1,5-Benzodiazepine derivatives were synthesized by the condensation reactions of o-phenylenediamine and ketones catalyzed by bismuth (III) salts under mild conditions. This method is easy, efficient, environment and eco-friendly, free of toxic catalysts, and gives good to excellent yields of 1, 5-benzodiazepines. 1. Introduction The synthesis of 1,5-benzodiazepines and their derivatives have attracted considerable attention of researchers, including pharmaceutical and organic synthetic chemists, in recent years because of their medicinal properties namely antianxiety, hypnotic, antidepressive, tranquilizing, antiinflammatory, anticonvulsant, antifeedant, antibacterial, and analgesic agents [1–4]. In addition, 1,5-benzodiazepines are valuable synthons used for the preparation of other fused ring compounds such as triazolo, oxazino or furano-benzodiazepines [5, 6]. Benzodiazepines derivatives are also used in industry as dyes for acrylic fibers in photography [7]. Due to their wide range of pharmacological activities and industrial and synthetic applications, the development of practical and green protocols continues to be a challenging endeavour in synthetic chemistry. In recent years, many methods for their preparation are reported in the literature. These include condensation reactions of o-phenylenediamine with α, β-unsaturated carbonyl compounds [8], β-haloketones [9], β-aminoketones [10] or ketones promoted by BF3·OEt2 [11], NaBH4 [12], polyphosphoric acid or SiO2 [13], ceric ammonium nitrate (CAN) [14], MgO/POCl3 [15], Yb(OTf)3 [16], Al2O3/P2O5 or AcOH under microwave conditions [17], Amberlyst-15 in ionic liquid [18], CeCl3/7H2O/NaI supported on silica gel [19], InBr3 [20], 1-butyl-3-methylimidazolium bromide ([bmim]Br) [21], Sc(OTf)3 [22], and Nb(Cl)3 [23]. However, many of these methodologies have one or more shortcomings, such as long reaction time, poor yields of the products, drastic reaction conditions, occurrence of several side products, expensive reagents, high catalyst loading, and tedious workup procedures. Bismuth (III) salts have emerged in the recent years as “eco-friendly” reagents suitable for green chemistry. They have received considerable attention as mild Lewis acids [24–27] for an array of organic transformations because the catalysts are inexpensive, relatively nontoxic, moisture and air tolerant, environmentally benign, and commercially available. Ionic liquid is used as an alternative to traditional solvents for organic reactions particularly in the area of green chemistry. Thus, considering the advantages and applications
References
[1]
H. Schutz, Benzodiazepines, Springer, Heidelberg, Germany, 1982.
[2]
J. K. Landquist, in Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees, Eds., vol. 1, p. 116, Pergamon, Oxford, UK, 1984.
[3]
L. O. Randall and B. Kamal, in Benzodiazepines, S. Garattini, E. Mussini, and L. O. Randall, Eds., p. 27, Raven Press, New York, NY, USA, 1973.
[4]
J. R. D. Baun, F. M. Pallos, and D. R. Baker, “5-furoyl-2,2,4-trimethyl-1,4-dihydro-1H-1,5-benzodiazepine as an anti-inflammatory agent,” US patent no. 3,978,227, 1976; Chem. Abstr. 1977, 86, 5498d.
[5]
M. C. Aversa, A. Ferlazzo, P. Giannetto, and F. H. Kohnke, “A convenient synthesis of novel [1,2,4]triazolo[4,3- a][1,5]benzodiazepine derivatives,” Synthesis, vol. 3, pp. 230–231, 1986.
[6]
A. Chimirri, S. Grasso, R. Ottana, G. Romeo, and M. Zapala, “Synthesis and stereochemistry of Novel [1,2,4] oxadiazolo[4,5-][1,5]benzodiazepine aerivatives,” Journal of Heterocyclic Chemistry, vol. 27, no. 2, pp. 371–374, 1990.
[7]
R. C. Haris and J. M. Straley, “Cationic polymethine dyes for acrylic fibers,” US patent no. 1,537,757, 1968; Chem. Abstr. 1970, 73, 100054w.
[8]
P. Stahlofen and W. Ried, “über heterocyclische Siebenringsysteme, V. Umsetzung von o-Phenylendiamin mit, β-Ungesttigten Carbonylverbindungen,” Chemische Berichte, vol. 90, pp. 815–824, 1957.
[9]
W. Ried and E. Torinus, “über heterocyclische Siebenringsysteme, X. Synthesen kondensierter 5-, 7- und 8-gliedriger Heterocyclen mit 2 Stickstoffatomen,” Chemische Berichte, vol. 92, pp. 2902–2916, 1959.
[10]
R. Gheorghe, E. Comanita, and B. Bogdan, “Synthesis and reactivity of mannich bases. XIV. Base-catalyzed cyclocondensation of β-aminoketones to 1,5-benzodiazepines and 1,4-naphthodiazepines,” Acta Chimica Slovenica, vol. 49, no. 3, pp. 575–585, 2002.
[11]
J. A. L. Herbert and H. Suschitzky, “Syntheses of heterocyclic compounds. Part XXIX. Substituted 2,3-dihydro-1H-1, 5-benzodiazepines,” Journal of the Chemical Society, Perkin Transactions, vol. 1, pp. 2657–2661, 1974.
[12]
H. R. Morales, A. Bulbarela, and R. Contreras, “New synthesis of dihydro-and tetrahydro-1,5-benzodiazepines by reductive condensation of o-phenylenediamine and ketones in the presence of sodium borohydride,” Heterocycles, vol. 24, no. 1, pp. 135–139, 1986.
[13]
D. I. Jung, T. W. Choi, Y. Y. Kim et al., “Synthesis of 1,5-benzodiazepine derivatives,” Synthetic Communications, vol. 29, no. 11, pp. 1941–1951, 1999.
[14]
R. Varala, R. Enugala, S. Nuvula, and S. R. Adapa, “Ceric ammonium nitrate (CAN) promoted efficient synthesis of 1,5-benzodiazepine derivatives,” Synlett, no. 7, pp. 1009–1014, 2006.
[15]
M. S. Balakrishna and B. Kaboudin, “A simple and new method for the synthesis of 1,5-benzodiazepine derivatives on a solid surface,” Tetrahedron Letters, vol. 42, no. 6, pp. 1127–1129, 2001.
[16]
M. Curini, F. Epifano, M. C. Marcotullio, and O. Rosati, “Ytterbium triflate promoted synthesis of 1,5-benzodiazepine derivatives,” Tetrahedron Letters, vol. 42, no. 18, pp. 3193–3195, 2001.
[17]
M. Pozarentzi, J. Stephanidou-Stephanatou, and C. A. Tsoleridis, “An efficient method for the synthesis of 1,5-benzodiazepine derivatives under microwave irradiation without solvent,” Tetrahedron Letters, vol. 43, no. 9, pp. 1755–1758, 2002.
[18]
J. S. Yadav, B. V. S. Reddy, B. Eshwaraiah, and K. Anuradha, “Amberlyst-15?: a novel and recyclable reagent for the synthesis of 1,5-benzodiazepines in ionic liquids,” Green Chemistry, vol. 4, no. 6, pp. 592–594, 2002.
[19]
G. Sabitha, G. S. Kiran Kumar Reddy, K. Bhaskar Reddy, N. Mallikarjuna Reddy, and J. S. Yadav, “A new, efficient and environmentally benign protocol for the synthesis of 1,5-benzodiazepines using cerium(III) chloride/sodium iodide supported on silica gel,” Advanced Synthesis and Catalysis, vol. 346, no. 8, pp. 921–923, 2004.
[20]
J. S. Yadav, B. V. S. Reddy, S. Praveenkumar, and K. Nagaiah, “Indium(III) bromide: a novel and efficient reagent for the rapid synthesis of 1,5-benzodiazepines under solvent-free conditions,” Synthesis, no. 3, pp. 480–484, 2005.
[21]
D. V. Jarikote, S. A. Siddiqui, R. Rajagopal, T. Daniel, R. J. Lahoti, and K. V. Srinivasan, “Room temperature ionic liquid promoted synthesis of 1,5-benzodiazepine derivatives under ambient conditions,” Tetrahedron Letters, vol. 44, no. 9, pp. 1835–1838, 2003.
[22]
S. K. De and R. A. Gibbs, “Scandium(III) triflate as an efficient and reusable catalyst for synthesis of 1,5-benzodiazepine derivatives,” Tetrahedron Letters, vol. 46, no. 11, pp. 1811–1813, 2005.
[23]
S. T. Gao, W. H. Liu, J. J. Ma, C. Wang, and Q. Liang, “NbCl as an efficient catalyst for the synthesis of 1,5-benzodiazepine derivatives,” Synthetic Communications, vol. 39, no. 18, pp. 3278–3284, 2009.
[24]
G. Sabitha, R. S. Babu, E. V. Reddy, and J. S. Yadav, “A novel, efficient, and selective cleavage of acetals using bismuth(III) chloride,” Chemistry Letters, no. 9, pp. 1074–1075, 2000.
[25]
H. Firouzabadi, I. Mohammadpoor-Baltork, and S. Kolagar, “A rapid, selective, and efficient method for deprotection of silyl ethers catalyzed by bismuth(III) salts,” Synthetic Communications, vol. 31, no. 6, pp. 905–909, 2001.
[26]
Y. Matano and T. Ikegami, in Organobismuth Chemistry, H. Suzuki and Y. Manato, Eds., chapter 2, pp. 21–245, Elsevier, New York, NY, USA, 2001.
[27]
N. M. Leonard, L. C. Wieland, and R. S. Mohan, “Applications of bismuth(III) compounds in organic synthesis,” Tetrahedron, vol. 58, no. 42, pp. 8373–8397, 2002.
[28]
A. C. Chaskar, B. P. Langi, A. Deorukhkar, and H. Deokar, “Bismuth chloride-sodium nitrite: a novel reagent for chemoselective N-nitrosation,” Synthetic Communications, vol. 39, no. 4, pp. 604–612, 2009.