JP2013184947A - Method for manufacturing biaryl compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method capable of manufacturing a biaryl compound from an aryl chloride compound that is low in reactivity, in the presence of a small amount of a catalyst and under a mild condition.SOLUTION: A method for manufacturing a biaryl compound is characterized by including a preparatory process of preparing a nanocluster catalyst comprising gold and palladium and a reaction process of synthesizing a biaryl compound from an aryl chloride compound in the presence of the nanocluster catalyst. A reducing agent is preferably added to the reaction process.

Description

  The present invention relates to a method for producing a biaryl compound.

Examples of the method for producing a biaryl compound include the Ullman reaction (see Non-Patent Document 1), which has been known for a long time as a homocoupling reaction of an aromatic halide using a metal catalyst.
As methods for producing a biaryl compound from an aryl chloride compound, methods described in Patent Document 1 and Non-Patent Document 2 are known.
In recent years, nanocluster catalysts have attracted attention, and application to various reactions and development of new reactions are expected. For example, Patent Document 2 describes a gold nanocluster catalyst.

JP 2011-46693 A JP 2011-32178 A

F. Ullman and J. Bielecki, Chem. Ber., Vol.34, p.2174 (1901) J.-H.Li, Y.-X.Xie, and D.-L.Yin, J. Org. Chem., Vol.68, p.9867 (2003)

In the method described in Patent Document 1, there is a problem that a large amount of copper is required at a high temperature in order to react an aryl chloride compound having low reactivity.
In addition, the method described in Non-Patent Document 2 has a problem that a special condition of carbon dioxide pressurization and a large excess of zinc are required.
An object of the present invention is to provide a method capable of producing a biaryl compound from an aryl chloride compound having low reactivity in the presence of a small amount of catalyst and under mild conditions.

The above-mentioned problem to be solved by the present invention has been solved by <1> shown below. It is shown below with <2>-<9> which are preferable embodiments.
<1> A method for producing a biaryl compound comprising a preparation step of preparing a nanocluster catalyst containing gold and palladium, and a reaction step of synthesizing a biaryl compound from an aryl chloride compound in the presence of the nanocluster catalyst. ,
<2> The method for producing a biaryl compound according to <1>, wherein a reducing agent is added in the reaction step.
<3> The method for producing a biaryl compound according to <2>, wherein the reducing agent is a compound selected from the group consisting of a primary alcohol compound, a secondary alcohol compound, a dialkylformamide, and a dialkyl sulfoxide. ,
<4> The method for producing a biaryl compound according to <2> or <3> above, wherein in the reaction step, the reducing agent or a mixed solvent of water and the reducing agent is used as a solvent.
<5> The method for producing a biaryl compound according to any one of <1> to <4>, wherein a basic compound is added in the reaction step.
<6> The above <1> to <5>, wherein the nanocluster catalyst includes at least one protective agent selected from the group consisting of polyvinylpyrrolidone, chitosan, starch, cellulose, polyvinyl alcohol, polyethylene glycol, and polyallylamine. A process for producing the biaryl compound according to any one of
<7> The method for producing a biaryl compound according to any one of <1> to <6>, wherein the nanocluster catalyst includes polyvinylpyrrolidone,
<8> The method for producing a biaryl compound according to any one of the above <1> to <7>, wherein an average particle diameter of nanoclusters containing gold and palladium in the nanocluster catalyst is 5 nm or less,
<9> Any one of the above <1> to <8>, wherein the aryl chloride compound is a compound represented by the formula (1), and the biaryl compound is a compound represented by the formula (2). The manufacturing method of the biaryl compound as described in one.

（式（１）及び式（２）中、Ａｒはそれぞれ独立に、芳香族基又は複素芳香族基を表す。）

(In the formula (1) and the formula (2), Ar independently represents an aromatic group or a heteroaromatic group.)

  According to the present invention, it was possible to provide a method capable of producing a biaryl compound from an aryl chloride compound having low reactivity in the presence of a small amount of catalyst and under mild conditions.

The method for producing a biaryl compound of the present invention includes a preparation step of preparing a nanocluster catalyst containing gold and palladium, and a reaction step of synthesizing a biaryl compound from an aryl chloride compound in the presence of the nanocluster catalyst. And
Hereinafter, the present invention will be described in detail.

The method for producing a biaryl compound of the present invention is a method for synthesizing a biaryl compound from an aryl chloride compound using a nanocluster catalyst containing gold and palladium.
Specifically, for example, a biaryl compound (Ar—Ar) is obtained by reacting an aryl chloride compound (Ar—Cl) in the presence of a nanocluster catalyst containing gold and palladium.
Aryl chloride compounds are less reactive than aryl iodide compounds and aryl bromide compounds, and in order to synthesize biaryl compounds, a large amount of metal catalyst, etc., or severe conditions such as high temperatures are required. There was a problem that there was.
As a result of detailed studies by the present inventors, by using a nanocluster catalyst containing gold and palladium, a biaryl compound is produced from a low-reactivity aryl chloride compound in the presence of a small amount of catalyst and under mild conditions. Found that you can.
In the method for producing a biaryl compound of the present invention, the metals used for the catalyst are gold and palladium. Therefore, the toxicity to the living body is low, and the safety and the environment are excellent.
As described above, since the method for producing a biaryl compound of the present invention can be performed under mild conditions, the amount of heat to be used can be reduced as compared with conventional methods.
The nanocluster catalyst containing gold and palladium used in the method for producing a biaryl compound of the present invention can be recovered and easily after the reaction is completed, and the catalyst can be reused.
Moreover, it is preferable that the manufacturing method of the biaryl compound of this invention reacts with the solvent which has water as a main component, and can reduce the amount of organic solvents to be used from the conventional method.
That is, the method for producing a biaryl compound of the present invention is a so-called green process because the amount of heat and the amount of organic solvent used can be suppressed, so that the environmental load is small, and the used catalyst can be recovered and reused.
Furthermore, the biaryl compound obtained by the method for producing a biaryl compound of the present invention includes organic electronic materials such as liquid crystal materials, pharmaceutical raw materials such as synthetic intermediates, agricultural chemicals, paints, dyes, adhesives, synthetic detergents, and cosmetics. It can be suitably used for the production of fine chemical products.
Furthermore, the method for producing a biaryl compound of the present invention can be suitably used for detoxification of toxic aryl chloride compounds such as polychlorinated biphenyl (PCB).

<Preparation process>
The method for producing a biaryl compound of the present invention includes a preparation step of preparing a nanocluster catalyst containing gold and palladium.
A “nanocluster” is an aggregate of atoms having a particle size of nanosize (preferably an average particle size of 0.5 to 10 nm). For example, gold as a metal is an inactive metal, but has a reaction activity by making a gold atom into a nano-order cluster. In the present invention, as a result of detailed studies by the present inventors, it has been found that the catalytic activity for synthesizing a biaryl compound from an aryl chloride compound appears only when both gold and palladium are contained.
The nanocluster catalyst containing gold and palladium is preferably a nanocluster containing at least a zero-valent gold atom and a zero-valent palladium atom.
The nanocluster catalyst containing gold and palladium may contain a metal other than gold and palladium.
As the metal other than gold and palladium, a transition metal other than gold and palladium is preferably exemplified, and a metal selected from the group consisting of a transition metal in the third period of the periodic table, silver, and platinum is more preferably exemplified. More preferred are metals selected from the group consisting of nickel, cobalt, iron, copper, silver, and platinum.
The average particle size of the nanocluster containing gold and palladium is preferably 0.5 to 10 nm, more preferably 0.5 to 8 nm, and still more preferably 0.8 to 5 nm. Within the above range, the catalytic activity is more excellent.
Moreover, it is preferable that the average particle diameter of the said nano cluster containing gold | metal | money and palladium is 2 nm or less from a viewpoint of catalyst activity.
The particle size distribution of the nanoclusters is preferably narrow, and 90% by number or more of the particles preferably have an average particle size of ± 2.0 nm, more preferably an average particle size of ± 1.0 nm, More preferably, the diameter is ± 0.7 nm.

The content ratio of the gold atom (Au) and the palladium atom (Pd) in the nanocluster catalyst containing gold and palladium is not particularly limited, but in terms of atomic ratio (molar ratio), Au: Pd = 5: 95 to 95 : 5, preferably Au: Pd = 10: 90 to 90:10, more preferably Au: Pd = 20: 80 to 80:20, and Au: Pd = 40: It is especially preferable that it is 60-60: 40.
The nanocluster catalyst containing gold and palladium particularly preferably includes at least a nanocluster of an alloy of gold and palladium, that is, a nanocluster in which a gold atom and a palladium atom are present in one cluster. In the above embodiment, the reactivity is particularly excellent.

The nanocluster catalyst containing gold and palladium is not particularly limited as long as it is a nanocluster containing at least a gold atom and a palladium atom, but a mixture of a nanocluster and a protective agent, a nanocluster-supported polymer compound, and the like. A preferred example is a mixture of nanoclusters and a protective agent (hereinafter, also referred to as “protected nanocluster”).
Preferred examples of the nanocluster-supported polymer compound include nanocluster-supported star polymers. Although there is no restriction | limiting in particular as a star polymer, It is preferable that it is a polymer which has the core site | part which shows hydrophobicity, and the linear site | part which shows 3 or more hydrophilicity.
The protective agent in the mixture of nanoclusters and protective agent (protective nanocluster) is not particularly limited as long as it acts as a stabilizer of the cluster structure of the nanocluster and the catalyst activity is not completely lost. However, a resin and a saccharide are preferable, a resin having an oxygen atom and / or a nitrogen atom, and a saccharide are more preferable. More preferred are resins having at least one selected structure and saccharides.
Specific examples of the protective agent include polyvinyl pyrrolidone (PVP), chitosan, starch, cellulose, polyvinyl alcohol (PVA), polyethylene glycol (PEG), and polyallylamine. Among these, polyvinylpyrrolidone (PVP) can be particularly preferably exemplified from the viewpoint of the catalytic activity of the nanocluster catalyst and the safety to the living body.
Note that a mixture of nanoclusters and polyvinylpyrrolidone is also referred to as polyvinylpyrrolidone-protected nanoclusters. The same applies to other protective agents.
The polyvinyl pyrrolidone that can be used in the present invention is not particularly limited, but the weight average molecular weight is preferably 1,000 to 200,000, more preferably 10,000 to 100,000, More preferably, it is 000-50,000.
The polyvinyl pyrrolidone that can be used in the present invention is preferably polyvinyl pyrrolidone having a Fikentscher K value of 10 to 100, more preferably polyvinyl pyrrolidone having a K value of 15 to 50, and a K value of 25. More preferred is ~ 35 polyvinyl pyrrolidone. The K value is a viscosity characteristic value that correlates with the molecular weight, and is calculated by applying a relative viscosity value (25 ° C.) measured by a capillary viscometer to the following Fikentscher equation.
K = (1.5 log η _rel −1) / (0.15 + 0.003c) + (300 clog η _rel + (c + 1.5 clog η _rel ) ² ) ^1/2 /(0.15c+0.003c ² )
η _rel : relative viscosity of polyvinyl pyrrolidone aqueous solution with respect to water c: polyvinyl pyrrolidone concentration (%) in polyvinyl pyrrolidone aqueous solution

  When a mixture of nanoclusters and a protective agent is used as the nanocluster catalyst containing gold and palladium, the content of the protective agent is 1 mol of the total amount of gold atoms and palladium atoms when the compound is a compound. When the number is a polymer, the number of moles of the monomer unit is preferably 10 to 1,000 moles, more preferably 20 to 500 moles, and further preferably 50 to 200 moles. preferable.

In the preparation step, there is no particular limitation other than merely preparing the nanocluster catalyst containing gold and palladium, and at least the nanocluster catalyst containing gold and palladium used in the reaction step described later may be prepared. .
For example, in the preparation step, not only a catalyst but also an aqueous solution of a nanocluster catalyst containing gold and palladium may be prepared, or a nanocluster catalyst containing the protective agent may be prepared.
Moreover, in the said preparation process, you may prepare the nanocluster catalyst itself containing the said gold | metal | money and palladium like the method shown below, for example.
A method for preparing the nanocluster catalyst containing gold and palladium is not particularly limited, but chloroauric acid (HAuCl ₄ , tetrachloroauric acid, tetrachloroauric acid) and tetrachloropalladic acid (H ₂ PdCl ₄ ). A method in which a reducing agent is allowed to act on an aqueous dispersion containing chlorobenzene is preferred, and a method in which a reducing agent is allowed to act on an aqueous dispersion containing chloroauric acid and tetrachloropalladium acid containing a protective agent is more preferred.
The reducing agent for preparing the nanocluster catalyst is not particularly limited as long as it is a compound that can be reduced to zero-valent gold and / or zero-valent palladium, but sodium borohydride is preferable. Moreover, the reducing agent at the time of preparing the nanocluster catalyst may be added after being dissolved in a solvent, and is preferably added as an aqueous solution.
Moreover, what was mentioned above can be used suitably as a protective agent. Further, the protective agent may be added to the reducing agent and mixed, or may be added to both the gold and / or palladium-containing liquid and the reducing agent.
Furthermore, as a method for preparing the nanocluster catalyst containing gold and palladium containing a metal other than gold and palladium, for example, as in the case of gold and palladium, a metal salt other than gold and palladium is dispersed in an acidic aqueous solution. The method of reducing is mentioned.

  The aqueous solution containing the nanocluster catalyst containing gold and palladium obtained by the above method may be used as it is in the reaction step, or a dialysis membrane or an ultrafiltration membrane may be used. The salt such as sodium chloride produced may be desalted and / or moisture removed. The solid content of the nanocluster catalyst containing gold and palladium obtained using a dialysis membrane or an ultrafiltration membrane may be dissolved or dispersed again in water and used as an aqueous solution or aqueous dispersion. The aqueous dispersion can be stored for a long time in a refrigerator or the like, and the solid content can be freeze-dried and stored as a solid. In addition, the lyophilized solid can be used after being redissolved or redispersed in a solvent other than water.

<Reaction process>
The method for producing a biaryl compound of the present invention includes a reaction step of synthesizing a biaryl compound from an aryl chloride compound in the presence of the nanocluster catalyst.
The amount of the nanocluster catalyst used in the reaction step is such that the total atomic amount (total molar amount) of gold atoms and palladium atoms in the nanocluster catalyst is 0.001 with respect to 1 mol of the aryl chloride compound used. It is preferably ˜50 atom%, more preferably 0.001 to 20 atom%, still more preferably 0.01 to 10 atom%, and particularly preferably 0.1 to 5 atom%.

The reaction temperature in the reaction step is not particularly limited as long as the reaction proceeds, but is preferably 50 ° C or lower, more preferably 0 to 50 ° C, and more preferably 10 to 45 ° C. More preferably.
The reaction time is not particularly limited as long as the reaction proceeds, and can be appropriately selected according to the reaction temperature, the amount of catalyst, etc., but is preferably 48 hours or less, more preferably 36 hours or less. Preferably, it is 24 hours or less.
There is no restriction | limiting in particular in the atmosphere in the said reaction process, What is necessary is just to carry out in a desired atmosphere, but it is preferable to carry out in an air atmosphere from the surface of cost.

In the reaction step, it is preferable to add a reducing agent. By adding a reducing agent, the reaction rate and catalytic activity are improved, and the reaction can be carried out under milder conditions.
The reducing agent used in the reaction step is not particularly limited as long as it can reduce gold and / or palladium in the nanocluster catalyst after the reaction, but it is a primary alcohol compound or a secondary alcohol compound. It is preferably a compound selected from the group consisting of dialkylformamide and dialkyl sulfoxide, more preferably a compound selected from the group consisting of primary alcohol compounds, secondary alcohol compounds and dialkylformamides. A primary alcohol compound and / or a dialkylformamide is more preferable, and a dialkylformamide is particularly preferable. With the above embodiment, the reaction rate and catalytic activity are improved, the reaction can be carried out under milder conditions, and the cost is excellent.
The primary alcohol compound and the secondary alcohol compound preferably have 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms, still more preferably 2 to 4 carbon atoms, and 2 or 3 carbon atoms. It is particularly preferred.
The number of carbon atoms of the alkyl group substituted on the nitrogen atom in the dialkylformamide and dialkyl sulfoxide is preferably 1 to 8, more preferably 1 to 4, still more preferably 1 or 2. It is particularly preferred that
The amount of the reducing agent used in the reaction step is not particularly limited, but it is preferably 0.5 mol or more with respect to 1 mol of the aryl chloride compound to be used, and the solvent amount is more preferably used. preferable. Moreover, when using the amount of solvent of a reducing agent in the said reaction process, it is still more preferable that it is 1 to 50 weight% with respect to the total weight (a reducing agent is also included) of the solvent to be used. In the above embodiment, the reaction rate and catalytic activity are excellent.

The solvent used in the reaction step may be an aqueous solvent or an organic solvent, but only one type may be used, or two or more types may be mixed and used at an arbitrary ratio. Good.
The solvent preferably contains water, and more preferably contains water as a main component (50% by weight or more of the total weight of the solvent). In the above embodiment, the amount of the organic solvent to be used can be reduced, and the cost is excellent.
The reaction solvent is preferably the reducing agent or a mixed solvent of water and the reducing agent, more preferably a mixed solvent of water and the reducing agent. In the above embodiment, the catalytic activity is high and the progress of the reaction can be promoted.
The mixing ratio of water and the reducing agent is preferably volume: water: reducing agent = 10: 1 to 1: 1, and more preferably 5: 1 to 1.2: 1. In the above embodiment, the catalytic activity is high and the progress of the reaction is promoted.
Organic solvents include amide compounds such as dimethylacetamide, ketone compounds such as acetone, nitrile compounds such as acetonitrile, ether compounds such as diethyl ether, dimethoxyethane, tetrahydrofuran and dioxane, aliphatic hydrocarbon compounds such as hexane and pentane, and benzene. Preferred examples include aromatic hydrocarbon compounds such as toluene and xylene.

In the reaction step, it is preferable to add a basic compound.
The basic compound that can be used in the present invention may be an inorganic base or an organic base, but is preferably a water-soluble basic compound.
The inorganic base is not particularly limited, and examples thereof include alkali metal hydroxides, carbonates and bicarbonates, alkaline earth metal hydroxides, carbonates and bicarbonates, and rare earth hydroxides. And, specifically, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, carbonate Examples include potassium hydrogen, calcium hydroxide, and calcium carbonate.
Although there is no restriction | limiting in particular as said organic base, For example, an amine compound is mentioned, For example, a triethylamine, diazabicycloundecene etc. are mentioned specifically ,.
Among these, potassium hydroxide, sodium hydroxide, cesium carbonate, potassium carbonate, sodium carbonate, and diazabicycloundecene are preferable.
Although there is no restriction | limiting in particular as the addition amount of the basic compound in the said reaction process, It is preferable that it is 0.5-10 mol with respect to 1 mol of usage-amounts of the aryl chloride compound to be used, and is 1-5 mol. It is more preferable.

The aryl chloride compound used in the reaction step is not particularly limited as long as it is a compound that inhibits the reaction or a compound that cannot synthesize a biaryl compound due to steric hindrance, etc., and a compound having at least one chlorine atom on an aromatic ring And may be a compound having two or more chlorine atoms on the aromatic ring. The aryl chloride compound may be a polymer compound.
For example, in the reaction step, two or more biarylation reactions may be performed on an arylpolychloride compound having two or more chlorine atoms on the aromatic ring, and the polychlorinated biphenyl (PCB) as described above is converted into a polychlorinated biphenyl (PCB). On the other hand, polyarylation (detoxification) may be performed.
The portion other than the chlorine atom on the aromatic ring in the aryl chloride compound is not particularly limited as long as it does not have a group that inhibits the reaction in the reaction step, but the aromatic ring is sufficient to exert the effects of the present invention. It is preferable not to have a bromine atom and an iodine atom.
Needless to say, the aryl chloride compound may be, for example, a biphenyl chloride compound, and the resulting biphenyl compound may be a terphenyl compound.
In the said reaction process, an aryl chloride compound may be used individually by 1 type, or 2 or more types may be used. When two or more kinds are used, for example, a homo-coupled body in which the same kind of aryl chloride compound is reacted or a cross-coupled body in which a different kind of aryl chloride compound is reacted is obtained.
In the reaction step, when an aryl chloride compound having two or more chlorine atoms on the aromatic ring is used, a multimer, a positional isomer or the like is obtained.

The aryl group in the aryl chloride compound is not particularly limited as long as it does not have a group that inhibits the reaction in the reaction step, but an aromatic ring group or a heteroaromatic ring group which may have a substituent is Preferred examples include a phenyl group, a naphthyl group, an anthranyl group, and a pyridyl group, which may have a substituent, and more preferred examples include a phenyl group and a pyridyl group that may have a substituent.
As said substituent, the monovalent substituent mentioned later is mentioned preferably.
Preferred examples of the aryl chloride compound include compounds represented by the following formula (1).

（式（１）中、Ａｒは、芳香族基又は複素芳香族基を表す。）

(In the formula (1), Ar represents an aromatic group or a heteroaromatic group.)

The aromatic group in Ar is not particularly limited as long as it is bonded to the chlorine atom on the aromatic ring, and may have any number of substituents on the aromatic ring.
The heteroaromatic group in Ar is not particularly limited as long as it is bonded to the chlorine atom on the aromatic ring, and may have any number of substituents on the heteroaromatic ring.
The aromatic group and heteroaromatic group may be a condensed ring in which two or more rings are condensed, and examples of the ring condensed with the aromatic group or heteroaromatic group include an aliphatic ring and a heterocyclic ring. , Aromatic rings, heteroaromatic rings, and condensed rings and bridged rings thereof.
The aromatic group is preferably an aromatic group having 6 to 20 carbon atoms which may have a substituent, and may have a phenyl group, a naphthyl group or an anthranyl group. It is more preferable that
The aromatic group is preferably a heteroaromatic group having 4 to 20 carbon atoms which may have a substituent, and may have a phenyl group, a naphthyl group or an anthranyl group. More preferably, it is a group.
As the heteroaromatic group, a heteroaromatic group having 1 to 20 carbon atoms which may have a substituent is preferable, and pyridine, furan, thiophene, which may have a substituent, Pyrrole, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, oxazole, isoxazole, thiazole, isothiazole, thiadiazole, oxadiazole, pyridazine, pyrimidine, pyrazine, 1,3,5- From a heteroaromatic ring selected from the group consisting of triazine, 1,2,4-triazine, 1,2,3-triazine, benzofuran, benzothiophene, indole, indazole, benzoxazole, quinoline, quinazoline, benzimidazole and benzotriazole A group in which one hydrogen atom on the aromatic ring is removed Preferred.

The substituent in the aromatic group and heteroaromatic group is preferably a group having low reactivity with the nanocluster catalyst (excluding chlorine atoms).
Examples of the substituent include a chlorine atom, a fluorine atom, an alkyl group, an aryl group, an aralkyl group, a heterocyclic group, a heteroaryl group, a cyano group, a hydroxyl group, a nitro group, an amino group, an alkylamino group, a dialkylamino group, Alkoxy group, aryloxy group, amide group, arylamino group, ureido group, sulfamoylamino group, alkylthio group, arylthio group, alkoxycarbonylamino group, sulfonamido group, carbamoyl group, sulfamoyl group, sulfonyl group, alkoxycarbonyl group , Heterocyclic oxy group, azo group, acyloxy group, carbamoyloxy group, silyloxy group, aryloxycarbonyl group, aryloxycarbonylamino group, imide group, heterocyclic thio group, sulfinyl group, phosphonyl group, acyl group, carboxy group or Such as sulfo group, and the like.
The alkyl group or the alkyl group in the structure in each group may be linear, branched, or cyclic, and has an unsaturated bond. May be.
Moreover, these substituents may be further substituted with the above-mentioned substituents. In this case, the bromine atom and the iodine atom may be substituted except when the aromatic ring has a bromine atom and an iodine atom. For example, the alkyl group may be a haloalkyl group substituted with a halogen atom, a carboxyalkyl group substituted with a carboxy group, or the like.
Among them, the substituent is a chlorine atom, a fluorine atom, a hydrocarbon group, or a structure selected from the group consisting of a hydrocarbon group, a carbonyl group, an ether bond, an imino bond, an ester bond, and an amide bond. It is more preferably a group bonded as described above, and further preferably a chlorine atom or an alkyl group.
The carbon number of the substituent is not particularly limited, but preferably 0 to 50 carbon atoms, more preferably 0 to 30 carbon atoms, and further preferably 0 to 20 carbon atoms. preferable.

  Preferred examples of the biaryl compound obtained by the method for producing a biaryl compound of the present invention include compounds represented by the following formula (2).

（式（２）中、Ａｒはそれぞれ独立に、芳香族基又は複素芳香族基を表す。）

(In the formula (2), Ar independently represents an aromatic group or a heteroaromatic group.)

The aromatic group and heteroaromatic group in Ar in the formula (2) have the same meanings as the aromatic group and heteroaromatic group in Ar in the formula (1), respectively, and preferred embodiments thereof are also the same.
Further, the two Ars in the formula (2) may be the same group or different groups. For example, when two or more compounds represented by the formula (1) are used, a homo-coupled product obtained by reacting the same kind of aryl chloride compound or a cross-coupled product obtained by reacting different kinds of aryl chloride compounds is obtained. In addition, when a compound represented by the formula (1) having two or more chlorine atoms on the aromatic ring is used, a multimer, a regioisomer or the like is generated.

The biaryl compound obtained by the method for producing a biaryl compound of the present invention can be purified by a known method such as column chromatography, recrystallization or distillation, if necessary.
In addition, the nanocluster catalyst containing gold and palladium used in the method for producing a biaryl compound of the present invention can be recovered by a known method, and washed and reused as necessary.
Specifically, for example, the nanocluster catalyst containing gold and palladium used in the method for producing a biaryl compound of the present invention is liquid-liquid extraction in an aqueous medium / organic solvent two-phase system, extraction with supercritical carbon dioxide, or the like. Thus, after the product is extracted from the reaction solution or the reaction residue, the remaining aqueous solution can be reused as it is as the nanocluster catalyst containing gold and palladium as it is or after the removal of the inorganic salt by dialysis.

EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to an Example.
Moreover, as long as there is no notice in particular, the instrument and apparatus etc. which are used in the following Examples can use a commercially available or well-known instrument and apparatus suitably if it is a range which does not deviate from the meaning of this invention.

Unless otherwise specified, the solvents used in the following examples were used as they are, as they are, primary solvents manufactured by Kanto Chemical Co., Inc. or Wako Pure Chemical Industries, Ltd.
Unless otherwise specified, the reagents are those manufactured by Nacalai Tesque Co., Ltd. or Kishida Chemical Co., Ltd. for general-purpose inorganic reagents, and manufactured by Tokyo Chemical Industry Co., Ltd. or Wako Pure Chemical Industries, Ltd. for general-purpose organic reagents. The thing of was used.
In addition, ¹ H NMR, ¹³ C NMR, and / or gas chromatography was used to identify the obtained biaryl compound.

<Preparation of polyvinylpyrrolidone-protected AuPd nanocluster catalyst>
All operations were performed in an air atmosphere, and milliQ water was used for the preparation of the polyvinylpyrrolidone-protected AuPd nanocluster catalyst (AuPd: PVP). In addition, milliQ water is water having a specific resistance value of 10 MΩ · cm or more obtained by passing an ion exchange resin a plurality of times and further passing through an ultrafiltration membrane.
Poly (N-vinyl-2-pyrrolidone) was added to an Erlenmeyer flask (200 mL) containing an aqueous tetrachloroauric acid (HAuCl ₄ ) solution (1 mM, 25 mL) and an aqueous tetrachloropalladate (H ₂ PdCl ₄ ) solution (1 mM, 25 mL). (555.5 mg, 40 kDa, K-30) was added and stirred, and then stirred at 0 ° C. for 30 minutes. Under stirring at 1,300 rpm, an aqueous sodium borohydride (NaBH ₄ ) solution (0.1 M, 5 mL) was added all at once and stirred for 1 hour. This solution was washed with water (20 ml × 3) by ultrafiltration (3,500 rpm, KUBOTA-5200, manufactured by Kubota Corporation) using a membrane tube (Varivaspin molecular weight (MWCO) = 10,000, manufactured by Sartorius). )did.
The obtained solid was diluted to 100 mL with water to prepare an Au _0.5 Pd _0.5 : PVP aqueous dispersion (5 mM, 100 mL). The average particle diameter of the AuPd nanocluster catalyst in the obtained Au _0.5 Pd _0.5 : PVP aqueous dispersion was 2.3 ± 0.2 nm.
When preparing a dispersion other than water, lyophilize after washing (Eyela FDU-2200 manufactured by Nippon Kagaku Kikai Co., Ltd.), and disperse the obtained powdered polyvinylpyrrolidone-protected AuPd nanocluster catalyst in various solvents. Used.
When preparing AuPd nanocluster catalyst other than gold: palladium = 1: 1, the usage ratio of tetrachloroauric acid (HAuCl ₄ ) aqueous solution (1 mM, 25 mL) and tetrachloropalladic acid (H ₂ PdCl ₄ ) aqueous solution Can be prepared by changing to a desired ratio.

<Preparation of polyvinylpyrrolidone-protected Au nanocluster catalyst>
A polyvinylpyrrolidone-protected Au nanocluster catalyst (Au: PVP, Au: PVP) was used in the same manner as the preparation of AuPd: PVP, except that a tetrachloropallaic acid aqueous solution was not used and a double amount of tetrachloroauric acid aqueous solution was used. 5 mM, 100 mL) was prepared.

<Preparation of polyvinylpyrrolidone-protected Pd nanocluster catalyst>
A polyvinylpyrrolidone-protected Pd nanocluster was prepared in the same manner as the preparation of AuPd: PVP, except that a tetrachloroauric acid aqueous solution was not used and a double amount of tetrachloropalladic acid (H ₂ PdCl ₄ ) aqueous solution was used. A catalyst (Pd: PVP, 5 mM, 100 mL) was prepared.

Example 1

All operations were performed in an air atmosphere.
To a 20 mL test tube, 4-chlorotoluene (0.1 mmol) and potassium hydroxide (0.3 mmol) were added, and dimethylformamide (DMF, 1 mL) and water (1.6 mL) were further added, and room temperature (27 ° C.). Was stirred at. After setting the reaction temperature to 27 ° C., 5 mM Au _0.5 Pd _0.5 : PVP aqueous solution (0.4 mL: 2 atom%) was added and stirred for 24 hours. After stopping the reaction with pH 7 phosphate buffer, the aqueous layer was extracted three times with ethyl acetate (5 mL), and the combined organic layer was extracted twice with water (5 mL) and then with saturated saline (5 mL). And dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, the solvent was distilled off, and the residue was dried to obtain an almost pure biaryl compound (4,4′-dimethylbiphenyl) (yield 98%).
In addition, further purification of the obtained biaryl compound can also be performed by a usual method (chromatography, recrystallization).

(Examples 2 to 17 and Comparative Examples 1 and 2)
The reaction was carried out in the same manner as in Example 1 except that the aryl chloride compound, catalyst, catalyst amount, reaction temperature, and reaction time described in Table 1 or 2 were changed. In Example 10, cesium carbonate (Cs ₂ CO ₃ ) was used instead of potassium hydroxide. The yields of the obtained biaryl compounds are shown in Table 1 and Table 2, respectively.

  In addition, the catalyst amount in Table 1 and Table 2 was described as the molar amount of the gold atom and the palladium atom used, based on the molar amount of the used aryl chloride compound (100 mol%).

Claims (9)

A preparation step of preparing a nanocluster catalyst containing gold and palladium; and
A method for producing a biaryl compound comprising a reaction step of synthesizing a biaryl compound from an aryl chloride compound in the presence of the nanocluster catalyst.   The method for producing a biaryl compound according to claim 1, wherein a reducing agent is added in the reaction step.   The method for producing a biaryl compound according to claim 2, wherein the reducing agent is a compound selected from the group consisting of a primary alcohol compound, a secondary alcohol compound, a dialkylformamide, and a dialkyl sulfoxide.   The method for producing a biaryl compound according to claim 2 or 3, wherein in the reaction step, the reducing agent or a mixed solvent of water and the reducing agent is used as a solvent.   The method for producing a biaryl compound according to claim 1, wherein a basic compound is added in the reaction step.   The nanocluster catalyst according to any one of claims 1 to 5, wherein the nanocluster catalyst includes at least one protective agent selected from the group consisting of polyvinylpyrrolidone, chitosan, starch, cellulose, polyvinyl alcohol, polyethylene glycol and polyallylamine. The manufacturing method of the biaryl compound of description.   The method for producing a biaryl compound according to any one of claims 1 to 6, wherein the nanocluster catalyst contains polyvinylpyrrolidone.   The manufacturing method of the biaryl compound as described in any one of Claims 1-7 whose average particle diameter of the nanocluster containing the gold | metal | money and palladium in the said nanocluster catalyst is 5 nm or less. The biaryl compound according to any one of claims 1 to 8, wherein the aryl chloride compound is a compound represented by the formula (1), and the biaryl compound is a compound represented by the formula (2). Manufacturing method.

(In the formula (1) and the formula (2), Ar independently represents an aromatic group or a heteroaromatic group.)