Quantitative analysis of dimethyl titanocene by iodometric titration, gas chromatography and NMR.

摘要

In this study we report the use of an automated iodometric titration method and a novel gas chromatography (GC) method for the quantitative analysis of dimethyl titanocene (DMT), a key raw material in drug synthesis. Both approaches are based on the reaction of DMT in toluene or tetrahydrofuran solutions with iodine. In the case of iodometric titration, excess iodine is titrated with a standardized aqueous sodium thiosulfate solution to a potentiometric end-point for the determination of DMT concentration. Alternatively, GC is employed to measure the concentration of iodomethane, a product of the reaction between DMT and iodine, in order to determine the concentration of DMT in the solution. Excellent agreement between iodometric titration, GC and NMR results using several DMT samples confirms the accuracy of the two methods and strongly supports the use of either method as a replacement to the expensive NMR for quantitative DMT analysis. The relatively few sources of error associated with the two methods, their ubiquitous nature and ease of application in routine analysis make them the analytical methods of choice, among all. Both methods have been validated according to ICH requirements. The use of iodometric titration method for DMT analysis is demonstrated with a couple of applications.