M. Bajić, Arvind Kumar, D. Boykin
1996
Citations
1
Influential Citations
8
Citations
Journal
Heterocyclic Communications
Abstract
The synthesis of 2,5-bis-(4-cyanophenyl)-furan by three different approaches is reported. Introduction 2,5-Bis-(4-cyanophenyl)-furan (1) is the key intermediate in the synthesis of 2,5-bis-amidinoarylfurans (1,2). The furan bis-amidines are valuable probes of the minor groove of DNA (3-5) and have been shown to hold promise as therapeutic agents (2). Previously, we reported the synthesis of 1 in four step process which began with the preparation of l,2-di-(4-brombenzoyl)ethene by the Friedel-Crafts reaction between bromobenzene and fumaryl chloride (1). During a program of study of 2,5-bis-amidinoarylfurans it became apparent that a more efficient method of synthesis of 1 was needed. This report describes our approaches to this problem. Results and Discussion Earlier a Claisen condensation approach to make the 1,4-diketone needed for the preparation of 2,5-bis-(4bromophenyl)-3-methylfuran was used(l). The reaction sequence outline in Scheme 1 was explored based upon the earlier approach. Reaction of 4-bromoacetophenone (2) with diethyl carbonate in the presence of sodium hydride gave the ester 3 in good yield. Reaction of the ester 3 with 4-bromophenacyl bromide gave the 1,4diketone 4. Acid catalyzed cyclodehydration of the 1,4-diketone 4 was achieved to give the furan ester 5 in good yield. Saponification of 5 gave the corresponding furan-3carboxylic acid. The carboxylic acid derivative was concuirently decarboxylated and converted into 1 by the action of CuCN in refluxing quinoline. The overall yield obtained from this four step approach was 26%. SCHEME 1 a) NaH, diethyl carbonate b) NaOEt, 4-bromophenacylbromide c) HCl, ethanol d) KOH, H20 e) quinoline, CuCN, reflux.