Dimethylformamide → 4-Cyano-3-methylbenzoic acid

HRID 587836Notes

Reaction equation

HRID 587836 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].[CH3:12][N:13](C)C=O>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:12]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11])#[N:13]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 821314-Bromo-3-methylbenzoic acid

Product 1

HCID 102410994-Cyano-3-methylbenzoic acid

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

4-Bromo-3-methylbenzoic acid (3.0 g) was dissolved in N,N-dimethylformamide (20 ml). The resulting solution was subjected to deaeration three times under argon atmosphere (i.e., the reaction solution was de-pressurized to 20 mmHg, and then brought back to atmospheric pressure under argon atmosphere). To the solution, zinc cyanide (1.6 g) and tetrakis(triphenylphosphine) palladium (0) (1.6 g) were added and the mixture was stirred under heating at 90° C. for 6 hours under argon atmosphere. After adjusting to room temperature, precipitates were filtered off. The filtrate was diluted with water, added with lithium hydroxide monohydrate (2.9 g) and washed twice with tert-butyl methyl ether. The aqueous phase was acidified with 2N hydrochloric acid and extracted twice with ethyl acetate. The organic phases were combined, washed with brine and dried over magnesium sulfate. After filtering off the drying agent, the solvent was distilled off under reduced pressure to obtain 4-cyano-3methylbenzoic acid as a crude product (1.9 g). Without further purification, the crude product was used for the next reaction.

Workup

  1. customAfter adjusting to room temperature
  2. customprecipitates
  3. filtrationwere filtered off
  4. additionThe filtrate was diluted with water
  5. additionadded with lithium hydroxide monohydrate (2.9 g)
  6. washwashed twice with tert-butyl methyl ether
  7. extractionextracted twice with ethyl acetate
  8. washwashed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationAfter filtering off the drying agent
  11. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-3faa8d47b4e64bfa87efb255db832277
Source dataset
uspto-grants-2016_01
Patent number
US09227923B2

Reaction notes

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