Synthesis and Characterization of Thioketal Diol

The schematic for thioketal diol synthesis is illustrated in Figure 1A. Bismuth (III) chloride was added to a dry boiling flask that was subsequently dried with a hot air gun under vacuum for about 5 minutes to ensure completely dry catalyst conditions. The flask was then purged with nitrogen and left under a positive pressure with nitrogen for the remainder of the reaction. Anhydrous acetonitrile was charged to the flask to dissolve the catalyst. 2,2-dimethoxypropane and thioglycolic acid were added to the flask, and the reaction was allowed to proceed for 24 hours while stirring at room temperature. The carboxyl-terminated intermediate was filtered with a Buchner funnel, rotary evaporated (Buchi Rotovap R-200, 35 °C), and dried under vacuum overnight. The carboxyl groups were then reduced to produce a hydroxyl-terminated TK. A 3-neck boiling flask was fitted to a 10 °C condenser capped with a 1-way glass stop-cock, a constant pressure dropping funnel, and a rubber stopper. The reactor was heated with a heat gun under vacuum for about 5 minutes to ensure completely dry reaction conditions. The reactor was then placed in an ice bath, purged with dry nitrogen, and maintained under positive pressure with nitrogen throughout the functionalization. Lithium aluminum hydride (LiAlH₄) was added to the 3-neck boiling flask and dissolved in diethyl ether. Using anhydrous techniques, anhydrous tetrahydrofuran was added to the boiling flask containing the carboxyl-terminated TK. The resulting solution was then transferred to the dropping funnel and added to the LiAlH₄ solution dropwise at 0 °C. After all of the TK solution was added, the ice bath was replaced with an oil bath and the reaction mixture was refluxed at 52°C for 6–8 hours. Unreacted LiAlH₄ was quenched by adding DI water dropwise followed by 1M sodium hydroxide to aid in product extraction. By-products of the reaction were filtered using a Buchner funnel and filtration flask, and a separation funnel and diethyl ether were used to extract and isolate the TK diol product. The solvent was removed by rotary evaporation and the product dried under vacuum overnight for a completely dry, solvent-free TK diol. Nuclear magnetic resonance spectroscopy (¹H NMR, Bruker 400 MHz NMR) in dimethylsulfoxide (DMSO) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) verified the chemical structure of the TK diol. Titration of a sample reacted with excess p-toluenesulfonyl isocyanate with tetrabutylammonium hydroxide was used to determine the hydroxyl (OH) number of the TK diol according to ASTM E1899-08.²⁴ The molecular weight (M_n) was calculated from the OH number using Eq (1):
$$M_n=\frac{56,100}{\text{OH}\text{Number}}$$