Hydrochloric Acid → (2,5-Dichlorophenyl)(pyridin-2-yl)methanone

HRID 2389223Notes

Reaction equation

HRID 2389223 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl.C(Cl)(=O)[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1.Cl.C([C:28](C)=[O:29])C(C)C>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:28]([C:16]1[CH:15]=[CH:20][CH:19]=[CH:18][N:17]=1)=[O:29]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 46851,4-DichlorobenzeneHCID 7909Methyl Isobutyl KetoneHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 6451240Aluminum(III) Chloride

Product 1

HCID 16638529(2,5-Dichlorophenyl)(pyridin-2-yl)methanoneYield 87%

Conditions

Temperature
60 °C

Procedure

183.8 g (1.25 mol) of 1,4-dichlorobenzene was weighed and then dissolved in a 1 L three-necked flask equipped with a stirrer, thermometer, cooling pipe, and nitrogen inlet tube by heating at 60° C. under a nitrogen atmosphere using an oil bath. Thereafter, 160.1 g (1.20 mol) of aluminum chloride was added, and 89.0 g (0.5 mol) of nicotinic acid chloride hydrochloride was added in small amounts under stirring over one hour. After completing the addition, internal temperature was raised to 90° C. to 100° C. and allowed to react. After confirming the disappearance of raw materials by way of thin-layer chromatography, the reaction liquid was allowed to cool to 70° C., and then 150 mL of MIBK (methyl isobutyl ketone) was added to dilute. After allowing the solution to cool to room temperature, the reaction liquid was gradually added to 1 L of 2 N HCl, the product was extracted into an acidic water, and then the liquid of organic layer was separated to remove excessive 1,4-dichlorobenzene. A sodium hydroxide solution of 4 mol/L was gradually added till the pH of the aqueous layer became 3 to 4, and the product was extracted with MIBK. The organic layer was washed using water and a sodium chloride solution, the organic layer was dried using magnesium sulfate, and then the solvent was removed by an evaporator. The approximate yield amount was 130 g. The course product was purified by means of column chromatography using a solvent of hexane/ethyl acetate as a developing solvent, whereby the intended product was obtained as a viscous liquid in an amount of 110 g and at a yield of 87%. A 1H-NMR spectrum of the resulting compound is shown in FIG. 1.

Workup

  1. dissolutiondissolved in a 1 L three-necked flask
  2. customequipped with a stirrer
  3. temperaturethermometer, cooling pipe, and nitrogen inlet tube
  4. additionthe addition, internal temperature
  5. temperaturewas raised to 90° C. to 100° C.
  6. customto react
  7. customthe reaction liquid
  8. temperatureto cool to 70° C.
  9. additionto dilute
  10. temperatureto cool to room temperature
  11. customthe reaction liquid
  12. extractionthe product was extracted into an acidic water
  13. customthe liquid of organic layer was separated
  14. customto remove excessive 1,4-dichlorobenzene
  15. additionA sodium hydroxide solution of 4 mol/L was gradually added till the pH of the aqueous layer
  16. extractionthe product was extracted with MIBK
  17. washThe organic layer was washed
  18. dry with materiala sodium chloride solution, the organic layer was dried
  19. customthe solvent was removed by an evaporator
  20. customThe course product was purified by means of column chromatography
  21. customwas obtained as a viscous liquid in an amount of 110 g and at a yield of 87%

Sources & evidence

ORD record
ord-42be4f1dc36246bb94eccf209d271368
Source dataset
uspto-grants-2012_09
Patent number
US08273499B2

Reaction notes

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