Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
CHPATER-III
Synthesis of 1,5-benzodiazepine and its derivatives
using silica gel supported sulfuric acid and cage type
mesoporous aluminosilicate catalysts
3.1. Introduction:
Benzodiazepines constitute an impotant class of biologically active
compounds and their synthesis has been receiving much attention in
the field of medicinal and pharmaceutical chemistry owing to their
application as anticonvulsant, anti-inflammatory, analgesic, sedative
agents,and hypnotic activity.1–6 The derivatives of 1,5-benzodiazepines
are also used as dyes for acrylic fibers in photography.7 In addition,
benzodiazepines are the useful precursors for the synthesis of other
fused ring compounds such as oxadiazolo-, oxazino- and triazolo-, or
furano-benzodiazepines.8–11 Benzodiazepines are generally synthesized
by the condensation of o-phenylenediamine (OPDA) with α,β-
unsaturated carbonyl compounds, β-haloketones or with ketones12
using acidic catalysts which are critical to enhance the condensation
process. Different reagents such as BF3-etherate, polyphosphoric acid,
NaBH4, MgO/POCl3, Yb(OTf)3, Ga(OTf)3, lead nitrate, L-proline, acetic
acid under microwave conditions, molecular iodine, and ionic liquids
have also been used for the synthesis of benzodiazepines.13–23
Recently the synthesis of benzodiazepines was also reported using
different solid acid catalysts such as sulfated zirconia, Al2O3/P2O5,
Ag3PW12O40, PVP-FeCl3, and zeolite catalysts.24–28 Unfortunately, many
of these catalysts suffer from one or more limitations such as drastic
reaction conditions, long reaction times, occurrence of several side
reactions, tedious work-up procedure and low yields. In addition, the
solid acid catalyst used previously had poor textural parameters such
as low surface area and pore volume which do not support a better
performance in the synthesis of benzodiazepines.
In recent years, ordered mesoporous silica materials have received
considerable importance because of their unique structures with
organized porosity, high specific surface area and pore volume, and
well-ordered mesopores that are considerably larger than zeolites and
zeotype molecular sieves, and find potential applications mainly in the
field of catalysis, adsorption, separation, sensors, and fuel cells.29-37
These materials can be prepared by using either a cationic or an
anionic or a neutral surfactant as a structure directing agent. There
are numerous reports which deal with the preparation of various types
of one and three dimensional mesoporous materials, such as MCM-
41, MCM-48, SBA-1, SBA-15, AMS, HMS, and MSU etc.37 Among the
various materials, materials with three-dimensional cage type pore
arrangements are more resistant to pore blocking, allow faster
diffusion of reactants, and provide more adsorption sites, which can
be easily accessible through three dimensional pore channels. In spite
of these interesting features, surprisingly, the majority of studies
published so for deal with phases having a one-dimensional pore
system, viz. MCM-41 and SBA-15.
Despite these interesting features, the KIT-5 materials have
several disadvantages including neutral framework, poor stability,
weak acidity, and low ion exchange capacity, which limit their
applications, especially in catalysis and adsorption. These problems
can be overcome by introducing the hetero-atoms in the silica
framework of KIT-5 materials. Moreover, the content of the hetero-
atoms in the silica framework is a major factor, which determines the
properties of the catalysts such as acidity and catalytic reactivity.
However, it is highly difficult to incorporate the metal atoms in the
silica framework of KIT-5 because the preparation of the materials
requires highly acidic medium where the solubility of the metal source
is very high. Moreover, at highly acidic medium, the hetero-atoms
exist only in the cationic forms rather than their corresponding oxo
species which suppress the contact between the hetero-atoms and the
silica species.
Therefore, particular interest was focused on the design and
fabrication of highly ordered mesoporous materials with three-
dimensional (3D) pore structures such as SBA-1 and KIT-5 as they are
believed to be more advantageous for catalytic applications than
phases having a 1D array of pores.34-38 Moreover, these materials can
offer more resistant to pore locking and allow faster diffusion of
reactants which are highly necessary to obtain a stable and a high
catalytic activity. Recently, Vinu et al. reported the preparation of
various mesoporous metallosilicate catalytic materials with 3D cage
type structure and investigated their catalytic activity in the alkylation
and acylation of aromatics.34,36,37,38 They found that the activity of the
3D mesoporous catalysts is much better than the catalysts with
unidimensional mesoporous structure. Among the 3D metallosilicate
catalysts, aluminium supported mesoporous KIT-5 material (AlKIT-5)
was found to be interesting as it possesses 3D mesostructure with
Fm3m symmetry and large cage type pores, a high acidity which
mainly comes from the Brönsted acid sites on the surface of the
catalyst, and a large pore diameter.37 These features are clearly
reflected in its high catalytic activity towards various acid catalyzed
reactions.37,38 The activity of the AlKIT-5 catalyst has been studied on
the acetylation of veratrole by acetic anhydride and it has been found
that the AlKIT-5(10) shows37 higher activity than that of the zeolites,
such as ZSM-5, HY, mordenite, and Hb. Although these materials
possess interesting textural and catalytic properties, unfortunately,
with the best of our knoeledge, there has been no publication available
on the synthesis of benzodiazepines using such materials as catalysts
in the open literature so far.
Here we are expressing first time for the synthesis of 1,5-
benzodiazepine using AlKIT-5 as the catalyst through a condensation
reaction between OPDA and ketones in acetonitrile. The effect of the
aluminium content of the catalyst and the catalyst concentration on
the above process has also been investigated in detail. We also
demonstrate the preparation of various derivatives of 1,5-
benzodiazepine using substituted OPDAs and various ketones.
3.2. Present work:
Initially we focused on the synthesis of 1,5-benzodiazepines using
10 mol% silica gel supported sulfuric acid39 and the results are
presented in Table 3.3. However, mesoporous AlKIT-5(10)40 catalyst
gave the better yields and recoverability than the previous catalyst.
Since AlKIT-5 is better choice, we focused our synthesis using this
catalyst. Thus, condensation of OPDA or substituted OPDA 1 with
various ketones 2 in acetonitrile at room temperature gave the
products 3(a-t) in good yields (Scheme 1).
HN
N
CH2
R1
R1
NH2
NH2
+ R1 C
O
CH2
R2
R2
R1 = Alkyl, Phenyl
R2 = H, Alkyl
1 3 (a-t)2
R = H, Cl
R RCH3CN, R.T
SiO2-H2SO4/ AlKIT-5
Scheme1: Synthesis of 1,5-benzodiazepines at R.T
The role and activity of the catalyst in this transformation was
shown in Table.3.1. The role of the Brönsted acid site of the AlKIT-5
catalyst in the formation of 1,5-benzodiazepines and the reaction
mechanism are clearly depicted in scheme 2.
Scheme 2: A plausible mechanism for the synthesis of 1,5-
benzodiazepines using AlKIT-5 catalyst at R.T
Table 3.1 shows the textural parameters and the acidity of the
AlKIT-5 samples with different ‘Al’ content. All the materials possess
well-ordered 3D mesostructure with cage type pores, high surface area
and large pore diameter. It can be seen from Table 3.1 that the acidity,
surface area, pore volume and pore diameter of the materials increase
with increasing the ‘Al’ content in the AlKIT-5. The specific surface
area, pore volume, pore diameter, cage diameter and the acidity of the
AlKIT-5(10) is found to be 989 m2/g, 0.68 cm3/g, 6 nm, 12 nm, and
0.51 mmol of NH3/g, respectively. These features make this material
special among other metal substituted mesoporous materials. As the
detailed characterization of the materials can be found in earlier
reports.37,38
Here, the acidity and the catalytic activity of the novel AlKIT-5
materials were investigated. This suggests that the amount of
NH2
NH2
RC
CH3
OH
NH2
NH R
NH2
N
R
R
O=CCH3
+
N
HN
R
R
NH
HN
R
R
HN
NH
C
C CH2
R
R
CH3 HN
N
C
C CH3
R
R
CH3
R
O=CCH3
-H2O
-H+
H+
-H2O
-H+
OSi
OAl
O
OO OO
H
tetrahedral ‘Al’ incorporation in AlKIT-5 materials increases
remarkably with decreasing the nSi/nAl ratio. Moreover, the catalytic
activity of the AlKIT-5 materials with different ratios on the BDPs
synthesis was investigated and the results are compared with silica
gel supported sulfuric acid (Table 3.3). Interestingly, among the
catalysts examined under the optimized reaction conditions, the
AlKIT-5(10) shows much higher activity. The silica and AlKIT-5
structures are given below.
OSi
OSi
OSi
OSi
OSi
OSi
OSi
O
O O O O O O O O O O OO OO
Structure 1: Silica structure
Structure 2: AlKIT-5 structure
The prepared 3D mesoporous aluminosilicate nanocage in a
“Highly Acidic Media” will give high Al content upto nSi/nAl = 10. From
the above structures, 3D silica is neutral in charge and AlKIT-5 is
acidic as per the charge shown on the structure. Therefore, the
conversion is superior over other catalysts37 such as AlKIT-5 catalysts
with the nSi/nAl ratio lower than 10, mordenite, zeolite HY, zeolite Hb,
and ZSM-5. The higher activity of the AlKIT-5(10) could be due to the
OSi
OAl
OSi
OAl
OSi
OSi
OAl
O
O O O O O O O O O O OO OO
H H H
fact that the sample exhibits three dimensional cage type porous
networks with a high surface area and comparable acidity, which
enhance the diffusion of the reactant molecules and allows the easy
access to all the active sites. These catalytic results also confirm that
the AlKIT-5(10) material indeed possesses more amount of tetrahedral
Al, which provides the Bronsted acid sites. The promising catalytic
activity of the materials encouraged us to discover these catalysts in
the synthesis of benzodiazepine and its derivatives (Scheme 1).
Table: 3.1. Textural parameters, acidity and the catalytic activity of the AlKIT-5 catalysts with different ‘Al’ content
S.No. Catalyst a0 (nm) nSi/nAl SBET (m2/g)
Vp (cm3/g) Dp BJH (nm)
Cage diameter
(nm)
Acidity (mmol/g)
Yield (%)
Gel Product
1 AlKIT-5(10) 18.44 7 10 989 0.68 6.0 12.0 0.50 97
2 AlKIT-5(28) 17.76 10 28 815 0.56 5.6 11.2 0.32 84
3 AlKIT-5(44) 16.97 12 44 713 0.45 5.2 10.3 0.14 75
4 SiO2-H2SO4
(10 mol %)
- - - - - - - - 97
ao unit cell constant; SBET specific surface area; Vp specific pore volume; Dp pore diameter; Reaction conditions: substrate = OPDA
and acetone, weight of the catalyst = 100 mg, reaction temperature = RT, solvent = acetonitrile.
Initially we have focused on the synthesis of 1,5-benzodiazepines
from o-phenylenediamines and ketones. Thus, OPDA was treated with
acetone in the presence of mesoporous AlKIT-5(10) in acetonitrile at
room temperature and the outcome results are also presented in Table
3.1. The catalyst was found to be highly active, affording 97% isolated
yield of 1,5-benzodiazepine in 30 min. In order to understand the role
of acidity ofAlKIT-5 on the yield of the final product, we carried out the
reaction using AlKIT-5 with different Al content. Among the catalysts
studied, AlKIT-5(10) was found to be highly active and selective. It
must also be noted that when the reaction was conducted without any
catalyst, the reaction was not occurred. These outcome results
indicate that the role and activity of the catalyst in this transformation
and dictate the activity of the catalyst. As AlKIT- 5(10) showed a much
higher activity than other catalysts used in this transformation under
the optimized reaction conditions, we have used AlKIT-5(10) for the
remaining reactions.
The synthesis of 1,5-benzodiazepines was also carried out over
different amounts of AlKIT-5(10) at room temperature for 30 min and
the outcome results are given in Table.3.2. Theweight of the catalyst
was increased between 25 and 150 mg. It was found that the yield
increases from 24% to 97% with increasing the weight of the catalyst
from 25 to 100 mg, respectively. This could be mainly due to the
availability of huge acidic sites on the porous surface of the
aluminosilicate catalysts as the weight of the catalyst is increased. It
must be noted that the yield of the product is remain constant with
the further increase of the weight of the catalyst from 100 to 150 mg.
Hence, we used the weight of the catalyst was 100 mg for the rest of
the studies.
Table: 3.2. Effect of the weight of AlKIT-5(10) on the synthesis of 1,5-
benzodiazepine
S.No. Weight of
AlKIT-5(10) (mg)
Reaction
time (min)
Yield (%)
1 25 30 24
2 50 30 52
3 100 30 97
4 150 30 97
Reaction conditions: substrate = OPDA and acetone, reaction temperature = RT, solvent = acetonitrile.
The effect of solvents on the synthesis of BDPs was also
investigated. Among various solvents like methylene chloride (87%),
tetrahydrofuran (THF) (89%), acetonitrile and methanol studied,
methanol and acetonitrile (97%) were found to be the excellent
solvents for this synthesis (Table 3.3, entry 1).
Table: 3.3. Synthesis of 1,5-benzodiazepines and its derivatives using silica gel supported sulfuric acid and AlKIT-
5(10) through a condensation reaction between a series of OPDA and various ketones
Entry Diamine (1) Ketone (2) Product (3) Timea
(min)
Yieldb
(%)
Timec
(min)
Yieldd
(%)
1 NH2
NH2
Acetone
HN
N3a
30 97 30 97
2 NH2
NH2
2-butatone
HN
N3b
40 95 60 95
3 NH2
NH2
2-pentatone
3c
HN
N
50 90 60 93
4 NH2
NH2
Methyl Iso Butyl
Ketone
HN
N3d
60 94 60 92
5 NH2
NH2
Acetophenone
HN
N3e
40 92 60 96
6 NH2
NH2
4-methyl
Acetophenone
HN
N
CH3
CH3
3f
50 96 60 96
7 NH2
NH2
4- Chloro
Acetophenone 3g
HN
N
Cl
Cl
50 95 60 95
8 NH2
NH2
Cyclopentanone
HN
N3h
60 92 60 92
9 NH2
NH2
2-Acetyl thiophene
3iN
HN
S
S
120 86 120 86
10 NH2
NH2
3-Acetyl thiophene
3j
N
HN
S
S
120 82 120 82
11 NH2
NH2Cl
Acetone
HN
N
3l
Cl
50 94 60 94
12 NH2
NH2Cl
2-butatone
HN
N
3k
Cl
60 92 60 92
13 NH2
NH2Cl
2-pentatone
3m
HN
NCl
120 88 120 88
14 NH2
NH2Cl
Methyl Iso Butyl
Ketone
HN
N3n
Cl
90 88 120 88
15
NH2
NH2Cl
Acetophenone
HN
N3o
Cl
120 90 120 92
16
NH2
NH2Cl
4-methyl
Acetophenone
HN
N
CH3
CH3
3p
Cl
120 90 120 90
17
NH2
NH2Cl
4- Chloro
Acetophenone 3q
HN
N
Cl
ClCl
120 85 120 86
18
NH2
NH2Cl
Cyclopentanone
HN
N3rCl
90 86 120 86
19
NH2
NH2Cl
2-Acetyl thiophene
3s N
HN
S
S
Cl
140 82 150 85
20 NH2
NH2Cl
3-Acetyl thiophene
3tN
HN
S
S
Cl
150 80 150 85
a Reaction time for the BDPs with silica gel supported sulfuric acid b Isolated yields for the BDPs with silica gel supported sulfuric acid c Reaction time for the BDPs with AlKIT-5
d Isolated yields for the BDPs with AlKIT-5
The excellent catalytic performance of the AlKIT-5(10) in the
synthesis of 1,5-benzodiazepine stimulated us to extend this process
for the synthesis of various derivatives of benzodiazepines using
various substituted OPDAs and a series of symmetrical and
unsymmetrical ketones and the results are shown in Table 3.3. In all
cases, the reactions are highly selective and are completed within 1.0–
2.5 h. The catalyst showed excellent activity in all the cases, affording
85–97% isolated yield of the corresponding derivatives of 1,5-
benzodiazepine. It was found that the catalyst showed superior
performance with high yields in a relatively shorter reaction time than
Ersorb-4 (E4), a clinoptylolite-type zeolite catalyst reported
previously.28 Furthermore, E4 needed a high temperature and a longer
reaction time to achieve high isolated yield of the final product
whereas AlKIT-5(10) was active even at room temperature. These
findings reveal the superior nature of our catalyst in this
transformation.
Chloro-substituted OPDA and substituted ketones were also used
with similar success to provide the corresponding benzodiazepines in
high yields, which are also of much interest with regard to biological
activity. Chloro-substituted benzodiazepines were prepared easily in
good yields by using this catalyst. Especially, chloro-substituted
OPDA and acetyl thiophenes were used to obtain the corresponding
thiophene derivatives of benzodiazepines. It was reported previously
that thiophene derivatives of 1,5-benzodiazepines possess good
biological activities.41 Cyclopentanone also worked well with chloro-
substituted OPDA.
It is also significant to note down the work-up of the reaction
mixture is very simple. The catalyst can be filtered out easily and the
solvent was evaporated. Recycling experiments were conducted to find
out the stability of the catalyst after the reaction. The catalyst was
easily separated by centrifuge and reused after activation at 5000C for
3.0–4.0 h. The efficiency of the recovered catalyst was verified with the
reaction of OPDA and acetone (Entry 1). Using the fresh catalyst, the
yield of product (3a) was 97%, while the recovered catalyst in the three
subsequent recyclization gave the yields of 95%, 93% and 90%,
respectively. The small reduction in the catalytic activity after three
cycles can be mainly due to the loss of the catalyst or catalyst
structure during the recovery process. These results reveal that the
catalyst can be recycled several times without lacking its activity. The
AlKIT-5 with 3D structure having better recyclable nature than silica
gel supported sulfuric acid.
Structural assignments of compounds (Table 3.3, 3a-3t) were
made based on IR, 1H NMR and MALDI-MS spectral data.
The compound 4a IR spectrum (Fig.5.1) showed the absorption
peaks at 3295, 2964, 1633, 1475 and 770 cm-1. The peak at 3295
cm−1 indicates the occurrence of –NH group in diazepine ring, peak at
2964 cm−1 indicates CH stretching, peak at 1633 cm-1 indicates the
presence of >C=N, peak at 1475 cm-1 indicates the presence of
conjugated >C=C< stretching, peak at 770 cm-1 assigns the aromatic –
CH bending and these peaks are confirmed the formation of diazepine.
The 1H NMR spectrum (300 MHz, CDCl3) for compound 3a (Fig.3.4)
showed the signals at δ 1.25 (s, 6H, 2CH3) was assigned to two methyl
groups on 4th position of benzodiazepine ring and signal at δ 2.14 (s,
2H, -CH2-) was assigned to -CH2- group in diazepine ring, and signal
at δ 2.28 (s, 3H, -CH3) indicates the methyl protons at 2nd position in
diazepine ring, and signal at δ 3.40 (brs, 1H, -NH) indicates the
presence of -NH proton in diazepine ring. The remaining signals at δ
6.65 (d, 1H, J = 8.2 Hz, Ar-H), 6.88-6.92 (m, 2H, J = 3.2 Hz, Ar-H),
7.05 (d, 1H, J = 8.2 Hz, Ar-H) confirms the presence of aromatic
protons.
MALDI-MS spectrum (Fig.3.5) for compound 3a showed molecular
ion peak at m/z [M+] =188, corresponds to molecular formula
C12H16N2 and which is equal to calculated mass 188.27g/mol.
All other compounds spectral data results are presented in
experimental section.
3.3. Conclusions:
BDPs are synthesized by using silica gel supported sulfuric acid
and AlKIT-5 catalysts. These two catalysts are heterogeneous and
additional to the present existing procedures. We designed and
synthesized some biologically active chloro and thiophene derivatives
of BDPs. We have established for the first time the synthesis of 1,5-
benzodiazepine using silica gel supported sulfuric acid and AlKIT-5
catalysts through a condensation reaction between substituted OPDA
and a series of symmetrical and unsymmetrical ketones at room
temperature in acetonitrile solvent. But AlKIT-5 showed better
performance in terms of yields and recyclability. The AlKIT-5 catalyst
was found to be highly active and selective, recyclable, affording a
high yield of benzodiazepines. The effect of the ‘Al’ content of the
catalyst and the catalyst concentration on the above process was
investigated. The catalyst was also successfully employed for the
preparation of various derivatives of 1,5-benzodiazepine using
substituted OPDAs and various ketones. In all cases, the reactions are
highly selective and are completed within 1.0–2.5 h. The catalyst
showed excellent activity in all the cases, affording 85–97% isolated
yield of the corresponding derivatives of 1,5-benzodiazepine. The high
activity of the catalyst is mainly due to its high acidity; excellent
textural parameters such as high surface area, large pore volume and
cage type 3D porous structure.
This method is quite simple and selective. The catalyst gave high
isolated yield of the derivatives of 1,5-benzodiazepine in a shorter
reaction time at room temperature and can be recycled several times.
We strongly hope that the highly stable AlKIT-5 catalyst could pave
the way for the production of 1,5-benzodiazepine and its derivatives
and create the platform for the commercialization of the process by
replacing the existing homogenous catalysts which suffered from
various drawbacks such as corrosion, toxicity, waste production, and
a high cost.
3.4. Experimental:
General procedure for the synthesis of 1,5-benzodiazepines: A
mixture of OPDA (1) (1 mmol), ketone (2) (2.5 mmol) and AlKIT-5 (100
mg) was stirred in acetonitrile (4 ml) at room temperature until thin
layer chromatography indicated the reaction was completed. Ethyl
acetate (10%) in hexane was used as the mobile phase and both the
reactant and the final product were spotted on the TLC plate. The
product retention factor (Rf) was observed at around 0.4-0.5. The
disappearance of the reactant spot on the TLC plate indicates the
completion of the reaction. After completion of the reaction, ethyl
acetate (20 ml) was added to the reaction mixture and the catalyst was
recovered by filtration. The organic layer was concentrated and the
crude product was purified by silica gel column chromatography using
ethyl acetate-n-hexane (1:9) as eluent to afford the desired product (3).
The spectral data of entry 1, 2, 4, 5, 8 and 11,42 entry 9, 10,43 and
entry 6, 7 and 1544 in Table 3.3 are in full agreement with the
reported literature and the spectral data of all the compounds are
described in the following sections.
Entry 1: 2,2,4-Trimethyl-2,3-duhydro-1H-1,5-benzodiazepine (3a):
To a mixture of o-phenylenediamine (0.108 g, 1 mmol), acetone (0.145
g, 2.5 mmol) and AlKIT-5 (0.100 g) was stirred at room temperature
for 30 min under 4 mL of acetonitrile solvent. The completion of
reaction was monitored by TLC. After completion of the reaction, 20
ml of ethyl acetate was added to the reaction mixture and the catalyst
was recovered by filtration. The organic layer was concentrated and
the crude product was purified by silica gel column chromatography
using ethyl acetate–n-hexane (1:9) as eluent to afford the desired
product 3a as yellow solid crystals (0.182 g, 97% yield): m.p. 137-
139°C. IR (KBr): νmax 3295, 2964, 1633, 1591, 1475, 770 cm−1
(Fig.3.3). 1HNMR (300 MHz, CDCl3): δ 1.25 (s, 6H, 2CH3), 2.14 (s, 2H, -
CH2-), 2.28 (s, 3H, -CH3), 3.40 (brs, 1H, -NH), 6.65 (d, 1H, J = 8.2 Hz,
Ar-H), 6.90 (d, 2H, J = 3.2 Hz, Ar-H) 7.05 (d, 1H, J = 8.2 Hz, Ar-H)
ppm (Fig.3.4). MALDI-MS: m/z [M+] = 188 (Fig.3.5). M.F. C12H16N2.
Entry 2: 2,4-Diethyl-2-methyl -2,3-dihydro-1H-1,5-benzo
diazepine (3b): To a solution of o-phenylenediamine (0.108 g,
1 mmol), 2-butanone (0.180 g, 2.5 mmol), and AlKIT-5 (0.100 g) in 4
mL of acetonitrile was added. The resulting mixture was stirred for 60
min at room temperature. The completion of the reaction was
monitored by TLC. 20 ml of ethyl acetate was added to the reaction
mixture and the catalyst was recovered by filtration. The mixture was
extracted from ethyl acetate, washed with water, brine and dried over
magnesium sulfate. The organic layer was concentrated and the crude
product was purified by silica gel column chromatography using ethyl
acetate – n-hexane (1:9) as eluent to afford the desired benzodiazepine
3b as a yellow solid (0.205 g, 95% yield): m.p. 137–139°C. IR (KBr):
νmax 3341, 2966, 1592, 1375, 750 cm−1 (Fig.3.6). 1HNMR (300 MHz,
CDCl3): δ 0.95 (t, 3H, J = 3.5 Hz, -CH3), 0.99-1.05 (m, 6H, 2CH3), 1.58
-1.64 (m, 2H, -CH2-), 2.12-2..21 (m, 2H, -CH2-), 2.55-2.63 (m, 2H, -
CH3), 3.57 (brs, 1H), 6.70-6.74 (m, 1H, Ar-H), 6.94-7.00 (m, 2H, Ar-H),
7.09–7.15 (m, 1H, Ar-H) ppm (Fig.3.7). MALDI-MS: m/z [M+] = 216
(Fig.3.8). M.F. C14H20N2.
Entry 3: 2-methyl-2,4-dipropyl -2,3-dihydro-1H-1,5-benzo
diazepine (3c): This compound was prepared as described in general
procedure from a solution of o-phenylenediamine (0.108 g, 1mmol),
and 2-pentanone (0.215 g, 2.5 mmol) in acetonitrile (4 mL) and AlKIT-
5 (0.100 g) were added. The reaction mixture was stirred at room
temperature for 60 min. The completion of reaction was monitored by
TLC. The catalyst was filtered off and phases were separated and the
aqueous layer was extracted with EtOAc (3x15 mL). The combined
organic phase was dried over MgSO4 and concentrated. The residue
was chromatographed using silica gel, eluting with n-hexane-EtOAc
(9:1), to give the desired product 3c as a yellow solid (0.227 g, 93%
yield): m.p. 140–142°C. IR (KBr): νmax 3341, 3060, 1589, 1371, 687
cm−1 (Fig.3.9). 1HNMR (300 MHz, CDCl3): δ 0.92-0.98 (m, 6H, 2CH3),
1.13 (s, 3H, -CH3), 1.18-1.36 (m, 4H, 2CH2), 1.52-1.62 (m, 1H, -CHa),
2.10-2.20 (m, 1H, -CHb), 2.51-2.59 (m, 4H, 2CH2), 3.05 (brs, 1H, -NH),
6.70-6.73 (m, 1H, Ar-H), 6.95-6.98 (m, 2H, Ar-H), 7.12-7.14 (m, 1H,
Ar-H) ppm (Fig.3.10). MALDI-MS: m/z [M+] = 244 (Fig.3.11). Anal.
Calcd. for C16H24N2: C, 78.64; H, 9.90; N, 11.46. Found: C, 78.50; H,
9.85; N, 11.
Entry 4: 2,4-diisobutyl -2methyl- -2,3-dihydro-1H-1,5-benzo
diazepine (3d): This compound was prepared according to the gereal
procedure, from o-phenylenediamine (0.108 g, 1 mmol) and methyl
isobutyl ketone (MIBK) (0.250 g, 2.5 mmol), was dissolved in
acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction
mixture was allowed to stir at room temperature for 60 min. The
completion of the reaction was monitored by TLC. 20 ml of ethyl
acetate was added to the reaction mixture and the catalyst was
recovered by filtration. The organic layer was concentrated and the
crude product was purified by silica gel column chromatography using
ethyl acetate–n-hexane (1:9) as eluent to afford resulting
benzodiazepine 3d yellow solid (0.250 g, 92% yield): mp -145-147°C.
IR (KBr): νmax 3403, 2955, 2353, 1674, 1464, 750 cm−1 (Fig.3.12).
1HNMR (300 MHz, CDCl3): δ 0.90-1.01 (m, 12H, 4CH3), 1.32 (s, 3H, -
CH3), 1.44-1.58 (m, 2H, 2CH of MIBK), 1.71-1.73 (m, 2H,-CH2-), 2.11-
2.30 (m, 2H,-CH2-), 2.43-2.46 (m, 2H,-CH2-), 3.13 (brs, 1H, -NH),
6.67-6.70 (m, 1H, Ar-H), 6.94-6.97 (m, 2H, Ar-H), 7.11-7.15 (m, 1H,
Ar-H) ppm (Fig.3.13). MALDI-MS: m/z[M+] = 272 (Fig.3.14). M.F.
C18H28N2.
Entry 5: 2-Methyl-2,4-diphenyl -2,3-dihydro-1H -1,5-benzo
diazepine (3e): To the 4 mL of acetonitrile, o-phenylenediamine (0.108
g, 1 mmol), acetophenone (0.300 g, 2.5 mmol) and AlKIT-5 (0.100 g)
were combined in a 100 mL round-bottom flask. The reaction mixture
was stirred for 60 min at room temperature. After completion of
reaction, 20 ml of ethyl acetate was added to the reaction mixture and
the catalyst was recovered by filtration. The organic layer was
concentrated and the crude product was purified by silica gel column
chromatography using ethyl acetate– n-hexane (1:9) as eluent to afford
the desired product 3e yellow crystalline solid. (0.299 g, 96% yield):
m.p. 152–154°C. IR (KBr): νmax 3278, 2960, 1634, 1466, 749 cm−1
(Fig.3.15). 1HNMR (300 MHz, CDCl3): δ 1.31 (s, 3H, -CH3), 2.29 (d, 1H,
J = 12.8 Hz, -CHa), 2.58 (d, 1H, J = 12.8 Hz, -CHb), 3.34 (brs, 1H, -
NH), 6.68-6.78 (m, 3H, Ar-H), 7.01-7.31 (m, 4H, Ar-H), 7.42-7.46 (m,
4H, Ar-H), 7.92-8.03 (m, 3H, Ar-H) ppm (Fig.3.16). MALDI-MS: m/z
[M+] = 312 (Fig.3.17). M.F. C22H20N2.
Entry 6: 2-Methyl-2,4-ditoluyl -2,3-dihydro-1H-1,5-benzo
diazepine (3f): The title compound was prepared using o-phenylene-
diamine (0.108 g, 1 mmol), 4-methyl acetophenone (0.335 g, 2.5
mmol), catalyst AlKIT-5 (0.100 g) and 4 mL of acetonitrile were
combined in a 100mL round-bottom flask. The reaction mixture was
stirred at room temperature for 60 min. The completion of reaction
was monitored by TLC. 20 ml of ethyl acetate was added to the
reaction mixture and the catalyst was recovered by filtration. The
organic layer was concentrated and the crude product was purified by
silica gel column chromatography using ethyl acetate – n-hexane (1:9)
as eluent to give desired product 3f as a pale yellow crystalline solid
(0.326 g, 96% yield): m.p. 210-2120C. IR(KBr): νmax 3307, 2974, 1603,
1471, 759 cm−1 (Fig.3.18). 1HNMR (300 MHz, CDCl3): δ 1.32 (s, 6H, -
CH3 of 4-methyl acetophenone), 2.40 (s, 3H, -CH3), 2.71-2.72 (s, 2H, -
CH2-), 3.05 (brs, 1H, -NH), 6.76-6.80 (m, 1H, Ar-H), 6.98-7.07 (m, 3H,
Ar-H), 7.23-7.33 (m, 5H, Ar-H), 7.84-7.93 (m, 3H, Ar-H) ppm
(Fig.3.19). MALDI-MS: m/z [M+] = 340 (Fig.3.20). M.F. C24H24N2.
Entry 7: 2,4-bis(4-chlorophenyl) -2-methyl-2,3-dihydro -1H-1,5-
benzodiazepine (3g): To a mixture of o-phenylenediamine (0.108 g, 1
mmol), 4-chloroacetophenone (0.385 g, 2.5 mmol) and AlKIT-5
(0.100 g) was stirred for 60 min at room temperature under 4 mL of
acetonitrile solvent. The completion of reaction was monitored by TLC.
After completion of reaction, 20 ml of ethyl acetate was added to the
reaction mixture and the catalyst was recovered by filtration. The
organic layer was concentrated, dried over MgSO4 and the crude
product was purified by silica gel column chromatography using ethyl
acetate–n-hexane (1:9) as eluent to afford the desired product 3g as
pale yellow crystalline solid (0.361 g, 95% yield): m.p.143–145°C. IR
(KBr): νmax 3332, 2974, 1607, 1468, 762 cm−1 (Fig.3.21). 1HNMR (300
MHz, CDCl3): δ 1.73 (s, 3H, -CH3), 2.86 (d, 1H, J = 13.3 Hz, -CHa),
3.04 (d, 1H, J = 13.3 Hz, -CHb), 3.42 (brs, -NH), 6.80–6.84 (m, 1H, Ar-
H), 7.02-7.12 (m, 2H, Ar-H), 7.18-7.22 (m, 4H, Ar-H), 7.27-7.30 (m,
1H, Ar-H), 7.45-7.58 (m, 4H, Ar-H) ppm (Fig.3.22). MALDI-MS: m/z
[M+] = 380 (Fig.3.23). M.F. C22H18Cl2N2.
Entry 8: 10-Spirocyclopentane -1, 2, 3, 9, 10, 10a -hexahydro
benzo [b] cyclopenta [e][1,4]-diazepine (3h): To a solution of o-
phenylenediamine (0.108 g, 1 mool), cyclopentanone (0.210 g, 2.5
mmol) and AlKIT-5 (0.100 g) in 4 mL of acetonitrile was added. The
resulting mixture was stirred for 60 min at room temperature. The
completion of reaction was monitored by TLC. 20 ml of ethyl acetate
was added to the reaction mixture and the catalyst was recovered by
filtration. The organic layer was extracted with ethyl acetate,
concentrated and dried over magnesium sulphate. The crude product
was purified by silica gel column chromatography using ethyl acetate-
n-hexane (1:9) as eluent to yield desired benzodiazepine 3h as a yellow
solid (0.220 g, 92% yield): m.p. 138–140°C. IR (KBr) νmax 3326, 2950,
1629, 1371, 676 cm−1 (Fig.3.24). 1HNMR (300 MHz, CDCl3): δ 1.25 (s,
1H, -CH of diazepine ring), 1.66–2.65 (m, 14H, 7CH2), 2.78 (brs, 1H, -
NH), 6.64-6.94 (m, 1H, Ar-H), 7.25 (dd, J = 1.4 Hz, 7.2 Hz, 2H, Ar-H),
7.85 (d, J = 7.2 Hz, 1H, Ar-H) ppm (Fig.3.25). MALDI-MS: m/z [M+]
= 240 (Fig.3.26). M.F. C16H20N2.
Entry 9: 2-Methyl -2,4-di(thiophen-2-yl) -2,3-dihydro-1H-1,5-
benzodiazepines (3i): To a solution of o-phenylenediamine (0.108 g, 1
mmol) and 2-acetyl thiophene (0.315 g, 2.5 mmol) in acetonitrile (4
mL) and AlKIT-5 (0.100 g) were added. The reaction mixture was
stirred at room temperature for 120 min. The completion of reaction
was monitored by TLC. The catalyst was filtered off and phases were
separated and the aqueous layer was extracted with EtOAc (3x15 mL).
The combined organic phase was dried over MgSO4 and concentrated.
The residue was chromatographed using silica gel, eluting with
hexane-EtOAc (9:1), to give the desired product 3i as a brown solid
(0.278 g, 86% yield): m.p. 92–93°C. IR (KBr): νmax 3373, 3106, 1615,
1487, 760 cm−1 (Fig.3.27). 1HNMR (300 MHz, CDCl3): δ 1.60 (s,1H, -
CH2a), 2.16 (s, 1H,- CH2b), 2.33 (s, 3H, -CH3), 3.73 (brs, 1H, -NH),
6.60–6.66 (m, 2H, thiophenyl-H), 6.71–6.99 (m, 4H, thiophenyl-H),
7.08-7.12 (m, 1H, Ar-H), 7.24-7.25 (m, 1H, Ar-H), 7.43-7.48 (m, 2H,
Ar-H) ppm (Fig.3.28). MALDI-MS: m/z [M+] = 324. M.F (Fig.3.29).
C18H16N2S2.
Entry 10: 2-Methyl -2,4-di(thiophen-3-yl) -2,3-dihydro-1H -1,5-
benzodiazepine (3j): o-phenylenediamine (0.108 g, 1 mmol) and 3-
acetyl thiophene (0.315 g, 2.5 mmol) was dissolved in acetonitrile (4
mL) and AlKIT-5 (0.100 g) were added. The reaction mixture was
allowed to stir for 120 min at room temperature. The completion of
reaction was monitored by TLC. 20 ml of ethyl acetate was added to
the reaction mixture and the catalyst was recovered by filtration. The
organic layer was concentrated and the crude product was purified by
silica gel column chromatography using ethyl acetate– n-hexane (1:9)
as eluent to afford the desired product 3j light yellow solid (0.265 g,
82% yield): m.p.112-114°C. IR (KBr) νmax 3303, 2920, 1600, 1468, 763
cm−1 (Fig.3.30). 1HNMR (300 MHz, CDCl3): δ 1.65 (s, 1H, -CHa), 1.74 (s,
1H, -CHb), 2.54 (s, 3H, -CH3), 3.46 (brs, 1H, -NH), 6.78-7.25 (m, 6H,
thiophenyl-H), 7.26-8.04 (m, 4H, Ar-H) ppm (Fig.3.31). MALDI-MS:
m/z [M+] = 324 (Fig.3.32). M.F. C18H16N2S2.
Entry 11: 2,2,4-Trimethyl -2,3-dihydro-7-chloro-1H-1,5-benzo
diazepine (3k): To a mixture of 4-chloro-1,2-phenylenediamine (0.142
g, 1 mmol), acetone (0.145 g, 2.5 mmol) and AlKIT-5 (0.100 g) was
stirred at room temperature for 60 min under 4 mL of acetonitrile
solvent. The completion of reaction was monitored bt TLC. After
completion of the reaction, 20 ml of ethyl acetate was added to the
reaction mixture and the catalyst was recovered by filtration. The
mixture was extracted from ethyl acetate, washed with water, brine
and dried over magnesium sulfate. The organic layer was concentrated
and the crude product was purified by silica gel column
chromatography using ethyl acetate–n-hexane (1:9) as eluent to afford
the desired product 3k as a yellow solid (0.209 g, 94%): m.p. 92-94°C.
IR (KBr): νmax 3282, 2962, 1630, 1453, 750 cm−1 (Fig.3.33). 1HNMR
(300 MHz, CDCl3): δ 1.33 (m, 6H, 2CH3), 2.22 (t, 2H, -CH2-), 2.34 (s,
3H, -CH3), 3.01 (brs, 1H, -NH), 6.63-6.72 (m, 1H,Ar-H), 6.90-6.95 (m,
1H, Ar-H), 7.03-7.12 (m, 1H, Ar-H) ppm (Fig.3.35). MALDI-MS: m/z
[M+] = 222 (Fig.3.36). M.F. C12H15ClN2.
Entry 12: 7-chloro -2,4-diethyl- 2-methyl -2,3-dihydro-1H-1,5-
diazepine (3l): This compound was prepared as described in general
procedure from a solution of 4-chloro-1,2-phenylenediamine (0.142 g,
1 mmol), 2-butanone (0.180 g, 2.5 mmol) and AlKIT-5 (0.100 g) in 4
mL of acetonitrile was added. The resulting mixture was stirred for 60
min at room temperature. The completion of reaction was monitored
by TLC. 20 ml of ethyl acetate was added to the reaction mixture and
the catalyst was recovered by filtration. The organic layer was
concentrated and the crude product was purified by silica gel column
chromatography using ethyl acetate– n-hexane (1:9) as eluent to afford
the desired product 3l as a yellow solid (0.230 g, 92% yield): m.p. 94-
96°C. IR (KBr): νmax 3424, 2971, 1596, 1499, 798 cm-1 (Fig.3.36).
1HNMR (300 MHz, CDCl3): δ 0.93 (t, J = 6.7 Hz, 3H, -CH3), 1.24-1.25
(m, 6H, 2CH3), 1.60-1.65 (m, 2H, -CH2-), 2.22 (m, 2H, -CH2-), 2.59 (q,
2H, J = 3.2 Hz, -CH2-), 3.10 (brs,1H, -NH), 6.62–6.71 (m, 1H, Ar-H),
6.88-6.93 (m, 1H, Ar-H), 7.04-7.14 (m, 1H, Ar-H) ppm (Fig.3.37).
MALDI-MS: m/z [M+] = 250 (Fig.3.38). Anal. Calcd. for C14H19ClN2: C,
67.05; H, 7.64; N, 11.17. Found: C, 67.00; H, 7.54; N, 11.10.
Entry 13: 7-chloro-2-methyl -2,4-dipropyl -2,3-dihydro-1H-1,5-
benzodiazepine (3m): To a solution of 4-choloro-1,2-phenylene
diamine (0.142 g, 1 mmol) and 2-pentanone (0.215 g, 2.5 mmol) in
acetonitrile (4 mL) and AlKIT-5 (0.100 g) were added. The reaction
mixture was stirred at room temperature for 120 min. The completion
of reaction was monitored by TLC. The catalyst was filtered off and
phases were separated and the aqueous layer was extracted with
EtOAc (3X15 mL). The combined organic phase was dried over MgSO4
and concentrated. The residue was chromatographed using silica gel,
eluting with hexane-EtOAc (9:1), to give the desired product 3m as a
reddish yellow solid (0.244 g, 88% yield): m.p. 160-162°C. IR (KBr):
νmax 3338, 2959, 1638, 1468, 806 cm-1 (Fig.3.39). 1HNMR (300 MHz,
CDCl3): δ 0.82-0.92 (m, 6H, 2CH3), 1.15 (s, 3H, -CH3), 1.23-1.49 (m,
4H, 2CH2), 1.58-1.68 (m, 2H, -CH2-), 2.02-2.10 (m, 2H, -CH2-), 2.39-
2.45 (m, 2H, -CH2-), 3.10 (brs, 1H, -NH), 6.51–6.60 (m, 1H, Ar-H),
6.77-6.82 (m, 1H, Ar-H), 6.93-7.02 (m, 1H, Ar-H) ppm (Fig.3.40).
MALDI-MS: m/z [M+ ] = 278 (Fig.3.41). Anal. Calcd. for C16H23ClN2:
C, 68.92; H, 8.31; N, 10.05. Found: C, 68.83; H, 8.21; N,10.00.
Entry 14: 7-chloro-2,4-diisobutyl -2-methyl -2,3-dihydro-1H-1,5-
benzodiazepine (3n): This compound was prepared according to the
general procedure, 4-chloro-1,2-phenylenediamine (0.142 g, 1 mmol)
and methyl isobutyl ketone (0.250 g, 2.5 mmol) was dissolved in
acetonitrile (4 mL) and AlKIT-5 (0.100 g) were added. The reaction
mixture was allowed to stir at room temperature for 120 min. The
completion of reaction was monitored by TLC. 20 ml of ethyl acetate
was added to the reaction mixture and the catalyst was recovered by
filtration. The mixture was extracted from ethyl acetate, washed with
water, brine and dried over magnesium sulfate. The organic layer was
concentrated and the crude product was purified by silica gel column
chromatography using ethyl acetate– n-hexane (1:9) as eluent to afford
the desired product 3n as light yellow solid (0.269 g, 88% yield):
m.p.140-142°C. IR (KBr): νmax 3196, 2959, 1589, 1496, 817 cm-1.
(Fig.3.42). 1HNMR (300 MHz, CDCl3): δ 0.98-1.02 (m, 12H, 4CH3), 1.25
(m, 2H, 2CH), 1.32 (s, 3H, -CH3), 1.70-1.73 (m, 2H, -CH2-), 2.15-2.20
(m, 2H, -CH2-), 2.38-2.42 (m, 2H, -CH2-), 3.50 (brs, 1H, -NH), 6.60–
6.67 (m, 1H, Ar-H), 6.86-6.94 (m, 1H, Ar-H), 7.04-7.13 (m, 1H, Ar-H)
ppm (Fig.3.43). MALDI-MS: m/z [M+] = 306 (Fig.3.44). Anal. Calcd. for
C18H27ClN2: C, 70.45; H, 8.87; N, 9.13. Found: C, 70.35; H, 8.76; N,
9.09.
Entry 15: 7-chloro-2-methyl -2,4-diphenyl-2,3-dihydro-1H-1,5-
benzodiazepine (3o): To the 4 mL of acetonitrile, 4-chloro-1,2-
phenylenediamine (0.142 g, 1 mmol), acetophenone (0.300 g, 2.5
mmol) and AlKIT-5 (0.100 g) were combined in a 100mL round-bottom
flask. The reaction was stirred at room temperature for 120 min. After
completion of reaction, 20 ml of ethylacetate was added to the reaction
mixture and the catalyst was recovered by fitration. The organic layer
was concentrated and the crude product was purified by silica gel
column chromatography using ethyl acetate – n-hexane (1:9) as eluent
to afford the desired product 3o yellow solid. (0.318 g, 92% yield):
m.p. 121–123°C. IR (KBr): νmax 3352, 3066, 1584, 1457, 835 cm-1
(Fig.3.45). 1HNMR (300 MHz, CDCl3): δ 1.76 (s, 3H, -CH3), 2.93-2.99
(d, 1H, J = 12.8 Hz, -CHa), 3.10-3.18 (d, 1H, J = 12.8 Hz, -CHb), 3.59
(brs, 1H, -NH), 6.83–6.84 (m, 1H, Ar-H), 6.96–7.04 (m, 1H, Ar-H),
7.16-7.33 (m, 8H, Ar-H), 7.53-7.59 (m, 4H, Ar-H) ppm (Fig.3.46).
MALDI-MS: m/z [M+]=346 (Fig.3.47). M.F. C22H19ClN2.
Entry 16: 7-chloro-2methyl -2,4-dip-toluyl -2,3-dihydro-1H-1,5-
benzodiazepine (3p): The title compound was prepared using 4-
chloro-1,2-phenylenediamine (0.142 g, 1 mmol), 4-methylaceto-
phenone (0.335 g, 2.5 mmol), catalyst AlKIT-5 (0.100 g) and 4 mL of
acetonitrile were combined in 100 mL round-bottom flask. The
reaction mixture was stirred at room temperature for 120 min. The
completion of reaction was monitored by TLC. 20 ml of ethyl acetate
was added to the reaction mixture and the catalyst was recovered by
filtration. The organic layer was concentrated and the crude product
was purified by silica gel column chromatography using ethyl acetate
– n-hexane (1:9) as eluent to afford the desired product 3p as a pale
yellow solid (0.336 g, 90% yield): m.p. 138-140°C, IR(KBr): νmax 3318,
2955, 1604, 1444, 817 cm-1 (Fig.3.48). 1HNMR (300 MHz, CDCl3): δ
1.72 (s, 3H, -CH3), 2.17 (s, 2H, -CH2-), 2.33 (s, 6H, 2CH3 of 4-methyl
acetophenone), 3.00 (brs, 1H, -NH), 6.80–6.81 (m, 1H, Ar-H), 7.06-
7.10 (m, 5H, Ar-H), 7.42-7.53 (m, 5H, Ar-H) ppm (Fig.3.49). MALDI-
MS: m/z [M+] = 374 (Fig.3.50). Anal. Calcd. for C24H23ClN2: C, 76.89;
H, 6.18; N, 7.47. Found: C, 76.79; H,6.08; N, 7.37.
Entry 17: 7-chloro-2,4-bis(4-chlorophenyl)-2-methyl -2,3-dihydro-
1H-1,5-benzodiazepine (3q): To a mixture of 4-chloro-1,2-phenylene
diamine (0.142 g, 1 mmol), 4-chloro acetophenone (0.385 g, 2.5 mmol)
and AlKIT-5 (0.100 g) was stirred for 120 min at room temperature
under 4 mL of acetonitrile solvent. The completion of reaction was
monitored by TLC. After completion of reaction, 20 ml of ethyl acetate
was added to the reaction mixture and the catalyst was recovered by
filtration. The organic layer was concentrated and the crude product
was purified by silica gel column chromatography using ethyl acetate
– n-hexane (1:9) as eluent to afford the desired product 3q as a yellow
solid (0.356 g, 86% yield): m.p. 145-147°C, IR (KBr): νmax 3265, 2967,
1588, 1475, 829 cm-1 (Fig.3.51). 1HNMR (300 MHz, CDCl3): δ 1.75 (s,
3H, -CH3), 2.86 (d, 1H, J = 12.8 Hz, -CH2-), 3.14 (d, 1H, J = 12.8 Hz, -
CH2-), 3.50 (brs, 1H, -NH), 6.74–6.84 (m, 1H, Ar-H), 6.98-7.06 (m,
1H, Ar-H), 7.19-7.29 (m, 4H, Ar-H), 7.42-7.52 (m, 5H, Ar-H) ppm
(Fig.3.52). MALDI-MS: m/z [M+] = 415 (Fig.3.53). Anal. Calcd. for
C22H17Cl3N2: C. 63.56; H, 4.12; N, 6.74. Found: C, 63.46; H, 4.06; N,
6.64.
Entry 18: 7-chloro-10-Spirocyclopentane -1, 2, 3, 9, 10, 10a
pentahydrobenzo [b] cyclopenta [e] [1,4]-diazepine (3r): To a
solution of 4-chloro-1,2-phenylenediamine (0.142 g, 1mmol),
cyclopentanone (0.210 g, 2.5 mmol), and AlKIT-5 (0.100 g) in 4 mL of
acetonitrile was added. The resulting mixture was stirred for 120 min
at room temperature. The completion of reaction was monitored by
TLC. 20 ml of ethyl acetate was added to the reaction mixture and the
catalyst was recovered by filtration. The organic layer was
concentrated and the crude product was purified by silica gel column
chromatography using ethyl acetate – n-hexane (1:9) as eluent to
afford the desired product 3r as a yellow solid (0.235 g, 86% yield):
m.p. 156-158°C. IR (KBr): νmax 3342, 2959, 1650, 1499, 837 cm-1
(Fig.3.54). 1HNMR (300 MHz, CDCl3): δ 1.88-2.10 (m, 12H, 6CH2),
2.90-2.95 (d, J = 13.2 Hz, 1H, -CH), 3.90-4.25 (m, 2H, -CH2-), 3.05
(brs, 1H, -NH), 6.63–6.64 (m, 1H, Ar-H), 6.73-6.77 (m, 1H, Ar-H),
7.87-7.90 (m, 1H, Ar-H) ppm (Fig.3.55). MALDI-MS: m/z [M+] = 274
(Fig.3.56). Anal. Calcd. for C16H19ClN2: C, 69.93; H, 6.97; N, 10.19.
Found: C, 69.83; H, 6.87; N, 10.09.
Entry 19: 7-chloro -2-methyl -2,4-di(thiophen-2-yl) -2,3-dihydro-
1H-1,5-benzodiazepine (3s): To a solution of 4-chloro-1,2-
phenylenediamine (0.142 g, 1 mmol) and 2-acetyl thiophene (0.315 g,
2.5 mmol) in acetonitrile (4 mL) and AlKIT-5(0.100 g) were added. The
reaction mixture was stirred at room temperature for 150 min. The
completion of reaction was monitored by TLC. The catalyst was filtered
off and phases were separated and the aqueous layer was extracted
with EtOAc (3X15 mL). The combined organic phase was dried over
MgSO4 and concentrated. The residue was chromatographed using
silica gel, eluting with n-hexane–EtOAc (9:1), to give the desired
product 3s as a yellow solid (0.304 g, 85% yield): m.p. 130-132°C, IR
(KBr): νmax 3303, 2967, 1577, 1471, 705 cm-1 (Fig.3.57). 1HNMR (300
MHz, CDCl3): δ 1.83 (s, 3H, -CH3), 2.99 (d, 1H, J = 13.2 Hz, -CH2-),
3.08 (d, 1H, J = 13.2 Hz, -CH2-), 3.58 (brs, 1H, -NH), 6.79–6.82 (m,
1H, Ar-H), 6.90-6.93 (m, 2H, Ar-H), 7.01-7.10 (m, 4H, Ar-H), 7.30-
7.40 (m, 1H, Ar-H), 7.63-7.69 (m, 1H, Ar-H) ppm (Fig.3.58). MALDI-
MS: m/z [M+] = 358 (Fig.3.59). Anal. Calcd. for C18H15ClN2S2: C, 60.24;
H, 4.21; N, 7.81. Found: C, 60.14; H, 4.15; N, 7.71.
Entry 20: 7-chloro-2-methyl -2,4-di(thiophen-3-yl) -2,3-dihydro-
1H-1,5-benzodiazepine (3t): 4-chloro-1,2-phenylenediamine (0.142 g,
1 mmol) and 3-acetyl thiophene (0.315 g, 2.5 mmol) was dissolved in
acetonitrile (4 mL) and AlKIT-5 (0.100 g) were added. The reaction
mixture was allowed to stir for 150 min at ambient temperature. The
completion of reaction was monitored by TLC. 20 ml of ethyl acetate
was added to the reaction mixture and the catalyst was recovered by
filtration. The organic layer was concentrated and the crude product
was purified by silica gel column chromatography using ethyl acetate
– n-hexane (1:9) as eluent to afford the desired benzodiazepine 3t as
light yellow crystalline solid (0.304 g, 85% yield): m.p.120-122°C, IR
(KBr): νmax 3394, 2962, 1592, 1469, 781 cm-1 (Fig.3.60). 1HNMR (300
MHz, CDCl3): δ 1.73 (s, 3H, -CH3), 2.86 (d, 1H, J = 13.2 Hz, CH2), 2.93
(d, 1H, J = 13.2 Hz, -CH2-), 3.43 (brs, 1H, -NH), 6.70 – 6.79 (m, 1H,
Ar-H), 6.99-7.01 (m, 2H, Ar-H), 7.10-7.17 (m, 1H, Ar-H), 7.20-7.30 (m,
5H, Ar-H) ppm (Fig.3.61). MALDI-MS: m/z [M+] = 358 (Fig.3.62). Anal.
Calcd. for C18H15ClN2S2: C, 60.24; H, 4.21; N, 7.81. Found: C, 60.14;
H, 4.15; N, 7.71.
Fig: 3.1. 1H NMR spectrum of o-phenylenediamine
Fig: 3.2. 1H NMR spectrum of 4-Chloro-1,2-phenylenediamine
Fig: 3.3. IR spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5-
benzodiazepine (3a)
Fig: 3.4. 1H NMR spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5-
benzodiazepine (3a)
Fig: 3.5. Mass spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5-
benzodiazepine (3a) (MW=188)
Fig: 3.6. IR spectrum of 2,4-Diethyl-2-methyl-2,3-dihydro-1H-1,5-
benzodiazepine (3b)
Fig: 3.7. 1H NMR spectrum of 2,4-diethyl-2-methyl-2,3-dihydro-1H-1,5-benzodiazepine (3b)
Fig: 3.8. Mass spectrum of 2,4-Diethyl-2-methyl-2,3-dihydro-1H-1,5-benzodiazepine (3b) (MW=216)
Fig: 3.9. IR spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H-1,5-
benzodiazepine (3c)
Fig: 3.10. 1H NMR spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H-
1,5-benzodiazepine (3c)
Fig: 3.11. Mass spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H-
1,5-benzodiazepine (3c) (MW=244)
Fig: 3.12. IR spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro-1H-1,5-
benzodiazepine (3d)
Fig: 3.13. 1H NMR spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro-
1H-1,5-benzodiazepine (3d)
Fig: 3.14. Mass spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro -1H-
1,5-benzodiazepine (3d) (MW=272)
Fig: 3.15. IR spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H-1,5-
benzodiazepine (3e)
Fig: 3.16. 1H NMR spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H-
1,5-benzodiazepine (3e)
Fig: 3.17. Mass spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H-
1,5-benzodiazepine (3e) (MW=312)
Fig: 3.18. IR spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H-1,5-
benzodiazepine (3f)
Fig: 3.19. 1H NMR spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H-
1,5-benzodiazepine (3f)
Fig: 3.20. Mass spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H-1,5-
benzodiazepine (3f) (MW=340)
Fig: 3.21. IR spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3g)
Fig: 3.22. 1H NMR spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3g)
Fig: 3.23. Mass spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3g) (MW=380)
Fig: 3.24. IR spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10, 10a-
hexahydrobenzo[b] cyclopenta [e][1,4]-diazepine (3h)
Fig: 3.25. 1H NMR spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10,
10a-hexahydrobenzo[b]cyclopenta[e][1,4]-diazepine (3h)
Fig: 3.26. Mass spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10, 10a-
hexahydrobenzo[b]cyclopenta[e][1,4]-diazepine(3h)(MW=240)
Fig: 3.27. IR spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3-dihydro-
1H-1,5-benzodiazepine (3i)
Fig: 3.28. 1H NMR spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3i)
Fig: 3.29. Mass spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3i) (MW=324(2T))
Fig: 3.30. IR spectrum of 2-methyl-2,4-di(thiophen-3-yl)-2,3-dihydro-
1H-1,5-benzodiazepine (3j)
Fig: 3.31. 1H NMR spectrum of 2-Methyl-2,4-di(thiophen-3-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3j)
Fig: 3.32. Mass spectrum of 2-Methyl-2,4-di(thiophen-3-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3j) (MW=324(3T))
Fig: 3.33. IR spectrum of 2,2,4-Trimethyl-2,3-dihydro-7-chloro-1H-
1,5-benzodiazepine (3k)
Fig: 3.34. 1H NMR spectrum of 2, 2, 4-Trimethyl-2,3-dihydro-7-chloro-
1H-1,5-benzodiazepine (3k)
Fig: 3.35. Mass spectrum of 2,2,4-Trimethyl-2,3-dihydro-7-chloro-1H-
1,5-benzodiazepine (3k) (MW=222)
Fig: 3.36. IR spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3-dihydro-
1H-1,5-benzodiazepine (3l)
Fig: 3.37. 1H NMR spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3-dihydro-1H-1,5-benzodiazepine (3l)
Fig: 3.38. Mass spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3l) (MW=250)
Fig: 3.39. IR spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3-dihydro-
1H-1,5-benzodiazepine (3m)
Fig: 3.40. 1H NMR spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3-
dihydro-1H-1,5-benzodiazepine (3m)
Fig: 3.41. Mass spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3-
dihydro-1H-1,5-benzodiazepine (3m) (MW=278)
Fig: 3.42. IR spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3n)
Fig: 3.43. 1H NMR spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3n)
Fig: 3.44. Mass spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3-
dihydro-1H-1,5-benzodiazepine (3n) (MW=306)
Fig: 3.45. IR spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3-dihydro-
1H-1,5-benzodiazepine (3o)
Fig: 3.46. 1H NMR spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3-
dihydro-1H-1,5-benzodiazepine (3o)
Fig: 3.47. Mass spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3-
dihydro-1H-1,5-benzodiazepine (3o) (MW=346)
Fig: 3.48. IR spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3-dihydro-
1H-1,5-benzodiazepine (3p)
Fig: 3.49. 1H NMR spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3-
dihydro-1H-1,5-benzodiazepine (3p)
Fig: 3.50. Mass spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3-
dihydro-1H-1,5-benzodiazepine (3p) (MW=374)
Fig: 3.51. IR spectrum of 7-chloro-2,4-bis (4-chlorophenyl)-2-methyl-
2,3-dihydro-1H-1,5-benzodiazepine (3q)
Fig: 3.52.1H NMR spectrum of 7-chloro-2,4-bis(4-chlorophenyl)-2-
methyl-2,3-dihydro-1H-1,5-benzodiazepine (3q)
Fig: 3.53. Mass spectrum of 7-chloro-2,4-bis(4-chlorophenyl)-2-
methyl-2,3-dihydro-1H-1,5-benzodiazepine(3q) (MW=415)
Fig: 3.54. IR spectrum of 7-chloro-10-Spirocyclopentane -1, 2, 3, 9,
10, 10a -pentahydrobenzo [b] cyclopenta [e] [1,4]-diazepine (3r)
Fig: 3.55. 1H NMR spectrum of 7-chloro-10-Spirocyclopentane-1, 2, 3,
9, 10, 10a -pentahydrobenzo [b] cyclopenta [e] [1,4]-diazepine (3r)
Fig: 3.56. Mass spectrum of 7-chloro-10-Spirocyclopentane -1, 2, 3, 9,
10,10a-pentahydrobenzo[b] cyclopenta [e] [1,4]-diazepine (3r) (MW=274)
Fig: 3.57. IR spectrum of 7-chloro-2-methyl-2,4-di(thiophen-2-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3s)
Fig: 3.58. 1H NMR spectrum of 7-chloro-2-methyl-2,4-di(thiophen-2-
yl)-2,3-dihydro-1H-1,5-benzodiazepine (3s)
Fig: 3.59. Mass spectrum of 7-chloro-2-methyl-2,4-di(thiophen-2-yl)-2,3-dihydro-1H-1,5-benzodiazepine(3s) (MW=358(2T))
Fig: 3.60. IR spectrum of 7-chloro-2-methyl-2,4-di(thiophen-3-yl)-2,3-
dihydro-1H-1,5-benzodiazepine (3t)
Fig: 3.61. 1H NMR spectrum of 7-chloro-2-methyl-2,4-di(thiophen-3-
yl)-2,3-dihydro-1H-1,5-benzodiazepine (3t)
Fig: 3.62. Mass spectrum of 7-chloro-2-methyl-2,4-di(thiophen-3-yl)-
2,3-dihydro-1H-1,5-benzodiazepine (3t) (MW=358 (3T))
References:
1. De Baun, J.R.; Pallos, F.M.; Baker, D.R. “5-Furoyl-2,2,4-
trimethyl-1,4-dihydro-1H-1,5-benzodiazepine as an anti-
inflammatory agent” US Patent 3,978,227, 1976.
2. De Baun, J.R.; Pallos, F.M.; Baker, D.R. Chem. Abstr. 86, 1977,
5498d.
3. Schultz, H. Benzodiazepines, Springer, Heidelberg. Vol.1,1982.
4. Smiley, R.K. Comprehensive Organic Chemistry, Pergamon,
Oxford 1979.
5. Landquist, J.K. Comprehensive Heterocyclic Chemistry, vol. 1,
Pergamon, Oxford, 1984, pp. 166, 170.
6. Randall, L.O.; Kappel, B. In: Garattini, S.; Mussini, E. (Eds.),
Benzodiazepines, Raven Press, New York, 1973, p. 27.
7. Haris, R.C.; Straley, J.M. U.S. Patent 1,537,757, 1968.
8. El-Sayed, A.M.; Abdel-Ghany, H.; El-Saghier, A.M.M. “A Novel
Synthesis of Pyrano(2,3-c)-, 1,3-Oxazino(2,3-b)-,1,2,4-
Triazolo(3,4-b)-, Oxazolo(2,3-b)-, Furano(3,2-c)-, and 3-
Substituted-(1,5) benzodiazepin -2-ones” Synth. Commun. 29,
1999, 3561-3572.
9. Xu, J.X.; Wu, H.T.; Jin, S. Chin. J. Chem. 17, 1999, 84-91.
10. Zhang, X.Y.; Xu, J.X.; Jin, S. Chin. J. Chem. 17, 1999, 404-410.
11. Kim, K.; Volkman, S.K.; Ellman, J.A. “Synthesis of 3-Substituted
1,4-Benzodiazepin-2-ones” J. Braz. Chem. Soc. 9, 1998, 375-380.
12. Reid, W.; Torinus, E. “Chemical Reports: About seven-heterocyclic
ring systems, X. Synthesis of condensed 5 -, 7 - and 8-membered
heterocyclic compounds with nitrogen atoms 2” Chem. Ber. 92,
1959, 2902-2916.
13. Herbert, J.A.L.; Suschitzky, L.H. “Syntheses of heterocyclic
compounds. Part XXIX. Substituted 2,3-dihydro-1H-1,5-
benzodiazepines” J. Chem. Soc. Perkin Trans. 1, 1974, 2657-
2661.
14. Morales, H.R.; Bulbarela, A.; Contreras, R. “New Synthesis of
Dihydro- and Tetrahydro-1,5-benzodiazepines by Reductive
Condensation of o-Phenylenediamine and Ketones in the Presence
of Sodium Borohydride” Heterocycles 24, 1986, 135-139.
15. Jung, D.I.; Choi, T.W.; Kim, Y.Y.; Kim, I.S.; Park, Y.M.; Lee, Y.G.;
Jung, D.H. “Synthesis Of 1,5-Benzodiazepine Derivatives ” Synth.
Commun. 29, 1999, 1941-1951.
16. Balakrishna, M.S.; Kaboudin, B. “A simple and new method for
the synthesis of 1,5-benzodiazepine derivatives on a solid surface”
Tetrahedron Lett. 42, 2001, 1127-1129.
17. Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. “Ytterbium
triflate promoted synthesis of 1,5-benzodiazepine derivatives”
Tetrahedron Lett. 42, 2001, 3193-3195.
18. Pan, X.Q.; Zou, J.P.; Hauang, Z.H.; Zhang, W. “Ga(OTf)3-
promoted condensation reactions for 1,5-benzodiazepines and
1,5-benzothiazepines” Tetrahedron Lett. 49, 2008, 5302-5308.
19. Kumar, R.; Chaudhary, P.; Nimesh, S.; Verma, A.K.; Chandra, R.
“An efficient synthesis of 1,5-benzadiazepine derivatives catalyzed
by silver nitrate” Green Chem. 8, 2006, 519-521.
20. Sivamurugan, V.; Deepa, K.; Palanichamy, M.; Murugesan, V.
“[(L)Proline]2Zn Catalysed Synthesis of 1,5-Benzodiazepine
Derivatives Under Solvent-Free Condition” Synth. Commun. 34,
2004, 3833-3846.
21. Minothora, P.; Julia, S.S.; Constantinos, A.T. “An efficient method
for the synthesis of 1,5-benzodiazepine derivatives under
microwave irradiation without solvent” Tetrahedron Lett. 43,
2002, 1755-1758.
22. Chen, W.Y.; Lu, J. “Molecular-Iodine-Catalyzed One-Pot Synthesis
of 1,5-Benzodiazepine Derivatives under Solvent-Free Conditions”
Synlett 2005, 1337-1339.
23. Jarikote, D.V.; Siddiqui, S.A.; Rajagopal, R.; Thomas, D.;
Lahotiands, R.J.; Srinivasan, K.V. “Room temperature ionic liquid
promoted synthesis of 1,5-benzodiazepine derivatives under
ambient conditions” Tetrahedron Lett. 44, 2003, 1835-1838.
24. Reddy, B.M.; Sreekanth, P.M.; Reddy, V.R. “Modified zirconia
solid acid catalysts for organic synthesis and transformations” J.
Mol. Catal. A: Chem. 225, 2005, 71-78.
25. Kaboudin, B.; Navaee, K. “Alumina/Phosphorus Pentoxide (APP)
as an Efficient Reagent for the Synthesis of 1,5-Benzodiazepines
under Microwave Irradiation” Heterocycles 55, 2001, 1443-1446.
26. Yadav, J.S.; Reddy, B.V.S.; Praveen kumar, S.; Nagaiah, K.;
Lingaiah, N.; Saiprasad, P.S. “Ag3PW12O40: A Novel and Recyclable
Heteropoly Acid for the Synthesis of 1,5-Benzodiazepines under
Solvent-Free Conditions” Synthesis 2004, 901-904.
27. Chari, M.A.; Syamasundar, K. “Polymer (PVP) supported ferric
chloride: an efficient and recyclable heterogeneous catalyst for
high yield synthesis of 1,5-benzodiazepinederivatives under
solvent free conditions and microwave irradiation” Catal.
Commun. 6, 2005, 67-70.
28. Hegedu, A.; Hell, Z.; Potor, A. “A Simple Environmentally-friendly
Method for the Selective Synthesis of 1,5-benzodiazepine
Derivatives using Zeolite Catalyst” Catal. Lett. 105, 2005, 229-
232.
29. Kresge, C.T.; Leonowicz, M.E.; Roth, W.J.; Vartuli, J.C.; Beck,
J.S. “Ordered mesoporous molecular sieves synthesized by a
liquid-crystal template mechanism” Nature 359, 1992, 710-712.
30. Corma, A. “From Microporous to Mesoporous Molecular Sieve
Materials and Their Use in Catalysis” Chem. Rev. 97, 1997, 2373-
2420.
31. Hartmann, M.; Vinu, A. “Mechanical Stability and Porosity
Analysis of Large-Pore SBA-15 Mesoporous Molecular Sieves by
Mercury Porosimetry and Organics Adsorption” Langmuir 18,
2002, 8010-8016.
32. Vinu, A.; Hossain, K.Z.; Kumar, G.S.; Ariga, K. “Adsorption of L-
histidine over mesoporous carbon molecular sieves” Carbon 44,
2006, 530-537.
33. Vinu, A.; Devassy, B.M.; Halligudi, S.B.; Bohlmann, W.;
Hartmann, M. “Highly active and selective AlSBA-15 catalysts for
the vapor phase tert-butylation of phenol” Appl. Catal. A: Gen.
281, 2005, 207-213.
34. Kleitz, F.; Liu, D.; Anilkumar, G.M.; Park, I.-S.; Solovyov, L.A.;
Shmakov, A.N.; Ryoo, R. “Large Cage Face-Centered-Cubic Fm3m
Mesoporous Silica: Synthesis and Structure” J. Phys. Chem. B
107, 2003, 14296-14300.
35. Vinu, A.; Murugesan, V.; Hartmann, M. “Adsorption of Lysozyme
over Mesoporous Molecular Sieves MCM-41 and SBA-15:
Influence of pH and Aluminum Incorporation” J. Phys. Chem. B
108, 2004, 7323-7330.
36. Vinu, A.; Krithiga, T.; Murugesan, V.; Hartmann, M. “Direct
Synthesis of Novel FeSBA-1 Cubic Mesoporous Catalyst and Its
High Activity in the tert-Butylation of Phenol” Adv. Mater. 16,
2004, 1817-1821.
37. Srinivasu, P.; Alam, S.; Balasubramanian, V.V.; Velmathi, S.;
Sawant, D.P.; Bohlmann, W.; Mirajkar, S.P.; Ariga, K.; Halligudi,
S.B.; Vinu, A. “Novel Three Dimensional Cubic Fm3m Mesoporous
Aluminosilicates with Tailored Cage Type Pore structure and High
Aluminium Content” Adv. Funct. Mater. 18, 2008, 640-651.
38. Balasubramanian, V.V.; Srinivasu, P.; Anand, C.; Pal, R.R.; Ariga,
K.; Velmathi, S.; Alam, S.; Vinu, A. “Highly active three-
dimensional cage type mesoporous aluminosilicates and their
catalytic performances in the acetylation of aromatics” Micropor.
Mesopor. Mater. 114, 2008, 303-311.
39. Shobha, D.; Adharvana Chari, M.; Mukkanti, K.; Ahn, K.H. “Silica
gel-supported Sulfuric acid catalyzed synthesis of 1,5-benzo-
diazepine derivatives” J.Heterocyclic Chem. 46, 2009, 1028-1033.
40. Shobha, D.; Chari, M.A.; Selvan, S.T.; Oveisi, H.; Mano, A.;
Mukkanti, K.; Vinu, A. “Room temperature synthesis of 1,5-
benzodiazepine and its derivatives using cage type mesoporous
aluminosilicate catalysts” Micropor. Mesopor. Mater. 129, 2010,
112-117.
41. Zhang, W.; Liu, R.; Huang, Q.; Zhang, P.; Koehler, K.F.; Harris,
B.; Skolnick, P.; Cook, J.M. “Syntheses of 5-thienyl and 5-furyl-
substituted benzodiazepines: probes of the pharmacophore for
benzodiazepine receptor agonists” Eur. J. Med. Chem. 30, 1995,
483-496.
42. Kiran, N.S.; Rajesh, K.; Prabhakar, P.; Paul Selvam, J.J.;
Venkateswarlu, Y. “A mild and efficient synthesis of benzo-
diazepines using La(NO3)3.6H2O as acatalyst under solvent-free
conditions” Catal. Commun. 8, 2007, 1635-1640.
43. Kuo, C.-W.; More, V.S.; Yao, C.-F. “NBS as an efficient catalyst for
the synthesis of 1,5-benzodiazepine derivatives under mild
conditions” Tetrahedron Lett. 47, 2006, 8523-8528.
44. Varala, R.; Enugala, R.; Adapa, R.S. “p-Nitrobenzoic Acid
Promoted Synthesis of 1,5-Benzodiazepine Derivatives” J. Brazil
Chem. Soc. 18, 2007, 291-296.