A cocrystal strategy for the precipitation of liquid 2,3-dimethyl pyrazine with hydroxyl substituted benzoic acid and a Hirshfeld surfaces analysis of them

Abstract

We here report the cocrystal strategy for the precipitation of liquid 2,3-dimethyl pyrazine (2,3-DMP) with the hydroxyl substituted benzoic acids: salicylic acid (SA), m-hydroxybenzoic acid (MHBA) and p-hydroxybenzoic acid (PHBA) under identical conditions, and obtained three cocrystals (cocrystal 1–3), respectively. Their crystal structures were characterized by single-crystal X-ray diffraction, IR spectra, differential scanning calorimetry (DSC), thermogravimetric analyses (TGA), hot stage microscopy (HSM) and X-ray powder diffraction (XRPD). Wherein, 1 forms a 1 : 2 2,3-DMP : SA cocrystal; 2 forms a 1 : 1 2,3-DMP : MPHA cocrystal and 3 forms a 1 : 1 : 1 2,3-DMP : PHBA : H₂O cocrystal. The structure determination shows that the three cocrystals are all primarily stabilized by a strong O–H⋯N hydrogen bonding interaction between 2,3-DMP and the hydroxyl substituted benzoic acid. We also prepared and analysed Hirshfeld surfaces and fingerprint plots of the reported cocrystals and reveal that the structures are stabilized by H⋯H, O–H⋯N, O–H⋯N, C–H⋯π, π⋯π and lone-pair⋯π intermolecular interactions. Additionally, what is interesting is that cocrystal 2 sublimes half the 2,3-DMP at about 110 °C during the heating procedure, while the other half sublimes at about 226 °C, which was confirmed by the XRPD measurement. This may be developed for the controlled release of 2,3-DMP.