Sulfuric Acid → 5-Hydroxy-2-methylbenzoic acid

HRID 524318Notes

Reaction equation

HRID 524318 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(=O)(=O)(O)[OH:13].N([O-])=O.[Na+].CC(=O)OCC>O>[OH:13][C:2]1[CH:3]=[CH:4][C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]

Participants

6

Reactant 4

HCID 1118Sulfuric Acid2×HCID 8857Ethyl AcetateHCID 103746145-Amino-2-methylbenzoic acidHCID 23668193Sodium Nitrite

Product 1

HCID 2351885-Hydroxy-2-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent4×

Procedure

To a mixture of 4.27 g 5-amino-2-methylbenzoic acid (see below), 6 ml concentrated sulfuric acid and 10 ml water, 50 ml ice are added, and a solution of 2.1 g sodium nitrite in 15 ml water is added drop wise, maintaining a temperature of the reaction mixture below 7° C. After stirring this mixture for further 30 min, it is added drop wise to a refluxing mixture of 20 ml concentrated sulfuric acid and 20 ml water. The resulting mixture is held under reflux for further 10 min and stirred over night allowing the temperature to cool down to RT. The mixture is portioned between water and EA, the phases are separated, the organic phase is dried over MgSO4, and the solvent is removed under reduced pressure. For further purification the remaining crude product is solved in diethyl ether, and the organic phase is washed with water, dried over MgSO4, and the solvent is removed under reduced pressure, resulting in 5-hydroxy-2-methylbenzoic acid as the product, which is used for the next step without further purification.

Workup

  1. additionare added
  2. temperaturemaintaining a temperature of the reaction mixture below 7° C
  3. additionit is added drop
  4. temperatureunder reflux for further 10 min
  5. stirringstirred over night
  6. customthe phases are separated
  7. dry with materialthe organic phase is dried over MgSO4
  8. customthe solvent is removed under reduced pressure
  9. customFor further purification the remaining crude product
  10. washthe organic phase is washed with water
  11. dry with materialdried over MgSO4
  12. customthe solvent is removed under reduced pressure
  13. customresulting in 5-hydroxy-2-methylbenzoic acid as the product, which
  14. customis used for the next step without further purification

Sources & evidence

ORD record
ord-5696992d9c3e41bb954bf9be3225a7c8
Source dataset
uspto-grants-2016_05
Patent number
US09340522B2

Reaction notes

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