Aspects of the chemistry of 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids and related compounds

Hadfield, JA, 1984. Aspects of the chemistry of 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids and related compounds. PhD, Nottingham Trent University.

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Abstract

The main topic in this investigation is an exploration of routes to spirolactones derived from 1-benzyl-l,2,3j4-tetrahydro- isoquinoline-1-carboxylic acids (tetrahydroisoquinaldic acids); by analogy with related cyclohexadienone spiro- -lactones, the iso- quinaldic acid lactones may be useful intermediates in the synthesis of more complex molecules such as bisbenzylisoquinolines. Previous work had established that oxidation of 1-benzyltetrahydroisoquinaldic acids having oxygen substituents on the 6 or 7 position occurs on the isoquinoline benzene ring and does not lead to spirolactone formation, necessitating the synthesis of acids without such substitution; no such acids have been described. As model compounds, a series of isosteric 1-benzyl-tetrahydronaphthalene-l-carboxylic acids were prepared by reaction of 1-lithiotetrahydronaphthalene carboxylic esters with benzyl halides. On chemical or anodic oxidation, acids with phenolic, methoxy, or sulphonamide functions on the 4'-benzyl position all gave good yields of spirolactones. In a novel synthesis of 1-benzyltetrahydroisoquinaldic acids without 6- or 7- alkoxy substituents, lithiation of N-pivaloyltetrahydroisoquinoline was used to introduce benzyl and carboxyl groups at the 1-position. None of the resulting acids gave spirolactones on chemical or anodic oxidation, but reaction of N-bromosuccinimide with a 4'-hydroxybenzyltetrahydro- isoquinaldic acid yielded a brominated cyclohexadienone spirolactone.

A study has been made of the scope of a reaction of 1-benzyl- tetrahydroisoquinaldic acids with trifluoroacetic anhydride in pyridine, which affords 7, 8-dihydroprotoberberines. It has been established that the reaction is synthetically useful only for dimethoxy- or trimethoxybenzyl acids and occurs via a N-trifluoro- acetyl acid.

A number of N-sulphonylcyclohexadienimine spirolactones have been prepared and subjected to attack by nucleophiles. Cyanide was successfully inserted into the cyclohexadiene moiety, accompanied by lactone ring opening.

An attempt to prepare a gem-dimethylphenylpyruvic acid was unsuccessful, but 3-thienylpyruvic acid has been prepared.

Item Type:	Thesis
Creators:	Hadfield, J.A.
Date:	1984
ISBN:	9781369325669
Identifiers:	Number Type PQ10290317 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	06 Jul 2021 10:32
Last Modified:	10 Apr 2024 15:37
URI:	https://irep.ntu.ac.uk/id/eprint/43344

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