In situ IR spectral identification of NH4H2PO4 structural evolution during crystallization in water–ethanol mixed solvent

Abstract

Both the crystallizing molecule without long-range ordered arrangement and the complex interactions between solvent, anti-solvent, and molecule crystal challenge the imaging of molecule configurations during anti-solvent crystallization. Here, the structural evolution of NH₄H₂PO₄ during anti-solvent crystallization was tracked by in situ ATR-IR spectroscopy. The NH₄H₂PO₄ molecule undergoes D_2d → C_2v → D_2d or C_2v → D_2d during anti-solvent crystallization, depending on both V(H₂O)/V(ethanol) ratio and the concentration of NH₄H₂PO₄ aqueous solution. Moreover, IR spectroscopy can also be used to confirm the anti-solvent role of ethanol in the NH₄H₂PO₄–H₂O–ethanol crystallization system. The volatilization of ethanol has been demonstrated as an effective approach to control the dissolution process of NH₄H₂PO₄, which can be used to study the crystallization–dissolution–recrystallization process. The present study can shed light on the anti-solvent crystallization physical and chemistry of NH₄H₂PO₄ from a molecule-level viewpoint.