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 = 105 °C, was solved by X-ray diffraction: monoclinic, space group P2/ n, with a = 13.8075(5) Å, b = 5.0221(2) Å, c = 21.4455(8) Å, β = 99.325(3)°, Mr = 331.37, V = 1467.44(10) Å, Z = 8 and R = 0.0395 (CCDC No. 985352). A recent paper by Raffo et al. (J Mol Struct 1070:86-93, ) (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. 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 = 94 °C, was identified and characterized. Polymorph II slowly transforms into polymorph I at room temperature. [ABSTRACT FROM AUTHOR]