The Astounding Chemistry of a 2-Amino-1,2-dihydroisoquinoline Derivative

Abstract

The cycloadducts of isoquinolinium N-phenyl imide 2 with C=C bonds are derivatives of 2-amino-1,2-dihydroisoquinoline. Their Nβ-vinylphenylhydrazine system is amenable to an acid-catalyzed [3,3]-sigmatropic shift; the formation of pentacyclic aminals is exemplified by 68. The dimethyl maleate adduct 11, C21H20N2O4, is exceptional by being converted on treatment with acid to bright-yellow crystals, C24H22N2O6 (additional C3H2O2). X-Ray crystal-structure analysis and NMR spectra reveal structure 13, and mechanistic studies indicated an initial β-elimination at the N−N bond of 11 to yield 18; this step is followed by a retro-Mannich-type cleavage that gives methyl isoquinoline-1-acetate (14) and methyl 2-(phenylimino)acetate (15), according to the sequence C21H20N2O4 (11)18C12H11NO2 (14)+C9H9NO2 (15). In the second act of the drama, electrophilic attack by 15-H+ on the ene-hydrazine group of a second molecule of 11 furnishes 13 by a polystep intramolecular redox reaction. All rate constants must be fine-tuned in this reaction cascade to give 13 in yields of up to 78% with an overall stoichiometry: 2 C21H20N2O4 (11)C24H22N2O6 (13)+C12H11NO2 (14)+aniline. Interception and model experiments confirmed the above pathway. A by-product, C33H31N3O6 (62), arises from an acid-catalyzed dimerization of 11 and subsequent elimination of 15.