Hydrochloric Acid → {[2-Methyl-3-(trifluoromethyl)phenyl]methyl}propanedinitrile

HRID 510403Notes

Reaction equation

HRID 510403 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].[CH3:6][C:7]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O.[BH4-].[Na+].Cl>C(O)C.O>[CH3:6][C:7]1[C:14]([C:15]([F:16])([F:17])[F:18])=[CH:13][CH:12]=[CH:11][C:8]=1[CH2:9][CH:2]([C:1]#[N:5])[C:3]#[N:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8010MalononitrileHCID 37191482-Methyl-3-(trifluoromethyl)benzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 86724884{[2-Methyl-3-(trifluoromethyl)phenyl]methyl}propanedinitrileYield 77%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

To a mixture of malononitrile (2.352 g, 35.6 mmol) in 95% Ethanol (50 mL) was added 2-methyl-3-(trifluoromethyl)benzaldehyde (6.7 g, 35.6 mmol). The reaction was stirred at rt for 18 h. Additional EtOH (20 mL) was added and the mixture was stirred for 20 minutes and cooled to 0° C. in an ice bath. Sodium borohydride (0.364 g, 9.61 mmol) was introduced to the vigorously stirred mixture and the reduction was complete in about 10 min. To the reaction mixture was added water (40 mL). 1N HCl was added in to quench the excess hydride. More water was added in until precipitation was complete. Filtration gave {[2-methyl-3-(trifluoromethyl)phenyl]methyl}propanedinitrile (6.5 g, 77%). To a mixture of {[2-methyl-3-(trifluoromethyl)phenyl]methyl}propanedinitrile (6.5 g, 27.3 mmol) in Ethanol (80 mL) was added hydrazine hydrate (2.68 mL, 54.6 mmol). The reaction mixture was heated at reflux temperature for 8 h. The reaction mixture was concentrated. The crude material was purified on a silica column (eluting with MeOH/DCM: 0˜10%) to give the product (3.5 g, 47%). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.47 (s, 3H) 3.69 (s, 2H) 7.11-7.37 (m, 2H) 7.51 (d, 1H); LC/MS: MS (ES+) m/e 271.2 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 20 minutes
  2. temperaturecooled to 0° C. in an ice bath
  3. waitthe reduction was complete in about 10 min
  4. customto quench the excess hydride
  5. additionMore water was added in until precipitation
  6. filtrationFiltration

Sources & evidence

ORD record
ord-8421f5930878447aa4307e520b06d416
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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