Observations on the pictet-spengler synthesis of 1,2,3,4-tetrahydro-β-carbolines
The Pictet-Spengler cyclisation of the benzylideneimine of tryptophan methyl ester in xylene, contrary to literature reports, occurs extremely slowly, if at all, in the absence of acids. The cyclisation is Bronsted acid catalysed and the rate of cyclisation is related to the pKa of the Bronsted acid and its concentration. All the acid catalysts studied give essentially the same stereoisomeric mixture of tetrahydro-β-carbolines (cis : trans, ca. 1.2 : 1). The benzylideneimine of tryptamine smoothly cyclises under the same conditions.