A Convenient Regioselective Synthesis of 2,4-Diarylfurans

Abstract

A facile three step process, under mild conditions, for the synthesis of 2,4-diarylfurans with the same or different substituents on the two aryl rings, starting from benzaldehydes and acetophenones, employing HallerÐBauer type cleavage of 2-aroyl-3,5-diarylfurans is described.Synthetic routes to 2,4-diarylfurans are limited. 1,2 Convenient procedures for preparing 2,4-diarylfurans with the same or different substitutents on the two aryl rings are even more rare. One method which seems to be general for preparation of both types of substituted 2,4-diarylfurans involves the condensation of acetophenones with 1-amino-4,6-diphenyl-2-pyridone and subsequent metallation of the ketimines with butyllithium at Ð78 ¡ C followed by reaction with phenacyl bromides. 3 The addition of dimethylsulfonium methylide to -alkoxy-α , -unsaturated ketones is also a useful approach for synthesis of 2,4diarylfurans. 4 For most substituents, both of these methods require synthesis of starting materials and the former one requires low temperature operations. For the latter approach synthesis of the required -alkoxy-α , -unsaturated ketones is a multistep process which sometimes involves the use of diazomethane. 4,5 Synthesis of 2,4-diarylfurans directly from phenacyl bromides by electrochemical methods 6 , by reaction with nickel carbonyl in DMF 7 , by reaction with cuprous chloride 8 , and by reaction with sodium telluride 9 have been reported. These methods suffer from two or more of the following disadvantages: only furans with the same substitutents on the two aryl rings may be made, many of the phenacyl bromides are not commercially available, only modest yields are obtained, key reagents are toxic, and specialized equipment is required. As part of a program focused on the development of antiinfective agents we needed a convenient method for preparation of relatively large quantities of 2,4-diarylfurans. 10 This report describes a simple three step synthetic method starting from benzaldehydes and acetophenones which can be used for preparation of 2,4-diarylfurans with the same or different substitutents on the two aryl rings. The approach employed is presented in the Scheme below. The reaction of one equivalent of substituted benzaldehydes 1 with two equivalents of substituted acetophenones 2 mediated by boron trifluoride etherate in benzene has been reported for the synthesis of a large

Synthesis of Alkali Metal Carboxylates and Carboxylic Acids Using “Wet” and “Anhydrous” Alkali Metal Hydroxides

“…“APH” has been successfully reacted with 2-aroyl- 347 , and 3-aroyl furans 349 and delivers the corresponding deacylated furanes 348 and 350 as well as the related benzoic acids in good yield and with extremely high regiocontrol (Scheme ). In those cases, the nature of the substituants attached to the aryl group part of the aroyl moiety as well as the solvent used do not seem to play a crucial role in both yields and regiocontrols (compare Scheme to Scheme , entry b).…”

Dicationic DNA Minor Groove Binders as Antimicrobial Agents

“…The insertion reaction yielded the expected 2,4-bis [4-cyanophenyl]furan. An alternate synthetic route into the 2,4-bis[phenyl]furan system was later developed [158]. 2,4-Bis [4-cyanophenyl]furan was converted into the corresponding amidines using the Pinner approach.…”

Antimicrobial activity of the DNA minor groove binders furamidine and analogs

“…An alternative route to the 2,4-bis[phenyl]furan system has been developed more recently. 44 2,4-Bis[4-cyanophenyl]furan was converted into the desired diamidines using Pinner methodology.…”