3-Methyl-1-phenyl-1H-pyrazole

white crystals

General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999percent purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98percent purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1, 2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.To the reaction flaskwas added phenylhydrazine (5.00 g, 0.046 mol), 4, 4-dimethyl-2-butanone (7.30 g, 0.055 mol Mol), 40 ml of ethanol, warmed to reflux, refluxed for 2 hours. To the reaction mixture was added dropwise concentrated hydrochloric acid (0.5 ml), continued It was refluxed for 2 hours.After the reaction was cooled to below 30 ° C, the reaction solution was pouredinto 200 ml water, extracted with 3 × 150 ml of acetic acid B Ester extraction, the resulting organic phase was washed with saturated aqueous sodium chloride(150 ml), dried over anhydrous magnesium sulfate, and concentrated underreduced pressure After the reduction, the residue was purified by columnchromatography (eluent: ethyl acetate: petroleum ether = 1:10) to obtain 5.00 gof 3-methyl-1-phenyl -1H- Pyrazole as a yellow oil, yield 68percent.To the reaction flask was added phenylhydrazine (5.00 g, 0.046 mol), 4, 4-dimethoxy-2-butanone (7.30 g, 0.055 mol), 40 ml of ethanol, warmed to reflux, refluxed for 2 hours. To the reaction mixture was added dropwise concentrated hydrochloric acid (0.5 ml) and refluxing was continued for 2 hours. After the reaction was cooled to below 30 , the reaction solution was poured into 200 ml water and extracted with 3 × 150 ml of ethyl acetate, the resulting organic phase was washed with saturated aqueous sodium chloride (150 ml), dried over anhydrous magnesium sulfate, after concentration under reduced pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:10) to obtain 5.00 g of 3-methyl-1-phenyl -1H- pyrazole as a yellow oil, yield 68percent.To the reaction flask was added phenylhydrazine (5.00 g, 0.046 mol), 4, 4-dimethoxy-2-butanone (7.30 g, 0.055 mol), 40 ml of ethanol, warmed to reflux, refluxed for 2 hours. To the reaction mixture was added dropwise concentrated hydrochloric acid (0.5 ml) and refluxing was continued for 2 hours. After the reaction was cooled to below 30 , the reaction solution was poured into 200 ml water and extracted with 3 × 150 ml of ethyl acetate, the resulting organic phase was washed with saturated aqueous sodium chloride (150 ml), dried over anhydrous magnesium sulfate, after concentration under reduced pressure, the residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1:10) to obtain 5.00 g of 3-methyl-1-phenyl -1H- pyrazole as a yellow oil, yield 68percent.To the reaction flask was added phenylhydrazine (5.00 g, 0.046 mol)4, 4-dimethoxy-2-butanone (7.30 g, 0.055 mol)Ethanol 40 ml, Heating up to reflux, Reflux for 2 hours.To the reaction solution was added concentrated hydrochloric acid (0.5 ml)Continue to reflux for 2 hours.After the reaction is cooled to below 30 ° C, The reaction solution was poured into 200 ml of water, Extracted with 3 x 150 ml of ethyl acetate, The resulting organic phase was washed with saturated aqueous sodium chloride solution (150 ml)Dried over anhydrous magnesium sulfate, After concentration under reduced pressure, The residue was purified by column chromatography (eluent: ethyl acetate: petroleum ether = 1: 10)Get 5.00 grams3-methyl-1-phenyl-1H-pyrazole, Yellow oil, the yield of 68percent.Phenylhydrazine (5.00 g, 0.046 mol) was added to the reaction flask, 4, 4-dimethoxy-2-butanone (7.30 g, 0.055 mol), Ethanol 40 ml, Warmed to reflux, Reflux for 2 hours.Concentrated hydrochloric acid (0.5 ml) was added dropwise to the reaction solution, Continue to reflow for 2 hours.After the reaction was cooled to below 30 , The reaction solution was poured into 200 ml of water, Extracted with 3x150 ml of ethyl acetate, The resulting organic phase was washed with saturated aqueous sodium chloride solution (150 ml)After washing, Dried over anhydrous magnesium sulfate, After concentration under reduced pressure, The residue is separated by column chromatography(Eluent: ethyl acetate: petroleum ether = 1: 10)5.00 g of 3-methyl-1-phenyl-1H-pyrazole were obtained, Yellow oil, yield 68percent.General procedure: To a Schlenk-type sealed-tube (with a Teflon high pressure valve and side arm) equipped with a stir bar, was treated with 1a (207 mg, 1.5 mmol), 2a (61 mg, 0.5 mmol), Cu(OAc)Preparation 1373-Methyl-1-phenyl-1 H-pyrazole3-Methyl-1 H-pyrazole (1 g, 12.18 mmol), phenylboronic acid (3 g, 24.36 mmol) and pyridine (2 mL, 24.36 mmol) were dissolved (160 mL) and Cu(AcO)3-Methyl-1H-pyrazole (1 g, 12.18 mmol), phenylboronic acid (3 g, 24.36 mmol) and pyridine (2 mL, 24.36 mmol) were dissolved (160 mL) and Cu(AcO)To 100 mL round bottom flask was added phenylhydrazine hydrochloride (5.00 g, 0.035 mol), 50 ml of ethanol was added to fully dissolve the 4, 4_-dimethoxy-2-butanone (5.10 g, 0.038 mol) was added to the reaction mixture, the reaction was warmed to reflux and maintained at reflux for 6 hours. After the reaction was stopped, cooled to room temperature, poured into 100 ml water and extracted with 3 X100 ml of ethyl acetate, the organic layer was washed with 50 ml of saturated aqueous sodium bicarbonate solution, washed with 2X50 mL of a saturated sodium chloride aqueous solution, dried over anhydrous sulfate magnesium sulfate, concentrated and column chromatography (eluent: ethyl acetate: petroleum ether = 1:10) to obtain 1.80 g of 3-methyl-1-phenyl -1H- pyrazole as a yellow oil, yield 30percent.

Molecular Weight:158.20
XLogP3:2.3
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:158.084398327
Monoisotopic Mass:158.084398327
Topological Polar Surface Area:17.8
Heavy Atom Count:12
Complexity:141
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes