Reacción #62826

Ecuación de reacción

Isatin

methyl isocyanate

2-ethylisothiourea hydrobromide

1-methylcarbamoylisatin

→

3-methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione

Rendimiento 75.0%

Disolventes

triethylamine

triethylamine

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrois produced in the mixture)
2. 2
   Temperaturathe mixture is refluxed for 2 hours
3. 3
   TemperaturaAfter cooling
4. 4
   workup.DISTILLATIONthe solvent is distilled off under reduced pressure
5. 5
   workup.ADDITIONTo 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)
6. 6
   TemperaturaAfter cooling
7. 7
   Filtraciónthe precipitates are taken by filtration
8. 8
   Lavadowashed with water, methanol (1 liter) and chloroform (1 liter) in this order
9. 9
   Otrodried

Procedimiento

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 %).

Fuente