JP4359641B2 - Production method of dialkylbisphenols - Google Patents

Description

  The present invention relates to a process for producing dialkylbisphenols, and more specifically, the following formula (2)

(Wherein R represents a C1 to C8 linear or branched alkyl or alkenyl group)
P-alkylphenol represented by the following formula (1), which is subjected to an oxidative coupling reaction in an organic solvent in the presence of a copper salt-amine compound complex:

(Wherein R is as defined above)
It relates to the manufacturing method of dialkyl bisphenol represented by these.

  Dialkyl bisphenols are useful as antibacterial and antioxidant compounds. For example, 2,2'-dihydroxy-5,5'-dipropylbiphenyl is synthesized by reducing magnolol isolated from Kokaku. (Non-Patent Document 1). Several production methods by oxidative coupling have been reported, but reactions with substrates having no substituent at the ortho-position generally have low coupling yield and regioselectivity. As one of highly selective production methods, for example, a method of reacting an alkylphenol in a chloroform solvent in the presence of aluminum chloride and ferric chloride (Non-Patent Document 2) has been proposed.

  However, the production method of dialkyl bisphenols shown in the above prior art uses expensive raw materials extracted and isolated from crude drugs by a complicated method as raw materials, or a highly corrosive reagent that requires careful handling, It uses a toxic solvent that is a concern for environmental pollution, and has disadvantages such as a low yield.

  As a production method capable of solving these problems, a method of oxidative coupling reaction of 2-naphthol in the presence of a copper salt-amine compound complex (Non-patent Document 3) has been proposed. The only substrate that has been described is 2-naphthol, and no p-alkylphenol is described.

Herbal medicine magazine, 39 (1), 76-79, 1985 Tetrahedron, 48 (43), 9483-9494, 1992 Tetrahedron, 41, 3313, 1985

  An object of the present invention is to provide a method for producing dialkylbisphenols in a good yield and a simple method using inexpensive raw materials.

  Therefore, as a result of intensive studies on a novel synthesis method in order to solve the above problems, the present inventors have found that a p-alkylphenol represented by the above formula (2) is a copper salt-amine compound in an organic solvent. It was found that dialkyl bisphenols represented by the above formula (1) can be obtained in good yield by selectively proceeding with the oxidative coupling reaction to form a complex with the present invention.

  Accordingly, the present invention provides a p-alkylphenol represented by the above formula (2) (wherein R represents a C1 to C8 linear or branched alkyl or alkenyl group) in an organic solvent, a copper salt-amine compound. An object of the present invention is to provide a process for producing dialkylbisphenols represented by the above formula (1) (wherein R is as defined above), wherein an oxidative coupling reaction is carried out in the presence of a complex.

BEST MODE FOR CARRYING OUT THE INVENTION

  The dialkylbisphenols of the above formula (1) of the present invention can be easily obtained by subjecting the p-alkylphenol of the formula (2) to an oxidative coupling reaction in an organic solvent in the presence of a copper salt-amine compound complex. It can be produced in good yield.

  The p-alkylphenols represented by the above formula (2) used in the reaction can be easily obtained on the market. For example, it can be easily obtained by reacting the corresponding acylphenol with hydrogen in the presence of a palladium catalyst. They can also be synthesized (J. Am. Chem. Soc., 56 (1), 158-159, 1934). This reaction is represented by the following reaction formula.

  Specific examples of p-alkylphenols include, for example, p-methylphenol, p-ethylphenol, p-propylphenol, p-isopropylphenol, p-butylphenol, p-isobutylphenol, p-pentylphenol, p-isopentyl. Phenol, p-hexylphenol, p-allylphenol, p-isopropenylphenol, p-2-ethylhexylphenol and the like can be mentioned.

  Moreover, the copper salt and amine compound used by this invention are also easily available on the market. Specific examples of the copper salt include cuprous chloride, cupric chloride, cupric sulfate, and cupric nitrate. These copper salts can be used in the form of anhydrides or hydrates, but hydrates are preferred because they are easier to handle. Although it does not specifically limit as an amine compound, For example, a C2-C7 linear or branched alkylamine, cyclic alkylamines, and aromatic amines are preferable, As an example, ethylamine, propylamine, Examples include isopropylamine, butylamine, isobutylamine, t-butylamine, isoamylamine, hexylamine, cyclohexylamine, aniline, benzylamine, and pyridine. In the present invention, an organic solvent is used for the reaction, but the type of the organic solvent is not particularly limited, and it is preferable that the formed copper salt-amine compound complex is easily dissolved or dispersed. Examples of the organic solvent in which the formed copper salt-amine compound complex is easily dissolved or dispersed include alcohols, and preferred examples include lower alcohols such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol. .

  The amount of these raw materials used can be appropriately selected, and the copper salt is about 0.8 to 2.0 moles, more preferably 0.9 to 1.5 moles relative to the raw material compound of formula (2) About twice the amount, the amine compound is about 1.6 to 3.0 mole times, more preferably about 1.8 to 2.5 mole times, and the organic solvent is, for example, about 3 to 20 times by weight, more preferably Can be exemplified by about 4 to 10 times by weight.

  The reaction is usually performed by adding a copper salt and an amine compound to an organic solvent and stirring at a temperature of 10 ° C. to 50 ° C. for 10 to 60 minutes to form a copper salt-amine compound complex, followed by a temperature of 10 ° C. to 80 ° C. P-alkylphenol can be added and stirred for 3 to 24 hours. In addition, since reaction is accelerated | stimulated by presence of oxygen, it is preferable to carry out, introducing air in a reaction liquid mixture.

  After completion of the reaction, the desired product can be obtained by a conventional method. For example, after cooling the reaction mixture to room temperature or lower, the insoluble part is collected by filtration, and the insoluble part is dissolved in an extraction solvent such as ethyl ether or ethyl acetate and then sufficiently washed with water. Dialkyl bisphenols can be obtained with good yield. If necessary, a very high-purity target product can be obtained by recrystallization in a hydrocarbon solvent such as hexane, cyclohexane or toluene.

  Specific examples of the dialkylbisphenols of the above formula (1) obtained by the production method of the present invention include, for example, 2,2′-dihydroxy-5,5′-dimethylbiphenyl, 2,2′-dihydroxy-5,5. '-Diethylbiphenyl, 2,2'-dihydroxy-5,5'-dipropylbiphenyl, 2,2'-dihydroxy-5,5'-diisopropylbiphenyl, 2,2'-dihydroxy-5,5'-dibutylbiphenyl 2,2′-dihydroxy-5,5′-diisobutylbiphenyl, 2,2′-dihydroxy-5,5′-dipentylbiphenyl, 2,2′-dihydroxy-5,5′-diisopentylbiphenyl, 2, 2'-dihydroxy-5,5'-dihexylbiphenyl, 2,2'-dihydroxy-5,5'-diallylbiphenyl, 2,2 - dihydroxy-5,5'-di-isopropenyl biphenyl, 2,2'-dihydroxy-5,5'-di - (2-ethylhexyl) and the like can be exemplified biphenyl.

  Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1
In a 2000 ml four-necked flask, 102 g of cupric chloride dihydrate and 600 g of methanol were added, 142 g of cyclohexylamine was added, and the mixture was stirred at 20-30 ° C. for 40 minutes. A solution obtained by dissolving 82 g of p-propylphenol in 200 g of methanol was added to this mixed solution, air was bubbled into the mixed solution of the flask (500 mL / min), and the mixture was vigorously stirred at 20 to 30 ° C. for 4 hours to be reacted. . After completion of the reaction, the reaction solution was filtered to remove insoluble matters, which were rinsed three times with 360 g of ethyl acetate. The washed insoluble material was put into a 3 L flask, 625 g of 2M hydrochloric acid and 902 g of ethyl acetate were added, and the mixture was stirred at room temperature for 30 minutes, and then the organic layer was separated. The organic layer was washed with 625 g of 1M hydrochloric acid and then washed twice with 400 g of water. The organic layer was heated under normal pressure to recover ethyl acetate. To this was added 328 g of toluene and the mixture was heated and stirred to reflux to completely dissolve the solid matter, and then cooled to 0 ° C. to precipitate crystals. The precipitated crystals were filtered and dried under reduced pressure to obtain 2,2′-dihydroxy-5,5′-dipropylbiphenyl (yield 80%) having a purity of 98% by HPLC method.

Examples 2-5
In Example 1, 2,2′-hydroxy-5,5′-dipropylbiphenyl was synthesized by reacting in the same manner using other amines and copper salts in place of cyclohexylamine and cupric chloride. The results are shown in Table 1.

Examples 6-12
In Example 1, 2,2′-dihydroxy-5,5′-dialkylbiphenyls were synthesized by performing the same reaction and post-treatment using other p-alkylphenols instead of p-propylphenol. The results are shown in Table 2.

[The invention's effect]
INDUSTRIAL APPLICABILITY According to the present invention, useful dialkyl bisphenols are extremely useful because they can be produced in a good yield and with a simpler method using inexpensive raw materials.

Claims (1)

Following formula (2)

(Wherein R represents a C1 to C8 linear or branched alkyl or alkenyl group)
P-alkylphenol represented by the following formula (1), which is subjected to an oxidative coupling reaction in an organic solvent in the presence of a cupric chloride-cyclohexylamine complex:

(Wherein R is as defined above)
The manufacturing method of dialkyl bisphenol represented by these.