Synthesis of Substituted Indoles Using Flow Microreactors

Significance

The synthesis of various indoles with throughputs of up to 20.1 mgh^-¹ per single channel reactor has been developed. When ­ketones 1 reacted with phenylhydrazine (Fischer synthesis) via [3,3]-sigmatropic rearrangement, substituted indoles 2 were obtained in moderate to excellent yields. The substrate scope was moderately studied. Three different conditions were ­investigated; homogenous catalysis (method 1); neat acid catalysis (method 2), and heterogeneous catalysis (method 3). The heterogeneous approach was shown to be the most efficient.