Hydrazine-Mediated One Pot Amination-Oxidation Reaction: Facile Synthesis of 4-Amino-β-carbolines and 4-Aminoisoquinolines

Article abstract of DOI:10.1021/jo00228a025

The conversion of the 4-oxo-2-benzoyl-1,2,3,4-tetrahydro-β-carbolines 1a and 1b, respectively, into their corresponding 4-amino-β-carbolines 2a and 2b was effected in 70percent yield in refluxing hydrazine.In contrast, phenylhydrazine, when heated with the 4-oxo derivative 1b, gave the pyridodiindole 18a.This compound derives its origin from an initial Fischer indole cyclization, followed by loss of the 2-benzoyl group and aromatization to the β-carboline.During investigation of the scope and mechanism of this new amination-oxidation reaction, it was found that an acidic hydrogen atom (position 2, NH) γ to the carbonyl group (C-4) was necessary to drive the reaction to completion.Although phenylhydrazones such as 20b and 20c, which carry electron-withdrawing groups, led to the formation of 2b at the expense of the Fischer indole products 18b and 18c, respectively, the yields in this seguence were only moderate.Hydrazine, consequently, appears to be the reagent of choice to effect this amination-oxidation reaction since Fischer indole cyclization cannot compete in this process.