Screening method for catalysts for the production of ester compounds

Abstract

This invention provides a method for selecting a catalyst that yields a higher selectivity for 2-acetoxypropanoate than for 3-acetoxypropanoate in a reaction that synthesizes 2-acetoxypropanoate from vinyl acetate, carbon monoxide, and a primary or secondary alcohol, using a metal complex catalyst consisting of a bidentate organophosphine ligand and Pd. [Solution] A metal complex catalyst consisting of a bidentate organophosphine ligand and Pd is used, which has an embedded packing rate of 77% or more when the phosphine ligand is coordinated to Pd.

Description

Technical Field

[0001] The present disclosure relates to a method for screening a catalyst used in a reaction for synthesizing a 2-acetoxypropanoic acid ester from vinyl acetate, carbon monoxide, and a primary or secondary alcohol, using a metal complex catalyst composed of a bidentate organophosphine ligand and Pd.

Background Art

[0002] Ester compounds are used as intermediate raw materials such as solvents, fragrances, emulsifiers, humectants, and pharmaceuticals. Conventionally, methods for synthesizing esters with a linear carbon chain portion have attracted attention. In recent years, however, methods for synthesizing esters with a branched carbon chain portion of carboxylic acids have attracted attention for purposes such as developing surfactants with new functions.

[0003] Patent Document 1 discloses a method for the carbonylation of vinyl acetate by reacting vinyl acetate with carbon monoxide in the presence of a source of hydroxy groups and a catalyst system comprising a combination of (a) a metal of Group VIIIB or a compound thereof and (b) a specific bidentate phosphine.

[0004] Patent Document 2 discloses a method for producing a propionic acid ester derivative by reacting a substituted vinyl compound, an alcohol compound, and carbon monoxide in the presence of a Group 8 metal compound of the periodic table, a phosphorus ligand, and a polymeric sulfonic acid compound.

[0005] Patent Document 3 discloses a method for producing a propionic acid ester derivative by reacting an olefinically unsaturated compound, alcohols, and carbon monoxide in the presence of at least one of a Group 10 metal compound and a neutral cocatalyst.

[0006] Patent Document 4 describes a method for producing 2-hydroxycarboxylic acid, which includes: (a) reacting an enol ester with carbon monoxide and a hydroxy compound in the presence of a palladium catalyst and a solvent to obtain a carbonylated ester; and (b) hydrolyzing the carbonylated ester with an acid catalyst to obtain 2-hydroxycarboxylic acid. Patent Document 4 describes vinyl acetate as the enol ester, dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2) as the palladium catalyst, methanol as the hydroxy compound, and lactic acid as the 2-hydroxycarboxylic acid.

[0007] Patent Document 5 describes a method for producing 2-hydroxy acid, which consists of: (1) reacting an enol acyl ester with carbon monoxide and a hydroxy compound to produce an acyloxy ester or a hydroxy ester or both; and (2) hydrolyzing the product of (1) to produce 2-hydroxy acid.

[0008] Patent Document 6 discloses a method for producing methyl 2-acetoxypropanoate by reacting vinyl acetate with a primary or secondary alcohol and carbon monoxide in the presence of a catalyst containing a palladium compound and a monodentate ligand such as 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl (SPhos).

[0009] Non-Patent Document 1 discloses a method for reacting an enol ester with methanol and carbon monoxide using a palladium complex catalyst in the presence of a basic cocatalyst such as a pyridine derivative.

[0010] Non-Patent Document 2 discloses a methoxycarbonylation reaction of vinyl acetate using a palladium catalyst containing a monodentate ligand such as triphenylphosphine.

Prior Art Documents

Patent Documents

[0011]

Patent Document 1

[0012] [Non-Patent Document 1] Bulletin of the Chemical Society of Japan, 1996, Vol. 69, pp. 1337-1345 [Non-Patent Document 2] ARKIVOC, 2012, (iii) pp. 66-75 [Overview of the Initiative] [Problems that the invention aims to solve]

[0013] However, conventional methods for producing ester compounds, particularly those using catalysts containing bidentate ligands, have resulted in insufficient selectivity for ester compounds. Bidentate ligands are expected to prevent catalyst deactivation through their chelating effect. Therefore, there is a need for a production method that can produce specific ester compounds with high selectivity using catalysts containing bidentate ligands. However, catalyst selection has required considerable trial and error and experimentation.

[0014] This disclosure provides a screening method that can efficiently select catalysts containing bidentate ligands capable of producing ester compounds with high selectivity. [Means for solving the problem]

[0015] This disclosure relates to the following [1]-[3]. [1] In the reaction for synthesizing 2-acetoxypropanoic acid ester from vinyl acetate, carbon monoxide, and a primary or secondary alcohol represented by the general formula (1), using a metal complex catalyst composed of two organic phosphine ligands and Pd, A method for screening a catalyst that employs a metal complex catalyst having an embedding filling rate of 77% or more when the phosphine ligand is coordinated to Pd as the metal complex catalyst. R 1 -OH (1) (In the formula, R 1 is a hydrocarbon group having 1 to 10 carbon atoms, the hydrocarbon group has no ethylenic double bond and triple bond, and may contain an alicyclic or aromatic ring, and may be an alicyclic or aromatic ring) [2] The screening method according to [1], which employs a metal complex catalyst having an embedding filling rate of 85% or less. [3] The screening method according to [1] or [2], wherein the bidentate organic phosphine ligand is represented by the general formula (2). X 1 (X 2 )-P-A 1 -Y-A 2 -P-X 3 (X 4 ) (2) (In the formula, A 1 and A 2 each independently represent a single bond or an alkylene group having 1 to 10 carbon atoms, Y represents a hydrocarbon structure having 4 to 20 carbon atoms with at least one ring structure, or a heterocyclic structure having 4 to 20 carbon atoms with 1 to 2 heteroatoms selected from oxygen atoms and nitrogen atoms, and the ring structure or heterocyclic structure is bonded to A 1 and A 2 , P represents a phosphorus atom, X 1 , X 2 , X 3 and X 4 each independently represent a hydrocarbon group having 4 to 30 carbon atoms with at least one secondary or tertiary carbon atom, and the secondary or tertiary carbon atom is bonded to the phosphorus atom respectively, X 1and X 2 They may be bonded to each other to form a ring structure, X 3 and X 4 They may be bonded to each other to form a ring structure, X 1 , X 2 , X 3 and X 4 (This may include at least one heteroatom selected from oxygen atoms and nitrogen atoms.) [Effects of the Invention]

[0016] The screening method described herein allows for the efficient selection of catalysts containing bidentate ligands that can produce ester compounds with high selectivity. [Brief explanation of the drawing]

[0017] [Figure 1] This graph shows the relationship between the embedding rate and the selectivity (%) of the branched ester in the example (100 × B-isomer (moles) / (B-isomer (moles) + L-isomer (moles))). [Modes for carrying out the invention]

[0018] Embodiments of the present invention are described below, but the present invention is not limited to these forms, and various modifications are possible within the scope of implementation of the present invention. In this disclosure, when "~" is used for a numerical range, the numbers at both ends are the upper and lower limits, respectively, and are included in the numerical range. If multiple upper or lower limits are listed, a numerical range can be created from all combinations of upper and lower limits. Similarly, if multiple numerical ranges are listed, separate numerical ranges can be created by individually selecting and combining upper and lower limits from those numerical ranges.

[0019] In this disclosure, "ethylenic double bond" means a double bond formed between carbon atoms excluding the carbon atoms that form the aromatic ring.

[0020] [Method for producing ester compounds] One embodiment of the method for producing an ester compound involves using a metal complex catalyst consisting of a bidentate organophosphine ligand and Pd to react vinyl acetate with carbon monoxide and a primary or secondary alcohol represented by general formula (1) to synthesize 2-acetoxypropanoate ester represented by general formula (3) as an alkoxycarbonylation reaction product. R 1 -OH (1) (R in the formula 1 (This refers to a hydrocarbon group having 1 to 10 carbon atoms, which does not have ethylenic double or triple bonds and may contain an alicyclic or aromatic ring.) [ka] (R in the formula 1 This is the same as general formula (1).

[0021] <Vinyl acetate> Commercially available vinyl acetate can be used. It is preferable that the vinyl acetate does not contain impurities that inhibit the reaction.

[0022] <Grade 1 or Grade 2 alcohol> General formula (1):R 1 R in primary or secondary alcohols represented by -OH 1 R is a hydrocarbon group having 1 to 10 carbon atoms, and the hydrocarbon group does not have ethylenic double and triple bonds, and may contain an alicyclic or aromatic ring, or may contain an alicyclic or aromatic ring. Specific examples of primary or secondary alcohols represented by general formula (1) include methanol, ethanol, 1-propanol, isopropyl alcohol, 1-butanol, isobutyl alcohol, sec-butyl alcohol, 1-hexanol, 1-octanol, 2-ethylhexanol, cyclohexanemethanol, and benzyl alcohol. From the viewpoint of improving the activity of the ester compound production reaction, ease of separation from the ester compound, and ease of availability, R 1It is preferable to use a primary or secondary alcohol represented by general formula (1), in which is an alkyl group having 1 to 5 carbon atoms; more preferably methanol or ethanol; and most preferably ethanol.

[0023] When the primary or secondary alcohol represented by general formula (1) is ethanol, it is also preferable to use bioethanol derived from plants. Commercially available bioethanol derived from plants may be used.

[0024] In the method for producing an ester compound according to one embodiment, the molar ratio of vinyl acetate to a primary or secondary alcohol represented by general formula (1) (vinyl acetate: primary or secondary alcohol) is preferably 1:0.5 to 1:100, more preferably 1:1 to 1:30, and even more preferably 1:1.2 to 1:20, in order to produce the ester compound in higher yield and with higher selectivity.

[0025] <Carbon monoxide> In one embodiment, it is preferable to use a gas containing carbon monoxide as the carbon monoxide. The gas containing carbon monoxide may be a gas containing only carbon monoxide, or it may be a gas containing carbon monoxide plus at least one selected from nitrogen gas, an inert gas such as argon, and hydrogen gas. It is preferable that the gas containing carbon monoxide does not contain oxidizing gases such as air or oxygen.

[0026] The amount of carbon monoxide used during the reaction is preferably such that the partial pressure of carbon monoxide in the reaction vessel, which is set to a gas atmosphere containing a reaction solution including vinyl acetate and a primary or secondary alcohol represented by general formula (1), is within the range of 0.05 to 20 MPa, more preferably within the range of 0.1 to 10 MPa, and even more preferably within the range of 0.5 to 6 MPa. It is particularly preferable to carry out the reaction while replenishing the carbon monoxide consumed during the reaction so that the partial pressure of carbon monoxide in the reaction vessel is maintained within the range of 0.5 to 6 MPa.

[0027] In this reaction, vinyl acetate, a primary or secondary alcohol, and carbon monoxide coordinate to the Pd metal complex catalyst, and these elements bond together through the action of Pd, thereby enabling the production of ester compounds. If the partial pressure of carbon monoxide in the reaction vessel during the reaction is 0.05 MPa or higher, the coordination of carbon monoxide to Pd proceeds smoothly. If the partial pressure of carbon monoxide in the reaction vessel during the reaction is 20 MPa or lower, carbon monoxide does not inhibit the coordination of vinyl acetate to Pd, and the reaction proceeds smoothly. Furthermore, there is no need to use expensive manufacturing equipment that can withstand high pressure, thus reducing equipment costs.

[0028] <Metal complex catalyst> The metal complex catalyst targeted by the screening method of one embodiment consists of a bidentate organophosphine ligand and palladium (Pd). This metal complex catalyst can be obtained by reacting a palladium-containing compound, which serves as a Pd source, with a bidentate organophosphine ligand.

[0029] The palladium-containing compound may be elemental Pd metal, inorganic salts of palladium such as nitrates and sulfates; sulfonates such as methanesulfonates and ethanesulfonates; salts of carboxylic acids such as formic acid and acetic acid; and complexes or complex salts. The palladium-containing compound used in the synthesis of the metal complex catalyst may be one type or two or more types.

[0030] Examples of ligands for the complex or complex salt include hydroxo; alkoxy ligands such as methoxy, ethoxy, propoxy, and butoxy; acyl ligands such as acetyl and propionyl; alkoxycarbonyl ligands such as methoxycarbonyl and ethoxycarbonyl; acetylacetonate ligands such as acetylacetonate and hexafluoroacetylacetonate; diene ligands such as cyclopentadienyl, dibenzylideneacetone, and cyclooctadiene; halogen ligands such as chlorine and bromine; carbon monoxide; H2O; phosphine ligands such as triphenylphosphine and tri(t-butyl)phosphine; and nitrogen-containing compounds such as NH3, NO, NO2, ethylenediamine, pyridine, and phenanthroline. Two or more different ligands may be coordinated.

[0031] Examples of complexes or complex salts include acetylacetone palladium, tetrakis(triphenylphosphine)palladium, and bis(tri-o-tolylphosphine)palladium diacetate.

[0032] Specific examples of palladium-containing compounds include at least one 0-valent or 2-valent palladium compound selected from palladium(II) chloride, palladium(II) nitrate, palladium(II) sulfate, palladium(II) acetate, bis(acetylacetonato)palladium(II) (Pd(acac)2), tris(dibenzylideneacetone)dipalladium(O) (Pd2(dba)3), and dipalladium(O)tris(dibenzylideneacetone)chloroform (Pd2(dba)3·CHCl3).

[0033] From the viewpoint of catalytic activity and economic efficiency, the amount of palladium-containing compound used (moles as metallic Pd) is preferably 0.01 to 20 moles, more preferably 0.05 to 10 moles, and even more preferably 0.1 to 5 moles per 100 moles of vinyl acetate. When the amount of palladium-containing compound used is 0.01 moles or more per 100 moles of vinyl acetate, the concentration of the catalytic reactive species (hydride complex, etc.) can be ensured. Therefore, the alkoxycarbonylation reaction that produces the ester compound represented by general formula (3) is effectively promoted, and high activity is obtained. On the other hand, using 20 moles or less is economically advantageous.

[0034] The bidentate organophosphine ligand is preferably the bidentate organophosphine ligand represented by general formula (2). X 1 (X 2 )-PA 1 -YA 2 -PX 3 (X 4 ) (2) (In the formula, A 1 and A 2 Each independently represents a single bond or an alkylene group having 1 to 10 carbon atoms, Y represents a hydrocarbon structure having 4 to 20 carbon atoms having at least one ring structure, or a heterocyclic structure having 4 to 20 carbon atoms having 1 to 2 heteroatoms selected from oxygen and nitrogen atoms, and the ring structure or heterocyclic structure is A 1 and A 2 It is bonded to, where P represents the phosphorus atom, and X 1 , X 2 , X 3 and X 4 Each of these independently represents a hydrocarbon group having 4 to 30 carbon atoms, each having at least one secondary or tertiary carbon atom, which is bonded to a phosphorus atom.

[0035] A 1 and A 2 Each of these independently represents a single bond or an alkylene group with 1 to 10 carbon atoms. In the case of a single bond, A 1 and / or A2 It is absent, and the phosphorus atom (P) is directly bonded to the ring structure or heterocyclic structure in Y. 1 and A 2 However, in the case of alkylene groups having 1 to 10 carbon atoms, one end of each alkylene group is directly bonded to the ring structure or heterocyclic structure in Y. As alkylene groups having 1 to 10 carbon atoms, linear alkylene groups having 1 to 5 carbon atoms are preferred, and methylene groups (-CH2-), ethylene groups (-CH2-CH2-), and propylene groups (-CH2-CH2-CH2-) are more preferred.

[0036] Y represents a hydrocarbon structure with 4 to 20 carbon atoms having at least one ring structure, or a heterocyclic structure with 4 to 20 carbon atoms having 1 to 2 heteroatoms selected from oxygen and nitrogen atoms. The ring structure or heterocyclic structure with 4 to 20 carbon atoms that Y has, composed of some or all of the hydrocarbons with 4 to 20 carbon atoms, is A 1 and A 2 It is directly bonded to. Examples of ring structures in hydrocarbon structures having 4 to 20 carbon atoms and having at least one ring structure include alicyclic structures and aromatic ring structures. Alicyclic structures may be bridged rings. Alicyclic structures that do not contain ethylenically unsaturated bonds are preferred. Examples of alicyclic structures include cyclobutane rings, cyclopentane rings, cyclohexane rings, cycloheptane rings, cyclooctane rings, cyclononane rings, cyclodecane rings, and cycloundecane rings. Examples of aromatic ring structures include benzene rings, naphthalene rings, anthracene rings, and fluorene rings. Examples of heterocyclic structures having 4 to 20 carbon atoms and having 1 to 2 heteroatoms selected from oxygen and nitrogen atoms include tetrahydrofuran rings, tetrahydropyran rings, pyrrolidine rings, piperidine rings, and piperazine rings. Y may be a composite structure of an aromatic ring and a heterocyclic structure, such as a xanthene ring. Hydrocarbon substituents such as alkyl groups may be bonded to the heterocyclic structure. The number of carbon atoms in the heterocyclic structure refers to the total number of carbon atoms contained in Y, including hydrocarbon substituents, etc. Y preferably does not contain ethylenically unsaturated bonds.

[0037] X1 , X 2 , X 3 and X 4 Each of these independently represents a hydrocarbon group with 4 to 30 carbon atoms, each having at least one secondary or tertiary carbon atom. The secondary or tertiary carbon atom is directly bonded to a phosphorus atom. 1 and X 2 They may be bonded to each other to form a ring structure. 3 and X 4 The same applies to X in this case. 1 and X 2 , or X 3 and X 4 The total number of carbon atoms is between 4 and 30. 1 , X 2 , X 3 and X 4 It may contain at least one heteroatom selected from oxygen atoms and nitrogen atoms. 1 , X 2 , X 3 and X 4 Specific examples include the t-butyl group and the adamantyl group.

[0038] The amount of bidentate organophosphine ligand used is preferably 0.5 to 5 moles, more preferably 1 to 4 moles, and even more preferably 1.5 to 3 moles, per 1 mole of Pd in ​​the palladium-containing compound. When the amount of bidentate organophosphine ligand used is 0.5 moles or more, the reaction-active species of the catalyst to which the bidentate organophosphine ligand is effectively coordinated is efficiently generated. As a result, the alkoxycarbonylation reaction is promoted, and the ester compound represented by general formula (3) is produced with higher selectivity. When the amount of bidentate organophosphine ligand used is 5 moles or less, the reaction to produce the ester compound represented by general formula (3) can be effectively promoted. This is because too much bidentate organophosphine ligand makes it difficult for carbon monoxide to coordinate, which can slow down the reaction rate of the alkoxycarbonylation reaction.

[0039] <Acidic compounds> In one embodiment of the method for producing an ester compound, it is preferable to carry out the reaction in the presence of an acidic compound. In this specification, "acidic compound" means a Brønsted acid, a salt of a Brønsted acid, or a Lewis acid. Preferably, it is a Brønsted acid or a salt of a Brønsted acid. The acidic compound functions as a hydridizing agent for Pd. This is presumed to promote the alkoxycarbonylation reaction.

[0040] Examples of acidic compounds include hydrochloric acid; nitric acid; sulfuric acid; alkano acids having 2 to 12 carbon atoms; alkyl sulfonic acids such as methanesulfonic acid and t-butylsulfonic acid; aryl sulfonic acids such as benzenesulfonic acid, naphthalenesulfonic acid, o-toluenesulfonic acid, m-toluenesulfonic acid, and p-toluenesulfonic acid; sulfonic acids such as chlorosulfonic acid, fluorosulfonic acid, trifluoromethanesulfonic acid, and 2-hydroxypropanesulfonic acid, and their salts; sulfonated ion exchange resins; perhalic acids such as perchloric acid; perfluorocarboxylic acids such as trichloroacetic acid and trifluoroacetic acid; orthophosphoric acid; phosphonic acids such as benzenephosphonic acid; sulfuric acid esters such as dimethyl sulfate; sulfonic acid esters such as methyl methanesulfonate and methyl trifluoromethanesulfonate; and ammonium salts and pyridinium salts thereof.

[0041] Because the acidity is appropriate, the acidic compound is preferably at least one selected from the group consisting of alkyl sulfonic acid, ammonium salt of alkyl sulfonic acid, pyridinium salt of alkyl sulfonic acid, aryl sulfonic acid, ammonium salt of aryl sulfonic acid, and pyridinium salt of aryl sulfonic acid, more preferably at least one selected from the group consisting of alkyl sulfonic acid and aryl sulfonic acid, and particularly preferably at least one selected from methanesulfonic acid and p-toluenesulfonic acid.

[0042] Acidic compounds may be used in combination of two or more types.

[0043] The amount of acidic compound used is preferably in the range of 0.05 to 10 moles, more preferably 0.1 to 7 moles, and even more preferably 0.2 to 5 moles, of the acidic compound's acid sites (i.e., protons) per mole of Pd. When the acidic compound has 0.05 moles or more acid sites, the catalyst's reactive species (hydride complex, etc.) are efficiently generated, effectively promoting alkoxycarbonylation. On the other hand, when the acidic compound has 10 moles or less acid sites, side reactions in the alkoxycarbonylation reaction can be effectively suppressed.

[0044] <Nitrogen-containing heterocyclic aromatic compounds> In one embodiment of the method for producing an ester compound, it is also preferable to carry out the reaction in the presence of a nitrogen atom-containing heterocyclic aromatic compound together with an acidic compound. This further promotes the reaction for producing the ester compound. This is presumed to be because, when a nitrogen atom-containing heterocyclic aromatic compound is present together with an acidic compound, the acidity of the catalyst is more easily adjusted to a range that promotes the alkoxycarbonylation reaction. In addition, it also has the effect of suppressing side reactions between vinyl acetate and primary or secondary alcohols represented by general formula (1). In this embodiment, if the acidic compound is a compound having a nitrogen atom-containing aromatic ring, the acidic compound can also function as a nitrogen atom-containing heterocyclic aromatic compound. An example of an acidic compound that also functions as a nitrogen atom-containing heterocyclic aromatic compound is picolinic acid.

[0045] Examples of nitrogen-containing heterocyclic aromatic compounds include pyridine, picoline, imidazole, pyrazole, and oxazole. Among these, the nitrogen-containing heterocyclic aromatic compound is preferably at least one selected from pyridine and picoline, and more preferably pyridine, because it allows for the production of ester compounds in higher yield and with higher selectivity. Two or more nitrogen-containing heterocyclic aromatic compounds may be used in combination.

[0046] The amount of nitrogen-containing heterocyclic aromatic compound used is preferably 0.1 to 50 moles, more preferably 1 to 30 moles, and even more preferably 5 to 25 moles, per mole of Pd. When the amount of nitrogen-containing heterocyclic aromatic compound used is 0.1 moles or more, the acidity tends to fall within the range that promotes the alkoxycarbonylation reaction, and the ester compound represented by general formula (3) is easily produced with high selectivity. On the other hand, when the amount of nitrogen-containing heterocyclic aromatic compound used is 50 moles or less, the nitrogen-containing heterocyclic aromatic compound does not inhibit the coordination of vinyl acetate to Pd, so the reaction for producing the ester compound proceeds smoothly and side reactions are suppressed.

[0047] <Solvent> In the method for producing the ester compound according to one embodiment, a solvent may be used as necessary. Preferably, the solvent is a chemical species that does not participate in the reaction with vinyl acetate, carbon monoxide, and a primary or secondary alcohol represented by general formula (1). Examples of such solvents include tetrahydrofuran, dioxane, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, n-propyl acetate, n-butyl acetate, n-heptane, acetonitrile, toluene, xylene, N-methylpyrrolidone, γ-butyrolactone, N,N-dimethylformamide, and N,N-dimethylacetamide. It is also possible to use the primary or secondary alcohol itself, represented by general formula (1), which is the reaction substrate, as the solvent. Two or more solvents may be used in combination.

[0048] Among these solvents, it is particularly preferable to use one or more selected from tetrahydrofuran, acetone, ethyl acetate, toluene, and xylene, as this allows for the production of ester compounds in higher yield and with higher selectivity. In particular, toluene is preferred from the viewpoint of solubility of metal complex catalysts, acidic compounds, and nitrogen atom-containing heterocyclic aromatic compounds, as well as ease of separation from the product.

[0049] The amount of solvent used is preferably in the range of 0.05 to 20 mol / liter, more preferably in the range of 0.1 to 10 mol / liter, and even more preferably in the range of 0.5 to 5 mol / liter. When the concentration of vinyl acetate in the reaction solution is 0.05 mol / liter or higher, the concentration of vinyl acetate in the reaction solution tends to fall within the range that promotes the alkoxycarbonylation reaction, making it easier to produce ester compounds in high yield. When the concentration of vinyl acetate in the reaction solution is 20 mol / liter or lower, it is easier to ensure a substrate concentration that allows the reaction to proceed smoothly, which is preferable.

[0050] <Reaction conditions> The reaction conditions in the method for producing the ester compound according to one embodiment can be appropriately determined depending on the type of ester compound to be produced, within the range in which the alkoxycarbonylation reaction between vinyl acetate, a primary or secondary alcohol represented by general formula (1), and carbon monoxide proceeds.

[0051] The reaction conditions preferably satisfy one or more of the following conditions: (a) reaction pressure, (b) reaction temperature, and (c) reaction time.

[0052] (a) Reaction pressure The partial pressure of carbon monoxide in the reaction vessel is preferably 0.05 to 20 MPa, more preferably 0.1 to 10 MPa, and even more preferably 0.5 to 6 MPa. By setting the partial pressure of carbon monoxide in the reaction vessel to 0.05 to 20 MPa, ester compounds can be produced in higher yield.

[0053] (b) reaction temperature The reaction temperature is preferably 60 to 140°C, and more preferably 80 to 120°C. A reaction temperature of 60°C or higher further promotes the alkoxycarbonylation reaction that produces the ester compound. A reaction temperature of 140°C or lower is preferable because it can suppress side reactions in the alkoxycarbonylation reaction.

[0054] (c) reaction time The reaction time is preferably 1 to 50 hours, and more preferably 10 to 20 hours. A reaction time of 1 hour or more allows for the production of ester compounds in higher yield. A reaction time of 50 hours or less can suppress side reactions associated with the formation of ester compounds.

[0055] [Ester compound: 2-acetoxypropanoate ester] The ester compound produced by the manufacturing method of one embodiment is a 2-acetoxypropanoate ester represented by general formula (3). In the manufacturing method of one embodiment, when vinyl acetate, carbon monoxide, and a primary or secondary alcohol represented by general formula (2) are reacted, a 3-acetoxypropanoate ester with a linear structure is produced as a by-product via alkoxycarbonylation, in addition to the branched 2-acetoxypropanoate ester. The 2-acetoxypropanoate ester can be converted into a compound useful as a solvent by ethanolylation, but the 3-acetoxypropanoate ester has a boiling point that is too high even after ethanolylation, making it unsuitable for use as a solvent. Therefore, it is desirable that the selectivity for the branched 2-acetoxypropanoate ester be high in the synthesis reaction. The 2-acetoxypropanoate ester is treated as the branched form (B-isomer), and the 3-acetoxypropanoate ester as the linear form (L-isomer). The selectivity of the 2-acetoxypropanoate ester in the reaction is evaluated as follows: Selectivity of the branched form (%): 100 × B-isomer (moles) / (B-isomer (moles) + L-isomer (moles)). If the selectivity of the branched form is 80% or higher, the selectivity of the 2-acetoxypropanoate ester is considered good.

[0056] <Burial filling rate> In organometallic complexes, the buried packing ratio is defined as the proportion of the volume of a sphere with the central metal as the origin, occupied by a particular ligand of interest. This sphere's volume represents the space around the metal atom that must be shared by different ligands when the ligand coordinates to the central metal. This is usually also called the first coordination sphere. In this disclosure, the buried packing ratio refers to the proportion of the volume occupied by bidentate organophosphine ligands within 3.5 Å of the metal center of the complex used as a catalyst.

[0057] In transition metal complexes, the way ligands wrap around the metal determines the stability, activity, and substrate selectivity of the resulting catalyst. In particular, catalyst design requires controlling the reaction characteristics and frequency of the reaction substrate by selecting ligands to coordinate to the central metal. Therefore, molecular exploration is necessary based on descriptors that can capture small electronic or structural differences in ligands. In this system, ligands often have a bulkiness that effectively shields the central metal, and it is thought that selectivity is influenced by steric effects, which restrict the space available to the reactants. Therefore, using descriptors that can capture structural differences as indicators for molecular exploration is extremely rational.

[0058] Traditionally, in the field of organometallic chemistry, the molecular descriptor Tolman's angle of cone [Reference 1] has been used as such an indicator, but this descriptor has been limited to phosphine ligands. In recent years, Taft [Reference 2], Charton [Reference 3], and Verloop [Reference 4] have proposed a molecular descriptor called the immersion-filling ratio. This uses the volume occupancy of the first coordination sphere around the metal atom of interest as an indicator, and is mainly used in the field of organometallic chemistry as one of the molecular descriptors that expresses steric effects applicable to a wider range of ligands, not just phosphines.

[0059] [References] References 1. Falivene, L.; Credendino, R.; Poater, A.; Petta, A.; Serra, L.; Oliva, R.; Scarano, V.; Cavallo, L.Organometallics 2016, 35, 2286. Reference 2. Hansch, C.; Leo, A.; Taft, RW Chem. Rev. 1991, 91, 165. Reference 3. Charton, M.; Charton, BJ Am. Chem. Soc. 1975, 97, 6472. Reference 4. Verloop, A.; Hoogenstraaten, W.; Tipker, J. Development and Application of New Steric Substituent Parameters in Drug Design 1976, 165.

[0060] <Method for calculating and determining the percentage of buried sutures> 1. Model creation The phosphorus ligand for which we want to calculate the packing efficiency is coordinated to Pd in ​​a bidentate manner, and then one hydrogen atom is added to the Pd to create a hydride complex, which is then created using GaussView version 6.0 [Reference 5]. The structure of this complex is then optimized using the quantum chemistry calculation software Gaussian16 [Reference 6]. The semi-empirical PM6 method is used as the calculation level, and Grimme's semi-empirical dispersion force correction method is used in the structure optimization calculation to take into account van der Waals dispersion interactions between atoms. Vibrational analysis is performed for all calculations, and by confirming that all obtained normal frequencies are positive, it is assumed that the system has converged to the bottom of the potential surface. 2. Method for determining the buried suture filling ratio Based on the stable structure of the hydride complex obtained in step 1 above, the burying and filling rate is calculated using the molecular descriptor calculation software SambVca 2 [References 1, 7]. First, the Gaussian log file of the above stable structure is converted to an xyz file format, and this is used as input for SambVca 2. All of the following operations can be performed using the input format of SambVca 2 or the GUI screen on its website [Reference 8]. First, define the center of the first coordination sphere as the Pd center, then select one atom from the list of atoms within the ligand to define the z-axis of the Cartesian coordinate system. Next, specify a different atom from the one previously selected to define the x-axis of the Cartesian coordinate system. This allows us to define the Cartesian coordinate system necessary for the analysis. Then, remove the hydrogen atoms bonded to the Pd. Next, define the radius of the first coordination sphere as 3.5 Å, and set the integration grid for calculating the molecular volume of the first coordination sphere and ligand to its default settings. Finally, set the system to include the molecular volume of the hydrogen atoms within the ligand in the calculation of the molecular volume, and perform the calculation.

[0061] [References] Reference 5. GaussView, Version 6, Dennington, Roy; Keith, Todd A.; Millam, John M. Semichem Inc., Shawnee Mission, KS, 2016. Reference 6. Gaussian 16, Revision C.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.Ochterski, JW; Martin, RL; Morokuma, K.; Farkas, O.; Foresman, JB; Fox, DJ Gaussian, Inc., Wallingford CT, 2016. Reference 7. Falivene, L. et al. Nat. Chem. 2019, 11, 872. Reference 8. This is the public page for the SambVca2.1 web application. http: / / www.aocdweb.com / OMtools / sambvca2.1 / index.html

[0062] <Screening Method> When considering candidate metal complex catalysts consisting of a bidentate organophosphine ligand and Pd for use in the reaction to synthesize 2-acetoxypropanoic acid ester from vinyl acetate, carbon monoxide, and a primary or secondary alcohol represented by general formula (1), catalysts can be efficiently screened by selecting catalysts in which the burial and packing ratio when the phosphine ligand coordinates to Pd, as calculated by the above method, is 77% or higher. There is no particular upper limit to the burial and packing ratio, but 85% or less is preferred, and 82% or less is more preferred. [Examples]

[0063] The present invention will be described in more detail below with reference to examples and comparative examples. However, the present invention is not limited to the following examples.

[0064] (Bidentate organophosphine ligands) Of the bidentate organophosphine ligands listed in Table 1, the precursors of bidentate organophosphine ligands 12 and 13, respectively, were prepared according to the "Synthesis of Precursor of Bidentate Organophosphine Ligand 12" and "Synthesis of Precursor of Bidentate Organophosphine Ligand 13" described below. For bidentate organophosphine ligand No. 14, a commercially available product (9,9-dimethyl-4,5-bis(di-tert-butylphosphinoxanthene, Sigma-Aldrich Co., Ltd.) was used. For Nos. 12 and 13, after synthesizing the organophosphine-borane complex, which is the precursor of the organophosphine ligand, the borane was removed during the synthesis reaction of ethyl 2-acetoxypropanoate to convert it to a Pd complex.

[0065] (Synthesis of 2-acetoxypropanoate ester) For the synthesis reactions of methyl 2-acetoxypropanoate from vinyl acetate, methanol, and carbon monoxide, Table 1, Nos. 1 to 11, presents the results of the synthesis reactions cited from the literature. For Nos. 12 and 13, ethyl 2-acetoxypropanoate was synthesized according to the method described in "Synthesis Reaction of Ethyl 2-acetoxypropanoate 1". For No. 14, ethyl 2-acetoxypropanoate was synthesized according to the method described in "Synthesis Reaction of Ethyl 2-acetoxypropanoate 2".

[0066] (Synthesis of a precursor of bidentate organophosphine ligand 12) Synthesis of t-Bu-DIOP borane complex The t-Bu-DIOP(trans-4,5-bis(di-tert-butylphoffinomethyl)-2,2-dimethyl-1,3-dioxolane)borane complex was synthesized by the following method.

[0067] (1) Synthesis of 2,2-dimethyl-trans-4,5-bis(tosyloxymethyl)-1,3-dioxolane In a 100 mL two-necked round-bottom flask that had been flame-dried, super-dehydrated methanol (Fujifilm Wako Pure Chemical Industries, Ltd., 18 mL) and dimethyl 2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate (Tokyo Chemical Industries, Ltd., 1.7 mL: 9.27 mmol) were added and stirred. After cooling to 0°C, sodium borohydride (Tokyo Chemical Industries, Ltd., 1.08 g: 28.6 mmol) was added, and the mixture was stirred at room temperature for 40 minutes. After stopping the reaction by adding water, the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. By concentrating and drying, 2,2-dimethyl-trans-4,5-bis(hydroxymethyl)-1,3-dioxolane was obtained (first-stage yield 58%). In a 50 mL two-necked round-bottom flask that had been flame-dried, pyridine (dehydrated, Kanto Chemical Co., Ltd., 8 mL) and the aforementioned 2,2-dimethyl-trans-4,5-bis(hydroxymethyl)-1,3-dioxolane (820 μL: 5.36 mmol) were added and stirred. After cooling to 0°C, p-toluenesulfonyl chloride (Tokyo Chemical Industries, Ltd., 3.09 g: 16.2 mmol) was added, and the mixture was stirred at room temperature for 24 hours. After diluting with water, the mixture was placed in a refrigerator at 0°C and left for 23 hours. After returning to room temperature, the resulting solid was filtered by suction, washed with water, and dried to obtain 2,2-dimethyl-trans-4,5-bis(tosyloxymethyl)-1,3-dioxolane (76%, second-stage yield 44%).

[0068] (2) Synthesis of di-tert-butylphosphineborane A 300 mL two-necked round-bottom flask that had been flame-dried was filled with super-dehydrated N,N-dimethylformamide (Fujifilm Wako Pure Chemical Industries, Ltd., 170 mL) and degassed by nitrogen gas bubbling. Sodium borohydride (Tokyo Chemical Industries, Ltd., 9.67 g: 256 mmol) was added and stirred to dissolve. After cooling to 0°C, di-tert-butylchlorophosphine (Tokyo Chemical Industries, Ltd., 15.8 mL: 83.0 mmol) was added dropwise and stirred at room temperature for 18 hours. Water was added to stop the reaction, diethyl ether was added to dilute the mixture, and the mixture was extracted with diethyl ether, washed with water, then saturated brine, and dried over anhydrous sodium sulfate. After concentration and drying, di-tert-butylphosphineborane was obtained by silica gel column chromatography in a hexane / ethyl acetate system (yield 92%).

[0069] (3) Synthesis of t-Bu-DIOP borane complex In a 300 mL two-necked round-bottom flask that had been flame-dried, the aforementioned di-tert-butylphosphineborane (2.61 g: 16.3 mmol) and anhydrous tetrahydrofuran (Tokyo Chemical Industries, Ltd., 50 mL) were added and stirred to dissolve. While cooled to -78°C, butyllithium cyclohexane solution (Sigma-Aldrich, Inc., 2.0 M, 9.1 mL: 18.2 mmol) was added dropwise, the temperature was raised to -10°C and stirred for 1 hour, and then cooled again to -78°C. Subsequently, the aforementioned tetrahydrofuran (30 mL) solution of 2,2-dimethyl-trans-4,5-bis(tosyloxymethyl)-1,3-dioxolane (1.91 g: 4.05 mmol), prepared in another 100 mL two-necked round-bottom flask that had been flame-dried, was added dropwise and stirred. After raising the temperature to room temperature and stirring for 17 hours, water was added dropwise to stop the reaction. The mixture was extracted with ethyl acetate, washed with saturated saline solution, and dried over anhydrous sodium sulfate. After concentration and drying, the precursor of bidentate organophosphine ligand 12 (trans-4,5-bis(di-tert-butylphosphinomethyl)-2,2-dimethyl-1,3-dioxolanediborane (t-Bu-DIOP borane)) was obtained by silica gel column chromatography in a hexane / ethyl acetate system (86%, third-step yield 38%).

[0070] (Synthesis of a precursor of bidentate organophosphine ligand 13) Synthesis of DTBPMCB borane complex The DTBPMCB (trans-1,2-bis(di-tert-butylphosphinomethyl)cyclobutane)borane complex was synthesized by the following method.

[0071] (1) Synthesis of trans-1,2-bis(tosyloxymethyl)cyclobutane In a 50 mL two-necked round-bottom flask, N,N-dimethylformamide (Sigma-Aldrich, 20 mL), trans-1,2-cyclobutanedicarboxylic acid (Pharma Block, 1.45 mg: 10.1 mmol), potassium carbonate (Kishida Chemical Co., Ltd., 5.55 g: 40.1 mmol), and iodomethane (Kishida Chemical Co., Ltd., 2.49 mL: 40 mmol) were added and stirred at room temperature for 20 hours. After dilution with ethyl acetate, the solution was extracted with ethyl acetate, washed with water, then saturated brine, and dried over anhydrous sodium sulfate. After concentration and drying, anhydrous tetrahydrofuran (Tokyo Chemical Industries, Ltd., 50 mL) was added and dissolved. In a separate 300 mL two-necked round-bottom flask that had been flame-dried, lithium aluminum hydride (Fujifilm Wako Pure Chemical Industries, Ltd., 2.31 g: 60.9 mmol) and tetrahydrofuran (35 mL) were added and stirred until dissolved, and then the aforementioned solution was added dropwise while cooled to 0°C. After heating under reflux for 14 hours, the mixture was cooled to 0°C, water and an aqueous sodium hydroxide solution were added, and the mixture was stirred for 1 hour to stop the reaction. After returning to room temperature, the inorganic salt precipitate was removed by Celite filtration, and the mixture was concentrated and dried to obtain trans-1,2-bis(hydroxymethyl)cyclobutane. In a 50 mL two-necked round-bottom flask that had been flame-dried, pyridine (Kanto Chemical Co., Ltd., anhydrous, 9 mL) and the aforementioned trans-1,2-bis(hydroxymethyl)cyclobutane (990 mg: 8.52 mmol) were added and stirred. After cooling to 0°C, p-toluenesulfonyl chloride (Tokyo Chemical Industries, Ltd., 5.06 g: 26.6 mmol) was added, and the mixture was stirred at room temperature for 25 hours. After stopping the reaction by adding water, the mixture was extracted with ethyl acetate, washed with hydrochloric acid, then saturated brine, and dried over anhydrous sodium sulfate. After concentration and drying, trans-1,2-bis(tosyloxymethyl)cyclobutane was obtained by silica gel column chromatography in a chloroform / methanol system (second-step yield 26%).

[0072] (2) Synthesis of di-tert-butylphosphineborane Di-tert-butylphosphineborane was obtained by the same method as in "Synthesis of bidentate organophosphine ligand 12".

[0073] (3) Synthesis of DTBPMCB borane complex In a 100 mL two-necked round-bottom flask that had been flame-dried, the aforementioned di-tert-butylphosphineborane (1.74 mg:10.9 mmol) and anhydrous tetrahydrofuran (Tokyo Chemical Industries, Ltd., 25 mL) were added and stirred to dissolve. While cooled to -78°C, butyllithium cyclohexane solution (Sigma-Aldrich, Inc., 2.0 M, 7 mL:14 mmol) was added dropwise, the temperature was raised to -10°C, and the mixture was stirred for 1 hour, then cooled again to -78°C. Subsequently, the aforementioned trans-1,2-bis(tosyloxymethyl)cyclobutane (1.12 mg:2.64 mmol) tetrahydrofuran (25 mL) solution, prepared in a separate 50 mL round-bottom flask, was added dropwise and stirred. After raising the temperature to room temperature and stirring for 19 hours, the reaction was stopped by adding water dropwise while cooling with ice. The mixture was extracted with ethyl acetate, washed with saturated saline solution, and dried over anhydrous sodium sulfate. After concentration and drying, the precursor of bidentate organophosphine ligand 13 (trans-1,2-bis(di-tert-butylphosphinomethyl)cyclobutanediborane (DTBPMCB borane)) was obtained by silica gel column chromatography in a hexane / ethyl acetate system (86%, third-step yield 23%).

[0074] (Synthesis reaction of 2-ethyl acetoxypropanoate 1) In a Schlenk reaction tube (20 mL), a stirring bar, an organophosphine-borane complex (16.8 μmol), a precursor of the organophosphine ligand, DABCO (1,4-diazabicyclo[2.2.2]octane) (84 μmol) as a deprotecting agent, and freeze-degassed toluene (1 mL) as a solvent for borane removal were added, and the mixture was stirred at 80°C for 8 hours. Next, after removing the toluene at 80°C under vacuum, the organophosphine ligand was extracted from the residue with freeze-degassed hexane. The extract was transferred to another Schlenk reaction tube (20 mL), and the hexane was removed at 80°C under vacuum. Subsequently, the organophosphine ligand was dissolved in freeze-degassed ethanol (Fujifilm Wako Pure Chemical Industries, Ltd., 0.28 mL: 4.8 mmol), and the mixture was transferred to a 40 mL stainless steel reaction vessel containing a stirring bar. In a reaction vessel containing an organophosphine ligand, PdCl2 (palladium chloride; Tanaka Kikinzoku Kogyo Co., Ltd., 1.5 mg, 8.4 μmol) as a palladium-containing compound and PTSA (p-toluenesulfonic acid monohydrate; Tokyo Chemical Industry Co., Ltd., 0.6 mg, 3.32 μmol) as an acidic compound were added to obtain a mixture of the organophosphine Pd complex and the acidic compound as a catalyst composition.

[0075] In a reaction vessel containing these catalyst compositions, vinyl acetate (Fujifilm Wako Pure Chemical Industries, Ltd.; 0.369 mL: 4.0 mmol), toluene as a solvent (Fujifilm Wako Pure Chemical Industries, Ltd.; 3.4 mL), and pyridine as a nitrogen atom-containing heterocyclic aromatic compound (Fujifilm Wako Pure Chemical Industries, Ltd.; 0.0135 mL: 168 μmol) were added under a nitrogen gas stream to obtain a reaction solution.

[0076] The amount of palladium chloride used in the reaction is 0.0021 moles per mole of vinyl acetate. The amount of organophosphine ligand used is 2 moles per mole of palladium chloride. The amount of PTSA (p-toluenesulfonic acid monohydrate) used is 0.395 moles per mole of palladium chloride, representing the acid site of PTSA. The amount of pyridine used is 20 moles per mole of palladium chloride. The amount of toluene used is 0.71 L per mole of ethanol (the amount at which the concentration of vinyl acetate in the reaction solution becomes 1.4 mol / L).

[0077] Next, using carbon monoxide gas, the reaction vessel was pressurized and depressurized three times between atmospheric pressure and 1 MPa, replacing the gas inside the reaction vessel with carbon monoxide gas. After that, the pressure inside the reaction vessel was increased to 5.0 MPa using carbon monoxide gas, and the reaction solution was stirred while reacting at 100°C for 24 hours to produce ethyl 2-acetoxypropanoate.

[0078] (Analysis of the product) The molar ratio (B / L) of the B-isomer (2-ethyl acetoxypropanoate) and the L-isomer (3-ethyl acetoxypropanoate) in the reaction products of synthesis reactions 1 and 2, and the selectivity of the branched compound were determined as follows.

[0079] The reaction solution after the reaction was analyzed using a gas chromatography system (instrument name: 6850 Series II, Agilent Technologies, Inc.) equipped with a flame ionization detector (FID) and a capillary column (J&W HP-1: inner diameter 0.32 mm, length 30 m, film thickness 0.25 μm). Quantitative analysis of the raw materials, the target ester compound, and by-reactants was performed using a calibration curve prepared with diethylene glycol dimethyl ether (Tokyo Chemical Industries, Ltd.) as the internal standard. The branched-type selectivity was calculated from the molar ratio (B / L) of the B and L isomers obtained by the following formula. Selectivity of branched branch = 100 × B / (B + L) %

[0080] (Synthesis reaction of ethyl 2-acetoxypropanoate 2) In a 120 mL stainless steel reaction vessel under a nitrogen gas stream, Pd2dba3 (tris(dibenzylideneacetone)dipalladium; Tokyo Chemical Industry Co., Ltd.; purity 77.8%, 69 mg, 58.6 μmol, 117 μmol as Pd) as a palladium source, 9,9-dimethyl-4,5-bis(di-tert-butylphosphinoxanthene) as a bidentate diphosphine ligand (Sigma-Aldrich Corporation; 117 mg, 234 μmol), methanesulfonic acid as an acidic compound (Tokyo Chemical Industry Co., Ltd.; 22.5 mg, 234 μmol), vinyl acetate (Resonac Corporation; 5 mL, 55 mmol), and ethanol (Fujifilm Wako Pure Chemical Industries, Ltd.; 55 mL) were added.

[0081] The amount of Pd2dba3 used is 0.001 ml per 1 ml of vinyl acetate. The amount of 9,9-dimethyl-4,5-bis(di-tert-butylphosphinoxanthene) used is 2 ml per 1 ml of palladium atoms in Pd2dba3. The amount of methanesulfonic acid used is equal to 2 ml of acid sites of methanesulfonic acid per 1 ml of palladium atoms in Pd2dba3. The amount of solvent containing ethanol used is 11 times the volume of vinyl acetate.

[0082] Next, using carbon monoxide gas, the reaction vessel was pressurized and depressurized three times between atmospheric pressure and 0.9 MPa, replacing the gas in the reaction vessel with carbon monoxide gas. After that, the pressure in the reaction vessel was increased to 0.7 MPa using carbon monoxide gas, and the reaction solution was stirred while reacting at 80°C for 1.5 hours to produce ethyl 2-acetoxypropanoate.

[0083] (Examples) Table 1 and Figure 1 show the results of the synthesis reactions of acetoxypropanoic acid esters No. 1 to No. 14. From Figure 1, it can be seen that when a bidentate phosphine ligand coordinates to Pd, if the burial packing rate is 77% or higher, the selectivity of the branched product exceeds 80%. Therefore, in the reaction to synthesize 2-acetoxypropanoic acid ester from vinyl acetate, carbon monoxide, and a primary or secondary alcohol, if a metal complex catalyst consisting of a bidentate organophosphine ligand with a burial packing rate of 77% or higher and Pd is selected, it is not necessary to perform the synthesis reaction of 2-acetoxypropanoic acid ester for each of the various ligands. According to this screening method, catalysts for the production of ester compounds can be efficiently selected. Judging from the trend in Figure 1, it is estimated that a burial packing rate of 85% or less is preferable, and 82% or less is more preferable.

[0084] [Table 1-1] [Table 1-2]

Claims

1. In a reaction to synthesize 2-acetoxypropanoate ester from vinyl acetate, carbon monoxide, and a primary or secondary alcohol represented by general formula (1), using a metal complex catalyst consisting of a bidentate organophosphine ligand and Pd, A catalyst screening method that employs a metal complex catalyst in which the phosphine ligand has an embedded packing rate of 77% or more when coordinated to Pd. R １ -OH (1) (In the formula R １ (This refers to a hydrocarbon group having 1 to 10 carbon atoms, which does not have ethylenic double or triple bonds and may contain an alicyclic or aromatic ring.)

2. The screening method according to claim 1, wherein a metal complex catalyst with an embedded filling rate of 85% or less is used.

3. The screening method according to claim 1 or 2, wherein the bidentate organophosphine ligand is represented by general formula (2). X １ (X ２ )-P-A １ -Y-A ２ -P-X ３ (X ４ ) (2) (wherein, A １ and A ２ each independently represent a single bond or an alkylene group having 1 to 10 carbon atoms, Y represents a hydrocarbon structure having 4 to 20 carbon atoms and having at least one ring structure, or a heterocyclic structure having 4 to 20 carbon atoms and having 1 to 2 heteroatoms selected from an oxygen atom and a nitrogen atom, and the ring structure or heterocyclic structure is bonded to A １ and A ２ ; P represents a phosphorus atom, and X １ , X ２ , X ３ and X ４ each independently represent a hydrocarbon group having 4 to 30 carbon atoms and having at least one secondary or tertiary carbon atom, and the secondary or tertiary carbon atom is bonded to the phosphorus atom respectively; X １ and X ２ may be bonded to each other to form a ring structure; X ３ and X ４ may be bonded to each other to form a ring structure; and X １ , X ２ , X ３ and X ４ may contain at least one heteroatom selected from an oxygen atom and a nitrogen atom.)

Images