2- Methylthio-3-acyl thiophene

Scheme 78 The reaction of a 1,3-diketone enolate with carbon disulfide leading to a 2-methylthio-3-acyl thiophene [126]...

The addition of the enolate of a 1,3-diketone to carbon disulfide generates a dianion, e.g. 55, which, following two successive S-alkylations, can produce 2-methylthio-3-acyl thiophenes 56. The first alkylation requires a 2-halo-carbonyl compound (a 2-halo-ketone in the example in Scheme 78) to allow the ring closure via an intramolecular aldol condensation and then a second with iodomethane to complete the sequence [126]. 

Lithiation of the methyl of (methylthio)benzene followed by acylation with an acyl chloride and acidification to pH 4-5 yields benzothiophene in good yields, but when aroyl chlorides are used, the mixture has to be heated in benzene. An attempted dehydration of the secondary alcohol (87.4) with hydrobromic acid led to S-demethylation and cyclization. Similar treatment of the isomeric 2-(2-methy thio-4-nitrophenyl)-l-phenylethanol gave a high yield of 6-nitro-2-phenyl-2,3-dihydrobenzo[fi]thiophene [2653]. 

Alkylthio-5-alkylthiophens are chloromethylated at position 3 by chloromethyl methyl ether. 3-Methylthiothiophen has been nitrated at position 2. The influence of the reaction conditions on the isomer distribution in the acylation of 2-methoxy-, 2-methylthio-, and 2-dimethyl-amino-thiophen has been studied. Azo-coupling and aminomethylation occur at position 3 of some 4,5-disubstituted 2-acylaminothiophens. 3-Acetylamino-2-benzoylthiophen yields the 4,5-dichloro-derivative with sulphuryl chloride, while 3-acetylamino- or 3-benzoylamino-4-carbonyl-thiophen derivatives are chlorinated at position 2. ... 

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