Polymorphism of Cooling Agent WS ‐3

ABSTRACT The synthetic cooling agent N ‐ethyl‐2‐isopropyl‐5‐methylcyclohexanecarboxamide (WS‐3) is a menthol derivative widely used in the food, personal care, and pharmaceutical industries. However, its polymorphic behaviour has not yet been reported. In this study, a systematic screening and characterization of WS‐3 crystal forms was conducted using solution, melt, and sublimation crystallization, together with mechanical grinding. Two anhydrous polymorphs (Form A and Form B) were discovered and characterized. Form A melts at a temperature approximately 6°C lower than that of Form B. The two forms are enantiotropic polymorphs with a transition temperature of 60°C–70°C. High‐quality single crystals of Form A were successfully grown via evaporative crystallization, and the crystal structure was determined by single‐crystal X‐ray diffraction. Form A crystallizes in the monoclinic crystal system, space group P 2 1 , with eight molecules per unit cell ( Z = 8, Z ′ = 4). The molecules are linked via intermolecular NH···O hydrogen bonds between amide groups into one‐dimensional chains, which further assemble into a three‐dimensional crystal structure. This study presents the first systematic investigation of the polymorphic behaviour of WS‐3, providing essential data for crystal form selection, quality control, and crystallization process optimization of this important synthetic cooling agent.