Analysis of residual products in benzyl chloride used for the industrial synthesis of quaternary compounds by liquid chromatography with diode-array detection

Abstract

In industrial and pharmaceutical processes, the study of residual products becomes essential to guarantee the quality of compounds and to eliminate or minimize toxic residual products. Knowledge about the origin of impurities (raw materials, processes, the contamination of industrial plants, etc.) is necessary in preventive treatment and in the control of a product's lifecycle. Benzyl chloride is used as raw material to synthesize several quaternary ammonium compounds, such as benzalkonium chloride, which may have pharmaceutical applications. Benzaldehyde, benzyl alcohol, toluene, chloro derivatives of toluene, and dibenzyl ether are compounds that may be found as impurities in technical benzyl chloride. We proposed a high-performance liquid chromatography method for the separation of these compounds, testing two stationary phases with different dimensions and particle sizes, with the application of photodiode array-detection. The linearity for four possible impurities (benzaldehyde, toluene, α,α-dichlorotoluene, and 2-chlorotoluene) ranged from 0.1 to 10 μg/mL, limits of detection from 11 to 34 ng/mL, and repeatability from 1 % to 2.9% for a 0.3-1.2 μg/mL concentration range. The method was applied to samples of technical benzyl chloride, and α,aα-dichlorotoluene and benzaldehyde were identified by spectral analysis and quantitated. The selection of benzyl chloride with lower levels of impurities is important to guarantee the reduction of residual products in further syntheses.