216 Heravi et al.
EXPERIMENTAL
A mixture of ketone (2.1 mmol), o-phenylenediamine
(1 mmol), and kaolin (0.05 g) was refluxed in
dichloroethane. After completion of reaction (moni-
tored by TLC), the reaction mixture was filtered. Af-
ter evaporation of solvent, products were obtained in
good yields. More purification was done by column
chromatography. They were identified through com-
paring with authentic samples. The recovered cata-
lyst was washed with diethyl ether and was reused.
All products gave satisfactory spectral data in
accordance with the assigned structures. For exam-
ple, for entry 1: light yellow solid: mp 138◦C (136–
SCHEME 1
2,3-dihydro-1H-1,5-benzodiazepines by the conden-
sation of o-phenylenediamine with ketones in the
presence of catalytic amount of kaolin under reflux-
ing dichloroethane (Scheme 1).
The syntheses were carried out simply by re-
fluxing a mixture of o-phenylenediamine (1 mmol),
ketone (2.1 mmol), and a catalytic amount of kaolin
in dichloroethane, whereupon the benzodiazepine
derivatives were obtained in almost quantitative
yields. The results are summarized in Table 1.
Cyclic and acyclic ketones and substituted aryl
ketones have been used for the synthesis of 1,5-
benzodiazepine derivatives. Kaolin is not soluble in
dichloroethane, so it can facilitate the separation of
products from the catalyst.
We investigated the reusability of the catalyst.
For this purpose, we first carried out the reaction of
o-phenylenediamine and acetophenone in the pres-
ence of the catalyst. After completing the reaction,
the catalyst was removed by a simple filtration and
washed with diethyl ether and subjected to a second
run of the reaction process with the same substrate.
The results of the first experiment and subsequent
experiments were almost consistent in yields after
three runs (86%, 84%, 81%).
In summary, a simple work-up procedure, con-
venient and efficient protocol for the synthesis of
2,3-dihydro-1H-1,5-benzodiazepines via the conden-
sation of o-phenylenediamine with different ketones,
using kaolin as a recyclable heterogeneous catalyst,
is reported. The simple experimental procedure to-
gether with ease of recovery and reuse of the catalyst
makes this method quite simple, more convenient,
and environmentally benign.
1
138◦C [18]). IR (KBr): 3340, 1650, 1600 cm−1. H
NMR (CDCl3, 400 MHz): 7–7.25 (m, 4H, Ar-H), 3.5
(br s, 1H, N H), 3(s, 2H, N C CH2), 2.5 (m, 3H,
N C CH3), 1.50–1.75 (s, 6H, 2CH3).
REFERENCES
[1] (a) Schultz, H. Benzodiazepines; Springer:
Heidelberg, 1982; (b) Smalley, R. K. In Com-
prehensive Organic Chemistry; Barton, D.; Ollis, W.
D. (Eds.); Pergamon: Oxford, 1979.
[2] Randall, L. O.; Kappel, B. In Benzodiazepines;
Garattini, S.; Mussini, E.; Randall, L. O. (Eds.); Ravan
Press: New York, 1973; Ch. 27 and references cited
therein.
[3] Harris, R. C.; Straley, J. M. US Patent 1968 1 537 757;
Chem Abstr 1970, 73, 100054w.
[4] De Baun, J. R.; Pallos, F. M. Baker, D. R. US Patent
1976 3 978 227; Chem. Abstr. 1977, 86, 5498d.
[5] Essaber, M.; Baouid, A.; Hasnaoui, A.; Benharreb, A.;
Lavergne, J. P. Synth Commun 2000, 28, 4097.
[6] El-Sayed, A. M.; Abdel-Ghany, H.; El-Saghier, A. M.
M. Synth Commun 1999, 29, 3561.
[7] (a) Xu, J. X.; Wu, H. T.; Jin, S. Chin J Chem 1999, 17,
84; (b) Zhang, X. Y.; Xu, J. X.; Jin, S. Chin J Chem
1999, 17, 404.
[8] Reddy, K. V. V.; Rao, P. S.; Ashok, D. Synth Commun
2000, 30, 1825.
[9] Stahlofen, P.; Ried, W. Chem Ber 1957, 90, 815.
[10] Ried, W.; Torinus, E. Chem Ber 1959, 92, 2902.
[11] Herbert, J. A. L.; Suschitzky, H. J Chem Soc, Perkin
Trans 1 1974, 2657.
[12] Morales, H. R.; Bulbarela, A.; Contreras, R. Hetero-
cycles 1986, 24, 135.
[13] Jung, D. I.; Choi, T. W.; Kim, Y. Y.; Kim, I. S.; Park,
Y. M.; Lee, Y. G.; Jung, D. H. Synth Commun 1999,
29, 1941.
[14] Balakrishna, M. S.; Kaboudin, B. Tetrahedron Lett
2001, 42, 1127.
[15] Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
Tetrahedron Lett 2001, 42, 3193.
[16] Jarikote, D. V.; Siddiqui, S. A.; Rajagopal, R.; Daniel,
T.; Lahoti, R. J.; Srinivasan, K. V. Tetrahedron Lett
2003, 44, 1835.
[17] Reddy, B. M.; Sreekanth, M. Tetrahedron Lett 2003,
44, 4447.
TABLE
1
Kaolin-Catalyzed
Benzodiazepines
Synthesis
of
1,5-
Entry
Ketone
Time (h)
Yield
1
2
3
4
5
6
7
Acetone
Acetophenone
3
4
3.5
5
5
3.5
6
90
90
87
85
84
92
90
4ꢁ-Methyl acetophenone
4ꢁ-Nitroacetophenone
4ꢁ-Hydroxy acetophenone
Ethyl methyl ketone
Cyclohexanone
Heteroatom Chemistry DOI 10.1002/hc