JP2014125449A - Method of manufacturing cyclic azine compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrial manufacturing method of efficiently manufacturing polysubstituted cyclic azine compound with high purity.SOLUTION: There is provided a method of manufacturing polysubstituted cyclic azine compound having {(the mol number of a transition metal in a transition metal compound)÷(the mol number of a compound represented by the general formula (2)) of 0.00001 to 0.009 in a coupling reaction of the component represented by the general formula (2) and a compound represented by the general formula (3) in a presence of the transition metal compound, a phosphine compound and a base. (2), where Ar, Arand Arrepresent a monovalent substituent having 1 to 40 carbon atoms, Xrepresents a chlorine atom, a bromine atom or an iodine atom. Y represents CH or a nitrogen atom. (3), where Arrepresents a monovalent substituent having 1 to 40 carbon atoms, Rrepresents a hydrogen atom, an alkyl group or a phenyl group.

Description

The present invention relates to a method for more efficiently producing a high-purity polysubstituted cyclic azine compound.

  The cyclic azine compound is used as an electronic material (for example, an electron transporting material of an organic electroluminescent element). The manufacturing method is described in many known literatures. For example, it is specifically described in JP2011-121934 (Patent Document 1), JP2011-063584 (Patent Document 2), and the like.

JP, 2011-121934, A JP, 2011-063584, A In general, it was thought that it was necessary to use many metal catalysts for the coupling reaction of a cyclic azine compound. For example, the method described in JP2011-121934 uses a large amount of 0.01 to 0.06 mole of palladium catalyst per mole of the cyclic azine compound as a substrate. In order to obtain a high-purity polysubstituted cyclic azine compound from a reaction solution using such a large amount of palladium catalyst, a purification operation by column chromatography is essential, which is not industrially satisfactory in terms of efficiency. It was. For this reason, a production method suitable for mass synthesis has been strongly desired.

  This invention solves the said subject, and the place made into the objective is to provide the industrial manufacturing method which manufactures a highly purified polysubstituted cyclic azine compound efficiently.

  As a result of intensive studies to solve the above problems, the present inventors have found that the desired high-purity polysubstituted cyclic azine compound can be efficiently produced by the production method of the present invention, and complete the present invention. It came to. That is, this invention relates to the manufacturing method of the cyclic azine compound represented by General formula (1) as follows.

  Cyclic azine compound represented by general formula (2) in the presence of a transition metal compound, a phosphine compound and a base

(In the formula, Ar ¹ , Ar ² , and Ar ³ each independently represent a monovalent substituent having 1 to 40 carbon atoms. X ¹ represents a chlorine atom, a bromine atom, or an iodine atom. Y Represents CH or a nitrogen atom.)
And boronic acid compound represented by the general formula (3)

(In the formula, Ar ⁴ represents a monovalent substituent having 1 to 40 carbon atoms. R ¹ each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a phenyl group, R ¹ may be linked to form a ring containing an oxygen atom and a boron atom.)
General formula (1)

(In the formula, Ar ¹ , Ar ² , Ar ³ , and Ar ⁴ each independently represent a monovalent substituent having 1 to 40 carbon atoms. Y represents CH or a nitrogen atom.)
In which {(number of moles of transition metal in transition metal compound) ÷ (number of moles of compound represented by general formula (2))} is 0.00001 to 0 0.009 is a method for producing a cyclic azine compound represented by the general formula (1).

  The method for producing a cyclic azine compound of the present invention provides an industrially very advantageous method for efficiently producing a target high-purity polysubstituted cyclic azine compound as compared with a conventionally known production method.

  Hereinafter, the present invention will be specifically described.

In the general formulas (1) and (2), Ar ¹ , Ar ² , and Ar ³ each independently represent a monovalent substituent having 1 to 40 carbon atoms.

  Although it does not specifically limit as a C1-C40 monovalent substituent, For example, a C6-C40 aryl group, a C3-C40 heteroaryl group, a C1-C40 alkyl Group, an alkoxyl group having 1 to 40 carbon atoms (these are each independently a methyl group, an ethyl group, a linear, branched or cyclic alkyl group having 3 to 18 carbon atoms, a methoxy group, an ethoxy group, and a carbon number. 3-18 linear, branched, or cyclic alkoxy groups, C6-C40 aryl groups, C6-C40 aryloxy groups, C3-C40 heteroaryl groups, which may be different A diarylamino group formed by bonding an aryl group having 6 to 18 carbon atoms and one or more substituents selected from the group consisting of halogen atoms), a cyano group, and the like. Among these, in terms of excellent production efficiency, an aryl group having 6 to 40 carbon atoms or a heteroaryl group having 3 to 40 carbon atoms (which are each independently a methyl group, an ethyl group, or a straight chain having 3 to 18 carbon atoms). Chain, branched or cyclic alkyl group, methoxy group, ethoxy group, linear, branched or cyclic alkoxy group having 3 to 18 carbon atoms, aryl group having 6 to 40 carbon atoms, aryloxy having 6 to 40 carbon atoms One or more selected from the group consisting of a group, a heteroaryl group having 3 to 40 carbon atoms, a diarylamino group formed by bonding two different aryl groups having 6 to 18 carbon atoms, and a halogen atom It may have a substituent.

In Ar ¹ , Ar ² , and Ar ³ , the aryl group having 6 to 40 carbon atoms is not particularly limited, and examples thereof include a phenyl group, a 4-methylphenyl group, a 3-methylphenyl group, and 2-methyl. Phenyl group, 4-ethylphenyl group, 3-ethylphenyl group, 2-ethylphenyl group, 4-n-propylphenyl group, 4-n-butylphenyl group, 4-isobutylphenyl group, 4-tert-butylphenyl group 4-cyclopentylphenyl group, 4-cyclohexylphenyl group, 2,4-dimethylphenyl group, 3,5-dimethylphenyl group, 3,4-dimethylphenyl group, biphenylyl group, terphenylyl group, 9-phenanthryl group, 9 , 9-dialkyl-fluoren-2-yl group, biphenylenyl group, naphthyl group, benzofluorenyl group, Benzofluorenyl group, fluoranthenyl group, a pyrenyl group, perylenyl group, a picenyl group, and the like. Among these, phenyl group, 4-methylphenyl group, 3-methylphenyl group, 2-methylphenyl group, biphenylryl group, 9-phenanthryl group, 9,9-dialkyl-fluorene in terms of stability of the cyclic azine compound. A 2-yl group and a naphthyl group are preferable.

In Ar ¹ , Ar ² , and Ar ³ , the heteroaryl group having ^{3 to} 40 carbon atoms is not particularly limited, and examples thereof include a quinolyl group, a pyridyl group, a furyl group, a thienyl group, an oxazolyl group, and a thiazolyl group. Benzothiophenyl group, dibenzofuranyl group, benzothiazolyl group, benzimidazolyl group, dibenzothiophenyl group, N-carbazolyl group and the like.

In Ar ¹ , Ar ² , and Ar ³ , the alkyl group having 1 to 40 carbon atoms is not limited to the following, but specifically includes a methyl group, a chloromethyl group, a trifluoromethyl group, ethyl Group, propyl group, isopropyl group, butyl group, sec-butyl group, tert-butyl group, pentyl group, propyne group, hexyl group, heptyl group, octyl group, stearyl group, trichloromethyl group, trifluoromethyl group, cyclopropyl Group, cyclohexyl group, 1,3-cyclohexadienyl group, 2-cyclopenten-1-yl group and the like.

In Ar ¹ , Ar ² , and Ar ³ , the alkoxy group having 1 to 40 carbon atoms is not limited to the following, but specifically includes a methoxy group, a chloromethoxy group, a trifluoromethoxy group, an ethoxy group. Group, propyloxy group, isopropyloxy group, butyloxy group, sec-butyloxy group, tert-butyloxy group, pentyloxy group, propyneoxy group, hexyloxy group, heptyloxy group, octyloxy group, stearyloxy group, trichloromethyl Examples thereof include an oxy group, a trifluoromethyloxy group, a cyclopropyloxy group, a cyclohexyloxy group, a 1,3-cyclohexadienyloxy group, and a 2-cyclopenten-1-yloxy group.

In Ar ¹ , Ar ² , and Ar ³ , the linear, branched, or cyclic alkyl group having ^{3 to} 18 carbon atoms is not limited to the following, and specifically includes a propyl group and an isopropyl group. Butyl group, sec-butyl group, tert-butyl group, pentyl group, propyne group, hexyl group, heptyl group, octyl group, stearyl group, trichloromethyl group, trifluoromethyl group, cyclopropyl group, cyclohexyl group, 1, Examples thereof include a 3-cyclohexadienyl group and a 2-cyclopenten-1-yl group.

In Ar ¹ , Ar ² , and Ar ³ , the linear, branched, or cyclic alkoxy group having ^{3 to} 18 carbon atoms is not limited to the following, but specifically, a propoxy group, isopropoxy group, and the like. Examples include a group, n-butoxy group, sec-butoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, stearyloxy group, trifluoromethoxy group and the like.

In Ar ¹ , Ar ² , and Ar ³ , the aryloxy group having 6 to 40 carbon atoms is not limited to the following, but specifically includes a phenoxy group, an o-triloxy group, and an m-triloxy group. P-triloxy group, 4-biphenyloxy group, 3-biphenyloxy group, 1-naphthyloxy group, 2-naphthyloxy group, p-tert-butylphenoxy group, 3-fluorophenoxy group, 4-fluorophenoxy group, etc. Can be illustrated.

Note that an aryl group having 6 to 40 carbon atoms in Ar ¹ , Ar ² , and Ar ³ (these are each independently a methyl group, an ethyl group, a straight chain, branched, or cyclic group having 3 to 18 carbon atoms) An alkyl group, a methoxy group, an ethoxy group, a linear, branched, or cyclic alkoxy group having 3 to 18 carbon atoms, an aryl group having 6 to 40 carbon atoms, an aryloxy group having 6 to 40 carbon atoms, or 3 to 40 carbon atoms. A heteroaryl group, a diarylamino group formed by bonding two different aryl groups having 6 to 18 carbon atoms, and one or more substituents selected from the group consisting of halogen atoms Is not particularly limited, and examples thereof include a phenyl group, a 4-methylphenyl group, a 3-methylphenyl group, a 2-methylphenyl group, a 4-ethylphenyl group, and a 3-ethylphenyl group. 2-ethylphenyl group, 4-n-propylphenyl group, 4-isopropylphenyl group, 2-isopropylphenyl group, 4-n-butylphenyl group, 4-isobutylphenyl group, 4-sec-butylphenyl group, 2 -Sec-butylphenyl group, 4-tert-butylphenyl group, 3-tert-butylphenyl group, 2-tert-butylphenyl group, 4-n-pentylphenyl group, 4-isopentylphenyl group, 4-neopentyl group Phenyl group, 2-neopentylphenyl group, 4-tert-pentylphenyl group, 4-n-hexylphenyl group, 4- (2′-ethylbutyl) phenyl group, 4-n-heptylphenyl group, 4-n-octyl Phenyl group, 4- (2′-ethylhexyl) phenyl group, 4-tert-octylphenyl group, 4-n-de Ruphenyl group, 3-cyclohexylphenyl group, 2-cyclohexylphenyl group, 4-n-dodecylphenyl group, 4-n-tetradecylphenyl group, 4-cyclopentylphenyl group, 4-cyclohexylphenyl group, 4- (4′- tert-butylcyclohexyl) phenyl group, 4-tritylphenyl group, 3-tritylphenyl group, 4- (4'-methylphenyl) phenyl group, 4- (3'-methylphenyl) phenyl group, 4- (4'- Methoxyphenyl) phenyl group, 4- (4′-n-butoxyphenyl) phenyl group, 2- (2′-methoxyphenyl) phenyl group, 3-methyl-4-phenylphenyl group, 3-methoxy-4-phenylphenyl Group, 3,5-diphenylphenyl group, 4-triphenylsilylphenyl group, 3-triphenylsilylphenyl group Group, 2,4-dimethylphenyl group, 2,5-dimethylphenyl group, 3,4-dimethylphenyl group, 3,5-dimethylphenyl group, 2,6-dimethylphenyl group, 2,4-diethylphenyl group 2,6-diethylphenyl group, 2,5-diisopropylphenyl group, 2,6-diisobutylphenyl group, 2,4-di-tert-butyl-2-methylphenyl group, 2,5-di-tert-butyl Phenyl group, 5-tert-butyl-2-methylphenyl group, 2,3,5-trimethylphenyl group, 2,3,6-trimethylphenyl group, 3,4,5-trimethylphenyl group, 4,6-di -Tert-butyl-2-methylphenyl group, 4-tert-butyl-2,6-dimethylphenyl group, 4-methoxyphenyl group, 3-methoxyphenyl group, 2-methoxy Siphenyl group, 4-ethoxyphenyl group, 3-ethoxyphenyl group, 2-ethoxyphenyl group, 4-n-propoxyphenyl group, 3-n-propoxyphenyl group, 4-isopropoxyphenyl group, 2-isopropoxyphenyl group 4-n-butoxyphenyl group, 4-isobutoxyphenyl group, 2-sec-butoxyphenyl group, 4-n-pentyloxyphenyl group, 4-isopentyloxyphenyl group, 2-isopentyloxyphenyl group, 4 -Neopentyloxyphenyl group, 2-neopentyloxyphenyl group, 4-n-hexyloxyphenyl group, 2- (2-ethylbutyl) oxyphenyl group, 4-n-octyloxyphenyl group, 4-n-decyloxy Phenyl group, 4-n-dodecyloxyphenyl group, 4-n-tetradecyloxy Phenyl group, 4-cyclohexyloxyphenyl group, 2-cyclohexyloxyphenyl group, 4-phenoxyphenyl group, 2-methyl-4-methoxyphenyl group, 2-methyl-5-methoxyphenyl group, 3-methyl-4-methoxy Phenyl group, 3-methyl-5-methoxyphenyl group, 3-ethyl-5-methoxyphenyl group, 2-methoxy-4-methylphenyl group, 3-methoxy-4-methylphenyl group, 2,4-dimethoxyphenyl group 2,5-dimethoxyphenyl group, 2,6-dimethoxyphenyl group, 3,4-dimethoxyphenyl group, 3,5-dimethoxyphenyl group, 3,5-diethoxyphenyl group, 3,5-di-n- Butoxyphenyl group, 2-methoxy-4-ethoxyphenyl group, 2-methoxy-6-ethoxyphenyl group, 3,4,5- Limethoxyphenyl group, 4- (9-carbazolyl) phenyl group, 3- (9-carbazolyl) phenyl group, 4-fluorophenyl group, 3-fluorophenyl group, 2-fluorophenyl group, 2,3-difluorophenyl group 2,4-difluorophenyl group, 2,5-difluorophenyl group, 2,6-difluorophenyl group, 3,4-difluorophenyl group, 3,5-difluorophenyl group, 4- (2-pyridyl) phenyl group 4- (3-pyridyl) phenyl group, 4- (4-pyridyl) phenyl group, 4- (1-naphthyl) phenyl group, 4- (2-naphthyl) phenyl group, 3- (1-naphthyl) phenyl group 3- (2-naphthyl) phenyl group, 1-naphthyl group, 2-naphthyl group, 4-methyl-1-naphthyl group, 6-methyl-2-naphthyl group, 6-n- Butyl-2-naphthyl group, 4-phenyl-1-naphthyl group, 6-phenyl-2-naphthyl group, 2-methoxy-1-naphthyl group, 4-methoxy-1-naphthyl group, 5-ethoxy-1-naphthyl Group, 6-ethoxy-2-naphthyl group, 7-methoxy-2-naphthyl group, 6-n-butoxy-2-naphthyl group, 6-n-hexyloxy-2-naphthyl group, 4-n-butoxy-1 -Naphthyl group, 7-n-butoxy-2-naphthyl group, 2-anthryl group, 9-anthryl group, 10-phenyl-9-anthryl group, 10- (3,5-diphenylphenyl) -9-anthryl group, 2-fluorenyl group, 9-methyl-2-fluorenyl group, 9-ethyl-2-fluorenyl group, 9-n-hexyl-2-fluorenyl group, 9-phenyl-2-fluorenyl group, 9,9- Methyl-2-fluorenyl group, 9,9-diethyl-2-fluorenyl group, 9,9-di-n-propyl-2-fluorenyl group, 9,9-di-n-octyl-2-fluorenyl group, 9, 9-diphenyl-2-fluorenyl group, 9,9'-spirobifluorenyl group, 9-phenanthryl group, 2-phenanthryl group, benzofluorenyl group, dibenzofluorenyl group, fluoranthenyl group, pyrenyl group , Chrysenyl group, perylenyl group, picenyl group, 4-biphenylyl group, 3-biphenylyl group, 2-biphenylyl group, p-terphenyl group, m-terphenyl group, o-terphenyl group and the like. Among these, Ar ¹ , Ar ² , and Ar ³ are each independently a phenyl group, a 4-methylphenyl group, a 3-methylphenyl group, a 2-methylphenyl group, in terms of the stability of the cyclic azine compound. 4-biphenylyl group, 4- (2-pyridyl) phenyl group, 4- (3-pyridyl) phenyl group, 4- (4-pyridyl) phenyl group, 9-anthryl group, 10-phenyl-9-anthryl group, A 9-phenanthryl group, a 9,9-dimethyl-2-fluorenyl group, a 1-naphthyl group, and a 2-naphthyl group are preferable.

A heteroaryl group having ^{3 to} 40 carbon atoms in Ar ¹ , Ar ² , and Ar ³ (these are each independently a methyl group, an ethyl group, a linear, branched, or cyclic alkyl group having 3 to 18 carbon atoms) Group, methoxy group, ethoxy group, C3-C18 linear, branched, or cyclic alkoxy group, C6-C40 aryl group, C6-C40 aryloxy group, C3-C40 The heteroaryl group may have one or more substituents selected from the group consisting of a heteroaryl group, a diarylamino group formed by bonding two different aryl groups having 6 to 18 carbon atoms, and a halogen atom. ) Is not particularly limited, for example, 4-quinolyl group, 4-pyridyl group, 4- (2-methyl) pyridyl group, 4- (2-ethyl) pyridyl group, 4-phenylpyridyl group, 3 Phenylpyridyl group, 2-phenylpyridyl group, 3-pyridyl group, 2-pyridyl group, 2,2′-bipyridyl group, 2,3′-bipyridyl group, 2,4′-bipyridyl group, 3-furyl group, 2 -Furyl group, 3-thienyl group, 2-thienyl group, 2-oxazolyl group, 2-thiazolyl group, 2-benzoxazolyl group, 2-benzothiazolyl group, 2-benzimidazolyl group, 2-dibenzothiophenyl group, 4 -A dibenzothiophenyl group, 2-dibenzofuranyl group, 4-dibenzofuranyl group, 2-thianthrenyl group, 4-phenoxathienyl group, etc. are mentioned. Of these, Ar ¹ , Ar ² , and Ar ³ are each independently a 4-quinolyl group, a 4-pyridyl group, a 4- (2-methyl) pyridyl group, and 4 in terms of the stability of the cyclic azine compound. -(2-ethyl) pyridyl group, 4-phenylpyridyl group, 3-phenylpyridyl group, 2-phenylpyridyl group, 3-pyridyl group, 2-pyridyl group, 2,2'-bipyridyl group, 2,3'- A bipyridyl group and a 2,4′-bipyridyl group are preferred.

  In general formula (1), Y represents CH or a nitrogen atom.

In the general formula (2), ^{X 1} represents a chlorine atom, a bromine atom, an iodine atom. Among these, it is preferable that it is a chlorine atom or a bromine atom from the availability of a cyclic azine compound. Moreover, in General formula (2), Y represents CH or a nitrogen atom.

In General Formulas (1) and (3), Ar ⁴ represents a monovalent substituent having 1 to 40 carbon atoms.

Although it does not specifically limit as said C1-C40 monovalent substituent, For example, a C6-C40 aryl group or a C3-C40 heteroaryl group, C1-C40 An alkyl group, an alkoxyl group having 1 to 40 carbon atoms (these are each independently a methyl group, an ethyl group, a linear, branched or cyclic alkyl group having 3 to 18 carbon atoms, a methoxy group, an ethoxy group, a carbon atom, A linear, branched, or cyclic alkoxy group having 3 to 18 carbon atoms, an aryl group having 6 to 40 carbon atoms, an aryloxy group having 6 to 40 carbon atoms, or a heteroaryl group having 3 to 40 carbon atoms, which may be different And a diarylamino group formed by bonding two aryl groups having 6 to 18 carbon atoms and one or more substituents selected from the group consisting of halogen atoms). Ar ⁴ is not particularly limited, and examples thereof include the same groups as the monovalent substituents exemplified above for Ar ¹ , Ar ² and Ar ³ except for a cyano group.

In General Formula (3), each R ¹ independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a phenyl group, and two R ¹ are linked to each other and include a ring containing an oxygen atom and a boron atom. May be formed. The ring containing two oxygen atoms and the boron atom R ¹ is linked, it may be mentioned ring represented by the following from (B-1) (B- 6).

  The present invention is characterized in that a cyclic azine compound represented by the general formula (2) and a boronic acid compound represented by the general formula (3) are reacted in the presence of a transition metal compound, a phosphine compound and a base. The method for producing a cyclic azine compound represented by the general formula (1).

  Although it does not specifically limit in the manufacturing method of this invention, Usually, the boronic acid compound represented by General formula (3) with respect to 1 mol of cyclic azine compounds represented by General formula (2) is 1. The reaction is carried out 0 to 3.0 times in moles. In order to synthesize the target cyclic azine compound with high selectivity, the boronic acid compound represented by the general formula (3) is preferably 1.0 to 2.0 times by mole, and 1.0 to 1 More preferably, the molar ratio is 5 times.

  Although it does not specifically limit as a transition metal compound, For example, a palladium compound or a nickel compound is mentioned. Although it does not specifically limit as a palladium compound, For example, palladium chloride (II), palladium bromide (II), palladium acetate (II), palladium acetylacetonate (II), dichlorobis (benzonitrile) palladium (II ), Dichlorobis (acetonitrile) palladium (II), dichlorobis (triphenylphosphine) palladium (II), dichlorotetraamminepalladium (II), dichloro (cycloocta-1,5-diene) palladium (II), palladium trifluoroacetate (II) ), Tris (dibenzylideneacetone) dipalladium (0), tris (dibenzylideneacetone) dipalladium chloroform complex (0), tetrakis (triphenylphosphine) palladium (0), and the like.

  Although it does not specifically limit as a nickel compound, For example, nickel halides, such as nickel fluoride (II), nickel chloride (II), nickel bromide (II), nickel iodide (II), nickel (0 ) Powder, inorganic salts such as nickel sulfate (II), nickel nitrate (II), nickel perchlorate (II), nickel formate (II), nickel oxalate (II), nickel acetate (II), nickel benzoate ( II), nickel acetylacetonate (II) and the like.

  In addition, what carried these transition metal compounds on carriers, such as carbon and a silica gel, can also be used for the manufacturing method of this invention.

  Although it does not specifically limit as a phosphine compound, For example, triphenylphosphine, tri (o-tolyl) phosphine, monodentate aryl phosphine such as tri (mesityl) phosphine, tri (cyclohexyl) phosphine, tri (isopropyl) phosphine, Monodentate alkyl phosphines such as tri (tert-butyl) phosphine, 2-dicyclohexylphosphino-2 ′, 4 ′, 6′-triisopropylbiphenyl, 1,2-bis (diphenylphosphino) ethane, 1,2-bis ( And bidentate phosphines such as diphenylphosphino) propane, 1,2-bis (diphenylphosphino) butane and 1,2-bis (diphenylphosphino) ferrocene. Among these, from the viewpoint of improving the reaction selectivity, tri (cyclohexyl) phosphine, tri (isopropyl) phosphine, tri (tert-butyl) phosphine, 2-dicyclohexylphosphino-2 ′, 4 ′, 6′-triisopropyl Monodentate alkyl phosphines such as biphenyl are preferred, and 2-dicyclohexylphosphino-2 ′, 4 ′, 6′-triisopropylbiphenyl is more preferred. As the phosphine compound, a complex prepared by mixing with a transition metal compound in advance may be used for the reaction, or a phosphine compound introduced into the reaction system through a different route from the transition metal compound and used in the reaction. It may be used.

  In the present invention, the amount of the transition metal compound used is defined by a mathematical formula represented by {(number of moles of transition metal in the transition metal compound) ÷ (number of moles of the compound represented by the general formula (2))}. Usually, it is in the range of 0.00001 to 0.009. When the amount of the transition metal compound used is less than 0.00001, the reaction rate is remarkably lowered, which is not industrially preferable. In addition, when the amount of transition metal compound used exceeds 0.009, the amount of by-products increases, and purification by column chromatography is required to obtain the desired high-purity cyclic azine compound. Industrially unfavorable. In addition, if the usage-amount of a transition metal compound is in the said range, the cyclic azine compound represented by General formula (1) can be efficiently manufactured with high purity. From the viewpoint of producing the target cyclic azine compound more selectively, (number of moles of transition metal in transition metal compound) ÷ (number of moles of compound represented by formula (2))} is 0.00001. Is preferably in the range of -0.005, more preferably in the range of 0.00001-0.001.

  Although it does not specifically limit as a base in this invention, For example, the mixture of an inorganic base, an organic base, or an inorganic base and an organic base is mention | raise | lifted. Although it does not specifically limit as a base, For example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, potassium phosphate, sodium phosphate etc., sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide Alkali metal alkoxides such as lithium-tert-butoxide, sodium-tert-butoxide, potassium-tert-butoxide, triethylamine, tributylamine, pyridine, preferably sodium hydroxide, potassium hydroxide, sodium carbonate, Examples thereof include potassium carbonate, potassium phosphate, and sodium phosphate. In addition, you may use a base for the manufacturing method of this invention as aqueous solution.

  The amount of the base used in the production method of the present invention is not particularly limited, but is usually in the range of 1 to 50 times moles relative to 1 mole of the cyclic azine compound represented by the general formula (2). . If it is said range, the target high purity cyclic azine compound can be manufactured efficiently. In addition, in order to synthesize | combine the target cyclic azine compound highly selectively, it is preferable that the usage-amount of a base is the range of 1-5 times mole.

  This reaction is usually performed in the presence of an inert solvent. The inert solvent is not particularly limited as long as it does not significantly inhibit the reaction performed in the production method of the present invention, and examples thereof include aromatic organic solvents such as benzene, toluene and xylene, diethyl Examples include ether organic solvents such as ether, tetrahydrofuran, dimethoxyethane, dioxane, acetonitrile, dimethylformamide, dimethyl sulfoxide, hexamethylphosphotriamide, and the like. Among these, ether-based organic solvents such as diethyl ether, dimethoxyethane, tetrahydrofuran, and dioxane are preferably used in that the target cyclic azine compound is highly selectively synthesized.

  The reaction performed in the production method of the present invention is not particularly limited, but is usually performed in an inert gas atmosphere such as nitrogen or argon, and is performed under normal pressure or under pressure. The reaction is usually carried out in the range of 20 to 300 ° C, preferably in the range of 30 to 150 ° C.

The reaction time required for the reaction performed in the production method of the present invention is as follows: cyclic azine compound represented by general formula (2), boronic acid compound represented by general formula (3), transition metal compound, phosphine compound, and base However, it may be selected from the range of several minutes to 72 hours.

Hereinafter, the present invention will be described specifically by way of examples. However, the present invention is not limited by these.
[Material purity measurement (HPLC analysis)]
Measuring device: Multistation LC-8020 (manufactured by Tosoh Corporation)
Measuring method: Column Inertsil ODS-3V (4.6 mmΦ × 250 mm) (manufactured by GL Sciences)
Detector UV detection (wavelength 254nm)
Eluent Methanol / Tetrahydrofuran = 9/1 (v / v ratio)
Example 1

  Compound C-1 (synthesized based on the method described in JP2011-121934A) 4.04 g (9.62 mmol), 1-naphthaleneboronic acid 2.15 g (12.5 mmol), tetrahydrofuran 50 mL, palladium acetate 2.16 mg (Pd atom is 0.0094 mmol, 0.00098 times mol with respect to the amount of compound C-1 used), 2-dicyclohexylphosphino-2 ′, 4 ′, 6′-triisopropylbiphenyl 9.17 mg (0.019 mmol) ) Was added to a 200 mL four-necked flask and heated at 60 ° C. for 10 minutes under a nitrogen atmosphere. To this solution, 16.9 g of a 20% aqueous potassium carbonate solution (3.46 g (25.0 mmol) as potassium carbonate) was added dropwise, and the mixture was further reacted at 75 ° C. for 7 hours. After completion of the reaction, the reaction solution was cooled to room temperature. Thereafter, 50 mL of pure water was added, and the mixture was stirred as it was at room temperature for 30 minutes. The precipitated white powder was collected by filtration and washed successively with pure water, methanol, and hexane. Then, it vacuum-dried at 70 degreeC, and obtained 4.90g of target compounds D-1 as white powder (yield 99%). The obtained product had a very high HPLC purity of 99.65%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.93%. The recovery rate during recrystallization of toluene was 88%.

Example 2
In Example 1, 1.08 mg of palladium acetate to be used (Pd atom is 0.0048 mmol, 0.00050 times mol with respect to the amount of compound C-1 to be used), 2-dicyclohexylphosphino- The same operation was performed except that 4.5 'mg (0.0096 mmol) of 2', 4 ', 6'-triisopropylbiphenyl and the reaction time was 13 hours, and 4.90 g of the target compound D-1 as a white powder. Obtained (yield 99%). The HPLC purity of the obtained target product was very high as 99.66%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.94%. The recovery rate during recrystallization of toluene was 88%.

  Example 3

  In Example 1, the same operation as in Example 1 was repeated except that 2.78 g (12.5 mmol) of 9-anthraceneboronic acid was used instead of 1-naphthaleneboronic acid and the reaction time was 10 hours. 2.40 g of 2 was obtained as a pale yellow powder (yield 100%). The obtained product had a very high HPLC purity of 99.54%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.91%. The recovery rate during toluene recrystallization was 90%.

  Example 4

  In Example 1, 4.31 g (9.62 mmol) of Compound C-2 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and the reaction time was 10 hours. Performed the same operation, and obtained 5.17g of target compound D-3 as white powder (yield 99%). The HPLC purity of the obtained target product was as high as 99.22%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.97%. The recovery rate during toluene recrystallization was 83%.

  Example 5

  In Example 1, 4.52 g (9.62 mmol) of Compound C-3 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and instead of 1-naphthaleneboronic acid. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 5.60 g of the target compound D-4 was obtained as a white powder (yield 99%). ). The HPLC purity of the obtained target product was as high as 99.31%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.90%. The recovery rate during toluene recrystallization was 85%.

  Example 6

  In Example 1, 5.23 g (9.62 mmol) of Compound C-4 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.48 g (12.5 mmol) of 4-biphenylboronic acid was used, and 6.31 g of the target compound D-5 was obtained as a yellow powder (yield 99%). The obtained product had a very high HPLC purity of 99.28%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.97%. The recovery rate during toluene recrystallization was 87%.

  Example 7

  In Example 1, 5.16 g (9.62 mmol) of Compound C-5 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and the reaction time was changed to 12 hours. Performed the same operation, and obtained 6.00g of the target compound D-6 as white powder (yield 99%). The HPLC purity of the obtained target product was as extremely high as 99.55%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.98%. The recovery rate during toluene recrystallization was 89%.

  Example 8

  In Example 1, 5.16 g (9.62 mmol) of Compound C-5 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 6.31 g of the target compound D-7 was obtained as a white powder (yield: 100%). ). The HPLC purity of the obtained target product was very high at 99.48%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.95%. The recovery rate during toluene recrystallization was 84%.

  Example 9

  In Example 1, 5.16 g (9.62 mmol) of Compound C-5 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was carried out except that 2.78 g (12.5 mmol) of 9-anthraceneboronic acid was used and the reaction time was 12 hours, to obtain 6.51 g of the target compound D-8 as a yellow powder (yield) 99%). The obtained product had a very high HPLC purity of 99.47%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.92%. The recovery rate during toluene recrystallization was 85%.

  Example 10

  In Example 1, 6.04 g (9.62 mmol) of Compound C-6 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 6.09 g of the target compound D-9 was obtained as a pale yellow powder (yield 99). %). The HPLC purity of the obtained target product was as extremely high as 99.51%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.90%. The recovery rate during toluene recrystallization was 89%.

  Example 11

  In Example 1, 5.00 g (9.62 mmol) of Compound C-7 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 6.15 g of the target compound D-10 was obtained as a white powder (yield 100%). ). The obtained product had a very high HPLC purity of 99.49%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.91%. The recovery rate during toluene recrystallization was 83%.

  Example 12

  In Example 1, 5.00 g (9.62 mmol) of Compound C-7 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (3-pyridyl) phenylboronic acid was used, and 6.13 g of the target compound D-11 was obtained as a white powder (yield 100%). ). The HPLC purity of the obtained target product was as extremely high as 99.44%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.98%. The recovery rate during toluene recrystallization was 81%.

  Example 13

  In Example 1, 5.00 g (9.62 mmol) of Compound C-7 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and the reaction time was 12 hours. Performed the same operation, and obtained 5.81g of target compound D-12 as white powder (yield 99%). The obtained product had a very high HPLC purity of 99.11%. Further, by performing recrystallization purification twice with toluene, the HPLC purity became 99.99%. The recovery rate during toluene recrystallization was 75%.

  Example 14

  In Example 1, 5.00 g (9.62 mmol) of Compound C-7 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.78 g (12.5 mmol) of 9-anthraceneboronic acid was used, and 6.33 g of the target compound D-13 was obtained as a yellow powder (yield 99%). The obtained product had a very high HPLC purity of 99.40%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.93%. The recovery rate during recrystallization of toluene was 88%.

  Example 15

  In Example 1, 4.77 g (9.62 mmol) of Compound C-8 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 5.92 g of the target compound D-14 was obtained as a white powder (yield 100%). ). The HPLC purity of the obtained target product was very high as 99.77%. Furthermore, by performing recrystallization purification once with toluene, the HPLC purity became 99.99%. The recovery rate during toluene recrystallization was 89%.

  Example 16

  In Example 1, 6.89 g (9.62 mmol) of Compound C-9 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 7.55 g of the target compound D-15 was obtained as a white powder (yield 99%). ). The HPLC purity of the obtained target product was very high as 99.62%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.97%. The recovery rate at the time of toluene recrystallization was 93%.

  Example 17

  In Example 1, 6.89 g (9.62 mmol) of Compound C-9 (synthesized based on the method described in JP2011-121934A) was used instead of Compound C-1, and the reaction time was 12 hours. Performed the same operation, and obtained 7.36g of target compound D-16 as white powder (yield 100%). The obtained product had a very high HPLC purity of 99.76%. Further, by performing recrystallization purification once with toluene, the HPLC purity became 99.93%. The recovery rate during toluene recrystallization was 92%.

  Example 18

  In Example 1, 5.58 g (9.62 mmol) of Compound C-10 (synthesized based on the method described in JP2011-063584) was used instead of Compound C-1, and 1-naphthaleneboronic acid was used instead. The same operation was performed except that 2.49 g (12.5 mmol) of 4- (2-pyridyl) phenylboronic acid was used, and 6.19 g of the target compound D-17 was obtained as a white powder (yield 98%). ). The HPLC purity of the obtained target product was very high as 99.16%. Further, by performing recrystallization purification twice with toluene, the HPLC purity became 99.91%. The recovery rate during toluene recrystallization was 74%.

Comparative Example 1
In Example 1, 216 mg of palladium acetate to be used (Pd atom is 0.962 mmol, 0.10 times mol of the amount of compound C-1 used), 2-dicyclohexylphosphino-2 ′, 4 ′, 6 ′ -The same operation was performed except having made 917 mg (1.92 mmol) of triisopropyl biphenyl, and 5.02g of target compound D-1 was obtained as gray powder (yield 102%). The HPLC purity of the obtained target product was as low as 97.51%. Even if recrystallization purification was performed once with toluene, the HPLC purity was improved only to 98.79%. The recovery rate during toluene recrystallization was 78%. In order to improve the HPLC purity to 99.9% or more, a purification operation by column chromatography was required.

Comparative Example 2
In Example 8, 216 mg of palladium acetate to be used (Pd atom is 0.962 mmol, 0.10 times mol of the amount of compound C-5 used), 2-dicyclohexylphosphino-2 ′, 4 ′, 6 ′ -The same operation was performed except having made 917 mg (1.92 mmol) of triisopropyl biphenyl, and 6.37g of target compound D-7 was obtained as gray powder (yield 101%). The HPLC purity of the obtained target product was as low as 96.11%. Even if recrystallization purification was performed once with toluene, the HPLC purity was improved only to 97.88%. The recovery rate during toluene recrystallization was 75%. In order to improve the HPLC purity to 99.9% or more, a purification operation by column chromatography was required.

Comparative Example 3
In Example 11, 216 mg of palladium acetate to be used (Pd atom is 0.962 mmol, 0.10 times mol of the amount of compound C-7 used), 2-dicyclohexylphosphino-2 ′, 4 ′, 6 ′ -The same operation was performed except having made 917 mg (1.92 mmol) of triisopropyl biphenyl, and 6.26g of target compound D-10 was obtained as gray powder (yield 102%). The HPLC purity of the obtained target product was as low as 97.08%. Even if recrystallization purification was performed once with toluene, the HPLC purity was improved only to 98.50%. The recovery rate during toluene recrystallization was 77%. In order to improve the HPLC purity to 99.9% or more, a purification operation by column chromatography was required.

Comparative Example 4
In Example 16, 216 mg of palladium acetate to be used (Pd atom is 0.962 mmol, 0.10 times mol of the amount of compound C-9 used), 2-dicyclohexylphosphino-2 ′, 4 ′, 6 ′ -The same operation was performed except having made 917 mg (1.92 mmol) of triisopropyl biphenyl, and 7.76g of target compound D-15 was obtained as gray powder (yield 102%). The HPLC purity of the obtained target product was as low as 97.24%. Even if recrystallization purification was performed once with toluene, the HPLC purity was improved only to 98.79%. The recovery rate during toluene recrystallization was 79%. In order to improve the HPLC purity to 99.9% or more, a purification operation by column chromatography was required.

  According to the present invention, it is possible to efficiently produce a high-purity polysubstituted cyclic azine compound that is useful as a constituent component of an organic electroluminescence device without performing a column chromatography operation that has been conventionally required. For this reason, the production method of the present invention is very important as a method for industrially producing a polysubstituted cyclic azine compound.

Claims (2)

Cyclic azine compound represented by general formula (2) in the presence of a transition metal compound, a phosphine compound and a base

(In the formula, Ar ¹ , Ar ² , and Ar ³ each independently represent a monovalent substituent having 1 to 40 carbon atoms. X ¹ represents a chlorine atom, a bromine atom, or an iodine atom. Y Represents CH or a nitrogen atom.)
And boronic acid compound represented by the general formula (3)

(In the formula, Ar ⁴ represents a monovalent substituent having 1 to 40 carbon atoms. R ¹ each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a phenyl group, R ¹ may be linked to form a ring containing an oxygen atom and a boron atom.)
General formula (1)

(In the formula, Ar ¹ , Ar ² , Ar ³ , and Ar ⁴ each independently represent a monovalent substituent having 1 to 40 carbon atoms. Y represents CH or a nitrogen atom.)
In which {(number of moles of transition metal in transition metal compound) ÷ (number of moles of compound represented by general formula (2))} is 0.00001 to 0 0.009 is a method for producing a cyclic azine compound represented by the general formula (1).   {(Number of moles of transition metal in transition metal compound) ÷ (number of moles of compound represented by general formula (2))} is 0.00001 to 0.005, characterized in that The manufacturing method of the cyclic azine compound of description.