WO2022092260A1 - Reaction method and device used in reaction therein - Google Patents

Reaction method and device used in reaction therein Download PDF

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WO2022092260A1
WO2022092260A1 PCT/JP2021/040001 JP2021040001W WO2022092260A1 WO 2022092260 A1 WO2022092260 A1 WO 2022092260A1 JP 2021040001 W JP2021040001 W JP 2021040001W WO 2022092260 A1 WO2022092260 A1 WO 2022092260A1
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compound
reaction
group
substituent
hydrocarbon group
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Japanese (ja)
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肇 伊藤
浩司 久保田
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国立大学法人北海道大学
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Definitions

  • the present invention relates to a novel reaction method. Further, the present invention relates to an apparatus used for the method, a method for producing a compound using the reaction, and the compound.
  • Non-Patent Documents 1 and 2 an aromatic compound having a leaving group and an aromatic boronic acid derivative or the like are reacted in the presence of a metal catalyst such as a palladium catalyst and linked to obtain an aromatic compound.
  • a metal catalyst such as a palladium catalyst
  • the ring reaction is known. Due to its synthetic chemical importance, the Nobel Prize in Chemistry was awarded in 2010 for "Development of cross-coupling reaction catalyzed by palladium" by Dr. Akira Suzuki, Dr. Eiichi Negishi and Dr. Richard Heck.
  • the cross-coupling reaction generally requires a relatively large amount of organic solvent because the reaction is carried out by dissolving a compound as a starting material in an organic solvent.
  • organic solvent may cause problems in terms of the working environment and safety of workers, protection of the global environment, and environmental load during treatment with organic solvents after use. Therefore, there is a demand for a cross-coupling reaction method that is less likely to cause problems in terms of work environment / safety, protection of the global environment, environmental load, and the like.
  • the organic synthetic reaction method in which the reaction raw materials are brought into direct contact with each other and does not use an organic solvent has a low environmental load and is academically and industrially interesting.
  • the mechanochemical method is attracting attention.
  • the mechanochemical method is a method of activating and reacting a solid raw material by applying mechanical energy to the solid raw material by means such as grinding, shearing, impact, and compression.
  • Non-Patent Document 3 reports a cross-coupling reaction method using a palladium catalyst that does not substantially use an organic solvent.
  • Patent Document 1 the present inventors can use various compounds as starting materials, and can efficiently carry out the reaction in a relatively short time under mild reaction conditions without substantially using an organic solvent.
  • This cross-coupling reaction method can form a chemical bond selected from CN, CB, CC, CO and CS bonds relatively efficiently, and reacts in high yield. The product can be obtained.
  • this cross-coupling method there are some points to be improved in terms of reaction time and yield.
  • the problem to be solved by the present invention is that a wide variety of compounds can be used as starting materials, an organic solvent can be substantially eliminated, and a reaction can be carried out in a short time in a high yield by a simple means. It is to provide a reaction method from which a product can be obtained. The problem to be solved by the present invention is to provide a reaction method having a higher yield than the conventional methods. The problem to be solved by the present invention is that a wide variety of compounds can be used as starting materials, an organic solvent can be substantially eliminated, and a reaction can be carried out in a short time in a high yield by a simple means. It is to provide a reaction apparatus capable of obtaining a product. The problem to be solved by the present invention is to provide a novel compound which has not been obtained so far.
  • the present inventors have improved the dispersibility of the metal catalyst and the dispersibility of the metal in a reaction method using a metal catalyst and a base (for example, a cross-coupling reaction method, etc.).
  • a wide variety of reactions can be achieved by suppressing the aggregation of the catalyst, and by reacting the organic solvent in an abundance of 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total, and at 60 to 500 ° C.
  • a above-mentioned compound can be used as a starting material and a reaction product can be obtained in a short time and in a high yield by a simple means, and the present invention has been completed.
  • the present inventors have found that a new compound that could not be synthesized so far can be obtained by using the above-mentioned novel reaction method (for example, a cross-coupling reaction method, etc.).
  • the invention was completed. That is, the present invention provides the following reaction method, apparatus, method for producing a new compound, and a new compound.
  • Item 1 An organic compound (A) having a melting group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher that reacts with the organic compound having a leaving group. It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C.
  • One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction.
  • a reaction method which is a reaction.
  • Item 2 A cross-coupling reaction method for forming one or more chemical bonds selected from CN bond, CB bond, CC bond, CO bond and CS bond, Item 1. The reaction method described in 1.
  • a 1 may have an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and m which may have a substituent. It represents either a valent aliphatic hydrocarbon group or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
  • Each of X independently represents a leaving group.
  • m is a number of X and represents an integer of 1 or more.
  • A2 may have an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, and n which may have a substituent.
  • n is a number of Y and represents an integer of 1 or more.
  • Y is independent of each other -B (OR 1 ) (OR 2 ) -NHR 3 -R 4 -OH -R 5 -SH Represents.
  • R 1 and R 2 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show.
  • R 1 and R 2 may be coupled to each other.
  • R 3 independently contains hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a substituent. It represents a monovalent aliphatic hydrocarbon group which may have a substituent or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent.
  • R 4 and R 5 has a single bond, a divalent aromatic hydrocarbon group which may have a substituent, and a divalent aliphatic hydrocarbon group which may have a substituent, respectively.
  • R 6 to R 9 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent.
  • R 6 and R 7 may be coupled to each other, and R 8 and R 9 may be coupled to each other.
  • Compound (II) represented by At least in the presence of metal catalysts and bases The abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total, and 60 to 500 ° C.
  • Item 3 The reaction method according to Item 1 or 2, wherein the reaction is carried out under the conditions of.
  • the leaving group is one or more groups selected from chloro, bromo, iodo, diazonium salt, trifluoromethanesulfonate and carboxylic acid derivative.
  • the compound represented by the formula (IIa) is an aromatic boronic acid selected from an aromatic boronic acid or an aromatic boronic acid ester.
  • the compound represented by the formula (IIb) is a diboronic acid ester selected from a diboronic acid alkyl ester, a diboronic acid alkylene glycol ester, a diboronic acid aryl ester, a diboronic acid arylene glycol ester, and a tetrahydroxydiborane.
  • Item 3. The method according to any one of Items 1 to 3.
  • Item 6 The abundance of the metal catalyst is 0.5 mol% or more and 25 mol% when the number of moles of leaving groups obtained by multiplying the number of moles of the compound (I) by a valence m is 100 mol%.
  • Item 2. The method according to any one of Items 1 to 5, which is described below.
  • Item 7 The method according to any one of Items 1 to 6, wherein the base contains at least one selected from an inorganic base, an alkali metal alkoxide and an organic base.
  • Item 8 The method according to any one of Items 1 to 7, wherein the abundance of the base is 0.5 equivalents or more and 10 equivalents or less with respect to 1 equivalent of compound (I).
  • the unsaturated hydrocarbon compound is not an aromatic compound, A chain compound with at least one carbon-carbon unsaturated double bond and / or at least one carbon-carbon unsaturated triple bond, or at least one carbon-carbon unsaturated double bond and / or at least one carbon- Cyclic compounds with carbon unsaturated triple bonds, Item 5.
  • Item 11 The method according to any one of Items 1 to 10, wherein a coordinating compound is further present in addition to the metal catalyst and the base.
  • Item 12 The abundance of the unsaturated hydrocarbon compound is Based on the total mass of the compound (I), the compound (II), the metal catalyst, and the base, or Based on the total mass of the compound (I), the compound (II), the metal catalyst, the base, and the coordinating compound.
  • Item 6. The method according to any one of Items 1 to 11, which is 0.01 to 3.0 ⁇ L / mg.
  • Item 13 At least a reaction vessel, a means for stirring the contents in the reaction vessel, and a temperature adjusting means in the reaction vessel are provided.
  • One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction.
  • Item 14 A method for producing a compound represented by any of the formula (IIIa) or (IIIb), which uses the method according to any one of Items 1 to 12.
  • p represents an integer of 5 to 30, and q represents an integer of 5 to 30.
  • Item 15 A compound represented by either formula (IIIa) or (IIIb). (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
  • the present invention a wide variety of compounds can be used as a starting material, an organic solvent can be substantially eliminated, and a reaction product can be obtained in a short time and in a high yield by a simple means.
  • a capable reaction method eg, a cross-coupling reaction method, etc.
  • the reaction product for example, a cross-coupling reaction product in which a chemical bond selected from CN, CB, CC, CO and CS bonds is formed, etc.
  • the present invention provides a novel compound that has not been obtained so far.
  • the first aspect of the present invention comprises an organic compound (A) having a leaving group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher that reacts with the organic compound having a leaving group. It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C.
  • a second aspect of the present invention comprises at least a reaction vessel, means for stirring the contents in the reaction vessel, and means for adjusting the temperature in the reaction vessel.
  • a third aspect of the present invention relates to a method for producing a compound represented by either formula (IIIa) or (IIIb) using the above reaction.
  • a fourth aspect of the present invention relates to a compound represented by either formula (IIIa) or (IIIb). (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
  • formula (IIIa) or (IIIb) In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.
  • the reaction method of the present invention is An organic compound (A) having a melting group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher reacting with the organic compound having a leaving group. It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C.
  • One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. It is a reaction, a reaction method.
  • the "organic compound (A) having a melting group having a melting group of 30 ° C. or higher” and the "organic compound (B) having a melting group of 30 ° C. or higher that reacts with an organic compound having a leaving group” used in the reaction of the present invention are Both are organic compounds solid at room temperature, and their melting points are 30 ° C. or higher, preferably 40 ° C.
  • the organic compound (A) and the organic compound (B) are not particularly limited as long as they each have a predetermined melting point and react with each other.
  • Examples of the organic compound (A) include the compound (I) described later, and examples of the organic compound (B) include the compound (II) described later. Further, the organic compound (A) and the organic compound (B) may be the same. The amount of the organic compound (B) used is appropriately adjusted in consideration of the equivalent ratio with the organic compound (A).
  • the equivalent ratio of the organic compound (A) to the organic compound (B) is not particularly limited as long as it is an equivalent ratio in 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 further preferably 2/1 to 1/2.
  • the mechanochemical method is a method in which mechanical energy is applied to an organic compound (A) and an organic compound (B) to cause a reaction. Mechanical energy can be mechanically generated by means such as grinding, shearing, impact, compression and the like. By applying such mechanical energy to the solid raw material, the solid raw material can be activated and reacted.
  • the reaction method of the present invention is an organic synthetic reaction method that does not use an organic solvent and reacts by directly contacting the reaction raw materials with each other and mixing them.
  • the reaction activity is high despite the low environmental load.
  • examples of the coupling reaction include a homocoupling reaction and a cross-coupling reaction, and examples thereof include CN bond, CB bond, CC bond, CO bond and CS bond. Included are cross-coupling reactions that form one or more chemical bonds selected from.
  • the present invention is characterized in that it is heated to a specific temperature during a reaction by a mechanochemical method.
  • a 1 may have an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and m which may have a substituent. It represents either a valent aliphatic hydrocarbon group or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
  • Each of X independently represents a leaving group.
  • m is a number of X and represents an integer of 1 or more.
  • reaction product eg, cross-coupling reaction with any of CB, CC, CN, CO, and CS bonds. It is not particularly limited as long as it produces (such as a cross-coupling reaction product in which one or more are formed).
  • reaction product eg, cross-coupling reaction with any of CB, CC, CN, CO, and CS bonds. It is not particularly limited as long as it produces (such as a cross-coupling reaction product in which one or more are formed).
  • Compound (I) can be used alone or in combination of two or more.
  • a commercially available product can be used as it is or after purification.
  • the number of carbon atoms of the m-valent aromatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 6 to 60, preferably 6 to 40, and more preferably 6 to 30.
  • m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
  • the m-valent aromatic hydrocarbon group which may have a substituent in A 1
  • the m-valent aromatic hydrocarbon group in which m is an integer of 2 or more is, for example, the monovalent aromatic. Examples thereof include those obtained by removing m-1 hydrogens from the aromatic ring in the group hydrocarbon group.
  • the number of carbon atoms of the m-valent aromatic heterocyclic group which may have a substituent in A 1 is not particularly limited, and is, for example, 4 to 60, preferably 4 to 40, and more preferably 4 to 30.
  • m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
  • the monovalent aromatic heterocyclic group having m 1, for example, a thiophenyl group (thiophene group or thienyl group), Sulfur-containing heteroaryl groups such as thienirenyl group (or thiofendiyl group), benzothienyl group (benzothiophene group), dibenzothienyl group (dibenzothiophene group), phenyldibenzothienylenyl group and dibenzothienylenylphenyl group; furanyl group (Or furan group), benzofuranyl group (benzofuran group), dibenzofuranyl group (dibenzofuran group), phenyldibenzofuranyl group, dibenzofuranylphenyl group and other oxygen-containing heteroaryl groups; pyridyl group (or pyridine group), pyridirenyl Group (or
  • a pyrrole group a silol group, a borol group, a phosphor group, a selenophene group, a gelmol group, an indol group, an inden group, a benzocilol group, a benzobolol group, a benzophosphole group, a benzoselenovene group, a benzogermol group, and a dibenzosylol group.
  • the m-valent aromatic heterocyclic group in which m is an integer of 2 or more is, for example, the monovalent aromatic. Examples thereof include those obtained by removing m-1 hydrogens from the aromatic ring in the group heterocyclic group. Further, benzo [1,2-c: 4,5-c'] bis [1,2,5] thiadiazole skeleton (benzobisthiadiazole group) and the like can be mentioned.
  • the carbon number of the m-valent aliphatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 2 to 60, preferably 3 to 40, and more preferably 5 to 30.
  • m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
  • Group hydrocarbon groups can be mentioned.
  • the monovalent fat examples thereof include those obtained by removing m-1 hydrogens from a group hydrocarbon group.
  • the number of carbon atoms of the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 2 to 60, preferably 3 to 40, and more preferably 5 to 30. ..
  • m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
  • the above-mentioned Examples thereof include monovalent unsaturated aliphatic hydrocarbon groups obtained by removing m-1 hydrogens.
  • the following groups can be exemplified as A1 in the formula ( I ) in the compound (I).
  • M-valent aromatic hydrocarbon group which may have a substituent in A 1 m-valent aromatic heterocyclic group which may have a substituent, and m-valent which may have a substituent.
  • the aliphatic hydrocarbon group of the above, or the substituent which may be possessed by an unsaturated aliphatic hydrocarbon group having an m-valent value which may have a substituent is a reaction (for example, cross-coupling) which is the object of the present invention. Reactions, etc.) are not particularly limited as long as they can be performed.
  • an alkyl group having 1 to 24 carbon atoms preferably 1 to 18, more preferably 1 to 12, and even more preferably 1 to 8 (for example, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group) is used.
  • aryl groups having 5 to 24 carbon atoms preferably 5 to 18, more preferably 5 to 12, still more preferably 5 to 8 (eg, phenyl group, naphthyl group, biphenyl group, etc.); 7 to 24 carbon atoms.
  • arylalkyl groups eg, monophenylmethyl group, monophenylpropyl group, triphenylmethyl group, etc.
  • 5 to 24 carbon atoms Preferably 5 to 18, more preferably 5 to 12, even more preferably 5 to 8 aryloxy groups (eg, phenoxy group, naphthyloxy group, biphenyloxy group, etc.); 4 to 24 carbon atoms, preferably 4 to 18 carbon atoms.
  • More preferably 4 to 12, still more preferably 4 to 8 heteroaryl groups eg, thiophenyl group, furanyl group, carbazole group, benzothiophenyl group, benzofuranyl group, indolyl group, pyrrolyl group, pyridyl group, etc.
  • Acrylic groups with 1 to 24 carbon atoms, preferably 1 to 18, more preferably 1 to 12, even more preferably 1 to 8 eg, acetyl group, propionyl group, pig).
  • the substituents may be crosslinked with each other, or the entire substituent may form a cyclic structure (aromatic group).
  • the substituent may further have a substituent.
  • the leaving group of compound (I) 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), and is a desired reaction of the present invention (for example).
  • Cross-coupling reaction, etc. is not particularly limited as long as it is a leaving group capable of carrying out.
  • the leaving group include a group selected from the group consisting of chloro, bromo, iodine, diazonium salt, trifluoromethanesulfonate, carboxylic acid derivative and the like.
  • Compound (I) can have a plurality of leaving groups.
  • the plurality of leaving groups may be the same or different.
  • the number m of the leaving group is not particularly limited as long as it is an integer and can carry out a reaction (for example, a cross-coupling reaction). For example, it can be 1 to 10, preferably 1 to 8, more preferably 1 to 6, and even more preferably 1 to 4.
  • Specific examples of the compound (I) used in the reaction method of the present invention include, for example, the compounds (I-1) to (I-26) used in Examples 1 to 77. , (I-200 to I-211) and compounds (I-27) to (I-54), and one or more selected from the group.
  • Me represents a methyl group
  • Ph represents a phenyl group.
  • Compound (II)> (Compound represented by formula (IIa)) Among the compounds (II) used in the reaction method of the present invention (for example, the cross-coupling reaction method, etc.), the formula (IIa); A2 - Yn (IIa)
  • a 2 may have an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, and n which may have a substituent.
  • n is a number of Y and represents an integer of 1 or more.
  • Y is independent of each other -B (OR 1 ) (OR 2 ) -NHR 3 -R 4 -OH -R 5 -SH Represents.
  • R 1 and R 2 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show.
  • R 1 and R 2 may be coupled to each other.
  • R 3 independently contains hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a substituent. It represents a monovalent aliphatic hydrocarbon group which may have a substituent or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent.
  • Each of R 4 and R 5 has a single bond, a divalent aromatic hydrocarbon group which may have a substituent, and a divalent aliphatic hydrocarbon group which may have a substituent, respectively.
  • a reaction product for example, a cross-coupling reaction with a CB bond, a CC bond, a CN bond, a CO bond and a C—. It is not particularly limited as long as it produces a cross-coupling reaction product (such as a cross-coupling reaction product) in which any one or more of S bonds are formed.
  • the n-valent aliphatic hydrocarbon group which may have a substituent or the unsaturated aliphatic hydrocarbon group having an n-valent value which may have a substituent is the formula (I) according to the compound (I), respectively.
  • the A1 group in the group has an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and a substituent.
  • the substituent in the A2 group in the formula (IIa) can be the same as the substituent in the A1 group in the formula ( I ) according to the compound (I). It should be noted that the A 2 group in the formula (IIa) and the A 1 group in the formula (I) according to the compound (I) are independently arbitrary structural groups, and may be the same or different. good.
  • examples of the compound represented by the formula (IIa) having ⁇ B (OR 1 ) (OR 2 ) as Y include aromatic boronic acid or aromatic boronic acid ester.
  • the aromatic boronic acid or aromatic boronic acid ester is not particularly limited as long as it reacts with compound (I) (for example, a cross-coupling reaction or the like) to give a reaction product in which a CC 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.
  • R 1 and R 2 in the -B (OR 1 ) (OR 2 ) group in the formula (IIa) are independently hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, respectively. Represents a monovalent aliphatic hydrocarbon group which may have a substituent. R 1 and R 2 may be coupled to each other.
  • the monovalent aromatic hydrocarbon group which may have a substituent and the monovalent aliphatic hydrocarbon group which may have a substituent are the formula (I) according to the compound (I). It is possible to use the same group 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 A1 group in the group. can.
  • R 1 and R 2 in the -B (OR 1 ) (OR 2 ) group in the formula (IIa) and A 1 in the formula (I) according to the compound (I) are independent groups, respectively. It may be the same or different.
  • the group in which R 1 and R 2 are bonded to each other is a group in which R 1 and R 2 form a cyclic structure together.
  • an aromatic group for example, a 1,2-phenylene group and the like can be mentioned.
  • a hydrocarbon group for example, an ethylene group, a 1,1,2,2-tetramethylethylene group (pinacholato group), a neopentylglycolato group, a propylene group and the like can be mentioned.
  • the aromatic boronic acid or aromatic boronic acid ester as the compound represented by the formula (IIa) can be used alone or in combination of two or more.
  • the aromatic boronic acid or aromatic boronic acid ester as the compound represented by the formula (IIa) a commercially available product can be used as it is or after purification.
  • Examples of the compound represented by the formula (IIa) having ⁇ NHR 3 as Y include aromatic amino compounds.
  • the aromatic amino compound is not particularly limited as long as it reacts with compound (I) (for example, a cross-coupling reaction or the like) to give a product in which a CN bond is formed.
  • R3 group in the -NHR 3 group in the formula ( IIa) hydrogen and a monovalent aromatic hydrocarbon group which may have a substituent may have a substituent, respectively.
  • a monovalent aromatic hydrocarbon group which may have a substituent a monovalent aromatic heterocyclic group which may have a substituent, and a monovalent which may have a substituent.
  • the monovalent unsaturated aliphatic hydrocarbon group which may have a substituent or a substituent has a substituent in the A1 group in the formula (I) according to the compound (I).
  • M-valent aromatic hydrocarbon group which may have a substituent m-valent aromatic heterocyclic group which may have a substituent, m-valent aliphatic hydrocarbon group which may have a substituent, Alternatively, it can be a group similar to the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
  • the aromatic amino compound as the compound represented by the formula (IIa) can be used alone or in combination of two or more.
  • a commercially available product can be used as it is or after purification.
  • examples of the compound represented by the formula (IIa) having ⁇ R4 -OH as Y 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 (I) (for example, a cross-coupling reaction or the like) to give a product in which a CO bond is formed.
  • the R4 group in the -R4 -OH group in the formula (IIa) has a divalent aromatic hydrocarbon group or a substituent which may independently have a single bond and a substituent. Represents a divalent aliphatic hydrocarbon group that may be present.
  • the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent is the formula (I) according to the compound (I). Similar to the m-valent aromatic hydrocarbon group which may have a substituent or the divalent group in the m-valent aliphatic hydrocarbon group which may have a substituent in the A1 group in the group. Can be the basis.
  • the R4 group in the -R4 -OH group in the formula (IIa) and the A2 group in the formula (IIa) are independent groups and may be the same or different.
  • aromatic compound having a hydroxyl group as the compound represented by the formula (IIa) one kind may be used alone or two or more kinds may be used in combination.
  • aromatic compound having a hydroxyl group as the compound represented by the formula (IIa) a commercially available product can be used as it is or after purification.
  • examples of the compound represented by the formula (IIa) having ⁇ R5 -SH as Y 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 (I) (for example, a cross-coupling reaction or the like) to give a product in which a CS bond is formed.
  • the R5 group in the -R5 - SH group in the formula (IIa) has a divalent aromatic hydrocarbon group or a substituent which may independently have a single bond and a substituent. Represents a divalent aliphatic hydrocarbon group that may be present.
  • the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent is the formula (I) according to the compound (I). Similar to the m-valent aromatic hydrocarbon group which may have a substituent or the divalent group in the m-valent aliphatic hydrocarbon group which may have a substituent in the A1 group in the group. Can be the basis.
  • the R5 group in the -R5 - SH group in the formula (IIa) and the A2 group in the formula (IIa) are independent groups and may be the same or different.
  • aromatic compound having a thiol group as the compound represented by the formula (IIa) one kind may be used alone or two or more kinds may be used in combination.
  • aromatic compound having a thiol group as the compound represented by the formula (IIa) a commercially available product can be used as it is or after purification.
  • R 6 and R 7 may be bonded to each other, and R 8 and R 9 may be bonded to each other.
  • the compound represented by is not particularly limited as long as it reacts with the compound (I) (for example, a cross-coupling reaction or the like) to produce a reaction product in which a CB bond is formed.
  • Examples of the compound represented by the formula (IIb) include one or more selected from the group consisting of a diboronic acid ester (diboronic acid tetraester, diboronic acid triester, diboronic acid diester or diboronic acid monoester) and diboronic acid. ..
  • Examples of the diboronic acid ester include one or more selected from the group consisting of diboronic acid alkyl ester, diboronic acid alkylene glycol ester, diboronic acid aryl ester, diboronic acid arylene glycol ester and the like.
  • Examples of diboronic acid include tetrahydroxydiborane.
  • the monovalent aromatic hydrocarbon groups as R 6 to R 9 in the formula (IIb) which may have a substituent include, for example, independently from a phenyl group, a naphthyl group, a biphenyl group and the like.
  • One or more groups selected from the group of The monovalent aliphatic hydrocarbon groups as R 6 to R 9 in the formula (IIb) which may have a substituent include, for example, independently each of a methyl group, an ethyl group, a propyl group and an isopropyl.
  • One or more selected from the group consisting of a group, a butyl group, an isobutyl group, a tert-butyl group and the like can be mentioned.
  • R 6 to R 9 in the formula (IIb) are monovalent aliphatic hydrocarbon groups which may have a substituent
  • R 6 and R 7 and R 8 and R 9 are mutual. It may be bound to.
  • R 6 -R 7 and R 8 -R 9 can each independently, for example, an ethylene group, a 1,1,2,2-tetramethylethylene group, a 2,2-dimethylpropylene group, a hexylene group (or). It may be one or more of the groups selected from the group consisting of 1,1,3-trimethylpropylene group) and the like.
  • the substituents and the number of the substituents that the aromatic hydrocarbon group and the aliphatic hydrocarbon group may have in R 6 to R 9 do not inhibit the reaction (for example, cross-coupling reaction, etc.). Not particularly limited.
  • the substituent include one or more groups 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 may have one or more. can. Further, the substituents may be crosslinked with each other, and may further have a substituent.
  • the diboronic acid esters are more specifically, for example, for example.
  • One or more species selected from the group consisting of bis (hexylene Glycolato) diboron, bis (catecholato) diboron, and the like can be mentioned.
  • the compound represented by the formula (IIb) can be used alone or in combination of two or more.
  • a commercially available product can be used as it is or after purification.
  • the amount of compound (II) used is appropriately adjusted in consideration of the equivalent ratio with compound (I).
  • the equivalent ratio of compound (I) to compound (II) is not particularly limited as long as it is an equivalent ratio in which a reaction (for example, a cross-coupling reaction) proceeds. ..
  • a reaction for example, a cross-coupling reaction
  • it is 10/1 to 1/10, preferably 5/1 to 1/5, more preferably 3/1 to 1/3, and further preferably 2/1 to 1/2.
  • compound (II) may be used alone or in combination of two or more.
  • one of the compounds represented by the formula (IIa) can be used alone or in combination of two or more.
  • one or more of the compounds represented by the formula (IIa) and one or more of the compounds represented by the formula (IIb) can be used in combination.
  • compound (II) a commercially available product can be used as it is or after purification.
  • Specific examples of the compound (II) used in the reaction method of the present invention include, for example, the compounds (II-1) to (II-25) used in Examples 1 to 77. , (II-45), (II-200 to II-202) and compounds (II-26) to (II-44).
  • Me represents a methyl group
  • Ph represents a phenyl group.
  • reaction product (III) obtained by the reaction method of the present invention for example, a cross-coupling reaction method or the like
  • reaction products (III-1) to obtained in Examples 1 to 77. (III-49), (III-300 to I-314) and the following compounds (III-50) to (III-118) can be mentioned.
  • Me represents a methyl group
  • t-Bu or But-t represents a tertiary butyl group
  • Ph represents a phenyl group.
  • reaction products obtained by the reaction method of the present invention are specifically described in (III-1) to (III-118) and (III-300) to (III-314) above.
  • compounds having various structures may be used.
  • compounds represented by the following formulas (IIIc) to (IIIf) can be mentioned.
  • the aromatic hydrocarbon group, the aromatic heterocyclic group and the substituent can be the same groups as the respective groups listed in the compound (I), respectively. ..
  • the compounds represented by these formulas (IIIc) to (IIIf) can be used as components of coloring materials, energy ray absorbing materials, information recording materials, wavelength conversion materials, indicator materials, sensor materials and the like.
  • Ar1 and Ar2 independently represent the formulas (Ar-1) to (Ar-3), respectively.
  • R 14 in (Ar-1), R 15 in (Ar-2), and R 16 in (Ar-3) all represent substituents.
  • r is an integer of 0 or 1 to 5
  • s in (Ar-2) is an integer of 0 or 1 to 7
  • t in (Ar-3) is an integer of 0 or 1 to 8.
  • the linking groups Q1 and Q2 are independently selected from the linking groups represented by the formulas (Q-1) to (Q-4). Q1 and Q2 may be the same or different from each other.
  • R 10 and R 11 are independently a cyano group, an alkyl group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or a substituent. Represents an aromatic heterocyclic group which may have a group.
  • R 12 has an alkyl group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or an aromatic which may have a substituent. Represents a heterocyclic group.
  • R 13 is a halogen atom, an alkoxyl group which may have a substituent or an amino group which may have a substituent, and an alkynyl group which may have a substituent.
  • An aromatic hydrocarbon group which may have a substituent or an aromatic heterocyclic group which may have a substituent.
  • R 20 , R 21 , R 22 and R 23 may independently have an alkyl group which may have a substituent, an alkynyl group which may have a substituent, and a substituent. It has an alkenyl group, an acyl group which may have a substituent, a carbonyl group, a carboxyl group, an alkoxyl group which may have a substituent, a silyl group which may have a substituent, and a substituent. Represents an amino group which may be present, an aromatic hydrocarbon group which may have a substituent, or an aromatic heterocyclic group which may have a substituent.
  • X 20 , X 21 , X 22 and X 23 independently represent an oxygen atom, a sulfur atom or an NR 24 , respectively.
  • Y 20 , Y 21 , Y 22 and Y 23 each independently represent an oxygen atom, an amino group which may have a substituent or CR 25 R 26 .
  • R 24 , R 25 and R 26 may independently have an alkyl group which may have a substituent and an aromatic hydrocarbon group or a substituent which may have a substituent. Represents an aromatic heterocyclic group.
  • a plurality of R 24, R 25 , and R 26 included in the formulas (IIId) and (IIIe) may be the same or different from each other. )
  • Rings A 40 and A 41 each independently represent an aromatic hydrocarbon group which may have a substituent or an aromatic heterocyclic group which may have a substituent.
  • R 40 and R 41 independently have an alkyl group which may have a substituent, an alkynyl group which may have a substituent, an alkenyl group which may have a substituent, and a substituent.
  • An acyl group which may have an acyl group, a carbonyl group, a carboxyl group, an alkoxyl group which may have a substituent, a silyl group which may have a substituent, and an amino group which may have a substituent.
  • the metal catalyst used in the reaction method of the present invention is the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (for example).
  • the reaction is not particularly limited as long as it can catalyze (promote) the reaction (for example, cross-coupling reaction, etc.).
  • the metal (element) constituting the metal catalyst is a typical metal (element) even if it is a transition metal (element) as long as it can catalyze (promote) the reaction between the compound (I) and the compound (II). It may be, and is not particularly limited.
  • transition metals (elements) include scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium, niobium, molybdenum, technesium, ruthenium, rhodium, palladium, silver, and cadmium.
  • One or more selected from the group consisting of hafnium, tantalum, tungsten, ruthenium, osmium, iridium, platinum, gold and the like can be mentioned.
  • a typical metal (element) for example, one or more selected from the group consisting of aluminum, gallium, germanium, indium, tin, antimony, thallium, lead, and bismuth can be mentioned.
  • transition metals (elements) belonging to the 4th to 6th periods can be mentioned from the viewpoint of catalytic activity and the like.
  • At least one selected from the group consisting of palladium, nickel, iron, ruthenium, platinum, rhodium, iridium, and cobalt is more preferable, and at least one selected from the group consisting of palladium, nickel, iron, and copper is more preferable. ..
  • metal catalyst various forms can be used, and examples thereof include one or more selected from the group consisting of the following (1) to (4) and the like.
  • Powdery or porous metal unit (2) Metal unit or metal compound supported on a carrier such as alumina, carbon, silica, zeolite (3) Metal salt (chloride, bromide, iodide, Nitrate, sulfate, carbonate, oxalate, acetate, oxide, etc.) (4) Complex compound of metal and complex (olefin complex, phosphine complex, amine complex, ammine complex, acetylacetonate complex, etc.)
  • a palladium catalyst is particularly preferably used as the metal catalyst.
  • the palladium catalyst include palladium (II) acetate, palladium (II) chloride, palladium (II) bromide, palladium (II) iodide, palladium acetylacetonate (II), and dichlorobis (benzonitrile) palladium (II).
  • a coordinating compound such as a phosphine compound can be used in coexistence with the metal catalyst from the viewpoint of allowing the reaction (for example, a cross-coupling reaction) to proceed with high selectivity.
  • the coordinating compound is used in a reaction (for example, a cross-coupling reaction, etc.) between the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)).
  • a reaction for example, a cross-coupling reaction, etc.
  • Coordinating compounds include, for example, aryl phosphin such as triphenylphosphine, tri (o-tolyl) phosphin, tri (mesityl) phosphin; tri (cyclohexyl) phosphine, tri (isopropyl) phosphine, tri (tert-butyl) phosphine.
  • aryl phosphin such as triphenylphosphine, tri (o-tolyl) phosphin, tri (mesityl) phosphin; tri (cyclohexyl) phosphine, tri (isopropyl) phosphine, tri (tert-butyl) phosphine.
  • Alkylphosphines 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'-diisopropoxy Biphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2', 4', 6'-triisopropylbiphenyl, 2- (di-tert-butylphosphino) -2', 4' , 6'-Triis
  • a coordinating compound such as a phosphine compound
  • a phosphine compound or an N-heterocarben compound may be mixed and prepared in advance for reaction.
  • a coordinating compound such as a phosphine compound
  • a phosphine compound or an N-heterocarben compound may be mixed and prepared in advance for reaction.
  • 2-dicyclohexylphosphino-2', 6'-dimethoxybiphenyl) [2- (2'-amino-1,1'-biphenyl)] palladium (II) methanesulfonic acid (SPhos Pd G3) should be used. Can be done.
  • a phosphine compound is preferably used as the coordinating compound.
  • the phosphine compound preferably contains an alkylphosphine.
  • the coordinating compound may be used alone or in combination of two or more.
  • As the coordinating compound a commercially available product can be used as it is or after purification.
  • the amount of the metal catalyst used or the amount of the metal catalyst used in the coexistence of the metal catalyst and the coordinating compound is not particularly limited as long as the reaction (for example, a cross-coupling reaction or the like) proceeds, and the organic Compound (A) (eg, said compound (I)) and said organic compound (B) (eg, said compound (II)), metal catalyst, base, unsaturated hydrocarbon compound used as needed, reaction generation. It can be appropriately determined in consideration of each type of compound, each amount, reaction temperature and the like.
  • the amount of the metal catalyst used is, for example, 0.5 mol% or more, preferably 0.1 mol% or more, based on the number of moles obtained by multiplying the molar amount of compound (I) by a valence (100%).
  • It can be more preferably 0.5 mol% or more, further preferably 1.0 mol% or more, and the upper limit is not particularly limited, but is 25 mol% or less, preferably 20 mol% or less, more preferably 15 mol. % Or less, more preferably 10 mol% or less.
  • the amount of the coordinating compound used is not particularly limited as long as the reaction (for example, cross-coupling reaction or the like) proceeds, and the organic compound (A) is used.
  • the compound (I) and the organic compound (B) for example, the compound (II)
  • a metal catalyst for example, a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, and a reaction product. It can be appropriately determined in consideration of the type, amount of each, reaction temperature, and the like.
  • the amount of the coordinating compound used is, for example, 10/1 to 1/10, preferably 5/1 to 1/5, as the molar ratio of the coordinating compound to the palladium catalyst (coordinating compound / palladium catalyst). It can be preferably 3/1 to 1/3, and more preferably 2/1 to 1/2.
  • the reaction method of the present invention comprises an organic compound (A) having a melting group having a melting group of 30 ° C. or higher, an organic compound (B) having a melting group of 30 ° C. or higher that reacts with an organic compound having a leaving group, and a catalyst.
  • Bases can be used.
  • the bases used in the reaction method of the present invention (for example, a cross-coupling reaction method, etc.) are the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II). )) Is not particularly limited as long as it can promote the reaction (for example, cross-coupling reaction, etc.).
  • Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, potassium hydrogencarbonate, rubidium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, potassium fluoride, cesium fluoride and the like.
  • Inorganic bases alkali hydrides such as sodium hydride, potassium hydride, etc .; sodium-methoxydo, sodium-ethoxydo, potassium-methoxyd, potassium-methoxyd, potassium-ethoxydo, lithium-tert-butoxide, sodium-tert-butoxide, potassium -Alkali metal alkoxides such as tert-butoxide; triethylamine, tributylamine, dimethylpropylamine, dimethylbutylamine, dimethylcyclohexylamine, dimethylbenzylamine, diisopropylmethylamine, diisopropylethylamine, pyridine, diazabicycloundecene (1,8-diazabicyclo) [5.4.0] Undec-7-ene), diazabicyclononen (1,5-diazabicyclo [4.3.0] nona-5-ene), 1,4-diazabicyclo [2.2.2] Octane,
  • the amount of the base used is not particularly limited as long as the amount of the base used is such that the reaction (for example, a cross-coupling reaction) proceeds, and the compound (I), the compound (II), the metal catalyst, the base, and the base are used as needed. It can be appropriately determined in consideration of each type and amount of unsaturated hydrocarbon compound and reaction product, reaction temperature and the like.
  • the amount of the base used is, 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, based on the equivalent of compound (1). Most preferably, it can be 1.4 equivalents or more.
  • the upper limit of the amount of the base used is not particularly limited, but may be, for example, 10.0 equivalents or less, preferably 5.0 equivalents or less, more preferably 4.0 equivalents or less, still more preferably 3.0 equivalents or less.
  • an unsaturated hydrocarbon compound can be further used if necessary.
  • Unsaturated hydrocarbon compounds are chain and / or cyclic compounds 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 promotes the reaction (cross-coupling reaction, etc.) between the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)).
  • the unsaturated hydrocarbon compound used in the present invention does not include aromatic compounds such as benzene and naphthalene. Further, the compound (I), the compound (II), the metal catalyst, and the compound corresponding to the coordinating compound are not included.
  • the unsaturated hydrocarbon compound has, for example, 5 to 24 carbon atoms, 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, nonadien, decadien 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, decine 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, cyclodecine and the like.
  • the unsaturated hydrocarbon compound may be used alone or in combination of two or more.
  • As the unsaturated hydrocarbon compound a commercially available product can be used as it is or after purification.
  • the amount used is not particularly limited as long as the amount used is such that the reaction (for example, a cross-coupling reaction) proceeds, and the organic compound (A) (for example, the compound (I)) is used. )) And the organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, the type and amount of each reaction product, and the reaction. It can be set as appropriate in consideration of temperature and the like.
  • the amount used is all raw materials (eg, compound (I), compound (II), metal catalyst (and, for example) added to carry out the reaction (eg, cross-coupling reaction, etc.)).
  • the coordinating compound Based on the total mass of the coordinating compound), the base, the reaction accelerator, etc.), for example, 0.01 ⁇ L / mg or more, preferably 0.05 ⁇ L / mg or more, more preferably 0.10 ⁇ L / mg or more.
  • it can be 3.0 ⁇ L / mg or less, preferably 1.0 ⁇ L / mg or less, and more preferably 0.50 ⁇ L / mg or less.
  • the present inventors observed the metal catalyst after the reaction using a transmission electron microscope, and found that the aggregation of the metal catalyst can be suppressed by using an unsaturated hydrocarbon compound. It is considered that the unsaturated hydrocarbon compound contributes to the suppression of aggregation of the metal catalyst and the improvement of the reactivity, and the reaction method of the present invention (for example, the cross-coupling reaction method, etc.) has an excellent effect.
  • the reaction method of the present invention for example, the cross-coupling reaction method, etc.
  • the present inventors can presume that it works. However, the present invention is not limited by such estimation.
  • the reaction method of the present invention (for example, a cross-coupling reaction method or the like) is carried out under the condition that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total. It can be said that such a condition is a condition in which an organic solvent is not substantially used.
  • the conditions in which the organic solvent is substantially not used are a mode in which the organic solvent is not used at all, a mode in which the solvent is not positively used, and a mode in which the organic solvent is used but the solvent effect is not exhibited. Represents one of the embodiments used only.
  • the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)) in total.
  • Is. Usually 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 maximum preferably 0 mL (without using an organic solvent). ..
  • 1 to 2 mL of organic solvent is used per 1 mmol of the reaction raw material in total.
  • the amount of the organic solvent used is small, at least a part of the reaction raw material is usually not dissolved in the organic solvent or the like at the start of the reaction. In some cases, all of them may exist in a solid state without being dissolved in an organic solvent or the like.
  • an organic solvent may be present in an amount of 0.7 mL or less per 1 mmol of the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)).
  • organic solvents used in reactions eg, cross-coupling reactions, etc.
  • aromatic solvents such as benzene, toluene, xylene, mesityismerene, decalin
  • ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, cyclopentylmethyl ether, etc .
  • methanol methanol.
  • Ethanol n-propanol, 2-propanol, 1-butanol, 1,1-dimethylethanol, tert-butanol, 2-methoxyethanol, ethylene glycol and other alcohol solvents; dichloromethane, chloroform, carbon tetrachloride, chlorobenzene , 1,2-Dichlorobenzene and other halogenated hydrocarbon solvents; polar solvents such as acetonitrile, N, N'-dimethylformamide, N, N'-dimethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, etc.
  • Ketone-based solvent such as acetone and methyl ethyl ketone; one or more selected from the group consisting of pyridine, acetic acid and the like.
  • Ketone-based solvent such as acetone and methyl ethyl ketone
  • one or more selected from the group consisting of pyridine, acetic acid and the like are preferred.
  • 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- Propearl, tert-butanol and dimethyl sulfoxide are preferred.
  • the reaction method of the present invention comprises an organic compound (A) having a melting point of 30 ° C. or higher, an organic compound (B) having a melting point of 30 ° C. or higher and reacting with an organic compound having a melting group, and a catalyst.
  • Other ingredients such as accelerators can be used.
  • the reaction method of the present invention is a cross-coupling reaction method
  • the compound (I), the compound (II), the metal catalyst, the coordinating compound, the unsaturated hydrocarbon compound, and the above can be used.
  • other components such as conventionally known cross-coupling reaction accelerators can be used.
  • the accelerator examples include water (pure water, ion-exchanged water, etc.), an organic solvent of less than 0.7 mL per 1 mmol of the organic compound (A) and the organic compound (B), and the like.
  • the amount of the accelerator used is not particularly limited as long as the amount used is such that the reaction (for example, a cross-coupling reaction) proceeds.
  • the compound (I), the compound (II), the metal catalyst, the base, the unsaturated hydrocarbon compound used as necessary, the type and amount of each reaction product, the reaction temperature, etc. are taken into consideration and appropriately determined. be able to.
  • the amount of the accelerator used can be, for example, 20.0 equivalents or less, preferably 10.0 equivalents or less, and more preferably 9.0 equivalents or less, based on the equivalent of compound (1). There is no particular lower limit to the amount used, but 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. Can be.
  • an organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are prepared in the presence of a catalyst.
  • the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in total and the temperature is 60 to 500 ° C.
  • the mechanical energy is applied to the organic compound (A) and the organic compound (B). ) Is reacted by the mechanochemical method.
  • the reaction method of the present invention is an organic synthetic reaction method that does not use an organic solvent and reacts by directly contacting the reaction raw materials with each other and mixing them.
  • the reaction activity is high despite the low environmental load.
  • Examples of such an organic synthesis reaction method include a mechanochemical method, which can also be adopted in the method of the present invention.
  • the mechanochemical method is a method of activating and reacting a solid raw material by applying mechanical energy to the solid raw material by means such as grinding, shearing, impact, and compression.
  • the reaction method of the present invention is a cross-coupling reaction method, for example, compound (I) and compound (II) are used, for example, in the presence of at least a metal catalyst and a base, and if necessary.
  • the reaction is carried out under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II), and the temperature is 60 to 500 ° C.
  • a reaction for example, a cross-coupling reaction or the like.
  • any mixable method such as shaking, rubbing, pressing, dispersion, kneading, and crushing may be used.
  • an apparatus that mechanically performs the mixing process.
  • a device for example Crushers for ball mills, rod mills, jet mills, SAG mills, etc.; Grinding machines such as rotary millstones and grinders; (Horizontal axis rotation) container rotation type mixer such as horizontal cylinder type, V type, double cone type, square cube type, S type and continuous V type; Horizontal cylindrical type, V type, double conical type, ball mill type, etc.
  • container rotary type mixer (with baffle blades) container rotary type mixer; (Rotating vibration) container rotary mixing device such as locking type and cross rotary type; (Horizontal axis rotation) fixed container type mixing device such as ribbon type, paddle type, single axis rotor type and bug mill type; (Vertical axis rotation) fixed container type mixer such as ribbon type, screw type, planet type, turbine type, high speed flow type, rotating disk type and Marler type; (Vibration) fixed container type mixer such as vibration mill type and sieve; (Fluidized) fluid-moving mixers such as non-uniform fluidized beds, swirling fluidized beds, riser pipe type and jot pump type; (Gravity) fluid motion type mixer such as gravity type and static mixer; One or more species selected from the group consisting of the above can be mentioned.
  • the method and the apparatus used are not particularly limited.
  • the powder mixing device described in Sakashita "Powder Mixing Process Technique" Coloring Material, 77 (2), 75-85 (2004), Table 5 and FIG. 9 can be referred to.
  • a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-screw ball mill and the like can be used.
  • the mixing rate at the time of mixing is not particularly limited, and the organic compound (A) (for example, the compound (I)) and the organic compound are not particularly limited.
  • shaking should be performed at 5 Hz or higher, preferably 10 Hz or higher, more preferably 20 Hz or higher. Can be done.
  • reaction temperature In the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), the reaction temperature (temperature inside the reaction vessel at the time of mixing) is 60 to 500 ° C.
  • the method for controlling the reaction temperature to 60 to 500 ° C. is not particularly limited, but a temperature control method used when carrying out a chemical reaction can be used.
  • a method of controlling the temperature inside the reaction vessel using warm air a method of covering the reaction vessel with a heat medium having a predetermined temperature to control the temperature inside the reaction vessel, and a method of providing a heating element to control the temperature inside the reaction vessel.
  • the method etc. can be mentioned.
  • a method of applying warm air generated by a heat gun to the reaction vessel to control the temperature inside the reaction vessel is preferable from the viewpoint of safety and ease of temperature control operation.
  • reaction atmosphere In the reaction method of the present invention (for example, a cross-coupling reaction method or the like), the reaction atmosphere (the atmosphere in the reaction vessel at the time of mixing) is not particularly limited, and the organic compound (A) (for example, the compound (I)) is not particularly limited. ), The organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, each type and amount of each reaction product, reaction temperature, etc. Can be determined as appropriate in consideration of. For example, it can be performed in an atmospheric atmosphere without particularly adjusting the atmosphere. Further, depending on the compound (I), compound (II), metal catalyst, base, unsaturated hydrocarbon compound and reaction product to be used, it may be carried out in an inert gas atmosphere such as nitrogen, helium, neon or argon. can.
  • an inert gas atmosphere such as nitrogen, helium, neon or argon.
  • reaction time In the reaction method of the present invention (for example, a cross-coupling reaction method or the like), the reaction time (mixing time; time for processing by mechanical means) is not particularly limited, and the organic compound (A) (for example, the compound) is not particularly limited. (I)), said organic compound (B) (eg, said compound (II)), metal catalyst, base, unsaturated hydrocarbon compound used as needed, each type and amount of reaction product, It can be appropriately determined in consideration of the reaction temperature and the like. For example, it can be 1 minute or longer, preferably 3 minutes or longer, and more preferably 5 minutes or longer.
  • the upper limit of the reaction time is not particularly limited, but can be, for example, 10 hours or less, preferably 5 hours or less, and more preferably 3 hours or less.
  • the abundance of the organic solvent is at least in the presence of a metal catalyst, a base, and an unsaturated hydrocarbon compound used as needed, in the presence of the compound (I).
  • a reaction product can be obtained in a short time and in a high yield.
  • the obtained reaction product can be purified as needed.
  • the method for purifying the reaction product is not particularly limited, and for example, methods such as recrystallization, column chromatography, and washing with a solvent can be used.
  • the reactor of the present invention comprises at least a reaction vessel, means for stirring the contents in the reaction vessel, and means for adjusting the temperature in the reaction vessel.
  • An organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are mixed in the presence of an organic solvent in the presence of a catalyst.
  • One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. It is a reaction, a device.
  • the apparatus used for the reaction method for reacting by the mechanochemical method is not particularly limited as long as it is an apparatus in which specific reaction raw materials are brought into direct contact with each other and reacted by the mechanochemical method. For example, by applying mechanical energy to a raw material having a melting point of 30 ° C.
  • the reaction vessel provided in the reaction apparatus of the present invention is not particularly limited as long as it is various reaction vessels that can be provided in the reaction apparatus of the compound, and the organic compound (A) (for example, the compound (I)).
  • the organic compound (B) for example, the compound (II)
  • a metal catalyst for example, the compound (II)
  • a base for example, the compound (II)
  • an unsaturated hydrocarbon compound used as needed, each type and amount of each reaction product, reaction temperature, atmosphere. , Reaction pressure, etc. can be taken into consideration and appropriately determined.
  • the ball mill jar, the kneader itself, etc. are used. It can be used as a reaction vessel.
  • the means for stirring the contents in the reaction vessel provided in the reaction device of the present invention is not particularly limited as long as it is various stirring means that can be provided in the reaction device for the compound.
  • the means by the apparatus for mechanically mixing treatment described in ⁇ Reaction conditions> of the above [Reaction method] can be used.
  • an apparatus for mechanically mixing for example, a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-screw ball mill and the like are preferably used.
  • the temperature adjusting means in the reaction vessel provided in the reaction apparatus of the present invention is particularly limited as long as it is a means for adjusting the temperature so that the reaction (for example, a cross-coupling reaction) is carried out at a temperature of 60 to 500 ° C. Not limited.
  • the temperature adjusting means described in (Reaction temperature) of ⁇ Reaction condition> of the above [Reaction method] can be used.
  • a method of heating the reaction vessel using warm air from a heat gun or the like is preferably used.
  • the reaction apparatus of the present invention further includes a measuring means, a depressurizing or pressurizing means, an atmosphere adjusting means (gas introduction or discharging means), a means for inputting various components, a means for taking out various components / reaction products, a means for purifying, and a means for analysis. It may be provided with various means that can be provided in the reaction apparatus of the compound, such as.
  • p is an integer of 5 to 30, preferably 5 to 20, more preferably 5 to 15, and even more preferably 5 to 10.
  • q is an integer of 5 to 30, preferably 5 to 20, more preferably 5 to 15, and even more preferably 5 to 10.
  • Specific examples of the method for producing the compound represented by the formula (IIIa) or (IIIb) include the methods described in Examples 1 to 4.
  • the compound represented by either the formula (IIIa) or (IIIb) corresponds to a low polymer of polythiophene or polyphenylene known as a conductive plastic, and has such a low molecular weight (low nuclei). ) Has not been known so far as a method for precisely synthesizing the compound. These compounds are useful in applications such as organic light emitting diodes (OLEDs), organic semiconductor materials, raw material compounds for synthesizing conductive organic materials, and conductivity control materials for conductive organic materials.
  • OLEDs organic light emitting diodes
  • each reagent is charged into a stainless steel ball mill jar, and Verder Scientific Co., Ltd. (formerly Lecce) is used. (Retsch)) ball mill MM400 type was used.
  • Verder Scientific Co., Ltd. originally Lecce
  • (Retsch) ball mill MM400 type was used.
  • the outside of the ball mill jar was heated at a predetermined temperature with a heat gun (manufactured by Takagi Co., Ltd., HG-1450B).
  • a heat gun manufactured by Takagi Co., Ltd., HG-1450B
  • Example 1 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of (I-1) as compound (I) and (II) as compound (II) under air. -1) was 0.36 mmol (2.4 equiv with respect to compound (I)), and palladium (II) acetate (Pd (OAc) 2 ) as a metal catalyst was 0.015 mmol (10 mol% with respect to compound (I)).
  • reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding cross-coupling reaction product (III-1). The isolated yield was 96%. IR analysis, PXRD analysis and EI-MS analysis were performed on the reaction product (III-1). The respective results are shown in FIGS. 1 to 3.
  • (I-1) was used as compound (I)
  • (II-1) was used as compound (II)
  • Pd (OAc) 2 was used as a metal catalyst
  • SPhos was used as a coordinating compound
  • CsF was used as a base.
  • the mixture was placed in a reaction vessel so as to have the same amount as in Example 1, and toluene was further added to the reaction vessel so that the concentration of compound (I) was 0.1 M (0.1 mol / L) and mixed.
  • the obtained mixed solution was heated at 120 ° C. for 24 hours to carry out a cross-coupling reaction.
  • Example 2 A cross-coupling reaction was carried out in the same manner as in Example 1 except that the compounds shown in Table 2 were used as the compound (I) and the compound (II) to obtain the corresponding reaction product (III) shown in Table 2.
  • the types of the corresponding reaction product (III) and the isolated yields thereof are also shown in Table 2.
  • Example 5 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of (I-3) as compound (I) and (II) as compound (II) under air. -5) as 0.36 mmol (2.4 equiv with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (10 mol% with respect to compound (I)), as a coordinating compound.
  • SPhos is 0.0225 mmol (15 mol% with respect to compound (I)), CsF as a base is 0.9 mmol (6.0 eq with respect to compound (I)), and water is 1.08 mmol (compound (I)) as a reaction accelerator.
  • 7.2 equiv) to I) 0.2 ⁇ L / mg of 1,5-cyclooctadien as an unsaturated hydrocarbon compound was added.
  • the lid of the ball mill jar was closed, attached to the ball mill, and the jar was shaken for 90 minutes while heating with a heat gun set at 250 ° C. to stir (30 Hz) to perform a cross-coupling reaction. After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate.
  • reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III) shown in Table 3 or Table 4.
  • the type of the corresponding reaction product (III) and the isolated yield thereof are shown in Table 3 or Table 4.
  • Example 29 to 31 Examples except that DavaPhos (2-dicyclohexylphosphino-2'-(N, N-dimethylamino) biphenyl) was used in place of SPhos in an amount of 4.5 mol% with respect to compound (I) as a coordinating compound.
  • the cross-coupling reaction was carried out in the same manner as in No. 21, and the isolated yield of the reaction product (III-19) was determined. The results are shown in Table 4.
  • Example 32 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-6) as compound (I) and (II) as compound (II) under air. -11) as 0.36 mmol (1.2 equiv with respect to compound (I)), SPhos Pd G3 as a metal catalyst and coordinating compound 0.009 mmol (3 mol% with respect to compound (I)) as a base.
  • CsF is 0.9 mmol (3.0 eq with respect to compound (I))
  • water is 1.11 mmol (3.7 evi with respect to compound (I)) as a reaction accelerator, and 1, as an unsaturated hydrocarbon compound, 1.
  • Example 48 After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding coupling products shown in Table 8.
  • Example 48 26.9 mg (0.03 mmol) of the reaction product (III-42) was obtained, and the isolated yield was 30%.
  • the isolated yields of each reaction product of Examples 49 and 50 are as shown in Table 8.
  • Example 51 to 55 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 equiv) of compound (I) shown in Table 9 and compound (II) shown in Table 9 were placed under air. 0.3 mmol (1.0 equiv), 0.015 mmol of Pd (OAc) 2 as a metal catalyst (5 mol% with respect to compound (I)), and t-Bu 3 P. HBF 4 (tri-tert) as a coordinating compound.
  • OAc Pd
  • HBF 4 tri-tert
  • Example 51 126.0 mg (0.292 mmol) of the reaction product (III-45) was obtained, and the isolated yield was 97%.
  • the types of each reaction product of Examples 52 to 55 and the isolated yields thereof are as shown in Table 9.
  • Example 56 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-13) as compound (I) and (II) as compound (II) under air. -5) was 0.36 mmol (1.2 equiv with respect to compound (I)), Pd (OAc) 2 was 0.009 mmol (3 mol% with respect to compound (I)) as a metal catalyst, and as a coordinating compound.
  • DavaPhos is 0.0135 mmol (4.5 mol% with respect to compound (I)), CsF as a base is 0.9 mmol (3.0 eq with respect to compound (I)), and water is 1.11 mmol (with respect to compound (I)) as a reaction accelerator.
  • 3.7 evi) was added to compound (I), and 0.2 ⁇ L / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound.
  • the lid of the ball mill jar was closed, and the jar was attached to the ball mill.
  • the jar was heated by a heat gun set to the temperature shown in Table 10 and shaken for 99 minutes to stir (25 Hz) to perform a cross-coupling reaction.
  • reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the reaction product (III-7). The isolated yield was 66%.
  • Example 57 The reaction was carried out in the same manner as in Example 56 except that (I-5) was used as the compound (I) to obtain a reaction product (III-7). The isolated yield was 88%.
  • Example 58 The reaction was carried out in the same manner as in Example 56 except that (I-200) was used as the compound (I) to obtain a reaction product (III-7). The NMR yield was 51%.
  • Example 59 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-201) as compound (I) and (II) as compound (II) under air. -200) 0.3 mmol (1.0 evi with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (5 mol% with respect to compound (I)), as a coordinating compound.
  • Example 59 the cross-coupling reaction was carried out in the same manner as in Example 59 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
  • Example 60 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-201) as compound (I) and (II) as compound (II) under air. -201) 0.45 mmol (1.2 equiv with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (5 mol% with respect to compound (I)), as a coordinating compound.
  • Example 60 the cross-coupling reaction was carried out in the same manner as in Example 60 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
  • Example 61 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-206) as compound (I) and (II) as compound (II) under air. -202) is 0.3 mmol (1.0 evi with respect to compound (I)), SPhos Pd G3 as a coordinating compound is 0.015 mmol (5 mol% with respect to compound (I)), and sodium-tert as a base. -Toxide 0.36 mmol (1.2 equiv with respect to compound (I)) and LAG (Liquid Assisted Gringing) 0.2 ⁇ L / mg were added.
  • Example 61 a cross cup was used in the same manner as in Example 61, except that toluene was used (Example 62), tetrahydrofuran was used (Example 63), and 1,5-cyclooctadiene was used (Example 64). A ring reaction was carried out to obtain a reaction product (III-303). The NMR yield was 46% in Example 62, 61% in Example 63, and 40% in Example 64.
  • Example 61 the cross-coupling reaction was carried out in the same manner as in Example 61 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
  • Example 65 to Example 77 In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, the compound (I) shown in Table 9 was added as 0.30 mmol (1.0 equiv) and the compound (II) as compound (II-45) under air. ) Is 0.36 mmol (1.2 equiv), Pd (OAc) 2 is 0.006 mmol (2 mol% with respect to compound (I)) as a metal catalyst, and t-Bu 3 P ⁇ HBF 4 (tri) as a coordinating compound.
  • Example 65 the reaction product (III-304) was obtained, the NMR yield was 99% or more, and the isolation yield was 77%.
  • the types, NMR yields, isolation yields and reaction conversion rates of each reaction product of Examples 66 to 77 are as shown in Table 9 (in the table, "-" is unmeasured or unmeasurable. ).
  • the cross-coupling reaction method according to the present invention is a cross-coupling reaction method carried out in a conventional organic solvent. It can be seen that the yield is significantly higher than that of. Further, as shown in Examples 1, 3, 42, 47 to 50 and Comparative Examples 1, 3, 40, 46 to 46, the cross-coupling reaction method according to the present invention causes a cross-coupling reaction in an organic solvent. It can be seen that the reaction product can be obtained even when a reaction raw material that cannot be carried out is used.
  • the cross-coupling reaction method according to the present invention was carried out under the conditions of 60 to 500 ° C., as compared with the cross-coupling reaction method carried out without heating. It can be seen that the yield is significantly higher. Further, as shown in Examples 5, 17, 22, 23, 32, 34 and Comparative Examples 5, 17, 22, 23, 29, 30, the cross-coupling reaction method according to the present invention is under the condition of no heating. It can be seen that the reaction product can be obtained even when a reaction raw material that cannot carry out the cross-coupling reaction is used. Further, Examples 61, 63 and 65 to 77 are examples in which a hydrocarbon compound is not used at all, and show a wide range of applicability of the reaction method of the present invention.
  • the cross-coupling reaction method according to the present invention uses a wide variety of compounds as starting materials, does not use an organic solvent, and is a reaction product in a short time and in a high yield by a simple means. It turns out that you can get.
  • the cross-coupling reaction can be performed even on a compound having low solubility in an organic solvent. From this, it can be seen that the present invention is an industrially very useful invention.

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Abstract

The present invention addresses the problem of providing a cross-coupling reaction method that can use a wide variety of compounds as starting materials, that can substantially not use organic solvent, and that can rapidly provide reaction products at high yields using a simple and convenient means. The present invention also addresses the problem of providing novel compounds that have not heretofore been obtainable. The following reaction method is provided as the solution: the reaction, by a mechanochemical procedure, of a leaving group-bearing organic compound (A) having a melting point of at least 30°C and an organic compound (B) that has a melting point of at least 30°C and is reactive with the leaving group-bearing organic compound, by the application of mechanical energy to the organic compound (A) and the organic compound (B) in the presence of a catalyst under conditions of a temperature of 60-500°C and an amount of organic solvent present of not more than 0.7 mL per 1 mmol of the total of the organic compound (A) and the organic compound (B).

Description

反応方法及びその反応に用いる装置Reaction method and equipment used for the reaction
　本発明は、新規な反応方法に関する。さらに、その方法に用いる装置、その反応を用いる化合物の製造方法及び化合物に関する。 The present invention relates to a novel reaction method. Further, the present invention relates to an apparatus used for the method, a method for producing a compound using the reaction, and the compound.
　医薬、液晶化合物、有機エレクトロルミネッセンス化合物、着色材料、エネルギー線吸収材料、情報記録材料、波長変換材料、インジケーター材料、センサー材料、有機発光ダイオード（ＯＬＥＤ）、有機半導体材料等の合成方法の一手段として、例えば、クロスカップリング反応が知られている。非特許文献１及び２には、脱離基を有する芳香族化合物と芳香族ボロン酸誘導体等とを、パラジウム触媒等の金属触媒の存在下で反応させて連結して芳香族化合物を得るクロスカップリング反応が知られている。そして、その合成化学的重要性から、鈴木章博士、根岸英一博士及びリチャード・ヘック博士の「パラジウム触媒によるクロスカップリング反応の開発」に対し、２０１０年にノーベル化学賞が授与されている。 As a means of synthesizing 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. In Non-Patent Documents 1 and 2, an aromatic compound having a leaving group and an aromatic boronic acid derivative or the like are reacted in the presence of a metal catalyst such as a palladium catalyst and linked to obtain an aromatic compound. The ring reaction is known. Due to its synthetic chemical importance, the Nobel Prize in Chemistry was awarded in 2010 for "Development of cross-coupling reaction catalyzed by palladium" by Dr. Akira Suzuki, Dr. Eiichi Negishi and Dr. Richard Heck.
　クロスカップリング反応は、一般的に、有機溶媒に出発原料となる化合物を溶かして反応が行われることから、比較的大量の有機溶媒を必要とする。しかし、近年、大量の有機溶媒の使用は、作業者の作業環境及び安全性、地球環境保護、及び使用後の有機溶媒処理時の環境負荷等の観点で問題が生じるおそれがある。したがって、作業環境・安全性、地球環境保護、環境負荷等の点で問題が生じにくいクロスカップリング反応方法が求められている。 The cross-coupling reaction generally requires a relatively large amount of organic solvent because the reaction is carried out by dissolving a compound as a starting material in an organic solvent. However, in recent years, the use of a large amount of organic solvent may cause problems in terms of the working environment and safety of workers, protection of the global environment, and environmental load during treatment with organic solvents after use. Therefore, there is a demand for a cross-coupling reaction method that is less likely to cause problems in terms of work environment / safety, protection of the global environment, environmental load, and the like.
　反応原料同士を直接接触させ、有機溶媒を使用しない有機合成反応法は、低環境負荷であり、学術的にも工業的にも興味深い。このような有機合成反応方法として、メカノケミカル法が注目されている。メカノケミカル法は、摩砕、せん断、衝撃、圧縮等の手段により機械的エネルギーを固体原料に対して加えることで、固体原料を活性化させて反応させる方法である。
　非特許文献３には、実質的に有機溶媒を使用しない、パラジウム触媒を用いるクロスカップリング反応方法は報告されている。しかし、反応例が少なく、出発原料や反応効率の点で改善すべき点が多くある。 The organic synthetic reaction method in which the reaction raw materials are brought into direct contact with each other and does not use an organic solvent has a low environmental load and is academically and industrially interesting. As such an organic synthesis reaction method, the mechanochemical method is attracting attention. The mechanochemical method is a method of activating and reacting a solid raw material by applying mechanical energy to the solid raw material by means such as grinding, shearing, impact, and compression.
Non-Patent Document 3 reports a cross-coupling reaction method using a palladium catalyst that does not substantially use an organic solvent. However, there are few reaction examples, and there are many points that need to be improved in terms of starting materials and reaction efficiency.
　本発明者らは、特許文献１により、種々の化合物を出発原料として用いることができ、実質的に有機溶媒を使用することなく、温和な反応条件で、比較的短時間で、効率よく反応を進行できるクロスカップリング反応方法を提案した。このクロスカップリング反応方法は、Ｃ－Ｎ、Ｃ－Ｂ、Ｃ－Ｃ、Ｃ－Ｏ及びＣ－Ｓ結合から選択される化学結合を比較的効率よく形成することができ、高収率で反応生成物を得ることができる。しかし、このクロスカップリング方法においても、反応時間や収率の点で改善すべき点があった。 According to Patent Document 1, the present inventors can use various compounds as starting materials, and can efficiently carry out the reaction in a relatively short time under mild reaction conditions without substantially using an organic solvent. We proposed a cross-coupling reaction method that can proceed. This cross-coupling reaction method can form a chemical bond selected from CN, CB, CC, CO and CS bonds relatively efficiently, and reacts in high yield. The product can be obtained. However, even in this cross-coupling method, there are some points to be improved in terms of reaction time and yield.
国際公開第２０２０／０８５３９６号International Publication No. 2020/085396
　本発明が解決しようとする課題は、多種多様な化合物を出発原料として用いることができ、実質的に有機溶媒を不使用とすることができ、簡便な手段により、短時間に高収率で反応生成物を得ることができる、反応方法を提供することである。
　本発明が解決しようとする課題は、これまでの方法よりも高収率の反応方法を提供することである。
　本発明が解決しようとする課題は、多種多様な化合物を出発原料として用いることができ、実質的に有機溶媒を不使用とすることができ、簡便な手段により、短時間に高収率で反応生成物を得ることができる、反応装置を提供することである。
　本発明が解決しようとする課題は、これまで得ることができなかった新規な化合物を提供することである。 The problem to be solved by the present invention is that a wide variety of compounds can be used as starting materials, an organic solvent can be substantially eliminated, and a reaction can be carried out in a short time in a high yield by a simple means. It is to provide a reaction method from which a product can be obtained.
The problem to be solved by the present invention is to provide a reaction method having a higher yield than the conventional methods.
The problem to be solved by the present invention is that a wide variety of compounds can be used as starting materials, an organic solvent can be substantially eliminated, and a reaction can be carried out in a short time in a high yield by a simple means. It is to provide a reaction apparatus capable of obtaining a product.
The problem to be solved by the present invention is to provide a novel compound which has not been obtained so far.
　本発明者等は、上記課題を解決するために鋭意検討を重ねた結果、金属触媒及び塩基を用いる反応方法（例えば、クロスカップリング反応方法等）において、金属触媒の分散性を向上させるとともに金属触媒の凝集を抑制すること、さらに、有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、及び６０～５００℃の条件で反応させることで、多種多様な化合物を出発原料として用いることができ、簡便な手段により、短時間に高収率で反応生成物を得ることができることを見出し、本発明を完成させるに至った。
　また、本発明者らは、前記の新規な反応方法（例えば、クロスカップリング反応方法等）を用いて、これまでに合成することができなかった新たな化合物を得ることができることを見出し、本発明を完成させるに至った。
　即ち、本発明は、以下の反応方法、装置、新規化合物の製造方法、及び新規化合物を提供するものである。 As a result of diligent studies to solve the above problems, the present inventors have improved the dispersibility of the metal catalyst and the dispersibility of the metal in a reaction method using a metal catalyst and a base (for example, a cross-coupling reaction method, etc.). A wide variety of reactions can be achieved by suppressing the aggregation of the catalyst, and by reacting the organic solvent in an abundance of 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total, and at 60 to 500 ° C. We have found that a above-mentioned compound can be used as a starting material and a reaction product can be obtained in a short time and in a high yield by a simple means, and the present invention has been completed.
In addition, the present inventors have found that a new compound that could not be synthesized so far can be obtained by using the above-mentioned novel reaction method (for example, a cross-coupling reaction method, etc.). The invention was completed.
That is, the present invention provides the following reaction method, apparatus, method for producing a new compound, and a new compound.
項１：融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、
　触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法であって、
　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、反応方法。
項２：Ｃ－Ｎ結合、Ｃ－Ｂ結合、Ｃ－Ｃ結合、Ｃ－Ｏ結合及びＣ－Ｓ結合から選択される１つ以上の化学結合を形成するクロスカップリング反応方法である、項１に記載の反応方法。
項３：式（Ｉ）：
　Ａ１－Ｘｍ　　　　　（Ｉ）
（式中、
Ａ１は、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基のいずれかを表す。
Ｘは、各々独立して、脱離基を表す。
ｍは、Ｘの数で１以上の整数を表す。）
で表される化合物（Ｉ）と、
　式（ＩＩａ）又は（ＩＩｂ）：
　Ａ２－Ｙｎ　　　　（ＩＩａ）
　（Ｒ６Ｏ）（Ｒ７Ｏ）Ｂ－Ｂ（ＯＲ８）（ＯＲ９）　　　　　（ＩＩｂ）
（式中、
Ａ２は、置換基を有していてもよいｎ価の芳香族炭化水素基、置換基を有していてもよいｎ価の芳香族複素環基、置換基を有していてもよいｎ価の脂肪族炭化水素基、又は置換基を有していてもよいｎ価の不飽和脂肪族炭化水素基を表す。
ｎは、Ｙの数で１以上の整数を表す。
Ｙは、各々独立して、
　－Ｂ（ＯＲ１）（ＯＲ２）
　－ＮＨＲ３
　－Ｒ４－ＯＨ
　－Ｒ５－ＳＨ
を表す。
Ｒ１及びＲ２は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ１とＲ２は相互に結合していてもよい。
Ｒ３は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の芳香族複素環基、置換基を有していてもよい１価の脂肪族炭化水素基、又は置換基を有していてもよい１価の不飽和脂肪族炭化水素基を表す。
Ｒ４及びＲ５は、各々独立して、単結合、置換基を有していてもよい２価の芳香族炭化水素基、置換基を有していてもよい２価の脂肪族炭化水素基を表す。
Ｒ６～Ｒ９は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ６とＲ７は相互に結合していてもよく、Ｒ８とＲ９は相互に結合していてもよい。）
で表される化合物（ＩＩ）を、
　少なくとも、金属触媒及び塩基の存在下、
　有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、及び
　６０～５００℃
の条件で反応させる、項１又は２に記載の反応方法。
項４：前記脱離基が、クロロ、ブロモ、ヨード、ジアゾニウム塩、トリフルオロメタンスルホネート及びカルボン酸誘導体から選ばれる１種以上の基であり、
　前記式（ＩＩａ）で表される化合物が、芳香族ボロン酸又は芳香族ボロン酸エステルから選ばれる芳香族ボロン酸類であり、
　前記式（ＩＩｂ）で表される化合物が、ジボロン酸アルキルエステル、ジボロン酸アルキレングリコールエステル、ジボロン酸アリールエステル、ジボロン酸アリーレングリコールエステル、及びテトラヒドロキシジボランから選ばれるジボロン酸エステル類である、
項１～３のいずれか１項に記載の方法。
項５：前記化合物（Ｉ）と前記化合物（ＩＩ）の当量比（化合物（Ｉ）／化合物（ＩＩ））が、１０／１～１／１０である、項１～４のいずれか１項に記載の方法。
項６：前記金属触媒の存在量が、化合物（Ｉ）のモル数に価数ｍをかけて得た脱離基モル数を１００モル％とした場合に、０．５モル％以上２５モル％以下である、項１～５のいずれか１項に記載の方法。
項７：前記塩基が、無機塩基、アルカリ金属アルコキシド及び有機塩基から選ばれる少なくとも１種を含む、項１～６のいずれか１項に記載の方法。
項８：前記塩基の存在量が、化合物（Ｉ）１当量に対して、０．５当量以上１０当量以下である、項１～７のいずれか１項に記載の方法。
項９：金属触媒及び塩基に加えて、さらに不飽和炭化水素化合物の存在下で反応させる、項１～８のいずれか１項に記載の方法。
項１０：前記不飽和炭化水素化合物が、芳香族化合物ではなく、
　少なくとも１つの炭素－炭素不飽和二重結合及び／又は少なくとも１つの炭素－炭素不飽和三重結合を有する鎖状化合物、又は
　少なくとも１つの炭素－炭素不飽和二重結合及び／又は少なくとも１つの炭素－炭素不飽和三重結合を有する環状化合物、
の１種以上である、項１～９のいずれか１項に記載の方法。
項１１：金属触媒及び塩基に加えて、さらに配位性化合物が存在している、項１～１０のいずれか１項に記載の方法。
項１２：前記不飽和炭化水素化合物の存在量が、
　前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、及び前記塩基の合計質量を基準として、又は、
　前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、前記塩基、及び配位性化合物の合計質量を基準として、
０．０１～３．０μＬ／ｍｇである、項１～１１のいずれか１項に記載の方法。
項１３：反応容器、反応容器内の収容物を撹拌する手段、及び反応容器内の温度調整手段、を少なくとも備え、
　融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法に用いる装置であって、
　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、装置。
項１４：項１～１２のいずれか１項に記載の方法を用いる、式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される化合物の製造方法。
Figure JPOXMLDOC01-appb-C000003
  （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。）
項１５：式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される化合物。
Figure JPOXMLDOC01-appb-C000004
  （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。） Item 1: An organic compound (A) having a melting group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher that reacts with the organic compound having a leaving group.
It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C. hand,
One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. A reaction method, which is a reaction.
Item 2: A cross-coupling reaction method for forming one or more chemical bonds selected from CN bond, CB bond, CC bond, CO bond and CS bond, Item 1. The reaction method described in 1.
Item 3: Equation (I):
A 1 -X m (I)
(During the ceremony,
A 1 may have an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and m which may have a substituent. It represents either a valent aliphatic hydrocarbon group or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
Each of X independently represents a leaving group.
m is a number of X and represents an integer of 1 or more. )
Compound (I) represented by
Equation (IIa) or (IIb):
A2 - Yn (IIa)
(R 6 O) (R 7 O) BB (OR 8 ) (OR 9 ) (IIb)
(During the ceremony,
A 2 may have an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, and n which may have a substituent. Represents a valent aliphatic hydrocarbon group or an n-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
n is a number of Y and represents an integer of 1 or more.
Y is independent of each other
-B (OR 1 ) (OR 2 )
-NHR 3
-R 4 -OH
-R 5 -SH
Represents.
R 1 and R 2 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show. R 1 and R 2 may be coupled to each other.
R 3 independently contains hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a substituent. It represents a monovalent aliphatic hydrocarbon group which may have a substituent or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent.
Each of R 4 and R 5 has a single bond, a divalent aromatic hydrocarbon group which may have a substituent, and a divalent aliphatic hydrocarbon group which may have a substituent, respectively. Represents.
R 6 to R 9 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show. R 6 and R 7 may be coupled to each other, and R 8 and R 9 may be coupled to each other. )
Compound (II) represented by
At least in the presence of metal catalysts and bases
The abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total, and 60 to 500 ° C.
Item 3. The reaction method according to Item 1 or 2, wherein the reaction is carried out under the conditions of.
Item 4: The leaving group is one or more groups selected from chloro, bromo, iodo, diazonium salt, trifluoromethanesulfonate and carboxylic acid derivative.
The compound represented by the formula (IIa) is an aromatic boronic acid selected from an aromatic boronic acid or an aromatic boronic acid ester.
The compound represented by the formula (IIb) is a diboronic acid ester selected from a diboronic acid alkyl ester, a diboronic acid alkylene glycol ester, a diboronic acid aryl ester, a diboronic acid arylene glycol ester, and a tetrahydroxydiborane.
Item 3. The method according to any one of Items 1 to 3.
Item 5: Item 1 to any one of Items 1 to 4, wherein the equivalent ratio of the compound (I) to the compound (II) (compound (I) / compound (II)) is 10/1 to 1/10. The method described.
Item 6: The abundance of the metal catalyst is 0.5 mol% or more and 25 mol% when the number of moles of leaving groups obtained by multiplying the number of moles of the compound (I) by a valence m is 100 mol%. Item 2. The method according to any one of Items 1 to 5, which is described below.
Item 7: The method according to any one of Items 1 to 6, wherein the base contains at least one selected from an inorganic base, an alkali metal alkoxide and an organic base.
Item 8: The method according to any one of Items 1 to 7, wherein the abundance of the base is 0.5 equivalents or more and 10 equivalents or less with respect to 1 equivalent of compound (I).
Item 9. The method according to any one of Items 1 to 8, wherein the reaction is further carried out in the presence of an unsaturated hydrocarbon compound in addition to a metal catalyst and a base.
Item 10: The unsaturated hydrocarbon compound is not an aromatic compound,
A chain compound with at least one carbon-carbon unsaturated double bond and / or at least one carbon-carbon unsaturated triple bond, or at least one carbon-carbon unsaturated double bond and / or at least one carbon- Cyclic compounds with carbon unsaturated triple bonds,
Item 5. The method according to any one of Items 1 to 9, which is one or more of the above.
Item 11. The method according to any one of Items 1 to 10, wherein a coordinating compound is further present in addition to the metal catalyst and the base.
Item 12: The abundance of the unsaturated hydrocarbon compound is
Based on the total mass of the compound (I), the compound (II), the metal catalyst, and the base, or
Based on the total mass of the compound (I), the compound (II), the metal catalyst, the base, and the coordinating compound.
Item 6. The method according to any one of Items 1 to 11, which is 0.01 to 3.0 μL / mg.
Item 13: At least a reaction vessel, a means for stirring the contents in the reaction vessel, and a temperature adjusting means in the reaction vessel are provided.
An organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are mixed in the presence of an organic solvent in the presence of a catalyst. An apparatus used for a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the amount of the organic compound (A) and the organic compound (B) is 0.7 mL or less per 1 mmol in total and the temperature is 60 to 500 ° C.
One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. A device that is a reaction.
Item 14: A method for producing a compound represented by any of the formula (IIIa) or (IIIb), which uses the method according to any one of Items 1 to 12.
Figure JPOXMLDOC01-appb-C000003
 (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
Item 15: A compound represented by either formula (IIIa) or (IIIb).
Figure JPOXMLDOC01-appb-C000004
 (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
　本発明により、多種多様な化合物を出発原料として用いることができ、実質的に有機溶媒を不使用とすることができ、簡便な手段により、短時間に高収率で反応生成物を得ることができる反応方法（例えばクロスカップリング反応方法等）が提供される。これにより、反応生成物（例えば、Ｃ－Ｎ、Ｃ－Ｂ、Ｃ－Ｃ、Ｃ－Ｏ及びＣ－Ｓ結合から選択される化学結合が形成されたクロスカップリング反応生成物等）を、実質的に有機溶媒を使用することなく、簡便な手段により、効率よく、短時間に高収率で製造することができる。
　また、本発明により、これまで得ることができなかった新規な化合物が提供される。 INDUSTRIAL APPLICABILITY According to the present invention, a wide variety of compounds can be used as a starting material, an organic solvent can be substantially eliminated, and a reaction product can be obtained in a short time and in a high yield by a simple means. A capable reaction method (eg, a cross-coupling reaction method, etc.) is provided. As a result, the reaction product (for example, a cross-coupling reaction product in which a chemical bond selected from CN, CB, CC, CO and CS bonds is formed, etc.) is substantially. It can be efficiently produced in a high yield in a short time by a simple means without using an organic solvent.
In addition, the present invention provides a novel compound that has not been obtained so far.
実施例１で得られた反応生成物ＩＩＩ－１に係るＩＲ　ａｎａｌｙｓｉｓである。IR analogysis according to the reaction product III-1 obtained in Example 1. 実施例１で得られた反応生成物ＩＩＩ－１に係るＰＸＲＤ　ａｎａｌｙｓｉｓである。PXRD analogysis according to the reaction product III-1 obtained in Example 1. 実施例１で得られた反応生成物ＩＩＩ－１に係るＥＩ－ＭＳ　ａｎａｌｙｓｉｓである。EI-MS analysis according to the reaction product III-1 obtained in Example 1.
　本発明の第１の態様は、融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、
　触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法であって、
　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、反応方法に関するものである。
　本発明の第２の態様は、反応容器、反応容器内の収容物を撹拌する手段、及び反応容器内の温度調整手段、を少なくとも備え、
　融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法に用いる装置であって、　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、装置に関するものである。
　本発明の第３の態様は、前記反応を用いる、式(IIIａ)又は(IIIｂ)のいずれかで表される化合物の製造方法に関するものである。
Figure JPOXMLDOC01-appb-C000005
  （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。）
　本発明の第４の態様は、式(IIIａ)又は(IIIｂ)のいずれかで表される化合物に関するものである。
Figure JPOXMLDOC01-appb-C000006
 （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。）
　以下、本発明の各態様について、詳細に説明する。 The first aspect of the present invention comprises an organic compound (A) having a leaving group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher that reacts with the organic compound having a leaving group.
It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C. hand,
One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. It relates to a reaction method, which is a reaction.
A second aspect of the present invention comprises at least a reaction vessel, means for stirring the contents in the reaction vessel, and means for adjusting the temperature in the reaction vessel.
An organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are mixed in the presence of an organic solvent in the presence of a catalyst. An apparatus used for a reaction method in which the amount of the organic compound (A) and the organic compound (B) is 0.7 mL or less per 1 mmol in total and the temperature is 60 to 500 ° C. by the mechanochemical method. One or more reactions selected from the group consisting of coupling reaction, alkylation reaction, halogenation reaction, hydrolysis reaction, oxidation reaction, reduction reaction, metallization reaction, radical reaction, metathesis reaction, and cyclization addition reaction. It is about the device.
A third aspect of the present invention relates to a method for producing a compound represented by either formula (IIIa) or (IIIb) using the above reaction.
Figure JPOXMLDOC01-appb-C000005
 (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
A fourth aspect of the present invention relates to a compound represented by either formula (IIIa) or (IIIb).
Figure JPOXMLDOC01-appb-C000006
 (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
Hereinafter, each aspect of the present invention will be described in detail.
［反応方法］
　本発明の反応方法は、
融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、
　触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法であって、
　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、反応方法である。
　本発明の反応に用いる「融点が３０℃以上の脱離基を有する有機化合物（Ａ）」及び「脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）」は、いずれも室温で固体の有機化合物であり、その融点は、３０℃以上、好ましくは４０℃以上、より好ましくは５０℃以上、さらに好ましくは６０℃以上、最も好ましくは８０℃以上である。
　有機化合物（Ａ）及び有機化合物（Ｂ）は、それぞれが所定の融点を有し、互いに反応する物であれば、とくに限定されない。有機化合物（Ａ）としては、例えば、後述の化合物（Ｉ）が挙げられ、有機化合物（Ｂ）としては、例えば、後述の化合物（ＩＩ）が挙げられる。また、有機化合物（Ａ）と有機化合物（Ｂ）は、同じものであってもよい。
　有機化合物（Ｂ）の使用量は、有機化合物（Ａ）との当量比を考慮し、適宜調整される。有機化合物（Ａ）と有機化合物（Ｂ）の当量比（化合物（Ａ）／化合物（Ｂ））は、反応が進行する当量比であれば特に制限されることはない。例えば１０／１～１／１０であり、好ましくは５／１～１／５であり、より好ましくは３／１～１／３であり、さらに好ましくは２／１～１／２である。
　メカノケミカル法は、機械的エネルギーを有機化合物（Ａ）及び有機化合物（Ｂ）に対して加えて反応させる方法である。機械的エネルギーは、摩砕、せん断、衝撃、圧縮等の手段により機械的に生成させることができる。このような機械的エネルギーを固体原料に対して加えることで、固体原料を活性化させて反応させることができる。本発明の反応方法は、反応原料同士を直接接触させて混合して反応させる、有機溶媒を使用しない有機合成反応方法であり、低環境負荷でありながら、反応活性が高い。
　前記反応のうち、カップリング反応としては、ホモカップリング反応、クロスカップリング反応が挙げられ、例えば、Ｃ－Ｎ結合、Ｃ－Ｂ結合、Ｃ－Ｃ結合、Ｃ－Ｏ結合及びＣ－Ｓ結合から選択される１つ以上の化学結合を形成するクロスカップリング反応が挙げられる。
　本発明は、メカノケミカル法による反応に際して、特定の温度に加熱することを特徴とする。 [Reaction method]
The reaction method of the present invention is
An organic compound (A) having a melting group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher reacting with the organic compound having a leaving group.
It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C. hand,
One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. It is a reaction, a reaction method.
The "organic compound (A) having a melting group having a melting group of 30 ° C. or higher" and the "organic compound (B) having a melting group of 30 ° C. or higher that reacts with an organic compound having a leaving group" used in the reaction of the present invention are Both are organic compounds solid at room temperature, 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 organic compound (A) and the organic compound (B) are not particularly limited as long as they each have a predetermined melting point and react with each other. Examples of the organic compound (A) include the compound (I) described later, and examples of the organic compound (B) include the compound (II) described later. Further, the organic compound (A) and the organic compound (B) may be the same.
The amount of the organic compound (B) used is appropriately adjusted in consideration of the equivalent ratio with the organic compound (A). The equivalent ratio of the organic compound (A) to the organic compound (B) (compound (A) / compound (B)) is not particularly limited as long as it is an equivalent ratio in 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 further preferably 2/1 to 1/2.
The mechanochemical method is a method in which mechanical energy is applied to an organic compound (A) and an organic compound (B) to cause a reaction. Mechanical energy can be mechanically generated by means such as grinding, shearing, impact, compression and the like. By applying such mechanical energy to the solid raw material, the solid raw material can be activated and reacted. The reaction method of the present invention is an organic synthetic reaction method that does not use an organic solvent and reacts by directly contacting the reaction raw materials with each other and mixing them. The reaction activity is high despite the low environmental load.
Among the above reactions, examples of the coupling reaction include a homocoupling reaction and a cross-coupling reaction, and examples thereof include CN bond, CB bond, CC bond, CO bond and CS bond. Included are cross-coupling reactions that form one or more chemical bonds selected from.
The present invention is characterized in that it is heated to a specific temperature during a reaction by a mechanochemical method.
＜化合物（Ｉ）＞
　本発明の反応方法で用いられる化合物（Ｉ）；
　Ａ１－Ｘｍ　　　　　（Ｉ）
（式中、
Ａ１は、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基のいずれかを表す。
Ｘは、各々独立して、脱離基を表す。
ｍは、Ｘの数で１以上の整数を表す。）
は、化合物（ＩＩ）と反応して反応生成物（例えば、クロスカップリング反応して、Ｃ－Ｂ結合、Ｃ－Ｃ結合、Ｃ－Ｎ結合、Ｃ－Ｏ結合及びＣ－Ｓ結合のいずれか１つ以上が形成されたクロスカップリング反応生成物等）を生成するものであれば特に限定されない。
　化合物（Ｉ）は、１種を単独で又は２種以上を組み合わせて用いることができる。
　化合物（Ｉ）は、市販品をそのまま又は精製して用いることができる。 <Compound (I)>
Compound (I) used in the reaction method of the present invention;
A 1 -X m (I)
(During the ceremony,
A 1 may have an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and m which may have a substituent. It represents either a valent aliphatic hydrocarbon group or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
Each of X independently represents a leaving group.
m is a number of X and represents an integer of 1 or more. )
Reacts with compound (II) to produce a reaction product (eg, cross-coupling reaction with any of CB, CC, CN, CO, and CS bonds. It is not particularly limited as long as it produces (such as a cross-coupling reaction product in which one or more are formed).
Compound (I) can be used alone or in combination of two or more.
As the compound (I), a commercially available product can be used as it is or after purification.
（式（Ｉ）中のＡ１基）
　Ａ１における置換基を有していてもよいｍ価の芳香族炭化水素基の炭素数は特に限定されず、例えば６～６０、好ましくは６～４０、より好ましくは６～３０である。
　ｍ価の芳香族炭化水素基において、ｍは１以上の整数であり、例えば１～１０、好ましくは１～６、より好ましくは１～４である。
　Ａ１における置換基を有していてもよいｍ価の芳香族炭化水素基において、ｍ＝１である１価の芳香族炭化水素基としては、例えば、フェニル基、ナフチル基、アントラセニル基（又はアントラセン基）、フェナントレニル基（又はフェナントレン基）、ビフェニル基、ターフェニル基、ピレニル基（又はピレン基）、ペリレニル基（又はペリレン基）、トリフェニレニル基（又はトリフェニレン基）、フルオレニル基等があげられる。
　また、Ａ１における置換基を有していてもよいｍ価の芳香族炭化水素基において、ｍが２以上の整数であるｍ価の芳香族炭化水素基としては、例えば、前記１価の芳香族炭化水素基中の芳香環から、ｍ－１個の水素を除いたものがあげられる。 ( A unit in formula (I))
The number of carbon atoms of the m-valent aromatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 6 to 60, preferably 6 to 40, and 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, and more preferably 1 to 4.
In the m-valent aromatic hydrocarbon group which may have a substituent in A 1 , the monovalent aromatic hydrocarbon group having m = 1 includes, for example, a phenyl group, a naphthyl group, and an anthrasenyl group (or). Anthracene group), phenanthrenyl group (or phenanthren group), biphenyl group, terphenyl group, pyrenyl group (or pyrene group), peryleneyl group (or perylene group), triphenylenyl group (or triphenylene group), fluorenyl group and the like.
Further, in the m-valent aromatic hydrocarbon group which may have a substituent in A 1 , the m-valent aromatic hydrocarbon group in which m is an integer of 2 or more is, for example, the monovalent aromatic. Examples thereof include those obtained by removing m-1 hydrogens from the aromatic ring in the group hydrocarbon group.
　Ａ１における置換基を有していてもよいｍ価の芳香族複素環基の炭素数は特に限定されず、例えば４～６０、好ましくは４～４０、より好ましくは４～３０である。
　Ａ１におけるｍ価の芳香族複素環基において、ｍは１以上の整数であり、例えば１～１０、好ましくは１～６、より好ましくは１～４である。
　Ａ１における置換基を有していてもよいｍ価の芳香族複素環基において、ｍ＝１である１価の芳香族複素環基としては、例えば、チオフェニル基（チオフェン基又はチエニル基）、チエニレニル基（又はチオフェンジイル基）、ベンゾチエニル基（ベンゾチオフェン基）、ジベンゾチエニル基（ジベンゾチオフェン基）、フェニルジベンゾチエニレニル基及びジベンゾチエニレニルフェニル基等の含硫黄ヘテロアリール基；フラニル基（又はフラン基）、ベンゾフラニル基（ベンゾフラン基）、ジベンゾフラニル基（ジベンゾフラン基）、フェニルジベンゾフラニル基及びジベンゾフラニルフェニル基等の含酸素ヘテロアリール基；ピリジル基（又はピリジン基）、ピリジレニル基（又はピリジンジイル基）、ピリミジニル基（又はピリミジン基）、ピラジル基（又はピラジン基）、キノリル基（又はキノリン基）、イソキノリル基（又はイソキノリン基）、カルバゾリル基（又はカルバゾール基）、９－フェニルカルバゾリル基、アクリジニル基（又はアクリジン基）、キナゾリル基（又はキナゾリン基）、キノキサリル基（又はキノキサリン基）、１，６－ナフチリジニル基、１，８－ナフチリジニル基及びポルフィリン基（又はポルフィリン環）等の含窒素ヘテロアリール基；ベンゾチアゾリル基（又はベンゾチアゾール基）、ベンゾチアジアゾール基等の二種以上のヘテロ原子（例えば、窒素と硫黄）を含むヘテロアリール基を含む。さらに、ピロール基、シロール基、ボロール基、ホスホール基、セレノフェン基、ゲルモール基、インドール基、インデン基、ベンゾシロール基、ベンゾボロール基、ベンゾホスホール基、ベンゾセレノフェン基、ベンゾゲルモール基、ジベンゾシロール基、ジベンゾボロール基、ジベンゾホスホール基、ジベンゾセレノフェン基、ジベンゾゲルモール基、ジベンゾチオフェン５－オキシド基、９Ｈ－フルオレン－９－オン基、ジベンゾチオフェン５，５－ジオキシド基、アザベンゾチオフェン基、アザベンゾフラン基、アザインドール基、アザインデン基、アザベンゾシロール基、アザベンゾボロール基、アザベンゾホスホール基、アザベンゾセレノフェン基、アザベンゾゲルモール基、アザジベンゾチオフェン基、アザジベンゾフラン基、アザカルバゾール基、アザフルオレン基、アザジベンゾシロール基、アザジベンゾボロール基、アザジベンゾホスホール基、アザジベンゾセレノフェン基、アザジベンゾゲルモール基、アザジベンゾチオフェン５－オキシド基、アザ－９Ｈ－フルオレン－９－オン基、アザジベンゾチオフェン５，５－ジオキシド基、ピリダジン基、トリアジン基、フェナントロリン基、ピラゾール基、イミダゾール基、トリアゾール基、オキサゾール基、イソオキサゾール基、チアゾール基、イソチアゾール基、オキサジアゾール基、チアジアゾール基、ベンゾピラゾル基、ベンゾイミダゾール基、ベンゾオキサゾール基、ベンゾオキサジアゾール基、５，６，７，８－テトラヒドロイソキノリン基、５，６，７，８－テトラヒドロキノリン基等があげられる。
　また、Ａ１における置換基を有していてもよいｍ価の芳香族複素環基において、ｍが２以上の整数であるｍ価の芳香族複素環基としては、例えば、前記１価の芳香族複素環基中の芳香環から、ｍ－１個の水素を除いたものがあげられる。また、ベンゾ［１，２－ｃ：４，５－ｃ′］ビス［１，２，５］チアジアゾール骨格（ベンゾビスチアジアゾール基）等があげられる。 The number of carbon atoms of the m-valent aromatic heterocyclic group which may have a substituent in A 1 is not particularly limited, and is, for example, 4 to 60, preferably 4 to 40, and more preferably 4 to 30.
In the m-valent aromatic heterocyclic group in A 1 , m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
In the m-valent aromatic heterocyclic group which may have a substituent in A 1 , as the monovalent aromatic heterocyclic group having m = 1, for example, a thiophenyl group (thiophene group or thienyl group), Sulfur-containing heteroaryl groups such as thienirenyl group (or thiofendiyl group), benzothienyl group (benzothiophene group), dibenzothienyl group (dibenzothiophene group), phenyldibenzothienylenyl group and dibenzothienylenylphenyl group; furanyl group (Or furan group), benzofuranyl group (benzofuran group), dibenzofuranyl group (dibenzofuran group), phenyldibenzofuranyl group, dibenzofuranylphenyl group and other oxygen-containing heteroaryl groups; pyridyl group (or pyridine group), pyridirenyl Group (or pyridinediyl group), pyrimidinyl group (or pyrimidine group), pyrazil group (or pyrazine group), quinolyl group (or quinoline group), isoquinolyl group (or isoquinolin group), carbazolyl group (or carbazole group), 9- Phenylcarbazolyl group, acridinyl group (or aclysine group), quinazolyl group (or quinazoline group), quinoxalyl group (or quinoxalin group), 1,6-naphthyldinyl group, 1,8-naphthyldinyl group and porphyrin group (or porphyrin ring) ) Etc., a nitrogen-containing heteroaryl group; a heteroaryl group containing two or more heteroatoms (eg, nitrogen and sulfur) such as a benzothiazolyl group (or benzothiazole group) and a benzothiazylazole group. Further, a pyrrole group, a silol group, a borol group, a phosphor group, a selenophene group, a gelmol group, an indol group, an inden group, a benzocilol group, a benzobolol group, a benzophosphole group, a benzoselenovene group, a benzogermol group, and a dibenzosylol group. , Dibenzoborol group, dibenzophosphole group, dibenzoselenophene group, dibenzogermol group, dibenzothiophene 5-oxide group, 9H-fluoren-9-one group, dibenzothiophene 5,5-dioxide group, azabenzothiophene group , Azabenzofuran group, azaindole group, azainden group, azabenzosyrole group, azabenzoborol group, azabenzophosphole group, azabenzoselenophene group, azabenzogermol group, azadibenzothiophene group, azadibenzofuran group, Azacarbazole group, azafluolene group, azadibenzocilol group, azadibenzoborol group, azadibenzophosphole group, azadibenzoselenophene group, azadibenzogermol group, azadibenzothiophene 5-oxide group, aza-9H-fluorene -9-on group, azadibenzothiophene 5,5-dioxide group, pyridazine group, triazine group, phenanthroline group, pyrazole group, imidazole group, triazole group, oxazole group, isooxazole group, thiazole group, isothiazole group, oxadi Examples thereof include an azole group, a thiadiazole group, a benzopyrazole group, a benzoimidazole group, a benzoxazole group, a benzoxaziazole group, a 5,6,7,8-tetrahydroisoquinoline group, a 5,6,7,8-tetrahydroquinoline group and the like. ..
Further, in the m-valent aromatic heterocyclic group which may have a substituent in A 1 , the m-valent aromatic heterocyclic group in which m is an integer of 2 or more is, for example, the monovalent aromatic. Examples thereof include those obtained by removing m-1 hydrogens from the aromatic ring in the group heterocyclic group. Further, benzo [1,2-c: 4,5-c'] bis [1,2,5] thiadiazole skeleton (benzobisthiadiazole group) and the like can be mentioned.
　Ａ１における置換基を有していてもよいｍ価の脂肪族炭化水素基の炭素数は特に限定されず、例えば２～６０、好ましくは３～４０、より好ましくは５～３０である。
　Ａ１におけるｍ価の脂肪族炭化水素基において、ｍは１以上の整数であり、例えば１～１０、好ましくは１～６、より好ましくは１～４である。
　Ａ１における置換基を有していてもよいｍ価の脂肪族炭化水素基において、ｍ＝１である１価の脂肪族炭化水素基としては、例えば、アルキル基、シクロオレフィン基等の飽和脂肪族炭化水素基があげられる。
　また、Ａ１における置換基を有していてもよいｍ価の脂肪族炭化水素基において、ｍが２以上の整数であるｍ価の脂肪族炭化水素基としては、例えば、前記１価の脂肪族炭化水素基から、ｍ－１個の水素を除いたものがあげられる。
　Ａ１における置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基の炭素数は特に限定されず、例えば２～６０、好ましくは３～４０、より好ましくは５～３０である。
　Ａ１におけるｍ価の不飽和脂肪族炭化水素基において、ｍは１以上の整数であり、例えば１～１０、好ましくは１～６、より好ましくは１～４である。
　Ａ１における置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基において、ｍ＝１である１価の芳香族炭化水素基としては、例えば、アルケニル基、アルキニル基等があげられる。
　また、Ａ１における置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基において、ｍが２以上の整数であるｍ価の不飽和脂肪族炭化水素基としては、例えば、前記１価の不飽和脂肪族炭化水素基から、ｍ－１個の水素を除いたものがあげられる。 The carbon number of the m-valent aliphatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 2 to 60, preferably 3 to 40, and more preferably 5 to 30.
In the m-valent aliphatic hydrocarbon group in A 1 , m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
In the m-valent aliphatic hydrocarbon group which may have a substituent in A 1 , the monovalent aliphatic hydrocarbon group having m = 1 includes, for example, a saturated fat such as an alkyl group and a cycloolefin group. Group hydrocarbon groups can be mentioned.
Further, in the m-valent aliphatic hydrocarbon group which may have a substituent in A 1 , as the m-valent aliphatic hydrocarbon group in which m is an integer of 2 or more, for example, the monovalent fat Examples thereof include those obtained by removing m-1 hydrogens from a group hydrocarbon group.
The number of carbon atoms of the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A 1 is not particularly limited, and is, for example, 2 to 60, preferably 3 to 40, and more preferably 5 to 30. ..
In the m-valent unsaturated aliphatic hydrocarbon group in A 1 , m is an integer of 1 or more, for example, 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
In the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A 1 , examples of the monovalent aromatic hydrocarbon group having m = 1 include an alkenyl group and an alkynyl group. Be done.
Further, in the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent in A 1 , as the m-valent unsaturated aliphatic hydrocarbon group in which m is an integer of 2 or more, for example, the above-mentioned Examples thereof include monovalent unsaturated aliphatic hydrocarbon groups obtained by removing m-1 hydrogens.
　化合物（Ｉ）における式（Ｉ）中のＡ１として、具体的には、例えば、下記の基を例示することができる。
　ナフチル基、アリール（例えば、フェニル等）ナフチル基、アルキレン（例えば、エチレン等）架橋を有するナフチル基、アリーレン（例えば、フェニレン等）架橋を有するナフチル基等のナフチル基；
　フェナントレニル基；
　アントラセニル基、アリール（例えば、フェニル等）アントラセニル基、ジアリール（例えば、ジナフチル等）アントラセニル基、ジアリールボリル（例えば、ビス（トリアルキルフェニル）ボリル等）アントラセニル基等のアントラセニル基；
　ピレニル基、アルキル（例えば、ｔｅｒｔ－ブチル等）ピレニル基等のピレニル基；
　ビフェニル基、アルキレン（例えば、プロピレン、イソプロピレン等）架橋を有するビフェニル基等のビフェニル基；
　ターフェニル基、テトラアリール（例えば、テトラフェニル等）ターフェニル基等のターフェニル基；
　トリフェニレニル基；
　２－アリール（例えば、フェニル等）エテニルフェニル基、１，２，２－トリアリール（例えば、トリフェニル等）エテニルフェニル基、２－アリール（例えば、フェニル等）エチニルフェニル基、フェニル基、アルキル（例えば、メチル）フェニル基、ジアルキル（例えば、ジメチル）フェニル基、アルコキシ（例えば、メトキシ）フェニル基、ジアルキルアミノ（例えば、ジメチルアミノ）フェニル基、ジアリール（例えば、ジフェニル）アミノフェニル基、パーフルオロアルキル（例えば、トリフルオロメチル）フェニル基、アルキル（例えば、エチル）オキシカルボニルフェニル基、アルカノイル（例えば、アシル）フェニル基等のフェニル基；
　アリール（例えば、フェニル等）置換カルバゾリル基；
　アントラセン－９．１０－ジオン基；
　アリール（例えば、フェニル等）置換チエニル基、チオフェン基、ベンゾチアジアゾール基；
　チオフェン基、ベンゾチアジアゾール基、
　フェニレン基、アリール（例えば、ビス（３，５－メチルフェニル）等）ポルフィリン環、ピレン－テトラーイル基、ベンゾ［１，２－ｃ：４，５－ｃ′］ビス［１，２，５］チアジアゾール骨格（ベンゾビスチアジアゾール基）；等の２価以上の価数を有する基等。 Specifically, for example, the following groups can be exemplified as A1 in the formula ( I ) in the compound (I).
Naphthalene groups, aryl (eg, phenyl, etc.) naphthyl groups, naphthyl groups with alkylene (eg, ethylene, etc.) crosslinks, naphthyl groups with arylene (eg, phenylene, etc.) crosslinks;
Phenantrenyl group;
Anthracenyl groups such as anthrasenyl groups, aryl (eg, phenyl, etc.) anthrasenyl groups, diallyl (eg, dinaphthyl) anthrasenyl groups, diallylboryl (eg, bis (trialkylphenyl) boryl, etc.) anthrasenyl groups;
Pyrenyl group, alkyl (eg, tert-butyl, etc.) Pyrenyl group such as pyrenyl group;
Biphenyl group, biphenyl group such as biphenyl group having alkylene (eg, propylene, isopropylene, etc.) crosslinks;
Turphenyl group, tetraaryl (eg, tetraphenyl, etc.) Turphenyl group such as terphenyl group;
Triphenylenyl group;
2-aryl (eg, phenyl, etc.) ethenylphenyl group, 1,2,2-triaryl (eg, triphenyl, etc.) ethenylphenyl group, 2-aryl (eg, phenyl, etc.) ethynylphenyl group, phenyl group, Alkyl (eg, methyl) phenyl group, dialkyl (eg, dimethyl) phenyl group, alkoxy (eg, methoxy) phenyl group, dialkylamino (eg, dimethylamino) phenyl group, diaryl (eg, diphenyl) aminophenyl group, perfluoro Phenyl groups such as alkyl (eg, trifluoromethyl) phenyl groups, alkyl (eg, ethyl) oxycarbonylphenyl groups, alkanoyl (eg, acyl) phenyl groups;
Aryl (eg, phenyl, etc.) substituted carbazolyl group;
Anthracene-9.10-dione group;
Aryl (eg, phenyl, etc.) substituted thienyl group, thiophene group, benzothiadiazole group;
Thiophene group, benzothiadiazole group,
Phenylene group, aryl (eg, bis (3,5-methylphenyl), etc.) porphyrin ring, pyrene-tetrayl group, benzo [1,2-c: 4,5-c'] bis [1,2,5] thiadiazole A group having a valence of 2 or more, such as a skeleton (benzobisthiadiazole group);
　Ａ１における置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基が有していてもよい置換基は、本発明が目的とする反応（例えばクロスカップリング反応等）を行える限り特に制限されない。
　置換基としては、例えば、炭素数１～２４、好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアルキル基（例えば、メチル基、エチル基、ｎ－プロピル基、イソプロピル基、ｎ－ブチル基、イソブチル基、ｔｅｒｔ－ブチル基、ペンチル基、ヘキシル基、オクチル基等）；炭素数１～２４、好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアルコキシ基（例えば、メトキシ基、エトキシ基、ｎ－プロポキシ基、イソプロポキシ基、ｎ－ブトキシ基、イソブトキシ基、ｔｅｒｔ－ブトキシ基、ペンチルオキシ基、ヘキシルオキシ基、オクチルオキシ基等）；炭素数３～２４、好ましくは３～１８、より好ましくは３～１２、さらに好ましくは３～８のシクロアルキル基（例えば、シクロプロピルオキシ基、シクロブチルオキシ基、シクロペンチルオキシ基、シクロヘキシルオキシ基等）；炭素数１～２４、好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアルケニル基（例えば、エテニル基、プロペニル基、ブテニル基、ペンテニル基、ヘキセニル基、オクテニル基等）；炭素数１～２４、好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアルキニル基（例えば、エチニル基、プロピニル基、ブチニル基、ペンチニル基、ヘキシニル基、オクチニル基等）；炭素数５～２４、好ましくは５～１８、より好ましくは５～１２、さらに好ましくは５～８のアリール基（例えば、フェニル基、ナフチル基、ビフェニル基等）；炭素数７～２４、好ましくは７～１９、より好ましくは７～１３、さらに好ましくは７～９のアリールアルキル基（例えば、モノフェニルメチル基、モノフェニルプロピル基、トリフェニルメチル基等）；炭素数５～２４、好ましくは５～１８、より好ましくは５～１２、さらに好ましくは５～８のアリールオキシ基（例えば、フェノキシ基、ナフチルオキシ基、ビフェニルオキシ基等）；炭素数４～２４、好ましくは４～１８、より好ましくは４～１２、さらに好ましくは４～８のヘテロアリール基（例えば、チオフェニル基、フラニル基、カルバゾール基、ベンゾチオフェニル基、ベンゾフラ二ル基、インドリル基、ピロリル基、ピリジル基等）；炭素数１～２４，好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアシル基（例えば、アセチル基、プロピオニル基、ブタノイル基、ペンタノイル基、ヘプタノイル基並びにそのアシル基に含まれるカルボニル基が、エステル基又はアミド基で置換された基等）；炭素数１～２４，好ましくは１～１８、より好ましくは１～１２、さらに好ましくは１～８のアミノ基（例えば、ジフェニルアミノ基、ジメチルアミノ基等）；フッ素、炭素数１～３０、好ましくは１～１２のフッ素含有炭化水素基等のフッ素含有基；シアノ基、ニトロ基等からなる群より選ばれる１種以上があげられる。
　置換基同士は、相互に架橋していてもよく、置換基全体で、環状構造（芳香族基）を形成してもよい。置換基は、さらに置換基を有してよい。 M-valent aromatic hydrocarbon group which may have a substituent in A 1 , m-valent aromatic heterocyclic group which may have a substituent, and m-valent which may have a substituent. The aliphatic hydrocarbon group of the above, or the substituent which may be possessed by an unsaturated aliphatic hydrocarbon group having an m-valent value which may have a substituent is a reaction (for example, cross-coupling) which is the object of the present invention. Reactions, etc.) are not particularly limited as long as they can be performed.
As the substituent, for example, an alkyl group having 1 to 24 carbon atoms, preferably 1 to 18, more preferably 1 to 12, and even more preferably 1 to 8 (for example, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group) is used. Group, n-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, octyl group, etc.); 8 alkoxy groups (eg, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, octyloxy group, etc.); carbon Number 3 to 24, preferably 3 to 18, more preferably 3 to 12, still more preferably 3 to 8 cycloalkyl groups (eg, cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, etc.) An alkenyl group having 1 to 24 carbon atoms, preferably 1 to 18, more preferably 1 to 12, still more preferably 1 to 8 alkenyl groups (for example, an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, an octenyl group, etc.) ); Alkinyl group having 1 to 24 carbon atoms, preferably 1 to 18, more preferably 1 to 12, still more preferably 1 to 8 (for example, ethynyl group, propynyl group, butynyl group, pentynyl group, hexynyl group, octynyl group). Etc.); aryl groups having 5 to 24 carbon atoms, preferably 5 to 18, more preferably 5 to 12, still more preferably 5 to 8 (eg, phenyl group, naphthyl group, biphenyl group, etc.); 7 to 24 carbon atoms. , Preferably 7 to 19, more preferably 7 to 13, still more preferably 7 to 9 arylalkyl groups (eg, monophenylmethyl group, monophenylpropyl group, triphenylmethyl group, etc.); 5 to 24 carbon atoms, Preferably 5 to 18, more preferably 5 to 12, even more preferably 5 to 8 aryloxy groups (eg, phenoxy group, naphthyloxy group, biphenyloxy group, etc.); 4 to 24 carbon atoms, preferably 4 to 18 carbon atoms. , More preferably 4 to 12, still more preferably 4 to 8 heteroaryl groups (eg, thiophenyl group, furanyl group, carbazole group, benzothiophenyl group, benzofuranyl group, indolyl group, pyrrolyl group, pyridyl group, etc.). Acrylic groups with 1 to 24 carbon atoms, preferably 1 to 18, more preferably 1 to 12, even more preferably 1 to 8 (eg, acetyl group, propionyl group, pig). A group in which a noyl group, a pentanoyl group, a heptanoyle group and a carbonyl group contained in the acyl group thereof are substituted with an ester group or an amide group, etc.); , More preferably 1-8 amino groups (eg, diphenylamino group, dimethylamino group, etc.); fluorine, fluorine-containing groups such as 1-30 carbon atoms, preferably 1-12 fluorine-containing hydrocarbon groups; cyano group. , One or more selected from the group consisting of nitro groups and the like.
The substituents may be crosslinked with each other, or the entire substituent may form a cyclic structure (aromatic group). The substituent may further have a substituent.
（式（Ｉ）中の脱離基）
　本発明の反応方法で用いられる化合物（Ｉ）の脱離基は、化学反応（例えば、クロスカップリング反応等）において、通常利用される脱離基であり、本発明の所期の反応（例えば、クロスカップリング反応等）を行うことができる脱離基であれば特に制限されない。
　脱離基は、例えば、クロロ、ブロモ、ヨード、ジアゾニウム塩、トリフルオロメタンスルホネート及びカルボン酸誘導体等からなる群より選択される基があげられる。好ましくはクロロ、ブロモ、ヨード、ジアゾニウム塩及びトリフルオロメタンスルホネートからなる群より選択される基であり、より好ましくはクロロ、ブロモ、ヨードからなる群より選択される基である。
　化合物（Ｉ）は、複数の脱離基を有することができる。この場合、複数の脱離基は、同一であっても異なっていてもよい。
　本発明において、脱離基の数ｍは、整数であって反応（例えば、クロスカップリング反応等）を行うことができる範囲であれば特に制限されない。例えば１～１０、好ましくは１～８、より好ましくは１～６、さらに好ましくは１～４とすることができる。 (Leaving group in formula (I))
The leaving group of compound (I) 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), and is a desired reaction of the present invention (for example). , Cross-coupling reaction, etc.) is not particularly limited as long as it is a leaving group capable of carrying out.
Examples of the leaving group include a group selected from the group consisting of chloro, bromo, iodine, diazonium salt, trifluoromethanesulfonate, carboxylic acid derivative and the like. It is preferably a group selected from the group consisting of chloro, bromo, iodine, diazonium salt and trifluoromethanesulfonate, and more preferably a group selected from the group consisting of chloro, bromo and iodine.
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 group is not particularly limited as long as it is an integer and can carry out a reaction (for example, a cross-coupling reaction). For example, it can be 1 to 10, preferably 1 to 8, more preferably 1 to 6, and even more preferably 1 to 4.
（化合物（Ｉ）の具体例）
　本発明の反応方法（例えば、クロスカップリング反応方法等）において用いられる化合物（Ｉ）の具体例としては、例えば、実施例１～７７で用いられる化合物（Ｉ－１）～（Ｉ－２６）、（Ｉ－２００～Ｉ－２１１）及び化合物（Ｉ－２７）～（Ｉ－５４）からなる群より選ばれる１種以上があげられる。なお、これらの構造式中、Ｍｅはメチル基を、Ｐｈはフェニル基を、それぞれ示す。
Figure JPOXMLDOC01-appb-C000007
 (Specific example of compound (I))
Specific examples of the compound (I) used in the reaction method of the present invention (for example, a cross-coupling reaction method or the like) include, for example, the compounds (I-1) to (I-26) used in Examples 1 to 77. , (I-200 to I-211) and compounds (I-27) to (I-54), and one or more selected from the group. In these structural formulas, Me represents a methyl group and Ph represents a phenyl group.
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000008
Figure JPOXMLDOC01-appb-C000008
＜化合物（ＩＩ）＞
（式（ＩＩａ）で表される化合物）
　本発明の反応方法（例えば、クロスカップリング反応方法等）で用いられる化合物（ＩＩ）のうち、式（ＩＩａ）；
　Ａ２－Ｙｎ　　　　（ＩＩａ）
（式中、
Ａ２は、置換基を有していてもよいｎ価の芳香族炭化水素基、置換基を有していてもよいｎ価の芳香族複素環基、置換基を有していてもよいｎ価の脂肪族炭化水素基、又は置換基を有していてもよいｎ価の不飽和脂肪族炭化水素基を表す。
ｎは、Ｙの数で１以上の整数を表す。
Ｙは、各々独立して、
　－Ｂ（ＯＲ１）（ＯＲ２）
　－ＮＨＲ３
　－Ｒ４－ＯＨ
　－Ｒ５－ＳＨ
を表す。
Ｒ１及びＲ２は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ１とＲ２は相互に結合していてもよい。
Ｒ３は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の芳香族複素環基、置換基を有していてもよい１価の脂肪族炭化水素基、又は置換基を有していてもよい１価の不飽和脂肪族炭化水素基を表す。Ｒ４及びＲ５は、各々独立して、単結合、置換基を有していてもよい２価の芳香族炭化水素基、置換基を有していてもよい２価の脂肪族炭化水素基を表す。）
で表される化合物は、化合物（Ｉ）と反応して反応生成物（例えば、クロスカップリング反応して、Ｃ－Ｂ結合、Ｃ－Ｃ結合、Ｃ－Ｎ結合、Ｃ－Ｏ結合及びＣ－Ｓ結合のいずれか１つ以上が形成されるクロスカップリング反応生成物等）を生成するものであれば特に限定されない。 <Compound (II)>
(Compound represented by formula (IIa))
Among the compounds (II) used in the reaction method of the present invention (for example, the cross-coupling reaction method, etc.), the formula (IIa);
A2 - Yn (IIa)
(During the ceremony,
A 2 may have an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, and n which may have a substituent. Represents a valent aliphatic hydrocarbon group or an n-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
n is a number of Y and represents an integer of 1 or more.
Y is independent of each other
-B (OR 1 ) (OR 2 )
-NHR 3
-R 4 -OH
-R 5 -SH
Represents.
R 1 and R 2 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show. R 1 and R 2 may be coupled to each other.
R 3 independently contains hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a substituent. It represents a monovalent aliphatic hydrocarbon group which may have a substituent or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent. Each of R 4 and R 5 has a single bond, a divalent aromatic hydrocarbon group which may have a substituent, and a divalent aliphatic hydrocarbon group which may have a substituent, respectively. Represents. )
The compound represented by the above reacts with the compound (I) and reacts with a reaction product (for example, a cross-coupling reaction with a CB bond, a CC bond, a CN bond, a CO bond and a C—. It is not particularly limited as long as it produces a cross-coupling reaction product (such as a cross-coupling reaction product) in which any one or more of S bonds are formed.
｛式（ＩＩａ）中のＡ２基｝
　式（ＩＩａ）中のＡ２基における、置換基を有していてもよいｎ価の芳香族炭化水素基、置換基を有していてもよいｎ価の芳香族複素環基、置換基を有していてもよいｎ価の脂肪族炭化水素基、又は置換基を有していてもよいｎ価の不飽和脂肪族炭化水素基としては、それぞれ、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基と同様の基とすることができる。
　また、式（ＩＩａ）中のＡ２基における置換基は、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における置換基と同様のものとすることができる。
　なお、式（ＩＩａ）中のＡ２基と化合物（Ｉ）に係る式（Ｉ）中のＡ１基は、それぞれ独立に任意の構造の基であって、同じであっても異なっていてもよい。 {A 2 groups in formula (IIa)}
The n-valent aromatic hydrocarbon group which may have a substituent, the n-valent aromatic heterocyclic group which may have a substituent, and the substituent in the A2 group in the formula (IIa). The n-valent aliphatic hydrocarbon group which may have a substituent or the unsaturated aliphatic hydrocarbon group having an n-valent value which may have a substituent is the formula (I) according to the compound (I), respectively. The A1 group in the group has an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and a substituent. It can be a good m-valent aliphatic hydrocarbon group or a group similar to an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
Further, the substituent in the A2 group in the formula (IIa) can be the same as the substituent in the A1 group in the formula ( I ) according to the compound (I).
It should be noted that the A 2 group in the formula (IIa) and the A 1 group in the formula (I) according to the compound (I) are independently arbitrary structural groups, and may be the same or different. good.
｛Ｙとして　－Ｂ（ＯＲ１）（ＯＲ２）　を有する式（ＩＩａ）で表される化合物｝
　本発明において、Ｙとして　－Ｂ（ＯＲ１）（ＯＲ２）　を有する式（ＩＩａ）で表される化合物としては、芳香族ボロン酸又は芳香族ボロン酸エステルがあげられる。芳香族ボロン酸又は芳香族ボロン酸エステルは、化合物（Ｉ）と反応（例えば、クロスカップリング反応等）をして、Ｃ－Ｃ結合が形成された反応生成物を与える限り、特に制限されない。
　芳香族ボロン酸エステルは、芳香族ボロン酸アルキルエステル、芳香族ボロン酸アルキレングリコールエステル、芳香族ボロン酸アリールエステル、芳香族ボロン酸アリーレングリコールエステルを含む。 {Compound represented by formula (IIa) having −B (OR 1 ) (OR 2 ) as Y}
In the present invention, examples of the compound represented by the formula (IIa) having −B (OR 1 ) (OR 2 ) as Y include aromatic boronic acid or aromatic boronic acid ester. The aromatic boronic acid or aromatic boronic acid ester is not particularly limited as long as it reacts with compound (I) (for example, a cross-coupling reaction or the like) to give a reaction product in which a CC 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.
　式（ＩＩａ）中の－Ｂ（ＯＲ１）（ＯＲ２）基におけるＲ１及びＲ２は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ１とＲ２は相互に結合していてもよい。
　ここで、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基は、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の脂肪族炭化水素基と同様の基とすることができる。
　なお、式（ＩＩａ）中の－Ｂ（ＯＲ１）（ＯＲ２）基におけるＲ１及びＲ２と化合物（Ｉ）に係る式（Ｉ）中のＡ１は、それぞれ独立した基であって、同じであっても異なっていてもよい。 R 1 and R 2 in the -B (OR 1 ) (OR 2 ) group in the formula (IIa) are independently hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, respectively. Represents a monovalent aliphatic hydrocarbon group which may have a substituent. R 1 and R 2 may be coupled 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 are the formula (I) according to the compound (I). It is possible to use the same group 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 A1 group in the group. can.
In addition, R 1 and R 2 in the -B (OR 1 ) (OR 2 ) group in the formula (IIa) and A 1 in the formula (I) according to the compound (I) are independent groups, respectively. It may be the same or different.
　本発明において、Ｒ１とＲ２が相互に結合した基としては、Ｒ１とＲ２が一緒に環状構造を形成したものである。芳香族基である場合には、例えば、１，２－フェニレン基等があげられる。また、炭化水素基である場合には、例えば、例えば、エチレン基、１，１，２，２－テトラメチルエチレン基（ピナコラト基）、ネオペンチルグリコラト基、プロピレン基等があげられる。
　式（ＩＩａ）で表される化合物としての芳香族ボロン酸又は芳香族ボロン酸エステルは、１種を単独で又は２種以上を組み合わせて用いることができる。
　式（ＩＩａ）で表される化合物としての芳香族ボロン酸又は芳香族ボロン酸エステルは、市販品をそのまま又は精製して用いることができる。 In the present invention, the group in which R 1 and R 2 are bonded to each other is a group in which R 1 and R 2 form a cyclic structure together. In the case of an aromatic group, for example, a 1,2-phenylene group and the like can be mentioned. In the case of a hydrocarbon group, for example, an ethylene group, a 1,1,2,2-tetramethylethylene group (pinacholato group), a neopentylglycolato group, a propylene group and the like can be mentioned.
The aromatic boronic acid or aromatic boronic acid ester as the compound represented by the formula (IIa) can be used alone or in combination of two or more.
As the aromatic boronic acid or aromatic boronic acid ester as the compound represented by the formula (IIa), a commercially available product can be used as it is or after purification.
｛Ｙとして　－ＮＨＲ３　を有する式（ＩＩａ）で表される化合物｝
　本発明において、Ｙとして　－ＮＨＲ３　を有する式（ＩＩａ）で表される化合物としては、芳香族アミノ化合物があげられる。芳香族アミノ化合物は、化合物（Ｉ）と反応（例えば、クロスカップリング反応等）して、Ｃ－Ｎ結合が形成された生成物を与える限り、特に制限されない。
　式（ＩＩａ）中の－ＮＨＲ３基におけるＲ３基としては、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の芳香族複素環基、置換基を有していてもよい１価の脂肪族炭化水素基、又は置換基を有していてもよい１価の不飽和脂肪族炭化水素基を表す。
　ここで、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の芳香族複素環基、置換基を有していてもよい１価の脂肪族炭化水素基、又は置換基を有していてもよい１価の不飽和脂肪族炭化水素基は、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基と同様の基とすることができる。
　式（ＩＩａ）で表される化合物としての芳香族アミノ化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　式（ＩＩａ）で表される化合物としての芳香族アミノ化合物は、市販品をそのまま又は精製して用いることができる。 {Compound represented by formula (IIa) having -NHR 3 as Y}
In the present invention, examples of the compound represented by the formula (IIa) having −NHR 3 as Y include aromatic amino compounds. The aromatic amino compound is not particularly limited as long as it reacts with compound (I) (for example, a cross-coupling reaction or the like) to give a product in which a CN bond is formed.
As the R3 group in the -NHR 3 group in the formula ( IIa), hydrogen and a monovalent aromatic hydrocarbon group which may have a substituent may have a substituent, respectively. Represents a good monovalent aromatic heterocyclic group, a monovalent aliphatic hydrocarbon group which may have a substituent, or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent. ..
Here, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a monovalent which may have a substituent. The monovalent unsaturated aliphatic hydrocarbon group which may have a substituent or a substituent has a substituent in the A1 group in the formula (I) according to the compound (I). M-valent aromatic hydrocarbon group which may have a substituent, m-valent aromatic heterocyclic group which may have a substituent, m-valent aliphatic hydrocarbon group which may have a substituent, Alternatively, it can be a group similar to the m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
The aromatic amino compound as the compound represented by the formula (IIa) can be used alone or in combination of two or more.
As the aromatic amino compound as the compound represented by the formula (IIa), a commercially available product can be used as it is or after purification.
｛Ｙとして　－Ｒ４－ＯＨ　を有する式（ＩＩａ）で表される化合物｝
　本発明において、Ｙとして　－Ｒ４－ＯＨ　を有する式（ＩＩａ）で表される化合物としては、水酸基を有する芳香族化合物があげられる。水酸基を有する芳香族化合物は、化合物（Ｉ）と反応（例えば、クロスカップリング反応等）して、Ｃ－Ｏ結合が形成された生成物を与える限り、特に制限されない。
　式（ＩＩａ）中の－Ｒ４－ＯＨ基におけるＲ４基としては、各々独立して、単結合、置換基を有していてもよい２価の芳香族炭化水素基又は置換基を有していてもよい２価の脂肪族炭化水素基を表す。なお、Ｒ４が単結合の場合は、水酸基がＡ２に直接結合する。
　ここで、置換基を有していてもよい２価の芳香族炭化水素基又は置換基を有していてもよい２価の脂肪族炭化水素基は、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における、置換基を有していてもよいｍ価の芳香族炭化水素基又は置換基を有していてもよいｍ価の脂肪族炭化水素基における２価の基と同様の基とすることができる。
　なお、式（ＩＩａ）中の－Ｒ４－ＯＨ基におけるＲ４基と、式（ＩＩａ）中のＡ２基は、それぞれ独立した基であって、同じであっても異なっていてもよい。
　式（ＩＩａ）で表される化合物としての水酸基を有する芳香族化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　式（ＩＩａ）で表される化合物としての水酸基を有する芳香族化合物は、市販品をそのまま又は精製して用いることができる。 {Compound represented by formula (IIa) having -R 4 -OH as Y}
In the present invention, examples of the compound represented by the formula (IIa) having −R4 - OH as Y 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 (I) (for example, a cross-coupling reaction or the like) to give a product in which a CO bond is formed.
The R4 group in the -R4 -OH group in the formula (IIa) has a divalent aromatic hydrocarbon group or a substituent which may independently have a single bond and a substituent. Represents a divalent aliphatic hydrocarbon group that may be present. When R 4 is a single bond, the hydroxyl group is directly bonded to A 2 .
Here, the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent is the formula (I) according to the compound (I). Similar to the m-valent aromatic hydrocarbon group which may have a substituent or the divalent group in the m-valent aliphatic hydrocarbon group which may have a substituent in the A1 group in the group. Can be the basis.
The R4 group in the -R4 -OH group in the formula (IIa) and the A2 group in the formula (IIa) are independent groups and may be the same or different.
As the aromatic compound having a hydroxyl group as the compound represented by the formula (IIa), one kind may be used alone or two or more kinds may be used in combination.
As the aromatic compound having a hydroxyl group as the compound represented by the formula (IIa), a commercially available product can be used as it is or after purification.
｛Ｙとして　－Ｒ５－ＳＨ　を有する式（ＩＩａ）で表される化合物｝
　本発明において、Ｙとして　－Ｒ５－ＳＨ　を有する式（ＩＩａ）で表される化合物としては、チオール基を有する芳香族化合物があげられる。チオール基を有する芳香族化合物は、化合物（Ｉ）と反応（例えば、クロスカップリング反応等）して、Ｃ－Ｓ結合が形成された生成物を与える限り、特に制限されない。
　式（ＩＩａ）中の－Ｒ５－ＳＨ基におけるＲ５基としては、各々独立して、単結合、置換基を有していてもよい２価の芳香族炭化水素基又は置換基を有していてもよい２価の脂肪族炭化水素基を表す。なお、Ｒ５が単結合の場合は、チオール基がＡ２に直接結合する。
　ここで、置換基を有していてもよい２価の芳香族炭化水素基又は置換基を有していてもよい２価の脂肪族炭化水素基は、化合物（Ｉ）に係る式（Ｉ）中のＡ１基における、置換基を有していてもよいｍ価の芳香族炭化水素基又は置換基を有していてもよいｍ価の脂肪族炭化水素基における２価の基と同様の基とすることができる。
　なお、式（ＩＩａ）中の－Ｒ５－ＳＨ基におけるＲ５基と、式（ＩＩａ）中のＡ２基は、それぞれ独立した基であって、同じであっても異なっていてもよい。
　式（ＩＩａ）で表される化合物としてのチオール基を有する芳香族化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　式（ＩＩａ）で表される化合物としてのチオール基を有する芳香族化合物は、市販品をそのまま又は精製して用いることができる。 {Compound represented by formula (IIa) having -R 5 -SH as Y}
In the present invention, examples of the compound represented by the formula (IIa) having −R5 -SH as Y 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 (I) (for example, a cross-coupling reaction or the like) to give a product in which a CS bond is formed.
The R5 group in the -R5 - SH group in the formula (IIa) has a divalent aromatic hydrocarbon group or a substituent which may independently have a single bond and a substituent. Represents a divalent aliphatic hydrocarbon group that may be present. When R 5 is a single bond, the thiol group directly bonds to A 2 .
Here, the divalent aromatic hydrocarbon group which may have a substituent or the divalent aliphatic hydrocarbon group which may have a substituent is the formula (I) according to the compound (I). Similar to the m-valent aromatic hydrocarbon group which may have a substituent or the divalent group in the m-valent aliphatic hydrocarbon group which may have a substituent in the A1 group in the group. Can be the basis.
The R5 group in the -R5 - SH group in the formula (IIa) and the A2 group in the formula (IIa) are independent groups and may be the same or different.
As the aromatic compound having a thiol group as the compound represented by the formula (IIa), one kind may be used alone or two or more kinds may be used in combination.
As the aromatic compound having a thiol group as the compound represented by the formula (IIa), a commercially available product can be used as it is or after purification.
（式（ＩＩｂ）で表される化合物）
　本発明の反応方法（例えば、クロスカップリング反応方法等）で用いられる化合物（ＩＩ）のうち、式（ＩＩｂ）；
　（Ｒ６Ｏ）（Ｒ７Ｏ）Ｂ－Ｂ（ＯＲ８）（ＯＲ９）　　　　　（ＩＩｂ）
（式中、Ｒ６～Ｒ９は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ６とＲ７は相互に結合していてもよく、Ｒ８とＲ９は相互に結合していてもよい。）
で表される化合物は、前記化合物（Ｉ）と反応（例えば、クロスカップリング反応等）して、Ｃ－Ｂ結合が形成された反応生成物を生成するものであれば特に限定されない。 (Compound represented by formula (IIb))
Among the compounds (II) used in the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), the formula (IIb);
(R 6 O) (R 7 O) BB (OR 8 ) (OR 9 ) (IIb)
(In the formula, R 6 to R 9 are independently hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic which may have a substituent. Represents a hydrocarbon group. R 6 and R 7 may be bonded to each other, and R 8 and R 9 may be bonded to each other.)
The compound represented by is not particularly limited as long as it reacts with the compound (I) (for example, a cross-coupling reaction or the like) to produce a reaction product in which a CB bond is formed.
　式（ＩＩｂ）で表される化合物としては、ジボロン酸エステル（ジボロン酸テトラエステル、ジボロン酸トリエステル、ジボロン酸ジエステル又はジボロン酸モノエステル）及びジボロン酸からなる群より選ばれる１種以上があげられる。
　ジボロン酸エステルとしては、例えばジボロン酸アルキルエステル、ジボロン酸アルキレングリコールエステル、ジボロン酸アリールエステル、ジボロン酸アリーレングリコールエステル等からなる群より選ばれる１種以上があげられる。ジボロン酸としては、例えば、テトラヒドロキシジボラン（Tetrahydroxydiborane）等があげられる。 Examples of the compound represented by the formula (IIb) include one or more selected from the group consisting of a diboronic acid ester (diboronic acid tetraester, diboronic acid triester, diboronic acid diester or diboronic acid monoester) and diboronic acid. ..
Examples of the diboronic acid ester include one or more selected from the group consisting of diboronic acid alkyl ester, diboronic acid alkylene glycol ester, diboronic acid aryl ester, diboronic acid arylene glycol ester and the like. Examples of diboronic acid include tetrahydroxydiborane.
　式（ＩＩｂ）中のＲ６～Ｒ９としての、置換基を有していてもよい１価の芳香族炭化水素基としては、例えば各々独立して、フェニル基、ナフチル基、ビフェニル基等からなる群より選択される１種以上の基があげられる。
　式（ＩＩｂ）中のＲ６～Ｒ９としての、置換基を有していてもよい１価の脂肪族炭化水素基としては、例えば各々独立して、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｔｅｒｔ－ブチル基等からなる群より選ばれる１種以上があげられる。
　また、式（ＩＩｂ）中のＲ６～Ｒ９が、置換基を有していてもよい１価の脂肪族炭化水素基である場合、Ｒ６とＲ７及びＲ８とＲ９は、相互に結合していてもよい。例えば、Ｒ６－Ｒ７及びＲ８－Ｒ９は、各々独立して、例えば、エチレン基、１，１，２，２－テトラメチルエチレン基、２，２－ジメチルプロピレン基、ヘキシレン基（又は１，１，３－トリメチルプロピレン基）等からなる群より選ばれる基の１種以上であってもよい。 The monovalent aromatic hydrocarbon groups as R 6 to R 9 in the formula (IIb) which may have a substituent include, for example, independently from a phenyl group, a naphthyl group, a biphenyl group and the like. One or more groups selected from the group of
The monovalent aliphatic hydrocarbon groups as R 6 to R 9 in the formula (IIb) which may have a substituent include, for example, independently each of a methyl group, an ethyl group, a propyl group and an isopropyl. One or more selected from the group consisting of a group, a butyl group, an isobutyl group, a tert-butyl group and the like can be mentioned.
Further, when R 6 to R 9 in the formula (IIb) are monovalent aliphatic hydrocarbon groups which may have a substituent, R 6 and R 7 and R 8 and R 9 are mutual. It may be bound to. For example, R 6 -R 7 and R 8 -R 9 can each independently, for example, an ethylene group, a 1,1,2,2-tetramethylethylene group, a 2,2-dimethylpropylene group, a hexylene group (or). It may be one or more of the groups selected from the group consisting of 1,1,3-trimethylpropylene group) and the like.
　前記Ｒ６～Ｒ９における、芳香族炭化水素基及び脂肪族炭化水素基が有していてもよい置換基及びその数は、反応（例えば、クロスカップリング反応等）を阻害するものでなければ特に限定されない。置換基としては、例えば、各々独立に、アルキル基、アリール基、アルコキシ基、アリールオキシ基等からなる群より選ばれる１種以上の基があげられ、これらの置換基は１つ以上有することができる。また、置換基同士は、相互に架橋していてもよく、更に置換基を有してよい。 The substituents and the number of the substituents that the aromatic hydrocarbon group and the aliphatic hydrocarbon group may have in R 6 to R 9 do not inhibit the reaction (for example, cross-coupling reaction, etc.). Not particularly limited. Examples of the substituent include one or more groups 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 may have one or more. can. Further, the substituents may be crosslinked with each other, and may further have a substituent.
　式（ＩＩｂ）で表される化合物において、ジボロン酸エステル類としては、より具体的には、例えば、
ビス（ピナコラト）ジボロン（Bis(pinacolato)diboron）、
ビス（ネオペンチルグリコラト）ジボロン（Bis(neopentylGlycolate)diboron）、
ビス（ヘキシレングリコラト）ジボロン（Bis(hexyleneGlycolato)diboron）、ビス（カテコラト）ジボロン（Bis(catecholato)diboron）等からなる群より選ばれる１種以上があげられる。
　式（ＩＩｂ）で表される化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　式（ＩＩｂ）で表される化合物は、市販品をそのまま又は精製して用いることができる。 In the compound represented by the formula (IIb), the diboronic acid esters are more specifically, for example, for example.
Bis (pinacolato) diboron,
Bis (neopentyl Glycolate) diboron,
One or more species selected from the group consisting of bis (hexylene Glycolato) diboron, bis (catecholato) diboron, and the like can be mentioned.
The compound represented by the formula (IIb) can be used alone or in combination of two or more.
As the compound represented by the formula (IIb), a commercially available product can be used as it is or after purification.
（化合物（ＩＩ）の使用量等）
　化合物（ＩＩ）の使用量は、化合物（Ｉ）との当量比を考慮し、適宜調整される。化合物（Ｉ）と化合物（ＩＩ）の当量比（化合物（Ｉ）／化合物（ＩＩ））は、反応（例えば、クロスカップリング反応等）が進行する当量比であれば特に制限されることはない。例えば１０／１～１／１０であり、好ましくは５／１～１／５であり、より好ましくは３／１～１／３であり、さらに好ましくは２／１～１／２である。 (Amount of compound (II) used, etc.)
The amount of compound (II) used is appropriately adjusted in consideration of the equivalent ratio with compound (I). The equivalent ratio of compound (I) to compound (II) (compound (I) / compound (II)) is not particularly limited as long as it is an equivalent ratio in which a reaction (for example, a cross-coupling 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 further preferably 2/1 to 1/2.
　本発明において、化合物（ＩＩ）は、１種を単独で又は２種以上を組み合わせて用いることができる。
　例えば、式（ＩＩａ）で表される化合物の１種を単独で又は２種以上を組み合わせて用いることができる。また、式（ＩＩａ）で表される化合物の１種以上と式（ＩＩｂ）で表される化合物の１種以上とを組み合わせて用いることができる。
　化合物（ＩＩ）は、市販品をそのまま又は精製して用いることができる。 In the present invention, compound (II) may be used alone or in combination of two or more.
For example, one of the compounds represented by the formula (IIa) can be used alone or in combination of two or more. Further, one or more of the compounds represented by the formula (IIa) and one or more of the compounds represented by the formula (IIb) can be used in combination.
As compound (II), a commercially available product can be used as it is or after purification.
（化合物（ＩＩ）の具体例）
　本発明の反応方法（例えば、クロスカップリング反応方法等）において用いられる化合物（ＩＩ）の具体例としては、例えば、実施例１～７７で用いられる化合物（ＩＩ－１）～（ＩＩ－２５）、（ＩＩ－４５）、（ＩＩ－２００～ＩＩ－２０２）及び化合物（ＩＩ－２６）～（ＩＩ－４４）からなる群より選ばれる１種以上があげられる。なお、これらの構造式中、Ｍｅはメチル基を、Ｐｈはフェニル基を、それぞれ示す。
Figure JPOXMLDOC01-appb-C000009
 (Specific example of compound (II))
Specific examples of the compound (II) used in the reaction method of the present invention (for example, a cross-coupling reaction method, etc.) include, for example, the compounds (II-1) to (II-25) used in Examples 1 to 77. , (II-45), (II-200 to II-202) and compounds (II-26) to (II-44). In these structural formulas, Me represents a methyl group and Ph represents a phenyl group.
Figure JPOXMLDOC01-appb-C000009
＜反応生成物＞
　本発明の反応方法（例えば、クロスカップリング反応方法等）により得られる反応生成物（ＩＩＩ）の具体例としては、例えば、実施例１～７７で得られた反応生成物（ＩＩＩ－１）～（ＩＩＩ－４９）、（ＩＩＩ－３００～Ｉ－３１４）と、下記の化合物（ＩＩＩ－５０）～（ＩＩＩ－１１８）があげられる。
　なお、これらの構造式中、Ｍｅはメチル基を、ｔ－Ｂｕ又はＢｕ－ｔはターシャリーブチル基を、Ｐｈはフェニル基を、それぞれ示す。
Figure JPOXMLDOC01-appb-C000010
  
Figure JPOXMLDOC01-appb-C000011
Figure JPOXMLDOC01-appb-C000012
Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000014
 <Reaction product>
Specific examples of the reaction product (III) obtained by the reaction method of the present invention (for example, a cross-coupling reaction method or the like) include, for example, the reaction products (III-1) to obtained in Examples 1 to 77. (III-49), (III-300 to I-314) and the following compounds (III-50) to (III-118) can be mentioned.
In these structural formulas, Me represents a methyl group, t-Bu or But-t represents a tertiary butyl group, and Ph represents a phenyl group.
Figure JPOXMLDOC01-appb-C000010
Figure JPOXMLDOC01-appb-C000011
Figure JPOXMLDOC01-appb-C000012
Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000014
　本発明の反応方法（例えば、クロスカップリング反応方法等）により得られる反応生成物は、上記（ＩＩＩ－１）～（ＩＩＩ－１１８）、（ＩＩＩ－３００）～（ＩＩＩ－３１４）で具体的にあげた化合物以外に、多様な構造の化合物であってもよい。
　例えば、下記式（ＩＩＩｃ）～（ＩＩＩｆ）で表される化合物があげられる。なお、式（ＩＩＩｃ）～（ＩＩＩｆ）に係る規定において、芳香族炭化水素基、芳香族複素環基及び置換基は、それぞれ化合物（Ｉ）においてあげられているそれぞれの基と同様の基とできる。
　これら式（ＩＩＩｃ）～（ＩＩＩｆ）で表される化合物は、着色材料、エネルギー線吸収材料、情報記録材料、波長変換材料、インジケーター材料、センサー材料等の成分として用いることができる。 The reaction products obtained by the reaction method of the present invention (for example, a cross-coupling reaction method, etc.) are specifically described in (III-1) to (III-118) and (III-300) to (III-314) above. In addition to the compounds listed in the above, compounds having various structures may be used.
For example, compounds represented by the following formulas (IIIc) to (IIIf) can be mentioned. In the provisions according to the formulas (IIIc) to (IIIf), the aromatic hydrocarbon group, the aromatic heterocyclic group and the substituent can be the same groups as the respective groups listed in the compound (I), respectively. ..
The compounds represented by these formulas (IIIc) to (IIIf) can be used as components of coloring materials, energy ray absorbing materials, information recording materials, wavelength conversion materials, indicator materials, sensor materials and the like.
Figure JPOXMLDOC01-appb-C000015
  （式（ＩＩＩｃ）中、
　Ａｒ１及びＡｒ２は、それぞれ独立に式（Ａｒ－１）～（Ａｒ－３）を表す。
Figure JPOXMLDOC01-appb-C000016
  　（Ａｒ－１）中のＲ１４、（Ａｒ－２）中のＲ１５、及び（Ａｒ－３）中のＲ１６は、いずれも置換基を表す。
　（Ａｒ－１）中ｒは０又は１～５の整数、（Ａｒ－２）中ｓは０又は１～７の整数、（Ａｒ－３）中ｔは０又は１～８の整数である。Ｒ１４、Ｒ１５及びＲ１６が複数ある場合、互いに同一又は異なっていてもよい。
　連結基Ｑ１及びＱ２は、それぞれ独立に式（Ｑ－１）～（Ｑ－４）で表される連結基群から選択される。Ｑ１とＱ２は、互いに同一又は異なっていてもよい。式中の＊は結合位置を表す。
Figure JPOXMLDOC01-appb-C000017
 　式（Ｑ－２）中、Ｒ１０及びＲ１１は、それぞれ独立に、シアノ基、置換基を有していてもよいアルキル基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。
　式（Ｑ－３）中、Ｒ１２は、置換基を有していてもよいアルキル基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。
　式（Ｑ－４）中、Ｒ１３は、ハロゲン原子、置換基を有していてもよいアルコキシル基又は置換基を有していてもよいアミノ基、置換基を有していてもよいアルキニル基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。）
Figure JPOXMLDOC01-appb-C000015
 (In equation (IIIc),
Ar1 and Ar2 independently represent the formulas (Ar-1) to (Ar-3), respectively.
Figure JPOXMLDOC01-appb-C000016
 R 14 in (Ar-1), R 15 in (Ar-2), and R 16 in (Ar-3) all represent substituents.
In (Ar-1) r is an integer of 0 or 1 to 5, s in (Ar-2) is an integer of 0 or 1 to 7, and t in (Ar-3) is an integer of 0 or 1 to 8. When there are a plurality of R 14 , R 15 and R 16 , they may be the same or different from each other.
The linking groups Q1 and Q2 are independently selected from the linking groups represented by the formulas (Q-1) to (Q-4). Q1 and Q2 may be the same or different from each other. * In the formula represents the bond position.
Figure JPOXMLDOC01-appb-C000017
 In the formula (Q-2), R 10 and R 11 are independently a cyano group, an alkyl group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or a substituent. Represents an aromatic heterocyclic group which may have a group.
In the formula (Q-3), R 12 has an alkyl group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or an aromatic which may have a substituent. Represents a heterocyclic group.
In the formula (Q-4), R 13 is a halogen atom, an alkoxyl group which may have a substituent or an amino group which may have a substituent, and an alkynyl group which may have a substituent. , An aromatic hydrocarbon group which may have a substituent or an aromatic heterocyclic group which may have a substituent. )
Figure JPOXMLDOC01-appb-C000018
 （式（ＩＩＩｄ）及び（ＩＩＩｅ）中、
　Ｒ２０、Ｒ２１、Ｒ２２及びＲ２３は、それぞれ独立に、置換基を有していてもよいアルキル基、置換基を有していてもよいアルキニル基、置換基を有していてもよいアルケニル基、置換基を有していてもよいアシル基、カルボニル基、カルボキシル基、置換基を有していてもよいアルコキシル基、置換基を有していてもよいシリル基、置換基を有していてもよいアミノ基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。
　Ｘ２０、Ｘ２１、Ｘ２２及びＸ２３は、それぞれ独立に、酸素原子、硫黄原子又はＮＲ２４を表す。
　Ｙ２０、Ｙ２１、Ｙ２２及びＹ２３は、それぞれ独立に、酸素原子、置換基を有しても良いアミノ基又はＣＲ２５Ｒ２６を表す。
　Ｒ２４、Ｒ２５及びＲ２６は、それぞれ独立に、置換基を有していてもよいアルキル基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。
　式（ＩＩＩｄ）及び（ＩＩＩｅ）に複数含まれるＲ２４、Ｒ２５及びＲ２６はそれぞれ同一でも異なっていてもよい。）
Figure JPOXMLDOC01-appb-C000018
 (In formulas (IIId) and (IIIe),
R 20 , R 21 , R 22 and R 23 may independently have an alkyl group which may have a substituent, an alkynyl group which may have a substituent, and a substituent. It has an alkenyl group, an acyl group which may have a substituent, a carbonyl group, a carboxyl group, an alkoxyl group which may have a substituent, a silyl group which may have a substituent, and a substituent. Represents an amino group which may be present, an aromatic hydrocarbon group which may have a substituent, or an aromatic heterocyclic group which may have a substituent.
X 20 , X 21 , X 22 and X 23 independently represent an oxygen atom, a sulfur atom or an NR 24 , respectively.
Y 20 , Y 21 , Y 22 and Y 23 each independently represent an oxygen atom, an amino group which may have a substituent or CR 25 R 26 .
R 24 , R 25 and R 26 may independently have an alkyl group which may have a substituent and an aromatic hydrocarbon group or a substituent which may have a substituent. Represents an aromatic heterocyclic group.
A plurality of R 24, R 25 , and R 26 included in the formulas (IIId) and (IIIe) may be the same or different from each other. )
Figure JPOXMLDOC01-appb-C000019
  （式（ＩＩＩｆ）中、
　環Ａ４０及び環Ａ４１は、それぞれ独立に、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表し、
　Ｒ４０及びＲ４１は、それぞれ独立に、置換基を有していてもよいアルキル基、置換基を有していてもよいアルキニル基、置換基を有していてもよいアルケニル基、置換基を有していてもよいアシル基、カルボニル基、カルボキシル基、置換基を有していてもよいアルコキシル基、置換基を有していてもよいシリル基、置換基を有していてもよいアミノ基、置換基を有していてもよい芳香族炭化水素基又は置換基を有していてもよい芳香族複素環基を表す。）
Figure JPOXMLDOC01-appb-C000019
 (In equation (IIIf),
Rings A 40 and A 41 each independently represent an aromatic hydrocarbon group which may have a substituent or an aromatic heterocyclic group which may have a substituent.
R 40 and R 41 independently have an alkyl group which may have a substituent, an alkynyl group which may have a substituent, an alkenyl group which may have a substituent, and a substituent. An acyl group which may have an acyl group, a carbonyl group, a carboxyl group, an alkoxyl group which may have a substituent, a silyl group which may have a substituent, and an amino group which may have a substituent. , An aromatic hydrocarbon group which may have a substituent or an aromatic heterocyclic group which may have a substituent. )
＜金属触媒＞
　本発明の反応方法（例えば、クロスカップリング反応方法等）で用いられる金属触媒は、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の反応（例えば、クロスカップリング反応等）を触媒（促進）し得るものであれば、特に制限されない。 <Metal catalyst>
The metal catalyst used in the reaction method of the present invention (for example, a cross-coupling reaction method or the like) is the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (for example). II) The reaction is not particularly limited as long as it can catalyze (promote) the reaction (for example, cross-coupling reaction, etc.).
　金属触媒を構成する金属（元素）は、前記化合物（Ｉ）と前記化合物（ＩＩ）の反応を触媒（促進）し得るものであれば、遷移金属（元素）であっても典型金属（元素）であってもよく、特に制限されない。
　遷移金属（元素）としては、例えば、スカンジウム、チタン、バナジウム、クロム、マンガン、鉄、コバルト、ニッケル、銅、亜鉛、イットリウム、ジルコニウム、ニオブ、モリブデン、テクネシウム、ルテニウム、ロジウム、パラジウム、銀、カドミウム、ハフニウム、タンタル、タングステン、レニウム、オスミウム、イリジウム、白金、金等からなる群より選ばれる１種以上があげられる。
　典型金属（元素）としては、例えば、アルミニウム、ガリウム、ゲルマニウム、インジウム、スズ、アンチモン、タリウム、鉛、ビスマスからなる群より選ばれる１種以上があげられる。 The metal (element) constituting the metal catalyst is a typical metal (element) even if it is a transition metal (element) as long as it can catalyze (promote) the reaction between the compound (I) and the compound (II). It may be, and is not particularly limited.
Examples of transition metals (elements) include scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium, niobium, molybdenum, technesium, ruthenium, rhodium, palladium, silver, and cadmium. One or more selected from the group consisting of hafnium, tantalum, tungsten, ruthenium, osmium, iridium, platinum, gold and the like can be mentioned.
As a typical metal (element), for example, one or more selected from the group consisting of aluminum, gallium, germanium, indium, tin, antimony, thallium, lead, and bismuth can be mentioned.
　本発明においては、触媒活性等の観点から、第４周期から第６周期に属する遷移金属（元素）があげられる。例えば、チタン、バナジウム、マンガン、鉄、コバルト、ニッケル、銅、亜鉛、モリブデン、ルテニウム、ロジウム、パラジウム、銀、タンタル、タングステン、レニウム、オスミウム、イリジウム、白金、金からなる群より選ばれる１種以上が好ましく、パラジウム、ニッケル、鉄、ルテニウム、白金、ロジウム、イリジウム、コバルトからなる群より選ばれる１種以上がより好ましく、パラジウム、ニッケル、鉄、銅からなる群より選ばれる１種以上がより好ましい。 In the present invention, transition metals (elements) belonging to the 4th to 6th periods can be mentioned from the viewpoint of catalytic activity and the like. 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, renium, osmium, iridium, platinum, and gold. Is preferable, at least one selected from the group consisting of palladium, nickel, iron, ruthenium, platinum, rhodium, iridium, and cobalt is more preferable, and at least one selected from the group consisting of palladium, nickel, iron, and copper is more preferable. ..
　金属触媒は、種々の形態のものを用いることができ、例えば以下（１）～（４）等からなる群より選ばれる１種以上があげられる。
（１）粉状又は多孔質形状の金属単体
（２）アルミナ、炭素、シリカ、ゼオライト等の担体に金属単体又は金属化合物を担持したもの
（３）金属の塩（塩化物、臭化物、ヨウ化物、硝酸塩、硫酸塩、炭酸塩、シュウ酸塩、酢酸塩、酸化物等）
（４）金属と錯体（オレフィン錯体、ホスフィン錯体、アミン錯体、アンミン錯体又はアセチルアセトナート錯体等）との錯化合物 As the metal catalyst, various forms can be used, and examples thereof include one or more selected from the group consisting of the following (1) to (4) and the like.
(1) Powdery or porous metal unit (2) Metal unit or metal compound supported on a carrier such as alumina, carbon, silica, zeolite (3) Metal salt (chloride, bromide, iodide, Nitrate, sulfate, carbonate, oxalate, acetate, oxide, etc.)
(4) Complex compound of metal and complex (olefin complex, phosphine complex, amine complex, ammine complex, acetylacetonate complex, etc.)
　本発明においては、金属触媒として、パラジウム触媒が特に好ましく用いられる。
　パラジウム触媒としては、例えば、酢酸パラジウム（ＩＩ）、塩化パラジウム（ＩＩ）、臭化パラジウム（ＩＩ）、ヨウ化パラジウム（ＩＩ）、パラジウムアセチルアセトナート（ＩＩ）、ジクロロビス（ベンゾニトリル）パラジウム（ＩＩ）、ビス（ジベンジリデンアセトン）パラジウム、ジクロロビス（アセトニトリル）パラジウム（ＩＩ）、ジクロロビス（トリフェニルホスフィン）パラジウム（ＩＩ）、ジクロロテトラアンミンパラジウム（ＩＩ）、ジクロロ（シクロオクタ－１，５－ジエン）パラジウム（ＩＩ）、ジクロロビス（トリシクロヘキシルホスフィン）パラジウム（ＩＩ）、パラジウムトリフルオロアセテート（ＩＩ）等の２価パラジウム化合物；トリス（ジベンジリデンアセトン）二パラジウム（０）、トリス（ジベンジリデンアセトン）二パラジウムクロロホルム錯体（０）、テトラキス（トリフェニルホスフィン）パラジウム（０）等の０価パラジウム化合物；等からなる群より選ばれる１種以上があげられる。
　金属触媒は、１種を単独で又は２種以上を組み合わせて用いることができる。
　金属触媒は、市販品をそのまま又は精製して用いることができる。 In the present invention, a palladium catalyst is particularly preferably used as the metal catalyst.
Examples of the palladium catalyst include palladium (II) acetate, palladium (II) chloride, palladium (II) bromide, palladium (II) iodide, palladium acetylacetonate (II), and dichlorobis (benzonitrile) palladium (II). , Bis (dibenzylideneacetone) palladium, dichlorobis (acetamide) palladium (II), dichlorobis (triphenylphosphine) palladium (II), dichlorotetraammine palladium (II), dichloro (cycloocta-1,5-diene) palladium (II) , Dichlorobis (tricyclohexylphosphine) palladium (II), palladium trifluoroacetate (II) and other divalent palladium compounds; tris (dibenzylideneacetone) dipalladium (0), tris (dibenzylideneacetone) dipalladium chloroform complex (0) ), Tetrakiss (triphenylphosphine) palladium (0) and the like; 0-valent palladium compound; etc.;
The metal catalyst may be used alone or in combination of two or more.
As the metal catalyst, a commercially available product can be used as it is or after purification.
（配位性化合物）
　本発明においては、高選択的に反応（例えば、クロスカップリング反応等）を進行させる観点から、金属触媒とともに、更にホスフィン化合物等の配位性化合物を共存させて用いることができる。
　配位性化合物は、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の反応（例えば、クロスカップリング反応等）に使用し得るものであれば、特に制限されない。
　配位性化合物としては、例えば、トリフェニルホスフィン、トリ（ｏ－トリル）ホスフィン、トリ（メシチル）ホスフィン等のアリールホスフィン；トリ（シクロヘキシル）ホスフィン、トリ（イソプロピル）ホスフィン、トリ（ｔｅｒｔ－ブチル）ホスフィン等のアルキルホスフィン；２－ジシクロヘキシルホスフィノ－２’，６’－ジメトキシビフェニル（ＳＰｈｏｓ）、２－ジシクロヘキシルホスフィノ－２’－（Ｎ，Ｎ－ジメチルアミノ）ビフェニル（ＤａｖｅＰｈｏｓ）、２－（ジ－ｔｅｒｔ－ブチルホスフィノ）－２’，４’，６’－トリイソプロピル－３，６－ジメトキシ－１，１’－ビフェニル（ｔＢｕＢｒｅｔｔＰｈｏｓ）、２－ジシクロヘキシルホスフィノ－２’，６’－ジイソプロポキシビフェニル、２－ジシクロヘキシルホスフィノ－２’－メチルビフェニル、２－ジシクロヘキシルホスフィノ－２’，４’，６’－トリイソプロピルビフェニル、２－（ジ－ｔｅｒｔ－ブチルホスフィノ）－２’，４’，６’－トリイソプロピルビフェニル、２－ジシクロヘキシルホスフィノ－３，６－ジメトキシ－２’，４’，６’－トリイソプロピルビフェニル、２－（ジシクロヘキシルホスフィノ）ビフェニル、２－（ジ－ｔｅｒｔ－ブチルホスフィノ）－２’－（Ｎ，Ｎ－ジメチルアミノ）ビフェニル等のＢｕｃｈｗａｌｄホスフィン配位子；１，２－ビス（ジフェニルホスフィノ）エタン、１，２－ビス（ジフェニルホスフィノ）プロパン、１，２－ビス（ジシクロヘキシルホスフィノ）エタン、１，２－ビス（ジフェニルホスフィノ）ブタン、１，２－ビス（ジフェニルホスフィノ）フェロセン等のニ座ホスフィン；１，３－ビス（２，６－ジイソプロピルフェニル）－４，５－ジヒドロ－１Ｈ－イミダゾリウムクロライド、１，３－ビス（２，６－ジイソプロピルフェニル）イミダゾリウムクロライド、１，３－ビス（２，４，６－トリメチルフェニル）－４，５－ジヒドロ－１Ｈ－イミダゾリウムクロライド等のＮ－ヘテロカルベン配位子；ｔ－Ｂｕ３Ｐ・ＨＢＦ４（トリ－ｔｅｒｔ－ブチルホスホニウムテトラフルオロボラート）等のトリアルキルホスホニウムテトラフルオロボラート等からなる群より選ばれる１種以上があげられる。 (Coordinating compound)
In the present invention, a coordinating compound such as a phosphine compound can be used in coexistence with the metal catalyst from the viewpoint of allowing the reaction (for example, a cross-coupling reaction) to proceed with high selectivity.
The coordinating compound is used in a reaction (for example, a cross-coupling reaction, etc.) between the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)). There are no particular restrictions as long as it is possible.
Coordinating compounds include, for example, aryl phosphin such as triphenylphosphine, tri (o-tolyl) phosphin, tri (mesityl) phosphin; tri (cyclohexyl) phosphine, tri (isopropyl) phosphine, tri (tert-butyl) phosphine. Alkylphosphines 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'-diisopropoxy Biphenyl, 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, 2- (di-tert-butyl) Buchwald phosphine ligands such as phosphino) -2'-(N, N-dimethylamino) biphenyl; 1,2-bis (diphenylphosphino) ethane, 1,2-bis (diphenylphosphino) propane, 1, Nite phosphines such as 2-bis (dicyclohexylphosphino) ethane, 1,2-bis (diphenylphosphino) butane, 1,2-bis (diphenylphosphino) ferrocene; 1,3-bis (2,6-diisopropyl) Phenyl) -4,5-dihydro-1H-imidazolium chloride, 1,3-bis (2,6-diisopropylphenyl) imidazolium chloride, 1,3-bis (2,4,6-trimethylphenyl) -4, From N-heterocarbene ligands such as 5-dihydro-1H-imidazolium chloride; trialkylphosphonium tetrafluoroborates such as t-Bu 3P · HBF 4 ( tri -tert-butylphosphonium tetrafluoroborate), etc. One or more species selected from the group of
　パラジウム触媒にホスフィン化合物等の配位性化合物を共存させる場合、上記パラジウム化合物とホスフィン化合物又はＮ－ヘテロカルベン化合物を事前に混合、調製したものを用いて反応させてもよい。例えば、（２－ジシクロヘキシルホスフィノ－２’，６’－ジメトキシビフェニル）［２－（２’－アミノ－１，１’－ビフェニル）］パラジウム（ＩＩ）メタンスルホン酸（ＳＰｈｏｓ　Ｐｄ　Ｇ３）を用いることができる。 When a coordinating compound such as a phosphine compound is allowed to coexist in a palladium catalyst, the above-mentioned palladium compound and a phosphine compound or an N-heterocarben compound may be mixed and prepared in advance for reaction. For example, (2-dicyclohexylphosphino-2', 6'-dimethoxybiphenyl) [2- (2'-amino-1,1'-biphenyl)] palladium (II) methanesulfonic acid (SPhos Pd G3) should be used. Can be done.
　本発明においては、配位性化合物としてホスフィン化合物が好ましく用いられる。
　ホスフィン化合物は、アルキルホスフィンを含むことが好ましい。
　配位性化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　配位性化合物は、市販品をそのまま又は精製して用いることができる。 In the present invention, a phosphine compound is preferably used as the coordinating compound.
The phosphine compound preferably contains an alkylphosphine.
The coordinating compound may be used alone or in combination of two or more.
As the coordinating compound, a commercially available product can be used as it is or after purification.
　金属触媒の使用量又は金属触媒と配位性化合物との共存物における金属触媒の使用量は、反応（例えば、クロスカップリング反応等）が進行する使用量であれば特に制限されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて使用される不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　金属触媒の使用量は、例えば、化合物（Ｉ）のモル量に価数を掛けて得たモル数を基準（１００％）として、０．５モル％以上、好ましくは０．１モル％以上、より好ましくは０．５モル％以上、さらに好ましくは１．０モル％以上とすることができ、上限値は特に限定されないが、２５モル％以下、好ましくは２０モル％以下、より好ましくは１５モル％以下、さらに好ましくは１０モル％以下とすることができる。 The amount of the metal catalyst used or the amount of the metal catalyst used in the coexistence of the metal catalyst and the coordinating compound is not particularly limited as long as the reaction (for example, a cross-coupling reaction or the like) proceeds, and the organic Compound (A) (eg, said compound (I)) and said organic compound (B) (eg, said compound (II)), metal catalyst, base, unsaturated hydrocarbon compound used as needed, reaction generation. It can be appropriately determined in consideration of each type of compound, each amount, reaction temperature and the like.
The amount of the metal catalyst used is, for example, 0.5 mol% or more, preferably 0.1 mol% or more, based on the number of moles obtained by multiplying the molar amount of compound (I) by a valence (100%). It can be more preferably 0.5 mol% or more, further preferably 1.0 mol% or more, and the upper limit is not particularly limited, but is 25 mol% or less, preferably 20 mol% or less, more preferably 15 mol. % Or less, more preferably 10 mol% or less.
　配位性化合物を金属触媒と共存させる場合、配位性化合物の使用量は、反応（例えば、クロスカップリング反応等）が進行する使用量であれば特に制限されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて使用される不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　配位性化合物の使用量は、例えば、配位性化合物とパラジウム触媒のモル比（配位性化合物／パラジウム触媒）として１０／１～１／１０、好ましくは５／１～１／５、より好ましくは３／１～１／３、さらに好ましくは２／１～１／２とすることができる。 When the coordinating compound is allowed to coexist with the metal catalyst, the amount of the coordinating compound used is not particularly limited as long as the reaction (for example, cross-coupling reaction or the like) proceeds, and the organic compound (A) is used. (For example, the compound (I)) and the organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, and a reaction product. It can be appropriately determined in consideration of the type, amount of each, reaction temperature, and the like.
The amount of the coordinating compound used is, for example, 10/1 to 1/10, preferably 5/1 to 1/5, as the molar ratio of the coordinating compound to the palladium catalyst (coordinating compound / palladium catalyst). It can be preferably 3/1 to 1/3, and more preferably 2/1 to 1/2.
＜塩基＞
　本発明の反応方法は、融点が３０℃以上の脱離基を有する有機化合物（Ａ）、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）及び触媒以外に、塩基を用いることができる。
　本発明の反応方法（例えば、クロスカップリング反応方法等）で用いられる塩基は、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の反応（例えば、クロスカップリング反応等）を促進し得るものであれば、特に制限されない。
　塩基として、例えば、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸水素カリウム、炭酸ルビジウム、炭酸セシウム、リン酸カリウム、リン酸ナトリウム、フッ化カリウム、フッ化セシウム等の無機塩基；水素化ナトリウム、水素化カリウム等の水素化アルカリ金属；ナトリウム－メトキシド、ナトリウム－エトキシド、カリウム－メトキシド、カリウム－メトキシド、カリウム－エトキシド、リチウム－ｔｅｒｔ－ブトキシド、ナトリウム－ｔｅｒｔ－ブトキシド、カリウム－ｔｅｒｔ－ブトキシド等のアルカリ金属アルコキシド；トリエチルアミン、トリブチルアミン、ジメチルプロピルアミン、ジメチルブチルアミン、ジメチルシクロヘキシルアミン、ジメチルベンジルアミン、ジイソプロピルメチルアミン、ジイソプロピルエチルアミン、ピリジン、ジアザビシクロウンデセン（１，８－ジアザビシクロ［５．４．０］ウンデカ－７－エン）、ジアザビシクロノネン（１，５－ジアザビシクロ［４．３．０］ノナ－５－エン）、１，４－ジアザビシクロ［２．２．２］オクタン、Ｎ－エチルモルホリン、Ｎ，Ｎ，Ｎ’，Ｎ’－テトラメチルエチレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’－テトラメチルプロピレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’－テトラメチルヘキサンジアミン、ビス（ジメチルアミノエチル）エーテル、Ｎ，Ｎ’，Ｎ’－トリメチルアミノエチルピペラジン、Ｎ，Ｎ，Ｎ’，Ｎ’’，Ｎ’’－ペンタメチルジエチレントリアミン等の第３級アミン塩基等の有機塩基；等からなる群より選ばれる１種以上があげられる。
　塩基は、１種を単独で又は２種以上を組み合わせて用いることができる。
　塩基は、市販品をそのまま又は精製して用いることができる。 <Base>
The reaction method of the present invention comprises an organic compound (A) having a melting group having a melting group of 30 ° C. or higher, an organic compound (B) having a melting group of 30 ° C. or higher that reacts with an organic compound having a leaving group, and a catalyst. Bases can be used.
The bases used in the reaction method of the present invention (for example, a cross-coupling reaction method, etc.) are the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II). )) Is not particularly limited as long as it can promote the reaction (for example, cross-coupling reaction, etc.).
Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, potassium hydrogencarbonate, rubidium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, potassium fluoride, cesium fluoride and the like. Inorganic bases; alkali hydrides such as sodium hydride, potassium hydride, etc .; sodium-methoxydo, sodium-ethoxydo, potassium-methoxyd, potassium-methoxyd, potassium-ethoxydo, lithium-tert-butoxide, sodium-tert-butoxide, potassium -Alkali metal alkoxides such as tert-butoxide; triethylamine, tributylamine, dimethylpropylamine, dimethylbutylamine, dimethylcyclohexylamine, dimethylbenzylamine, diisopropylmethylamine, diisopropylethylamine, pyridine, diazabicycloundecene (1,8-diazabicyclo) [5.4.0] Undec-7-ene), diazabicyclononen (1,5-diazabicyclo [4.3.0] nona-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'-trimethylaminoethyl piperazine, N, N, N', N'', N''-organic such as tertiary amine bases such as pentamethyldiethylenetriamine. One or more selected from the group consisting of bases; etc. may be mentioned.
As the base, one type can be used alone or two or more types can be used in combination.
As the base, a commercially available product can be used as it is or after purification.
　塩基の使用量は、反応（例えば、クロスカップリング反応等）が進行する使用量であれば特に制限されず、化合物（Ｉ）、化合物（ＩＩ）、金属触媒、塩基、必要に応じて使用される不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　塩基の使用量は、例えば、化合物（１）の当量を基準として、０．５当量以上、好ましくは０．８当量以上、より好ましくは１．０当量以上、さらに好ましくは１．２当量以上、最も好ましくは１．４当量以上とすることができる。塩基の使用量の上限は特に限定されないが、例えば１０．０当量以下、好ましくは５．０当量以下、より好ましくは４．０当量以下、さらに好ましくは３．０当量以下とすることができる。 The amount of the base used is not particularly limited as long as the amount of the base used is such that the reaction (for example, a cross-coupling reaction) proceeds, and the compound (I), the compound (II), the metal catalyst, the base, and the base are used as needed. It can be appropriately determined in consideration of each type and amount of unsaturated hydrocarbon compound and reaction product, reaction temperature and the like.
The amount of the base used is, 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, based on the equivalent of compound (1). Most preferably, it can be 1.4 equivalents or more. The upper limit of the amount of the base used is not particularly limited, but may be, for example, 10.0 equivalents or less, preferably 5.0 equivalents or less, more preferably 4.0 equivalents or less, still more preferably 3.0 equivalents or less.
＜不飽和炭化水素化合物＞
　本発明の反応方法（例えば、クロスカップリング反応方法等）においては、必要に応じて不飽和炭化水素化合物をさらに用いることができる。不飽和炭化水素化合物は、分子中に少なくとも１つの炭素－炭素不飽和二重結合又は少なくとも１つの炭素－炭素不飽和三重結合を有する、鎖状及び／又は環状の化合物である。
　不飽和炭化水素化合物は、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の反応（クロスカップリング反応等）を促進し得るものであれば、特に制限されることはない。
　本発明で用いられる不飽和炭化水素化合物には、例えばベンゼンやナフタレン等の芳香族化合物が含まれない。また、前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、前記配位性化合物に相当する化合物が含まれない。 <Unsaturated hydrocarbon compound>
In the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), an unsaturated hydrocarbon compound can be further used if necessary. Unsaturated hydrocarbon compounds are chain and / or cyclic compounds 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 promotes the reaction (cross-coupling reaction, etc.) between the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)). There are no particular restrictions as long as it can be obtained.
The unsaturated hydrocarbon compound used in the present invention does not include aromatic compounds such as benzene and naphthalene. Further, the compound (I), the compound (II), the metal catalyst, and the compound corresponding to the coordinating compound are not included.
　不飽和炭化水素化合物の炭素数は、例えば５～２４、好ましくは５～１８、より好ましくは５～１２、さらに好ましくは６～１０、最も好ましくは６～８である。
　１つの炭素－炭素不飽和二重結合を有する不飽和炭化水素化合物としては、例えば、ヘキセン、ヘプテン、オクテン、ノネン、デセン等からなる群より選ばれる１種以上があげられる。
　１つの炭素－炭素不飽和二重結合を有する不飽和炭化水素化合物としては、例えば、シクロヘキセン、シクロヘプテン、シクロオクテン、シクロデセン等からなる群より選ばれる１種以上があげられる。
　２つの炭素－炭素不飽和二重結合を有する不飽和炭化水素化合物としては、例えば、ヘキサジエン、ヘプタジエン、オクタジエン、ノナジエン、デカジエン等からなる群より選ばれる１種以上があげられる。
　２つの炭素－炭素不飽和二重結合を有する不飽和炭化水素化合物としては、例えば、シクロヘキサジエン、シクロヘプタジエン、シクロオクタジエン、シクロデカジエン等からなる群より選ばれる１種以上があげられる。
　１つの炭素－炭素不飽和三重結合を有する不飽和炭化水素化合物としては、例えば、ヘキシン、ヘプチン、オクチン、デシン等からなる群より選ばれる１種以上があげられる。
　１つの炭素－炭素不飽和三重結合を有する環状化合物（4）として、例えば、シクロオクチン、シクロデシン等からなる群より選ばれる１種以上があげられる。
　不飽和炭化水素化合物は、１種を単独で又は２種以上を組み合わせて用いることができる。
　不飽和炭化水素化合物は、市販品をそのまま又は精製して用いることができる。 The unsaturated hydrocarbon compound has, for example, 5 to 24 carbon atoms, 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, nonadien, decadien 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, decine 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, cyclodecine and the like.
The unsaturated hydrocarbon compound may be used alone or in combination of two or more.
As the unsaturated hydrocarbon compound, a commercially available product can be used as it is or after purification.
　不飽和炭化水素化合物を使用する場合の使用量は、反応（例えば、クロスカップリング反応等）が進行する使用量であれば特に制限されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて使用される不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　不飽和炭化水素化合物を使用する場合の使用量は、反応（例えば、クロスカップリング反応等）を行うために加えた全ての原料（例えば、化合物（Ｉ）、化合物（ＩＩ）、金属触媒（及び配位性化合物）、塩基、反応促進剤等）の質量の総和を基準として、例えば０．０１μＬ／ｍｇ以上、好ましくは０．０５μＬ／ｍｇ以上、より好ましくは０．１０μＬ／ｍｇ以上であり、例えば３．０μＬ／ｍｇ以下、好ましくは１．０μＬ／ｍｇ以下、より好ましくは０．５０μＬ／ｍｇ以下とすることができる。 When the unsaturated hydrocarbon compound is used, the amount used is not particularly limited as long as the amount used is such that the reaction (for example, a cross-coupling reaction) proceeds, and the organic compound (A) (for example, the compound (I)) is used. )) And the organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, the type and amount of each reaction product, and the reaction. It can be set as appropriate in consideration of temperature and the like.
When using an unsaturated hydrocarbon compound, the amount used is all raw materials (eg, compound (I), compound (II), metal catalyst (and, for example) added to carry out the reaction (eg, cross-coupling reaction, etc.)). Based on the total mass of the coordinating compound), the base, the reaction accelerator, etc.), for example, 0.01 μL / mg or more, preferably 0.05 μL / mg or more, more preferably 0.10 μL / mg or more. For example, it can be 3.0 μL / mg or less, preferably 1.0 μL / mg or less, and more preferably 0.50 μL / mg or less.
　本発明の反応方法において、不飽和炭化水素化合物を用いると、使用しない場合と比べて、顕著な反応性の向上が認められる場合があった。通常、実質的に無溶媒条件で機械的手段による処理を行い固相反応させると、出発原料である化合物（Ｉ）、化合物（ＩＩ）、金属触媒、塩基、及び反応生成物の拡散が効率的に行うことが困難である。特に、金属触媒の拡散を効率的に行うことが困難であり、クロスカップリング反応が進行しにくくなるおそれがある。
　また、本発明者らは、後述の実施例６０～６３、６５～７７のように、不飽和炭化水素化合物を用いない場合であっても、不飽和炭化水素化合物を用いた場合と同等の収率で反応を進めることが可能であることを見出した。 In the reaction method of the present invention, when an unsaturated hydrocarbon compound was used, a remarkable improvement in reactivity was observed as compared with the case where it was not used. Usually, when a solid phase reaction is carried out by treatment by mechanical means under a substantially solvent-free condition, the diffusion of the starting materials, compound (I), compound (II), a metal catalyst, a base, and a reaction product, is efficient. It is difficult to do. In particular, it is difficult to efficiently diffuse the metal catalyst, and the cross-coupling reaction may be difficult to proceed.
Further, the present inventors have the same yield as the case where the unsaturated hydrocarbon compound is used even when the unsaturated hydrocarbon compound is not used as in Examples 60 to 63 and 65 to 77 described later. We found that it was possible to proceed with the reaction at a rate.
　本発明者らは、透過型電子顕微鏡を用いて反応後の金属触媒を観察したところ、不飽和炭化水素化合物を使用することで、金属触媒の凝集を抑制することができることを見出した。
　不飽和炭化水素化合物は、金属触媒の凝集抑制に寄与するとともに反応性の向上に寄与していると考えられ、本発明の反応方法（例えば、クロスカップリング反応方法等）が、優れた効果を奏すると本発明者らは推定できる。しかし、本発明は、このような推定により何ら限定されない。 The present inventors observed the metal catalyst after the reaction using a transmission electron microscope, and found that the aggregation of the metal catalyst can be suppressed by using an unsaturated hydrocarbon compound.
It is considered that the unsaturated hydrocarbon compound contributes to the suppression of aggregation of the metal catalyst and the improvement of the reactivity, and the reaction method of the present invention (for example, the cross-coupling reaction method, etc.) has an excellent effect. The present inventors can presume that it works. However, the present invention is not limited by such estimation.
＜溶媒＞
　本発明の反応方法（例えば、クロスカップリング反応方法等）は、有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下となる条件で行われる。このような条件は、実質的に有機溶媒を使用しない条件であるといえる。なお、本発明において、実質的に有機溶媒を使用しない条件とは、有機溶媒を全く使用しない態様、積極的に溶媒を用いない態様、及び有機溶媒を使用するものの溶媒効果が発揮されないほどに微量しか使用しない態様のいずれかを表す。 <Solvent>
The reaction method of the present invention (for example, a cross-coupling reaction method or the like) is carried out under the condition that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total. It can be said that such a condition is a condition in which an organic solvent is not substantially used. In the present invention, the conditions in which the organic solvent is substantially not used are a mode in which the organic solvent is not used at all, a mode in which the solvent is not positively used, and a mode in which the organic solvent is used but the solvent effect is not exhibited. Represents one of the embodiments used only.
　本発明において、有機溶媒の存在量は、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の合計１ｍｍｏｌ当り０．７ｍＬ以下である。通常０．５ｍＬ以下、好ましくは０．２ｍＬ以下、より好ましくは０．１ｍＬ以下、さらに好ましくは０．０５ｍＬ以下、最も好ましくは０．０２ｍＬ以下、最大限好ましくは０ｍＬ（有機溶媒不使用）である。
　例えば、一般的なクロスカップリング反応では、反応原料の合計１ｍｍｏｌ当たり、１～２ｍＬの有機溶媒が使用される。本発明は、有機溶媒の使用量が少ないことから、反応原料は、通常、反応開始時に少なくとも一部が有機溶媒等に溶解していない。場合によっては全てが有機溶媒等に溶解することなく、固体状態で存在し得る。 In the present invention, the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)) in total. Is. Usually 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 maximum preferably 0 mL (without using an organic solvent). ..
For example, in a typical cross-coupling reaction, 1 to 2 mL of organic solvent is used per 1 mmol of the reaction raw material in total. In the present invention, since the amount of the organic solvent used is small, at least a part of the reaction raw material is usually not dissolved in the organic solvent or the like at the start of the reaction. In some cases, all of them may exist in a solid state without being dissolved in an organic solvent or the like.
　本発明において、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））と前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））の合計１ｍｍｏｌ当り０．７ｍＬ以下存在してもよい有機溶媒としては、反応（例えば、クロスカップリング反応等）で使用される有機溶媒があげられる。
　例えば、ベンゼン、トルエン、キシレン、メシチレンデュレン、デカリン等の芳香族系溶媒；ジエチルエーテル、ジイソプロピルエーテル、ジブチルエーテル、テトラヒドロフラン、ジメトキシエタン、１，４－ジオキサン、シクロペンチルメチルエーテル、等のエーテル系溶媒；メタノール、エタノール、ｎ－プロパノ－ル、２－プロパノール、１－ブタノール、１，１－ジメチルエタノール、ｔｅｒｔ－ブタノール、２－メトキシエタノール、エチレングリコール等のアルコール系溶媒；ジクロロメタン、クロロホルム、四塩化炭素、クロロベンゼン、１，２－ジクロロベンゼン等のハロゲン化炭化水素系溶媒；アセトニトリル、Ｎ，Ｎ’－ジメチルホルムアミド、Ｎ，Ｎ’－ジメチルアセトアミド、Ｎ－メチル－２－ピロリドン、ジメチルスルホキシド、等の極性溶媒等；アセトン、メチルエチルケトン等のケトン系溶媒；ピリジン、酢酸等からなる群より選ばれる１種以上があげられる。特に、ベンゼン、トルエン、キシレン、クロロベンゼン、ジエチルエーテル、ジブチルエーテル、シクロペンチルメチルエーテル、テトラヒドロフラン、１，４－ジオキサン、ジクロロメタン、クロロホルム、アセトン、アセトニトリル、Ｎ，Ｎ’－ジメチルホルムアミド、メタノール、エタノール、２－プロパール、ｔｅｒｔ－ブタノール、ジメチルスルホキシドが好ましい。 In the present invention, an organic solvent may be present in an amount of 0.7 mL or less per 1 mmol of the organic compound (A) (for example, the compound (I)) and the organic compound (B) (for example, the compound (II)). Examples include organic solvents used in reactions (eg, cross-coupling reactions, etc.).
For example, aromatic solvents such as benzene, toluene, xylene, mesityrendurene, decalin; ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, cyclopentylmethyl ether, etc .; methanol. , Ethanol, n-propanol, 2-propanol, 1-butanol, 1,1-dimethylethanol, tert-butanol, 2-methoxyethanol, ethylene glycol and other alcohol solvents; dichloromethane, chloroform, carbon tetrachloride, chlorobenzene , 1,2-Dichlorobenzene and other halogenated hydrocarbon solvents; polar solvents such as acetonitrile, N, N'-dimethylformamide, N, N'-dimethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, etc. ; Ketone-based solvent such as acetone and methyl ethyl ketone; one or more selected from the group consisting of pyridine, acetic acid and the like. In particular, 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- Propearl, tert-butanol and dimethyl sulfoxide are preferred.
＜その他の成分＞
　本発明の反応方法は、融点が３０℃以上の脱離基を有する有機化合物（Ａ）、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）及び触媒以外に、促進剤等のその他の成分を用いることができる。
　例えば、本発明の反応方法がクロスカップリング反応方法である場合には、前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、前記配位性化合物、前記不飽和炭化水素化合物、及び前記溶媒以外に、従来既知のクロスカップリング反応の促進剤等のその他の成分を用いることができる。
　促進剤としては、例えば水（純水、イオン交換水等）や、有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ未満の有機溶媒等があげられる。
　促進剤の使用量は、反応（例えば、クロスカップリング反応等）が進行する使用量であれば特に制限されない。例えば、化合物（Ｉ）、化合物（ＩＩ）、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。促進剤の使用量は、例えば、化合物（１）の当量を基準として、２０．０当量以下、好ましくは１０．０当量以下、より好ましくは９．０当量以下とすることができる。使用量の下限は特にないが、例えば０．５当量以上、好ましくは０．８当量以上、より好ましくは１．０当量以上、さらに好ましくは１．２当量以上、最も好ましくは１．４当量以上とすることができる。 <Other ingredients>
The reaction method of the present invention comprises an organic compound (A) having a melting point of 30 ° C. or higher, an organic compound (B) having a melting point of 30 ° C. or higher and reacting with an organic compound having a melting group, and a catalyst. Other ingredients such as accelerators can be used.
For example, when the reaction method of the present invention is a cross-coupling reaction method, the compound (I), the compound (II), the metal catalyst, the coordinating compound, the unsaturated hydrocarbon compound, and the above. In addition to the solvent, other components such as conventionally known cross-coupling reaction accelerators can be used.
Examples of the accelerator include water (pure water, ion-exchanged water, etc.), an organic solvent of less than 0.7 mL per 1 mmol of the organic compound (A) and the organic compound (B), and the like.
The amount of the accelerator used is not particularly limited as long as the amount used is such that the reaction (for example, a cross-coupling reaction) proceeds. For example, the compound (I), the compound (II), the metal catalyst, the base, the unsaturated hydrocarbon compound used as necessary, the type and amount of each reaction product, the reaction temperature, etc. are taken into consideration and appropriately determined. be able to. The amount of the accelerator used can be, for example, 20.0 equivalents or less, preferably 10.0 equivalents or less, and more preferably 9.0 equivalents or less, based on the equivalent of compound (1). There is no particular lower limit to the amount used, but 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. Can be.
＜反応条件＞
　本発明は、融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件において、機械的エネルギーを有機化合物（Ａ）及び有機化合物（Ｂ）に対して加えるメカノケミカル法により反応させるものである。
　本発明の反応方法は、反応原料同士を直接接触させて混合して反応させる、有機溶媒を使用しない有機合成反応方法であり、低環境負荷でありながら、反応活性が高い。このような有機合成反応方法として、メカノケミカル法が挙げられ、本発明の方法においても採用することができる。メカノケミカル法は、摩砕、せん断、衝撃、圧縮等の手段により機械的エネルギーを固体原料に対して加えることで、固体原料を活性化させて反応させる方法である。
　例えば、　本発明の反応方法がクロスカップリング反応方法である場合には、例えば、化合物（Ｉ）と、化合物（ＩＩ）を、少なくとも金属触媒及び塩基の存在下、さらに、必要に応じて使用される不飽和炭化水素化合物の存在下、有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、６０～５００℃の条件で反応させるものである。本発明においては、反応（例えば、クロスカップリング反応等）を行う際に、各成分を混合することが好ましい。 <Reaction conditions>
In the present invention, an organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are prepared in the presence of a catalyst. Under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in total and the temperature is 60 to 500 ° C., the mechanical energy is applied to the organic compound (A) and the organic compound (B). ) Is reacted by the mechanochemical method.
The reaction method of the present invention is an organic synthetic reaction method that does not use an organic solvent and reacts by directly contacting the reaction raw materials with each other and mixing them. The reaction activity is high despite the low environmental load. Examples of such an organic synthesis reaction method include a mechanochemical method, which can also be adopted in the method of the present invention. The mechanochemical method is a method of activating and reacting a solid raw material by applying mechanical energy to the solid raw material by means such as grinding, shearing, impact, and compression.
For example, when the reaction method of the present invention is a cross-coupling reaction method, for example, compound (I) and compound (II) are used, for example, in the presence of at least a metal catalyst and a base, and if necessary. In the presence of the unsaturated hydrocarbon compound, the reaction is carried out under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II), and the temperature is 60 to 500 ° C. In the present invention, it is preferable to mix each component when carrying out a reaction (for example, a cross-coupling reaction or the like).
　混合する方法は、振とう、擦り合わせ、押圧、分散、混練、解砕等の混合可能ないずれの方法を用いてもよい。混合に際しては、機械的に混合処理を行う装置を用いることが好ましい。
　そのような装置として、例えば、
　ボールミル、ロッドミル、ジェットミル、ＳＡＧミル等の粉砕機；
　回転式石臼、擂潰機（らいかいき）等の磨砕機；
　水平円筒型、Ｖ型、二重円錐型、正方立方体型、Ｓ型及び連続Ｖ型等の（水平軸回転）容器回転型混合装置；
　水平円筒型、Ｖ型、二重円錐型及びボールミル型等の（邪魔板羽根付き）容器回転型混合装置；
　ロッキング型及びクロスロータリー型等の（回転振動）容器回転型混合装置；
　リボン型、パドル型、単軸ロータ型及びバグ・ミル型等の（水平軸回転）固定容器型混合装置；
　リボン型、スクリュー型、遊星型、タービン型、高速流動型、回転円盤型及びマーラー型等の（垂直軸回転）固定容器型混合装置；
　振動ミル型及びふるい等の（振動）固定容器型混合装置；
　不均一流動層、旋回流動層、上昇管付き型及びジョットポンプ型等の（流動化）流体運動型混合装置；
　重力型及びスタティックミキサー等の（重力）流体運動型混合装置；
等からなる群より選ばれる１種以上があげられる。
　本発明においては、クロスカップリング反応が進行する限り、その方法及び使用される装置は、特に制限されることはない。
　例えば、混合装置について、坂下「粉体混合プロセス技術」色材、７７（２）、７５－８５（２００４）の表５及び図９等記載の粉体混合装置を参照することができる。
　例えば、ボールミル、二軸混練機、遊星ボールミル、ＳＰＥＸミキサーミル、二軸ボールミル等を用いることができる。 As the mixing method, any mixable method such as shaking, rubbing, pressing, dispersion, kneading, and crushing may be used. At the time of mixing, it is preferable to use an apparatus that mechanically performs the mixing process.
As such a device, for example
Crushers for ball mills, rod mills, jet mills, SAG mills, etc.;
Grinding machines such as rotary millstones and grinders;
(Horizontal axis rotation) container rotation type mixer such as horizontal cylinder type, V type, double cone type, square cube type, S type and continuous V type;
Horizontal cylindrical type, V type, double conical type, ball mill type, etc. (with baffle blades) container rotary type mixer;
(Rotating vibration) container rotary mixing device such as locking type and cross rotary type;
(Horizontal axis rotation) fixed container type mixing device such as ribbon type, paddle type, single axis rotor type and bug mill type;
(Vertical axis rotation) fixed container type mixer such as ribbon type, screw type, planet type, turbine type, high speed flow type, rotating disk type and Marler type;
(Vibration) fixed container type mixer such as vibration mill type and sieve;
(Fluidized) fluid-moving mixers such as non-uniform fluidized beds, swirling fluidized beds, riser pipe type and jot pump type;
(Gravity) fluid motion type mixer such as gravity type and static mixer;
One or more species selected from the group consisting of the above can be mentioned.
In the present invention, as long as the cross-coupling reaction proceeds, the method and the apparatus used are not particularly limited.
For example, for the mixing device, the powder mixing device described in Sakashita "Powder Mixing Process Technique" Coloring Material, 77 (2), 75-85 (2004), Table 5 and FIG. 9 can be referred to.
For example, a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-screw ball mill and the like can be used.
　本発明の反応方法（例えば、クロスカップリング反応方法等）において、混合を行う際の混合速度は、特に限定されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））、前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　例えば、本発明の反応方法（例えば、クロスカップリング反応方法等）において、各成分の混合をボールミルにより行う際には、振とうを５Ｈｚ以上、好ましくは１０Ｈｚ以上、より好ましくは２０Ｈｚ以上で行うことができる。 In the reaction method of the present invention (for example, a cross-coupling reaction method or the like), the mixing rate at the time of mixing is not particularly limited, and the organic compound (A) (for example, the compound (I)) and the organic compound are not particularly limited. (B) (For example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, the type and amount of each reaction product, the reaction temperature, etc., as appropriate. Can be determined.
For example, in the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), when mixing each component by a ball mill, shaking should be performed at 5 Hz or higher, preferably 10 Hz or higher, more preferably 20 Hz or higher. Can be done.
（反応温度）
　本発明の反応方法（例えば、クロスカップリング反応方法等）において、反応温度（混合時の反応容器内温度）は、６０～５００℃である。
　反応温度を６０～５００℃に制御する方法は特に限定されないが、化学反応を行う際に用いられる温度制御方法を用いることができる。例えば、温風を用いて反応容器内の温度を制御する方法、反応容器を所定の温度の熱媒体で覆い反応容器内の温度を制御する方法、発熱体を設けて反応容器内温度を制御する方法等があげられる。
　本発明においては、例えば、ヒートガンにより発生させた温風を反応容器に当て反応容器内の温度を制御する方法が、安全性や温度制御操作の容易性の観点等から好ましい。 (Reaction temperature)
In the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), the reaction temperature (temperature inside the reaction vessel at the time of mixing) is 60 to 500 ° C.
The method for controlling the reaction temperature to 60 to 500 ° C. is not particularly limited, but a temperature control method used when carrying out 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 having a predetermined temperature to control the temperature inside the reaction vessel, and a method of providing a heating element to control the temperature inside the reaction vessel. The method etc. can be mentioned.
In the present invention, for example, a method of applying warm air generated by a heat gun to the reaction vessel to control the temperature inside the reaction vessel is preferable from the viewpoint of safety and ease of temperature control operation.
（反応雰囲気）
　本発明の反応方法（例えば、クロスカップリング反応方法等）において、反応雰囲気（混合時の反応容器内の雰囲気）は、特に限定されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））、前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　例えば、特に雰囲気調整を行わず、大気雰囲気で行うことができる。また、使用する化合物（Ｉ）、化合物（ＩＩ）、金属触媒、塩基、及び不飽和炭化水素化合物や反応生成物に応じて、窒素、ヘリウム、ネオン、アルゴン等の不活性ガス雰囲気で行うことができる。 (Reaction atmosphere)
In the reaction method of the present invention (for example, a cross-coupling reaction method or the like), the reaction atmosphere (the atmosphere in the reaction vessel at the time of mixing) is not particularly limited, and the organic compound (A) (for example, the compound (I)) is not particularly limited. ), The organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as necessary, each type and amount of each reaction product, reaction temperature, etc. Can be determined as appropriate in consideration of.
For example, it can be performed in an atmospheric atmosphere without particularly adjusting the atmosphere. Further, depending on the compound (I), compound (II), metal catalyst, base, unsaturated hydrocarbon compound and reaction product to be used, it may be carried out in an inert gas atmosphere such as nitrogen, helium, neon or argon. can.
（反応時間）
　本発明の反応方法（例えば、クロスカップリング反応方法等）において、反応時間（混合時間；機械的手段による処理を行う時間）は、特に限定されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））、前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度等を考慮し、適宜定めることができる。
　例えば、１分以上、好ましくは３分以上、より好ましくは５分以上とすることができる。反応時間の上限は特に限定されないが、例えば、１０時間以下、好ましくは５時間以下、より好ましくは３時間以下とすることができる。
　本発明の反応方法（例えば、クロスカップリング反応方法等）は、少なくとも、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物の存在下、有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、及び６０～５００℃という条件を特に採用することで、短時間で、高収率で反応生成物を得ることができる。 (Reaction time)
In the reaction method of the present invention (for example, a cross-coupling reaction method or the like), the reaction time (mixing time; time for processing by mechanical means) is not particularly limited, and the organic compound (A) (for example, the compound) is not particularly limited. (I)), said organic compound (B) (eg, said compound (II)), metal catalyst, base, unsaturated hydrocarbon compound used as needed, each type and amount of reaction product, It can be appropriately determined in consideration of the reaction temperature and the like.
For example, it can be 1 minute or longer, preferably 3 minutes or longer, and more preferably 5 minutes or longer. The upper limit of the reaction time is not particularly limited, but can be, for example, 10 hours or less, preferably 5 hours or less, and more preferably 3 hours or less.
In the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), the abundance of the organic solvent is at least in the presence of a metal catalyst, a base, and an unsaturated hydrocarbon compound used as needed, in the presence of the compound (I). And by particularly adopting the conditions of 0.7 mL or less per 1 mmol of compound (II) and 60 to 500 ° C., a reaction product can be obtained in a short time and in a high yield.
（反応後の処理等）
　本発明の反応方法（例えば、クロスカップリング反応方法等）においては、得られた反応生成物を、必要に応じて精製することができる。反応生成物の精製方法は、特に制限されず、例えば、再結晶、カラムクロマトグラフィー、溶媒による洗浄等の方法を用いることができる。 (Processing after reaction, etc.)
In the reaction method of the present invention (for example, a cross-coupling reaction method, etc.), the obtained reaction product can be purified as needed. The method for purifying the reaction product is not particularly limited, and for example, methods such as recrystallization, column chromatography, and washing with a solvent can be used.
［反応装置］
　本発明の反応装置は、反応容器、反応容器内の収容物を撹拌する手段、及び反応容器内の温度調整手段、を少なくとも備え、
　融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法に用いる装置であって、
　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、装置である。
　メカノケミカル法により反応させる反応方法に用いる装置としては、特定の反応原料同士を直接接触させてメカノケミカル法で反応させる装置であれば、特に限定されない。例えば、摩砕、せん断、衝撃、圧縮等の手段により機械的エネルギーを、融点が３０℃以上（室温（２５℃）で固体）である原料に対して加えることで、原料を活性化させて反応させるものである。
　本発明の反応装置に備えられている反応容器は、化合物の反応装置に備えることができる各種の反応容器であれば特に限定されず、前記有機化合物（Ａ）（例えば、前記化合物（Ｉ））、前記有機化合物（Ｂ）（例えば、前記化合物（ＩＩ））、金属触媒、塩基、必要に応じて用いられる不飽和炭化水素化合物、反応生成物の各々の種類や各々の量、反応温度、雰囲気、反応圧力等を考慮して、適宜定めることができる。例えば、本発明において、機械的に混合処理を行う装置（例えば、ボールミル、二軸混練機、遊星ボールミル、ＳＰＥＸミキサーミル、二軸ボールミル等）を用いる場合には、ボールミルジャー、混練機自体等を反応容器として用いることができる。
　本発明の反応装置に備えられている反応容器内の収容物を撹拌する手段は、化合物の反応装置に備えることができる各種の撹拌手段であれば特に限定されない。本発明においては、前記［反応方法］の＜反応条件＞に記載した、機械的に混合処理を行う装置による手段を用いることができる。機械的に混合処理を行う装置としては、例えば、ボールミル、二軸混練機、遊星ボールミル、ＳＰＥＸミキサーミル、二軸ボールミル等が好ましく用いられる。 [Reactor]
The reactor of the present invention comprises at least a reaction vessel, means for stirring the contents in the reaction vessel, and means for adjusting the temperature in the reaction vessel.
An organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are mixed in the presence of an organic solvent in the presence of a catalyst. An apparatus used for a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the amount of the organic compound (A) and the organic compound (B) is 0.7 mL or less per 1 mmol in total and the temperature is 60 to 500 ° C.
One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. It is a reaction, a device.
The apparatus used for the reaction method for reacting by the mechanochemical method is not particularly limited as long as it is an apparatus in which specific reaction raw materials are brought into direct contact with each other and reacted by the mechanochemical method. For example, by applying mechanical energy to a raw material having a melting point of 30 ° C. or higher (solid at room temperature (25 ° C.)) by means such as grinding, shearing, impact, or compression, the raw material is activated and reacted. It is something that makes you.
The reaction vessel provided in the reaction apparatus of the present invention is not particularly limited as long as it is various reaction vessels that can be provided in the reaction apparatus of the compound, and the organic compound (A) (for example, the compound (I)). , The organic compound (B) (for example, the compound (II)), a metal catalyst, a base, an unsaturated hydrocarbon compound used as needed, each type and amount of each reaction product, reaction temperature, atmosphere. , Reaction pressure, etc. can be taken into consideration and appropriately determined. For example, in the present invention, when a device that mechanically performs mixing processing (for example, a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-screw ball mill, etc.) is used, the ball mill jar, the kneader itself, etc. are used. It can be used as a reaction vessel.
The means for stirring the contents in the reaction vessel provided in the reaction device of the present invention is not particularly limited as long as it is various stirring means that can be provided in the reaction device for the compound. In the present invention, the means by the apparatus for mechanically mixing treatment described in <Reaction conditions> of the above [Reaction method] can be used. As an apparatus for mechanically mixing, for example, a ball mill, a twin-screw kneader, a planetary ball mill, a SPEX mixer mill, a twin-screw ball mill and the like are preferably used.
　本発明の反応装置に備えられている反応容器内の温度調整手段は、６０～５００℃の温度下で反応（例えば、クロスカップリング反応等）が行われるように温度調整する手段であれば特に限定されない。本発明においては、前記［反応方法］の＜反応条件＞の（反応温度）に記載した温度調整手段を用いることができる。例えば、ヒートガン等による温風を用いて反応容器を加熱する方法が好ましく用いられる。
　本発明の反応装置は、さらに、計量手段、減圧又は加圧手段、雰囲気調整手段（気体導入又は排出手段）、各種成分の投入手段、各種成分・反応生成物の取出手段、精製手段、分析手段等の、化合物の反応装置に備えることができる各種の手段を備えていてもよい。 The temperature adjusting means in the reaction vessel provided in the reaction apparatus of the present invention is particularly limited as long as it is a means for adjusting the temperature so that the reaction (for example, a cross-coupling reaction) is carried out at a temperature of 60 to 500 ° C. Not limited. In the present invention, the temperature adjusting means described in (Reaction temperature) of <Reaction condition> of the above [Reaction method] can be used. For example, a method of heating the reaction vessel using warm air from a heat gun or the like is preferably used.
The reaction apparatus of the present invention further includes a measuring means, a depressurizing or pressurizing means, an atmosphere adjusting means (gas introduction or discharging means), a means for inputting various components, a means for taking out various components / reaction products, a means for purifying, and a means for analysis. It may be provided with various means that can be provided in the reaction apparatus of the compound, such as.
［式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される化合物及びその製造方法］
　本発明の反応方法、特に、クロスカップリング反応方法を用いることで、式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される新規化合物を製造することができる。
Figure JPOXMLDOC01-appb-C000020
  （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。） [Compound represented by either formula (IIIa) or (IIIb) and a method for producing the same]
By using the reaction method of the present invention, particularly the cross-coupling reaction method, a novel compound represented by either the formula (IIIa) or (IIIb) can be produced.
Figure JPOXMLDOC01-appb-C000020
 (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
　式(IIIａ)において、ｐは５～３０の整数であり、好ましくは５～２０、より好ましく
は５～１５、さらに好ましくは５～１０である。
　式(IIIｂ)において、ｑは５～３０の整数であり、好ましくは５～２０、より好ましく
は５～１５、さらに好ましくは５～１０である。
　式(IIIａ)又は(IIIｂ)のいずれかで表される化合物の製造方法としては、具体的には、例えば、実施例１～４に記載した方法があげられる。
　式(IIIａ)又は(IIIｂ)のいずれかで表される化合物は、導電性プラスチックとして知られているポリチオフェン又はポリフェニレンの低重合物に相当するものであるが、このような低分子量（低核体）の化合物を精密に合成する方法はこれまで知られていなかった。
　これらの化合物は、有機発光ダイオード（ＯＬＥＤ）や有機半導体材料、導電性有機材料の合成用原料化合物、導電性有機材料用の電導度制御材等の用途において有用である。 In formula (IIIa), p is an integer of 5 to 30, preferably 5 to 20, more preferably 5 to 15, and even more preferably 5 to 10.
In formula (IIIb), q is an integer of 5 to 30, preferably 5 to 20, more preferably 5 to 15, and even more preferably 5 to 10.
Specific examples of the method for producing the compound represented by the formula (IIIa) or (IIIb) include the methods described in Examples 1 to 4.
The compound represented by either the formula (IIIa) or (IIIb) corresponds to a low polymer of polythiophene or polyphenylene known as a conductive plastic, and has such a low molecular weight (low nuclei). ) Has not been known so far as a method for precisely synthesizing the compound.
These compounds are useful in applications such as organic light emitting diodes (OLEDs), organic semiconductor materials, raw material compounds for synthesizing conductive organic materials, and conductivity control materials for conductive organic materials.
　以下、本発明を実施例及び比較例により詳細に説明する。これらの実施例は、本発明の一態様にすぎない。本発明は、これらの例によって何ら限定されるものではない。
　本実施例で使用した化合物は、特に記載しない限り、市販品をそのまま精製することなく使用した。
　本実施例で使用した化合物（Ｉ）、化合物（ＩＩ）、配位性化合物及び反応生成物は、それぞれ下記のとおりである。なお、これらの構造式中、Ｍｅはメチル基、Ｅｔはエチル基、ｉＰｒ又はｉ－Ｐｒはイソプロピル基、ｔＢｕ又はｔ－Ｂｕはターシャリーブチル基、Ｂ(Ｐｉｎ)はボロン酸ピナコールエステル基、ＯＴｆはトリフルオロメタンスルホニル基をそれぞれ示す。 Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. These examples are only one aspect of the present invention. The present invention is not limited to these examples.
Unless otherwise specified, the compounds used in this example were used as they were without purification.
The compounds (I), compound (II), coordinating compounds and reaction products used in this example are as follows. In these structural formulas, Me is a methyl group, Et is an ethyl group, iPr or i-Pr is an isopropyl group, tBu or t-Bu is a tertiary butyl group, B (Pin) is a boronic acid pinacol ester group, and OTf. Represent each trifluoromethanesulfonyl group.
［化合物（Ｉ）］
Figure JPOXMLDOC01-appb-C000021
Figure JPOXMLDOC01-appb-I000022
[Compound (I)]
Figure JPOXMLDOC01-appb-C000021
Figure JPOXMLDOC01-appb-I000022
［化合物（ＩＩ）］
Figure JPOXMLDOC01-appb-C000023
 [Compound (II)]
Figure JPOXMLDOC01-appb-C000023
［配位性化合物］
Figure JPOXMLDOC01-appb-C000024
 [Coordinating compound]
Figure JPOXMLDOC01-appb-C000024
［反応生成物］
Figure JPOXMLDOC01-appb-C000025
Figure JPOXMLDOC01-appb-C000026
  
Figure JPOXMLDOC01-appb-C000027
 [Reaction product]
Figure JPOXMLDOC01-appb-C000025
Figure JPOXMLDOC01-appb-C000026
Figure JPOXMLDOC01-appb-C000027
　実施例及び比較例において、ボールミルを用いてクロスカップリング反応を行う際には、ステンレス製ボールミルジャーに各試薬を投入し、ヴァーダー・サイエンティフィック社（Verder Scientific Co.,Ltd.（旧レッチェ社（Retsch））製のボールミルＭＭ４００型を使用した。
　ボールミルを用いてクロスカップリング反応を行う際の加熱は、ヒートガン（Takagi社製,HG-1450B）でボールミルジャーの外側を所定の温度で加熱した。
　ヒートガンの設定温度と、ボールミルジャー内部の温度（反応系の温度）の関係をThermographic imageを用いて確認したところ、次のとおりであった。 In Examples and Comparative Examples, when performing a cross-coupling reaction using a ball mill, each reagent is charged into a stainless steel ball mill jar, and Verder Scientific Co., Ltd. (formerly Lecce) is used. (Retsch)) ball mill MM400 type was used.
For heating when performing the cross-coupling reaction using a ball mill, the outside of the ball mill jar was heated at a predetermined temperature with a heat gun (manufactured by Takagi Co., Ltd., HG-1450B).
When the relationship between the set temperature of the heat gun and the temperature inside the ball miller (temperature of the reaction system) was confirmed using a Thermographic image, it was as follows.
Figure JPOXMLDOC01-appb-T000028
Figure JPOXMLDOC01-appb-T000028
［実施例１］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－１）を０．１５ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－１）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して２．４　ｅｑｉｖ）、金属触媒として酢酸パラジウム（ＩＩ）（Ｐｄ（ＯＡｃ）２）を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０２２５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてフッ化セシウム（ＣｓＦ）を０．９ｍｍｏｌ（化合物（Ｉ）に対して３．０　ｅｑｉｖ）、反応促進剤として水を１．０８ｍｍｏｌ（化合物（Ｉ）に対して７．２　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら９０分間振とうして撹拌（３０Ｈｚ）しクロスカップリング反応を行った。
Figure JPOXMLDOC01-appb-C000029
 [Example 1]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of (I-1) as compound (I) and (II) as compound (II) under air. -1) was 0.36 mmol (2.4 equiv with respect to compound (I)), and palladium (II) acetate (Pd (OAc) 2 ) as a metal catalyst was 0.015 mmol (10 mol% with respect to compound (I)). ), SPhos as a coordinating compound 0.0225 mmol (15 mol% with respect to compound (I)), cesium fluoride (CsF) as a base 0.9 mmol (3.0 equiv with respect to compound (I)), 1.08 mmol of water (7.2 eq with respect to compound (I)) was added as a reaction accelerator, and 0.2 μL / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was shaken for 90 minutes while heating with a heat gun set at 250 ° C. to stir (30 Hz) to perform a cross-coupling reaction.
Figure JPOXMLDOC01-appb-C000029
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで対応するクロスカップリング反応生成物（ＩＩＩ－１）を単離した。単離収率（Ｉｓｏｌａｔｅｄ　ｙｉｅｌｄ）は９６％であった。
　反応生成物（ＩＩＩ－１）について、ＩＲ　ａｎａｌｙｓｉｓ、ＰＸＲＤ　ａｎａｌｙｓｉｓ及びＥＩ－ＭＳ　ａｎａｌｙｓｉｓを行った。それぞれの結果を図１～図３に示す。 After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding cross-coupling reaction product (III-1). The isolated yield was 96%.
IR analysis, PXRD analysis and EI-MS analysis were performed on the reaction product (III-1). The respective results are shown in FIGS. 1 to 3.
［比較例１］
　化合物（Ｉ）として（Ｉ－１）を、化合物（ＩＩ）として（ＩＩ－１）を、金属触媒としてＰｄ（ＯＡｃ）２を、配位性化合物としてＳＰｈｏｓを、及び塩基としてＣｓＦを、それぞれ実施例１と同量となるように反応容器に入れ、さらに化合物（Ｉ）の濃度が０．１Ｍ（０．１ｍｏｌ／Ｌ）となるようにトルエンを反応容器に加えて混合した。得られた混合液を１２０℃で２４時間加熱し、クロスカップリング反応を行った。反応後、実施例１と同様にして反応生成物（ＩＩＩ－１）の単離を試みたが、反応生成物（ＩＩＩ－１）の生成を確認できず、ＮＭＲ収率（ＮＭＲ　ｙｉｅｌｄ）収率は０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）と判断された。 [Comparative Example 1]
(I-1) was used as compound (I), (II-1) was used as compound (II), Pd (OAc) 2 was used as a metal catalyst, SPhos was used as a coordinating compound, and CsF was used as a base. The mixture was placed in a reaction vessel so as to have the same amount as in Example 1, and toluene was further added to the reaction vessel so that the concentration of compound (I) was 0.1 M (0.1 mol / L) and mixed. The obtained mixed solution was heated at 120 ° C. for 24 hours to carry out a cross-coupling reaction. After the reaction, an attempt was made to isolate the reaction product (III-1) in the same manner as in Example 1, but the formation of the reaction product (III-1) could not be confirmed, and the NMR yield (NMR yield) yield. Was determined to be 0% (nr; No Reaction).
［実施例２～４］
　化合物（Ｉ）及び化合物（ＩＩ）として表２に示すものを用いたほかは実施例１と同様にして、クロスカップリング反応を行い表２に示す対応する反応生成物（ＩＩＩ）を得た。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表２に併せて示す。 [Examples 2 to 4]
A cross-coupling reaction was carried out in the same manner as in Example 1 except that the compounds shown in Table 2 were used as the compound (I) and the compound (II) to obtain the corresponding reaction product (III) shown in Table 2. The types of the corresponding reaction product (III) and the isolated yields thereof are also shown in Table 2.
［比較例２～４］
　化合物（Ｉ）及び化合物（ＩＩ）として表２に示すものを用いたほかは比較例１と同様にして、クロスカップリング反応を行うとともに表２に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。対応する反応生成物（ＩＩＩ）の種類及びそのＮＭＲ収率を表２に併せて示す。 [Comparative Examples 2 to 4]
The cross-coupling reaction was carried out in the same manner as in Comparative Example 1 except that the compounds shown in Table 2 were used as the compound (I) and the compound (II), and the NMR yield of the corresponding reaction product (III) shown in Table 2 was obtained. I asked for the rate. The types of the corresponding reaction products (III) and their NMR yields are also shown in Table 2.
Figure JPOXMLDOC01-appb-T000030
Figure JPOXMLDOC01-appb-T000030
［実施例５］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－３）を０．１５ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－５）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して２．４　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０２２５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して６．０　ｅｑｉｖ）、反応促進剤として水を１．０８ｍｍｏｌ（化合物（Ｉ）に対して７．２　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら９０分間振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで対応する反応生成物（ＩＩＩ－５）を単離した。単離収率は９９％であった。結果を表３に示す。 [Example 5]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of (I-3) as compound (I) and (II) as compound (II) under air. -5) as 0.36 mmol (2.4 equiv with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (10 mol% with respect to compound (I)), as a coordinating compound. SPhos is 0.0225 mmol (15 mol% with respect to compound (I)), CsF as a base is 0.9 mmol (6.0 eq with respect to compound (I)), and water is 1.08 mmol (compound (I)) as a reaction accelerator. 7.2 equiv) to I), 0.2 μL / mg of 1,5-cyclooctadien as an unsaturated hydrocarbon compound was added. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was shaken for 90 minutes while heating with a heat gun set at 250 ° C. to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III-5). The isolated yield was 99%. The results are shown in Table 3.
［比較例５］
　ヒートガンでジャーを加熱しなかったほかは、実施例５と同様にして、クロスカップリング反応を行うとともに反応生成物（ＩＩＩ－５）のＮＭＲ収率を求めたが、反応生成物（ＩＩＩ－５）の生成を確認できず、ＮＭＲ収率は０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）と判断された。結果を表３に示す。 [Comparative Example 5]
The cross-coupling reaction was carried out and the NMR yield of the reaction product (III-5) was determined in the same manner as in Example 5 except that the jar was not heated with a heat gun. ) Could not be confirmed, and the NMR yield was determined to be 0% (nr; No Reaction). The results are shown in Table 3.
［実施例６～２９］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表３又は表４に示す化合物（Ｉ）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、表３又は表４に示す化合物（ＩＩ）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．００９ｍｍｏｌ（化合物（Ｉ）に対して３ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０１３５ｍｍｏｌ（化合物（Ｉ）に対して４．５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して３．０　ｅｑｉｖ）、反応促進剤として水を１．１１ｍｍｏｌ（化合物（Ｉ）に対して３．７　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、表３又は表４に示す温度に設定したヒートガンでジャーを加熱しながら表３又は表４に示す時間振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで表３又は表４に示す対応する反応生成物（ＩＩＩ）を単離した。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表３又は表４に示す。 [Examples 6 to 29]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, in air, add 0.3 mmol (1.0 eq) of compound (I) shown in Table 3 or 4 to Table 3 or Table 4. Compound (II) shown is 0.36 mmol (1.2 equiv with respect to compound (I)), Pd (OAc) 2 as a metal catalyst is 0.009 mmol (3 mol% with respect to compound (I)), and coordination. 1. 35 mmol of SPhos as a compound (4.5 mol% with respect to compound (I)), 0.9 mmol of CsF as a base (3.0 eq with respect to compound (I)), and water as a reaction accelerator. 11 mmol (3.7 evi with respect to compound (I)) and 0.2 μL / mg of 1,5-cyclooctadien as an unsaturated hydrocarbon compound were added. Close the lid of the ball mill jar, attach it to the ball mill, and stir (30 Hz) with shaking for the time shown in Table 3 or 4 while heating the jar with a heat gun set to the temperature shown in Table 3 or Table 4 to cross cup. A ring reaction was performed.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III) shown in Table 3 or Table 4. The type of the corresponding reaction product (III) and the isolated yield thereof are shown in Table 3 or Table 4.
［実施例２９～３１］
　配位性化合物として、ＳＰｈｏｓに代えてＤａｖａＰｈｏｓ（２－ジシクロヘキシルホスフィノ－２′－（Ｎ，Ｎ－ジメチルアミノ）ビフェニル）を化合物（Ｉ）に対して４．５ｍｏｌ％用いたほかは、実施例２１と同様にクロスカップリング反応を行うとともに反応生成物（ＩＩＩ－１９）の単離収率を求めた。結果を表４に示す。 [Examples 29 to 31]
Examples except that DavaPhos (2-dicyclohexylphosphino-2'-(N, N-dimethylamino) biphenyl) was used in place of SPhos in an amount of 4.5 mol% with respect to compound (I) as a coordinating compound. The cross-coupling reaction was carried out in the same manner as in No. 21, and the isolated yield of the reaction product (III-19) was determined. The results are shown in Table 4.
［比較例６～２８］
　化合物（Ｉ）及び化合物（ＩＩ）として表３又は表４に示すものを用い、ヒートガンでジャーを加熱しなかったほかは、実施例６～２９と同様にし、クロスカップリング反応を行うとともに表３又は表４に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。対応する反応生成物（ＩＩＩ）の種類及びそのＮＭＲ収率を表３又は表４に示す。なお、反応生成物（ＩＩＩ）の生成を確認できない場合は、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 6 to 28]
The compound (I) and the compound (II) shown in Table 3 or Table 4 were used, and the same as in Examples 6 to 29 except that the jar was not heated with a heat gun, and the cross-coupling reaction was carried out and Table 3 was performed. Alternatively, the NMR yield of the corresponding reaction product (III) shown in Table 4 was determined. The type of the corresponding reaction product (III) and its NMR yield are shown in Table 3 or Table 4. When the formation of the reaction product (III) could not be confirmed, the NMR yield was set to 0% (nr; No Reaction).
［実施例３２］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－６）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－１１）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）、金属触媒及び配位性化合物としてＳＰｈｏｓ　Ｐｄ　Ｇ３を０．００９ｍｍｏｌ（化合物（Ｉ）に対して３ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して３．０　ｅｑｉｖ）、反応促進剤として水を１．１１ｍｍｏｌ（化合物（Ｉ）に対して３．７　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら６０分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで対応する反応生成物（ＩＩＩ－２１）を単離した。単離収率は７９％であった。結果を表４に示す。 [Example 32]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-6) as compound (I) and (II) as compound (II) under air. -11) as 0.36 mmol (1.2 equiv with respect to compound (I)), SPhos Pd G3 as a metal catalyst and coordinating compound 0.009 mmol (3 mol% with respect to compound (I)) as a base. CsF is 0.9 mmol (3.0 eq with respect to compound (I)), water is 1.11 mmol (3.7 evi with respect to compound (I)) as a reaction accelerator, and 1, as an unsaturated hydrocarbon compound, 1. 5-Cyclooctadiene was added at 0.2 μL / mg. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was heated by a heat gun set at 250 ° C. and shaken for 60 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III-21). The isolated yield was 79%. The results are shown in Table 4.
［比較例２９］
　ヒートガンでジャーを加熱しなかったほかは実施例３２と同様にして、クロスカップリング反応を行うとともに反応生成物（ＩＩＩ－２１）のＮＭＲ収率を求めた。反応生成物（ＩＩＩ－２１）の生成を確認できず、ＮＭＲ収率は０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）と判断された。結果を表４に示す。 [Comparative Example 29]
The cross-coupling reaction was carried out and the NMR yield of the reaction product (III-21) was determined in the same manner as in Example 32 except that the jar was not heated with a heat gun. The formation of the reaction product (III-21) could not be confirmed, and the NMR yield was judged to be 0% (nr; No Reaction). The results are shown in Table 4.
Figure JPOXMLDOC01-appb-T000031
Figure JPOXMLDOC01-appb-T000031
Figure JPOXMLDOC01-appb-T000032
Figure JPOXMLDOC01-appb-T000032
［実施例３３～３７］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表５に示す化合物（Ｉ）を０．１５ｍｍｏｌ（１．０　ｅｑｉｖ）、表５に示す化合物（ＩＩ）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して２．４　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０２２５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して６．０　ｅｑｉｖ）、反応促進剤として水を１．０８ｍｍｏｌ（化合物（Ｉ）に対して７．２　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら５分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで表５に示す対応する反応生成物（ＩＩＩ）を単離した。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表５に併せて示す。 [Examples 33 to 37]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of the compound (I) shown in Table 5 and the compound (II) shown in Table 5 were added to the compound (I) shown in Table 5. 0.36 mmol (2.4 equiv with respect to compound (I)), 0.015 mmol of Pd (OAc) 2 as a metal catalyst (10 mol% with respect to compound (I)), and SPhos as a coordinating compound. 0225 mmol (15 mol% relative to compound (I)), 0.9 mmol CsF as base (6.0 evi relative to compound (I)), 1.08 mmol water as reaction accelerator (relative to compound (I)) 7.2 eq), 0.2 μL / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was heated by a heat gun set at 250 ° C. and shaken for 5 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III) shown in Table 5. The types of the corresponding reaction product (III) and the isolated yields thereof are also shown in Table 5.
［比較例３０～３３］
　化合物（Ｉ）及び化合物（ＩＩ）として表５に示すものを用い、ヒートガンでジャーを加熱せず、９０分振とうして撹拌（３０Ｈｚ）したほかは、実施例３３～３７と同様にして、クロスカップリング反応を行うとともに表５に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。結果を表５に示す。なお、対応する反応生成物（ＩＩＩ）の生成を確認できない場合は、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 30 to 33]
Using the compounds shown in Table 5 as the compound (I) and the compound (II), the jar was not heated with a heat gun, and the mixture was stirred by shaking for 90 minutes (30 Hz) in the same manner as in Examples 33 to 37. The cross-coupling reaction was carried out and the NMR yield of the corresponding reaction product (III) shown in Table 5 was determined. The results are shown in Table 5. When the formation of the corresponding reaction product (III) could not be confirmed, the NMR yield was set to 0% (nr; No Reaction).
Figure JPOXMLDOC01-appb-T000033
Figure JPOXMLDOC01-appb-T000033
［実施例３８～４３］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表６に示す化合物（Ｉ）を０．１５ｍｍｏｌ（１．０ｅｑｉｖ）、表６に示す化合物（ＩＩ）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して２．４ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０２２５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して６．０ｅｑｉｖ）、反応促進剤として水を１．０８ｍｍｏｌ（化合物（Ｉ）に対して７．２ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら５分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで表６に示す対応する反応生成物（ＩＩＩ）を単離した。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表６に示す。 [Examples 38 to 43]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of the compound (I) shown in Table 6 and 0 of the compound (II) shown in Table 6 were placed in an air. .36 mmol (2.4 equiv with respect to compound (I)), 0.015 mmol of Pd (OAc) 2 as a metal catalyst (10 mol% with respect to compound (I)), and 0.0225 mmol of SPhos as a coordinating compound (10 mol% with respect to compound (I)). 7. 2eqiv), 0.2 μL / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was heated by a heat gun set at 250 ° C. and shaken for 5 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III) shown in Table 6. The types of the corresponding reaction product (III) and the isolated yields thereof are shown in Table 6.
［比較例３４、３６～３９、４１］
　化合物（Ｉ）及び化合物（ＩＩ）として表６に示すものを用い、ヒートガンでジャーを加熱しなかったほかは、実施例３８～４３と同様にして、クロスカップリング反応を行うとともに表６に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。対応する反応生成物（ＩＩＩ）の種類及びそのＮＭＲ収率を表６に示す。なお、対応する反応生成物（ＩＩＩ）の生成を確認できない場合は、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 34, 36-39, 41]
The cross-coupling reaction was carried out and shown in Table 6 in the same manner as in Examples 38 to 43 except that the compounds (I) and (II) shown in Table 6 were used and the jar was not heated with a heat gun. The NMR yield of the corresponding reaction product (III) was determined. The types of the corresponding reaction products (III) and their NMR yields are shown in Table 6. When the formation of the corresponding reaction product (III) could not be confirmed, the NMR yield was set to 0% (nr; No Reaction).
［比較例３５、４０、４２］
　化合物（Ｉ）及び化合物（ＩＩ）として表６に示す化合物を、金属触媒としてＰｄ（ＯＡｃ）２を、配位性化合物としてＳＰｈｏｓを、及び塩基としてＣｓＦを、それぞれ実施例３８～４３と同量となるように反応容器に入れ、さらに化合物（Ｉ）の濃度が０．１Ｍ（０．１ｍｏｌ／Ｌ）となるようにトルエンを反応容器に加えて混合した。得られた混合液を１２０℃で２４時間加熱し、クロスカップリング反応を行うとともに表６に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表６に示す。なお、対応する反応生成物（ＩＩＩ）の生成を確認できない場合は、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 35, 40, 42]
The compounds shown in Table 6 as compound (I) and compound (II), Pd (OAc) 2 as a metal catalyst, SPhos as a coordinating compound, and CsF as a base, respectively, in the same amounts as in Examples 38 to 43. The compound (I) was placed in a reaction vessel so as to have a concentration of 0.1 M (0.1 mol / L), and toluene was added to the reaction vessel and mixed. The obtained mixed solution was heated at 120 ° C. for 24 hours to carry out a cross-coupling reaction, and the NMR yield of the corresponding reaction product (III) shown in Table 6 was determined. The types of the corresponding reaction product (III) and the isolated yields thereof are shown in Table 6. When the formation of the corresponding reaction product (III) could not be confirmed, the NMR yield was set to 0% (nr; No Reaction).
Figure JPOXMLDOC01-appb-T000034
Figure JPOXMLDOC01-appb-T000034
［実施例４４～５０］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表７に示す化合物（Ｉ）を０．１５ｍｍｏｌ（１．０ｅｑｉｖ）、表７に示す化合物（ＩＩ）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して２．４ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０２２５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して６．０ｅｑｉｖ）、反応促進剤として水を１．０８ｍｍｏｌ（化合物（Ｉ）に対して７．２ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら５分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで表７に示す対応する反応生成物（ＩＩＩ）を単離した。対応する反応生成物（ＩＩＩ）の種類及びその単離収率を表７に示す。 [Examples 44 to 50]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.15 mmol (1.0 eq) of the compound (I) shown in Table 7 and 0 of the compound (II) shown in Table 7 were placed in an air. .36 mmol (2.4 equiv with respect to compound (I)), 0.015 mmol of Pd (OAc) 2 as a metal catalyst (10 mol% with respect to compound (I)), and 0.0225 mmol of SPhos as a coordinating compound (10 mol% with respect to compound (I)). 7. 2eqiv), 0.2 μL / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was heated by a heat gun set at 250 ° C. and shaken for 5 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III) shown in Table 7. The types of the corresponding reaction product (III) and the isolated yields thereof are shown in Table 7.
［比較例４３～４９］
　化合物（Ｉ）及び化合物（ＩＩ）として表７に示す化合物を、金属触媒としてＰｄ（ＯＡｃ）２を、配位性化合物としてＳＰｈｏｓを、及び塩基としてＣｓＦを、それぞれ実施例４４～５５と同量となるように反応容器に入れ、さらに化合物（Ｉ）の濃度が０．１Ｍ（０．１ｍｏｌ／Ｌ）となるようにトルエンを反応容器に加えて混合した。得られた混合液を１２０℃で２４時間加熱し、クロスカップリング反応を行うとともに表７に示す対応する反応生成物（ＩＩＩ）のＮＭＲ収率を求めた。対応する反応生成物（ＩＩＩ）の種類及びそのＮＭＲ収率を表７に併せて示す。なお、対応する反応生成物（ＩＩＩ）の生成を確認できない場合は、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 43 to 49]
The compounds shown in Table 7 as compound (I) and compound (II), Pd (OAc) 2 as a metal catalyst, SPhos as a coordinating compound, and CsF as a base are in the same amounts as in Examples 44 to 55, respectively. The compound (I) was placed in a reaction vessel so as to have a concentration of 0.1 M (0.1 mol / L), and toluene was added to the reaction vessel and mixed. The obtained mixed solution was heated at 120 ° C. for 24 hours to carry out a cross-coupling reaction, and the NMR yield of the corresponding reaction product (III) shown in Table 7 was determined. The types of the corresponding reaction products (III) and their NMR yields are also shown in Table 7. When the formation of the corresponding reaction product (III) could not be confirmed, the NMR yield was set to 0% (nr; No Reaction).
Figure JPOXMLDOC01-appb-T000035
Figure JPOXMLDOC01-appb-T000035
［実施例４８～５０］
　直径５　ｍｍのステンレス製のボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－２３）（ｐｉｇｍｅｎｔ　ｖｉｏｌｅｔ　２３）を０．１ｍｍｏｌ（１．０ｅｑｕｉｖ）、表８に示す化合物（ＩＩ）を０．２４ｍｍｏｌ（２．４ｅｑｕｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１ｍｍｏｌ（化合物（Ｉ）に対して１０ｍｏｌ％）、配位性化合物としてＳＰｈｏｓを０．０１５ｍｍｏｌ（化合物（Ｉ）に対して１５ｍｏｌ％）、塩基としてＣｓＦを０．６ｍｍｏｌ（化合物（Ｉ）に対して６．０ｅｑｕｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら９０分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、濾過することで無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで表８に示す対応するカップリング生成物を単離した。なお、実施例４８では、反応生成物（ＩＩＩ－４２）が２６．９ｍｇ（０．０３ｍｍｏｌ）得られ、単離収率は３０％であった。実施例４９及び５０の各反応生成物の単離収率は、表８に示すとおりである。 [Examples 48 to 50]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.1 mmol (1.0 equiv) of (I-23) (pigment violet 23) as compound (I) was added to the table under air. Compound (II) shown in 8 was 0.24 mmol (2.4 equiv), Pd (OAc) 2 was 0.01 mmol (10 mol% with respect to compound (I)) as a metal catalyst, and SPhos was 0. 015 mmol (15 mol% with respect to compound (I)), 0.6 mmol of CsF as base (6.0 equiv with respect to compound (I)), 0.2 μL of 1,5-cyclooctadiene as unsaturated hydrocarbon compound / Mg was added. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was heated by a heat gun set at 250 ° C. and shaken for 90 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the inorganic salt was removed by filtration. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the corresponding coupling products shown in Table 8. In Example 48, 26.9 mg (0.03 mmol) of the reaction product (III-42) was obtained, and the isolated yield was 30%. The isolated yields of each reaction product of Examples 49 and 50 are as shown in Table 8.
［比較例４７、４９、５１］
　化合物（Ｉ）及び化合物（ＩＩ）として表８に示す化合物を用い、ヒートガンでジャーを加熱しなかったほかは、実施例４８～５０と同様にし、クロスカップリング反応を行った。表８に示す対応する反応生成物（ＩＩＩ）の生成を１Ｈ－ＮＭＲで確認できなかった。なお、表８では、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 47, 49, 51]
The compounds shown in Table 8 were used as compound (I) and compound (II), and the cross-coupling reaction was carried out in the same manner as in Examples 48 to 50 except that the jar was not heated with a heat gun. The formation of the corresponding reaction product (III) shown in Table 8 could not be confirmed by 1H-NMR. In Table 8, the NMR yield was set to 0% (nr; No Reaction).
［比較例４８、５０、５２］
　化合物（Ｉ）及び化合物（ＩＩ）として表８に示す化合物を、金属触媒としてＰｄ（ＯＡｃ）２を、配位性化合物としてＳＰｈｏｓを、及び塩基としてＣｓＦを、それぞれ実施例４８～５０と同量となるように反応容器に入れ、さらに化合物（Ｉ）の濃度が０．１Ｍ（０．１ｍｏｌ／Ｌ）となるようにトルエンを反応容器に加えて混合した。得られた混合液を１２０℃で２４時間加熱し、クロスカップリング反応を行った。表８に示す対応する反応生成物（ＩＩＩ）の生成を１Ｈ－ＮＭＲで確認できなかった。なお、表８では、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 48, 50, 52]
The compounds shown in Table 8 as compound (I) and compound (II), Pd (OAc) 2 as a metal catalyst, SPhos as a coordinating compound, and CsF as a base are in the same amounts as in Examples 48 to 50, respectively. The compound (I) was placed in a reaction vessel so as to have a concentration of 0.1 M (0.1 mol / L), and toluene was added to the reaction vessel and mixed. The obtained mixed solution was heated at 120 ° C. for 24 hours to carry out a cross-coupling reaction. The formation of the corresponding reaction product (III) shown in Table 8 could not be confirmed by 1H-NMR. In Table 8, the NMR yield was set to 0% (nr; No Reaction).
Figure JPOXMLDOC01-appb-T000036
Figure JPOXMLDOC01-appb-T000036
［実施例５１～５５］
　直径５ｍｍのステンレス製のボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表９に示す化合物（Ｉ）を０．３ｍｍｏｌ（１．０ｅｑｕｉｖ）、表９に示す化合物（ＩＩ）を０．３ｍｍｏｌ（１．０ｅｑｕｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、配位性化合物としてｔ－Ｂｕ３Ｐ・ＨＢＦ４（トリ－ｔｅｒｔ－ブチルホスホニウムテトラフルオロボラート）を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、塩基としてＮａ（Ｏ－ｔｅｒｔ－Ｂｕ）（ナトリウム－ｔｅｒｔ－ブトキシド）を０．４５ｍｍｏｌ（化合物（Ｉ）に対して１．５ｅｑｕｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２００℃に設定したヒートガンでジャーを加熱しながら３０分間振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、濾過することで無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、クルード混合物をシリカゲルカラムクロマトグラフィーで精製することで対応する反応生成物（ＩＩＩ）を単離した。なお、実施例５１では、反応生成物（ＩＩＩ－４５）が１２６．０ｍｇ（０．２９２ｍｍｏｌ）得られ、単離収率は９７％であった。実施例５２～５５の各反応生成物の種類及びその単離収率は、表９に示すとおりである。 [Examples 51 to 55]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 equiv) of compound (I) shown in Table 9 and compound (II) shown in Table 9 were placed under air. 0.3 mmol (1.0 equiv), 0.015 mmol of Pd (OAc) 2 as a metal catalyst (5 mol% with respect to compound (I)), and t-Bu 3 P. HBF 4 (tri-tert) as a coordinating compound. -Butylphosphonium tetrafluoroborate) is 0.015 mmol (5 mol% with respect to compound (I)) and Na (O-tert-Bu) (sodium-tert-butoxide) as a base is 0.45 mmol (compound (I)). 1,5-Cyclooctadiene was added as an unsaturated hydrocarbon compound in an amount of 1.5 equiv) at 0.2 μL / mg. The lid of the ball mill jar was closed, attached to the ball mill, and the jar was shaken for 30 minutes while heating with a heat gun set at 200 ° C. to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the inorganic salt was removed by filtration. After removing dichloromethane with an evaporator, the crude mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III). In Example 51, 126.0 mg (0.292 mmol) of the reaction product (III-45) was obtained, and the isolated yield was 97%. The types of each reaction product of Examples 52 to 55 and the isolated yields thereof are as shown in Table 9.
［比較例５３～５７］
　化合物（Ｉ）及び化合物（ＩＩ）として表９に示すものを用い、ヒートガンでジャーを加熱せず、９０分振とうして撹拌（３０Ｈｚ）したほかは、実施例５１～５５と同様にし、クロスカップリング反応を行った。表９に示す対応する反応生成物（ＩＩＩ）の生成を１Ｈ－ＮＭＲで確認できなかった。なお、表９では、ＮＭＲ収率を０％（ｎ．ｒ；Ｎｏ　Ｒｅａｃｔｉｏｎ）とした。 [Comparative Examples 53 to 57]
Using the compounds shown in Table 9 as the compound (I) and the compound (II), the jar was not heated with a heat gun, and the mixture was stirred by shaking for 90 minutes (30 Hz) in the same manner as in Examples 51 to 55, and crossed. A coupling reaction was performed. The formation of the corresponding reaction product (III) shown in Table 9 could not be confirmed by 1H-NMR. In Table 9, the NMR yield was set to 0% (nr; No Reaction).
Figure JPOXMLDOC01-appb-T000037
Figure JPOXMLDOC01-appb-T000037
［実施例５６］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－１３）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－５）を０．３６ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．００９ｍｍｏｌ（化合物（Ｉ）に対して３ｍｏｌ％）、配位性化合物としてＤａｖａＰｈｏｓを０．０１３５ｍｍｏｌ（化合物（Ｉ）に対して４．５ｍｏｌ％）、塩基としてＣｓＦを０．９ｍｍｏｌ（化合物（Ｉ）に対して３．０　ｅｑｉｖ）、反応促進剤として水を１．１１ｍｍｏｌ（化合物（Ｉ）に対して３．７　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、表１０に示す温度に設定したヒートガンでジャーを加熱しながら９９分間振とうして撹拌（２５Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、ショートシリカゲルカラムクロマトグラフィーに通して触媒及び無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、反応混合物をシリカゲルカラムクロマトグラフィーで精製することで反応生成物（ＩＩＩ－７）を単離した。単離収率は６６％であった。 [Example 56]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-13) as compound (I) and (II) as compound (II) under air. -5) was 0.36 mmol (1.2 equiv with respect to compound (I)), Pd (OAc) 2 was 0.009 mmol (3 mol% with respect to compound (I)) as a metal catalyst, and as a coordinating compound. DavaPhos is 0.0135 mmol (4.5 mol% with respect to compound (I)), CsF as a base is 0.9 mmol (3.0 eq with respect to compound (I)), and water is 1.11 mmol (with respect to compound (I)) as a reaction accelerator. 3.7 evi) was added to compound (I), and 0.2 μL / mg of 1,5-cyclooctadiene was added as an unsaturated hydrocarbon compound. The lid of the ball mill jar was closed, and the jar was attached to the ball mill. The jar was heated by a heat gun set to the temperature shown in Table 10 and shaken for 99 minutes to stir (25 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the catalyst and the inorganic salt were removed by passing through short silica gel column chromatography. After removing dichloromethane with an evaporator, the reaction mixture was purified by silica gel column chromatography to isolate the reaction product (III-7). The isolated yield was 66%.
［実施例５７］
　化合物（Ｉ）として（Ｉ－５）を用いたほかは、実施例５６と同様にして反応を行い、反応生成物（ＩＩＩ－７）を得た。単離収率は８８％であった。
［実施例５８］
　化合物（Ｉ）として（Ｉ－２００）を用いたほかは、実施例５６と同様にして反応を行い、反応生成物（ＩＩＩ－７）を得た。ＮＭＲ収率は５１％であった。 [Example 57]
The reaction was carried out in the same manner as in Example 56 except that (I-5) was used as the compound (I) to obtain a reaction product (III-7). The isolated yield was 88%.
[Example 58]
The reaction was carried out in the same manner as in Example 56 except that (I-200) was used as the compound (I) to obtain a reaction product (III-7). The NMR yield was 51%.
［実施例５９］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－２０１）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－２００）を０．３ｍｍｏｌ（化合物（Ｉ）に対して１．０　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、配位性化合物としてｔＢｕ３Ｐを０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、塩基としてナトリウム－ｔｅｒｔ－ブトキシドを０．４５ｍｍｏｌ（化合物（Ｉ）に対して１．５　ｅｑｉｖ）、不飽和炭化水素化合物として１，５－シクロオクタジエンを０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、１２０℃に設定したヒートガンでジャーを加熱しながら６０分間振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。反応転化率は９５％を超えており、反応生成物（ＩＩＩ－３００）及び（ＩＩＩ－３０１）が得られた。反応生成物（ＩＩＩ－３００）と（ＩＩＩ－３０１）の生成比率（ＧＣ－Ｒａｔｉｏ）は、（ＩＩＩ－３００）／（ＩＩＩ－３０１）として、１２／８８であった。 [Example 59]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-201) as compound (I) and (II) as compound (II) under air. -200) 0.3 mmol (1.0 evi with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (5 mol% with respect to compound (I)), as a coordinating compound. 0.015 mmol of tBu3P (5 mol% with respect to compound (I)), 0.45 mmol of sodium-tert-butoxide as a base (1.5 equiv with respect to compound (I)), 1, as an unsaturated hydrocarbon compound 5-Cyclooctadiene was added at 0.2 μL / mg. The lid of the ball mill jar was closed, and the jar was attached to the ball mill. The jar was heated by a heat gun set at 120 ° C. and shaken for 60 minutes to stir (30 Hz) to perform a cross-coupling reaction. The reaction conversion was over 95% and reaction products (III-300) and (III-301) were obtained. The production ratio (GC-Ratio) of the reaction products (III-300) and (III-301) was 12/88 as (III-300) / (III-301).
［比較例５８］
　実施例５９において、ヒートガンによるジャーの加熱を行わなかった以外は、実施例５９と同様にしてクロスカップリング反応を行ったが、反応転化率は５％未満であり、反応生成物は得られなかった。 [Comparative Example 58]
In Example 59, the cross-coupling reaction was carried out in the same manner as in Example 59 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
［実施例６０］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－２０１）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－２０１）を０．４５ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、配位性化合物としてｔＢｕＢｒｅｔｔＰｈｏｓを０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、塩基としてナトリウム－ｔｅｒｔ－ブトキシドを０．３６ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、１２０℃に設定したヒートガンでジャーを加熱しながら６０分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行ない、
反応生成物（ＩＩＩ－３０２）を得た。ＮＭＲ収率は１０％であった。 [Example 60]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-201) as compound (I) and (II) as compound (II) under air. -201) 0.45 mmol (1.2 equiv with respect to compound (I)), Pd (OAc) 2 as a metal catalyst 0.015 mmol (5 mol% with respect to compound (I)), as a coordinating compound. 0.015 mmol of tBuBrettPhos (5 mol% with respect to compound (I)) and 0.36 mmol of sodium-tert-butoxide as a base (1.2 equiv with respect to compound (I)) were added. Close the lid of the ball mill jar, attach it to the ball mill, shake the jar for 60 minutes while heating it with a heat gun set at 120 ° C, and stir (30 Hz) to perform a cross-coupling reaction.
The reaction product (III-302) was obtained. The NMR yield was 10%.
［比較例５９］
　実施例６０において、ヒートガンによるジャーの加熱を行わなかった以外は、実施例６０と同様にしてクロスカップリング反応を行ったが、反応転化率は５％未満であり、反応生成物は得られなかった。 [Comparative Example 59]
In Example 60, the cross-coupling reaction was carried out in the same manner as in Example 60 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
［実施例６１］
　直径５ｍｍのステンレス製ボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、化合物（Ｉ）として（Ｉ－２０６）を０．３ｍｍｏｌ（１．０　ｅｑｉｖ）、化合物（ＩＩ）として（ＩＩ－２０２）を０．３ｍｍｏｌ（化合物（Ｉ）に対して１．０　ｅｑｉｖ）、配位性化合物としてＳＰｈｏｓ　Ｐｄ　Ｇ３を０．０１５ｍｍｏｌ（化合物（Ｉ）に対して５ｍｏｌ％）、塩基としてナトリウム－ｔｅｒｔ－ブトキシド０．３６ｍｍｏｌ（化合物（Ｉ）に対して１．２　ｅｑｉｖ）及びＬＡＧ（Ｌｉｑｕｉｄ　Ａｓｓｉｓｔｅｄ　Ｇｒｉｎｇｉｎｇ）を０．２μＬ／ｍｇ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、２５０℃に設定したヒートガンでジャーを加熱しながら６０分振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行ない、反応生成物（ＩＩＩ－３０３）を得た。ＮＭＲ収率は２４％であった。 [Example 61]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, 0.3 mmol (1.0 eq) of (I-206) as compound (I) and (II) as compound (II) under air. -202) is 0.3 mmol (1.0 evi with respect to compound (I)), SPhos Pd G3 as a coordinating compound is 0.015 mmol (5 mol% with respect to compound (I)), and sodium-tert as a base. -Toxide 0.36 mmol (1.2 equiv with respect to compound (I)) and LAG (Liquid Assisted Gringing) 0.2 μL / mg were added. Close the lid of the ball mill jar, attach it to the ball mill, shake the jar for 60 minutes while heating it with a heat gun set at 250 ° C, and stir (30 Hz) to perform a cross-coupling reaction, and the reaction product (III-303). ) Was obtained. The NMR yield was 24%.
［実施例６２～６４］
　実施例６１において、トルエンを使用（実施例６２）、テトラヒドロフランを使用（実施例６３）、１，５－シクロオクタジエンを使用（実施例６４）した以外は、実施例６１と同様にしてクロスカップリング反応を行ない、反応生成物（ＩＩＩ－３０３）を得た。ＮＭＲ収率は、実施例６２が４６％、実施例６３が６１％、実施例６４が４０％であった。 [Examples 62 to 64]
In Example 61, a cross cup was used in the same manner as in Example 61, except that toluene was used (Example 62), tetrahydrofuran was used (Example 63), and 1,5-cyclooctadiene was used (Example 64). A ring reaction was carried out to obtain a reaction product (III-303). The NMR yield was 46% in Example 62, 61% in Example 63, and 40% in Example 64.
［比較例６０］
　実施例６１において、ヒートガンによるジャーの加熱を行わなかった以外は、実施例６１と同様にしてクロスカップリング反応を行ったが、反応転化率は５％未満であり、反応生成物は得られなかった。 [Comparative Example 60]
In Example 61, the cross-coupling reaction was carried out in the same manner as in Example 61 except that the jar was not heated by the heat gun, but the reaction conversion was less than 5% and no reaction product was obtained. rice field.
［実施例６５～実施例７７］
　直径５ｍｍのステンレス製のボールの入った１．５ｍＬステンレス製ボールミルジャーに、空気下で、表９に示す化合物（Ｉ）を０．３０ｍｍｏｌ（１．０ｅｑｕｉｖ）、化合物（ＩＩ）として（ＩＩ－４５）を０．３６ｍｍｏｌ（１．２ｅｑｕｉｖ）、金属触媒としてＰｄ（ＯＡｃ）２を０．００６ｍｍｏｌ（化合物（Ｉ）に対して２ｍｏｌ％）、配位性化合物としてｔ－Ｂｕ３Ｐ・ＨＢＦ４（トリ－ｔｅｒｔ－ブチルホスホニウムテトラフルオロボラート）を０．００９ｍｍｏｌ（化合物（Ｉ）に対して３ｍｏｌ％）、塩基としてＫＯＡｃ（カリウムアセトアセトナート）を０．９ｍｍｏｌ（化合物（Ｉ）に対して３．０ｅｑｕｉｖ）及び水を６０μＬ加えた。ボールミルジャーの蓋をしめ、ボールミルに装着し、１００℃に設定したヒートガンでジャーを加熱（内部温度５０℃）しながら１０分間振とうして撹拌（３０Ｈｚ）してクロスカップリング反応を行った。
　反応終了後、反応混合物をジクロロメタンで抽出し、硫酸マグネシウムで乾燥した。その後、濾過することで無機塩を除いた。エバポレーターでジクロロメタンを除いたのち、クルード混合物をシリカゲルカラムクロマトグラフィーで精製することで対応する反応生成物（ＩＩＩ）を単離した。なお、実施例６５では、反応生成物（ＩＩＩ－３０４）が得られ、ＮＭＲ収率は９９％以上、単離収率は７７％であった。実施例６６～７７の各反応生成物の種類、ＮＭＲ収率、単離収率及び反応転化率は、表９に示すとおりである（表中、「－」は未測定又は測定不能である。）。 [Example 65 to Example 77]
In a 1.5 mL stainless steel ball mill jar containing a stainless steel ball having a diameter of 5 mm, the compound (I) shown in Table 9 was added as 0.30 mmol (1.0 equiv) and the compound (II) as compound (II-45) under air. ) Is 0.36 mmol (1.2 equiv), Pd (OAc) 2 is 0.006 mmol (2 mol% with respect to compound (I)) as a metal catalyst, and t-Bu 3 P · HBF 4 (tri) as a coordinating compound. -Tart-butylphosphonium tetrafluoroborate) 0.009 mmol (3 mol% with respect to compound (I)), KOAc (potassium acetoacetonate) as a base 0.9 mmol (3.0 equiv with respect to compound (I)) ) And 60 μL of water were added. The lid of the ball mill jar was closed, the jar was attached to the ball mill, and the jar was heated by a heat gun set at 100 ° C. (internal temperature 50 ° C.) and shaken for 10 minutes to stir (30 Hz) to perform a cross-coupling reaction.
After completion of the reaction, the reaction mixture was extracted with dichloromethane and dried over magnesium sulfate. Then, the inorganic salt was removed by filtration. After removing dichloromethane with an evaporator, the crude mixture was purified by silica gel column chromatography to isolate the corresponding reaction product (III). In Example 65, the reaction product (III-304) was obtained, the NMR yield was 99% or more, and the isolation yield was 77%. The types, NMR yields, isolation yields and reaction conversion rates of each reaction product of Examples 66 to 77 are as shown in Table 9 (in the table, "-" is unmeasured or unmeasurable. ).
Figure JPOXMLDOC01-appb-T000038
Figure JPOXMLDOC01-appb-T000038
　実施例１における反応生成物（ＩＩＩ－１）について、ＩＲ　ａｎａｌｙｓｉｓ、ＰＸＲＤ　ａｎａｌｙｓｉｓ及びＥＩ－ＭＳ　ａｎａｌｙｓｉｓを行った。それぞれの結果を図１～図３に示す。 IR analysis, PXRD analysis and EI-MS analysis were performed on the reaction product (III-1) in Example 1. The respective results are shown in FIGS. 1 to 3.
　実施例１～４、３８、４２～５０及び比較例１～４、３５、４０、４２～４９から、本発明に係るクロスカップリング反応方法は、従来の有機溶媒中で行うクロスカップリング反応方法と比較して、収率が大幅に高くなっていることがわかる。さらに、実施例１、３、４２、４７～５０と比較例１、３、４０、４６～４６にあるように、本発明に係るクロスカップリング反応方法は、有機溶媒中でクロスカップリング反応を行うことができない反応原料を用いた場合でも、反応生成物を得られることがわかる。 From Examples 1 to 4, 38, 42 to 50 and Comparative Examples 1 to 4, 35, 40, 42 to 49, the cross-coupling reaction method according to the present invention is a cross-coupling reaction method carried out in a conventional organic solvent. It can be seen that the yield is significantly higher than that of. Further, as shown in Examples 1, 3, 42, 47 to 50 and Comparative Examples 1, 3, 40, 46 to 46, the cross-coupling reaction method according to the present invention causes a cross-coupling reaction in an organic solvent. It can be seen that the reaction product can be obtained even when a reaction raw material that cannot be carried out is used.
　実施例５～３７、比較例５～３３から、本発明に係るクロスカップリング反応方法は、６０～５００℃の条件で行うことで、加熱をしないで行うクロスカップリング反応方法と比較して、収率が大幅に高くなっていることがわかる。さらに、実施例５、１７、２２、２３、３２、３４と比較例５、１７、２２、２３、２９、３０にあるように、本発明に係るクロスカップリング反応方法は、加熱をしない条件ではクロスカップリング反応を行うことができない反応原料を用いた場合でも、反応生成物を得られることがわかる。
　また、実施例６１、６３及び６５～７７は、炭化水素化合物を全く使用しない例であり、本発明の反応方法の適用可能性の広さを示すものである。 From Examples 5 to 37 and Comparative Examples 5 to 33, the cross-coupling reaction method according to the present invention was carried out under the conditions of 60 to 500 ° C., as compared with the cross-coupling reaction method carried out without heating. It can be seen that the yield is significantly higher. Further, as shown in Examples 5, 17, 22, 23, 32, 34 and Comparative Examples 5, 17, 22, 23, 29, 30, the cross-coupling reaction method according to the present invention is under the condition of no heating. It can be seen that the reaction product can be obtained even when a reaction raw material that cannot carry out the cross-coupling reaction is used.
Further, Examples 61, 63 and 65 to 77 are examples in which a hydrocarbon compound is not used at all, and show a wide range of applicability of the reaction method of the present invention.
　実施例１～５６から、本発明に係るクロスカップリング反応方法は、多種多様な化合物を出発原料として、有機溶媒を使用することなく、簡便な手段により、短時間に高収率で反応生成物を得ることができることがわかる。特に、有機溶媒に対する溶解性が低い化合物に対しても、クロスカップリング反応を行うことが可能となることがわかる。
　これより、本発明は、産業上非常に有用な発明であることがわかる。 From Examples 1 to 56, the cross-coupling reaction method according to the present invention uses a wide variety of compounds as starting materials, does not use an organic solvent, and is a reaction product in a short time and in a high yield by a simple means. It turns out that you can get. In particular, it can be seen that the cross-coupling reaction can be performed even on a compound having low solubility in an organic solvent.
From this, it can be seen that the present invention is an industrially very useful invention.

Claims (15)

  1. 　融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、
    　触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法であって、
    　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、反応方法。     An organic compound (A) having a melting group having a melting group of 30 ° C. or higher and an organic compound (B) having a melting group of 30 ° C. or higher reacting with the organic compound having a leaving group.
    It is a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the abundance of the organic solvent is 0.7 mL or less per 1 mmol of the organic compound (A) and the organic compound (B) in the presence of a catalyst and the temperature is 60 to 500 ° C. hand,
    One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. A reaction method, which is a reaction.
  2. 　Ｃ－Ｎ結合、Ｃ－Ｂ結合、Ｃ－Ｃ結合、Ｃ－Ｏ結合及びＣ－Ｓ結合から選択される１つ以上の化学結合を形成するクロスカップリング反応方法である、請求項１に記載の反応方法。 The first aspect of the present invention is a cross-coupling reaction method for forming one or more chemical bonds selected from CN bond, CB bond, CC bond, CO bond and CS bond. Reaction method.
  3. 　式（Ｉ）：
    　Ａ１－Ｘｍ　　　　　（Ｉ）
    （式中、
    Ａ１は、置換基を有していてもよいｍ価の芳香族炭化水素基、置換基を有していてもよいｍ価の芳香族複素環基、置換基を有していてもよいｍ価の脂肪族炭化水素基、又は置換基を有していてもよいｍ価の不飽和脂肪族炭化水素基のいずれかを表す。
    Ｘは、各々独立して、脱離基を表す。
    ｍは、Ｘの数で１以上の整数を表す。）
    で表される化合物（Ｉ）と、
    　式（ＩＩａ）又は（ＩＩｂ）：
    　Ａ２－Ｙｎ　　　　（ＩＩａ）
    　（Ｒ６Ｏ）（Ｒ７Ｏ）Ｂ－Ｂ（ＯＲ８）（ＯＲ９）　　　（ＩＩｂ）
    （式中、
    Ａ２は、置換基を有していてもよいｎ価の芳香族炭化水素基、置換基を有していてもよいｎ価の芳香族複素環基、置換基を有していてもよいｎ価の脂肪族炭化水素基、又は置換基を有していてもよいｎ価の不飽和脂肪族炭化水素基を表す。
    ｎは、Ｙの数で１以上の整数を表す。
    Ｙは、各々独立して、
    　－Ｂ（ＯＲ１）（ＯＲ２）
    　－ＮＨＲ３
    　－Ｒ４－ＯＨ
    　－Ｒ５－ＳＨ
    を表す。
    Ｒ１及びＲ２は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ１とＲ２は相互に結合していてもよい。
    Ｒ３は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の芳香族複素環基、置換基を有していてもよい１価の脂肪族炭化水素基、又は置換基を有していてもよい１価の不飽和脂肪族炭化水素基を表す。
    Ｒ４及びＲ５は、各々独立して、単結合、置換基を有していてもよい２価の芳香族炭化水素基、置換基を有していてもよい２価の脂肪族炭化水素基を表す。
    Ｒ６～Ｒ９は、各々独立して、水素、置換基を有していてもよい１価の芳香族炭化水素基、置換基を有していてもよい１価の脂肪族炭化水素基を表す。Ｒ６とＲ７は相互に結合していてもよく、Ｒ８とＲ９は相互に結合していてもよい。）
    で表される化合物（ＩＩ）を、
    　少なくとも、金属触媒及び塩基の存在下、
    　有機溶媒の存在量が、化合物（Ｉ）及び化合物（ＩＩ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、及び
    　６０～５００℃
    の条件で反応させる、請求項１又は２に記載の反応方法。     Equation (I):
    A 1 -X m (I)
    (During the ceremony,
    A 1 may have an m-valent aromatic hydrocarbon group which may have a substituent, an m-valent aromatic heterocyclic group which may have a substituent, and m which may have a substituent. It represents either a valent aliphatic hydrocarbon group or an m-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
    Each of X independently represents a leaving group.
    m is a number of X and represents an integer of 1 or more. )
    Compound (I) represented by
    Equation (IIa) or (IIb):
    A2 - Yn (IIa)
    (R 6 O) (R 7 O) BB (OR 8 ) (OR 9 ) (IIb)
    (During the ceremony,
    A 2 may have an n-valent aromatic hydrocarbon group which may have a substituent, an n-valent aromatic heterocyclic group which may have a substituent, and n which may have a substituent. Represents a valent aliphatic hydrocarbon group or an n-valent unsaturated aliphatic hydrocarbon group which may have a substituent.
    n is a number of Y and represents an integer of 1 or more.
    Y is independent of each other
    -B (OR 1 ) (OR 2 )
    -NHR 3
    -R 4 -OH
    -R 5 -SH
    Represents.
    R 1 and R 2 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show. R 1 and R 2 may be coupled to each other.
    R 3 independently contains hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, a monovalent aromatic heterocyclic group which may have a substituent, and a substituent. It represents a monovalent aliphatic hydrocarbon group which may have a substituent or a monovalent unsaturated aliphatic hydrocarbon group which may have a substituent.
    Each of R 4 and R 5 has a single bond, a divalent aromatic hydrocarbon group which may have a substituent, and a divalent aliphatic hydrocarbon group which may have a substituent, respectively. Represents.
    R 6 to R 9 each independently contain hydrogen, a monovalent aromatic hydrocarbon group which may have a substituent, and a monovalent aliphatic hydrocarbon group which may have a substituent. show. R 6 and R 7 may be coupled to each other, and R 8 and R 9 may be coupled to each other. )
    Compound (II) represented by
    At least in the presence of metal catalysts and bases
    The abundance of the organic solvent is 0.7 mL or less per 1 mmol of the compound (I) and the compound (II) in total, and 60 to 500 ° C.
    The reaction method according to claim 1 or 2, wherein the reaction is carried out under the conditions of.
  4. 　前記脱離基が、クロロ、ブロモ、ヨード、ジアゾニウム塩、トリフルオロメタンスルホネート及びカルボン酸誘導体から選ばれる１種以上の基であり、
    　前記式（ＩＩａ）で表される化合物が、芳香族ボロン酸又は芳香族ボロン酸エステルから選ばれる芳香族ボロン酸類であり、
    　前記式（ＩＩｂ）で表される化合物が、ジボロン酸アルキルエステル、ジボロン酸アルキレングリコールエステル、ジボロン酸アリールエステル、ジボロン酸アリーレングリコールエステル、及びテトラヒドロキシジボランから選ばれるジボロン酸エステル類である、
    請求項１～３のいずれか１項に記載の方法。     The leaving group is one or more groups selected from chloro, bromo, iodo, diazonium salt, trifluoromethanesulfonate and carboxylic acid derivative.
    The compound represented by the formula (IIa) is an aromatic boronic acid selected from an aromatic boronic acid or an aromatic boronic acid ester.
    The compound represented by the formula (IIb) is a diboronic acid ester selected from a diboronic acid alkyl ester, a diboronic acid alkylene glycol ester, a diboronic acid aryl ester, a diboronic acid arylene glycol ester, and a tetrahydroxydiborane.
    The method according to any one of claims 1 to 3.
  5. 　前記化合物（Ｉ）と前記化合物（ＩＩ）の当量比（化合物（Ｉ）／化合物（ＩＩ））が、１０／１～１／１０である、請求項１～４のいずれか１項に記載の方法。 The one according to any one of claims 1 to 4, wherein the equivalent ratio of the compound (I) to the compound (II) (compound (I) / compound (II)) is 10/1 to 1/10. Method.
  6. 　前記金属触媒の存在量が、化合物（Ｉ）のモル数に価数ｍをかけて得た脱離基モル数を１００モル％とした場合に、０．５モル％以上２５モル％以下である、請求項１～５のいずれか１項に記載の方法。 The abundance of the metal catalyst is 0.5 mol% or more and 25 mol% or less when the number of moles of leaving groups obtained by multiplying the number of moles of the compound (I) by a valence m is 100 mol%. , The method according to any one of claims 1 to 5.
  7. 　前記塩基が、無機塩基、アルカリ金属アルコキシド及び有機塩基から選ばれる少なくとも１種を含む、請求項１～６のいずれか１項に記載の方法。 The method according to any one of claims 1 to 6, wherein the base contains at least one selected from an inorganic base, an alkali metal alkoxide and an organic base.
  8. 　前記塩基の存在量が、化合物（Ｉ）１当量に対して、０．５当量以上１０当量以下である、請求項１～７のいずれか１項に記載の方法。 The method according to any one of claims 1 to 7, wherein the abundance of the base is 0.5 equivalent or more and 10 equivalent or less with respect to 1 equivalent of compound (I).
  9. 　金属触媒及び塩基に加えて、さらに不飽和炭化水素化合物の存在下で反応させる、請求項１～８のいずれか１項に記載の方法。 The method according to any one of claims 1 to 8, wherein the reaction is further carried out in the presence of an unsaturated hydrocarbon compound in addition to a metal catalyst and a base.
  10. 　前記不飽和炭化水素化合物が、芳香族化合物ではなく、
    　少なくとも１つの炭素－炭素不飽和二重結合及び／又は少なくとも１つの炭素－炭素不飽和三重結合を有する鎖状化合物、又は
    　少なくとも１つの炭素－炭素不飽和二重結合及び／又は少なくとも１つの炭素－炭素不飽和三重結合を有する環状化合物、
    の１種以上である、請求項１～９のいずれか１項に記載の方法。     The unsaturated hydrocarbon compound is not an aromatic compound,
    A chain compound with at least one carbon-carbon unsaturated double bond and / or at least one carbon-carbon unsaturated triple bond, or at least one carbon-carbon unsaturated double bond and / or at least one carbon- Cyclic compounds with carbon unsaturated triple bonds,
    The method according to any one of claims 1 to 9, which is one or more of the above.
  11. 　金属触媒及び塩基に加えて、さらに配位性化合物が存在している、請求項１～１０のいずれか１項に記載の方法。 The method according to any one of claims 1 to 10, wherein a coordinating compound is further present in addition to the metal catalyst and the base.
  12. 　前記不飽和炭化水素化合物の存在量が、
    　前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、及び前記塩基の合計質量を基準として、又は、
    　前記化合物（Ｉ）、前記化合物（ＩＩ）、前記金属触媒、前記塩基、及び配位性化合物の合計質量を基準として、
    ０．０１～３．０μＬ／ｍｇである、請求項１～１１のいずれか１項に記載の方法。     The abundance of the unsaturated hydrocarbon compound is
    Based on the total mass of the compound (I), the compound (II), the metal catalyst, and the base, or
    Based on the total mass of the compound (I), the compound (II), the metal catalyst, the base, and the coordinating compound.
    The method according to any one of claims 1 to 11, which is 0.01 to 3.0 μL / mg.
  13. 　反応容器、反応容器内の収容物を撹拌する手段、及び反応容器内の温度調整手段、を少なくとも備え、
    　融点が３０℃以上の脱離基を有する有機化合物（Ａ）と、脱離基を有する有機化合物と反応する融点が３０℃以上の有機化合物（Ｂ）を、触媒の存在下、有機溶媒の存在量が有機化合物（Ａ）及び有機化合物（Ｂ）の合計１ｍｍｏｌ当り０．７ｍＬ以下、温度が６０～５００℃の条件でメカノケミカル法により反応させる反応方法に用いる装置であって、
    　前記反応が、カップリング反応、アルキル化反応、ハロゲン化反応、加水分解反応、酸化反応、還元反応、メタル化反応、ラジカル反応、メタセシス反応、環化付加反応からなる群より選ばれる1種以上の反応である、装置。     A reaction vessel, a means for stirring the contents in the reaction vessel, and a means for adjusting the temperature in the reaction vessel are provided at least.
    An organic compound (A) having a melting point of 30 ° C. or higher and an organic compound (B) having a melting point of 30 ° C. or higher that reacts with the organic compound having a melting group are mixed in the presence of an organic solvent in the presence of a catalyst. An apparatus used for a reaction method in which the reaction is carried out by the mechanochemical method under the conditions that the amount of the organic compound (A) and the organic compound (B) is 0.7 mL or less per 1 mmol in total and the temperature is 60 to 500 ° C.
    One or more of the above reactions selected from the group consisting of a coupling reaction, an alkylation reaction, a halogenation reaction, a hydrolysis reaction, an oxidation reaction, a reduction reaction, a metallization reaction, a radical reaction, a metathesis reaction, and a cyclization addition reaction. A device that is a reaction.
  14. 　請求項１～１２のいずれか１項に記載の方法を用いる、式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される化合物の製造方法。
    Figure JPOXMLDOC01-appb-C000001
      （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。）     A method for producing a compound represented by any of the formula (IIIa) or (IIIb), which uses the method according to any one of claims 1 to 12.
    Figure JPOXMLDOC01-appb-C000001
     (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
  15. 　式（ＩＩＩａ）又は（ＩＩＩｂ）のいずれかで表される化合物。
    Figure JPOXMLDOC01-appb-C000002
      （式中、ｐは５～３０の整数、ｑは５～３０の整数を表す。）     A compound represented by either formula (IIIa) or (IIIb).
    Figure JPOXMLDOC01-appb-C000002
     (In the formula, p represents an integer of 5 to 30, and q represents an integer of 5 to 30.)
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