Sulfuric Acid → 3-Methoxy-2-MethylBenzoic Acid

HRID 2225930Notes

Reaction equation

HRID 2225930 reaction equation
N[C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.N([O-])=O.[Na+].[OH-].[Na+].[CH3:23][O:24]S(OC)(=O)=O>O.CO>[CH3:23][O:24][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6]

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 6497Dimethyl Sulfate2×HCID 14798Sodium Hydroxide2×HCID 27336993-Amino-2-methylbenzoic acidHCID 23668193Sodium Nitrite

Product 1

HCID 70214833-Methoxy-2-MethylBenzoic AcidYield 88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

3-Amino-2-methylbenzoic acid (140.3 g, 0.93 mol, reacted in four portions) in 5.7 mass equivalents of methanol was treated with 1.5 mole equivalents of concentrated sulfuric acid. The mixture was heated to 55° C. and 1.05 mole equivalent of sodium nitrite dissolved in twice its mass of water was fed to the reaction over 30 to 45 minutes, maintaining the temperature between 55 and 65° C. 4.5 mole equivalents of 25% aqueous sodium hydroxide was added over one-half hour, followed by a half-hour feed of 2 mole equivalents of dimethylsulfate at 50 to 60° C. After one-half hour the batch was assayed by GC. Additional sodium hydroxide and dimethylsulfate were added in portions until complete conversion was obtained, The methanol remaining was removed by vacuum, and the residue was partitioned between ethyl acetate and water made acidic with sulfuric acid. The ethyl acetate was removed under vacuum. The combined residues (152.8 g) dissolved in 350 g warm methanol were poured into a mixture of 278 g concentrated sulfuric acid and 1 liter water. The resulting precipitate was collected by filtration, washed with water, and dried in vacuo, giving 135.8 g (88%) of material which was 96% pure as determined by GC.

Workup

  1. customwas fed to the reaction over 30 to 45 minutes
  2. temperaturemaintaining the temperature between 55 and 65° C
  3. waitfollowed by a half-hour
  4. customat 50 to 60° C
  5. waitAfter one-half hour the batch was assayed by GC
  6. customwas obtained
  7. customThe methanol remaining was removed by vacuum
  8. customthe residue was partitioned between ethyl acetate and water
  9. customThe ethyl acetate was removed under vacuum
  10. dissolutionThe combined residues (152.8 g) dissolved in 350 g
  11. temperaturewarm methanol
  12. additionwere poured into a mixture of 278 g concentrated sulfuric acid and 1 liter water
  13. filtrationThe resulting precipitate was collected by filtration
  14. washwashed with water
  15. customdried in vacuo

Sources & evidence

ORD record
ord-539e83a8697f4e459986d8d8e79d709e
Source dataset
uspto-grants-1994_09
Patent number
US05344958

Reaction notes

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