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

HRID 1458453Notes

Reaction equation

HRID 1458453 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.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.O>[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 764302-BromothiazoleHCID 812191,3-Bis(diphenylphosphino)propane2×HCID 6883421-Bromo-4-(dimethoxymethyl)benzeneHCID 5462224Magnesium

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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-bromobenzaldehyde dimethyl acetal (for preparation see J. Org. Chem. 56, 4280 (1991)) in 677 ml of THF is added dropwise thereto within a period 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 within a period of 30 min to a reddish suspension of 31.7 ml (338 mmol) of 2-bromothiazole (Fluka, Buchs, Switzerland) and 5.39 g (9.95 mmol) of DPPP in 1.68 litres of THF. The mixture is stirred at room temperature for 12 hours; a further 5.39 g of DPPP are added and the mixture is stirred for a further 7 hours. 840 ml of water are added and the mixture is stirred for 10 min; the THF is evaporated off using a rotary evaporator and the residue is stirred for 1.5 hours in 1.0 litre of ether and 340 ml of 2N HCl. The aqueous phase is separated off and extracted 2× with ethyl acetate. The organic phases are washed 2× 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 the title compound: TLC: Rf =0.21 (hexane/ethyl acetate 3:1); m.p: 91°-92° C.; Anal. (C10H7NOS) calc. C 63.47, H 3.73, N 7.40, S 16.94: found C 63.14, H 3.79, N 7.27, S 17.08; 1 H-NMR (CDCl3) δ 10.05 (s, HCO), 8.15 (d, J=8, 2H), 7.95 (m, 3H), 7.45 (d, J=3, 1H).

Workup

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

Sources & evidence

ORD record
ord-3b85c56a358942eeb9b417e1271088c0
Source dataset
uspto-grants-1998_12
Patent number
US05849911

Reaction notes

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