Formation of multi-component crystals with a series of pyridinium-carboxyacrylate zwitterions

Abstract

The reaction between acetylenedicarboxylic acid and nicotinamide or isonicotinamide produces two new zwitterionic molecules, namely (Z)-2-(3-carbamoylpyridin-1-ium-1-yl)-3-carboxyacrylate (1) and (Z)-2-(4-carbamoylpyridin-1-ium-1-yl)-3-carboxyacrylate (2), as well as a salt by-product, 4-carbamoylpyridinium acetylenedicarboxylate (2a). The solid-state behaviour of the zwitterions has been investigated by altering variables such as the solvent(s) used for synthesis and crystallisation, and the temperature at which these occur. Zwitterions 1 and 2, as well as a previously reported zwitterion, (Z)-2-(4-cyanopyridin-1-ium-1-yl)-3-carboxyacrylate (3), were combined with various small organic co-formers in an attempt to form multi-component crystals via both mechanochemical and solution methods. Three new hydrated salts were formed with melamine (1·melamine, 2·melamine, and 3·melamine), all of which display extensive charge-assisted hydrogen-bonding networks. Zwitterions 1 and 2 also form the characteristic R²₂(8) hydrogen-bond motif between the amide group and melaminium. Based on these observed trends in hydrogen bonding, further crystallisation experiments were attempted with molecules with similar hydrogen bonding capability to melamine. Although single crystals were not obtained, six potential salts have been identified based on PXRD, NMR and IR data. Compared to the number of co-formers used, the discovery of only three salts per zwitterion is unusual – a Cambridge Structural Database analysis indicates that this may be due to the robust nature of the hydrogen bonds between zwitterions themselves.