Fischer indole synthesis on unsymmetrical ketones. The effect of the acid catalyst

Abstract

The products of the Fischer indole synthesis on the unsymmetrical ketones MeCO·CHR¹R²(R¹= H or Me; R²= Me or Ar) have been found to vary with the acid catalyst, and particularly with the concentration of phosphoric oxide dissolved in orthophosphoric acid. Ethyl, phenethyl, and p-nitrophenethyl methyl ketones give mixtures of substituted 1H-indoles [(II) and (III)] while isopropyl methyl ketone gives a mixture of substituted 1H-(III) and 3H-indoles (IV). In all of the reactions the proportion of the 2-substituted indole (III) increases from 0% in acid mixtures such as 90%(w/w) orthophosphoric acid or 30%(w/w) sulphuric acid, to become the major component in the mixtures near 83%(w/w) phosphoric oxide in water or 70%(w/w) sulphuric acid. A mechanistic interpretation of these results is presented.