Exploring the structural landscape of 2-aminopyrazines via co-crystallizations

Abstract

A correlation between the electrostatic charge on the hydrogen-bond acceptor sites of 2-aminopyrazine derivatives and the ability of the compound to form intermolecular hydrogen bonds with carboxylic acids in the solid state has been established. The charge on the hydrogen-bond acceptor can be modulated which leads to a predictable lowering of the supramolecular yield of the reaction. The outcome of all reactions was screened using IR spectroscopy, and twelve new crystal structures are reported to verify the spectroscopic assignments, and to examine the exact nature of the primary intermolecular interactions. The binding preference of carboxylic acids towards the two possible binding sites of 2-aminopyrazines has also been examined, and the main driving force for the assembly of the heteromer between bases and carboxylic acids is the two-point O–H⋯N/O⋯H–N synthon. However, seven out of twelve times carboxylic acids also bind via a single-point O–H⋯N synthons. This ‘synthon crossover’ is unavoidable due to highly competitive binding sites present in the N-heterocyclic bases chosen.