Cocrystals/salt of 1-naphthaleneacetic acid and utilizing Hirshfeld surface calculations for acid–aminopyrimidine synthons

Abstract

A series of cocrystals/salts of aminopyrimidine derivatives (2-aminopyrimidine, 2-amino-4,6-dimethylpyrimidine, and 2,4,6-triaminopyrimidine) with 1-naphthaleneacetic acid are successfully prepared to revisit the robustness of acid–aminopyrimidine synthons (linear heterotetramer (LHT) and heterotrimer (HT)) and their behavior, with a changing environment at the 4,6 position of the aminopyrimidine ring. Furthermore, attempts have also been made to verify the formation of cocrystal/salt using ΔpK_a values. The cocrystals/salt were characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and their structural determinations were carried out by single-crystal X-ray diffraction (SCXRD). Hirshfeld surface analysis and computational studies (interaction energy calculations and energy frameworks) were performed to gain a better understanding of the overall occurrence of LHT and HT synthons.