Isatin → 3-Methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione

Participants

Reaction Conditions

Reaction Steps

Isatin (294.3 g) is suspended in tetrahydrofuran (3 liter) and thereto are added with stirring triethylamine (279 ml) and methyl isocyanate (129.8 ml) at 15° C. The mixture is stirred at 20°-25° C. for 2.5 hours (1-methylcarbamoylisatin is produced in the mixture). To the reaction mixture are added 2-ethylisothiourea hydrobromide (444.2 g) and triethylamine (55.8 ml), and the mixture is refluxed for 2 hours. After cooling, the solvent is distilled off under reduced pressure. To the residue [i.e. 3-methyl-4-hydroxy-4-(2-ethylisothioureido)carbonyl-2-oxo1,2,3,4-tetrahydroquinazoline] is added 10% hydrochloric acid (4 liter) and the mixture is stirred at 70° C. for 4 hours. After cooling, the precipitates are taken by filtration, washed with water, methanol (1 liter) and chloroform (1 liter) in this order and then dried to give 3-methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione (369.2 g, yield 75 %).

Provenance & Evidence