JP5423212B2 - Method for producing aminoazaboracyclopentene compound - Google Patents

Description

  The present invention relates to a method for producing an aminoazaboracyclopentene (aminoazaborol) compound. Azaboracyclopentene compound is a compound useful as a metal complex ligand for metal-containing thin film formation, polymerization catalyst, medicine, agricultural chemicals, etc., and as a polymerization catalyst, it can be used as a polymerization catalyst for olefins. It is disclosed (for example, see Patent Document 1).

  Conventionally, as a method for producing an aminoazaboracyclopentene compound, a method of synthesis using dibutyltin dichloride is known (for example, see Non-Patent Documents 1 to 3).

Japanese Patent Laid-Open No. 9-110917

Organometallics, 2004, 23, 5626 Organometallics, 2008, 27, 2408 Organometallics, 2002, 21, 4323

  The conventional method using an organic tin compound has a problem that the yield can be improved only by using an expensive metal, and an industrial tin compound having an extremely high toxicity must be used. There was a problem as a manufacturing method.

  The object of the present invention is to solve the above-mentioned problems, and in a method using a specific dihalogeno metal compound, the aminoazaboracyclopentene compound is produced in a high yield via a specific intermediate (novel compound). It is to provide a manufacturing method.

  The subject of the present invention is that the general formula (1)

General formula (1)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms.)
And an alkoxyazaboracyclopentene compound represented by the general formula (2)

(Wherein, ^{R 6} and ^{R 7} are a linear or branched alkyl group having 1 to 9 carbon atoms, ^{M a} represents a monovalent metal atom. In addition, ^{R 6} and ^{R 7} are bonded to each other to form a ring May be formed.)
A reaction with an organometallic amide compound represented by the general formula (3):

（式中、Ｒ^１〜Ｒ^４、Ｒ^６及びＲ^７は前記と同義である。）
で示されるアミノアザボラシクロペンテン化合物の製造方法によって解決される。

(In the formula, R ^{1 to} R ⁴ , R ⁶ and R ⁷ are as defined above.)
It solves by the manufacturing method of the aminoazaboracyclopentene compound shown by these.

  According to the present invention, a method for producing an azaboracyclopentene compound can be provided in a high yield by a method using an inexpensive and less toxic metal. The azaboracyclopentene compound is a useful compound as a metal complex ligand for forming a metal-containing thin film, for a polymerization catalyst, for medicine, for agricultural chemicals, and the like.

  The present invention is to provide a novel method for producing an alkoxyazaboracyclopentene compound. The reaction of the present invention comprises the following three reaction steps.

(1) General formula (4)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. Show.)
Allylamine dilithio compound represented by the general formula (5)

(In the formula, M ^b represents a divalent metal atom, and Y represents a halogen atom.)
Is reacted with a dihalogeno metal compound represented by the general formula (6)

(Wherein R ^{1 to} R ⁴ and M ^b are as defined above.)
A reaction step for producing an azametallacyclopentene compound represented by (hereinafter referred to as a cyclization reaction step).

(2) General formula (6)

(Wherein R ^{1 to} R ⁴ and M ^b are as defined above.)
Azametallacyclopentene compound represented by the general formula (7)

(In the formula, X represents a halogen atom.)
And a trihalogenoboron represented by the general formula (8)

(In the formula, R ⁵ represents a linear or branched alkyl group having 1 to 5 carbon atoms.)
Is reacted with an ether represented by the general formula (1)

(In the formula, R ^{1 to} R ⁵ are as defined above.)
A reaction step for producing an alkoxyazaboracyclopentene compound represented by (hereinafter referred to as a boron exchange reaction step).

(3) General formula (1)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms.)
And an alkoxyazaboracyclopentene compound represented by the general formula (2)

(Wherein, ^{R 6} and ^{R 7} are a linear or branched alkyl group having 1 to 9 carbon atoms, ^{M a} represents a monovalent metal atom. In addition, ^{R 6} and ^{R 7} are bonded to each other to form a ring May be formed.)
A reaction with an organometallic amide compound represented by the general formula (3):

(In the formula, R ^{1 to} R ⁴ , R ⁶ and R ⁷ are as defined above.)
A production method of a method for producing an aminoazaboracyclopentene compound represented by (hereinafter referred to as an amination step).

(1) Cyclization reaction step The allylamine dilithio salt used in the cyclization reaction step of the present invention is represented by the general formula (4). In the general formula (4), R ¹ represents a linear or branched alkyl group having 1 to 5 carbon atoms. Specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl A linear or branched alkyl group having 1 to 5 carbon atoms, such as a group, an n-butyl group, an isobutyl group, a tert-butyl group, and an n-pentyl group. R ^{2 to} R ⁴ represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. Specific examples include a hydrogen atom; a methyl group, an ethyl group, and n-propyl. A linear or branched alkyl group having 1 to 5 carbon atoms such as a group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group.

  The allylamine dilithio compound is obtained by reacting allylamine (or a salt thereof) with an organolithium compound (see, for example, Non-Patent Document 4). Examples of the organic lithium compound include methyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium, and the like. Preferably, n-butyllithium is used. In addition, you may use these lithium compounds individually or in mixture of 2 or more types.

  In addition, as the allylamine dilithium compound, once synthesized, it can be used after isolation or synthesized in the reaction system, and when ethers are used as a solvent during the synthesis, You may use as it is as a substrate of a boron exchange reaction process, without removing from a reaction liquid.

The dihalogeno metal compound used in the cyclization reaction step of the present invention is used in the general formula (5). In the general formula (5), ^Mb is a divalent metal atom (including a monoalkylated trivalent metal atom), for example, zinc, magnesium, iron, copper, monoalkylaluminum. Zinc and magnesium are preferable. Y is a halogen atom, for example, a fluorine atom, a chlorine atom, an iodine atom, or a bromine atom.

  The amount of the dihalogeno metal compound to be used is preferably 0.5 to 1.5 mol, more preferably 0.8 to 1.2 mol, with respect to 1 mol of allylamine dilithio.

  The cyclization reaction step of the present invention is preferably carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, diethyl ether, tetrahydrofuran, dimethoxyethane, dioxane, etc. Ethers; aliphatic hydrocarbons such as hexane, cyclohexane, and methylcyclohexane; aromatic hydrocarbons such as toluene and xylene are exemplified, and ethers are preferably used, and diethyl ether and tetrahydrofuran are more preferably used. These solvents may be used alone or in admixture of two or more. When ethers are used, the next boron exchange reaction step is required unless the ethers are removed from the reaction solution after completion of the reaction. It can also be used as a reaction substrate.

  Although the usage-amount of the said solvent is suitably adjusted with the uniformity of a reaction liquid, stirring property, etc., Preferably it is 0.5-100g with respect to 1g of allylamine dilithio bodies, More preferably, it is 3-30g.

  The cyclization reaction step of the present invention is performed, for example, by a method of mixing an allylamine dilithio compound, a dihalogeno metal compound and a solvent and reacting them with stirring. The reaction temperature at that time is preferably −78 to 50 ° C., more preferably −10 to 40 ° C., and the reaction pressure is not particularly limited.

  In addition, as a method of using the allylamine dilithio compound prepared in the reaction system as it is, after synthesizing an allylamine dilithio compound by reacting allylamine (or a salt thereof) with an organolithium compound, a dihalogeno metal compound is then synthesized. And a method of reacting by adding a solvent or a method of separately reacting an allylamine dilithio compound obtained by reacting allylamine (or a salt thereof) with an organolithium compound in a dihalogeno metal compound and a solvent. It is done.

  The azametallacyclopentene compound obtained by the cyclization reaction step of the present invention has the general formula (1)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. shown, ^{M b} represents a divalent metal atom.)
It is a compound shown by these.

  The azametallacyclopentene compound obtained by the cyclization reaction step of the present invention can be used in the boron exchange reaction step as it is after it has been synthesized or isolated in the reaction system.

(2) Boron exchange reaction step The trilogenoboron used in the boron exchange reaction of the present invention is represented by the general formula (7). In the general formula (7), X represents a halogen atom, and is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. The ether compound is represented by the general formula (8). In the general formula (8), R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms. Specifically, for example, methyl group, ethyl group, n-propyl group, isopropyl A linear or branched alkyl group having 1 to 5 carbon atoms, such as a group, n-butyl group, sec-butyl group, tert-butyl group and n-pentyl group;

  The amount of the trihalogenoboron used is preferably 0.5 to 1.5 mol, more preferably 0.8 to 1.2 mol, per 1 mol of the azametallacyclopentene compound.

  The boron exchange reaction step of the present invention is performed, for example, by a method in which an azametallacyclopentene compound, trihalogenoboron (if necessary, a solvent solution thereof) and an ether compound are mixed and reacted with stirring. The reaction temperature at that time is preferably −78 to 50 ° C., more preferably −30 to 40 ° C., and the reaction pressure is not particularly limited.

  The target alkoxyazaboracyclopentene compound is obtained by the boron exchange reaction of the present invention. After completion of the reaction, it is isolated by a known method such as neutralization, extraction, filtration, concentration, distillation, recrystallization, column chromatography and the like. -Purified.

  In the present invention, in the case where the cyclization reaction step and the boron exchange step are carried out continuously, as a preferred embodiment, for example, a lithium compound, allylamine and a solvent are mixed to synthesize a solution containing an allylamine dilithio compound. Then, a dihalogeno metal compound (a solvent solution thereof if necessary) is reacted to prepare a solution containing an azametallacyclopentene compound in the reaction system. Furthermore, a method for producing an alkoxyazaboracyclopentene compound by adding and reacting trihalogenoboron (if necessary, a solvent solution thereof) and an ether compound represented by the general formula (8) to the reaction solution can be mentioned.

  In a more preferred embodiment, a lithium compound, allylamine, and an ether compound (which function as a solvent in the cyclization reaction step (that is, do not participate in the reaction) and act as a reaction substrate in the boron exchange reaction step) are mixed and mixed. After synthesizing a solution containing a thio compound (a solution containing an ether compound as a solvent), then reacting a dihalogeno metal compound (a solvent solution thereof if necessary) to contain a azametallacyclopentene compound in the reaction system (an ether compound) Is prepared as a solvent. Furthermore, a method of producing an alkoxyazaboracyclopentene compound by adding trihalogenoboron (if necessary, a solvent solution thereof) to the reaction solution and reacting with the ether compound remaining in the previous reaction step can be mentioned.

  That is, in the cyclization reaction step, the ether compound in the present invention can be used as a part of the solvent (for example, a mixed solvent of an ether compound and an aliphatic hydrocarbon) in the case of a solvent or a mixed solvent. In addition, it is desirable that the type of ether compound to be reacted is the same in order to produce a single alkoxyazaboracyclopentene compound.

  Furthermore, an ether compound can also be used as a solvent when synthesizing the allylamine dilithio compound that is the raw material compound of the present invention, and the boron compound is left in the boron exchange reaction step through the cyclization reaction step while the ether compound remains. It can also be used as a reaction substrate.

  In addition, the alkoxyazaboracyclopentene compound obtained by the boron exchange reaction step of the present invention can be used once in the amination reaction step after being synthesized or isolated in the reaction system.

(3) Amination process The organometallic amide compound used in the amination process of the present invention is:
It is shown in the general formula (2). In the general formula (2), R ⁶ and R ⁷ represent a linear or branched alkyl group having 1 to 9 carbon atoms, such as a methyl group, ethyl group, n-propyl group, isopropyl group, n- Examples thereof include a butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, a hexyl group, a heptyl group, an octyl group, and a nonyl group. Further, the M ^a represents a monovalent metal atom, for example, lithium atom, sodium atom, may be mentioned as potassium atom, preferably a lithium atom.

  As a specific example of the metal compound, for example, lithium alkylamide is preferably used. In addition, you may use these organometallic compounds in mixture of 2 or more types.

  The amount of the organometallic amide compound used in the amination step of the present invention is preferably 0.5 to 1.5 mol, more preferably 0.8 to 1.2 mol, relative to 1 mol of the alkoxyazaboracyclopentene compound. It is.

  The step of the present invention is preferably carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane, dioxane and the like; Aliphatic hydrocarbons such as hexane, cyclohexane and methylcyclohexane; aromatic hydrocarbons such as toluene and xylene are mentioned, preferably ethers, more preferably diethyl ether and tetrahydrofuran. In addition, you may use these solvents individually or in mixture of 2 or more types.

  Although the usage-amount of the said solvent is suitably adjusted with the uniformity of a reaction liquid, stirring property, etc., Preferably it is 0.5-100g with respect to 1g of allylamine dilithio bodies, More preferably, it is 3-30g.

  The amination step of the present invention is performed, for example, by a method of mixing an alkoxyazaboracyclopentene compound, an organometallic amide compound and a solvent and reacting them with stirring. The reaction temperature at that time is preferably −78 to 50 ° C., more preferably −30 to 40 ° C., and the reaction pressure is not particularly limited.

  The target aminoazaboracyclopentene compound can be obtained by the amination process of the present invention, but is isolated by a known method such as neutralization, extraction, filtration, concentration, distillation, recrystallization, column chromatography, etc. after completion of the reaction. -Purified.

  The aminoazaboracyclopentene compound, which is the object of the present invention, and the azametallacyclopentene compound and alkoxyazaboracyclopentene compound, which are synthetic intermediates thereof, are often not always stable against moisture and oxygen in the atmosphere. Therefore, it is desirable to carry out the reaction, operation, post-treatment, etc. under anhydrous conditions or inert gas conditions.

  In addition, when each reaction step can maintain continuity, the three steps can be performed continuously without isolating and purifying the intermediate obtained in each step. Specifically, By using an ether compound composed of an alkoxy group introduced in the boron exchange reaction step as a solvent for the three steps, all steps can be performed continuously, and the aminoazaboracyclopentene compound that is the final product Can be efficiently manufactured.

  Examples of the aminoazaboracyclopentene compound produced by the present invention include compounds represented by the following formulas (9) to (18).

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Example 1 (Synthesis of 4-tert-butyl-3-diisopropylamino-4-aza-3-boracyclopentene (compound (23)))
(Synthesis of tert-butylamine dilithio compound)
The reaction solution was maintained at around 0 ° C. in a mixed solution of 2.3 g (20 mmol) of tert-butylallylamine and 20 ml of diethyl ether under an argon atmosphere in a 100-ml flask equipped with a stirrer, thermometer and dropping funnel. Then, a 1.6 mol / l n-butyllithium hexane solution (25 ml (40 mmol) was slowly added dropwise. Then, the reaction solution was allowed to react for 20 hours with stirring to 25 ° C. (at this point, tert-butylamine diyl). A diethyl ether solution of tert-butylamine dilithio compound was prepared by adding 50 ml of diethyl ether to the reaction solution.

(Reaction step 1: cyclization reaction step)
A solution prepared by dissolving 6.4 g (20 mmol) of anhydrous zinc iodide in 25 ml of diethyl ether in an argon atmosphere was added to a 200-ml flask equipped with a stirrer, a thermometer, and a dropping funnel. -A solution of a diethyl ether solution of butylamine dilithio compound was slowly added dropwise at 0 ° C, and the reaction solution was allowed to react for 2 hours while stirring the reaction solution (at this time, 4-tert-butyl-4-aza-3 -Zincacyclopentene is produced.)

(Reaction process 2: boron exchange reaction process)
Next, 20 ml of a hexane solution of 5.0 g (20 mmol) of tribromoborane was gently added dropwise to the reaction solution while maintaining the temperature of the reaction solution at around −30 ° C., and reacted at 25 ° C. for 2 hours with stirring. . After completion of the reaction, the reaction solution was filtered in an argon atmosphere, the filtrate was concentrated, and the concentrate was distilled under reduced pressure (100 ° C., 6.6 kPa) to give 4-tert-butyl-3-ethoxy- as a colorless liquid. 2.1 g of 4-aza-3-boracyclopentene was obtained (isolation yield; 63%).
4-tert-Butyl-3-ethoxy-4-aza-3-bolacyclopentene was a novel compound represented by the following physical property values.

¹ H-NMR (DMSO-d ₆ , δ (ppm)); 1.20 (3H, t), 1.28 (9H, s), 3.65 (2H, m), 3.95 (2H, q ), 6.02 (1H, m), 7.03 (1H, m)
MS (m / z); 167

(Reaction step 3: amination step)
In a 10-ml flask equipped with a stirrer, thermometer and dropping funnel, 0.17 g (1.0 mmol) of tert-butyl-3-ethoxy-4-aza-3-boracyclopentene and 5 ml of diethyl ether were added under an argon atmosphere. While maintaining the reaction solution at around 0 ° C., 1.0 ml (1.0 mmol) of a 1.0 mol / l lithium diisopropylamide / diethyl ether solution was slowly added dropwise to the mixed solution. Subsequently, it was made to react to 25 degreeC for 2 hours, stirring a reaction liquid. After completion of the reaction, the obtained reaction solution was concentrated under reduced pressure, and 5 ml of hexane was added to the concentrate and stirred. Thereafter, the mixture was filtered in an argon atmosphere, and the obtained filtrate was concentrated, and then the concentrate was distilled under reduced pressure (100 ° C., 66 kPa) to give 4-tert-butyl-3-diisopropylamino-4-aza as a colorless liquid. 0.20 g of -3-boracyclopentene was obtained (isolation yield; 90%).

  The physical properties of 4-tert-butyl-3-diisopropylamino-4-aza-3-boracyclopentene were as follows.

^{_{1 H-NMR (C 6 H}} 6 -d 6, δ (ppm)); 1.23 (12H, d), 1.33 (9H, s), 3.65 (2H, m), 3.71 ( 2H, quint) 6.42 (1H, m), 6.73 (1H, m)
MS (m / z); 222

  From the above results, the allylamine dilithio compound of the present invention is reacted with a dihalogeno metal compound containing a divalent metal atom, and further via azametallacyclopentene compound containing a divalent metal atom, further trihalogeno boron and It has been found that an alkoxyazaboracyclopentene compound can be produced by reacting an ether compound, and an aminoazaboracyclopentene compound can be produced by reacting it with an organometallic amide compound as a raw material.

  The present invention relates to a method for producing an aminoazaboracyclopentene compound. An aminoazaboracyclopentene compound is a useful compound as a metal complex ligand, for example, for forming a metal-containing thin film, for a polymerization catalyst, for pharmaceuticals, and for agricultural chemicals.

Claims (5)

General formula (1)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms.)
And an alkoxyazaboracyclopentene compound represented by the general formula (2)

(In the formula, ^{R 6} and ^{R 7} are a linear or branched alkyl group having 1 to 9 carbon atoms, ^{M a} lithium atom, a sodium atom or a potassium atom. Note that, ^{R 6} and ^{R 7} are bound to each other And may form a ring.)
A reaction with an organometallic amide compound represented by the general formula (3):

(In the formula, R ^{1 to} R ⁴ , R ⁶ and R ⁷ are as defined above.)
The manufacturing method of the aminoazaboracyclopentene compound shown by these. General formula (6)

(In the formula, R ¹ represents a linear or branched alkyl group having 1 to 5 carbon atoms , R ^{2 to} R ⁴ represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. shown, ^{M b} is zinc, magnesium or monoalkyl aluminum.)
Azametallacyclopentene compound represented by the general formula (7)

(In the formula, X represents a halogen atom.)
And a trihalogenoboron represented by the general formula (8)

(In the formula, R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms.)
Is reacted with an ether represented by the general formula (1)

(In the formula, R ^{1 to} R ⁵ are as defined above.)
The manufacturing method of the azaboracyclopentene compound of Claim 1 which manufactures the alkoxyazaboracyclopentene compound shown by these. General formula (4)

(In the formula, R ¹ is a linear or branched alkyl group having 1 to 5 carbon atoms, R ^{2 to} R ⁴ are a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. Show.)
Allylamine dilithio compound represented by the general formula (5)

(In the formula, M ^b represents zinc, magnesium or monoalkylaluminum , and Y represents a halogen atom.)
Is reacted with a dihalogeno metal compound represented by the general formula (6)

(Wherein R ^{1 to} R ⁴ and M ^b are as defined above.)
The manufacturing method of the azabolacyclopentene compound of Claim 2 which manufactures the azametallacyclopentene compound shown by these. General formula (4)

(In the formula, R ¹ represents a linear or branched alkyl group having 1 to 5 carbon atoms , R ^{2 to} R ⁴ represent a hydrogen atom or a linear or branched alkyl group having 1 to 5 carbon atoms. Show. )
Allylamine dilithio compound represented by the general formula (5)

(In the formula, M ^b represents zinc, magnesium or monoalkylaluminum , and Y represents a halogen atom.)
A dihalogeno metal compound represented by the general formula (8):

(In the formula, R ⁵ represents a linear or branched alkyl group having 1 to ⁵ carbon atoms .)
And then reacting in a solvent containing an ether compound represented by the general formula (7)

(In the formula, X represents a halogen atom.)
Is reacted with a trihalogenoboron represented by the general formula (1)

(In the formula, R ^{1 to} R ⁵ are as defined above.)
The manufacturing method of the azaboracyclopentene compound of Claim 1 which manufactures the alkoxyazaboracyclopentene compound shown by these. The method for producing an azaboracyclopentene compound according to claim 1, wherein M ^a is a lithium atom .