Studies on Cycloadducts of Thebaine and Thioaldehydes

McQuillan, James Thomas (1993) Studies on Cycloadducts of Thebaine and Thioaldehydes. PhD thesis, University of Glasgow.

Abstract

A new route to the synthesis of 14beta-alkylmorphinans, of interest as potential analgesics, has been developed. Several such morphinans have been produced by desulphurisation of the Diels-Alder cycloadducts of thebaine and thioaldehydes, or of related, rearranged codeinones. Several methods of desulphurisation were explored. For example the 8alpha-ethoxycarbonyl-7-thia cycloadduct (49a) gave the 6,7-didehydro-14beta-ethyl acetate derivative (114) on desulphurisation with Raney nickel, and also with tri-n-butyltin hydride; the (19S)-anilinoenone and thiobenzaldehyde codeinone derivatives (131) and (138), each gave 8beta,14beta-methano derivatives, i.e. (132) and (139), respectively, with Raney nickel; while the ethyl ester codeinone derivative (86) gave the 8beta,14beta-alkylcodone (128) on treatment with aluminium amalgam. Raney nickel was found to be the best method for desulphurisation. The Diels-Alder cycloadducts of thebaine and thioaldehydes were known to undergo molecular rearrangements under certain conditions. Several new rearrangements of these cycloadducts were encountered during this project. For example the 7-thia cycloadduct (49a) of thebaine and ethyl thioxoacetate gave a cyclopropane derivative (85) and a lactone (176) when treated with base under different conditions. As a necessary adjunct to studies on Raney nickel desulphurisation in ethanol, the chemistry of various codeinone acetals was investigated. For example, the cycloadduct (49b) of thebaine and p-nitrothiobenzaldehyde was converted in hot ethanolic ethoxide into a rearranged, 6,6-diethoxy derivative (99). Surprisingly, when this acetal was treated with methanolic methoxide, exchange of the hindered 6alpha-ethoxy group occurred, to give the corresponding 6beta-ethyl -6alpha-methyl acetal (102).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: G W Kirby
• Keywords: Organic chemistry
• Date of Award: 1993
• Depositing User: Enlighten Team
• Unique ID: glathesis:1993-74658
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 17:18
• Last Modified: 27 Sep 2019 17:18
• URI: https://theses.gla.ac.uk/id/eprint/74658