Advanced prototype using second harmonic generation (SHG) for pre-screening of conglomerates

Up to know, the enantiomers of component A (a chiral intermediate schematized in figure 1) have been separated by means of chiral chromatography. A less expensive method applicable to industrial production was requested. The resolution by preferential crystallization, which requires a stable conglomerate, could be one of the alternative routes. In this study, the screening of potential conglomerates was performed by using the Second Harmonic Generation (SHG). Among the 109 crystallization attempts with different counter ions and solvents, 51 crystalline salts were obtained; a single conglomerate-forming system has been detected (with sulfamic acid). Resolution by means of preferential crystallization has been achieved with this salt. This paper underlines the potential of SHG method as a pre high throughput technique for spotting chiral discrimination in the solid state.