Reductive-cyclization -5-methoxybenzoate

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

Hydroxybenzo[6]thiophene has been isolated from coal tar.42 It may be prepared from 6-aminobenzo[fr]thiophene by standard procedures.241 6-Methoxybenzo[h]thiophene may be prepared by decarboxylation of the corresponding 2-carboxylic acid,341 and 6-ethoxybenzo[6]thiophene is obtained by reduction of 6-(ethoxy)-thioindoxyl (Section VI, 1,2). 6-Methoxy-5-methylbenzo[6]thiophene is obtained by cyclization of (3-methoxy-4-methylphenylthio)-acetaldehyde dimethyl acetal (Section IV,B).617 The product previously described542 as 6-hydroxy-3-phenylbenzo[6]thiophene has now been shown to be the 2-phenyl isomer.307 6-Methoxy-818 and 6-methoxy-5-methyl-benzo[6]thiophene617 are demethylated by pyridine hydrochloride. 

Acrolein cyanhydrin 211 was converted into its methoxymethyl ether 212, in turn alkylated with 1,3-dibromopropane to give the key 6-carbon synthon 213. m-Methoxybenzoic acid was utilized as the ring A component. Reductive alkylation via dianion 215 led to dihydroaromatic intermediate 216 which was decarboxylated with ensuing aromatization using lead tetraacetate (or, alternatively, anodic oxidation) to afford 217 in excellent yield. Unmasking of the carbonyl function generated known enone 218 ° (see Volume 2, pp. 693,697), which was condensed with 2-methyl-1,3-cyclopentanedione 12 to produce prochiral trione 219 in high yield. The latter had been cyclized previously to (+) 15c and thence converted into estrone. Alternatively, trione 219 was cyclo-dehydrated to the well-known estrone precursor estrapentaene 193 (see Volume 2, pp. 697, 701, 705). 

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See also in sourсe #XX -- [ ]

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