A NOVEL X-RAY-POWDER DIFFRACTOMETRIC METHOD FOR STUDYING THE REACTIONBETWEEN PSEUDOEPHEDRINE ENANTIOMERS

The opposite enantiomers of pseudoephedrine were observed to react in the solid state to form the racemic compound. A novel powder X-ray dif fractometric method was developed for studying the kinetics and mechan ism of this reaction. The powder X-ray diffraction patterns of the ena ntiomers were identical, but the racemic compound exhibited a differen t pattern because of its different crystal structure. The powder patte rns of the enantiomers and the racemic compound revealed that the 4.62 and 4.25 Angstrom lines were unique to the enantiomers and the racemi c compound, respectively. Teflon holders were filled with equimolar mi xtures of the two enantiomers, and the integrated intensities of the 4 .62 and 4.25 Angstrom lines were measured at 30-min intervals over a p eriod of 8 h. Thus, the disappearance of the crystalline enantiomers a nd the appearance of the crystalline racemic compound were quantified simultaneously. The rate of disappearance of the crystalline enantiome rs followed a diffusion-controlled reaction model originally proposed by Jander in 1927. During the kinetic experiment, the sum of the weigh t fractions of the enantiomers and the racemic compound progressively decreased from an initial value of unity suggesting the existence of a n intermediate noncrystalline phase. The presence of the noncrystallin e 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-c rystalline amorphous intermediate in this solid-solid reaction.