Facile synthesis of novel alpha-methylene-pyrazole-carboxylate substituted imines and trans-beta-lactams: Versatile synthons for diverse heterocyclic molecules

摘要

A simple, facile, and high yielding stereoselective approach for the integration of -methylene-pyrazole-carboxylates at the -lactam nucleus is described. These monocyclic -lactams have been synthesized by treatment of 2-phenoxy/benzylthio/phenylthio ethanoic acids or acetoxyacetyl chloride/phthalimidoacetyl chloride 5a-e with novel -methylene-pyrazole-carboxylate imines 4a-c using Et3N and POCl3 in refluxing toluene. All of the newly synthesized -methylene-pyrazole carboxylate imines 4a-c and their -lactam derivatives 6a-h have been fully characterized by spectroscopic techniques such as FTIR, NMR (H-1, C-13, and C-13 DEPT-135), 2D-NMR (COSY and HSQC), and elemental analyses (CHN). The cycloaddition reaction was found to be highly stereoselective leading to the exclusive formation of trans--lactams 6a-h and trans configuration was assigned with respect to coupling constant values of C3-H and C4-H. The novel -lactams 6a-h bearing -methylene-pyrazole-carboxylate ring system will serve as useful synthons for highly functionalized acids, acetohydrazides/pyrazolones, alcohols, pyrazole carboxamides, peptides, and promising biologically active agents.