Benzofurans ester groups

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

A series of benzofuran derivatives bearing an ester group at the 2-position has been prepared by the irradiation of quinone intermediates. Dihydrobenzofurans have medicinal importance, and the interesting feature of this work is that cyclization occurs with rearrangement of groups, via the spirocyclopropane intermediate (41). 

The aldehyde group of laevulinic aldehyde reacted preferentially with the ester phosphorane (38), while the 2-acetyl groups of the benzofurans (39) were selectively methylenated with methylenetriphenylphosphorane. The aldehyde group was protected as the dimethylacetal in the synthesis of the steroidal a-methylene-aldehyde (40). 

By elaboration of benzofurans, dibenzofurans can be obtained. The annelation of 4-isopropyl-7-methylbenzofuran-2-carbaldehyde (393) by Wittig reaction with 2-carboxy-l-methoxycarbonylethyltriphenylphosphorane gave the itaconic half ester (394), which on treatment with hot acetic acid cyclized to the dibenzofuran (395). Functional group modification furnished cannabifuran (396) (82JCS(P1)1605). 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

Benzofurans and benzothiophenes are sometimes obtained by condensation of active methylene and aldehyde groups in ortho substituents on the benzene ring. " The starting materials in the furan series are conveniently prepared in situ torn phenolic aldehydes and a-halo ketones or CL-halo esters. 

Esters (21), readily formed from 2-hydroxy-l,2,2-triphenylethanone and carboxylic acids, undergo efficient photocyclization to the benzofuran (22), which then yields the benzophenanthro[9,10-d]furan (23) by the usual 6ji-oxidative closure process of the cis stilbene moiety (Ashraf et al. Chapter 4). The overall reaction is so convenient that the authors propose the triphenylethanone as a new photolabile protecting group for carboxylic acids. 

The formation of a ketene (some are too unstable to be isolated) from a CHCOCl group and TEA is believed to be a step in the cyclization of o-formyl(or <7-acyl)phenoxyacetic acid. Conversion of this into a furan ring is accompanied by decarboxylation. Two other methods of producing the ketene were applied successfully to the synthesis of a benzofuran. A ketene may also be generated in situ by heating a 4-toluenesulphonyl ester with TEA. Recent work on benzo-furans has been reviewed [3894]. 

Photolysis of the CT complex of benzofuran and tetranitromethane at 435 nm in CH2CI2 gives the epimeric pairs of adducts (60 - 63), the nitronic ester (64), and smaller amounts of dimeric products. There is, however, a marked solvent effect. In acetonitrile similar photolysis gives the same group of products with the addition of epimeric dinitro (65) and hydroxynitro (66) adducts, together with 3-nitrobenzofuran while in l,l,l,3,3,3-hexafluoropropan-2-oI mainly dimeric... 

Intramolecular aldol/Perkin type condensation of ort/to-formylaryloxyacetic acids and arylthioacetic esters produces benzofuran and benzothiophene-2-esters respectively, as illustrated below. ortho-Formyl- or ortho-acylaryl benzyl ethers, in which the benzyl group carries an electron-withdrawing substituent, can be comparably closed to produce 2-arylbenzofurans, using potassium fluoride or caesium fluoride on alumina. 

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