Structural evidence of polymorphism and conformational isomorphism of a somewhat flexible molecule: m-anisic acid

m-Anisic acid is generally recognized as a safe (GRAS) flavouring substance. Its GRAS status and the functional groups present in the molecule make it an interesting candidate for pharmaceutical co-crystallization studies. The knowledge of m-anisic acid crystalline structure/polymorphic behaviour is important information for its applications. In this work, a crystalline structure of m-anisic acid form I, T (fus) = 105 A degrees C, was solved by X-ray diffraction: monoclinic, space group P2(1)/n, with a = 13.8075(5) , b = 5.0221(2) , c = 21.4455(8) , beta = 99.325(3)A degrees, Mr = 331.37, V = 1467.44(10) (3), Z = 8 and R = 0.0395 (CCDC No. 985352). A recent paper by Raffo et al. (J Mol Struct 1070:86-93, 2014) (CCDC No. 985637) also resolved the structure, and within experimental error, the two structures are equal. The molecular flexibility of m-anisic acid results in the presence of two conformers in the unit cell, a rare case of conformational isomorphism. These two conformers were found by ab initio calculations to differ in energy by 4.9 kJ mol(-1). Solid samples were generated by crystallization from solutions and by melt cooling. Using a multidisciplinary approach involving thermal analysis (DSC, PLTM), infrared spectroscopy and X-ray powder diffraction, a new monotropic solid form II, T (fus) = 94 A degrees C, was identified and characterized. Polymorph II slowly transforms into polymorph I at room temperature.