Mechanism of the Doebner–Miller lepidine synthesis

Abstract

The formation of lepidine from 4-anilinobutan-2-one in ethanol in the presence of HCl or FeCl3 has been studied. The FeCl3-catalysed reaction proceeds almost quantitatively, while the HCl-catalysed reaction gave a lower yield (less than 50%). The reaction in ethanolic HCl gave aniline, butan-2-one, and 4-ethoxybutan-2-one besides lepidine, while the similar reaction in dioxan gave methyl vinyl ketone instead of 4-ethoxybutan-2-one, together with the above products. The yield of butan-2-one is equimolar to that of lepidine, which suggests oxidation by methyl vinyl ketone. The rates of formation of lepidine from 4-anilinobutan-2-one in ethanolic HCl or FeCl3 at 65° have been measured by u.v. spectrophotometry of lepidine. The rate is expressed as: v=k[l]2[HCl] in the presence of HCl, while v=k′[l][FeCl3] in the presence of FeCl3, where [l] is the concentration of 4-anilinobutan-2-one. N-Benzylaniline and N-allylaniline are oxidized by FeCl3 or by acidic methyl vinyl ketone to form N-benzylideneaniline and N-allylideneaniline, respectively, but N-ethylaniline is not oxidized under the same conditions. These oxidizing agents are effective in the order: HCl–methyl vinyl ketone < FeCl3; the substrates are reactive in the order: N-ethylaniline N-allylaniline < N-benzylaniline. A mechanism for the lepidine formation from 4-anilinobutan-2-one which involves an enamine–aldimine intermediate is postulated and discussed.