Simple spectrophotometry method for the determination of sulfur dioxide in an alcohol-thionyl chloride reaction.

Thionyl chloride is often used to convert alcohols into more reactive alkyl chloride, which can be easily converted to many compounds that are not possible from alcohols directly. One important reaction of alkyl chloride is nucleophilic substitution, which is typically conducted under basic conditions. Sulfur dioxide, the by-product from alcohol-thionyl chloride reactions, often reacts with alkyl chloride to form a sulfonyl acid impurity, resulting in yield loss. Therefore, the alkyl chloride is typically isolated to remove the by-products including sulfur dioxide. However, in our laboratory, the alkyl chloride formed from alcohol and thionyl chloride was found to be a potential mutagenic impurity, and isolation of this compound would require extensive safety measures. As a result, a flow-through process was developed, and the sulfur dioxide was purged using a combination of vacuum degassing and nitrogen gas sweeping. An analytical method that can quickly and accurately quantitate residual levels of sulfur dioxide in the reaction mixture is desired for in-process monitoring. We report here a simple ultraviolet (UV) spectrophotometry method for this measurement. This method takes advantage of the dramatic change in the UV absorbance of sulfur dioxide with respect to pH, which allows for accurate quantitation of sulfur dioxide in the presence of the strong UV-absorbing matrix. Each sample solution was prepared using 2 different diluents: 1) 50 mM ammonium acetate in methanol +1% v/v hydrochloric acid, pH 1.3, and 2) 50 mM ammonium acetate in methanol +1% glacial acetic acid, pH 4.0. The buffer solutions were carefully selected so that the UV absorbance of the sample matrix (excluding sulfur dioxide) at 276 nm remains constant. In the pH 1.3 buffer system, sulfur dioxide shows strong UV absorbance at 276 nm. Therefore, the UV absorbance of sample solution is the sum of sulfur dioxide and sample matrix. While in the pH 4.0 buffer system, sulfur dioxide has negligible UV absorbance at 276 nm, and the UV absorbance is attributed only to sample matrix. Quantitation of sulfur dioxide is achieved by subtracting the UV absorbance of sample solution at pH 4.0 from that at pH 1.3. The method is simple but sensitive, with a limit of quantitation of 80 μg L(-1). The method linearity was demonstrated from 2 mg L(-1) to 40 mg L(-1) with an R(2) of 0.998, and the spiked recovery ranges from 94% to 105% within the same range. The results are comparable with those obtained using inductively coupled plasma-atomic emission spectrometry (ICP-AES) and gas chromatography-mass spectrometry (GC-MS), suggesting that this method is accurate.