The synthesis and structural characterisation of novel 4- and 5- membered nitrogen heterocycles derived from azoacetates

Azo-drugs are among the earliest fully synthetic chemotherapeutic agents known (Prontosil 1935). However the synthesis and application of phenylazo compounds in the area of medicinal chemistry has largely been restricted to derivatives of primary aromatic amines. This has been due, in the most part, to a perceived view that azo compounds not containing two aromatic groups are unstable. The syntheses of a number of novel heterocycles including important medicinal structures directly linked to an arylazo moiety are reported. The literature survey introduces a range of four and five membered heterocycles with established pharmaceutical activity. In particular the attention is drawn to molecules containing the azo functional group. This thesis contains a chapter detailing the introduction of a variety of alkyl and aryl groups into novel �-lactam molecules bearing the arylazo and arylazoxy functional groups. The succeeding chapter investigates the role of the azocarbinol group as an intermediate in the rearrangement of azoacetates to N-acyl hydrazides. The deacetylation reactions of azoacetates derived from L-threonine are also described. This work resulted in the synthesis of novel oxazolidinone and hydantoin species, also with phenylazo attachments. The final chapter describes the incorporation of a cyanide unit into heterocyclic compounds through intermolecular cyclisations of a range of substituted azoacetates when potassium cyanide is employed as base. It is shown that the azo group may be incorporated into the cyclic system to produce pyrazoles, or as an exocyclic pendant group attached to a 2- iminopyrrolidin-5-one; X-ray crystal structures of these compounds are reported. The 2- iminopyrrolidin-5-one was easily modified to produce the corresponding pyrrolidine-2,5-dione (succinimide) derivative. All of the heterocycles reported were generated from azoacetates derived from simple, cheap and readily available starting materials (ethylacetoacetate and L-threonine), thus showing azoacetates to be versatile and valuable building blocks in the field of heterocyclic chemistry.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Dublin City University

Year dc:date.issued

2009

Author dc:creator

• O'Halloran, Neil

• Chemistry

Language dc:language

en