Synthesis of spiroheterocycles by oxidation of sulphonamides

Musto, D.R., 1981. Synthesis of spiroheterocycles by oxidation of sulphonamides. PhD, Nottingham Trent University.

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Abstract

The oxidation of l-benzyl-l, 2,3,4-tetrahydroisoq'uinoline-1-carboxylic acids to isoquinaldic spirodlenelactones and the reaction of these with nucleophiles may provide an efficient route to substituted benzylisoquinolines and to bisbenzylisoquinolines. Accordingly the oxidation of the model compound 3-(4-hydroxyphenyl)-propanoic acid to 1-oxaspirodsca-[4.5]-6,9-diene-2,8-dione was studied in an unsuccessful attempt to improve on published low-yield procedures. The use of acidic sulphonamides as "phenol equivalents" in the oxidative sequence was then considered. N-chloro-sulphonamides derived from p-anisidine on reaction with silver cations in methanol gave chloro-substituted N-sulphonyl-4.,4-dimethoxycyclohexa-2,5-dienimines, but anodic oxidation of methanolic solutions of p-anisidine or p-toluidine sulphonamides gave high yields of the desired N-sulphonylimines. Similarly anodic oxidation in aceto-nitrile of p-sulphonamidophenoxyalkanoic acids or alcohols, or of p-sulphonsinid phenylalkanoic acids or alcohols- gave fair to excellent yields of the corresponding spirocyclohexadienimines. It appears that 5-nismbered spiroheterocycles form more readily than do 6-membered, and that phenoxyalkanoic siibstrates cyclise more efficiently than do the corresponding phenylalkanoic compounds. Oxidation of substrates to spiro products using lead tetraacetate gave more side reactions, but allowed preparation of imines on a larger scale than by electrochemical procedures.

The spiro-imines are smoothly hydrolysed by neutral alumina to the corresponding spirodienones, thus providing a good route to these compounds. Preliminary studies suggest that spirolactone imines undergo dienone-phenol rearrangements, and that attack by nucleophiles takes place at the ring rather than at the lactone.

An efficient synthesis of a 1-(4-p-tosylamidobenayl)-tetrahydroisoquino-line-1-carboxylic acid was carried out, and the acid subjected to anodic oxidation under a variety of conditions. No evidence of spirolactone formation was obtained. The oxidation of 1-(N-Sulphonyl-4-aminobenzyl)-isoquinolines in an attempt to prepare aporphines related to glaziovine failed to give the desired products.

Item Type:	Thesis
Creators:	Musto, D.R.
Date:	1981
ISBN:	9781369316001
Identifiers:	Number Type PQ10183395 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	24 Sep 2020 13:43
Last Modified:	16 Aug 2023 10:59
URI:	https://irep.ntu.ac.uk/id/eprint/40911

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