4-Chlorobenzoic Acid → (2-Amino-5-chlorophenyl)(4-chlorophenyl)methanone

HRID 1061862Notes

Reaction equation

HRID 1061862 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C1C=CC=CC=1.[Cl:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1>[Cl-].[Cl-].[Zn+2].S(Cl)(Cl)=O>[NH2:25][C:24]1[CH:26]=[CH:27][C:21]([Cl:20])=[CH:22][C:23]=1[C:6]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=1)=[O:8]

Participants

6

Reactant 3

HCID 63184-Chlorobenzoic AcidHCID 7412Benzoyl chlorideHCID 78124-Chloroaniline

Product 1

HCID 12388852(2-Amino-5-chlorophenyl)(4-chlorophenyl)methanoneYield 38.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 21.0 g (0.135 mol) of p-chlorobenzoic acid and 20 ml of thionyl chloride were heated under reflux to give a clear solution. Removal of the excess of thionyl chloride under reduced pressure obtained white solid and immediately used for the next reaction. To the benzoyl chloride heated to 120° C. was added in portions with stirring 6.3 g (0.05 mol) of 4-chloroaniline. The mixture was heated to 180° C. and 8.5 g (0.063 mol) of ZnCl2 was added. The temperature was gradually increased to about 205° C. and kept there for 2 h. After cooling to 120° C., 60 ml of 3NHCl was added and the mixture stirred and heated to reflux. The hot acid layer was decanted and this procedure repeated two or three times. The water-insoluble residue was dissolved in 80 ml of 70% sulfuric acid and reflux for 8 h and then, after cooling poured into a large amount of ice water. The reaction mixture was neutralized with aqueous ammonia hydroxy and extracted with ethyl acetate, dried over Na2SO4. The solvent was removed and the residue was crystallized from 95% ethanol to give the title compound as golden yellow crystal 5.1 g, and yield 38.5%, m.p. 106-107° C.

Workup

  1. temperaturewere heated
  2. temperatureunder reflux
  3. customto give a clear solution
  4. customRemoval of the excess of thionyl chloride under reduced pressure
  5. customobtained white solid
  6. customimmediately used for the next reaction
  7. additionwas added in portions
  8. temperatureThe temperature was gradually increased to about 205° C.
  9. temperatureAfter cooling to 120° C.
  10. addition60 ml of 3NHCl was added
  11. temperatureheated to reflux
  12. customThe hot acid layer was decanted
  13. dissolutionThe water-insoluble residue was dissolved in 80 ml of 70% sulfuric acid
  14. temperaturereflux for 8 h
  15. temperatureafter cooling
  16. additionpoured into a large amount of ice water
  17. extractionextracted with ethyl acetate
  18. dry with materialdried over Na2SO4
  19. customThe solvent was removed
  20. customthe residue was crystallized from 95% ethanol

Sources & evidence

ORD record
ord-22065f000d7c44119408df25dc77793e
Source dataset
uspto-grants-2005_11
Patent number
US06960611B2

Reaction notes

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