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Title: Synthetic approaches to derivatives of tropane
Author: Howarth, Nicola
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1991
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This thesis is a continuation of the work by Bathate, which had shown that intramolecular cyclisation of trans-1- (benzylamino)-4-chlorocycloheptane and hept-2-ene gave the corresponding nortropane and nortrop-6-ene derivatives. Problems were experienced in the reproducibility of Bathgate's route. Therefore, the intramolecular cyclisation step warranted further development. The best yields of cyclised products were attained when the solvent was changed to acetone. Other approaches to nortropane were sought. Reasonable yields of the cyclised material were only obtained when the nitrogen function was protected with a benzyl or p-methoxybenzyl group. 4-Benzyl aminocycloheptanone was successfully synthesised and its monocyclic amino-ketone and bicyclic amino-alcohol tautomers were found to be in equilibrium. Selected attempts to dealkylate/debenzylate tertiary amines, in view of obtaining nortrop-6-ene, gave variable results with expectations from the literature not always being fulfilled. It was decided to investigate the dealkylation/debenzylation of tertiary amines in a systematic way. Debenzylation of simple piperidine models was achieved using most of the procedures attempted but debenzylation of N-benzylnortropane and N- benzylnortrop-6-ene was unsuccessful. Removal of the p- methoxybenzyl group from N-p-methoxybenzylnortrop-6-ene was partly accomplished using ?-chloroethylchloroformate to afford nortrop-6-ene. Application of the intramolecular cyclisation route to substituted 1,3-cycloheptadienes was explored. The two dienes choosen for this purpose were 1,3-cycloheptadien-6-ol and 1, 3-cycloheptadien-6-one. Both can be prepared from tropone. No difficulties were encountered with the initial nitroso cycloaddition but problems arose later in the pathway using 1,3- cycloheptadien-6-ol due to complications with the hydroxyl protecting group. However, synthesis of N-benzylnortropan-3-one and N-benzylnortrop-6-en-3-one ethylene acetal was achieved from 1, 3-cycloheptadien-6-one ethylene acetal. The epoxidation of azabicyclic alkenes with m-chloroperoxy benzoic acid was examined. Both N-carbethoxy-1,4-dihydro napthalen-1,4-imine and N-carbethoxy-1,4-dihydroanthracen-l,4- imine gave stereospecifically the corresponding exo- epoxides. Epoxidation of N-carbethoxy-2-azabicyclo [2.2.2] oct-5-ene, though was non-stereospecific. Treatment of N-benzyl-2-azabicyclo [2.2.1] hept-5-ene, 5,8-dimethoxy-1,4-dihydronapthalen-l,4-imine and 9-methyl-5,8-dimethoxy-l,4-dihydronapthalen-l,4-imine with m-chloro peroxybenzoic acid resulted in failure, even after protonation to avoid N-oxide formation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available