Amorphous mesoporous iron aluminophosphate catalyst for the synthesis of 1,5-benzodiazepines

Article abstract of DOI:10.1016/S1872-2067(10)60120-9

A simple and versatile method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones in the presence of solvents and under solvent-free conditions that used an amorphous mesoporous iron aluminophosphate as catalyst was developed. Hig

Full text of DOI:10.1016/S1872-2067(10)60120-9

CHINESE JOURNAL OF CATALYSIS
Volume 31, Issue 11, 2010
Online English edition of the Chinese language journal
RESEARCH PAPER
Cite this article as: Chin J Catal, 2010, 31: 1321–1327.
Amorphous Mesoporous Iron Aluminophosphate Catalyst
for the Synthesis of 1,5-Benzodiazepines
A. V. VIJAYASANKAR1, S. DEEPA1, B. R. VENUGOPAL2, N. NAGARAJU1,*
1Department of Chemistry, Catalysis Research Laboratory, St. Joseph’s College Research Centre, Shanthi Nagar, Bangalore 560027, India
2Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Abstract: A simple and versatile method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones in the presence of
solvents and under solvent-free conditions that used an amorphous mesoporous iron aluminophosphate as catalyst was developed. High
yields with excellent selectivity were obtained with a wide variety of ketones under mild reaction conditions. The catalyst had the advan-
tages of ease of preparation, ease of handling, simple recovery, reusability, non toxicity, and being inexpensive.
Key words: benzodiazepine; amorphous metal aluminophosphate; mesoporous iron aluminophosphate; o-phenylenediamine; ketone;
solvent free synthesis
Benzodiazepines and their derivatives have broad and im-
portant pharmacological properties [1–4]. They are widely
used as anticonvulsant, analgesic, hypnotic, sedative, and
antidepressive agents. In addition, 1,5-benzodiazepines are key
intermediates for the synthesis of various fused ring benzodi-
azepines derivatives [5–7]. Due to their wide biological, in-
dustrial, and synthetic applications [8–10], the synthesis of
these compounds has received a great deal of attention. The
general and simplest method to construct the ring skeletons of
1,5-benzodiazepine is the acid catalyzed reactions of
o-phenylenediamines (OPDA) or o-aminothiophenol (o-ATP)
with ketones, D,E-unsaturated carbonyl compound, or
ȕ-haloketones [11,12].
been used to improve reaction efficiency. The main disadvan-
tages of these catalysts are that they get lost in the work-up
procedure, cannot be recovered or reused, and are highly toxic
and expensive [24]. Therefore, a better catalyst for the synthe-
sis of 1,5-benzadiazepines is needed to achieve mild reaction
conditions, operational simplicity, economic viability, and
selectivity.
The use of heterogeneous catalysts such as Al2O3/P2O5 [25]
and sulfated zirconia [26] is advantageous. The application of
aluminophosphates as heterogeneous catalytic materials in
organic synthesis is growing significantly. Our group has re-
cently reported the catalytic activity of amorphous metal alu-
minophosphates as effective and recyclable materials in or-
ganic transformations [27–30]. To synthesize diazepines by an
effective and environmentally benign route, we have con-
densed OPDA with various ketones in the presence of metal
aluminophosphates as catalyst. This solvent-free protocol
using a heterogeneous catalyst provides an excellent route for
an eco-friendly and economic synthesis of benzodiazepines.
We report for the first time a facile method for the synthesis of
1,5-benzodiazepines by the condensation of OPDA with ke-
tones with an amorphous mesoporous iron aluminophosphate
catalyst in the presence of a solvent and under solvent-free
conditions.
Many of the synthesis methods of 1,5-benzodiazepines suf-
fer from one or more limitations, such as long reaction times,
occurrence of side reactions [13], severe reaction conditions,
low yields, use of corrosive chemicals (e.g., HCl gas,
trifluoroacetic acid) and hazardous reagents (e.g., pyridine,
piperidine, halogenated hydrocarbon), high-boiling solvent
(e.g., dimethylformamide), and tedious work-up procedures.
Catalysts such as BF3-Et2O [14], NaBH4 [15], ceric ammonium
nitrate [16], PPA/SiO2 [17], MgO/POCl3 [18], Yb(OTf)3 [19],
AcOH under microwave conditions [20], NBS [21], poly-
mer-supported FeCl3Sc(OTf)3 [22], and ionic liquids [23] have
Received date:. 6 April 2010.
*Corresponding author. Tel: +91-9886765750; Fax: +91-8022245831; E-mail: nagarajun@yahoo.com
Copyright © 2010, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60120-9

A. V. Vijayasankar et al. / Chinese Journal of Catalysis, 2010, 31: 1321–1327
1 Experimental
Compound a: Yellow solid; mp 137–139 °C; IR (KBr, cm–1)
1
v 3295, 1633, 1593, 1437; H NMR (CDCl3) į 1.35 (s, 6H,
1.1 Catalyst preparation
2CH3), 2.23 (s, 2H, CH2), 2.38 (s, 3H, CH3), 2.98 (br s, 1H,
NH), 6.74–7.27 (m, 4H, C6H4); 13C NMR (CDCl3) į 29.9, 30.5,
45.1, 68.5, 121.8, 122.1, 125.6, 126.8, 137.9, 140.6, 172.5.
Compound b: Yellow solid; mp 137–138 °C; IR (KBr, cm–1)
The iron aluminophosphate (FeAlP) catalyst was prepared
by co-precipitation [27–30]. Aluminum nitrate (Al(NO3)3·
9H2O), ferric nitrate (Fe(NO3)3·9H2O), and 85% H3PO4 in a
definite molar ratio (Al:Fe:P = 0.95:0.025:1) were dissolved in
500 ml of deionized water and stirred vigorously. The solution
1
v 3327, 1635, 1568, 1442; H NMR (CDCl3) į 0.95–1.66 (m,
6H, 2CH3), 1.71–2.13 (m, 4H, CH2), 2.37 (s, 3H, CH3), 2.69 (q,
2H, CH2), 3.65 (br s, 1H, NH), 6.75–7.57 (m, 3H, C6H3); 13C
NMR (CDCl3) į 8.6, 11.2, 26.8, 35.6, 35.7, 42.3, 70.5, 121.8,
125.1, 126.2, 127.1, 137.8, 140.6, 175.6.
o
was heated to 60–70 C, and then 28% ammonia was added
continuously till a precipitate was obtained (pH 9). The pre-
cipitate was filtered, washed with deionized water, dried at 120
13C NMR (CDCl3), į: 8.6, 11.2, 26.8, 35.6, 35.7, 42.3, 70.5,
121.8, 125.1, 126.2, 127.1, 137.8, 140.6, 175.6.
o
oC, and calcined at 550 C for 5 h. The obtained catalyst is
denoted FeAlP-550.
Compound c: Yellow solid; mp 144–145 °C; IR (KBr, cm–1),
1
v 3322, 1630, 1595; H NMR (CDCl3) į 0.73–1.65 (m, 16H,
1.2 General procedure for the synthesis of
1,5-benzodizepines
2CH2 and 4CH3), 2.35–2.52 (m, 2H, CH2), 2.85 (q, 1H, CH),
3.78 (br s, 1H, NH), 6.67–7.42 (m, 4H, C6H4); 13C NMR
(CDCl3) į 7.5, 7.8, 11.5, 12.2, 28.1, 28.3, 35.5, 46.1, 68.9,
117.7, 118.1, 125.6, 132.7, 140.0, 142.4, 173.6.
Compound d: Yellow solid; mp 138–139 °C; IR (KBr, cm–1)
v 3327, 1620, 1568, 1430, 1372; 1H NMR (CDCl3) į 1.20–2.50
(m, 15H, 7CH2 and CH), 3.90 (br s, 1H, NH), 6.55–7.77 (m,
4H, C6H4); 13C NMR (CDCl3) į 23.1, 24.3, 24.5, 28.8, 33.5,
38.2, 39.2, 54.2, 67.1, 118.8, 119.2, 126.8, 132.1, 139.3, 143.4,
178.2.
Compound e: Yellow solid; mp 137–139 °C; IR (KBr, cm–1),
v 3322, 1626, 1568, 1442, 1365; 1H NMR (CDCl3) į 0.85–2.36
(m, 19H, 9CH2 and CH), 3.48 (br s, 1H, NH), 6.85–7.60 (m,
4H, C6H4); 13C NMR (CDCl3) į 21.5, 21.7, 23.4, 23.5, 24.5,
25.1, 33.2, 34.4, 39.3, 40.6, 52.4, 63.1, 121.5, 126.4, 129.6,
138.2, 142.4, 178.5.
A mixture of OPDA (1 mmol) and ketone (2.5 mmol), 5 ml
of solvent (when used), and 0.2 g of catalyst were mixed in a
100 ml round bottom flask and heated with stirring in a tem-
perature controlled oil bath at 80 oC (Scheme 1). The progress
of reaction was monitored by thin layer chromatography. The
reaction mixture was treated with 1:1 (v/v) water and CH2Cl2
and centrifuged to separate the solid catalyst. The organic layer
was concentrated and the product was separated by silica gel
(100–200 mesh) column chromatography using an ethyl ace-
tate-n-hexane (2:8) mixture as eluent.
1.3 Characterization of product
The yield and structure of the products were characterized
by their melting point and FTIR, 1H NMR, 13C NMR, and mass
spectrometry (MS). Melting points were recorded on an Elec-
trothermal melting point apparatus. FTIR spectra were re-
corded using a Nicolet IR 200 instrument and the KBr pellet
technique. 1H and 13C NMR spectra were recorded on a Bruker
DSX-300 spectrometer at 300/400 MHz and 75/100 MHz,
respectively. Chemical shifts are reported downfield from
tetramethylsilane (TMS). Multiplicity is indicated using the
following abbreviations: s (singlet), d (doublet), dd (double
doublet), t (triplet), m (multiplet), and bs (broad singlet). The
mass spectra of the filtrate were recorded on an automated
GC-MS Shimadzu QP 5000 GC-17A, EI-Mode Model.
Compound f: Yellow solid; mp 136–137 °C; IR (KBr, cm–1),
v 3328, 1623, 1550, 1442, 1360; 1H NMR (CDCl3) į 1.15–2.45
(m, 19H, 9CH2 and CH), 3.95 (br s, 1H, NH), 6.52–7.70 (m,
4H, C6H4); 13C NMR (CDCl3) į 22.7, 23.1, 24.3, 24.5, 27.2,
28.1, 33.5, 34.3, 38.2, 39.2, 54.2, 55.4, 67.1, 118.8, 119.2,
126.8, 132.1, 139.3, 143.4, 178.2.
Compound g: Yellow solid; mp 151–152 °C; IR (KBr, cm–1),
1
v 3332, 1637, 1598, 1426; H NMR (CDCl3) į 1.70 (s, 3H,
CH3), 2.95 (d, 1H, CH2), 3.15 (d, 1H, CH2), 3.35 (br s, 1H,
NH), 6.65–7.10 (m, 2H, C6H4), 7.25–7.48 (m, 10H, C6H5),
7.55–7.68 (m, 2H, C6H4); 13C NMR (CDCl3) į 29.7, 41.4, 74.3,
121.6, 122.0, 125.4, 126.7, 127.3, 127.4, 128.3, 128.5, 128.8,
129.6, 138.1, 139.2, 140.6, 145.3, 166.3.
Compound h: Pale yellow crystalline solid; mp 98–99 oC; IR
(KBr, cm–1) v 3318, 1630, 1598; 1H NMR (300 MHz, CDCl3) į
1.72 (s, 3H), 2.26 (s, 3H), 2.32 (s, 3H), 2.98 (d, 1H), 3.05 (d,
1H), 3.43 (br s, 1H, NH), 6.74–6.76 (m, 1H), 6.98–7.02 (m,
6H), 7.21–7.23 (m, 1H), 7.47–7.50 (m, 4H); 13C NMR (75
MHz, CDCl3) į 20.7, 21.2, 29.8, 42.9, 73.1, 121.3, 121.4,
125.2, 126.0, 127.1, 128.5, 128.6, 128.9, 129.2, 136.4, 137.0,
138.2, 139.7, 140.3, 145.0, 166.8.
R1
H
N
NH2
O
R2
FeAlP-550
+
R1
R2
NH2
R1
N
o-Phenylenediamine
Ketones
1,5-Benzodiazepines (a-l)
Scheme 1. Condensation of OPDA with ketones for the synthesis of
1,5-benzodiazepines.
o
Compound i: Yellowish solid; mp 114–116 C; IR (KBr,

A. V. Vijayasankar et al. / Chinese Journal of Catalysis, 2010, 31: 1321–1327
cm–1), v 3325, 1135, 1640, 1594, 1190; H NMR (200 MHz,
1
Table 2 Effect of catalyst under different reaction conditions for the
CDCl3) į 1.71 (s, 3H), 2.85 (d, 1H), 2.98 (d, 1H), 3.73 (s, 3H),
3.77 (s, 3H), 6.65–6.78 (m, 4H), 6.95–7.02 (m, 2H), 7.18–7.25
(m, 2H), 7.42–7.55 (m, 4H).
condensation of OPDA and cyclohexanone
Entry
Catalyst
blank
Yielda (%)
traceb
1
2
o
Compound j: Yellow crystalline solid; mp 219–220 C; IR
Al(OH)3-120
Al(OH)3-550
AlP-120
30
(KBr, cm–1) v 3339, 1636, 1599; 1H NMR (200 MHz, CDCl3) į
1.65 (s, 3H), 2.77 (d, 1H), 2.89 (d, 1H), 4.18 (br s, NH),
6.57–6.64 (m, 4H), 6.81–7.00 (m, 1H), 7.10–7.18 (m, 1H),
7.28–7.55 (m, 4H); 13C NMR (75 MHz, CDCl3) į 29.2, 42.0,
72.6, 114.4, 114.6, 120.5, 120.9, 124.9, 125.8, 127.0, 128.2,
130.0, 137.9, 139.5, 155.3, 158.6, 166.8.
3
25
4
54
5
AlP-550
58
6
FeP-120
68
7
FeP-550
70
8
Fe(OH)3-120
Fe(OH)3-550
FeAlP-120
FeAlP-550
65
9
69
Compound k: Yellow solid; mp 145–146 oC; IR (KBr, cm–1)
v 3325, 1640, 1589, 1198, 574; 1H NMR (200 MHz, CDCl3) į
1.72 (s, 3H), 2.87 (d, 1H), 3.00 (d, 1H), 2.65 (br s, NH),
6.97–6.98 (m, 1H), 7.00–7.04 (m, 6H), 7.18–7.24 (m, 1H),
7.45–7.48 (m, 4H).
10
11
70
94
Reaction conditions: diamine 1 mmol, ketone 2.5 mmol, catalyst 0.3 g in
5 ml of ethanol, 80 oC, 120 min.
aIsolated yield. bIsolated yield after 10 h.
o
Compound l: Red crystalline solid; mp 156–158 C; IR
(KBr, cm–1) v 3325, 1642, 1597; 1H NMR (300 MHz, CDCl3) į
1.83 (s, 3H), 2.96 (d, 1H), 3.27 (d, 1H), 3.52 (br s, NH),
6.97–6.98 (m, 1H), 7.00–7.02 (m, 6H), 7.21–7.22 (m, 1H),
7.45–7.47 (m, 4H); 13C NMR (75 MHz, CDCl3) į 30.0, 42.9,
73.4, 121.3, 122.2, 123.5, 123.4, 126.8, 127.6, 127.7, 129.6,
137.2, 138.8, 144.6, 146.9, 148.4, 154.1, 163.8.
alumina (Al(OH)3), aluminium phosphate (AlP), iron phos-
phate (FeP), and hydrated iron oxide (Fe2O3·xH2O) calcined at
o
120 and 550 C. This was because the preparation of iron
aluminophosphate by the procedure followed in the present
work had the possibility of the formation of these materials
along with iron aluminophosphate. Hence, we also wanted to
characterize the catalytic activity, if any, of these materials.
The catalytic activity of the various materials expressed as
the percentage of isolated yield of product in the condensation
of OPDA and cyclohexanone is presented in Table 2. The
condensation reaction did not give much yield of the expected
product in the absence of a catalyst. The reaction was very slow
with only traces of products in the absence of a catalyst. All the
materials were found to be active for the condensation reaction
between OPDA and cyclohexanone in the presence of ethanol
as solvent. There was not much difference in their catalytic
activity and the effect of the temperature of calcination, except
in the case of iron aluminophosphate. FeAlP calcined to 550 oC
exhibited excellent catalytic activity and resulted in the best
isolated yield of diazepines.
2 Results and discussion
2.1 Effect of solvent in the condensation of OPDA and
cyclohexanone
Initially, a reaction between OPDA and cyclohexanone was
carried out for the evaluation of FeAlP-550 as the catalyst
under different reaction conditions (Table 1). In the first stage,
the effect of solvent was studied using the different solvents of
CH2Cl2, H2O, C2H5OH, C2H2Cl2, and CHCl3 as well as under
solvent-free conditions. The reaction in the different solvents
needed long reaction time and gave low yield. From among the
o
tested solvents, ethanol was chosen as the solvent at 80 C
(Table 1, entry 3).
2.3 Efficiency of catalyst under solvent-free conditions at
different temperatures
2.2 Catalyst screening
Although the target catalyst was iron aluminophosphate, the
catalytic activity studies were also conducted using hydrated
The reaction was further investigated under solvent-free
conditions at different temperatures in the presence of the
active FeAlP-550 catalyst. The reaction did not proceed rapidly
at room temperature (rt) under solvent-free conditions. How-
ever, the yield after 2 h was found to be 50% (Table 3). When
the reaction was allowed to continue for 10 h, a product yield of
85% was achieved. When the reaction temperature was in-
creased, a higher yield of diazepines of 96% was obtained at 80
oC. The yield was a function of temperature under solvent-free
conditions. An optimum temperature of 80 oC was required for
a better yield, which is explained in the mechanism (Scheme
Table 1 Optimization of solvent conditions for the reaction of OPDA
and cyclohexanone using FeAlP-550 as catalyst
Entry
Temperature (oC)
Solvent
dichlolromethane
water
Yield* (%)
1
50
100
80
60
20
94
69
57
2
3
ethanol
4
85
dichloroethane
chloroform
5
65
* Isolated yield.

A. V. Vijayasankar et al. / Chinese Journal of Catalysis, 2010, 31: 1321–1327
Table 4 Synthesis of benzodiazepines using FeAlP-550 as an efficient
Table 3 Effect of reaction temperature for the condensation of OPDA
and reusable catalyst
and cyclohexanone under solvent-free conditions using FeAlP-550 as
catalyst
Cycle
Yielda (%)
Yieldb (%)
Entry
Temperature (oC)
Yielda (%)
1
2
3
4
96
90
43
20
94
88
85
69
1
2
3
4
rt
54
80
rt
50
78
96
85b
aIsolated yield in the absence of solvents. Reaction conditions: diamine 1
mmol, ketone 2.5 mmol, catalyst 0.3 g, 80 oC.
bIsolated yield in the presence of solvent (ethanol). Reaction conditions:
diamine 1 mmol, ketone 2.5 mmol, catalyst 0.2 g in 5 ml ethanol, 80 oC.
Reaction conditions: diamine 1 mmol, ketone 2.5 mmol, catalyst 0.2 g,
120 min. aIsolated yield. bIsolated yield after 10 h.
2). This gave a sufficient number of ketones available on the
surface of the catalyst to propagate the reaction.
reactivity depended on the substituent on the benzene. In the
presence of electron withdrawing groups such as –OH, –Br,
and –NO2, the condensation reaction proceeded smoothly to
give good yields of benzodiazepines (Table 5, entries 10–12).
Whereas the presence of electron releasing groups such as
methyl and methoxy groups on the benzene nucleus of aceto-
phenone only gave poor yields (Table 5 entries 8 and 9) of
benzodiazepines even after long reaction times.
2.4 Reusability of catalyst in the condensation of OPDA
and cyclohexanone
We also investigated the reusability of the FeAlP-550 cata-
lyst, both in the presence of ethanol and under solvent-free
conditions. The catalyst was recovered by dissolving the reac-
tion mixture in 1:1 (v/v) water and CH2Cl2 and filtered to
separate the solid catalyst. The catalyst was separated by sim-
2.6 Mechanism for the condensation of OPDA and
ketones over FeAlP-550 catalyst
o
ple filtration, washed with acetone, dried at 120 C, and cal-
cined at 550 oC. The catalyst was reused at least four times in
the same reaction without appreciable loss in catalytic activity.
The results of the catalyst reusability are shown in Table 4.
From the above observations on the reactivity of various
ketones in the presence of FeAlP-550 as the catalyst, we pro-
pose the reaction mechanism shown in Scheme 2. The catalyst
FeAlP-550 has surface acid sites. The oxygen atom of the
ketones is adsorbed through its lone pair electrons on the sur-
face acid sites of the catalyst, and the amino groups of OPDA
attack the carbonyl group of the ketone to give the intermediate
diimine (A and B). A 1,3-hydrogen shift to the attached methyl
group then occurred to form an isomeric enamine, which cy-
clizes to afford the seven-member ring. An alternative mecha-
nism involving the aldol condensation of ketones to give
D,E-unsaturated carbonyl compound which subsequently un-
dergoes 1,4-addition was ruled out because such an aldol
condensation does not occur in ketones with a D-hydrogen in
the presence of FeAlP. The reaction conditions are mild and no
side products or decomposition of the products were observed.
The better catalytic activity of FeAlP-550 over that of the
other catalysts reported may be attributed to its mesoporous
texture and amorphous nature, which gave a higher concentra-
tion of active acid sites on its surface [30]. We have previously
reported a correlation between the textural/structural properties
and catalytic activity of these materials in organic transforma-
tions like transesterification and alkylation reactions [28, 29].
Since larger crystallites have only a small percentage of the
reactive sites on the surface, smaller crystallites or amorphous
materials possess a much higher surface concentration of sites,
and it is this morphological difference that makes FeAlP an
efficient catalyst.
2.5 Synthesis of benzodiazepines both in the presence of
ethanol as solvent and under solvent-free conditions
To look at the application of FeAlP as a general catalyst for
the synthesis of 1,5-benzodiazepines, the condensation reac-
tions under optimized conditions using a variety of aliphatic,
alicyclic ketones, and substituted acetophenones were carried
out. The results are presented in Table 5. All the ketones con-
densed smoothly with OPDA in the presence of FeAlP-550
without forming any side products. The only noticeable dif-
ference in the reactivity of the various ketones was in the time
taken to get a significant yield of the expected diazepine
products. It is noteworthy that the condensation of the various
ketones with OPDA in the presence of FeAlP-550 was superior
in terms of yield and selectivity for products as compared to
other catalysts reported in the literature.
Under the optimum conditions, aliphatic ketones gave a
product yield in the range of 87%–94% after 45 min, which
depended on the nature of the ketone. Cyclic ketones such as
cyclohexanone, cycloheptanone, and cyclopentanone (Table 5,
entries 4–6) also produced the corresponding fused-ring ben-
zodiazepines in good yields but after a longer time (a120 min)
as compared to the aliphatic ketones (Table 5, entries 1–3).
The condensation activity of acetophenones and its deriva-
tives was found to be better than that of cyclic ketones. The

A. V. Vijayasankar et al. / Chinese Journal of Catalysis, 2010, 31: 1321–1327
Table 5 Condensation of OPDA and ketones catalyzed by FeAlP-550 catalyst under different reaction conditions
Melting point (oC)
Entry
1
Ketone
O
Diazepine derivative
Time (min)
Yielda (%)
Yieldb (%)
Expt.
Reported
H
N
45
94
94
140
137–139
a
N
H
N
O
2
3
45
45
95
90
88
87
140
140
137–138
144–145
b
N
H
N
Et
Et
Me
O
c
N
Et
O
O
O
H
N
4
5
120
120
89
94
81
96
137
139
138–139
137–139
d
N
H
N
e
N
H
N
6
7
8
120
75
83
92
89
68
90
87
135
152
99
136–137
151–152
143
f
N
H
N
Ph
O
g
Ph
N
Ph
O
Ph Me
H
N
120
h
N
Ph Me
O
Ph OMe
H
N
9
120
80
85
84
83
86
84
81
85
85
117
217
146
157
114–116
219–220
145–146
156–158
i
N
Ph OMe
MeO
O
Ph
OH
H
N
10
11
12
j
Ph OH
Ph Br
N
HO
Br
O
H
N
80
k
N
Ph Br
O
Ph NO2
H
N
80
l
N
Ph NO2
O2N
Reaction conditions: diamine 1 mmol, ketone 2.5 mmol, catalyst 0.3 g in 5 ml ethanol or 0.2 g in solvent-free conditions, 80 oC.
aIn the presence of ethanol. bUnder solvent free conditions.
2.7 Advantages of the FeAlP-550 catalyst
nificant loss in activity. Thus, the present data showed the
efficient reusability of the catalyst. As compared to other acid
catalysts reported in the literature, iron aluminophosphate was
superior in terms of a higher conversion, short reaction time,
and small amount of catalyst needed. Also, this method does
not require any expensive reagents or special care to exclude
moisture from the reaction medium.
The catalyst preparation is simple and involves readily
available non-hazardous and inexpensive reagents. The sepa-
ration of the product from the reaction mixture does not require
any tedious workup procedure. The recovered catalyst can be
reused at least four to five times (Table 4) without any sig-

A. V. Vijayasankar et al. / Chinese Journal of Catalysis, 2010, 31: 1321–1327
R1
R2
Lewis acid catalyst
O
H
N
R1
R2
R2
R1
N
N
N
H
H
+
R2
R1
R1
R2
N
H
N
H
A
B
H
N
R1
R2
R1
R2
N
N
H
N
+
R1
R1
Scheme 2. Mechanism for the condensation of OPDA and ketones over a FeAlP-550 catalyst.
mun, 1999, 29: 3561
7
8
9
Reddy K V V, Rao P S, Ashok D. Synth Commun, 2000, 30: 1825
3 Conclusions
Haris R C, Straley J M. US 1 537 757. 1968
Heravi M M, Motamedi R, Siefi N, Bamoharram F F. J Mol
Catal A, 2006, 249: 1
Iron aluminophosphate was a highly efficient heterogene-
ous,
recyclable
catalyst
for
the
synthesis
of
10 Gringauz A, Introduction to Medicinal Chemistry. New York:
Wiley-VCH, 1999
1,5-benzodiazepines by the condensation of OPDA with a wide
variety of ketones. This method has easy workup, solvent-free
conditions, fast reaction rate, good yields, and high selectivity,
which make it attractive for large scale operations. This method
is effective for the preparation of 1,5-benzodiazepines from
both electron-rich and electron-deficient ketones and
o-phenylenediamine derivatives under mild reaction condi-
tions. The activity of the catalyst was attributed to its amor-
phous mesoporous nature and surface acid sites that allowed
the reaction to be completed in a short time with high yield and
100% selectivity for the desired product.
11 Ried W, Stahlofen P. Chem Ber, 1957, 90: 815
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135
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D H. Synth Commun, 1999, 29: 1941
18 Balakrishna M S, Kaboudin B. Tetrahedron Lett, 2001, 42: 1127
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Acknowledgments
We thank NMR centre, Indian Institute of Science, Banga-
lore, India, for NMR analysis and Mr. Prasad, Anthem bio-
sciences, Bangalore, India, for GC-MS analysis.
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