Furan Carboxylic Acids and Esters

The cycloaddition of diarylketones and some aldehydes across the furan 2,3-double bond proceeds regioselectively to afford oxetanodihydrofurans proton-catalysed cleavage of the acetal linkage produces 3-substituted furans.  

The nucleophilic displacement of halide from furfuryl halides often produces mixtures of products resulting from straightforward displacement on the one hand and displacement with nucleophilic addition to C-5 on the other the second mode proceeds through a non-aromatic intermediate which then isomerises to aromatic product. 

Save for their easy decarboxylation, furan acids (and their esters) are unexceptional. Carbon dioxide is easily lost from either a- or p-acids and presumably involves ring-protonated intermediates and a decarboxylation analogous to that of p-keto-acids, at least in those examples where copper is not utilised. 

Nitration of 3-furoic acid takes place normally, and at C-5 a-acids sometimes undergo /p c -substitution with decarboxylation, for example 2-furoic acid gives mainly the 5-nitro-derivative but accompanied by some 2,5-dinitro-furan.  

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Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

Gandini and Rieumont26,119 have carried out an extensive examination of the polymerizability of several vinyl esters of furan carboxylic acids and of the causes of the autoinhibition which most of them display with free-radical initiation. The compounds studied were the vinyl esters of 2-furoic, 2-furylacetic, 2-furylpropionic, 2-furylacrylic and sorbic acid. All these derivatives, showed the same strong indifference towards radical polymerization. Only when treated with large doses (10—30%) of initiator did they give small yields of oligomers. The structure of all these products was carefully studied by spectroscopic and other techniques. Invariably, it was... 

As in the furan series, the loss of an OH or an -OR group is very favored in pyrrole carboxylic acids and esters, (53)->[51]. The presence of an N—H group in a-pyrrole carboxylic esters causes also the elimination of an ROH fragment,41 (53)->[54]. 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The values were determined and the... 

Dimethyl acetylenedicarboxylate gave first a similar adduct (2) which then added further molecules of furan yielding (3) and subsequently (4). Between 1931 and 1940 the reactions of acetylenedi-carboxylic acid and its dimethyl ester with a number of nitrogen containing heterocyclic compounds were examined, and structures were proposed for the products. Apart from an unpublished investigation of the products from pyridine and dimethyl acetylenedicar-... 

In a disclosure regarding the use of alicyclic carboxylic acid oxycarbonylmethyl esters and their use as odorants and perfumes, a composition was described in which two furan compounds were components <2005W02005108534>. 4,5-Dimethyl-3-hydroxy-2(577)-furanone 80 and 3a,6,6,9a-tetramethyldodecahydronaphtho[2,l- ]-furan 18 were present in <2% in the described perfume. In another fragrance-related application, compound 18 was a component of a perfume composition which was added to a shampoo formulation designed to enhance permeation as well as provide desired fragrant effects <2002JPP2002241238>. The fused tricyclic furan 18 was incorporated as 20% of the perfume mixture of which that was a component of the shampoo in 0.7%. 

The isomeric Step 4 ester, 5-(4-fluorophenyl)-4-(4-(methylthio)-phenyl)thiophene-2-carboxylic acid methyl ester, (I), has been prepared (3). The Step 5 furan derivative, (II), 3-(4-fluorophenyl)-4-(4-(methyl-sulfonyl)phenyl)furan has also been prepared and is described (3). 

Hydroxy-1,2,2-triphenylethanone based carboxylic esters upon irradiation with a medium pressure mercury lamp resulted in a rapid and quantitative photolysis to afford the carboxylic acid and benzo[ft]phenanthro[9,10-tf]furan. No yield was reported for this synthetic transformation <03TL3151 >. 

Reactives of Side-Chains of Monocyclic Thiophens. - The rate constants for the esterification of some 3-, 4-, and 5-substituted thiophen-2-carboxylic acids and of some 2- and 4-substituted thiophen-3-carboxylic acids with diazodiphenylmethane in methanol solution have been measured, and linear correlations gave information about the transmission of substituent effects. The rates of alkaline hydrolysis of ethyl thiophen-2-carboxylate in ethanol-water and DMSO-water media have been measured and compared with those of other heterocyclic esters. The kinetics of iodination of 2-acetylthiophen in methanol-water, using different carboxylate buffers, have been studied.Basicity constants have been measured for j3-(2-thienyl)-acrylamides and compared with those of the corresponding benzene and furan derivatives. The acidity constants of ( )-a-phenyl-j3-(2-thienyl)-acrylic acids and analogous furan-, selenophen-, and pyridine-substituted compounds have been measured, and have been rationalized by an equation involving separate contributions of polar, conjugative, and steric effects of the heterocycles. ... 

Gopichand et al. (407) isolated two new acyclic sesquiterpene hydrocarbons (483) and (484) from the gorgonian Plexaurella grisea as well as (-h)-a-santalene (485), which is well-known from terrestrial source. Bowden et al. (408) described new sesquiterpene furans from Sinularia capillosa and S.firma, all of which were structurally related. The furanoquinol (486) was the predominant isolate and was accompanied by the related furanoquinone (487) which may be an artifact. In addition they found the methylfurans (488-492), the furan methyl esters (493-496), and the furan carboxylic acids (497-500). A related methylfuran (501) has been obtained from the Mediterranean alcyona-cean, Alcyonum palmatum (409). 

Almost every major structural class discussed to date has featured at least one nonsteroidal antiinflammatory carboxylic acid. It is thus perhaps not surprising to find a dibenzoheterocycle serving as the nucleus for one of these agents, furobufen (34). Straightforward Friedel-Crafts acylation of dibenzo-furan (33) with succinic anhydride affords a mixture of 2- and 3-acylated products, with the latter predominating. The mixture is esterified with methanol, and the methyl ester of the 3-isomer is separated by fractional crystallization. Hydrolysis back to the... 

Anodic oxidation of fiirans in acetic acid leads to the 2,5-diacetoxy-2,5-dihydro-furan 58 [185, 186]which is readily converted to 2-acetoxyfiiran, This has proved a valuable intermediate for the synthesis of butenolides [187]. Reactions in moist acetonitrile yield the 2,5-dihydro-2,5-dihydroxyfurans which can be oxidised to the maleic anhydride 59 [188], Oxidation of furan-2-carboxylic acid in methanol and sulphuric acid is a route to the ester of a-ketoglutaric acid [189]. 

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