Anthranilic Acid → Quinazolin-4-one, 1,3-dihydro-3-phenyl-2-thio-

HRID 568999Notes

Reaction equation

HRID 568999 reaction equation
[C:1]1([N:7]=[C:8]=[S:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10](O)(=[O:18])[C:11]1[C:12](=[CH:14][CH:15]=[CH:16][CH:17]=1)[NH2:13]>>[C:1]1([N:7]2[C:10](=[O:18])[C:11]3[C:12](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:13][C:8]2=[S:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

3

Reactant 2

HCID 227Anthranilic AcidHCID 7673Phenyl Isothiocyanate

Product 1

HCID 680914Quinazolin-4-one, 1,3-dihydro-3-phenyl-2-thio-Yield 61.1%

Procedure

Phenyl isothiocyanate (28.3 g) was added to anthranilic acid (28.7 g) in absolute alcohol (250 ml) and heated at reflux for 4.5 hours. The mixture was cooled to room temperature and the solid removed by filtration to give 32.5 g of 3-phenyl-2,3-dihydro-2-thioxoquinazolin-4(1H)-one, mp 287°-291° C. Sulphuryl chloride (5.4 ml) was added dropwise at room temperature to a suspension of this product (32.5 g) in chloroform (250 ml). The mixture was heated at reflux for 4 hours. When cool, it was poured into water (400 ml), filtered and the solid washed with dichloromethane. The organic layer was separated from the filtrate, dried and concentrated in vacuo. The residue was extracted with ether, filtered and the filtrate concentrated in vacuo to give an oil which solidified on standing. This was recrystallised from cyclohexane to give crude 2-chloro-3-phenylquinazolin-4(3H)-one, mp 102°-5° C. (shown to be 90% pure by high pressure liquid phase chromatography (hplc). A mixture of this product (3.85 g), imidazole (1.02 g) and potassium carbonate (2.07 g) in acetonitrile (60 ml) was heated at reflux for 4 hours. The mixture was cooled to room temperature, and concentrated in vacuo. The residue was chromatographed on silica using light petroleum (bp 60°-80° C.)/ethyl acetate (1:1) as eluant. The resulting solid was recrystallised from cyclohexane to give 0.8 g of 3-phenyl-2-(imidazol-1-yl)-quinazolin-4(3H)-one, mp 163°-5° C. (Compound 1).

Workup

  1. temperatureheated
  2. temperatureat reflux for 4.5 hours
  3. customthe solid removed by filtration

Sources & evidence

ORD record
ord-c8e0b523ecd04e10b9d36ae4019cd037
Source dataset
uspto-grants-1988_03
Patent number
US04731106

Reaction notes

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