Nitric Acid → HCID 20738653, compound

HRID 2217376Notes

Reaction equation

HRID 2217376 reaction equation
[N+:1]([O-:4])(O)=[O:2].S(=O)(=O)(O)O.O[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=1[C:18]([OH:20])=[O:19].[C:21](=[O:24])([O-])[O-].[K+].[K+].S(OC)(O[CH3:31])(=O)=O>CC(C)=O>[CH3:31][O:20][C:18](=[O:19])[C:12]1[CH:11]=[CH:16][C:15]([N+:1]([O-:4])=[O:2])=[C:14]([O:24][CH3:21])[C:13]=1[CH3:17]

Participants

7

Reactant 5

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 6497Dimethyl SulfateHCID 112796-Methylsalicylic AcidHCID 11430Potassium Carbonate

Product 1

HCID 20738653HCID 20738653, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
-50 °C

Procedure

To a stirring mixture of fuming nitric acid (18.7 mL, 0.40 mol) and concentrated sulfuric acid (2.53 mL, 47.5 mmol) at −50° C. was added 3-hydroxy-o-toluic acid (5.0 g, 32.9 mmol) drop-wise maintaining the reaction temperature at −50° C. After five minutes, the reaction mixture was poured into crushed ice (200 gram) and was extracted with ethyl acetate (400 mL). The ethyl acetate layer was washed with water, dried (anhydrous magnesium sulfate), filtered and concentrated to give a crude product which was a 1:1 mixture of the desired mononitrated product and the undesired bisnitrated product. The crude mixture was re-dissolved in acetone (170 mL). To the resulting solution was added potassium carbonate (20.9 g, 151.0 mmole) and dimethyl sulfate (10.7 mL, 113.2 mmole). The reaction mixture was refluxed for one hour and concentrated. The resulting orange residue was washed with water and air dried and subjected to flash chromatography over silica gel eluting with 10% ethyl acetate/hexane. Product fractions were concentrated under reduced pressure to give 3-methoxy-2-methyl-4-nitro-benzoic acid methyl ester as a solid (1.88 g, 25%). 1H NMR (CDCl3) δ: 2.55 (s, 3H), 3.91 (s, 3H), 3.94 (s, 3H), 7.61 (d, 1H, J=8.5 Hz), 7.68 (d, 1H, J=8.6 Hz).

Workup

  1. additionthe reaction mixture was poured
  2. extractionwas extracted with ethyl acetate (400 mL)
  3. washThe ethyl acetate layer was washed with water
  4. dry with materialdried (anhydrous magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product which
  8. additiona 1:1 mixture of the desired mononitrated product
  9. temperatureThe reaction mixture was refluxed for one hour
  10. concentrationconcentrated
  11. washThe resulting orange residue was washed with water and air
  12. customdried
  13. concentrationProduct fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-ee9c3ec1c76547be8cbfde96dc7b25ff
Source dataset
uspto-grants-2008_08
Patent number
US07407980B2

Reaction notes

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