Furan acids, decarboxylation

A carboxyl group is removed from a heterocyclic nucleus in much the same way as from an aromatic nucleus (method 13), i.e., by thermal decomposition. The pyrolysis is catalyzed by copper or copper salts and is frequently carried out in quinoline solution. The reaction is important in the synthesis of various alkyl and halo furans. Furoic acid loses carbon dioxide at its boiling point (205°) to give furan (85%). A series of halo furans have been made in 20-97% yields by pyrolysis of the corresponding halofuroic acids. The 5-iodo acid decarboxylates at a temperature of 140°, whereas the 3- and 5-chloro acids requite copper-bronze catalyst at 250°. ... 

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. 

Manufacture. Furan is produced commercially by decarbonylation of furfural in the presence of a noble metal catalyst (97—100). Nickel or cobalt catalysts have also been reported (101—103) as weU as noncatalytic pyrolysis at high temperature. Furan can also be prepared by decarboxylation of 2-furoic acid this method is usually considered a laboratory procedure. 

Studies are restricted to syntheses of Group 2B - organometallics and mainly to mercurials. Early studies of reactions of mercuric salts with furan- and thiophencarboxylic acids or their salts have been thoroughly reviewed (7-4). More recently several tetrafluoropyridyl derivatives have been prepared by decarboxylation [Eqs. (78) (87), (79) (88), or (80),... 

Recently, researchers have detected 2,5-dimethylfuran and 2-methylfuran and normal alkanes in kerogen of the 2.7 x 109 year old Belingwe, Rhodesia stromatolites, by the method of pyrolysis/ GC/MS [26]. They concluded that although furans could probably be derived from many compounds, their probable origin is in bacterial and algal sugars, and that the alkanes are either products of decarboxylation of fatty acids or unaltered constituents of ancient organisms. 

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

Investigations of the mechanism of decarboxylation of hexuronic acids have largely involved kinetic and tracer studies. When either D-xylo-5-hexulosonic acid or D-glucuronic acid is converted into 27 in acidified, tritiated water, the resulting 27 contains 18% and 15%, respectively, of the activity of the solvent as carbon-bound tritium.21 Further degradation studies showed that the isotope is situated on the furan ring at either position 3 or 4, or both these atoms correspond to C-3 or C-4 of the starting uronic acid. 

Efficient synthesis of 2-chlorofuran is best achieved by decarboxylation of 2-chlorofuran-5-carboxylic acid (63JGU1397) or via the lithium derivative of furan. When furan or 3-bromofuran were treated in turn with ethyl-lithium and hexachloroethane, 2-chlorofuran (48%) or 3-chlorofuran (54%) was formed, uncontaminated by any polychlorinated products (73SC213). Chlorodesilylation of ethyl 5-trimethylsilyl-2-furoate with sul-furyl chloride in acetonitrile gave the 5-chloro ester in —85% yield (91MI4). 

There are examples of ipso attack during the nitration of pyrroles, furans and thiophenes and in the corresponding benzo-fused systems. Reactions resulting in nitro-dealkylation, nitrodeacylation, nitro-decarboxylation and nitro-dehalogenation are to be found in the monograph reactivity chapters of CHEC. Treatment of the 3-azophenylindole (64) with nitric acid in acetic acid at room temperature gives 80% of the 3-nitroindole (65) (81JCS(P2)628). 

Pyrrole-2-carboxylic acid easily loses the carboxylic group thermally. Pyrrole-3-carboxylic acid and furan-2- and -3-carboxylic acids also readily decarboxylate on heating to about 200°C. Thiophene-carboxylic acids require higher temperatures or a copper-quinoline catalyst. In furans, 2-carboxylic acid groups are lost more readily than 3-carboxylic acid groups (Scheme 64). 

Various 3-methylcoumarilic acids substituted in the benzene ring by alkyl or methoxyl groups have been thus prepared, then decarboxylated to the corresponding benzofurans,10 208 e.g., 3-methyl-4,7-dimethoxy-benzofuran 2-naphthol233 leads to 3-methylnaphtho[2,l-6]furan (79), guaiacol to ethyl 7-methoxy-3-methyl coumarilate.234... 

Ring opening is common in the alkali metal and liquid ammonia reduction of furans unless an anion stabilizing group is present, so most work has been done with derivatives of furancarboxylic acids. Treatment of furan-2-carboxylic acid with lithium and ammonia at -78 °C followed by rapid addition of ammonium chloride affords 2,5-dihydrofuran-2-carboxylic acid (80%). Reductive alkylation similarly gives 2-alkyl-2,5-dihydrofuran-2-carboxylic acids. This method has been used in a synthesis of rosefuran, the intermediate dihydrofuran (66) being converted into the product (67) by oxidative decarboxylation with... 

Carbonation of lithiofurans is a useful method for obtaining these compounds. Furan-2-carboxylic acid (pKa 3.15) is a stronger acid than the 3-carboxylic acid (pKa 4.0) because of the inductive effect of the ring oxygen, and both are stronger than benzoic acid. Furancarboxylic acids can be decarboxylated by the copper-quinoline method or merely by heating. The 2-carboxylic acids are more easily decarboxylated than the 3-isomers, so furan-3-carboxylic acid can be obtained by stepwise decarboxylation of the tetracarboxylic acid via the 2,3,4-tricarboxylic acid and the 3,4-dicarboxylic acid. A more convenient source of the 3-carboxylic acid is by partial hydrolysis and decarboxylation of the readily available diethyl furan-3,4-dicarboxylate (71S545). 

The halo-furans and -benzo[f>]furans are particularly important as precursors of the lithio derivatives (Section 3.11.3.9). Direct halogenation of furan (Section 3.11.2.2.5) is unsatisfactory, and halofurans are prepared by decarboxylation of halofurancarboxylic acids, from chloromercurio compounds, by decarboxylative halogenation of furancarboxylic acids or by partial dehalogenation of polyhalofurans. 

Decarboxylation of halofurancarboxylic acids is usually carried out with copper and quinoline at 150-230 °C and the product often distills from the reaction mixture (71BSF242). Heating chloromercuriofurans with iodine and potassium iodide in water yields iodofurans. Thus 3,4-bis(chloromercurio)-2,5-dimethylfuran yields the diiodo compound (41%), and tetrakis(chloromercurio)furan yields tetraiodofuran (67%). Boiling sodium furan-2,5-dicar-boxylate with potassium iodide and iodine in water yields the diiodofuran, and 2,5-dibromofuran (78%) is similarly available from sodium 5-bromofuran-2-carboxylate, potassium bromide and bromine (74ZOR1341). 

Ring contraction of coumarins is used for the preparation of benzo[Z>]furans. Alkaline degradation of the 3-halo-, 4-halo- or 3,4-dihalo-coumarins gives the coumarilic acids (Scheme 104). The coumarilic acids are decarboxylated to the corresponding benzo[Z> ]f urans. Basic mercury(II) oxide oxidation of 4-phenylcoumarin (neoflavanoid) yields the 3-phenyl-benzo[/>]furan (71IJC1316). 

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