The general procedure for the synthesis of 3-(chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one from 3-(hydroxymethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one was as follows: 3-(hydroxymethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one (1.638 kg, 68 wt%. 8.625 mol) and N-methylpyrrolidone (8.9 L) were added to a 30 L reaction vessel to form a suspension. The suspension was aged at room temperature for 10 hours. Subsequently, the slurry was cooled to 2 °C, filtered through a 4 L sintered glass funnel and the filter cake (mainly composed of NaCl) was washed with N-methylpyrrolidone (2.23 L). The water content of the combined filtrate and wash solution was determined to be 5750 μg/mL.The resulting solution was transferred to a 75 L flask equipped with a 2 N NaOH scrubber to capture the off-gas generated during the reaction. Thionyl chloride (0.795 L, 10.89 mol) was added slowly over a period of 1 h and the reaction temperature was raised to 35 °C. The reaction was carried out by HPLC analysis. The reaction process was confirmed by HPLC analysis and it was found that additional addition of thionyl chloride (0.064 L, 0.878 mol) was required to achieve complete conversion. Subsequently, the reaction solution was warmed up to 50 °C and degassed under 60 torr vacuum (via a 2 N NaOH scrubber) while a slight jet of nitrogen was passed at a flow rate of 4 L/min. The degassing process was continued for 10 h until the sulfur dioxide content of the solution was less than 5 mg/mL as determined by quantitative GC/MS.Eventually, a tan solution of 3-(chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one in N-methylpyrrolidone was obtained, with a total weight of 13.0 kg, and the content was determined to be 9.63 wt%, which was calculated as a product of 1.256 kg in 97% yield.
