Investigation of Stability and Structure in Three Homochiral and Heterochiral Crystalline Forms of 3-Phenyllactic Acid

3-Phenyllactic acid (3PLA) is a new example of a chiral compound that can form a conglomerate or a racemic crystal upon crystallization of racemic 3PLA. In this study, homochiral crystals (1), heterochiral racemic crystals (2) (reported here for the first time), and conglomerates (3) of 3PLA were prepared, and the thermal stability, crystal structures, and spectroscopic properties of 1−3 were investigated. Crystals of 1 and 3 formed from aqueous solution as needles (orthorhombic, P212121), while crystals of 2 formed from 3:1 hexanes−ethyl acetate as rectangular blocks (monoclinic, P21/c). The pure enantiomer and conglomerates are unusual in that they exhibit slightly greater thermodynamic stability than the racemic form (Δ(ΔHfus) = 4.0 kJ/mol) despite having considerably lower density (Δρcalc = 3.7%) and less efficient molecular packing in accordance with Wallach’s Rule. Considering that molecules of 3PLA adopt essentially identical conformations in the homochiral and heterochiral crystals, the higher stability in crystals of pure enantiomer (1 and 3) results from stronger hydrogen-bonding interactions via homochiral packing as compared to heterochiral packing in racemic crystals (2). 3PLA therefore provides a unique test system to investigate the influence of surface energetics and solvation in biasing homochiral vs heterochiral nucleation to develop methods for enantioseparation via crystallization.