Ketones Trofimov pyrrole synthesis

The Trofimov pyrrole synthesis (the Trofimov Reaction) refers to the conversion of ketones to pyrroles in the presence of NH2OH, KOH and DMSO at elevated temperatures. The reaction was shown to occur via hydroxylamine and 0-vinylhydroxylamine intermediates. 

Over the last decades, a novel branch of the pyrrole chemistry, based on the reaction of ketones (ketoximes) with acetylenes in the superbase catalytic systems (the Trofimov reaction), has emerged and keeps progressing rapidly. New facile and highly efficient approaches to the diverse compounds of the pyrrole series have been developed. The investigations in this line are gathering momentum. Not only the discoverers and developers of novel pyrrole synthesis (the authors of this monograph) but many other research teams both in Russia and abroad are engaged in these studies. 

General synthesis of pyrroles and 1-vinylpyrroles by the reaction of ketoximes with acetylenes and their synthetic equivalents (vinyl halides and dihaloethanes) in the presence of the strongly basic KOH/DMSO system (Trofimov reaction) has been reviewed ° in recent years. Therefore, in the present work this reaction will be described very shortly. In principle, pyrrole (51) synthesis can be carried out as a one-pot procedure by treating ketones (49) with hydroxylamine and then reacting the ketoximes (50) formed with acetylenes (equation 22). 

Extention of the reaction of ketoximes with acetylene to oximes of hydroxyalkyl ketones can lead to the synthesis of inaccessible, functionally substituted pyrroles and A-vinyl derivatives. However, the methyl a- and /3-hydroxyalkyl ketoximes used by Trofimov et al. (80ZOR410) appeared to react with acetylene in the KOH/DMSO system in an abnormal way. 

Two-step synthesis of pyrroles from ketones and acetylenes via the Trofimov reaction 03MI20. 

In the 1980s, Boris A. Trofimov published several manuscripts describing the synthesis of pyrroles and vinylpyrroles from ketones, hydroxylamine and acetylene. The reaction was believed to occur via hydroxylimine formation, followed by O-vinylation, rearrangement, then ring closure. The Trofimov reaction has been studied in limited detail but has been shown to have application to the synthesis of a variety of pyrroles. 

Synthesis of pyrroles from ketones (through ketoximes) and propyne-allene mixture, a large-scale side product of hydrocarbons pyrolysis, essentially expands the preparative possibilities of the Trofimov reaction. 5-Methyl-substituted pyrroles, having diverse substituents in the positions 2 and 3, become readily available for the first time. 

For 40 years since its discovery, the reaction of ketones (ketoximes) with acetylene has recommended itself as a reliable preparative tool for wide application in chemistry of pyrroles and their N-vinyl derivatives. Systematic development of novel syntheses of pyrroles, and especially N-vinylpyrroles via the Trofimov reaction, is still progressing. There is reason to hope that this will lead not only to the further enhancement of the preparative importance of this synthesis but also to the discovery of its new variants and analogs. The increased availability of N-vinylpyrroles stimulates synthetic, physical-chemical [507,729-755], and theoretical [756-759] investigations in the field and also works on polymerization and practical application of these compounds [697-700,709-728]. 

Mikhaleva, A.L and E.Yu. Schmidt. 2002. Two-step synthesis of pyrroles from ketones and acetylenes through the Trofimov reaction. In Selected Methods for Synthesis and Modification of Heterocycles, vol. 1, ed. V.G. Kartsev, pp. 334-352. Moscow, Russia IBS Press. 

Schmidt, E.Yu., A.I. Mikhaleva, A.M. VasU tsov et al. 2005. A straightforward synthesis of pyrroles from ketones and acetylene A one-pot version of the Trofimov reaction. Arkivoc vii 11-17. 

Mikhaleva, A.I., E.Yn. Schmidt, A.V. Ivanov et al. 2007. Selective synthesis of 1-vinyl-pyrroles directly from ketones and acetylene Modification of the Trofimov reaction. Zh Org Khim 43 (2) 236-238. 

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