Methyl Isocyanate → 1-Methyl-3-(4-cyano-3-(dimethylamino)-5-isothiazolyl)urea

Participants

Reaction Steps

Ten drops of dibutyltin diacetate were added to a solution of 3.0 g of 5-amino-4-cyano-3-(dimethylamino)-isothiazole and 1.9 g of methyl isocyanate in 25 ml of tetrahydrofuran. The solution was heated under reflux for two hours, at which time thin-layer chromatographic analysis indicated the reaction to be 40% complete. After the addition of 5 ml more of dibutyltin diacetate and 2 ml more of methyl isocyanate, heating was continued for 90 minutes. Thin-layer chromatographic analysis indicated the reaction to be 60% complete. An additional 15 ml of tetrahydrofuran to dissolve the precipitate which had formed, 10 drops of dibutyltin diacetate, and 3 ml of methyl isocyanate were added and heating was continued for three hours. Thin-layer chromatographic analysis indicated approximately 90% conversion to the desired product. The reaction mixture was stirred at ambient temperature overnight, 2 ml more of methyl isocyanate were added, and the solution was heated under reflux for 1 hour. Thin-layer chromatographic analysis indicated 95% completion. The reaction mixture was cooled to -10°, the solid was collected by filtration and washed with water. Purification was accomplished by recrystallization from 300 ml of methanol to give a solid, m.p. 240°-241°. A second crop of solid, m.p. 240°-241°, was also collected to give a total yield of 6.2 g of 1-methyl-3-(4-cyano-3-(dimethylamino)-5-isothiazolyl)urea. The nmr spectrum was consistent with the assigned structure.

Provenance & Evidence