Water → 4-(1,3-Thiazol-2-yl)benzaldehyde

HRID 1068915Notes

Reaction equation

HRID 1068915 reaction equation
[Mg].CO[CH:4]([O:12]C)[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1.Br[C:15]1[S:16][CH:17]=[CH:18][N:19]=1.O>C1COCC1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Ni](Cl)Cl>[S:16]1[CH:17]=[CH:18][N:19]=[C:15]1[C:8]1[CH:7]=[CH:6][C:5]([CH:4]=[O:12])=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 764302-BromothiazoleHCID 6883421-Bromo-4-(dimethoxymethyl)benzeneHCID 5462224Magnesium

Product 1

HCID 105356554-(1,3-Thiazol-2-yl)benzaldehyde

Reagents, catalysts & solvents 2

HCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalyst2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

Under argon, 9.2 g (379 mmol) of magnesium are placed in 84 ml of THF and heated to 60° C. A solution of 82.6 g (357 mmol) of 4-bromo-benzaldehyde dimethyl acetal (for preparation see J. Org. Chem. 56, 4280 (1991)) in 677 ml of THF is then added dropwise thereto in the course of 30 min and the mixture is stirred at boiling temperature for a further 40 min. The Grignard solution is cooled, decanted into a dropping funnel and added dropwise in the course of 30 min to a reddish suspension of 31.7 ml (338 mmol) of 2-bromo-thiazole and 5.39 g (9.95 mmol) of 1,3-bis(diphenylphosphino)propane-nickel(II) chloride (Aldrich; Milwaukee/USA) in 1.68 liters of THF. The reaction mixture is stirred at RT for 12 hours; a further 5.39 g of 1,3bis(diphenylphosphino)-propane-nickel(II) chloride are added and stirring is continued for a further 7 hours. 840 ml of water are added, stirring is carried out for 10 min, the THF is evaporated off in a rotary evaporator and the residue is stirred in 1.0 liter of diethyl ether and 340 ml of 2N HCl for 1.5 hours. The aqueous phase is separated off and extracted twice with ethyl acetate. The organic phases are washed twice with 0.5N HCl, water, sat. NaHCO3 solution, water and brine, dried (Na2SO4) and concentrated by evaporation. Chromatography (SiO2; hexane/ethyl acetate=4:1) and digestion in hexane yield 4-(thiazol-2-yl)-benzaldehyde; TLC: Rf=0.21 (hexane/ethyl acetate=3:1); m.p. 91-92° C.

Workup

  1. customfor a further 40 min
  2. temperatureThe Grignard solution is cooled
  3. customdecanted into a dropping funnel
  4. stirringThe reaction mixture is stirred at RT for 12 hours
  5. stirringstirring
  6. waitis continued for a further 7 hours
  7. stirringstirring
  8. waitis carried out for 10 min
  9. customthe THF is evaporated off in a rotary evaporator
  10. stirringthe residue is stirred in 1.0 liter of diethyl ether
  11. wait340 ml of 2N HCl for 1.5 hours
  12. customThe aqueous phase is separated off
  13. extractionextracted twice with ethyl acetate
  14. washThe organic phases are washed twice with 0.5N HCl, water, sat. NaHCO3 solution, water and brine
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-95685d1f83274a2da2f9235a0ec70857
Source dataset
uspto-grants-2001_06
Patent number
US06251911B1

Reaction notes

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