Hydrochloric Acid → (3-Bromo-4-methylphenyl)methanamine hydrochloride

HRID 662101Notes

Reaction equation

HRID 662101 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].OS(O)(=O)=O.[Br:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:16]#[N:17].[OH-].[Na+].[ClH:24]>C1COCC1.CCOCC.O>[ClH:24].[Br:12][C:13]1[CH:14]=[C:15]([CH2:16][NH2:17])[CH:18]=[CH:19][C:20]=1[CH3:21]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 140048403-Bromo-4-methylbenzonitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 68632621(3-Bromo-4-methylphenyl)methanamine hydrochlorideYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To LiAlH4 (1M in ether) (400 mL, 400 mmol) in a 2 L 3-neck flask with mechanical stirring under nitrogen at −5° C. was added concentrated H2SO4 (10.94 mL, 219 mmol) dropwise. Gas evolution was observed and the solution became cloudy and the foamy mixture was not as easy to stir. Temperature got as high as 3° C. The addition took 28 min. This mixture was stirred for 60 min and then the 3-bromo-4-methylbenzonitrile (37.3 g, 190 mmol) in THF (850 mL) was added over 18 min (max temp=10° C.). The slightly peach-colored mixture was stirred in the ice bath. After 30 min water (90 mL) was added carefully to give a white mixture, followed by 2M sodium hydroxide. After adding 100 mL, a solid that appeared to be amenable to filtration had formed. This was stirred for 30 min. The slightly waxy solid was filtered off and the single-phase filtrate washed with brine, dried and evaporated. This gave a slightly cloudy yellowish oil, 39.64 g (>100%) that was re-dissolved in ether (350 mL), filtered to remove some solid, and to the oil was added 1M hydrogen chloride in ether (1 eq based on starting nitrile, 190 mmol, 190 mL) slowly with stirring under nitrogen, This gave a solid that was collected by vacuum filtration and sucked dry, then dried under high vacuum to give 41.34 g (92%) of a white solid that the lab HPLC showed to be 98.8% pure with a retention time of 1.56 min. LC-MS m/z 200, 202 (M+H)+, 1.05 min (ret time).

Workup

  1. customgot as high as 3° C
  2. additionThe addition
  3. stirringThis mixture was stirred for 60 min
  4. customto give a white mixture
  5. additionAfter adding 100 mL
  6. filtrationto be amenable to filtration
  7. customhad formed
  8. stirringThis was stirred for 30 min
  9. filtrationThe slightly waxy solid was filtered off
  10. washthe single-phase filtrate washed with brine
  11. customdried
  12. customevaporated
  13. customThis gave a slightly cloudy yellowish oil, 39.64 g (>100%) that
  14. filtrationfiltered
  15. customto remove some solid
  16. stirringwith stirring under nitrogen
  17. customThis gave a solid
  18. filtrationthat was collected by vacuum filtration
  19. customsucked dry
  20. customdried under high vacuum

Sources & evidence

ORD record
ord-2e41a3e2874849d68ed03ca24178b14e
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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