Studies of intramolecular S_RN1 reactions of carbanions derived from 2-(o-halobenzyl)amides and 3-(o-halobenzyl)imides: application to the synthesis of succinimido[3,4-b]indane, a potential anticonvulsant

The possibility of inducing intramolecular SRN! reactions in two 2-(o-halobenzyl)- amides, 2-(o-iodobenzyl)-N,N,N’N’-tetramethylsuccinamide (77) and 2-(o-iodobenzyl)- N,N,N’N’-tetramethylglutaramide (80), and three 3-(o-halobenzyl)imides, 3-(oiodobenzyl)succinimide (99), 3-(α-cyano-o-bromobenzyl)succinimide (82) and 3-(oiodobenzyl)glutarimide (108), was investigated. All of these substrates were prepared during the course of the investigation. Treatment of 77 and 80 with excess potassium amide in liquid ammonia under photostimulated conditions afforded reasonably good yields of the expected cyclized products, 1,2-bis-(N,N-dimethylcarboxamido)indane (78) and 1,3-bis-(N,N-dimethylcarboxamido)-1,2,3,4-tetrahydronaphthalene (81), respectively. When imide 99 was subjected to similar conditions, it also underwent the expected cyclization, affording succinimido[3,4-b]indane (61) in acceptable yield. Mechanistic investigations revealed that all of the above reactions appear to occur via intramolecular S_RN1 processes. Attempts to induce similar cyclization reactions with 3-(α-cyano-o-bromobenzyl)- succinimide (82) and 3-(o-iodobenzyl)glutarimide (108) proved unsatisfactory. Substrate 82 failed to undergo cyclization to give the desired succinimido[3,4-b]indane-8-carbonitrile (83). Instead, 3-(α-cyano-α-phenylmethyleno)succinimide (107) was formed as the sole isolable product, presumably via an intramolecular β-hydrogen atom abstraction process. 3-(o-Iodobenzyl)glutarimide (108) did not undergo the desired cyclization to give 1,2,3,4,5,6-hexahydro- 1,5-methano-3-benzazocine-2,4-dione (62) either, presumably because of steric hindrance. This study was undertaken with the objective of investigating the possibility of inducing intramolecular S_RN1 reactions in appropriately substituted amide and imide derivatives. The specific substrates, 77, 80, 82, 99 and 108, were selected for the study because it appeared that intramolecular S_RN1 reactions with these substrates would result in the formation of products that might be useful in the development of new anticonvulsant agents. In this context, the preparation of succinimido[3,4-b]indane (61), which seemed likely to possess antiepileptic properties, fulfilled our proposed objective of applying novel chemistry to the preparation of a new potential anticonvulsant agent. The successful cyclization of 77 and 80 into the expected products, 1,2-bis-(N,Ndimethylcarboxamido)indane (78) and 1,3-bis-(N,N-dimethylcarboxamido)-1,2,3,4- tetrahydronaphthalene (81), respectively, also represented the application of novel chemistry to the formation of two other benzo-fused systems. The synthetic and mechanistic investigations undertaken during this study are expected to extend the scope of the synthetic utility of intramolecular S_RN1 chemistry.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1992

Author dc:creator

• Dandekar, Sushama A.

Chair dc:contributor.committeechair

• Wolfe, James F.

Committee members dc:contributor.committeemember

• Kingston, David G. I.
• Mason, John G.
• Tanko, James M.
• Gibson, Harry W.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-10242005-124048

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/40096