1-Benzyl-4-bromo-1H-pyrazole

General procedure: 1-benzyl-4-chloro-3, 5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3, 5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSOStep 1: Preparation of l-benzyl-4-bromo-lH-pyrazole [00167] Sodium hydride (0.2 g, 60 percent, 5.1 mmol) was added to a solution of 4-bromo-lH- pyrazole (0.5 g, 3.4 mmol) in N, N-dimethylformamide (10 mL) at 0 °C and stirred at room temperature for 30 minutes. The reaction mixture was cooled to 0 °C, added benzyl bromide (0.485 mL, 4.08 mmol) and stirred at room temperature for 2 h. The reaction mixture was diluted with ice-water (30 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic extract was washed with water (30 mL), brine (30 mL), dried over anhydrous sodium sulfate and evaporated. The crude material was purified by combiflash purifier using 7percent ethyl acetate in hexane to afford the title compound l-benzyl-4-bromo-lH-pyrazole (0.7 g, 87percent yield) as a colorless liquid. Calculated M+H: 236.99; Found M+H: 236.9.A 100 mL round bottom flask was charged with 4-bromopyrazole (4.41 g, 30 mmol), tetrabutylammonium bromide [(484] mg, 1.5 mmol) and potassium hydroxide pellets (3.37 g, 60 mmol). After the mixture was sonicated for 15 min, benzyl chloride (5.2 [ML, ] 45 mmol) was added dropwise and the resulting mixture was stirred overnight. Ethyl ether (20 mL), water (20 mL), and diluted hydrochloric acid (1 [ML, ] [10percent)] were added under stirring. The organic layer was washed with water [(2X20] mL) and dried over MgS04. The solvent was removed under reduced pressure and the product was purified by flash chromatography on silica gel (hexane/ethyl acetate 10: 1) to provide the desired product as a white solid (6.74 g, 95percent yield). Mp [51-52 °C] (lit. [44-45 °C, ] See Jones, R. G. [J.] Am. [CHEM.] Soc. 1949, [71, ] [3994).APOS;H NMR] (400 MHz, CDC13) : [8] 7.53 (s, 1H), 7.42-7. 33 (m, 4H), 7.28-7. 22 (m, 2H), 5.29 (s, 2H); [13C] NMR (100 MHz, CDC13) : [6] 140.4, 136.2, 129. 8, 129.4, 128.8, [128.] 3, 93. 9, 57.1.A 100 mL round bottom flask was charged with 4-bromopyrazole (4.41 g, 30 mmol), tetrabutylammonium bromide [(484] mg, 1.5 mmol) and potassium hydroxide pellets (3.37 g, 60 mmol). After the mixture was sonicated for 15 min, benzyl chloride (5.2 [ML, ] 45 mmol) was added dropwise and the resulting mixture was stirred overnight. Ethyl ether (20 mL), water (20 mL), and diluted hydrochloric acid (1 [ML, ] [10%)] were added under stirring. The organic layer was washed with water [(2X20] mL) and dried over MgS04. The solvent was removed under reduced pressure and the product was purified by flash chromatography on silica gel (hexane/ethyl acetate 10: 1) to provide the desired product as a white solid (6.74 g, 95% yield). Mp [51-52 C] (lit. [44-45 C, ] See Jones, R. G. [J.] Am. [CHEM.] Soc. 1949, [71, ] [3994).'H NMR] (400 MHz, CDC13) : [8] 7.53 (s, 1H), 7.42-7. 33 (m, 4H), 7.28-7. 22 (m, 2H), 5.29 (s, 2H); [13C] NMR (100 MHz, CDC13) : [6] 140.4, 136.2, 129. 8, 129.4, 128.8, [128.] 3, 93. 9, 57.1.4-bromopyrazole (14.7 g, 0.1 mol), benzyl chloride (17.1 g, 0.1 mol), Tetrabutylammonium hydroxide (1.3 g, 0.005 mol), dissolved in 10 ml of dimethyl sulfoxide (DMSO), Potassium hydroxide solution was added dropwise [potassium hydroxide solution: a solution obtained by dissolving 11.2 g (0.20 mol) of potassium hydroxide in 5 ml of water], The reaction is exothermic. After the addition is completed, it is stirred at room temperature overnight, and diluted with water.Extracted with ethyl acetate, dried, concentrated product, and then distilled under reduced pressure to give 20.5 g of product.The yield was 86.5%.General procedure: 1-benzyl-4-chloro-3, 5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3, 5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSO5) was added and the vial was capped. The reaction proceeded with continuous and vigorous stirring until no starting material remained as indicated by TLC (1 h). The remaining oxidants were reduced with solid sodium bisulfite until starch iodide paper tested negative. Water (5 mL) was added and the mixture was extracted with 1:1 hexanes/diethyl ether (3 x 5 mL). The combined organic fractions were dried (MgSO4) and concentrated to yield crude product that was purified by flash chromatography (14 x 1 cm), 9:1 hexane/ethyl acetate eluent. Pure 1-benzyl-4-chloro-3, 5-dimethyl-1H-pyrazole was obtained as a pale yellow oil (215 mg, 93% yield).

Molecular Weight:237.10
XLogP3:2.5
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:235.99491
Monoisotopic Mass:235.99491
Topological Polar Surface Area:17.8
Heavy Atom Count:13
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes