4-Hydroxybenzaldehyde → p-(Difluoromethoxy)benzaldehyde

HRID 1701141Notes

Reaction equation

HRID 1701141 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1.Cl[CH:13]([F:15])[F:14]>O1CCOCC1.O>[F:14][CH:13]([F:15])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 6372Chlorodifluoromethane3×HCID 14798Sodium Hydroxide3×

Product 1

HCID 2736986p-(Difluoromethoxy)benzaldehydeYield 59.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Sodium hydroxide (48 g; 1.2 mole) is added to a stirred suspension of p-hydroxybenzaldehyde (48.9 g; 0.4 mole) in dioxane (142 ml) and water (87 ml). The mixture is heated to 70° C. and chlorodifluoromethane (33 g) added slowly. When this addition is completed, 50% sodium hydroxide solution (32 ml) is added to the reaction mixture, followed by the slow addition of chlorodifluoromethane (33 g). This recharging is repeated three times, and a total of 96 g (2.4 mole) of sodium hydroxide and 133 g (1.54 mole) of (1.54 mole) of chlorodifluoromethane is used in the reaction. The reaction mixture is cooled down, diluted with water (1500 ml) and extracted with ether several times. The ether layers are combined, washed with 10% sodium hydroxide and then dried over magnesium sulfate. Concentration of the ethereal solution yields 39 g (57%) of a yellow oil. This oil is purified by chromatography on a silica gel column using a mixture of hexane:methylene chloride (1:3), to afford 27 g (39%) of title product.

Workup

  1. additionWhen this addition
  2. temperatureThe reaction mixture is cooled down
  3. extractionextracted with ether several times
  4. washwashed with 10% sodium hydroxide
  5. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-0e297ddeaf134399ae50ae6fb1301aef
Source dataset
uspto-grants-1980_03
Patent number
US04191768

Reaction notes

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