Sulfuric Acid → 3-Methoxy-2-MethylBenzoic Acid

HRID 260805Notes

Reaction equation

HRID 260805 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+].S(OC)([O:26][CH3:27])(=O)=O>O.CO>[CH3:27][O:26][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 Acid2×HCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 27336993-Amino-2-methylbenzoic acidHCID 23668193Sodium Nitrite

Product 1

HCID 70214833-Methoxy-2-MethylBenzoic Acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Procedure

Ground 3-amino-2-methylbenzoic acid (17 g, 0.11 mole) was mixed with methanol (120 mL) in a 1-13-neck round bottom flask provided with a mechanical stirrer and a thermometer. To this mixture, concentrated sulfuric acid, 15.5 mL, was added dropwise with stirring. Upon the addition, the temperature of the mixture went up to 50° C. The addition time was 2 minutes. Following the addition, the flask was placed on a pre-heated oil bath and the temperature of 50°-55° C. inside the flask was maintained. Thereafter, a dropwise addition of sodium nitrite solution (8.1 g in 17 mL of water) was started. When the temperature reached 62° C., the heating under the oil bath was turned off. After additional 10 min on the oil bath (the heater still turned off), the temperature dropped to 55° C., at which point sodium hydroxide (50% aqueous, 55 g) diluted water (55 mL) was added dropwise over 30 minutes, followed by water (55 mL) in one portion, and dimethyl sulfate (25 mL) dropwise in two portions (15 mL plus 10 mL) over 30 minutes with 20 minutes apart. The reaction mixture was allowed to cool to room temperature whereupon it was poured over concentrated sulfuric acid, 40 mL, diluted with water (360 mL), the product collected by filtration, and dried in vacuo over 24 hours to give 3-methoxy-2-methylbenzoic acid (12 g). 1H-NMR (CDCl3) δppm 2.50 (s, 3H), 3.85 (s, 3H), 7.03 (d 1H, Ar), 7.22 (dd, 1H, C-5), 7.59 (d, 1H, Ar).

Workup

  1. customprovided with a mechanical stirrer
  2. additionUpon the addition
  3. customwent up to 50° C
  4. additionthe addition
  5. customthe flask was placed on a pre-heated oil bath
  6. temperaturethe temperature of 50°-55° C. inside the flask was maintained
  7. customreached 62° C.
  8. waitAfter additional 10 min on the oil bath (the heater still turned off
  9. additionwas added dropwise over 30 minutes
  10. filtrationthe product collected by filtration
  11. customdried in vacuo over 24 hours

Sources & evidence

ORD record
ord-6b4717947e13434f97245d646a45e287
Source dataset
uspto-grants-1996_06
Patent number
US05530028

Reaction notes

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