Chemical characterization, absolute configuration and optical purity of (1S)-(+)- and (1R)-(–)-10-camphorsulfonic acid

Comprehensive chemical characterization for two isomers of camphorsulfonic acid (CSA), occasionally used in the manufacture of active pharmaceutical ingredients (APIs), was performed by nuclear magnetic resonance (NMR) spec­troscopy, high-resolution mass spectroscopy in negative electrospray ionization mode and gas chromatography/mass spectrometry (GC/MS) in electron ionization mode. Electronic circular dichroism (ECD) spectra together with quantum chemical calculations using time-dependent density functional theory (TD-DFT) were used to assign the stereochemistry for CSA for the first time and these assignments were then confirmed by single-crystal X-ray dif­­frac­tion. As crystals were grown under the same conditions of high supersaturation using a mixed solvent without water removal, the crystal structures of the two enanti­omers contained one ordered mol­ecule of water in the asymmetric unit. The crystals of the (+)-enanti­omer have a 1S,4R con­figuration and the H atom of the sulfonic acid group combines with the water mol­ecule to form a hydro­nium ion, namely, hydro­nium (1S,4R)-(7,7-dimethyl-2-oxobi­cyclo­[2.2.1]heptan-1-yl)methane­sul­fon­ate, H3O+·C10H15O4S−. The crystals of the (−)-enanti­omer have a 1R,4S configuration. The determination of the optical purity of CSA using NMR spectroscopy with a chiral solvating agent, (1R,2R)-1,2-di­phenyl­ethane-1,2-di­amine, and GC/MS with a chiral column has been well explored. The results showed that the examined samples of these two isomers of CSA proved to be enanti­omerically pure. In particular, for (1R)-(−)-10-camphorsulfonic acid, this is, to our knowledge, the first description on its spectral characterization in a scientific context.