, 2006, 16(2), 113–115
Thus, we described an efficient protocol for the synthesis of
2,3-dihydro-1H-1,5-benzodiazepines from o-phenylenediamines
and ketones having hydrogens at the α-position using air- and
water-tolerant zirconyl(IV) chloride as a catalyst under solvent-
free conditions.
O
H
N
NH2
NH2
Cat. ZrOCl2·8H2O
room temperature
N
References
Scheme 2
1
(a) H. Schutz, Benzodiazepines, Springer, Heidelberg, 1982; (b) J. K.
Landquist, in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky
and C. W. Rees, Pergamon, Oxford, 1984, vol. 1, pp. 166–170; (c) R. I.
Fryer, in The Chemistry of Heterocyclic Compounds, ed. E. C. Taylor,
Wiley, New York, 1991, vol. 50, ch. II.
L. O. Randall and B. Kappel, Benzodiazepines, eds. S. Garattini, E. Mussini
and L. O. Randall, Raven Press, New York, 1973, p. 27.
R. C. Haris and J. M. Straley, US Patent 1537757, 1968 (Chem. Abstr.,
1970, 73, 100054w).
under solvent-free conditions. The crude products were purified
by recrystallization from diethyl ether–hexane or by silica gel
column chromatography. All of the products were characterised
by 1H NMR, 13C NMR and IR spectroscopy; mass spectrometry;
elemental analysis and melting point measurements. The scope
and generality of this procedure are illustrated with respect to
various o-phenylenediamines and a wide range of ketones and
the results are presented in Table 1. This method offers several
advantages such as high conversions, shorter reaction times,
cleaner reaction profiles, high regioselectivity in the case of
unsymmetrical ketones, solvent-free conditions, simple experi-
mental and work-up procedures.
2
3
4
5
J. R. De Baun, F. M. Pallos and D. R. Baker, US Patent 3978227, 1976
(Chem. Abstr., 1977, 86, 5498d).
(a) M. C. Aversa, A. Ferlazzo, P. Gionnetto and F. H. Kohnke, Synthesis,
1986, 230; (b) M. Essaber, A. Baouid, A. Hasnaoui, A. Benharref and
J. P. Lavergne, Synth. Commun., 1998, 28, 4097; (c) A. M. El-Sayed,
H. Abdel-Ghany and A. M. M. El-Saghier, Synth. Commun., 1999, 29,
3561; (d) A. Chimirri, S. Grasso, R. Ottana, G. Romeo and M. Zappala,
J. Heterocycl. Chem., 1990, 27, 371.
Melting points are uncorrected. 1H and 13C NMR spectra were recorded
†
on a Varian Gemini 200 MHz spectrometer. Chemical shifts d (ppm)
relative to TMS as an internal standard are reported. Electron spray
ionization mass spectra (ES-MS) were recorded on a Water-Micromass
Quattro-II spectrometer. IR spectra were recorded on a Varian spectro-
meter. All of the reagents used were of AR grade and used without further
purification. Column chromatography employed silica gel of 60–120 mesh.
General procedure for the preparation of 2,3-dihydro-1,5-benzo-
diazepines. A mixture of o-phenylenediamines (1 mmol), a ketone
(2.5 mmol) and ZrOCl2·8H2O (0.1 mmol) was stirred at room tem-
perature for an appropriate time (Table 1). After completion of the
reaction, as indicated by TLC, the reaction mixture was diluted with
water and extracted with ethyl acetate (3×10 ml). The combined organic
layers were dried (Na2SO4) and concentrated in vacuo to afford a crude
compound. The crude compounds were purified by recrystallization with
diethyl ether–hexane or by silica gel column chromatography to afford
pure desired compounds.
6
7
(a) P. Stahlhofen and W. Ried, Chem. Ber., 1957, 90, 815; (b) W. Reid
and E. Torinus, Chem. Ber., 1959, 92, 2902; (c) J. A. L. Herbert and
H. Suschitzky, J. Chem. Soc., Perkin Trans. 1, 1974, 2657; (d) G. Kaupp,
U. Pogodda and J. Schmeyers, Chem. Ber., 1994, 127, 2249.
(a) M. S. Balakrishna and B. Kaboudin, Tetrahedron Lett., 2001, 42,
and R. Contreras, Heterocycles, 1986, 24, 135; (d) B. Kaboudin and
K. Navaee, Heterocycles, 2001, 55, 1443.
8
9
J. S. Yadav, B. V. S. Reddy, S. Praveenkumar and K. Nagaiah, Synthesis,
2005, 480.
The zirconyl(IV) chloride catalyst (Aldrich) was used; it could also be
10 M. Dehnicke, Z. Anorg. Allgem. Chem., 1964, 121, 331.
synthesised conveniently from ZrCl4 and Cl2O.10
2,3-Dihydro-2,2,4-trimethyl-1H-1,5-benzo[b][1,4]diazepine 3a (R =
1
= R'' = H, R' = Me): H NMR (200 MHz, CDCl3) d: 1.35 (s, 6H), 2.20
(s, 2H), 2.35 (s, 3H), 2.95 (br. s, 1H, NH), 6.65–7.30 (m, 4H). 13C NMR
(50 MHz, CDCl3) d: 29.5, 30.6, 44.9, 67.9, 121.4, 122.2, 125.1, 126.8,
137.5, 140.8, 171.6. IR (KBr, n/cm–1): 3340, 1650, 1600. ES/MS, m/z:
189 (M + H, 100%). Found (%): C, 76.29; H, 8.62; N, 14.95. Calc. for
C12H16N2 (%): C, 76.56; H, 8.57; N, 14.88.
Received: 2nd September 2005; Com. 05/2572
Mendeleev Commun. 2006 115