JP2018154570A - Method for producing di-substituted dicyanoaryl or dicyanoheteroaryl with electron-donating groups - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing di-substituted dicyano(hetero) aryl with electron-donating groups in high yields.SOLUTION: According to a method, in the presence of a palladium catalyst and a base, phthalonitrile derivative and 4-substituted phenylboronic acid ester derivative are subjected to a reaction, to produce, e.g. the following Ac-VPn.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a disubstituted product of an electron donating group of dicyanoaryl or dicyanoheteroaryl (hereinafter abbreviated as dicyano (hetero) aryl).

A disubstituted product of an electron donating group of dicyano (hetero) aryl such as formulas (1) to (5) is a useful compound group expected to be applied to a light emitting material (Non-patent Document 1, etc.).

Non-Patent Document 1 discloses that 4- (9,9-dimethyl-9,10-dihydroacridin-10-yl) -phenyl boronic ester (6) and 4,5-dichlorophthalonitrile (7) are converted to tetrakis. It is disclosed that Ac-VPN (2) was obtained in a yield of 34% by a coupling reaction in the presence of (triphenylphosphine) palladium, potassium iodide, and tripotassium phosphate.

In Non-Patent Document 1, 4- (phenoxazin-10-yl) -phenyl boronic acid ester (8) and 4,5-dichlorophthalonitrile (7) are mixed with tetrakis (triphenylphosphine) palladium, iodine. Discloses that Px-VPN (3) was obtained in a yield of 31% by a coupling reaction in the presence of potassium fluoride and tripotassium phosphate.

  Non-Patent Document 2 discloses a cross-coupling reaction of an organoboron compound with a palladium catalyst.

Adv. Funct. Mater. 2016, 26, 1813-1821 Chem. Rev. 1995, 95, 2457-2483

In the coupling reaction described in Non-Patent Document 1, a mono-substituted product of an electron-donating group is generated in addition to a di-substituted product of an electron-donating group of dicyano (hetero) aryl. The yield of disubstituted groups is low.
An object of the present invention is to provide a method for producing a disubstituted product of an electron donating group of dicyano (hetero) aryl in a high yield.

  As a result of repeated studies to achieve the above object, the present invention including the following aspects has been completed.

[1] A compound represented by the formula [III], comprising reacting a compound represented by the formula [I] with a compound represented by the formula [II] in the presence of a palladium catalyst and a base. Manufacturing method.

（式〔I〕中、
Ｇ¹およびＧ²は、それぞれ独立に、Ｃ（Ｒ¹⁰）またはＮを示し、且つ
Ｒ¹⁰は、水素原子、アルキル基またはアリール基を示す。）

(In the formula [I],
G ¹ and G ² each independently represent C (R ¹⁰ ) or N, and R ¹⁰ represents a hydrogen atom, an alkyl group or an aryl group. )

（式〔II〕中、
Ｒ¹およびＲ²は、それぞれ独立に、水素原子またはアルキル基を示し、またはＲ¹とＲ²が結合してアルキレン基であってもよく、
Ｒ³〜Ｒ⁵は、それぞれ独立に、アルキル基またはアリール基を示し、
ｐは、Ｒ³の数を示し且つ０〜４いずれかの整数であり、
ｎは、Ｒ⁴の数を示し且つ０〜４いずれかの整数であり、
ｍは、Ｒ⁵の数を示し且つ０〜４いずれかの整数であり、
−Ｙ−は、単結合、−Ｏ−、−Ｓ−、−ＣＨ₂−、−ＣＨＲ^a−、または−ＣＲ^bＲ^c−を示し、且つ
Ｒ^a、Ｒ^b、およびＲ^cは、それぞれ独立に、アルキル基を示す。）

(In the formula [II],
R ¹ and R ² each independently represent a hydrogen atom or an alkyl group, or R ¹ and R ² may be bonded to form an alkylene group;
R ^{3 to} R ⁵ each independently represents an alkyl group or an aryl group,
p represents the number of R ³ and is an integer of 0 to 4,
n represents the number of R ⁴ and is an integer of 0 to 4,
m represents the number of R ⁵ and is an integer of 0 to 4,
—Y— represents a single bond, —O—, —S—, —CH ₂ —, —CHR ^a —, or —CR ^b R ^c —, and R ^a , R ^b , and R ^c are each independently Represents an alkyl group. )

（式〔III〕中、
Ｇ¹およびＧ²は、それぞれ独立に、Ｃ（Ｒ¹⁰）またはＮを示し、
Ｒ¹⁰は、水素原子、アルキル基またはアリール基を示し、
Ｒ³〜Ｒ⁵は、それぞれ独立に、アルキル基またはアリール基を示し、
ｐは、Ｒ³の数を示し且つ０〜４いずれかの整数であり、
ｎは、Ｒ⁴の数を示し且つ０〜４いずれかの整数であり、
ｍは、Ｒ⁵の数を示し且つ０〜４いずれかの整数であり、
−Ｙ−は、単結合、−Ｏ−、−Ｓ−、−ＣＨ₂−、−ＣＨＲ^a−、または−ＣＲ^bＲ^c−を示し、且つ
Ｒ^a、Ｒ^b、およびＲ^cは、それぞれ独立に、アルキル基を示す。）

(In the formula [III],
G ¹ and G ² each independently represent C (R ¹⁰ ) or N;
R ¹⁰ represents a hydrogen atom, an alkyl group or an aryl group,
R ^{3 to} R ⁵ each independently represents an alkyl group or an aryl group,
p represents the number of R ³ and is an integer of 0 to 4,
n represents the number of R ⁴ and is an integer of 0 to 4,
m represents the number of R ⁵ and is an integer of 0 to 4,
—Y— represents a single bond, —O—, —S—, —CH ₂ —, —CHR ^a —, or —CR ^b R ^c —, and R ^a , R ^b , and R ^c are each independently Represents an alkyl group. )

  According to the production method of the present invention, there is almost no by-product of a monosubstituted product of an electron donating group of dicyano (hetero) aryl, and a disubstituted product of an electron donating group of dicyano (hetero) aryl is produced in a high yield. can do.

  The production method of the present invention includes a compound represented by formula [I] (hereinafter sometimes referred to as compound [I]) and a compound represented by formula [II] (hereinafter sometimes referred to as compound [II]). .).

式〔I〕中、Ｇ¹およびＧ²は、それぞれ独立に、Ｃ（Ｒ¹⁰）またはＮを示す。 (Compound [I])

In the formula [I], G ¹ and G ² each independently represent C (R ¹⁰ ) or N.

In the formula [I], R ¹⁰ represents a hydrogen atom, an alkyl group or an aryl group.
Examples of the alkyl group in R ¹⁰ include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, n-pentyl group, n -C1-6 alkyl groups, such as -hexyl group, can be mentioned.
Examples of the aryl group for R ¹⁰ include C6-10 aryl groups such as a phenyl group and a naphthyl group.

式〔IV〕中、Ｇ¹およびＧ²は、式〔I〕中の、Ｇ¹およびＧ²と同じものである。 As compound [I], a commercially available product may be used, or a compound synthesized by a known method may be used. Compound [I] can be synthesized, for example, by a reaction in which the amide group of the compound represented by formula [IV] is converted to a cyano group by pyridine and trifluoroacetic acid.

Wherein [IV], G ¹ and G ² are, in the formula [I] is the same as the G ¹ and G ^2.

(Compound [II])

In the formula [II], R ¹ and R ² each independently represent a hydrogen atom or an alkyl group, or R ¹ and R ² may be bonded to each other to be an alkylene group.
Examples of the alkyl group in R ¹ and R ² include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, and n-pentyl. And C1-6 alkyl groups such as a group and n-hexyl group.
Examples of the alkylene group for R ¹ and R ² include a methylene group, an ethane-1,2-diyl group, a butane-2,3-diyl group, a 2,3-dimethylbutane-2,3-diyl group, propane-1, A 3-diyl group can be exemplified.

In formula [II], R < ³ > -R < ⁵ > shows an alkyl group or an aryl group each independently.
Examples of the alkyl group in R ^{3 to} R ⁵ include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, and n-pentyl. And C1-6 alkyl groups such as a group and n-hexyl group.
The aryl group in R ³ to R ^5, mention may be made of phenyl group, C6-10 aryl group such as a naphthyl group.

In the formula [II], p, n and m represent the numbers of R ³ , R ⁴ and R ⁵ and are each independently an integer of 0 to 4.

In formula [II], —Y— represents a single bond, —O—, —S—, —CH ₂ —, —CHR ^a —, or —CR ^b R ^c —. R ^a , R ^b and R ^c each independently represents an alkyl group.
^Examples of the alkyl group in R ^a , R ^b and R ^c include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, a t-butyl group, Examples thereof include C1-6 alkyl groups such as n-pentyl group and n-hexyl group. Of these, a methyl group is preferred.

式〔V〕中、Ｘは、ハロゲノ基を示す。式〔V〕中、Ｒ³、Ｒ⁴、Ｒ⁵、ｐ、ｎ、ｍおよびＹは、式〔II〕中のＲ³、Ｒ⁴、Ｒ⁵、ｐ、ｎ、ｍおよびＹと同じものである。 As the compound [II], a compound synthesized by a known method can be used. Compound [II] is obtained by, for example, reacting a compound represented by the formula [V] with alkyl lithium, and then 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and It can be synthesized by reacting.

In the formula [V], X represents a halogeno group. Wherein [V], ^{R 3, R 4, R 5} , p, n, m and Y are the same as ^{R 3, R 4, R 5} , p, n, m and Y in the formula [II] is there.

  Compound [II] can be used in an amount of preferably 2 to 10 mol per 1 mol of compound [I]. In addition, the part comprised by the condensed ring group which consists of three rings, and an arylene group in compound [II] has an electron donating property.

  In the production method of the present invention, the reaction between the compound [I] and the compound [II] is carried out in the presence of a palladium catalyst and a base.

(Palladium catalyst)
The palladium catalyst used in the present invention may be one in which a catalytically active species is generated outside the system and added to the system, or a catalyst precursor is added in the system to generate a catalytically active species in the system. It may be a thing. The palladium catalyst used in the present invention preferably contains a palladium complex and a ligand as the catalytically active species, and more preferably contains 1 mol of palladium complex and 0.001 to 100 mol of ligand. More preferred are those containing 1 mol of palladium complex and 0.001 to 5 mol of ligand.

  The ligand constituting the catalytically active species is not particularly limited. Examples of the ligand include triethylphosphine, tricyclohexylphosphine, tri (tert-butyl) phosphine, triphenylphosphine, 1,1′-bis (diphenylphosphino) ferrocene [dppf], 9,9-dimethyl-4, Phosphorus compounds such as 5-bis (diphenylphosphino) xanthene [XANTphos], nitrogen compounds such as 2,2′-bipyridyl and 1,10-phenanthroline, and olefins such as 1,5-cyclooctadiene [COD] A compound etc. can be mentioned.

  The palladium complex constituting the catalytically active species includes dichlorobis (triphenylphosphine) palladium, dichlorobis [tris (2-methoxyphenyl) phosphine] palladium, palladium [tetrakis (triphenylphosphine)], [tris (dibenzylideneacetone)] di Palladium, dichlorobis [dicyclopentyl (2-methoxyphenyl) phosphine] palladium, dichlorobis [dicyclopentyl (2,6-dimethoxyphenyl) phosphine] palladium, bis [ditert-butyl (3,5-ditert-butylphenyl) phosphine ] Dichloropalladium, palladium acetate, palladium trifluoroacetate, palladium methanesulfonate, palladium toluenesulfonate, palladium chloride, palladium bromide, palladium iodide Bis (acetonitrile) palladium (II) dichloride, bis (benzonitrile) palladium (II) dichloride, tetrakis (both) tetrakis (acetonitrile) palladium (II), 1,10-phenanthroline palladium dichloride, 1,10-phenanthroline palladium diacetate 2,2′-bipyridinepalladium dichloride, 2,2′-bipyridinepalladium diacetate, and the like. Of these, dichlorobis (triphenylphosphine) palladium is preferred. These can be used individually by 1 type or in combination of 2 or more types.

  The palladium catalyst is an amount such that the palladium element is preferably 0.0001 to 100 mol, more preferably 0.0001 to 5 mol, still more preferably 0.0001 to 1 mol, relative to 1 mol of the compound [I]. It can be present in the reaction between compound [I] and compound [II].

(base)
Examples of the base used in the present invention include hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, lithium carbonate, lithium hydrogen carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, cesium carbonate and the like. Carbonate, lithium acetate, sodium acetate, acetate such as potassium acetate, phosphate such as trisodium phosphate, tripotassium phosphate, sodium methoxide, sodium ethoxide, alkoxide such as potassium tertiary butoxide, etc. Examples thereof include metal hydrides such as sodium hydride and potassium hydride, organic bases such as pyridine, picoline, lutidine, triethylamine, tributylamine, diisopropylethylamine and N, N-dicyclohexylmethylamine. Of these, carbonates are preferred, and sodium carbonate is more preferred. These can be used individually by 1 type or in combination of 2 or more types.
The base can be used in an amount of preferably 1 to 10 mol, more preferably 1 to 5 mol, relative to 1 mol of the compound represented by the formula [II].

The reaction of compound [I] and compound [II] can be carried out in a solvent or without solvent. Solvents that can be used in this reaction include water; alcohol solvents such as methanol, ethanol, 2-propanol, tert-butyl alcohol, trifluoroethanol, and hexafluoroisopropanol; aromatic solvents such as toluene and xylene; diethyl ether And ether solvents such as tetrahydrofuran and 2-methyltetrahydrofuran; halogen solvents such as dichloromethane and chloroform.
The temperature during the reaction is preferably -20 to 200 ° C, more preferably 0 to 150 ° C. The time required for the reaction varies depending on the amount of catalyst used, reaction scale, etc., but is preferably 0.1 to 200 hours, more preferably 0.1 to 50 hours.

  After completion of the reaction between the compound [I] and the compound [II], known separation or purification operations such as distillation, extraction, adsorption, chromatography, and crystallization can be performed.

  The production method of the present invention is a method for producing a compound represented by the formula [III] (hereinafter sometimes referred to as compound [III]).

In the prior art, the compound represented by the formula [IIIb] is by-produced, but according to the present invention, there is almost no by-product of the compound represented by the formula [IIIb].
G ¹ , G ² , and R ¹⁰ in the formulas [III] and [IIIb] are the same as those in the formula [I]. In the formulas [III] and [IIIb], R ^{3 to} R ⁵ , p, n, m, and Y are the same as those in the formula [II]. X in the formula [IIIb] represents a halogeno group.

  Next, an Example is shown and this invention is demonstrated in detail. However, the present invention is not limited to these examples.

Comparative Example 1
To a 100 mL flask, 9,9-dimethyl-10- (4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl) -9,10-dihydroacridine ( Hereinafter, it may be referred to as APN) 1.04 g (2 equivalents), 4,5-dichlorophthalonitrile (hereinafter sometimes referred to as DCPN) 0.25 g (1.27 mmol), potassium iodide 0.42 g (2 equivalents) ), 1.10 g (4 equivalents) of potassium phosphate and 31.8 mg (2 mol%) of tetrakis (triphenylphosphine) palladium (0) were added, and 20 mL of dehydrated dioxane was further added. Thereafter, decompression and argon substitution were repeated 5 times. The resulting liquid was heated to reflux for 66 hours under an argon atmosphere.

Thereafter, it was cooled, water, dichloromethane and activated carbon were added thereto, and the mixture was filtered through celite to separate an organic layer and an aqueous layer. The aqueous layer was extracted twice with dichloromethane.
The organic layer obtained by Celite filtration and the organic layer obtained by extraction were combined, washed with water, and then with saturated brine. The washed organic layer was dried over magnesium sulfate, filtered, and concentrated to give 1.29 g of crude product. By purifying the crude product by silica gel column chromatography (eluent: n-hexane / dichloromethane), 0.75 g of APN was recovered and crude 6-chloro-4 '-(9,9-dimethylacridine-10 (9H 0.11 g of) -yl)-[1,1′-biphenyl] -3,4-dicarbonitrile was obtained. Crude 6-chloro-4 '-(9,9-dimethylacridin-10 (9H) -yl)-[1,1'-biphenyl] -3,4-dicarbonitrile was further chromatographed on silica gel (eluent: n 6-Chloro-4 '-(9,9-dimethylacridin-10 (9H) -yl as a mono-substituted product as 0.06 g of a pale yellow solid by purification with n-hexane) )-[1,1′-biphenyl] -3,4-dicarbonitrile was obtained (yield 10.6%). Disubstituted products were not obtained.

Example 1
In a 100 mL flask, 0.1549 g (0.4 mmol) of 4,5-diiodophthalonitrile (hereinafter sometimes referred to as DIPN) and 0.3515 g (2.1 equivalents) of APN were placed. Thereafter, decompression and argon substitution were repeated three times. 16 mL of dehydrated THF and 4 mL of ion exchange water were added. Depressurization and argon substitution were repeated three times. Thereto were added 90.8 mg (2.1 equivalents) of sodium carbonate and 28.7 mg (10 mol%) of trans-dichlorobis (triphenylphosphine) palladium (II). Depressurization and argon substitution were repeated 5 times. The resulting liquid was stirred at 70 ° C. for 17 hours under an argon atmosphere.

Thereafter, it was cooled, water, dichloromethane and activated carbon were added thereto, and the mixture was filtered through celite to separate an organic layer and an aqueous layer. The aqueous layer was extracted twice with dichloromethane.
The organic layer obtained by Celite filtration and the organic layer obtained by extraction were combined, washed with water, and then with saturated brine. The washed organic layer was dried over magnesium sulfate, filtered, and concentrated to obtain 0.37 g of a crude product. It was applied to 2 g of silica gel and purified by silica gel chromatography (eluent: n-hexane / benzene) to obtain 0.2398 g (yield 84.6%) of Ac-VPN as a disubstituted product.

Claims (1)

In the presence of a palladium catalyst and a base, the formula [I]

(In the formula [I],
G ¹ and G ² each independently represent C (R ¹⁰ ) or N, and R ¹⁰ represents a hydrogen atom, an alkyl group or an aryl group. ) And a compound represented by
Formula [II]

(In the formula [II],
R ¹ and R ² each independently represent a hydrogen atom or an alkyl group, or R ¹ and R ² may be bonded to form an alkylene group;
R ^{3 to} R ⁵ each independently represents an alkyl group or an aryl group,
p represents the number of R ³ and is an integer of 0 to 4,
n represents the number of R ⁴ and is an integer of 0 to 4,
m represents the number of R ⁵ and is an integer of 0 to 4,
—Y— represents a single bond, —O—, —S—, —CH ₂ —, —CHR ^a —, or —CR ^b R ^c —, and R ^a , R ^b , and R ^c are each independently Represents an alkyl group. And a compound represented by formula [III]

(In the formula [III],
G ¹ and G ² each independently represent C (R ¹⁰ ) or N;
R ¹⁰ represents a hydrogen atom, an alkyl group or an aryl group,
R ^{3 to} R ⁵ each independently represents an alkyl group or an aryl group,
p represents the number of R ³ and is an integer of 0 to 4,
n represents the number of R ⁴ and is an integer of 0 to 4,
m represents the number of R ⁵ and is an integer of 0 to 4,
—Y— represents a single bond, —O—, —S—, —CH ₂ —, —CHR ^a —, or —CR ^b R ^c —, and R ^a , R ^b , and R ^c are each independently Represents an alkyl group. The manufacturing method of the compound represented by this.