4-Iodo-1-(phenylmethyl)-1H-pyrazole

To a stirred suspension of 4-iodo-lH-pyrazole (1.50 g, 7.73 mmol) and potassium carbonate (2.67 g, 19.3 mmol) in acetone was added benzyl bromide (0.96 mL, 8.07 mmol) and the reaction was refluxed for 3 h. After cooling to room temperature the mixture was concentrated onto silica gel in vacuo and eluted through a short silica plug (sequential elution - hexane, 10percent diethyl ether in hexanes) to provide the title compound as a white solid (2.12 g, 97percent yield). Literature reference - Tetrahedron Letters, 2001, p863.Step 1. 1-Benzyl-4-iodo-1H-pyrazole; A 250-mL round-bottomed flask was charged with 4-iodo-1H-pyrazole (17 g, 87.63 mmol, 1.00 equiv) in N, N-dimethylformamide (150 mL) To this was added sodium hydride (3.6 g, 105.00 mmol, 1.20 equiv, 70percent) in several batches at 0° C., followed by addition of 1-(bromomethyl)benzene (16.5 g, 96.49 mmol, 1.10 equiv) dropwise at 0° C. The resulting solution was allowed to warm up to room temperature and stirred for 2 hours at room temperature. The reaction was then quenched by the addition of water/ice (200 mL). The resulting solution was extracted with ethyl acetate (3.x.200 mL). Combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator affording 1-benzyl-4-iodo-1H-pyrazole as yellow solid (22 g, 80percent).To a solution of 4-iodo-1H-pyrazole (1.40 g, 7.20 mmol) in actone (20 mL) were added (bromomethyl) benzene (1.44 g, 8.42 mmol) and potassium carbonate (2.80 g, 20.00 mmol) at rt. The mixture was refluxed for 3 h. The mixture was cooled to rt and filtered through a Celite pad. The filter cake was washed with EtOAc. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 5/1 to give a white solid product (1.40 g, 68.0) .[1084]MS (ESI, pos. ion) m/z: 285.1 [M+1]a) 1-Benzyl-4-iodo- 1H-pyrazole (A 147) 4-lodo-1 H-pyrazole (1.00 g, 5.16 mmol) in DMF (15 mL) was cooled to 0 °C before sodium hydride (60percent w/w dispersion in mineral oil, 258 mg, 6.44 mmol) was added. After 15 minutes, benzyl bromide (0.674 mL, 6.44 mmol) was added and the mixture stirred at room temperature. After two hours, the mixture was added to water (200 mL), cooled at 4 °C for one hour then filtered. The collected solid was washed with cyclohexane (2 x 3 mL) and air dried to give the title compound as a white solid (0.859 g, 59percent). H NMR (400 MHz, CDCI16.0 g of the base pyrazole was added to acetonitrile, stirred for 20 minutes, incubated at 10 to 20 ° C with 56.0 g of ammonium nitrate and 26.0 g of solid iodine, Stir the mixture for 8 hours, add saturated sodium bisulfite washing, MTBE extraction twice, magnesium sulfate drying, concentrated dry MTBE, 0 ° C n-heptane beater for half an hour, filtered iodobenzyl pyrazole 15.0g, GC purity 98 percent Yield 52percent.0.323 g of benzyl chloride was added dropwise to a solution of 57.0 g of 4-iodopyrazole, 20.0 g of potassium hydroxide and 2.9 g of TBAB in a solution at room temperature, After the dropwise addition, the mixture was stirred at about constant temperature for about 48 hours. The organic layer was washed three times with 40 ° C water and dried over magnesium sulfate to give 66.0 g of a yellow oil product with a GC purity of 97.0percent and a yield of 79percent.16.0 g of the base pyrazole was added to acetonitrile, stirred for 20 minutes, incubated at 10 to 20 C with 56.0 g of ammonium nitrate and 26.0 g of solid iodine, Stir the mixture for 8 hours, add saturated sodium bisulfite washing, MTBE extraction twice, magnesium sulfate drying, concentrated dry MTBE, 0 C n-heptane beater for half an hour, filtered iodobenzyl pyrazole 15.0g, GC purity 98 % Yield 52%.General procedure: Step 1: 1-methyl-4-iodopyrazole 1H-4-iodopyrazole (20 g), potassium carbonate (28.45 g) and acetone (120 mL) were added into a round bottomed flask (250 mL) and agitated for 10 min. Then iodomethane (17.56 g) was added and the mixture was agitated at room temperature over night. After that, the mixture was filtrated and concentrated, the residue was recrystallized from n-hexane to prodce 1-methyl-1H-4-iodopyrazole (15 g) as white acicular crystal. 1H-NMR (300Hz, CDCl3) delta: 7.48 (s, 1H), 7.40 (s, 1H), 3.92 (s, 3H).

Molecular Weight:284.10
XLogP3:2.5
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:283.98105
Monoisotopic Mass:283.98105
Topological Polar Surface Area:17.8
Heavy Atom Count:13
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes