Toluene → 2-Amino-5-cyano-N,3-dimethylbenzamide

HRID 1663511Notes

Reaction equation

HRID 1663511 reaction equation
[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9](Br)=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].[C-:14]#[N:15].[K+].C1(C)C=CC=CC=1>O=O>[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9]([C:14]#[N:15])=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 1140TolueneHCID 9032Potassium CyanideHCID 442275752-amino-5-bromo-N,3-dimethylbenzamide2×

Product 1

HCID 251572822-Amino-5-cyano-N,3-dimethylbenzamideYield 81.8%

Reagents, catalysts & solvents 1

HCID 977OxygenSolvent4×

Conditions

Temperature
45 °C

Procedure

A stirred mixture of 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Reference Example 1) (20.0 g, 0.082 mol), potassium cyanide (10.4 g, 0.159 mol) and oxygen-free ethanol (60 mL) was heated at 45° C. A slurry of chloronaphthalenylbis(triphenylphosphine)nickel (i.e. the product of Example 1, a mixture of 1- and 2-isomers) (4.01 g, 5.36 mmol) in oxygen-free ethanol (60 mL) was added in four portions to the reaction mixture. Each addition was completed in about 18 minutes, and after the first addition subsequent additions were begun approximately 50, 75, and 105 minutes after the previous addition was complete. Oxygen-free ethanol (15 mL) was added to the reaction mixture after the second addition to facilitate stirring. After the fourth addition was complete, the reaction mixture was stirred for 5.7 h at 45° C., and then more chloro-naphthalenylbis(triphenylphosphine)nickel (0.5 g, 0.67 mmol) in oxygen-free ethanol (10 mL) was added over 10 minutes. After stirring overnight at 45° C., toluene (100 mL) was added, and the solvent was evaporated under reduced pressure. More toluene (150 mL) was added, and the solvent was again evaporated under reduced pressure. The resulting solid was slurried in toluene (120 mL), filtered, and washed with toluene (100 mL) and water (2×70 mL). The solid was dried overnight in a vacuum-oven at 50° C. to give the title compound as a white solid (12.68 g, 81.8% yield). A portion of the product was recrystallized from acetonitrile to give an analytical sample melting at 204.0-204.5° C.

Workup

  1. additionwas added in four portions to the reaction mixture
  2. additionEach addition
  3. custom50, 75, and 105 minutes
  4. additionafter the previous addition
  5. additionafter the second addition
  6. additionAfter the fourth addition
  7. stirringthe reaction mixture was stirred for 5.7 h at 45° C.
  8. stirringAfter stirring overnight at 45° C.
  9. customthe solvent was evaporated under reduced pressure
  10. additionMore toluene (150 mL) was added
  11. customthe solvent was again evaporated under reduced pressure
  12. filtrationfiltered
  13. washwashed with toluene (100 mL) and water (2×70 mL)
  14. customThe solid was dried overnight in a vacuum-oven at 50° C.

Sources & evidence

ORD record
ord-b95aa7cf4dab432caa6e2080b8b4e893
Source dataset
uspto-grants-2011_10
Patent number
US08034968B2

Reaction notes

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