Benzaldehyde → 2-1H-indol-3-yl-3-phenylacrylonitrile

HRID 1094597Notes

Reaction equation

HRID 1094597 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]#[N:12])=[CH:2]1.CO.[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C[O-].[Na+]>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10](=[CH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]#[N:12])=[CH:2]1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 887Methanol2×HCID 351795Indole-3-acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 666408512-1H-indol-3-yl-3-phenylacrylonitrileYield 44.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(1H-Indol-3-yl)-3-phenylacrylonitrile was prepared by the addition of 3-indolylacetonitrile (2.02 g, 12.9 mmol), MeOH (18 mL), benzaldehyde (1.60 mL, 15.5 mmol), and a 25% wt solution of sodium methoxide in MeOH (3.2 mL, 14.2 mmol) to a 50 mL flask. The solution was allowed to stir at ambient temperature under N2 for 16 h. The reaction solution was diluted with DCM (20 mL), molecular sieves (250 mg) were added, and the solution was allowed to reflux for 1 hour. The reaction was quenched with the addition of sat. NH4Cl (20 mL). The organic phase was partitioned, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was chromatographed (SiO2, 100% hexane to 5% EtOAc) to yield 1.4 g (44% yield) of 2-1H-indol-3-yl-3-phenyl-acrylonitrile; 1H NMR (CDCl3) δ 8.42 (1H, br s), 7.97 (1H, d), 7.87 (2H, m), 7.63 (1H, s), 7.60 (1H, d), 7.37-7.48 (4H, m), 7.25-7.33 (2H, m); TLC (SiO2 plate, 5:1 hexane/EtOAc) Rf=0.35; MS (ESI): 245 (MH+).

Workup

  1. additionwere added
  2. temperatureto reflux for 1 hour
  3. customThe reaction was quenched with the addition of sat. NH4Cl (20 mL)
  4. customThe organic phase was partitioned
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was chromatographed (SiO2, 100% hexane to 5% EtOAc)

Sources & evidence

ORD record
ord-ffb7d303d0684c07ae4cf6668b20c199
Source dataset
uspto-grants-2012_03
Patent number
US08133992B2

Reaction notes

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