JPS6328053B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () (In the formula, n is 1 to 4, R represents a hydrogen atom, alkyl, alkoxy, phenoxy, or halogen, and when n is 2 to 4, R may be the same or different. represents alkyl, phenyl or substituted phenyl) by oxidizing a substituted-2-hydroxy aromatic ketone represented by the general formula () (wherein n and R have the same meanings as above) The present invention relates to a method for producing a dihydroxybenzene derivative represented by the following formula. The dihydroxybenzene derivative represented by the above general formula () is itself important as an industrial chemical, and is not only used as various antioxidants and polymerization inhibitors, but is also an important intermediate for pharmaceuticals and agricultural chemicals, and is An object of the invention is to provide a method for producing such dihydroxybenzene derivatives at low cost and with industrial advantage. Such dihydroxybenzene derivatives are usually obtained by reacting a compound having an acetyl group or formyl group at the ortho position of the hydroxyl group on the benzene ring with hydrogen peroxide in the presence of an alkali such as potassium hydroxide. This method has long been known as the Durkin reaction (American Chemical Journal, Vol. 42 (6), No. 477-498).
p. 1903). However, this method is known to be impractical, as the reaction may not proceed depending on the substituents, and even if the reaction does occur, the yield is extremely low. As a way to improve these shortcomings, for example,
(A) Method using tetramethylammonium hydroxide as alkali (Journal of the
Chemical Society. , pp. 1615-1619 1953
(2003), (B) A method of reacting an alkali metal hydroxide with hydrogen peroxide in a mixed solution of a water-soluble organic solvent and water (Japanese Patent Application Laid-Open No. 1983-4128). However, method (A) has a low yield, and
Tetramethylammonium and hydroxide are required in excessive amounts (approximately 3 times the mole), which is not suitable for industrial production, and method (B) uses a water-soluble organic solvent, so Not only separation of products from, but also separation and purification (extraction)
The drawback is that separation and recovery of the solvent used in the process and the water-soluble organic solvent requires a great deal of expense. Furthermore, it has the disadvantage that the waste water load is extremely large, and it cannot necessarily be said to be an industrially advantageous production method. Therefore, the present inventor conducted research to improve the drawbacks of the above method and produce dihydroxybenzene derivatives industrially advantageously. The present inventors have discovered that by using a heterogeneous solvent system of a solvent and water and a catalyst, it is possible to obtain the desired product with high selectivity in an industrially advantageous manner, leading to the completion of the present invention. That is, the present invention involves the treatment of substituted-2-hydroxy aromatic ketones represented by the general formula () with hydrogen peroxide and an alkali in the presence of a catalyst in a heterogeneous solvent system of a water-insoluble organic solvent and water. This is a method for producing a dihydroxybenzene derivative represented by the general formula (), which is characterized by carrying out a reaction. The present invention will be explained in detail below. The reaction is usually carried out by dissolving the substituted-2-hydroxyaromatic ketones and the catalyst in a heterogeneous solvent of water and a water-insoluble organic solvent, to which hydrogen peroxide and an alkali are added. . In the substituted 2-hydroxy aromatic ketones used in the present invention, n is 1, 2, 3 or 4 in the general formula (), R is a hydrogen atom, and the alkyl group is, for example, methyl, Examples include ethyl, isopropyl, n-propyl, t-butyl, n-butyl, n-octyl, etc., and examples of alkoxy groups include methoxy, ethoxy,
Examples of the halogen atom include propoxy, butoxy, octyloxy, and the like, and examples of the halogen atom include fluoro, chloro, and brome. As A, examples of the alkyl group include methyl, ethyl, propyl,
Examples include isopropyl, butyl, t-butyl, octyl, etc., and examples of substituted phenyl include phenyl groups substituted with alkyl, alkoxy, phenoxy, halogen, amino groups, etc. in this case,
When n is 2 to 4, R may be different from each other. The reaction solvent is not particularly limited as long as it is insoluble in water, but it is advantageous from the viewpoint of the reaction to dissolve the substituted 2-hydroxy aromatic ketones as raw materials, and it is more preferable to dissolve the product dihydroxybenzene derivative. It is preferable to extract and dissolve at the end of the reaction, such as benzene,
Toluene, xylene, hexane, petroleum benzine,
Aromatic or aliphatic hydrocarbons such as chlorobenzene, dichlorobenzene, chloroform dichloromethane, carbon tetrachloride, ethyl ether, isopropyl ether, methyl-n-propyl ketone, methyl isobutyl ketone, amyl alcohol, isoamyl alcohol, halogenated carbons A solvent insoluble in water and inert to the reaction, such as hydrogen, ether, ketone, or alcohol, may be used alone or in a mixture. In this reaction, the amount of alkali used is usually preferably in the range of 1 to 2.5 mol per mol of the substituted 2-hydroxy aromatic ketone as a raw material, but 2.5 mol or more is also applicable. Further, hydrogen peroxide is preferably in the range of 1 to 2.5 moles, but 2.5 moles or more is also applicable. Examples of the alkali include alkali metal hydroxides, alkali metal carbonates, and alkaline earth metal hydroxides. In this reaction, for example, various surfactants such as organic quaternary ammonium salts, phosphonium salts, alkylbenzene sulfonates, tertiary amines or pyridines are used as catalysts. Specific examples of these include the following. (Organic quaternary ammonium salts) Tetraethylammonium chloride (or bromide or hydroxide) Tetrabutylammonium chloride (or bromide or hydroxide) Benzyltrimethylammonium chloride (or bromide or hydroxide) Benzyltriethylammonium chloride (or bromide or hydroxide) ) Tricaprylmethylammonium chloride (or bromide or hydroxide) Capryltrimethylammonium chloride (or bromide or hydroxide) Dodecyltrimethylammonium chloride (or bromide or hydroxide) Cetyltrimethylammonium chloride (or bromide or hydroxide) Caprylic benzyldimethylammonium Chloride (or bromide or hydroxide) Dodecylbenzyldimethylammonium chloride (or bromide or hydroxide) (phosphonium salts) Tetraphenylphosphonium chloride (or bromide) Tetrabutylphosphonium chloride (or bromide) Tricaprylethylphosphonium chloride (or bromide) Cetyltriethylphosphonium chloride (or bromide) (tertiary amine) Trimethylamine, triethylamine, tributylamine (pyridines) Pyridine, α-, β, - or γ-picoline,
2,4-lutidine, 2,6-lutidine (alkylbenzenesulfonate) Sodium caprylbenzenesulfonate (or potassium or ammonium) Sodium dodecylbenzenesulfonate (or potassium or ammonium) Sodium cetylbenzenesulfonate (or potassium or ammonium) (Other various surfactants) Higher fatty acid salts, alkylnaphthalene sulfonates, polyoxyethylene alkylethyl, polyoxyethylene alkyl phenol ethers, polyoxyethylene fatty acid esters, higher aliphatic alcohols These can be used alone or in mixtures. .
The amount of the catalyst to be used is arbitrary within the range of 1/200 to 2 times the weight of the substituted 2-hydroxy aromatic ketone as the raw material, but is generally 1/100 to the same weight. The catalyst used here can be recovered and reused after the reaction is completed. The reaction temperature is preferably in the range of -5 to 60°C, but temperatures outside these ranges are also applicable. Extraction from the reaction mixture thus obtained,
The target dihydroxybenzene derivative can be extracted by known methods such as separation, concentration, distillation, and crystallization. The present invention will be explained below with reference to Examples. Example 1 In a four-neck flask equipped with a stirrer, a thermometer, and a nitrogen blowing tube, 15 g (0.1 mol) of 2-hydroxy-5-methylacetetophenone, 0.7 g of tetrabutylammonium hydroxide, 3 g of pyridine,
Add 30 ml of methyl isobutyl ketone and 45 ml of water, and add 6.8 g (0.12 mol) of 60% hydrogen peroxide at 0-10° C. while blowing nitrogen. Further, 13.7 g (0.12 mol) of a 35% aqueous solution of caustic soda was added dropwise at the same temperature. After the completion of dropping, keep at the same temperature for 3 hours. After the reaction is complete, add dilute hydrochloric acid to make it weakly acidic. The organic layer is separated, and the aqueous layer is extracted twice with 15 ml of methyl isobutyl ketone, and the methyl isobutyl ketone is distilled off from the resulting organic layer to obtain 4-methylhydroxybenzene with a conversion rate of 100% and selectivity.
Obtained with a yield of 97%. Tetrabutylammonium hydroxide and pyridine can be recovered by making the aqueous layer strongly alkaline with caustic soda and extracting it twice with 15 ml of methyl isobutyl ketone. Example 2 When the reaction was carried out in the same manner as in Example 1 except that pyridine was not used in Example 1, 4-methyl-dihydroxybenzene was obtained at a conversion rate of 83% and a selectivity of 93%. Examples 3 to 8 Comparative Examples In Example 1, the reaction conditions and reaction scale were the same, and the other conditions were as shown in Table 1. The results shown in Table 1 were obtained.

[Table] Example 9 60% hydrogen peroxide 12.4g (0.22mole), 35%
The reaction was carried out in the same manner as in Example 2 except that 25 g (0.22 mole) of NaOH was used and toluene was used instead of methyl isobutyl ketone, and the conversion rate of 4-methyldihydroxybenzene was 98% and the selectivity was 92%.
It came out. Examples 10 to 13 In Example 1, substitution-2 shown in Table 2 was substituted for 2-hydroxy-5-methylacetophenone.
The reaction was carried out under the same conditions as in Example 1 except that -hydroxy aromatic ketone was used, and the results shown in Table 2 were obtained.

[Table] Example 14 Example 8 except that 1 g of sodium dodecylbenzenesulfonate was used in place of Emulgen 903.
React and post-process in the same manner as 4-methyl-1,
2-dihydroxybenzene conversion rate 80%, selectivity
Got it with 91%. Example 15 The reaction was carried out in the same manner as in Example 14, except that 2-hydroxy-5-phenoxyacetophenone was used instead of 2-hydroxy-5-methylacetophenone.
After post-treatment, 4-phenoxy-1,2-dihydroxybenzene was obtained with a conversion rate of 79% and a selectivity of 90%. Example 16 Reaction and post-treatment were carried out in the same manner as in Example 15, except that 2-hydroxyacetophenone was used instead of 2-hydroxy-5-phenoxyacetophenone, and 6 g of trimethylamine was used instead of sodium dodecylbenzenesulfonate. The conversion rate was 92% and the selectivity was 95.
% of 1,2-dihydroxybenzene was obtained.

Claims (1)

[Claims] 1. General formula (In the formula, n is 1 to 4, R represents a hydrogen atom, a halogen atom, an alkyl, an alkoxy, or a phenoxy group, and when n is 2 to 4, R may be the same or different. In addition, A represents alkyl, phenyl, or substituted phenyl. A general formula characterized by the reaction of hydrogen and alkali (In the formula, n and R have the same meanings as above.) A method for producing a dihydroxybenzene derivative represented by the following.