Vibrational Spectroscopic Study of the Cocrystal Products Formed by Cinchona Alkaloids with 5-Nitrobarbituric Acid

X-ray powder diffraction, differential scanning calorimetry, infrared absorption spectroscopy, and Raman spectroscopy have been used to study the phenomenon of cocrystal formation in the molecular complexes formed by 5-nitrobarbituric acid with four cinchona alkaloids. The cocrystal products were found to contain varying degrees of hydration, ranging from no hydration in the nitrobarbiturate-quinidine cocrystal up to a 4.5-hydrate species in the nitrobarbiturate-cinchonine cocrystal. For the nitrobarbiturate cocrystals with cinchonine, cinchonidine, and quinidine, the predominant interaction was with the quinoline ring system of the alkaloid. However, for quinine, the predominant interaction was with the quinuclidine group of the alkaloid. These properties serve to demonstrate the utility of 5-nitrobarbituric acid as a preferred reagent for chemical microscopy, since the differing range of hydrate and structural types would serve to easily differentiate the cinchona alkaloids from each other, even when different compounds contained the same absolute configurations at their dissymmetric centers.