1-(4-chloropyridin-2-yl)ethanone Chemical Properties

Melting point:

35 - 37°C

Boiling point:

238℃

Density 

1.233

Flash point:

98℃

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Chloroform (Sparingly), Methanol (Slightly)

pka

1.06±0.10(Predicted)

form 

Solid

color 

Off-White to Pale Yellow

Safety Information

HazardClass 

IRRITANT

HS Code 

2933399990

1-(4-chloropyridin-2-yl)ethanone Usage And Synthesis

Uses

1-(4-Chloropyridin-2-yl)ethanone is a useful reagent for the asymmetric synthesis of pyridylalkylamines.

Synthesis

4-Chloro-2-cyanopyridine (60 g, 0.42 mol) was dissolved in THF (1000 ml) in a 2-liter three-necked flask fitted with a stirrer and a thermometer under a protective atmosphere of N2 and cooled to 0°C by an ice bath. Commercially available magnesium methyl iodide (200 ml of a 3M solution of THF, 0.6 mol) was added slowly and dropwise over the course of about 45 min. A clarified dark colored solution was initially formed. The rate of dropwise acceleration of the methylmagnesium iodide was adjusted to maintain the reaction temperature between 0-10°C. After addition, a green suspension was obtained, which was continued to be stirred at 0°C for 2 hours. Subsequently, ice water (1500 mL) was added to the reaction mixture. 2M HCl was slowly added until the pH of the reaction mixture reached 2 and the temperature was about 25°C. The mixture was stirred for another 15 minutes. Multiple extractions (using EtOAc and water) were then performed. The combined organic phases were washed with saturated aqueous sodium chloride solution and dried with Na2SO4. All solvents were removed by distillation under reduced pressure in a rotary evaporator to give 66 g of yellow brown oily crude product. The crude product was purified by column chromatography (800 g silica gel 60, eluent MTBE). The target fractions confirmed by TLC analysis were collected, combined and the solvents removed to afford 1-(4-chloropyridyl)-2-acetophenone (51 g, 0.32 mol, 76% yield) as a clarified, dark-colored oil. lC-MS: tR = 1.829 min (UV = 220 nm), tR = 1.842 min (TIC, [M + H]+ = 156); 1H NMR (300 MHz, CDCl3) δ 8.58 (d, 1H), 8.03 (dd, J = 2.1,0.4,1H), 7.47 (dd, J = 5.2,2.1,1H), 2.71 (d, J = 3.2, 3H).

References

[1] Tetrahedron Asymmetry, 2006, vol. 17, # 6, p. 1007 - 1016
[2] Patent: US2012/220587, 2012, A1. Location in patent: Page/Page column 19
[3] Tetrahedron Asymmetry, 2005, vol. 16, # 20, p. 3427 - 3435

1-(4-chloropyridin-2-yl)ethanone(60159-37-7)Related Product Information

• 5-Chloro-2,3-difluoropyridine
• Pyridinethione
• ETHANONE,1-(4-CHLORO-3-PYRIDINYL)-
• 1-(4-CHLORO-BENZENESULFONYL)-PIPERAZINE
• ETHYL 1-(4-CYANOPHENYL)-4-PIPERIDINECARBOXYLATE
• 1-(4-Nitrophenyl)-1H-pyrazole
• 1-(4-TRIFLUOROMETHYLPHENYL)PIPERIDINE-4-CARBOXYLIC ACID
• 1-(4-TRIFLUOROMETHYLPHENYL)PIPERIDINE-4-CARBOXYLIC ACID ETHYL ESTER
• 3,5,6-Trichloropyrid
• 4-Chloro-2,6-diacetylpyridine
• 1-(4-chloropyridin-2-yl)ethanone
• 4,8-Dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-β]pyridin-11-one (Loratadine Impurity)