Polymorphism in Isomeric Dihydroxybenzoic Acids

Multifunctional molecules are capable of assembling via different supramolecular synthons, or hydrogen bond motifs, between the same or different functional groups, leading to the possibility of polymorphism. We have employed sublimation and melt crystallization to generate two new crystalline polymorphs of 3,5-dihydroxybenzoic acid (DHBA), and a second form for 2,3-dihydroxybenzoic acid and 3,4-dihydroxybenzoic acid each. Since hydroxybenzoic acids tend to give solvate/hydrate crystal structures by solution crystallization, solvent-free methods are necessary to obtain single crystals of unsolvated forms. In addition to guest-free polymorphs, a new hydrate polymorph of 3,4-dihydroxybenzoic acid was crystallized from cold water. Polymorphs of dihydroxybenzoic acids differ in the number of symmetry-independent molecules (Z'), the nature of the hydrogen bond synthon, the molecular packing, and the unit cell parameters. Structural and thermal characterization of polymorphic phases shows that the commercial material matches with the high Z' phase for 2,3-DHBA, 3,5-DHBA, and 3,4-DHBA hydrate even though a low Z' crystal structure is known in each case. Solventless crystallization conditions at high temperature are a practical method to generate new guest-free polymorphs and high Z' crystal structures for high affinity functional group compounds.