JP2019119693A - Synthesis method of organoboron compound - Google Patents

Abstract

To construct a technology capable of synthesizing an organoboron compound at high efficiency and low cost simply with less process number, without need for complicated chemical means or agents requiring attention on handling.SOLUTION: There is provided a synthesis method of an organoboron compound having a process for reacting organic chloride and a dispersoid in which sodium is dispersed in a dispersion solvent in a reaction solvent to obtain an organic sodium compound, a process for reacting the resulting organic sodium compound and boron trihalide such as boron trichloride to obtain the organoboron compound.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a method of synthesizing organoboron compounds.

  Organic boron compounds are used in total synthesis of natural products, medicines and pesticides, electronic materials such as liquid crystals and organic EL, and organic synthesis reactions of various functional materials such as intermediates thereof.

For example, various sodium tetraarylborates such as sodium tetraphenylborate serve as a substrate for Suzuki-Miyaura cross coupling and function as a donor of an organic group, as well as a palladium catalyst (Pd (PtBu ₃ ) ₂ ) It has been utilized for various organic synthesis reactions, such as reportedly participating in arylated ring-opening below (for example, nonpatent literature 1). In addition, sodium tetraphenylborate is used as a reagent for determination of potassium, ammonium, rubidium, cesium and the like, and has a wide variety of uses.

Conventionally, sodium tetraphenylborate prepares the corresponding Grignard reagent (R-MgX) from organic halide (RX), which is reacted with sodium tetrafluoroborate (NaBF ₄ ) for about 48 hours, and saturated carbonated It can be obtained by adding sodium aqueous solution and extracting with diethyl ether (see Non-patent Document 1 etc.).

Vasu, Dhananjayan et al., "Palladium-assisted" aromatic metamorphosis "of dibenzothiophenes into triphenylenes., 54 (24), p7162-7166, 2015, Angewandte Chemie International Edition

  Here, the Grignard reagent used in the synthesis process is obtained by reacting an organic halide with metallic magnesium in an anhydrous solvent such as tetrahydrofuran (hereinafter referred to as "THF") or ether. However, conventional methods using Grignard reagents have long reaction times, which increases costs. In addition, since the reactivity in the synthesis of Grignard reagents is generally higher in organic bromide (R-Br) and organic iodide (RI) than organic chloride (R-Cl), etc. Usually, organic bromides or organic iodides have been widely used, but organic bromides and organic iodides are expensive. On the other hand, although organic chlorides are less expensive than other organic halides, their reactivity during synthesis is low, so the yield of the target Grignard reagent tends to decrease. In particular, upon synthesis of an aromatic Grignard reagent, an alkenyl Grignard reagent, etc., it is not possible to synthesize a target Grignard reagent with a high yield, and the yield may be influenced by a substituent on an aromatic ring. Are known. In addition, in the preparation of Grignard reagents which are easily homo-coupled, such as aromatic Grignard reagents, strict temperature control or the like is also required in order to suppress the induction of homo-coupling which causes a decrease in yield. is there. In addition, organic magnesium bromide, which is widely used as a Grignard reagent from the viewpoint of reactivity etc., is a bromine-containing compound, but bromine is limited in the area to be mined and has high toxicity and human persistence etc. Is decreasing. Therefore, there is also a problem that the amount of circulation decreases and it becomes difficult to obtain the target organic bromide. Therefore, the method of using the Grignard reagent in the synthesis process of the organoboron compound can not sufficiently satisfy the market requirements from the industrial and economic viewpoints.

  Therefore, there has been a demand for construction of a technique capable of efficiently and inexpensively synthesizing an organic boron compound using easily available reagents in a small number of steps in a simple and short time without requiring a complicated chemical method.

  As a result of repeated researches to solve the above problems, the present inventors reacted a dispersion obtained by dispersing an organic halide and sodium in a dispersion solvent in a reaction solvent to obtain an organic sodium compound, and subsequently obtained It was found that the organic boron compound can be efficiently synthesized by reacting the selected organic sodium compound and the boron trihalide. Since such a synthesis method uses a dispersion in which sodium is easily dispersed in a dispersion solvent, an organic boron compound can be synthesized under mild conditions. In addition, organic boron compounds can be synthesized inexpensively and in high yield with a small number of processes using easily available reagents, without the need for complicated chemical methods. The present inventors have completed the present invention based on these findings.

That is, the present invention is a method for synthesizing an organoboron compound,
In the reaction solvent, the general formula I (R ¹ -X)
[Wherein, R ¹ represents an aliphatic hydrocarbon group which may have a substituent which does not react with sodium, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, Or an aromatic heterocyclic group, wherein X is a halogen atom] and a reaction in which sodium is dispersed in a dispersion solvent is reacted with
General Formula II (R ¹ -Na)
[Wherein in the formula, R ¹ is the same as R ¹ in formula I] and obtaining an organic sodium compound shown,
The obtained organic sodium compound is reacted with boron trihalide,
General Formula III (NaB (R ¹ ) ₄ )
[Wherein in the formula, R ¹ is the same as R ¹ in formula I] have to obtain an organic boron compound shown, and.

  According to this configuration, it is possible to provide a synthesis method of an organic boron compound which can stably and efficiently synthesize an organic boron compound from an organic halide via an organic sodium compound. According to this configuration, by using a dispersion in which sodium is easy to handle and dispersed in a dispersion solvent, a complicated chemical method is not required under mild conditions, and the number of steps is simple and short. The organic boron compounds can be synthesized inexpensively, which is very advantageous economically and industrially. In particular, the use of sodium dispersion eliminates the need for the addition of saturated aqueous sodium carbonate solution as in the prior art. In addition, since the reaction proceeds under mild conditions, an organosodium compound can be efficiently obtained without inducing a side reaction such as a wurtz reaction in which organic halides are coupled to each other. Can be synthesized in high yield and high purity. In addition, sodium is a technology with excellent sustainability because it is widely distributed on the earth. Also, using inexpensive organic chloride as a starting compound is economically advantageous, and there are no problems such as uneven distribution of the origin of bromine which is a problem in organic bromide and difficulty of obtaining it, There is also no problem such as the need for a high load disposal facility at the time of industrialization. Furthermore, the organic boron compound synthesized by the synthesis method of the organic boron compound of the present configuration can be suitably used for Suzuki-Miyaura coupling etc., and is a dispersion in which sodium used in the present configuration is dispersed in a dispersion solvent The body also has a function as a base during the Suzuki-Miyaura coupling. Therefore, the synthesis method of the organic boron compound of the present configuration can be used in various technical fields such as synthesis of functional materials such as medicines and pesticides and electronic materials.

  Another feature is that the molar ratio of the dispersion of sodium dispersed in the dispersion solvent to the organic halide is 2 or more.

  According to this configuration, by optimizing the use amount of the organic halide and the dispersion in which sodium is dispersed in the dispersion solvent, the organic boron compound can be synthesized with higher efficiency and high purity.

It is a figure which summarizes the synthetic | combination conditions and result of Example 1 which examined the synthesis | combination of the organic boron compound by reaction with the organic sodium compound synthesize | combined using SD and boron trihalide.

  Hereinafter, the synthesis method of the organic boron compound according to the embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described later.

The synthesis method of the organic boron compound according to the present embodiment is shown in the following general formula II by reacting the organic halide shown in the following general formula I with a dispersion in which sodium is dispersed in the dispersion solvent in the reaction solvent. A step of obtaining an organosodium compound (step 1), and a step of reacting the obtained organosodium compound and boron trihalide to obtain an organoboron compound represented by the general formula III (NaB (R ¹ ) ₄ ) And 2).

(Step 1)
Step 1 is a step of reacting an organic halide represented by the following general formula I with a dispersion in which sodium is dispersed in a dispersion solvent to obtain an organic sodium compound represented by the following general formula II in a reaction solvent.

The organic halide according to the present embodiment is an organic compound containing a covalently bonded halogen atom, and is a starting compound in the method for synthesizing the organic boron compound according to the present embodiment. Here, the general formula I showing the organic halide is R ¹ -X, and in the general formula I (R ¹ -X), R ¹ is a fat which may have a substituent which does not react with sodium Group hydrocarbon group, alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, or aromatic heterocyclic group. When it has a substituent having reactivity with sodium, it is not preferable because a dispersion obtained by dispersing the substituent and sodium in a dispersion solvent reacts to induce a side reaction. Therefore, when a compound having a substituent having reactivity with sodium as R ¹ is used as a starting compound, it is necessary to protect the substituent with a suitable protecting group or the like.

  The aliphatic hydrocarbon group may be linear or branched or saturated or unsaturated. Moreover, there is no restriction | limiting in particular also about the chain length. When it has a substituent, the substituent is not particularly limited as long as it does not react with sodium. Also, the number of substituents and the introduction position are not particularly limited. Examples of the aliphatic hydrocarbon group include, but are not limited to, an alkyl group having 1 to 20 carbon atoms, particularly preferably an alkyl group having 3 to 20 carbon atoms, an alkenyl group and an alkynyl group. . Specifically, as the alkyl group, methyl group, ethyl group, propyl group, butyl group, methyl group, ethyl group, propyl group, isopropyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group Group, n-pentyl group, isopentyl group, neopentyl group, t-pentyl group, s-pentyl group, 2-methylbutyl group, 1-ethylpropyl group, 2-ethylpropyl group, n-hexyl group, isohexyl group, neohexyl group T-Hexyl, 2,2-dimethylbutyl, 2-methylpentyl, 3-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1-propylpropyl, n-heptyl, isoheptyl, s-heptyl group, t-heptyl group, 2,2-dimethylpentyl group, 3,3-dimethylpentyl group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 1-ethyl pentyl 2-ethylpentyl group, 3-ethylpentyl group, 1-propylbutyl group, 2-propylbutyl group, n-octyl group, isooctyl group, t-octyl group, neooctyl group, 2,2-dimethylhexyl group, 3 , 3-dimethylhexyl group, 4,4-dimethylhexyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, 1-propylpentyl group, 2-propylpentyl group, 3-propylpentyl group, n-nonyl group, isononyl group, t-nonyl group, 1-methyloctyl group Group, 2-methyloctyl group, 3-methyloctyl group, 4-methyloctyl group, 5-methyloctyl group, 6-methyloctyl group, n-decyl group, isodecyl group, t-decyl group, 1-methylnonyl group, 2-Methylnonyl , 3-methylnonyl group, 4-methylnonyl group, 5-methylnonyl group, 6-methylnonyl group, 7-methylnonyl but group, and the like, not limited thereto. Examples of the alkenyl group include ethenyl group, propenyl group, butenyl group, pentenyl group, hexenyl group, heptenyl group, octenyl group and the like, but are not limited thereto. Examples of the alkynyl group include, but are not limited to, ethynyl group, propynyl group, butynyl group, pentynyl group, heptynyl group, octynyl group and the like.

  The aliphatic hydrocarbon group may have a substituent. The substituents may have one or more, and when having a plurality of substituents, they may be the same or different from each other. As a substituent, an aliphatic hydrocarbon group which may have a substituent, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, an aromatic heterocyclic group, an alkoxy group, cycloalkoxy Group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group and aralkylthio group are alicyclic heterocyclic thio group, aromatic Examples thereof include, but are not limited to, heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocyclic amino group, acyl group and the like. It is not a thing. In addition, as an aliphatic hydrocarbon group, the thing similar to the thing shown above is shown below as an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, and an aromatic heterocyclic group. And the same as the

  The alkoxy group is preferably an alkoxy group having 1 to 10 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group and a hexyloxy group. It is not limited to these. The cycloalkoxy group is preferably a cyclopropoxy group having a carbon number of 3 to 10, and examples thereof include a cyclobutoxy group, a cyclopentyloxy group and a cyclohexyloxy group. The aryloxy group is preferably an aryloxy group having a carbon number of 6 to 20. Specific examples thereof include, but are not limited to, a phenyloxy group and a naphthyloxy group. The aralkyloxy group is preferably an aralkyloxy group having 7 to 11 carbon atoms, and specific examples thereof include a benzyloxy group and a phenethyloxy group. The alicyclic heterocyclic oxy group and the aromatic heterocyclic oxy group include an alicyclic heterocyclic group and an aromatic heterocyclic group which are shown below as a heterocyclic part.

  The alkylthio group is preferably an alkylthio group having 1 to 20 carbon atoms, and examples thereof include methylthio group, ethylthio group, propylthio group, butylthio group, pentylthio group, hexylthio group and the like, but are not limited thereto. . The cycloalkylthio group is exemplified by a cycloalkylthio group having 3 to 10 carbon atoms, and specific examples thereof include a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, a cyclohexylthio group and the like. It is not limited. The arylthio group is preferably an arylthio group having a carbon number of 6 to 20. Specific examples thereof include, but are not limited to, a phenylthio group, a naphthylthio group and the like. The aralkylthio group is preferably, for example, an aralkylthio group having 7 to 11 carbon atoms, and specific examples thereof include, but not limited to, a benzylthio group, a phenethylthio group and the like. The alicyclic heterocyclic thio group and the aromatic heterocyclic thio group include an alicyclic heterocyclic group and an aromatic heterocyclic group which are shown below as a heterocyclic part.

  The alicyclic hydrocarbon group is not particularly limited in the number of ring members, regardless of whether the bond between the ring constituting atoms is saturated or unsaturated. In addition, those having a ring assembly such as a fused ring or a spiro ring as well as a single ring are included. The alicyclic hydrocarbon group is not limited thereto, but is preferably a cycloalkyl group having 3 to 10 carbon atoms, particularly preferably 3 to 7 carbon atoms, preferably 4 to 10 carbon atoms, Particularly preferably, 4 to 7 cycloalkenyl groups are exemplified. Specific examples of the cycloalkyl group include, but are not limited to, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group and the like. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, cyclooctenyl group and the like.

  The alicyclic hydrocarbon group may have a substituent. The substituents may have one or more, and when having a plurality of substituents, they may be the same or different from each other. There is also no particular restriction on the position of the substituent. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.

  The alicyclic heterocyclic group is a non-aromatic heterocyclic group having one or more hetero atoms as ring-constituting atoms. In addition to single rings, those having a ring assembly such as a fused ring or a spiro ring are also included. The bonds between the ring-constituting atoms are either saturated or unsaturated, and the number of ring members is not particularly limited. The hetero atom is not particularly limited as long as it does not react with sodium as a ring member atom. The number of heteroatoms is not particularly limited, and there is no limitation on the position of heteroatoms. As a hetero atom, Preferably, an oxygen atom, a nitrogen atom, a sulfur atom etc. are illustrated. For example, an alicyclic heterocyclic group whose number of carbon atoms is preferably 2 to 7, particularly preferably 2 to 5, and the number of hetero atoms is preferably 1 to 5, particularly preferably 1 to 3. Can be mentioned. In addition, when it has a plurality of hetero atoms, it may be the same type of atoms or different types of atoms. As the alicyclic heterocyclic group, a nitrogen-containing alicyclic heterocyclic group such as a monocyclic 4-membered azetidinyl group, a 5-membered cyclic pyrrolidinyl group, a 6-membered cyclic piperidyl group, a piperazinyl group, etc. Oxygen-containing alicyclic heterocyclic groups such as three-membered cyclic oxiranyl ring, four-membered oxetanyl group, five-membered tetrahydrofuryl group, six-membered tetrahydropyranyl group, etc., single ring Sulfur-containing alicyclic heterocyclic group such as 5-membered cyclic tetrahydrothiophenyl group, nitrogen-containing oxygen alicyclic heterocyclic group such as monocyclic 6-membered cyclic morpholinyl group, monocyclic 6-membered ring Although nitrogen-containing sulfur alicyclic heterocyclic group etc., such as a thiomorpholinyl group, etc. are mentioned, it does not limit to these.

  The alicyclic heterocyclic ring may have a substituent. The substituents may have one or more, and when having a plurality of substituents, they may be the same or different from each other. There is also no particular restriction on the position of the substituent. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.

  The aromatic hydrocarbon group is not particularly limited as long as it has an aromatic ring. In addition to single rings, those having a ring assembly such as a fused ring or a spiro ring are also included. The number of ring members is also not particularly limited. For example, an aromatic hydrocarbon group having preferably 6 to 22 and particularly preferably 6 to 14 carbon atoms can be mentioned. As the aromatic hydrocarbon group, monocyclic 6-membered ring phenyl group, etc., bicyclic naphthyl group, pentalenyl group, indenyl group, azulenyl group etc., tricyclic biphenylenyl group, indasenyl group, acenaphthyrenyl group, fluorenyl group Group, phenalenyl group, phenanthryl group, anthryl group etc., tetracyclic fluorantenyl, aceanthrenyl group, triphenylenyl group, pyrenyl group, naphthacenyl group etc., pentacyclic perylenyl group, tetraphenylenyl etc., hexacyclic Examples thereof include pentacenyl group of the formula, heptacyclic rubicenyl group, coronenyl group, heptacenyl group and the like, but not limited thereto. Particularly preferred is a phenyl group.

  The aromatic hydrocarbon group may have a substituent. The substituents may have one or more, and when having a plurality of substituents, they may be the same or different from each other. There is also no particular restriction on the position of the substituent. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group. Particularly preferred is an alkyl group such as a normal nonyl group.

  The aromatic heterocyclic group is an aromatic heterocyclic group having one or more hetero atoms as ring-constituting atoms. In addition to single rings, those having a ring assembly such as a fused ring or a spiro ring are also included. The number of ring members is also not particularly limited. The hetero atom is not particularly limited as long as it does not react with sodium as a ring member atom. The number of heteroatoms is not particularly limited, and there is no limitation on the position of heteroatoms. As a hetero atom, Preferably, an oxygen atom, a nitrogen atom, a sulfur atom etc. are illustrated. For example, an aromatic heterocyclic group in which the number of carbon atoms is preferably 1 to 5, particularly preferably 3 to 5, and the number of heteroatoms is preferably 1 to 4, particularly preferably 1 to 3 is It can be mentioned. In addition, when it has a plurality of hetero atoms, it may be the same type of atoms or different types of atoms.

  For example, as a monocyclic aromatic heterocyclic group, a nitrogen-containing aromatic ring such as a 5-membered cyclic pyrrolyl group, pyrazolyl group, pyridyl group, imidazolyl group, etc., a 6-membered cyclic pyrazinyl group, pyrimidinyl group, pyridazinyl group, etc. -Containing heterocyclic group, oxygen-containing aromatic heterocyclic group such as 5-membered cyclic furyl group, oxygen-containing aromatic heterocyclic group such as 5-membered cyclic thienyl group, 5-membered cyclic oxazolyl group, isoxazolyl group, Examples thereof include nitrogen-containing oxygen aromatic heterocyclic groups such as frazanyl groups, and nitrogen-containing sulfur aromatic heterocyclic groups such as 5-membered cyclic thiazolyl groups and isothiazolyl groups, but are not limited thereto.

  As the polycyclic aromatic heterocyclic group, bicyclic indolizinyl group, isoindolyl group, indolyl group, indazolyl group, indazolyl group, purinyl group, isoquinolyl group, quinolyl group, phthalazinyl group, naphthyridinyl group, quinoxalinyl group, quinazolinyl group, cinnorinyl group And nitrogen-containing aromatic heterocyclic groups such as tricyclic carbazolyl group, carbazolyl group, carborinyl group, phenathridinyl group, acridinyl group, perimidinyl group, phenanthrolinyl group, phenazinyl group, etc., bicyclic benzofuranyl group, isobenzofuranyl group A sulfur-containing aromatic heterocyclic group such as an oxygen-containing aromatic heterocyclic group such as a nyl group and a benzopyranyl group, a bicyclic benzothienyl group and the like, a tricyclic thianthrenyl group and the like, and a bicyclic benzoxazolyl group Nitrogen-containing oxygen aromatic heterocyclic group such as benzoisoxazolyl group, bicyclic benzothiazolyl group, Nitrogen-containing sulfur aromatic heterocyclic groups such as nzisothiazolyl group and tricyclic phenothiazinyl group, and oxygen-containing sulfur aromatic heterocyclic groups such as tricyclic phenoxatyinyl group etc. It is not limited to these.

  The aromatic heterocyclic group may have a substituent. The substituents may have one or more, and when having a plurality of substituents, they may be the same or different from each other. There is also no particular restriction on the position of the substituent. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.

X is a halogen atom, specifically a chlorine atom, a bromine atom, an iodine atom or a fluorine atom, preferably a chlorine atom or a fluorine atom. Therefore, as the organic halide represented by the general formula I, an organic halide represented by the general formula I ^a [R ¹ -Cl] or the general formula I ^b [R ¹ -F] can be preferably used. It is thus economically more advantageous to use cheap organic chlorides as starting compounds. In addition, there is no problem of uneven distribution of origin of the raw material of the raw material which is a problem in organic bromide which is a kind of organic halide, difficulty in obtaining, etc., the necessity of high load disposal facility at the time of industrialization There is no problem.

  As the organic halides which are the starting compounds, those commercially available may be used, or those produced by methods known in the art may be used.

  A dispersion in which sodium is dispersed in a dispersion solvent (hereinafter sometimes abbreviated as “SD” which is an abbreviation of Sodium Dispersion) is a dispersion of sodium as fine particles in an insoluble solvent, or sodium as a liquid It is dispersed in an insoluble solvent in the state. Examples of sodium include metallic sodium and alloys containing metallic sodium. The average particle size of the fine particles is preferably less than 10 μm, and particularly preferably less than 5 μm. The average particle size was represented by the diameter of a sphere having a projected area equivalent to the projected area obtained by image analysis of a photomicrograph.

  As a dispersion solvent, a solvent known in the art can be used as long as sodium can be dispersed as fine particles or sodium can be dispersed in a liquid state in an insoluble solvent and the reaction between the starting compound organic halide and SD is not inhibited. Can be used. Examples thereof include aromatic solvents such as xylene and toluene, normal paraffin solvents such as normal decane, heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof.

  As SD, it is preferable to use one having an activity such that the yield of phenyl sodium is 99.0% or more based on chlorobenzene added when the reaction is carried out in a reaction solvent at 2.1 molar equivalents or more with respect to chlorobenzene. By using such highly active SD, organic boron compounds can be synthesized more efficiently. In order to maintain the activity of SD high, it is preferable to store in a container with high gas barrier properties such as a glass vial. However, storage in a container with low gas barrier properties is not excluded, and in that case, it is used immediately, for example, within several weeks, preferably within 3 weeks after production of SD.

  As the reaction solvent in step 1, solvents known in the art can be used as long as they do not inhibit the reaction of the starting compound organic halide with SD. For example, ether solvents, paraffin solvents such as normal paraffin type and cyclo paraffin types, aromatic solvents, amine solvents, heterocyclic compound solvents can be used. As the ether solvent, a cyclic ether solvent is preferable, and tetrahydrofuran (hereinafter sometimes abbreviated as “THF”) can be preferably used. As the paraffin solvents, cyclohexane, normal hexane, normal decane and the like are particularly preferable. As the aromatic solvent, xylene, toluene, benzene and the like can be preferably used. Ethylenediamine etc. can be preferably used as an amine solvent. Tetrahydrothiophene etc. can be utilized as a heterocyclic compound solvent. Moreover, only 1 type may be used for these, and it can also be used as a mixed solvent combining 2 or more types. Here, the above-mentioned dispersion solvent and reaction solvent may be of the same type or different types.

The reaction temperature in step 1 is not particularly limited when a paraffinic solvent is used as the solvent, and can be appropriately set according to the type and amount of the starting compound organic halide, SD and the reaction solvent, the reaction pressure, etc. . Specifically, the reaction temperature is preferably set to a temperature that does not exceed the boiling point of the reaction solvent. The reaction temperature can be set at a high temperature because the pressure is higher than the boiling point under atmospheric pressure. The reaction can also be carried out at room temperature, preferably 0-100 ° C., particularly preferably 20-80 ° C., more preferably room temperature to 50 ° C. Although there is no need to provide temperature control means for special heating or cooling, etc., temperature control means may be provided if necessary. On the other hand, when a solvent other than paraffinic solvent is used, low temperature, preferably around 0 ° C., to prevent reaction of the solvent with phenyl sodium etc. which is a suitable example of R ¹ -Na produced in the reaction of Step 1. Good to do. Here, by adding the organic halide and equimolar equivalent of THF, it is possible to effectively suppress the formation of biphenyl and maintain a good reaction rate. Therefore, the target compound can be efficiently synthesized by appropriately controlling the type and addition amount of the reaction solvent.

  The reaction time of step 1 is also not particularly limited, and may be appropriately set according to the type and amount of the starting compound organic halide, SD, and the reaction solvent, the reaction pressure, the reaction temperature, and the like. Usually, it is carried out for 15 minutes to 24 hours, preferably for 20 minutes to 6 hours.

The step 1 is suitable to be carried out under atmospheric pressure and normal pressure conditions since reagents such as SD and reaction solvents can be stably handled under the atmosphere. However, since phenyl sodium, which is a preferable example of R ¹ -Na to be produced, is highly active and is protonated by moisture when air is mixed in even a little, it is filled with argon gas, nitrogen gas, etc. as necessary. You may carry out under inert gas atmosphere.

General formula II which shows the organosodium compound obtained by the step 1 is R ¹ -Na, wherein the halogen atom of the organic halide shown in the general formula I (R ¹ -X) which is the starting compound is substituted by sodium is there. Thus, in the general formula II (R ¹ -Na), R ¹ is the same as R ¹ of the general formula I as described above, Na is sodium atom. The obtained organic sodium compound may be purified by purification means known in the art such as column chromatography, distillation, recrystallization and the like. In addition, the organic halide which is the unreacted and remaining starting compound may be recovered, and may be configured to be subjected to the reaction of Step 1 again. The reaction may be performed in an inert gas atmosphere filled with argon gas, nitrogen gas or the like as in the production.

(Step 2)
Step 2 is a step of reacting the organosodium compound represented by the above general formula II obtained by the step 1 with boron trihalide to obtain an organoboron compound represented by the following general formula III of the final target compound.

  As boron trihalide, although boron trichloride, boron trifluoride, boron tribromide, boron triiodide and the like can be used, boron trichloride is preferable.

Boron trichloride (BCl ₃ ) is a compound in which three chlorine atoms are covalently bonded to a boron atom, and is a compound exhibiting strong Lewis acidity. Since boron trichloride has a boiling point of about 12 ° C., it becomes a gas at normal temperature. Therefore, boron trichloride can be selected from ether solvents such as diethyl ether, halogenated hydrocarbon solvents such as carbon tetrachloride and dichloromethane, paraffin solvents such as normal hexane and normal heptane, and aromatic solvents such as xylene and toluene. Or the like dissolved in a suitable solvent such as.

  As boron trihalides such as boron trichloride, those commercially available may be used, or those produced by methods known in the art may be used.

  Step 2 may be performed by adding a boron trihalide such as boron trichloride to the reaction product obtained by step 1, or the reaction product obtained by step 1 may be purified by methods known in the art. The reaction may be carried out by adding a boron trihalide such as boron trichloride in the presence of a reaction solvent. As the reaction solvent, the same one as in Step 1 can be used.

The reaction temperature in step 2 is not particularly limited when a paraffinic solvent is used as a reaction solvent, and can be appropriately set according to the type and amount of organic sodium compound, SD and reaction solvent, reaction pressure and the like. Specifically, the reaction temperature is preferably set to a temperature that does not exceed the boiling point of the reaction solvent. The reaction temperature can be set at a high temperature because the pressure is higher than the boiling point under atmospheric pressure. The reaction can also be carried out at room temperature, preferably 0-100 ° C., particularly preferably 20-80 ° C., more preferably room temperature to 50 ° C. Although there is no need to provide temperature control means for special heating or cooling, etc., temperature control means may be provided if necessary. On the other hand, when a solvent other than paraffinic solvent is used, low temperature, preferably around 0 ° C., to prevent reaction of the solvent with phenyl sodium etc. which is a suitable example of R ¹ -Na produced in the reaction of Step 1. Good to do.

  The reaction time of step 2 is also not particularly limited, and is appropriately set according to the type and amount of organic sodium compound, SD, boron trihalide such as boron trichloride, and reaction solvent, reaction pressure, reaction temperature, etc. do it. The reaction is usually performed for 5 minutes to 2 hours, preferably 10 minutes to 1 hour.

  In addition, it is necessary to carry out step 2 in an inert gas atmosphere filled with argon gas, nitrogen gas or the like from the viewpoint of handling of boron trihalide and the like. Moreover, it is preferable to perform the process 2 by the continuous system using a glass lining container, a microreactor, etc. to which corrosion resistance was provided.

By the reaction of step 2, an organic boron compound represented by the general formula III (NaB (R ¹ ) ₄ (Na ⁺ B ⁻ (R ¹ ) ₄ )) of the desired final target compound can be obtained.

In the organoboron compound represented by the general formula III (NaB (R ¹ ) ₄ ), four substituents R ¹ derived from sodium of the organosodium compound represented by the general formula II (R ¹ -Na) are covalently bonded to a boron atom Together with sodium derived from the organosodium compound shown in the general formula II (R ¹ -Na). Thus, in general formula III, R ¹ corresponds to R ¹ in general formula I and general formula II described above, and Na corresponds to sodium in general formula II derived from SD. As the organic boron compound represented by the general formula III, sodium tetraarylborate can be particularly preferably mentioned.

  The reaction scheme in the method of synthesizing the organoboron compound according to the present embodiment is summarized below.

Reaction scheme
R ¹ -X + SD → R ¹ -Na (Step 1)
_{^{4R 1 -Na + BCl 3 → NaB}} (R 1) 4 (Na + B - (R 1) 4) + 3NaCl ( Step 2)

The amounts of SD and boron trichloride used in the method of synthesizing the organic boron compound according to this embodiment can be appropriately set according to the types and amounts of the starting compound and the reaction solvent. Preferably, the organic halide: SD molar ratio is reacted in an amount of 1: 2 or more. More preferably, the reaction is performed at 1: 2 or more and 3 or less. Further, the molar ratio of boron trichloride: R ¹ -Na is preferably reacted to be 1: 4 or more and 6 or less. More preferably, the reaction is carried out at 1: 4 or more and 5 or less. By reacting in this amount, organic boron compounds can be synthesized with high efficiency and high purity. Here, the amount of substance of SD means the amount of substance in terms of alkali metal contained in SD.

  The organoboron compound finally synthesized in the method of synthesizing the organoboron compound according to this embodiment may be purified by a purification means known in the art such as recrystallization. In addition, it may be configured to recover the organic halide and the organic sodium compound and the like remaining unreacted and to be used again for the synthesis of the organic boron compound.

  In the method of synthesizing the organoboron compound according to the present embodiment, the organoboron compound can be stably and efficiently synthesized by using SD. By using SD which is easy to handle, the organic boron compound can be easily and inexpensively synthesized in a short time with a small number of steps, under mild conditions, without the need for complicated chemical methods, so that the economy is economical. And industrially very advantageous. Sodium is a technology with excellent sustainability because it is widely distributed on the earth. On the other hand, when solid metallic sodium is used, the reaction temperature is low at room temperature, and the reaction is required to be carried out at a high temperature such as the melting point (98 ° C.) of metallic sodium. By conducting the reaction at such a high temperature, the Wurtz reaction in which organic halides are coupled is induced, the organic sodium compound can not be synthesized efficiently, and the yield of the organic boron compound is lowered. In addition, if solid metallic sodium is added, it is assumed that a severe local reaction with anomalous heat generation will occur around the solid metallic sodium in the reaction system, so that a side reaction such as a homocoupling reaction is induced. Ru. On the other hand, by using SD, the reaction can be allowed to proceed under mild conditions, and SD can be uniformly dispersed in the reaction system as a fluid, thereby inducing a side reaction such as Wurtz reaction. It is possible to efficiently obtain the organosodium compound, and thus to synthesize the organoboron compound in high yield and high purity.

  The organic boron compound synthesized by the method for synthesizing the organic boron compound of the present embodiment can be suitably used for Suzuki-Miyaura coupling and the like. The Suzuki-Miyaura coupling is a reaction of a palladium catalyst and an organic boron compound in the presence of a base, and it is necessary to add a base separately in the reaction. That is, by adding a base, the carbon-boron bond of the organoboron compound is activated, and the palladium-catalyzed reaction proceeds only when such an activated state is achieved. With regard to the base, SD added in the method for synthesizing an organic boron compound according to this embodiment can play a role as a base required for Suzuki-Miyaura coupling as sodium hydroxide, and a base addition step It is economically and industrially advantageous also in that it is not necessary to provide it separately. Thus, the synthesis method of the organic boron compound according to the present embodiment can be used in various technical fields such as synthesis of functional materials such as medicines and pesticides and electronic materials.

  EXAMPLES Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples. As SD in the following examples, a dispersion in which metallic sodium is dispersed as fine particles in normal paraffin oil is used, and the substance mass of SD is a numerical value in terms of metallic sodium contained in SD.

(Example 1) Synthesis of organoboron compound by reaction of organosodium compound synthesized using SD and boron trihalide In this example, the synthesis was performed using SD under the synthesis conditions summarized in FIG. The synthesis of organoboron compounds by the reaction of organosodium compounds and boron trichloride compounds was studied.

(Experiment No. 1)
In 2 ml of hexane, 4.0 molar equivalents of chlorobenzene (2.0 mmol) and 8.4 molar equivalents of SD were reacted at 25 ° C. for 30 minutes to obtain phenyl sodium. Subsequently, 1.0 molar equivalent of a solution of boron trichloride in hexane (1 M in hexane = 0.5 mmol = 0.5 ml) is added to the produced phenyl sodium and reacted at -78 ° C for 1 hour, then reacted at 25 ° C for 1 hour To obtain sodium tetraarylborate. Evaluation of the synthesized sodium tetraarylborate was performed by measurement by ¹ H NMR. The yield was calculated by showing the ratio of sodium tetraarylborate actually obtained to sodium tetraarylborate which can be theoretically generated from boron trichloride added to the reaction system as a percentage. The yield was 22%.

(Experiment No. 2)
In 2 ml of hexane, 4.0 molar equivalents of chlorobenzene (2.0 mmol) and 8.4 molar equivalents of SD were reacted at 25 ° C. for 30 minutes to obtain phenyl sodium. Subsequently, after cooling to −78 ° C., 1.0 molar equivalent of a boron trichloride solution in hexane (1 M in hexane = 0.5 mmol = 0.5 ml) and 1 ml of THF were sequentially added to the formed phenyl sodium to give 3.5 ml of THF The mixture was reacted in hexane / THF (= 2.5 ml / 1 ml) for 1 hour and then at 25 ° C. for 1 hour to obtain sodium tetraarylborate. Evaluation of the synthesized sodium tetraarylborate was performed by measurement by ¹ H NMR. The yield was calculated in the same manner as in Experiment No. 1 above. The yield was 54%.

(Experiment No. 3)
In 2.5 ml of hexane, 5.0 molar equivalents of chlorobenzene (2.5 mmol) and 10.5 molar equivalents of SD were reacted at 25 ° C. for 30 minutes to obtain phenyl sodium. Subsequently, after cooling to −78 ° C., 1.0 mol equivalent of boron trichloride in hexane (1 M in hexane = 0.5 mmol = 0.5 ml) and then THF 1 ml were sequentially added to the formed phenyl sodium to give 4 ml of THF The mixture was reacted in hexane / THF (= 3 ml / 1 ml) for 1 hour and then at 25 ° C. for 1 hour to obtain sodium tetraarylborate. Evaluation of the synthesized sodium tetraarylborate was performed by measurement by ¹ H NMR. The yield was calculated in the same manner as in Experiment No. 1 above. The yield was 70%.

(Experiment No. 4)
In 2.5 ml of hexane, 5.0 molar equivalents of chlorobenzene (2.5 mmol) and 10.5 molar equivalents of SD were reacted at 25 ° C. for 30 minutes to obtain phenyl sodium. Subsequently, after cooling to −78 ° C., 1.0 mol equivalent of boron trichloride in hexane (1 M in hexane = 0.5 mmol = 0.5 ml) and then THF 1 ml were sequentially added to the formed phenyl sodium to give 4 ml of THF The mixture was reacted in hexane / THF (= 3 ml / 1 ml) for 1 hour and then at 25 ° C. for 3 hours to obtain sodium tetraarylborate. Evaluation of the synthesized sodium tetraarylborate was performed by measurement by ¹ H NMR. The yield was calculated in the same manner as in Experiment No. 1 above. The yield was 77%.

(Experiment No. 5)
In 2.5 ml of hexane, 5.0 molar equivalents of 4-chlorotoluene (2.5 mmol) and 10.5 molar equivalents of SD were reacted at 25 ° C. for 30 minutes to obtain 4-methylphenyl sodium. Subsequently, after cooling to −78 ° C., 1.0 molar equivalent of a boron trichloride solution in hexane (1 M in hexane = 0.5 mmol = 0.5 ml) and 1 ml of THF are sequentially added to the formed 4-methylphenyl sodium The mixture was reacted in 4 ml of hexane / THF (= 3 ml / 1 ml) for 1 hour and then at 25 ° C. for 3 hours to obtain sodium tetraarylborate. Evaluation of the synthesized sodium tetraarylborate was performed by measurement by ¹ H NMR. The yield was calculated in the same manner as in Experiment No. 1 above. The yield was 80%.

  From the results of the above experiment numbers 1 to 5, sodium tetraarylborate can be obtained from chlorobenzene via phenyl sodium, and synthesis of sodium tetraarylborate can be performed with particularly high yield by optimizing the synthesis conditions. It can be understood that it is possible.

  The present invention relates to a synthesis method of an organoboron compound, and all technical fields utilizing the organoboron compound synthesized by such a synthesis method, in particular, preferably as an intermediate of coupling reaction such as Suzuki-Miyaura coupling. It can be used and is particularly useful in the field of manufacturing of medical and agricultural chemicals and electronic materials.

Claims (2)

A method of synthesizing an organoboron compound, comprising
In the reaction solvent, the general formula I (R ¹ -X)
[Wherein, R ¹ represents an aliphatic hydrocarbon group which may have a substituent which does not react with sodium, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, Or an aromatic heterocyclic group, and X is fluorine or chlorine, and a reaction in which sodium is dispersed in a dispersion solvent is reacted with
General Formula II (R ¹ -Na)
[Wherein in the formula, R ¹ is the same as R ¹ in formula I] and obtaining an organic sodium compound shown,
The obtained organic sodium compound is reacted with boron trihalide,
General Formula III (NaB (R ¹ ) ₄ )
[Here, in the formula, R ¹ of the general formula a is same as R ¹ of I] to obtain an organic boron compound shown, has a city, a method of synthesizing an organic boron compound.   The method for synthesizing an organic boron compound according to claim 1, wherein the molar ratio of the dispersion of the sodium dispersed in the dispersion solvent to the organic halide is 2 or more.

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