阅读说明：本技术 苯胺衍生物的制造方法 (Process for producing aniline derivative ) 是由 寺井诚弥 于 2019-03-13 设计创作，主要内容包括：由式(4)[R<Sup>1</Sup>’～R<Sup>5</Sup>’表示氢原子、式(2)或式(5),R<Sup>1</Sup>’～R<Sup>5</Sup>’中的至少一个为由式(5)表示的基团。(Ar<Sup>1</Sup>～Ar<Sup>3</Sup>与下述相同。)]表示的化合物的制法,其中,在催化剂和碱的存在下使由式(1)[R<Sup>1</Sup>～R<Sup>5</Sup>相互独立地表示氢原子或由式(2)(Ar<Sup>1</Sup>、Ar<Sup>2</Sup>表示芳基,Ar<Sup>3</Sup>表示亚芳基,Ar<Sup>1</Sup>～Ar<Sup>3</Sup>中的任两个可结合以形成环。)表示的基团,R<Sup>1</Sup>～R<Sup>5</Sup>中的至少一个为氢原子。]表示的胺化合物与由式(3)(X表示卤素原子等,R<Sup>6</Sup>～R<Sup>8</Sup>表示烷基等。)表示的化合物反应后进行脱保护,该制法在脱保护的过程中不需要大量过剩的碱和氧,是适于有效率的且工业的制法的苯胺衍生物的制法。<Image he="900" wi="700" file="DDA0002677075740000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(Represented by the formula (4) [ R ] 1 '～R 5 ' represents a hydrogen atom, formula (2) or formula (5), R 1 '～R 5 At least one of' is a group represented by formula (5). (Ar) 1 ～Ar 3 The same as described below. )]A process for producing a compound represented by the formula (1) [ R ] 1 ～R 5 Independently of each other, a hydrogen atom or a compound represented by the formula (2) (Ar) 1 、Ar 2 Represents aryl, Ar 3 Represents an arylene group, Ar 1 ～Ar 3 Any two of which may combine to form a ring. ) A group represented by R 1 ～R 5 At least one of which is a hydrogen atom.]An amine compound represented by the formula (3) (X represents a halogen atom or the like, R) 6 ～R 8 Represents an alkyl group or the like. ) The compound shown in the above (a) is reacted and then deprotected, and this production method does not require a large excess amount of a base or oxygen in the deprotection process, and is a production method of an aniline derivative suitable for an efficient and industrial production method.)

1. A process for producing an aniline derivative represented by the formula (4), which comprises subjecting an amine compound represented by the formula (1) and a carbazole compound represented by the formula (3) to a coupling reaction in the presence of a catalyst and a base, and then deprotecting the silyl group,

[ solution 1]

In the formula, R¹～R⁵Independently of each other, a hydrogen atom or a group represented by the formula (2), R¹～R⁵At least one of which is a hydrogen atom,

[ solution 2]

In the formula, Ar¹And Ar²Independently represent aryl group having 6 to 20 carbon atoms, Ar³Ar represents an arylene group having 6 to 20 carbon atoms¹～Ar³Any two of which may be joined and form a ring together with the nitrogen atom,

[ solution 3]

Wherein X represents a halogen atom or a pseudo-halogen group, R⁶～R⁸Can be represented by Z¹A substituted alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms, Z¹Represents an alkoxy group having 1 to 20 carbon atoms, a halogen atom, a nitro group or a cyano group,

[ solution 4]

In the formula, R^1’～R^5’Independently represent a hydrogen atom, a group represented by formula (2), or a group represented by formula (5), R^1’～R^5’Is a group represented by formula (5),

[ solution 5]

In the formula, Ar¹～Ar³The same meanings as described above are indicated.

2. The method for producing an aniline derivative according to claim 1, wherein R is ⁶～R⁸Is an alkyl group having 1 to 10 carbon atoms or an aryl group having 6 to 10 carbon atoms.

3. The method for producing an aniline derivative according to claim 2, wherein R is⁶～R⁸2 of these are methyl groups and the remaining 1 is a tert-butyl group.

4. The method for producing an aniline derivative according to any one of claims 1 to 3, wherein the base is sodium tert-butoxide.

5. The method for producing an aniline derivative according to any one of claims 1 to 4, wherein the catalyst is a palladium catalyst.

6. The method for producing an aniline derivative according to any one of claims 1 to 5, wherein the coupling reaction is performed at 40 to 100 ℃.

7. The method for producing an aniline derivative according to any one of claims 1 to 6, wherein the deprotection is performed using a fluoride ion.

8. The method for producing an aniline derivative according to any one of claims 1 to 7, wherein R is¹～R⁵All are hydrogen atoms.

Technical Field

The present invention relates to a method for producing an aniline derivative.

Background

In an organic electroluminescence (hereinafter referred to as organic EL) device, a charge-transporting thin film made of an organic compound is used as a light-emitting layer and a charge injection layer. In particular, the hole injection layer is responsible for charge transfer between the anode and the hole transport layer or the light emitting layer, and plays an important role in realizing low-voltage driving and high luminance of the organic EL element.

The methods of forming the hole injection layer are roughly classified into a dry method represented by a vapor deposition method and a wet method represented by a spin coating method, and if these methods are compared, the wet method can efficiently produce a thin film having high flatness over a large area. Therefore, in the present time of increasing the area of organic EL displays, a hole injection layer that can be formed by a wet process is desired.

In view of such actual circumstances, the present inventors have developed aniline derivatives that can be applied to various wet processes while imparting a thin film capable of realizing excellent EL element characteristics in the case of application to a hole injection layer of an organic EL element; aniline derivatives having good solubility in organic solvents used therein (see, for example, patent document 1).

As one of the methods for producing such aniline derivatives, patent document 1 discloses, for example, a method in which an amine compound (a) and a halocarbazole compound (B) in which an NH group is protected with a benzyl group are coupled in the presence of a catalyst, and the benzyl group is deprotected, as shown in the following scheme.

[ solution 1]

[ solution 2]

However, when the carbazole compound protected with a benzyl group is used, a large excess of base and oxygen is necessary in the deprotection step, and there is a problem that it is not suitable for an industrial production method.

Disclosure of Invention

Problems to be solved by the invention

The present invention has been made in view of the above circumstances, and an object thereof is to provide a method for producing an aniline derivative which does not require a large excess of a base and oxygen in the deprotection step and is suitable for an efficient and industrial production method.

Means for solving the problems

The present inventors have made intensive studies to achieve the above object, and as a result, have found that: the present inventors have completed the present invention by carrying out a coupling reaction between an amine compound and a carbazole compound having an NH group protected with a predetermined silyl group and then desilylating the resulting product, thereby efficiently producing an aniline derivative without requiring a large excess of a base and oxygen.

Namely, the present invention provides:

1. a process for producing an aniline derivative represented by the formula (4), which comprises subjecting an amine compound represented by the formula (1) and a carbazole compound represented by the formula (3) to a coupling reaction in the presence of a catalyst and a base, and then deprotecting the silyl group,

[ solution 3]

In the formula, R¹～R⁵Independently of each other, a hydrogen atom or a group represented by the formula (2), R¹～R⁵At least one of which is a hydrogen atom,

[ solution 4]

In the formula, Ar¹And Ar²Independently represent aryl group having 6 to 20 carbon atoms, Ar³Ar represents an arylene group having 6 to 20 carbon atoms¹～Ar³Any two of which may be joined and form a ring together with the nitrogen atom,

[ solution 5]

Wherein X represents a halogen atom or a pseudo-halogen group, R⁶～R⁸Can be represented by Z¹A substituted alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms, Z¹Represents an alkoxy group having 1 to 20 carbon atoms, a halogen atom, a nitro group or a cyano group,

[ solution 6]

In the formula, R^1’～R^5’Independently represent a hydrogen atom, a group represented by formula (2), or a group represented by formula (5), R^1’～R^5’Is a group represented by formula (5),

[ solution 7]

In the formula, Ar¹～Ar³The same meanings as described above are indicated.

2.1 the process for producing an aniline derivative, wherein R is⁶～R⁸Is an alkyl group having 1 to 10 carbon atoms or an aryl group having 6 to 10 carbon atoms.

3.2 the process for producing an aniline derivative, wherein R is⁶～R⁸2 of these are methyl groups and the remaining 1 is a tert-butyl group.

4.1 to 3, wherein the base is sodium tert-butoxide.

5.1 to 4, wherein the catalyst is a palladium catalyst.

6.1 to 5, wherein the coupling reaction is carried out at 40 to 100 ℃.

7.1 to 6, wherein the deprotection is carried out using a fluoride ion.

8.1 to 7, wherein R represents an aniline derivative¹～R⁵All are hydrogen atoms.

ADVANTAGEOUS EFFECTS OF INVENTION

In the method for producing an aniline derivative of the present invention, since a raw material in which the NH group of the carbazole compound is protected with a silyl group is used, a large excess of base and oxygen is not necessary in the deprotection process, and the target aniline derivative can be efficiently produced.

Drawings

FIG. 1 is a diagram showing an HPLC chart of CZ5 obtained in example 1.

FIG. 2 is an enlarged view showing a range of 0 to 300mAU in the vertical axis of FIG. 1.

FIG. 3 is a diagram showing an HPLC chart of CZ5 obtained in comparative example 1.

FIG. 4 is an enlarged view showing the range of 0 to 300mAU on the vertical axis in FIG. 3.

Detailed Description

The present invention will be described in more detail below.

The process for producing an aniline derivative according to the present invention is characterized in that after a coupling reaction between an amine compound represented by the formula (1) and a carbazole compound represented by the formula (3) is carried out in the presence of a catalyst and a base, a silyl group on a nitrogen atom at the carbazole moiety is deprotected.

[ solution 8]

In the above formula (1), R¹～R⁵Independently represent a hydrogen atom or a group represented by the formula (2), and R is a group represented by the formula (3) for coupling reaction with the carbazole compound¹～R⁵At least one of them must be a hydrogen atom.

[ solution 9]

In the formula (2), Ar¹And Ar²Independently represent aryl group having 6 to 20 carbon atoms, Ar³Ar represents an arylene group having 6 to 20 carbon atoms¹～Ar³Any two of which may be joined and form a ring with the nitrogen atom.

Specific examples of the aryl group having 6 to 20 carbon atoms include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, and 9-phenanthryl.

Specific examples of the arylene group having 6 to 20 carbon atoms include benzene-1, 2-diyl (o-phenylene), benzene-1, 3-diyl (m-phenylene), benzene-1, 4-diyl (p-phenylene), naphthalene-1, 2-diyl, naphthalene-1, 3-diyl, naphthalene-1, 4-diyl, naphthalene-1, 5-diyl, naphthalene-1, 6-diyl, naphthalene-1, 7-diyl, and naphthalene-1, 8-diyl.

In addition, as Ar¹～Ar³Examples of the ring which is formed by combining any two of them together with a nitrogen atom include a carbazole ring and the like.

Among these, Ar¹And Ar²Phenyl, 1-naphthyl and 2-naphthyl are preferred, and phenyl is more preferred.

In addition, Ar³Benzene-1, 2-diyl, benzene-1, 3-diyl and benzene-1, 4-diyl are preferable, and benzene-1, 4-diyl is more preferable.

Therefore, the group represented by formula (2) is preferably a group represented by formula (2A), more preferably a group represented by formula (2A-1).

[ solution 10]

[ solution 11]

Examples of the compound represented by the formula (1) which can be preferably used in the production method of the present invention include the above-mentioned R¹～R⁵A compound represented by the following formula (1A) wherein all are hydrogen atoms, R²And R⁴A compound represented by the following formula (1B) which is a 4-diphenylaminophenyl group, R¹、R²And R⁴And a compound represented by the following formula (1C) which is a 4-diphenylaminophenyl group, but is not limited thereto.

[ solution 12]

In the formula (3), X represents a halogen atom or a pseudo-halogen group, and R⁶～R⁸Can be represented by Z¹A substituted alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms, Z¹Represents an alkoxy group having 1 to 20 carbon atoms, a halogen atom, a nitro group or a cyano group.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like.

Examples of the pseudohalogen group include (fluoro) alkylsulfonyloxy groups such as methylsulfonyloxy, trifluoromethanesulfonyloxy and nonafluorobutanesulfonyloxy; and aromatic sulfonyloxy groups such as benzenesulfonyloxy and toluenesulfonyloxy.

Among these, X is preferably a halogen atom, more preferably a bromine atom or an iodine atom, in view of availability, reactivity or the like of the raw material.

The substitution position of X is not particularly limited, and the para-position is preferred for the nitrogen atom of carbazole.

Examples of the alkyl group having 1 to 20 carbon atoms include straight-chain, branched-chain and cyclic alkyl groups, and examples thereof include straight-chain or branched-chain alkyl groups having 1 to 20 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl groups; and a C3-20 cyclic alkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a bicyclobutyl group, a bicyclopentyl group, a bicyclohexyl group, a bicycloheptyl group, a bicyclooctyl group, a bicyclononyl group, and a bicyclodecyl group.

Examples of the aryl group having 6 to 20 carbon atoms include the same aryl groups as described above.

Examples of the alkyl group having 1 to 20 carbon atoms include a straight-chain or branched-chain alkoxy group having 1 to 20 carbon atoms such as a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, a tert-butoxy group, a n-pentoxy group, a n-hexoxy group, a n-heptoxy group, a n-octoxy group, a n-nonoxy group, a n-decoxy group and the like, and a cyclic alkoxy group having 3 to 20 carbon atoms such as a cyclopentoxy group, a cyclohexoxy group and the like.

In these, R⁶～R⁸Preferably an alkyl group having 1 to 10 carbon atoms and an aryl group having 6 to 10 carbon atoms, and more preferably an alkyl group having 1 to 5 carbon atoms.

More specifically, R is preferred⁶～R⁸A combination of 2 of methyl groups and the remaining 1 of t-butyl groups; r⁶～R⁸A combination of 2 of which are phenyl groups and the remaining 1 of which are tert-butyl groups; r⁶～R⁸All are isopropyl, more preferably R⁶～R⁸A combination of 2 of methyl groups and the remaining 1 of t-butyl groups.

Examples of the compound represented by the formula (3) that can be preferably used in the production method of the present invention include, but are not limited to, compounds represented by the following formula (3A), and in particular, compounds represented by the formula (3A-1).

The compound represented by formula (3) can be obtained by a known method in which the corresponding carbazole is reacted with a triorganic halide such as trialkylsilyl chloride in the presence of a base such as NaH.

[ solution 13]

(in the formula, R⁶～R⁸And X represents the same meaning as described above. )

[ solution 14]

In the coupling reaction of the amine compound represented by the formula (1) and the carbazole compound represented by the formula (3), the feed ratio of the amine compound represented by the formula (1) to the carbazole compound represented by the formula (3) is represented by a mass (molar) ratio, and the carbazole compound is preferably about 1 to 5, more preferably about 1.1 to 2, relative to the target NH group 1 of the amine compound to be reacted.

Examples of the catalyst used in the above reaction include copper catalysts such as copper chloride, copper bromide, and copper iodide; pd (PPh)₃)₄(tetrakis (triphenylphosphine) palladium), Pd (PPh)₃)₂Cl₂(bis (triphenylphosphine) dichloropalladium), Pd (dba)₂(bis (dibenzylideneacetone) palladium), Pd₂(dba)₃(tris (dibenzylideneacetone) dipalladium), Pd (P-t-Bu)₃)₂(bis (tris (tert-butylphosphino)) palladium), Pd (OAc)₂Palladium catalysts such as (palladium acetate) and the like. These catalysts may be used alone, or 2 or more of them may be used in combination.

In addition, these catalysts may be used together with known appropriate ligands.

Examples of such ligands include triphenylphosphine, tri-o-tolylphosphine, diphenylmethylphosphine, phenyldimethylphosphine, trimethylphosphine, triethylphosphine, tributylphosphine, tri-t-butylphosphine, di-t-butyl (phenyl) phosphine, di-t-butyl (4-dimethylaminophenyl) phosphine, 1, 2-bis (diphenylphosphino) ethane, 1, 3-bis (diphenylphosphino) propane, tertiary phosphines such as 1, 4-bis (diphenylphosphino) butane and 1, 1' -bis (diphenylphosphino) ferrocene, trimethyl phosphite, triethyl phosphite, triphenyl phosphite and other phosphite triesters, and in the present invention, di-t-butyl (phenyl) phosphine is preferably used.

The amount of the catalyst used may be about 0.1 to 100 mol%, preferably about 1 to 10 mol%, more preferably about 2 to 5 mol%, and still more preferably about 2 mol%, based on 1 mol of the target NH group to be reacted in the amine compound represented by formula (1).

When the ligand is used, the amount of the ligand used can be 0.1 to 5 equivalents, preferably 1 to 2 equivalents, based on the metal complex used.

Examples of the base include simple alkali metals such as lithium, sodium, potassium, lithium hydride, sodium hydride, potassium hydroxide, t-butoxyllithium, t-butoxysodium, t-butoxypotassium, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate, alkali metal hydroxides, alkali metal alkoxides, alkali metal carbonates, and alkali metal hydrogen carbonates; sodium tert-butoxide is preferred in view of efficiently carrying out the coupling reaction, for example, alkali earth metal carbonates such as calcium carbonate.

The amount of the base used is preferably about 1 to 2 equivalents, more preferably about 1.2 to 1.5 equivalents, based on the target NH group to be reacted of the amine compound represented by the formula (1).

In the case where all of the raw material compounds are solid, the above reaction is carried out in a solvent from the viewpoint of efficiently obtaining the target coupling product. When a solvent is used, the kind thereof is not particularly limited as long as it does not adversely affect the reaction. Specific examples thereof include aliphatic hydrocarbons (e.g., pentane, N-hexane, N-octane, N-decane, decalin), halogenated aliphatic hydrocarbons (e.g., chloroform, dichloromethane, dichloroethane, and carbon tetrachloride), aromatic hydrocarbons (e.g., benzene, nitrobenzene, toluene, o-xylene, m-xylene, p-xylene, and mesitylene), halogenated aromatic hydrocarbons (e.g., chlorobenzene, bromobenzene, o-dichlorobenzene, m-dichlorobenzene, and p-dichlorobenzene), ethers (e.g., diethyl ether, diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, 1, 2-dimethoxyethane, 1, 2-diethoxyethane), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, di-N-butyl ketone, and cyclohexanone), amides (e.g., N-dimethylformamide and N, N-dimethylacetamide), lactams, and lactones (e.g., N-methylpyrrolidone), γ -butyrolactone, etc.), ureas (N, N-dimethylimidazolidinone, tetramethylurea, etc.), sulfoxides (dimethyl sulfoxide, sulfolane, etc.), nitriles (acetonitrile, propionitrile, butyronitrile, etc.), etc., and these solvents may be used alone or in combination of 2 or more.

Among these, aromatic hydrocarbons are particularly preferable, and toluene is more preferable.

The reaction temperature may be suitably set in a range from the melting point to the boiling point of the solvent used, and is preferably about 0 to 200 ℃ in particular, and more preferably about 20 to 150 ℃, and if the yield of the coupling product is further improved, it is more preferably about 40 to 100 ℃.

After the reaction, the coupling product can be obtained by post-treatment according to a conventional method.

Next, the silyl group on the nitrogen atom of the carbazole moiety in the coupling product obtained is deprotected.

Deprotection can be appropriately selected from known methods, and in the present invention, deprotection is preferably performed using fluoride ions.

The desilylating agent to be used as the fluoride ion source is not particularly limited, and can be appropriately selected from known desilylating agents and used.

Specific examples thereof include tetrabutylammonium fluoride (TBAF), tetraethylammonium fluoride, tetramethylammonium fluoride, hydrates thereof, pyridinium hydrogen fluoride complex, cesium fluoride, potassium hydrogen fluoride, sodium fluoride, lithium fluoride, calcium fluoride, and the like, and among these, TBAF is preferable.

The amount of the desilylating agent to be used may be about 1 to 5 equivalents, preferably about 1.2 to 2 equivalents, based on the total N-Si bonds in the coupling product.

A solvent can also be used in this reaction, and specific examples of the solvent that can be used include ethers, and tetrahydrofuran is more preferred, as described above.

The reaction temperature may be from the melting point to the boiling point of the solvent, and is preferably about 0 to 100 ℃, more preferably about 0 to 30 ℃, and further preferably about 25 ℃.

After the reaction, the reaction mixture was worked up by a conventional method to obtain the desired aniline derivative represented by the following formula (4).

[ solution 15]

In the formula, R^1’～R^5’Independently represent a hydrogen atom, a group represented by the formula (2) or a group represented by the formula (5), R^1’～R^5’Is a group represented by formula (5).

[ solution 16]

Preferred aniline derivatives obtained by the production method of the present invention include aniline derivatives represented by the following formulae (4A) to (4D), but are not limited thereto.

[ solution 17]