Catalysis Communications 6 (2005) 6770

www.elsevier.com/locate/catcom

Polymer (PVP) supported ferric chloride: an ecient and recyclable

heterogeneous catalyst for high yield synthesis of 1,5-benzodiazepine
derivatives under solvent free conditions and microwave irradiation
M. Adharvana Chari *, K. Syamasundar
Department of Chemistry, College of Engineering, JNT University, Kukatpally, Hyderabad 500 072, India

Received 19 July 2004; revised 15 October 2004; accepted 22 October 2004

Available online 8 December 2004

Abstract

Polymer (PVP) supported ferric chloride catalyzes eciently the condensation of o-phenylenediamines with ketones under sol-
vent free conditions to aord the corresponding 1,5-benzodiazepine derivatives in high yields. The reaction proceeds eciently under
ambient conditions giving excellent yields (8596%).
2004 Published by Elsevier B.V.

Keywords: o-phenylenediamines; Ketones; Polymer (PVP) supported ferric chloride; Benzodiazepines

1. Introduction shortcomings such as long reaction times, expensive re-

Benzodiazepines and their derivatives are important
class of bioactive molecules and are widely used as anti-
convulsant, antianxiety, analgesic, seditative, antide-
pressive and hypnotic, and antiinamatory agents
[13]. Some of the benzodiazepine derivatives are used
as dyes for acrylic bers [4] in photography. Particu-
larly, 1,5-benzodiazepines are useful precursors for the
synthesis of some fused ring benzodiazepine derivatives
[5], such as triazolo-, oxadiazolo-, oxazino-, or fur-
anobenzodiazepines. Due to their wide range of applica-
tions these compounds have received a great deal of
attention in connection with their synthesis. Many re-
agents have been reported in the literature [6] for this
condensation including BF3-etherate, NaBH4, polyph-
osphoric acid, Yb(OTf)3 and MgO/POCl3, and sulph-
ated zirconia. Recently, these condensations have been
reported even in an ionic liquid medium [7,8]. However,
many of these methodologies are associated with several
agents, harsh conditions, low-product yields, occurrence
of several side products and diculty in recovery and
reusability of the catalysts. Generally, benzodiazopines
are synthesised by the condensation of o-phenylene
diamines with a,b-unsaturated carbonyl compounds or
with ketones.
In recent years, the organic reactions on solid sup-
ported reagents [9] have received considerable impor-
tance in organic synthesis because of their ease of
handling, enhanced reaction rates, greater selectivity,
simple workup, and recoverability of catalysts. Among
the various heterogeneous catalysts, particularly, poly-
mer supported reagents have advantages of low cost,
ease of preparation, and catalyst recycling. Since the
reaction is heterogeneous in nature, the catalyst can con-
veniently be separated by simple ltration.
2. Results and discussion

*
Corresponding author. Fax: +91 40 23060056. In view of recent surge in the use of heterogeneous
E-mail address: drmac@redimail.com (M. Adharvana Chari). catalysts [10,11]. We wish to report a simple, convenient

1566-7367/$ - see front matter 2004 Published by Elsevier B.V.

doi:10.1016/j.catcom.2004.10.009
68 M. Adharvana Chari, K. Syamasundar / Catalysis Communications 6 (2005) 6770
and ecient method for the preparation of 1,5-benzodi-
azepine derivatives using a polymer (PVP) supported
ferric chloride as an inexpensive and eco-friendly cata-
lyst and was prepared by using known procedure [12].
This method not only aords the products in excellent
yields but also avoids the problems associated with cat-
alyst cost, handling, safety and pollution. This catalyst
can act as eco-friendly for a variety of organic transfor-
mations, non-volatile, recyclable, non-explosive, easy to
handle, and thermally robust. Enhanced reaction rates
and improved selectivity were obtained in the presence
of this heterogeneous catalyst. In view of the emerging
importance of the heterogeneous catalyst, we wish to
explore the use of PVP supported FeCl3 as recyclable
catalyst for the synthesis of 1,5-benzodiazepines
(Scheme 1).
FeCl3 is an inexpensive and powerful oxidant used
for the transformation of a wide range of functional
groups. A wide range of structurally varied acetonides
have been subjected to cleavage with FeCl3 supported
on polymer to provide the corresponding carbonyl com-
pounds it is note worthy that unlike other oxidative
hydrolytic methods.
The treatment of o-phenylenediamine with acetone in
the presence of polymer (PVP) supported ferric chloride
causes the formation of 2,3-dihydro-2,2,4-trimethyl-1H-
1,5-benzo[b][1,4]diazepine in 96% yield. In a similar
fashion, various ketones reacted smoothly with o-pheny-
lenediamines under these reaction conditions to give the
corresponding 1,5-benzodiazepine derivatives in 8596%
yield under solvent free conditions. The reactions
proceeded eciently in high yields at reux temperature.
The crude products were puried either by recrys-
tallization from n-hexane or by silica gel column chro-
matography. The reaction of cyclic ketones with
o-phenylenediamine in the presence of this catalyst aor-
ded fused ring 1,5-benzodiazepine derivatives in good
yields. All the products were characterized by IR, 1H
NMR, and mass spectral analysis and also by compari-
son with authentic samples. The reactions of various ke-
tones with o-phenylenediamines in the presence of
polymer (PVP) supported ferric chloride are superior
in terms of yields and reaction rates and the results are
presented in Table 1. The rate enhancement under
microwave irradiation may be attributed to the eective
absorption of microwaves by the polar media. Thus
microwaves have been applied to accelerate reaction
rates and to improve the yields of the products. The clas-
sical synthesis of 1,5-benzodiazepine derivatives requires
H R'
O
NH2 Polymer supported FeCl3 N R''
R + R'-C-R'' R R''
NH2 N
1
R'
2 3
Scheme 1.
long reaction time at reux temperature to moderate
yields. In general, microwave assisted reactions are
clean, rapid and aord higher yields than those obtained
by conventional methods. o-phenylenediamine and ke-
tone were mixed with dry catalyst and subjected to
microwave irradiation at 450 W using BPL, BMO-
700T microwave oven for an appropriate time. The
advantage of the use of heterogeneous catalyst for this
transformation is the ease of catalyst/substrate separa-
tion provided by a heterogeneous catalyst. Since the
products were weakly soluble in the ionic phase, they
were easily separated by simple extraction with ether.
However, the products were obtained of the same purity
as in the rst run, but the yields were gradualy decreased
in runs carried out using recycled catalyst. For example,
the reaction of o-phenylenediamine and acetone aorded
the corresponding 2,3-dihydro-1,5-benzodiazepine in
92%, 88%, 86%, and 80% yields over four cycles. The
results of the reactions at microwave irradiation condi-
tions are compared with the reux conditions and short
reaction times were observed, which is more economy
in terms of time. Compared to conventional method,
enhanced reaction rates, improved yields and high selec-
tivity are the features obtained in microwave irradiation.
3. Experimental
3.1. General procedure for the synthesis 2,3-dihydro-1,5-
benzodiazepines
A mixture of o-phenylenediamine (1 mmol), ketone
(2.5 mmol), and polymer (PVP) supported ferric chlo-
ride (5 mol%) were mixed in a pyrex test tube and sub-
jected to microwave irradiation for an appropriate time
(Table 1). The reaction was monitored by TLC, NMR
and mass were used for analysis of the products. After
completion of the reaction, 10 ml of CH2Cl2 was added
to the reaction mixture and the catalyst was recovered
by ltration. The organic layer was concentrated and
the products was puried by silica gel column (100
200 mesh) and eluted with ethyl acetaten-hexane (2:8)
to aord pure compound in 8098% yield. The wet cat-
alyst was recycled and no appreciable change in activity
was noticed after a few cycles. The spectral data of the
some of the compounds are given below.
3.2. Catalyst preparation
Powdered poly(4-vinylpyridine) (1 g) was resolved in
10 ml of standard solution of 0.1 M of FeCl3 in water. 1
mmol (161 mg) of FeCl3 was added. After the solution
had been stirred for 30 min at 30 C. The solid PVP
Fe(III) was ltered to obtain. The excessive ferric ions
in complex were washed by deionized water. The solid
powder was dried under vacuum at 65 C for 24 h.
 M. Adharvana Chari, K. Syamasundar / Catalysis Communications 6 (2005) 6770 69

Table 1
Microwave assisted, polymer (PVP) supported catalysed ecient synthesis of 1,5-benzodiazepines
Entry Diamine Ketone Producta Conventional Microwave irradiationc
b
Time (ms) Yield (%) Time (s) Yield (%)b
NH2 H
N
a CH3COCH3 30 92 30 98
NH2
N

H Ph
NH2 N Me
b PhCOCH3 40 90 45 95
NH2
N Ph

H
NH2 N
c CH3COCH2CH3 40 90 45 95
NH2
N

H
NH2 N
d CH3CH2COCH2CH3 40 88 50 95
NH2
N

NH2 O H
N
e 50 87 60 92
NH2
N

NH2 O H
N
f 50 85 60 92
NH2
N

H
Me NH2 N
Me
g CH3COCH3 30 92 45 96
NH2
N

Me H
NH2 Me N
h CH3COCH3CH3 40 90 45 92
NH2
N

Me H
NH2 Me N
i CH3CH2COCH2CH3 40 88 40 90
NH2
N

H Ph
Me NH2 Me N Me
j PhCOCH3 45 88 60 95
NH2
N Ph

H
Me NH2 Me N
k CH3COCH3 50 87 60 95
Me NH2
Me N

H
PhCO NH2 PhCO N
l CH3COCH3 50 87 90 92
NH2
N

H Ph
PhCO NH2 PhCO N Me
m PhCOCH3 65 85 90 90
NH2
N Ph

a 1
All products were characterized by IR, H NMR, and mass spectra.
b
Isolated and unoptimized yields.
c
Pulsed irradications (15-s interval) at 450 W using BPL-BMO 700T microwave oven.

The absorbed amounts are ferric ions in complex were
obtained using UV spectrophotometer. The catalyst is
washed with solvents and dried then reused for subse-
quent reactions. In polymer supported FeCl3, the poly-
mer is strongly holding the catalyst. So without loss of
any FeCl3 catalyst can be recovered.
Spectral data for selected compounds:
3b: Solid, m.p. 150152 C, 1H NMR (CDCl3) d: 1.80
(s, 3H), 2.95 (d, 1H, J = 12.8 Hz), 3.15 (d, 1H, J = 12.8
Hz) 3.45 (brs, NH), 6.557.0 (m, 3H), 7.157.35 (m, 7H),
7.557.65 (m, 4H). 13C NMR (proton decoupled,
CDCl3) d: 29.7, 42.9, 73.3, 121.2, 121.4, 125.2, 126.1,
70 M. Adharvana Chari, K. Syamasundar / Catalysis Communications 6 (2005) 6770
126.8, 126.9, 127.8, 128.1, 128.5, 129.5, 137.9, 139.5,
139.9, 147.4, 167.3. EIMS: m/z: 312 [M+], 297, 235,
194, 103, 77, 40. IR (KBr) m: 3320, 1631, 1597.
3d: Solid, m.p. 143145 C, 1H NMR (CDCl3) d:
0.701.0 (m, 10H), 1.201.38 (m, 4H), 1.501.65 (m,
2H), 2.402.60 (m, 2H), 2.87 (q, 1H, J = 6.8 Hz), 3.65
(brs, NH), 6.58 (d, 1H, J = 8.0 Hz), 6.65 (t, 1H,
J = 8.0 Hz), 6.90 (t, 1H, J = 8.0 Hz), 7.38 (d, 1H,
J = 8.0 Hz). 13C NMR (proton decoupled, CDCl3) d:
7.4, 7.8, 11.4, 12.1, 28.0, 28.4, 35.6, 46.2, 68.8, 117.5,
118.0, 126.7, 132.8, 13.9, 142.4, 173.8. EIMS: m/z: 244
[M+], 229, 215, 194, 103, 77, 40. IR (KBr) m: 3320,
1631, 1597.
All other products were characterised by spectral (IR,
1
H NMR and mass) data and by comparison with those
of authentic samples and also by the mixed melting
points with the authentic samples.
4. Conclusion
We have developed a simple, convenient and eective
method for easy synthesis of 2,3-dihydro-1,5-ben-
zodiazepines by the condensation of ketones with o-
phenylenediamines using polymer supported FeCl3 as
catalyst in solvent free conditions under microwave irra-
diation. Present methodology oers very attractive fea-
tures such as reduced reaction times, higher yields and
economic viability of the catalyst, and mild nature of
FeCl3 when compared with conventional methods as
well as with other catalysts, which will have wide scope
in organic synthesis. The simple procedure combined
with ease of recovery and reuse of this catalyst make this
method economic, benign and a waste-free chemical
process for the synthesis of 1,5-benzodiazepines of bio-
logical importance. The operational simplicity of the
procedure is also attractive. The catalyst can be pre-
pared easily with readily available inexpensive reagents
which is heterogeneous and non-hazardous. This cat-
alyst is possessing consistent results when compared to
other heterogeneous catalysts like SiO2NaHSO4 or
SiO2FeCl3 results. However, the products were ob-
tained of the same purity as in the rst run, but the
yields were gradually decreased in runs carried out using
recycled catalyst. For example, the reaction of o-pheny-
lenediamine and acetone aorded the corresponding 2,3-
dihydro-1,5-benzodiazepine in 92%, 88%, 86% and 80%
yields over four cycles. When the SiO2NaHSO4 or
SiO2FeCl3 catalysts are used then the results are 90%,
86%, 84%,76%. This indicates that the stability of these
catalysts is less than that of polymer supported catalysts.
Polymer supported catalysts are more selective than
other heterogeneous catalysts. To our knowledge, this
is rst time report of an ecient general method for
the synthesis of 1,5-benzodiazepine derivatives by using
a simple catalyst.
Acknowledgement
The authors are thankful to Prinicipal, JNTU College
of Engineering, Kukatpally, for facilities.
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