JP2019189569A - Phosphine compound, crosslinked composition, and manufacturing method of aromatic amine compound - Google Patents

Abstract

To provide a phosphine compound capable of constituting a transition metal complex excellent in reaction speed and selectivity as a catalyst.SOLUTION: There is provided a phosphine compound represented by the formula (I). In the formula Ar represents each independently an aryl group which may be substituted, Rrepresents each independently a linear, branched or cyclic alkyl group, Rrepresents each independently a linear, branched or cyclic alkyl group, alkoxy group or aryl group which may be substituted, or neighboring 2 Rare bound each other to form a ring, and n represents an integer of 0 to 4.SELECTED DRAWING: None

Description

  The present invention relates to a phosphine compound, a catalyst composition, and a method for producing an aromatic amine compound.

  Transition metal complexes containing transition metals such as palladium serve as catalysts for various reactions. Various phosphine compounds have been proposed as ligands for transition metal complexes. For example, Non-Patent Documents 1 and 2 describe phosphine compounds containing a pyrrole skeleton or a pyrazole skeleton, and an aromatic amine compound is obtained.

Chem. Eur. J. et al. 2004, 10, 2983. Tetrahedron Letters, 2006, 47, 1727.

  A transition metal complex having excellent reaction rate and selectivity is required as a catalyst in various reactions. An object of this invention is to provide the phosphine compound which can comprise the transition metal complex excellent in the reaction rate and selectivity as a catalyst.

The first embodiment is a phosphine compound represented by the following formula (I). In the formula, each Ar independently represents an optionally substituted aryl group. Each R ¹ independently represents a linear, branched or cyclic alkyl group. Each R ² independently represents a linear, branched or cyclic alkyl group, an alkoxy group or an aryl group which may be substituted, or two adjacent R ^{2 s} connected to each other to form a ring; It may be. n represents an integer of 0 to 4.

  The second aspect is a catalyst composition containing the phosphine compound and a transition metal.

  A 3rd aspect is a manufacturing method of an aromatic amine compound including making an aromatic halide and an amine react in presence of the said catalyst composition.

  A fourth aspect is a method for producing a biaryl compound, comprising reacting an aromatic halide and an aryl boron compound in the presence of the catalyst composition.

  ADVANTAGE OF THE INVENTION According to this invention, the phosphine compound which can comprise the transition metal complex excellent in the reaction rate and selectivity as a catalyst can be provided.

  Hereinafter, the present invention will be described in detail based on embodiments. However, the embodiment described below exemplifies a phosphine compound or the like for embodying the technical idea of the present invention, and the present invention is not limited to the phosphine compound or the like shown below. In this specification, Bn is a benzyl group, Me is a methyl group, iPr is an isopropyl group, Ph is a phenyl group, Cy is a cyclohexyl group, Ac is an acetyl group, and dba is dibenzylideneacetone.

Phosphine Compound The phosphine compound has a structure represented by the following formula (I). Thereby, when forming a complex with a transition metal, it is possible to achieve an excellent reaction rate and selectivity in a synthesis reaction of an aromatic amine compound, a biaryl compound or the like. Furthermore, the target compound can be obtained with an excellent yield for various substrates.

In the formula, each Ar independently represents an optionally substituted aryl group. Each R ¹ independently represents a linear, branched or cyclic alkyl group. Each R ² independently represents a linear, branched or cyclic alkyl group, an alkoxy group or an aryl group which may be substituted, or two adjacent R ^{2 s} connected to each other to form a ring; It may be. n represents an integer of 0 to 4.

  Ar is, for example, a phenyl group or a phenyl group substituted with a substituent selected from the group consisting of an alkyl group and an alkoxy group. Examples of the alkyl group that can be substituted on the phenyl group include a linear or branched alkyl group having 1 to 10 carbon atoms and a cyclic alkyl group having 3 to 10 carbon atoms. The alkyl group preferably has 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms. Specific examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and a 2-ethylhexyl group. , Cyclopropyl group, cyclopentyl group, cyclohexyl group, adamantyl group and the like.

  Examples of the alkoxy group that can be substituted on the phenyl group include linear or branched alkylalkoxy groups having 1 to 10 carbon atoms and cyclic alkylalkoxy groups having 3 to 10 carbon atoms. The carbon number of the alkyl moiety in the alkylalkoxy group is preferably 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a sec-butoxy group, a pentyloxy group, a hexyloxy group, a heptyloxy group, an octyl group, and a 2-ethylhexyloxy group. Is mentioned.

Each R ¹ independently represents a linear, branched or cyclic alkyl group. Examples of the alkyl group for R ¹ include a linear or branched alkyl group having 1 to 10 carbon atoms and a cyclic alkyl group having 3 to 10 carbon atoms. The alkyl group for R ¹ is preferably a linear or branched alkyl group having 3 to 10 carbon atoms, or a cyclic alkyl group having 3 to 10 carbon atoms, more preferably a straight chain having 4 to 8 carbon atoms. A chain or branched alkyl group, or a cyclic alkyl group having 3 to 10 carbon atoms. Specific examples of the alkyl group for R ¹ include a tert-butyl group, a 2-ethylhexyl group, a cyclopentyl group, a cyclohexyl group, and an adamantyl group.

R ² each independently represents a linear, branched or cyclic alkyl group, an alkoxy group, or an optionally substituted aryl group. Two adjacent R ² may be connected to each other to form a ring. Preferred embodiments of the alkyl group and alkoxy group in R ² are the same as those of the alkyl group and alkoxy group that can be substituted for the above-described phenyl group. A preferred embodiment of the aryl group in R ² is the same as Ar. Two R ² adjacent the bond to each other to form a ring, examples of the ring formed, for example 8-membered aliphatic ring from 5-, aromatic rings such as the 6-membered.

  Specific examples of the phosphine compound represented by the formula (I) include the following compounds.

  The phosphine compound represented by the formula (I) can be combined with a transition metal compound to combine various aromatic amine compounds, biaryl compounds, and substituted styrene derivatives in a carbon-nitrogen bond reaction. It is useful as a catalyst for carbon-carbon bond reaction.

Method for Producing Phosphine Compound The phosphine compound represented by the formula (I) is, for example, Angew. Chem. Int. Ed. , 2011, 50, 3294. Etc., and can be produced by the following synthesis route.

Catalyst composition The catalyst composition contains at least one phosphine compound and a transition metal. The catalyst composition can be obtained, for example, by mixing a phosphine compound and a transition metal compound in an appropriate solvent. Examples of the transition metal compound include tetravalent palladium compounds such as sodium hexachloropalladium (IV) tetrahydrate and potassium hexachloropalladium (IV); palladium (II) chloride, palladium (II) bromide, palladium acetate ( II), palladium (II) acetylacetonate, dichlorobis (benzonitrile) palladium (II), dichlorobis (acetonitrile) palladium (II), dichlorobis (triphenylphosphine) palladium (II), dichlorotetraammine palladium (II), dichloro ( Divalent palladium compounds such as cycloocta-1,5-diene) palladium (II), palladium (II) trifluoroacetate; bis (dibenzylideneacetone) palladium (0), tris (dibenzylideneacetone) Dipalladium (0), tris (dibenzylideneacetone) dipalladium (0) chloroform complex, tetrakis (triphenylphosphine) palladium (0) a palladium compound such as zero-valent palladium compound and the like. Also, nickel acetate, nickel chloride, (N, N, N ′, N′-tetramethylethylenediamine) nickel dichloride, [1,1′-bis (diphenylphosphino) ferrocene] nickel dichloride, [1,3-bis ( And nickel compounds such as [diphenylphosphino) propane] nickel dichloride, [1,4-bis (diphenylphosphino) butane] nickel dichloride, bis (cyclopentadienyl) nickel. Of these, palladium compounds are preferred from the viewpoint of catalytic activity and selectivity.

  The ratio of the transition metal compound in the catalyst composition to the phosphine compound as the ligand is, for example, 1 mol or more and 5 mol or less, preferably 1.2 mol, with respect to 1 mol of the transition metal contained in the transition metal compound. More than 3 moles.

  The catalyst composition can catalyze various reactions. For example, synthesis of aromatic amine compounds from aromatic halides and amines, synthesis of biaryl compounds by coupling aromatic halides with aromatic boron compounds, etc., substituted styrene derivatives by reaction of aromatic halides with olefins Reactions such as synthesis of In particular, the catalyst composition can be used for synthesis of aromatic amine compounds, synthesis of biaryl compounds, and the like. In particular, in the synthesis of an aromatic amine compound, a secondary amine compound can be selectively synthesized when a primary amine compound is used as a substrate.

  The conditions for the catalytic reaction can be appropriately selected from the commonly used conditions. For example, the amount of the catalyst composition used is 0.5 mol% or more and 10 mol% or less, preferably 0.5 mol% or more and 2 mol% or less as a transition metal compound with respect to a substrate such as an aromatic halide. It is. Examples of the reaction solvent include ether solvents such as tetrahydrofuran, dimethoxyethane, 1,4-dioxane and cyclopentylmethyl ether, alcohol solvents such as t-butanol, aromatic solvents such as toluene and xylene, dimethyl sulfoxide, dimethylformamide and the like. An aprotic polar solvent or the like can be used. As reaction temperature, it can be set as 20 to 160 degreeC, for example. The reaction time is, for example, 10 minutes to 48 hours, preferably 60 minutes to 3 hours. The reaction atmosphere is usually performed in an inert gas atmosphere such as nitrogen or argon.

  When the catalyst composition is used for an aromatic amine compound synthesis reaction, a biaryl compound synthesis reaction, or the like, a base is used for the reaction. As the base, alkali metal alkoxides such as sodium t-butoxide and potassium t-butoxide, alkali metal carbonates such as cesium carbonate and potassium carbonate, alkali metal phosphates such as potassium phosphate, and the like are used. The usage-amount of a base is 1.2 equivalent or more and 3 equivalent or less with respect to substrates, such as an aromatic halide.

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. In the examples, nuclear magnetic resonance spectra (NMR) were measured using JNM-ECZ400S (manufactured by JEOL RESONANCE). ¹ H-NMR showed a chemical shift with tetramethylsilane (TMS) as an internal standard, ¹³ C-NMR with CDCl ₃ , and ³¹ P-NMR with H ₃ PO ₄ as an internal standard. The high resolution mass spectrometry spectrum (HRMS) was measured by electrospray ionization (ESI) using Exact Plus (manufactured by Thermo Scientific).

(Example 1)
Synthesis of phosphine compound L1

  Under an argon atmosphere, propargyl bromide 1 (2.34 g, 12 mmol, 1.2 equiv) was added dropwise at 0 ° C. to a reaction vessel to which magnesium (438 mg, 18 mmol, 1.5 equiv) and ether (15 mL) were added. After stirring at room temperature for 1 hour, the reaction solution was ice-cooled, and acetophenone (1.17 mL, 10 mmol) was added dropwise. After removing the ice bath and reacting at room temperature for 2 hours, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted 3 times with ethyl acetate. The collected organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. By purifying the residue by column chromatography, a mixture (2.1: 1) of α-allenol 2 and homopropargyl alcohol 3 was quantitatively obtained as a yellow liquid.

Under an argon atmosphere, the reaction vessel was charged with imine (544 mg, 3 mmol), copper chloride (14.9 mg, 0.15 mmol, 5 mol%), carbene hydrochloride IPr.HCl (63.8 mg, 0.15 mmol, 5 mol%), NaOtBu ( 43.2 mg, 0.45 mmol, 15 mol%) was added. Further, a mixture of α-allenol 2 and homopropargyl alcohol 3 (992 mg, 4.2 mmol, 1.4 equiv, 2/3 = 2.1: 1) and toluene (9 mL) were added, followed by stirring at 80 ° C. for 2 hours. . 1M hydrochloric acid solution was added, and the mixture was extracted 3 times with ethyl acetate. The collected organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography to obtain α-aminoallene 4 as a white solid in a yield of 75%.
¹ H NMR (CDCl ₃ ) δ 4.25 (br s, 1H), 5.04-5.12 (m, 2H), 5.43 (s, 1H), 6.60 (d, J = 7.5 Hz, 2H), 6.70 (d, J = 7.5 Hz, 1H), 7.11-7.47 (m, 12H);
¹³ C NMR (CDCl ₃ ) δ 57.8, 80.9, 108.6, 113.4, 117.6, 126.6, 127.1, 127.5, 127.6, 128.52, 128.54, 129.1, 134.7, 141.3, 147.0, 209.2;
HRMS (ESI) calcd.for C ₂₂ H ₁₉ N ([M + H] ⁺ ): 298.1590, found: 298.1584.

In an argon atmosphere, α-aminoarene 4 (149 mg, 0.5 mmol) and 1-bromo were added to a solution of Pd (PPh ₃ ) ₂ Cl ₂ (17.5 mg, 0.025 mmol, 5 mol%) in diisopropylamine (1.5 mL). 2-Iodobenzene (212 mg, 0.75 mmol, 1.5 equiv) was added, and the mixture was stirred at 90 ° C. for 1 hr. The crude product was dissolved in toluene (3 mL), and then oxidized by adding 2,3-dichloro-5,6-dicyano-p-benzoquinone (136 mg, 0.6 mmol, 1.2 equiv). The crude product was passed through a short column of Florisil and purified by silica gel column chromatography to obtain tetraarylpyrrole 5 as a yellow solid in a yield of 85%.
¹ H NMR (CDCl ₃ ) δ 6.91-6.95 (m, 2H), 6.99-7.02 (m, 2H), 7.05-7.08 (m, 4H), 7.11-7.18 (m, 8H), 7.23-7.31 (m, 3H), 7.59 (d, J = 7.5 Hz, 1H);
¹³ C NMR (CDCl ₃ ) δ 122.8, 123.0, 123.5, 124.0, 124.5, 125.4, 125.9, 126.5, 126.6, 126.7, 127.6, 127.8, 128.8, 130.2, 130.5, 131.1, 131.9, 132.8, 133.0, 135.3, 136.4, 140.1;
HRMS (ESI) calcd.for C ₂₈ H ₂₀ BrN ([M + H] ⁺ ): 450.0852, found: 450.0851.

Under an argon atmosphere, nBuLi (1.62 M in hexane, 0.97 mL, 1.575 mmol, 1.05 equiv) was added to tetraarylpyrrole 5 (676 mg, 1.5 mmol) at −78 ° C. and stirred for 1 hour. Thereafter, chlorodicyclohexylphosphine (0.35 mL, 1.575 mmol, 1.05 equiv) was added at −78 ° C., and the mixture was stirred for 12 hours while naturally warming to room temperature. Water was added, and the mixture was extracted three times with diethyl ether. The collected organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography to obtain the target phosphine compound L1 in a yield of 66% as a white solid.
¹ H NMR (CDCl ₃ ) δ 0.65-0.74 (m, 2H), 1.05-1.35 (m, 10H), 1.57-1.61 (m, 4H), 1.70-1.78 (m, 6H), 6.89-6.91 (m, 2H), 6.94 (s, 1H), 6.97-7.01 (m, 5H), 7.08-7.12 (m, 5H), 7.19-7.31 (m, 6H), 7.43-7.45 (m, 1H);
³¹ P NMR (CDCl ₃ ) δ -10.1;
HRMS (ESI) calcd.for C ₄₀ H ₄₂ NP ([M + H] ⁺ ): 568.3128, found: 568.3114.

The phosphine compounds L2 to L6 were obtained by the same synthesis method as described above. Identification data is shown below.
L2: ¹ H NMR (CDCl ₃ ) δ 0.66-0.75 (m, 2H), 1.02-1.36 (m, 10H), 1.55-1.61 (m, 4H), 1.70-1.78 (m, 6H), 3.79 (s, 3H), 6.78-6.82 (m, 2H), 6.88-6.91 (m, 3H), 6.95-7.10 (m, 10H), 7.21-7.24 (m, 2H), 7.27-7.30 (m, 1H), 7.42- 7.45 (m, 1H);
³¹ P NMR (CDCl ₃ ) δ -10.1;
HRMS (ESI) calcd.for C ₄₁ H ₄₄ NOP ([M + H] ⁺ ): 598.3233, found: 598.3215.

L3: ¹ H NMR (CDCl ₃ ) δ 0.65-0.74 (m, 2H), 1.05-1.36 (m, 10H), 1.55-1.60 (m, 4H), 1.69-1.78 (m, 6H), 3.74 (s, 3H), 6.64-6.67 (m, 2H), 6.89-7.01 (m, 8H), 7.10-7.12 (m, 2H), 7.20-7.30 (m, 6H), 7.42-7.45 (m, 1H);
³¹ P NMR (CDCl ₃ ) δ -10.1;
HRMS (ESI) calcd.for C ₄₁ H ₄₄ NOP ([M + H] ⁺ ): 598.3233, found: 598.3220.

L4: ¹ H NMR (CDCl ₃ ) δ 0.66-0.75 (m, 2H), 1.02-1.13 (m, 6H), 1.18-1.27 (m, 2H), 1.33-1.36 (m, 2H), 1.54-1.61 ( m, 4H), 1.70-1.78 (m, 6H), 3.67 (s, 3H), 6.55 (d, J = 9.0 Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H), 6.92 (s, 1H ), 6.99-7.01 (m, 2H), 7.09-7.11 (m, 5H), 7.18-7.31 (m, 6H), 7.42-7.44 (m, 1H);
³¹ P NMR (CDCl ₃ ) δ -10.0;
HRMS (ESI) calcd.for C ₄₁ H ₄₄ NOP ([M + H] ⁺ ): 598.3233, found: 598.3222.

L5: ¹ H NMR (CDCl ₃ ) δ 0.14-0.66 (m, 2H), 1.00-1.19 (m, 10H), 1.43-1.58 (m, 4H), 1.65-1.72 (m, 4H), 1.92-2.04 ( m, 2H), 2.43 (s, 3H), 6.74 (s, 1H), 6.95-7.30 (m, 18H);
³¹ P NMR (CDCl ₃ ) δ 1.4;
HRMS (ESI) calcd.for C ₄₁ H ₄₄ NP ([M + H] ⁺ ): 582.3284, found: 582.3277.

L6: ¹ H NMR (CDCl ₃ ) δ 0.29-0.47 (m, 2H), 1.04-1.12 (m, 8H), 1.17-1.30 (m, 2H), 1.44-1.59 (m, 4H), 1.65-1.75 ( m, 4H), 2.13-2.21 (m, 2H), 3.78 (s, 3H), 6.72-6.74 (m, 1H), 6.79 (s, 1H), 6.95-7.02 (m, 8H), 7.08-7.13 ( m, 5H), 7.18-7.29 (m, 4H);
³¹ P NMR (CDCl ₃ ) δ -0.9;
HRMS (ESI) calcd.for C ₄₁ H ₄₄ NOP ([M + H] ⁺ ): 598.3233, found: 598.3227.

(Example 2-1)
Coupling reaction between aryl chloride and amine: Synthesis of aromatic amine compounds

In an argon atmosphere, Pd (dba) ₂ (2.9 mg, 0.005 mmol, 0.5 mol%), phosphine compound L1 (3.4 mg, 0.006 mmol, 0.6 mol%), 1,4-dioxane was added to the reaction vessel. (0.9 mL) was added and heated to reflux for 2 minutes. The solution was diluted with 4-chlorotoluene (127 mg, 1 mmol), benzylamine (126 mg, 1.2 mmol, 1.2 equiv), NaOtBu (144 mg, 1.5 mmol, 1.5 equiv), H ₂ O (14.4 μL, 0 0.8 mmol, 0.8 equiv), 1,4-dioxane (2.1 mL) was added to the reaction vessel sealed. After stirring for 10 minutes at room temperature, the mixture was stirred for 1 hour under reflux. The reaction solution was passed through a short column of sodium sulfate and silica gel and then concentrated. The residue was purified by column chromatography to obtain a coupling product with a yield of 99%. The yield of diarylate was less than 1%.

(Examples 2-2 to 2-11)
The reaction was carried out in the same manner as in Example 2-1, except that the amine compounds shown in the following table were used instead of benzylamine, and the reaction time was changed as shown in the following table. A group amine compound was obtained. The results are shown in the table below.

(Examples 3-1 to 3-3)
The reaction was conducted in the same manner as in Example 2-1, except that the aromatic halide shown in the following table was used instead of 4-chlorotoluene, and the reaction time was changed as shown in the following table. The desired aromatic amine compound was obtained. The results are shown in the table below.

(Examples 4-1 to 4-4)
The reaction was carried out in the same manner as in Example 2-1 except that the phosphine compounds shown in the following table were used in place of the phosphine compound L1, and the desired aromatic amine compound was obtained. The results are shown in the table below.

(Examples 5-1 to 5-6)
2 equivalents of cesium carbonate was used instead of sodium t-butoxide as a base, t-butanol was used instead of 1,4-dioxane as a solvent, and aromatic halogens shown in the following table instead of 4-chlorotoluene The reaction was conducted in the same manner as in Example 2-1, except that the compound was used, the amine compound shown in the table below was used instead of benzylamine, and the reaction time was changed as shown in the table below. However, the desired aromatic amine compound was obtained. The results are shown in the table below.

(Example 6)
Coupling reaction of aryl chloride and aryl boron compounds: Synthesis of biaryl compounds

Under an argon atmosphere, Pd (dba) ₂ (2.9 mg, 0.005 mmol, 0.5 mol%), phosphine compound L1 (3.4 mg, 0.006 mmol, 0.6 mol%), potassium phosphate (637 mg) , 3 mmol), 4-chlorotoluene (127 mg, 1 mmol), phenylboronic acid (183 mg, 1.5 mmol) and toluene (3 mL) were added, and the mixture was stirred under reflux for 12 hours. The reaction solution was passed through a short column of sodium sulfate and silica gel and then concentrated. The residue was purified by column chromatography to obtain a coupling product in a yield of 86%.

  From the above, by using the phosphine compound of the present invention as a ligand, it was possible to synthesize an aromatic amine compound with high yield in a short time. In addition, monoaryls could be selectively synthesized in the synthesis of aromatic amine compounds. Furthermore, even when a weak base such as cesium carbonate was used in place of the strong base, the aromatic amine compound could be synthesized with high yield. Furthermore, the biaryl compound was obtained in good yield in the coupling reaction between the aromatic halide and the aromatic boron compound.

Claims (8)

A phosphine compound represented by the following formula (I).
(In the formula, each Ar independently represents an optionally substituted aryl group. Each R ¹ independently represents a linear, branched or cyclic alkyl group. Each R ² independently represents It represents a linear, branched or cyclic alkyl group, an alkoxy group or an optionally substituted aryl group, or two adjacent R ² groups may be linked to each other to form a ring, where n is 0. Represents an integer from 4 to 4.)   The phosphine compound according to claim 1, wherein Ar represents a phenyl group or a phenyl group substituted with a substituent selected from the group consisting of an alkyl group and an alkoxy group. The phosphine compound according to claim 1 or 2, wherein R ¹ represents a cyclohexyl group, a tert-butyl group, or a 1-adamantyl group.   A catalyst composition comprising the phosphine compound according to any one of claims 1 to 3 and a transition metal.   The catalyst composition according to claim 4, wherein the transition metal comprises palladium.   The catalyst composition according to claim 4 or 5, which is used for aromatic amine synthesis or biaryl compound synthesis.   A process for producing an aromatic amine compound, comprising reacting an aromatic halide with an amine in the presence of the catalyst composition according to any one of claims 4 to 6.   A method for producing a biaryl compound, comprising reacting an aromatic halide and an aryl boron compound in the presence of the catalyst composition according to any one of claims 4 to 6.