27258-33-9

930-36-9

68-12-2

27258-33-9

Example 1. Synthesis of 1-methyl-1H-pyrazole-5-carbaldehyde To a dry 50 mL reaction flask was added 1.642 g (20 mmol) of 1-methylpyrazole dissolved in 30 mL of anhydrous THF. The reaction mixture was cooled to -20 °C and 8 mL (20 mmol, 2.5 M hexane solution) of n-butyllithium solution was added slowly with stirring. The reaction was kept at -20 °C with stirring for 2.5 hours. Subsequently, 4.7 mL (4.39 g, 60 mmol) of anhydrous N,N-dimethylformamide was slowly added at -20 °C under vigorous stirring and the reaction was continued at this temperature for 1 hour. Upon completion of the reaction, the mixture was poured into 100 mL of 1 M acetic acid/sodium acetate buffer (pH 4.5) and 50 mL of methyl tert-butyl ether (MTBE) was added to separate the organic layer. The organic layer was washed with 50 mL of saturated sodium carbonate solution to remove excess acetic acid (note: extraction with ethyl acetate may result in residual N,N-dimethylformamide in the final product). The organic layer was separated, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by vacuum distillation (boiling point: 67 °C, 21 mbar). The products of the three preparations were combined and distilled to give 5.969 g (54 mmol, 90% yield) of 1-methyl-1H-pyrazole-5-carbaldehyde. 1H NMR (300 MHz, CDCl3): δ 4.18 (s, 3H, CH3-N), 6.91 (d, 1H, 3J = 2.0 Hz, CH=CN), 7.53 (d, 1H, 3J = 2.0 Hz, CH=N), 9.87 (s, 1H, CHO) ppm. 13C NMR (100 MHz, CDCl3): δ 39.31 (CH3-N), 114.78 (CH=C-N), 138.54 (CH=N), 138.98 (CH=C-N), 179.83 (CHO) ppm.