SIEGELINDE BAUERMEISTER, AGNES M. MODRO, TOM A. MODRO, and ANDRZEJ ZWIERZAK. Can. J. Chem. 69,811 (1991). Five N-(2-chloroethyl)phosphorotriamidates, (RNH)2P(0)NHCH2CH2Cl, have been synthesized, and their behavior under strongly basic conditions was studied. For N-alkyl derivatives (R = Me, PhCH2), base-promoted intramolecular displacement of chloride yielded the N-phosphorylated aziridine, (RNH)?P(0)NC2H4, as the exclusive cyclization product. For N-aryl derivatives (R = Ar), both the aziridine and the 1,3,2-diazaphospholidine, RNHP(0)NHCH2CH2NR, products could be obtained in comparable yields. The N-aromatic cyclic products are mutually interconvertible: 1,3,2-diazaphospholidines rearrange to the corresponding aziridines upon treatment with base, while bromide ions catalyze the reverse isomerization.Key words: phosphoramidates acidity, N-phosphorylated aziridines -1,3,2-diazaphospholidines isomerization, 1,3 vs. 1,5 cyclization.SIEGELINDE BAUERMEISTER, AGNES M. MODRO, TOM A. MODRO et ANDRZEJ ZWIERZAK. Can. J. Chem. 69, 81 1 (1991). On a rCalisC la synthkse de cinq N-(2-chlorokthyl)phosphorotriamidates, (RNH)2P(0)NHCH2CH2C1, et on a CtudiC leur comportement dans des conditions fortement basiques. Pour les dCrivCs N-alkylCs (R = Me, PhCH2), le dCplacement intramolkculaire du chlorure, catalysC par les bases, fournit l'aziridine N-phosphorylke, (RNH)2P(0)NC2H4, comme seul produit de cyclisation. Pour les dCrivCs N-arylks (R = Ar), on peut obtenir avec des rendements comparables l'aziridine ainsi que la 1,3,2-diazaphospholidine, RNHP(O)NHCH?CH~NR. Les produits cycliques N-aromatiques sont mutuellement interconvertibles; les 1,3,2-diazaphospholidines se transposent en aziridines correspondantes par traitement avec des bases alors que les ions bromures catalysent l'isomtrisation inverse.Mots elks : acidit6 de phosphoramidates, isomerisation aziridines N-phosphorylCes -1,3,2-diazaphospholidines, cyclisations 1,3 vs. 1,5.[Traduit par la rkdaction]The phosphoramide mustard 1 is believed to be the active metabolite d t h e anti-tumor alkylating drug, cyclophosphamide, its cytotoxic action involving the cross-linking produced in cellular DNA (1). The alkylating reactivity of 1 is attributed to its intramolecular cyclization to-the aziridinium ion, followed by the intermolecular reaction of that intermediate with a biological nucleophile (2). N-Phosphorylated aziridines (e.g., aphamide 2 ) are known inhibitors of cell division, the property Intramolecular reactivity of a system of type 1 can, however, involve not only the 1,3 displacement of chloride ion (aziridinium ion formation), but also the 1,5 substitution in the NPNCCCl system, yielding the 1,3,2-diazaphospholidine product.Such cyclization was in fact postulated (4) and demonstrated (5) for the nonenzymatic hydrolysis of cyclophosphamide itself. Similarly, a compound like 2 may undergo a nucleophilic ring opening reaction not only with an external nucleophile, but via the attack of the endocyclic nitrogen, yielding the isomeric 1,3,2-diazaphospholidine skeleton. Su...
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