JP2002069022A - Method for producing oxidative coupling reactant of phenolic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially useful method for producing 2,2'- dihydroxybiphenyls from a phenolic compound in high selectivity and yield. SOLUTION: In this method for producing an oxidative coupling reactant by oxidative coupling reaction of the phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst, the above reaction is carried out by batchwise method and oxidative reaction is advanced while regulating the oxygen concentration in reaction solution to <=33 mg/L until conversion of the phenolic compound which is a raw material attains 70% after starting the reaction or the reaction is carried out by a continuous communication system and oxidative coupling reaction is advanced while regulating the oxygen concentration of the reaction solution in a stationary state of the reaction to <=33 mg/L.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an oxidative coupling reactant generated by an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst. More specifically, the present invention relates to a method for producing an oxidative coupling reactant with high selectivity by performing an oxidative coupling reaction of a phenolic compound under controlled oxygen concentration.

[0002]

2. Description of the Related Art 2,2'-Dihydroxybiphenyl and its derivatives, or 2,2'-dihydroxy-1,1'-
Binaphthyl and its derivatives are used for various purposes.For example, they are used as a raw material for stabilizers of organic compounds and polymers, and as a part of a skeleton of a ligand of a transition metal complex used for a catalytic reaction. ing. In particular, 6,6 '
Those having axial asymmetry, such as disubstituted-2,2'-dihydroxybiphenyl derivatives and 2,2'-dihydroxy-1,1'-binaphthyl derivatives, are subjected to optical resolution to form a coordination catalyst for asymmetric catalysts. Often used as part of a skeleton as a child. Such biphenols are synthesized by subjecting a corresponding phenolic compound to an oxidative coupling reaction, and many methods using inexpensive air or oxygen as an oxidizing agent during the reaction have been known for a long time. Catalysts for accelerating the reaction include stoichiometric or more basic compounds such as sodium hydroxide and barium hydroxide, as well as iron,
Transition metal complexes such as copper and vanadium are used. Although the detailed reaction mechanism of each reaction has not been completely elucidated, a reaction mechanism via a phenoxy radical species has been proposed in many cases.

As a catalyst for industrial synthesis of biphenols, it is generally more advantageous to use a small amount of a transition metal complex as a catalyst than to use a stoichiometric amount of a base in terms of catalyst cost. Among complex catalysts,
In particular, copper-amine based catalysts are excellent in activity and have been studied in depth. For example, J. Org. Chem., 1983, 48, 4948
As described in J. Org. Chem., 1984, 49, 4456, phenol can be obtained by bubbling oxygen in methanol in the presence of a catalyst comprising cupric chloride and an ethylenediamine substituted with an alkyl group. 2,
A method for synthesizing 2'-dihydroxybiphenyls is known. However, according to this method, the produced 2,2'-dihydroxybiphenyl is 5 at the beginning of the reaction.
Although it shows a selectivity of 4-66%, it undergoes a further secondary oxidation reaction over time to be converted into benzofurans and dioxepins, so that the final 2,2
The selectivity of 2'-dihydroxybiphenyls is several percent. This is because oxygen is bubbled without paying special attention at a dilute catalyst concentration of about 0.001 mol / L,
The oxygen concentration in the reaction solution is expected to be a high concentration close to the saturation concentration in the reaction solvent, and it is presumed that further secondary oxidation reaction has proceeded.

Further, Tetrahedron Letters, 1983, 24, 5
611 contains Cu in acetonitrile_FourCl _FourO_Two(CH_ThreeCN)_ThreeAs
Oxidation of Phenolic Compounds Using a Novel Cluster Catalyst
Although the coupling reaction has been reported,
Reaction, the oxygen concentration in the solution is estimated to be low
Highly at least 50% of the saturation concentration in the reaction solvent
As a result, the yield remains at about 60%. This
On the other hand, in the method described in WO 99/46227,
Ethylenediamine substituted with cuprous chloride and alkyl group
1,2-dichlorobenzene in the presence of a catalyst consisting of
By bubbling air through a particular solvent
Phenolic compound with high selectivity and yield of around 90%
Of 2,2'-dihydroxybiphenyls from products
A method is disclosed. The oxygen concentration in the solution in this case is
Since the air is bubbled, when pure oxygen is used
At most about 20% compared to the saturated oxygen concentration in the reaction solvent
It is only a rare catalyst concentration of about 0.005mol / L
, The oxygen concentration is relatively easy to rise
It is expected that the reaction is progressing in the state.

In the above method, the reaction is carried out in a specific solvent such as 1,2-dichlorobenzene. However, the solvent having a high boiling point (180 ° C.) is distilled off to produce 2,2 ′ produced.
The removal of dihydroxybiphenyls is too time and energy consuming to be economically feasible in industrial scale synthesis. Rather, it is more economical to react in a poor solvent for the desired 2,2'-dihydroxybiphenyl such as methanol, remove the precipitated target substance by filtration, and wash or recrystallize. Methanol is also cheaper. It is not preferable to use a large amount of an organic halide such as dichlorobenzene as a solvent from the viewpoint of environmental protection. Thus, using a specific solvent,
Although a method for improving the selectivity of 2'-dihydroxybiphenyls has been proposed, the relationship between the oxygen concentration in the reaction solution and the selectivity of 2,2'-dihydroxybiphenyl as the target product has been proposed. Did not receive any attention, and the oxygen concentration was rather focused only on the subject of kinetic studies.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrially useful method for producing 2,2'-dihydroxybiphenyls from phenolic compounds with high selectivity and yield. As an industrial production method, it is natural that the target product is efficiently synthesized with a high selectivity and a high yield, but in addition, the cost of the raw materials such as reagents and solvents, the energy cost, the production time, etc. are also taken into consideration. It is important that the manufacturing cost of the product is low and that the method has a small influence on the environment. The present invention solves these problems, and furthermore, proposes a new method which enables production of 2,2'-dihydroxybiphenyls with high selectivity by a simple method.

[0007]

Means for Solving the Problems The present inventors have proposed 2,2 '
-Details of a method for producing 2,2'-dihydroxybiphenyls by an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst with the aim of developing a method for improving the selectivity of dihydroxybiphenyls As a result of intensive studies, there is a correlation between the oxygen concentration in the oxidative coupling reaction solution and the selectivity of the target product, and the reaction is controlled while controlling the oxygen concentration in the reaction solution at a low concentration depending on the degree of the reaction. The present inventors have found that by proceeding, the selectivity to the target substance is enhanced, and arrived at the present invention.

That is, the gist of the present invention is that in the production of an oxidative coupling reactant by an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst, the reaction is carried out by a batch method and the reaction is started. Thereafter, until the conversion of the phenolic compound as a raw material reaches 70%, the oxidative coupling reaction proceeds while maintaining the oxygen concentration in the reaction solution at 33 mg / L or less. In the method for producing the oxidative coupling reactant.

Another aspect of the present invention is to provide an oxidative coupling reactant by an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst. Wherein the oxidative coupling reaction proceeds while maintaining the oxygen concentration in the reaction solution in the steady state at 33 mg / L or less.

In a preferred embodiment of the present invention, in the method for producing an oxidative coupling reactant of a phenolic compound, the phenolic compound has one hydroxyl group bonded to an aromatic ring having aromaticity, and Having a structure having a hydrogen atom in at least one of the para position and the two ortho positions of the hydroxyl group; the catalyst comprises a transition metal compound, particularly a transition metal compound of the first transition cycle, preferably copper. Or a catalyst system comprising copper and an amine compound, such as a catalyst system comprising a copper halide and ethylenediamine or an ethylenediamine derivative wherein at least one hydrogen atom of the amino group of ethylenediamine is substituted by an alkyl group. Some things can be mentioned.

According to another preferred embodiment of the present invention, in the method for producing an oxidative coupling reactant of a phenolic compound, the phenolic compound has a structure represented by the general formula (1); The reactant has a structure represented by the general formula (2). Further, in a methanol solvent, in the presence of a catalyst system composed of cupric chloride and tetramethylethylenediamine, the reactant has a structure represented by the general formula (1) In the formula, R ¹ and R ³ in the formula are an alkyl group or an alkoxy group having 1 to 7 carbon atoms, R ² is a hydrogen atom, R ⁴ is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or A phenolic compound which is a halogen atom, which is subjected to an oxidative coupling reaction to produce a 2,2'-dihydroxybiphenyl derivative represented by the general formula (2) corresponding to the compound; And a method for producing an oxidative coupling reactant of a reactive compound.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The present invention provides an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst,
In the production of 2'-dihydroxybiphenyls, the reaction proceeds while controlling the oxygen concentration in the reaction solution to a low concentration, so that the target 2,2'-dihydroxybiphenyls can be efficiently produced with high selectivity and yield. It is a good manufacturing method.
This method is based on a new viewpoint that suppresses a very unstable chemical species called a phenoxy radical species from undergoing a side reaction by a reactive oxygen molecule. It can be expected to be widely applied to various catalyst systems which are thought to promote the oxidative coupling reaction via the catalyst.

In the method of the present invention, the oxygen concentration in the reaction solution is controlled to a predetermined low concentration. However, when the reaction is carried out by a batch method, the conversion of the phenolic compound as a raw material is reduced to 70% after the start of the reaction. Until the oxygen concentration in the reaction solution reaches 3
It is necessary to keep the concentration at 3 mg / L or less, and when the reaction is performed in a continuous flow system, it is necessary to keep the oxygen concentration in the reaction solution in the steady state of the reaction at 33 mg / L or less. If the concentration is higher than this concentration, the selectivity and yield of the target product are undesirably reduced. The method of the present invention generally comprises
The reaction is performed at an oxygen concentration of 33 mg / L or less.
It is 24 mg / L or less, more preferably 18 mg / L or less.

In carrying out the reaction, the oxygen concentration in the reaction solution can be measured simply and instantly by using a measuring instrument such as an oxygen concentration meter. The operation related to the measurement of the oxygen concentration in the reaction solution using an oximeter consists of immersing the sensor portion of an oximeter having an oxygen permeable membrane at the tip into the reaction solution, and measuring the concentration based on the signal sent from the sensor portion. It is a simple operation such as reading the measured value displayed on the meter main body.

In the oxidative coupling reaction of the phenolic compound of the present invention, oxygen used as an oxidizing agent includes:
Either pure oxygen gas or oxygen-containing gas in which air or oxygen is diluted with an inert gas such as nitrogen may be used. The amount of oxygen used must be at least the oxygen amount necessary for the reaction (theoretically, 25 mol% of oxygen molecules of the raw material phenolic compound) or more. In addition, as a method for introducing pure oxygen or a gas containing oxygen into the reaction system, a method of supplying these oxygen-containing gases while bubbling from a feed pipe immersed in the reaction solution, or a method of aerating and stirring the upper surface of the reaction solution. Alternatively, various methods such as a method of taking into a liquid by spontaneous dissolution or the like can be adopted.

In the present invention, the oxygen concentration in the reaction solution is adjusted to 3
Although it is necessary to maintain the concentration at a low concentration of 3 mg / L or less, in the batch reaction, from the start of the reaction until the oxidative coupling reaction of the starting phenolic compound reaches a desired level, that is, the starting phenolic compound The conversion is maintained at a low concentration while the conversion is 70% or less, whereby the selectivity of the target oxidative coupling reactant can be increased. In this reaction, it is preferable to keep the oxygen concentration in the solution as low as possible even after the conversion of the reaction exceeds 70%, because this leads to improvement in selectivity. In a batch reaction,
As the conversion rate increases and the concentration of the phenolic compound as the raw material decreases, the reaction rate decreases, and the rate of consumption of oxygen consumed in the reaction system slows down. It is difficult to keep the oxygen concentration in the solution low if the supply is continued. In order to keep the oxygen concentration low, it is conceivable to adopt a method such as reducing the oxygen supply rate or decreasing the stirring speed in the reactor to reduce the gas-liquid interface area to reduce the oxygen dissolving efficiency. On the other hand, disadvantages such as a prolonged reaction time also occur. In order to efficiently carry out the process industrially, it is generally desirable that the period in which the oxygen concentration is kept low is appropriately divided at an appropriate time. By setting a period such that the conversion of the reaction is 70% or less as the period for keeping the concentration low, it is possible to raise both the selectivity and the yield of the oxidative coupling reactant of the target product to a high level. is there.

On the other hand, in the continuous reaction, the conversion rate in the reactor at the time of the steady operation is appropriately changed by changing the conditions such as the concentration of the catalyst and the raw material, the residence time and the like in consideration of the raw material cost, the productivity of the target product, and the like. Various settings can be made by performing the setting, but the setting is usually made in the range of 1 to 99%, preferably 10 to 99%. At any set conversion rate, it is necessary to maintain the oxygen concentration in the reaction solution in the steady state at a low concentration of 33 mg / L or less, whereby the target product can be obtained with a high selectivity. .

Examples of the phenolic compound which can be used as a raw material in the present invention include an aromatic monool or polyol, a condensed ring aromatic monool or polyol,
All types of compounds such as a heterocyclic aromatic monol or a polyol are targeted, and specific examples of each type are shown below. Specific examples of the aromatic monol include phenol; 2-methylphenol, 4-i-propylphenol, 2,6-dimethylphenol,
5-diethylphenol, 2,4-di-n-propylphenol, 4-methoxyphenol, 3,4-dimethylphenol, 3,4,5-trimethylphenol, 2,
3,5-trimethylphenol, 2-triethylsilylphenol, 2-bromo-4-methoxyphenol, 4
(Substituted) phenols such as -phenylphenol and 2,6-diphenylphenol; and aromatic polyols such as 1,2-dihydroxybenzene, 1,3-
Dihydroxybenzene, 1,4-dihydroxybenzene, 1,2,3-trihydroxybenzene, 1,2,4
-Trihydroxybenzene, 4-t-butyl-1,2-
Examples thereof include poly (substituted) phenols such as dihydroxybenzene and 2,5-dimethyl-1,3-dihydroxybenzene.

Examples of the condensed ring aromatic monol include 1-naphthol, 2-naphthol, 3-methyl-2-naphthol, 2-methyl-1-naphthol, and 4-t-butyl-1.
-Naphthol, 3,6-di-tert-butyl-2-naphthol, 6-bromo-2-naphthol, 7-methoxy-2-
Naphthol, 5,6,7,8-tetrahydro-2-naphthol, 3-hydroxy-2-naphthalene acid, 3-hydroxy-2-naphthalene acid methyl ester, 9-phenanthrol, etc., and a condensed ring aromatic polyol In the above, 1,4-dihydroxynaphthalene, 2,3-dihydroxynaphthalene, 2,7-dihydroxynaphthalene,
1,2-dihydroxynaphthalene, 6-bromo-1,2
-Dihydroxynaphthalene and the like. Further, in the heterocyclic aromatic monol, 2-pyridinol, 3-pyridinol, 4-pyridinol, 8-hydroxyquinoline, 2-hydroxyquinoline, 1-isoquinolinol,
4-methyl-2-hydroxyquinoline, 6-hydroxy-2-methylquinoline, 6-hydroxyquinoline, 7-
Hydroxyquinoline, 2-hydroxypipemyridine, 2
A nitrogen-containing or oxygen-containing heterocyclic aromatic monol such as -hydroxydibenzofuran; and the heterocyclic aromatic polyols include 2,3-dihydroxypyridine and 2,4-
Dihydroxypyridine, 2,8-quinolinediol,
Examples include nitrogen-containing heterocyclic aromatic polyols such as 1,8-naphthylidene-2,7-diol, 1,3-isoquinolinediol, and 4,6-dihydroxypyrimidine.

Among these phenolic compounds, particularly, one hydroxyl group is bonded to an aromatic ring having aromaticity, and two hydroxyl groups are bonded to the para-position of the hydroxyl group.
A monol type having a structure having a hydrogen atom in at least one of the two ortho positions is preferable. Examples of such phenolic compounds include, for example, phenol, 4-methoxyphenol, 3,4-dimethylphenol, 3,4,5-trimethylphenol, 2,6-diphenylphenol, 1-naphthol, 2-methyl- 1
-Naphthol, 4-t-butyl-1-naphthol, 2-
Naphthol, 3-methyl-2-naphthol, 5,6
7,8-tetrahydro-2-naphthol, 8-hydroxyquinoline, 4-methyl-2-pyridinol, 6-hydroxyquinoline and the like.

In the present invention, a more preferred phenolic compound is a phenolic compound having a structure represented by the following general formula (1).

Embedded image

(Wherein R ¹ is a hydrogen atom, carbon atom 1-14)
Represents an alkyl group, a cycloalkyl group, an alkoxy group, an aryl group, or a silyl group or a siloxy group which may be substituted with a lower alkyl group; R ² and R ⁴
Each independently represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, an alkoxy group or a halogen atom, and R ³ represents an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group, an alkoxy group, an aryl group, Or a silyl group or a siloxy group which may be substituted with a lower alkyl group. )

Specific examples of the compound include 4-methylphenol, 4-n-nonylphenol, 4-t-butylphenol, 4-trimethylsiloxyphenol,
2,4-di-n-dodecylphenol, 2,4-dicyclohexylphenol, 2,4-diphenylphenol, 2,4-bis (trimethylsilyl) phenol,
2,4-diadamantylphenol, 2-cyclopropyl-4-t-butoxyphenol, 2,3,4-trimethylphenol, 2,3,4,5-tetramethylphenol, 2,4-di-t-butoxy -5-fluorophenol, 3,4,5-trimethoxyphenol, 3-chloro-4-trimethylsilylphenol, 2-trimethylsilyl-3-methoxy-4-phenyl-5-chlorophenol, 2,4-di-t- Butoxy-3,5-dimethylphenol, 2-neopentyl-3-bromo-4-trimethyl-5-iodophenol and the like.

Among the phenolic compounds, most preferably,
In the general formula (1), R ¹ and R ³ are an alkyl group or an alkoxy group having 1 to 7 carbon atoms, R ² is a hydrogen atom, and R ⁴ is a hydrogen atom or 1 to 3 carbon atoms. A phenolic compound that is an alkyl group or a halogen atom. Specifically, 2,4-di-t-butylphenol, 2,4-di-t-pentylphenol,
2,4-di-t-butyl-5-methylphenol, 2-
t-butyl-4-methoxyphenol, 2-t-butyl-4,5-dimethylphenol, 2-methoxy-4-i
-Propylphenol, 2,4-di-t-butoxy-5
-Ethylphenol, 2,4,5-trimethylphenol, 2-i-propyl-4-methyl-5-bromophenol, 2-t-butyl-4-methyl-5-chlorophenol and the like.

The above-mentioned phenolic compound is oxidatively coupled using oxygen as an oxidizing agent in the presence of a catalyst to produce an oxidative coupling reactant. The oxidative coupling reaction may take various forms. Are known. It can be broadly divided into two types, a carbon-carbon coupling reaction and a carbon-oxygen coupling reaction. Carbon-
In carbon-coupling reactions, the substituent at the location on the aromatic ring where the coupling takes place must be a hydrogen atom, and formally, two hydrogen atoms are abstracted out and form a new bond between the locations. Coupling is taking place. Normally, a coupling reaction occurs at the ortho and para positions of the hydroxyl group, so that it can be further classified into ortho-ortho, ortho-para and para-para carbon-carbon coupling reactions. . In the coupling reaction, not only a dimer is formed, but also a compound having two or more hydrogen atoms at the ortho position and the para position on the aromatic ring, may be a trimer, an oligomer or a polymer.

In the carbon-oxygen coupling reaction,
This is a reaction in which the hydrogen atom of the hydroxyl group of one phenolic compound and the ortho- or para-position hydrogen atom of another phenolic compound are abstracted to form a bond. In some cases, Still further, the various types of reactions described above may combine to give products of complex structure.

The present invention can be applied to all types of the above-mentioned oxidative coupling reactions. Among them, carbon-carbon coupling reactions between ortho-ortho positions and between para-para positions can be considered. And particularly effective in the oxidative coupling reaction between ortho-ortho positions using a phenolic compound having a hydrogen atom at the ortho position as a raw material as shown in the general formula (1). A preferable oxidative coupling reactant generated when the phenolic compound represented by the general formula (1) is used is a 2,2′-dihydroxybiphenyl derivative represented by the following general formula (2).

[0028]

Embedded image

(In the formula, R ^{1 to} R ⁴ have the same meaning as defined in the general formula (1).) As specific examples of these 2,2′-dihydroxybiphenyl derivatives, 5,5′-dimethyl- 2,2′-dihydroxybiphenyl, 5,5′-di-t-butyl-2,2′-
Dihydroxybiphenyl, 3,3 ', 4,4', 5
5'-hexamethyl-2,2'-dihydroxybiphenyl, 4,4 ', 5,5', 6,6'-hexamethoxy-
2,2′-dihydroxybiphenyl, 5,5′-di-n
-Decyl-6,6'-difluoro-2,2'-dihydroxybiphenyl, 3,3'-dicyclohexyl-5
5'-di-t-butoxy-2,2'-dihydroxybiphenyl, 3,3'-dineopentyl-4,4'-dichloro-5,5'-dicyclopropyl-6,6'-diethoxy-2,2 '-Dihydroxybiphenyl, 3,3'-bis (trimethylsiloxy) -4,4'-diethyl-5
5'-bis (triethylsilyl) -6,6'-dibromo-2,2'-dihydroxybiphenyl and the like.

Further preferred oxidative coupling reactants are, in the general formula (1), R ¹ and R ³ are an alkyl group or an alkoxy group having 1 to 7 carbon atoms, R ² is a hydrogen atom, R ⁴ is such that an alkyl group or a halogen atom consists 1-3 hydrogen atoms or carbon atoms, the most preferred results from the phenolic compound include 2,2'-dihydroxy biphenyl derivatives. Specifically, 3,3 ',
5,5′-tetra-t-butyl-2,2′-dihydroxybiphenyl, 3,3 ′, 5,5′-tetra-t-butoxy-2,2′-dihydroxybiphenyl, 3,3 ′,
5,5′-tetra-t-pentyl-2,2′-dihydroxybiphenyl, 3,3 ′, 5,5′-tetra-t-butyl-6,6′-dimethyl-2,2′-dihydroxybiphenyl, 3,3'-di-t-butyl-5,5'-dimethyl-6,6'-dichloro-2,2'-dihydroxybiphenyl, 3,3'-di-n-propoxy-5,5'-
Di-t-butyl-6,6'-dibromo-2,2'-dihydroxybiphenyl and the like.

The catalyst which can be used in the oxidative coupling reaction of the present invention includes, for example, sodium hydroxide, sodium hydrogen carbonate, barium hydroxide having a stoichiometric amount or more, which have been used in this type of reaction. In addition to basic compounds such as ammonia and the like, it is conceivable to use any catalyst system such as a transition metal compound which is generally assumed to undergo a reaction via a phenoxy radical species. However, from the viewpoint of catalyst cost in industrial production, it is advantageous to employ a catalyst system containing a transition metal compound that requires a small amount of use as a catalyst. Specific examples include copper chloride, copper catalysts such as copper acetate, silver oxide,
Silver nitrate, silver catalysts such as silver carbonate, lead oxides, lead catalysts such as lead acetate, and others, iron chloride, manganese oxide, ruthenium oxide, and the like, particularly, scandium, titanium, vanadium, chromium, manganese, Iron, cobalt,
A catalyst system comprising a transition metal compound of the first transition period selected from copper and zinc is preferred. Specific compounds thereof include trifluorooxyvanadium, bis (acetylacetonato) oxyvanadium, chromium oxide, tri (acetylacetonato) manganese, iron trichloride hexahydrate, cobalt acetate, nickel acetate, nickel chloride, Zinc chloride and the like can be mentioned.

More preferably, the catalyst system comprises copper, and specific compounds thereof include cupric sulfate, cupric nitrate,
Cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, cuprous iodide, cupric iodide, cupric bis (acetylacetonate), cuprous oxide, oxidized Cupric or the like. In particular, it is preferable to use the copper catalyst together with the amine compound, and in that case, it is preferable to use a copper halide. Specifically, cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, cuprous iodide, cupric iodide or hydrates thereof are the most preferred. Preferably, it is cuprous chloride, cupric chloride or a hydrate thereof.

Examples of the amine compound used together with the copper catalyst include trimethylamine, triethylamine, tripropylamine, tributylamine, diethylamine, dipropylamine, pyridine, piperidine, γ-picoline, ethylenediamine, propylenediamine, N,
N-diethylnicotinamide and the like. Among them, more preferred are diamines having chelating properties, and particularly preferred are ethylenediamine and ethylenediamine in which at least one of four hydrogen atoms bonded to two nitrogen atoms of ethylenediamine is substituted with an alkyl group. It is a derivative. Specifically, N-methylethylenediamine, N-ethylethylenediamine, N, N
-Dimethylethylenediamine, N, N'-di-t-butylethylenediamine, N, N, N'-tri-i-propylethylenediamine, N, N, N ', N'-tetramethylethylenediamine, N, N, N' , N'-tetraethylethylenediamine and the like.

The method of the present invention for promoting the oxidative coupling reaction of a phenolic compound in the presence of a catalyst is not particularly limited except that the oxygen concentration in the reaction solution is kept at a predetermined low concentration as described above. Commonly known general methods can be employed. A solvent is used for the reaction, and any solvent may be used without particular limitation as long as it does not adversely affect the oxidative coupling reaction, but a solvent having a polarity suitable for dissolving the phenolic compound can be used. Is preferred. Specific examples include alcohols such as methanol, ethanol, and benzyl alcohol; nitriles such as acetonitrile and propyl nitrile; ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane; ketones such as acetone and diethyl ketone; Esters such as ethyl and methyl propionate,
Aromatic hydrocarbons such as benzene, toluene and xylene,
Examples include pyridines such as pyridine and 4-methylpyridine, halogenated hydrocarbons such as dichloromethane, chloroform, methyl iodide, chlorobenzene, dichlorobenzene and dibromobenzene, and water. Of these,
By using a solvent that is a good solvent for the starting phenolic compound and a poor solvent for the 2,2′-dihydroxybiphenyl derivative produced by the reaction, the target product can be obtained as a solid from the reaction solution. This is advantageous in the recovery operation.

When a catalyst and a phenolic compound are added to the above solvent and oxygen or air is introduced therein, the oxidative coupling reaction starts to proceed. As a method of introducing oxygen or air, etc., a method of bubbling from a feed pipe into a solution is effective, but an upper part of the liquid surface may be ventilated. The reaction temperature is not particularly limited, but generally a temperature of 10 to 100 ° C is used, preferably 20 to 80 ° C, and more preferably 30 to 70 ° C. The pressure is not particularly limited, either. However, in order to keep the oxygen concentration in the solution low as in the present invention, if the oxygen partial pressure is too high, it becomes difficult to achieve the oxygen partial pressure. Atmospheric pressure (0.000098-0.098MP
a), preferably 0.01 to 0.5 atm (0.00098 to 0.04 atm)
95 MPa), more preferably 0.01 to 0.3 atm (0.000 atm).
The range is preferably 98 to 0.0294 MPa).

As a reaction mode, usually, oxygen or an oxygen-containing gas is introduced from a feed pipe into a reactor in which a reaction solution containing a predetermined amount of a catalyst and a raw material phenolic compound in a solvent is incorporated. Is preferably used. In addition, while supplying an oxygen-containing gas, a catalyst, and a raw material phenolic compound to a reactor by dissolving them in a solvent as necessary, a facility that performs a reaction while continuously extracting a constant amount of the contents in the reactor is used. A flow reaction operation can also be employed. The supply rate of the oxygen-containing gas, the catalyst, the raw material phenolic compound, etc. is appropriately determined according to reaction conditions such as the conversion rate in a steady state, the oxygen concentration in the reaction solution, and the stirring speed. Can be extracted semi-continuously.

Various methods can be used for purifying the generated oxidative coupling reactant. When the oxidative coupling reactant is present in a solid state in the reaction solution, the solid substance is removed by filtration. Separation and washing of the obtained solid with a fresh solvent to wash away the catalyst and the like, purification by a recrystallization method, and the like. On the other hand, when the oxidative coupling reactant is dissolved in the solvent, the catalyst system and the oxidative coupling reactant are separated by an extraction method using an appropriate solvent, and the solvent of the solution containing the oxidative coupling reactant is separated. Examples thereof include a method of distilling the solution or removing the solution from the solution by recrystallization.

In the oxidative coupling reaction of the present invention,
In the general formula (1), R ¹ and R ³ are an alkyl group or an alkoxy group having 1 to 7 carbon atoms, R ² is a hydrogen atom, R ⁴ is a hydrogen atom, and 1 to 3 carbon atoms. When a most preferred phenolic compound which is an alkyl group or a halogen atom is used as a raw material, and a corresponding most preferred 2,2′-dihydroxybiphenyl derivative represented by the general formula (2) is synthesized from this compound, a methanol solvent is used. During,
It is desirable that oxygen be introduced in the presence of a catalyst system comprising cupric chloride and tetramethylethylenediamine to cause the oxidative coupling reaction to proceed. In this case, the generated 2,2′-dihydroxybiphenyl derivative often precipitates in the methanol solution, so that the purification of the target substance can be completed by simple operations such as filtration and washing.

When the amount of the methanol solvent used is too large and the reaction solution is in a dilute state, the amount of dissolved oxygen may increase and adversely affect the selectivity of the target product. It is desirable to limit. Usually, 0.1 to 10 to the weight of the phenolic compound used as a raw material
It is desirable to use a fold, preferably 0.5 to 8 fold, more preferably 1 to 5 fold (weight ratio). Regarding the amount of cupric chloride used as a component of the catalyst, if the amount used is too small and the oxygen consumption rate is low, the oxygen concentration in the solution tends to increase, so reactions at very low concentrations should be avoided. Yes, usually 0.05% for the phenolic compound used
It is desirable to use an amount of .about.30 mol%, preferably 0.1-20 mol%, more preferably 0.5-10 mol%. Regarding the amount of tetramethylethylenediamine used as the other component of the catalyst, if the amount is extremely small with respect to copper, the reaction activity is reduced. Therefore, the ratio of the nitrogen atom of tetramethylethylenediamine to copper is usually N / Cu ratio. It is desirably 0.2 to 100, preferably 0.5 to 50, and more preferably 1 to 10.

[0040]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist.

Reference Example 1 In order to confirm the progress of the oxidation coupling reaction and the state of change in the oxygen concentration in the solution, and how the oxygen concentration in the solution changes due to the change in the stirring speed, The following experiment was performed. First, the following reactor was prepared. Radius driven by mechanical stirrer in the center of 200ml four-necked flask
A 3 cm Teflon (registered trademark) stirring blade was attached, and an air blowing tube, a sensor for measuring oxygen concentration, and a Dimroth were attached to the other three ports, respectively. The oxygen concentration meter used was an O ₂ Transmitter 4500 (sensor part: φ12 mm type) manufactured by METTLERTOLEDO, and the oxygen concentration was measured at the sensor part and the temperature of the solution was also measured. In addition, a bubbler was attached to the end of the Jimroth to provide an extra air outlet.

A sufficient nitrogen atmosphere was passed through the reactor to form a nitrogen atmosphere, and cupric chloride dihydrate was added to the reactor in a nitrogen atmosphere.
697 g (4.09 mmol) of tetramethylethylenediamine in 0.1 g
637 g (5.48 mmol) and 35 ml of methanol were added and stirred to obtain a homogeneous solution. Further, 2,4 was added to 100 ml of methanol.
-Di-t-butyl-5-methylphenol 45.0g (204.2mmo
l) The dissolved solution was added. The temperature was raised while stirring while keeping the inside of the system under a nitrogen atmosphere. When the temperature of the solution reached 50.0 ° C., air was bubbled into the solution from an air blowing tube to start the reaction. The air supply is about 25ml
/ min, and the temperature of the solution was kept at 50.0 ° C during the reaction.

During the reaction, the solution was sampled at appropriate times and analyzed by high performance liquid chromatography to determine the conversion of the raw materials. Also, the stirring speed of the mechanical stirrer
Perform the reaction by changing to 100, 200, 300, 400, 600 rpm,
The oxygen concentration in the solution in the reaction was measured. As a result, it was found that the state of change in the oxygen concentration with the progress of the reaction at each stirring speed had a relationship as shown in the graph of FIG. That is, the higher the stirring speed, the higher the oxygen concentration in the system (in the reaction solution), and in the state where the raw material concentration at the beginning of the reaction is high, the reaction speed is high and the oxygen consumption speed is high. Also, the oxygen concentration in the system (in the reaction solution) remains low. In particular, stirring speed 10
At 0 to 200 rpm, the oxygen concentration in the system (in the reaction solution) is almost 0 mg / L until the raw material conversion rate is around 30%. When the reaction proceeds and the reaction rate decreases due to a decrease in the raw material concentration in the system (in the reaction solution), the oxygen consumption rate also decreases, so the oxygen concentration in the system (in the reaction solution) gradually increases. At any stirring speed, the oxygen concentration finally approaches 66 mg / L in the air-saturated state at 50.0 ° C.

<Example 1> 200 ml in the same manner as in Reference Example 1.
Attach a 3 cm radius Teflon stirring blade driven by a mechanical stirrer to the center of the four-necked flask, and air blow tubes, thermometer (oxygen concentration measurement sensor), Dimroth (air exhaust Outlet).
Three devices as described above were prepared, and the same catalyst and raw materials were charged to the respective containers in the same manner as in Reference Example 1 at the same scale. The stirring speed of each of the three devices was 200 rpm and 400 rp.
m and 700 rpm. The temperature of each of the three devices was raised to 50.0 ° C., and the reaction was started by bubbling air at a supply rate of about 25 ml / min. During the reaction, each reaction was followed by sampling the solution at appropriate times and analyzing it by high performance liquid chromatography.

The relationship between the oxygen concentration in the reaction solution and the conversion is as follows:
This is as in the case of the stirring speed of 200 rpm and 400 rpm in FIG. In the case of 700 rpm, the oxygen concentration is 29 mg / L at a conversion rate of 70%. At the time when the raw materials almost disappeared, the reaction was terminated, and the target product was filtered to obtain 3,3 ′,
5,5′-Tetra-t-butyl-6,6′-dimethyl-2,2′-dihydroxybiphenyl was recovered. The target substance was sufficiently washed with methanol and dried under reduced pressure under heating. Then, the yield was measured and the purity was analyzed. The results are shown in Table 1 below. The selectivity of the target substance was determined from the yield of the target substance with respect to the conversion rate of the raw materials, based on the result of liquid chromatography immediately before the completion of the reaction.

[0046]

[Table 1]

From Table 1, it can be seen that the selectivity and yield of the target product increase when the stirring speed is low. Further, it can be seen from Reference Example 1 that the oxygen concentration in the liquid during the reaction was kept low when the stirring speed was low, but these results indicate that the reaction proceeds while keeping the oxygen concentration in the liquid during the reaction low. This indicates that the selectivity and yield of the target product can be improved.

<Example 2> Using the same reactor and charging conditions as in Example 1, the stirring speed was maintained at 400 rpm, and the air supply was maintained at about 25 ml / min. The oxidative coupling reaction of -t-butyl-5-methylphenol was performed in multiple batches. At various times during each reaction, the solution was sampled and analyzed in the same manner to determine the selectivity of the target substance and the raw material conversion at that time. Further, the oxygen concentration in the solution at that time was estimated from the raw material conversion rate using the result at 400 rpm in the graph of FIG. As a result, between the oxygen concentration in the solution and the selectivity of the target product 3,3 ', 5,5'-tetra-t-butyl-6,6'-dimethyl-2,2'-dihydroxybiphenyl, FIG. It has been found that there is a relationship as shown in FIG. That is, it can be seen that when the reaction is performed with the oxygen concentration in the solution lowered, the selectivity of biphenol is improved.

[0049]

According to the method of the present invention, 2,2'-dihydroxybiphenyls can be obtained from phenolic compounds by oxidative coupling reaction with a high selectivity and a simple operation method of controlling the oxygen concentration in the reaction solution. Since it can be produced in a high yield, it is an industrially extremely useful method.

[Brief description of the drawings]

FIG. 1 shows the progress of the oxidative coupling reaction and the change in oxygen concentration in the solution, and the relationship between the stirring speed and the oxygen concentration in the solution. The horizontal axis represents the conversion (%) of the phenolic compound, and the vertical axis represents the absolute oxygen concentration (mg / L) in the solution.

FIG. 2 shows the relationship between oxygen concentration in solution and selectivity of oxidative coupling reactants. The horizontal axis represents the absolute oxygen concentration in the solution (mg / L), and the vertical axis represents the selectivity (%) of the biphenol compound.

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Iwao Nakajima 1000 Kamoshita-cho, Aoba-ku, Yokohama-shi, Kanagawa Prefecture Mitsubishi Chemical Corporation Yokohama Research Laboratory (72) Inventor Yuzo Kasuga 1000 Kamoshida-cho, Aoba-ku, Yokohama-shi, Kanagawa Mitsubishi Chemical Corporation Yokohama Research Laboratory (72) Inventor Nao Urata 3-1-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki Prefecture Mitsubishi Chemical Corporation Tsukuba Research Laboratory F-term (reference) FE13 4H039 CA41 CD10

Claims (10)

[Claims] (1) In the production of an oxidative coupling reactant by an oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst, the reaction is carried out by a batch method, and after the start of the reaction, Until the conversion of the compound reaches 70%, the oxygen concentration in the reaction solution is reduced to 3%.
A method for producing an oxidative coupling reactant of a phenolic compound, wherein the oxidative coupling reaction is allowed to proceed while maintaining the concentration at 3 mg / L or less. 2. In the production of an oxidative coupling reactant by the oxidative coupling reaction of a phenolic compound using oxygen as an oxidizing agent in the presence of a catalyst, the reaction is carried out by a continuous flow system, and the reaction solution in a steady state of the reaction is obtained. A method for producing an oxidative coupling reactant of a phenolic compound, wherein the oxidative coupling reaction is allowed to proceed while maintaining the oxygen concentration in the medium at 33 mg / L or less. 3. The phenolic compound has one hydroxyl group bonded to an aromatic ring having aromaticity, and
The method for producing an oxidative coupling reactant according to claim 1 or 2, wherein the method has a structure having a hydrogen atom in at least one of the para position and two ortho positions of the hydroxyl group. 4. The method for producing an oxidation coupling reactant according to claim 1, wherein the catalyst is a catalyst system containing a transition metal compound. 5. The method for producing an oxidative coupling reactant according to claim 4, wherein the catalyst is a catalyst system containing a transition metal compound of the first transition period. 6. The method for producing an oxidative coupling reactant according to claim 5, wherein the catalyst is a catalyst system containing copper. 7. The process for producing an oxidative coupling reactant according to claim 6, wherein the catalyst is a catalyst system containing copper and an amine compound. 8. The catalyst according to claim 1, wherein the catalyst is a copper halide and at least one of ethylenediamine or an amino group of ethylenediamine.
The method for producing an oxidative coupling reactant according to claim 7, wherein the catalytic system comprises an ethylenediamine derivative in which two hydrogen atoms are substituted with an alkyl group. 9. A phenolic compound represented by the following general formula (1):
The oxidative coupling reactant according to any one of claims 1 to 8, wherein the oxidative coupling reactant has a structure represented by the following general formula (2). Manufacturing method. Embedded image (Wherein, R ¹ represents a hydrogen atom or a silyl group or a siloxy group which may be substituted with an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group, an alkoxy group, an aryl group or a lower alkyl group; ² and R ⁴ each independently represent a hydrogen atom or an alkyl group consisting of 1 to 6 carbon atoms, an alkoxy group or a halogen atom, and R ³ represents an alkyl group consisting of 1 to 14 carbon atoms, a cycloalkyl group, an alkoxy group , Represents a silyl group or a siloxy group which may be substituted with an aryl group or a lower alkyl group.) (In the formula, R ^{1 to} R ⁴ are the same as those defined in the general formula (1).) 10. In a methanol solvent, in the presence of a catalyst system consisting of cupric chloride and tetramethylethylenediamine,
R ¹ and R ³ in the general formula (1) are an alkyl group or an alkoxy group having 1 to 7 carbon atoms, R ² is a hydrogen atom, and R ⁴
Is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or a halogen atom, is subjected to an oxidative coupling reaction to give a 2,2′-dihydroxybiphenyl derivative represented by the general formula (2) corresponding to the compound. The method for producing an oxidative coupling reactant according to any one of claims 1 to 9, wherein the reactant is produced.