Reaction of amines and oxygen nucleophiles with 5-nitrocoumaran-2-one: nucleophilic and general base catalysis of hydrolysis

Abstract

The reaction of nitrocoumaranone (1) with bases was studied using aqueous solution. Primary and secondary amines react to yield the 2-hydroxy-5-nitrophenylacetamide. A negligible deuterium oxide solvent isotope effect and a large Brønsted β_n confirm the nucleophilic pathway and a class II aminolysis. Carboxylic acids, phosphate, and heterocyclic amines yield the acid product, and the low Brønsted β, deuterium oxide solvent isotope effect of 2–3, and comparison with reactivity against 4-nitrophenyl acetate indicate a general-base catalysed path. Tertiary alkylamines (yielding acid) are more efficient than predicted from the general base Brønsted relationship, are less efficient than the primary amines of similar pK_a, and have negligible deuterium oxide solvent isotope effect; these data and comparison with 4-nitrophenyl acetate reactivity indicate a nucleophilic mechanism.

Consideration of frontier orbitals and stereoelectronic factors indicates that the E1cB mechanism is an ‘allowed’ process which must be suppressed by the efficiency of trapping of the keten intermediate by the neighbouring hydroxy function.