2-Acetyl-3-aminobenzo thiophenes

These derivatives may be obtained by reduction of the appropriate nitro derivative catalytically or with a metal-acid system, or by Beckmann or Hofmann rearrangements of suitable acyl or carboxamido derivatives. 4-Aminobenzo[6]thiophene has also been prepared by means of a Bucherer reaction with 4-hydroxybenzo[6 Jthiophene. Several 5-aminobenzo[6]thiophenes have been prepared by cyclization reactions of p-acetamino-phenylthio derivatives. 6-Acetaminobenzo[6 Jthiophenes may be obtained from the corresponding 6-acetyl derivative by Schmidt or Beckmann rearrangements. 7-Aminobenzo[6 ]thiophene can also be prepared from 7-hydroxybenzo[6 ]thiophene by a Bucherer reaction (70AHC(ll)l77). 

Catalytic cyclodehydrogenation of 5-amino-2-ethylthiophenol affords 6-aminobenzo[6]thiophene.239,241 6-Acetamido-2,3-di-bromo-,77 6-acetamido-2-bromo-3-methyl-,102 6-acetamido-3-bromo-2-methyl-,102 and 6-acetamido-3-bromobenzo[f>]thiophene107 may be obtained from the corresponding 6-acetyl compound by means of the Schmidt reaction. In some cases the 6-acetamido compound is accompanied by a smaller amount of the amine sulfate.102,107 6-Aminobenzo[6]thiophene may be converted into 6-chloro- or 6-cyanobenzo[6]thiophene by means of the Sandmeyer reaction.241... 

Acetamidobenzo[b] thiophene is obtained by reductive acetylation of the 3-nitro compound with Fe-Ac0H-Ac20.393 Unstable 3-aminobenzo-[b] thiophene is best prepared in situ by decarboxylation of the corresponding 2-carboxyIic acid.389... 

The 5-acetyl derivative of (538) has been converted into the 5-NHj, 5-CO2H, and 5-CH2C02H compounds. From the amino-compound the 5-bromo-derivative was obtained upon diazotization, which upon treatment with potassium amide in liquid ammonia gave a mixture of the 4-amino-(major) and 5-amino-isomers. The compound (538) was converted into the iST-oxide, which upon nitration in sulphuric acid gave 4-nitrothieno-[2,3-Z>]pyridine 7-oxide. Nitration in acetic acid, on the other hand, gave the isomeric 5-nitro-derivative. Several reactions were carried out with these nitro-compounds. In a manner similar to that described for (538) and (539), the compounds (542)—(544) were prepared from 3-aminobenzo[6]-thiophen, 2-aminothieno[2,3- ]thiophen, and 5-aminobenzo[6]thiophen... 

Pentane-2,4-dione reacts with 3-chloro-l,2-benzisothiazole in the presence of sodium ethoxide to form 2-acetyl-3-aminobenzo[6]thiophen (71%). Under similar conditions, ethyl acetoacetate and diethyl malonate each give mainly ethyl 3-aminobenzo[6]thiophen-2-carboxylate (160). Under modified conditions diethyl malonate gives, in addition, some of the expected diethyl (l,2-benzisothiazol-3-yl)malonate, whereas ethyl cyano-acetate forms only ethyl (l,2-benzisothiazol-3-yl)cyanoacetate, irrespective of conditions. Mechanisms were considered involving iS-substituted o-cyanothiophenols as possible intermediates in the reactions leading to benzo[6]thiophen (see Scheme 8). The reactions constitute a useful... 

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