Methyl iodide → 1h-Indole-3-acetonitrile, 6-nitro-

HRID 1004207Notes

Reaction equation

HRID 1004207 reaction equation
CN([CH2:4][C:5]1[C:9]2[CH:10]=[CH:11][C:12]([N+:14]([O-:16])=[O:15])=[CH:13][C:8]=2[NH:7][CH:6]=1)C.[C:17](#[N:19])C.CI.[C-]#N.[Na+]>O>[N+:14]([C:12]1[CH:13]=[C:8]2[C:9]([C:5]([CH2:4][C:17]#[N:19])=[CH:6][NH:7]2)=[CH:10][CH:11]=1)([O-:16])=[O:15]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 6342AcetonitrileHCID 8929Sodium CyanideHCID 233856-Nitrogramine

Product 1

HCID 2523851h-Indole-3-acetonitrile, 6-nitro-Yield 70.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 44.27 g (0.204 mol) of 6-nitrogramine (12) [Jackson B. Hester J. Org. Chem., 29: 1158 (1964)] in 450 ml of acetonitrile 44.59 g (0.31 mol) of methyl iodide was added at 0-5° C. over a period of an hour. The reaction mixture was stirred at room temperature for three hours, then a solution of 26.6 g (0.543 mol) of sodium cyanide in 225 ml of water added at once. The reaction mixture was heated at 32° C. overnight, cooled to room temperature and the product extracted 3 times with a total of 800 ml of ethyl acetate and 300 ml of water. The combined extracts were washed with water, 1N-HCl solution, a saturated sodium bicarbonate solution, dried on MgSO4 and the solvent evaporated in vacuo. The orange-brown residue (41.3 g) was dissolved in 200 ml of warm ethyl acetate and passed through a small pad of silica gel to produce 28.9 g (70.4%) of (6-nitro-1H-indolyl-3-yl)-acetonitrile (13) as a yellow solid after evaporation of the solvent.

Workup

  1. temperatureThe reaction mixture was heated at 32° C. overnight
  2. temperaturecooled to room temperature
  3. extractionthe product extracted 3 times with a total of 800 ml of ethyl acetate and 300 ml of water
  4. washThe combined extracts were washed with water, 1N-HCl solution
  5. dry with materiala saturated sodium bicarbonate solution, dried on MgSO4
  6. customthe solvent evaporated in vacuo
  7. dissolutionThe orange-brown residue (41.3 g) was dissolved in 200 ml of warm ethyl acetate

Sources & evidence

ORD record
ord-d738b849f8174bfa869bbda5116db955
Source dataset
uspto-grants-2000_04
Patent number
US06048887

Reaction notes

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