JP6869614B2 - Phosphine compound and a catalyst for coupling using this as a ligand - Google Patents

Description

The present invention relates to a phosphine compound and a coupling catalyst using the phosphine compound as a ligand.

Palladium catalysts are useful as catalysts in various organic synthesis reactions, but the selection of a phosphine ligand is important for exhibiting the catalytic action of a desired organic synthesis reaction (for example, by Jiro Tsuji, Palladium). Reagents and Catalysts, Wiley, 2004). For example, as a palladium catalyst showing high activity in a carbon-nitrogen bond formation reaction by coupling using a palladium compound of an aryl halide and a primary or secondary amine as a catalyst, tri (tert-butyl) phosphine (for example, Patent Document 1) ), 2-Dicyclohexylphosphino-1,1'-biphenyl compound (for example, Patent Document 2) 2- (di-tert-butyl) phosphino-1,1'-biphenyl compound (for example, Non-Patent Document 1) and the like. Palladium catalysts used as phosphine ligands are known.

Among the carbon-nitrogen bond forming reactions, the coupling reaction between an aryl halide and 9H-carbazole which gives 9-aryl-9H-carbazole (for example, Patent Documents 3 and 4) useful as an intermediate of an organic electronic material is synthesized. It is a chemically effective reaction. Tri-tert-butylphosphine, 2-dicyclohexylphosphino-1,1'-biphenyl, 2-dicyclohexylphosphino-2', 6'-diisopropoxy-1,1'-biphenyl as palladium-catalyzed phosphine ligands , 2-Dicyclohexylphosphino-2', 4', 6'-triisopropyl-1,1'-biphenyl, 1- (2-dicyclohexylphosphinophenyl) naphthalene, or 9- (2-dicyclohexylphenyl) phenanthrene. When the coupling reaction (carbon-nitrogen bond forming reaction) between 4-bromoanisole and 9H-carbazole was examined, the yield of the target product, 9- (4-methoxyphenyl) -9H-carbazole, was not always satisfactory. It was not (Comparative Example 1-7).

Japanese Unexamined Patent Publication No. 10-139742 U.S. Patent Application Publication No. 2002/156295 International Publication No. WO2013 / 062043 Pamphlet International Publication No. WO2014 / 181878 Pamphlet

Chemical Reviews, Vol. 116, pp. 12564-12649, 2016

Since 9-aryl-9H-carbazole is an industrially useful compound, the development of a phosphine ligand that provides better yield and selectivity in the production of 9-aryl-9H-carbazole using a palladium catalyst has been developed. It is desired.

As a result of diligent studies in view of the above problems, the present inventors have found that a palladium catalyst having a phosphine compound represented by the following general formula (1) as a ligand is a catalyst for producing 9-aryl-9H-carbazole. It was found that the activity was particularly high, and the present invention was completed. That is, the present invention
(I) General formula (1)

(In the formula, Ar represents a pyrenyl group which may be substituted with a methyl group, an ethyl group, or a linear or branched alkyl group having 3 to 4 carbon atoms.)
Phosphine compound represented by;
(Ii) The 1-pyrenyl group or 4-pyrenyl group, wherein Ar may be substituted with a methyl group, an ethyl group, or a linear or branched alkyl group having 3 to 4 carbon atoms. Phosphine compounds;
(Iii) The phosphine compound according to (i), wherein Ar is a 1-pyrenyl group;
(Iv) In the method for producing 9-aryl-9H-carbazole by a catalytic N-aryllation reaction of 9H-carbazole, a palladium catalyst composed of a palladium compound and the phosphine compound according to (i) is used. Method for Producing -aryl-9H-Carbazole;
(V) The production method according to (iv), wherein the palladium compound is bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, palladium acetate or π-allylpalladium chloride dimer;
It is about.

In the present invention, by using the phosphine compound of the present invention as a ligand, a palladium catalyst showing high activity in the N-aryllation reaction of 9H-carbazole can be obtained, so that the economic efficiency of 9-aryl-9H-carbazole can be obtained. It is possible to provide a rich and efficient manufacturing method.

The present invention will be described in detail below.

Examples of the pyrenyl group represented by Ar include a 1-pyrenyl group, a 2-pyrenyl group, and a 4-pyrenyl group. A 1-pyrenyl group or a 4-pyrenyl group is preferable because it has high catalytic activity in the 9-aryllation reaction and the raw material can be easily obtained in the synthesis of the phosphine compound.

These pyrenyl groups are linear or branched with 3 to 4 carbon atoms exemplified by a methyl group, an ethyl group, or a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group. It may be substituted with an alkyl group. That is, the specifics of Ar are not particularly limited, but 1-pyrenyl group, 2-pyrenyl group, 4-pyrenyl group, 2-methylpyrene-1-yl group, 2-methylpyrene-4-yl group, 1-Methylpyrene-2-yl group, 1-methylpyrene-4-yl group, 4-methylpyrene-1-yl group, 4-methylpyrene-2-yl group, 2-ethylpyrene-1-yl group, 2-ethylpyrene-4 -Il group, 1-ethylpyrene-2-yl group, 1-ethylpyrene-4-yl group, 2-propylpyrene-1-yl group, 2-propylpyrene-4-yl group, 1-propylpyrene-2-yl group Group, 1-propylpyrene-4-yl group, 2-isopropylpyrene-1-yl group, 2-isopropylpyrene-4-yl group, 1-isopropylpyrene-2-yl group, 1-isopropylpyrene-4-yl group , 2-tert-butylpyrene-1-yl group, 2-tert-butylpyrene-4-yl group, 1-tert-butylpyrene-2-yl group, 1-tert-butylpyrene-4-yl group, 2,7-dimethyl Pyrene-1-yl group, 2,7-dimethylpyrene-4-yl group, 2,7-diethylpyrene-1-yl group, 2,7-diethylpyrene-4-yl group, 2,7-di-tert -Butylpyrene-1-yl group, 2,7-di-tert-butylpyrene-4-yl group and the like can be mentioned.

The group represented by Ar has high catalytic activity in the 9-aryllation reaction and is easily available as a raw material in the synthesis of a phosphine compound. Therefore, it is a methyl group, an ethyl group, or a linear or branched group having 3 to 4 carbon atoms. A 1-pyrenyl group which may be substituted with an alkyl group of, or a 4-pyrenyl group which may be substituted with a methyl group, an ethyl group, or a linear or branched alkyl group having 3 to 4 carbon atoms is preferable. 1-Pyrenyl group, 4-Pyrenyl group, 2,7-Dimethylpyrene-1-yl group, 2,7-Dimethylpyrene-4-yl group, or 2,7-di-tert-butylpyrene-4-yl group More preferred.

The phosphine compound (1) of the present invention is not particularly limited, and for example, compounds having the structures shown in the following (1-1) to (1-39) can be specifically exemplified. Me is a methyl group, Et is an ethyl group, Pr is a propyl group, iPr is an isopropyl group, and tBu is a tert-butyl group.

Among the phosphine compounds shown in (1-1) to (1-39), (1-1), in that the catalytic activity in the 9-aryllation reaction is high and the raw material in the synthesis of the phosphine compound is easily available. The phosphine compound shown in (1-3), (1-34), (1-35), (1-38), or (1-39) is preferable.

The phosphine compound (1) of the present invention is prepared according to, for example, the method described in Journal of the American Chemical Society, Vol. 126, pp. 13028-13032, 2004 or the method disclosed in Reference Example 1. It can be produced by reacting a nylphenyl metal reagent with di-tert-butylchlorophosphine. The phosphine compound of the present invention can also be produced by reacting di-tert-butylchlorophosphine with 1- (2-halophenyl) pyrene according to the method described in Advanced Synthesis & Catalysis, Vol. 350, pp. 652-656 (2008). Can be obtained.

The palladium catalyst of the present invention can be prepared by mixing the phosphine compound (1) and the palladium compound. Examples of the palladium compound include zero-valent palladium compounds such as bis (dibenzylideneacetone) palladium and tris (dibenzylideneacetone) dipalladium, palladium chloride, palladium bromide, palladium acetate, π-allyl palladium chloride dimer, and bis (acetylacetonato). ) Divalent palladium compounds such as palladium, dichlorobis (acetonitrile) palladium, and dichlorobis (benzonitrile) palladium can be exemplified. Bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, palladium acetate or π-allylpalladium chloride dimer are preferred because of their high catalytic activity in the 9-aryllation reaction.

The molar ratio of the phosphine compound (1) and the palladium compound used in the preparation of the palladium catalyst of the present invention is preferably in the range of phosphine compound (1): palladium compound = 1: 5 to 10: 1, and the phosphine compound (1). ): Palladium compound = more preferably in the range of 2: 5-5: 1.

The palladium catalyst of the present invention may be prepared in a solvent, and the solvent includes tetrahydrofuran, diethyl ether, cyclopentylmethyl ether, 1,4-dioxane, methyl-tert-butyl ether, 1,2-dimethoxyethane and the like. Examples thereof include ether solvents, aliphatic hydrocarbon solvents such as pentane, hexane and cyclohexane, and aromatic hydrocarbon solvents such as o-xylene, m-xylene, p-xylene, toluene and benzene. O-xylene, toluene, tetrahydrofuran or 1,4-dioxane is preferable because of its high catalytic activity in the 9-aryllation reaction.

The palladium catalyst of the present invention can be used in a coupling reaction or the like without being isolated after being prepared in a reaction system. Further, it may be isolated by a method familiar to those skilled in the art such as concentration and recrystallization.

The coupling catalyst of the present invention is effective as a catalyst for a coupling reaction that forms a carbon-nitrogen bond, such as the 9-aryllation reaction of 9H-carbazole and the buckwald-heartwig amination reaction according to the present invention. It can also be used as a catalyst for coupling reactions that form carbon-carbon bonds, such as Suzuki coupling, Kumada coupling, Negishi coupling, Stille coupling, Sonogashira coupling, and Heck reaction. ..

Next, the present invention will be described in more detail with reference to Examples, Reference Examples and Comparative Examples, but the present invention is not limited thereto.

Bruker ASCEND 400 (400 MHz) was used for ^{1 H-NMR measurement. 1 1} H-NMR was _{measured using deuterated chloroform (CDCl 3} ) as a measurement solvent and tetramethylsilane (TMS) as an internal standard substance. In addition, commercially available reagents were used. HPLC was measured using Waters 2690. Absorption at 254 nm was detected using ZORBAX Eclipse XDB-C18 as the column and a mixed solvent of methanol / tetrahydrofuran = 9/1 as the eluent. GC was measured using Shimadzu GC-14B.

Comparative Example-1

Under an argon atmosphere, 9H-carbazole 167 mg (1.0 mmol), 4-bromoanisole 187 mg (1.0 mmol), tris (dibenzylideneacetone) dipalladium 13.8 mg (15 μmol), sodium tert-butoxide 125 mg (1) in a reaction vessel. .3 mmol), 2 mL of toluene and 10.5 mg (30 μmol) of 2-dicyclohexylphosphino-1,1'-biphenyl were added. After sealing the reaction vessel, the mixture was stirred at 120 ° C. for 12 hours. After cooling the reaction vessel to room temperature, the formation of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 14%). The mixture was purified by silica gel column chromatography (hexane: ethyl acetate = 20: 0-19: 1) to give a white solid of 9- (4-methoxyphenyl) -9H-carbazole.

^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ (ppm): 8.14 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 8.9 Hz, 2H), 7.42-7 .24 (m, 6H), 7.11 (d, J = 8.9Hz, 2H), 3.91 (s, 3H).
Comparative Example-2
2-Dicyclohexylphosphino-1,1'-biphenyl All the same as Comparative Example-1 except that 12.0 mg (30 μmol) of 1- (2-dicyclohexylphosphinophenyl) naphthalene was used instead of 10.5 mg (30 μmol). The operation was carried out, and the production of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 26%).

Comparative Example-3
2-Dicyclohexylphosphino-1,1'-biphenyl All the same as Comparative Example-1 except that 13.5 mg (30 μmol) of 9- (2-dicyclohexylphosphinophenyl) phenanthrene was used instead of 10.5 mg (30 μmol). The operation was carried out, and the production of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 26%).

Comparative Example-4
The same operation as in Comparative Example-1 except that 8.7 mg (30 μmol) of tri-tert-butylphosphonium tetrafluoroborate was used instead of 10.5 mg (30 μmol) of 2-dicyclohexylphosphino-1,1'-biphenyl. , And the production of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 19%).

Comparative Example-5
2-Dicyclohexylphosphino-1,1'-biphenyl 10.5 mg (30 μmol) was replaced with 2-dicyclohexylphosphino-2', 6'-diisopropoxy-1,1'-biphenyl 14.0 mg (30 μmol). The same operation as in Comparative Example-1 was carried out except for the use, and the production of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 12%).

Comparative Example-6
2-Dicyclohexylphosphino-1,1'-biphenyl 10.5 mg (30 μmol) instead of 2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-1,1'-biphenyl 14.3 mg (30 μmol) ) Was used, and the same operation as in Comparative Example-1 was carried out, and the production of 9- (4-methoxyphenyl) -9H-carbazole was confirmed by gas chromatography (GC yield 44%).

Reference example-1

2. Under an argon atmosphere, 2.99 g (12.1 mmol) of 1-pyrenboroic acid, 3.76 g (13.3 mmol) of 2-bromoiodobenzene, 700 mg (0.61 mmol) of tetrakis (triphenylphosphine) palladium were placed in a reaction vessel. 15 mL (7.5 mmol) of 0M-sodium carbonate aqueous solution, 20 mL of toluene and 15 mL of ethanol were added. The reaction mixture was heated to 90 ° C. and stirred for 9 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent hexane) to give 1- (2-bromophenyl) pyrene (white solid, 3.20 g, 9.0 mmol, yield 75%).

^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ (ppm): 8.25-8.16 (m, 3H), 8.11 (brs, 2H), 8.03-7.99 (m, 2H), 7.89 (d, J = 7.8Hz, 1H), 7.80 (d, J = 7.8Hz, 1H), 7.70 (d, J = 9.2Hz, 1H), 7.48-7 .47 (m, 2H), 7.38-7.34 (m, 1H).
Example-1

Under an argon atmosphere, a solution of 1.43 g (4.0 mmol) of 1- (2-bromophenyl) pyrene in 25 mL of tetrahydrofuran is cooled to −78 ° C., and then 1.8 mL (4.8 mmol) of a 2.7 M butyllithium hexane solution is added. In addition, the mixture was stirred for 1 hour. At the same temperature, 396 mg (4.0 mmol) of cuprous iodide was added to this mixture, 0.91 mL (4.8 mmol) of di-tert-butylchlorophosphine was added dropwise, and the mixture was stirred at 70 ° C. for 14 hours. .. After cooling the reaction mixture to room temperature, 150 mL of ethyl acetate was added, and the mixture was washed successively with 40 mL of saturated aqueous ammonium chloride solution, 50 mL (3 times) of 12% aqueous ammonia solution, and 50 mL of saturated aqueous sodium chloride solution. After the organic layer was dried over sodium sulfate, the solid was filtered off and the solvent was removed from the filtrate under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent hexane / chloroform) to give 1- [2- (di-tert-butylphosphino) phenyl] pyrene (pale yellow solid, 510 mg, 1). .2 mmol, yield 30%).

^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ (ppm): 8.19-8.13 (m, 2H), 8.12-8.01 (m, 4H), 7.99-7.94 (m) , 1H), 7.92-7.86 (m, 2H), 7.72-7.67 (m, 1H), 7.51-7.44 (m, 2H), 7.42-7.35 (M, 1H) 1.21 (d, J = 11.6Hz, 9H), 1.04 (d, J = 11.6Hz, 9H).
_{^{31 P-NMR (CDCl 3,}} 161MHz) δ (ppm): 19.3.
Example-2
Under an argon atmosphere, 9H-carbazole 167 mg (1.0 mmol), 4-bromoanisole 187 mg (1.0 mmol), tris (dibenzylideneacetone) dipalladium 13.8 mg (15 μmol), sodium tert-butoxide 125 mg (1) in a reaction vessel. .3 mmol), 2 mL of toluene and 12.7 mg (30 μmol) of 1- [2- (di-tert-butylphosphino) phenyl] pyrene were added. After sealing the reaction vessel, the mixture was stirred at 120 ° C. for 12 hours. After cooling the reaction solution to room temperature, it was confirmed by gas chromatography that 9- (4-methoxyphenyl) -9H-carbazole was produced at 96% with respect to 9H-carbazole. 25 mL of water was added to the reaction solution, and the mixture was extracted 3 times with 20 mL of ethyl acetate. The ethyl acetate layer was washed with saturated brine (20 mL) and dehydrated with anhydrous sodium sulfate. After filtration, the solvent was distilled off and purified by silica gel column chromatography (hexane / ethyl acetate = 8/1) to obtain 9- (4-methoxyphenyl) -9H-carbazole as a white solid (259 mg, yield). 95%).

^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ (ppm): 8.14 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 8.9 Hz, 2H), 7.42-7 .24 (m, 6H), 7.11 (d, J = 8.9Hz, 2H), 3.91 (s, 3H).
Example-3

Under an argon atmosphere, (4-bromophenyl) phenylamine 248 mg (1.0 mmol), 9H-carbazole 176 mg (1.1 mmol), tris (dibenzylideneacetone) dipalladium 4.6 mg (5.0 μmol), 1 -[2- (Di-tert-butylphosphino) phenyl] pyrene 14.8 mg (35 μmol), sodium tert-butoxide 144 mg (1.5 mmol) and 3 mL of o-xylene were added and then heated to 140 ° C. to 15 Stirred for hours. After cooling the reaction solution to room temperature, 25 mL of water, 20 mL of ethyl acetate and 9- (p-tolyl) -9H-carbazole as an internal standard substance were added, and the mixture was stirred until the ethyl acetate layer became uniform. 0.2 mL of the ethyl acetate layer was collected, diluted with 4 mL of tetrahydrofuran, and analyzed by HPLC. As a result, 9- [4- (phenylamino) phenyl] -9H-carbazole was added to (4-bromophenyl) phenylamine. It was confirmed that 98% was generated. The ethyl acetate layer was washed with saturated saline (20 mL) and dehydrated with anhydrous sodium sulfate. After filtration, the solvent was distilled off and purified by silica gel column chromatography (hexane / ethyl acetate = 8/1) to obtain 9- [4- (phenylamino) phenyl] -9H-carbazole as a white solid (324 mg). , Yield 97%).

^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ (ppm): 8.17-8.12 (m, 2H), 7.44-7.31 (m, 8H), 7.30-7.23 (m) , 4H), 7.22-7.17 (m, 2H), 7.04-6.98 (m, 1H), 5.88 (brs, 1H).

Claims (5)

General formula (1)

(In the formula, Ar represents a pyrenyl group which may be substituted with a methyl group, an ethyl group, or a linear or branched alkyl group having 3 to 4 carbon atoms.)
A phosphine compound represented by. The phosphine compound according to claim 1, wherein Ar is a 1-pyrenyl group or a 4-pyrenyl group, which may be substituted with a methyl group, an ethyl group, or a linear or branched alkyl group having 3 to 4 carbon atoms. The phosphine compound according to claim 1, wherein Ar is a 1-pyrenyl group. In the method for producing 9-aryl-9H-carbazole by a catalytic 9-aryllation reaction of 9H-carbazole, a 9-aryl-containing a palladium catalyst composed of a palladium compound and the phosphine compound according to claim 1 is used. Method for producing 9H-carbazole. The production method according to claim 4, wherein the palladium compound is bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, palladium acetate or π-allylpalladium chloride dimer.