JP7065654B2 - Method for synthesizing α, β-unsaturated carboxylic acid - Google Patents

Description

The present invention relates to a method for synthesizing α, β-unsaturated carboxylic acid.

In recent years, many methods of using CO ₂ as a raw material for chemical synthesis have been proposed for the purpose of reducing greenhouse gases such as carbon dioxide (CO ₂ ). As one of them, it has been proposed to produce an unsaturated carboxylic acid such as acrylic acid from CO ₂ and an alkene as raw materials.

For example, a method for producing an acrylate by reacting CO ₂ with ethylene in the presence of a homogeneous catalyst containing a nickel complex and a base has been proposed (Non-Patent Document 1). In this method, an olefin-nickel complex is reacted with CO ₂ in a tetrahydrofuran (THF) solvent to form a nickel lactone complex, and then a strong base such as sodium alkoxide is added to cleave the lactone ring. An acrylate complex is obtained, and the acrylate ligand of the obtained acrylate complex is replaced with an olefin ligand to release acrylate (sodium acrylate).

Further, a method of reacting CO ₂ with ethylene using a zero-valent molybdenum complex having a triphosphine ligand as a homogeneous catalyst has also been reported (Non-Patent Document 2).

Further, in Patent Document 1, a) a transition metal-alkene complex is reacted with CO ₂ to generate metallalactone, and b) metallalactone is used as an alkali metal hydroxide or an alkaline earth metal hydroxide. Reaction with a base selected from a strong alkali metal base or a strong alkaline earth metal base to form an adduct of an alkali metal salt or alkaline earth metal salt of α, β-unsaturated carboxylic acid and a transition metal complex. , C) Reacting the adduct with alken to release the alkali metal salt or alkaline earth metal salt of α, β-unsaturated carboxylic acid to regenerate the transition metal-alkene complex, α, β-unsaturated carboxylic acid. A method for synthesizing an alkali metal salt or an alkaline earth metal salt is disclosed.
Further, Patent Document 2 discloses a method for synthesizing a β-unsaturated carboxylic acid or a salt thereof by reacting a metallalactone intermediate in a solvent in the presence of a halide.

US Pat. No. 8,697,909 International Publication No. 2014/198469

Lejkowski, M. L. et al., “The first catalytic synthesis of an acrylate from CO2 and an alkene-A rational approach”, Chem. Eur. J. 18, 14017–14025 (2012) Hanna et al., “Ancillary Ligand Effects on Carbon Dioxide-Ethylene Coupling at Zerovalent Molybdenum”, Organometallics, 2014, 33, 3425-3432

As described above, in order to obtain an acrylate (acrylic acid salt), a metallalactone complex is used as an intermediate. However, the subsequent β-hydrogen desorption reaction and reductive dehydrogenation reaction are carried out as described above with bases (specific examples, sodium tert-butoxide (t-BuONa), sodium bis (trimethylsilyl) amide (specific examples). It has been shown that the reaction itself does not proceed in the absence of (NaHMDS), a mixture of lithium iodide (LiI) and ammonia (NH ₃ ), sodium phenoxide (PhONa), etc.).

Therefore, the target product obtained as an acrylate is a salt of α, β-unsaturated carboxylic acid and the cation of the base (alkali metal salt in the above specific example). That is, the cation of the alkali metal salt is supplied from the base existing in the reaction solution. In other words, the theoretical maximum amount of the target product obtained from one reaction is limited by the amount of base added to the reaction solution. The value obtained by dividing the amount of product obtained from the above reaction by the amount of catalyst is generally called the turnover number (TON = number of moles of product / number of moles of catalyst) and is used for comparison of catalytic activity. .. As described above, the theoretical maximum production amount of the target product is limited by the amount of base, for example, when 0.1 mmol of the catalyst is used and 10 mmol of the base is added (100 equivalents with respect to the catalyst), it is obtained. It means that the amount of acrylate to be obtained is at most 10 mmol (TON = 100).

As described above, the reason why the base is consumed and not regenerated during the reaction is that the product α, β-unsaturated carboxylic acid has a higher proton donating property than the conjugate acid of the base. .. That is, the acid dissociation constant (pKa) of the α, β-unsaturated carboxylic acid is about 3 to 5 depending on the structure. On the other hand, the acid dissociation constant of the conjugate acid of the base is 7 or more for phenol and about 14 or more for alcohol. As a result, after the α, β-unsaturated carboxylate and phenol or alcohol which are conjugate acids of the base are generated with the reaction, the weak acid phenol or alcohol reacts with the carboxylate to regenerate phenoxide or alkoxide. There is no.

The present invention has been made in view of the above circumstances, and by applying a base that is regenerated from a conjugate acid to a base even if the reaction proceeds, instead of the base becoming its conjugate acid and being consumed at the same time as the reaction. The purpose is to improve the amount of α, β-unsaturated carboxylic acid produced while suppressing the amount of base used.

As a result of diligent research, the present inventors activated the metallalactone complex, which is a stable reaction intermediate, with Lewis acid, and further, the acid dissociation constant (pKa) of the conjugate acid is lower than that of α, β-unsaturated carboxylic acid (). That is, it was found that the production efficiency of α, β-unsaturated carboxylic acid was improved by applying a (strongly acidic) base, and the base was not consumed by the reaction and was regenerated.

［式中、Ｍは、遷移金属を表し、Ｌはそれぞれ独立して単座配位子であるか、又はＬは協働して二座配位子を形成する。］
［２］ 前記塩基は窒素原子を含み、前記窒素原子が非共有電子対を有している［１］に記載のα,β－不飽和カルボン酸の合成方法。
［３］ 前記塩基がアニリン化合物、Ｎ－ジメチルアニリン化合物、ピリジン化合物、及びピラジン化合物からなる群から選ばれる少なくとも１種の化合物である［１］又は［２］に記載のα,β－不飽和カルボン酸の合成方法。
［４］ 前記塩基がハロゲン化アニリン、ハロゲン化ピリジン、及び２－メチルピラジンからなる群から選ばれる少なくとも１種の化合物である［１］～［３］のいずれか１に記載のα,β－不飽和カルボン酸の合成方法。 That is, the present invention has the following configurations.
[1] A method for synthesizing α, β-unsaturated carboxylic acid, in which an alken and carbon dioxide are reacted with a transition metal complex in the presence of Lewis acid and a base, and the following formula (1) is used as an intermediate. The metal lactone compound represented by (1) is formed and the Lewis acid and the base are allowed to act on the metal lactone compound, and the acid dissociation constant (pKa1) of the conjugated acid of the base and the α, β-unsaturated carboxylic acid are included. A method for synthesizing an α, β-unsaturated carboxylic acid whose relationship with the acid dissociation constant (pKa2) of an acid is pKa1 <pKa2.

[In the formula, M represents a transition metal, L is a monodentate ligand independently, or L cooperates to form a bidentate ligand. ]
[2] The method for synthesizing an α, β-unsaturated carboxylic acid according to [1], wherein the base contains a nitrogen atom and the nitrogen atom has an unshared electron pair.
[3] The α, β-unsaturated according to [1] or [2], wherein the base is at least one compound selected from the group consisting of an aniline compound, an N-dimethylaniline compound, a pyridine compound, and a pyrazine compound. Method for synthesizing carboxylic acid.
[4] The α, β- Method for synthesizing unsaturated carboxylic acid.

According to the present invention, the base is not consumed as a conjugate acid thereof with the reaction, but even if the reaction proceeds, the base is regenerated from the conjugate acid to the base to generate α, β-unsaturated carboxylate. It is possible to improve efficiency.

Hereinafter, the present invention will be described in detail.
In the present invention, a transition metal complex is reacted with an alkene and carbon dioxide in the presence of a Lewis acid and a base to form a metal lactone compound having a specific structure, and the metal lactone compound is made to have the Lewis acid and the base. It is a method for synthesizing α, β-unsaturated carboxylic acid, which comprises the action of. Further, the relationship between the acid divergence constant (pKa1) of the conjugate acid of the base and the acid divergence constant (pKa2) of the α, β-unsaturated carboxylic acid is pKa1 <pKa2.

(Formation of metal lactone compound)
<Metal lactone compound with a specific structure>
In the method for synthesizing α, β-unsaturated carboxylic acid of the present embodiment, the transition metal complex is reacted with an alkene and carbon dioxide in the presence of Lewis acid and a base, and the following formula (1) is used as an intermediate. A metal lactone compound having a specific structure represented by is obtained.

In the formula (1), M represents a transition metal, and is an element belonging to Group 6 (preferably Cr, Mo, W) of the periodic table, an element belonging to Group 7 (preferably Re), and an element belonging to Group 8 (preferably). Contains at least one element selected from the group consisting of Fe, Ru), elements belonging to Group 9 (preferably Co, Rh), and elements belonging to Group 10 (preferably Ni, Pd, Pt). Of these, nickel, molybdenum, cobalt, iron, rhodium, ruthenium, palladium, platinum, renium and tungsten are preferable, nickel, molybdenum, palladium, platinum, cobalt, iron, rhodium and ruthenium are more preferable, and nickel, platinum, And palladium are particularly preferred.

In formula (1), L is a ligand having a coordinating ability to the transition metal and is a monodentate ligand independently of each other, or L cooperates to form a bidentate ligand. ..

The ligand contains at least one atom or atomic group selected from the group consisting of a phosphorus atom, a nitrogen atom, an oxygen atom, and a carben group as an atom or an atomic group coordinated to the transition metal. You may. The ligand can be selected from, for example, phosphine, phosphite, amine, and N-heterocyclic carbene. In the ligand, at least one atom or atomic group coordinated with the transition metal is preferably at least one selected from the group consisting of a phosphorus atom, an amine and a carben group, and is preferably a phosphorus atom and / or an amine. It is more preferable to have.

When the ligand contains at least one phosphorus atom coordinated to the transition metal, it is preferred that at least one group is attached to the phosphorus atom via a secondary or tertiary carbon atom. More preferably, at least two groups are attached to the phosphorus atom via a secondary or tertiary carbon atom. Suitable groups attached to the phosphorus atom via a secondary or tertiary carbon atom are, for example, a methyl group, an adamantyl group, a tert-butyl group, a cyclohexyl group, a sec-butyl group, an isopropyl group, a phenyl group. , Trill group, xylyl group, mesityl group, naphthyl group, fluorenyl group, or anthrasenyl group. Of these, a group having a high electron donating property is desirable, and specifically, a methyl group, a tert-butyl group, and a cyclohexyl group are preferable.

When the ligand comprises at least one N-heterocyclic carbene coordinated to the transition metal, preferably at least one group is at least one α-nitrogen atom of the carbene group via a secondary or tertiary carbon atom. Is bound to. Suitable groups attached to the nitrogen atom via the tertiary carbon atom are, for example, an adamantyl group, a tert-butyl group, an isopropyl group, a phenyl group, or a 2,6-diisopropylphenyl group, the adamantyl group. It is preferably a tert-butyl group or a 2,6-diisopropylphenyl group.

Specific examples of ligands containing at least one phosphorus atom that can be used in the present invention include trialkylphosphines such as trimethylphosphine and tricycloalkylphosphines such as tricyclohexylphosphine (PCy3) as monodentate ligands. Triarylphosphine such as triphenylphosphine and tri (4-fluoromethylphenyl) phosphine; triheteroarylphosphine such as tri-2-furanylphosphine; phospholan ligand such as triphenylphosphine oxide, etc. 2 As the locus ligand, bis (diphenylphosphine) methane (dppm), 1,2-bis (diphenylphosphino) ethane (dppe), 1,3-bis (diphenylphosphino) propane (dpppp), 1, 4-Bis (diphenylphosphine) butane (dppb), 1,5-bis (diphenylphosphino) pentane (dpppe), 1,6-bis (diphenylphosphino) hexane, 1,1'-bis (diphenylphosphino) ) Ferrocene, 1,2-bis (dipentafluorophenylphosphine) ethane, 1,2-bis (dicyclohexylphosphine) ethane, 1,3-bis (dicyclohexylphosphine) propane, 1,4-bis (dicyclohexylphosphine) Fino) butane, 1,2-bis (di-t-butylphosphine) ethane, 1,2-bis (diphenylphosphino) benzene, 1,2-bis (bis (3,5-dimethylphenyl) phosphino) ethane , 1,3-bis (bis (3,5-dimethylphenyl) phosphine) propane, 1,4-bis (bis (3,5-dimethylphenyl) phosphino) butane, 1,2-bis (cyclohexylphosphino) ethane , 1,4-bis (bis (3,5-di-t-butylphenyl) phosphine) butane, 1,4-bis (bis (3,5-dimethoxyphenyl) phosphino) butane, 2,2'-bis ( Diphenylphosphine) -1,1'-binaphthyl, 2,2'-bis (bis (3,5-dimethylphenyl) phosphine) -1,1'-binaphthyl, (2S, 3S)-(-)-bis ( Diphenylphosphine) butane, (S, S) -1,2-bis [(2-methoxyphenyl) phenylphosphino] ethane ((S, S) -DIPAMP), (R, R)-(-)-2 , 3-Bis (tert-butylmethylphosphine) quinoxalin (QuinoxP ^* ), (R, R) -1,2-bis (tert-butylmethylphosphine) Fino) Benzene (BenzP ^* ), 1,1,1-tris (diphenylphosphinemethyl) ethane, 1,1,1-tris (bis (3,5-dimethylphenyl) phosphinomethyl) ethane, 1,1,1 1-Tris (diphenylphosphine) methane, Tris (2-diphenylphosphinoethyl) phosphine, (oxydi-2,1-phenylene) bis (diphenylphosphine), 4,5-bis (diphenylphosphine) -9,9 -Dimethylxanthene, 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene, etc. may be mentioned. Among them, 1,2-bis (diphenylphosphino) ethane (dppe), 1,2-bis (dicyclohexylphosphino) ethane, 1,2-bis (di-t-butylphosphino) ethane, 1,3- Bis (dicyclohexylphosphino) propane and BenzP ^* are preferred.

In addition to the above ligands, transition metal complexes include halides, amines, amides, oxides, phospholes, carboxylates, acetylacetonates, arylsulfonates or alkylsulfonates, hydrides, carbon monoxides, olefins. , Dienes, cycloolefins, nitriles, aromatics and heterocyclic aromatics, ethers, phosphorus trifluoride, phosphols, phospholebenzenes, and monodentate, bidentate, and polydentate phosphinites, phosphonite, phosphoramidite, and phosphite coordinations. It may also have at least one additional ligand selected from the offspring.

Specific examples of the metal lactone compound that can be suitably used in this embodiment include those represented by the following formula (2).

The description of M in the formula (2) is the same as that in the formula (1). Each of X in the formula (2) is a nitrogen atom or a phosphorus atom independently.

In formula (2), R ¹ represents a single bond or divalent aliphatic or aromatic hydrocarbon group, or a nitrogen-containing group. The divalent aliphatic hydrocarbon group includes chain and cyclic saturated and unsaturated hydrocarbon groups, and the number of carbon atoms thereof is preferably 1 to 12, more preferably 1 to 6. Examples of such an aliphatic hydrocarbon group include chain and cyclic alkylene groups and alkenylene groups. Divalent aromatic hydrocarbon groups include divalent hydrocarbon groups derived from monocyclic aromatic hydrocarbons (benzene, toluene, xylene, etc.) having one benzene ring and two or more, usually 2-4. Included are divalent hydrocarbon groups derived from polycyclic aromatic hydrocarbons with benzene rings (naphthalene, biphenyl, terphenyl, etc.). Further, the divalent aromatic hydrocarbon group may be a divalent residue of the heterocyclic aromatic compound. Examples of the heterocyclic aromatic compound include furan, thiophene, pyrrol, pyrazole, imidazole, isoxazole, thiazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, indol, thianaften, benzimidazole, benzoxazole. , Benzothiazole, benzotriazole, purine, quinoline, isoquinoline, thinoline, quinoxalin, dibenzothiophene, aclysine, phenanthroline and the like.
Examples of the nitrogen-containing group include a -NR- group (in the formula, R is hydrogen or an alkyl group having 1 to 4 carbon atoms).

In formula (2), R ² , R ³ , R ⁴ and R ⁵ each independently represent a monovalent aliphatic or aromatic hydrocarbon group, preferably linear or branched with 1 to 6 carbon atoms. It is an aliphatic hydrocarbon group or an alicyclic hydrocarbon group having 3 to 6 carbon atoms. Specific aliphatic hydrocarbon groups include methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, t-butyl group, n-pentyl group, isopentyl group and t. -Pentyl group, n-hexyl group, isohexyl group, 2-hexyl group, dimethylbutyl group, ethylbutyl group and the like can be mentioned. Specific examples of the alicyclic hydrocarbon include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

In formula (2), X represents a nitrogen atom or a phosphorus atom, but when X is a nitrogen atom, n is 0, and R ¹ and R ⁴ are bonded to each other to form a 5- or 6-membered complex fragrance. It may form a ring and at least one of R ² and R ³ may be an aliphatic hydrocarbon group or an aromatic hydrocarbon group having 3 or more carbon atoms.

≪Transition metal complex≫
The metal lactone compound having the above-mentioned specific structure can be obtained by reacting a transition metal complex with an alkene and carbon dioxide in the presence of a Lewis acid and a base. The transition metal complex is not particularly limited as long as it can catalyze the reaction between CO ₂ and other raw material compounds in order to obtain a desired compound. For example, Non-Patent Documents 1 and 2 and Patent Documents described above. Known transition metal complexes as described in 1 and 2 can be used.

Specific examples of the transition metal complex used to obtain the above-mentioned metal lactone compound having a specific structure include those represented by the following formula (3).

The description of M and L in the formula (3) is the same as that in the formula (1).

Moreover, as a specific example of the metal lactone compound that can be suitably used in this embodiment, the one represented by the following formula (4) can be mentioned.

The description of M in the formula (4) is the same as that in the formula (1). The description of R ¹ , R ² , R ³ , R ⁴ , and R ⁵ in the formula (4) is the same as that in the formula (2).

In the present embodiment, other components may be blended in addition to the transition metal complex. The other components are not particularly limited as long as they do not impair the effects of the present invention.

≪Alkene and CO _2≫
The alkenes that can be used in the present invention are, for example, ethylene, propylene, isobutene, 1,3-butadiene, piperylene, 1-butene, 1-pentene, 1-hexene, 1-heptene, 1-octene, 1-nonene, 1-. Decene and styrene. Of these, ethylene, propylene, 1,3-diene and styrene are preferable, and ethylene is more preferable. These may be gaseous or liquid, depending on the type.
CO ₂ can be used in a gaseous, liquid, or supercritical state. Although it is possible to use gas mixtures containing CO ₂ that are available on an industrial scale, it is desirable that they be substantially free of carbon monoxide.
"Substantially free of carbon monoxide" means that the CO content is 100 ppm (0.01% by volume) by volume or less with respect to 100% by volume of the gas mixture.

CO ₂ and alkenes may also contain an inert gas such as nitrogen or a noble gas. However, the content of the inert gas is preferably less than 20% by volume based on the total volume of CO ₂ and alkene in the reactor.

(Production of α, β-unsaturated carboxylic acid)
In the method for synthesizing α, β-unsaturated carboxylic acid of the present embodiment, the Lewis acid and the base are allowed to act on the metal lactone compound formed as an intermediate to form a lactone ring by β-hydrogen desorption. Cleavage and subsequent reductive desorption occur to form an unsaturated carboxylic acid complex, and the unsaturated carboxylic acid complex exchanges a ligand with alken to generate α, β-unsaturated carboxylic acid.

≪Lewis acid≫
The Lewis acid used in the present invention interacts with the carbonyl oxygen (O of C = O) of the metal lactone compound (MO (C = O) _-CH2 -CH-) which is an intermediate, thereby. It activates the lactone ring and facilitates subsequent cleavage of the lactone ring.

As used herein, "Lewis acid" is a substance capable of receiving an electron pair.
Lewis acids include metal salts such as alkali metal salts and alkaline earth metal salts, boron compounds such as boron halide, boron alkylated and boron alkyl halide, and aluminum such as aluminum halide, alkyl aluminum and alkyl aluminum halide. Compounds are given as an example.
One type of Lewis acid may be used alone, or two or more types may be used in combination.

Examples of the alkali metal salt include lithium iodide (LiI), sodium iodide (NaI), sodium bromide (NaBr), and lithium bromide (LiBr). Examples of the alkaline earth metal salt include magnesium chloride (MgCl ₂ ) and magnesium bromide (MgBr ₂ ).

Examples of the boron compound include those represented by the following formula (5).
BX _m R ⁶ _3-m (5)
[In formula (4), each R ⁶ independently represents an alkyl group. m represents an integer of 0 to 3. X indicates a halogen group]

The alkyl group selected as R ⁶ preferably has 1 to 10 carbon atoms, and more preferably 1 to 5 carbon atoms. Halogen groups are fluorine, chlorine, bromine and iodine.
As the boron compound, boron fluoride is preferable.

Examples of the aluminum compound include those represented by the following formula (6).
AlX _m R ⁶ _3-m (6)
[The explanation of R6, m, and X in the equation ( ⁵ ) is the same as that of the equation (5)].
As the aluminum compound, aluminum chloride, ethyl dichloride, and diethyl aluminum chloride are preferable.

≪Base≫
The base (B) of the present invention abstracts hydrogen from the hydride intermediate (having an MH structure) generated by the cleavage of the lactone ring described above, and proceeds with the subsequent formation of an unsaturated carboxylic acid complex by reductive elimination. Let me. Since the conjugate acid (BH) of the base produced at that time is a stronger acid than the unsaturated carboxylic acid also produced, the proton of the conjugate acid of the base is donated to the unsaturated carboxylic acid. As a result, it is presumed that the base is regenerated and the base contributes to the reaction again.

In the present embodiment, pKa1 <pKa2 is the relationship between the acid dissociation constant (pKa1) of the conjugate acid (BH) of the base (B) and the acid dissociation constant (pKa2) of the α, β-unsaturated carboxylic acid. It is preferable that it holds.
When pKa1 <pKa2 is established, the proton of the conjugate acid (BH) of the base (B) is donated to the unsaturated carboxylic acid, and the base is regenerated to keep the concentration of the base in the reaction system constant. can.

As long as pKa1 <pKa2, the value of pKa1 is not limited, but pKa1 is usually -4.0 to 4.0, preferably -3.0 to 3.5, and -2.0 to 3. It is more preferably 0.
When pKa1 is equal to or higher than the lower limit of the above range, hydrogen extraction of the hydride intermediate produced by cleavage of the lactone ring proceeds efficiently, and the yield of unsaturated carboxylic acid is improved. When pKa1 is not more than the upper limit of the above range, the proton of the conjugate acid of the base is efficiently donated to the unsaturated carboxylic acid, so that the concentration of the base of the reaction system can be kept constant, and α, β- The yield of unsaturated carboxylic acid is improved.
As long as pKa1 <pKa2, the value of pKa2 is not limited, but pKa2 is usually 3.0 to 6.0, preferably 3.5 to 5.0, and 4.0 to 5.0. Is more preferable. When pKa2 is equal to or higher than the lower limit of the above range, the proton of the conjugate acid of the base is efficiently donated to the unsaturated carboxylic acid, so that the concentration of the base of the reaction system can be kept constant.
In the present specification, "pKa" can be measured by a conventionally known method, and is measured in water in the case of a water-soluble compound and in dimethyl sulfoxide or acetonitrile in the case of a water-insoluble compound. be able to.
The pKa of known compounds is, for example, pKa published by Organic Chemistry Info (database provided by Reich Group, University of Wisconsin, USA) and Dissociation Constants of organic Acids and Bases (Prof. Liming Zhang @ UC Santa Barbara). The values listed in the list) can be used.

The base of the present embodiment preferably contains a nitrogen atom and has an unshared electron pair on the nitrogen atom. The base acts as a base via an unshared electron pair on the nitrogen atom, abstracts hydrogen from the hydride intermediate produced by cleavage of the lactone ring, and subsequently produces an unsaturated carboxylic acid complex by reductive desorption. To proceed.

Specific examples of the above-mentioned base include an aniline compound, an N-dimethylaniline compound, a pyridine compound, and a pyrazine compound.
One type of base may be used alone, or two or more types may be used in combination.

［式（７）中のＸの説明は式（５）と同様であり、ｘは０～５の整数を表す］
アニリン化合物としては、２－ブロモアニリン、３－ブロモアニリン、４－ブロモアニリン、２－クロロアニリン、３－クロロアニリン、４－クロロアニリン、２－フッ化アニリン、３－フッ化アニリン、４－フッ化アニリン、２－ヨードアニリン等が例として挙げられ、２－クロロアニリン、２－ブロモアニリン、２－フッ化アニリン、２－ヨードアニリンが好ましい。 Examples of the aniline compound include those represented by the following formula (7).

[The explanation of X in the equation (7) is the same as that of the equation (5), and x represents an integer of 0 to 5].
Examples of aniline compounds include 2-bromoaniline, 3-bromoaniline, 4-bromoaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-fluorinated aniline, 3-fluorinated aniline, and 4-huh. Examples include chemical aniline, 2-iodoaniline and the like, with 2-chloroaniline, 2-bromoaniline, 2-fluorinated aniline and 2-iodoaniline being preferred.

［式（８）中のＸの説明は式（５）と同様であり、ｘの説明は式（７）と同様である。］
Ｎ－ジメチルアニリン化合物としては、３－ブロモ－Ｎ，Ｎ－ジメチルアニリン、４－ブロモ－Ｎ，Ｎ－ジメチルアニリン、３－クロロ－Ｎ，Ｎ－ジメチルアニリン、４－クロロ－Ｎ，Ｎ－ジメチルアニリン等が例として挙げられる。 Examples of the N-dimethylaniline compound include those represented by the following formula (8).

[The explanation of X in the equation (8) is the same as that of the equation (5), and the explanation of x is the same as that of the equation (7). ]
Examples of the N-dimethylaniline compound include 3-bromo-N, N-dimethylaniline, 4-bromo-N, N-dimethylaniline, 3-chloro-N, N-dimethylaniline, 4-chloro-N, N-dimethyl. Aniline and the like are examples.

［式（９）中のＸの説明は式（５）と同様であり、ｘの説明は式（７）と同様である。］
ピリジン化合物としては、２－クロロピリジン、３－クロロピリジン、４－クロロピリジン、２－ブロモピリジン、３－ブロモピリジン、４－ブロモピリジン、２，６－クロロピリジン、２，６－フッ化ピリジン等が例として挙げられ、２－クロロピリジン、３－クロロピリジン、４－クロロピリジン、２－ブロモピリジン、３－ブロモピリジン、４－ブロモピリジン、２，６－ブロモピリジン、２，６－クロロピリジンが好ましい。 Examples of the pyridine compound include those represented by the following formula (9).

[The explanation of X in the equation (9) is the same as that of the equation (5), and the explanation of x is the same as that of the equation (7). ]
Examples of the pyridine compound include 2-chloropyridine, 3-chloropyridine, 4-chloropyridine, 2-bromopyridine, 3-bromopyridine, 4-bromopyridine, 2,6-chloropyridine, 2,6-fluoropyridine and the like. Examples include 2-chloropyridine, 3-chloropyridine, 4-chloropyridine, 2-bromopyridine, 3-bromopyridine, 4-bromopyridine, 2,6-bromopyridine and 2,6-chloropyridine. preferable.

［式（１０）中、Ｒ^７はそれぞれ独立に炭素数が１～４のアルキル基を示す。ｙは０～４の整数を示す。］
Ｒ^７として選択されるアルキル基は、炭素数が１～４であることが好ましく、１～３であることがより好ましい。
ピラジン化合物としては、２－メチルピラジン、２－エチルピリジン、２－イソプロピルピラジン、２－メチル－３－エチルピラジン等が例として挙げられ、２－メチルピラジン、２－エチルピリジン、２－イソプロピルピラジンが好ましい。 Examples of the pyrazine compound include those represented by the following formula (10).

[In formula (10), R ⁷ independently represents an alkyl group having 1 to 4 carbon atoms. y indicates an integer from 0 to 4. ]
The alkyl group selected as R ⁷ preferably has 1 to 4 carbon atoms, and more preferably 1 to 3 carbon atoms.
Examples of the pyrazine compound include 2-methylpyrazine, 2-ethylpyridine, 2-isopropylpyrazine, 2-methyl-3-ethylpyrazine and the like, and 2-methylpyrazine, 2-ethylpyridine and 2-isopropylpyrazine are examples. preferable.

≪Reaction conditions≫
In the method for synthesizing α, β-carboxylic acid of the present embodiment, a metal lactone compound having a specific structure as an intermediate is obtained by reacting alken and carbon dioxide with a transition metal complex in the presence of Lewis acid and a base. It is a method for synthesizing α, β-carboxylic acid, which comprises forming the metal lactone compound and allowing the Lewis acid and the base to act on the metal lactone compound.
This reaction is preferably carried out using a solvent. That is, it is preferable to carry out the reaction by allowing the transition metal complex, the base and the Lewis acid to be present in the solvent, introducing alken and CO ₂ into them, and contacting them with the transition metal complex. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as chlorobenzene, ethers such as tetrahydrofuran (THF), dimethylformamide, dimethylsulfoxide and the like. These may be used alone or in combination of two or more. Preferred solvents are THF and toluene.

The reaction method may be carried out in a batch system, a semi-batch system, a continuous system, or a combination of a batch system, a semi-batch system and a continuous system. In the case of the batch type, a transition metal complex, a base, a Lewis acid, an alkene, and then CO ₂ are introduced into the solvent in the reactor to carry out the reaction. In the case of the half-batch type, the transition metal complex, the base, the Lewis acid, and the alkene are preliminarily charged in the solvent in the reactor, and the reaction is carried out by continuously introducing CO ₂ into the reactor. In the case of the continuous type, the transition metal complex is charged in the solvent in the reactor, and the reaction is carried out by continuously introducing the base, Lewis acid, alkene, and CO ₂ into the reactor. In the case of continuous type, the liquid phase of the reaction mixture is mixed while supplying the reaction raw material into a fixed bed method, a fluidized bed method, a moving bed method, a suspension bed method, a stirring mixture type or a loop type reactor. It can be carried out by various methods such as a extraction method. When a loop reactor is used, a circulation system that circulates a base, a Lewis acid, an alkene, and CO ₂ is preferable. In a stirring and mixing reactor, under liquid phase conditions, gaseous alken and CO ₂ are used in batch or continuous mode, and the alken and CO ₂ are used in the gas phase portion of the reactor and in the reactor. It may be supplied to either one of the liquid phase portions, or may be supplied to both the gas phase portion and the liquid phase portion of the reactor.
Further, as the reaction device, a known reaction device can be appropriately used depending on the reaction type to be adopted.

The reaction temperature is preferably 50 to 250 ° C, more preferably 80 to 200 ° C. The pressure is usually 1 to 10 MPa, preferably 2 to 8 MPa in absolute pressure.
The molar ratio of alkene to CO ₂ (alkene / CO ₂ ) supplied to the reactor is usually 0.5 to 8, preferably 1 to 4.
The molar ratio of the alkene to the transition metal complex (alkene / transition metal complex) supplied to the reactor is usually 1 to 100, preferably 2 to 50.
The molar ratio of CO ₂ to the transition metal complex (CO ₂ / transition metal complex) supplied to the reactor is usually 1 to 100, preferably 1 to 25.

When the reaction is carried out in a batch system, a semi-batch system, and the above-mentioned continuous system and circulation system, the amount of Lewis acid added is preferably 20 to 2000 mol% with respect to 100 mol% of the number of moles of the transition metal complex. 50 to 1500 mol% is more preferable, and 100 to 1000 mol% is even more preferable. When the amount of Lewis acid added is not less than the lower limit of the above range, cleavage of the lactone ring proceeds efficiently, and the efficiency of producing α, β-unsaturated carboxylic acid is increased. When the amount of Lewis acid added is not more than the upper limit of the above range, the amount of Lewis acid used can be suppressed, which is economical.

When the reaction is carried out in a batch system, a semi-batch system, and the above-mentioned continuous system and circulation system, the amount of the base added is preferably 20 to 2000 mol% with respect to 100 mol% of the number of moles of the transition metal complex, and is 50. It is more preferably ~ 1500 mol%, still more preferably 100-1000 mol%. When the amount of the base added is not less than the lower limit of the above range, the cleavage of the lactone ring proceeds efficiently, and the efficiency of producing α, β-unsaturated carboxylic acid is increased. When the amount of the base added is not more than the upper limit of the above range, the amount of the base used can be suppressed, which is economical.

The number of moles of base added is preferably 0.2 to 5, more preferably 0.5 to 3, and 0, with respect to the number of moles of Lewis acid added, which is represented by (number of moles of base added / number of moles of Lewis acid added). .8 to 2 is more preferable. When the number of moles of base added to the number of moles of Lewis acid added is equal to or greater than the lower limit of the above range, hydrogen in the hydride intermediate produced by cleavage of the lactone ring is extracted, and subsequent reductive desorption efficiently proceeds. , Α, β-Unsaturated carboxylic acid production efficiency is increased. .. When the number of moles of base added is equal to or less than the upper limit of the above range with respect to the number of moles of Lewis acid added, the amount of base can be relatively reduced, which is economical.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

[Example 1]
(1) Synthesis of BenzP Ligand Under a nitrogen atmosphere, 1,2- (dichlorophosphino) benzene (1.6 g, 5.92 mmol) was dissolved in 30 mL of tetrahydrofuran (THF) and cooled to −78 ° C. A THF solution of t-butylmagnesium chloride (1.7 M, 7.38 mL, 12.6 mmol) was gradually added dropwise thereto, and the mixture was stirred at room temperature for 4 hours. This was further gradually added dropwise to a THF (30 mL) dispersion solution of magnesium particles (40 mesh, 1.12 g, 46 mmol), and the mixture was stirred at room temperature for 18 hours. Then, THF was distilled off in vacuum, dispersed in 20 mL of diethyl ether, and then the obtained suspension was filtered on diatomaceous earth (“Celite” (registered trademark) manufactured by Celite Corporation). Diethyl ether was distilled off in vacuum to obtain an oily phospha cycle (1.09 g, 59%) represented by the following formula (11), which is an intermediate of the target product.

In a nitrogen atmosphere, phospha cycle (528 mg, 2.1 mmol) was dissolved in 20 mL of dichloromethane, methyl trifluoromethanesulfonate (MeOTf) (360 mg, 2.2 mmol) was added thereto, and the mixture was stirred at room temperature for 4 hours. Then, dichloromethane was distilled off from dichloromethane in vacuum, dispersed in 30 mL of diethyl ether, and then cooled to −35 ° C. A diethyl ether solution (3.0 M, 740 μL, 2.2 mmol) of methyl magnesium bromide (MeMgBr) was gradually added dropwise thereto, and the mixture was stirred at room temperature for 18 hours. Then, the obtained suspension was filtered on Celite®. Diethyl ether was distilled off in vacuum, the precipitated white solid was dispersed in 30 mL of pentane, and the suspension was filtered again on Celite®. Pentane was distilled off in vacuum to obtain 1,2 bis (t-butylmethylphosphino) benzene (BenzP) (388 mg, 66%) represented by the following formula (12), which is the target product.

(2) Synthesis of (BenzP) Ni (COD) Metal Complex 1 and 2 bis (t-butylmethylphosphino) benzene (BenzP) (338 mg, 1.20 mmol) in THF 10 mL is added to nickel bis 1,5-cyclo. It was gradually added dropwise to 15 mL of a THF solution of octadiene (Ni (COD) ₂ ) (362.7 mg, 1.32 mmol), and the mixture was stirred at room temperature for 18 hours. Then, THF was distilled off in vacuum, 10 mL of pentene cooled to −35 ° C. was added, and the solution was quickly separated (where unreacted (excessive) Ni (COD) ₂ remains as a precipitate). .. This was filtered on Celite®. Pentane was distilled off in vacuum, and the obtained yellow solid was dissolved in as small amount (about 3 to 4 mL) of diethyl ether as possible, and allowed to stand at −35 ° C. for 24 hours. The precipitated yellow acicular crystals and the supernatant were separated, and the crystals were dried in vacuum for 3 hours. As a result, a transition metal complex (BenzP) Ni (COD) represented by the following formula (13) was obtained.

(3) Acrylic acid synthesis reaction Under a nitrogen atmosphere, (BenzP) Ni (COD) (0.01 mmol, 4.5 mg), 2-bromopyridine (0.02 mmol, 2 equivalents with respect to the transition metal complex), aluminum tri. Chloride (AlCl ₃ , 0.02 mmol, 2 equivalents to the transition metal complex) was weighed into a pressure resistant NMR tube and suspended in d8-THF. A pressure-resistant NMR tube was connected to the vacuum line, and after cooling the NMR tube with liquid nitrogen, the internal gas (mainly N ₂ ) was degassed (cooling remained unchanged). Then, a gas cylinder filled with ethylene gas was connected to the vacuum line, and ethylene gas was introduced into the NMR tube (4 equal volumes with respect to the transition metal complex).

Once the pressure-resistant NMR tube was returned to room temperature and allowed to stand for 10 minutes, carbon dioxide (for transition metal complexes) was placed in the pressure-resistant NMR tube using a gas cylinder filled with carbon dioxide in the same manner as in the introduction of ethylene gas. 4 equal doses) were introduced. The pressure resistant NMR tube was heated at 50 ° C. and the product was analyzed by ³¹ P-NMR and ¹ H-NMR. The yield of acrylic acid after 24 hours was 21.0%. The residual ratio of 2-bromopyridine, which is a base after the reaction (ratio of non-protonated bases), was 100% (below the detection limit in NMR).
The pKa of acrylic acid is 4.25 and the pKa of the conjugate acid of 2-bromopyridine is 0.79.

[Comparative Example 1]
The procedure was the same as in Example 1 except that sodium 2-chlorophenoxide (2Cl-PhONa) was used as the base. The yield of acrylic acid after 24 hours was 9.0%. On the other hand, sodium 2-chlorophenoxide reacted with CO ₂ and the residual rate was 0%.
The pKa of the conjugate acid of sodium 2-chlorophenoxide is 8.49.

[Comparative Example 2]
The procedure was the same as in Example 1 except that sodium 2-chlorophenoxide (2Cl-PhONa) was used as the base and LiI was used as the Lewis acid. The yield of acrylic acid after 24 hours was 4.9%. On the other hand, sodium 2-chlorophenoxide reacted with CO ₂ and the residual rate was 0%.

[Comparative Example 3]
The procedure was the same as in Example 1 except that sodium 2-chlorophenoxide (2Cl-PhONa) and Lewis acid were not added to the base. The yield of acrylic acid after 24 hours was 0%. In addition, sodium 2-chlorophenoxide reacted with CO ₂ and the residual rate was 0%.

[Comparative Example 4]
The procedure was the same as in Example 1 except that Lewis acid was not added. The yield of acrylic acid after 24 hours was 0%, and the residual ratio of 2-bromopyridine was 100%.

Table 1 shows the yields of acrylic acids of Examples 1 and Comparative Examples 1 to 4 and the residual ratio of bases.

As shown in Table 1, it was found that in Example 1 to which the present invention was applied, the residual ratio of the base was 100%, and acrylic acid could be obtained in a high yield accordingly.

Claims (2)

It is a method for synthesizing α, β-unsaturated carboxylic acid, and is represented by the following formula (1) as an intermediate by reacting alken and carbon dioxide with a transition metal complex in the presence of Lewis acid and a base. The metal lactone compound is formed and the Lewis acid and the base are allowed to act on the metal lactone compound, and the acid dissociation constant (pKa1) of the conjugated acid of the base and the acid of the α, β-unsaturated carboxylic acid are included. The relationship with the deviation constant (pKa2) is pKa1 <pKa2, and
A method for synthesizing α, β-unsaturated carboxylic acid, wherein the base is at least one compound selected from the group consisting of an aniline compound, an N-dimethylaniline compound, a pyridine compound, and a pyrazine compound .

[In the formula, M represents a transition metal, L is a monodentate ligand independently, or L cooperates to form a bidentate ligand. ] The method for synthesizing an α, β-unsaturated carboxylic acid according to claim 1, wherein the base is at least one compound selected from the group consisting of halogenated aniline, halogenated pyridine, and 2-methylpyrazine.