JP4542838B2 - Method for producing arylamine - Google Patents

Description

  The present invention relates to a method for producing arylamines, particularly triarylamines or diarylamines, which are useful as materials for electronic materials, such as positive charge transport materials in organic semiconductor devices, or intermediates thereof, with high purity and at low cost.

The present invention falls within the category of reactions classified as Ullmann condensation reactions when synthesizing arylamine compounds.
The Ullmann condensation reaction is a method of synthesizing an arylamine by reacting an aromatic amine compound and an aromatic halogen compound, preferably an aromatic iodide compound, in the presence of a base and a copper catalyst. Discovered by Ullmann (see Non-Patent Document 1). This reaction generally takes a long reaction time, and usually requires a high temperature of 200 ° C. or higher to achieve a practical arylation rate. Therefore, decomposition of the raw material, oxidation of the product, disproportionation, A large amount of by-products are generated by the quantification reaction or the like.

  These by-products are different from the target compound in ionization potential and electron density distribution in the frontier orbitals, leading to a decrease in the electrical characteristics of the organic semiconductor device, so that the arylamine compound used is required to have a very high purity. For example, regarding the influence of impurities on the mobility of a hole transport material, it has been reported that the hole mobility is lowered by the addition of an impurity having a small ionization potential (see Non-Patent Documents 2 to 4). In order to obtain high mobility, it is pointed out that impurities form hole traps, and at least impurities with a small ionization potential by-produced by oxidation or dimerization of the product are not included as much as possible. It becomes the condition of. In addition, it has been reported that arylamine derivatives exhibit high mobility when the electron density distribution of the frontier orbitals in neutral and cation radical states is small (see Non-Patent Document 5), and the polarity generated by oxidation The presence of an impurity having a group causes a decrease in electrical characteristics. For this reason, it is necessary to eliminate these by-products in the materials for electronic materials as much as possible, but their separation and purification is very difficult, and they must be repeatedly purified by recrystallization or column chromatography, resulting in high costs. There was a problem.

  In the Ullmann reaction, a method for suppressing a by-product that adversely affects electrical characteristics has been reported. For example, a method of synthesizing a styryl compound or an arylamine compound by reacting a halogenated aromatic compound with a large excess of an aromatic amine compound (see Patent Documents 1 and 2), a halogenated aromatic compound and an aromatic amine compound, In the synthesis of an arylamine compound having a fluorene skeleton by reacting, a method of reducing the amount of copper catalyst used to suppress by-products (see Patent Document 3), halogenated aromatic compounds and aromatic amine compounds A method for suppressing by-products by combining an inert gas atmosphere and inorganic sulfite when synthesizing a triarylamine derivative by reacting with a copper powder catalyst and a base (see Patent Document 4) Although in all cases, by-products are suppressed, coloring impurities, oxides, decomposition products, etc. are still produced, and materials for electronic materials or their It had to be highly purified for use as the body.

  In order to produce a high purity arylamine compound, it is preferable to react at a lower temperature. An aromatic amine compound and an iodinated aromatic compound are mixed in an aromatic solvent, a copper catalyst, potassium hydroxide, and a tertiary amine. A method for producing a triarylamine compound that reacts at 120 to 150 ° C. in the presence of the compound has been proposed (see Patent Documents 5 to 10). However, in these methods, the reaction proceeds efficiently even at a low temperature, but the yield and purity are not satisfactory, and the above problems have not been solved.

  As another method for synthesizing an arylamine compound at a low temperature, a chlorinated aromatic compound or a brominated aromatic compound and an aromatic amine compound in an aromatic solvent in the presence of a palladium catalyst, a phosphine compound and a base, Although a method of reacting at ~ 140 ° C (see Patent Documents 11 to 15 and Non-Patent Documents 6 to 9) has been proposed, a palladium compound is very expensive and is difficult to separate and recover after the reaction. The production method is not particularly advantageous, and the yield and purity are not satisfactory.

JP-A-9-258465 Japanese Patent Laid-Open No. 11-282180 JP 2000-178237 A JP 2000-239235 A JP-A-9-323958 JP 9-323959 A Japanese Patent Laid-Open No. 10-212267 Japanese Patent Laid-Open No. 10-212268 JP 10-212269 A Japanese Patent Laid-Open No. 10-312073 JP 10-139742 A Japanese Patent Laid-Open No. 10-195031 Japanese Patent Laid-Open No. 10-310561 Japanese Patent Laid-Open No. 11-5769 JP 2002-275130 A “Hemiche Berichte”, 1920, 36 p. 2382 “The Journal of Applied Physics”, 1972, 43, p. 5033 “Physical Review Letters”, 1976, 37, p. 1360 “The Journal of Physical Chemistry”, 1984, 88, p. 4714f Journal of Electrophotographic Society, 1990, 29, 4 p. 366 “Angevante Chemie International English Ed.”, Vol. 37, 1998, p. 2046 “Journal of The American Chemical Society”, 1998, 120, p. 9722 “The Journal of Organic Chemistry”, 1996, 61 p. 1133 “Tetrahedron Letters”, 1995, Vol. 36, No. 21, p. 3609

  It is an object of the present invention to synthesize very high purity arylamines, particularly triarylamines or diarylamines, by suppressing impurities that adversely affect electrical characteristics when synthesizing arylamine compounds in the Ullmann reaction. Another object of the present invention is to provide a method for producing a material for electronic materials, for example, a positive charge transport material in an organic semiconductor element, or a material suitable for use as an intermediate thereof at low cost.

The above object is achieved by the following method.
(I) A method for producing an arylamine, comprising reacting an aromatic amine compound and an aromatic halogen compound in the presence of a copper catalyst and a base in the presence of at least one compound selected from the following compound group A.
Compound group A:
Cytosine, 5-fluorocytosine, N-acetylcytosine, N-benzoylcytosine, 5-methylcytosine, isocytosine, uracil, thymine, dihydrothymine, 1-methyluracil, 3-methyluracil, 6-methyluracil, 5-aminouracil , 6-aminouracil, 5-fluorouracil, 5-formyluracil, 1,3-dimethyluracil, 1-methylthymine, 5-ethyluracil, 6-amino-1-methyluracil, 5,6-diaminouracil, 4-chloro Uracil, 5-chlorouracil, 5-n-propyluracil, 1,3,6-trimethyluracil, 1,3,5-trimethyluracil, 6-amino-1-ethyluracil, 6-amino-1,3-dimethyl Uracil, 5,6-diamino-1,3-dimethyluracil, 2,4-di Droxypyrimidine-5-carboxylic acid, orotic acid, isoorotic acid, 5-bromoorotic acid, 5-aminoorotic acid, 5- (hydroxymethyl) -6-methyluracil, 5-nitrouracil, 6-propylideneaminouracil, 6-amino-1-methyl-5-nitrosouracil, 6-amino-1-methyl-5- (methylamino) uracil, trifluorothymine, thymine-1-acetic acid, 1-cyclohexyluracil, barbituric acid, isobarbi Tool acid, alloxan, 5-methyl-2-thiouracil, 6-methyl-2-thiouracil, purine, 6-methylpurine, 2-aminopurine, adenine, 6-cyanopurine, 1-methyladenine, N-methyladenine, 3-methyladenine, 9-methyladenine, 6-methoxypurine, 2-methylpurine -6-ol, 6-methylpurin-2-ol, 8-methylpurin-6-ol, 2,6-diaminopurine, 2-fluoroadenine, 6-chloropurine, 6-dimethylaminopurine, 9-ethyl Adenine, 6-ethoxypurine, 6-o-methylguanine, 2-methylpurine-6-thiol, 9-methylpurine-6-thiol, 2-amino-6-chloropurine, 6-isopropoxypurine, 2,6 -Diamino-7-ethylpurine, 6-ethylmercaptopurine, 2,6-dichloropurine, 6-butoxypurine, 2- (dimethylamino) -9-methylpurin-6-ol, 2-amino-9-butylpurine -6-ol, purine-2,6,8-trithiol, N-cyclopentyl-9-methylpurin-6-amine, ethyladenine-9-acetate DL-dihydrozeatin, N, N-dihydroxyethyladenine, 6-benzylaminopurine, 6-benzyloxypurine, uric acid, guanine, 1-methylguanine, 7-methylguanine, 2-amino-6,9- Dihydropurine-8-thiol, xanthine, hypoxanthine, theophylline, theobromine, caffeine, 1,3-dimethyl-1H-quinazoline-2,4-dione, octahydrocyclopentapyrimidin-4-one, 8-aza-6 -Aminopurine, 4- (4-hydroxy-3,5-dimethylphenyl) octahydropyrano [4,3-a] pyrimidin-2-one, hexahydroquinazoline-2,4-dione, 1H-quinazoline-2 , 4-dithione, 2,4-pteridinediol, and 1,3,6,6-tetramethylhexahydro Opirano [3,2-a] pyrimidine-2,4-dione.
The invention of the present application has the structure described in the scope of claims, but the following are also described for reference.

  According to the present invention, a material for electronic materials, for example, a positive charge transport material in an organic semiconductor element, or an arylamine useful as an intermediate thereof, particularly a triarylamine or diarylamine compound can be produced with extremely high purity and low cost. Have high practicality.

The present invention will be described in further detail.
The present invention relates to the production of arylamines, particularly materials for electronic materials, such as positive charge transport materials in organic semiconductor devices, or a group of triarylamines or diarylamines useful as intermediates thereof, using an Ullmann condensation reaction. This is a novel production method in which a reaction is carried out in the presence of a catalyst, a base, and at least one of the compounds represented by formula (A). As a result of repeated studies to solve the problems in conventional arylamine production, the present inventor compared with the conventionally proposed arylamine synthesis method by carrying out the reaction in the presence of the compound represented by the general formula (A). And it discovered that by-products, such as an oxidation product and a dimerization product, can be suppressed very highly. These compounds are thought to act to capture various active oxygen species such as superoxide, hydroperoxy radical, hydroxy radical, hydrogen peroxide, and singlet oxygen that can be generated in the reaction system during the Ullmann reaction. The arylamine compound synthesized here contains almost no polar group substitution impurities or impurities with low ionization potential that cause deterioration of electrical properties generated by oxidation reaction, so it can be used as a material for electronic materials or its intermediate by extremely easy purification. Can be used.

R1 and R2 each independently represent a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, or a heterocyclic residue.
A plurality of R3 are each independently a hydrogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, hydroxy group, oxy group, carboxyl group, carbonyl group, carbamoyl group, sulfonyl group, phosphoryl group, sulfanyl group, thio group, A nitro group, an amino group, a cyano group, a halogen atom, or a heterocyclic residue is represented.
p and q represent 0 or 1;
r represents an integer of 4 to 8.
When either R1 or R2 is adjacent to R3, or when there are a plurality of R3 and they are adjacent, each may be linked to form a ring.
When a plurality of R3 are present on the same carbon atom, they may form an oxo group, a thioxo group, or ═N (R4).
R4 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a hydroxy group, an oxy group, a formyl group, a carbonyl group, or a heterocyclic residue.

  Here, the 6-membered ring in the general formula (A) is composed of 2 nitrogen atoms and 4 carbon atoms, and represents a bond between the atoms--the line (broken line) represents a single bond or a double bond. . Specifically, the compound represented by the general formula (A) of the present invention has a basic skeleton represented by the following general formulas A-1 to A-10.

In the formula, R1, R2, R3, and r have the same meaning as described above.
The compounds represented by formula (A) can be used alone or in combination of two or more.
In the compound represented by the general formula (A), the alkyl groups represented by R1 to R4 are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl Represents a linear, branched or cyclic alkyl group such as hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl.
The alkenyl groups represented by R1 to R4 are vinyl, allyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, A linear, branched or cyclic alkenyl group such as hexadienyl, dodecatrienyl and the like is represented.
The alkynyl group represented by R1 to R4 represents a linear, branched or cyclic alkynyl group such as ethynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, cyclooctynyl, cyclononynyl, cyclodecynyl and the like.
The aryl group represented by R1 to R4 represents a 6- to 10-membered monocyclic or polycyclic aryl group such as phenyl, naphthyl, phenanthryl, anthryl and the like.

The hydroxy group represented by R3 and R4 represents a hydroxy group and an alkali metal salt or alkaline earth metal salt thereof.
The oxy groups represented by R3 and R4 are alkoxy groups such as methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, dodecyloxy, octadecyloxy; phenoxy, tolyloxy, xylyloxy, Aryloxy groups such as naphthyloxy; carbonyloxy groups such as acetyloxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, valeryloxy, octanoyloxy, benzoyloxy, naphthoyloxy; N-methylaminocarbonyloxy, N -Butylaminocarbonyloxy, N-hexylaminocarbonyloxy, N-decylaminocarbonyloxy, N-tetradecylaminocarbonyloxy, N-o Alkylaminocarbonyloxy groups such as tadecylaminocarbonyloxy; arylaminocarbonyloxy groups such as N-phenylaminocarbonyloxy and N-naphthylaminocarbonyloxy; hydroxysulfonyloxy, methylsulfonyloxy, phenylsulfonyloxy, tolylsulfonyloxy and the like Sulfonyloxy group and its alkali metal salt or alkaline earth metal salt; hydroxyphosphoryloxy, dihydroxyphosphoryloxy, methoxyphosphoryloxy, dimethoxyphosphoryloxy, diethoxyphosphoryloxy, dipropoxyphosphoryloxy, phenylphosphonyloxy, methylphenylphosphoryl Oxy, ethoxyphenyl phosphoryloxy, phenoxyphosphoryloxy, diphenoxyphosphoryloxy It represents a phosphoryloxy group and its alkali metal salt or alkaline earth metal salt.

The carboxyl group represented by R3 represents a carboxyl group and an alkali metal salt or alkaline earth metal salt thereof.
The carbonyl groups represented by R3 and R4 are alkylcarbonyl groups such as acetyl, propionyl, butyryl, pentanoyl, hexanoyl, valeryl and octanoyl; arylcarbonyl groups such as benzoyl and naphthoyl; methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, n -Alkoxycarbonyl groups such as butoxycarbonyl, tert-butoxycarbonyl, n-hexyloxycarbonyl, n-decyloxycarbonyl, n-dodecyloxycarbonyl, n-octadecyloxycarbonyl; aryloxycarbonyl groups such as phenoxycarbonyl and naphthyloxycarbonyl Represents.
The carbamoyl group represented by R3 is carbamoyl; monosubstituted carbamoyl groups such as N-methylcarbamoyl, N- (tert-butyl) carbamoyl, N-dodecylcarbamoyl, N-octadecylcarbamoyl, N-phenylcarbamoyl; N, N-dimethyl It represents a disubstituted carbamoyl group such as carbamoyl, N, N-dihexylcarbamoyl, N, N-didecylcarbamoyl, N, N-diphenylcarbamoyl, N-methyl-N-phenylcarbamoyl and the like.

The sulfonyl group represented by R3 is a sulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, hexylsulfonyl, octylsulfonyl, dodecylsulfonyl, hexadecylsulfonyl, phenylsulfonyl, naphthylsulfonyl, tolylsulfonyl and the like. Alkali metal salt or alkaline earth metal salt is represented.
The phosphoryl group represented by R3 is a phosphoryl group such as hydroxyphosphoryl, dihydroxyphosphoryl, methoxyphosphoryl, dimethoxyphosphoryl, diethoxyphosphoryl, dipropoxyphosphoryl, phenylphosphonyl, methylphenylphosphoryl, ethoxyphenylphosphoryl, phenoxyphosphoryl, and diphenoxyphosphoryl. And alkali metal salts or alkaline earth metal salts thereof.
The sulfanyl group represented by R3 represents a sulfanyl group and an alkali metal salt or alkaline earth metal salt thereof.

The thio group represented by R3 is methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio, heptylthio, octylthio, nonylthio, decylthio, undecylthio, dodecylthio, tridecylthio, tetradecylthio, pentadecylthio, hexadecylthio, heptadecylthio, octadecylthio, nonadecylthio, Linear, branched or cyclic alkylthio groups such as icosylthio, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio, cycloheptylthio, cyclooctylthio, cyclononylthio, cyclodecylthio; phenylthio, tolylthio, xylylthio, naphthylthio 6 to 10-membered monocyclic or polycyclic arylthio groups such as phenanthrylthio and anthrylthio; Represents benzoylthio, arylcarbonyl thio group such as a naphthyl carbonyl thio; ylcarbonyl thio, propyl carbonyl thio, butylcarbonyl thio, pentylcarbonyl thio, hexyl carbonyl thio, alkylcarbonyl thio group such as octyl carbonyl thio.
The amino group represented by R3 is amino; N-methylamino, N-butylamino, N-hexylamino, N-decylamino, N-tetradecylamino, N-octadecylamino, N-phenylamino, N-naphthylamino, etc. Monosubstituted amino groups of N, N-diethylamino, N, N-diheptylamino, N, N-dioctylamino, N, N-dodecylamino, N, N-octadecylamino, N, N-diphenylamino and the like Represents a substituted amino group.
The halogen atom represented by R3 represents fluorine, chlorine, bromine or iodine.

The heterocyclic residue represented by R1 to R4 represents a heterocyclic group containing 1 to 4 atoms selected from 5 to 10-membered monocyclic or bicyclic nitrogen, oxygen and sulfur. , Tetrahydrofuran, furan, pyran, tetrahydrothiophene, thiophene, pyrrolidine, pyridine, pyrrole, pyrazine, azepine, azocine, azonin, azecine, oxazole, thiazole, pyrimidine, pyridazine, triazine, triazole, tetrazole, imidazole, pyrazole, morpholine, thiomorpholine , Piperidine, piperazine, quinoline, isoquinoline, indole, isoindole, quinoxaline, phthalazine, quinolidine, quinazoline, quinoxaline, naphthyridine, chromene, benzofuran, benzothiophene and the like.
These R1 to R4 substituents may further have a substituent such as a hydroxy group, an alkyl group, an alkoxy group, an aryl group, a carboxyl group, an oxo group, a nitro group, a cyano group, a halogen, a sulfonic acid, and a phosphonic acid. The substituent is not particularly limited as long as it does not participate in the reaction.

When either R1 or R2 is adjacent to R3, or when there are a plurality of R3 and they are adjacent, each may be linked to form a ring.
Rings formed by linking R3 adjacent to any of R1 and R2 include pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, pyrazolidine, imidazole, triazole, tetrazole, isoxazole, oxazole, oxadiazole, osothiazole, Examples thereof include 5- to 8-membered heterocyclic rings containing one or more nitrogen atoms such as thiazole, thiazoline, thiazolidine, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, tetrazine, oxazine, morpholine, thiazine and the like.
Rings formed by connecting two adjacent R3s include saturated rings such as cyclobutane, cyclopentane and cyclohexane; partially saturated rings such as cyclobutene, cyclopentene, cyclopentadiene, cyclohexene and cyclohexadiene; aromatics such as benzene and naphthalene Ring: pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, pyrazolidine, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, furan, tetrahydrofuran, pyran, tetrahydropyran, thiophene, tetrahydrothiophene, thiopyran And 5- to 8-membered heterocycles containing at least one nitrogen atom, oxygen atom, and sulfur atom such as thiane.
These linked rings may further have a substituent, and the substituent is not particularly limited as long as it does not participate in the reaction. Specific examples include hydroxy group, alkyl group, alkoxy group, aryl group, carboxyl group, oxo group, nitro group, cyano group, halogen, sulfonic acid, phosphonic acid and the like.

  When a plurality of R3 are present on the same carbon atom, they may form a double bond to form an oxo group, a thioxo group, or ═N (R4).

  Specific examples of the compound represented by the general formula (A) include pyrimidine derivatives, cyclopentapyrimidine derivatives, quinazoline derivatives, purine derivatives, pyrazolopyrimidine derivatives, azapurine derivatives, pteridine derivatives, furanopyrimidine derivatives, pyranopyrimidine derivatives, Examples include thiopyranopyrimidine derivatives and pyrimidopyrimidine derivatives.

Specific examples of the compound represented by formula (A) are shown below, but the present invention is not limited thereto.
(A) Pyrimidine derivatives; cytosine, 5-fluorocytosine, 1-amino-4,6-dimethylpyrimidinone, 4-methoxy-1-methylpyrimidinone, N-acetylcytosine, N-benzoylcytosine, 5-methyl Cytosine, 1- (tetrahydropyran-2-yl) cytosine, cytidine, 2′-deoxycytidine, 5-methyl-2′-deoxycytidine, 2 ′, 3′-dideoxycytidine, N-acetylcytidine, 2′-deoxy Cytidine 5′-monophosphate, 2′-deoxycytidine 3′-ammonium monophosphate, cytidine acid, isocytosine, 2-amino-3,6-dimethylpyrimidinone, 2-amino-6-phenylpyrimidinone, 5- (2-Amino-4-hydroxy-1-methyl-6-oxo-1,6-dihydro-5-pyrimidyl) pentanoic acid, urasi , Thymine, dihydrothymine, 1-methyluracil, 3-methyluracil, 6-methyluracil, 5-aminouracil, 6-aminouracil, 5-fluorouracil, 5-formyluracil, 1,3-dimethyluracil, 1- Methylthymine, 5-ethyluracil, 6-amino-1-methyluracil, 5,6-diaminouracil, 4-chlorouracil, 5-chlorouracil, 5-n-propyluracil, 1,3,6-trimethyluracil, 1 , 3,5-trimethyluracil, 6-amino-1-ethyluracil, 6-amino-1,3-dimethyluracil, 5,6-diamino-1,3-dimethyluracil, 2,4-dihydroxypyrimidine-5 Carboxylic acid, orotic acid, isoorotic acid, 5-bromoorotic acid, 5-aminoorotic acid, 6-amino -2,4-dihydroxy-5-nitrosopyrimidine, 5- (hydroxymethyl) -6-methyluracil, 5-nitrouracil, 1-allyl-6-aminouracil, 6-propylideneaminouracil, 6-amino-1 -Methyl-5-nitrosouracil, 6-amino-1-methyl-5- (methylamino) uracil, 6-chloro-4-imino-1,3-dimethyl-3,4-dihydro-2-pyrimidinone, trifluoro Thymine, thymine-1-acetic acid, 1-cyclohexyluracil, 5- (1,3,4-oxadiazol-2-yl) uracil, uridine, thymidine, uridylic acid, thymidylic acid, barbituric acid, isobarbituric acid Alloxan, 5-methyl-2-thiouracil, 6-methyl-2-thiouracil and the like.

  (B) Cyclopentapyrimidine derivatives; octahydrocyclopentapyrimidin-4-one, octahydrocyclopentapyrimidine-4-thione, 3-phenylhexahydrocyclopentapyrimidine-2,4-dione, 2-thio-5,6 -Trimethylene-2,3,5,6-tetrahydropyrimidin-4 (1H) -one, 5,6-trimethylene-5,6-dihydro-2,4 (1H, 3H) -pyrimidinone, 6-tert-butylhexa Hydrocyclopentapyrimidine-2,4-dione, 1-benzyl-6-tert-butylhexahydrocyclopentapyrimidine-2,4-dione, 6-tert-butyl-2-thiooctahydrocyclopentapyrimidin-4-one 1-benzyl-6-tert-butyl-3-phenylhexahydrocyclopenta Limidine-2,4-dione, 3-methyl-2-thiooctahydrocyclopentapyrimidin-4-one, 3-cyclohexyl-7-methylhexahydrocyclopentapyrimidine-2,4-dione, 3-cyclohexyl-7a- Hydroxyhexahydrocyclopentapyrimidine-2,4-dione, 4,5,7,7-tetramethyloctahydrocyclopentapyrimidin-2-one, 7-hydroxy-1,3-dimethyl-4-thiooctahydrocyclopenta Pyrimidin-2-one, 2-imino-3-phenyloctahydrocyclopentapyrimidin-2-thione, 3-benzyl-2-thiooctahydrocyclopentapyrimidin-4-one, 2-thioxo-3-p-tolylocta Hydrocyclopentapyrimidin-4-one, 3-isopropyl-2-thio Seo octahydrocyclopenta pyrimidin-4-one, 4-phenyl-imino octahydrocyclopenta-2-thione or the like.

  (C) quinazoline derivative; quinazoline, 3,4-dihydroquinazoline, 1,2,3,4-tetrahydroquinazoline, 3-phenyl-3,4-dihydro-1H-quinazoline-2-thione, 3-phenyl-3H- Quinazolin-4-one, 4- [1] naphthyl-3,4-dihydro-1H-quinazoline-2-thione, 1H-quinazoline-2,4-dione, 1,3-dimethyl-1H-quinazoline-2,4 -Dione, 1,3-benzoyl-1H-quinazoline-2,4-dione, 3-ethyl-1-methyl-1H-quinazoline-2, 4-dione, 6-hydroxy-1H-quinazoline-2,4-dione 2-methyl-3,4-dihydroquinazoline, 1-methyl-1,2,3,4-tetrahydroquinazoline, 1H-quinazoline-2,4-dithione, 3-allyl-3,4-dihi Droquinazoline, 4-amino-1H-quinazoline-2-thione, 2-thioxo-2,3-dihydro-1H-quinazolin-4-one, 2-oxo-1,2,5,6,7,8-hexa Hydroquinazoline-4-carboxylic acid, 3-benzyl-3,4,5,6,7,8-hexahydro-1H-quinazolin-2-one, 4a-hydroxyhexahydroquinazoline-2,4-dione, 2-phenyl Octahydroquinazolin-4-one, 3-hydroxymethyl-1-methyloctahydroquinazolin-4-one, decahydro-3-methylquinazoline, hexahydroquinazoline-2,4-dione, 2-thiooctahydroquinazoline-4- ON, 8a-hydroxy-1-phenyl-4-thiophen-2-yl-octahydroquinazoline-2-thione, 3-methyl-2 Thioxooctahydroquinazolin-4-one, 2,2-dimethyloctahydroquinazolin-4-one, 3- (2-hydroxyethyl) -2-thiooctahydroquinazolin-4-one, 3-isopropyl-1-methyl Hexahydroquinazoline-2,4-dione, 1-acetyl-3-isopropylhexahydroquinazoline-2,4-dione, and the like.

  (D) Purine derivatives; purine, 6-methylpurine, 2-aminopurine, adenine, 6-cyanopurine, 1-methyladenine, N-methyladenine, 3-methyladenine, 9-methyladenine, 6-methoxypurine, 2-methylpurin-6-ol, 6-methylpurin-2-ol, 8-methylpurin-6-ol, 2,6-diaminopurine, 2-fluoroadenine, 6-chloropurine, 6-dimethylaminopurine, 9-ethyladenine, 6-ethoxypurine, 6-O-methylguanine, 2-methylpurine-6-thiol, 9-methylpurine-6-thiol, 2-amino-6-chloropurine, 6-isopropoxypurine, 2,6-diamino-7-ethylpurine, 6-ethylmercaptopurine, 2,6-dichloropurine, 6-butoxypurine, 2 (Dimethylamino) -9-methylpurin-6-ol, 6-bromopurine, 6- (1-piperidyl) purine, 9-tetrahydro-2-furanylpurin-6-ylamine, 6- (4-morpholinyl) purine, 2 -Amino-9-butylpurin-6-ol, N- (2-furylmethyl) purin-6-amine, purine-2,6,8-trithiol, N-cyclopentyl-9-methylpurin-6-amine, ethyl Adenine-9-acetate, DL-dihydrozeatin, N, N-dihydroxyethyladenine, 6-benzylaminopurine, 6-benzyloxypurine, uric acid, 2,6,8, -trichloro-7-methylpurine, 6- (Trichloromethyl) purine, 6-chloro-9-tetrahydro-2H-pyran-2-ylpurine, guanine, 1-methylgua 7-methylguanine, 2-amino-6,9-dihydropurine-8-thiol, 2-amino-8-bromo-1,9-dihydropurin-6-one, 2′-deoxyinosine, adenosine, 1 -Methyladenosine, adenylic acid, 2 ', 3'-dideoxyadenosine, 2', 5'-dideoxyadenosine, guanosine, 8-bromoguanosine, guanylic acid, 2'-deoxyguanosine, 2'-deoxyguanosine-5'- Sodium monophosphate, guanosine-5′-sodium diphosphate, xanthine, hypoxanthine, 2-bromohypoxanthine, inosine, 2 ′, 3′-o-isopropylidene inosine, inosine-5′-sodium monophosphate, Inosinic acid, inosine-5′-diphosphate sodium, theophylline, theobromine, caffeine, uri Acid etc.

(E) pyrazolopyrimidine derivatives; 4-aminopyrazolo [3,4-d] pyrimidine and the like.
(F) azapurine derivatives; 8-aza-6-aminopurine, 8-azaguamine and the like.
(G) pteridine derivative; 2-amino-4-pteridinol, 2,4-pteridinediol, 2-amino-4,6-pterindiol, 2-amino-6,7-dimethyl-4-pteridinol, 2,4- Diamino-6,7-diisopropylpteridine, 2,4-diamino-6-pteridinemethanol, 5,6,7,8-tetrahydro-4-pteridinol, 2,4,7-triamino-6-phenylpteridine and the like.
(I) Furanopyrimidine derivatives; 1,3,6-trimethyl-6,7-dihydrofuro [3,2-d] pyrimidine-2,4- (1H, 3H) dione and the like.

(J) pyranopyrimidine derivatives; 6-allyl-5-hydroxy-8-methyl-2,4-diaza-9-oxabicyclo [4,3,0] nonan-3-one, 6,7,8-tris Benzyloxy-1,3-dimethyloctahydropyrano [3,2-a] pyrimidine, 4- (4-hydroxy-3,5-dimethylphenyl) octahydropyrano [4,3-a] pyrimidine-2- On etc.
(K) Thiopyranopyrimidine derivatives; 1,3,6,6-tetramethylhexahydrothiopyrano [3,2-a] pyrimidine-2,4-dione and the like.
(L) pyrimidopyrimidine derivatives; 2,6-dimethyldecahydropyrimido [5,6-a] pyrimidine, 1,4,6-trimethyl-5-phenylhexahydropyrimido [5,6-a] pyrimidine- 2,7-dione and the like.

Among these, a pyrimidine derivative, a cyclopentapyrimidine derivative, a quinazoline derivative, and a purine derivative are preferable, and a pyrimidine derivative and a purine derivative are more preferable.
Particularly preferred among pyrimidine derivatives and purine derivatives are cytosine, 5-fluorocytosine, N-acetylcytosine, N-benzoylcytosine, 5-methylcytosine, isocytosine, uracil, thymine, dihydrothymine, 1-methyluracil, 3-methyl. Uracil, 6-methyluracil, 5-aminouracil, 6-aminouracil, 5-fluorouracil, 5-formyluracil, 1,3-dimethyluracil, 1-methylthymine, 5-ethyluracil, 6-amino-1-methyluracil 5,6-diaminouracil, 4-chlorouracil, 5-chlorouracil, 5-n-propyluracil, 1,3,6-trimethyluracil, 1,3,5-trimethyluracil, 6-amino-1-ethyl Uracil, 6-amino-1,3-dimethylurasi 5,6-diamino-1,3-dimethyluracil, 2,4-dihydroxypyrimidine-5-carboxylic acid, orotic acid, isoorotic acid, 5-bromoorotic acid, 5-aminoorotic acid, 5- (hydroxymethyl)- 6-methyluracil, 5-nitrouracil, 6-propylideneaminouracil, 6-amino-1-methyl-5-nitrosouracil, 6-amino-1-methyl-5- (methylamino) uracil, trifluorothymine, Thymine-1-acetic acid, 1-cyclohexyluracil, barbituric acid, isobarbituric acid, alloxan, 5-methyl-2-thiouracil, 6-methyl-2-thiouracil, purine, 6-methylpurine, 2-aminopurine, Adenine, 6-cyanopurine, 1-methyladenine, N-methyladenine, 3-methyladenine 9-methyladenine, 6-methoxypurine, 2-methylpurin-6-ol, 6-methylpurin-2-ol, 8-methylpurin-6-ol, 2,6-diaminopurine, 2-fluoroadenine 6-chloropurine, 6-dimethylaminopurine, 9-ethyladenine, 6-ethoxypurine, 6-o-methylguanine, 2-methylpurine-6-thiol, 9-methylpurine-6-thiol, 2-amino -6-chloropurine, 6-isopropoxypurine, 2,6-diamino-7-ethylpurine, 6-ethylmercaptopurine, 2,6-dichloropurine, 6-butoxypurine, 2- (dimethylamino) -9- Methylpurin-6-ol, 2-amino-9-butylpurin-6-ol, purine-2,6,8-trithiol, N-cyclopentyl- 9-methylpurine-6-amine, ethyladenine-9-acetate, DL-dihydrozeatin, N, N-dihydroxyethyladenine, 6-benzylaminopurine, 6-benzyloxypurine, uric acid, guanine, 1-methylguanine 7-methylguanine, 2-amino-6,9-dihydropurine-8-thiol, xanthine, hypoxanthine, theophylline, theobromine, and caffeine, and it is preferable to react in the presence of one or more of these.

Among these, thymine, dihydrothymine, 1-methyluracil, 3-methyluracil, 6-methyluracil, 5-aminouracil, 6-aminouracil, 5-fluorouracil, 5-formyluracil, 1,3-dimethyluracil are more preferable. 1-methylthymine, 5-ethyluracil, 6-amino-1-methyluracil, 5,6-diaminouracil, 4-chlorouracil, 5-chlorouracil, 5-n-propyluracil, 1,3,6-trimethyl Uracil, 1,3,5-trimethyluracil, 6-amino-1-ethyluracil, 6-amino-1,3-dimethyluracil, 5,6-diamino-1,3-dimethyluracil, 2,4-dihydroxypyrimidine -5-carboxylic acid, orotic acid, isoorotic acid, 5-bromoorotic acid, 5-amino Rotinoic acid, alloxan, 5- (hydroxymethyl) -6-methyluracil, 5-nitrouracil, 6-propylideneaminouracil, 6-amino-1-methyl-5-nitrosouracil, 6-amino-1-methyl- Pyrimidine derivatives such as 5- (methylamino) uracil, trifluorothymine, thymine-1-acetic acid, 1-cyclohexyluracil, 5-methyl-2-thiouracil and 6-methyl-2-thiouracil.
These compounds are known methods (for example, “Organic Chemistry of Biological Substances” published by Tokyo Chemical Dojinsha, 1978, pages 267-302; “Organic Chemistry of Nucleic Acid Bases” published by Chemical Dojinsha, 1979, 6-19 pages) Those that can be synthesized by this method or that can be purchased can be used as they are added to the reaction system.

  These compounds represented by the general formula (A) (hereinafter sometimes referred to as additives) are used in an amount of 0.01 to 10 mol, preferably 0.1 to 8 mol, relative to 1 mol of the copper catalyst. More preferably, it is used in the range of 0.3 to 5 mol. By making the usage-amount of an additive into the said range, the fall of a yield and the production | generation of a new coloring impurity are prevented, obtaining the sufficient impurity suppression effect, and it is preferable.

  The aromatic halogen compound used in the present invention is a compound represented by the following general formula (1).

In the formula, Q represents a chlorine atom, a bromine atom or an iodine atom. q1 represents an integer of 0 to 5. Ra represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, a disubstituted amino group, a nitro group, a heterocyclic residue, a halogen atom, or a group represented by -L1-Rb. When q1 is 2 or more, the plurality of Ras may be the same or different, and a plurality of Ras may form a ring. L1 represents a divalent linking group, and Rb represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, a disubstituted amino group, a nitro group, a heterocyclic residue, or a halogen atom.
The aromatic halogen compound represented by the formula (1) is more preferably a compound represented by the following general formula (2) or (3).

In formulas (2) and (3), Q represents the same meaning as described above. X represents a divalent linking group. q2 represents an integer of 0 to 3, and when q2 is 0, it represents a single bond. When q2 is 2 or more, X may be the same or different. X is preferably -C (R15) (R16)-, an oxygen atom, a sulfur atom, -N (R17)-, a cycloalkylene group, an arylene group, a divalent heterocyclic residue, -N = N-, or- C (R15) = C (R16)-, more preferably a 3-10 membered cycloalkylene group, a 6-10 membered monocyclic or bicyclic arylene group, a furylene group, a thienylene group, a pyridylene group. is there. In the formulas (2) and (3), R1 to R17 are each independently a hydrogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, alkoxy group, aryloxy group, disubstituted amino group, nitro group, heterocyclic ring Represents a residue or a halogen atom. A ring may be further formed by two groups in R1 to R5 or R6 to R17.
R6 to R17 may have another structure represented by the formula (3) through a divalent linking group. In this case, in the structure represented by a plurality of formulas (3), the connecting sites of both may be the same or different.

  In the general formulas (2) and (3), R1 to R17 are specifically hydrogen atoms; methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, Linear, branched or cyclic alkyl groups having 1 to 20 carbon atoms such as pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl; vinyl, Allyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, Linear, branched, or cyclic alkenyl groups having 2 to 20 carbon atoms such as tacadecenyl, nonadecenyl, icocenyl, hexadienyl, dodecatrienyl; ethynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, cyclooctynyl, cyclononynyl, cyclodecynyl, etc. A linear, branched or cyclic alkynyl group having 2 to 20 carbon atoms; a monocyclic or di- to tetracyclic aryl group such as phenyl, naphthyl, phenanthryl, anthryl; methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyl C1-C20 alkoxy groups such as oxy, heptyloxy, octyloxy, nonyloxy, decyloxy, dodecyloxy, octadecyloxy; aryloxy groups such as phenoxy, naphthyloxy; dimethylamino, N Di-substituted amino groups such as ethyl-N-phenylamino, diphenylamino, N-phenyl-N-naphthylamino; nitro groups; heterocyclic residues such as furyl, thienyl, pyridyl; fluorine atoms, chlorine atoms, bromine atoms, iodine Represents a halogen atom such as an atom. Preferably a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a disubstituted amino group, a nitro group, a heterocyclic residue, and a halogen atom, more preferably a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, and a nitro group. is there. Examples of the divalent linking group include an alkylene group (preferably having 1 to 10 carbon atoms), a cycloalkylene group (preferably 3 to 10 members), an arylene group (preferably 6 to 10 members), and a divalent heterocycle. A residue is mentioned preferably, Among these, a cycloalkylene group, an arylene group, a furylene group, a thienylene group, and a pyridylene group are particularly preferable.

  In the general formulas (1), (2), and (3), Ra, Rb, L1, R1 to R17 may further have a substituent and are not particularly limited as long as they do not participate in the reaction. Specifically, alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl; vinyl, allyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, Alkenyl groups such as dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, icocenyl, hexadienyl, dodecatrienyl, etc .; ethynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, cyclooctyl, cyclodecyl Groups: monocyclic or di- to tetracyclic aryl groups such as phenyl, naphthyl, phenanthryl, anthryl, etc .; methoxy, ethoxy, Alkoxy groups such as poxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy; aryloxy groups such as phenoxy, naphthyloxy; dimethylamino, N-ethyl-N-phenylamino, diphenylamino, N -Disubstituted amino groups such as phenyl-N-naphthylamino; nitro groups; heterocyclic residues such as furyl, thienyl, pyridyl; halogen atoms such as fluorine atom, chlorine atom, bromine atom, iodine atom and the like. Preferably a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a disubstituted amino group, a nitro group, a heterocyclic residue, and a halogen atom, more preferably a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, and a nitro group. is there.

  Moreover, you may form a ring further by two groups in several Ra, R1-R5, or R6-R17. Specifically, saturated rings such as cyclobutane, cyclopentane, and cyclohexane; partially saturated rings such as cyclopentene, cyclohexene, and cyclooctene; aromatic rings such as benzene and naphthalene; pyrrolidine, pyridine, pyran, oxolane, thiolane, oxane, thiane, and the like A heterocycle is mentioned. A saturated ring and an aromatic ring are preferable.

The cycloalkylene group in X of the general formula (3) specifically represents cyclopentylene, cyclohexylene, cycloheptylene and the like. The arylene group specifically represents phenylene, naphthylene, anthrylene, phenanthrylene, pyrenylene and the like.
Q represents a chlorine atom, a bromine atom or an iodine atom, preferably a bromine atom or an iodine atom.

  The aromatic amine compound used in the present invention is preferably a compound represented by the following general formula (4).

In formula (4), q3 represents an integer of 0 to 5. Rc represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, a disubstituted amino group, a nitro group, a heterocyclic residue, a halogen atom or a group represented by -L2-Re. Rd represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, a disubstituted amino group, a nitro group, a heterocyclic residue, a halogen atom or a group represented by -L2-Re. Represent. L2 represents a divalent linking group. Re represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, a disubstituted amino group, a nitro group, a heterocyclic residue, or a halogen atom. When q3 is 2 or more, each Rc may be the same or different, and a plurality of Rc may form a ring. The groups represented by Rc, Rd, Re, and L2 may each have a substituent.
The aromatic amine compound used in the present invention is more preferably a compound represented by the following general formula (5) or (6).

In formulas (5) and (6), Y represents a divalent linking group. q4 represents an integer of 0 to 3, and when q4 is 0, it represents a single bond. When q4 is 2 or more, Y may be the same or different. Y is preferably -C (R34) (R35)-, an oxygen atom, a sulfur atom, -N (R36)-, a cycloalkylene group, an arylene group, a divalent heterocyclic residue, -N = N-, or- C (R34) = C (R35)-, more preferably a 3 to 10-membered cycloalkylene group, a 6 to 10-membered monocyclic or bicyclic arylene group, a furylene group, a thienylene group, or a pyridylene group. is there. R18 to R36 each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, an amino group, a nitro group, a heterocyclic residue, or a halogen atom. Moreover, you may form a saturated ring, an unsaturated ring, and a heterocyclic ring by two groups in R18-R23 or R24-R36.
R24 to R36 may have another structure represented by the formula (6) through a divalent linking group. In this case, in the structure represented by a plurality of formulas (6), both of the connecting sites may be the same or different.

  In the general formulas (5) and (6), R18 to R36 are specifically hydrogen atoms; methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, Linear, branched or cyclic alkyl groups having 1 to 20 carbon atoms such as pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl; vinyl, Allyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl Linear, branched, or cyclic C2-C20 alkenyl groups such as octadecenyl, nonadecenyl, icocenyl, hexadienyl, dodecatrienyl, etc .; ethynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, cyclooctynyl, cyclononynyl, cyclodecynyl, etc. A linear, branched or cyclic alkynyl group having 2 to 20 carbon atoms; a monocyclic or bicyclic aryl group such as phenyl or naphthyl; methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyl C1-C20 alkoxy groups such as oxy, nonyloxy, decyloxy, dodecyloxy, octadecyloxy; aryloxy groups such as phenoxy, naphthyloxy; amino groups; methylamino, n-hexylamino, phenoxy It represents furyl, thienyl, a heterocyclic residue such as pyridyl; arylamino, dimethylamino, N- ethyl -N- phenylamino, diphenylamino, N- phenyl--N--substituted amino groups such naphthylamino; nitro group. Preferred are a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, an amino group, a substituted amino group, a nitro group, a heterocyclic residue, and a halogen atom, and more preferred are a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, amino Group, a substituted amino group.

  In the general formulas (4), (5), and (6), Rc, Rd, Re, L2, and R18 to R36 may further have a substituent and are not particularly limited as long as they do not participate in the reaction. Specifically, alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl; vinyl, allyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, Alkenyl groups such as dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, icocenyl, hexadienyl, dodecatrienyl, etc .; ethynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, cyclooctyl, cyclodecyl Groups; monocyclic or di- to tetracyclic aryl groups such as phenyl, naphthyl, phenanthrene and anthracene; methoxy, ethoxy, Alkoxy groups such as ropoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy; aryloxy groups such as phenoxy, naphthyloxy; amino groups; methylamino, n-hexylamino, phenylamino, dimethylamino N-ethyl-N-phenylamino, diphenylamino, substituted amino groups such as N-phenyl-N-naphthylamino; nitro groups; heterocyclic residues such as furyl, thienyl, pyridyl and the like. Preferred are a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, an amino group, a substituted amino group, a nitro group, and a heterocyclic residue, and more preferred are a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, an amino group, and a substituent. It is an amino group. Examples of the divalent linking group include an alkylene group (preferably having 1 to 10 carbon atoms), a cycloalkylene group (preferably 3 to 10 members), an arylene group (preferably 6 to 10 members), and a divalent heterocycle. A residue is mentioned preferably, Among these, a cycloalkylene group, an arylene group, a furylene group, a thienylene group, and a pyridylene group are particularly preferable.

  Moreover, you may form a ring further by two groups in several Rc, R18-R23, or R24-R36. Specifically, saturated rings such as cyclobutane, cyclopentane and cyclohexane; partially saturated rings such as cyclopentene, cyclohexene and cyclooctene; aromatic rings such as benzene and naphthalene; pyrrolidine, pyrrole, piperidine, pyridine, morpholine, thiomorpholine, piperazine, Examples include heterocycles such as azacycloheptane, azacycloheptene, azacycloheptatriene, oxolane, thiolane, oxane, thiane. A saturated ring and an aromatic ring are preferable.

Specifically, the cycloalkylene group in Y of the general formula (6) represents cyclopentylene, cyclohexylene, cycloheptylene and the like. The arylene group specifically represents phenylene, naphthylene, anthrylene, phenanthrylene, pyrenylene and the like.
The amount of the aromatic amine compound used varies depending on the individual reaction, such as the number of reaction sites of the aromatic amine compound and the aromatic halogen compound, the reaction temperature, and when the aromatic halogen compound is used as a substrate and solvent. It is 0.1-20 mol normally with respect to 1 mol of halogen compounds, Preferably it is 0.3-10 mol.

The copper catalyst used in the present invention is not particularly limited, and a catalyst usually used in the Ullmann condensation reaction can be used. For example, copper powder, cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, copper iodide, cuprous oxide, cupric oxide, copper sulfate, copper nitrate, copper carbonate, water Examples include cupric oxide, and copper chloride, copper bromide, and copper iodide are preferable. The amount of these copper catalysts used is usually 0.001 to 0.4 mol, preferably 0.005 to 0.3 mol, more preferably 0.01 to 0.2 mol, per halogen atom in the aromatic halogen compound. Is a mole.
If necessary, a promoter such as lithium iodide, sodium iodide, potassium iodide, rubidium iodide, cesium iodide or the like can be added. When these promoters are added, the amount used is 0.001 to 0.4 mol, preferably 0.005 to 0.3 mol, more preferably 0.01 to 0 mol, per mol of the aromatic halogen compound. .2 moles.

Examples of the base used in the present invention include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide and other alkali metal hydroxides, lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate, carbonate Alkali metal carbonates such as cesium, alkali metal phosphates such as trilithium phosphate, trisodium phosphate, tripotassium phosphate, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, lithium-tert-butoxide, sodium- Examples thereof include alkali metal alkoxides such as tert-butoxide and potassium-tert-butoxide. Among the above, the alkali metal alkoxide may be added to the reaction system as it is, or prepared from an alkali metal, an alkali metal hydride, an alkali metal hydroxide, etc. and an alcohol. Of these bases, alkali metal carbonates and alkali metal alkoxides are preferred.
These bases are used in an amount of 0.6 to 4.0 molar equivalents, preferably 0.8 to 3.0 molar equivalents, more preferably 1.0 to 2.0 molar equivalents relative to the aromatic amine compound.

In the production method of the present invention, a reaction solvent may not be used, but an aromatic compound or an aliphatic compound can be used as a reaction solvent as necessary. Specific examples include the following solvents having a boiling point of 100 ° C. or higher at 1 atmosphere.
(I) Aromatic hydrocarbon compounds that may be halogenated: toluene, xylene, mesitylene, durene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, diphenylmethane, chlorobenzene, 1,2-dichlorobenzene, 1,2,4- Trichlorobenzene and the like.
(Ii) Hydrogenated aromatic hydrocarbon compounds in which the ring skeleton is partially hydrogenated, such as dihydro, tetrahydro, hexahydro, octahydro, decahydro, etc .: 1,4-dihydronaphthalene, 1,2,3, 4-tetrahydronaphthalene, 9,10-dihydroanthracene, 9,10-dihydrophenanthrene, 4,5,9,10-tetrahydropyrene, 1,2,3,6,7,8-hexahydropyrene, dodecahydrotriphenylene, etc. .
(Iii) saturated aliphatic compounds: octane, nonane, decane, undecane, dodecane, tridecane, 2-methyldodecane, 4-ethylundecane, tetradecane, pentadecane, 3,3-dimethyltridecane, hexadecane, heptadecane, 2-methyl- 4-ethyltetradecane and the like.
(Iv) Unsaturated aliphatic compounds: 2-heptin, 3-heptin, 2-octene, 3-nonene, 1-decyne, 1-undecene, 4-dodecene, 3,3-dimethyl-1-decene, 1,3 , 5-dodecatriene, 5-tridecene, 3-methyl-4-ethyl-2-decene, 1-dodecyne, 3-dodecene-1-yne, 1-tridecyne, 5,5-dimethyl-3-undecene-1- In, 5-ethynyl-1,3-dodecadiene and the like, ocimene, myrcene, squalene and the like.
(V) Saturated alicyclic compounds: dicyclohexyl, decahydronaphthalene, dodecahydrofluorene and the like.
(Vi) Unsaturated alicyclic compounds: α-terpinene, β-terpinene, γ-terpinene, terpinolene, (+)-α-ferrandolene, (−)-β-ferrandolene, (−)-1-p- Menten, (+)-3-Mentene, Dipentene, (+)-Limonene, (+)-Sabinene, (+)-α-Pinene, (+)-β-Pinene, (-)-β-Cadinene, (- )-[Beta] -caryophyllene, (-)-[beta] -santalene, (-)-[alpha] -cedrene, (+)-[beta] -selinene, (-)-[beta] -bisabolene, [alpha] -humulene and the like.

Among the above solvents, alkylbenzenes such as toluene, xylene, diethylbenzene, and diisopropylbenzene, and terpenes such as α-terpinene, β-terpinene, γ-terpinene, ferrandrene, and terpinolene are preferable. When these solvents are used, the effect of suppressing the generation of impurities is improved, and a high yield and high purity arylamine can be produced.
These aromatic compounds and aliphatic compounds can be used as a solvent singly or in combination of two or more. When these reaction solvents are used, they are usually used in a proportion of 100 to 1000 ml with respect to 1 mol of the aromatic halogen compound as a raw material.

The reaction temperature in the present invention is in the range of 80 to 250 ° C. When the aromatic halogen compound used is a chlorine compound or a bromine compound, the reaction time varies depending on the reaction conditions, but is usually about 1 to 12 hours. When the aromatic halide used is an iodine compound, the reaction proceeds very efficiently at a reaction temperature of 80 to 130 ° C., and the reaction time in this case varies depending on the raw material used and the organic salt to be added. About 1 to 3 hours.
The reaction pressure in the present invention can be sufficiently suppressed even at normal pressure to suppress impurities and may be carried out by a reduced pressure reaction depending on the situation. The degree of decompression can be appropriately set in consideration of costs and the like, and even if a slight decompression is effective, it is usually preferable to carry out at 80 kPa or less. Further, it is preferable that the degree of vacuum is not excessively high from the viewpoint of capturing the raw material used during the reaction. A preferable range of the degree of reduced pressure during the reaction is 70 to 5 kPa, and more preferably 60 to 10 kPa. When a reaction solvent is used, the degree of vacuum at which the reaction solvent does not distill off is selected, or the degree of vacuum at which the reaction is carried out while refluxing the solvent is selected.
In the present invention, it is also preferable to introduce an inert gas at the time of the reaction because the production of by-products is further prevented. As the inert gas, for example, nitrogen, helium, neon, argon, krypton, xenon, or the like can be used. Among these, inexpensive nitrogen is preferable. When introducing the inert gas, it is preferable to perform the reaction while introducing the inert gas after sufficiently replacing the inside of the reaction system with the inert gas at room temperature. Substitution with an inert gas in the reaction system is usually performed by repeatedly reducing the pressure in the reaction system to 8 kPa or less, more preferably 4 kPa or less, and even more preferably 2 kPa or less, and then returning to normal pressure with an inert gas. It is more preferable to react while introducing the inert gas from the lower part of the reactor. It is preferable to carry out the reaction at a residual oxygen in the reactor of 5% or less, preferably 1% or less, more preferably 0.1% or less.

  Specific examples of arylamines that can be synthesized in the present invention are shown below, but the present invention is not limited thereto.

  EXAMPLES Next, although an Example demonstrates this invention further more concretely, this invention is not limited to these. The purity was evaluated by high performance liquid chromatography (hereinafter abbreviated as HPLC).

Example 1
Synthesis of N, N′-diphenyl-N, N′-bis (4-ethoxyphenyl)-(9,9′-bianthracene) -10,10′-diamine (I-12) N- (4-ethoxyphenyl) ) -N-phenylamine 14.6 g (73.9 mmol), 9,9′-diiodo-10,10′-bianthracene 14.9 g (24.6 mmol), potassium carbonate 20.4 g (147.8 mmol), sulfuric acid Copper pentahydrate 1.0 g (4.0 mmol) and thymine 2.52 g (20.0 mmol) were mixed and reacted at 235 to 245 ° C. for 3 hours in a nitrogen atmosphere. After the reaction, 75 ml of toluene and 50 ml of water were added and separated, washed with water, and the organic layer was dried over anhydrous sodium sulfate. After the desiccant was filtered off, toluene was concentrated under reduced pressure and 42 ml of ethyl acetate was added. After cooling and crystallization, the product was filtered off to obtain 17.3 g (yield 94.4%) of the target compound (I-12) as white crude crystals. . HPLC content (column: GL Science Inertsil ODS-3), eluent: acetonitrile / water (V / V = 70/30), detection UV: 300 nm, flow rate: 1.0 ml / min) was 99.5%. . The impurities are 0.012% for oxidation product A having a polar group, 0.030% for oxidation product B, 0% for oxidation product C, and dimerization products C and D having a small ionization potential. 0%.

Examples 2-8
In Example 1, it synthesize | combined by the method similar to Example 1 except having changed the molar ratio of the thymine with respect to a copper catalyst.

Comparative Example 1
Synthesis was performed in the same manner as in Example 1 except that the additive (thymine) was not used in Example 1.
The results of Examples 1 to 8 and Comparative Example 1 are shown in Table 1.

Example 9
Synthesis of 4,4 ′, 4 ″ -tris (N-1-naphthyl-N-phenylamino) triphenylamine (I-37) 10.4 g of 4,4 ′, 4 ″ -triiodotriphenylamine ( 17.0 mmol), N, N-di (1-naphthylphenyl) amine 22.4 g (102 mmol), potassium hydroxide 5.7 g (102 mmol), cuprous bromide 1.46 g (10.2 mmol), orotic acid 1.59 g (10.2 mmol) and 10 ml of terpinolene were mixed and reacted at 115 to 125 ° C. for 6 hours under a nitrogen atmosphere. After the reaction, the reaction mixture was concentrated under reduced pressure to distill off the reaction solvent, and 70 ml of toluene and 40 ml of water were added for liquid separation. 70 ml of methanol was added to the organic layer and cooled and crystallized to obtain 11.5 g (yield: 85.5%) of the target compound (I-37) as pale yellow crude crystals. Melting point 204-205 ° C. HPLC content (column: ODS-80TM, eluent: methanol / tetrahydrofuran (V / V = 95/5), buffer: triethylamine, phosphoric acid 0.2% each, detection UV: 254 nm, flow rate: 1.0 ml / min) was 99.5%. The impurities were 0.003% of the oxidation product F having a polar group, 0.001% of the oxidation product G, and 0% of the dimerization product H and the dimerization product I having a small ionization potential. It was.

Examples 10-21
Synthesis was performed in the same manner as in Example 9 except that the additive (orotic acid) in Example 9 was changed to that in Table 2.

Comparative Example 2
Synthesis was performed in the same manner as in Example 9 except that the additive (orotic acid) was not used in Example 9.
The results of Examples 9 to 21 and Comparative Example 2 are shown in Table 2.

Example 22
Synthesis of 9-phenylcarbazole (Exemplary Compound II-1) 16.47 g (98.52 mmol) of carbazole, 31.0 g (197.04 mmol) of bromobenzene, 5.53 g (98.52 mmol) of potassium hydroxide, cuprous chloride 0.4 g (8.0 mmol) and alloxan 5.7 g (40, 0 mmol) were mixed, and reacted for 6 hours while returning bromobenzene distilled out at 115 to 125 ° C. in a nitrogen atmosphere in the reaction system. After the reaction, 50 ml of toluene and 100 ml of water were added for liquid separation, washed with water, and the organic layer was dried over anhydrous sodium sulfate. After the desiccant was filtered off, toluene was concentrated under reduced pressure and 352 ml of methanol was added to crystallize to obtain 22.7 g (yield 94.7%) of the target compound (II-1) as white crude crystals. Melting point 96-97 ° C. HPLC content (column: ODS-80TM, eluent: acetonitrile / water (V / V = 65/35), buffer: triethylamine, acetic acid 0.1% each, detection UV: 254 nm, flow rate: 1.0 ml / min) Was 99.8%. Further, the dimerization product J and the dimerization product K having a small ionization potential were both 0%.

Examples 23-35
Synthesis was performed in the same manner as in Example 22 except that the additive (alloxan) in Example 22 was changed to that in Table 3.

Comparative Example 3
Synthesis was performed in the same manner as in Example 22 except that the additive (alloxan) was not used in Example 22.
The results of Examples 22 to 35 and Comparative Example 3 are shown in Table 3.

  From the results of Tables 1 to 3, when the reaction is carried out in the presence of additives, by-products with different electron density distributions and by-products with small ionization potentials that cause deterioration in electrical properties are highly suppressed, It is clear that high purity arylamines can be synthesized. In addition, it can be seen from the results in Table 1 that a higher impurity suppression effect can be obtained by appropriately selecting the amount of additive used.

Claims (1)

A process for producing an arylamine, comprising reacting an aromatic amine compound and an aromatic halogen compound in the presence of a copper catalyst and a base in the presence of at least one compound selected from the following compound group A.
Compound group A:
Cytosine, 5-fluorocytosine, N-acetylcytosine, N-benzoylcytosine, 5-methylcytosine, isocytosine, uracil, thymine, dihydrothymine, 1-methyluracil, 3-methyluracil, 6-methyluracil, 5-aminouracil , 6-aminouracil, 5-fluorouracil, 5-formyluracil, 1,3-dimethyluracil, 1-methylthymine, 5-ethyluracil, 6-amino-1-methyluracil, 5,6-diaminouracil, 4-chloro Uracil, 5-chlorouracil, 5-n-propyluracil, 1,3,6-trimethyluracil, 1,3,5-trimethyluracil, 6-amino-1-ethyluracil, 6-amino-1,3-dimethyl Uracil, 5,6-diamino-1,3-dimethyluracil, 2,4-di Droxypyrimidine-5-carboxylic acid, orotic acid, isoorotic acid, 5-bromoorotic acid, 5-aminoorotic acid, 5- (hydroxymethyl) -6-methyluracil, 5-nitrouracil, 6-propylideneaminouracil, 6-amino-1-methyl-5-nitrosouracil, 6-amino-1-methyl-5- (methylamino) uracil, trifluorothymine, thymine-1-acetic acid, 1-cyclohexyluracil, barbituric acid, isobarbi Tool acid, alloxan, 5-methyl-2-thiouracil, 6-methyl-2-thiouracil, purine, 6-methylpurine, 2-aminopurine, adenine, 6-cyanopurine, 1-methyladenine, N-methyladenine, 3-methyladenine, 9-methyladenine, 6-methoxypurine, 2-methylpurine -6-ol, 6-methylpurin-2-ol, 8-methylpurin-6-ol, 2,6-diaminopurine, 2-fluoroadenine, 6-chloropurine, 6-dimethylaminopurine, 9-ethyl Adenine, 6-ethoxypurine, 6-o-methylguanine, 2-methylpurine-6-thiol, 9-methylpurine-6-thiol, 2-amino-6-chloropurine, 6-isopropoxypurine, 2,6 -Diamino-7-ethylpurine, 6-ethylmercaptopurine, 2,6-dichloropurine, 6-butoxypurine, 2- (dimethylamino) -9-methylpurin-6-ol, 2-amino-9-butylpurine -6-ol, purine-2,6,8-trithiol, N-cyclopentyl-9-methylpurin-6-amine, ethyladenine-9-acetate DL-dihydrozeatin, N, N-dihydroxyethyladenine, 6-benzylaminopurine, 6-benzyloxypurine, uric acid, guanine, 1-methylguanine, 7-methylguanine, 2-amino-6,9- Dihydropurine-8-thiol, xanthine, hypoxanthine, theophylline, theobromine, caffeine, 1,3-dimethyl-1H-quinazoline-2,4-dione, octahydrocyclopentapyrimidin-4-one, 8-aza-6 -Aminopurine, 4- (4-hydroxy-3,5-dimethylphenyl) octahydropyrano [4,3-a] pyrimidin-2-one, hexahydroquinazoline-2,4-dione, 1H-quinazoline-2 , 4-dithione, 2,4-pteridinediol, and 1,3,6,6-tetramethylhexahydro Opirano [3,2-a] pyrimidine-2,4-dione.