JP2021120361A - Method for synthesizing carboxylic acid compound - Google Patents

Abstract

To provide a technique capable of easily, simply synthesizing carboxylic acid compounds at a few numbers of process without using a device needing a cumbersome temperature control, safety management or the like, expensive reagents or those needing cautions in handling.SOLUTION: There is provided a method capable of synthesizing a carboxylic acid compound by reacting a multiple bond-including organic compound with carbon dioxide in a reaction solvent under the existence of a dispersing element in which an alkali metal is dispersed in a dispersion solvent.SELECTED DRAWING: Figure 1

Description

The present invention relates to a method for synthesizing a carboxylic acid compound.

_{Reducing the emission of carbon dioxide (hereinafter sometimes abbreviated as "CO 2} "), which accounts for the majority of greenhouse gases that are a factor in global warming, is an urgent issue. While suppressing the amount of such CO ₂ generated, there is an increasing need to build a CO _{2 immobilization technology that fixes CO 2} contained in the atmosphere and in the exhaust gas emitted from power plants and factories. Various techniques have been studied as CO ₂ immobilization techniques, including, for example, _{a chemical immobilization method in which CO 2} is converted into a useful organic compound and effectively utilized.

However, since CO ₂ is a chemically inactive compound, its use as a carbon resource is currently limited. Therefore, if such CO ₂ can be used for the synthesis of organic compounds useful as organic synthetic materials, it will be important from the viewpoint of the development of new carbon resources and the development of organic synthesis reaction methods.

For example, various methods for synthesizing carboxylic acid compounds from _{CO 2 have been studied.} Patent Document 1 reports that a carboxy group can be introduced by reacting 9,9'-bifluorenylidene in diethyl ether with carbon dioxide in the presence of elemental sodium metal at room temperature.

Here, the carboxylic acid compound is a general term for organic compounds having a carboxy group, and the carboxy group refers to natural substances such as biomolecules such as amino acids and fatty acids, and electrons such as pharmaceuticals, pesticides, liquid crystals and organic EL. It is an atomic group that is often contained in the molecular structure of a functional substance such as a material, and the compound described in Patent Document 1 is also an intermediate of a compound that induces an endogenous apoptosis signal transduction pathway useful as an anticancer agent or the like. Further, the carboxy group can induce various atomic groups such as amides, esters and acyl halides by substituting its hydroxyl group with another atom, and such atomic groups are also included in the molecular structure of many natural substances and functional substances. Included in. Therefore, the construction of carboxylic acid compound synthesis technology can contribute to various technical fields such as life science research, drug discovery research, and electronic material research.

U.S. Patent Application Publication No. 2017/0105963

However, the technique described in Patent Document 1 required 48 hours for the reaction, and the yield was as low as 33%. In addition, in general, when a simple substance of metal such as simple substance of metallic sodium is put into the reaction system, the temperature distribution in the reaction system becomes uneven due to local heat generation or the like, and the reaction conditions are generally stabilized. Difficult.

Therefore, the CO ₂ is constructed of CO ₂ fixation technology for stably and efficiently converted to useful organic compounds utilized as the carbon resource being sought.

As a result of repeated studies to solve the above problems, the present inventors contain multiple bonds in the molecular structure in the presence of a dispersion in which an alkali metal such as sodium is dispersed in a dispersion solvent in the reaction solvent. It has been found that by reacting an organic compound with CO ₂ , a carboxy group can be introduced into the organic compound and a carboxylic acid compound can be synthesized. Such a method for synthesizing a carboxylic acid compound can _{stably and efficiently convert an organic compound and CO 2} into a carboxylic acid compound without causing local heat generation or the like. The present inventors have completed the present invention based on these findings.

That is, the present invention is a method for synthesizing a carboxylic acid compound, which is characterized by a multiple bond-containing organic compound and carbon dioxide in the presence of a dispersion in which an alkali metal is dispersed in a dispersion solvent in a reaction solvent. The point is that a carboxylic acid compound is synthesized by reacting.

According to this configuration, a carboxylic acid compound can be synthesized by introducing a carboxy group derived from _{CO 2} into the organic compound containing multiple bonds in the molecule. Further, according to this configuration, by using a dispersion in which an alkali metal is dispersed in a dispersion solvent, complicated temperature control and safety control are not required, and care must be taken in expensive reagents and handling. Carboxylic acid compounds can be synthesized without the need for reagents. Therefore, it is economically and industrially very advantageous because the carboxylic acid compound can be synthesized inexpensively and stably by using reagents that are easily available and handled. Since alkali metals, particularly sodium and the like are metals that are extremely widely distributed on the earth, the method for synthesizing the carboxylic acid compound having this constitution is also excellent in sustainability. The method of synthesizing carboxylic acid compound of the present arrangement, the CO ₂ is CO ₂ fixation technology of converting into useful organic compound used as a carbon resource, it is also useful as the utilization technologies of novel carbon resources. In addition, the method for synthesizing the carboxylic acid compound of this constitution is total synthesis of natural products, organic synthesis of medical and agricultural chemicals, electronic materials such as liquid crystals and organic EL, and organic synthesis of a wide variety of functional materials such as intermediates thereof. It can be used for reactions and the like.

Another characteristic configuration is to synthesize the carboxylic acid compound according to claim 1, wherein the multiple bond-containing organic compound is an organic compound whose multiple bonds are reduced by Birch reduction.

According to this configuration, CO can be added to organic compounds that can be targeted for birch reduction, such as organic compounds having double bonds, organic compounds having triple bonds, organic compounds having aromatic rings, and heterocyclic compounds containing multiple bonds. _{By introducing a carboxy group derived from 2, the} corresponding carboxylic acid compound can be synthesized stably and efficiently.

Another characteristic configuration is that the multiple bond-containing organic compound is stilbene, and diphenylsuccinic acid is synthesized by reacting stilbene with carbon dioxide.

According to this configuration, diphenylsuccinic acid can be stably and efficiently synthesized from stilbene.

It is a figure which summarizes the synthesis condition and result of Example 1 which examined the synthesis method (synthesis from stilbene) of a carboxylic acid compound.

Hereinafter, the method for synthesizing the carboxylic acid 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 method for synthesizing a carboxylic acid compound according to the present embodiment is a method for synthesizing a carboxylic acid by reacting a multiple bond-containing organic compound with CO _{2 in the presence of a dispersion in which an alkali metal is dispersed in a dispersion solvent.} It includes a step of synthesizing a compound.

The multiple bond-containing organic compound is a compound containing one or more multiple bonds in the molecule, and is a starting compound of the method for synthesizing a carboxylic acid compound according to the present embodiment. Here, the multiple bond means that the chemical bond between adjacent atoms is due to a multiple bond such as a double bond or a triple bond. When two or more multiple bonds are included, both double bonds and triple bonds, etc. are included even if they contain two or more multiple bonds of the same type, such as those containing two or more double bonds or triple bonds. It may contain different types of multiple bonds, such as. Examples of the atom forming the multiple bond include a carbon atom, a nitrogen atom, an oxygen atom, and the like, but the atom is not particularly limited. Therefore, a multiple bond is formed between the same adjacent atoms such as between carbon atoms, or between different atoms such as between carbon atoms and nitrogen atoms. It may be a thing.

The multiple bond-containing organic compound is preferably a compound that can be the target of Birch reduction. For example, it accepts electrons from an alkali metal derived from a dispersion in which an alkali metal is dispersed in a dispersion solvent and is in a semi-stable state as a radical anion. It is preferably a compound that can exist. Specific examples thereof include an organic compound having a double bond, a compound having a triple bond, an organic compound having an aromatic compound, and an organic compound having a heterocyclic compound containing a multiple bond.

Examples of the multiple bond-containing organic compound include compounds represented by the general formula I. The compound represented by the general formula I shows an example in which one multiple bond is involved in the introduction of a carboxy group derived from _{CO 2, but the compound contains two or more multiple bonds in the molecule, and the multiple bonds thereof are included.} Those in which all or part of the _{compound is involved in the introduction of a carboxy group derived from CO 2} may also be included as a multiple bond-containing organic compound.

In general formula I

Indicates a multiple bond that bonds between adjacent atoms X ^a and X ^b, and is exemplified by a double bond or a triple bond.

X ^a and X ^b are adjacent atoms forming a multiple bond, and are not particularly limited as long as a multiple bond can be formed between them, but they are independently carbon atoms, nitrogen atoms, or oxygen atoms, respectively. Is exemplified. X ^a and X ^b may be the same atom or different atoms. Preferably, ^{both X a} and X ^b are carbon atoms.

R ^a and R ^b independently have an aliphatic hydrocarbon group which may have a substituent which does not react with a hydrogen atom and an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, and an aromatic group. Group hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group. , Arylthio group, Aralkylthio group is an alicyclic heterocyclic thio group, an aromatic heterocyclic thio group, an alkylamino group, a cycloalkylamino group, an arylamino group, an aralkylamino group, an alicyclic heterocyclic amino group, an aromatic. Group heterocyclic amino group or silyl group. Having a substituent that is reactive with sodium is not preferable because the substituent and the dispersion in which the alkali metal is dispersed in a dispersion solvent react with each other to induce a side reaction. Therefore, when a multiple bond-containing organic compound having a substituent having reactivity with an alkali metal is used as a starting compound, it is necessary to protect the substituent with an appropriate protecting group or the like.

Aliphatic hydrocarbon groups may be linear or branched, saturated or unsaturated. In addition, there is no particular limitation on the chain length. When it has a substituent, the substituent is not particularly limited as long as it does not react with sodium. Further, the number of substituents and the introduction position are not particularly limited. Examples of the aliphatic hydrocarbon group are not limited to these, but preferably 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. ..

Specific examples of the aliphatic hydrocarbon group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group and 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 group, 2,2-dimethylbutyl group, 2-methylpentyl group, 3-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1-propylpropyl group, n-heptyl group, isoheptyl group, 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 group, 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, 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 Examples thereof include, but are not limited to, a group, a 2-methylnonyl group, a 3-methylnonyl group, a 4-methylnonyl group, a 5-methylnonyl group, a 6-methylnonyl group, and a 7-methylnonyl group. Examples of the alkenyl group include, but are not limited to, an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group and the like. Examples of the alkynyl group include, but are not limited to, an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a heptynyl group, an octynyl group and the like.

The aliphatic hydrocarbon group may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Examples of the substituent include 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, a halogen atom and an alkoxy group. , Cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group are alicyclic heterocyclic thio group. , Aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocyclic amino group, silyl group and the like. It is not limited to. The aliphatic hydrocarbon group is the same as that shown above, and is an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, an aromatic heterocyclic group, a halogen atom, or an alkoxy group. , Cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group are alicyclic heterocyclic thio groups. , Aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocyclic amino group, silyl group are shown below. The same can be mentioned.

The alicyclic hydrocarbon group has no particular limitation on the number of ring members, regardless of whether the bonds between the ring-constituting atoms are saturated or unsaturated. Further, not only a single ring but also one having a ring set such as a condensed ring or a spiro ring is included. The alicyclic hydrocarbon group is not limited to these, 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, cycloalkynyl groups and the like are exemplified. Specific examples of the cycloalkyl group include, but are not limited to, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group and the like. Examples of the cycloalkenyl group include, but are not limited to, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group and the like. Further, examples of the cycloalkynyl group include, but are not limited to, a cyclooctynyl group and the like.

The alicyclic hydrocarbon group may have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

The alicyclic heterocyclic group is a non-aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only monocyclic rings but also those having a ring set such as a fused ring and a spiro ring are included. The number of ring members is not particularly limited regardless of whether the bond between the ring-constituting atoms is saturated or unsaturated. The hetero atom is not particularly limited as long as it does not react with sodium as a ring-constituting atom. The number of heteroatoms is not particularly limited, and the positions of heteroatoms are also not limited. As the hetero atom, preferably, an oxygen atom, a nitrogen atom, a sulfur atom and the like are exemplified. For example, an alicyclic heterocyclic group having a carbon atom number of preferably 2 to 7, particularly preferably 2 to 5, and a heteroatom number of preferably 1 to 5, particularly preferably 1 to 3. Can be mentioned. When it has a plurality of heteroatoms, it may be an atom of the same type or an atom of a different type. Examples of the alicyclic heterocyclic group include a nitrogen-containing alicyclic heterocyclic group such as a monocyclic 4-membered ring-type azetidinyl group, a 5-membered ring-type pyrrolidinyl group, a 6-membered ring-type piperidyl group, and a piperazinyl group. Oxygen-containing alicyclic heterocyclic groups such as three-membered ring-type oxylanyl groups, four-membered ring-type oxetanyl groups, five-membered ring-type tetrahydrofuryl groups, and six-membered ring-type tetrahydropyranyl groups, monocyclic Sulfur-containing alicyclic heterocyclic groups such as 5-membered tetrahydrothiophenyl groups, nitrogen-containing oxygen-containing alicyclic heterocyclic groups such as monocyclic 6-membered ring morpholinyl groups, and monocyclic 6-membered ring-type Examples thereof include a nitrogen-containing sulfur alicyclic heterocyclic group such as a thiomorpholinyl group, but the present invention is not limited thereto.

The alicyclic heterocycle may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

The aromatic hydrocarbon group is not particularly limited as long as it has an aromatic ring. Not only monocyclic rings but also those having a ring set such as a fused ring and a spiro ring are included. There is no particular limitation on the number of members. For example, an aromatic hydrocarbon group having preferably 6 to 22 carbon atoms, particularly preferably 6 to 14 carbon atoms can be mentioned. Examples of the aromatic hydrocarbon group include a monocyclic six-membered ring phenyl group, a bicyclic naphthyl group, a pentarenyl group, an indenyl group, an azulenyl group, and the like, a tricyclic biphenylenyl group, an indacenyl group, an acenaphthylenyl group, and a fluorenyl group. Group, phenalenyl group, phenanthryl group, anthryl group, etc., tetracyclic fluoranthenyl, acetylenyl group, triphenylenyl group, pyrenyl group, naphthacenyl group, etc., pentacyclic perylenel group, tetraphenylenyl group, etc. Examples thereof include, but are not limited to, a pentasenyl group of the formula, a rubicenyl group of the seven-ring type, a coronenyl group, a heptasenyl group and the like. Particularly preferably, it is a phenyl group.

The aromatic hydrocarbon group may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

An aromatic heterocyclic group is an aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only monocyclic rings but also those having a ring set such as a fused ring and a spiro ring are included. There is no particular limitation on the number of members. The hetero atom is not particularly limited as long as it does not react with sodium as a ring-constituting atom. The number of heteroatoms is not particularly limited, and the positions of heteroatoms are also not limited. As the hetero atom, preferably, an oxygen atom, a nitrogen atom, a sulfur atom and the like are exemplified. For example, an aromatic heterocyclic group having a carbon atom number of preferably 1 to 5, particularly preferably 3 to 5, and a heteroatom number of preferably 1 to 4, particularly preferably 1 to 3. Can be mentioned. When it has a plurality of heteroatoms, it may be an atom of the same type or an atom of a different type.

For example, as the monocyclic aromatic heterocyclic group, a nitrogen-containing fragrance such as a five-membered cyclic pyrrolyl group, pyrazolyl group, pyridyl group, imidazolyl group, etc., and a six-membered cyclic pyrazinyl group, pyrimidinyl group, pyridadinyl group, etc. Group heterocyclic group, oxygen-containing aromatic heterocyclic group such as 5-membered frill group, oxygen-containing aromatic heterocyclic group such as 5-membered thienyl group, 5-membered oxazolyl group, isooxazolyl group, Examples thereof include, but are not limited to, a nitrogen-containing oxygen-containing aromatic heterocyclic group such as a frazanyl group, a nitrogen-containing sulfur-containing sulfur aromatic heterocyclic group such as a five-membered ring-type thiazolyl group, and an isothiazolyl group.

The polycyclic aromatic heterocyclic group includes a bicyclic indridinyl group, an isoindryl group, an indrill group, an indazolyl group, a prynyl group, an isoquinolyl group, a quinolyl group, a phthalazinyl group, a naphthyldinyl group, a quinoxalinyl group, a quinazolinyl group, and a cinnolinyl group. Group, etc., tricyclic carbazolyl group, carbolinyl group, phenatridinyl group, acridinyl group, perimidinyl group, phenanthrolinyl group, phenazinyl group and other nitrogen-containing aromatic heterocyclic groups, bicyclic benzofuranyl group, isobenzofla Oxygen-containing aromatic heterocyclic groups such as nyl group and benzopyranyl group, sulfur-containing aromatic heterocyclic groups such as bicyclic benzothenyl group, tricyclic thiantranyl group, bicyclic benzoxazolyl group, etc. Nitrogen-containing oxygen aromatic heterocyclic groups such as benzoisooxazolyl groups, nitrogen-containing sulfur aromatic heterocyclic groups such as bicyclic benzothiazolyl groups, benzoisothiazolyl groups, and tricyclic phenothiazinyl groups, tricyclics. Examples thereof include oxygen-containing sulfur-containing aromatic heterocyclic groups such as the phenoxatiinyl group of the formula, but the present invention is not limited thereto.

The aromatic heterocyclic group may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

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 3 to 10 carbon atoms, and examples thereof include a cyclobutoxy group, a cyclopentyloxy group, and a cyclohexyloxy group. The aryloxy group is preferably an aryloxy group having 6 to 20 carbon atoms, and 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. Examples of the alicyclic heterocyclic oxy group and the aromatic heterocyclic oxy group include the alicyclic heterocyclic group and the aromatic heterocyclic group shown above as the heterocyclic portion. In addition, these may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

The alkylthio group is preferably an alkylthio group having 1 to 20 carbon atoms, and examples thereof include, but are not limited to, a methylthio group, an ethylthio group, a propylthio group, a butylthio group, a pentylthio group, and a hexylthio group. .. Examples of the cycloalkylthio group include a cycloalkylthio group having 3 to 10 carbon atoms, and specific examples thereof include a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, and a cyclohexylthio group. It is not limited. The arylthio group is preferably an arylthio group having 6 to 20 carbon atoms, and specific examples thereof include, but are not limited to, a phenylthio group and a naphthylthio group. The aralkylthio group is preferably an aralkylthio group having 7 to 11 carbon atoms, and specific examples thereof include, but are not limited to, a benzylthio group and a phenethylthio group. Examples of the alicyclic heterocyclic thio group and the aromatic heterocyclic thio group include the alicyclic heterocyclic group and the aromatic heterocyclic group shown above as the heterocyclic portion. In addition, these may further have a substituent. The substituents may have one or more, and when they have a plurality of substituents, they may be the same or different from each other. Further, the position of the substituent is not particularly limited. Examples of the substituent include those exemplified as the substituent of the aliphatic hydrocarbon group, and the same ones.

The silyl group has 1 to 3 aliphatic hydrocarbon groups, alicyclic hydrocarbon groups, alicyclic heterocyclic groups, aromatic hydrocarbon groups, aromatic heterocyclic groups and other substituents on silicon. It is the basis of the value. Examples of the substituent of the aliphatic hydrocarbon group, the alicyclic hydrocarbon group, the alicyclic heterocyclic group, the aromatic hydrocarbon group, the aromatic heterocyclic group and the like include the same as those described above. Specific examples thereof include, but are not limited to, a dimethylsilyl group, a diphenylsilyl group, a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a dimethyl-t-butylsilyl group, a diphenyl-t-butylsilyl group and the like. No.

R ^a and R ^b may be the same group or different groups.

R ^a and R ^b may be combined with each other to form a ring. Therefore, the multiple bond may form a part of the ring. The ^{ring formed by the bond between R a} and R ^b is not particularly limited, and examples thereof include a pyridine ring and a pyrazine ring.

Further, R ^a and R ^b may be located at the cis position with respect to the double bond when the multiple bond connecting the adjacent atoms X ^a and X ^{b is a double bond.} Further, it may be located at the transformer position. Further, R ^a and R ^b may be located at the cis position or at the trans position with respect to the ring plane when ^{R a} and R ^{b are coupled to each other to form a ring.} You may. Therefore, in the general formula I etc., ^{the bond between R a} and X ^a and the bond between R ^{b and} X ^b are represented by wavy lines, but this indicates that there is no particular limitation on the absolute configuration. There is.

Specific examples of the multiple bond-containing organic compound include, but are not limited to, stilbene, styrene, pyrazine, and pyridine.

As the multiple bond-containing organic compound, a commercially available compound may be used, or a compound produced by a method known in the art may be used.

In the method for synthesizing a carboxylic acid compound according to the present embodiment, CO ₂ is separated and recovered from a medium containing _{CO 2} such as atmospheric gas and exhaust gas emitted from _{CO 2} emission sources such as thermal power plants and factories. Can be used. It is also possible to use CO ₂ from dry ice or a CO _{2 cylinder.} Therefore, the method for synthesizing a carboxylic acid compound _{can be used as a CO 2} immobilization technique and can contribute to global environmental conservation.

From the viewpoint of preventing side reactions, CO ₂ is preferably dehydrated before being subjected to the reaction, and from the viewpoint of safety management, it is preferable to use CO 2 containing as little oxygen as possible.

The dispersion in which the alkali metal used in the method for synthesizing the carboxylic acid compound according to the present embodiment is dispersed in a dispersion solvent is a dispersion in which the alkali metal is dispersed as fine particles in an insoluble solvent, or an alkali metal is dispersed in an insoluble solvent in a liquid state. It is dispersed in. Examples of the alkali metal include sodium, potassium, lithium and alloys containing these metals. The average particle size of the fine particles is preferably less than 100 μm, particularly preferably less than 50 μm, further preferably less than 30 μm, still more 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 micrograph.

Hereinafter, a dispersion in which an alkali metal is dispersed in a dispersion solvent may be abbreviated as “SD”. SD is an abbreviation for Sodium Dispersion, and is designated as SD because a dispersion using sodium as an alkali metal is used in the examples described below. However, the SD code does not exclude alkali metals other than sodium.

The concentration of the alkali metal contained in SD is also not particularly limited, and examples thereof include those having a concentration of 5 wt% or more and 30 wt% or less.

As the dispersion solvent, a solvent known in the art can be used as long as the alkali metal can be dispersed as fine particles or the alkali metal can be dispersed in an insoluble solvent in a liquid state. For example, mineral oils such as normal paraffin solvents such as normal decane, normal hexane, normal heptane, and normal pentane, aromatic solvents such as xylene and toluene, heterocyclic solvent such as tetrahydrothiophene, or mixed solvents thereof. And so on.

It is preferable to use SD having an activity in which the yield of phenylsodium with respect to the added chlorobenzene is 99.0% or more when the reaction is carried out in a reaction solvent in an amount of 2.1 molar equivalent or more with respect to chlorobenzene. , Patent No. 6449527). By using such a highly active SD, the carboxylic acid compound can be synthesized more efficiently. In order to maintain high SD activity, it is preferable to store it in a container having a high gas barrier property such as a glass vial. However, it does not exclude storage in a container having a low gas barrier property, and in that case, it is used immediately after the production of SD, for example, within a few weeks, preferably within 3 weeks.

In the method for synthesizing a carboxylic acid compound according to the present embodiment, as the solvent used as the reaction solvent, a solvent known in the art can be used as long as the reaction of the method is not inhibited. In particular, an aprotic polar solvent is preferred. For example, a nitrogen-containing heterocyclic solvent, an ether solvent, a paraffin solvent such as normal paraffin or cycloparaffin, an aromatic solvent, an amine solvent, or a heterocyclic compound solvent can be used. As the nitrogen-containing heterocyclic solvent, 1,3-dimethyl-2-imidazolidinone (hereinafter, may be abbreviated as "DMI") or the like can be preferably used. As the ether solvent, a cyclic ether solvent is preferable, and tetrahydrofuran (hereinafter, may be abbreviated as "THF") or the like can be preferably used. As the paraffin solvent, cyclohexane, normal hexane, normal decane and the like are particularly preferable. As the aromatic solvent, xylene, toluene, benzene and the like are preferable. As the amine solvent, ethylenediamine or the like can be preferably used. As the heterocyclic compound solvent, tetrahydrothiophene or the like can be used. In addition, only one of these may be used, or two or more of these may be used in combination as a mixed solvent. In particular, it is preferable to use an aprotic solvent because the dianion generated by the reaction of the multiple bond-containing organic compound with SD may extract protons from the reaction solvent, and DMI can be particularly preferably used. Although highly soluble THF can be used, when THF is used, it is preferable to set the reaction temperature to 30 ° C. or lower in order to suppress the decomposition of the reaction solvent. Here, the same type of dispersion solvent and reaction solvent may be used, or different types may be used.

The reaction temperature in the method for synthesizing the carboxylic acid according to the present embodiment is not particularly limited, and can be appropriately set depending on the type and amount of the starting compound, the multiple bond-containing organic compound, SD and the reaction solvent, the 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. Under pressure, the reaction temperature can be set at a high temperature because it is higher than the boiling point under atmospheric pressure. The reaction can also be carried out at room temperature, preferably 0 to 100 ° C, more preferably 0 to 80 ° C, still more preferably 0 to 50 ° C. Particularly preferably, it can be carried out at 30 ° C. or lower from the viewpoint of efficiently dissolving _{CO 2.} By reacting at 30 ° C. or lower in this way, _{the solubility of gas such as CO 2} is improved, and the reaction solvent such as THF is less likely to be decomposed, so that there is an advantage that side reactions are less likely to occur. Further, in the reaction, it is not necessary to provide special temperature control means for heating, cooling, etc., but temperature control means may be provided if necessary.

The reaction time in the method for synthesizing the carboxylic acid compound according to the present embodiment is also not particularly limited, and depends on the types and amounts of the starting compound, the multiple bond-containing organic compound, SD and the reaction solvent, as well as the reaction pressure and reaction temperature. It may be set appropriately. It is usually carried out for 5 minutes to 24 hours, preferably 10 minutes to 6 hours.

As a general rule, the method for synthesizing the carboxylic acid compound according to the present embodiment is preferably carried out in an inert gas atmosphere filled with argon gas, nitrogen gas or the like.

The method for synthesizing a carboxylic acid compound according to the present embodiment can be carried out in a reactor having a large blade such as a full zone blade or a max blend blade. By carrying out the reaction in such a reactor, the solubility of a gas such as carbon dioxide is improved, and the power input density can be lowered, so that there is an advantage that the temperature of the reactant can be prevented from rising.

In the method for synthesizing the carboxylic acid compound according to the present embodiment, the amount of SD and the multiple bond-containing organic compound used should be appropriately set according to the type and amount of SD, the multiple bond-containing organic compound, the reaction solvent, and the like. Can be done. In terms of molar equivalent ratio, SD is preferably reacted in an amount of 2 or more, more preferably 2 or more, and 4 or less with respect to the multiple bond 1 to be introduced into the carboxy group. Therefore, the amount of SD used is preferably determined depending on the molar equivalent of the multiple bond-containing organic compound and the number of multiple bonds to be introduced into the carboxy group contained in one molecule of the multiple bond-containing organic compound. For example, assuming that the number of multiple bonds to be introduced into the carboxy group contained in the multiple bond-containing organic compound is y, the molar equivalent ratio of the multiple bond-containing organic compound: SD is preferably 1: 2 × y or more. The reaction is preferably 1: 2 × y or more and 1: 4 × y or less. By reacting in this amount, the carboxylic acid compound can be synthesized stably and efficiently. On the other hand, if the amount of SD becomes too large, post-processing of the SD remaining after the reaction is required, which may complicate the operation. Here, the amount of substance of SD means the amount of substance in alkali metal equivalent contained in SD.

In the method for synthesizing a carboxylic acid compound according to the present embodiment _{, CO 2} is introduced into the multiple bond-containing organic compound as a carboxy group by reacting the _{multiple bond-containing organic compound as a starting compound with CO 2 in the presence of SD.} The carboxylic acid compound is obtained.

In the method for synthesizing a carboxylic acid compound according to the present embodiment, the carboxylic acid compound is a compound containing one or more carboxy groups in the molecule. The number of carboxy groups contained in the carboxylic acid compound is not particularly limited, and for example, a monocarboxylic acid compound containing one carboxy group, a dicarboxylic acid compound containing two carboxy groups, and a tricarboxylic acid containing three carboxy groups. Examples include compounds.

The introduction of the carboxy group into the multiple bond-containing organic compound may be introduced into both adjacent atoms forming the multiple bond, or may be introduced into one of them. Further, one carboxy group may be introduced into one atom, or two or more carboxy groups may be introduced. The introduction of a carboxy group may reduce the degree of unsaturation of the multiple bond, such as the triple bond being converted to a double bond or a single bond, the double bond being converted to a single bond, and so on. It may exist in the molecule as it is without changing the degree of unsaturation.

When the unsaturated bond-containing compound is the compound represented by the above general formula I, for example, the carboxylic acid compound represented by the general formula II can be obtained.

In general formula II

Is a chemical bond that bonds between adjacent atoms X ^a and X ^b , indicating a single bond or a multiple bond, and examples thereof include a single bond or a double bond.

X ^a and X ^b in the general formula II is the general formula represents a X ^a and X ^b and same atoms I, also, R ^a and R ^b in the general formula II, and of the general formula I R ^a and R ^b Represents the same group. n ^a and n ^b are, for example, an integer of 0 to 2 independently when the chemical bond that bonds ^{X a} and X ^{b is a single bond, and the chemical bond that bonds X a} and X ^b. Is an integral number of 0 to 1 when is a double bond, and in any case ^{at least one of n a} and n ^b is an integer of 1 or more. Therefore, the carboxy group may be introduced into at least one or both of ^{X a} and X ^b.

Further, when the obtained carboxylic acid compound is a dicarboxylic acid compound into which 2 carboxy groups have been introduced, the introduced 2 carboxy groups have two chemical bonds that bond between ^{adjacent atoms X a} and X ^b. In the case of a double bond, it may be located at the cis position or the trans position with respect to the double bond. When R ^a and R ^b are bonded to each other to form a ring, the introduced carboxy group may be located at the cis position or at the trans position with respect to the ring plane. May be good.

Typically, when a compound containing a double bond as a starting compound is used as an unsaturated bond-containing compound, the synthesis reaction of the carboxylic acid compound can proceed as shown in the following reaction scheme I.

Therefore, when stilbene is used as the starting compound, diphenylsuccinic acid can be synthesized (reaction scheme IA), and when styrene is used as the starting compound, phenylsuccinic acid can be synthesized (reaction scheme IB).

In addition, the synthetic reaction of the carboxylic acid compound can proceed as shown in the following reaction scheme II. In the reaction scheme II, the double bond is regenerated by the elimination of the hydrogen atom following the addition of the carboxy group. For example, a reaction in which a multiple bond-containing compound is an aromatic compound and a carboxy group is introduced into the double bond of the aromatic compound can be preferably exemplified.

Therefore, when pyrazin is used as a starting compound, picolinic acid can be synthesized by oxidizing it after the reaction (reaction scheme IIA), and when pyridine is used as a starting compound, it is oxidized after the reaction to produce isonicotinic acid. It can be synthesized (reaction scheme IIB) or picolinic acid can be synthesized (reaction scheme IIC). Furthermore, a carboxy group can be introduced into a plurality of multiple bonds, and for example, dipicolinic acid can be synthesized when pyridine is used as a starting compound (reaction scheme IID).

In the method for synthesizing a carboxylic acid compound according to the present embodiment, the obtained carboxylic acid compound may be purified by a purification means known in the art. For example, the obtained carboxylic acid compound is subjected to extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the obtained concentrate is concentrated and used as a purification carrier such as silica gel chromatography. Can be purified with.

As described above, according to the method for synthesizing a carboxylic acid compound according to the present embodiment, a carboxylic acid compound is synthesized by introducing a carboxy group derived from _{CO 2 into the organic compound containing multiple bonds in the molecule.} It is possible to provide a method for synthesizing a carboxylic acid compound. According to this embodiment, a carboxylic acid compound can be synthesized under mild conditions by using a dispersion in which an alkali metal is dispersed in a dispersion solvent. Therefore, complicated temperature control, safety control, and the like are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, it is economically and industrially very advantageous because the carboxylic acid compound can be synthesized inexpensively, stably and efficiently in a short time with a small number of steps by using reagents that are easily available and handled. .. In addition, the inconvenience due to local heat generation or the like as in the case of using a single metal does not occur, the synthetic reaction of the carboxylic acid compound can proceed stably, and the carboxylic acid compound can be efficiently synthesized. Further, since alkali metals, particularly sodium and the like are metals that are extremely widely distributed on the earth, the method for synthesizing the carboxylic acid compound of the present embodiment is also excellent in sustainability. The method of synthesizing carboxylic acid compound of the present embodiment, the CO ₂ is CO ₂ fixation technology of converting into useful organic compound used as a carbon resource, it is also useful as the utilization technologies of novel carbon resources. Further, the method for synthesizing the carboxylic acid compound according to the present embodiment is for total synthesis of natural products, medical pesticides, electronic materials such as liquid crystals and organic EL, and a wide variety of functional materials such as intermediates thereof. It can be used for organic synthesis reactions and the like.

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

(Example 1) Examination of synthesis method of carboxylic acid compound (synthesis from stilbene) In this example, trans-stilbene was used as a starting compound in the presence of SD according to the synthesis conditions summarized in FIG. The synthesis of the carboxylic acid compound of was examined.

The stir bar and trans-stilbene (0.19 g, 1.05 mmol, 1 molar equivalent) were placed in a Schlenk tube and replaced with nitrogen. After adding THF (4.00 ml) and stirring, SD (0.2227 g, 2.4 mmol, 2.3 mol eq) was added and the mixture was reacted at 30 ° C. for 10 minutes. Then, CO ₂ (dry ice) was blown in for 10 minutes. After the reaction, the reaction solution was transferred to a separating funnel, separated with 10 ml each of 1N HCl and ethyl acetate, and the aqueous layer was removed. 10 ml of saturated brine was added to the organic layer, and the mixture was separated to remove the aqueous layer. The organic layer was transferred to a flask and dehydrated by adding sodium sulfide. Sodium sulfide was removed by suction filtration, and the filtrate was transferred to an eggplant flask, which was evaporated to obtain the final product.

Since the final product is expected to be a carboxylic acid compound (a dicarboxylic acid compound in which two carboxy groups have been introduced), the final product was esterified for identification by GC / MS. Esterification and identification by GC / MS were performed as follows. The stir bar and the final product obtained above were placed in a Schlenk tube and replaced with nitrogen. Methanol (2.0 ml) and thionyl chloride (0.5 ml) were added, and the mixture was reacted overnight (16 hours). After the reaction, the reaction solution was dropped into saturated aqueous sodium hydrogen carbonate, and the solution extracted with ethyl acetate was subjected to GC / MS. As a result, the diester compound was produced in a yield of about 47% (total of Treo form and Elytro form) as the final product, the hydrogen adduct of the by-product was produced in about 37%, and the rest was the unreacted starting compound. .. Therefore, by reacting a multiple bond-containing compound containing multiple bonds in its molecule, such as styrene, with CO _{2 in} the presence of SD, a carboxy group derived from CO ₂ can be introduced and a carboxylic acid compound can be synthesized. Understandable.

The present invention relates to all technical fields in which a carboxylic acid compound is required, particularly, total synthesis technology of natural products, medical pesticides, pesticides, electronic materials such as liquid crystal and organic EL, and intermediates thereof. This is a useful technology in the organic synthesis technology of a wide variety of functional materials.

Claims (3)

In the reaction solvent, in the presence of a dispersion in which the alkali metal is dispersed in the dispersion solvent
A method for synthesizing a carboxylic acid compound, which synthesizes a carboxylic acid compound by reacting a multiple bond-containing organic compound with carbon dioxide. The method for synthesizing a carboxylic acid compound, which comprises synthesizing the carboxylic acid compound according to claim 1, wherein the multiple bond-containing organic compound is an organic compound whose multiple bonds are reduced by Birch reduction. The method for synthesizing a carboxylic acid compound according to claim 1 or 2, wherein the multiple bond-containing organic compound is stilbene, and diphenylsuccinic acid is synthesized by reacting stilbene with carbon dioxide.

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