CS246718B1 - Process for preparing 4-benzyloxy-4--hydroxydiphenylsulfone - Google Patents

Abstract

4-Benzyloxy-4'-hydroxydiphenylsulfone is prepared by benzylation of 4,4'-dihydroxydiphenylsulfone with benzyl chloride using sodium ethanolate or methanolate in ethanol or methanol solution or using potassium hydroxide in methanol or using aqueous potassium or sodium hydroxide solution. The resulting mixture of monobenzylated or dibenzylated 4,4- -dihydroxydiphenylsulfone, or a mixture of monobenzylated and unreacted sulfone, is separated based on the different solubility of the sulfones in the solvents.

Description

The present invention provides a process for the preparation of 4-benzyloxy-4‘-hydroxydiphenylsulfone by benzylation of 4,4‘-dihydroxydiphenylsulfone with benzylaochloride and a process for its isolation from the reaction mixture.

Although 4-benzyloxy-4'-hydroxydiphenylsulfone is used as an intermediate in the preparation of a number of yellow, two-equivalent components of different types (NSR 2 841 835, 2 915 025, 1928 554, French Pat. 2 010 661), it does not do so; the preparation described in the available patent or scientific literature. Benzylation of phenols is generally carried out by the Williams reaction, benzylation with benzyl bromide or benzyl chloride in an alkaline medium (Organic Synthesis 25 September 1945).

The above-mentioned drawbacks have no process for the preparation of 4-benzyloxy-4'-hydroxydiphenylsulfone by benzylation of 4,4'-dihydroxydiphenylsulfone with benzyl chloride according to the invention, characterized in that the benzylation is carried out with sodium ethanolate in ethanol or potassium hydroxide in methanol or potassium or sodium hydroxide in sodium. water at 80 to 100 ° C and the isolation of 4-benzyloxy-4'-hydroxydiphenylsulfone from a mixture of mono- and dibenzylated 4,4'-dihydroxydiphenylsulfone is carried out based on the different solubility of the monobenzylated and dibenzylated derivative in ethanol, methanol or acetonitrile and isolation of 4- benzyloxy-4'-hydroxydiphenylsulfone from a mixture of monobenzylated and non-benzylated 4,4'-dihydroxydiphenylsulfone is carried out by washing unreacted 4,4'-dihydroxydiphenylsulfone with hot water.

4-Benzyloxy-4‘-hydroxydiphenylsulfone is prepared by treatment of benzyl chloride with the monosodium salt of 4,4‘-dihydroxydiphenylsulfone (I) ·

The preparation of 4,4'-dihydroxydiphenylsulfone disodium salt I was carried out either by treatment of 4,4‘-dihydroxydiphenylsulfone with sodium ethoxide in anhydrous ethanol or with potassium hydroxide in ethanol, methanol or water. To the alkaline solutions 4,4‘-dihydroxydiphenylsulfone is added either directly or dissolved in ethanol or methanol, or by evaporation of the solvent (ethanol, methanol) in dimethylsulfoxide. After stirring or heating briefly, benzyl chloride, either alone or dissolved in methanol, ethanol or dimethylsulfoxide, is added dropwise to the solution of sodium 4,4‘-dihydroxydiphenylsulfone I. The use of sodium ethanolate or methoxide in ethanol, methanol or dimethylsulfoxide solution or potassium hydroxide solution in methanol always results in a mixture of monobenzylated and dibenzylated 4,4'-dihydroxydiphenylsulfone II and III, when an aqueous potassium hydroxide solution is used a mixture of monobenzylated sulfone II and As a result, the separation of the resulting sulfone mixture resulting in 4'-benzyloxy-4'-hydroxydiphenylsulfone II of the desired purity is important. In the case of a mixture of monobenzylated and dibenzylated sulfone II and ΠΙ, the two products are separated on the basis of their substantially different solubilities in ethanol, methanol or acetonitrile. While the monobenzylated sulfone II is well soluble in methanol, ethanol and acetonitrile, the dibenzylated sulfone III is practically insoluble in these solvents. Thus, the reaction mixture is cooled and acidified, the precipitated dibenzylated dihydroxydiphenylsulfone III derivative is filtered off with suction and 4-benzyloxy-4'-hydroxydiphenylsulfone II is precipitated from the filtrate on ice. If the reaction is carried out in an aqueous-alkaline medium, unreacted 4,4'-dihydroxydiphenylsulfone I is present in the reaction mixture in addition to monobenzylated sulfone II, and therefore the acidified reaction mixture or the final product must be boiled with water to thereby 4,4'-dihydroxydiphenylsulfone. It is taken up in solution and removed by filtration. After cooling, the unreacted 4,4‘-dihydroxydiphenylsulfone is recovered from the aqueous solution and can be used again for benzylation.

Analytical determination of the individual sulfone derivatives is performed by chromatography on a silica gel layer mounted on an aluminum support using a 5: 1 benzenethyl acetate solution. Detection is by spraying an alkaline solution of the diazonium salt.

Example 1

1.4 g of sodium (0.06 mol) was dissolved in 400 ml of ethanol, and 15 g (0.06 mol) of 4,4'-dihydroxydiphenylsulfone dissolved in 20 ml of ethanol was added thereto, after heating for 30 minutes, the solution was added dropwise. 7.6 ml (8.4 g; 0.06 mol) of benzyl chloride in 5 ml of ethanol, the solution was heated to boiling for eight hours, after which the suspension was cooled, acidified with concentrated hydrochloric acid to congo and the dibenzylhydroxyphenylsulfone III precipitated. 165 DEG-168 DEG C., 4-benzyloxy-4 ' -hydroxydiphenylsulfone, was precipitated from the filtrate with an ice yield of 15.8 g (75% of theory) and chromatographed with traces of the dibenzyl derivative.

Example 2

1.4 g of sodium (0.06 mol) was dissolved in 440 ml of ethanol and 15 g of 4,4‘-dihydroxy-diphenylsulfone were introduced into the ethanolate solution. After boiling for one hour, the ethanol was completely evaporated and 50 ml of dimethylsulfoxide was added to the dry residue, and after the sodium dihydroxydiphenylsulfone was dissolved, 7.6 ml (0.06 mol) of benzyl chloride was added dropwise to the reaction solution. After heating at 80 ° C for six hours, the solution was poured on ice and the precipitated product was aspirated. After drying, the reaction product was stirred with 400 ml of hot ethanol and after cooling, the filtrate was separated by dibenzylated sulfone. From the ethanolic filtrate, 4-benzyloxy-4'-hydroxydiphenylsulfone was ice-precipitated. Melting point: 166 DEG-168 DEG C., yield: 14.8 g (70% of theory).

Example 3

3.4 g of potassium hydroxide (0.06 mol) was dissolved in 250 ml of methanol and 15 g of 4,4‘-dihydroxydiphenylsulfone were introduced into the solution. A solution of 7.6 ml (0.06 mol) of benzyl chloride in 20 ml of methanol was added dropwise to the boiling solution. After heating for 6 hours, the reaction was complete and the resulting product was obtained in the same manner as in Example 2, with the same yield.

Example 4 g of potassium hydroxide (0.07 mol) was dissolved in 850 ml of distilled water, and 12.5 g (0.05 mol) of 4,4‘-dihydroxydiphenylsulfone was added to the solution. After dissolution, 12.4 g (11.2 mL) of benzyl chloride was added to the solution, and the suspension was stirred at 20 ° C for six hours. The reaction was terminated by boiling for 1 hour. After cooling, the solution was acidified with concentrated hydrochloric acid and the precipitated product was filtered off with suction. M.p. 150-160 ° C. The precipitated product was stirred with hot water, the insoluble matter was filtered off with suction, and the filter was washed again with hot water. Chromatographically pure 4-benzyloxy-4‘-hydroxydibenzylsulfone was obtained in a yield of 16.5 g (94%).

Claims (1)

A process for preparing 4-benzyloxy-4‘-hydroxydiphenylsulfone of formula II - ( ₂ ) - ( _2- ) benzylation of 4,4'-dihydroxydiphenylsulfone of formula I (1) ynAlez with benzyl chloride, characterized in that the benzylation is carried out with sodium ethanolate in ethanol or potassium hydroxide in methanol or potassium hydroxide, or sodium in water at 80 to 100 ° C and the isolation of 4-benzyloxy-4'-hydroxydiphenylsulfone II from the mixture of mono- and dibenzylated 4,4'-dihydroxydiphenylsulfone is performed based on the different solubility of the monobenzylated and dibenzylated derivative in ethanol, methanol or acetonitrile; isolation of 4-benzyloxy-4'-hydroxydiphenylsulfone II from a mixture of monobenzylated and non-benzylated 4,4'-dihydroxydiphenylsulfone is carried out by washing unreacted 4,4'-dihydroxydiphenylsulfone with hot water.