribution No. 1739 from Instituto de Química, UNAM.
[3] S. Schreiber, V. Getslev, M. M. Backer, R. Weizman and C.
G. Pick, Pharmacology Biochemistry and Behavior, 64, 75, (1999).
[4] A. Fitton and R. C. Heel, Drugs 40, 722 (1990).
[5] S. Miyano and N. Abe, Chem. Pharm. Bull., 20, 1588 (1972).
[6] K. Matsuo, M. Yoshida, M. Ohta and K. Tanaka, Chem.
Pharm. Bull., 33, 4057 (1985).
[7] Y. Tamura, L. C. Chen, M. Fujita and Y. Kita, J. Heterocyclic
Chem., 17, 1 (1980).
[8] E. Cortés and M. P. Sánchez, J. Heterocyclic Chem., 36, 611
(1999).
[9] E. Cortés and R. Salazar, J. Heterocyclic Chem., 38, 663
(2001).
[10] E. Cortés, M. I. Becerra and Y. M. Osornio, J. Heterocyclic
Chem., 34, 1833 (1997).
[11] E. Cortés and L. A. Araluce A., J. Heterocyclic Chem., 34,
745 (1997).
This compound was obtained as an orange solid in 60%
yield, mp 85°; ir. (chloroform): ν N-H 3412, C=O 1597, C-N
-1
1
1390 and 1286, C-O 1177 and 1035 cm ; H nmr (deuteri-
ochloroform): δ 1.14 and 1.16 (s, 6H, C -CH ), 2.21 (d, 1H, J =
2
3
16.5 Hz, 2-H ) and 2.32 (d, 1H, J = 16.5 Hz, 2-H ), 2.44 (d,
a
b
1H, J = 15.6 Hz, 4-H ) and 2.58 (d, 1H, J = 15.6 Hz, 4-H ),
a
b
3.80 (s, 3H, C -OCH ), 3.81 (s, 3H, C -OCH ), 6.12 (d, 1H,
4'
3
2''
3
J = 3.6 Hz, 11-H), 6.28 (d, 1H, J = 1.8 Hz, 9-H), 6.40 (bs, 2H, -
NH, deuterium oxide exchangeable), 6.58 (d, 1H, J = 7.5, 6-H),
6.58 (dt, 1H, J = 1.5, 8.1 Hz, 5''-H), 6.59 ( dd, 1H, J = 1.8, 8.6
Hz, 7-H), 6.61 (dt, 1H, J = 2.1, 6.2 Hz, 4''-H), 6.73 (dd, 1H, J =
1.2, 7.6 Hz, 3''-H), 6.79 and 7.01 (AA'BB', 4H, J = 9.0 Hz,
phenyl protons of "D" ring), 7.09 (dd, 1H, J = 1.8, 8.7 Hz, 6''-
+
+
H); ms: m/z 486 (M) ; 488 [M+2] .
Anal. Calcd. for C N O S: C, 71.57; H, 6.21; N, 5.76.
H
29 30
2 3
Found: C, 71.48; H, 6.28; N, 5.65.