Thiophene synthesis, Vilsmeier-Haack reaction

The synthesis of 5- and 6-(N,N-di- -propyl)amino-4,5,6,7-tetrahydrobenzo[ ]thiophene (34 and 35) has been described previously (Chapter 2). Using a Vilsmeier-Haack reaction, a formyl moiety was introduced on the 2-position of the thiophene ring.240 An excess of N-methylformanilide was used which could be easily removed by column chromatography. Reduction of the formaldehydes 65 and 68 with NaBFC yielded the hydroxymethyl compounds 66 and 69. From compound 65, the aldoxime 67 was synthesised, using hydroxylamine.HCl in ethanol and 5N NaOH-solution. 

The Vilsmeier-Haack reaction has been used in die synthesis of thiophenes with potential anti-inflammatory properties. The electron-rich ring of the thiophene system makes it an ideal nucleophile for the Vilsmeier-Haack... 

---