Benzene → 4-Trifluoromethylnicotinamide

HRID 2379042Notes

Reaction equation

HRID 2379042 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:9](O)=[O:10].S(Cl)(Cl)=O.C1C=CC=CC=1.C[N:25](C)C=O>>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:9]([NH2:25])=[O:10]

Participants

5

Reactant 4

HCID 241BenzeneHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 27775493-Pyridinecarboxylic acid, 4-(trifluoromethyl)-

Product 1

HCID 27826434-Trifluoromethylnicotinamide

Procedure

A solution comprising 3 g of 4-trifluoromethyl-3-pyridine carboxylic acid, 6.7 ml of thionyl chloride and 20 ml of benzene, was refluxed under heating for 1.5 hours in the presence of a catalytic amount of dimethylformamide. Excess thionyl chloride and benzene were distilled off. Then, the residue was dissolved in 5 ml of ethyl acetate. This solution was gradually dropwise added to 20 ml of ammonia under cooling with ice. After completion Of the dropwise addition, the mixture was stirred at room temperature for 30 minutes. Then, water and ethyl acetate were distilled off under reduced pressure. The residue was extracted with heated ethyl acetate to obtain 2.1 g of 4-trifluoromethyl-3-pyridine carboxamide (melting point: 162.7° C.) as the desired product.

Workup

  1. temperaturewas refluxed
  2. distillationExcess thionyl chloride and benzene were distilled off
  3. dissolutionThen, the residue was dissolved in 5 ml of ethyl acetate
  4. additionThis solution was gradually dropwise added to 20 ml of ammonia
  5. temperatureunder cooling with ice
  6. additionAfter completion Of the dropwise addition
  7. distillationThen, water and ethyl acetate were distilled off under reduced pressure
  8. extractionThe residue was extracted with heated ethyl acetate

Sources & evidence

ORD record
ord-109bb273249443da87b089659cc65c98
Source dataset
uspto-grants-1994_11
Patent number
US05360806

Reaction notes

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