Ammonium Chloride → 2-Chloro-8-phenyl-5,6,7,8-tetrahydroquinazoline

HRID 451127Notes

Reaction equation

HRID 451127 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[N:3]=1.[Cl-].[NH4+]>CC(C)=O.O.[Zn]>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[N:3]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 580752532,4-Dichloro-8-phenyl-5,6,7,8-tetrahydroquinazoline

Product 1

HCID 580755572-Chloro-8-phenyl-5,6,7,8-tetrahydroquinazolineYield 52.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2,4-dichloro-8-phenyl-5,6,7,8-tetrahydroquinazoline (51.9 mg, 0.186 mmol), ammonium chloride (13.0 mg, 0.243 mmol) and zinc (130 mg, 1.988 mmol) in acetone (0.75 mL) and water (0.75 mL) was heated at 90° C. with stirring for 2 h. The reaction mixture was filtered through a short plug of diatomaceous earth (Celite®). The solvent was removed in vacuum, and the residue was partitioned between dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 2-chloro-8-phenyl-5,6,7,8-tetrahydroquinazoline (24.1 mg, 0.097 mmol, 52.4% yield) as white solid. LC-MS (M+H)+=245.1. 1H NMR (500 MHz, CDCl3) δ ppm 8.39 (1H, s), 7.27 (2H, t, J=7.6 Hz), 7.16-7.23 (1H, m), 6.95 (2H, d, J=7.3 Hz), 4.21 (1H, t, J=6.0 Hz), 2.72-2.91 (2H, m), 2.14-2.26 (1H, m), 1.95-2.06 (1H, m), 1.81-1.93 (1H, m), 1.71-1.81 (1H, m).

Workup

  1. filtrationThe reaction mixture was filtered through a short plug of diatomaceous earth (Celite®)
  2. customThe solvent was removed in vacuum
  3. customthe residue was partitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed in vacuum
  9. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c179e3f87d7e45c2b004f53b4ef9edc1
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

Loading…