8136
K. P. Guzen et al. / Tetrahedron Letters 47 (2006) 8133–8136
cyclopentanone (4e) and methyl vinyl ketone (4f)
Table 3, entries 7–9) were also used, but no reaction
was observed.
8. Reddy, B. M.; Sreekanth, P. M. Tetrahedron Lett. 2003,
4, 4447.
4
(
9
. (a) Chen, W.-Y.; Lu, J. Synlett 2005, 1337; (b) Kumar, R.;
Chaudhary, P.; Nimesh, S.; Verma, A. K.; Chandra, R.
Green Chem. 2006, 8, 519; (c) Bandgar, B. P.; Patil, A. V.;
Chavan, O. S. J. Mol. Catal. A—Chem. 2006, 256, 99–
In summary, we have shown that 1,5-benzodiazepinic
heterocyclic can be efficiently prepared using ultrasound
irradiation as a tool for creating diverse compound
libraries. Considering the easiness of the preparation
of initial reactants, convenient synthesis, and isolation
of products and good chemical yields of the described
transformations, this route provides a new valuable
entry to 1,5-benzodiazepines. The obtained compounds
represent valuable starting points for the development
of compounds of biological interest. The limitations
and the scope of this methodology are under investiga-
tion and will be reported in due course.
1
05.
1
1
0. Einhorn, C.; Einhorn, J.; Luche, J.-L. Synthesis 1989, 787.
1. Manson, T. J. Chem. Soc. Rev. 1997, 26, 447.
12. (a) Cintas, P.; Luche, J.-L. Green Chem. 1999, 1, 115; (b)
Clark, J.; Macquarrie, D. In Handbook of Green Chemistry
and Technology; Blackwell Science: Oxford, 2002; pp 372–
3
96, Chapter 16; (c) Lenard a˜ o, E. J.; Freitag, R. A.;
Dabdoub, M. J.; Batista, A. C. F.; Silveira, C. C. Quim.
Nova 2003, 26, 123.
1
1
1
3. Stefani, H. A.; Cella, R.; Dorr, F. A.; de Pereira, C. M. P.;
Gomes, F. P.; Zeni, G. Tetrahedron Lett. 2005, 46,
2
001.
4. Stefani, H. A.; Pereira, C. M. P.; Almeida, R. B.; Braga,
R. C.; Guzen, K. P.; Cella, R. Tetrahedron Lett. 2005, 46,
Acknowledgements
6
833.
5. (a) Cella, R.; Stefani, H. A. Tetrahedron 2006, 62, 5656; (b)
Cella, R.; Orf a˜ o, A. T. G.; Stefani, H. A. Tetrahedron Lett.
2006, 47, 5075.
The authors would like thank FAPESP (Grant 03/
0
1751-8 and fellowship 03/13897-7), CAPES and CNPq
for financial support.
16. General experimental procedure: A suspension of o-phenyl-
enediamine (1a) (0.108 g, 1.0 mmol), carbonyl compound
(
2 or 4) (1.1 mmol) and APTS (10 mol %) in 5 mL of
CH Cl was irradiated in a water bath of an ultrasonic
cleaner for 20 min. Then, the reaction was concentrated
under vacuum. Purification by silica gel chromatography
2
2
References and notes
1
. (a) Schutz, H. Benzodiazepines; Springer: Heidelberg,
982; (b) Smalley, R. K. In Comprehensive Organic
Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon:
Oxford, 1979; Vol. 4, p 600; (c) Landquist, J. K. In
Comprehensive Heterocyclic Chemistry; Katritzky, A. R.,
Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 1, p 166,
(
eluting with hexane–ethyl acetate, 8:2–6:4) yielded 1,5-
1
benzodiazepines (Tables 2 and 3).
1
Compound 3a: Yield: 83%. H NMR (300 MHz, CDCl ):
3
d ppm 7.37–7.33 (m, 2H), 7.23–7.18 (m, 2H), 2.8 (s, 2H),
1
3
2
.33 (s, 6H). C NMR (75 MHz, CDCl
3
): d ppm 157.9;
1
40.4; 127.6; 125.0; 43.3; 2727. MS: m/z (%) 173 (14); 172
1
70; (d) Randall, L. O.; Kappel, B. In Benzodiazepines;
(
100); 171 (41); 157 (15); 77 (10).
1
Garattini, S., Mussini, E., Randall, L. O., Eds.; Raven
Press: New York, 1973; p 27, and references cited therein.
. Atwal, K. S.; Bergey, J. L.; Hedberg, A.; Moreland, S. J.
Med. Chem. 1987, 30, 635.
. Merluzzi, V.; Hargrave, K. D.; Labadia, M.; Grozinger,
K.; Skoog, M.; Wu, J. C.; Shih, C.-K.; Eckner, K.; Hattox,
S.; Adams, J.; Rosenthal, A. S.; Faanes, R.; Eckner, R. J.;
Koup, R. A.; Sullivan, J. L. Science 1990, 250, 1411.
. (a) Di Braccio, M.; Grossi, G.; Romoa, G.; Vargiu, L.;
Mura, M.; Marongiu, M. E. Eur. J. Med. Chem. 2001, 36,
3
Compound 3f: Yield: 82%. H NMR (300 MHz, CDCl ):
d ppm 7.86 (t, J = 6 Hz, 2H), 7.75 (s, 1H), 7.68 (d,
J = 8.4 Hz, 1H), 7.45 (d, J = 8.3 Hz, 1H), 7.14 (t,
J = 8.2 Hz, 2H), 2.87 (s, 2H), 2.38 (s, 3H), 2.35 (s, 3H).
2
3
1
3
3
C NMR (75 MHz, CDCl ): d ppm 194.2; 159.6; 158.9;
1
4
1
43.2; 139.3; 133.6; 132.3; 130.1; 127.6; 125.6; 115.4; 115.1;
3.5; 27.6. MS: m/z (%) 295 (12); 294 (65); 199 (100);
23 (25).
4
1
Compound 5a: Yield: 85%. H NMR (300 MHz, CDCl
3
):
d ppm 7.14–7.12 (m, 1H), 6.99 (m, 2H), 6.74–6.73 (m, 1H),
9
35; (b) Tranquillini, M. E.; Cassara, P. G.; Corsi, M.;
1
3
2
.94 (br s, 1H), 2.36 (s, 3H), 2.22 (s, 2H), 1.34 (s, 6H).
C
Curotto, G.; Donati, D.; Finizia, G.; Pentassuglia, G.;
Polinelli, S.; Tarzia, G.; Ursini, A.; Van Amsterdam, F. T.
M. Arch. Pharm. 1997, 330, 353.
. Jarikote, D. V.; Siddiqui, S. A.; Rajagopal, R.; Daniel, T.;
Lahoti, R. J.; Srinivasan, K. V. Tetrahedron Lett. 2003, 44,
835.
. Varala, R.; Enugala, R.; Nuvula, S.; Adapa, S. R. Synlett
006, 1009.
3
NMR (75 MHz, CDCl ): d ppm 172.6; 141.0; 138.2; 127.1;
1
25.8; 122.3; 121.9; 68.6; 45.3; 30.7; 30.1. MS: m/z (%) 189
(
8); 188 (49); 173 (100); 92 (13).
5
1
Compound 5b: Yield: 78%. H NMR (300 MHz, CDCl
3
):
d ppm 6.86 (d, J = 4.1 Hz 2H), 6.58 (t, J = 4.5 Hz 1H),
1
1
3
2
.38 (s, 3H), 2.26 (s, 3H), 2.14 (s, 2H), 1.31 (s, 6H).
C
6
7
NMR (75 MHz, CDCl ): d ppm 171.5; 140.6; 137.4; 134.2;
3
2
1
25.0; 124.4; 120.2; 69.3; 45.1; 30.5; 29.8; 18.4. MS: m/z
. Yadav, J. S.; Reddy, B. V. S.; Praveenkumar, S.; Nagaiah,
K. Synthesis 2005, 480.
(
%) 2002 (22); 187 (100); 172 (5); 146 (39); 77 (10).