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

HRID 34548

Reaction equation

HRID 34548 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[CH3:12][N:13]=[C:14]=[O:15].C[NH:17][C:18]([N:20]1C2C(=CC=CC=2)C(=O)C1=O)=[O:19].Br.C(SC(=N)N)C>O1CCCC1.C(N(CC)CC)C>[CH3:12][N:13]1[C:4]2([C:2](=[O:3])[NH:20][C:18](=[O:19])[NH:17]2)[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[NH:1][C:14]1=[O:15]

Participants

7

Reactant 4

HCID 7054IsatinHCID 12228Methyl IsocyanateHCID 200213S-Ethylisothiuronium bromideHCID 2835543N-(methylcarbamoyl)isatin

Product 1

HCID 142299883-Methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trioneYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
70 °C

Procedure

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 %).

Workup

  1. customis produced in the mixture)
  2. temperaturethe mixture is refluxed for 2 hours
  3. temperatureAfter cooling
  4. distillationthe solvent is distilled off under reduced pressure
  5. 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. temperatureAfter cooling
  7. filtrationthe precipitates are taken by filtration
  8. washwashed with water, methanol (1 liter) and chloroform (1 liter) in this order
  9. customdried

Sources & evidence

ORD record
ord-5590a2d8fe894688ad10925b9cbadf48
Source dataset
uspto-grants-1988_08
Patent number
US04762839

Linked notes

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