Bromide ion → (2-Aminophenyl)(3-methylphenyl)methanone

HRID 921263Notes

Reaction equation

HRID 921263 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[CH:4]=1.[Br-].[NH2:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[C:14]#N.Cl.[OH-:21].[Na+]>BrC(Br)C.C(OCC)C.C([O-])(O)=O.[Na+]>[NH2:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[C:14]([C:3]1[CH:4]=[C:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1)=[O:21]

Participants

10

Reactant 6

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 115603-BromotolueneHCID 14798Sodium HydroxideHCID 729132-AminobenzonitrileHCID 5462224Magnesium

Product 1

HCID 14835336(2-Aminophenyl)(3-methylphenyl)methanone

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 3283Diethyl EtherSolvent3×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To a 250 mL round-bottomed flask charged with magnesium (0.947 g, 39.0 mmol) and diethyl ether (50.0 ml) was added 2 drops of dibromoethane. The reaction mixture was heated to 60° C. for 5 min and then removed from the heat. Next, 1-bromo-3-methylbenzene (5 g, 29.2 mmol) in diethyl ether (50 ml) was added slowly in portions until reflux was achieved. The remaining bromide was added dropwise to maintain reflux. After the addition, the reaction mixture was refluxed for 3 hrs. Next, 2-aminobenzonitrile (1.151 g, 9.74 mmol) in diethyl ether (50.0 ml) was added slowly over 10 min. The resulting mixture was refluxed overnight. The volume of the reaction mixture was reduced to ⅓ and 100 g of crushed ice and 50 ml of 6N HCl was added while stirring. After 3 hrs at room temperature, the pH was adjusted to pH 8 with 5N NaOH and the reaction was diluted with sat NaHCO3 (50 mL). The two phases were separated and the aqueous layer was extracted with ethyl acetate (2×200 mL). The combined organic layers were dried with MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 70% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 80 g) to provide Intermediate A-23 (1.84 g, 89%). 1H NMR (400 MHz, DMSO-d6) δ 7.44-7.23 (m, 6H), 7.08 (br. s., 2H), 6.86 (d, J=8.1 Hz, 1H), 6.50 (t, J=7.5 Hz, 1H), 2.38 (s, 3H).

Workup

  1. customremoved from the heat
  2. temperatureuntil reflux
  3. temperatureto maintain
  4. temperaturereflux
  5. additionAfter the addition
  6. temperaturethe reaction mixture was refluxed for 3 hrs
  7. temperatureThe resulting mixture was refluxed overnight
  8. customThe two phases were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (2×200 mL)
  10. dry with materialThe combined organic layers were dried with MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 70% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 80 g)
  14. customto provide Intermediate A-23 (1.84 g, 89%)

Sources & evidence

ORD record
ord-09c817aa478446b582b545ae7c42b89b
Source dataset
uspto-grants-2016_03
Patent number
US09273014B2

Reaction notes

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