4-Bromotoluene → 5-Bromo-4-(4-methylphenyl)pyrimidine

HRID 274583Notes

Reaction equation

HRID 274583 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]1([CH3:15])[CH:13]=[CH:12][C:11](Br)=[CH:10][CH:9]=1.[Mg].[Cl-].[NH4+]>CCOCC>[Br:1][C:2]1[C:3]([C:11]2[CH:12]=[CH:13][C:8]([CH3:15])=[CH:9][CH:10]=2)=[N:4][CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 78054-BromotolueneHCID 25517Ammonium ChlorideHCID 783445-BromopyrimidineHCID 5462224Magnesium

Product 1

HCID 200930065-Bromo-4-(4-methylphenyl)pyrimidine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 5-bromopyrimidine (15.9 g, 0.1 mmol) in ether (200 ml) was added a Grignard reagent (prepared from p-tolyl bromide (20.52 g, 0.12 mmol), magnesium (2.92 g, 0.1 mmol) and ether (100 ml) dropwise at room temperature during 10 minutes. After the addition, the resulting suspension was heated under reflux for 1 hour and allowed to stand overnight. The reaction mixture was treated with aqueous ammonium chloride and then the ether layers were collected. The aqueous layers were extracted with methylene chloride and the extracts were combined with the ether layers and concentrated to dryness. The residue was purified by column chromatography on silica gel and then dissolved in acetone (100 ml). To the acetone solution was added a solution of potassium permanganate in acetone until red color disappeared, manganese dioxide was removed from the reaction mixture by filtration. The filtrate was concentrated to dryness and the residue was purified by column chromatography on silica gel. Recrystallization from hexane afforded colorless needles (12.8 g, 51%), m.p. 81°-82° C.

Workup

  1. additionAfter the addition
  2. temperaturethe resulting suspension was heated
  3. temperatureunder reflux for 1 hour
  4. customthe ether layers were collected
  5. extractionThe aqueous layers were extracted with methylene chloride
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by column chromatography on silica gel
  8. dissolutiondissolved in acetone (100 ml)
  9. additionTo the acetone solution was added a solution of potassium permanganate in acetone until red color
  10. custommanganese dioxide was removed from the reaction mixture by filtration
  11. concentrationThe filtrate was concentrated to dryness
  12. customthe residue was purified by column chromatography on silica gel
  13. customRecrystallization from hexane afforded colorless needles (12.8 g, 51%), m.p. 81°-82° C.

Sources & evidence

ORD record
ord-b3c6ea516f8d4fe58bffb76198509a97
Source dataset
uspto-grants-1995_02
Patent number
US05389641

Reaction notes

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