2-Acetyl-4-methylpyridine

Crystals

Solid

2-Acetyl-4-methylpyridine is an aromatic ketone.

To a stirred solution of 2-nitrile-4-methylpyridine {31.19 g, 229 mmol; that was prepared by us from the corresponding 4-methylpyridine 1-oxide according to the reported procedure [17] and [46], [Referential Example 16] 1-(6-Methoxy-3-pyridazinyl)-5-(4-methyl-2-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] 1) 1-(4-methyl-2-pyridyl)ethanone; A 1.58M solution of n-butyllithium in hexane (17 ml) was added dropwise over 10 minutes to a solution of 2-bromo-4-picoline (3.0 g) in diethylether (45 ml) at -78°C, and the solution was stirred for 20 minutes. N, N-dimethyl acetamide (2.5 ml) was added dropwise to the reaction liquid, and the temperature of the reaction liquid was gradually elevated to room temperature, and the mixture was stirred for 2 hours. Water and ethyl acetate were added to the reaction liquid and the phases were separated, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane-ethyl acetate) to give 1-(4-methyl-2-pyridyl)ethanone (1.64 g, 70percent) as an oily product. 1) 1-(4-Methyl-2-pyridyl)-1-ethanone Under cooling to -78°C, n-butyllithium (a 1.58 M solution in hexane, 22 mL) was added dropwise to a solution of 2-bromo-4-picoline (4.0 g) in diethyl ether (60 mL) over 5 minutes, and then the resultant mixture was stirred for 5 minutes. N, N-Dimethyl acetamide (3.3 mL) was added dropwise to the reaction solution, and the mixture was gradually warmed to room temperature, and stirred for 14.5 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After separation by filtration, a residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (ethyl acetate-hexane), to obtain 1-(4-methyl-2-pyridyl)-1-ethanone (1.86 g, 59percent) as an oily product. To a stirred solution of 2-nitrile-4-methylpyridine {31.19 g, 229 mmol; that was prepared by us from the corresponding 4-methylpyridine 1-oxide according to the reported procedure [17] and [46], 1H NMR (270 MHz, CDCl3) delta 8.57 (1H, d, J = 5.1 Hz), 7.53-7.52 (1H, m), 7.35-7.32 (1H, m), 2.44 (3H, m)} in dry benzene (300 mL)-anhydrous Et2O (230 mL) was added dropwise 2 M solution of MeMgI/Et2O (149.0 mL, 298 mmol) at 0 °C under N2 over 1 h. The reaction mixture was warmed to room temperature, stirred under N2 for 1 h, and then cooled to 0 °C. After aqueous NH4Cl (120 mL) was added dropwise to the mixture at 0 °C, the resulting mixture was warmed to room temperature and stirred for 1 h. The aqueous layer was removed, and the organic layer was washed with water, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane/AcOEt = 8:1) to afford 16.20 g of General procedure: Manganese dioxide (1.04 g) was added to a solution of (2-methoxypyridin-4-yl)methanol (417 mg) in ethyl acetate (5 mL), followed by refluxing for 1.5 hours. Manganese dioxide (1.04 g) was added thereto, followed by refluxing for 1.5 hours. The reaction mixture was cooled to room temperature, the insoluble materials were filtered off, and the solvent was distilled off under reduced pressure. The obtained residues were purified by silica gel column chromatography (hexane:ethyl acetate=9:1'4:6), whereby 2-methoxyisonicotinic aldehyde (260 mg) was obtained as a colorless oily materialGeneral procedure: To a solution of the appropriate acetophenone derivative in CH2CI2 (2 mL per 1 mmol of the substrate, unless stated otherwise), were added NEt3 (1.2 eq) and TMFOTf (1.1 eq.) at 0 C. The mixture was allowed to warm to 25 C and stirred for 16 h. The reaction mixture was then again cooled to 0 C and NBS (1.1 eq.) was added. The mixture was stirred at 0 C for 15-30 min. The crude mixture was absorbed on silica and quickly filtered through a pad of silica gel (hexane: EtOAc; 1:1, unless stated otherwise) to provide the desired bromo-acetophenone, which was used directly in the next step

Molecular Weight:135.16
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:135.068413911
Monoisotopic Mass:135.068413911
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes