Hydrochloric Acid → 4-(Aminomethyl)-2-bromobenzonitrile

HRID 657321Notes

Reaction equation

HRID 657321 reaction equation
[Br:1][C:2]1[CH:9]=[C:8]([CH2:10][N:11]2C(=O)C3C(=CC=CC=3)C2=O)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O.NN.Cl>CCO>[NH2:11][CH2:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Br:1])[CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24654Hydrazine hydrate (1:1)HCID 578135192-bromo-4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzonitrile

Product 1

HCID 578132844-(Aminomethyl)-2-bromobenzonitrileYield 75.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 2-bromo-4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzonitrile (8.0 g, 23.5 mmol) in EtOH (150 mL) was added hydrazine hydrate (85%, 2.76 g). The mixture was refluxed for 3 h. At room temperature 2 N HCl (60 mL) was added (pH=3), and the mixture was filtered and rinsed with water (50 mL×4). The filtrate was evaporated to about 150 mL and filtered again. After addition of NaHCO3 to adjust the pH=9, the filtrate was extracted with CH2Cl2 (100 mL×3). The combined extracts were washed with brine and dried over anhydrous sodium sulfate. After removing the solvent, 1N HCl in MeOH (50 mL) was added and the solvent was evaporated to afford crude material as a white solid. Recrystallization from MeOH-Et2O yielded 4.3 g of the product, 4-(aminomethyl)-2-bromobenzonitrile (yield: 75.8%). 1H NMR (400 MHz, D2O) δ 4.21 (S, 2H), 7.43 (dd, J=8.0 Hz, J=1.2 Hz, 1H), 7.71 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz, D2O): δ42.3, 115.5, 118.0, 125.6, 128.4, 133.4, 135.5, 139.9; HPLC: retention time: 4.709 min; purity: 99.7%.

Workup

  1. temperatureThe mixture was refluxed for 3 h
  2. filtrationthe mixture was filtered
  3. washrinsed with water (50 mL×4)
  4. customThe filtrate was evaporated to about 150 mL
  5. filtrationfiltered again
  6. additionAfter addition of NaHCO3
  7. extractionthe filtrate was extracted with CH2Cl2 (100 mL×3)
  8. washThe combined extracts were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customAfter removing the solvent, 1N HCl in MeOH (50 mL)
  11. additionwas added
  12. customthe solvent was evaporated
  13. customto afford crude material as a white solid
  14. customRecrystallization from MeOH-Et2O

Sources & evidence

ORD record
ord-4191d95a2e7d4e1fa2ed4729740f1190
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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