Diethyl 3,4-Furan dicarboxylate

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). 

Furan carboxylic acids are usually prepared by ring synthesis using the Feist-Benary and Paal-Knorr methods (Section 3.12.2.2). However, furancarboxylic acids can also be prepared by reaction of lithiofurans with carbon dioxide. A convenient source of furan-3-carboxylic acid (517) is the commercially available diethyl furan-3,4-dicarboxylate (518) (71S545). 

Access to a 1,4-dicarbonyl substrate has been realised in several ways. Examples include alkylation of imines with 2-alkoxy-allyl halides (equivalents of 2-halo-ketones),addition of /3-ketoester anions to nitroalkenes, followed by Nef reaction,and rhodium-catalysed carbonylation of 2-substituted acrolein acetals. The dialdehyde (as a mono-acetal) necessary for a synthesis of diethyl furan-3,4-dicarboxylate was obtained by two successive Claisen condensations between diethyl succinate and ethyl formate, as shown in the sequence below. 

Two similar approaches (Schemes 41 and 42) were described for the synthesis of racemic lactaral (19.1). Both converged to the preparation of the THP ether of lactarol (19.4), which was then converted easily into lactaral using standard methods. In the first of these syntheses (Scheme 41) 128) the mesitoate 26.139, prepared from diethyl furan-3,4-dicarboxylate by conventional steps, was coupled with the lithium derivative of the allylic bromide 26.140 to give 19.4, albeit in very low yield. A much more efficient synthesis of 19.4 162) was completed by coupling chloride 26.142 with the Grignard reagent 26.141 in the... 

Presumably for similar reasons, cathodic reduction of diethyl terephthalate and diethyl furan- and thiophene-2,5-dicarboxylate [51-53] in a buffered ethanolic solution of pH 4.2 affords the aldehyde ester under controlled potential electrolysis (CPE) conditions (in the interval between —1.50 and —1.65 V). Diethyloxalate [77] is reduced at a mercury cathode in acidic medium to give the ethyl hemiacetal of ethyl glyoxylate (38-50% yield). In contrast, diethyl and monoethyl phthalate gave phthalide under similar conditions [21,78]. 

Furan dicarboxylic acid, 6, was prepared by a five-step procedure. Cold acrolein was added slowly to a stirred solution of HCl-saturated absolute ethanol at about 0° to form 3-chloropropionaldehyde diethyl acetal,(6). 

Oxidation of diethyl 3,6-hexanooxepin-4,5-dicarboxylate with ruthenium(VIII) oxide, generated from ruthenium(III) chloride and sodium periodate in situ, gives the corresponding hexa-no-bridged furan 1 a with loss of two carbon atoms (see Houben-Weyl, Vol. E6a, p 77).200 201 One of the central methylene groups can be replaced by a carbonyl group to give lb.200... 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

Diethyl 4-(furan-2-yl)-2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylate (3c) Reaction time 4 min yield 98%... 

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