Novel process for the synthesis of class I antiarrhythmic agent (+/-)-cibenzoline and its analogs

TitleNovel process for the synthesis of class I antiarrhythmic agent (+/-)-cibenzoline and its analogs
Publication TypeJournal Article
Year of Publication2008
AuthorsGholap, AR, Paul, V, Srinivasan, KV
JournalSynthetic Communications
Volume38
Issue17
Pagination2967-2982
Date PublishedAUG
ISSN0039-7911
KeywordsBenzophenone, cibenzoline, cyclopropanation, diaryl cyanoolefin
Abstract

Synthesis of (+/-)-cibenzoline and its analogs has been achieved by a simple sequence of reactions. The diaryl cyanoolefin intermediate 3 could be prepared by Knoevenagel condensation of benzophenone with ethylcyanoacetate to form the tetra-substituted olefin intermediate 2 followed by Krapcho deethoxycarbonylation or from beta-hydroxynitrile intermediate 2' followed by the elimination of hydroxyl group respectively. The 2,2-diphenylcyclopropanecarbonitrile 4 was synthesized from intermediate 3 by cyclopropanation, which was converted to (+/-)-2-(2,2-diphenylcyclopropyl)-2-imidazoline 5 by reaction with ethylenediamine in the presence of a catalytic amount of sulfur. Moreover, the obtained 2-imidazolines were smoothly oxidized to the corresponding imidazoles 6 in good to moderate yields.

DOI10.1080/00397910802006388
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)0.937
Divison category: 
Organic Chemistry