1H-1,2,4-Triazole → 4-(1H-1,2,4-triazol-1-yl)benzaldehyde

HRID 1600573Notes

Reaction equation

HRID 1600573 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].F[C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1>N1C=CC=CC=1.[Cu-]=O>[N:1]1([C:13]2[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 680234-Fluorobenzaldehyde

Product 1

HCID 27764884-(1H-1,2,4-triazol-1-yl)benzaldehyde

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 1049PyridineSolvent

Procedure

To a solution of 2-methoxy-N-(3,5-dimethylbenzoyl) glycine methyl ester (16.7 g, 66.5 mmol) in toluene (70 ml) under nitrogen atmosphere is added phosphorus thrichloride (6.0 ml, 68.7 mmol) at room temperature. The reaction mixture is heated at 70° C. for 16 h. Then, trimethyl phosphite (8.1 ml, 68.7 mmol) is added dropwise to the stirred mixture at 70° C. and stirring is continued for further 2 h at 70° C. The solvent is evaporated in vacuo. The residue is diluted with hexane, filtered, and washed with ethyl acetate. The combined filtrate is concentrated in vacuo and the crude material is purified by column chromatography on silica with ethyl acetate to give trimethyl 2-(3,5-dimethylbenzoyl)amino-phosphonoacetate. A mixture of 1,2,4-triazole (4.06 g, 58.7 mmol), potassium carbonate (9.05 g, 65.5 mmol), 4-fluorobenzaldehyde (6.3 ml, 58.7 mmol), and copper(I) oxide (0.26 g, 1.82 mmol) in pyridine (30 ml) is heated under nitrogen atmosphere at reflux overnight. After pyridine is distilled, the residue is diluted with chloroform, filtered, and washed with chloroform. The combined filtrate is washed with water, dried over magnesium sulfate, and concentrated in vacuo. The crude material is purified by column chromatography on silica with hexane/ethyl acetate (1:2) to give 4-(1,2,4-triazol-1-yl)-benzaldehyde and with ethyl acetate/methanol (19:1) to give 4-(1,3,4-triazol-1-yl)-benzaldehyde.

Workup

  1. temperatureis heated under nitrogen atmosphere
  2. temperatureat reflux overnight
  3. distillationAfter pyridine is distilled
  4. additionthe residue is diluted with chloroform
  5. filtrationfiltered
  6. washwashed with chloroform
  7. washThe combined filtrate is washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe crude material is purified by column chromatography on silica with hexane/ethyl acetate (1:2)

Sources & evidence

ORD record
ord-fa2e2f77673747b19ecc145bb2ef70cf
Source dataset
uspto-grants-1999_11
Patent number
US05977075

Reaction notes

Loading…