These common heterocyclic compound, 624-75-9, name is 2-Iodoacetonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 624-75-9
The compound obtained in Example 21 (4.6 g, 15.35 mmol) and potassium carbonate (10.6 g, 76.73 mmol) were added to acetone (100 mL) and refluxed for 2 hours by heating. To this reaction mixture was dropwise added iodoacetonitrile (1.34 mL, 18.42 mmol), and refluxed over 2 hours. The acetone was removed by vacuum distillation, and to the residue were added water (200 mL) and ethyl acetate (200 mL). The organic layer was dried over anhydrous magnesium sulfate and distillated in a vacuum. The concentrate was subjected to column chromatography (silica gel, ethyl acetate-hexane 2:3 v/v) to afford a mixture of 2:1 of [4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile and [4-(2-chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile as yellow oil. These two regioisomers (4.78 g, 92%) were used in the next reaction step without separation.[4-(2-Chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.29 (s, 3H), 3.71 (s, 3H), 5.19 (s, 2H), 6.73 (s, 1H), 6.75 (s, 1H), 6.85 (s, 1H), 7.06 (d, J=4.4 Hz, 1H), 7.26 (s, 1H), 7.79 (s, 1H), 8.24 (d, J=4.8 Hz, 1H); 13C NMR (CDCl3) delta 21.53, 39.97, 55.29, 110.91, 111.12, 113.65, 115.67, 118.75, 121.59, 121.65, 122.78, 130.58, 132.37, 140.16, 143.28, 149.68, 151.45, 151.79, 159.71, 162.33.[4-(2-Chloropyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl]acetonitrile: 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.83 (s, 3H), 4.94 (s, 2H), 6.63 (s, 1H), 6.74 (s, 1H), 6.92-6.96 (m, 2H), 7.19 (s, 1H), 7.93 (s, 1H), 8.17 (d, J=5.2 Hz, 1H); 13C NMR (CDCl3) delta 21.56, 37.78, 55.48, 112.15, 113.91, 117.08, 118.16, 119.88, 121.36, 122.48, 128.46, 139.57, 141.60, 142.19, 142.85, 149.78, 151.95, 160.48.To a solvent mixture of THF and water (4:1, 10 mL) were added the mixture prepared in Example 22 (300 mg, 0.89 mmol), 3-pyridineboronic acid (0.13 g, 1.06 mmol), dichlorobis(triphenylphosphine)palladium (II) (31 mg, 0.04 mmol) and potassium carbonate (130 mg, 0.89 mmol), and stirred at 70 C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled at room temperature, washed with ice water (100 mL) and extracted with ethyl acetate (100 mL×3). The organic extract was dried over anhydrous magnesium sulfate and distilled under vacuum. The residue was subjected to prep-TLC using a solvent mixture of ethyl acetate/hexane to purify the desired products.Purification yield by prep-TLC (silica gel, ethyl acetate-hexane, 2:1, v/v): (62 mg, 55%); m.p. 81-82 C.; 1H NMR (CDCl3) delta 2.39 (s, 3H), 3.80 (s, 3H), 4.95 (s, 2H), 6.73 (s, 1H), 6.80 (s, 1H), 6.94 (s, 1H), 7.11 (d, J=5.0 Hz, 1H), 7.34 (dd, J=3.0, 4.8 Hz, 1H), 7.54 (s, 1H), 8.00 (s, 1H), 8.15 (d, J=7.8 Hz, 1H), 8.54 (d, J=5.1 Hz, 1H), 8.60 (d, J=4.4 Hz, 1H), 8.89 (s, 1H); 13C NMR (CDCl3) delta 21.62, 37.79, 55.50, 112.38, 114.08, 116.81, 118.15, 119.21, 120.35, 122.59, 123.59, 128.90, 134.30, 134.78, 139.57, 140.71, 141.57, 141.97, 148.02, 149.92, 150.34, 154.99, 160.48.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 624-75-9.
Reference:
Patent; LEE, So Ha; Yoo, Kyung Ho; Oh, Chang Hyun; Han, Dong Keun; El-Deeb, Ibrahim Mustafa; Park, Byung Sun; Jung, Su Jin; US2011/15395; (2011); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com