Cyclosdditions with Acylhydrazones. Selective Diastereomeric Pyrazolidine Synthesis and Nitrile Acylimine Synthons

Abstract

Arylaldehydes N-acylhydrazones 1 undergo dipolar cycloadditions to N-arylmaleimides 2 to give two diasterkmeric kinetic and thermodynamic pyrazolidines 3 and 4. Oxidation of 3 and 4 gave the corresponding pyrazolines 5 which were also obtained directly from compounds 1 and 2 in nitrobenzene.The present investigation offers an easy access Fo nitFile acylimine synthons 6.A general principle for the synthesis of five-membered heterocycles has been intrg 1 duced with the revolutionary development of the 1,3-dipolar cycloadditions .However the reaction depends on the availability of the precursors, especially those needed for the generation of the appropriate 1.3-dipolar species.Thus, although many nitrile imines have been successfully obtained from the appropriate precursors1, their N-acyl derivatives have not, to the best of our knowledge, been reported.Recent reports showed that arylaldehyde N-phenylhydrazones undergo [3+21 2 cycloadditions to maleimides and acetylene dicarhoxylates .We have now investigated the reaction of arylaldehyde N-acylhydrazones 1 with N-arylmaleimides 2 as a representative dienophile.When a mixture of (1: Ar = Ar' = Ph, 0.1 mmol) and N-phenylmaleimide & (0.12 -01) was heated at 170-180°C for 1.5 h, a 6 0 % yield of crystalline compound I 3250 (NH), 1740 cm-' (C.0).90 MHz H-nmr (DMSO-d6): Signals for one H each at 5 4.22 (d, Ha), 4.90 (s, Hb), 5.95 (d, Hc), and 3.50 (s, NH) ppm; Jah=O, Jac=7Hz.