3,4-Dichlorophenol → 2-(3,4-Dichlorophenoxy)nicotinaldehyde

HRID 1246628Notes

Reaction equation

HRID 1246628 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])([O-])=O.[K+].[K+].Cl[C:17]1[N:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=[O:20]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[O:9][C:17]1[N:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=[O:20]

Participants

6

Reactant 3

HCID 72583,4-DichlorophenolHCID 11430Potassium CarbonateHCID 7376072-Chloro-3-pyridinecarboxaldehyde

Product 1

HCID 219046872-(3,4-Dichlorophenoxy)nicotinaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under N2 in a 250 mL round-bottomed flask fitted with a reflux condenser and magnetic stirrer, 3,4-dichlorophenol (2.9 g, 17.8 mmol) was added to a suspension of K2CO3 (7.0 g, 51 mmol) in 70 mL of anhydrous DMF. After stirring the mixture for 15 min., 2-chloronicotinaldehyde (2.4 g, 17 mmol prepared according to the method in J. Heterocycl. Chem. 1995, 32, 1595) was added and the mixture was heated to 90–100° C. for 5 h. After allowing the reaction to cool to room temperature overnight, the mixture was diluted with water and extracted three times with EtOAc. The aqueous layer was then extracted with additional EtOAc and the organic layers were combined, washed with water and brine and dried over Na2SO4. Removal of the solvent in vacuo gave a brown solid which was further dried under vacuum overnight and then recrystallized from EtOAc to give the title product as tan crystals, 1.6 g; m.p. 97–99° C. A second crop of tan crystals weighing 0.716 g was later obtained, and concentration of the filtrate provided an additional 2.65 g of nearly pure title product; δH (CDCl3, 400 MHz) 7.08 (1H, dd), 7.17 (1H, m), 7.43 (1H, d), 7.49 (1H, d), 8.25 (1H, dd), 8.33 (1H, dd), 10.50 (1H, s).

Workup

  1. customUnder N2 in a 250 mL round-bottomed flask fitted with a reflux condenser and magnetic stirrer
  2. addition1995, 32, 1595) was added
  3. temperaturethe mixture was heated to 90–100° C. for 5 h
  4. customthe reaction
  5. extractionextracted three times with EtOAc
  6. extractionThe aqueous layer was then extracted with additional EtOAc
  7. washwashed with water and brine
  8. dry with materialdried over Na2SO4
  9. customRemoval of the solvent in vacuo
  10. customgave a brown solid which
  11. customwas further dried under vacuum overnight
  12. customrecrystallized from EtOAc

Sources & evidence

ORD record
ord-dd03d76f50194af3b53145103e35bf90
Source dataset
uspto-grants-2006_10
Patent number
US07129234B2

Reaction notes

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