Studies of thieno[b]pyridine derivatives

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Holmes, D., 1985. Studies of thieno[b]pyridine derivatives. PhD, Nottingham Trent University.

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Abstract

The work described in this thesis continues previous studies in these laboratories on the chemistry of thieno[3,2-b]pyridines and extends it to new topics and the thieno[2,3-b]pyridine system.

The overall aim of the project was the synthesis of thienopyridine analogues of quinoline alkaloids. With this end in view a study of the chemistry of these systems was undertaken in order to be able to plan the synthesis of such analogues.

Firstly the preparation of thieno[3,2-b]pyridines developed in these laboratories was applied to the production of the related [2,3-b] derivatives which were then converted into chloro compounds. The methods successful for the [3,2-b] fused compounds failed in this case but with other reagents the desired conversions were achieved.

A study of the nucleophilic substitution of chloro compounds in both systems was then undertaken and some erroneous conclusions reported previously were corrected. In all cases it was found that chlorine atoms JT - to the pyridine nitrogen atom were readily displaced but those a - to the nitrogen atom were much more resistant to displacement.

The use of 13C n.m.r. spectroscopy in structure determination has been studied. The spectra of a large number of compounds were recorded and the resonances assigned; this method was of particular use in investigating keto-enol tautomerism.

Electrophilic substitution reactionson the parent systems have been reported in the literature but little work has been carried out on other derivatives. The reactions of a number of derivatives with electrophiles were studied and some interesting differences in both site and degree of reaction were observed.

The use of isatoic anhydrides in the reparation of quinolines has been applied to the synthesis of some related thienopyridines. The novel thiophene analogues of isatoic anhydrides were prepared and used to produce analogues of several 2-aryl-4-quinolone alkaloids.

Several routes to thienopyridine analogues of furoquinoline alkaloids were investigated. The preparation of angularly fused tricyclic systems was quite straightforward but linear fusion was more difficult to achieve.