Polymorphism in co-crystals: a metastable form of the ionic co-crystal 2 HBz·1 NaBz crystallised by flash evaporation

Abstract

While polymorphism is a wide spread phenomenon, the number of reported polymorphic co-crystals is still very limited. Here we report the synthesis and structural characterisation of such a rare case of polymorphism with a co-crystal of benzoic acid (HBz) and sodium benzoate (NaBz). Flash evaporation yielded a new polymorph of this ionic co-crystal with a stoichiometry of 2 HBz?1 NaBz. The thermodynamic relationship between the known and the new polymorph was determined to be of enantiotropic nature. At room temperature, this new form B is metastable. While the known form A is composed of one dimensional tapes, form B is built from infinite rods. The coordination sphere of sodium, however, in both forms is octahedral and the packing around it is dense.

Microphase Separation with Small Amphiphilic Molecules: Crystal Structure of Preservatives Sodium Benzoate (E 211) and Potassium Benzoate (E 212)

“…A co‐crystal with the composition 2HBz · 1NaBz (two formula units HBz and one formula unit NaBz) could be structurally characterized. Furthermore a second polymorph of this co‐crystal (form B) could be crystallized by flash evaporation and also structurally characterized 12. In a review we compared these two polymorphs with analogue co‐crystals of HBz and benzoates with different cations 13…”

Three cocrystals and a cocrystal salt of pyrimidin-2-amine and glutaric acid

“…Polymorphism in cocrystals, however, is rarely reported. In 2010, there were about 50 characterized cocrystal polymorphs, accounting for about 1.4% of the characterized cocrystals (Butterhof et al, 2012). The low number of cocrystal polymorphs compared to single-component crystals could be due to research into cocrystal polymorphs still being in its infancy and this fact may be regarded as another confirmation of the observation that ' .…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…A more challenging aspect is to quantify nanocrystals in an amorphous material. Scherrer broadening (broadening of the diffraction peaks due to a reduction in crystallite size) may reduce the diffracted intensity for a crystalline material such that it becomes [205] √ (ATR) √ √ √ Nitrofurantoin cocrystal solvate, hydrates, salts [206] √ √ √ √ √ Nitrofurantoin cocrystal hydrate [126] √ √ √ √ √ Caffeine cocrystal polymorph, hydrate and solvates [116] √ [207] √ √ √ √ Salicylic acid cocrystal polymorphs [118] √ √ Felodipine cocrystal polymorph [115] √ √ √ Benzoic acid cocrystal polymorph [208] √ √ √ Glycine cocrystal polymorph [166] √ √ Vanillic acid cocrystal hydrate [125] √ √ √ √ Agomelatin cocrystal polymorph [209] √ √ √ √ Diclofenac cocrystal polymorph hydrate [104] √ √ (VT) √ √ Nicotinamide cocrystal polymorph [210] √ √ √ √ √ Phenazine cocrystal polymorph and solvate [105] √…”