A Novel X-ray Powder Diffractometric Method for Studying the Reaction between Pseudoephedrine Enantiomers

Abstract

The opposite enantiomers of pseudoephedrine were observed to react in the solid state to form the racemic compound. A novel powder X-ray diffractometric method was developed for studying the kinetics and mechanism of this reaction. The powder X-ray diffraction patterns of the enantiomers were identical, but the racemic compound exhibited a different pattern because of its different crystal structure. The powder patterns of the enantiomers and the racemic compound revealed that the 4.62 and 4.25 A lines were unique to the enantiomers and the racemic compound, respectively. Teflon holders were filled with equimolar mixtures of the two enantiomers, and the integrated intensities of the 4.62 and 4.25 A lines were measured at 30-min intervals over a period of 8 h. Thus, the disappearance of the crystalline enantiomers and the appearance of the crystalline racemic compound were quantified simultaneously. The rate of disappearance of the crystalline enantiomers followed a diffusion-controlled reaction model originally proposed by Jander in 1927. During the kinetic experiment, the sum of the weight fractions of the enantiomers and the racemic compound progressively decreased from an initial value of unity suggesting the existence of an intermediate noncrystalline phase. The presence of the noncrystalline phase was confirmed by a steady increase in the background of the X-ray patterns. Thus, the unique ability of the X-ray method to quantify only the crystalline phases has demonstrated the existence of a non-crystalline amorphous intermediate in this solid-solid reaction.

Determination of the Optical Purity of Ibuprofen Using X-ray Powder Diffraction

“…2 These techniques depend on the presence of a diffraction line in the XRPD pattern of one of the components of the mixture which is absent in the pattern of the other component. 5 It is important to realize that this method cannot be used if the mixtures either contain amorphous material or exist as conglomerates or solid solutions 2-(4-Isobutylphenyl)propanoic acid (ibuprofen) is the most widely used nonsteroidal anti-inflammatory agent. These may be easily distinguished by examination of the binary melting point phase diagram of the mixture of interest.…”

Characterization of Polymorphs of a Novel Quinolinone Derivative, TA-270 (4-Hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone).

“…7,8) Several techniques for solid state measurements have been reported in the study of polymorphs: microscopy, infrared (IR) spectroscopy, 9) differential scanning calorimetry (DSC), [10][11][12] powder X-ray diffractometry, 13,14) and solid state NMR spectroscopy. [15][16][17][18][19][20][21] In the present study, the characterization of various crystalline forms of TA-270 was examined as a preformulation study. To confirm the molecular state of the polymorphic forms, powder X-ray diffractometry, thermal analysis, IR spectroscopy and solid state 13 C-NMR spectroscopy were performed.…”

Adaptive Aggregation and Chirality Recognition of Neuroactive Substances and their Building Blocks: A Vibrational Spectroscopic and Microscopic Study

“…The hydrogen bonded chains are connected by weak aromatic C-H• • •O interactions (2.2 Å) along the a axis and by van der Waals interactions of the phenyl and the methyl group in another dimension. The formation of needle-like racemic pseudoephedrine crystals was reported by Duddu et al and characterized by its X-ray diffraction pattern[173].…”

“…7.35) is a white powder. Its melting temperature is 119 • C [173]. So far, the crystal structure of racemic pseudoephedrine has not been determined.…”

“…This would lead to the conclusion that the enantiopure crystals are more stable than racemic pseudoephedrine. However, a negative Gibbs free energy (∆G = −0.55 kcal•mol −1 ) was determined for the formation of the racemate from opposite enantiomers in the solid state by X-ray powder diffraction [173]. This rather points at a higher stability of the racemate.…”