The synthesis of 4–methyl–3–thiosemicarbazide (MTSC) using N,N–diisopropylethylamine as base

Abstract

4-Methyl-3-thiosemicarbazide (MTSC) is an intermediate for the synthesis of 5-t-butyl-2-methylamino-1,3,4-thiadiazole (BTDA), the precursor of tebuthiuron, a broad-spectrum herbicide. The current production process for MTSC being used at Sanachem's Devchem plant in Sasolburg entails the hydrazinolysis of ammonium N-methyldithiocarbamate. This method affords only a 60-65% yield of MTSC with purity of only 93-94%, while the manufacturing of BTDA of high purity (>98%) and yield requires MTSC of good quality (>97%). The current method also generates approximately 4kg of effluent for each kilogram of product. The effluent contains high concentrations of ammonium salts. An alternative base for the preparation of the methyldithiocarbamate intermediate was required. N,N-Diisopropylethylamine (DIPEA) has been evaluated as a potential base for the preparation of the N-methyldithiocarbamate intermediate. The N,Ndiisopropylethylammonium N-methyldithiocarbamate intermediate proved to be significantly more stable than its counterparts (Na+, 1<, NH/), resulting in a decrease in the formation of the by-products thiocarbohydrazide (TCH) and dimethylthiourea (DMTU). MTSC yields of 70-75% and purities of 97.5-98.5% were attained. Using DIPEA as base also reduced the amount of effluent produced. For each kilogram of MTSC only two kilograms of effluent were produced. This resulted in a reduction of waste disposal cost. On completion of a factorial design, it was concluded that the yield of MTSC had to be sacrificed for purity. A yield of 73% and a purity of 98% for MTSC could be attained under the conditions for maximum purity. DIPEA proved to be an excellent alternative to NH40H as base for the preparation of Nmethyldithiocarbamate as precursor of MTSC. Not only could better yields and purity for MTSC be achieved, but also a decrease in raw material cost. Using DIPEA as base is more cost effective than using NH40H because it can be recovered and reused.