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Title: Studies on the synthesis and reactivity of fused 3,4-isoxazoles
Author: Duffy, Kevin James
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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This thesis is concerned with the synthesis of various fused, 3,4-isoxazoles by the thermal cyclisation of 2-nitroaryl and 2-nitroheteroaryl acetic acid derivatives and the exploitation of the uses of these compounds in heterocyclic synthesis by their reduction to afford 2-aminoaryl and heteroaryl ketones followed by the annulation of these latter derivatives. Heating solutions of 2-(3-nitropyrid-2-yl)propanedioate esters under reflux in inert solvents afforded isoxazolo[4,3-b]pyridine-3-carboxylate derivatives. The successful application of this novel synthesis on a large scale was crucially dependent on the physical removal of the corresponding alcohol component from the reaction mixture. The thermal cyclisation of various 2-substituted 2-(3-nitropyrid-2-yl)ethanoates was also examined and in the case of cyano derivatives afforded the anticipated isoxazolo[4,3-b]pyridines but was less successful for substrates containing keto groups. 2-(3-Nitropyrid-2-yl)ethanoate failed to cyclise to afford the parent isoxazolo[4,3-b]pyridine. Evidence is presented for the involvement of ketene intermediates in these thermal cyclisation reactions. Reduction of the isoxazol[4,3-b]pyridine-3-carboxylate derivatives gave either 2-(3-aminopyrid-2-yl)-2-hydroxyethanoate or 2-(3-aminopyrid-2-yl)-2-oxoethanoate derivatives depending on the substrate, the former compounds being converted into the latter by oxidation with manganese dioxide. Annulation of the 2-(3-aminopyrid-2-yl)-2-oxoethanoates produced then gave a variety of substituted 1,5-napthyridin-2(1H)-one derivatives. The chemical transformations of these new 1,5-napthyridine derivatives was also briefly examined. 1,7-Napthyridin-2(1H)-one derivatives were also prepared by a similar sequence of reactions commencing with the thermal cyclisation of diethyl 2-(3-nitropyrid-4-yl)propanedioate to give ethyl isoxazolo[3,4-c]pyridine-3-carboxylate followed by reductive ring opening of the latter and subsequent annulation of ethyl 2-(3-aminopyrid-4-yl)-2-oxoethanoate so produced.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available