[Synthesis]
The general procedure for the synthesis of 3-acetyl-1-methyl-1H-pyrazole and 1-methyl-5-acetyl-pyrazole from 3-acetylpyrazole and iodomethane was as follows: to a stirred solution of 1-(1H-pyrazol-5-yl)acetophenone (8.24 g, 74.8 mmol) and potassium carbonate (20.58 g, 149 mmol) in acetonitrile (50 mL) was added iodomethane ( 4.68 mL, 74.8 mmol). The reaction mixture was stirred at room temperature for 3 days. Upon completion of the reaction, water was added to the mixture and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuum. The crude product was purified by silica gel column chromatography (5:1 to 2:1 linear gradient of hexane/ethyl acetate) to afford 1-(1-methyl-1H-pyrazol-5-yl)ethanone (1.20 g, 9.67 mmol, 13% yield, less polar fraction, eluted first) and 1-(1-methyl-1H-pyrazol-3-yl)ethanone (5.40 g, 43.5 mmol , 58% yield, more polar fraction, eluted subsequently).NMR hydrogen spectral (500 MHz, CDCl3) data for 1-(1-methyl-1H-pyrazol-5-yl)ethanone: δ 7.47 (d, J=2.0 Hz, 1H), 6.83 (d, J=2.1 Hz, 1H), 4.17 (s, 3H), 2.52 (s, 3H). Mass spectrum (M+H)+: 125.2. NMR hydrogen spectrum (500 MHz, CDCl3) data of 1-(1-methyl-1H-pyrazol-3-yl)ethanone: δ 7.38 (d, J=2.3Hz, 1H), 6.78 (d, J=2.4Hz, 1H), 3.98 (s, 3H), 2.57 (s, 3H). Mass spectrum (M+H)+: 125.2. |