The derivatization, solid-state characterization, and crystallization of a pharmaceutical precursor that expresses color polymorphism in the solid-state

The following thesis is divided into two sections. The first section involves the investigation of a pharmaceutical intermediate (ROY) that crystallizes into conformational polymorphs that differ dramatically in color. The ROY molecule adopts a dramatically different conformation in each crystal form, leading to changes in the electron distribution in the molecule. The changes in the electronics are detectable by both 13 C solid-state NMR and infrared spectroscopy. We hypothesize that the observed changes in crystal color are the result of the molecular conformation in each crystal form. The hypothesis is tested by the preparation and investigation of the solid-state properties of a series of derivatives of the ROY molecule.;The second section of this thesis investigates the crystallization of the ROY molecule in a lab-scale crystallizer. Recent interest has centered on the effect of impurity or additive molecules on the crystallization of organic molecules. The majority of this research has centered on molecules that adopt strong intermolecular hydrogen bonding networks in the crystal lattice. The ROY molecule, on the other hand, does not exhibit strong intermolecular hydrogen bonding in the solid-state, allowing for a situation in which the effect of weak, non-bonding interactions on the crystallization of polymorphs can be probed. ROY is crystallized alone or in the presence of one of the derivatives investigated in the first portion of this thesis. The crystals obtained from the different crystallization conditions are investigated in terms of crystal form, shape, size distribution, and thermal properties in an effort to investigate the effect of impurity or additive molecules on the crystallization of polymorphs. The results indicate that weak, non-bonding interactions can have a dramatic effect on the crystallization of polymorphs.