Method for producing 2-naphthalene derivative

Abstract

To provide a production method that enables the selective acquisition of a high-purity 2-naphthalene derivative while controlling impurities that are difficult to be removed.SOLUTION: A method for producing a 2-naphthalene derivative includes reacting a sulfonyloxy compound with an organometallic halide in the presence of a nickel compound within a solvent. A residence time of a reaction solution in the reaction is within 1 minute.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention provides a method for producing a 2-naphthalene derivative with higher purity and at lower cost than conventional methods. [Background technology]

[0002] 2-Naphthalene derivatives are widely used as intermediates in the production of organic electroluminescent (hereinafter referred to as organic EL) materials and are extremely useful compounds.

[0003] In recent years, particularly in the display field, the development of flexible displays that can be folded or rolled has progressed in earnest. Polymer films that replace glass are needed to make displays flexible, and the use of polymer films having naphthalene rings has been proposed. Polymer films without naphthalene rings may be scratched, dented, or even cracked when processed into displays and used, but polymer films with naphthalene rings are excellent in optical properties, heat resistance, bending resistance, and handling, and are therefore expected to prevent breakage of flexible displays due to bending or impact (see, for example, Patent Document 1).

[0004] A method using the Suzuki-Miyaura coupling reaction is generally known as a method for synthesizing 2-naphthalene derivatives (see, for example, Non-Patent Document 1). However, this method has problems in that the raw materials, 2-bromonaphthalene and 2-naphthaleneboronic acid, are very expensive, have unstable quality, and are difficult to procure steadily. In addition, this method produces a large amount of binaphthyl compounds as a by-product, which is very difficult to purify and remove, so controlling the side reactions remains an issue. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2021-194816 [Non-patent literature]

[0006] [Non-Patent Document 1] Tetrahedron Letters, 2004, Vol. 45, Pages 6527-6530 Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to solve the above problems, to control the by-production of impurities which are difficult to remove, and to provide a method for selectively producing a 2-naphthalene derivative. [Means for solving the problem]

[0008] As a result of intensive research aimed at solving the above problems, the present inventors have discovered a production method in which a sulfonium compound, a nickel compound, and an organometallic halide are rapidly diffused in a liquid to react with each other, and the residence time of the reaction liquid is controlled to an extremely short time, thereby controlling impurities that are difficult to remove and selectively obtaining a high-purity 2-naphthalene derivative, and have completed the present invention. That is, the present invention is as follows.

[0009] General formula (1): [ka] (In the formula, R 1 represents a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C2-6 alkenyl group, a nitro group, a cyano group, an aldehyde group, an amino group, a hydroxyl group, a thiol group, a sulfo group, a sulfonamide group, or a carboxyl group or an ester group thereof, and A represents a phenyl group which may be substituted by 1 or 2 substituents selected from the group consisting of a C1-6 alkyl group, a mono- or di-C1-6 alkylamino group, a C1-6 alkyl group, and a nitro group, or a halo-C1-3 alkyl group. In the presence of a nickel compound, a sulfonyloxy compound represented by the general formula (2): [ka] (In the formula, Ar is a C6-20 aryl group, M is MgX or MgXLiCl, and X represents a chlorine atom, a bromine atom, or an iodine atom.) In a solvent, the compound is reacted with an organometallic halide represented by the general formula (3): [ka] (In the formula, R 1 and Ar have the same meanings as defined above), characterized in that the residence time of the reaction solution in the reaction is 1 minute or less. Effect of the Invention

[0010] According to the production method of the present invention, it is possible to selectively and efficiently produce 2-naphthyl derivatives, which are extremely useful organic synthesis intermediates in the field of organic electroluminescence. In addition, since the production method of the present invention can suppress the by-production of impurities that are difficult to remove, it is expected to be industrially useful. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described in detail below with reference to the preferred embodiments thereof. First, the terms used in the present specification and claims will be described. Each term has the following meaning unless otherwise specified.

[0012] In the present invention, the "C1-6 alkyl group", alone or in combination with other terms, means a monovalent group of a linear or branched aliphatic saturated hydrocarbon having 1 to 6 carbon atoms, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, and isomers thereof.

[0013] In the present invention, the "C1-6 alkoxy group", alone or in combination with other terms, means a group RO- (wherein R is the above-mentioned C1-6 alkyl group), and examples thereof include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, a hexyloxy group, and isomers thereof.

[0014] In the present invention, the term "C2-6 alkenyl group", alone or in combination with other terms, means a monovalent group of a linear or branched aliphatic unsaturated hydrocarbon containing at least one double bond and having 2 to 6 carbon atoms, and examples thereof include a vinyl group, an allyl group, an isopropenyl group, a 1-butenyl group, a 2-butenyl group, a 1,3-butadienyl group, a 2-pentenyl group, and isomers thereof.

[0015] In the present invention, the term "carboxyl group or ester group thereof" refers to a -COOR' group (wherein R' is a hydrogen atom, the above-mentioned C1 to 6 alkyl group, a C6 to 20 aryl group, or a C7 to 26 aralkyl group).

[0016] In the present invention, the term "mono- or di-C1-6 alkylamino group" refers to a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group. The term "mono-C1-6 alkylamino group" refers to a group in which one of the above-mentioned C1-6 alkyl groups is bonded to an amino group. Examples of the mono-C1-6 alkylamino group include a methylamino group, an ethylamino group, an n-propylamino group, an isopropylamino group, an n-butylamino group, an n-pentylamino group, and an n-hexylamino group. The term "di-C1-6 alkylamino group" refers to a group in which two of the above-mentioned "C1-6 alkyl groups" are bonded to an amino group. The two alkyl groups may be the same or different. Examples of the di-C1-6 alkylamino group include a dimethylamino group, a diethylamino group, an N,N-diisopropylamino group, an N-methyl-N-ethylamino group, an N-isopropyl-N-methylamino group, an Nn-butyl-N-methylamino group, an N-tert-butyl-N-methylamino group, an N-methyl-Nn-pentylamino group, an Nn-hexyl-N-methylamino group, and an N-isopropyl-N-ethylamino group.

[0017] In the present invention, a "halo C1-3 alkyl group" means the above-mentioned C1-3 alkyl group substituted with one or more halogen atoms, and examples thereof include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a dichloromethyl group, and a trichloromethyl group.

[0018] In the present invention, the term "C6-20 aryl group" refers to a monovalent group of a monocyclic or polycyclic hydrocarbon compound having 6 to 20 carbon atoms, either alone or in combination with other terms, containing at least one aromatic ring. For example, an example of the former is phenyl, and an example of the latter is a monovalent group of a ring-assembled aromatic hydrocarbon compound such as biphenylyl and terphenylyl, and a monovalent group of a condensed polycyclic aromatic compound such as naphthyl, tetrahydronaphthyl, anthryl, pyrenyl, indenyl, fluorenyl, acenaphthylenyl, phenanthryl, and phenalenyl. These may be substituted with one or more arbitrary substituents that do not participate in the reaction. Examples of such substituents include C1-6 alkyl groups, C1-6 alkoxy groups, C3-6 cycloalkyl groups, C6-20 aryl groups, and C2-20 heteroaryl groups.

[0019] In the present invention, the term "C7-26 aralkyl group" refers to a C1-6 alkyl group substituted with the above-mentioned C6-20 aryl group. "C6-20 aryl" and "C1-6 alkyl" are as defined above. Examples of the C7-26 aralkyl group include benzyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, and phenylhexyl.

[0020] In the present invention, a "C3-6 cycloalkyl group" means a monovalent group of a cyclic aliphatic saturated hydrocarbon having 3 to 6 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

[0021] In the present invention, the term "C2-20 heteroaryl group" refers to a monovalent group of a monocyclic or condensed polycyclic heterocyclic compound having 2 to 20 carbon atoms containing at least one aromatic ring, and examples thereof include furyl, benzofuranyl, dibenzofuranyl, thienyl, benzothienyl, dibenzothienyl, pyrrolyl, indolyl, carbazolyl, imidazolyl, benzimidazolyl, pyrazolyl, oxazolyl, benzoxazolyl, thiazolyl, benzothiazolyl, furazanyl, pyridyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, azepinyl, quinolyl, tetrahydroisoquinolyl, indolizinyl, cinnolinyl, purinyl, carbonylyl, phenanthrolinyl, and imidazopyrimidinyl. These may be substituted with one or more arbitrary substituents that are not involved in the reaction. Examples of such a substituent include a C1-6 alkyl group, a C1-6 alkoxy group, a C3-6 cycloalkyl group, a C6-20 aryl group, and a C2-20 heteroaryl group.

[0022] Next, the production method of the present invention will be described in detail. The present invention relates to a compound represented by general formula (1): [ka] (In the formula, R 1 represents a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C2-6 alkenyl group, a nitro group, a cyano group, an aldehyde group, an amino group, a hydroxyl group, a thiol group, a sulfo group, a sulfonamide group, a carboxyl group or an ester group thereof, and A represents a phenyl group which may be substituted by 1 or 2 substituents selected from the group consisting of a C1-6 alkyl group, a mono- or di-C1-6 alkylamino group, a C1-6 alkyl group and a nitro group, or a halo-C1-3 alkyl group. In the presence of a nickel compound, a sulfonyloxy compound represented by the general formula (2): [ka] (In the formula, Ar is a C6-20 aryl group, M is MgX or MgXLiCl, and X represents a chlorine atom, a bromine atom, or an iodine atom.) In a solvent, the reaction is carried out with an organometallic halide represented by the general formula (3): [ka] (In the formula, R 1 and Ar have the same meanings as defined above), characterized in that the residence time of the reaction solution in the reaction is 1 minute or less.

[0023] In one embodiment of the invention, the method comprises the steps of: (1) preparing a solution containing the sulfonyloxy compound represented by the general formula (1) and a nickel compound; (2) preparing a solution containing the organometallic halide represented by the general formula (2); and (3) A step of mixing the solution from step (1) and the solution from step (2) and reacting them. The present invention is characterized by comprising:

[0024] In the compound of the general formula (1), R 1 R is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C2-6 alkenyl group, a nitro group, a cyano group, an aldehyde group, an amino group, a hydroxyl group, a thiol group, a sulfo group, a sulfonamide group, a carboxyl group, or an ester group thereof. 1 is preferably a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a carboxyl group or an ester group thereof, and more preferably a hydrogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a carboxyl group or an ester group thereof.

[0025] In the compound of the general formula (1), A is a phenyl group which may be substituted with 1 or 2 substituents selected from the group consisting of a C1-6 alkyl group, a mono- or di-C1-6 alkylamino group, a C1-6 alkyl group, and a nitro group, or a halo-C1-3 alkyl group. A is preferably a phenyl group which may be substituted with 1 or 2 substituents selected from the group consisting of an alkyl group having 1 to 3 carbon atoms, a mono- or di-C1-3 alkylamino group, a C1-3 alkyl group, and a nitro group, or a halo-C1-3 alkyl group.

[0026] The nickel compound used in the present invention is not particularly limited, but can be appropriately selected according to the target compound. From the viewpoint of improving reactivity and easy availability, nickel compounds containing polydentate phosphine ligands are preferred, and nickel (II) complexes with bidentate phosphine ligands are more preferred. For example, 1,2-bis(diphenylphosphino)ethane nickel(II) chloride, 1,3-bis(diphenylphosphino)propane nickel(II) chloride, 1,4-bis(diphenylphosphino)butane nickel(II) chloride, 1,5-bis(diphenylphosphino)pentane nickel(II) chloride, 1,3-bis(dicyclohexylphosphino)propane nickel(II) chloride, 1,4-bis(dicyclohexylphosphino)butane nickel(II) chloride, 1,2-bis(diphenylphosphino)ethane nickel(II) bromide, 1,3-bis(diphenylphosphino)propane nickel(II) bromide, 1,4-bis(diphenylphosphino)butane nickel(II) bromide , 1,5-bis(diphenylphosphino)pentanenickel(II) bromide, 1,3-bis(dicyclohexylphosphino)propanenickel(II) bromide, 1,4-bis(dicyclohexylphosphino)butanenickel(II) bromide, etc. However, it is preferable to exclude iron-containing [1,1'-bis(diphenylphosphino)ferrocene]dichloronickel(II) etc. from the viewpoint of yield and reaction control.

[0027] In the present invention, the amount of the nickel compound used is not particularly limited, but is usually in the range of 0.01 to 10 mol % relative to the compound represented by general formula (1), and from the viewpoint of reaction, the range of 0.1 to 6.0 mol % is preferable.

[0028] In the present invention, the organometallic halide represented by the general formula (2) refers to so-called Grignard reagents and Turbo Grignard reagents, and can be obtained according to the same preparation method as that of known Grignard reagents, specifically, by reacting magnesium with the corresponding halogenoaromatic compound (Ar-X: where Ar and X are as defined above). In the general formula (2), Ar is a C6-20 aryl group, M is MgX or MgXLiCl, and X is a chlorine atom, a bromine atom, or an iodine atom. Ar is, for example, a phenyl group or a naphthyl group which may be substituted with at least one substituent selected from the group consisting of a C1-6 alkyl group and a C1-6 alkoxy group, preferably a phenyl group, a phenyl group substituted with one or more C1-6 alkyl groups or C1-6 alkoxy groups, a naphthyl group, or a naphthyl group substituted with one or more C1-6 alkyl groups or C1-6 alkoxy groups, more preferably a phenyl group. X is selected from a chlorine atom, a bromine atom, and an iodine atom, preferably a chlorine atom, a bromine atom, more preferably a bromine atom.

[0029] The amount of the organometallic halide used is not particularly limited, but can be appropriately selected depending on the mixing method. For example, it is usually in the range of 0.5 to 3.0 mol, preferably 0.9 to 1.5 mol, per 1 mol of the compound represented by the general formula (1).

[0030] The solvent used in the present invention is not particularly limited as long as it is not involved in the reaction. For example, hydrocarbon solvents such as hexane and heptane; aromatic solvents such as toluene and xylene; ether solvents such as tetrahydrofuran; ketone solvents such as acetone and methyl ethyl ketone; halogen solvents such as methylene chloride, etc. may be used alone or in combination of two or more of these solvents.

[0031] The amount of the solvent used is not particularly limited, but is preferably 0.1 to 50 times, and particularly preferably about 1 to 25 times, the amount of the sulfonyloxy compound represented by the general formula (1).

[0032] The reaction temperature in the production method of the present invention is preferably in the range of 0 to 100°C. To promote the reaction, 20 to 40°C is more preferable. The reaction pressure may be any of increased pressure, reduced pressure, and atmospheric pressure, but atmospheric pressure is preferable. The reaction atmosphere may be either air or an inert gas atmosphere, but an inert gas atmosphere such as nitrogen or argon is preferable.

[0033] The residence time in the production method of the present invention can be appropriately set depending on the amounts and types of starting materials and solvents used, reaction conditions such as reaction temperature, the reaction apparatus used, etc., but from the viewpoint of suppressing the by-production of impurities that are difficult to remove, such as binaphthyl compounds, the residence time of the reaction liquid is preferably 1 minute or less, more preferably 30 seconds or less, and particularly preferably 10 seconds or less. Note that the residence time of the reaction liquid means the residence time of the reaction reagents (starting materials, catalyst, and solvent) necessary for the reaction in the reaction vessel.

[0034] The mixing method in the production method of the present invention is not particularly limited, but a method capable of controlling the residence time of the reaction solution to an extremely short time is preferable. For example, the reaction can be rapidly carried out by using a flow reactor or a CSTR (continuous tank reactor) as a reaction apparatus, or by contacting each reaction agent by charging them all at once.

[0035] For example, a flow reactor that can be used in the production method of the present invention includes a liquid feed tube, a reaction tank, and an exhaust tube. In one embodiment of the production method of the present invention using a flow reactor, a solution containing a sulfonyloxy compound represented by the general formula (1) and a solution containing an organic halide represented by the general formula (2) are fed to the reaction tank from separate liquid feed tubes. The nickel compound may be fed to the reaction tank from a further separate liquid feed tube, or may be added to the solution containing the sulfonyloxy compound represented by the general formula (1) and fed to the reaction tank. The reaction liquid formed by the reaction reagents fed to the reaction tank is sequentially discharged from the reaction tank through an exhaust tube and subjected to the subsequent post-treatment (deactivation) step, and it is preferable to adjust the flow rate (mL / min) so that the residence time in the reaction tank (i.e., the time from when the reaction reagent is supplied from the liquid feed tube into the reaction tank to when the reaction liquid is discharged outside the reaction tank (exhaust tube)) is within 1 minute.

[0036] The production method of the present invention may also be carried out by a mixing method in which each reactant is contacted by being charged all at once. For example, the mixing method may be carried out by preparing a solution containing a sulfonyloxy compound and a nickel compound represented by general formula (1) and a solution containing an organic halide represented by general formula (2) separately, and charging one of them into a reaction vessel containing the other all at once. In the present invention, the term "charged all at once" does not mean a slow mixing method such as dripping or dispensing of the reactants, but means an addition and mixing performed all at once in an extremely short time (for example, several seconds). Specifically, the production method of the present invention may also be carried out by a mixing method in which the entire amount of the solution containing the organic halide represented by general formula (2) is charged all at once into a reaction vessel to which the entire amount of the solution containing the sulfonyloxy compound and a nickel compound represented by general formula (1) has been added. The reaction solution formed by charging all at once is promptly subjected to the subsequent post-treatment (deactivation) step, but it is preferable to treat the reaction vessel so that the residence time (i.e., the time until the reactants are discharged out of the reaction vessel or are subjected to deactivation treatment in the reaction vessel) is within 1 minute.

[0037] After the reaction is completed, the reaction solution obtained can be post-treated by a conventional method. The post-treatment method is not particularly limited, but for example, the organometallic halide in the reaction solution obtained is deactivated (quenched) with water or an acidic aqueous solution (dilute hydrochloric acid, etc.), and then washed to remove acid components and inorganic salts from the reaction system. If desired, the compound of the general formula (3) may be further separated and purified by a conventional method such as distillation, recrystallization, or chromatography, depending on the properties of the compound of the general formula (3). EXAMPLES

[0038] The present invention will be described below with reference to specific examples, but the present invention is not limited to the contents of the examples.

[0039] The purity of the reaction solutions and target products obtained in the examples and comparative examples was measured by gas chromatography (GC) and high performance liquid chromatography (HPLC).

[0040] <Gas Chromatography (GC)> GC device: GC-2030 (manufactured by Shimadzu Corporation) Column: HP-Ultra1 (Agilent Technologies) (ID 0.32 mm x 25 m, 0.52 μm) Column temperature: 100℃ → [heat up at 10℃ / min] → 280℃ [hold for 10 min] Vaporization chamber temperature: 280℃ Detector temperature: 300℃ Carrier gas: Helium gas Detector: Flame ionization detector (FID)

[0041] <High performance liquid chromatography (HPLC)> Detector: SPD-20A (Shimadzu Corporation) Oven: CTO-20A (Shimadzu Corporation) Pump: LC-20AD (Shimadzu Corporation) Column: ODS-80Tm (Tosoh Corporation) Column temperature: 40℃ Mobile phase: Acetonitrile: Water = 700:300 (0-40 min) Flow rate: 1.0mL / min Wavelength: 254nm

[0042] (Synthesis Example 1) Using a 1L glass flask equipped with a stirrer, a thermometer, a U-shaped tube, and a reflux condenser, 80.0g (0.55mol) of 2-naphthol (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 111.9g (0.58mol) of p-toluenesulfonyl chloride (manufactured by Tokyo Chemical Industry Co., Ltd.), and 800g of methylene chloride were added under an argon atmosphere, and 61.8g (0.61mol) of triethylamine (manufactured by Tokyo Chemical Industry Co., Ltd.) was added dropwise at 10 to 20°C while stirring to proceed with the reaction. After reacting at the same temperature for 1 hour, the mixture was washed with an aqueous 1M hydrochloric acid solution, and the aqueous layer was separated. The obtained organic layer was washed with water, and the solvent was distilled off by a concentration operation under normal pressure, after which 408g of ethyl acetate was poured in and the mixture was heated to about 70°C to dissolve. Next, the mixture was gradually cooled to an internal temperature of 5 to 10°C, and the precipitated crystals were subjected to solid-liquid separation using a Nutsche flask. The obtained crystals were dried at 40° C. under reduced pressure to obtain 144.8 g of 2-naphthyl p-toluenesulfonate with a GC purity of 99.9% in a yield of 88%.

[0043] <Example 1> (Preparation of solution A (2-naphthyl p-toluenesulfonate + catalyst / toluene solution)) Under an argon atmosphere, 20.9 g (0.07 mol) of 2-naphthyl p-toluenesulfonate (manufactured by Manac Corporation), 2.3 g (4.21 mmol) of 1,3-bis(diphenylphosphino)propanenickel(II) chloride (manufactured by Tokyo Chemical Industry Co., Ltd.), and 350 g of toluene were mixed to prepare solution A. (Preparation of solution B (Grignard reagent / tetrahydrofuran solution)) Using a 100mL glass flask equipped with a stirrer, thermometer, U-shaped tube, and reflux condenser, 0.8g (0.03mol) of magnesium (Yamaishi Metals Co., Ltd.) and 53.4g of tetrahydrofuran were added under argon atmosphere, and 4.7g (0.03mol) of bromobenzene (Manac Co., Ltd.) was added dropwise at an internal temperature of 20-30°C while stirring, and the mixture was reacted at the same temperature for 1 hour to obtain a 0.5M phenylmagnesium bromide tetrahydrofuran solution. This was designated as Solution B. (Production of 2-phenylnaphthalene) The reaction was carried out by sending solution A (4.00 mL / min) and solution B (2.13 mL / min) from each of the two sending tubes provided in the flow reactor and mixing them in a discharge tube (inner diameter 1.0 mm, length 68 cm) connected to a T-shaped tube mixer (φ1.5 mm) (GL Science Co., Ltd. flange-type three-way joint) fixed under a 20-30°C water bath. The reaction solution that passed through the reaction tube and discharge tube was quenched by directly injecting it into a sample bottle filled with dilute hydrochloric acid. The HPLC reaction purity at this time was 96.3% (binaphthyl compound 0.41%, target product / binaphthyl compound ratio = 235). The resulting reaction mixture may then be purified using a purification means such as column chromatography.

[0044] <Example 2> The reaction was carried out under the same conditions as in Example 1, except that the flow rates were changed to Solution A (4.00 mL / min) and Solution B (1.55 mL / min). The HPLC reaction purity at this time was 93.4% (binaphthyl compound 0.48%, target product / binaphthyl compound ratio=195).

[0045] <Example 3> The reaction was carried out under the same conditions as in Example 1, except that the flow rates were changed to Solution A (4.00 mL / min) and Solution B (2.76 mL / min). The HPLC reaction purity at this time was 95.8% (binaphthyl compound 0.20%, target product / binaphthyl compound ratio=479).

[0046] <Example 4> The reaction was carried out under the same conditions as in Example 1, except that the flow rates were changed to Solution A (4.00 mL / min) and Solution B (3.84 mL / min). The HPLC reaction purity at this time was 94.9% (binaphthyl compound 0.14%, target product / binaphthyl compound ratio=678).

[0047] <Example 5> Except for changing the toluene used in the preparation of solution A to methylene chloride, the reaction was carried out under the same conditions as in Example 1. The HPLC purity at this time was 57.5% (binaphthyl compound 0.24%, target product / binaphthyl ratio=240).

[0048] <Example 6> Except for changing the 2-naphthyl p-toluenesulfonate used in the preparation of solution A to 2-naphthyldimethylsulfamate, the reaction was carried out under the same conditions as in Example 1. The HPLC purity at this time was 90.3% (binaphthyl compound 0.14%, target product / binaphthyl compound ratio=645).

[0049] <Example 7> Except for changing the bromobenzene used in the preparation of solution B to 4-bromotoluene (manufactured by Manac Corporation), the reaction was carried out under the same conditions as in Example 1. The HPLC reaction purity at this time was 92.0% (binaphthyl compound 0.28%, target product / binaphthyl compound ratio=329).

[0050] <Example 8> Except for changing the bromobenzene used in the preparation of solution B to 4-bromoanisole (manufactured by Manac Corporation), the reaction was carried out under the same conditions as in Example 1. The HPLC reaction purity at this time was 94.7% (binaphthyl compound 0.23%, target product / binaphthyl compound ratio=412).

[0051] <Example 9> A stirrer, 298 mg (1.0 mmol) of 2-naphthyl p-toluenesulfonate (manufactured by Manac Co., Ltd.), 32.5 mg (0.06 mmol) of 1,3-bis(diphenylphosphino)propane nickel (II) chloride (manufactured by Tokyo Chemical Industry Co., Ltd.), and 250 mg of THF were charged into an argon-substituted test tube, and stirring was started with a magnetic stirrer. Next, the internal temperature was adjusted to 20 to 30 degrees in an oil bath, and then 6.0 mL (3.0 mmol) of 0.5 M phenylmagnesium bromide tetrahydrofuran solution prepared in Example 1 was injected all at once with a syringe and reacted. Instantaneous boiling was observed during the reaction. Thirty seconds after injection, dilute hydrochloric acid was added to perform quenching. The HPLC purity at this time was 77.3% (binaphthyl body 0.3%, target product / binaphthyl ratio = 258).

[0052] <Example 10> Except for changing the nickel compound to 31.6 mg (0.06 mmol) of 1,2-bis(diphenylphosphino)ethanenickel(II) chloride, the reaction was carried out under the same conditions as in Example 9. The HPLC reaction purity at this time was 85.6% (binaphthyl compound 0.4%, target product / binaphthyl compound ratio=214).

[0053] <Comparative Example 1> After replacing the atmosphere in a 100mL glass four-neck flask equipped with a stirring device, a cooling tube, a thermometer, and a dropping funnel with argon, 298mg (1.0mmol) of 2-naphthyl p-toluenesulfonate (manufactured by Manac Co., Ltd.), 32.5mg (0.06mmol) of 1,3-bis(diphenylphosphino)propane nickel (II) chloride (manufactured by Tokyo Chemical Industry Co., Ltd.), and 250mg of THF were charged and stirring was started. Next, the internal temperature was adjusted to 20-30°C in an oil bath, and 6.0mL (3.0mmol) of 0.5M phenylmagnesium bromide tetrahydrofuran solution prepared in Example 1 was dropped by a syringe pump over about 3 hours to react. After the reaction was completed, dilute hydrochloric acid was added to perform quenching. The HPLC reaction purity at this time was 68.5% (binaphthyl 12.1%, target product / binaphthyl ratio = 5.7).

[0054] <Comparative Example 2> Except for adjusting the internal temperature of the oil bath to 60 to 65° C., the reaction was carried out under the same conditions as in Comparative Example 1. The HPLC reaction purity at this time was 76.6% (binaphthyl compound 6.4%, target product / binaphthyl compound ratio=12).

[0055] <Comparative Example 3> Except for changing the toluene used in the preparation of solution A to methylene chloride (170 mg) and changing the amount of 1,3-bis(diphenylphosphino)propanenickel(II) chloride added to 2.7 mg (0.005 mmol), the reaction was carried out under the same conditions as in Comparative Example 1. The HPLC reaction purity at this time was 49.1% (binaphthyl compound 3.3%, target product / binaphthyl compound ratio=15).

[0056] <Comparative Example 4> Except for changing the nickel compound to 39.2 mg (0.06 mmol) of bis(triphenylphosphine)nickel(II) dichloride, the reaction was carried out under the same conditions as in Comparative Example 2. The HPLC reaction purity at this time was 68.5% (binaphthyl compound 7.2%, target product / binaphthyl compound ratio=9.5). [Industrial Applicability]

[0057] According to the manufacturing method of the present invention, it is possible to selectively and efficiently manufacture 2-naphthyl derivatives, which are useful organic synthesis intermediates in the field of organic electroluminescence. In particular, as shown in Examples 1 to 9, by controlling the residence time of the reaction solution to an extremely short time using a specific reaction device (flow reactor) or a mixing method (lump-injection), it is possible to suppress the by-production of impurities that are difficult to remove, such as binaphthyl derivatives, and therefore it is expected to be industrially useful.

Claims

1. General formula (1): 【Chemistry 1】 (In the formula, R １ represents a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C2-6 alkenyl group, a nitro group, a cyano group, an aldehyde group, an amino group, a hydroxyl group, a thiol group, a sulfo group, a sulfonamide group, or a carboxyl group or an ester group thereof; A represents a phenyl group which may be substituted by 1 or 2 substituents selected from the group consisting of a C1-6 alkyl group, a mono- or di-C1-6 alkylamino group, a C1-6 alkyl group, and a nitro group, or a halo-C1-3 alkyl group. A sulfonyloxy compound represented by the general formula (2): 【Chemistry 2】 (wherein Ar is a C6-20 aryl group, M is MgX or MgX LiCl, and X represents a chlorine atom, a bromine atom, or an iodine atom). In a solvent, a compound represented by the general formula (3): 【Chemistry 3】 (In the formula, R １ and Ar have the same meanings as defined above), characterized in that the residence time of the reaction solution in the reaction is 1 minute or less.

2. The production method comprises: (1) reacting a compound represented by general formula (1): 【Chemistry 4】 In the formula, R １ and A have the same meaning as in claim 1. preparing a solution containing a sulfonyloxy compound represented by the formula: (2) General formula (2): 【Chemistry 5】 (In the formula, Ar and M are defined as in claim 1.) preparing a solution containing an organometallic halide represented by the formula: (3) A step of mixing the solution of step (1) and the solution of step (2) and reacting them. The method of claim 1 , comprising:

3. 3. The method according to claim 1, wherein in the general formula (2), Ar is a phenyl group, M is MgX, and X is a bromine atom, a chlorine atom, or an iodine atom.

4. The method according to claim 1 or 2, wherein the nickel compound is a compound that forms a bidentate phosphine ligand.

5. The method according to claim 1 or 2, wherein the reaction apparatus used in the reaction is a flow reactor.

6. 6. The method according to claim 5, wherein the flow reactor comprises a liquid delivery pipe, a reaction tank, and a discharge pipe, the solution containing the sulfonyloxy compound represented by the general formula (1) and the solution containing the organic halide represented by the general formula (2) are delivered to the reaction tank from separate liquid delivery pipes, and the residence time of the reaction liquid in the reaction tank is 1 minute or less.

7. 3. The method according to claim 1, wherein the reaction is carried out by simultaneously adding a solution containing the sulfonyloxy compound represented by the general formula (1) and the nickel compound and a solution containing the organic halide represented by the general formula (2).

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