Factors Controlling Persistent Needle Crystal Growth: The Importance of Dominant One-Dimensional Secondary Bonding, Stacked Structures, and van der Waals Contact

Needle crystals can cause filtering and handling problems in industrial settings, and the factors leading to a needle crystal morphology have been investigated. The crystal growth of the amide and methyl, ethyl, isopropyl, and t-butyl esters of diflunisal have been examined, and needle growth has been observed for all except the t-butyl ester. Their crystal structures show that the t-butyl ester is the only structure that does not contain molecular stacking. A second polymorph of a persistent needle forming phenylsulfonamide with a block like habit has been isolated. The structure analysis has been extended to known needle forming systems from the literature. The intermolecular interactions in needle forming structures have been analyzed using the PIXEL program, and the properties driving needle crystal growth were found to include a 1D motif with interaction energy greater than -30 kJ/mol, at least 50% vdW contact between the motif neighbors, and a filled unit cell which is a monolayer. Crystal structures are classified into persistent and controllable needle formers. Needle growth in the latter class can be controlled by choice of solvent. The factors shown here to be drivers of needle growth will help in the design of processes for the production of less problematic crystal products.