1,4-Diazepines bearing thieno(2,3-b)thiophene and cyclohexene carboxylate moieties

Article abstract of DOI:10.1080/10426500500366350

Bis[thieno(3,2-b)-1,4-diazepine] (4) and bis[imidazo(1′,2′) thieno(3,2-b)-1,4-diazepine (7) derivatives were prepared starting with thieno(2,3-b)thiophenes (1) and (2), respectively. Also, benzodiazepine derivatives (11a-f) were prepared via a reaction of

Full text of DOI:10.1080/10426500500366350

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1,4-Diazepines Bearing
Thieno(2,3-b)Thiophene and
Cyclohexene Carboxylate
Moieties
Ahmed M. M. El-Saghier a , Mansour A. Makhlouf b &
Mahmoud F. Farhat b
a Chemistry Department, South Valley University,
Sohag, Egypt
b Chemistry Department, Al-Fateh University,
Tripoli, Libya
Available online: 01 Feb 2007
To cite this article: Ahmed M. M. El-Saghier, Mansour A. Makhlouf & Mahmoud F.
Farhat (2006): 1,4-Diazepines Bearing Thieno(2,3-b)Thiophene and Cyclohexene
Carboxylate Moieties, Phosphorus, Sulfur, and Silicon and the Related Elements,
181:7, 1569-1582
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Phosphorus, Sulfur, and Silicon, 181:1569–1582, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500366350
1,4-Diazepines Bearing Thieno(2,3-b)Thiophene
and Cyclohexene Carboxylate Moieties
Ahmed M. M. El-Saghier
Chemistry Department, South Valley University, Sohag, Egypt
Mansour A. Makhlouf
Mahmoud F. Farhat
Chemistry Department, Al-Fateh University, Tripoli, Libya
Bis[thieno(3,2-b)-1,4-diazepine] (4) and bis[imidazo(1ꢀ,2ꢀ)thieno(3,2-b)-1,4-diaz-
epine (7) derivatives were prepared starting with thieno(2,3-b)thiophenes (1) and
(2), respectively. Also, benzodiazepine derivatives (11a–f) were prepared via a re-
action of cyclohexenone carboxylates (8a–f) with cyclohexylamine and chloroacetyl
chloride followed by cyclization. Also, dibenzoazepines (13) and (14a,b) were pre-
pared via a reaction of (8a) with o-phenylenediamine and o-aminophenol or o-
aminothiophenol.
Keywords 1,4-Diazepine; imidazothieno-1,4-diazepines; thienodiazepine; thienothio-
phene
Benzodiazepines have been widely employed in clinical practice as anx-
iolytics, sedative-hypnotics, anticonvulsants, vasopressin antagonists,
and HIV reverse transcriptase inhibitors.1−3 There have been sev-
eral reports concerning the pharmacological activity of benzodiazepines
with chloro-substituents in the C-7 position of the benzene ring of benzo-
diazepine dereivatives.4−7 On the other hand, the synthesis of tricyclic
1,4-benzodiazepines as well as their 1,5-isomers8,9 has attracted atten-
tion recently.10−16 The reason to study thieno[2,3-b]diazepine deriva-
tives was their structural relationship with tranquilizer Clobazam.17
Because of the bioisosterity of the two rings, replacement of the benzene
nucleus by a thiophene ring may provide pharmacologically active
compounds.
Received January 4, 2005; accepted August 10, 2005.
Address correspondence to Mansour A. Makhlouf, Al-Fateh University, Chemistry
Department, Faculty of Science, P.O. Box 13203, Tripoli Libya. E-mail: mf farhat@
yahoo.com
1569

1570
A. M. M. El-Saghier et al.
RESULT AND DISCUSSION
In an extension of our work of benzodiazepines,18 3,4-diamino-
2,5-dibenzoylthieno[2,3-b]-thiophene (1) and 3,4-diaminothieno[2,3-
b]thiophene-2,5-dicarbonitrile (2) were selected as starting materials
for the synthesis of thienodiazepins and were prepared by a reaction
of malononitrile, CS2, and phenacyl bromide or chloroacetonitrile in
1:1:2 molar ratios under phase-transfer catalysis conditions, respec-
tively (Scheme 1).19
SCHEME 1
Thus, the reaction of compound (1) with two moles of chloroacetyl
chloride in dry chloroform containing a few drops of pyridine gave
the corresponding 2,5-dibenzoyl-3,4-bis(chloroacetamido)thieno[2,3-
b]thiophene (3). On treating compound (3) with methanol saturated
with ammonia gas in a closed system, it underwent intramolecu-
lar cyclization to furnish the promising bis(2,3-dihydro-5-phenyl-1H-
thieno[3,2-b]-1,4-diazepin-2-one) (4). However, the latter compound
was also obtained upon heating compound (1) with ethylglycinate hy-
drochloride in pyridine (Scheme 2).
SCHEME 2

Diazopines-Bearing Thieno and Thiophene Moieties
1571
The incorporation of the imidazolyl moiety in imidazothien-
odiazepine system was achieved by converting the cyano groups of
compound (2) into a dihydroimidazolyl residue, followed by some substi-
tution reaction . Thus, the interaction of compound (2) with ethylene-
diamine in the presence of carbon disulfide afforded 3,4-diamino-
2,5-bis(4,5-dihydro-1H-imidazolyl)thieno[2,3-b]thiophene (5).20 The
treatment of compound (5) with chloroacetyl chloride furnished 3,4-
chloroacetamido-2,5-bis(4,5-dihydro-1H-2-imidazolyl)thieno[2,3-b]thi-
ophene (6), which underwent further cyclization reaction upon refluxing
in ethanol in the presence of triethylamine to afford bis(2,3,5,6-
tetrahydro-1H,-imidazo[1ꢀ,2ꢀ-d]thieno[3,2-b]-1,4-diazepin-2-one) (7)
(Scheme 3).
SCHEME 3
On the other hand, the synthesis of 2,3,4,5,6,7-hexahydro-6,8-
diphenylbenzo-1,4-diazepin-3,5-diones (11a–f) were carried out in three
steps; the first step included the reaction of cyclohexenone carboxy-
lates (8a–f)21 with cyclohexyl amine by refluxing in p-xylene in the
presence of triethylamine as a catalyst to give the corresponding cyclo-
hexylamide derivatives (9a–f). These compounds were detected by IR,
where the C O ester disappeared; the NH, C O of the amide prod-
uct appeared; the 1H-NMR showed the positions of NH, and cyclo-
hexane and the ethoxy groups disappeared. In the second step, the
amide derivatives (9a–f) were allowed to react with chloroacetyl chlo-
ride to afford the corresponding N-chloroacetamide derivatives (10a–
f). In the final step, compounds (10a–f) heated under reflux with
ammonium carbonate to give benzodiazepinone derivatives (11a–f)
(Scheme 4).
Similarly, the interaction of cyclohexenone ester with o-
phenylenediamine gave the corresponding amide derivative (12),

1572
A. M. M. El-Saghier et al.
SCHEME 4
which was heated under reflux in ethanol containing aq. NaOH
to afford the corresponding dibenzodiazepine derivative (13). Also,
compound (13) was obtained in a one-pot reaction by heating compound
(8a) with o-phenylene diamine under reflux in p-xylene in the presence
of TEA as a base (Scheme 5).
In contrast, a dibenzothiazepine and dibenzoxazepine derivative was
prepared via heating (8a) with o-aminothiophenol or o-aminophenol in
p-xylene containing TEA as a base (Scheme 6).
EXPERIMENTAL
All melting points were determined on a Koffler melting points ap-
paratus and are uncorrected. 1H-NMR spectra were recorded on a
Varian 390 at 90 MHz spectrometer using TMS as internal refer-
ence (chemical shifts in δ, ppm), and IR in KBr were obtained on
a Nicolet 710 FT-IR spectrophotometer (νmax in cm−1). The elemen-
tal analysis was carried out on a Perkin Elmer 240◦C elemental
analyzer.

Diazopines-Bearing Thieno and Thiophene Moieties
1573
SCHEME 5
2,5-Dibenzoyl-3,4-bis(chloroactamido)thieno[2,3-b]
thiophene (3)
A stirred solution of 3,4-diamino-2,5-dibenzoylthieno[2,3-b]thiophene
(1) (1.9 g, 5 mmol) in 20 mL of dry chloroform and 0.5 mL of pyridine
was stirred at r.t. Subsequently, (12 mmol) of chloroacetyl chloride was
added dropwise, and the reaction mixture was allowed to stand for 2 h.
The reaction mixture was washed with water, and the chloroform layer
dried, and evaporated. The solid formed was separated as white needles,
2.17g (87%), m.p. 142◦C (from ethanol). IR 3250(NH), 1690, 1660(C O)
1
cm−1. H NMR δ: 9.10(s, 2H, 2NH), 7.20–7.80(m, 10H, arom.), 3.90(s,
4H, 2CH2). Anal. calcd for C24H16N2O4S2Cl2: C, 54.42; H, 3.03; N, 5.27;
S, 12.07; Cl, 13.34. Found: C, 54.81; H, 3.12; N, 5.39; S, 12.11; Cl, 13.22.
SCHEME 6

1574
A. M. M. El-Saghier et al.
Bis[2,5-Dihydro-5-phenyl-1H-Thieno[3,2-b]-1,4-diazepione] (4)
Method A
Compound (3) (0.5 g, 1 mmol) was stirred in 20 mL of methanol satu-
rated with NH3 in a closed system for 4 h. The solution was evaporated
under reduced pressure, and the residual solid was collected by filtra-
tion as a white powder, 0.31 g (69%).
Method B
A suspension of compound (1) (0.38 g, 1 mmol) in 25 mL of dry pyri-
dine and (0.28 g, 2 mmol) of ethylglycinate hydrochloride. The mixture
was refluxed in an air condenser for 4 h (about 5 mL of pyridine was
evaporated (lost) during this time). The lost amount of pyridine and
another amount (0.28 g, 2 mmol) of ethylglycinate hydrochloride were
added to the reaction mixture and completed the reflux for 16 h. The
reaction mixture evaporated to its half volume, cooled, and poured into
ice-cooled water; the solid formed was separated as white crystals, 0.26
g (56%), m.p. 256◦C (from acetone). IR 3441, 3285(NH), 1660(C O),
1632(C C) cm−1 1H NMR δ: 9.20(s, 2H, 2NH), 7.30–7.90 (m, 10H,
.
arom.), 3.63 (s, 4H, 2CH2). Anal. calcd. for C24H16N4O2S2: C, 63.14;
H, 3.53; N, 12.27; S, 14.04. Found: C, 63.17; H, 3.51; N, 12.32; S, 14.11.
3,4-Diamino-2,5-di[4ꢀ,5ꢀ-dihydro-1ꢀH-imidazoly]thieno[2,3-
b]thiophene (5)
To a suspension of (2) (0.44 g, 2 mmol), ethylenediamine (3 mL) and
carbon disulfide (1 mL) were added dropwise. The reaction mixture was
heated on a water bath for 2 h. The precipitated solid was triturated
with ethanol (10 mL) and filtered off to give golden yellow crystals,
0.47 g (77%), m.p. 197◦C (from ethanol). IR 3420, 3330, 3285, 3120 (NH,
NH2), 1630(C C) cm−1. 1H NMR δ : 8.90 (s, 2H, 2NH), 6.20 (s, 2H, NH2),
4.00–4.30 (d, 4H, 2CH2). Anal. calcd. for C12H14N6S2: C, 47.04; H, 4.61;
N, 27.43; S, 20.93. Found: C, 47.21; H, 4.71; N, 27.25; S, 20.90.
3,4-Dichloroacetamido-2,5-di[4ꢀ,5ꢀ-dihydro-
1ꢀH-imidazoly]thieno[2,3-b]thiophene (6)
A stirred solution of compound (5) (0.31 g, 1 mmol) in 30 mL of chloro-
form (dry) and (0.2 g, 2 mmol) of triethylamine was stirred at r.t. Subse-
quently (0.22 g, 2.2 mmol) of chloroacetyl chloride was added dropwise
with stirring, and the reaction mixture was allowed to stand at r.t.
for 2 h. The reaction mixture was washed with water, and the chloro-
form layer was dried and evaporate. The solid formed was separated by

Diazopines-Bearing Thieno and Thiophene Moieties
1575
filteration 0.3 g (65%), m.p. 201◦C (from benzene). IR 3410, 3120(NH),
1
1660(C O), 1620(C C) cm−1. H NMR δ: 9.10 (s, 2H, 2NH), 8.60 (s,
2H, 2NH), 3.10 (s, 4H, 2CH2), 3.70(d, 8H, 4CH2). Anal. calcd. for
C16H16N6O2S2Cl2: C, 41.83; H, 3.51; N, 18.29; S, 13.96; Cl, 15.44. Found:
C, 41.96; H, 3.44; N, 18.35; S, 14.01; Cl, 15.39.
Bis[2,3,5,6-Tetrahydro-1H-imidazo(1ꢀ,2ꢀ-d)thieno
[3,2-b]-1,4-diazepin- 2-one (7)
Compound (6) (0.46 g, 1 mmol) in 30 mL of dry dioxane and (0.2 g,
2 mmol) of triethylamine was heated under reflux for 2 h. The pre-
cipitate that separated after cooling was washed with water as white
crystals, 0.21 g ( 56%), m.p. 267d◦C (from dioxane). IR 3430, 3280(NH),
1
1670(C O), 1620(C C) cm−1. H NMR δ: 9.10 (s, 2H, 2NH), 3.65 (s,
4H, 2CH2), 3.40–3.70 (d, 8H, 4CH2). Anal. calcd. for C16H14N6O2S2: C,
49.73; H, 3.65; N, 21.75; S, 16.59. Found: C, 49.91; H, 3.74; N, 21.68; S,
16.66.
6-(N-Cyclohexylcarboxamido)-3,5-diaryl-2-cyclohexenone
derivatives (9a–f)
General Procedure
A mixture of (8a–f) (5 mmol) and cyclohexylamine (0.5 g, 5 mmol) in
30 mL of p-xylene in the presence of a catalytic amount of triethylamine
(few drops) was refluxed for 6 h. The precipitated product was filtered
off and recrystallized from the proper solvents.
6-Cyclohexylamido-3,5-diphenylcyclohex-2-enone (9a)
From (8a) and cyclohexylamine, a yellow solid 1.4 g (75%), m. p.
135–136◦C (from dioxane). IR 3420(NH), 1710, 1668(C O), 1610(C N)
cm−1 1H NMR δ : 8.90 (s, 1H, NH), 7.00–8.01 (m, 10 H, arom.),
.
5.21 (s, 1H, CH), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO-CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C25H27NO2: C, 80.40; H, 7.29; N, 3.75.
Found: C, 80.33; H, 7.41; N, 3.68.
6-Cyclohexylamido-3-p-chlorophenyl-5-phenylcyclohex-2-
enone (9b)
From (8b) and cyclohexylamine, a pale yellow solid 1.54 g (77%),
m.p. 195◦C (from dioxane). IR 3410(NH), 1710, 1668(C O), 1610(C C)
cm−1
.
1H NMR δ: 8.90 (s, 1H, NH), 7.00–8.01 (m, 9H, arom.),

1576
A. M. M. El-Saghier et al.
5.21 (s, 1H, CH), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H,
CH2-cyclohexane). Anal. calcd. for C25H29NO2Cl: C, 73.61; H, 6.42; N,
3.44; Cl, 8.69. Found: C, 73.73; H, 6.32; N, 3.31; Cl, 8.69.
6-Cyclohexylamido-3-phenyl-5-p-methoxypheny
lcyclohex-2-enone (9c)
From (8c) and cyclohexylamine, yellow solid 1.4 g (72%), m.p. 290d◦C
1
(from ethanol). IR 3410(NH), 1715, 1670(C O), 1610(C C) cm−1. H
NMR δ : 8.90 (s, 1H, NH), 7.00–8.01 (m, 9H, arom.), 5.21 (s, 1H, CH),
3.70 (s, 3H, CH3), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C26H29NO3: C, 77.39; H, 7.24; N, 3.48.
Found: C, 77.42; H, 7.11; N, 3.52.
6-Cyclohexylamido-3-phenyl-5-p-chloropheny-
lcyclohex-2-enone (9d)
From (8d) and cyclohexylamine, pale yellow solid 1.6 g (81%), m.p.
267◦C (from benzene). IR 3410(NH), 1710, 1668(C O), 1610(C C)
cm−1
.
1H NMR δ : 8.90 (s, 1H, NH), 7.00–8.01(m, 9H, arom.),
5.21(s, 1H, CH), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO CH cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C25H26NO2Cl: C, 73.61; H, 6.42; N, 3.44;
Cl, 8.69. Found: C, 73.73; H, 6.22; N, 3.31; Cl, 8.69.
6-Cyclohexylamido-3-p-chlorophenyl-5-p-methoxypheny-
lcyclohex-2-enone (9e)
From (8e) and cyclohexylamine, a white solid 1.8 g (85%), m.p. 202◦C
(from CHCl3). IR 3410(NH), 1715, 1670(C O), 1610(C C) cm−1 1H
.
NMR δ : 8.90 (s, 1H, NH), 7.20–7.90 (m, 8H, arom.), 5.21 (s, 1H, CH),
3.70 (s, 3H, CH3), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C26H28NO3Cl: C, 71.63; H, 6.24; N, 3.21;
Cl, 8.13. Found: C, 71.73; H, 6.32; N, 3.31; Cl, 8.24.
6-Cyclohexylamido-3-p-methoxyphenyl-5-
phenylcyclohex-2-enone (9f)
From (8f) and cyclohexylamine, white solid 1.5 g (75%), m.p. 177◦C
(from methanol). IR 3410(NH), 1715, 1670(C O), 1610(C C) cm−1
.

Diazopines-Bearing Thieno and Thiophene Moieties
1577
1H NMR δ : 8.90 (s, 1H, NH), 7.00–8.01 (m, 9H, arom.), 5.21 (s, 1H,
CH), 3.70 (s, 3H, CH3), 2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd,
3H, CO CH-cyclohexanone, CH2-Cyclohexanone), 1.50–2.10 (m, 11H,
CH2-cyclohexane). Anal. calcd. for C26H29NO3: C, 77.39; H, 7.24; N,
3.48. Found: C, 77.42; H, 7.11; N, 3.52.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3,5-
diarylcyclohex-2-enone derivatives (10a–f)
General Procedure
A stirred solution of compounds (9a–f) (5 mmol) in 30 mL of
chloroform (dry) and (5 mmol) of pyridine was stirred at r.t. Sub-
sequently, (1.16 g, 12 mmol) of chloroacetyl chloride was added
dropwise, and the reaction was stirred for 2 h. The reaction mix-
ture was left overnight and then evaporated to its half-volume
and was neutralized with sodium bicarbonate solution. The pre-
cipitated solid was filtered off and recrystallized from the proper
solvents.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3,5-
diphernylcyclohex-2-enone (10a)
From (9a) and chloroacetyl chloride, a red solid, 1.7 g ( 75%), m.p. 181◦C
1
(from ethanol). IR 1710, 1668, 1660(C O), 1610(C C) cm−1. H NMR
δ: 7.00–8.01 (m, 10 H, arom.), 5.21 (s, 1H, CH), 3.60 (s, 2H, CH2) 2.80-
3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H, CO CH-cyclohexanone, CH2-
Cyclohexanone), 1.50–2.10 (m, 11H, CH2-cyclohexane). Anal. calcd. for
C27H28NO3Cl: C, 72.07; H, 6.27; N, 3.11; Cl, 7.89. Found: C, 72.15; H,
6.21; N, 3.21; Cl, 7.90.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3-p-
chlorophenyl-5-phernylcyclohex-2-enone (10b)
From (9b) and chloroacetyl chloride, a brown solid, 1.7 g ( 70%), m.p.
173◦C (from ethanol). IR 1710, 1668, 1660 (C O), 1610 (C C) cm−1. 1H
NMR δ: 7.00–8.01 (m, 9H, arom.), 5.21 (s, 1H, CH), 3.60 (s, 2H, CH2),
2.80–3.00 (m, 1H, CH Ph), 2.10–2.30 (dd, 3H, CO CH-cyclohexanone,
CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-cyclohexane). Anal. calcd.
for C27H27NO3Cl2: C, 66.94; H, 5.62; N, 2.90; Cl, 14.64. Found: C, 67.15;
H, 5.52; N, 2.83; Cl, 14.62.

1578
A. M. M. El-Saghier et al.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3-phenyl-5-
p-methoxyphernyl-cyclohex-2-enone (10c)
From (9c) and chloroacetyl chloride, a gray solid, 1.58 g (66%), m.p.
156◦C (from ethanol). IR 1715, 1670, 1660 (C O), 1610 (C C) cm−1
.
1H NMR δ: 7.00–8.01 (m, 9H, arom.), 5.21(s, 1H, CH), 3.60(s, 2H,
CH2), 3.70(s, 3H, CH3), 2.80–3.00(m, 1H, CH Ph), 2.10–2.30(dd, 3H,
CO CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10(m, 11H, CH2-
cyclohexane). Anal. calcd. for C28H30NO4Cl: C, 70.06; H, 6.30; N, 2.92;
Cl, 7.40. Found: C, 70.15; H, 6.17; N, 2.99; Cl, 7.51.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3-phenyl-5-
p-chlorophernylcyclohex-2-enone (10d)
From (9d) and chloroacetyl chloride, a deep yellow solid, 1.71 g (71%),
m.p. 216◦C (from ethanol). IR 1710, 1668, 1660(C O), 1610(C C) cm−1
.
1H NMRδ: 7.00–8.01(m, 9H, arom.), 5.21 (s, 1H, CH), 3.60(s, 2H, CH2),
2.80–3.00(m, 1H, CH Ph), 2.10–2.30(dd, 3H, CO-CH-cyclohexanone,
CH2-Cyclohexanone), 1.50–2.10(m, 11H, CH2-cyclohexane). Anal.calcd.
for C27H27NO3Cl2: C, 66.94; H, 5.62; N, 2.90; Cl, 14.64. Found: C, 66.97;
H, 5.41; N, 2.97; Cl, 14.71.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3-p-
chlorophenyl-5-P-methoxy-phernylcyclohex-2-enone (10e)
From (9e) and chloroacetyl chloride, a brown solid, 1.51 g (59%), m.p.
179◦C (from ethanol). IR 1715, 1670, 1660(C O), 1610(C C) cm−1
.
1H NMR δ: 7.20–7.90(m, 8H, arom.), 5.21 (s, 1H, CH), 3.90 (s, 2H,
CH2), 3.70 (s, 3H, CH3), 2.80–3.00(m,1H, CH Ph), 2.10–2.30(dd, 3H,
CO-CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C28H29NO3Cl2: C, 67.47; H, 5.86; N, 2.81;
Cl, 14.23. Found: C, 67.32; H, 5.78; N, 2.81; Cl, 14.17.
6-(N-Chloroacetamido-N-cyclohexylcarboxamido)-3-p-
methoxyphenyl-5-phernylcyclo-hex-2-enone (10f)
From (9f) and chloroacetyl chloride, a pale brown solid, 1.49 g ( 62%),
m.p. 184◦C (from ethanol). IR 1715, 16701660(C O), 1610(C C) cm−1
.
1H NMR δ: 7.00–8.01 (m, 9H, arom.), 5.21(s, 1H, CH), 3.90 (s, 2H,
CH2), 3.70 (s, 3H, CH3), 2.80-3.00(m, 1H, CH Ph), 2.10–2.30 (dd, 3H,
CO CH-cyclohexanone, CH2-cyclohexanone), 1.50–2.10 (m, 11H, CH2-
cyclohexane). Anal. calcd. for C28H30NO4Cl: C, 70.06; H, 6.30; N, 2.92;
Cl, 7.40. Found: C, 70.13; H, 6.33; N, 2.99; Cl, 7.55.

Diazopines-Bearing Thieno and Thiophene Moieties
1579
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6,8-diaryl-1,4-
benzodiazepin-3,5-dione (11a–f)
General Procedure
A solution of (10a–f) (5 mmol) in acetonitrile (20 mL) containing
sodium iodide (0.75 g, 5 mmol) and ammonium carbonate (2 g) was
stirred at r.t. for 24 h. The precipitate was filtered off and washed with
dichloromethane. The combined filterate was washed with water, dried,
and evaporated, and the solid that formed filtered off and recrystallized
from the proper solvents.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6,8-diphenyl-1,4-
benzodiazepin-3,5-dione (11a)
From (10a), a white solid, 1.56 g (76%), m.p. 198◦C (from ethanol).
1
IR 3420(NH), 1670,1668(C O), 1610(C C) cm−1. H NMR δ : 8.90(s,
1H, NH), 7.00–8.01(m, 10H, arom.), 5.21(s, 1H,
CH), 4.10(s,
2H, CH2), 2.80–3.00(m, 1H, CH Ph), 2.10–2.30 (d, 2H, CH2-
cyclohexanone), 1.50–2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for
C27H28N2O2: C, 78.61; H, 6.84; N, 6.79. Found: C, 78.69; H, 6.71; N,
6.92.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6-phenyl-8-P-
chlorophenyl-1,4-benzodiazepin-3,5-dione (11b)
From (10b), a white solid, 1.45 g (65%), m.p. 210◦C (from ethanol).
1
IR 3410(NH), 1670, 1668(C O), 1610(C C) cm−1. H NMR δ : 8.90(s,
1H, NH), 7.00–8.01(m, 9H, arom.), 5.21(s, 1H, CH), 4.10(s, 2H, CH2),
2.80–3.00(m, 1H, CH Ph), 2.10–2.30(d, 2H, CH2-cyclohexanone), 1.50–
2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for C27H27N2O2Cl: C,
72.55; H, 6.09; N, 6.28; Cl, 7.95. Found: C, 72.68; H, 5.91; N, 6.91; Cl,
7.89.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6-p-methoxyphenyl-8-
phenyl-1,4-benzodiazepin-3,5-dione (11c)
From 10c, a white solid, 1.56g (71%), m.p. 226◦C (from ethanol). IR
1
3410(NH), 1670,1660(C O), 1610(C C) cm−1. H NMR δ : 8.90(s, 1H,
NH), 7.00–8.01(m, 9H, arom.), 5.21(s, 1H, CH), 4.10(s, 2H, CH2),
3.70(s, 3H, CH3), 2.80–3.00(m, 1H, CH Ph), 2.10–2.30(d, 2H, CH2-
cyclohexanone), 1.50–2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for
C28H30N2O3: C, 75.99; H, 6.83; N, 6.33. Found: C, 76.09; H, 6.71; N,
6.49.

1580
A. M. M. El-Saghier et al.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6-p-chlorophenyl-8-
phenyl-1,4 -benzodiazepin-3,5-dione (11d)
From (10d), a white solid, 1.78 g (80%), m.p. 256◦C (from ethanol).
1
IR 3410(NH), 1680, 1668(C O), 1610(C C) cm−1. H NMR δ : 8.90(s,
1H, NH), 7.00–8.01(m, 9H, arom.), 5.21(s, 1H, CH), 4.10(s, 2H, CH2),
2.80–3.00(m, 1H, CH Ph), 2.10–2.30(d, 2H, CH2-cyclohexanone), 1.50–
2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for C27H27N2O2Cl: C,
72.55; H, 6.09; N, 6.28; Cl, 7.95. Found: C, 72.71; H, 5.92; N, 6.15; Cl,
7.89.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6-p-methoxyphenyl-8-p-
chlorophenyl-1,4-benzodiazepin-3,5-dione (11e)
From (10e), a white solid, 1.5 g (63%), m.p. 283◦C (from ethanol). IR
3410(NH), 1670, 1660(C O), 1610(C C) cm−1. 1H NMR δ : 8.90(s, 1H,
NH), 7.20–7.90(m, 8H, arom.), 5.21(s, 1H, CH), 4.10(s, 2H, CH2),
3.70(s, 3H, CH3), 2.80–3.00(m, 1H, CH Ph), 2.10–2.30(d, 2H, CH2-
cyclohexanone), 1.50–2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for
C28H29N2O3Cl: C, 70.50; H, 6,13; N, 5.87; Cl, 7.43. Found: C, 70.67; H,
5.99; N, 5.90; Cl, 7.53.
2,3,6,7-Tetrahydro-1H-4-cyclohexyl-6-phenyl-8-p-
methoxyphenyl-1,4-benzodiazepin-3,5-dione (11f)
From (10f), a gray solid, 1.87 g (85%), m.p. 198◦C (from p-xylene).
1
IR 3410(NH), 1670, 1660(C O), 1610(C C) cm−1. H NMR δ : 8.90(s,
1H, NH), 7.00–8.01(m, 9H, arom.), 5.21(s, 1H, CH), 4.10(s, 2H, CH2),
3.70(s, 3H, CH3), 2.80–3.00(m, 1H, CH Ph), 2.10–2.30(d, 2H, CH2-
cyclohexanone), 1.50–2.10(m, 11H, CH2-cyclohexane). Anal. calcd. for
C28H30N2O3: C, 75.99; H, 6.83; N, 6.33. Found: C, 76.14; H, 6.22; N, 6.29.
6-N-(2-Anilino)carboxamido-4,5,6-trihydro-3,5-diphenyl-2-
cyclohexenone (12)
A mixture of (8a) (1.6 g , 5 mmol), o-phenylenediamine (0.54 g, 5 mmol),
and triethylamine (0.5 g, 5 mmol) in 30 mL of p-xylene. The reaction
mixture was heated under reflux for 3 h, and the solid formed was sepa-
rated as pale yellow crystals, 1.28 g ( 67%), m.p. 205◦C (from xylene). IR
3420, 3320, 3285(NH, NH2), 1710, 1668(C O) cm−1. 1H NMR δ : 9.20(s,
1H, NH), 7.00–7.90(m, 14H, arom.), 6.10(s, 2H, NH2), 5.21(s, 1H, CH),
2.80–3.00(m, 1H, CH Ph), 2.10–2.30(dd, 3H, CO CH-cyclohexanone,

Diazopines-Bearing Thieno and Thiophene Moieties
1581
CH2-cyclohexanone). Anal. calcd. for C25H22N2O2: C, 78.51; H, 5.80; N,
7.32. Found: C, 78.60; H, 5.73; N, 7.50.
8,9-Dihydro-8,10-diphenyl 1H,6H-dibenzo-1,4-diazepines (13)
Compound (12) (1.9 g, 5 mmol) in 30 mL of ethanol and 5 mL (10%
NaOH) was heated under reflux for 7 h. The separated solids were
collected by filteration as a white solid, 0.9 g (50%), m.p. 196◦C (from
dioxane). IR 3420, 3380(NH), 1680(C O) cm−1. 1H NMR δ : 9.10(s, 1H,
NH), 8.80(s, 1H, NH) 7.20–8.10(m, 14 H, arom.), 5.21(s, 1H, CH), 2.80–
3.00(m,1H, CH Ph), 2.10–2.30 (dd, 3H, CO CH-cyclohexanone, CH2-
Cyclohexanone). Anal. calcd. for C25H20N2O: C, 82.39; H, 5.53; N, 7.69.
Found: C, 82.26; H, 5.39; N, 7.71.
8,9-Dihydro-8,10-diphenyl 1H,6H-dibenzo-1,4-diazepines (13)
and (14 a,b)
General Procedure
A mixture of (8a) (1.6 g, 5 mmol) and o-phenylenediamine (0.54 g,
5 mmol) or o-aminothiophenol (0.6 g, 5 mmol), or o-aminophenol
(0.55 g, 5 mmol) in 30 mL of p-xylene and triethylamine (5 mmol).
The reaction mixture was heated under reflux for 7 h. The separated
solids were collected by filteration and recrystallized from the proper
solvents.
8,9-dihydro-8,10-diphenyl 1H,6H-dibenzo-1,4-thiazepines
(14a)
Yellow solid, 1.0 g (56%), m.p. 291◦C (from benzene). IR 3420(NH),
1675(C O) cm−1 1H NMR δ : 9.10(s, 1H, NH), 7.100–8.10(m, 14H,
.
arom.), 5.21(s, 1H, CH), 2.80–3.00(m, 1H, CH Ph), 2.10–2.20(d, 2H,
CH2-cyclohexanone). Anal. calcd. for C25H19NSO: C, 78.71; H, 5.07; N,
3.68. Found: C, 79.07; H, 4.91; N, 3.59.
8,9-Dihydro-8,10-diphenyl-1H,6H-dibenzo-1,4-oxazepines 14b
White solid, 1.0 g (56%), m.p. 319◦C (from dioxane). IR 3420(NH),
1675(C O) cm−1 1H NMR δ : 9.10(s,1H,NH), 7.100–8.10(m, 14H,
.
arom.), 5.21(s, 1H, CH), 2.80–3.00(m, 1H, CH Ph), 2.10–2.20(d, 2H,
CH2-Cyclohexanone). Anal. calcd. for C25H19NO2: C, 82.17; H, 5.24; N,
3.83. Found: C, 82.28; H, 5.08; N, 3.92.

1582
A. M. M. El-Saghier et al.
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