Efficient Synthesis and Spectral Determination of 11-[(o-; m-; and p-substituted)-phenyl]-8-chloro-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.5570410221

A new synthesis to obtain eleven novel derivatives of 11-[(o-; m-; and p-substituted)-phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10, 11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones with possible pharmacological activity in the central nervous system in two efficient steps has been developed. The final products were obtained by condensation and cyclization between 3-[4-chloro-1,2-phenylenediamine]-5,5-dimethyl-2-cyclohexenone with (o-; m-; and p-substituted)benzaldehyde. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and high resolution in ms.

Full text of DOI:10.1002/jhet.5570410221

Mar-Apr 2004
277
Efficient Synthesis and Spectral Determination of 11-[(o-; m-; and
p-substituted)-phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones
Eduardo Cortés Cortés*[a][1], Miryan Adaya Baños [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
Estancia Post-Doctoral, Instituto de Química, UNAM
Received July 22, 2003
A new synthesis to obtain eleven novel derivatives of 11-[(o-; m-; and p-substituted)-phenyl]-8-chloro-
3,3-dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones with possible pharmacological
activity in the central nervous system in two efficient steps has been developed. The final products were
obtained by condensation and cyclization between 3-[4-chloro-1,2-phenylenediamine]-5,5-dimethyl-2-
cyclohexenone with (o-; m-; and p-substituted)benzaldehyde. The structure of all products was corroborated
1
13
by ir, H-nmr, C-nmr and high resolution in ms.
J. Heterocyclic Chem., 41, 277 (2004).
Clozapine is a piperidine derivative of the benzodiazepine
family and it is an atypical antipsychotic agent with proven
efficacy in the management of refractory schizophrenia [3-
4], and is particularly significant because it lacks extrapyra-
midal side-effects in humans [5]. Recently, research has
been carried out on this compound to confirm its pharmaco-
logical activity as an antipsychotic drug [6-10].
ones II, 1-11 (Figure 1), in two efficient steps, as shown in
Scheme 1.
We have previously reported the synthesis of the diben-
zodiazepine derivatives: dibenzo[b,e][1,4]diazepines [11];
1H-dibenzo[b,e][1,4]diazepin-1-ones [12] which have
potentially useful pharmacological properties.
To continue with the development program directed
towards synthesis, spectral properties and determination of
useful pharmacological properties of 1,5 and 1,4-benzodi-
azepine derivatives; we describe in this report the synthe-
sis and spectral properties of eleven new compounds 11-
[(o-; m-; and p-substituted)phenyl]-8-chloro-3,3-dimethyl-
2,3,4,5,10,11- hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-
Treatment of 4-chloro-1,2-phenylendiamine with 5,5-
dimethyl-1,3-cyclohexanedione at reflux in anhydrous
benzene with a Dean-Stark apparatus was performed for
26 hours to obtain the 3-[4-chloro-1,2-phenylenediamine]-
5,5-dimethyl-2-cyclohexenone I, which has been obtained
in 60% yields.
A mixture of 1 x 10-3 mole of compound I, 1 x 10-3 mole
of the corresponding (o-; m-; and p-substituted)benzaldehyde
in the presence of 0.5 mL of acetic acid at reflux in 5 mL of
ethanol for 1 hour and 45 minutes afforded the 1H-
dibenzo[b,e][1,4]diazepin-1-ones I I, 1-11 in 61-90% yields.
The infrared spectra of compounds 1-11 displayed
absorptions at 3413-1311 cm-1 for N-H stretching, at
1621-1616 cm-1 for C=O stretching, at 1368-1248, and
1394-1235 cm-1 for C-N stretching at 1394-1390 and
1235-1280 cm-1 for C-O stretching and the corresponding
absorptions for aromatic and R-substituents.
In the 1H-nmr spectra the presence of two singlet signals
at δ 1.06-1.08 and 1.11-1.14 were assigned to the methyl

278
E. Cortés Cortés, M. A. Baños and O. García-Mellado de Cortés
Vol. 41
[M–(76+R)]+. The main fragmentation pathway is consis-
tent with the assigned structures and the mass spectra of
the compound 1-11 includes ions of m/z corresponding to
molecular ion [M]+; [M-CH3]+; [M-(NH2)]+; [M-R]+; [M-
(R+NH2)]+; [M-(77+R)]+ (the base peak); [M-(C4H9)]+;
[M-(C5H8O)]+; [M-(C5H9O)]+ and m/z 83.
The proposed fragmentation pathways leading to the for-
mation 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 m olecular ion and the principal frag-
ment ion was determined by exact mass measurements.
protons at C-3. The presence of a doublet at δ 2.01-2.22 and
2.18-2.31 was consistent with the methylene protons at C-2;
the presence of other doublet signals at δ 2.38-2.62 and
2.45-3.31 was assigned to the methylene protons on C-4.
The presence of a singlet at δ 5.85-6.16 was consistent with
the methine proton on C-11. The presence of a broad deu-
terium oxide exchangeable proton signal at δ 8.22-9.02 was
consistent with N-H. The presence of a three-proton multi-
plet signal at δ 6.27-6.96 was assigned to the aromatic pro-
tons at C-6, C-7; and C-9 of the dibenzodiazepine frame-
work. The other aromatic protons, which are members of an
AA'BB' system, appeared as a multiplet resonating at δ
6.62-7.96. Signals for the R-substituents are also observed.
The 13C-nmr spectral data for compounds 1-11 are given
in Table 1. The signals were confirmed by using HET-
COR, COSY, FLOCK, NOESY, and DEPT nmr experi-
ments operating at 300 and 500 MHz. The mass spectra of
compounds 1-11 exhibit a stable molecular ion with a rela-
tive abundance of 13-47%. The base peak is the ion at m/z
EXPERIMENTAL
The ir spectra were recorded on a Nicolet Magna TR-750 spec-
1
trophotometer. The H-nmr spectra were recorded on a Varian
13
Unity 300 spectrometer operating at 300 MHz and the C-nmr
spectra were recorded on a Varian Unity 500 spectrometer operat-
Table 1
C NMR Spectral Data for Compounds 1-11
13
Compounds
R
1
o-Cl
2
3
p-Cl
4
5
6
7
o-Br
8
9
p-Br
10
m-NO
11
p-NO
2
m-Cl
o-OCH m-OCH p-OCH
m-Br
3
3
3
2
C-1
C-2
192.3
49.3
193.5
49.5
192.9
49.3
193.0
49.4
193.2
49.4
194.0
49.8
193.8
49.7
193.2
49.3
193.3
49.5
193.0
49.2
192.9
49.2
C-4
44.0
44.9
44.6
44.7
44.7
46.1
46.0
43.9
45.0
44.6
44.3
C-4a
C-5a
C-6
C-7
C-8
155.1
130.8
122.0
119.7
136.5
119.9
138.9
54.0
109.3
133.3
133.0
126.3
127.3
129.3
128.3
27.4
154.3
129.7
122.0
122.7
135.7
120.2
138.2
56.9
119.7
133.6
126.5
127.3
121.1
125.1
126.3
27.5
142.1
129.6
120.9
119.8
135.7
119.8
138.3
56.1
110.1
132.0
128.1
127.6
127.2
127.6
128.1
27.7
156.4
129.6
122.1
120.0
136.6
119.3
139.0
53.0
109.8
132.0
154.9
120.7
126.9
127.7
126.9
27.4
153.9
129.6
120.8
119.2
135.7
119.8
138.3
56.9
110.4
132.1
124.6
153.9
128.5
119.8
128.5
27.0
153.0
129.7
122.5
122.9
135.7
122.8
138.4
57.3
112.0
132.1
128.1
113.7
158.2
113.7
128.1
27.7
154.3
130.1
122.4
121.5
135.9
120.8
138.3
58.0
110.1
132.5
127.9
126.9
127.4
133.1
128.8
28.0
146.9
130.2
122.1
121.7
137.1
121.3
139.5
55.4
119.1
132.2
125.8
127.9
130.1
128.0
130.0
27.3
142.8
129.7
122.8
120.4
135.7
120.2
138.3
56.6
110.5
132.2
130.9
128.7
127.7
128.7
130.9
27.4
154.6
135.3
121.6
122.6
145.6
120.2
147.4
56.2
109.7
137.9
119.6
127.9
133.1
128.5
121.0
27.1
151.7
129.5
119.6
119.6
135.9
119.5
138.4
55.9
109.1
131.9
127.1
122.6
127.7
122.6
127.1
27.3
C-9
C-9a
C-11
C-11a
C-1'
C-2'
C-3'
C-4'
C-5'
C-6'
C-3(CH )
3
28.3
28.6
28.4
27.7
27.1
28.9
28.6
28.4
28.6
28.4
28.2
OCH
-
-
-
55.0
54.4
55.1
-
-
-
-
-
3
13
Note: The numbering of the phenyl ring is only for the assignment of the chemical shifts of the carbon in C nmr spectra.

Mar-Apr 2004
Efficient Synthesis and Spectral Determination
279
ing at 125 MHz in deuteriochloroform solution containing tetram-
ethylsilane as the internal standard with chemical shifts δ (ppm)
expressed downfield from tetramethylsilane. The mass spectra
were measured on a JEOL JMS-AC505 and JEOL MS-SX 102A
high-resolution mass spectrometer with accurate mass determina-
tion 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. Compounds I was prepared following
methods developed by us, with modifications [12].
2.60 (d, 1H, J=16.0 Hz, 4-Hb), 5.86 (s, 1H, 11-H); 6.41 (d, 1H,
J=8.4 Hz, 6-H); 6.52 (d, 1H, J=2.1 Hz, 9-H); 6.62 (dd, 1H, J=2.0,
8.5 Hz, 7-H); 7.05 and 7.08 (AA'BB', 4H, J=8.5 Hz, phenyl pro-
tons of "D" ring), 8.47 (bs, 2H, N-H, deuterium oxide exchange-
+
+
+
able); ms: m/z 386 (M ); 388 [M+2] ; 390 [M+4] .
Anal. Calcd. for C C N O: C, 65.12, H, 5.21; N, 7.23.
Found: C, 65.01; H, 5.12, N, 7.32.
H
21 20 l2
2
11 - [ (o-Methoxy)-phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4).
This compound was obtained as a brown solid in 65% yield,
mp 230°; ir (chloroform): ν N-H 3413, C=O 1618, C-N 1368 and
General Procedure for the Synthesis of the 11-[(o-; m-; and p-
Substituted)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one, II, 1-11.
-1
1270, C-O 1392 and 1249 cm ; H-nmr (deuteriochloroform): δ
1
1.08 and 1.13 (s, 6H, C -CH ); 2.21 (d, 1H, J=16.1 Hz, 2-Ha);
3
2.25 (d, 1H, J=16.1 Hz, 2-Hb); 2.55 (d, 1H, J=16.3 Hz, 4-Ha);
3
-3
A mixture of 1 x 10 mole of the 2-cyclohexenone I; 1 x 10
-3
mole of corresponding (o-; m-; and p-substituted)benzaldehyde,
0.5 mL of acetic acid in 5.0 mL ethanol was heated at reflux for 1
hour and 45 minutes. The reaction mixture was cooled to room
temperature and evaporated in vacuo to yield a semisolid. The
residual semisolid was purified by crystallization from hexane-
ethyl acetate to yield compounds II, 1-11, in 61-90%.
2.56 (d, 1H, J=16.3 Hz, 4-Hb); 3.94 (s, 3H, -OCH ), 6.13 (s, 1H,
3
11-H); 6.27 (d, 1H, J=8.3 Hz, 6-H); 6.34 (d, 1H, J=2.0 Hz, 9-H);
6.55 (dd, 1H, J=2.1, 8.6 Hz, 7-H); 6.62 (dt, 1H, J=1.7, 7.3 Hz, 4'-
H); 6.67 (dd, 1H, J=1.3, 7.8 Hz, 3'-H); 6.81 (dd, 1H, J=1.6, 8.1
Hz, 6'-H); 7.05 (dt, 1H, J=1.1, 7.4 Hz, 5'-H); 8.31 (bs, 2H, N-H,
+
+
deuterium oxide exchangeable); ms: m/z 382 (M ); 384 [M+2] .
Anal. Calcd. for C ClN O : C, 69.01; H, 6.06; N, 7.32.
Found: C, 69.15, H, 6.14, N, 7.23.
H
22 23
2 2
11 - [ (o-Chloro)phenyl]-8-chloro-3, 3-dimethyl-2, 3, 4, 5, 10, 11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (1).
11-[(m-Methoxy)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (5).
This compound was obtained as a brown solid in 83% yield;
mp 210°; ir (chloroform): ν N-H 3413, C=O 1621, C-N 1367 and
-1
1279, C-O 1391 and 1246 cm ; H-nmr (deuteriochloroform): δ
1
This compound was obtained as a brownish solid in 75% yield;
mp 220°, ir (chloroform) ν N-H 3414, C=O 1619; C-N 1368 and
1.06 and 1.12 (s, 6H, C -CH ), 2.04 (d, 1H, J=16.5 Hz, 2-Ha),
3
3
-1
1
and 2.18 (d, 1H, J=15.9 Hz, 2-Hb); 2.62 (s, 1H, J=16.1, 4-Ha);
2.63 (s, 1H, J=16.3 Hz, 4-Hb); 5.98 (s, 1H, 11-H); 6.48 (d, 1H,
J=8.4 Hz, 6-H); 6.49 (dd, 1H, J=2.1, 8.7 Hz, 7-H); 6.56 (d, 1H,
J=2.4 Hz, 9-H); 6.76 (dt, 1H, J=1.8; 7.5 Hz, 4'-H); 7.00 (dd, 1H,
J=1.2, 7.0 Hz, 3'-H); 7.09 (dd, 1H, J=1.8, 8.0 Hz, 6'-H); 7.35 (dt,
1H, J=1.2, 7.6 Hz, 5'-H); 9.02 (bs, 2H, N-H, deuterium oxide
1269, C-O 1393 and 1260 cm ; H-nmr (deuteriochloroform): δ
1.06 and 1.12 (s, 6H, C -CH ), 2.20 (d, 1H, J=16.2 Hz, 2-Ha);
2.30 (d, 1H, J=16.2 Hz, 2-Hb); 2.50 (d, 1H, J=16.2 Hz, 4-Ha);
3
3
2.60 (d, 1H, J=16.2 Hz, 4-Hb). 3.65 (s, 3H, OCH ), 5.87 (s, 1H,
3
11-H); 6.42 (d, 1H, J=8.4 Hz, 6-H); 6.51 (d, 1H, J=2.2 Hz, 9-H);
6.60 (dd, 1H, J=2.1, 8.4 Hz, 7-H); 6.63 (d, 1H, J=2.1 Hz, 2'-H);
6.70 (dd, 1H, J=2.1, 8.0 Hz, 5'-H); 7.02 (dd, 1H, J=1.5, 9.0 Hz, 6'-
H); 7.05 (dd, 1H, J=2.2, 7.8 Hz, 4'-H); 8.35 (bs, 2H, N-H, deu-
+
+
+
exchangeable); ms: m/z 386 (M ); 388 [M+2] ; 390 [M+4] .
Anal. Calcd. for C Cl N O: C, 65.12; H, 5.21; N, 7.23.
Found: C, 65.00; H, 5.28; N, 7.33.
H
21 20
2 2
+
+
terium oxide exchangeable); ms: m/z 382 (M ); 384 [M+2] .
Anal. Calcd. for C ClN O : C, 69.01; H, 6.06; N, 7.32.
Found: C, 69.12; H, 5.98; N, 7.24.
H
22 23
2 2
11 - [ (m-Chloro)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (2).
11-[( p-Methoxy)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (6).
This compound was obtained as a brown solid in 85% yield;
mp 205°, ir (chloroform): ν N-H 3415; C=O 1618; C-N 1368 and
-1
1
1280, C-O 1390 and 1248 cm ; H-nmr (deuteriochloroform): δ
This compound was obtained as a brown solid in 90% yield;
mp 145°, ir (chloroform ): ν N-H 3415; C=O 1616; C-N 1369
1.07 and 1.13 (s, 6H, C -CH ), 2.21 (d, 1H, J=16.5 Hz, 2-Ha);
3
3
-1
and 1263, C-O 1392 and 1235 cm ; H-nmr (deuteriochloro-
1
2.30 (d, 1H, J=16.2 Hz, 2-Hb); 2.52 (d, 1H, J=16.2 Hz, 4-Ha);
2.59 (d, 1H, J=16.0 Hz, 4-Hb); 5.87 (s, 1H, 11-H), 6.40 (d, 1H,
J=8.5 Hz, 6-H); 6.51 (d, 1H, J=2.2 Hz, 9-H); 6.55 (dd, 1H, J=2.2,
8.5 Hz, 7-H); 6.98 (dd, 1H, J=1.8, 9.0 Hz, 4'-H); 7.05 (dd, 1H,
J=1.8, 9.0 Hz, 5'-H); 7.06 (dd, 1H, J=1.2,9.0 Hz, 6'-H); 7.07 (d,
1H, J=1.6 Hz, 2'-H); 8.22 (bs, 2H, N-H, deuterium oxide
form): δ 1.08 and 1.14 (s, 6H, C -CH ); 2.05 (d, 1H, J=16.2 Hz,
3
3
H-2a); 2.21 (d, 1H, J=16.2 Hz, 2-Hb); 2.38 (d, 1H, J=16.0 Hz, 4-
Ha); 3.31 (d, 1H, J=16.0 Hz, 4-Hb); 3.69 (s, 3H, -OCH3); 5.86 (s,
1H, 11-H); 6.33 (d, 1H, J=8.4 Hz, 6-H); 6.44 (d, 1H, J=1.8 Hz, 9-
H); 6.66 (dd, 1H, J=1.9, 8.7 Hz, 7-H);6.67 and 6.96 (AA'BB', 4H,
J=9.0 Hz, phenyl protons of "D" ring); 8.40 (bs, 2H, N-H, deu-
+
+
+
exchangeable); ms: m/z 386 (M ); 388 [M+2] , 390 [M+4] .
Anal. Calcd. for C H Cl N O: C, 65.12; H, 5.21, N, 7.23.
+
+
terium oxide exchangeable); ms: m/z 382 (M ); 384 [M+2] .
Anal. Calcd. for C ClN O : C, 69.01; H, 6.06; N, 7.32.
Found: C, 68.93; H, 6.15; N, 7.39.
21 20 2 2
Found: C, 65.22, H, 5.29; N, 7.13.
H
22 23
2 2
11 - [ (p-Chloro)phenyl]-8-chloro-3, 3-dimethyl-2, 3, 4, 5, 10, 11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (3).
11 - [ (o-Bromo)phenyl]-8-chloro-3, 3-dimethyl-2, 3, 4, 5, 10, 11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (7).
This compound was obtained as a brown solid in 84% yield,
mp 160°; ir (chloroform): ν N-H 3413, C=O 1619; C-N 1368 and
This compound was obtained as a brown solid in 61% yield;
mp 220°; ir (chloroform): ν N-H 3413, C=O 1618; C-N 1367 and
-1
1287, C-O 1390 and 1245 cm ; H-nmr (deuteriochloroform): δ
1
-1
1
1.08 and 1.12 (s, 6H, C -CH ); 2.19 (d, 1H, J=15.8 Hz, 2-Ha),
1270; C-O 1393 and 1242 cm ; H-nmr (deuteriochloroform): δ
1.06 and 1.13 (s, 6H, C -CH ); 2.22 (d, 1H, J=16.3 Hz; 2-Ha);
3
2.30 (d, 1H, J=16.3 Hz, 2-Hb); 2.52 (d, 1H, J=16.2 Hz, 4-Ha);
3
3
3

280
Vol. 41
E. Cortés Cortés, M. A. Baños and O. García-Mellado de Cortés
2.31 (d, 1H, J=16.3 Hz, 2-Hb); 2.47 (d, 1H, J=16.0 Hz, 4-Ha);
2.48 (d, 1H, J=16.0 Hz, 4-Hb); 6.16 (s, 1H, 11-H); 6.36 (d, 1H,
J=8.3 Hz, 6-H); 6.43 (d, 1H, J=2.0 Hz, 9-H); 6.61 (dd, 1H, J=2.1,
8.4 Hz, 7-H); 6.73 (dt, 1H, J=2.5, 7.6 Hz, 4'-H); 6.93 (dd, 1H,
J=2.3, 8.0 Hz, 3'-H); 6.94 (dd, 1H, J=2.3, 9.0 Hz, 6'-H); 7.48 (dt,
1H, J=2.5, 9.0 Hz, 5'-H); 8.25 (bs, 2H, N-H, deuterium oxide
J=8.4 Hz, 6-H); 6.54 (d, 1H, J=2.3 Hz, 9-H); 6.62 (dd, 1H, J=2.4,
8.7 Hz, 7-H); 7.02 (d, 1H, J=2.3 Hz, 2'-H); 7.32 (dd, 1H, J=2.1,
7.9 Hz, 5'-H); 7.50 (dd, 1H, J=1.8, 7.7 Hz, 4'-H); 7.91 (dd, 1H,
J=1.8, 8.1 Hz, 6'-H); 8.52 (bs, 2H, N-H, deuterium oxide
+
+
exchangeable); ms: m/z 397 (M ); 399 [M+2] .
Anal. Calcd. for C ClN O : C, 63.39; H, 5.07; N, 10.56.
Found: C, 63.49, H, 5.00; N, 10.64.
H
21 20
3 3
+
+
+
exchangeable); ms: m/z 430 (M ); 432 [M+2] ; 434 [M+4] .
Anal. Calcd. for C ClBrN O: C, 58.42; H, 4.67; N, 6.49.
Found: C, 58.30, H, 4.74; N, 6.41.
H
21 20
2
11 - [ (p-Nitro)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (11).
11-[(m-Bromo)phenyl]-8-chloro-3, 3-dimethyl-2, 3, 4, 5, 10, 11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (8).
This compound was obtained as a brown solid in 86% yield,
mp 165; ir: ν N-H 3411, C=O 1620; C-N 1367 and 1251, C-O
-1
1
This compound was obtained as a brownish solid in 76% yield,
mp 228°; ir (chloroform): ν N-H 3413; C=O 1619; C-N 1368 and
1391 and 1246 cm ; H-nmr (deuteriochloroform): δ 1.08 and
1.11 (s, 6H, C -CH ); 2.18 (d, 1H, J=16.7 Hz, 2-Ha); 2.28 (d, 1H,
3
3
-1
1
1268; C-O 1392 and 1242 cm ; H-nmr (deuteriochloroform): δ
J=16.2 Hz, 2-Hb); 2.61 (d, 1H, J=16.2 Hz, 4-Ha); 2.62 (d, 1H,
J=16.2 Hz, 4-Hb); 5.92 (s, 1H, 11-H); 6.50 (d, 1H, J=8.4 Hz, 6-
H); 6.61 (d, 1H, J=2.2 Hz, 9-H); 6.96 (dd, 1H, J=2.0, 9.0 Hz, 7-
H); 7.32 and 7.96 (AA'BB'), 4H, J=8.6 Hz, phenyl protons of "D"
ring); 8.80 (bs, 2H, N-H, deuterium oxide exchangeable); ms:
1.07 and 1.12 (s, 6H, C -CH ); 2.01 (d, 1H, J=16.0 Hz, 2-Ha);
3
3
2.2. (d, 1H, J=16.0 Hz, 2-Hb); 2.57 (d, 1H, J=16.0 Hz, 4-Ha);
2.58 (d, 1H, J=16.0 Hz, 4-Hb); 5.67 (s, 1H, 11-H); 6.54 (d, 1H,
J=8.4 Hz, 6-H); 6.60 (d, 1H, J=2.4 Hz, 9-H); 6.67 (dd, 1H, J=2.1,
8.4 Hz, 7-H); 7.05 (dd, 1H, J=2.1, 7.8 Hz, 5'-H); 7.06 (d, 1H,
J=2.1 Hz, 2'-H); 7.11 (dd, 1H, J=1.8, 7.5 Hz, 4'-H); 7.12 (dd, 1H,
J=1.6, 7.5 Hz, 6'-H); 8.91 (bs, 2H, N-H, deuterium oxide
+
+
m/z 397 (M ); 399 [M+2] .
Anal. Calcd. for C ClN O : C, 63.39; H, 5.07; N, 10.56.
Found: C, 63.25; H, 5.17, N, 10.48.
H
21 20
3 3
+
+
+
exchangeable); ms: m/z 430 (M ); 432 [M+2] ; 434 [M+4] .
Anal. Calcd. for C ClBrN O: C, 58.42; H, 4.67; N, 6.49.
Found: C, 58.53; H, 4.75; N, 6.40.
Acknowledgements.
H
21 20
2
We wish to thank J. Pérez for his assistance in the acquisition
of the mass spectral data; H. Ríos for the nmr determination, and
R. Patiño and M. Adaya for the ir determination.
11-[( p-Bromo)phenyl]-8-chloro-3, 3-dimethyl-2, 3, 4, 5, 10, 11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (9).
This compound was obtained as a brownish solid in 85% yield;
mp 155°; ir (chloroform): ν N-H 3413, C=O 1618, C-N 1370 and
REFERENCES AND NOTES
-1
1272; C-O 1390 and 1250 cm ; H-nmr (deuteriochloroform): δ
1
[1] Author to whom correspondence should be addressed.
[2] Contribution No. 2460 from Instituto de Química, UNAM.
[3] S. Schreiber, V. Getslev, M. M. Backer, R. Weizman and C. G.
Pink, Pharmacology Biochemistry and Behavior, 64, 75 (1999).
[4] A. Fitton and R. C. Heel, Drugs, 40, 722 (1990).
[5] J. Angst, D. Bente, P. Berwer, H. Heimann, H. Helmohen and
H. Hippus, Pharmakopsychiatr. Neuro-Psychopharmakol., 4, 201 (1971).
[6] J. F. Nash, H. Y. Meltzer and G. A. Gudelsky, Eur. J.
Pharmacol., 151, 463-469 (1988).
[7] M. Picker, Pharmacol. Biochem. Behav., 30, 603 (1998).
[8] M. J. Picker and C.A. Massie, Pharmacol. Biochem. Behav.,
31, 953 (1988).
[9] C. D. Kilts, C. M. Anderson, G. Bissette, T. D. Ely and C. B.
Nemeroff, Biochem. Pharmacol., 37, 1547 (1988).
1.06 and 1.12 (s, 6H, C -CH ); 2.20 (d, 1H, J=15.8 Hz, 2-Ha);
3
3
2.30 (d, 1H, J=15.8, 2-Hb); 2.50 (d, 1H, J=16.8 Hz, 4-Ha); 2.58
(d, 1H, J=16.8 Hz, 4-Hb); 5.85 (s, 1H, 11-H); 6.38 (d, 1H, J=8.4
Hz, 6-H); 6.49 (d, 1H, J=2.2 Hz, 9-H); 6.64 (dd, 1H, J=2.1; 8.5
Hz, 7-H); 6.97 and 7.24 (AA'BB', 4H, J=8.5 Hz, phenyl protons
of the "D" ring); 8.24 (bs, 2H, N-H, deuterium oxide exchange-
+
+
+
able); ms: m/z 430 (M ); 432 [M+2] ; 434 [M+4] .
Anal. Calcd. for C ClBrN O: C, 58.42; H, 4.67; N, 6.49.
Found: C, 58.54; H, 4.60; N, 6.58.
H
21 20
2
11 - [ (m-Nitro)phenyl]-8-chloro-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (10).
This compound was obtained as a brown solid in 62% yield;
mp 150, ir (chloroform): ν N-H 3411; C=O 1619; C-N 1351 and
[10] B. A. B. McMillen, E. A Da Vanzo, A. H. Song, S. M. Scott
and M. E. Rodríguez, Eur. J. Pharmacol., 160, 149 (1989).
[11] E. Cortés C., P. Muñoz I., M. Martínez G. and M. O. Zepeda
R., J. Heterocyclic Chem. 33, 1723 (1996).
-1
1248; C-O 1392 and 1274 cm , H-nmr (deuteriochloroform): δ
1
1.06 and 1.12 (s, 6H, C -CH ); 2.22 (d, 1H, J=16.3 Hz, 2-Ha);
3
3
2.32 (d, 1H, J=16.2 Hz, 2-Hb); 2.43 (d, 1H, J=16.2 Hz, 4-Ha);
2.45 (d, 1H, J=16.2 Hz, 4-Hb); 5.99 (s, 1H, 11-H); 6.45 (d, 1H,
[12] E. Cortés C., A. M. Hernández S., and O. García M., J.
Heterocyclic Chem. 39, 55 (2002).