Methanol → 3H-Indole, 2,3,3-trimethyl-5-nitro-

HRID 2306530Notes

Reaction equation

HRID 2306530 reaction equation
[N+:1]([O-:4])([O-])=[O:2].[Na+].[CH3:6][C:7]1[C:15]([CH3:17])([CH3:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=1.[OH-].[Na+].CO>S(=O)(=O)(O)O>[N+:1]([C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:6])[C:15]2([CH3:17])[CH3:16])([O-:4])=[O:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 154273H-Indole, 2,3,3-trimethyl-HCID 24268Sodium Nitrate

Product 1

HCID 975513H-Indole, 2,3,3-trimethyl-5-nitro-Yield 60%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Conditions

Temperature
2.5 °C

Procedure

Sodium nitrate (3.84 g, 45.2 mmol) was dissolved in concentrated sulphuric acid (100 ml). After cooling in ice, this solution was added to a solution of 2,3,3-trimethylindole (6.65 g, 41 .8 mmol) in concentrated sulphuric acid (100 ml) such that the temperature was maintained in the range 0-5° C. The reaction was stirred at 0-5° C. for 90 minutes after completing the addition, then allowed to warm to room temperature and stirred for a further 16 hours. The mixture was poured onto ice (200 g) then made basic by the addition of 50% aqueous sodium hydroxide solution to pH12 (pH paper). The crude product was collected by filtration and washed with water until the washings were neutral (˜1000 ml). The off-yellow solid was dried at the pump, dissolved in ethyl acetate (250 ml) and dried further (MgSO4). The solution was filtered and the red filtrate was rotary evaporated to dryness. The solid was dissolved in chloroform:ethyl acetate (95:5, 30 ml) and purified by silica flash chromatography. This gave a dark yellow solid, 5.12 g, 25 mmol, 60% yield. UV analysis (methanol) showed a single peak with λmax=300 nm. Mass spectrometry (MALDI-TOF with a gentisic acid matrix) gave m/z=203.8 (for C11H12N2O2=204.23). 1H NMR:δ=1.97 (s, 6H), 2.95 (s, 3H), 8.58 (d, J=10 Hz, 1H), 8.70 (s, 1H), 8.78 (d, J=10 Hz, 1H).

Workup

  1. temperatureAfter cooling in ice
  2. additionthe addition
  3. temperatureto warm to room temperature
  4. stirringstirred for a further 16 hours
  5. additionThe mixture was poured onto ice (200 g)
  6. filtrationThe crude product was collected by filtration
  7. washwashed with water until the washings
  8. customThe off-yellow solid was dried at the pump
  9. dissolutiondissolved in ethyl acetate (250 ml)
  10. dry with materialdried further (MgSO4)
  11. filtrationThe solution was filtered
  12. customthe red filtrate was rotary evaporated to dryness
  13. dissolutionThe solid was dissolved in chloroform:ethyl acetate (95:5, 30 ml)
  14. custompurified by silica flash chromatography
  15. customThis gave a dark yellow solid, 5.12 g, 25 mmol, 60% yield

Sources & evidence

ORD record
ord-43d90b926f48487a88e70a1eac4367f9
Source dataset
uspto-grants-2004_12
Patent number
US06828116B1

Reaction notes

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