Method for producing 2-arylazole compounds

Abstract

This invention provides a clean method for producing 2-arylazole compounds that involves a direct arylation reaction without requiring copper salts. [Solution] By using a palladium catalyst having a specific tertiary phosphine compound as a ligand, the direct arylation reaction between the azole compound and the aryl compound having a leaving group proceeds rapidly without adding a copper salt to the system, and the 2-arylazole compound is obtained in good yield.

Description

[Technical Field]

[0001] The present invention relates to a method for producing 2-arylazole compounds using a palladium catalyst having a tertiary phosphine compound as a ligand. [Background technology]

[0002] 2-arylazole compounds, which have an aromatic group at the 2-position of the azole ring and are condensed with other aromatic rings at the 4 and 5 positions, exhibit low LUMO levels and are therefore useful as organic semiconductors used in organic thin-film solar cells, organic thin-film transistors, organic LEDs, etc. 2-arylazole compounds can be produced by Suzuki-Miyaura coupling, Stille coupling, or Tamao-Kumada coupling reactions using a starting material having a halogen atom at the 2-position of the azole ring and organometallic reagents such as arylboric acid, aryltin, and arylGrignard.

[0003] On the other hand, the raw materials containing halogen atoms are expensive, and the organometallic reagents are unstable and difficult to handle. Therefore, in recent years, direct arylation reactions, in which the hydrogen atom at the 2-position of the azole ring is activated by a transition metal catalyst and coupled with aryl halides, have attracted attention as a method for producing 2-arylazole compounds.

[0004] Patent Document 1 discloses that in the reaction between imidazole and halogenated benzene, when a cobalt-salen complex is used as a catalyst and a copper salt as a co-catalyst, direct arylation to the 2-position of the imidazole ring proceeds.

[0005] Patent Document 2 discloses that a 2-arylazole compound can be obtained by reacting an azole compound such as benzimidazole, benzoxazole, or benzothiazole with an aryl halide in the presence of a strong base and a catalytic amount of copper salt.

[0006] Furthermore, Non-Patent Document 1 discloses that in the reaction between azole compounds such as benzothiazole and aryl halides, the use of a palladium catalyst and a copper salt as a co-catalyst promotes direct arylation to the 2-position of the imidazole ring. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] International Patent Publication No. 2004 / 069394 [Patent Document 2] U.S. Patent Publication No. 2009 / 0076266 [Non-patent literature]

[0008] [Non-Patent Document 1] Journal of the American Chemical Society, Vol. 132, pp. 3674-3675, 2010. [Overview of the project] [Problems that the invention aims to solve]

[0009] However, conventional methods require an excess amount of copper salt equivalent to 4 to 40 times the catalyst as a co-catalyst (Patent Document 1, Non-Patent Document 1), and even when copper salt is used as a catalyst, it is used in an amount equivalent to 10 times that of a typical palladium catalyst (Patent Document 2), which presents problems from the standpoint of environmental compatibility and economic feasibility.

[0010] Therefore, there was a need for a clean method of producing 2-arylazole compounds that involved a direct arylation reaction but did not require copper salts. [Means for solving the problem]

[0011] In order to solve the above problem, the present inventors have conducted intensive studies and found that by using a palladium catalyst having a specific tertiary phosphine compound as a ligand, the direct arylation reaction between an azole compound and an aryl compound having a leaving group proceeds rapidly without adding a copper salt into the system, and a 2-arylazole compound can be obtained in good yield, which has led to the completion of the present invention.

[0012] That is, the present invention is constituted by the following gist. [1] The following general formula (1)

[0013]

Chemical Formula

[0014]

Chemical Formula

[0015]

Chemical Formula

[0016] [ka] (In the formula, R 1 R represents an aliphatic group with 1 to 8 carbon atoms. 2 and R 3 Each of these independently represents a hydrogen atom, an aliphatic group with 1 to 8 carbon atoms, an aromatic hydrocarbon group with 6 to 12 nuclei, or a heteroaromatic group with 3 to 6 nuclei. Biarylphosphine compounds represented by the following general formula (4b)

[0017] [ka] (In the formula, R 4 The method for producing the product according to [1] or [2], wherein is a cyclic aliphatic group having 3 to 20 carbon atoms. The product is at least one selected from the group consisting of a bisadamantylphosphine compound represented by ) and tri(tert-butyl)phosphine. [4] The method for producing the product according to [2], wherein the palladium complex is a paradacycle or tris(dibenzylideneacetone)dipalladium. [5] The method for producing an organic acid according to [1] above, wherein the organic acid is an aliphatic carboxylic acid. [6] The method for producing the product according to [5], wherein the aliphatic carboxylic acid is pivalic acid, acetic acid, or 1-adamantanecarboxylic acid. [7] The manufacturing method according to [1], wherein X is an oxygen atom or a sulfur atom. [8] The manufacturing method according to [1], wherein the leaving group represented by Y is a halogen atom or a sulfonyloxy group. [9] The manufacturing method according to [1], wherein n is 1 or 2. [Effects of the Invention]

[0018] By using the manufacturing method according to one embodiment of the present invention, 2-arylazole compounds useful as organic semiconductors can be efficiently produced. [Modes for carrying out the invention]

[0019] Embodiments of the present invention will be described in detail below. However, the present invention is not limited thereto, and various modifications are possible within the scope described. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included within the technical scope of the present invention. In this specification, unless otherwise specified, "P~Q" representing a numerical range means "greater than or equal to P and less than or equal to Q".

[0020] The manufacturing method according to an embodiment of the present invention (hereinafter sometimes referred to as "the manufacturing method of this embodiment") is based on the following general formula (1)

[0021] [ka] (In the formula, rings A, X, and n have the same meaning as above.) An azole compound represented by the following general formula (2)

[0022] [ka] The compound represented by (wherein Ar and Y have the same meanings as above) is reacted with a palladium catalyst having a tertiary phosphine compound as a ligand, a base, and an organic acid to obtain the following general formula (3)

[0023] [ka] This is a method for producing a 2-arylazole compound represented by the formula (wherein rings A, X, n, and Ar have the same meanings as above).

[0024] Examples of aromatic hydrocarbon rings with 6 to 20 nuclear atoms represented by ring A include not only benzene rings, but also linking rings such as biphenyl rings and terphenylyl rings, and condensed rings such as pentalene rings, indene rings, naphthalene rings, azulene rings, heptalene rings, indacene rings, acenaphthylene rings, fluorene rings, phenalene rings, anthracene rings, phenanthrene rings, fluorantene rings, acephenatylene rings, tetracene rings, triphenylene rings, and pyrene rings. Aromatic hydrocarbon rings with 6 to 10 nuclear atoms are preferred because the raw materials are readily available, and benzene rings are more preferred. Ring A may have one or more groups selected from the group consisting of halogen atoms, cyano groups, nitro groups, hydroxyl groups, carboxyl groups, amino groups, aliphatic groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, aromatic hydrocarbon groups having 6 to 10 nuclei, and heteroaromatic groups having 3 to 6 nuclei. The C1-C8 aliphatic group that ring A may have may be linear, branched, or cyclic aliphatic group, specifically a methyl group, cyclohexylmethyl group, ethyl group, 2-cyclopentylethyl group, propyl group, 2-propyl group, 2,2-dimethylpropyl group, 3-cyclopropylpropyl group, 1-methylethyl group, cyclopropyl group, butyl group, 2-methylbutyl group, 3-methylbutyl group, 2-butyl group, 3-methylbutan-2-yl group, tert-butyl group, cyclobutyl group, pentyl group, 2-methylpentyl group, 3-ethylpentyl group, 2,4-dimethylpentyl group, 2-pentyl group, 2-methylpentan-2-yl group, 4,4-dimethylpentan-2-yl group Examples include the 3-pentyl group, 3-ethylpentan-3-yl group, cyclopentyl group, 2,5-dimethylcyclopentyl group, 3-ethylcyclopentyl group, hexyl group, 2-methylhexyl group, 3,3-dimethylhexyl group, 4-ethylhexyl group, 2-hexyl group, 2-methylhexane-2-yl group, 5,5-dimethylhexane-2-yl group, 3-hexyl group, 2,4-dimethylhexane-3-yl group, cyclohexyl group, 4-ethylcyclohexyl group, 4,4-dimethylcyclohexyl group, heptyl group, 2-heptyl group, 3-heptyl group, 4-heptyl group, octyl group, 2-octyl group, 3-octyl group, 4-octyl group, and cyclooctyl group.

[0025] The alkoxy group having 1 to 4 carbon atoms that ring A may have may be linear, branched, or cyclic alkyloxy group. Specific examples include methoxy group, ethoxy group, 1-methylethyloxy group, 1,1-dimethylethyloxy group, propyloxy group, 1-methylpropyloxy group, cyclopropyloxy group, butyloxy group, cyclobutyloxy group, and the like.

[0026] Examples of aromatic hydrocarbon groups with 6 to 10 nuclear atoms that ring A may have include phenyl groups, indenyl groups, naphthyl groups, and the like.

[0027] Examples of heteroaromatic groups with 3 to 6 nuclear atoms that ring A may have include pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyridyl, pyrimidyl, pyrazyl, and 1,3,5-triazinyl groups.

[0028] Furthermore, ring A is preferably a double bond, and in this case the azole compound is represented by the following general formulas (1a) to (1c).

[0029] [ka] Examples of chalcogen atoms represented by X include oxygen atoms, sulfur atoms, selenium atoms, tellurium atoms, etc., and oxygen atoms or sulfur atoms are preferred because the azole compound (1) is readily available.

[0030] Examples of nitrogen atoms that may be substituted, represented by X, include nitrogen atoms substituted with aliphatic groups having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, 1-methylethyl, butyl, 2-butyl, tert-butyl, and cyclobutyl groups, and nitrogen atoms substituted with aromatic groups having 5 to 10 nuclear atoms, such as phenyl, tolyl, trifluoromethylphenyl, 2,4-dimethylphenyl, 3,5-dimethylphenyl, mesityl, naphthyl, thienyl, furyl, and pyridyl groups.

[0031] n represents an integer from 1 to 3 if ring A is an aromatic hydrocarbon ring, and 1 or 2 if ring A is a double bond. 1 or 2 is preferred because the azole compound (1) is readily available.

[0032] Examples of aromatic hydrocarbon groups represented by Ar with 6 to 20 nuclear atoms include, in addition to the phenyl group, linking ring groups such as the biphenylyl group, terphenylyl group, and naphthylphenyl group, and fused ring groups such as the naphthyl group, acenaphthyleneyl group, phenanthryl group, anthranyl group, fluoranthenyl group, pyrenyl group, triphenylenyl group, chrysenyl group, fluorenyl group, triptycenyl group, and perilenyl group.

[0033] Examples of heteroaromatic groups represented by Ar with 5 to 14 nuclear atoms include pyrazolyl, imidazolyl, thienyl, furyl, benzofuranyl, benzothienyl, dibenzofuranyl, dibenzothienyl, pyrimidyl, pyrazinyl, pyridyl, bipyridyl, terpyridinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, acridinyl, and phenanthrolinyl groups.

[0034] The aromatic hydrocarbon group with 6 to 20 nuclei atoms represented by Ar and the heteroaromatic group with 5 to 14 nuclei atoms may be substituted with one or more groups selected from the group consisting of halogen atoms, cyano groups, nitro groups, hydroxyl groups, carboxyl groups, amino groups, aliphatic groups with 1 to 8 carbon atoms, alkoxy groups with 1 to 4 carbon atoms, aromatic hydrocarbon groups with 6 to 10 nuclei atoms, and heteroaromatic groups with 3 to 6 nuclei atoms. Examples of the aliphatic group with 1 to 8 carbon atoms, the alkoxy group with 1 to 4 carbon atoms, the aromatic hydrocarbon group with 6 to 10 nuclei atoms, and the heteroaromatic group with 3 to 6 nuclei atoms are the same as those exemplified in the aliphatic group with 1 to 8 carbon atoms, the alkoxy group with 1 to 4 carbon atoms, the aromatic hydrocarbon group with 6 to 10 nuclei atoms, and the heteroaromatic group with 3 to 6 nuclei atoms that ring A may have.

[0035] Examples of leaving groups represented by Y include halogen atoms such as chlorine, bromine, and iodine; sulfonyloxy groups such as benzenesulfonyloxy, toluenesulfonyloxy, methanesulfonyloxy, and trifluoromethanesulfonyloxy; alkoxy groups; carboxyl groups; hydroxyl groups; cyano groups; and alkylthio groups. Halogen atoms or sulfonyloxy groups are preferred due to their good reactivity, and chlorine, bromine, iodine, or trifluoromethanesulfonyloxy groups are particularly preferred.

[0036] The azole compound (1) used in the manufacturing method of this embodiment can be manufactured according to the methods disclosed in Journal of Heterocyclic Chemistry, Vol. 45, pp. 811-819, 2008; Journal of Materials Chemistry A, Vol. 7, pp. 14153-14162, 2019; and The Journal of Organic Chemistry, Vol. 75, pp. 495-497, 2010. Alternatively, commercially available products may be used. When n is 2 or 3, azole compound (1) produces positional isomers based on the nitrogen atom at position 3 of the azole ring, and the manufacturing method of this embodiment is applicable to either of these. Examples of azole compounds (1) include those of the following formulas: (1b-1) to (1b-3), (1c-1) to (1c-3), (1d-1) to (1d-3), (1e-1) to (1e-3), (1f-1) to (1f-3), (1g-1) to (1g-3), (1h-1) to (1h-3), and (1i-1) to (1i-3). However, the azole compound (1) used in the manufacturing method of this embodiment is not limited to these.

[0037] [ka]

[0038] [ka] Compound (2) used in the production method of the present embodiment can be easily produced by a person skilled in the art. Alternatively, a commercially available product may be used.

[0039] The production method of the present embodiment is carried out in the presence of a palladium catalyst having a tertiary phosphine compound as a ligand, without using a copper salt. The palladium catalyst having a tertiary phosphine compound as a ligand is obtained by reacting a tertiary phosphine compound with a palladium salt or a palladium complex, and the resulting product may be isolated before use. From the viewpoint of high catalytic activity, it is preferable that the palladium catalyst having a tertiary phosphine compound as a ligand is generated in the reaction system and used without isolation. The molar ratio of the tertiary phosphine compound to the palladium salt or palladium complex is preferably in the range of 1:10 to 10:1, and more preferably in the range of 1:5 to 5:1 from the viewpoint of good reaction yield.

[0040] There is no particular limitation on the amount of the palladium catalyst having a tertiary phosphine compound as a ligand used in the production method of the present embodiment, but from the viewpoint of good reaction yield, the amount is preferably 0.001 to 20 mol percent, more preferably 0.1 to 5 mol percent, relative to the azole compound (1).

[0041] As the tertiary phosphine compound, the following general formula (4a)

[0042]

Chemical Formula

[0043] [ka]

[0044] [ka]

[0045] [ka]

[0046] [ka]

[0047] [ka]

[0048] [ka]

[0049] [ka]

[0050] [ka]

[0051] [ka]

[0052] [ka]

[0053] [ka]

[0054] [ka] As the biarylphosphine compound (4a), (4a-1) or (4a-18) are preferred due to their good reactivity.

[0055] Furthermore, as a tertiary phosphine compound, the following general formula (4b)

[0056] [ka] (In the formula, R 4 represents a cyclic aliphatic group having 3 to 20 carbon atoms. It is preferable that the compound is a bisadamantylphosphine compound represented by ). 4Examples of cyclic aliphatic groups having 3 to 20 carbon atoms represented by include monocyclic aliphatic groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and cyclooctyl group, and polycyclic aliphatic groups such as dekalinyl group, pinenyl group, bicyclo[2,2,1]heptynyl group, camphanyl group, bicyclo[2,2,2]octanyl group, adamantyl group, and diamantyl group. Cyclopentyl group, cyclohexyl group, and adamantyl group are preferred due to their good reactivity. Specifically, examples of bisadamantylphosphine compounds (4b) include those of the following formulas (4b-1) to (4b-11), but the bisadamantylphosphine compounds (4b) used in the production method of this embodiment are not limited thereto.

[0057] [ka]

[0058] [ka]

[0059] [ka] As the bisadamantylphosphine compound (4b), (4b-3), (4b-4), or (4b-10) are preferred due to their good reactivity.

[0060] Tri(tert-butyl)phosphine is preferred as the tertiary phosphine compound used in the manufacturing method of this embodiment.

[0061] The tertiary phosphine compound used in the manufacturing method of this embodiment can be produced, for example, by following the methods disclosed in non-patent literature (Angewandte Chemie, International Edition, Vol. 54, pp. 12447-12451, 2015, etc.). Alternatively, commercially available products may be used.

[0062] The tertiary phosphine compounds used in the production method of this embodiment react with Bronsted acids such as tetrafluoroboric acid, hexafluorophosphate, hexafluoroantimonic acid, trifluoromethanesulfonic acid, hydrogen chloride, and hydrogen bromide, or Lewis acids such as borane, triethylborane, and triphenylborane to give chemically acceptable salts thereof. However, since the production method of this embodiment is carried out in the presence of a base, the same effect can be obtained by substituting the exemplified tertiary phosphine compounds with chemically acceptable salts thereof.

[0063] Examples of palladium salts used in the manufacturing method of this embodiment include palladium chloride, palladium acetate, palladium trifluoroacetate, and palladium nitrate.

[0064] Examples of palladium complexes used in the manufacturing method of this embodiment include palladium complex compounds such as π-allyl palladium chloride dimer, palladium acetylacetonate, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, dichlorobis(acetonitrile)palladium, and dichlorobis(benzonitrile)palladium, as well as the palladium cycle represented by the following formulas (5-1) to (5-8). In the following formulas (5-1) to (5-8), "Me" represents a methyl group and "Ph" represents a phenyl group.

[0065] [ka]

[0066] [ka] As the palladium complex used in the manufacturing method of this embodiment, a palladium complex compound or palladium cycle having dibenzylideneacetone is preferred in terms of high catalytic activity, and tris(dibenzylideneacetone)dipalladium(Pd2(dba)3) or the palladium cycle represented by formula (5-3) is particularly preferred.

[0067] The manufacturing method of this embodiment is carried out in the presence of a base. Examples of the base include metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, calcium hydroxide, and barium hydroxide; metal carbonates such as sodium carbonate, potassium carbonate, barium carbonate, lithium carbonate, cesium carbonate, and rubidium carbonate; metal acetates such as potassium acetate and sodium acetate; metal phosphates such as potassium phosphate and sodium phosphate; metal fluoride salts such as sodium fluoride, potassium fluoride, and cesium fluoride; and metal alkoxides such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium isopropyl oxide, potassium tert-butoxide, and sodium tert-butoxide. Metal carbonates are preferred in terms of good reaction yield, and potassium carbonate or cesium carbonate are particularly preferred. There are no particular restrictions on the amount of base used, but in terms of good reaction yield, the molar ratio of azole compound (1) to base is preferably in the range of 1:0.5 to 1:20, and more preferably in the range of 1:1 to 1:10.

[0068] The manufacturing method of this embodiment is carried out in the presence of an organic acid. The organic acid may be aliphatic carboxylic acids such as formic acid, acetic acid, chloroacetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, 2-methylpropionic acid, pivalic acid, butyric acid, valeric acid, cyclohexanecarboxylic acid, 1-adamantanecarboxylic acid, oxalic acid, malonic acid, adipic acid, malic acid, and citric acid; aromatic carboxylic acids such as benzoic acid, 4-methoxybenzoic acid, 4-nitrobenzoic acid, 2,4-dinitrobenzoic acid, 4-trifluoromethylbenzoic acid, 2,4,6-trimethylbenzoic acid, 3-chlorobenzoic acid, salicylic acid, and phthalic acid; valine, leucine, isoleucine, and thalic acid. Examples of organic acids include amino acids such as onine, methionine, phenylalanine, tryptophan, lysine, histidine, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine, and sulfonic acids such as benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid, nonafluorobutane-1-sulfonic acid, methanesulfonic acid, and camphorsulfonic acid. Aliphatic carboxylic acids are preferred in terms of good reaction yield, and acetic acid, pivalic acid, or 1-adamantanecarboxylic acid are particularly preferred. There are no particular restrictions on the amount of organic acid used, but in terms of good reaction yield, the molar ratio of azole compound (1) to organic acid is preferably in the range of 1:0.1 to 1:10, and more preferably in the range of 1:0.3 to 1:3. Since the manufacturing method of this embodiment is carried out in the presence of a base, the organic acid reacts rapidly with the base to form a salt. Therefore, the same effect can be obtained by substituting the exemplified organic acids with chemically acceptable salts thereof.

[0069] The manufacturing method of this embodiment may be carried out in the presence of a co-ligand.The coligands include triphenylphosphine, trimethylphosphine, tributylphosphine, tri(tert-butyl)phosphine, tricyclohexylphosphine, tert-butyldiphenylphosphine, 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, 2-(diphenylphosphino)-2'-(N,N-dimethylamino)biphenyl, 2-(di-tert-butylphosphino)biphenyl, 2-(dicyclohexylphosphino)biphenyl, bis(diphenylphosphino)methane, and 1,2-bis(diphenyl Phosphine compounds such as phosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-bis(diphenylphosphino)ferrocene, tri(2-furyl)phosphine, tri(o-tolyl)phosphine, tris(2,5-xylyl)phosphine, (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, and 1,3-bis(diisopropylphenyl)imidazole-2-ylidene N-heterocyclic carbene compounds such as 1,3-dimethytylimidazole-2-ylidene, 1,3-di-t-butylimidazole-2-ylidene, 1,3-diadamantylimidazole-2-ylidene, and 1,3-dicyclohexylimidazole-2-ylidene; nitrogen-containing heterocyclic compounds such as pyridine, phenanthroline, and 2,2'-bipyridine; N,N,N',N'-tetramethylmethylenediamine, N,N,N',N'-tetramethylethylenediamine (TMEDA), N,N,N',N'-tetraethylethylenediamine, and N,N,N',N'-tetramethylethylenediamine. Examples of diamine compounds include phenylethylenediamine, N,N,N',N'-tetramethylpropylenediamine, N,N,N',N'-tetramethylbutylenediamine, N,N,N',N''-pentamethyldiethylenetriamine (PMDETA), and spartein. Phosphine compounds or diamine compounds are preferred in terms of good reaction yield, with tri(tert-butyl)phosphine, tri(cyclohexyl)phosphine, bis(adamantyl)butylphosphine (PAd2Bu), TMEDA, and PMDETA being particularly preferred.

[0070] The manufacturing method of this embodiment can be carried out in a solvent. The solvent is not particularly limited as long as it does not inhibit the reaction, and includes aliphatic hydrocarbon solvents such as hexane, heptane, decane, and tridecane; ether solvents such as diisopropyl ether, dibutyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 2-methyltetrahydrofuran, 1,4-dioxane, and 1,2-dimethoxyethane; aromatic hydrocarbon solvents such as benzene, toluene, xylene, mesitylene, and tetralin; carbonate ester solvents such as ethylene carbonate, propylene carbonate, dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate, and 4-fluoroethylene carbonate; ethyl acetate, butyl acetate, methyl propionate, ethyl propionate, and butyric acid. Examples of solvents include ester solvents such as methyl and γ-lactone; amide solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), and N-methylpyrrolidone (NMP); urea solvents such as N,N,N',N'-tetramethylurea (TMU) and N,N'-dimethylpropyleneurea (DMPU); sulfoxide solvents such as dimethyl sulfoxide (DMSO); alcohol solvents such as methanol, ethanol, 2-propanol, butanol, octanol, benzyl alcohol, ethylene glycol, propylene glycol, diethylene glycol, triethylene glycol, and 2,2,2-trifluoroethanol; nitromethane; water; and these may be mixed in any ratio. As solvents used in the production method of this embodiment, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, ether solvents, amide solvents, sulfoxide solvents, water, or mixtures thereof are preferred in terms of good reaction yield, and toluene, xylene, or CPME are particularly preferred.

[0071] The manufacturing method of this embodiment can be carried out at a temperature appropriately selected from 0°C to 240°C, and is preferably carried out at a temperature appropriately selected from 70°C to 200°C, and more preferably at a temperature appropriately selected from 90°C to 150°C, in order to obtain a good reaction yield.

[0072] The manufacturing method of this embodiment is preferably carried out under an inert gas atmosphere such as argon gas or nitrogen gas.

[0073] The 2-arylazole compound (3) can be obtained by conventional processing after the completion of the manufacturing method of this embodiment. If necessary, it may be purified using general methods well known to those skilled in the art, such as washing, precipitation, filtration, dialysis, column chromatography, preparative HPLC, and Soxhlet extraction.

[0074] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples.

[0075] The 2-arylazole compounds synthesized in the examples are 1 Structural analysis was performed using 1H-NMR measurements. 1 For 1H-NMR measurements, a Bruker ASCEND HD (400MHz; manufactured by Bruker) was used. 1 ¹H-NMR was performed using deuterated chloroform (CDCl3) as the measurement solvent and tetramethylsilane (TMS) as the internal standard.

[0076] Example 1

[0077] [ka] In a 10 mL Schlenk tube with a dry, greaseless stopcock, benzo[1,2-d:4,5-d']bisthiazole (28.8 mg, 150 μmol), 1-bromo-3,5-di-tert-butylbenzene (80.7 mg, 300 μmol), paradacycle (5-3) (1.1 mg, 15 μmol), and tertiary phosphine compound (4a-1) (1.1 mg, 30 μmol) were added. The reaction vessel was transferred to a glove box, where organic acid (pivalic acid) (15.3 mg, 150 μmol), base (potassium carbonate) (103 mg, 750 μmol), and solvent (CPME) (0.5 mL) were added. The mixture was stirred at room temperature for 1 hour and then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. 1,3,5-trimethoxybenzene (25.2 mg, 150 μmol; internal standard) was added to the resulting crude product. The mixture was dissolved in CDCl3. 1 ¹H-NMR analysis revealed that the target 2,6-bis(3,4-di-tert-butylphenyl)benzo[1,2-d:4,5-d']bisthiazole was obtained in 95% yield. 1 H-NMR(CDCl3,400MHz)δ(ppm):8.56(s,2H),7.96(d,J=2.0Hz,4H),7.60(t,J=2.0Hz,2H),1.42(s,36H). Examples 2-5 In Example 1, the amount of base equivalent (Examples 2-5), reaction solvent (Examples 3-5), and type of base (Example 5) were changed, while other conditions were carried out in accordance with Example 1. The results of the reaction are shown in Table 1.

[0078] [Table 1] Example 6

[0079] [ka] Palladium complex (5-3) (1.1 mg, 15 μmol) and tertiary phosphine compound (4a-1) (1.1 mg, 30 μmol) were added to a 10 mL Schlenk tube with a dry, greaseless stopcock. The reaction vessel was transferred to a glove box, where benzothiazole (40.5 mg, 300 μmol), bromobenzene (47.0 mg, 300 μmol), organic acid (pivalic acid) (15.3 mg, 150 μmol), base (potassium carbonate) (62.1 mg, 550 μmol), and solvent (CPME) (0.6 mL) were added. The mixture was stirred at room temperature for 1 hour, then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature, and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. To the obtained crude product, 1,3,5-trimethoxybenzene (25.2 mg, 150 μmol; internal standard) was added. The mixture was dissolved in CDCl3. 1 Analysis using 1H-NMR revealed that the target 2-phenylbenzothiazole was obtained in 95% yield. 1 H-NMR (CDCl3,400MHz)δ(ppm):8.11~8.07(m,3H),7.91(d,J=8.0Hz,1H),7.52~7.45(m,4H),7.39(dd,J=16.0,1.2Hz,1H). Examples 7-13 In Example 6, the leaving group Y (Example 7), palladium complex (Examples 10-12), tertiary phosphine compound (Examples 7-10, 12), type and equivalent amount of base (Examples 10-12), equivalent amount of organic acid (Examples 10-12), reaction solvent (Examples 10-12), and reaction temperature (Examples 10-12) were changed, while other conditions were carried out in accordance with Example 6. The results of the reaction are shown in Table 2.

[0080] [Table 2] Example 13

[0081] [ka] Palladium complex (Pd2(dba)3·CHCl3) (1.1 mg, 15 μmol) and tertiary phosphine compound (4b-10) (1.1 mg, 30 μmol) were added to a 10 mL Schlenk tube with a dry, greaseless stopcock. The reaction vessel was transferred to a glove box, where benzothiazole (40.5 mg, 300 μmol), 2-bromo-5-methylthiophene (47.0 mg, 300 μmol), organic acid (pivalic acid) (15.3 mg, 150 μmol), base (cesium carbonate) (62.1 mg, 550 μmol), and solvent (toluene) (0.6 mL) were added. The mixture was stirred at room temperature for 1 hour, then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. 1,3,5-trimethoxybenzene (25.2 mg, 150 μmol; internal standard) was added to the resulting crude product. The mixture was dissolved in CDCl3. 1 ¹H-NMR analysis revealed that the target 2-(5-methylthiophen-2-yl)benzothiazole was obtained in 69% yield. 1 H-NMR(CDCl3,400MHz)δ(ppm):8.00(d,J=8.0Hz,1H),7.82(d,J=8.0Hz,1H),7.47~7 .43(m,2H),7.34(dd,J=16.0,1.2Hz,1H),6.80(dd,J=3.6,1.2Hz,1H),2.55(s,3H). Examples 14-28 In Example 13, the type and equivalent amount of the palladium complex (Examples 14, 15), the type and equivalent amount of the tertiary phosphine compound (Examples 14, 23, 28), the type of organic acid (Examples 25, 26), the reaction solvent (Example 27), the type and equivalent amount of the coligand (Examples 16-23), and the reaction temperature (Example 27) were changed, while other conditions were carried out in accordance with Example 13. The results of the reaction are shown in Table 3.

[0082] [Table 3] Example 29

[0083] [ka] Pd2(dba)3·CHCl3 (1.3 mg, 13 μmol) and tertiary phosphine compound (4b-4) (2.4 mg, 50 μmol) were added to a 10 mL Schlenk tube with a dry, greaseless stopcock. The reaction vessel was transferred to a glove box, where benzothiazole (33.8 mg, 250 μmol), 2-chloro-5-methylthiophene (33.2 mg, 250 μmol), pivalic acid (12.8 mg, 125 μmol), cesium carbonate (122 mg, 375 μmol), and toluene (0.5 mL) were added. The mixture was stirred at room temperature for 1 hour, then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. To the obtained crude product, 1,3,5-trimethoxybenzene (21.0 mg, 125 μmol; internal standard) was added. The mixture was dissolved in CDCl3. 1 ¹H-NMR analysis revealed that the target 2-(5-methylthiophen-2-yl)benzothiazole was obtained in 66% yield.

[0084] Example 30

[0085] [ka] Pd2(dba)3·CHCl3 (1.3 mg, 13 μmol) and tertiary phosphine compound (4b-10) (2.2 mg, 50 μmol) were added to a 10 mL Schlenk tube with a dry, greaseless stopcock. The reaction vessel was transferred to a glove box, where benzothiazole (33.8 mg, 250 μmol), 2-bromo-5-phenylthiophene (59.8 mg, 250 μmol), TMEDA (2.9 mg, 25 μmol), pivalic acid (12.8 mg, 125 μmol), cesium carbonate (122 mg, 375 μmol), and toluene (0.5 mL) were added. The mixture was stirred at room temperature for 1 hour, then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. 1,3,5-trimethoxybenzene (21.0 mg, 125 μmol; internal standard) was added to the resulting crude product. The mixture was dissolved in CDCl3. 1 ¹H-NMR analysis revealed that the target 2-(5-phenylthiophen-2-yl)benzothiazole was obtained in 90% yield. 1 H-NMR (CDCl3,400MHz)δ(ppm):8.03(d,J=8.0Hz,1H),7.87(d,J=8.0Hz,1H),7.69(d,J=8.0Hz,2H),7.63(d,J=8.0Hz,1H),7.48~7.34(m,6H). Example 31

[0086] [ka] In a 10 mL Schlenk tube with a dry, greaseless stopcock, thiazolo[5,4-d]thiazole (7.1 mg, 50 μmol), 1-bromo-3,5-di-tert-butylbenzene (26.9 mg, 50 μmol), Pd2(dba)3·CHCl3 (1.0 mg, 10 μmol), and tri-tert-butylphosphonium tetrafluoroborate (1.2 mg, 40 μmol) were added. The reaction vessel was transferred to a glove box, where pivalic acid (5.1 mg, 50 μmol), cesium carbonate (48.8 mg, 150 μmol), and toluene (0.5 mL) were added. The mixture was stirred at room temperature for 1 hour, then at 120 °C for 24 hours. After the reaction was complete, it was cooled to room temperature and distilled water (3 mL) and chloroform (3 mL) were added. The organic layer was separated and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the low-boiling components were removed by vacuum distillation. To the obtained crude product, 1,3,5-trimethoxybenzene (12.6 mg, 75 μmol; internal standard) was added. The mixture was dissolved in CDCl3. 1 ¹H-NMR analysis revealed that the target 2,5-bis(3,4-di-tert-butylphenyl)-thiazolo[5,4-d]thiazole was obtained in 72% yield. 1 H-NMR (CDCl3,400MHz)δ(ppm):7.82(d,J=2.0Hz,4H),7.55(t,J=2.0Hz,2H),1.40(s,36H). As described above, 2-arylazole compounds could be produced in high yield by the method described in the examples.

Claims

1. The following general formula (1) 【Chemistry 1】 (In the formula, Ring A represents an aromatic hydrocarbon ring with 6 to 20 nuclear atoms, or a double bond, which may be substituted. X represents a chalcogen atom or a nitrogen atom that may be substituted. n represents an integer from 1 to 3 if ring A is an aromatic hydrocarbon ring, and 1 or 2 if ring A has a double bond. Azole compounds represented by the following general formula (2) 【Chemistry 2】 (In the formula, Ar represents an aromatic hydrocarbon group with 6 to 20 optionally substituted nuclear atoms, or a heteroaromatic group with 5 to 14 optionally substituted nuclear atoms. (Y represents a leaving group.) The compound shown is reacted with a palladium catalyst having a tertiary phosphine compound as a ligand, a base, and an organic acid in the presence of the following general formula (3). 【Transformation 3】 A method for producing a 2-arylazole compound represented by the formula (wherein rings A, X, n, and Ar have the same meanings as described above).

2. The method for producing a palladium catalyst having a tertiary phosphine compound as a ligand, in a reaction system from a tertiary phosphine compound and a palladium salt or palladium complex, as described in claim 1.

3. A tertiary phosphine compound is given by the following general formula (4a) 【Chemistry 4】 (In the formula, R １ R represents an aliphatic group with 1 to 8 carbon atoms. ２ and R ３ Each of these independently represents a hydrogen atom, an aliphatic group with 1 to 8 carbon atoms, an aromatic hydrocarbon group with 6 to 12 nuclei, or a heteroaromatic group with 3 to 6 nuclei. The biarylphosphine compound represented by the following general formula (4b) 【Transformation 5】 (In the formula, R ４ The method for producing a product according to claim 1 or 2, wherein is at least one selected from the group consisting of a bisadamantylphosphine compound represented by ) and tri(tert-butyl)phosphine.

4. The production method according to claim 2, wherein the palladium complex is paradacycle or tris(dibenzylideneacetone)dipalladium.

5. The method for producing an organic acid according to claim 1, wherein the organic acid is an aliphatic carboxylic acid.

6. The production method according to claim 5, wherein the aliphatic carboxylic acid is pivalic acid, acetic acid, or 1-adamantanecarboxylic acid.

7. The manufacturing method according to claim 1, wherein X is an oxygen atom or a sulfur atom.

8. The manufacturing method according to claim 1, wherein the leaving group represented by Y is a halogen atom or a sulfonyloxy group.

9. The manufacturing method according to claim 1, wherein n is 1 or 2.

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