JP6084874B2 - Synthesis method of compound by Sonogashira-Hagiwara reaction using palladium nanoparticles as catalyst - Google Patents

Description

  The present invention relates to a method for synthesizing a compound using a palladium nanoparticle catalyst, and more particularly, to a compound synthesis reaction by Sonogashira-Kashihara reaction.

  The Sonogashira-Hagiwara reaction is widely known as an alkyne coupling reaction, and is used in the production of functional compounds for electronic materials, medical materials, and the like. In general, palladium and copper salts are used as catalysts for Sonogashira-Hagiwara reaction. The palladium catalyst generally used for Sonogashira-Hagiwara reaction is a homogeneous palladium catalyst, which has high catalytic activity, but is unstable in the air, and it is difficult to separate and reuse the catalyst from the product. have. On the other hand, heterogeneous palladium catalysts have been widely used in recent years because they can handle palladium easily and are easily separated and reused from products. Therefore, there are problems that the catalytic activity is insufficient in the Sonogashira-Hagiwara reaction, and the reaction rate becomes slow due to the stirring property and the solvent species. Since a heterogeneous catalyst undergoes a reaction on the catalyst surface, it is very important to increase the surface area in order to increase the catalyst efficiency. There is a report (Patent Document 1) in which a perovskite-type composite oxide containing palladium is used as a catalyst for Sonogashira-Hagiwara reaction. However, not only is the cost high due to the large amount of catalyst used, but also sufficient because the catalytic activity is low. Since the reaction rate has not been obtained, the problem has not been solved.

International Publication No. 2005-105719 Pamphlet

  The object of the present invention is to synthesize a compound efficiently by the Sonogashira-Hagiwara reaction using a palladium catalyst that effectively exhibits the activity of palladium, without the problems of the homogeneous and heterogeneous palladium catalysts described above. It is to provide a synthesis method that can be used.

  As a result of intensive studies by the present inventors, the reaction proceeds very efficiently by using palladium nanoparticles prepared by alkaline treatment of a heterogeneous palladium catalyst as a catalyst for Sonogashira-Hagiwara reaction. The present inventors have found that the amount can be reduced and have arrived at the present invention.

（式中、Ｒ_１は、アリール基、複素環基またはアルケニル基を示し、Ｘは、ハロゲン原子または、−ＯＳＯ_２Ｗ（Wは、アルキル基またはアリール基を示す。）を示す。）

（式中、Ｒ_２は、アルキル基、シクロアルキル基、アリール基、複素環基、アルケニル基、アルキニル基またはトリアルキル置換シリル基を示す。）

（式中、Ｒ_１は、一般式（１）と同一の基を示し、Ｒ_２は、一般式（２）と同一の基を示す。） That is, the gist of the present invention is as follows.
(1) In the presence of palladium nanoparticles prepared by dispersing a heterogeneous palladium catalyst in an alkali solution and treating with an alkali, the compound represented by the following general formula (1) and the following general formula (2 A method for synthesizing the compound represented by the general formula (3), wherein the compound represented by the general formula (3) is reacted.

(In the formula, R ₁ represents an aryl group, a heterocyclic group or an alkenyl group, and X represents a halogen atom or —OSO ₂ W (W represents an alkyl group or an aryl group).)

(Wherein R ₂ represents an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkenyl group, an alkynyl group or a trialkyl-substituted silyl group.)

(In the formula, R ₁ represents the same group as in general formula (1), and R ₂ represents the same group as in general formula (2).)

（式中、Ａは、希土類元素から選ばれる少なくとも１種の元素を示し、Ａ’は、アルカリ土類金属から選ばれる少なくとも１種の元素を示し、Ｂは、遷移元素（希土類元素、ＣｕおよびＰｄを除く。）およびＡｌから選ばれる少なくとも１種の元素を示し、ｘは、０≦ｘ≦１．０の原子割合を示し、ｙは、０≦ｙ＜０．５の原子割合を示し、ｚは、０＜ｚ＜０．５の原子割合を示す。） (2) The method for synthesizing a compound according to (1), wherein the heterogeneous palladium catalyst is a palladium-containing perovskite complex oxide represented by the following general formula (4).

(In the formula, A represents at least one element selected from rare earth elements, A ′ represents at least one element selected from alkaline earth metals, and B represents a transition element (rare earth element, Cu and And at least one element selected from Al, x represents an atomic ratio of 0 ≦ x ≦ 1.0, y represents an atomic ratio of 0 ≦ y <0.5, z represents an atomic ratio of 0 <z <0.5.)

（式中、Ｌｎは、Ｌａ、Ｐｒ、Ｎｄ、Ｓｍ、ＥｕおよびＧｄから選択される少なくとも１種の必須成分と、Ｙ、Ｃｅ、Ｙｂ、Ｃａ、ＳｒおよびＢａから選択される少なくとも１種の任意成分とからなる元素を示し、Ｍは、Ｃｒ、Ｍｎ、Ｆｅ、Ｃｏ、ＮｉおよびＡｌから選択される少なくとも１種の元素を示し、ｘは、０．００１≦ｘ≦０．４の原子割合を示し、ｙは、０≦ｙ≦０．５の原子割合を示す。） (3) The method for synthesizing a compound according to (1), wherein the heterogeneous palladium catalyst is represented by the following general formula (5).

(Wherein Ln is at least one essential component selected from La, Pr, Nd, Sm, Eu and Gd, and at least one arbitrary selected from Y, Ce, Yb, Ca, Sr and Ba) And M represents at least one element selected from Cr, Mn, Fe, Co, Ni and Al, and x represents an atomic ratio of 0.001 ≦ x ≦ 0.4. Y represents an atomic ratio of 0 ≦ y ≦ 0.5.)

  In the method for synthesizing the compound of the present invention, since the amount of palladium used is reduced by using a nano-sized palladium catalyst, it is possible to reduce the environmental burden and the production cost due to the discharge of the synthesis reaction catalyst. Therefore, the method for synthesizing the compound of the present invention can be effectively used in, for example, industrial uses of the Sonogashira-Hagiwara reaction, for example, in the production of pharmaceutical intermediates, synthetic polymer materials, liquid crystal materials, optical materials and the like. it can.

<Heterogeneous palladium catalyst>
The heterogeneous palladium catalyst in the present invention means a palladium catalyst used in a solid state. Heterogeneous palladium catalysts are used in the chemical industry because they can be easily handled by immobilizing the palladium catalyst on an inorganic compound, etc., and can be separated and recovered from the product. It is often used in mass production.

  The heterogeneous palladium catalyst is obtained by immobilizing palladium on a support of an inorganic compound having a complicated structure such as zeolite, silica gel, alumina, or activated carbon. Since a heterogeneous catalyst undergoes a reaction on the catalyst surface, it is very important to increase the surface area in order to increase the catalyst efficiency. In the present invention, by treating the heterogeneous catalyst with an alkali, the surface area is increased by reducing the particle size to the nanoscale, and the catalyst efficiency is significantly increased.

In the present invention, the catalyst used for preparing the palladium nanoparticles is not limited as long as it is a heterogeneous palladium catalyst. From the standpoint of availability and handling, it is preferably a polymer-supported palladium complex, palladium-carbon, palladium-alumina, palladium-silica gel, palladium-containing perovskite-type composite oxide, and more preferably palladium-containing perovskite-type composite oxide. It is.
In the perovskite complex oxide containing palladium as a composition, those represented by the following general formula (4) are used.

（式中、Ａは、希土類元素から選ばれる少なくとも１種の元素を示し、Ａ’は、アルカリ土類金属から選ばれる少なくとも１種の元素を示し、Ｂは、遷移元素（希土類元素、ＣｕおよびＰｄを除く。）およびＡｌから選ばれる少なくとも１種の元素を示し、ｘは、０≦ｘ≦１．０の原子割合を示し、ｙは、０≦ｙ＜０．５の原子割合を示し、ｚは、０＜ｚ＜０．５の原子割合を示す。）

(In the formula, A represents at least one element selected from rare earth elements, A ′ represents at least one element selected from alkaline earth metals, and B represents a transition element (rare earth element, Cu and And at least one element selected from Al, x represents an atomic ratio of 0 ≦ x ≦ 1.0, y represents an atomic ratio of 0 ≦ y <0.5, z represents an atomic ratio of 0 <z <0.5.)

  In the general formula (4), examples of the rare earth element represented by A include Sc (scandium), Y (yttrium), La (lanthanum), Ce (cerium), Pr (praseodymium), Nd (neodymium), Pm ( Promethium), Sm (samarium), Eu (europium), Gd (gadolinium), Tb (terbium), Dy (dysprosium), Ho (holmium), Er (erbium), Tm (thulium), Yb (ytterbium), Lu ( Lutetium). Preferably, Y, La, Ce, Pr, and Nd are mentioned. These rare earth elements may be used alone or in combination of two or more.

  In the general formula (4), examples of the alkaline earth metal represented by A ′ include Be (beryllium), Mg (magnesium), Ca (calcium), Sr (strontium), Ba (barium), and Ra ( Radium). Preferably, Sr is mentioned. These alkaline earth metals may be used alone or in combination of two or more.

  In the general formula (4), it is preferable that A and A ′ use an alkaline earth metal represented by A ′ with respect to the rare earth element represented by A at an atomic ratio of 0.5 or less. It is preferable to use a rare earth element alone.

  In the general formula (1), as the transition element represented by B (excluding rare earth elements, Cu and Pd), for example, in the periodic table (IUPAC, 1990), the atomic number 22 (Ti) to the atom Examples include each element of 30 (Zn), atomic number 40 (Zr) to atomic number 48 (Cd), and atomic number 72 (Hf) to atomic number 80 (Hg) (excluding Cu and Pd).

As transition elements (excluding rare earth elements and Pd) represented by B and Al, Cr (chromium), Mn (manganese), Fe (iron), Co (cobalt), Ni (nickel), Zn (zinc) and Al It is preferable that the transition element selected from (aluminum) is an optional element, and further, the transition element selected from Mn, Fe, Co, and Al is an optional element.
Moreover, in the perovskite type complex oxide containing palladium as a composition, those represented by the following general formula (6) are preferably used.

（式中、Ａは、Ｙ、Ｌａ、Ｃｅ、Ｐｒ、Ｎｄから選ばれる少なくとも１種の元素を示し、Ｂは、Ｍｎ、Ｆｅ、Ｃｏ、Ａｌから選ばれる少なくとも１種の元素を示し、ｙは、０＜ｙ＜０．５の原子割合を示し、ｚは、０＜ｚ＜０．５の原子割合を示す。）

(In the formula, A represents at least one element selected from Y, La, Ce, Pr, and Nd, B represents at least one element selected from Mn, Fe, Co, and Al, and y represents , 0 <y <0.5, and z represents an atomic ratio of 0 <z <0.5.)

As such a perovskite type complex oxide containing palladium as a composition, more specifically, for example, La _1.00 Fe _0.57 Cu _0.38 Pd _0.05 O ₃ , La _0.90 Ce _0.10 Fe _0.57 Cu _0.38 Pd _0.05 O ₃ , La _1.00 Fe _0.57 Co _0.38 Pd _0.05 O ₃ , LayFeyPd _0.05 O ₃ , La _1.00 Cu _{0 .95 Pd 0.05 O 3, La 0.90} Ce 0.10 Al 0.95 Pd 0.05 O 3, La 1.00 Fe 0.57 Mn 0.38 Pd 0.05 O 3, La 1. ₀₀ Mn _0.95 Pd _0.05 O ₃ , La _1.00 Co _0.95 Pd _0.05 O ₃ , Pr _0.90 Sr _0.10 Mn _0.90 Pd _0.10 O ₃ , Nd _0.50 Y _0.50 Fe _0.57 Cu _0.38 Pd _0.05 O ₃ , La _1.05 Fe _0.57 Co _0.38 Pd _0.05 O _{3 + δ} , La _1.02 Fe _0.95 Pd _0.05 And O _{3 + δ} .

  In the perovskite complex oxide containing palladium as a composition, those represented by the following general formula (5) are also preferably used.

（式中、Ｌｎは、Ｌａ、Ｐｒ、Ｎｄ、Ｓｍ、ＥｕおよびＧｄから選択される少なくとも１種の必須成分と、Ｙ、Ｃｅ、Ｙｂ、Ｃａ、ＳｒおよびＢａから選択される少なくとも１種の任意成分とからなる元素を示し、Ｍは、Ｃｒ、Ｍｎ、Ｆｅ、Ｃｏ、ＮｉおよびＡｌから選択される少なくとも１種の元素を示し、ｘは、０．００１≦ｘ≦０．４の原子割合を示し、ｙは、０≦ｙ≦０．５の原子割合を示す。）

(Wherein Ln is at least one essential component selected from La, Pr, Nd, Sm, Eu and Gd, and at least one arbitrary selected from Y, Ce, Yb, Ca, Sr and Ba) And M represents at least one element selected from Cr, Mn, Fe, Co, Ni and Al, and x represents an atomic ratio of 0.001 ≦ x ≦ 0.4. Y represents an atomic ratio of 0 ≦ y ≦ 0.5.)

  In the general formula (5), Ln necessarily includes at least one essential component selected from La, Pr, Nd, Sm, Eu and Gd, and preferably at least selected from La, Nd and Gd. Contains one species. These elements may be used alone or in combination of two or more.

In the general formula (5), Ln may or may not contain at least one arbitrary component selected from Y, Ce, Yb, Ca, Sr and Ba.
For example, when the above-mentioned optional components are included, the layered perovskite complex oxide of the present invention can be represented by, for example, the following general formula (7), where Ln is an essential component and Ln ′ is an optional component.

  In the general formula (7), z represents the atomic ratio of the optional component Ln ′, for example, 0.01 ≦ z ≦ 0.5, and preferably 0.1 ≦ z ≦ 0.5. . That is, when the optional component Ln ′ is contained, the atomic ratio is preferably 0.5 or less.

In the general formula (5), the atomic ratio y of M is 0 ≦ y ≦ 0.5, that is, M is an optional component and may or may not be included. When included, the atomic ratio is 0.5 or less.
In the general formula (5), the atomic ratio x of Pd is 0.001 ≦ x ≦ 0.4, that is, an atomic ratio of 0.4 or less, and preferably 0.005 ≦ x ≦ 0.05. It is. If the atomic ratio of Pd exceeds 0.4, Pd may be difficult to dissolve, and further, an increase in cost is inevitable.
In the general formula (5), Cu is contained in the layered perovskite complex oxide in the atomic ratio of the remaining M and Pd (1-xy).

As such a layered perovskite complex oxide containing palladium, more specifically, for example, La ₂ Cu _0.95 Pd _0.05 O ₄ , Pr ₂ Cu _0.95 Pd _0.05 O ₄ Nd ₂ Cu _0.6 Pd _0.4 O ₄ , Nd ₂ Cu _0.8 Pd _0.2 O ₄ , Nd ₂ Cu _0.95 Pd _0.05 O ₄ , Nd ₂ Cu _0.99 Pd _0.01 O ₄ , Nd ₂ Cu _0.995 Pd _0.005 O ₄ , Nd ₂ Cu _0.999 Pd _0.001 O ₄ , Gd ₂ Cu _0.95 Pd _0.05 O ₄ , Gd ₂ Cu _0.94 Pd _{0 .01} O _3.95 , Gd ₂ Cu _0.99 5Pd _0.005 O ₄ , (La _0.6 Sr _0.4 ) ₂ Cu _0.95 Pd _0.05 O ₄ , (La _0.6 Sr _{0. 4) 2} Cu _{0.9 Pd 0.01 O 3.95, (Gd 0.6} Sr 0.4) 2 Cu 0.94 Pd 0.01 O 3.95, (Nd 0.92 Ce 0.08) 2 Cu 0.95 Pd 0 _.05 O ₄ , (La _0.5 Y _0.5 ) ₂ Cu _0.95 Pd _0.05 O _{4 and the} like.

  Such a perovskite type complex oxide containing palladium as a composition is not particularly limited, and an appropriate method for preparing the complex oxide, such as a coprecipitation method, a citric acid complex method, an alkoxide method, etc. Can be manufactured.

  In the coprecipitation method, for example, a mixed salt aqueous solution containing the salt of each element described above at a predetermined stoichiometric ratio is prepared, and a neutralizing agent is added to the mixed salt aqueous solution to perform coprecipitation. The precipitate is dried and then heat-treated.

  Examples of the salt of each element include inorganic salts such as sulfate, nitrate, chloride, and phosphate, and organic acid salts such as acetate and oxalate. Further, the mixed salt aqueous solution can be prepared, for example, by adding the salt of each element to water at a ratio that gives a predetermined stoichiometric ratio and stirring and mixing.

Thereafter, a neutralizing agent is added to the mixed salt aqueous solution to cause coprecipitation. Examples of the neutralizing agent include ammonia, for example, organic bases such as amines such as triethylamine and pyridine, and inorganic bases such as caustic soda, caustic potash, potassium carbonate, and ammonium carbonate.
The neutralizing agent is added so that the pH of the solution after adding the neutralizing agent is about 6 to 10.

  The obtained coprecipitate is washed with water as necessary, and dried by, for example, vacuum drying or ventilation drying, and then heat-treated at, for example, about 500 to 1000 ° C., preferably about 600 to 950 ° C. A perovskite complex oxide can be obtained.

  Further, in the citric acid complex method, for example, a citric acid mixed salt aqueous solution containing citric acid and the salt of each element described above is prepared so that the salt of each element described above has a predetermined stoichiometric ratio, This citric acid mixed salt aqueous solution is dried and solidified to form a citric acid complex of each element described above, and then the obtained citric acid complex is pre-baked and then heat-treated.

  Examples of the salt of each element include the same salts as described above. For the citric acid mixed salt aqueous solution, for example, a mixed salt aqueous solution is prepared in the same manner as described above, and an aqueous citric acid solution is added to the mixed salt aqueous solution. It can be prepared by adding.

  Thereafter, the citric acid mixed salt aqueous solution is dried to form a citric acid complex of each element described above. Drying quickly removes moisture at a temperature at which the formed citric acid complex does not decompose, for example, from room temperature to 150 ° C. Thereby, a citric acid complex of each element described above can be formed.

  The formed citric acid complex is subjected to heat treatment after calcination. Pre-baking may be performed by heating at 250 ° C. or higher in a vacuum or an inert atmosphere, for example. Thereafter, the perovskite type complex oxide can be obtained by heat treatment at about 500 to 1000 ° C., preferably about 600 to 950 ° C.

  Further, in the alkoxide method, for example, a mixed alkoxide solution containing the alkoxide of each of the above elements excluding the noble metal containing Pd in the above stoichiometric ratio is prepared, and a salt of the noble metal containing Pd is added to the mixed alkoxide solution. After adding the aqueous solution containing and making it precipitate by hydrolysis, the obtained deposit is dried and heat-processed.

  Examples of the alkoxide of each element include an alcoholate formed from each element and an alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, and an alkoxy alcoholate of each element represented by the following general formula (8). Can be mentioned.

（式中、Ｅは、各元素を示し、Ｒ_３は、水素原子または炭素数１〜４のアルキル基を示し、Ｒ_４は、炭素数１〜４のアルキル基を示し、ｉは、１〜３の整数、ｊは、２〜３の整数を示す。）

(In the formula, E represents each element, R ₃ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ₄ represents an alkyl group having 1 to 4 carbon atoms, and i represents 1 to 1) (An integer of 3 and j represents an integer of 2 to 3)

More specifically, examples of the alkoxy alcoholate include methoxyethylate, methoxypropylate, methoxybutyrate, ethoxyethylate, ethoxypropylate, propoxyethylate, butoxyethylate, and the like.
And a mixed alkoxide solution can be prepared by, for example, adding the alkoxide of each element to an organic solvent so that it may become said stoichiometric ratio, and stirring and mixing.

  The organic solvent is not particularly limited as long as the alkoxide of each element can be dissolved. For example, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, ketones, esters and the like are used. Preferably, aromatic hydrocarbons such as benzene, toluene and xylene are used.

  Thereafter, an aqueous solution containing a noble metal salt containing Pd at a predetermined stoichiometric ratio is added to the mixed alkoxide solution to cause precipitation. Examples of the aqueous solution containing a noble metal salt containing Pd include an aqueous nitrate solution, an aqueous chloride solution, an aqueous hexaammine chloride solution, an aqueous dinitrodiammine nitric acid solution, hexachloroacid hydrate, and potassium cyanide salt.

  The resulting precipitate is dried by, for example, vacuum drying or ventilation drying, and then heat-treated at, for example, about 500 to 1000 ° C., preferably about 500 to 850 ° C., so that the perovskite complex oxide Can be obtained.

  In such an alkoxide method, for example, a mixed solution containing a precious metal organometallic salt containing Pd is mixed with the mixed alkoxide solution described above to prepare a uniform mixed solution, and water is added thereto to cause precipitation. Thereafter, the obtained precipitate can be dried and then heat-treated.

  Examples of organometallic salts of noble metals containing Pd include noble metal carboxylates containing Pd formed from acetates, propionates, etc., for example, the following general formula (9) or the following general formula (10): And metal chelate complexes of noble metals containing Pd, such as diketone complexes of noble metals containing Pd formed from diketone compounds.

（式中、Ｒ_５は、炭素数１〜４のアルキル基、炭素数１〜４のフルオロアルキル基またはアリール基、Ｒ_６は、炭素数１〜４のアルキル基、炭素数１〜４のフルオロアルキル基、アリール基または炭素数１〜４のアルキルオキシ基、Ｒ７は、水素原子または炭素数１〜４のアルキル基を示す。）

(In the formula, R ₅ is an alkyl group having 1 to 4 carbon atoms, a fluoroalkyl group having 1 to 4 carbon atoms or an aryl group, and R ₆ is an alkyl group having 1 to 4 carbon atoms and a fluoro having 1 to 4 carbon atoms. An alkyl group, an aryl group, or an alkyloxy group having 1 to 4 carbon atoms, R7 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

（式中、Ｒ_８は、水素原子または炭素数１〜４のアルキル基を示す。）

(In the formula, R ₈ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.)

In the general formula (9) and the general formula (10), examples of the alkyl group having 1 to 4 carbon atoms of R ₅ , R ₆ , R ₇ and R ₈ include methyl, ethyl, propyl, isopropyl, n- Examples include butyl, s-butyl, t-butyl and the like. Moreover, as a C1-C4 fluoroalkyl group of R5 and R6, trifluoromethyl etc. are mentioned, for example. Examples of the aryl group for R ₅ and R ₆ include phenyl. Examples of the alkyloxy group having 1 to 4 carbon atoms of R ₆ include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, s-butoxy, t-butoxy and the like.

  More specific examples of the diketone compound include 2,4-pentanedione, 2,4-hexanedione, 2,2-dimethyl-3,5-hexanedione, 1-phenyl-1,3-butanedione, -Trifluoromethyl-1,3-butanedione, hexafluoroacetylacetone, 1,3-diphenyl-1,3-propanedione, dipivaloylmethane, methyl acetoacetate, ethyl acetoacetate, t-butyl acetoacetate It is done.

  Moreover, the solution containing the organometallic salt of the noble metal containing Pd is prepared, for example, by adding the organometallic salt of the noble metal containing Pd to the organic solvent so as to have the above stoichiometric ratio and stirring and mixing. be able to. Examples of the organic solvent include the organic solvents described above.

  Then, the solution containing the organometallic salt of the noble metal containing Pd prepared in this way is mixed with the above mixed alkoxide solution to prepare a uniform mixed solution, and then water is added to this to precipitate. The resulting precipitate is dried by, for example, vacuum drying or ventilation drying, and then heat-treated at, for example, about 400 to 1000 ° C., preferably about 500 to 850 ° C., thereby obtaining a perovskite complex oxide. Can be obtained.

  Moreover, in order to carry | support palladium in the obtained perovskite type complex oxide, it does not restrict | limit in particular, A well-known method can be used. For example, a solution of a salt containing palladium may be prepared, and the salt-containing solution may be impregnated in a perovskite complex oxide and then fired. The amount of palladium supported on the perovskite complex oxide is, for example, 20 parts by weight or less, preferably 0.5 to 5 parts by weight with respect to 100 parts by weight of the perovskite complex oxide.

<Preparation of palladium nanoparticles and nanoparticles>
In the present invention, nanoparticles are prepared by subjecting a heterogeneous palladium catalyst to an alkali treatment.

  Examples of the alkali used for the alkali treatment in the present invention include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium acetate, Alkali metal acetates such as potassium acetate, alkali metal phosphates such as sodium phosphate and potassium phosphate; alkaline earth metal hydroxides such as barium hydroxide and calcium hydroxide, alkaline earths such as barium carbonate and calcium carbonate Alkali earth metal acetates such as alkali metal carbonates, calcium acetate and barium acetate, alkaline earth metal phosphates such as barium phosphate and calcium phosphate; ammonia, amines and the like. Furthermore, amines such as diethylamine, diisopropylamine and triethylamine, and organic alkalis such as pyridine, morpholine, quinoline, piperidine, diazabicycloundecene (DBU) and anilines may be used. These alkalis 1 type or 2 types may be mixed and used.

As the alkali used for the alkali treatment of the present invention, alkali metal hydroxide, alkali metal carbonate, and alkali metal phosphate are preferable.
The usage-amount of an alkali is 20-4500 weight part normally with respect to palladium containing perovskite type complex oxide, Preferably it is 20-100 weight part, More preferably, it is 85-90 weight part. Moreover, the density | concentration of the aqueous alkali solution used for an alkali treatment is 0.05-saturation concentration normally, Preferably it is 15-20 weight%.

  In the present invention, the alkali treatment is performed by dispersing a heterogeneous palladium catalyst in an alkaline aqueous solution. The heterogeneous palladium catalyst may be charged in the alkaline aqueous solution all at once, or the heterogeneous palladium catalyst may be charged in several times. In order to disperse | distribute a heterogeneous palladium catalyst efficiently in an alkaline solution, it is preferable to stir. The reaction temperature is usually in the range of 0 to 100 ° C, and preferably 20 to 60 ° C from the viewpoint of reaction efficiency. The reaction time varies depending on the reaction temperature and the type of heterogeneous palladium catalyst and alkali, but is usually completed in 30 minutes to 24 hours. Preferably, it is 30 minutes to 4 hours.

  The palladium nanoparticles in the present invention prepared by alkali treatment have a particle diameter of 1000 nm or less, preferably 30 nm or less. The particle diameter is measured by particle size distribution measurement by the photon correlation method. Identification of the structure of the palladium nanoparticles is difficult by alkali treatment of heterogeneous palladium. Therefore, the palladium nanoparticles are defined by treating the heterogeneous catalyst with an alkali and the particle size (particle size is 1000 nm or less, preferably 30 nm or less).

  Moreover, you may implement this alkali treatment 2-3 times according to the production | generation degree of a palladium nanoparticle.

  The alkali suspension obtained by the alkali treatment can be used as it is in the Sonogashira-Hagiwara reaction as a catalyst, but the suspension is preferably filtered through a 0.1 μm membrane filter. By filtering with a 0.1 μm filter, the particle diameter can be reduced to 1000 nm or less, and the reaction efficiency can be improved.

  Moreover, the alkali suspension solution prepared by alkali treatment and containing the palladium nanoparticles of the present invention can be concentrated and dried. As a method for concentration and drying, it is sufficient that the aqueous solution is evaporated under reduced pressure or the like to solidify the lysate, and a rotary evaporator, a centrifugal evaporator, freeze drying, spray drying, or the like can be used.

  In addition, the solid heterogeneous palladium particles concentrated and dried can be used for the Sonogashira-Hagiwara reaction as a catalyst. By solidifying the palladium nanoparticles, the handling property is improved on the reaction surface and the like as compared with the case of using them in a solution.

<Soto-Hagiwara reaction>
First, general formula (1) and general formula (2) will be described.

（式中、Ｒ_１は、アリール基、複素環基またはアルケニル基を示し、Ｘは、ハロゲン原子または、−ＯＳＯ_２Ｗ（Wは、アルキル基またはアリール基を示す。）を示す。）

(In the formula, R ₁ represents an aryl group, a heterocyclic group or an alkenyl group, and X represents a halogen atom or —OSO ₂ W (W represents an alkyl group or an aryl group).)

（式中、Ｒ_２は、アルキル基、シクロアルキル基、アリール基、複素環基、アルケニル基、アルキニル基またはトリアルキル置換シリル基を示す。）

(Wherein R ₂ represents an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkenyl group, an alkynyl group or a trialkyl-substituted silyl group.)

Specific examples of the aryl group represented by R ₂ R ₁ and of the general formula (1) (2), a phenyl group, a naphthyl group, a tolyl group, a xylyl group, a biphenyl group, anthryl group, phenanthryl group and azulenyl Group and the like.

Aryl group represented by R ₂ R ₁ and the general formula (2) of the general formula (1) may be substituted with other groups, the substituent is not particularly limited, a hydrocarbon group, a hetero atom Substituents corresponding to the purpose and use, such as a containing hydrocarbon group, can be mentioned as appropriate. For example, an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group, such as a vinyl group and a 1-methylvinyl group , An allenyl group having 2 to 4 carbon atoms such as 1-propenyl group and allyl group, for example, an alkynyl group having 2 to 4 carbon atoms such as ethynyl group, 1-propynyl group and 1-propargyl group, for example, cyclopropyl group, C3-C6 cycloalkyl group such as cyclobutyl group, cyclopentyl group and cyclohexyl group, for example, cycloalkenyl group such as cyclopentenyl group and cyclohexenyl group, such as benzyl group, α-methylbenzyl Group, aralkyl group having 7 to 11 carbon atoms such as phenethyl group, phenyl group, for example, methoxy group, ethoxy group C 1-6 alkoxy group such as propoxy group, iso-propoxy group, n-butoxy group, iso-butoxy group, sec-butoxy group, tert-butoxy group, phenoxy group, for example, formyl group, acetyl group, propionyl Group, alkanoyl group having 1 to 6 carbon atoms such as n-butyryl group and iso-butyryl group, benzoyl group such as formyloxy group, acetyloxy group, propionyloxy group, n-butyryloxy group and iso-butyryloxy group C1-C6 alkanoyloxy group, benzoyloxy group, carboxyl group, for example, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, iso-propoxycarbonyl group, n-butoxycarbonyl group, isobutoxycarbonyl group, tert-butoxyca A C2-C7 alkoxycarbonyl group such as a rubonyl group, a carbamoyl group, such as an N-methylcarbamoyl group, an N-ethylcarbamoyl group, an N-propylcarbamoyl group, an N-isopropylcarbamoyl group, an N-butylcarbamoyl group, etc. such as N- mono- _{-C 1-4} alkylcarbamoyl group, for example, N, N- dimethylcarbamoyl group, N, N- diethylcarbamoyl group, N, N- dipropylcarbamoyl group, N, N- N, such as dibutyl carbamoyl group , N-di-C _1-4 alkylcarbamoyl group such as 1-acetylidinylcarbonyl group, 1-azetidinylcarbonyl group, 1-pyrrolidinylcarbonyl group, 1-piperidinylcarbonyl group, N-methyl Cyclic aminocarbonyl such as piperazinylcarbonyl group and morpholinocarbonyl group , For example, fluorine, chlorine, bromine, mono- such as a halogen atom, such as chloromethyl group, dichloromethyl group, trifluoromethyl group, trifluoroethyl group such as iodine -, di - or tri - halogeno -C _{1- 4-} alkyl group, oxo group, amidino group, imino group, amino group, for example, mono- _C1-4 alkylamino group such as methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, for example Di-C _1-4 alkylamino groups such as dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, for example, acetylidinyl group, azetidinyl group, pyrrolidinyl group, pyrrolinyl group, pyrrolyl group, imidazolyl Group, pyrazolyl group, imidazolidinyl group, piperidino group, In addition to carbon atom and one nitrogen atom such as ruphorino group, dihydropyridyl group, pyridyl group, N-methylpiperazinyl group, N-ethylpiperazinyl group, etc., it was selected from oxygen atom, sulfur atom, nitrogen atom, etc. 3 to 6 membered cyclic amino group which may contain 1 to 3 heteroatoms, such as formamide group, acetamide group, trifluoroacetamide group, propionylamide group, butyrylamide group, isobutyrylamide group, etc. C1-C6 alkanoylamide group, benzamide group, carbamoylamino group, for example, N-methylcarbamoylamino group, N-ethylcarbamoylamino group, N-propylcarbamoylamino group, N-isopropylcarbamoylamino group, N- N—C _1-4 alkylcarbamoylamino group such as butylcarbamoylamino group However, N, N-di-C ₁ such as N, N-dimethylcarbamoylamino group, N, N-diethylcarbamoylamino group, N, N-dipropylcarbamoylamino group, N, N-dibutylcarbamoylamino group, etc. _-4 alkylcarbamoylamino groups, for example, alkylenedioxy groups having 1 to 3 carbon atoms such as methylenedioxy group and ethylenedioxy group, hydroxy groups, epoxy groups (-O-), nitro groups, cyano groups, mercapto groups , Sulfo group, sulfino group, phosphono group, sulfamoyl group, for example, N-methylsulfamoyl group, N-ethylsulfamoyl group, N-propylsulfamoyl group, N-isopropylsulfamoyl group, N-butyl C1-C6 monoalkylsulfamoyl groups such as sulfamoyl groups such as N, N-dimethyls Di-C _1-4 alkylsulfamoyl groups such as rufamoyl group, N, N-diethylsulfamoyl group, N, N-dipropylsulfamoyl group, N, N-dibutylsulfamoyl group, for example, methylthio group Alkylthio group having 1 to 6 carbon atoms such as ethylthio group, propylthio group, isopropylthio group, n-butylthio group, sec-butylthio group, tert-butylthio group, phenylthio group, for example, methylsulfinyl group, ethylsulfinyl group, propyl C1-C6 alkyl sulfinyl groups, such as sulfinyl groups and butyl sulfinyl groups, phenyl sulfinyl groups, for example, methylsulfonyl groups, ethylsulfonyl groups, propylsulfonyl groups, butylsulfonyl groups, etc., alkylsulfonyl groups having 1-6 carbon atoms And phenylsulfonyl group Etc. The above groups may be substituted with 1 to 5 of these substituents.

The heterocyclic group represented by _{R 2 R 1} and of the general formula (1) (2), for example, 2- or 3-thienyl group, 2- or 3-furyl group, 2- or 3-pyronyl Group, 2-, 3- or 4-pyridyl group, 2-, 4- or 5-oxazolyl group, 2-, 4- or 5-thiazolyl group, 3-, 4- or 5-pyrazolyl group, 2-, 4- or 5-imidazolyl group, 3-, 4- or 5-isoxazolyl group, 3-, 4- or 5-isothiazolyl group, 3- or 5- (1,2,4-oxadiazolyl) group, 1,3 , 4-oxadiazolyl group, 3- or 5- (1,2,4-thiadiazolyl) group, 1,3,4-thiadiazolyl group, 4- or 5- (1,2,3-thiadiazolyl) group, 1,2 , 5-thiadiazolyl group, 1,2,3-tria 5-membered ring group containing 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like in addition to carbon atom such as ryl group, 1,2,4-triazolyl group, 1H- or 2H-tetrazolyl group For example, N-oxide-2-, 3- or 4-pyridyl group, 2-, 4- or 5-pyrimidinyl group, N-oxide-2-, 4- or 5-pyrimidinyl group, thiomorpholinyl group, morpholinyl group, Oxoimidazinyl group, dioxotriazinyl group, pyrrolidinyl group, piperidinyl group, pyranyl group, thiopyranyl group, 1,4-oxazinyl group, 1,4-thiazinyl group, 1,3-thiazinyl group, piperazinyl group, Carbon such as triazinyl group, oxotriazinyl group, 3- or 4-pyridazinyl group, pyrazinyl group, N-oxide-3- or 4-pyridazinyl group In addition to atoms, a 6-membered cyclic group containing 1 to 4 heteroatoms selected from oxygen, sulfur, nitrogen, etc., for example, benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo [1,5-b ] Pyridazinyl group, triazolo [4,5-b] pyridazinyl group, benzimidazolyl group, quinolyl group, isoquinolyl group, cinnolinyl group, phthalazinyl group, quinazolinyl group, quinoxalinyl group, indolizinyl group, quinolidinyl group, 1,8-naphthyridinyl group, purinyl Group, pteridinyl group, dibenzofuranyl group, carbazolyl group, acridinyl group, phenanthridinyl group, chromanyl group, benzoxazinyl group, phenazinyl group, phenothiazinyl group, phenoxazinyl group, oxygen atom, sulfur Selected from atoms, nitrogen atoms, etc. In addition to carbon atoms such as bicyclic or tricyclic fused ring groups containing 1 to 4 terror atoms, for example, 5 to 8 membered rings containing 1 to 4 heteroatoms such as oxygen atoms, sulfur atoms and nitrogen atoms Or the condensed ring etc. are mentioned.

Formula heterocyclic group represented by R ₂ R ₁ and the general formula (2) (1) may be substituted with other groups, the substituent is not particularly limited, a hydrocarbon group, a hetero Substituents corresponding to the purpose and use such as an atom-containing hydrocarbon group can be appropriately mentioned. For example, the same substituents as described above can be mentioned. The above groups may be substituted with 1 to 5 of these heterocyclic groups.

The alkenyl group represented by _{R 2 R 1} and of the general formula (1) (2), for example, vinyl group, allyl group, methallyl group, isopropenyl group, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl group, butenyl group, pentenyl group, hexenyl group, heptynyl group, octenyl group, nonenyl group, decenyl group, undecenyl group, dodecenyl group, tetradecenyl group, hexadecenyl group, octadecenyl group, etc. There are 18 alkenyl groups.

Alkenyl group represented by R ₂ R ₁ and the general formula (2) of the general formula (1) may be substituted with other groups, the substituent is not particularly limited, a hydrocarbon group, a hetero atom Substituents corresponding to the purpose and use, such as a containing hydrocarbon group, can be mentioned as appropriate. For example, the same substituents as described above can be mentioned. In these substituents, 1 to 5 alkenyl groups may be substituted.
X in the general formula (1) represents a halogen atom or —OSO ₂ W (W represents an alkyl group or an aryl group).

Examples of the alkyl group represented by W include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group and the like.
Examples of the aryl group represented by W include a phenyl group and a naphthyl group.
Examples of the halogen atom represented by X include chlorine, bromine, iodine and the like. X is preferably a chlorine atom, a bromine atom, an iodine atom, —SO ₂ Ph, or —SO ₂ Me.

Examples of the alkyl group represented by R ₂ in the general formula (2) include methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, iso-pentyl, Examples thereof include alkyl groups having 1 to 18 carbon atoms such as sec-pentyl, hexyl, heptyl, n-octyl, isooctyl, 2-ethylhexyl, nonyl, decyl, isodecyl, dodecyl, tetradecyl, hexadecyl, octadecyl and the like.

  The alkyl group may have a substituent, and the substituent is not particularly limited, and substituents corresponding to the purpose and use such as a hydroxyl group, a hydrocarbon group, a heteroatom-containing hydrocarbon group, and the like can be mentioned as appropriate. It is done. For example, the same substituents as described above can be mentioned.

The alkynyl group represented by _{R 2} in the general formula (2), for example, ethynyl, 2-propynyl, 3-hexynyl, and an alkynyl group having 2 to 10 carbon atoms such as 1-octenyl. The alkynyl group may have a substituent, and the substituent is not particularly limited, and examples thereof include substituents corresponding to the purpose and application such as a hydrocarbon group and a heteroatom-containing hydrocarbon group. For example, the same substituents as described above can be mentioned. 1 to 5 of these substituents may be substituted on the heterocyclic group.

Examples of the trialkyl-substituted silyl group represented by R ₂ in the general formula (2) include 1 to 3 carbon atoms such as trimethylsilyl group, triethylsilyl group, tripropylsilyl group, dimethyl t-butylsilyl group, and tridecylsilyl group. A silyl group in which three 10 alkyl groups are substituted is exemplified.
And in the reaction of the compound represented by the general formula (1) and the compound represented by the general formula (2), a compound represented by the following general formula (3) is generated.

（式中、Ｒ_１およびＲ_２は、一般式（１）および一般式（２）に同じ。）

(In the formula, R ₁ and R ₂ are the same as those in the general formula (1) and the general formula (2).)

  In the method for synthesizing the compound of the present invention, the reaction between the compound represented by the general formula (1) and the compound represented by the general formula (2) is represented by the following formula (A). The reaction is carried out in the presence of palladium nanoparticles and a base given by the Sakakibara reaction and prepared by alkali treatment of the heterogeneous palladium catalyst described above. In the present invention, the reaction efficiency can be greatly improved by applying palladium nanoparticles prepared by alkaline treatment of a heterogeneous palladium catalyst as a palladium catalyst for Sonogashira-Hagiwara coupling.

In this reaction, examples of the base include ammonia, for example, di- or trialkylamines such as diethylamine and triethylamine, organic bases such as pyridine, morpholine, quinoline, piperidine, DBU (diazabicycloundecene), anilines, For example, hydroxides such as sodium hydroxide and potassium hydroxide, for example, carbonates such as sodium carbonate (Na ₂ CO ₃ ), potassium carbonate (K ₂ CO ₃ ), cesium carbonate (Cs ₂ CO ₃ ), for example, Examples thereof include inorganic salts such as phosphates such as sodium phosphate (Na ₃ PO ₄ ) and potassium phosphate (K ₃ PO ₄ ). Such bases may be used alone or in combination of two or more.

  In this reaction, the blending ratio of the compound represented by the general formula (1) and the compound represented by the general formula (2) is not particularly limited. For example, in the general formula (2), The compound represented is 0.1-10 equivalent with respect to the compound represented by the said General formula (1), Preferably, 0.5-3 equivalent is mix | blended.

In this reaction, the palladium-containing perovskite complex oxide is not particularly limited, but is added in an amount of, for example, 0.001 to 10 mol%, preferably 0.01 to 5 mol% as the palladium content.
In this reaction, the base is not particularly limited, but may be, for example, 1 equivalent or more, and may be used in a large amount as a reaction solvent in some cases.

And this reaction is, for example, reaction pressure 0 to 5000 KPa, preferably 0 to 3000 KPa, reaction temperature −20 to 250 ° C., preferably 0 to 180 ° C., reaction time 0.1 to 72 hours, preferably 0 The reaction is performed for 5 to 24 hours.
In order to accelerate the reaction, it is also effective to heat by microwave irradiation.

  In this reaction, a reaction solvent may be used, and as such a reaction solvent, for example, a protic polar solvent such as water, for example, alcohols such as methanol, ethanol, isopropanol (IPA), and glycol, for example, Aprotic polar solvents such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), acetonitrile, piperidine, such as the amines described above For example, ethers such as dioxane and tetrahydrofuran (THF), and aromatic hydrocarbons such as benzene, toluene and xylene. These reaction solvents may be used alone or in combination of two or more.

  In this reaction, an additive for promoting the reaction can be added. Examples of such additives include organic ammonium halides such as tetra-n-butylammonium bromide (TBAB). In addition, 1-200 mol% of additives are added, for example.

  More specifically, this reaction is performed, for example, by subjecting the compound represented by the general formula (1) and the compound represented by the general formula (2) to an alkali treatment from a heterogeneous palladium catalyst. The compound represented by the above general formula (3) can be obtained by adding the prepared palladium nanoparticles and base together with the reaction solvent in the above ratio and reacting under the above reaction conditions.

In the method for synthesizing the compound of the present invention, the compound represented by the general formula (3) can be synthesized with high yield by the Sonogashira-Hagiwara reaction in the presence of palladium nanoparticles.
Further, in the method for synthesizing the compound of the present invention, since the amount of palladium used is reduced by using a nano-sized palladium catalyst, it is possible to reduce the environmental burden and the production cost due to the discharge of the synthesis reaction catalyst. Therefore, the method for synthesizing the compound of the present invention can be effectively used in, for example, industrial uses of the Sonogashira-Hagiwara reaction, for example, in the production of pharmaceutical intermediates, synthetic polymer materials, liquid crystal materials, optical materials and the like. it can.

EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated further in detail, these Examples do not limit this invention at all.
The palladium content in the aqueous solution containing palladium nanoparticles is measured by atomic absorption spectrometry, the particle size of palladium nanoparticles is measured by a submicron particle analyzer, and the reaction conversion rate and purity are measured by gas chromatography under the following conditions. did.

[Measurement conditions for atomic absorption analysis]
Device: Z-2000
Measuring principle: Graphite furnace method photometry / BKG correction format: Polarized Zeeman method

[Measurement conditions of submicron particle analyzer]
Equipment: DeltaNano
Measurement principle: Photon correlation method Dispersion medium: Water Ultrasound: None

[Measurement conditions for gas chromatography]
Device: GC14B manufactured by Shimadzu Corporation
Detector: TCD
Column: 10% Silicon SE-30 2m
Mobile phase: He
Flow rate: 50 mL / min
Temperature: 100-300 ° C (10 ° C / min)

[Production Example 1] Preparation of aqueous potassium carbonate-containing potassium carbonate solution from LaFe _0.95 Pd _0.05 O ₃ (Hokuko Chemical Co., Ltd.) LaFe _0.95 Pd _0.05 O _{3 in} 40 g of 20 wt% aqueous potassium carbonate solution 92 mg was added and stirred as a suspension at room temperature for 2 hours. The suspension was filtered through a 0.1 μm membrane filter to obtain 38.6 g of an alkaline aqueous solution containing palladium nanoparticles. The Pd content in the obtained alkaline aqueous solution was 0.41 mg, and the palladium particles in the alkaline aqueous solution had a particle size of 32 to 600 nm.

Production Example 2 _Nd 2 _Cu 0.95 _{Pd 0.05} palladium nanoparticles containing preparation 20 wt% aqueous potassium carbonate solution 40g of aqueous potassium carbonate solution from _{O 4 Nd 2 Cu 0.95 Pd 0.05} O 4 157mg was added The mixture was stirred as a suspension at room temperature for 2 hours. The suspension was filtered through a 0.1 μm membrane filter to obtain 39.2 g of an alkaline aqueous solution containing palladium nanoparticles. The Pd content in the obtained alkaline aqueous solution was 1.12 mg, and the palladium particles in the alkaline aqueous solution had a particle size of 15 to 1000 nm.

The Production Example 3 _{Nd 2 Cu 0.95 Pd 0.05 Nd 2} Cu 0.95 Pd 0.05 O 4 157mg to prepare 20 wt% aqueous potassium phosphate 40g of palladium nanoparticles containing potassium phosphate from O ₄ In addition, the suspension was stirred at room temperature for 2 hours. The suspension was filtered through a 0.1 μm membrane filter to obtain 39.2 g of an aqueous potassium phosphate solution containing palladium nanoparticles. The aqueous solution was concentrated under reduced pressure to obtain 9.0 g of solid palladium nanoparticle-containing potassium phosphate. The Pd content in the obtained potassium phosphate was 12.8 mg, and the palladium particles had a particle size of 15 to 1000 nm.

Production Example 4] _LaFe 0.95 _{Pd 0.05} O to prepare 20 wt% aqueous potassium phosphate 200g of palladium nanoparticles containing potassium phosphate from _{3 LaFe} 0.95 _{Pd 0.05} O _{3 461.0mg} added, The suspension was stirred at room temperature for 2 hours. The suspension was filtered through a 0.1 μm membrane filter to obtain 197.3 g of an aqueous potassium carbonate solution containing palladium nanoparticles. This aqueous solution was concentrated under reduced pressure to obtain 49.1 g of solid palladium nanoparticle-containing potassium phosphate. The Pd content in the obtained potassium phosphate was 3.83 mg, and the palladium particles had a particle size of 32 to 600 nm.

[Example 1] Synthesis example of diphenylacetylene by Sonogashira-Hagiwara reaction (1)
Iodobenzene and phenylacetylene were reacted in the presence of the palladium nanoparticles produced in Production Example 1 as shown in the following reaction formula (B).

2.04 g (0.01 mol) of iodobenzene, 1.53 g (0.015 mol) of phenylacetylene, and 4.22 g (0.02 mol) of potassium phosphate were added with a stirrer, a thermometer and a refluxer. Into a 50 mL round bottom flask purged with nitrogen, 20 mL of methyl cellosolve / water (1: 1) was weighed and added.
Next, 10.02 g of an alkaline aqueous solution containing a palladium nanoparticle catalyst from LaFe _0.95 Pd _0.05 O ₃ synthesized in Production Example 1 (Pd amount is 0.01 mol% with respect to iodobenzene) was added, The mixture was heated in an oil bath and heated to reflux at 80 ° C. for 8 hours. After completion of the reaction, 15 mL of toluene and 10 mL of water were added to separate the organic layer. The organic layer was concentrated by an evaporator, and the obtained concentrated residue was purified by silica gel column chromatography to obtain the desired product.
In addition, the addition amount of palladium nanoparticles is represented by mol% with respect to iodobenzene. For example, 0.01 mol% represents that 1.0 × 10 ⁻⁶ mol of palladium nanoparticles is added as Pd.

The conversion rate was calculated | required by following Formula (1), analyzing the organic layer after the said reaction with a gas chromatograph.

For diphenylacetylene and iodobenzene, these toluene solutions were individually measured in advance and the relative sensitivity was determined and corrected.
Also, the turnover number (Turnover number (TON)) was determined as the number of moles of diphenylacetylene obtained per mole of palladium from the amount of added palladium and the conversion rate of diphenylacetylene.
The results are shown in Table 1.

[Examples 2 to 3] Synthesis example of diphenylacetylene by Sonogashira-Hagiwara reaction (2)
In the presence of the palladium nanoparticles produced in Production Examples 3 to 4, iodobenzene and phenylacetylene were reacted as shown in the general formula (B).
2.04 g (0.01 mol) of iodobenzene, 1.53 g (0.015 mol) of phenylacetylene, and 4.22 g (0.02 mol) of potassium phosphate were added with a stirrer, a thermometer and a refluxer. Into a 50 mL round bottom flask purged with nitrogen, 20 mL of methyl cellosolve / water (1: 1) was weighed and added.
Subsequently, the palladium nanoparticles synthesized in Production Examples 3 to 4 were added so that the amount of Pd was 0.01 mol% with respect to iodobenzene, heated in an oil bath, and heated to reflux at 80 ° C. for 8 hours. After completion of the reaction, 15 mL of toluene and 10 mL of water were added to separate the organic layer. The organic layer was concentrated by an evaporator, and the obtained concentrated residue was purified by silica gel column chromatography to obtain the desired product.

In addition, the addition amount of palladium nanoparticles is represented by mol% with respect to iodobenzene. For example, 0.01 mol% represents that 1.0 × 10 ⁻⁶ mol of palladium nanoparticles is added as Pd.
Further, conversion, correction of iodobenzene and diphenylacetylene, and calculation of the turnover number were performed in the same manner as in Example 1.

The results are shown in Table 1.
In addition, Table 1 shows the results of using the catalyst described in Patent Document 1 (International Publication No. 2005-105719 pamphlet) as a comparative example.

[Examples 4 to 11] Synthesis example of 4-substituted diphenylacetylene by Sonogashira-Hagiwara reaction (1)
In the presence of the palladium nanoparticles produced in Production Example 1 described above, 4-iodolane and phenylacetylene were reacted as shown in the following reaction formula (C).

4-iodolane (0.01 mol), 1.53 g (0.015 mol) of phenylacetylene and 4.22 g (0.02 mol) of potassium phosphate under the same conditions as in Example 1 The reaction was carried out using (Examples 2 to 9).
The conversion rate was obtained by the following equation (2) by analyzing the organic layer after the reaction by gas chromatography.

In addition, about 4-substituted diphenylacetylene and 4-iodolane, these toluene solutions were measured separately beforehand, and the relative sensitivity was calculated | required and correct | amended.
The turnover number (turnover number (TON)) was determined as the number of moles of 4-substituted diphenylacetylene obtained per mole of palladium from the amount of added palladium and the conversion rate of 4-substituted diphenylacetylene.
The results are shown in Table 2.

[Examples 12 to 19] Synthesis example of 2-substituted diphenylacetylene by Sonogashira-Hagiwara reaction (2)
In the presence of the palladium nanoparticles produced in Production Example 4 described above, 4-iodolane and phenylacetylene were reacted as shown in Reaction Formula (C).
4-iodolane (0.01 mol), 1.53 g (0.015 mol) of phenylacetylene, 4.22 g (0.02 mol) of potassium phosphate were added to a nitrogen apparatus equipped with a stirrer, a thermometer and a refluxer. To the substituted 50 mL round bottom flask, 20 mL of methyl cellosolve / water (1: 1) was weighed and added.

Next, 1.36 g of palladium nanoparticles synthesized in Production Example 5 (Pd amount is 0.01 mol% with respect to 4-iodolane) was added, heated in an oil bath, and heated to reflux at 80 ° C. for 8 hours. . After completion of the reaction, 15 mL of toluene and 10 mL of water were added to separate the organic layer. The organic layer was concentrated by an evaporator, and the obtained concentrated residue was purified by silica gel column chromatography to obtain the desired product. In addition, the addition amount of palladium nanoparticles is represented by mol% with respect to 4-iodobenzene. For example, 0.01 mol% represents that 1.0 × 10 ⁻⁶ mol of palladium nanoparticles is added as Pd. Yes.

The conversion rate, correction of 4-substituted diphenylacetylene and 4-iodolane, and calculation of the turnover number were calculated in the same manner as in Examples 4 to 11.
The results are shown in Table 3.

    As described above, the catalyst for palladium nanoparticles is superior to the case of using a conventional palladium catalyst, and the method for synthesizing the compound of the present invention can be used for industrial uses of Sonogashira-Hagiwara reaction, for example, pharmaceutical intermediates. It can be effectively used for the synthesis of body, synthetic polymer material, liquid crystal material, optical material and the like.

Claims (1)

The complex oxide in which the heterogeneous palladium catalyst is a palladium-containing perovskite complex oxide represented by the following general formula (4) or the following general formula (5), an alkali is an alkali metal hydroxide, an alkali metal carbonate salt, in the presence of palladium nanoparticles prepared by alkali treatment is dispersed in an alkaline aqueous solution comprising one or two kinds selected from alkali metal phosphate is represented by the following general formula (1) And a compound represented by the following general formula (2) are reacted: A method for synthesizing the compound represented by the general formula (3).

[Wherein, R ₁ represents an aryl group, a heterocyclic group or an alkenyl group, and X represents a halogen atom or —OSO ₂ W (W represents an alkyl group or an aryl group). ]

[Wherein R ₂ represents an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkenyl group, an alkynyl group or a trialkyl-substituted silyl group. ]

[Wherein, R ₁ represents the same group as in general formula (1), and R ₂ represents the same group as in general formula (2). ]

[In the formula, A represents at least one element selected from rare earth elements, A ′ represents at least one element selected from alkaline earth metals, and B represents a transition element (rare earth element, Cu and And at least one element selected from Al, x represents an atomic ratio of 0 ≦ x ≦ 1.0, y represents an atomic ratio of 0 ≦ y <0.5, z represents an atomic ratio of 0 <z <0.5. ]

[Wherein Ln is at least one essential component selected from La, Pr, Nd, Sm, Eu and Gd, and at least one arbitrary selected from Y, Ce, Yb, Ca, Sr and Ba And M represents at least one element selected from Cr, Mn, Fe, Co, Ni and Al, and x represents an atomic ratio of 0.001 ≦ x ≦ 0.4. Y represents an atomic ratio of 0 ≦ y ≦ 0.5. ]