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

Participants

Reaction Steps

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.

Provenance & Evidence