Nitric Acid → 3-Methyl-5-nitroisoquinoline

HRID 2117314Notes

Reaction equation

HRID 2117314 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.OS(O)(=O)=O.[N+:17]([O-])([OH:19])=[O:18].[OH-].[Na+]>ClCCl.CO>[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([N+:17]([O-:19])=[O:18])[CH:8]=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric Acid2×HCID 143063-MethylisoquinolineHCID 14798Sodium Hydroxide

Product 1

HCID 2749733-Methyl-5-nitroisoquinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

3-Methylisoquinoline (2.14 g, 14.9 mmol) was added portionwise to ice-cooled concentrated H2SO4 (10 ml) keeping the internal temperature below 10° C. A nitrating mixture of concentrated H2SO4 (2 ml) and fuming nitric acid (2 ml) was then added dropwise keeping the internal temperature below 15° C. After stirring for 30 minutes, TLC indicated reaction was complete. The acid was neutralized by adding the mixture to an excess of 4N aqueous NaOH (180 ml) with ice-cooling. The mixture was extracted with dichloromethane (2×150 ml), then dried (Na2SO4) and evaporated to give the crude product (2.69 g) as a yellow solid. Flash column chromatography using as eluant 5% methanol in dichloromethane gave a pure sample of the title compound (660 mg) and a sample (1.95 g) containing ca. 10% of the 8-nitro isomer.

Workup

  1. customthe internal temperature below 10° C
  2. additionwas then added dropwise
  3. customthe internal temperature below 15° C
  4. customreaction
  5. temperaturecooling
  6. extractionThe mixture was extracted with dichloromethane (2×150 ml)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customto give the crude product (2.69 g) as a yellow solid

Sources & evidence

ORD record
ord-99f2199625fc4282a3f6f94a90709397
Source dataset
uspto-grants-2008_10
Patent number
US07442701B2

Reaction notes

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