3-Chloroaniline → 7-Chloro-2-methylquinoline

HRID 1493500Notes

Reaction equation

HRID 1493500 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH:9](=O)/[CH:10]=[CH:11]/[CH3:12]>Cl.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:3]=[C:4]2[C:6]([CH:9]=[CH:10][C:11]([CH3:12])=[N:5]2)=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 79323-ChloroanilineHCID 447466Crotonaldehyde

Product 1

HCID 1383957-Chloro-2-methylquinoline

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 313Hydrochloric AcidSolvent

Procedure

To a solution of m-chloroaniline (25.51 g, 0.2 mol) in 100 mL of 6N HCl kept at reflux is added dropwise with stirring 85% aqueous crotonaldehyde (14.7 g, in 2.6 g of water). After an additional 45 minutes at reflux, the mixture is cooled and extracted with ethyl ether to remove tars. To the vigorously stirred solution is added ZnCl2 (27.2 g, 0.20 mol). A tan gum ball is formed. The mixture is then refluxed for a total of three hours to give a clear brown solution. Upon cooling, a gummy solid is formed which is filtered and triturated with 2-propanol followed by ethyl ether and dried in vacuo to give the quinaldine HCl-ZnCl2 complex. The 7-chloroquinaldine is then isolated by dissolving the complex into 150 mL of water and 50 mL of NH4OH, and concentrated to yield the crude product (tan solid 15.77 g, 44.4%). Purification of the crude product is achieved by flash chromatography, (silica Merck 60, methylene chloride:ethyl acetate 98:2). Removal of the solvent affords a light tan solid (11.1 g, 31.3%), m.p. dec. 68°-70° C. (lit: 42%, m.p. 75°-77° C.).

Workup

  1. temperatureat reflux
  2. additionis added dropwise
  3. temperatureAfter an additional 45 minutes at reflux
  4. temperaturethe mixture is cooled
  5. extractionextracted with ethyl ether
  6. customto remove tars
  7. customA tan gum ball is formed
  8. temperatureThe mixture is then refluxed for a total of three hours
  9. customto give a clear brown solution
  10. temperatureUpon cooling
  11. customa gummy solid is formed which
  12. filtrationis filtered
  13. customtriturated with 2-propanol
  14. customdried in vacuo
  15. customto give the quinaldine HCl-ZnCl2 complex

Sources & evidence

ORD record
ord-6477d3e35e6047558f1fc54534a1c0c3
Source dataset
uspto-grants-1991_06
Patent number
US05021576

Reaction notes

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