Benzo thiophenes from thiophenols

Benzothiophenes have always been of interest for medicinal chemistry and can be found in a number of marketed drugs such as Sertaconazole (Gineder-mofix), Zileuton (Leutrol) and Raloxifene (Evista). The classical synthesis of benzo thiophenes starts from thiophenols, reacting with bromoacetaldehyde dimethyl acetal, followed by cycUzation using strong acid. An alternative and more convenient route was also described starting from benzaldehydes which... 

By analogy with benzo[Z ]furans, benzo[Z ]thiophenes can be obtained from thiophenolates and a-hdXo ketones ... 

Benzo[ ] thiophene, colourless crystals, mp 32°C, bp 22FC, has a smell similar to that of naphthalene. It is present in the naphthalene fraction of coal tar and can be prepared from sodium thiophenolate and bromoacetaldehyde diethyl acetal. Benzo[ ]thiophene occurs in roasted coffee beans. 

Both benzo[ >]thiophenes and benzo[ >]furans can be obtained from the thiophenol or phenol respectively, by S-/0-alkylation with bromoacetaldehyde acetal and then acid-catalysed ring closure involving intramolecular electrophilic attack on the ring. 

Substituted naphtho[lr]furans and benzo[fc]furans were easily accessible by treatment of naphthols/substituted phenols with nitroallylic acetates through a substitution-elimination process promoted by cesium carbonate (13CEJ4344). Aminobenzo[l)]furan could be obtained by a one-pot con-densation-cyclization sequence from ethyl glycolate with chloropyridine (13BMCL2781). An intramolecular cyclization of 2-(gem-dibromovinyl) phenols(thiophenols) produced 2-bromobenzo[lr]furans(thiophenes) in the presence of Cu (13OBC4095). 

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