Polymorphism and crystallization of p-aminobenzoic acid

p-Aminobenzoic acid (PABA) crystallizes in two different polymorphic forms: the α-polymorph, which is the commercially available form and appears as long, fibrous needles, and the β-polymorph, which appears in the form of prisms. The thermodynamic stability and crystallization from different solvents have been studied experimentally. The system is found to be enantiotropic with a transition temperature of 25°C, below which the β-form is the stable polymorph. The compound has been crystallized from 13 different solvents, either by slow cooling after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Needles were obtained from all solvents by both methods. In water and in ethyl acetate, at slow cooling below 20̊C, the prismatic β-form is obtained, however, often together with the needles. The β-form crystals usually needed hours or days to grow at the very slow cooling used, while needles usually appeared in seconds. By careful control of supersaturation and temperature, cooling crystallization can be performed to produce the pure β-form in water and in ethyl acetate. The influence of the solvent is explained by analysis of the crystal structures versus the possible interaction of the solvent molecules with the solute in solution. The α-form structure is governed by carboxylic acid dimers and is kinetically favored since it is believed that the corresponding dimers easily form in the solution, especially in less polar solvents.