Solventless lactam synthesis by intramolecular cyclizations of alpha-iminoester derivatives under microwave irradiation.

Fatima-Zohra Zradni,Jack Hamelin,Aicha Derdour

doi:10.3390/12030439

Abstract

We have previously reported a new synthesis of amides from esters and amines under microwave irradiation, offering much higher yields than those achieved with conventional heating [1]. We have now extended these studies to the ring closure of neat iminoesters I2, I3 and I4-I6 to give five- and six-membered ring lactams L5, L6 and larger lactams L7-L9 (where I means imine and L means lactam), respectively, under both classical heating conditions and microwave irradiation.

Highlights

Lactams are of considerable interest in a number of areas, ranging from drug discovery to the polymer industry, and their synthesis has been, and still is, a topic of significant interest for organic chemists
Encouraged by our recent results on the synthesis of amides under microwave irradiation [1], and by other publications in which this original synthetic method was used, we report that neat imines can be utilised for lactam synthesis by simple cyclization either under classical heating conditions or under microwave irradiation (Scheme 1)
The aim of the present paper is to present and discuss a simple and new strategy for the formation of C-C bonds through a direct alkylation of α-iminoesters under solvent free conditions, using potassium tert-butoxide as base, and the cyclisation of the products under microwave irradiation to synthesize five- to ten-membered ring lactams

Summary

Introduction

Lactams are of considerable interest in a number of areas, ranging from drug discovery to the polymer industry, and their synthesis has been, and still is, a topic of significant interest for organic chemists. Among the numerous methods developed radical strategies [2], especially intramolecular cyclizations of unsaturated α-carbamoyl radicals [3,4] or in our case imines, have been. Molecules 2007, 12 shown to be some of the best tools for the construction of a variety of lactam skeletons ranging from βlactams to medium- or larger sized ones. Encouraged by our recent results on the synthesis of amides under microwave irradiation [1], and by other publications in which this original synthetic method was used, we report that neat imines can be utilised for lactam synthesis by simple cyclization either under classical heating conditions or under microwave irradiation (Scheme 1). Scheme 1 R Cl H3N PhCHO CO2Me (i).

Objectives

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Results

Conclusion