Dimethylamine → 2,4-Xylenol, 6-chloro-alpha(sup 4)-(dimethylamino)-

HRID 1157210Notes

Reaction equation

HRID 1157210 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].[CH3:10][NH:11][CH3:12].[CH2:13]=O>C(O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:10][N:11]([CH3:13])[CH3:12])[CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9]

Participants

6

Reactant 3

HCID 674Dimethylamine2×HCID 712Formaldehyde2×HCID 68982-Chloro-6-methylphenol

Product 1

HCID 30681252,4-Xylenol, 6-chloro-alpha(sup 4)-(dimethylamino)-Yield 66%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

A solution of 2-chloro-6-methyl phenol (5.0 g, 0.035 mol) in ethanol (25 mL) at room temperature was treated with dimethyl amine (3.95 mL of a 40% solution of dimethylamine in water, 0.035 mol) followed by formaldehyde (2.85 mL of a 37% solution of formaldehyde in water, 0.035 mol). The reaction was heated to reflux for 24 h. At this time, the reaction mixture was cooled to room temperature and concentrated under vacuum. The resulting oil was diluted with water (200 mL) and acidified to pH=2 by addition of a 1N aqueous hydrochloric acid solution. The water layer was extracted with ethyl acetate (300 mL). The ethyl acetate layer was discarded. The water layer was made basic to pH=10 by the addition of a 1N aqueous sodium hydroxide solution and was extracted with ethyl acetate (2×350 mL). The organics were washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting oil was dried under high vacuum overnight to afford 2-chloro-4-dimethylaminomethyl-6-methyl-phenol (2b) (4.62 g, 66%) as an off-white solid; EI(+)-HRMS m/z calcd for C10H14ClNO (M+) 199.0764, found 199.0767. Molecular Weight=199.6822; Exact Mass=199.0764

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 24 h
  3. concentrationconcentrated under vacuum
  4. additionThe resulting oil was diluted with water (200 mL)
  5. additionacidified to pH=2 by addition of a 1N aqueous hydrochloric acid solution
  6. extractionThe water layer was extracted with ethyl acetate (300 mL)
  7. additionThe water layer was made basic to pH=10 by the addition of a 1N aqueous sodium hydroxide solution
  8. extractionwas extracted with ethyl acetate (2×350 mL)
  9. washThe organics were washed with a saturated aqueous sodium chloride solution
  10. dry with materialdried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum
  13. customThe resulting oil was dried under high vacuum overnight

Sources & evidence

ORD record
ord-3eb993bc67e44f0ba2391adc6ab55df6
Source dataset
uspto-grants-2010_10
Patent number
US07807674B2

Reaction notes

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