Furans ring fission

Table 4.26. Ring fission of furans and pyrroles by acceptor-substituted carbene complexes. Starting Material Reagents, Conditions Product Yield Ref.

Bromo-2-pyrones and 3-bromocoumarins give furan- and benzofuran-2-carboxylic acids by ring fission and subsequent closure, e.g. (228) — (229) (116) or (117) — (230). Pyrone rings are opened by aqueous acid in some cases, probably by successive protonation and attack of a water molecule, e.g. dehydroacetic acid (231) gives (233) which immediately forms (232) or (234) with HC1 or H2S04, respectively. 

Oxidative ring fission of furans using the commercially available reagent pyridinium chlorochromate (PCC) has been studied as well (80T661). Experimental evidence supports the preliminary formation of intermediate (87) formed by 1,4-electrophilic attack of chlorochromate anion upon the furan ring. This intermediate then breaks down by heterolytic cleavage of the Cr—O bonds to afford initially the cis enedione which isomerizes to the trans product. Treatment of (88) with sodium hydroxide in methanol effects ring closure with formation of the 4-methoxycyclopentenone (89 Scheme 22). 

Later, Linda and Marino84, 90, 180 were able to compare the relative reactivities of all four fundamental systems (furan, thiophene, selenophene, and pyrrole) toward bromination by molecular bromine in acetic acid. Unfortunately, the comparison could not be made on the unsubstituted rings for the following reasons first, the rates of substitution for furan and pyrrole were too high to be followed by standard kinetic techniques second, furan and pyrrole undergo ring fission and/or polymerization under the influence of the hydrobromic acid formed in the reaction finally, furan tends to give addition as well as substitution products in the reaction with bromine.1818. 

Such analogies clearly lead to the supposition that the unsubstituted furan ring may arise by the fission of a 3-carbon fragment from the cyclized isopentane unit this idea is far from new in the furocoumarin field 158), but its applicability to the furoquinoline series became obvious only after the structures of alkaloids such as orixine, lunacrine, and balfourodine had been established 14). 

Organic Reactions contains a review of the fission of benzyl ethers, including cyclic benzyl ethers, by hydrogenation.43 Ring fission of furans has been reviewed by Jones and Taylor.44 Burwell45 has written an excellent and detailed report on the cleavage of ethers, in which he discusses also the theoretical problems involved he concludes with some indications for the fission of sulfides, a subject that is treated also by Tarbell and Hamish.46... 

The aldehyde group stabilizes the furfural stmcture against the acid-catalyzed fission of the furan ring that readily occurs in furan and alkyl furan derivatives. Basic-type stabilizers, such as tertiary amines, can be used to inhibit oxidation of the furan structure [3]. Furfural can be oxidized to furoic acid or reduced to furfuryl alcohol which can be converted to furan by a catalyzed decarbonylation reaction. On an industrial scale furfural is the source for furfuryl alcohol, tetrahydrofurfuryl alcohol, furan, and tetrahydrofuran. Nitro-furan compounds derived from furfural are used as bactericides in humans. 

From the dioxetane intermediate described above, other compounds can be formed, which in turn, may have biological effects. Dioxetane intermediate may be opened by nucleophilic compounds (e.g., a solvent molecule) in a way different from that leading to the aldehyde that is, it leaves the C-C bond unaffected, therefore avoiding fission of the furan ring. 

When substituted furans are hydrogenated, ring transformations are also possible. These take place by hydrogenolytic fission of the ring followed by recyclization, e.g.,233... 

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