Azobisisobutyronitrile → 6-Bromo-2-phenethyl-1-phthalazinone

HRID 1037624Notes

Reaction equation

HRID 1037624 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:7](=[O:8])O[CH2:5]2.C1C(=O)N(Br)C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C.[CH:32]1[CH:33]=[CH:34][C:35]([CH2:38][CH2:39][NH:40][NH2:41])=[CH:36][CH:37]=1.OS(O)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)(Cl)Cl.C(O)C.C(OCC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:7](=[O:8])[N:40]([CH2:39][CH2:38][C:35]1[CH:36]=[CH:37][CH:32]=[CH:33][CH:34]=1)[N:41]=[CH:5]2

Participants

9

Reactant 5

HCID 6547AzobisisobutyronitrileHCID 61100Phenelzine SulfateHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 6031445-Bromophthalide

Product 1

HCID 667323206-Bromo-2-phenethyl-1-phthalazinoneYield 65%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

A solution of 5-bromophthalide (1.0 g, 4.7 mmol, 1.0 equiv) and NBS (850 mg, 4.7 mmol, 1.0 equiv) in carbon tetrachloride (15 mL) was treated with AIBN (50 mg, cat.) and heated to reflux overnight. The hot reaction mixture was filtered and the filtrate concentrated to a yellowish solid (1.38 g, quant.). Crude 1H NMR indicated this material contained ca. 80% of the desired 3,5-dibromophthalide, and it was carried on without further purification. An aliquot of this crude material (250 mg, 0.69 mmol, 1.0 equiv) in 95% ethanol (6 mL) was treated with phenelzine sulfate (175 mg, 0.75 mmol, 1.1 equiv) and NaHCO3 (250 mg, 2.8 mmol, 4.0 equiv). After stirring overnight at ambient temperature, the reaction mixture was diluted with diethyl ether, washed with dilute NaOH, dilute HCl, and saturated NaHCO3, then dried over Na2SO4 and concentrated. Purification of the residue using flash silica gel chromatography (gradient of 3-12% ethyl acetate/hexanes) provided 6-bromo-2-phenethyl-1-phthalazinone (147 mg, 0.45 mmol, 65%) as a white solid. This crude phthalazinone (147 mg, 0.45 mmol) was converted, via Methods 1 and 2, to compound 13 (81 mg, 62%) which was isolated as a white solid. [M−H]−=293.1 m/z. Activity: A

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. filtrationThe hot reaction mixture was filtered
  4. concentrationthe filtrate concentrated to a yellowish solid (1.38 g, quant.)
  5. customwas carried on without further purification
  6. washwashed with dilute NaOH, dilute HCl, and saturated NaHCO3
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification of the residue

Sources & evidence

ORD record
ord-3271b866277e4959b19fccd73f1f7398
Source dataset
uspto-grants-2013_10
Patent number
US08546564B2

Reaction notes

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