Sulfuric Acid → 2-Methoxy-4-methylbenzoic acid

HRID 1904414Notes

Reaction equation

HRID 1904414 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH-].[Na+].S(OC)(O[CH3:18])(=O)=O.S(=O)(=O)(O)O>O>[CH3:18][O:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 57882-Hydroxy-p-toluic acidHCID 6497Dimethyl SulfateHCID 14798Sodium Hydroxide

Product 1

HCID 5971642-Methoxy-4-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
10 °C

Procedure

A stirred mixture of 2-hydroxy-4-methylbenzoic acid (75 g, 0.50 mol), sodium hydroxide (42 g, 1.0 mol) and water (250 ml) was cooled to 10° C. and treated dropwise with dimethyl sulphate (126 g, 1.0 mol). The mixture was stirred for 6 days, poured into water (4000 ml), acidified with sulfuric acid and extracted with dichloromethane (4×600 ml). The extracts were combined, washed with water, dried over sodium sulfate and the solvent was evaporated off under reduced pressure. The resulting oil was treated with aqueous sodium hydroxide (1000 ml of 2M) and heated under reflux for 2 hours. The mixture was acidified with hydrochloric acid and extracted with dichloromethane (3×300 ml). The combined extracts were dried over sodium sulfate and the solvent was evaporated off under reduced pressure to give the crude product as an oil. The crude product was purified by column chromatography (silica gel, chloroform) and recrystallized from chloroform-hexane to yield 2-methoxy-4-methylbenzoic acid as a colorless crystalline solid, having a melting point of 108°-109° C.

Workup

  1. extractionextracted with dichloromethane (4×600 ml)
  2. washwashed with water
  3. dry with materialdried over sodium sulfate
  4. customthe solvent was evaporated off under reduced pressure
  5. additionThe resulting oil was treated with aqueous sodium hydroxide (1000 ml of 2M)
  6. temperatureheated
  7. temperatureunder reflux for 2 hours
  8. extractionextracted with dichloromethane (3×300 ml)
  9. dry with materialThe combined extracts were dried over sodium sulfate
  10. customthe solvent was evaporated off under reduced pressure
  11. customto give the crude product as an oil
  12. customThe crude product was purified by column chromatography (silica gel, chloroform)
  13. customrecrystallized from chloroform-hexane

Sources & evidence

ORD record
ord-e62244f42ede4971804a069a20a5a61e
Source dataset
uspto-grants-1989_06
Patent number
US04837333

Reaction notes

Loading…