Methanol → (4-(4-Chlorophenoxy)phenyl)(methyl)sulfane

Participants

Reaction Conditions

Reaction Steps

4-(4′-Chlorophenoxy)phenyl sulfonyl chloride (3.0 kg), 3, was dissolved in three liters of toluene and the solution was added dropwise, with stirring, to 3.6 kg of trimethyl phosphite which had been preheated to 60° C. The reaction was exothermic and the reaction was allowed to heat to 80°-90° C. during the addition. Thin layer chromatography indicated a mixture of the desired thioether and two baseline products. The mixture was refluxed until the pot temperature rose to ˜130° C. The mixture was cooled to ˜60° C. and 1 liter of methanol was added. Potassium hydroxide solution (4.5 kg of 45% aqueous solution) was added dropwise, slowly, with rapid stirring to the reaction mixture. The addition was very exothermic and the pot temperature was controlled to 65°-80° C. The mixture was then refluxed for 2 hrs. More toluene (6 liters) was added and the mixture cooled to ˜60° C. The lower aqueous layer was separated and the organic layer washed with 3 liters of water. The organic layer was stripped to a low volume and 9 liters of isopropanol charged to the hot mixture. The solution was distilled until ˜3.5 liters of distillate had been collected. The mixture was held at 45° C. for several hours and was then cooled to ˜−10° C. and stirred several hours. The white, crystalline product was collected, washed with cold isopropanol and dried to yield 1.9 kg of 4-(4′-chlorophenoxy)phenyl methyl sulfide, 4.

Provenance & Evidence