Toluene → 1,2-Dihydroquinazoline

HRID 472150Notes

Reaction equation

HRID 472150 reaction equation
[C:1]1(C)C=CC=CC=1.Br[C:9]1[CH:10]=[CH:11][C:12]([NH2:17])=[C:13]([CH:16]=1)[CH2:14][NH2:15]>CCOC(C)=O>[NH:17]1[C:12]2[C:13](=[CH:16][CH:9]=[CH:10][CH:11]=2)[CH:14]=[N:15][CH2:1]1

Participants

4

Reactant 2

HCID 1140TolueneHCID 229568372-(Aminomethyl)-4-bromoaniline

Product 1

HCID 125313371,2-Dihydroquinazoline

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To toluene (200 mL), 5-bromo-2-amino-benzylamine (9.5 g, 47.2 mmol) and trimethylbenzoic orthoester (8.2 g, 47.2 mmol) were added, followed by p-toulensulfonic acid (1.35 g, 7.1 mmol). The resulting suspension was stirred at reflux for 50 hours. The reaction mixture was cooled at r.t., diluted with AcOEt (150 mL), washed with saturated sodium bicarbonate, then with water. The organic layer was dried and concentrated to provide the intermediate dihydroquinazoline as a light brown solid (8.5 g; 63%). This intermediate is dissolved in DCM (20 mL) at r.t., then MnO2 (5.1 g) was added. The resulting mixture was stirred at r.t. for 48 hrs, then filtered on celite. The filtrate was concentrated to provide the title product as white solid (8.1 g, 95%). C14H9BrN2; MW: 285.15; MS m/z: 286 (M+1). 1H-NMR (300 MHz, d6-DMSO) ppm: 7.58-7.61 (m, 3H), 8.02 (d, 1H), 8.17 (dd, 1H), 8.49-8.56 (m, 3H), 9.70 (s, 1H).

Workup

  1. temperatureat reflux for 50 hours
  2. washwashed with saturated sodium bicarbonate
  3. customThe organic layer was dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-25a11194e9ad429196f2ec263c583192
Source dataset
uspto-grants-2014_01
Patent number
US08633208B2

Reaction notes

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