Additives for mechanochemical reactions, mechanochemical methods, ligand compounds, and complexes

Abstract

The present invention addresses the problem of providing mechanochemical reaction additive that can be handled in air, that can be easily synthesized, that when used in a mechanochemical reaction can increase the activity of the mechanochemical reaction, and that can be applied to a wide variety of substrates under gentle conditions. Provided as a solution is a mechanochemical reaction additive comprising at least a ligand compound (Lx) or a salt thereof, wherein the ligand compound (Lx) is one or more compounds from among phosphorus-based compounds, bipyridine compounds, and N-heterocyclic carbene-based compounds, the ligand compound (Lx) has a polymer chain in the molecule thereof, and the polymer chain is one or more polymer chains from among polyethers, polyamides, polyesters, and polyurethanes.

Description

Technical Field

[0001] The present invention relates to a novel additive for mechanochemical reactions, a novel mechanochemical reaction method, a novel ligand compound, and a novel complex.

Background Art

[0002] As one means of synthesis methods for pharmaceuticals, liquid crystal compounds, organic electroluminescence compounds, coloring materials, energy ray absorbing materials, information recording materials, wavelength conversion materials, indicator materials, sensor materials, organic light emitting diodes (OLEDs), organic semiconductor materials, etc., for example, cross-coupling reactions are known. Non-Patent Documents 1 and 2 disclose a cross-coupling reaction in which an aromatic compound having a leaving group and an aromatic boronic acid derivative are reacted and linked in the presence of a metal compound such as a palladium catalyst to obtain an aromatic compound. And, due to its synthetic chemical importance, the "Development of Cross-Coupling Reactions by Palladium Catalysts" by Dr. Akira Suzuki, Dr. Ei-ichi Negishi, and Dr. Richard F. Heck was awarded the Nobel Prize in Chemistry in 2010.

[0003] In general, cross-coupling reactions are carried out by dissolving the starting compound in an organic solvent, so a relatively large amount of organic solvent is required. However, in recent years, the use of a large amount of organic solvents may cause problems from the viewpoints of the working environment and safety of workers, global environmental protection, and the environmental load during the treatment of used organic solvents. Therefore, a cross-coupling reaction method that is less likely to cause problems in terms of working environment, safety, global environmental protection, environmental load, etc. is required. Non-Patent Document 3 reports a cross-coupling reaction method using a palladium catalyst that substantially does not use an organic solvent. However, there are few reaction examples and many points to be improved in terms of starting materials and reaction efficiency.

[0004] An organic synthesis reaction method that directly contacts reaction raw materials with each other without using an organic solvent is of low environmental impact and is interesting both academically and industrially. As such an organic synthesis reaction method, the mechanochemical reaction method has attracted attention. The mechanochemical reaction method is a method in which mechanical energy is applied to solid raw materials by means such as grinding, shearing, impact, and compression to activate and react the solid raw materials. The inventors of the present invention proposed, in Patent Document 1, a mechanochemical reaction method that can use various compounds as starting materials, can carry out a cross-coupling reaction efficiently in a relatively short time under mild reaction conditions substantially without using an organic solvent, and can proceed the reaction efficiently. This mechanochemical reaction method can relatively efficiently form a chemical bond selected from C-N, C-B, C-C, C-O, and C-S bonds, and can obtain a reaction product in a high yield. However, even in this mechanochemical reaction method, there were points to be improved in terms of substrate application range, reaction efficiency, reaction activity, reaction time, and the like.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0007] The mechanochemical reaction method can perform a reaction by applying mechanical energy to reaction raw materials through grinding, shearing, impact, compression, etc. using a ball mill or the like, under conditions of not using a solvent or substantially not using an organic solvent. Therefore, since high-value-added organic molecules can be synthesized while suppressing waste derived from environmentally harmful organic solvents, it has attracted great attention. In particular, the mechanochemical cross-coupling reaction using a metal compound (metal catalyst) such as palladium has been attracting attention as a new method for solving various synthetic problems in the conventional solution-based systems using solvents. However, at present, catalysts, ligands, etc. used in the mechanochemical cross-coupling reaction are being diverted from catalysts and ligands developed for cross-coupling reactions in solution systems.

[0008] The problem to be solved by the present invention is to provide an additive for mechanochemical reaction that can be handled under air, can be easily synthesized, can enhance the activity of the mechanochemical reaction when used in the mechanochemical reaction, and is applicable to a wide range of substrates under mild conditions. Another problem to be solved by the present invention is to provide a mechanochemical reaction method that is applicable to a wide range of substrates under mild conditions without using a solvent or substantially without using an organic solvent, has high reaction activity, and can obtain reaction products in high yield in a short time. Yet another problem to be solved by the present invention is to provide a ligand compound having a novel structure or a salt thereof that can be handled under air, can be easily synthesized, exhibits high activity in the mechanochemical reaction, and can be used in a mechanochemical method applicable to a wide range of substrates under mild conditions, and a complex containing the ligand compound or a salt thereof and a metal atom.

Means for Solving the Problems

[0009] As a result of intensive studies to solve the above problems, the present inventors have found that a novel ligand compound (Lx) having a specific structure or a salt thereof can be handled under air, can be easily synthesized, and exhibits high activity when used in mechanochemical reactions, particularly the Suzuki-Miyaura cross-coupling reaction, and thus have completed the present invention. This ligand compound (Lx) or a salt thereof, particularly the ligand compound (Ly) or a salt thereof, exhibits extremely high activity compared to ligand compounds used in conventional solution-based cross-coupling reactions. The present invention provides the following additives for mechanochemical reactions, a mechanochemical reaction method, a novel ligand compound (Ly) or a salt thereof, and a novel complex.

[0010] [Item 1] An additive for a mechanochemical reaction, comprising at least a ligand compound (Lx) or a salt thereof, wherein the ligand compound (Lx) is one or more selected from phosphorus compounds, bipyridine compounds, and N-heterocyclic carbene compounds, and the ligand compound (Lx) has a polymer chain in the molecule, and the polymer chain is one or more selected from polyethers, polyamides, polyesters, and polyurethanes.

[0011] [Item 2] The additive for a mechanochemical reaction according to Item 1, further comprising a metal compound.

[0012] [Item 3] An additive for a mechanochemical reaction, comprising a complex composed of at least a ligand compound (Lx) or a salt thereof and a metal atom, wherein the ligand compound (Lx) is one or more selected from phosphorus compounds, bipyridine compounds, and N-heterocyclic carbene compounds, and the ligand compound (Lx) has a polymer chain in the molecule, and the polymer chain is one or more selected from polyethers, polyamides, polyesters, and polyurethanes.

[0013] [Item 4] The ligand compound (Lx) has the following structure (La), (Lb), or (Lc); [Chemical formula] (Each group in formulas (La), (Lb), and (Lc) is as follows. Cy 1 , Cy 2 , Cy 3 is, independently of one another, a group selected from the group consisting of an aromatic hydrocarbon group having 6 to 30 carbon atoms, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 20 carbon atoms, and a heterocyclic group having 1 to 20 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other).)

[0014] Ht is a group represented by any one of the following formulas (Ht1) to (Ht10). [Chemical formula]

[0015] R 11 , R 12 , R 13 , R 21 , R 22 , R 31 is, independently of one another, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. R 11 , R 12 , R 13 , R 21 , R 22 , R31 When there are a plurality of them, they may be the same as or different from each other.

[0016] A 11 , A 12 , A 13 , A 21 , A 22 , A 31 , A 32 , A 33 is, independently of each other, a direct bond, an alkylene group having 1 to 24 carbon atoms, a cycloalkylene group having 3 to 24 carbon atoms, an alkenylene group having 1 to 24 carbon atoms, an alkynylene group having 1 to 24 carbon atoms, an arylene group having 6 to 24 carbon atoms, an aryleneoxy group having 6 to 24 carbon atoms, an arylenesulfide group having 6 to 24 carbon atoms, a heteroarylene group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an ester group (-COO- or -OCO-), an ether group, a thioether group, an amide group, a urethane group, a carbonate group, and an amine group having 0 to 24 carbon atoms, and a group formed by bonding two or more of them may be used. A 11 , A 12 , A 13 , A 21 , A 22 , A 31 , A 32 , A 33 When there are a plurality of them, they may be the same as or different from each other.

[0017] Poly 11 , Poly 12 , Poly 13 , Poly 21 , Poly 22 , Poly 31 is, independently of each other, one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters, and polyurethanes. Poly 11 , Poly 12 , Poly 13 , Poly 21 , Poly 22 , Poly 31 When there are a plurality of them, they may be the same as or different from each other.

[0018] E 11 、E 12 、E 13 、E 21 、E 22 、E 31 is, independently of each other, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen and sulfur. When there are a plurality of them, they may be the same or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. E 11 、E 12 、E 13 、E 21 、E 22 、E 31 When there are a plurality of Es, they may be the same or different from each other.

[0019] Xa - is a monovalent anion, and Xb - is a divalent anion or two monovalent anions.

[0020] p1, q1, r1, s1, t1, u1 are, independently of each other, 0 or an integer of 1 or more, and p1 + q1 + r1 ≧ 1. Further, p1 + s1 is 0 or an integer equal to or less than the number of substitutable positions in the Cy 1 group, q1 + t1 is 0 or an integer equal to or less than the number of substitutable positions in the Cy 2 group, and r1 + u1 is 0 or an integer equal to or less than the number of substitutable positions in the Cy 3 group. p2, q2, s2, t2 are, independently of each other, 0 or an integer of 1 or more, and p2 + q2 ≧ 1, 4 ≧ p2 + s2 ≧ 0, 4 ≧ q2 + t2 ≧ 0. p3 is an integer of 1 or more, and s3 is an integer of 0 or 1 or more. Further, p3 + s3 is an integer equal to or less than the number of substitutable positions in the Ht group.

[0021] One or more of each R 11 、R 12 、R 13 、A 11 、A 12 、A 13 Two or more of them may combine to form a carbocyclic ring or a heterocyclic ring. One or more of each R 21 、R 22 、A 21 、A 22 Two or more of them may combine to form a carbocyclic ring or a heterocyclic ring. One or more of each R 31 、A 31 、A 32 、A 33 Two or more of them may combine to form a carbocyclic ring or a heterocyclic ring.

[0022] In formulas (La), (Lb), and (Lc), Cy 1 、Cy 2 、Cy 3 、R 11 、R 12 、R 13 、R 21 、R 22 、R 31 、A 11 、A 12 、A 13 、A 21 、A 22 、A 31 、A 32 、A 33 、E 11 、E 12 、E 13 、E 21 、E 22 、E 31Each may independently have a substituent. The substituent in each group is a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur; when there are a plurality, they may be the same or different from each other), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. When there are a plurality, they may be the same or different from each other.) The mechanochemical reaction additive according to any one of items 1 to 3, represented by .

[0023] [Item 5] The mechanochemical reaction additive according to any one of items 1 to 4, wherein the polymer chain is a polyalkylene ether.

[0024] [Item 6] The mechanochemical reaction additive according to any one of items 2 to 5, wherein the metal atom contained in the metal compound or the metal atom contained in the complex is one or more selected from the group consisting of Mg, Ca, Sr, Ba, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ru, Pd, Ag, Re, Ir, Pt, Pb, Bi, Al, and Sn.

[0025] [Item 7] A mechanochemical reaction method using the mechanochemical reaction additive according to any one of items 1 to 6.

[0026] [Item 8] The following structure (La), (Lb), or (Lc); [Chemical formula] (Each group in formulas (La), (Lb), and (Lc) is as follows.) Cy 1 、Cy 2 、Cy 3 is, independently of each other, a group selected from the group consisting of an aromatic hydrocarbon group having 6 to 30 carbon atoms, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 20 carbon atoms, and a heterocyclic group having 1 to 20 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other).

[0027] Ht is a group represented by any one of the following formulas (Ht1) to (Ht7).

Chemical formula

[0028] R 11 、R 12 、R 13 、R 21 、R 22 、R 31 is, independently of each other, an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. When there are a plurality of R 11 、R 12 、R 13 、R 21 、R 22 、R 31 , they may be the same as or different from each other.

[0029] A 11 、A 12 、A 13 、A 21 、A22 、A 31 、A 32 、A 33 is, independently of each other, a direct bond, an alkylene group having 1 to 24 carbon atoms, a cycloalkylene group having 3 to 24 carbon atoms, an alkenylene group having 1 to 24 carbon atoms, an alkynylene group having 1 to 24 carbon atoms, an arylene group having 6 to 24 carbon atoms, an aryleneoxy group having 6 to 24 carbon atoms, an arylenesulfide group having 6 to 24 carbon atoms, a heteroarylene group having 3 to 24 carbon atoms (the hetero atom is one or more selected from the group consisting of oxygen, nitrogen and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an ester group (-COO- or -OCO-), an ether group, a thioether group, an amide group, a urethane group, a carbonate group, and a group selected from the group consisting of amine groups having 0 to 24 carbon atoms, and two or more of them may be bonded. A 11 、A 12 、A 13 、A 21 、A 22 、A 31 、A 32 、A 33 When there are a plurality of As, they may be the same as or different from each other.

[0030] Poly 11 、Poly 12 、Poly 13 、Poly 21 、Poly 22 、Poly 31 is, independently of each other, one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters and polyurethanes. Poly 11 、Poly 12 、Poly 13 、Poly 21 、Poly 22 、Poly 31 When there are a plurality of Polys, they may be the same as or different from each other.

[0031] E 11 、E 12 、E 13 、E 21 、E 22 、E 31is, independently of each other, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. E 11 , E 12 , E 13 , E 21 , E 22 , E 31 When there are a plurality of them, they may be the same or different from each other.

[0032] Xa - is a monovalent anion, and Xb - is a divalent anion or two monovalent anions.

[0033] p1, q1, r1, s1, t1, u1 are each independently 0 or an integer of 1 or more, and p1 + q1 + r1 ≥ 1. Further, p1 + s1 is 0 or an integer not exceeding the number of substitutable positions in the Cy 1 group, q1 + t1 is 0 or an integer not exceeding the number of substitutable positions in the Cy 2 group, and r1 + u1 is 0 or an integer not exceeding the number of substitutable positions in the Cy 3 group. p2, q2, s2, t2 are each independently 0 or an integer of 1 or more, and p2 + q2 ≥ 1, 4 ≥ p2 + s2 ≥ 0, 4 ≥ q2 + t2 ≥ 0. p3 is an integer of 1 or more, and s3 is 0 or an integer of 1 or more. Further, p3 + s3 is an integer not exceeding the number of substitutable positions in the Ht group.

[0034] Each one or more R 11 , R 12 , R13 、A 11 、A 12 、A 13 may be combined with two or more to form a carbocyclic ring or a heterocyclic ring. One or more Rs each 21 、R 22 、A 21 、A 22 may be combined with two or more to form a carbocyclic ring or a heterocyclic ring. One or more Rs each 31 、A 31 、A 32 、A 33 may be combined with two or more to form a carbocyclic ring or a heterocyclic ring.

[0035] In formulas (La), (Lb) and (Lc), Cy 1 、Cy 2 、Cy 3 、R 11 、R 12 、R 13 、R 21 、R 22 、R 31 、A 11 、A 12 、A 13 、A 21 、A 22 、A 31 、A 32 、A 33 、E 11 、E 12 、E 13 、E 21 、E 22 、E 31Each may independently have a substituent. The substituent in each group is an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality, they may be the same or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group, and when there are a plurality, they may be the same or different from each other.) The ligand compound (Ly) represented by or a salt thereof.

[0036] [Item 9] A complex composed of at least the ligand compound (Ly) or a salt thereof described in Item 8 and a metal atom. [Advantages of the Invention]

[0037] According to the present invention, there is provided an additive for mechanochemical reaction that can be handled under air, can be easily synthesized, can enhance the activity of the mechanochemical reaction by being used in the mechanochemical reaction, and is applicable to a wide range of substrates under mild conditions. According to the present invention, there is provided a mechanochemical reaction method that can be applied to a wide range of substrates under mild conditions without using a solvent or substantially using an organic solvent, has high reaction activity, and can obtain a reaction product in a high yield in a short time. According to the present invention, there are provided a ligand compound (Ly) having a novel structure or a salt thereof that can be handled under air, can be easily synthesized, shows high activity in mechanochemical reactions, and can be used in mechanochemical methods applicable to a wide range of substrates under mild conditions, and a complex containing the ligand compound (Ly) or a salt thereof and a metal atom. [Brief Description of the Drawings]

[0038]

Figure 1

Figure 2

[0039] Hereinafter, the additive for mechanochemical reaction, the mechanochemical reaction method, the ligand compound or its salt, and the complex of the present invention will be described in detail.

[0040] [Additive for Mechanochemical Reaction] The additive for mechanochemical reaction is used in a mechanochemical reaction method after being converted in the reaction system. The mechanochemical reaction method is a method of adding mechanical energy to a substrate, a catalyst, etc. and causing a reaction. The mechanical energy can be mechanically generated by means such as grinding, shearing, impact, compression, etc. By applying such mechanical energy to a substrate, a catalyst, etc., the substrate, the catalyst, etc. can be activated and caused to react. The mechanochemical reaction method is an organic synthesis reaction method that directly contacts and mixes the components contained in the reaction system to cause a reaction, does not use an organic solvent, and has a high reaction activity while having a low environmental load.

[0041] The additive for mechanochemical reaction according to one embodiment of the present invention contains at least a ligand compound (Lx) or a salt thereof. Further, it may contain a metal compound. Also, the additive for mechanochemical reaction according to one embodiment of the present invention contains a complex composed of at least a ligand compound (Lx) or a salt thereof and a metal atom.

[0042] [Ligand Compound (Lx) or Its Salt] The ligand compound (Lx) contained in the mechanochemical reaction additive of the present invention is one or more of a phosphorus-based compound, a bipyridine-based compound, and an N-heterocyclic carbene-based compound, the ligand compound has a polymer chain in the molecule, and the polymer chain is one or more of a polyether, a polyamide, a polyester, and a polyurethane. In the present invention, it is preferable that the polymer chain can be complexed with a metal compound (catalyst) during a mechanochemical reaction and can accelerate the reaction while at least partially destroying the crystalline portion of the substrate. The inventors speculate that the flexible and fluid polymer chain (solid polymer domain) is complexed with the catalyst, improving the dispersion of the substrate near the catalyst and enabling efficient reaction acceleration. However, the present invention is not limited by such a speculation. Examples of the phosphorus-based ligand compounds include one or more compounds represented by the following formula (La); examples of the bipyridine-based ligand compounds include one or more compounds represented by the following formula (Lb); and examples of the N-heterocyclic carbene-based ligand compounds include one or more compounds represented by the following formula (Lc). These compounds may be in the form of a salt.

[0043] The content of the ligand compound (Lx) or a salt thereof is not particularly limited as long as it is an amount that allows a mechanochemical reaction, for example, a Suzuki-Miyaura cross-coupling reaction, to proceed when the mechanochemical reaction additive is added to the reaction system, and can be appropriately determined taking into consideration the types and amounts of the substrate, metal compound, base and unsaturated hydrocarbon compound used as necessary, and reaction products, as well as the reaction temperature, etc. The amount of the ligand compound (Lx) or a salt thereof used can be, for example, a molar ratio of the ligand compound (Lx) to the metal compound (ligand compound (Lx) / metal compound) of 10 / 1 to 1 / 10, preferably 5 / 1 to 1 / 5, more preferably 3 / 1 to 1 / 3, and even more preferably 2 / 1 to 1 / 2.

[0044] (Compound represented by formula (La)) [Chemical formula] In the compound represented by formula (La), three groups such as a cyclic group are bonded to a phosphorus atom, and one or more polymer chains selected from the group consisting of polyether, polyamide, polyester, and polyurethane are bonded to one or more of these groups. In the present invention, a salt of the compound represented by formula (La) may be used.

[0045] Cy in formula (La) 1 , Cy 2 , Cy 3 each independently represents any one of an aromatic hydrocarbon group having 6 to 30 carbon atoms, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 20 carbon atoms, and a heterocyclic group having 1 to 20 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur; when there are a plurality of them, they may be the same or different from each other). These groups may have substituents.

[0046] Examples of the aromatic hydrocarbon group having 6 to 30 carbon atoms include a phenyl group, a naphthyl group, an anthracenyl group (or anthracene group), a phenanthrenyl group (or phenanthrene group), a biphenyl group, a group in which two or more phenyl groups are bonded by a divalent linking group, a terphenyl group, a pyrenyl group (or pyrene group), a perylenyl group (or perylene group), a triphenylenyl group (or triphenylene group), a fluorenyl group, and the like.

[0047] Examples of aliphatic hydrocarbon groups having 1 to 20 carbon atoms include alkyl groups having 1 to 20 carbon atoms (e.g., methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, octyl group, etc.); alkenyl groups having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., ethenyl group, propenyl group, butenyl group, pentenyl group, hexenyl group, octenyl group, etc.); alkynyl groups having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group, octynyl group, etc.).

[0048] Examples of alicyclic hydrocarbon groups having 3 to 20 carbon atoms include cycloalkyl groups having 3 to 20 carbon atoms, preferably 3 to 18 carbon atoms, more preferably 3 to 12 carbon atoms, still more preferably 3 to 8 carbon atoms (e.g., cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, etc.).

[0049] Examples of the complex cyclic group having 1 to 20 carbon atoms (the hetero atom is one or more selected from the group consisting of oxygen, nitrogen and sulfur. When there are a plurality of them, they may be the same or different from each other) include, for example, a pyridyl group (or pyridine group), a pyridylenyl group (or pyridinediyl group), a pyrimidinyl group (or pyrimidine group), a pyrazyl group (or pyrazine group), a quinolyl group (or quinoline group), an isoquinolyl group (or isoquinoline group), a carbazolyl group (or carbazole group), a 9-phenylcarbazolyl group, an acridinyl group (or acridine group), a quinazolyl group (or quinazoline group), a quinoxalyl group (or quinoxaline group), a 1,6-naphthyridinyl group, a 1,8-naphthyridinyl group, and a porphyrin group (or porphyrin ring), etc. nitrogen-containing heteroaryl groups; oxygen-containing heteroaryl groups such as a furanyl group (or furan group), a benzofuranyl group (benzofuran group), a dibenzofuranyl group (dibenzofuran group), a phenyldibenzofuranyl group, and a dibenzofuranylphenyl group; sulfur-containing heteroaryl groups such as a thiophenyl group (thiophene group or thienyl group), a thienylenyl group (or thiophenediyl group), a benzothienyl group (benzothiophene group), a dibenzothienyl group (dibenzothiophene group), a phenyldibenzothienylenyl group, and a dibenzothienylenylphenyl group; and heteroaryl groups containing two or more hetero atoms (for example, nitrogen and sulfur) such as a benzothiazolyl group (or benzothiazole group) and a benzothiadiazole group.Furthermore, pyrrole group, silole group, borole group, phosphole group, selenophene group, germole group, indole group, indene group, benzosilole group, benzoborole group, benzophosphole group, benzoselenophene group, benzogermole group, dibenzosilole group, dibenzoborole group, dibenzophosphole group, dibenzoselenophene group, dibenzogermole group, dibenzothiophene 5-oxide group, 9H-fluoren-9-one group, dibenzothiophene 5,5-dioxide group, azabenzothiophene group, azabenzofuran group, azaindole group, azaindene group, azabenzosilole group, azabenzoborole group, azabenzophosphole group, azabenzoselenophene group, azabenzogermole group, azadibenzothiophene group, azadibenzofuran group, azacarbazole group, azafluorene group, azadibenzosilole group, azadibenzoborole group, azadibenzophosphole group, azadibenzoselenophene group, azadibenzogermole group, azadibenzothiophene 5-oxide group, aza-9H-fluoren-9-one group, azadibenzothiophene 5,5-dioxide group, pyridazine group, triazine group, phenanthroline group, pyrazole group, imidazole group, triazole group, oxazole group, isoxazole group, thiazole group, isothiazole group, oxadiazole group, thiadiazole group, benzopyrazole group, benzimidazole group, benzoxazole group, benzoxadiazole group, 5,6,7,8-tetrahydroisoquinoline group, 5,6,7,8-tetrahydroquinoline group, etc. may be mentioned.

[0050] R in formula (La) 11 , R 12 , R 13 are those corresponding to the substituents of Cy 1 , Cy 2 , Cy 3 . R 11 , R 12 , R 13Examples of the group include, independently of each other, an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. The amino group having 0 carbon atoms is a primary amino group, the amino group having 1 carbon atom is a secondary amino group, and the amino group having 2 or more carbon atoms is a secondary amino group, a tertiary amino group, or a quaternary amino group. R 11 、R 12 、R 13 When there are a plurality of R 11 、R 12 、R 13 , they may be the same or different from each other. Further, R

[0051] Examples of the alkyl group having 1 to 24 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a pentyl group, a hexyl group, an octyl group, and the like. Examples of the alkoxy group having 1 to 24 carbon atoms include a methoxy group, an ethoxy group, a butoxy group, and the like. Examples of the cycloalkyl group having 3 to 24 carbon atoms include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and the like. Examples of the alkenyl group having 2 to 24 carbon atoms include an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, an octenyl group, and the like. Examples of the alkynyl group having 2 to 24 carbon atoms include an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a hexynyl group, an octynyl group, and the like. Examples of the aryl group having 6 to 24 carbon atoms include a phenyl group, a naphthyl group, an anthracenyl group (or anthracene group), a phenanthrenyl group (or phenanthrene group), a biphenyl group, a group in which two or more phenyl groups are bonded by a divalent linking group, a terphenyl group, a pyrenyl group (or pyrene group), a perylenyl group (or perylene group), a triphenylenyl group (or triphenylene group), a fluorenyl group, and the like. Examples of the heteroaryl group having 3 to 24 carbon atoms include the Cy 1 , Cy 2 , Cy 3 and groups similar to the "heterocyclic group having 1 to 20 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same or different from each other.)" in Cy

[0052] A in formula (La) 11 , A 12 , A 13 is a group corresponding to Cy 1 , Cy 2 , Cy 3 bonded to a phosphorus atom and a linking group for bonding a polymer chain. A 11 , A 12 , A 13 are each independently a direct bond, an alkylene group having 1 to 24 carbon atoms, a cycloalkylene group having 3 to 24 carbon atoms, an alkenylene group having 1 to 24 carbon atoms, an alkynylene group having 1 to 24 carbon atoms, an arylene group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylsulfide group having 6 to 24 carbon atoms, a heteroarylene group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same or different from each other.), an ester group (-COO- or -OCO-), an ether group, a thioether group, an amide group, a urethane group, a carbonate group, or a group selected from the group consisting of amine groups having 0 to 24 carbon atoms, and may be a combination of two or more. When there are a plurality of A 11 , A 12 , A 13 , they may be the same or different from each other. Further, when there are a plurality of A 11 , A 12 , A 13may have a substituent. Preferably, it is an ether group or an ester group.

[0053] Poly in formula (La) 11 Poly 12 Poly 13 are each independently one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters, and polyurethanes. Poly 11 Poly 12 Poly 13 If there are a plurality of them, they may be the same as or different from each other. Among these, one or more polymer chains selected from the group consisting of polyethers, polyamides, and polyesters are preferred, and one or more selected from the group consisting of polyoxyalkylene, aliphatic polyamide, and aliphatic polyester are preferred. Particularly preferably, it is one or more selected from the group consisting of polyoxyethylene, polyoxypropylene, and polyoxybutylene. Most preferably, it is polyoxyethylene. When having two or more polymer chains, it may be any of random copolymerization, block copolymerization, and alternating copolymerization. The number of repeating units of the polymer chain can be, for example, 10 or more. If it is less than 10, it may not exhibit the characteristics of a polymer chain. The upper limit of the number of repeating units is not particularly limited, but it can be, for example, 100,000 or less, preferably 10,000 or less, more preferably 1,000 or less. If it exceeds 100,000, the function as a ligand may decrease. Also, the number average molecular weight of the polymer chain can be a value of, for example, 200 or more, preferably 400 or more, more preferably 500 or more, and can be a value of, for example, 10,000 or less, preferably 8,000 or less, more preferably 5,000 or less.

[0054] E in formula (La) 11 E 12 E 13 corresponds to the end group of the polymer chain. E 11 E 12 E 13is, independently of each other, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 1 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. E 11 , E 12 , E 13 When there are a plurality of them, they may be the same as or different from each other. Also, E 11 , E 12 , E 13 may have a substituent. E 11 , E 12 , E 13 Specific examples of the alkyl group, alkoxy group, cycloalkyl group, alkenyl group, alkynyl group, aryl group, heteroaryl group, etc. in 13 are the same groups as those listed for the above R 11 , R 12 , R 13 .

[0055] In formula (La), p1, q1, r1, s1, t1, u1 are each independently an integer of 0 or 1 or more, and p1 + q1 + r1 ≥ 1. Further, p1 + s1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy1 group, q1 + t1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy2 group, and r1 + u1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy3 group. Preferably, 2 ≥ p1 + q1 + r1 ≥ 1, 4 ≥ s1 + t1 + u1 ≥ 0.

[0056] In formula (La), one or more R's each 11 , R 12 , R 13 , A 11 , A 12 , A 13Two or more of them may combine to form a carbocyclic ring or a heterocyclic ring. For example, two Rs 11 may combine to form a ring, and R 11 and A 11 may combine to form a ring, and R 11 and R 12 may combine to form a ring. The substituent in each group in formula (La) is a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. When there are a plurality of them, they may be the same or different. When there are a plurality of substituents, they may be the same as or different from each other. Further, specific examples of the alkyl group, alkoxy group, cycloalkyl group, alkenyl group, alkynyl group, aryl group, heteroaryl group, etc. in the substituent are the same groups as those exemplified for the above R 11 、R 12 、R 13 . In addition, these substituents do not reduce the catalytic activity in the mechanochemical reaction of the metal compound.

[0057] Examples of the compound represented by formula (La) include compounds represented by the following (La1) to (La5), and compounds in which one or more alkyl groups having 1 to 6 carbon atoms are bonded to the rings of these compounds.

Chemical formula

[0058] (Compound represented by formula (Lb))

Chemical formula

[0059] R in formula (Lb) 21 , R 22 corresponds to the substituent of bipyridine. When there are a plurality of R 21 , R 22 , they may be the same as or different from each other. Also, R 21 , R 22 may have a substituent. R 21 , R 22 are each independently the same groups as those described for R 11 , R 12 , R 13 in the above (compound represented by formula (La)).

[0060] A in formula (Lb) 21 , A 22 corresponds to a group equivalent to the bipyridine moiety and a linking group that binds the polymer chain. When there are a plurality of A 21 , A 22 , they may be the same as or different from each other. Also, A 21 , A 22 may have a substituent. A 21 , A 22 are each independently the same as A 11 , A 12 , A13 is the same basis as that described above.

[0061] Poly in formula (Lb) 21 Poly 22 is, independently of one another, one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters and polyurethanes. When there are a plurality of Poly 21 Poly 22 they may be the same as or different from one another. Poly 21 Poly 22 is, independently of one another, the same as that described for Poly 11 Poly 12 Poly 13 in the above (compound represented by formula (La)).

[0062] E in formula (La) 21 E 22 corresponds to the end group of the polymer chain. When there are a plurality of E 21 E 22 they may be the same as or different from one another. Further, E 21 E 22 may have a substituent. E 21 E 22 is, independently of one another, the same basis as that described for E 11 E 12 E 13 in the above (compound represented by formula (La)).

[0063] In formula (Lb), one or more each of R 21 R 22 A 21 A 22 may combine such that two or more of them form a carbocyclic ring or a heterocyclic ring. For example, two R 21 may combine to form a ring, R 21 and A 21 may combine to form a ring, and R 21 and R 22 may combine to form a ring. Each group in formula (Lb) may have a substituent. The substituents are the same as those described for the substituents in the above (compound represented by formula (La)).

[0064] p2, q2, s2, and t2 are each independently 0 or an integer of 1 or more, and p2 + q2 ≥ 1, 4 ≥ p2 + s2 ≥ 0, and 4 ≥ q2 + t2 ≥ 0.

[0065] Examples of the compound represented by formula (Lb) include compounds represented by the following (Lb1) to (Lb4), and compounds in which one or more alkyl groups having 1 to 6 carbon atoms are bonded to the rings of these compounds.

Chemical formula

[0066] In formulas (Lb1) to (Lb4), nb1 to nb6 are each independently the number of repeating units of the polyoxyethylene chain, for example, 1000 or less, preferably 500 or less, more preferably 200 or less, and can be, for example, 8 or more, preferably 10 or more, more preferably 112 or more. Also, nb1 to nb6 can be values such that the number average molecular weight of the polyoxyethylene chain is, for example, 200 or more, preferably 400 or more, more preferably 500 or more, and can be values such that it is, for example, 10,000 or less, preferably 8,000 or less, more preferably 5,000 or less.

[0067] (Compound represented by formula (Lc))

Chemical formula

[0068] Ht in formula (Lb) is a group represented by any one of the following formulas (Ht1) to (Ht10). [Chemical]

[0069] Xa - is a monovalent anion, and Xb - is a divalent anion or two monovalent anions. Examples of the monovalent anion include, for example, F - , Cl - , Br ー , I - , NO 3 - , CH 3 COO - , OH - , BF 4 - and the like. Examples of the divalent anion include, for example, SO 4 2- , CO 3 2- and the like. When two monovalent anions are included, they may be the same or different from each other.

[0070] (Ht7) The A in 32 is a group selected from the group consisting of a direct bond, an alkylene group having 1 to 24 carbon atoms, a cycloalkylene group having 3 to 24 carbon atoms, an alkenylene group having 1 to 24 carbon atoms, an alkynylene group having 1 to 24 carbon atoms, an arylene group having 6 to 24 carbon atoms, an aryleneoxy group having 2 to 24 carbon atoms, a heteroarylene group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same or different from each other), an ester group (-COO- or -OCO-), an ether group, a thioether group, an amide group, a urethane group, a carbonate group, and an amine group having 0 to 24 carbon atoms, and a combination of two or more thereof may be used. A 32 When there are a plurality of A, they may be the same or different from each other.

[0071] R in formula (Lc) 31 corresponds to a substituent of N-heterocyclic carbene. R 31When there are a plurality of them, they may be the same as or different from each other. Also, R 31 may have a substituent. R 31 is, independently of each other, a group similar to that described for R 11 in the (compound represented by formula (La)). 12 R 13 in the (compound represented by formula (La)).

[0072] A in formula (Lc) 31 is a group corresponding to an N - heterocyclic carbene moiety and a linking group that binds a polymer chain. When there are a plurality of A 31 they may be the same as or different from each other. Also, A 31 may have a substituent. A in formula (Lc) 31 is a group similar to that described for A 11 in the (compound represented by formula (La)). 12 A 13 in the (compound represented by formula (La)).

[0073] Poly in formula (Lc) 31 is, independently of each other, one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters, and polyurethanes. When there are a plurality of Poly 31 they may be the same as or different from each other. Poly 31 is similar to that described for Poly 11 in the (compound represented by formula (La)). 12 Poly 13 in the (compound represented by formula (La)).

[0074] E in formula (Lc) 31 corresponds to the end group of the polymer chain. When there are a plurality of E 31 they may be the same as or different from each other. Also, E 31 may have a substituent. E 31 is a group similar to that described for E 11 in the (compound represented by formula (La)). 12 E 13 in the (compound represented by formula (La)).

[0075] In formula (Lc), each of one or more Rs 31 , A 31 may be such that two or more of them are combined to form a carbocyclic ring or a heterocyclic ring. For example, two Rs 31 may be combined to form a ring, and R 31 and A 31 may be combined to form a ring, and two As 31 may be combined to form a ring. Each group in formula (Lc) may have a substituent. The substituents are the same as those described for the substituents in the above (compound represented by formula (La)).

[0076] In formula (Lc), p3 is an integer of 1 or more, and s3 is an integer of 0 or 1 or more. Further, p3 + s3 is an integer not more than the number of substitutable positions in the Ht group.

[0077] Examples of the compound represented by formula (Lc) include compounds represented by the following (Lc1) to (Lc14), and compounds in which one or more alkyl groups having 1 to 6 carbon atoms are bonded to the rings of these compounds. [Chemical formula]

[0078] [Chemical formula]

[0079] In formulas (Lc1) to (Lc22), nc1 to nc30 are each independently the number of repeating units of the polyoxyethylene chain, for example, 1000 or less, preferably 500 or less, more preferably 200 or less, and can be, for example, 10 or more, preferably 15 or more. Further, nc1 to nc30 can each independently be a value such as 200 or more, preferably 400 or more, more preferably 500 or more, and can be a value such as 10,000 or less, preferably 8,000 or less, more preferably 5,000 or less. Note that Me is a methyl group, iPr is an isopropyl group, and X- is a monovalent anion, for example, F - , Cl - , Br - , I - , BF 4 - and so on.

[0080] The ligand compound (Lx) of the present invention may be in the form of its salt. The means for converting to the salt form is not particularly limited and can be carried out based on well-known techniques in the field of organic chemistry and the like. Preferred examples of the salt include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, etc., organic acid salts such as acetate, fumarate, maleate, oxalate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, etc., inorganic salts such as sodium, potassium, lithium, calcium, magnesium, etc., and salts with organic bases such as tromethamine, arginine, lysine, diethanolamine, triethanolamine, trimethylamine, etc.

[0081] <Metal compound> The metal compound contained in the additive for mechanochemical reaction of the present invention, for example, the metal compound contained in the additive for mechanochemical reaction used in the Suzuki-Miyaura cross-coupling reaction, is not particularly limited as long as it can catalyze (promote) the reaction of the substrate. In the additive for mechanochemical reaction of the present invention, the metal compound functions as a metal catalyst together with the ligand compound (Lx).

[0082] The metal (element) constituting the metal compound may be a transition metal (element) or a typical metal (element) as long as it can catalyze (promote) the reaction of the substrate, and is not particularly limited.

[0083] Examples of the transition metal (element) include one or more selected from the group consisting of scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium, niobium, molybdenum, technetium, ruthenium, rhodium, palladium, silver, cadmium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, platinum, gold, and the like.

[0084] Examples of the typical metal (element) include one or more selected from the group consisting of aluminum, gallium, germanium, indium, tin, antimony, thallium, lead, and bismuth.

[0085] In the present invention, from the viewpoint of catalytic activity and the like, transition metals (elements) belonging to the 4th to 6th periods are exemplified. For example, one or more selected from the group consisting of titanium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, molybdenum, ruthenium, rhodium, palladium, silver, tantalum, tungsten, rhenium, osmium, iridium, platinum, and gold are preferable, one or more selected from the group consisting of palladium, nickel, iron, ruthenium, platinum, rhodium, iridium, and cobalt are more preferable, and one or more selected from the group consisting of palladium, nickel, iron, and copper are even more preferable.

[0086] Metal compounds can be used in various forms, and examples thereof include one or more selected from the group consisting of the following (1) to (4). (1) A simple metal in powder form or porous form (2) Those in which a simple metal or a metal compound is supported on a carrier such as alumina, carbon, silica, or zeolite (3) Metal salts (chlorides, bromides, iodides, nitrates, sulfates, carbonates, oxalates, acetates, oxides, etc.) (4) Complex compounds of a metal and a complex (olefin complex, phosphine complex, amine complex, ammine complex, acetylacetonate complex, etc.)

[0087] In the present invention, as the metal compound, a palladium compound (palladium catalyst) is particularly preferably used. Examples of the palladium compound (palladium catalyst) include divalent palladium compounds such as palladium(II) acetate, palladium(II) chloride, palladium(II) bromide, palladium(II) iodide, palladium(II) acetylacetonate, dichlorobis(benzonitrile)palladium(II), bis(dibenzylideneacetone)palladium, dichlorobis(acetonitrile)palladium(II), dichlorobis(triphenylphosphine)palladium(II), dichlorotetraamminepalladium(II), dichloro(cycloocta-1,5-diene)palladium(II), dichlorobis(tricyclohexylphosphine)palladium(II), palladium(II) trifluoroacetate, etc.; zero-valent palladium compounds such as tris(dibenzylideneacetone)dipalladium(0), tris(dibenzylideneacetone)dipalladium chloroform complex(0), tetrakis(triphenylphosphine)palladium(0), etc. One or more selected from the group consisting of these are mentioned. The metal compound can be used alone or in combination of two or more. The metal compound can be used as a commercially available product as it is or after purification.

[0088] The content of the metal compound is not particularly limited as long as it is an amount that allows a mechanochemical reaction, such as a Suzuki-Miyaura cross-coupling reaction, etc., to proceed when a mechanochemical reaction additive is added to the reaction system. It can be appropriately determined in consideration of the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate, the base and unsaturated hydrocarbon compound used as necessary, the reaction product, etc., and the reaction temperature. The amount of the metal compound used can be, for example, 0.05 mol% or more, preferably 0.1 mol% or more, more preferably 0.5 mol% or more, still more preferably 1.0 mol% or more, based on the number of moles obtained by multiplying the molar amount of the compound (H) having a leaving group in the substrate by the valence (100%). The upper limit is not particularly limited, but can be 25 mol% or less, preferably 20 mol% or less, more preferably 15 mol% or less, still more preferably 10 mol% or less.

[0089] <Complex> The complex contained in the additive for mechanochemical reaction of the present invention, for example, the complex contained in the additive for mechanochemical reaction used in the Suzuki-Miyaura cross-coupling reaction, includes at least a complex composed of a ligand compound (Lx) or a salt thereof and a metal atom. The ligand compound (Lx) is one or more selected from a phosphorus compound, a bipyridine compound, and an N-heterocyclic carbene compound. The ligand compound (Lx) has a polymer chain in the molecule, and the polymer chain is one or more selected from polyether, polyamide, polyester, and polyurethane.

[0090] Examples of the ligand compound (Lx) or a salt thereof constituting the complex include the ligand compound (Lx) or a salt thereof described in <Ligand compound (Lx) or a salt thereof> of the [Additive for mechanochemical reaction]. Preferably, it is a ligand compound represented by formula (La), (Lb), or (Lc). Examples of the metal atom constituting the complex include the metal atoms constituting the metal compounds described in <Metal compound> of the [Additive for mechanochemical reaction]. Preferably, transition metal atoms are preferred, preferably palladium, silver, copper, gold, ruthenium, iron, nickel, and palladium, silver, copper, gold, ruthenium are particularly preferred.

[0091] The complex can be obtained by mixing and reacting at least a ligand compound (Lx) or a salt thereof and a metal compound that supplies a metal atom. During the reaction, heating or the like can be carried out as necessary. The reaction molar ratio of the ligand compound (Lx) or its salt to the metal compound is not particularly limited. The reaction molar ratio of the ligand compound (Lx) or its salt can be adjusted according to the valence of the metal atom in the complex.

[0092] <Other components> The additive for mechanochemical reaction according to the present invention may contain the ligand compound (Lx) or its salt, the metal compound contained as necessary, and "other components" which are components other than the complex composed of the ligand compound (Lx) or its salt and the metal atom. Examples of the other components include ligand compounds or their salts other than the ligand compound (Lx) or its salt, complexes composed of ligand compounds or their salts other than the ligand compound (Lx) or its salt and metal atoms, bases, unsaturated hydrocarbon compounds, reaction accelerators, solvents, and the like.

[0093] Examples of the ligand compound or its salt other than the ligand compound (Lx) include arylphosphines such as triphenylphosphine, tri(o-tolyl)phosphine, and tri(mesityl)phosphine; alkylphosphines such as tri(cyclohexyl)phosphine, tri(isopropyl)phosphine, and tri(tert-butyl)phosphine; Buchwald phosphine ligands such as 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (DavePhos), 2-(di-tert-butylphosphino)-2',4',6'-triisopropyl-3,6-dimethoxy-1,1'-biphenyl (tBuBrettPhos), 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropylbiphenyl, 2-(dicyclohexylphosphino)biphenyl, and 2-(di-tert-butylphosphino)-2'-(N,N-dimethylamino)biphenyl; bidentate phosphines such as 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)propane, 1,2-bis(dicyclohexylphosphino)ethane, 1,2-bis(diphenylphosphino)butane, and 1,2-bis(diphenylphosphino)ferrocene; N-heterocyclic carbene ligands such as 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazolium chloride, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, and 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-1H-imidazolium chloride; t-Bu 3 P·HBF 4 One or more selected from the group consisting of trialkylphosphonium tetrafluoroborates such as (tri-tert-butylphosphonium tetrafluoroborate) are exemplified.

[0094] Examples of the complex composed of a ligand compound other than the ligand compound (Lx) or a salt thereof and a metal atom include complexes composed of a ligand compound other than the ligand compound (Lx) or a salt thereof and the metal atom. Regarding the base, unsaturated hydrocarbon compound, reaction accelerator, and solvent, for example, the compounds and amounts used described in <Base>, <Unsaturated Hydrocarbon Compound>, <Reaction Accelerator>, and <Solvent> in the following [Mechanochemical Reaction Method] are used.

[0095] [Mechanochemical Reaction Method] The mechanochemical reaction method according to the present invention reacts a substrate using at least the [Additive for Mechanochemical Reaction]. In the mechanochemical reaction method of the present invention, a reaction accelerator or the like can be used in combination.

[0096] <Additive for Mechanochemical Reaction> The additive for mechanochemical reaction used in the mechanochemical reaction method of the present invention contains at least a ligand compound (Lx) or a salt thereof, and further contains a metal compound. In addition, the additive for mechanochemical reaction used in the mechanochemical reaction method of the present invention contains at least a complex composed of a ligand or a salt and a metal atom.

[0097] As the additive for mechanochemical reaction used in the mechanochemical reaction method of the present invention, those described in the [Additive for Mechanochemical Reaction] are used. Examples of the ligand compound (Lx) or a salt thereof contained in the additive for mechanochemical reaction include the ligand compound (Lx) or a salt thereof described in <Ligand Compound (Lx) or a Salt Thereof> of the [Additive for Mechanochemical Reaction]. Preferably, it is a ligand compound represented by formula (La), (Lb), or (Lc). Examples of the metal compound contained in the additive for mechanochemical reaction include the metal compounds described in the <metal compound> of the [additive for mechanochemical reaction]. Preferably, it is a transition metal compound, preferably a palladium compound. Examples of the complex contained in the additive for mechanochemical reaction include complexes composed of a ligand compound represented by the formula (La), (Lb) or (Lc) described in the <ligand compound (Lx) or its salt> of the [additive for mechanochemical reaction] and a transition metal atom. As the transition metal atom, palladium, silver, copper, gold, ruthenium, iron, nickel are preferable, and palladium, silver, copper, gold, ruthenium are particularly preferable.

[0098] The amount of the additive for mechanochemical reaction used is not particularly limited as long as the amount of the ligand compound (Lx) in the additive for mechanochemical reaction or the ligand compound (Lx) in the complex is an amount that allows a mechanochemical reaction, for example, a Suzuki-Miyaura cross-coupling reaction, etc. to proceed. It can be appropriately determined in consideration of the type and amount of each of the substrate, metal compound, base and unsaturated hydrocarbon compound used as necessary, reaction product, reaction temperature, etc. As the amount of the additive for mechanochemical reaction used, for example, the amount of the ligand compound (Lx) used in the reaction system can be such that the molar ratio of the ligand compound (Lx) to the metal compound (ligand compound (Lx) / metal compound) is 10 / 1 to 1 / 10, preferably 5 / 1 to 1 / 5, more preferably 3 / 1 to 1 / 3, still more preferably 2 / 1 to 1 / 2.

[0099] <metal compound> In the mechanochemical reaction method of the present invention, for example, in the Suzuki-Miyaura cross-coupling reaction method, a metal compound capable of catalyzing (promoting) the reaction of the substrate can be used. The metal compound exhibits a function as a metal catalyst together with the ligand compound (Lx) or its salt. As the metal compound, the same metal compounds as those described in the <metal compound> of the [additive for mechanochemical reaction] can be used. In the mechanochemical reaction method of the present invention, as the metal compound, a palladium compound (palladium catalyst) is particularly preferably used.

[0100] The metal compound may be contained in the mechanochemical reaction additive, or may be used separately from the mechanochemical reaction additive. The metal compound and the ligand compound (Lx) or a salt thereof can be added into the reaction system separately to carry out the mechanochemical reaction. Further, the two may be mixed and reacted in advance. When an N-heterocyclic carbene-based ligand compound or a salt thereof is used as the ligand compound (Lx) or a salt thereof, it is preferable to mix and react with the metal compound in advance.

[0101] The amount of the metal compound used is not particularly limited as long as the mechanochemical reaction, for example, the Suzuki-Miyaura cross-coupling reaction, etc. proceeds, and it can be appropriately determined in consideration of the types and amounts of each of the ligand compound (Lx) or a salt thereof, the metal compound, the substrate, the base and unsaturated hydrocarbon compound used as necessary, the reaction product, etc., and the reaction temperature. The amount of the metal compound used can be, for example, 0.05 mol% or more, preferably 0.1 mol% or more, more preferably 0.5 mol% or more, still more preferably 1.0 mol% or more, based on the number of moles obtained by multiplying the molar amount of the compound having a leaving group among the substrates by the valence (100%), and the upper limit value is not particularly limited, but can be 25 mol% or less, preferably 20 mol% or less, more preferably 15 mol% or less, still more preferably 10 mol% or less.

[0102] <Substrate> The substrate used in the mechanochemical reaction method of the present invention is a compound (H) having a leaving group and a compound (B) that reacts with an organic compound having a leaving group. Both the compound (H) and the compound (B) are organic compounds that are solid at room temperature (25°C), and their melting points are 30°C or higher, preferably 40°C or higher, more preferably 50°C or higher, still more preferably 60°C or higher, and most preferably 80°C or higher. The compound (H) and the compound (B) are not particularly limited as long as each has a predetermined melting point and they react with each other. Examples of the compound (H) and the compound (B) include the compounds described below. Also, the compound (H) and the compound (B) may be the same. The amount of the compound (B) used is appropriately adjusted in consideration of the equivalent ratio with the compound (H). The equivalent ratio of the compound (H) to the compound (B) (compound (H) / compound (B)) is not particularly limited as long as it is an equivalent ratio at which the reaction proceeds. For example, it is 10 / 1 to 1 / 10, preferably 5 / 1 to 1 / 5, more preferably 3 / 1 to 1 / 3, and even more preferably 2 / 1 to 1 / 2.

[0103] (Compound (H)) Examples of the compound (H) used in the mechanochemical reaction method of the present invention include compounds represented by the following formula (H1). A 400 -X m (H1) (In the formula, A 400 represents any one of an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, an m-valent aliphatic hydrocarbon group which may have a substituent, or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent. X each independently represents a leaving group. m represents an integer of 1 or more, which is the number of Xs.) The compound (H) is not particularly limited as long as it reacts with the compound (B) to produce a reaction product (for example, a cross-coupling reaction product in which one or more of a C-B bond, a C-C bond, a C-N bond, a C-O bond, and a C-S bond are formed). The compound (H) can be used alone or in combination of two or more. The compound (H) can be used as a commercially available product as it is or after purification.

[0104] {The A 400 group in the formula (H)} A 400The carbon number of the m-valent aromatic hydrocarbon group which may have a substituent in A is not particularly limited, and is, for example, 6 to 60, preferably 6 to 40, more preferably 6 to 30. In the m-valent aromatic hydrocarbon group, m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, more preferably 1 to 4. A 400 In the m-valent aromatic hydrocarbon group which may have a substituent in A, examples of the monovalent aromatic hydrocarbon group where m = 1 include a phenyl group, a naphthyl group, an anthracenyl group (or anthracene group), a phenanthrenyl group (or phenanthrene group), a biphenyl group, a terphenyl group, a pyrenyl group (or pyrene group), a perylenyl group (or perylene group), a triphenylenyl group (or triphenylene group), a fluorenyl group, and the like. Also, in A 400 In the m-valent aromatic hydrocarbon group which may have a substituent in A, examples of the m-valent aromatic hydrocarbon group where m is an integer of 2 or more include those obtained by removing m - 1 hydrogens from the aromatic ring in the above monovalent aromatic hydrocarbon group.

[0105] A 400 The carbon number of the m-valent aromatic heterocyclic group which may have a substituent in A is not particularly limited, and is, for example, 4 to 60, preferably 4 to 40, more preferably 4 to 30. A 400 In the m-valent aromatic heterocyclic group in A, m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, more preferably 1 to 4. A 400In the m-valent aromatic heterocyclic group which may have a substituent, examples of the monovalent aromatic heterocyclic group where m = 1 include sulfur-containing heteroaryl groups such as thiophenyl group (thiophene group or thienyl group), thienylenyl group (or thiophenediyl group), benzothienyl group (benzothiophene group), dibenzothienyl group (dibenzothiophene group), phenyldibenzothienylenyl group and dibenzothienylenylphenyl group; oxygen-containing heteroaryl groups such as furanyl group (or furan group), benzofuranyl group (benzofuran group), dibenzofuranyl group (dibenzofuran group), phenyldibenzofuranyl group and dibenzofuranylphenyl group; nitrogen-containing heteroaryl groups such as pyridyl group (or pyridine group), pyridylenyl group (or pyridinediyl group), pyrimidinyl group (or pyrimidine group), pyrazyl group (or pyrazine group), quinolyl group (or quinoline group), isoquinolyl group (or isoquinoline group), carbazolyl group (or carbazole group), 9-phenylcarbazolyl group, acridinyl group (or acridine group), quinazolyl group (or quinazoline group), quinoxalyl group (or quinoxaline group), 1,6-naphthyridinyl group, 1,8-naphthyridinyl group and porphyrin group (or porphyrin ring); and heteroaryl groups containing two or more heteroatoms (for example, nitrogen and sulfur) such as benzothiazolyl group (or benzothiazole group) and benzothiadiazole group.Furthermore, examples include a pyrrole group, a silole group, a borole group, a phosphole group, a selenophene group, a germole group, an indole group, an indene group, a benzosilole group, a benzoborole group, a benzophosphole group, a benzoselenophene group, a benzogermole group, a dibenzosilole group, a dibenzoborole group, a dibenzophosphole group, a dibenzoselenophene group, a dibenzogermole group, a dibenzothiophene 5-oxide group, a 9H-fluoren-9-one group, a dibenzothiophene 5,5-dioxide group, an azabenzothiophene group, an azabenzofuran group, an azaindole group, an azaindene group, an azabenzosilole group, an azabenzoborole group, an azabenzophosphole group, an azabenzoselenophene group, an azabenzogermole group, an azadibenzothiophene group, an azadibenzofuran group, an azacarbazole group, an azafluorene group, an azadibenzosilole group, an azadibenzoborole group, an azadibenzophosphole group, an azadibenzoselenophene group, an azadibenzogermole group, an azadibenzothiophene 5-oxide group, an aza-9H-fluoren-9-one group, an azadibenzothiophene 5,5-dioxide group, a pyridazine group, a triazine group, a phenanthroline group, a pyrazole group, an imidazole group, a triazole group, an oxazole group, an isoxazole group, a thiazole group, an isothiazole group, an oxadiazole group, a thiadiazole group, a benzopyrazole group, a benzimidazole group, a benzoxazole group, a benzoxadiazole group, a 5,6,7,8-tetrahydroisoquinoline group, a 5,6,7,8-tetrahydroquinoline group, and the like. Also, A 400 In the m-valent aromatic heterocyclic group which may have a substituent in A, examples of the m-valent aromatic heterocyclic group where m is an integer of 2 or more include those obtained by removing m - 1 hydrogens from the aromatic ring in the above-mentioned monovalent aromatic heterocyclic group. Further, examples include a benzo[1,2-c:4,5-c′]bis[1,2,5]thiadiazole skeleton (benzobisthiadiazole group) and the like.

[0106] A 400 The number of carbon atoms of the m-valent aliphatic hydrocarbon group which may have a substituent in A is not particularly limited, and is, for example, 2 to 60, preferably 3 to 40, more preferably 5 to 30. A400 In the m-valent aliphatic hydrocarbon group in A, m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, more preferably 1 to 4. A 400 In the m-valent aliphatic hydrocarbon group which may have a substituent in A, examples of the monovalent aliphatic hydrocarbon group where m = 1 include saturated aliphatic hydrocarbon groups such as an alkyl group and a cycloolefin group. Also, A 400 In the m-valent aliphatic hydrocarbon group which may have a substituent in A, examples of the m-valent aliphatic hydrocarbon group where m is an integer of 2 or more include those obtained by removing m - 1 hydrogens from the above monovalent aliphatic hydrocarbon group. A 400 The number of carbon atoms of the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A is not particularly limited, for example, 2 to 60, preferably 3 to 40, more preferably 5 to 30. A 400 In the m-valent unsaturated aliphatic hydrocarbon group in A, m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, more preferably 1 to 4. A 400 In the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A, examples of the monovalent aromatic hydrocarbon group where m = 1 include an alkenyl group and an alkynyl group. Also, A 400 In the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A, examples of the m-valent unsaturated aliphatic hydrocarbon group where m is an integer of 2 or more include those obtained by removing m - 1 hydrogens from the above monovalent unsaturated aliphatic hydrocarbon group.

[0107] A in formula (H1) in compound (H) 400 Specifically, for example, the following groups can be exemplified. Naphthyl group, aryl (for example, phenyl, etc.) naphthyl group, naphthyl group having an alkylene (for example, ethylene, etc.) bridge, naphthyl group having an arylene (for example, phenylene, etc.) bridge, etc.; Phenanthrenyl group; Anthracenyl groups such as anthracenyl group, aryl (e.g., phenyl, etc.) anthracenyl group, diaryl (e.g., dinaphthyl, etc.) anthracenyl group, diarylboril (e.g., bis(trialkylphenyl)boril, etc.) anthracenyl group; Pyrenyl groups such as pyrenyl group, alkyl (e.g., tert-butyl, etc.) pyrenyl group; Biphenyl groups such as biphenyl group, biphenyl group having an alkylene (e.g., propylene, isopropylene, etc.) bridge; Terphenyl groups such as terphenyl group, tetraaryl (e.g., tetraphenyl, etc.) terphenyl group; Triphenylenyl group; 2-Aryl (e.g., phenyl, etc.) ethenylphenyl group, 1,2,2-triaryl (e.g., triphenyl, etc.) ethenylphenyl group, 2-aryl (e.g., phenyl, etc.) ethynylphenyl group, phenyl group, alkyl (e.g., methyl) phenyl group, dialkyl (e.g., dimethyl) phenyl group, alkoxy (e.g., methoxy) phenyl group, dialkylamino (e.g., dimethylamino) phenyl group, diaryl (e.g., diphenyl) aminophenyl group, perfluoroalkyl (e.g., trifluoromethyl) phenyl group, alkyl (e.g., ethyl) oxycarbonylphenyl group, alkanoyl (e.g., acyl) phenyl group, etc. phenyl groups; Aryl (e.g., phenyl, etc.) substituted carbazolyl group; Anthracene-9,10-dione group; Aryl (e.g., phenyl, etc.) substituted thienyl group, thiophene group, benzothiadiazole group; Thiophene group, benzothiadiazole group; Groups having a valence of divalent or higher such as phenylene group, aryl (e.g., bis(3,5-methylphenyl), etc.) porphyrin ring, pyrene-tetrayl group, benzo[1,2-c:4,5-c′]bis[1,2,5]thiadiazole skeleton (benzobisthiadiazole group); etc. are included.

[0108] A 400The substituent that an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, an m-valent aliphatic hydrocarbon group which may have a substituent, or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent may have is not particularly limited as long as the reaction targeted by the present invention (for example, cross-coupling reaction, etc.) can be carried out. Examples of the substituent include an alkyl group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, octyl group, etc.); an alkoxy group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, octyloxy group, etc.); a cycloalkyl group having 3 to 24 carbon atoms, preferably 3 to 18 carbon atoms, more preferably 3 to 12 carbon atoms, still more preferably 3 to 8 carbon atoms (e.g., cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, etc.); an alkenyl group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., ethenyl group, propenyl group, butenyl group, pentenyl group, hexenyl group, octenyl group, etc.); an alkynyl group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (e.g., ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group, octynyl group, etc.); an aryl group having 5 to 24 carbon atoms, preferably 5 to 18 carbon atoms, more preferably 5 to 12 carbon atoms, still more preferably 5 to 8 carbon atoms (e.g., phenyl group, naphthyl group, biphenyl group, etc.); an arylalkyl group having 7 to 24 carbon atoms, preferably 7 to 19 carbon atoms, more preferably 7 to 13 carbon atoms, still more preferably 7 to 9 carbon atoms (e.g., monophenylmethyl group, monophenylpropyl group, triphenylmethyl group, etc.); an aryloxy group having 5 to 24 carbon atoms, preferably 5 to 18 carbon atoms, more preferably 5 to 12 carbon atoms, still more preferably 5 to 8 carbon atoms (e.g., phenoxy group, naphthyloxy group, biphenyloxy group, etc.); a heteroaryl group having 4 to 24 carbon atoms, preferably 4 to 18 carbon atoms, more preferably 4 to 12 carbon atoms, still more preferably 4 to 8 carbon atoms (e.g., thiophenyl group, furanyl group, carbazolyl group, benzothiophenyl group, benzofuranyl group, indolyl group, pyrrolyl group, pyridyl group, etc.);An acyl group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (for example, an acetyl group, a propionyl group, a butanoyl group, a pentanoyl group, a heptanoyl group, and a group in which the carbonyl group contained in the acyl group is substituted with an ester group or an amide group, etc.); an amino group having 1 to 24 carbon atoms, preferably 1 to 18 carbon atoms, more preferably 1 to 12 carbon atoms, still more preferably 1 to 8 carbon atoms (for example, a diphenylamino group, a dimethylamino group, etc.); a fluorine-containing group such as fluorine, a fluorine-containing hydrocarbon group having 1 to 30 carbon atoms, preferably 1 to 12 carbon atoms; one or more selected from the group consisting of a cyano group, a nitro group, etc. are mentioned.; The substituents may be crosslinked with each other, and the whole substituents may form a cyclic structure (aromatic group). The substituent may further have a substituent.

[0109] {Leaving group in formula (H1)} The leaving group of the compound (H) used in the reaction method of the present invention is a leaving group usually used in a chemical reaction (for example, a cross-coupling reaction, etc.), and is not particularly limited as long as it can carry out the intended reaction of the present invention (for example, a cross-coupling reaction, etc.). Examples of the leaving group include a group selected from the group consisting of chloro, bromo, iodo, diazonium salt, trifluoromethanesulfonate, and carboxylic acid derivatives. Preferably it is a group selected from the group consisting of chloro, bromo, iodo, diazonium salt, and trifluoromethanesulfonate, and more preferably a group selected from the group consisting of chloro, bromo, and iodo. The compound (I) can have a plurality of leaving groups. In this case, the plurality of leaving groups may be the same or different. In the present invention, the number m of the leaving groups is an integer and is not particularly limited as long as the reaction (for example, a cross-coupling reaction, etc.) can be carried out. For example, it can be 1 to 10, preferably 1 to 8, more preferably 1 to 6, still more preferably 1 to 4.

[0110] {Specific examples of compound (H)} Specific examples of the compound (H) used in the mechanochemical reaction method of the present invention, such as the Suzuki-Miyaura cross-coupling reaction method, include, for example, one or more selected from the group consisting of aromatic halides such as the compounds (H1) to (H13) used in Examples 201 to 234.

[0111] (Compound (B)) Examples of the compound (B) used in the mechanochemical reaction method of the present invention include compounds represented by the following formula (B1) and / or (B2).

[0112] {Compound (B1)} Compound (B1) is represented by the following formula. A 500 -Y n (B1) (In the formula, A 500 represents an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, an n-valent aliphatic hydrocarbon group which may have a substituent, or an n-valent unsaturated aliphatic hydrocarbon group which may have a substituent. n represents an integer of 1 or more based on the number of Y. Y is each independently -B(OR 501 )(OR 502 ) -NHR 503 -R 504 -OH -R 505 -SH. R 501 and R 502 each independently represent hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, or a monovalent aliphatic hydrocarbon group which may have a substituent. R 501 and R 502 may be bonded to each other. R 503R each independently represents a hydrogen atom, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, a monovalent aliphatic hydrocarbon group which may have a substituent, or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent. 504 and R 505 each independently represents a single bond, a divalent aromatic hydrocarbon group which may have a substituent, or a divalent aliphatic hydrocarbon group which may have a substituent. The compound represented by the formula (I) is not particularly limited as long as it reacts with compound (H) to produce a reaction product (for example, a cross-coupling reaction product in which one or more of a CB bond, a CC bond, a CN bond, a CO bond, and a CS bond are formed by a cross-coupling reaction, and the like).

[0113] -A in formula (B1) 502 Base- A in formula (B1) 502 The n-valent aromatic hydrocarbon group which may have a substituent, the n-valent aromatic heterocyclic group which may have a substituent, the n-valent aliphatic hydrocarbon group which may have a substituent, and the n-valent unsaturated aliphatic hydrocarbon group which may have a substituent in the group are each represented by A in formula (H1) relating to compound (H). 501 In the group, it may be the same as the m-valent aromatic hydrocarbon group which may have a substituent, the m-valent aromatic heterocyclic group which may have a substituent, the m-valent aliphatic hydrocarbon group which may have a substituent, or the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent. In addition, A in formula (B1) 502 The substituent in the group is A in formula (H1) of compound (H). 400 The substituents in the group may be the same as those in the group. In addition, A in formula (B1) 502 A in formula (H1) relating to the group and compound (H) 400 The groups are each independently a group of any structure and may be the same or different.

[0114] -Y as -B (OR 501 )(OR 502A compound represented by formula (B1) having - As Y, -B(OR 501 )(OR 502 Examples of the compound represented by formula (B1) having ) include aromatic boronic acids or aromatic boronic acid esters. The aromatic boronic acid or aromatic boronic acid ester is not particularly limited as long as it reacts with compound (H) (e.g., cross-coupling reaction, etc.) to give a reaction product in which a C-C bond is formed. Aromatic boronic acid esters include aromatic boronic acid alkyl esters, aromatic boronic acid alkylene glycol esters, aromatic boronic acid aryl esters, and aromatic boronic acid arylene glycol esters.

[0115] In formula (B1), -B(OR 501 )(OR 502 ) group, R 501 and R 502 each independently represent hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, or a monovalent aliphatic hydrocarbon group which may have a substituent. R 501 and R 502 may be bonded to each other. Here, the monovalent aromatic hydrocarbon group which may have a substituent and the monovalent aliphatic hydrocarbon group which may have a substituent can be the same groups as the m-valent aromatic hydrocarbon group which may have a substituent and the m-valent aliphatic hydrocarbon group which may have a substituent in the A 400 group in formula (H1) related to compound (H). In addition, R 501 and R 502 in the -B(OR 501 )(OR 502 ) group in formula (B1) and A 400 in formula (H1) related to compound (H) are independent groups and may be the same or different.

[0116] R 501 and R 502 groups bonded to each other include R 501 and R 502They together form a cyclic structure. When it is an aromatic group, for example, a 1,2-phenylene group etc. can be mentioned. When it is a hydrocarbon group, for example, an ethylene group, a 1,1,2,2-tetramethylethylene group (pinacolato group), a neopentyl glycolato group, a propylene group etc. can be mentioned. As the aromatic boronic acid or aromatic boronic acid ester as the compound represented by formula (B1), one kind can be used alone or two or more kinds can be used in combination. As the aromatic boronic acid or aromatic boronic acid ester as the compound represented by formula (B1), a commercially available product can be used as it is or after purification.

[0117] -Y is -NHR 503 The compound represented by formula (B1) having Y is -NHR 503 Examples of the compound represented by formula (B1) having -NHR as Y include aromatic amino compounds. The aromatic amino compound is not particularly limited as long as it reacts with compound (I) (for example, cross-coupling reaction etc.) to give a product in which a C-N bond is formed. -NHR in formula (B1) 503 The R 503 in the group represents, independently of each other, hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, a monovalent aliphatic hydrocarbon group which may have a substituent, or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent. Here, the monovalent aromatic hydrocarbon group which may have a substituent, the monovalent aromatic heterocyclic group which may have a substituent, the monovalent aliphatic hydrocarbon group which may have a substituent, or the monovalent unsaturated aliphatic hydrocarbon group which may have a substituent can be the same groups as the m-valent aromatic hydrocarbon group which may have a substituent, the m-valent aromatic heterocyclic group which may have a substituent, the m-valent aliphatic hydrocarbon group which may have a substituent, or the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in the A 400 in the group in formula (I) related to compound (I). The aromatic amino compound as the compound represented by formula (B1) can be used alone or in combination of two or more. The aromatic amino compound as the compound represented by formula (B1) can be used as a commercially available product as it is or after purification.

[0118] -Y is -R 504 Compound represented by formula (B1) having -OH In the present invention, Y is -R 504 Examples of the compound represented by formula (B1) having -OH include aromatic compounds having a hydroxyl group. The aromatic compound having a hydroxyl group is not particularly limited as long as it reacts with compound (H) (for example, cross-coupling reaction, etc.) to give a product in which a C-O bond is formed. -R in formula (B1) 504 R in the -OH group 504 The groups each independently represent a single bond, a divalent aromatic hydrocarbon group which may have a substituent, or a divalent aliphatic hydrocarbon group which may have a substituent. When R 504 is a single bond, the hydroxyl group is directly bonded to A 502 . Here, the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent can be the same as the divalent group in the m-valent aromatic hydrocarbon group which may have a substituent or the m-valent aliphatic hydrocarbon group which may have a substituent in the A 400 group in formula (H1) related to compound (H). In addition, the -R 504 group in the -OH group and the A 504 group in formula (B1) are independent groups and may be the same or different. 502 The aromatic compound having a hydroxyl group as the compound represented by formula (B1) can be used alone or in combination of two or more. The aromatic compound having a hydroxyl group as the compound represented by formula (B1) can be used as a commercially available product as it is or after purification.

[0119] -R as Y 505 -A compound represented by formula (B1) having -SH In the present invention, -R as Y 505 -Examples of the compound represented by formula (B1) having -SH include aromatic compounds having a thiol group. The aromatic compound having a thiol group is not particularly limited as long as it reacts with compound (H) (for example, cross-coupling reaction, etc.) to give a product in which a C-S bond is formed. -R in formula (B1) 505 -R in the -SH group 505 Each independently represents a single bond, a divalent aromatic hydrocarbon group which may have a substituent, or a divalent aliphatic hydrocarbon group which may have a substituent. When R 505 is a single bond, the thiol group is directly bonded to A 502 . Here, the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent can be the same as the divalent group in the m-valent aromatic hydrocarbon group which may have a substituent or the m-valent aliphatic hydrocarbon group which may have a substituent in the A 400 group in formula (H1) related to compound (H). Note that -R 504 -R in the -SH group 505 group and A 502 group in formula (B1) are each independent groups and may be the same or different. The aromatic compound having a thiol group as the compound represented by formula (B1) can be used alone or in combination of two or more. The aromatic compound having a thiol group as the compound represented by formula (B1) can be used as a commercial product as it is or after purification.

[0120] {Compound (B2)} Compound (B2) is represented by the following formula. (R 601 O)(R 602 O)B-B(OR 603 )(OR 604)(B2) (In the formula, R 601 ~R 604 each independently represents hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, or a monovalent aliphatic hydrocarbon group which may have a substituent. R 601 and R 602 may be bonded to each other, and R 603 and R 604 may be bonded to each other.) The compound (B2) is not particularly limited as long as it reacts with the compound (H) (for example, a cross-coupling reaction or the like) to produce a reaction product in which a C-B bond is formed.

[0121] Examples of the compound represented by the formula (B2) include one or more selected from the group consisting of diboronates (tetraalkyl diboronates, trialkyl diboronates, dialkyl diboronates, or monoalkyl diboronates) and diboronic acids. Examples of the diboronates include one or more selected from the group consisting of alkyl diboronates, alkylene glycol diboronates, aryl diboronates, arylene glycol diboronates, and the like. Examples of the diboronic acids include, for example, Tetrahydroxydiborane.

[0122] Examples of the monovalent aromatic hydrocarbon group which may have a substituent as R 601 ~R 604 in the formula (B2) include one or more selected from the group consisting of, for example, a phenyl group, a naphthyl group, a biphenyl group, and the like, each independently. Examples of the monovalent aliphatic hydrocarbon group which may have a substituent as R 601 ~R 604 in the formula (B2) include one or more selected from the group consisting of, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a tert-butyl group, and the like, each independently. Also, R 601 ~R 604When it is a monovalent aliphatic hydrocarbon group which may have a substituent, R 601 and R 602 and R 603 and R 604 may be bonded to each other. For example, R 601 -R 602 and R 603 -R 604 may each independently be one or more groups selected from the group consisting of, for example, an ethylene group, a 1,1,2,2-tetramethylethylene group, a 2,2-dimethylpropylene group, a hexylene group (or a 1,1,3-trimethylpropylene group), and the like.

[0123] In the above R 601 ~R 604 the substituent and the number thereof which the aromatic hydrocarbon group and the aliphatic hydrocarbon group may have are not particularly limited as long as they do not inhibit the reaction (for example, cross-coupling reaction, etc.). Examples of the substituent include one or more groups each independently selected from the group consisting of an alkyl group, an aryl group, an alkoxy group, an aryloxy group, and the like, and these substituents can have one or more. Further, the substituents may be cross-linked to each other and may further have a substituent.

[0124] In the compound represented by the formula (B2), more specifically, examples of the diboronates include Bis(pinacolato)diboron, Bis(neopentylGlycolate)diboron, Bis(hexyleneGlycolato)diboron, Bis(catecholato)diboron, and the like, and one or more selected from the group consisting thereof can be mentioned. The compound represented by the formula (B2) can be used alone or in combination of two or more. The compound represented by the formula (B2) can be used as a commercial product as it is or after purification.

[0125] (Usage amount of compound (B), etc.) The usage amount of compound (B) is appropriately adjusted in consideration of the equivalent ratio with compound (H). The equivalent ratio of compound (H) to compound (B) (compound (H) / compound (B)) is not particularly limited as long as it is an equivalent ratio at which the reaction (for example, cross-coupling reaction, etc.) proceeds. For example, it is 10 / 1 to 1 / 10, preferably 5 / 1 to 1 / 5, more preferably 3 / 1 to 1 / 3, and even more preferably 2 / 1 to 1 / 2.

[0126] In the present invention, compound (B) can be used alone or in combination of two or more. For example, one kind of the compound represented by formula (B1) can be used alone or in combination of two or more. Also, one or more of the compounds represented by formula (B1) and one or more of the compounds represented by formula (B2) can be used in combination. Compound (B) can be used as a commercially available product as it is or after purification.

[0127] <Base> In the mechanochemical reaction method of the present invention, in addition to the ligand compound (Lx) or a salt thereof, the metal compound, and the substrate (the compound (H) and the compound (B)), a base can be used as necessary. The base is not particularly limited as long as it can promote the mechanochemical reaction (for example, Suzuki-Miyaura cross-coupling reaction, etc.). The base does not contain a compound corresponding to the ligand compound (Lx) or a salt thereof, the metal compound, and the substrate (the compound (H) and the compound (B)). Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, rubidium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, potassium fluoride, cesium fluoride; alkali metal hydrides such as sodium hydride, potassium hydride; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium methoxide, potassium ethoxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide; organic bases such as tertiary amine bases including triethylamine, tributylamine, dimethylpropylamine, dimethylbutylamine, dimethylcyclohexylamine, dimethylbenzylamine, diisopropylmethylamine, diisopropylethylamine, pyridine, diazabicycloundecene (1,8-diazabicyclo[5.4.0]undec-7-ene), diazabicyclononene (1,5-diazabicyclo[4.3.0]non-5-ene), 1,4-diazabicyclo[2.2.2]octane, N-ethylmorpholine, N,N,N’,N’-tetramethylethylenediamine, N,N,N’,N’-tetramethylpropylenediamine, N,N,N’,N’-tetramethylhexanediamine, bis(dimethylaminoethyl)ether, N,N’,N’-trimethylaminoethylpiperazine, N,N,N’,N’’,N’’-pentamethyldiethylenetriamine; and one or more selected from the group consisting of these. The base can be used alone or in combination of two or more. The base can be used as a commercially available product as it is or after purification.

[0128] The amount of the base used is not particularly limited as long as the mechanochemical reaction (for example, Suzuki-Miyaura cross-coupling reaction, etc.) proceeds, and can be appropriately determined in consideration of the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the base, the unsaturated hydrocarbon compound used as necessary, the reaction product, etc., and the reaction temperature. The amount of the base used can be, for example, 0.5 equivalent or more, preferably 0.8 equivalent or more, more preferably 1.0 equivalent or more, still more preferably 1.2 equivalent or more, and most preferably 1.4 equivalent or more, relative to 1 equivalent of the compound (H). The upper limit of the amount of the base used is not particularly limited, and can be, for example, 10.0 equivalents or less, preferably 5.0 equivalents or less, more preferably 4.0 equivalents or less, and still more preferably 3.0 equivalents or less.

[0129] <Unsaturated hydrocarbon compound> In the mechanochemical reaction method of the present invention, an unsaturated hydrocarbon compound can be used as needed in addition to the ligand compound (Lx) or a salt thereof, the metal compound, the substrate (the compound (H) and the compound (B)), and the base. The unsaturated hydrocarbon compound is a chain-like and / or cyclic compound having at least one carbon-carbon unsaturated double bond or at least one carbon-carbon unsaturated triple bond in the molecule. The unsaturated hydrocarbon compound is not particularly limited as long as it can promote a mechanochemical reaction (for example, Suzuki-Miyaura cross-coupling reaction, etc.). The unsaturated hydrocarbon compound does not contain aromatic compounds such as benzene and naphthalene. Further, the unsaturated hydrocarbon compound does not contain compounds corresponding to the ligand compound (Lx) or a salt thereof, the metal compound, the substrate, and the base.

[0130] The number of carbon atoms of the unsaturated hydrocarbon compound is, for example, 5 to 24, preferably 5 to 18, more preferably 5 to 12, still more preferably 6 to 10, and most preferably 6 to 8. Examples of the unsaturated hydrocarbon compound having one carbon-carbon unsaturated double bond include one or more selected from the group consisting of hexene, heptene, octene, nonene, decene, and the like. Examples of the unsaturated hydrocarbon compound having one carbon-carbon unsaturated double bond include one or more selected from the group consisting of cyclohexene, cycloheptene, cyclooctene, cyclodecene, and the like. Examples of the unsaturated hydrocarbon compound having two carbon-carbon unsaturated double bonds include one or more selected from the group consisting of hexadiene, heptadiene, octadiene, nonadiene, decadiene, and the like. Examples of the unsaturated hydrocarbon compound having two carbon-carbon unsaturated double bonds include one or more selected from the group consisting of cyclohexadiene, cycloheptadiene, cyclooctadiene, cyclodecadiene, and the like. Examples of the unsaturated hydrocarbon compound having one carbon-carbon unsaturated triple bond include one or more selected from the group consisting of hexyne, heptyne, octyne, decyne, and the like. Examples of the cyclic compound (4) having one carbon-carbon unsaturated triple bond include one or more selected from the group consisting of cyclooctyne, cyclodecyne, and the like. The unsaturated hydrocarbon compound can be used alone or in combination of two or more. The unsaturated hydrocarbon compound can be used as a commercial product as it is or after purification.

[0131] When using the unsaturated hydrocarbon compound, the amount used is not particularly limited as long as the mechanochemical reaction (for example, Suzuki-Miyaura cross-coupling reaction, etc.) proceeds. Considering the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the base, the unsaturated hydrocarbon compound, the reaction product, etc., and the reaction temperature, etc., it can be appropriately determined. When using the unsaturated hydrocarbon compound, the amount used is, for example, 0.01 μL / mg or more, preferably 0.05 μL / mg or more, more preferably 0.10 μL / mg or more, and for example, 3.0 μL / mg or less, preferably 1.0 μL / mg or less, more preferably 0.50 μL / mg or less, based on the total mass of all the raw materials (for example, the ligand compound (Lx) or its salt, the metal compound, the compound (H), the compound (B), the base, etc.) added for carrying out the mechanochemical reaction (for example, Suzuki-Miyaura cross-coupling reaction, etc.).

[0132] In the reaction method of the present invention, when an unsaturated hydrocarbon compound is used, although it depends on the types and amounts used of the ligand compound (Lx) or its salt, the metal compound, and the substrates (compound (H) and compound (B)), it is possible to significantly improve the reaction activity as compared with the case where it is not used. Regarding this point, the present inventors presume as follows. When performing a solid-phase reaction (for example, a Suzuki-Miyaura cross-coupling reaction) by a mechanochemical reaction under substantially solvent-free conditions, it is often difficult to efficiently perform the diffusion of the ligand compound (Lx) or its salt, the metal compound, the substrates (compound (H) and compound (B)), the base, and the reaction product, particularly the diffusion of the metal compound, and there is a risk that the cross-coupling reaction will not proceed easily. When the present inventors observed the metal compound after the reaction using a transmission electron microscope, they found that by using an unsaturated hydrocarbon compound, aggregation of the metal compound can be suppressed and the diffusion of the metal compound can be efficiently performed. It is considered that the unsaturated hydrocarbon compound contributes to the suppression of aggregation of the metal compound and also to the improvement of the reaction activity, and the present inventors presume that the reaction method of the present invention (for example, a cross-coupling reaction method, etc.) exhibits excellent effects. However, the present invention is not limited by such presumption at all.

[0133] <Reaction promoter> In the mechanochemical reaction method of the present invention, in addition to the ligand compound (Lx) or its salt, the metal compound, the substrates (compound (H) and compound (B)), the base, and the unsaturated hydrocarbon compound, a reaction promoter can be used as needed. As the reaction promoter, components known as reaction promoters for various reactions (for example, Suzuki-Miyaura cross-coupling reaction, etc.) performed by the mechanochemical reaction method can be used. Further, the reaction promoter does not contain compounds corresponding to the ligand compound (Lx) or its salt, the metal compound, the substrate, the base, and the unsaturated hydrocarbon compound. Among these, it is preferable to use water (such as pure water, ion-exchanged water, etc.) and / or an organic solvent. The amount of the organic solvent used is less than 0.7 mL per 1 mmol in total of the compound (H) and the compound (B). The amount of the reaction accelerator used is not particularly limited as long as the mechanochemical reaction (such as a cross-coupling reaction, etc.) proceeds. For example, it can be appropriately determined in consideration of the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the base, the unsaturated hydrocarbon compound, the reaction product, etc., and the reaction temperature. The amount of the accelerator used can be, for example, 20.0 equivalents or less, preferably 10.0 equivalents or less, more preferably 9.0 equivalents or less, based on the equivalent of the compound (1). There is no particular lower limit for the amount used, but it can be, for example, 0.5 equivalent or more, preferably 0.8 equivalent or more, more preferably 1.0 equivalent or more, still more preferably 1.2 equivalent or more, and most preferably 1.4 equivalent or more.

[0134] <Solvent> In the mechanochemical reaction method of the present invention, a solvent can be used in addition to the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the base, the unsaturated hydrocarbon compound, and the reaction accelerator. In the mechanochemical reaction method of the present invention (such as the Suzuki-Miyaura cross-coupling reaction method, etc.), the amount of the organic solvent present is 0.7 mL or less per 1 mmol in total of the compound (H) and the compound (B). Such conditions can be said to be conditions where substantially no organic solvent is used. In the present invention, the condition of substantially not using an organic solvent means any one of a mode of not using an organic solvent at all, a mode of actively not using a solvent, and a mode of using only a very small amount of an organic solvent such that the solvent effect is not exhibited.

[0135] In the present invention, the amount of the organic solvent present is 0.7 mL or less per 1 mmol in total of the substrates (the compound (H) and the compound (B)). Usually it is 0.5 mL or less, preferably 0.2 mL or less, more preferably 0.1 mL or less, still more preferably 0.05 mL or less, most preferably 0.02 mL or less, and most preferably 0 mL (no use of the organic solvent). For example, in a general cross-coupling reaction, 1 to 2 mL of an organic solvent is used per 1 mmol in total of the reaction raw materials. Since the amount of the organic solvent used in the present invention is small, the reaction raw materials usually, at the start of the reaction, at least a part of the substrates is not dissolved in an organic solvent or the like. In some cases, all of them may exist in a solid state without being dissolved in an organic solvent or the like.

[0136] In the present invention, examples of the organic solvent that may be present in an amount of 0.7 mL or less per 1 mmol in total of the substrates (the compound (H) and the compound (B)) include organic solvents used in reactions (for example, cross-coupling reactions, etc.). For example, aromatic solvents such as benzene, toluene, xylene, mesitylene, durene, decalin, etc.; ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, cyclopentyl methyl ether, etc.; alcohol solvents such as methanol, ethanol, n-propanol, 2-propanol, 1-butanol, 1,1-dimethylethanol, tert-butanol, 2-methoxyethanol, ethylene glycol, etc.; halogenated hydrocarbon solvents such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, etc.; polar solvents such as acetonitrile, N,N-dimethylformamide, N,N'-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, etc.; ketone solvents such as acetone, methyl ethyl ketone, etc.; one or more selected from the group consisting of pyridine, acetic acid, etc. are mentioned. In particular, one or more selected from the group consisting of benzene, toluene, xylene, chlorobenzene, diethyl ether, dibutyl ether, cyclopentyl methyl ether, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, acetone, acetonitrile, N,N-dimethylformamide, methanol, ethanol, 2-propanol, tert-butanol, dimethyl sulfoxide, etc. are preferred.

[0137] <Other components> In the mechanochemical reaction method of the present invention, various components can be used in addition to the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the reaction accelerator, the base, the unsaturated hydrocarbon compound, and the solvent. For example, a ligand compound having no predetermined polymer chain can be mentioned. Such a ligand compound may be used in combination with one or more of the formulas (La), (Lb), and (Lc).Examples of ligand compounds other than the ligand compound (Lx) include arylphosphines such as triphenylphosphine, tri(o-tolyl)phosphine, and tri(mesityl)phosphine; alkylphosphines such as tri(cyclohexyl)phosphine, tri(isopropyl)phosphine, and tri(tert-butyl)phosphine; Buchwald phosphine ligands such as 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (DavePhos), 2-(di-tert-butylphosphino)-2',4',6'-triisopropyl-3,6-dimethoxy-1,1'-biphenyl (tBuBrettPhos), 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-(di-tert-butylphosphino)-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropylbiphenyl, 2-(dicyclohexylphosphino)biphenyl, and 2-(di-tert-butylphosphino)-2'-(N,N-dimethylamino)biphenyl; bidentate phosphines such as 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)propane, 1,2-bis(dicyclohexylphosphino)ethane, 1,2-bis(diphenylphosphino)butane, and 1,2-bis(diphenylphosphino)ferrocene; N-heterocyclic carbene ligands such as 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazolium chloride, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, and 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-1H-imidazolium chloride; t-Bu. 3 P·HBF 4 Examples of these include one or more selected from the group consisting of trialkylphosphonium tetrafluoroborates such as (tri-tert-butylphosphonium tetrafluoroborate).

[0138] <Use of the mechanochemical reaction method> The mechanochemical reaction method of the present invention can be applied to one or more reactions selected from the group consisting of coupling reactions, alkylation reactions, halogenation reactions, hydrolysis reactions, oxidation reactions, reduction reactions, metalation reactions, radical reactions, metathesis reactions, and cycloaddition reactions. Among these, examples of the coupling reaction include a homocoupling reaction and a cross-coupling reaction. For example, a cross-coupling reaction that forms one or more chemical bonds selected from C-N bonds, C-B bonds, C-C bonds, C-O bonds, and C-S bonds can be mentioned. In particular, it is preferably used for the Suzuki-Miyaura cross-coupling reaction.

[0139] <Reaction conditions> The mechanochemical reaction method of the present invention is an organic synthesis reaction method that directly contacts and mixes each component to cause a reaction, does not use an organic solvent, has a low environmental load, and has high reaction activity. For example, by applying mechanical energy to each component by means such as mixing, grinding, shearing, impact, and compression, the raw materials are activated and reacted. The reaction conditions can be appropriately determined according to the type of reaction. Examples of the mechanochemical reaction include one or more reactions selected from the group consisting of coupling reactions, alkylation reactions, halogenation reactions, hydrolysis reactions, oxidation reactions, reduction reactions, metalation reactions, radical reactions, metathesis reactions, and cycloaddition reactions.

[0140] (Reaction apparatus) When performing the mechanochemical reaction of the present invention, a reaction apparatus for applying mechanical energy to each component is used. The method of applying mechanical energy to each component is not particularly limited, and examples include methods such as shaking, rubbing, pressing, dispersing, kneading, and crushing. Examples of the apparatus used when performing the mechanochemical reaction of the present invention include, for example, Grinders such as ball mills, rod mills, jet mills, and SAG mills; Grinders such as rotary mortars and pounding machines (raikaiki); Horizontal cylindrical, V-shaped, double conical, cubic, S-shaped, continuous V-shaped, etc. (horizontal axis rotation) container rotation type mixing devices; Horizontal cylindrical, V-shaped, double conical, and ball mill type, etc. (with baffle blades) container rotation type mixing devices; Rocking type and cross rotary type, etc. (rotary vibration) container rotation type mixing devices; Ribbon type, paddle type, single shaft rotor type, and bug mill type, etc. (horizontal axis rotation) fixed container type mixing devices; Ribbon type, screw type, planetary type, turbine type, high-speed flow type, rotating disk type, and muller type, etc. (vertical axis rotation) fixed container type mixing devices; Vibrating mill type and sieve, etc. (vibration) fixed container type mixing devices; Fluidized bed, swirling fluidized bed, riser pipe type, and jet pump type, etc. (fluidization) fluid motion type mixing devices; Gravity type and static mixer, etc. (gravity) fluid motion type mixing devices; One or more selected from the group consisting of etc. are exemplified. In the present invention, as long as the cross-coupling reaction proceeds, the method and the apparatus used are not particularly limited. For example, an apparatus for mechanically performing a mixing process can be used. A mixing device can preferably be used. As the mixing device, for example, reference can be made to the powder mixing devices described in Table 5 and Figure 9, etc. of Sakashita "Powder Mixing Process Technology" Color Materials, 77(2), 75-85(2004). Specifically, a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-shaft ball mill, etc. can be used.

[0141] The reaction apparatus used in the mechanochemical reaction method of the present invention may further be provided with various means that can be provided in a reaction apparatus for a compound, such as a measuring means, a decompression or pressurization means, an atmosphere adjusting means (gas introduction or discharge means), an input means for various components, an extraction means for various components and reaction products, a purification means, an analysis means, etc.

[0142] When using a mixing device in the mechanochemical reaction method of the present invention, the mixing rate is not particularly limited, and can be appropriately determined in consideration of the types and amounts of each of the substrate (such as the compound (H) and compound (B)), the ligand compound (Lx) or its salt, the metal compound, the compound such as the base and unsaturated hydrocarbon compound used as necessary, the reaction temperature, etc. For example, in the mechanochemical reaction method, when mixing each component by a ball mill, shaking can be performed at a vibration frequency of 5 Hz or more, preferably 10 Hz or more, more preferably 20 Hz or more.

[0143] (Reaction temperature) In the mechanochemical reaction method of the present invention, for example, in the Suzuki-Miyaura cross-coupling reaction method, etc., the reaction temperature (the temperature inside the reaction vessel) is not particularly limited. The reaction temperature is below the temperature at which each compound used, such as the substrate, the ligand compound (Lx) or its salt, does not thermally decompose, and is, for example, 20°C or higher and 500°C or lower, more preferably 35°C or higher and 500°C or lower. If the reaction temperature is less than 20°C, the reaction efficiency may decrease. The method for controlling the reaction temperature is not particularly limited, but the temperature control method used when performing a chemical reaction can be used. For example, a method of controlling the temperature inside the reaction vessel using warm air, a method of covering the reaction vessel with a heat medium at a predetermined temperature to control the temperature inside the reaction vessel, a method of providing a heating element to control the temperature inside the reaction vessel, etc. can be mentioned. In the present invention, for example, a method of controlling the temperature inside the reaction vessel by applying warm air generated by a heat gun to the reaction vessel is preferable from the viewpoints of safety and ease of temperature control operation.

[0144] (Reaction atmosphere) In the mechanochemical reaction method of the present invention, for example, in the Suzuki-Miyaura cross-coupling reaction method, etc., the reaction atmosphere (the atmosphere inside the reaction vessel) is not particularly limited. It can be appropriately determined in consideration of the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the unsaturated hydrocarbon compound and base used as necessary, the reaction product, etc., and the reaction temperature. For example, it can be carried out in the atmospheric atmosphere without particularly adjusting the atmosphere. It can also be carried out in an inert gas atmosphere such as nitrogen, helium, neon, argon, etc.

[0145] (Reaction time) In the mechanochemical reaction method of the present invention, for example, in the Suzuki-Miyaura cross-coupling reaction method, etc., the reaction time (the time for performing the treatment by mechanical means) is not particularly limited. Considering the types and amounts of each of the ligand compound (Lx) or its salt, the metal compound, the substrate (the compound (H) and the compound (B)), the unsaturated hydrocarbon compound and base used as necessary, the reaction product, etc., and the reaction temperature, etc., it can be appropriately determined. For example, it can be 1 minute or more, preferably 3 minutes or more, more preferably 5 minutes or more. The upper limit of the reaction time is not particularly limited, but for example, it can be 48 hours or less, preferably 10 hours or less, more preferably 5 hours or less, still more preferably 3 hours or less.

[0146] [Treatment after reaction, etc.] In the mechanochemical reaction method of the present invention, for example, in the Suzuki-Miyaura cross-coupling reaction method, etc., the obtained reaction product can be purified as necessary. The purification method of the reaction product is not particularly limited, and for example, methods such as recrystallization, column chromatography, washing with a solvent, etc. can be used.

[0147] [Ligand compound (Ly) or its salt] The ligand compound (Ly) or its salt according to the present invention is a ligand compound or its salt represented by the formula (La), (Lb) or (Lc). These ligand compounds (Ly) correspond to the ligand compounds represented by the formula (La), (Lb) or (Lc) described in the <ligand compound (Lx) or its salt> of the [additive for mechanochemical reaction].

[0148] The method for producing the ligand compound (Ly) is not particularly limited. For example, a method of reacting a polymer compound having a reactive group with a ligand compound having a functional group that reacts with the reactive group, a method of synthesizing a polymer compound in the presence of a ligand compound having a functional group, and the like can be mentioned.

[0149] Examples of the compound having a polyether as the polymer chain include a method of reacting a polyether having a reactive group at one end (for example, polyoxyalkylene) with a ligand compound having a functional group that reacts with the reactive group in the polyether, a method of reacting a cyclic ether with a ligand compound having a functional group that reacts with the cyclic ether, and the like. Examples of the compound having a polyamide as the polymer chain include a method of reacting a polyamide having a reactive group at one end with a ligand compound having a functional group that reacts with the reactive group in the polyamide, a method of reacting a cyclic amide such as caprolactam with a ligand compound having a functional group that reacts with the cyclic amide, and the like. Examples of the compound having a polyester as the polymer chain include a method of reacting a polyester having a reactive group at one end with a ligand compound having a functional group that reacts with the reactive group in the polyester, a method of reacting a cyclic ester with a ligand compound having a functional group that reacts with the cyclic ester, and the like. Examples of the compound having a polyurethane as the polymer chain include a method of reacting a polyurethane having a reactive group at one end with a ligand compound having a functional group that reacts with the reactive group in the polyurethane.

[0150] The ligand compound (Ly) of the present invention can be converted into a desired salt form. The means for conversion into the salt form is not particularly limited and can be carried out based on well-known techniques in the field of organic chemistry and the like. Preferred examples of the salt include, for example, inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, etc., organic acid salts such as acetate, fumarate, maleate, oxalate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, etc., inorganic salts such as sodium, potassium, lithium, calcium, magnesium, etc., and salts with organic bases such as tromethamine, arginine, lysine, diethanolamine, triethanolamine, trimethylamine, etc.

[0151] [Complex composed of ligand compound (Ly) or its salt and metal atom] In the complex composed of the ligand compound (Ly) or its salt according to the present invention and a metal atom, the ligand compound (Ly) is a ligand compound or its salt represented by the formula (La), (Lb) or (Lc) described in <ligand compound (Lx) or its salt> of the [additive for mechanochemical reaction]. Further, in the complex composed of the ligand compound (Ly) or its salt according to the present invention and a metal atom, the metal atom is the same as the metal atom described in <complex> of the [additive for mechanochemical reaction]. Furthermore, in the complex composed of the ligand compound (Ly) or its salt according to the present invention and a metal atom, the metal atom is the same as the method for producing the complex described in <complex> of the [additive for mechanochemical reaction].

Examples

[0152] Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. These Examples are merely one aspect of the present invention. The present invention is not limited by these Examples in any way. The compounds used in this Example were used as commercially available products without purification as long as not otherwise specified. In Examples and Comparative Examples, Me represents a methyl group, Et represents an ethyl group, iPr represents an isopropyl group, and tBu or t-Bu represents a tertiary butyl group, respectively.

[0153] In the examples and comparative examples, when the reaction was carried out using a ball mill, each reagent was charged into a stainless steel ball mill jar, and a ball mill MM400 type manufactured by Verder Scientific Co., Ltd. (former Retsch) was used. When heating during the reaction using the ball mill, the outside of the ball mill jar was heated at a predetermined temperature with a heat gun (HG-1450B manufactured by Takagi). When the relationship between the set temperature of the heat gun and the temperature inside the ball mill jar (the temperature of the reaction system) was confirmed using a thermographic image, it was as follows.

[0154] [Table 1]

[0155] [Synthesis of Phosphorus Ligand Compound (La)] [Example 1] [Production of Phosphorus Ligand Compound (La101)] The phosphorus ligand compound (La101) was produced according to the following reaction schemes S1 to S3. [Chemical Formula]

[0156] ·S1: Production of Compound (1c) In a 1.5 mL stainless steel ball mill jar containing stainless steel balls with a diameter of 5 mm, under air, 0.7 mmol of compound (1b), 2.0 equiv (relative to compound (1b)) of compound (1a), palladium(II) acetate (Pd(OAc) 2 ) at 3.0 mol% (relative to compound (1b)), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) at 4.5 mol% (relative to compound (1b)), potassium phosphate (K 3 PO 4) was added at 3.0 equiv (relative to compound (1b)), water (H 2 O) was added at 3.7 equiv (relative to compound (1b)), and 1,5-cyclooctadiene (1,5-cod) was added at 0.2 μL / mg (relative to the total amount in the system). The lid of the ball mill jar was closed, attached to the ball mill, and shaken for 5 minutes (stirred at 30 Hz) while heating the jar with a heat gun set at 250 °C (internal temperature 120 °C) to perform the cross-coupling reaction, and compound (1c) was obtained. Compound (1c) was isolated by column chromatography, and the isolated yield was 57%.

[0157] ·S2: Preparation of compound (1e) Into the reaction vessel, 1.0 mmol (1.0 equiv) of the compound (1c) obtained in S1, 1.0 equiv of n-butyllithium (nBuLi) (relative to compound (1c)), and diethyl ether (Et 2 O) were added in an amount such that the concentration of compound (1c) was 0.35 M (0.35 mol / L), and the mixture was stirred at room temperature (25 °C) for 2 hours. Then, chlorodiphenylphosphine (Ph 2 PCl) was added at 1.1 equiv (relative to compound (1c)) at 0 °C, and then the mixture was stirred at room temperature (25 °C) for 24 hours to carry out the reaction, and compound (1d) was obtained. Compound (1d) was isolated by column chromatography, and the isolated yield was 86%. Into the reaction vessel, 0.88 mmol (1.0 equiv) of the obtained compound (1d), 1.5 equiv of tetra-n-butylammonium fluoride (TBAF) (relative to compound (1d)), and diethyl ether were added in an amount such that the concentration of compound (1d) was 0.44 M (0.44 mol / L), and the mixture was stirred at room temperature (25 °C) for 2 hours to carry out the reaction, and compound (1e) was obtained. Compound (1e) was isolated by column chromatography, and the isolated yield was 84%.

[0158] ·S3: Preparation of phosphorus-based ligand compound (La101) Into the reaction vessel, 0.62 mmol (3.0 equiv) of compound (1e), 1.0 equiv of compound (1f) (relative to compound (1e)), cesium carbonate (Cs 2 CO 3) was added in an amount of 8.0 equiv (relative to compound (1f)), and N,N-dimethylformamide (DMF) was added in an amount such that compound (1e) became 0.02 M (0.02 mol / L). The reaction was carried out by stirring at 100 °C for 24 hours to obtain a ligand compound (L1). The phosphorus-based ligand compound (La101) was isolated by recrystallization, and the isolated yield was 89%.

[0159] <Example 2> (Production of phosphorus-based compound (La102)) The phosphorus-based ligand compound (La102) was produced according to the following reaction schemes S1 to S3.

Chemical formula

[0160] In S1, compound (1c) was obtained in the same manner as in Example 1. In S2, compound (2d) was obtained in the same manner as in Example 1, except that chlorocyclohexylphosphine ((C 2 H 6 H 11 ) 2 PCl) was used instead of chlorodiphenylphosphine (Ph The isolated yield of compound (2d) was 86%. Also, compound (2e) was obtained in the same manner as in Example 1, except that compound (2d) was used instead of compound (1d). The isolated yield of compound (2e) was 99%. In S3, the phosphorus-based ligand compound (La102) was obtained in the same manner as in Example 1, except that compound (2e) was used instead of compound (1e). The isolated yield of the phosphorus-based ligand compound (La102) was 92%.

[0161] <Example 3> (Production of phosphorus-based ligand compound (La103))

Chemical formula

[0162] <Example 4> (Production of phosphorus-based compound (La104))

Chemical formula

[0163] <Example 5> (Production of phosphorus-based compound (La105))

Chemical formula

[0164] [Use in the mechanochemical synthesis of phosphorus-based ligand compound (La)] <Examples 201 to 234, Comparative Examples 201 to 247> In Examples 201 to 234 and Comparative Examples 201 to 247, the substrates (Compound (H), Compound (B)), phosphorus-based ligand compounds (La), and polyether-based compounds (E) used, and the reaction products (P) obtained in Examples 201 to 234 and Comparative Examples 201 to 247 are as follows. Among the phosphorus-based ligand compounds (La), (La101) to (La105) correspond to the ligand compounds (Lx) and (Ly) according to the present invention.

[0165] (Compound (H)) [Chemical formula]

[0166] (Compound (B)) [Chemical formula]

[0167] (Phosphorus-based ligand compound) [Chemical formula]

[0168] (Polyether-based compound (E)) [Chemical formula]

[0169] (Reaction product (P)) [Chemical formula]

[0170] [Accelerating effect of mechanochemical coupling reaction of phosphorus-based ligand compound] <Example 201> Into a 1.5 mL stainless steel ball mill containing stainless steel balls with a diameter of 5 mm, under air, 0.3 mmol (1.0 equiv) of (H1) as compound (H), 1.2 equiv of (B1) as compound (B) (relative to compound (H)), palladium(II) acetate (Pd(OAc) 2 ) at 3.0 mol% (relative to compound (H)), 6.0 mol% of a phosphorus-based ligand compound (La101) as ligand compound (La) (relative to compound (H)), cesium fluoride (CsF) at 3.0 equiv (relative to compound (H)), water at 3.7 equiv (relative to compound (H)), and 1,5-cyclooctadiene (1,5-cod) were added in an amount of 0.2 μL / mg. The lid of the ball mill jar was closed, it was attached to the ball mill, and while heating the jar from the outside with a heat gun so that the internal temperature of the ball mill jar reached 45 °C, stirring (30 Hz) was carried out for 20 minutes to perform a cross-coupling reaction. The NMR yield of the corresponding reaction product (P1) was 99%. The results are shown in Table 2.

[0171] <Examples 202 to 210, Comparative Examples 201 to 204> Using the ones shown in Table 2 as the phosphorus-based ligand compound (La), and setting the reaction time (stirring time) as the time shown in Table 2, a cross-coupling reaction was carried out in the same manner as in Example 201 to obtain a reaction product (P1). The NMR yields of the reaction product (P1) are also shown in Table 2.

[0172] <Comparative Examples 205 to 208> Using the ones shown in Table 2 as the ligand compound (La), and using (E1) at 6.0 mol% as the polyether-based compound (E) (relative to compound (H)), and setting the reaction time (stirring time) as the time shown in Table 2, a cross-coupling reaction was carried out in the same manner as in Example 201 to obtain a reaction product (P1). The NMR yields of the reaction product (P1) are also shown in Table 2.

[0173]

Table 2

[0174] <Examples 211 to 217, Comparative Examples 209 to 212> Using 4.5 mol% (relative to compound (H)) of those shown in Table 2 as the phosphorus-based ligand compound (La), and setting the reaction time (stirring time) to the time shown in Table 2, a cross-coupling reaction was carried out in the same manner as in Example 201 to obtain a reaction product (P1). The NMR yield of the reaction product (P1) is also shown in Table 3.

[0175] <Comparative Example 213> Using La9 as 4.5 mol% (relative to compound (H)) as the phosphorus-based ligand compound (La), setting the reaction time (stirring time) to 60 minutes, and using (E1) as 6.0 mol% (relative to compound (H)) as the polyether-based compound (E), a cross-coupling reaction was carried out in the same manner as in Example 201 to obtain a reaction product (P1). The NMR yield of the reaction product (P1) was 48%. The results are also shown in Table 3.

[0176]

Table 3

[0177] [Application to Coupling Reaction in Organic Solvent System] <Comparative Examples 214 to 216> Into the reaction vessel, 0.3 mmol (1.0 equiv) of (H1) as compound (H), 1.2 equiv of (B1) as compound (B) (relative to compound (H)), palladium(II) acetate (Pd(OAc) 2 ) as 3.0 mol% (relative to compound (H)) of the metal compound, the compounds shown in Table 4 as the phosphorus-based ligand compound (La) as 4.5 mol% (relative to compound (H)), cesium fluoride (CsF) as 3.0 equiv (relative to compound (H)), water as 3.7 equiv (relative to compound (H)), and toluene was added in an amount such that the concentration of compound (H) was 0.1 M (0.1 mol / L). The reaction vessel was heated while maintaining the internal temperature at 50°C and stirred for 180 minutes to carry out a cross-coupling reaction. The NMR yields of the corresponding reaction products (P1) are shown in Table 4.

[0178]

Table 4

[0179] [Reactions of Various Halogenated Organic Compounds] <Example 218> Into a 1.5 mL stainless steel ball mill jar containing a 5 mm diameter stainless steel ball, 76.1 mg (0.2 mmol) of (H2)(2-bromo-9,9’-spirobi[fluorene) as compound (H), 1.3 mg (0.006 mmol) of palladium(II) acetate (Pd(OAc) 2 ) as a metal compound, 91.1 mg (0.6 mmol) of cesium fluoride (CsF), 13 μL of water (3.7 equiv with respect to compound (H)), 52 μL of 1,5-cyclooctadiene (1,5-cod) (0.2 μL / mg), 55.3 mg (0.012 mmol) of (La101) as a phosphorus-based ligand compound (La), and 36.5 mg (0.24 mmol) of (B2) ((4-methoxyphenyl)boronic acid) as compound (B) were added. Then, the lid of the ball mill jar was closed, attached to the ball mill, and stirred (30 Hz) for 30 minutes while heating with a heat gun (set temp.: 70 °C) (internal temperature of the ball mill jar: 45 °C) to carry out the reaction. The NMR yield of the corresponding reaction product (P4) was 99%. The results are shown in Table 5. After completion of the reaction, the reaction mixture was dissolved in dichloromethane, filtered, and then dichloromethane was removed with an evaporator. The crude product was purified by silica gel column chromatography to obtain 77.7 mg (isolation yield 92%) of the target product (P4).

[0180] <Examples 219 to 227, Comparative Examples 217 to 236> As the compound (H), compound (B), and phosphorus-based ligand compound (La), those shown in Table 5 were used respectively. A cross-coupling reaction was carried out in the same manner as in Example 218 except that the reaction time (stirring time) was the time shown in Table 5, and the reaction product (P) shown in Table 5 was obtained. The NMR yield of the reaction product (P) is also shown in Table 5. When the formation of the reaction product (P) could not be confirmed by 1H-NMR, the NMR yield was taken as 0% (n.r.; No Reaction).

[0181] <Comparative Example 237> Using (H5) as the compound (H), (B1) as the compound (B), and (La106) as the phosphorus-based ligand compound (La), and using (E1) as the polyether-based compound (E) at 6.0 mol% (relative to the compound (H)), a cross-coupling reaction was carried out in the same manner as in Example 218 except that the reaction time (stirring time) was 90 minutes, and the reaction product (P5) was obtained. The NMR yield of the reaction product (P5) is also shown in Table 5.

[0182]

Table 5

[0183] [Reaction with Organic Chloride] <Example 228> Into a 1.5 mL stainless steel ball mill jar containing a 5 mm diameter stainless steel ball, under air, 0.3 mmol (1.0 equiv) of (H8) as the compound (H), 1.2 equiv of (B1) as the compound (B) (relative to the compound (H)), and palladium(II) acetate (Pd(OAc) 2(0) was added in an amount of 3.0 mol% (relative to compound (H)), (La102) as the phosphorus-based ligand compound (La) was added in an amount of 6.0 mol% (relative to compound (H)), cesium fluoride (CsF) was added in an amount of 3.0 equiv (relative to compound (H)), water was added in an amount of 3.7 equiv (relative to compound (H)), and 1,5-cyclooctadiene (1,5-cod) was added in an amount such that it was 0.2 μL / mg. The lid of the ball mill jar was closed, it was attached to the ball mill, and while heating the jar from the outside with a heat gun so that the internal temperature of the ball mill jar became 45 °C, stirring (30 Hz) was carried out for 30 minutes to conduct the cross-coupling reaction. The NMR yield of the corresponding reaction product (P12) was 99%. The results are shown in Table 6.

[0184] <Examples 229 to 231, Comparative Examples 238 to 245> As compound (H) and the phosphorus-based ligand compound (La), those shown in Table 6 were used respectively, and in the same manner as in Example 228, a cross-coupling reaction was carried out to obtain the reaction product (P) shown in Table 6. The NMR yields of the reaction products (P) are also shown in Table 5. When the formation of the reaction product (P) could not be confirmed by 1H-NMR, the NMR yield was taken as 0% (n.r.; No Reaction).

[0185]

Table 6

[0186] [Reaction of Organosolvent-Insoluble Organic Pigments] <Example 232> Into a 1.5 mL stainless steel ball mill jar containing stainless steel balls with a diameter of 5 mm, under air, (H12) as compound (H) was 0.1 mmol (1.0 equiv), (B7) as compound (B) was 2.4 equiv (relative to compound (H)), and palladium(II) acetate (Pd(OAc) 2(0) was added in an amount of 10.0 mol% (relative to compound (H)), (La101) as the phosphorus-based ligand compound (La) was added in an amount of 20.0 mol% (relative to compound (H)), cesium fluoride (CsF) was added in an amount of 6.0 equiv (relative to compound (H)), water was added in an amount of 7.2 equiv (relative to compound (H)), and 1,5-cyclooctadiene (1,5-cod) was added in an amount such that it was 0.2 μL / mg. The lid of the ball mill jar was closed, it was attached to the ball mill, and while heating the jar from the outside with a heat gun so that the internal temperature of the ball mill jar became 80 °C, stirring (30 Hz) was carried out for 90 minutes to conduct a cross-coupling reaction. The NMR yield of the corresponding reaction product (P16) was 88%. The results are shown in Table 7.

[0187] <Example 233, Comparative Example 246> A cross-coupling reaction was carried out in the same manner as in Example 232, except that the compounds shown in Table 7 were used as compound (H), compound (B), and the phosphorus-based ligand compound (La), respectively, to obtain the reaction product (P) shown in Table 7. The NMR yield of the reaction product (P) is also shown in Table 7.

[0188] <Example 234> Under air, into a 1.5 mL stainless steel ball mill jar containing stainless steel balls with a diameter of 5 mm, 0.05 mmol (1.0 equiv) of (H13) as compound (H), 4.8 equiv of (B8) as compound (B) (relative to compound (H)), palladium(II) acetate (Pd(OAc) 2 ) was added in an amount of 10.0 mol% (relative to compound (H)), (La102) as the phosphorus-based ligand compound (La) was added in an amount of 20.0 mol% (relative to compound (H)), cesium fluoride (CsF) was added in an amount of 12.0 equiv (relative to compound (H)), water was added in an amount of 7.2 equiv (relative to compound (H)), and 1,5-cyclooctadiene (1,5-cod) was added in an amount such that it was 0.2 μL / mg. The lid of the ball mill jar was closed, it was attached to the ball mill, and while heating the jar from the outside with a heat gun so that the internal temperature of the ball mill jar became 80 °C, stirring (30 Hz) was carried out for 90 minutes to conduct a cross-coupling reaction. The NMR yield of the corresponding reaction product (P17) was 84%. The results are shown in Table 7.

[0189] <Comparative Example 247> As the compound (H), the compounds shown in Table 7 were used for the compound (B) and the phosphorus ligand compound (La), respectively, and a cross-coupling reaction was carried out in the same manner as in Example 234 to obtain the reaction product (P17) shown in Table 7. The NMR yield of the reaction product (P17) is also shown in Table 7.

[0190] [Table 7]

[0191] [Synthesis of Bipyridine Ligand Compound (Lb)] <Example 301> [Chemical Formula] Under a nitrogen atmosphere, 0.5 mmol (122.1 mg) of 2,2'-bipyridine-4,4'-dicarboxylic acid, 2.05 equiv (relative to 2,2'-bipyridine-4,4'-dicarboxylic acid) of PEG-2000 monomethyl ether (monomethyl ether of polyethylene glycol with a number average molecular weight of 2,000), 341.2 mg of chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (TCFH), 280 μL of N-methylimidazole (NMI) and 55 mL of acetonitrile (MeCN) were placed in a two-necked round-bottom flask and stirred at room temperature (25 °C) for 24 hours. Then, after removing the solvent with an evaporator, it was purified by reprecipitation from a diethyl ether / dichloromethane solution to obtain 1.699 g of the bipyridine ligand compound (Lb103). The isolated yield was 70%.

[0192] [Use of Bipyridine Ligand Compound (Lb) in Mechanochemical Synthesis] The bipyridine ligand compounds (Legand (Lb)) used in Examples 401 to 411 and Reference Examples 401 to 403 are as follows, respectively. [Chemical Formula] In the bipyridine-based ligand compound (Lb101), m1 in the formula is the number of repeating units (about 12) corresponding to a number average molecular weight of 550 when it is polyoxyethylene. In the bipyridine-based ligand compound (Lb102), m2 in the formula is the number of repeating units (about 22) corresponding to a number average molecular weight of 1,000 when it is polyoxyethylene. In the bipyridine-based ligand compound (Lb103), m3 in the formula is the number of repeating units (about 45) corresponding to a number average molecular weight of 2,000 when it is polyoxyethylene. In the bipyridine-based ligand compound (Lb104), m4 in the formula is the number of repeating units (about 45) corresponding to a number average molecular weight of 2,000 when it is polyoxyethylene.

[0193] <Examples 401 to 404, Reference Example 401> [Chemical formula] Into a 5 mL stainless steel ball mill jar containing a 10 mm diameter stainless steel ball, under air, 1.0 mmol (1.0 equiv) of 1H-indole, 0.6 equiv (relative to 1H-indole) of bis(pinacolato)diboron, and as a metal compound, (1,5-Cyclooctadiene)(methoxy)iridium(I) Dimer ([Ir(cod)(OMe)] 2 ) was added at 0.75 mol% (relative to 1H-indole), and the compound shown in Table 8 was added as a bipyridine-based ligand compound (Ligand (Lb)) at 1.5 mol% (relative to 1H-indole). The lid of the ball mill jar was closed, attached to the ball mill, and the reaction was carried out by shaking and stirring at a vibration frequency of 30 Hz for 60 minutes while heating the ball mill jar from the outside with a heat gun so that the internal temperature of the ball mill jar reached 40°C. The NMR yields of the corresponding reaction products were as shown in Table 8.

[0194] [Table 8]

[0195] <Examples 405 to 407, Reference Examples 402 to 404>

Chem.

[0196] <Example 408> Palladium(II) acetate (Pd(OAc) 2 ) as a metal compound was used in an amount of 2.5 mol% (relative to trans-3-phenylacrylic acid), and a bipyridine-based ligand compound (Lb103) as a bipyridine-based ligand compound (Ligand (Lb)) was used in an amount of 5 mol% (relative to trans-3-phenylacrylic acid). Otherwise, the reaction was carried out in the same manner as in Example 405 to obtain a reaction product. The NMR yields of the corresponding reaction products were as shown in Table 9.

[0197] <Reference Example 405> Using the bipyridine-based ligand compound (Lb107) as the bipyridine-based ligand compound (Ligand(Lb)), and adding 145.6 mg of polyethylene glycol (number average molecular weight 2,000), the reaction was carried out in the same manner as in Example 405 to obtain a reaction product. The NMR yield of the corresponding reaction product was as shown in Table 9.

[0198]

Table 9

[0199] [Synthesis of N - heterocyclic carbene - based compound (Lc)] <Example 501>

Chemical formula

[0200] <Example 502> As the substrate, the compound represented by the following formula (PEG - 4000 - methyl - 2 - chloroethyl ether); Cl - CH 2 CH 2 -(-OCH 2 CH 2 -) px -OCH 3 (In the formula, px is the number of repeating units (about 91) corresponding to a number average molecular weight of 4000 when it is polyoxyethylene.) N-heterocyclic carbene compound (Lc102) was obtained in the same manner as in Example 501 except that 0.1 mmol (1.0 equiv) was used. The isolated yield was 95%.

[0201] <Example 503> N-heterocyclic carbene compound (Lc103) was obtained in the same manner as in Example 501 except that 0.5 mmol (5.0 equiv) of 1-(2,6-diisopropylphenyl)imidazole was used instead of 1-methylimidazole. The isolated yield was 84%.

[0202] [Use in mechanochemical synthesis of N-heterocyclic carbene compounds (Lc)] The N-heterocyclic carbene compounds (Legand (Lc)) used in Examples 601 to 603 and Reference Examples 601 and 602 are as follows. Note that Lc105 is a mixture of an esterified product of Lc101, PEG-4000 methyl ether, and benzoic acid. [Chemical formula] In the N-heterocyclic carbene compounds (Lc101) to (Lc103), (Lc105), px in the formula is the number of repeating units (about 91) corresponding to a number average molecular weight of 4000 when it is polyoxyethylene.

[0203] <Examples 601 to 603, Reference Examples 601, 602> [Chemical formula] Into a 1.5 mL stainless steel ball mill containing a 5 mm diameter stainless steel ball, under air, 46.6 mg (0.2 mmol, 1.0 equiv) of 4-bromobiphenyl, 36.5 mg (0.24 mmol, 1.2 equiv (relative to 4-bromobiphenyl)) of 4-methoxyphenylboronic acid, 1.3 mg (0.006 mmol, 3 mol% (relative to 4-bromobiphenyl)) of palladium acetate as a metal compound, 0.012 mmol of the compound shown in Table 10 as an N-heterocyclic carbene-based compound (Legand (Lc)) (56.0 mg in the case of Lc101; 6 mol% (relative to 4-bromobiphenyl)), 82.9 mg (0.6 mmol, 3.0 equiv (relative to 4-bromobiphenyl)) of potassium carbonate, 45 μL of tetrahydrofuran (0.2 μL / mg based on the total mass of 4-bromobiphenyl, 4-methoxyphenylboronic acid, potassium carbonate, palladium acetate and N-heterocyclic carbene-based compound), and 13 μL of water (3.7 equiv (relative to 4-bromobiphenyl)) were added. The lid of the ball mill was closed, attached to the ball mill, and the ball mill was externally heated using a heat gun set at 100 °C while shaking and stirring at a vibration frequency of 30 Hz for 60 minutes to carry out the reaction (Suzuki-Miyaura cross-coupling (carbon-carbon coupling) reaction). After completion of the reaction, the reaction mixture was passed through a short silica gel column chromatography with ethyl acetate / dichloromethane (1:1, v:v) to remove the catalyst and inorganic salts. After removing the solvent with an evaporator, the NMR yield was measured, and the NMR yield of the corresponding reaction product was as shown in Table 10.

[0204] <Examples 604, 605, Reference Example 603> Using the compound shown in Table 10 as an N-heterocyclic carbene-based compound (Legand (Lc)), the reaction was carried out in the same manner as in Examples 601 to 603 except that the reaction time was 30 minutes to obtain the reaction product. The NMR yield of the corresponding reaction product was as shown in Table 10.

[0205] [Table 10]

[0206] From Examples 1 to 5, it can be seen that the novel phosphorus-based ligand compounds (La101) to (La105) according to the present invention can be handled under air and can be easily synthesized. Further, from Examples 201 to 234, it can be seen that the novel phosphorus-based ligand compounds (La101) to (La105) according to the present invention exhibit high activity in mechanochemical reactions and constitute an additive for mechanochemical reactions and a mechanochemical reaction method applicable to a wide range of substrates under mild conditions.

[0207] Examples 201 to 210 and Comparative Examples 201 to 208 are examples showing the influence of the presence or absence of a polymer chain in the phosphorus-based ligand compound (La) on the mechanochemical reaction. When the phosphorus-based ligand compound (La) has a polymer chain (Examples 201 to 210), it can be seen that a high yield can be achieved in a short time as compared with the case where the phosphorus-based ligand compound (La) does not have a polymer chain (Comparative Examples 201 to 208). Further, it can be seen that ligand compounds of the biphenyl type such as the phosphorus-based ligand compounds (La101) and (La102) can activate the reaction more.

[0208] Examples 207 to 217 and Comparative Examples 209 to 213 are examples showing the influence of the length (number of repeating units) of the polymer chain in the phosphorus-based ligand compound (La) and the amount of the phosphorus-based ligand compound (La) used on the mechanochemical reaction. When the phosphorus-based ligand compound (La) has a polymer chain (Examples 207 to 217), it can be seen that a high yield can be achieved in a short time as compared with the case where the phosphorus-based ligand compound (La) does not have a polymer chain (Comparative Examples 209 to 213). Further, in Comparative Example 213 in which a polymer compound having the same structure as the polymer chain introduced into the phosphorus-based ligand compound (La) was added, the yield was low and the activity of the mechanochemical reaction was not improved. From this, it can be seen that introducing a polymer chain into the phosphorus-based ligand compound (La) is the key to improving the performance of the phosphorus-based ligand compound (La) in mechanochemical reactions. When the polymer chain in the phosphorus-based ligand compound (La) is long (Examples 211 to 213), it can be seen that a high yield can be achieved in a short time compared to the case where the polymer chain is short (Examples 214 to 217). When the amount of the phosphorus-based ligand compound (La) used is increased (Examples 207 to 210), it can be seen that a high yield can be achieved in a short time compared to the case where the amount of the phosphorus-based ligand compound (La) used is small (Examples 211 to 213).

[0209] Comparative Example 214 used a phosphorus-based ligand compound (La) having no polymer chain in the molecule, and Comparative Examples 215 and 216 used a ligand compound (Lx) having a polymer chain in the molecule, and are examples of performing a cross-coupling reaction in a solution system. From Comparative Examples 214 to 216, it can be seen that the ligand compound (Lx) having a polymer chain in the molecule shows only the same activity as the phosphorus-based ligand compound (La) having no polymer chain in the solution reaction. From this, it can be seen that the ligand compound (Lx) having a polymer chain in the molecule according to the present invention is a ligand compound specialized for the mechanochemical reaction method.

[0210] Examples 218 to 227 and Comparative Examples 217 to 237 are examples in which various compounds are used as substrates. The mechanochemical reaction method according to the present invention is significantly improved in terms of yield, reaction time, etc. compared to the mechanochemical reaction method using conventionally known ligands. For example, it can be seen that the reaction proceeds efficiently even when a polycyclic aromatic boronic acid with low reactivity (Examples 227, Comparative Examples 226 and 236) is used as the substrate. From this, it can be seen that the mechanochemical reaction additive according to the present invention, the ligand compound (Lx) used in the mechanochemical reaction method, and the ligand compound (Ly) according to the present invention show activities superior to the ligand compounds that have been optimized in the conventional mechanochemical reactions.

[0211] Examples 228 to 231 and Comparative Examples 238 to 245 are examples in which aryl chloride with low reactivity is used as the substrate. It can be seen that the mechanochemical reaction method according to the present invention has a significantly improved yield compared to the mechanochemical reaction method using a conventionally known ligand, and is useful for a wide range of substrates.

[0212] Examples 232 to 234 and Comparative Examples 246 and 247 are examples in which compounds ((H12) and (H13)) that are insoluble in organic solvents are used as the substrate. It can be seen that the mechanochemical reaction method according to the present invention has a significantly improved yield compared to the mechanochemical reaction method using a conventionally known ligand, and is useful for a wide range of substrates. From this, it can be understood that the additive for mechanochemical reaction, the mechanochemical reaction method, and the ligand compound (Ly) of the present invention can cause a mechanochemical reaction under mild conditions using a compound that is hardly soluble in an organic solvent, such as an organic pigment, as the substrate, and even when a substrate that cannot react in an organic solvent is used, a reaction product can be obtained. Therefore, it can be understood that it is useful for the synthesis of various functional materials.

[0213] From Examples 301 and 401 to 408, it can be seen that the novel bipyridine-based ligand compounds (Lb101) to (Lb104) according to the present invention can be handled under air, show high activity in mechanochemical reactions, and constitute an additive for mechanochemical reactions and a mechanochemical reaction method applicable to a wide range of substrates under mild conditions.

[0214] From Examples 501 to 503 and 601 to 605, it can be seen that the novel N-heterocyclic carbene-based ligand compounds (Lc101) to (Lc103) according to the present invention can be handled under air, show high activity in mechanochemical reactions, and constitute an additive for mechanochemical reactions and a mechanochemical reaction method applicable to a wide range of substrates under mild conditions.

[0215] [Action mechanism of ligand compound] <Reference Example 701> A DSC analysis was performed on a ball-milled mixture of aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) and the following phosphorus-based ligand compound (La111) obtained by ball-milling at 45 °C for 30 minutes (vibration frequency 30 Hz). The results are shown in Figure 1. In Figure 1, peaks at 55.5 °C and 104.7 °C can be observed respectively, suggesting that two identical meltings of aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) and the phosphorus-based ligand compound (La111) occurred.

Chemical formula

[0216] <Reference Example 702> In the absence of the phosphorus-based ligand compound (La111), a DSC analysis was performed on a sample obtained by ball-milling at 45 °C for 30 minutes (vibration frequency 30 Hz). The results are shown in Figure 2. In Figure 2, the melting point of aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) treated by ball-milling was observed as a peak at 111.9 °C.

[0217] From Reference Examples 701 and 702, in the mixture of aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) and the phosphorus-based ligand compound (La111), the melting point of aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) changed to 104.7 °C and the peak became significantly broader, suggesting that the polyethylene glycol chain interacts with aryl bromide BrAr (1-bromo-3,5-diphenylbenzene) and partially forms an amorphous phase containing aryl bromide at the interface of the phase separation structure. It was verified from the thermal analysis in Reference Examples 701 and 702 that, since the ligand compound (Lx) of the metal catalyst has a polymer chain such as polyether in the molecule, the crystal phase of the reaction substrate in the solid state partially changes to an amorphous phase under mechanochemical conditions, forming a phase-separated structure. At this time, it is important to form an amorphous phase in the vicinity of the metal catalyst that serves as the reaction center, and it is presumed that this enhances the reaction activity and realizes a highly efficient reaction.

Claims

1. Comprising at least a ligand compound (Lx) or a salt thereof, wherein the ligand compound (Lx) is one or more selected from the group consisting of phosphine compounds, bipyridine compounds, and N - heterocyclic carbene compounds, the ligand compound (Lx) has a polymer chain in the molecule, the polymer chain is one or more selected from the group consisting of polyethers, polyamides, polyesters, and polyurethanes, and is an additive for mechanochemical reactions for cross - coupling reactions.

2. The additive for mechanochemical reactions according to claim 1, further comprising a metal compound.

3. Comprising at least a complex composed of a ligand compound (Lx) or a salt thereof and a metal atom, wherein the ligand compound (Lx) is one or more selected from the group consisting of phosphine compounds, bipyridine compounds, and N - heterocyclic carbene compounds, the ligand compound (Lx) has a polymer chain in the molecule, the polymer chain is one or more selected from the group consisting of polyethers, polyamides, polyesters, and polyurethanes, and is an additive for mechanochemical reactions for cross - coupling reactions.

4. The ligand compound (Lx) has the following structure (La), (Lb), or (Lc): 【Chemical Formula 1】 (Each group in formulas (La), (Lb), and (Lc) is as follows. Cy １ 、Cy ２ 、Cy ３ is, independently of one another, a group selected from the group consisting of an aromatic hydrocarbon group having 6 to 30 carbon atoms, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 3 to 20 carbon atoms, and a heterocyclic group having 1 to 20 carbon atoms (the hetero atom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other). Ht is a group represented by any one of the following formulas (Ht1) to (Ht10). 【Chemical Formula 2】 R １１ 、 R １２ 、 R １３ 、 R ２１ 、 R ２２ 、 R ３１ is, independently of each other, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. R １１ 、 R １２ 、 R １３ 、 R ２１ 、 R ２２ 、 R ３１ When there are a plurality of them, they may be the same as or different from each other. A １１ 、 A １２ 、 A １３ 、 A ２１ 、 A ２２ 、 A ３１ 、 A ３２ 、 A ３３ is, independently of each other, a direct bond, an alkylene group having 1 to 24 carbon atoms, a cycloalkylene group having 3 to 24 carbon atoms, an alkenylene group having 1 to 24 carbon atoms, an alkynylene group having 1 to 24 carbon atoms, an arylene group having 6 to 24 carbon atoms, an aryleneoxy group having 6 to 24 carbon atoms, an arylenesulfide group having 6 to 24 carbon atoms, a heteroarylene group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality, they may be the same as or different from each other.), an ester group (—COO— or —OCO—), an ether group, a thioether group, an amide group, a urethane group, a carbonate group, and an amine group having 0 to 24 carbon atoms, and a group formed by bonding two or more of them may be used. A １１ 、 A １２ 、 A １３ 、 A ２１ 、 A ２２ 、 A ３１ 、 A ３２ 、 A ３３ When there are a plurality of A, they may be the same as or different from each other. Poly １１ 、Poly １２ 、Poly １３ 、Poly ２１ 、Poly ２２ 、Poly ３１ is, independently of one another, one or more polymer chains selected from the group consisting of polyethers, polyamides, polyesters and polyurethanes. Poly １１ 、Poly １２ 、Poly １３ 、Poly ２１ 、Poly ２２ 、Poly ３１ may be the same as or different from one another when there are a plurality of them. E １１ 、E １２ 、E １３ 、E ２１ 、E ２２ 、E ３１ is, independently of each other, a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality of them, they may be the same as or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group. E １１ 、E １２ 、E １３ 、E ２１ 、E ２２ 、E ３１ When there are a plurality of Es, they may be the same as or different from each other. Xa － is a monovalent anion, and Xb － is a divalent anion or two monovalent anions. p1, q1, r1, s1, t1, and u1 are each independently an integer of 0 or more, and p1 + q1 + r1 ≥ 1. Further, p1 + s1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy １ group, q1 + t1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy ２ group, r1 + u1 is an integer of 0 or less than or equal to the number of substitutable positions in the Cy ３ group. p2, q2, s2, t2 are each independently 0 or an integer of 1 or more, and p2 + q2 ≥ 1, 4 ≥ p2 + s2 ≥ 0, 4 ≥ q2 + t2 ≥ 0. p3 is an integer of 1 or more, and s3 is 0 or an integer of 1 or more. Further, p3 + s3 is an integer not exceeding the number of substitutable positions in the Ht group. One or more Rs each １１ 、R １２ 、R １３ 、A １１ 、A １２ 、A １３ may combine in two or more to form a carbocyclic ring or a heterocyclic ring. One or more of each R ２１ 、R ２２ 、A ２１ 、A ２２ Two or more of them may combine to form a carbocyclic ring or a heterocyclic ring. One or more Rs each ３１ , A ３１ , A ３２ , A ３３ may be combined with two or more to form a carbocyclic ring or a heterocyclic ring. In formulas (La), (Lb), and (Lc), Cy １ , Cy ２ , Cy ３ , R １１ , R １２ , R １３ , R ２１ , R ２２ , R ３１ , A １１ , A １２ , A １３ , A ２１ , A ２２ , A ３１ , A ３２ , A ３３ , E １１ , E １２ , E １３ , E ２１ , E ２２ , E ３１ may each independently have a substituent. The substituent in each group is a group selected from the group consisting of an alkyl group having 1 to 24 carbon atoms, an alkoxy group having 1 to 24 carbon atoms, an alkylthio group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, an alkenyl group having 2 to 24 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, an aryl group having 6 to 24 carbon atoms, an aryloxy group having 6 to 24 carbon atoms, an arylthio group having 6 to 24 carbon atoms, a heteroaryl group having 3 to 24 carbon atoms (the heteroatom is one or more selected from the group consisting of oxygen, nitrogen, and sulfur. When there are a plurality, they may be the same as or different from each other.), an acyl group having 1 to 24 carbon atoms, an amino group having 0 to 24 carbon atoms, a halogen group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, and a carboxyl group, and when there are a plurality, they may be the same as or different from each other.) The additive for mechanochemical reactions according to claim 1 or 3, represented by the above.

5. The additive for mechanochemical reactions according to claim 1 or 3, wherein the polymer chain is a polyalkylene ether.

6. The metal atom contained in the metal compound or the metal atom contained in the complex is one or more selected from the group consisting of Mg, Ca, Sr, Ba, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ru, Pd, Ag, Re, Ir, Pt, Pb, Bi, Al, Sn. The additive for mechanochemical reactions according to claim 2 or 3.

7. A mechanochemical reaction method using the additive for mechanochemical reactions according to claim 1 or 3.

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