Aminobenzo thiophenes

Aminobenzo[ ]thiophene is apparently less stable than its 2-isomer, and is usually characterized as a salt or an acyl derivative.550... 

Aminothiophenes and 3-aminobenzo[ ]thiophene undergo thermal [2 + 2] cycloaddition reactions with activated alkynes. The reactions are solvent dependent thus, in nonpolar solvents at 30 C, 3-pyrrolidinothiophene adds to DMAD to give a [2 + 2] cycloadduct which is ultimately converted into a phthalic ester. In methanol, however, the tricyclic product 239 is formed (Scheme 104). 

A three-component approach to a series of 2-aminobenzo[ thiophenes in moderate yields (at best) has been devised, affording for instance the system 2, which was obtained upon heating of the acetophenone 3 with elemental sulfur and allylamine in the presence of sodium acetate <07JOC3122>. 

Aminobenzo[b] thiophenes (87) were reacted with EMME at 110-140°C to give jV-[benzo[fe]thien-6-yl]aminomethylenemalonates in 91-93% yields (88AP241). 

Direct cyclization of a related aminothiophene (48) occurred on treatment with phosphorus oxychloride to give 49,52 and ring closure between the thiophene ring and the side chain in the p-nitrophenyl-hydrazones (50) with polyphosphoric acid yielded 51. On heating, 2,3-diacetamidobenzo[ft]thiophene eliminated acetic acid and water to give 2-methylbenzothieno[2,3-d]imidazole (52),54,JJ but successful conditions could not be found for cyclization of 2-acetamido-3-phenyl-aminobenzo[6]thiophene.55... 

Cyclic secondary amines have been added to the C-2—C-3 bond of benzo[6]thiophene and 3-methylbenzo[6]thiophene in the presence of an alkali metal salt of the amine (Scheme 39) (78JOC4379). Aromatization of the adducts with stoichiometric amounts of sulfur leads to the corresponding 2-aminobenzo[6]thiophenes. 

Reaction of thiooxindole with HMPT at 160 °C produces 2-dimethyl-aminobenzo[6]thiophene (73T321). The use of other amines in HMPT leads to the corresponding 2-amino derivatives. Direct reaction of thiooxindole with amines leads in most... 

Several 2-aminobenzo[6]thiophenes have also been synthesized from the corresponding... 

Aminobenzo[6]thiophenes may be prepared by reduction of the 2-nitro derivatives to form the hydrochloride salts, or by rearrangement of the oxime of 2-acetyIbenzo[6]thio-... 

A variety of substituted 3-aminobenzo[6]thiophenes have been obtained by ring closure reactions of nitriles (equation 57). Various o -cyanophenylthioacetyl derivatives, when treated with base, yield the 3-amino derivatives (Section 3.15.2.2.3). The benzonitriles may be obtained by displacement of the o-nitro group from o -nitrobenzonitriles (74JOC3440). 2-Arylthio-l-chloroenamines are cyclized to 3 -dialkylaminobenzo[6]thiophenes in the presence of Lewis acid catalysts (equation 58). The 1 -chloroenamines may be prepared from t-amides or ynamines <8lH(15)l 179>. 

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). 

The benzene ring has been proposed as an isosteric replacement in a dipeptide to enforce either the tram l1 1 or the cis conformation 312>31 (Scheme 1). Similarly, 2-(amino-methyl)pyrrole-l-acetic acid (8, R = H) has been proposed as a cis peptide bond mimic,141 having the same number of atoms between the amino and carboxylic acid functions as in a dipeptide. Several other amino- and carboxy-substituted aromatic structures have been used as spacers in peptides 2-, 3-, and 4-aminobenzoic acids (Abz, e.g., 7), 2-, 3-, and 4-(amino-methyl)benzoic acids (Amb, e.g., 2), 2-, 3-, and 4-(aminophenyl)acetic acids (APha, e.g., 5), 2- (4), 3-, and 4-(aminomethylphenyl)acetic acid (Ampa), (aminomethyl)pyrrole-, -thiophene-, and -furancarboxylic acids 6, (aminomethyl)pyrrole- 8 and -thienylacetic acids, and aminobiphenylcarboxylic acids. 

IR spectroscopy has been used to show that 2-aminobenzo[6]thio-phenes normally exist solely as the amino tautomer,112-114 and that 2 ii2,ii3 an(j 3-hydroxybenzo[6]thiophenes117,147 exist solely as the keto tautomers, except that compounds with an adjacent carbonyl-containing group exist mainly as the enols.109,116,147> 148 3-Hydroxy-2-nitrobenzo[6]thiophene-l,1-dioxide exists as a mixture of the keto and enol forms.149... 

The UV spectrum of 3,3-dimethyl-2-imino-2,3-dihydrobenzo[i>]-thiophene (14) is quite similar to that of 2,3-dihydrobenzo[6]thio-phene.118 On the other hand, the spectrum of 2-aminobenzo[6]thio-phene diverges from that of 14, but closely matches that of benzol-thiophene. 2-Aminobenzo[6]thiophene exists, therefore, mainly as the amino tautomer.112-114 On the contrary, thiooxindole (15) exists in solution mainly as the oxo form since its spectrum closely resembles that of the thiolactone (16) and the imine (14).113... 

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