JP5790129B2 - Novel naphthalene metal compound and process for producing the same - Google Patents

Description

  The present invention relates to a naphthalene metal compound and a method for producing the same.

  Since aromatic boronic acid compounds are chemically stable and easy to handle, they are used in a wide range of fields as coupling reaction reagents. Examples of conventionally known aromatic boronic acid compounds include numerous compounds such as phenylboronic acid, o-tolylboronic acid, and 2-acetylphenylboronic acid. Among these, an aromatic boronic acid compound having an acyl group such as 2-acetylphenylboronic acid has a feature that it can be easily derivatized to other compounds by utilizing the reactivity of carbonyl carbon.

  The aromatic boronic acid compound is usually produced by a conventionally known method (for example, Non-Patent Document 1). Specifically, by reacting a halogenated aromatic compound with an organolithium compound such as n-butyllithium, followed by a reaction with a trialkylborate, followed by a reaction with an acid, an aromatic boronic acid compound Is manufactured.

J. et al. Organomet. Chem. 2000 Vol. 611, Vol. 392

  In order to produce a naphthylboronic acid compound having an acyl group, the above-mentioned reaction is carried out using a halogenated acylnaphthalene compound obtained by a halogenation reaction of an acylnaphthalene compound (for example, reaction of bromine, N-halosuccinimide, etc.) as a raw material. Can be done. However, in the halogenation reaction of acyl naphthalene compounds, a large number of regiosubstituted isomers and polysubstituted isomers are produced as by-products at the same time, requiring complicated purification steps and by-product treatment steps for isolating the target compound. Become. For this reason, the above-described production method is not necessarily rational as a method for producing a naphthylboronic acid compound having an acyl group. Therefore, there are few report examples as a naphthyl boronic acid compound which has an acyl group.

  For the reasons described above, a method for selectively and efficiently producing a naphthylboronic acid compound having an acyl group, specifically, a 1-acylnaphthalen-2-ylboronic acid compound and a method for producing the same are not known.

  Accordingly, the present invention provides a naphthalene metal compound that is an intermediate for selectively and efficiently producing a 1-acylnaphthalen-2-ylboronic acid compound, an organometallic reagent comprising the naphthalene metal compound, and the naphthalene It aims at providing the manufacturing method of a metal compound.

  As a result of intensive studies to solve the above problems, the present inventors have used a naphthalene metal compound represented by the general formula (4), whereby a 1-acylnaphthalene-2- represented by the general formula (1) is used. It has been found that ilboronic acid compounds can be produced with high selectivity and efficiency.

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ¹ and R ² may be independently bonded to a naphthalene ring to form a ring, or R ¹ and R ² may be directly bonded to form a ring, and R ³ is independently And a C1-C18 linear, branched or cyclic alkyl group, a C1-C18 linear, branched or cyclic alkoxy group, and a carbon number which may have a C1-C6 substituent. Represents a 4 to 14 aryl group, or an aryloxy group having 4 to 14 carbon atoms which may have a substituent having 1 to 6 carbon atoms, and n represents an integer of 0 to 3. R ⁴ is independently selected. It represents a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms Te .R ⁵ is Li, represents MgX or ZnX, X is It represents an androgenic atom.)
That is, the present invention relates to the general formula (4)

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ¹ and R ² may be independently bonded to a naphthalene ring to form a ring, or R ¹ and R ² may be directly bonded to form a ring, and R ³ is independently And a C1-C18 linear, branched or cyclic alkyl group, a C1-C18 linear, branched or cyclic alkoxy group, and a carbon number which may have a C1-C6 substituent. Represents a 4 to 14 aryl group, or an aryloxy group having 4 to 14 carbon atoms which may have a substituent having 1 to 6 carbon atoms, and n represents an integer of 0 to 3. R ⁴ is independently selected. It represents a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms Te .R ⁵ is Li, represents MgX or ZnX, X is It represents an androgenic atom.)
The naphthalene metal compound represented by these, its manufacturing method, and the organometallic reagent containing a naphthalene metal compound.

  Hereinafter, the present invention will be described in detail.

In the naphthalene metal compound represented by the general formula (4), R ¹ and R ² each independently represent a hydrogen atom or a linear alkyl group having 1 to 17 carbon atoms, and R ¹ and R ^{2 having} the carbon number. The total is an integer from 0 to 17. Although it does not specifically limit as a C1-C17 linear alkyl group, For example, a methyl group, an ethyl group, n-propyl group, n-butyl group, n-pentyl group, n-heptyl group, n-undecyl group , N-heptadecyl group and the like. R ¹ and R ² can be independently bonded to Ar to form a ring, but the number of bonds is not limited. Further, the position of the bond is not limited as long as it is other than the 2-position of the naphthalene ring. In addition, R ¹ and R ² can be directly bonded to form a ring structure.

In the naphthalene metal compound represented by the general formula (4), each R ³ is independently a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, a linear, branched or cyclic group having 1 to 18 carbon atoms. An alkoxy group, an aryl group having 4 to 14 carbon atoms which may have a substituent having 1 to 6 carbon atoms, or an aryloxy group having 4 to 14 carbon atoms which may have a substituent having 1 to 6 carbon atoms Represents.

  The linear, branched or cyclic alkyl group having 1 to 18 carbon atoms is not particularly limited. For example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group, a tert-butyl group, Examples include pentyl group, hexyl group, heptyl group, octyl group, stearyl group, trichloromethyl group, trifluoromethyl group, cyclopropyl group, cyclohexyl group and the like. Among these, a methyl group, an ethyl group, a tert-butyl group, a hexyl group, and a trifluoromethyl group are preferably used.

  Although it does not specifically limit as a C1-C18 linear, branched or cyclic alkoxy group, For example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, n-butoxy group, sec-butoxy group, tert- Examples include butoxy group, pentyloxy group, hexyloxy group, stearyloxy group, trichloromethyloxy group, trifluoromethoxy group, cyclopropyloxy group, cyclohexyloxy group and the like. Among these, a methoxy group, an ethoxy group, a tert-butoxy group, a hexyloxy group, and a trifluoromethoxy group are preferably used.

  Of the aryl group having 4 to 14 carbon atoms that may have a substituent having 1 to 6 carbon atoms, or the aryloxy group having 4 to 14 carbon atoms that may have a substituent having 1 to 6 carbon atoms, Although it does not specifically limit as a C1-C6 substituent, A methyl group, an ethyl group, n-propyl group, isopropyl group, n-butyl group, tert-butyl group, n-hexyl group, cyclohexyl group, trichloromethyl Group, trifluoromethyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, tert-butoxy group, n-hexyloxy group, cyclohexyloxy group, trichloromethyloxy group, Examples thereof include a trifluoromethyloxy group, and the aryl group having 4 to 14 carbon atoms is not particularly limited, but examples thereof include a phenyl group and biphenylyl. Terphenyl group, naphthyl group, fluorenyl group, phenanthryl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 3-quinolyl group, 4-quinolyl group, 2-indolyl group, 3-indolyl group, 2 -Furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-oxazolyl group, 2-thiazolyl group, 2-benzoxazolyl group, 2-benzothiazolyl group, 2-benzothiophenyl group, 3 -Benzothiophenyl group, 2-benzimidazolyl group, 2-dibenzothiophenyl group, 3-dibenzothiophenyl group, 2-dibenzofuranyl group, 3-dibenzofuranyl group, etc., and aryl having 4 to 14 carbon atoms The oxy group is not particularly limited, and examples thereof include a phenoxy group, a phenylphenoxy group, a biphenylphenoxy group, and a naphthoxy group. Fluorenyloxy group, phenanthryloxy group, 2-pyridyloxy group, 3-pyridyloxy group, 4-pyridyloxy group, 3-quinolinyloxy group, 4-quinolinyloxy group, 2-indolyloxy group, 3-in Drilloxy group, 2-furyloxy group, 3-furyloxy group, 2-thienyloxy group, 3-thienyloxy group, 2-oxazolyloxy group, 2-thiazolyloxy group, 2-benzoxazolyloxy group, 2-benzothiazolyloxy group, 2-benzothiophenyloxy group, 3-benzothiophenyloxy group, 2-benzoimidazolyloxy group, 2-dibenzothiophenyloxy group, 3-dibenzothiophenyloxy group, 2-dibenzo A furanyloxy group, 3-dibenzofuranyloxy group, etc. are mentioned. Among these, examples of the substituent having 1 to 6 carbon atoms include methyl group, ethyl group, tert-butyl group, n-hexyl group, trifluoromethyl group, methoxy group, ethoxy group, tert-butoxy group, and n-hexyloxy. Group, trifluoromethyloxy group is preferably used, and examples of the aryl group having 4 to 14 carbon atoms include phenyl group, biphenylyl group, naphthyl group, fluorenyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, A 2-furyl group and a 3-furyl group are preferably used, and examples of the aryloxy group having 4 to 14 carbon atoms include phenoxy group, phenylphenoxy group, naphthoxy group, fluorenyloxy group, 2-pyridyloxy group, 3- Pyridyloxy group, 4-pyridyloxy group, 2-furyloxy group and 3-furyloxy group are preferably used. Here, the number and position of the substituents are not particularly limited for the substituent having 1 to 6 carbon atoms.

  In the naphthalene metal compound represented by the general formula (4), n represents an integer of 0 to 3, and the position of the substituent is not particularly limited as long as it is other than the 2-position of the naphthalene ring.

In the naphthalene metal compound represented by the general formula (4), each R ⁴ independently represents a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms. Although it does not specifically limit as a C1-C6 linear, branched or cyclic alkyl group, For example, a methyl group, an ethyl group, n-propyl group, n-butyl group, tert-butyl group, n-hexyl group Cyclohexyl group and the like.

In the naphthalene metal compound represented by the general formula (4), R ⁵ represents Li, MgX or ZnX, and X represents a halogen atom. Li represents lithium. Mg represents magnesium. Zn represents zinc. Although it does not specifically limit as a halogen atom, For example, chlorine, a bromine, and an iodine are preferable.

  The 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) is synthesized by a four-step reaction using the 1-acylnaphthalene compound represented by the general formula (2) as a starting material.

(In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ represent the same group as the naphthalene metal compound represented by the general formula (4). N represents an integer of 0 to ^3. )
As the 1-acylnaphthalene compound represented by the general formula (2), a commercially available reagent is used as it is, or a naphthalene compound and a carboxylic acid halide (for example, acetyl chloride, acetyl bromide, etc.) in the presence of a Lewis acid such as aluminum chloride. ) Can also be used (Friedel-Crafts alkanoylation reaction, for example, see Non-Patent Document 2).

The Journal of Organic Chemistry, 2004, Vol. 69, Vol. 693-6956, The 1-acylnaphthalene compound represented by the general formula (2) is not particularly limited, and examples thereof include 1-acetylnaphthalene and 1-propanoylnaphthalene. 1-butanoylnaphthalene, 1-valerylnaphthalene, 1-hexanoylnaphthalene, 1-acetyl-4-methoxynaphthalene, 1-acetyl-4-ethoxynaphthalene, 1-acetyl-4-methylnaphthalene, 1-acetyl- 8-methoxynaphthalene, 1-acetyl-8-ethoxynaphthalene, acenaphthen-1-one, 2,3-dihydro-1H-phenalen-1-one, 2,3-dihydro-4-methyl-1H-phenalen-1- ON, 5,8-di-tert-butyl Lu-2,3-dihydro-1H-phenalen-1-one, 8- (dihydroxyboryl) acenaphthen-1-one, 9- (dihydroxyboryl) -2,3-dihydro-1H-phenalen-1-one, 9 -(Dihydroxyboryl) -2,3-dihydro-4-methyl-1H-phenalen-1-one, 9- (dihydroxyboryl) -5,8-di-tert-butyl-2,3-dihydro-1H-phenalene -1-one etc. are mentioned.

  The naphthalene enol silyl ether compound represented by the general formula (3) can be synthesized using a known enol silyl etherification method (for example, Non-Patent Document 4). Specifically, it can be synthesized by reacting the 1-acylnaphthalene compound represented by the general formula (2) with a silylating agent in the presence of a base (first step) (for example, Non-Patent Document 3). reference).

The Journal of Organic Chemistry, 1976, Vol. 41, No. 20, No. 3307 The base used in the enol silyl etherification reaction is not particularly limited. For example, alkali metal hydrogen such as sodium hydride or potassium hydride , Organodiethyl bases such as lithium diethylamide, lithium (isopropyl) cyclohexylamide, lithium-bis (dimethylsilyl) amide, lithium diisopropylamide, triphenylmethane lithium, lithium (2,2,6,6-tetramethyl) piperidineamide Kind. As these bases, commercially available reagents can be used as they are. The amount of the base used is not particularly limited. For example, the base is selected from a range of 0.9 to 5 moles per mole of the 1-acylnaphthalene compound represented by the general formula (2), and 0.9 to 2 A range of double moles is preferred. If it is the range of 0.9-5 times mole, reaction will fully advance, and if it is the range of 0.9-2 times mole, it is economically preferable.

  The silylating agent used for the enol silyl etherification reaction is not particularly limited, and examples thereof include chlorotrimethylsilane, chlorotriethylsilane, chloro-tert-butyldimethylsilane, and chlorotriisopropylsilane. As these silylating agents, commercially available reagents can be used as they are. The amount of the silylating agent to be used is not particularly limited. For example, the amount of the silylating agent is selected from a range of 0.9 to 5 times moles relative to 1 mole of the 1-acylnaphthalene compound represented by the general formula (2). A range of ˜2 times mole is preferred. If it is the range of 0.9-5 times mole, reaction will fully advance, and if it is the range of 0.9-2 times mole, it is economically preferable.

  The silylating agent used in the enol silyl etherification reaction can be used after being dissolved in a solvent, or can be used as it is. When used by dissolving, it is preferable to use the same solvent as the solvent in which the 1-acylnaphthalene compound represented by the general formula (2) is dissolved.

  The enol silyl etherification reaction is usually performed in an organic solvent. The organic solvent is not particularly limited as long as it does not inhibit the reaction. However, a hydrocarbon solvent such as hexane or cyclohexane, or an ether solvent such as diethyl ether, tetrahydrofuran, dimethoxyethane, or cyclopentylmethyl ether is preferably used. Although the usage-amount of a reaction solvent is not specifically limited, It is 1-40 weight ratio normally with respect to 1-acylnaphthalene compound represented by General formula (2).

  The reaction temperature of the enol silyl etherification reaction is preferably in the range of −78 to 100 ° C., more preferably −10 to 50 ° C. in terms of operability and economy.

  The reaction time of the enol silyl etherification reaction varies depending on the concentration of the 1-acylnaphthalene compound represented by the general formula (2), the base and the silylating agent, the reaction temperature, and the like. Done in a range.

  The naphthalene enol silyl ether compound represented by the general formula (3) synthesized by the above reaction can be separated from other components in the reaction solution by a liquid separation operation. Furthermore, it can be purified with high purity by an operation such as distillation.

  The aromatic boronic acid compound represented by the general formula (1) is obtained by using a naphthalene enol silyl ether compound represented by the general formula (3) as a raw material, a reaction with an organolithium compound (second stage), a trialkyl borate, (3rd stage) and acid reaction (4th stage). This series of reactions is usually performed without isolation and purification of the product at each reaction stage (one-pot synthesis).

In the reaction with the organic lithium compound (second stage), by reacting the naphthalene enol silyl ether compound represented by the general formula (3) with a generally known organic lithium compound, the general formula (4) in which R ⁵ is lithium is used. ) Is synthesized. In this reaction, surprisingly, the hydrogen at the 2-position of the naphthalene ring can be selectively exchanged for lithium.

  Although it does not specifically limit as an organic lithium compound, For example, n-butyllithium, sec-butyllithium, tert-butyllithium etc. are mentioned. Commercially available reagents can be used for these, and those prepared from any organic halogen compound and metallic lithium can also be used.

  Although it does not specifically limit as the usage-amount of an organolithium compound, For example, it is chosen from the range of 0.9-10 times mole with respect to 1 mol of naphthalene enol silyl ether compounds represented by General formula (3). The range of 9-5 moles is preferred. If it is the range of 0.9-10 times mole, reaction will fully advance, and if it is the range of 0.9-5 times mole, it is economically preferable.

  Tertiary amines such as tetramethylethylenediamine, triethylamine, and triethylenediamine can be added to the reaction with the organolithium compound. A tertiary amine has a function of increasing the reaction activity of the organolithium compound. Although the addition amount of a tertiary amine is not specifically limited, For example, it is chosen from the range of 0.5-5 times mole with respect to the said organolithium compound, Preferably it is 0.9 times mole-2 times mole.

  The reaction with the organolithium compound is usually performed in an organic solvent. The organic solvent is not particularly limited as long as it does not inhibit the reaction, but an ether solvent such as diethyl ether, THF, dioxane or the like, or a hydrocarbon solvent such as hexane, benzene, toluene or the like is preferably used. It is preferable to use a previously dehydrated organic solvent. Although the usage-amount of a reaction solvent is not specifically limited, It is 1-40 weight ratio normally with respect to the naphthalene enol silyl ether compound represented by General formula (3).

  The reaction temperature in the reaction with the organolithium compound is preferably in the range of −78 to 100 ° C., more preferably −40 to 80 ° C. in terms of operability and economy.

  The reaction time in the reaction with the organolithium compound varies depending on the concentration of the naphthalene enol silyl ether compound represented by the general formula (3), the tertiary amine and the organolithium compound, the reaction temperature, and the like. The range is 24 hours.

By the above operation, a naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium is synthesized.

Furthermore, by reacting a naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium with a magnesium salt such as magnesium chloride or magnesium bromide or a zinc salt such as zinc chloride or zinc bromide, Corresponding naphthalene magnesium compounds or naphthalene zinc compounds can be synthesized. That is, the naphthalene metal compound represented by the general formula (4) can be synthesized.

  The naphthalene metal compound represented by the general formula (4) is not particularly limited. For example, 1-acetylnaphthalen-2-yllithium, 1-propionylnaphthalen-2-yllithium, 1-butyrylnaphthalene-2- Yllithium, 1-valerylnaphthalen-2-yllithium, 1-hexanoylnaphthalen-2-yllithium, 1-acetyl-4-methoxynaphthalen-2-yllithium, 1-acetyl-4-ethoxynaphthalene-2- Yllithium, 1-acetyl-4-methylnaphthalen-2-yllithium, 1-acetyl-8-methoxynaphthalen-2-yllithium, 1-acetyl-8-ethoxynaphthalen-2-yllithium, 8-lithioacenaphthene -1-one, 9-lithio-2,3-dihydro-1H-phenalen-1-one 9-lithio-2,3-dihydro-4-methyl-1H-phenalen-1-one, 9-lithio-5,8-di-tert-butyl-2,3-dihydro-1H-phenalen-1-one, etc. Is mentioned.

The reaction of the naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium and the magnesium salt or zinc salt is usually a naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium. It is carried out by adding magnesium salts or zinc salts to the reaction solution produced.

The reaction temperature in the reaction of the naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium and the magnesium salt or zinc salt is preferably in the range of −78 to 100 ° C. -40-80 degreeC is more preferable.

The reaction time in the reaction of the naphthalene metal compound represented by the general formula (4) in which R ⁵ is lithium and the magnesium salt or zinc salt is usually in the range of several minutes to 24 hours.

  Although it is difficult to isolate the naphthalene metal compound represented by the general formula (4), it can be stored in an organic solvent that does not react with the naphthalene metal compound in an inert gas atmosphere for a long time in a cool and dark place. it can. That is, the naphthalene metal compound represented by the general formula (4) can be stored as a solution in the synthesized solvent for a long time in a cool dark place under an inert gas atmosphere. Moreover, the reaction liquid from which the naphthalene metal compound represented by the general formula (4) is obtained and another solvent can be mixed and stored for a long time in a mixed solvent.

  Accordingly, the naphthalene metal compound represented by the general formula (4) is not particularly limited as long as it does not react with the naphthalene metal compound, but ether solvents such as diethyl ether, THF, dioxane or the like, or hexane, benzene, toluene. It can be obtained as an organometallic reagent in an organic solvent such as a hydrocarbon solvent, or in a mixed solvent composed of a plurality of organic solvents selected from the group consisting of the organic solvent.

  The concentration of the naphthalene metal compound represented by the general formula (4) in the organometallic reagent having the naphthalene metal compound represented by the general formula (4) is usually in the range of 0.1 to 50% by weight. The range of 1-30 weight% is preferable at the point of the ease of handling.

  The naphthalene metal compound represented by the general formula (4) or the organometallic reagent having the naphthalene metal compound is used as, for example, a nucleophilic reaction reagent or a polymerization initiator.

The naphthalene metal compound represented by the general formula (4) can be identified by derivatization to another compound. For example, when a naphthalene metal compound represented by the general formula (4) is reacted with water or alcohol, a derivative in which R ⁵ is substituted with hydrogen is obtained. When dimethylformamide is reacted, R ⁵ is a formyl group. When a trialkyl borate is obtained, a derivative in which R ⁵ is substituted with a boronic ester group is obtained.

  The reaction with the trialkylborate (the third stage) performed after the reaction with the organolithium compound (the second stage) is a reaction solution in which the naphthalene metal compound represented by the general formula (4) is generated. It is performed by contacting with.

  The trialkyl borate is not particularly limited, and examples thereof include trimethyl borate, triethyl borate, triisopropyl borate, tri-n-amyl borate, tributyl borate, 2-isopropoxy-4,4,5,5-tetramethyl-1, 3,2-dioxaborolane and the like can be mentioned. Although the usage-amount of a trialkyl borate is not specifically limited, For example, it is chosen from the range of 0.9-10 times mole with respect to 1 mol of naphthalene metal compounds represented by General formula (4), 0.9-3 A range of double moles is preferred. If it is the range of 0.9-10 times mole, reaction will fully advance, and if it is the range of 0.9-3 times mole, it is preferable also for economical efficiency.

  In the reaction with the trialkyl borate, the trialkyl borate can be used by dissolving in an organic solvent. The organic solvent is not particularly limited as long as it does not inhibit the reaction, but an ether solvent such as diethyl ether, THF, dioxane or the like, or a hydrocarbon solvent such as hexane, benzene, toluene or the like is preferably used. It is preferable to use a previously dehydrated organic solvent. Of these, the organic solvent used in the reaction with the organic lithium compound (second stage) is particularly preferably used as it is. Although the usage-amount of a reaction solvent is not specifically limited, It is the range of 1-10 weight ratio normally with respect to a trialkyl borate.

  The reaction with the trialkyl borate is usually performed in an organic solvent. The organic solvent is not particularly limited as long as it does not inhibit the reaction. Usually, the solvent used in the reaction with the organic lithium compound (second stage) is used as it is.

  The reaction temperature in the reaction with the trialkyl borate is preferably in the range of −78 to 100 ° C., more preferably −20 to 50 ° C. from the viewpoint of experimental operation and economy.

  The reaction time in the reaction with the trialkyl borate varies depending on the concentration of the naphthalene metal compound represented by the general formula (4) and the trialkyl borate, the reaction temperature, etc., but is usually in the range of several minutes to 24 hours. .

  By the above reaction, a naphthyl boronic acid ester compound is synthesized.

  Furthermore, the boronic acid ester group and silyl ether group of the naphthyl boronic acid ester compound are hydrolyzed by bringing the reaction solution obtained above into contact with an acid (fourth stage), which is represented by the general formula (1). A 1-acylnaphthalen-2-ylboronic acid compound is obtained.

  Examples of the acid include, but are not limited to, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, ammonium chloride, ammonium sulfate, ammonium nitrate, and ammonium phosphate.

  The acid can usually be used as an aqueous solution. The acid concentration is not particularly limited, but is preferably 0.01 to 5 mol / L.

  The amount of the acid used varies depending on the amount of the compound used in the reaction and is not particularly limited. However, it is preferable to add the acid until the reaction solution from which the naphthyl boronic acid ester compound is obtained becomes acidic.

  Although it does not specifically limit as reaction temperature in reaction with an acid, 0-50 degreeC is preferable.

  Although it does not specifically limit as reaction time in reaction with an acid, Several minutes-24 hours are preferable.

  The 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) synthesized by the above reaction can be isolated and purified by operations such as extraction, recrystallization and silica gel chromatography.

  Since the naphthalene metal compound represented by the general formula (4) can easily react with other compounds as a nucleophile, it is expected to be used as an intermediate for compounds used in medical pesticides and electronic materials. The

  The compound that reacts with the naphthalene metal compound represented by the general formula (4) is not particularly limited. For example, trimethyl borate, triethyl borate, triphenyl borate, 2-isopropoxy-4, 4, 5, Borates such as 5-tetramethyl-1,3,2-dioxaborolane, aldehydes such as formaldehyde and acetaldehyde, carbonyl compounds such as acetone and ethyl methyl ketone, ester compounds such as ethyl acetate, methyl methacrylate, ethyl methacrylate Α, β-unsaturated ester compounds such as, halogenated alkyls such as bromoethane and iodomethane, disulfide compounds such as dimethyl disulfide and diallyl disulfide, epoxy compounds such as propylene oxide and bisphenol A diglycidyl ether, Examples thereof include nitrile compounds such as butyronitrile and acrylonitrile. Among these, in particular, 1-acylnaphthalen-2-ylboronic acid compounds obtained by reacting with borates are very useful as intermediates for materials for electronic materials.

  The naphthalene metal compound represented by the general formula (4) of the present invention is expected to be used as an anionic polymerization initiator. Specific examples include, but are not limited to, aromatic vinyl monomers such as styrene, alphamethylstyrene, p-methylstyrene, and vinylnaphthalene, and conjugated dienes such as 1,3-butadiene, isoprene, and 1,3-pentadiene. Application to copolymerization of monomers is expected, and the obtained polymer is used as a component of elastomer products such as tires and belts.

  The naphthalene metal compound represented by the general formula (4) is a novel compound and easily reacts with electron-accepting organic compounds such as ketones, esters, nitriles, and trialkyl borates. Available for manufacturing.

  As a specific example, a reaction of a naphthalene metal compound represented by the general formula (4) and a trialkyl borate can be mentioned. A 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) is highly selective. And can be manufactured efficiently.

  Since the 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) has a carbonyl group, it is possible to produce various derivatives using the reactivity of the carbonyl group. is there. Therefore, if the 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) is used, a compound that has been difficult to produce can be produced. Eventually, for example, the development of new materials in medical and agricultural chemicals and electronic materials is expected.

  Therefore, a general formula (1) for selectively and efficiently producing a 1-acylnaphthalen-2-ylboronic acid compound represented by the general formula (1) that is particularly useful as an intermediate for medical and agricultural chemicals and electronic materials ( The naphthalene metal compound represented by 4) is very useful.

The present invention will be described in more detail with reference to the following examples, but the present invention should not be construed as being limited thereto.
[ ¹ H, ¹³ C-NMR measurement]
Measuring device: Gemini200 manufactured by Varian
[Gas chromatography measurement]
Device: GC-17A manufactured by Shimadzu Corporation
Column: capillary column (GL Science NB-5)
Carrier gas: helium Column temperature: 150 ° C. → 10 ° C./min→300° C.
Injection: 280 ° C
Detector: FID
Synthesis Example 1 (Synthesis of α-trimethylsilyloxy-1-vinylnaphthalene)
To a 200 mL eggplant-shaped flask containing 65 mL of lithium diisopropylamide (1.1 M hexane-THF mixed solution, 72 mmol), 28 g of a THF solution containing 10 g (58.8 mmol) of 1-acetylnaphthalene was added dropwise at the same temperature. For 1 hour. Next, 9.2 mL of chlorotrimethylsilane was added in an ice bath, and the mixture was stirred at the same temperature for 0.5 hours and further at room temperature for 1.5 hours, and then 70 mL of 5% aqueous sodium hydrogen carbonate solution was added to complete the reaction. The resulting reaction solution was transferred to a separatory funnel and the organic layer was extracted with toluene. The organic layer was washed with saturated brine and dried over magnesium sulfate.
The concentrated solution obtained by distilling off the solvent was purified by distillation under reduced pressure (90 ° C./0.5 torr) to obtain 14.4 g of a colorless oil.

It was confirmed by ¹ H, ¹³ C-NMR synthesis of α-trimethylsilyloxy-1-vinylnaphthalene (target compound A).

¹ H-NMR (CDCl ₃ ) δ: 8.30-8.35 (m, 1H), 7.80-7.87 (m, 2H), 7.39-7.56 (m, 4H), 4 .77 (d, J = 1 Hz, 1H), 4.63 (d, J = 1 Hz, 1H), 0.16 (s, 9H)
¹³ H-NMR (CDCl ₃ ) δ: 156.84, 137.17, 133.57, 130.89, 128.55, 128.05, 126.17, 126.09, 125.86, 125.62, 124.96, 96.59, 0.24

Example 1 (Synthesis of 2- (1-acetyl) naphthylboronic acid)
To a 200 mL eggplant-shaped flask, 5.22 g (44.9 mmol) of tetramethylethylenediamine was added, and 28 mL (1.6 M, 44.8 mmol) of n-butyllithium-hexane solution was added in an ice bath. At the same temperature, a mixed solution consisting of 5.45 g (22.5 mmol) of α-trimethylsilyloxy-1-vinylnaphthalene obtained in Synthesis Example 1 and 30 mL of hexane was added dropwise, followed by stirring at room temperature for 17 hours. Next, a mixed solution consisting of 4.35 g (41.9 mmol) of trimethylborate and 30 mL of tetrahydrofuran was dropped, and the mixture was stirred at room temperature for 2 hours.

  The reaction was terminated by adding 70 mL of 3.5% aqueous hydrochloric acid solution to pH = 6.

  The reaction solution was transferred to a separatory funnel and the organic phase was extracted. The organic phase was treated with saturated brine and magnesium sulfate, then concentrated and vacuum dried to obtain 4.65 g of a brown viscous oil. By adding 70 mL of hexane to the obtained brown viscous oily substance, 2.38 g of a light brown powder was obtained.

  When the elemental analysis of the light brown powder obtained here was conducted, it was confirmed that the obtained compound contains a boron element. Therefore, it is considered that the target compound 2- (1-acetyl) naphthylboronic acid was synthesized.

Furthermore, as a result of inducing the obtained light brown powder to 2 ′-(4-chlorophenyl) -1′-acetonaphthone by the method described later and comparing its ¹ H- and ¹³ C-NMR, the light brown powder was It was identified as the desired 2- (1-acetyl) naphthylboronic acid.

<Induction method to 2 '-(4-chlorophenyl) -1'-acetonaphthone>
In a 100 mL eggplant-shaped flask, 2.05 g (9.34 mmol) of 2- (1-acetyl) naphthylboronic acid obtained in Example 1, 1.87 g of p-bromochlorobenzene (1.05 times equivalent), tetrakistriphenyl Phosphine palladium (0.10 g), tetrahydrofuran (20 mL) and 20 wt% aqueous sodium carbonate solution (12.4 g) were added, and the mixture was stirred under reflux for 15 hours. After cooling the reaction solution to room temperature, the organic layer was extracted with toluene. The organic phase was washed with water and saturated brine, and then dried over magnesium sulfate. The organic phase was concentrated and purified by silica gel chromatography (developing solution: hexane / toluene = 2/1 volume ratio) to obtain pale yellow crystals.

¹ H- and ¹³ C-NMR of this crystal was consistent with that of 2 ′-(4-chlorophenyl) -1′-acetonaphthone reported in WO200007119800.

Claims (7)

A naphthalene metal compound represented by the general formula (4).

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ³ are each independently a straight-chain having 1 to 18 carbon atoms, branched or cyclic alkyl group, a linear, branched or cyclic alkoxy group having 1 to 18 carbon atoms, n represents an integer of 0 to 3 .R ⁴ is .R ⁵ representing each independently a straight chain of 1 to 6 carbon atoms, branched or cyclic alkyl group represents a Li.) The naphthalene metal compound according to claim 1, wherein n = 0. A method for producing a naphthalene metal compound represented by general formula (4), comprising reacting a naphthalene enol silyl ether compound represented by general formula (3) with an organolithium compound.

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ³ are each independently a straight-chain having 1 to 18 carbon atoms, branched or cyclic alkyl group, a linear, branched or cyclic alkoxy group having 1 to 18 carbon atoms, n represents an integer of 0 to 3 .R ⁴ is .R ⁵ representing each independently a straight chain of 1 to 6 carbon atoms, branched or cyclic alkyl group represents a Li.) A naphthalene metal represented by the general formula (4), wherein the 1-acylnaphthalene compound represented by the general formula (2) is reacted with a silylating agent in the presence of a base and further an organolithium compound is reacted. Compound production method.

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ³ are each independently a straight-chain having 1 to 18 carbon atoms, branched or cyclic alkyl group, a linear, branched or cyclic alkoxy group having 1 to 18 carbon atoms, n represents an integer of 0 to 3 .R ⁴ is .R ⁵ representing each independently a straight chain of 1 to 6 carbon atoms, branched or cyclic alkyl group represents a Li.) 5. The method for producing a naphthalene metal compound according to claim 3, wherein n = 0. An organometallic reagent comprising a naphthalene metal compound represented by the general formula (4).

(Wherein, ^{R 1} and ^{R 2} are each independently straight-chain alkyl group having a hydrogen atom or a C 1 to C 17, and the total number of carbon atoms of ^{R 1} and ^{R 2} is an integer of 0-17. R ³ are each independently a straight-chain having 1 to 18 carbon atoms, branched or cyclic alkyl group, a linear, branched or cyclic alkoxy group having 1 to 18 carbon atoms, n represents an integer of 0 to 3 .R ⁴ is .R ⁵ representing each independently a straight chain of 1 to 6 carbon atoms, branched or cyclic alkyl group represents a Li.) The organometallic reagent according to claim 6, wherein n = 0.