Bis(2-phenylaminoethyl)amine hydrochloride (1) is readily prepared by reaction of bis(2-chloroethyl)amine hydrochloride and four molar equivalents of aniline in methanol solvent at low temperature. The crude is purified with vacuum distillation. From the reaction of bis(2-phenylaminoethyl)amine and POCl3, the bicyclic compound (2) was only obtained. Reactions proceed in high yield, under mild conditions. The structures of prepared compounds were confirmed by 1H NMR, 31P NMR, 13C NMR spectroscopy and X-ray cristallographie.

Cyclophosphamide, an alkylating agent prepared over 45 years ago by Arnold [1], has become very widly used in cancer chemotherapy. An unique mode of action involves hydroxylation of the heterocycle, followed by breakdown to generate phosphoramide mustard, which is a potent to DNA alkylator [2]. Other agents containing the masked bis(2-chloroethyl)amine group are also in clinical use, or pre-clinical evalution. These include the phenylbutyric acide compound chlorambucil and the phenylanine derivative melphalan [3].

Since the first synthesis of phosphoramid mustard and evaluation of its antitumor activities, investigation of the chemistry and biological activity of phosphoramide mustards has been vigorously pursued in many research laboratories. Friedman and co-workers [4,5] have prepared aliphatic,

Two-step Synthesis of 2, 8-Diphenyl-2, 5, 8-Triaza-1- Phosphabicyclo [3.3.0] Octane 1-Oxide

Mahdi Jalalifar *, Shirinbek Khalikov

Departman of Chemistry, Tajik National University, Dushanbe, Tajikistan

Copyright © 2012 by Modern Scientific Press Company, Florida, USA

Int. J. Modern Org. Chem. 2012, 1(2): 129-135 130

aromatic and cyclic phosphorodiamidate, phosphorotriamidates, phosphorodiamidic monoesters, phosphoroamidic diesters, as well as various phosphorodiamidic acids and phosphoramidic acid monoesters of N,N-bis(2-chloroethyl)amine .

Subsequently, the same authors have reported the synthesis of the diamide derivatives via a phosphoramidochloridate prepared by reacting N,N-bis(2-chloroethyl)phosphoramidodichloridate with phenols [6-9]. The antitumor activities of these compounds were investigated and it is reported that some of them have shown activity.

This work reports the synthesis synthesis of 2, 8-diphenyl-2, 5, 8-triaza-1-phosphabicyclo [3.3.0] octane 1-oxide. These cyclization reactions as a route to interesting heterocyclic ring systems were briefly explored. Reaction pathway for the preparation of target compounds 2 in Scheme1.