Benzo thiophene-2-carboxylic acid formation

Another reaction of such azides attached to the benzene part of benzo[7>]thiophene is the formation of benzoxazoles when heated in a mixture of carboxylic acid and PPA. The mechanism has been discussed in detail (79AG(E)900) and involves insertion of the singlet nitrene into the anhydride, followed by migration of the acyloxy group to the ortho position, and cyclization. The 5- and 6-azides thus given angularly fused benzoxazoles (Scheme 147). 

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. 

Ring-closure techniques are more commonly used to obtain 3-alkylbenzo[6]thiophenes. Thus, acid-catalyzed cyclization of arylthio methyl ketones gives the 3-alkylbenzo[6]thio-phenes in good yield, with little rearrangement (equation 3). Formation of the 3-aryl-benzo[6]thiophenes by this approach is complicated, however, by rearrangement to the 2-isomer (Section 3.15.2.3.2). 3-Methylbenzo[f> Jthiophene is also obtained by decarboxylation of the corresponding 2-carboxylic acid (equation 4), readily available from ar-mer-captocinnamic acids (Section 3.15.2.1.1). 

When a 2-alkylbenzo[b]thiophene undergoes Friedel-Crafts acylation with A1C13-cinnamoyl chloride, the resulting 3-ketone cyclizes spontaneously into the 4-position with loss of benzene to give the cyclic ketone 124.515 With 2-bromobenzo[b]thiophene, a similar reaction gives a mixture of 124 [R = Cl (sic)] and the 2-Br, 3-COCH2CHPh2 substituted benzo[f>]thiophene derivative with 2-methoxybenzo[h]thiophene, the ether is demethylated to give 124(R = OH).516 The formation of other cyclic ketones by intramolecular cyclization of carboxylic acids will be considered in Section IV,M. 

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