Catalytic carbonylation of esters

Abstract

Disclosed herein are catalytic carbonylation processes using a catalyst system having a ligand salt and a transition metal compound, the ligand salt being a precursor to a carbene ligand.

Description

[0001] Cross-reference to related applications This application claims priority to U.S. Provisional Application No. 63 / 531,226, filed August 7, 2023, which is incorporated herein by reference. Background Technology

[0002] Catalytic carbonylation is a catalytic reaction in which carbon monoxide is added to an organic substrate. Carbonylation is widely used in industry to produce a variety of commercially useful products, such as acid anhydrides, carboxylic acids, and esters. However, to achieve the desired yield using inexpensive metal catalysts, the required catalyst loading is typically high. Commonly used transition metal catalysts can be very expensive and experience sudden and dramatic price spikes based on availability and demand.

[0003] Common catalysts for the carbonylation of esters are phosphine-based transition metal catalysts, such as those comprising one or more triphenylphosphine ligands. Triphenylphosphine transition metal catalysts typically achieve suboptimal turnaround numbers, resulting in relatively high amounts of ligands or metals used. This makes such catalysts an unattractive alternative to more commonly used but expensive transition metal complexes. Therefore, there is a need in the art for improved catalytic methods for the carbonylation of substrates such as esters. This disclosure addresses these and other needs. Summary of the Invention

[0004] In one aspect, a method is disclosed comprising carbonylating an ester in a reactor containing carbon monoxide or a source thereof in the presence of a catalyst system; wherein the ester has a structure represented by formula (I): , Where R 1 It is a hydrocarbon group; The catalyst system includes: Ligand precursor salts having the structure represented by formula (II): , The dashed lines (----) represent optional covalent bonds; Where R 2 and R 3 Independently selected from C1-C4 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclocycloalkyl, or bicycloheterocycloalkyl; Where R 4 for hydrogen, –C(R 5-7 ), where R 5 To R 7 Each of them is independently hydrogen or an unsubstituted C1-C4 alkyl group, or –C(=R 8)(R 7 ), wherein R 7 is hydrogen or unsubstituted C1-C4 alkyl, and wherein R 8 is -CH2 or unsubstituted C2-C4 alkyl; wherein X is halide, BF4, or PF6; a Group 8, 9, or 10 transition metal compound; and a halide source. DETAILED DESCRIPTION

[0005] I. Definitions “Carbonylation” means a reaction in which carbon monoxide is introduced into an organic substrate using carbon monoxide gas or a source thereof. For example, methyl propionate can be carbonylated in the presence of carbon monoxide or a source thereof to produce propanoic acid anhydride as well as other reaction products, including acetic acid and methyl acetate.

[0006] “Hydrocarbyl” encompasses C1-C24 alkyl, C2-C24 alkenyl, and C2-C24 alkynyl, whether straight-chained or branched. The hydrocarbyl group can be optionally substituted, in which at least one hydrogen of the hydrocarbyl group has been replaced by a non-hydrogen group, such as a halide group, a hydroxyl group, an ether group, a thiol group, a sulfide group, a carboxylic acid group, a carboxylate group, a phosphoric acid group, a phosphate group, a sulfonic acid group, a sulfonate group, a nitro group, a cyano group, a cycloalkyl group, a cycloalkenyl group, a cycloalkynyl group, an aryl group, a heteroaryl group, and the like.

[0007] “Alkyl” means a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, i-pentyl, sec-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. The alkyl group can be cyclic or acyclic. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol groups as described herein. “Alkyl” can be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like, up to and including C1-C24 alkyl.

[0008] "Cycloalkyl" means a non-aromatic carbon-based ring consisting of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. "Heterocycloalkyl" is a non-aromatic carbon-based ring type of cycloalkyl group in which at least one of the ring's carbon atoms is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuranyl. Cycloalkyl and heterocycloalkyl groups can be substituted or unsubstituted. Cycloalkyl and heterocycloalkyl groups can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol.

[0009] "Bicyclic cycloalkyl" or "bicyclic heterocycloalkyl" refers to compounds in which two or more cycloalkyl or heterocycloalkyl groups are fused together. Non-limiting examples of bicyclic cycloalkyl groups include, but are not limited to, (1r,4r)-bicyclo[2.1.1]hexane, (1s,4s)-bicyclo[2.2.1]heptane, (1R,6S)-bicyclo[4.2.0]octane, adamantane, and the like. Non-limiting examples of bicyclic heterocycloalkyl groups include, but are not limited to, any of the foregoing groups in which at least one of the carbon atoms is replaced with a heteroatom such as nitrogen, oxygen, sulfur, or phosphorus.

[0010] "Alkenyl" means a hydrocarbon having 2 to 24 carbons in which the structural formula contains at least one carbon-carbon double bond. Asymmetric structures such as (A 1 A 2 )C=C(A 3 A 4 ) are intended to include both E and Z isomers. Alkenyl groups can be substituted with one or more groups including alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, among others.

[0011] "Cycloalkenyl" means a non-aromatic carbocyclic ring consisting of at least three carbon atoms and containing at least one carbon-carbon double bond (i.e., C=C). Examples of cycloalkenyl groups include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornenyl, and the like. The term "heterocycloalkenyl" is a type of cycloalkenyl group and is included within the meaning of the term "cycloalkenyl," wherein at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Cycloalkenyl groups and heterocycloalkenyl groups can be substituted or unsubstituted. Cycloalkenyl groups and heterocycloalkenyl groups can be substituted with one or more groups including alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, and the like.

[0012] "Alkynyl" means a hydrocarbon group of 2 to 24 carbon atoms, where the structural formula contains at least one carbon-carbon triple bond. Alkynyl groups can be unsubstituted or substituted with one or more groups including alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, and the like.

[0013] "Cycloalkynyl" means a non-aromatic carbocyclic ring consisting of at least seven carbon atoms and containing at least one carbon-carbon triple bond. Examples of cycloalkynyl groups include cycloheptatrienyl, cyclooctatrienyl, cyclononatrienyl, and the like. The term "heterocycloalkynyl" is a type of cycloalkenyl group and is included within the meaning of the term "cycloalkynyl," wherein at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. Cycloalkynyl groups and heterocycloalkynyl groups can be substituted or unsubstituted. Cycloalkynyl groups and heterocycloalkynyl groups can be substituted with one or more groups including alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, and the like.

[0014] "Aryl" refers to a group containing any carbon-based aromatic group, including but not limited to benzene, naphthalene, phenyl, biphenyl, anthracene, etc. Aryl groups can be substituted or unsubstituted. Aryl groups can be substituted by one or more groups, including but not limited to alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, -NH2, carboxylic acid, ester, ether, halide, hydroxyl, ketone, azide, nitro, silyl, sulfonyl-oxo, or thiol. Furthermore, aryl groups can be monocyclic or contain polycyclic structures, which are fused ring structures or linked by one or more bridging groups (such as carbon-carbon bonds). For example, aryl groups can include biaryl groups, where two aryl groups are linked together via a fused ring structure, as in naphthalene, or via one or more carbon-carbon bonds, as in biphenyl.

[0015] "Heteroaryl" means an aromatic group having at least one heteroatom incorporated into a ring of aromatic groups. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, wherein N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. Heteroaryl groups can be substituted or unsubstituted. Heteroaryl groups can be substituted by one or more groups, including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol groups as described herein. Heteroaryl groups can be monocyclic or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furanyl, imidazolyl, pyrimidinyl, tetrazolyl, thiophene, pyridinyl, pyrroleyl, N-methylpyrroleyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, pyrazinyl, benzofuranyl, benzodioxazolyl, benzothiophene, indolyl, inazolyl, benzimidazolyl, imidazopyridyl, pyrazolopyridyl, and pyrazolopyrimidinyl. Other non-limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, thiopheneyl, pyrazolyl, imidazoleyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazoleyl, imidazole[1,2-b]pyridinyl, imidazole[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl and pyrido[2,3-b]pyrazinyl.

[0016] "Halides" refers to F, Cl, Br, or I.

[0017] The term "transition metal" can be referenced from the IUPAC definition, which defines a transition metal as an element whose atoms have a partially filled d-subshell, or an element that can produce cations with incomplete d-subshells. Alternatively, "transition metal" can refer to any element in the d-block of the periodic table, including metals of Groups 3–12. In one aspect, "transition metal" can be a Group 8, 9, or 10 element, such as nickel, rhodium, or iridium.

[0018] "Carbene" refers to a molecule containing a neutral carbon atom with a divalent charge and two unshared valence electrons, i.e., a molecule containing "-C:". "Carbene salt" or "carbene salt" refers to a compound in which the carbene has been converted into a salt containing a positively charged atom and a negatively charged counterion.

[0019] "Synthesis gas" refers to a gaseous mixture containing carbon monoxide, hydrogen, and, in some cases, carbon dioxide.

[0020] "Reactor" means any suitable vessel that can be used to carry out catalytic reaction methods. A reactor can be a small laboratory-scale reactor or a large commercial-scale reactor. Smaller reactors include, but are not limited to, steel pressure reactors lined with glass or TEFLON (PTFE). In other respects, a reactor can be a Hastelloy autoclave with a suitable volume. In some respects, the reactor can be equipped with an infrared spectral probe for in-situ monitoring of the reaction mixture.

[0021] "Molar ratio" refers to the number of moles of one substance relative to the number of moles of another substance.

[0022] "TON" or "Turbocharged" refers to the number of moles of reaction products divided by the number of moles of pre-catalyst or catalyst added to the reactor.

[0023] "Partial pressure" refers to the pressure of a component gas in the atmosphere of the reaction medium. If the gas occupies the entire volume of the original mixture at the same temperature, it is the nominal pressure of that component gas. The partial pressure of a gas in a reactor can be measured using methods known in the art.

[0024] II. Catalytic carbonylation Previous studies on transition metal catalysts (such as nickel catalysts) for carbonylation reactions have typically been reported only in conjunction with tertiary phosphine or amine ligands. Such ligands are prone to methylation or oxidation, leading to catalyst decomposition or side reactions. High loadings of transition metals are required, which defeats the purpose of shifting to low-cost metals. The method of this invention is characterized by the inclusion of carbene ligands (such as...) N Catalysts or precatalyst systems containing heterocyclic carbene (NHC) ligands. These catalyst systems exhibit high activity at relatively low catalyst loadings, showing promise for developing processes that can compete with industry-standard catalysts. The homogeneous nature of these catalysts makes them well-suited for rapid implementation within existing infrastructures for large-scale carbonylation processes.

[0025] The selectivity of the catalyst for carbonylation (as opposed to hydrogenation) also optionally allows the use of syngas in the presence of hydrogen and carbon monoxide. A wide range of available carbene (e.g., NHC) ligands and precursors of these ligands provide convenient methods for modulating reactivity. One advantage of the disclosed catalytic method is that the ligands can be used in combination with simple transition metal salts or compounds. The described method can be used in carbonylation reactions for the synthesis of a wide variety of carboxylic acids, anhydrides, esters, alkyl acetates, and other large-scale commercial chemicals.

[0026] Typically, carbonylation reactions convert esters (such as alkyl esters) to acid anhydrides (and other products, such as acetic acid and acetyl esters) in a carbon monoxide atmosphere. In one aspect, the method involves carbonylating the ester in a reactor containing carbon monoxide or a source thereof in the presence of a catalyst system. This catalyst system typically comprises a catalyst system containing a ligand or ligand precursor salt, a Group 8, 9, or 10 transition metal compound, and a halide source. Therefore, this method allows for the in-situ formation of a carbene catalyst from a catalytic precursor (e.g., a salt of a carbene ligand).

[0027] When ligand precursor salts are used, they can be present in the catalyst system in an amount equal to or greater than that of the transition metal compound. For example, in some aspects, the salt can be present in the catalyst system in a molar ratio of 1:1 to 10:1 relative to the transition metal compound. For example, the salt can be present in the catalyst system in a molar ratio of 2:1, 5:1, or 10:1 relative to the transition metal compound, or in other words, as a ligand precursor salt in an amount of 2, 5, or 10 equivalents relative to the transition metal compound.

[0028] The catalytic reaction can be carried out at various suitable temperatures. In one aspect, carbonylation is carried out at a temperature of at least 50°C. In another aspect, carbonylation is carried out at a temperature of at least 180°C, for example, 180°C to 200°C. In yet another aspect, carbonylation is carried out at a temperature of at least 200°C, for example, 200°C to 220°C.

[0029] Carbonylation can typically be carried out at a suitable time, which can depend on a variety of factors. However, reaction products can be monitored to determine when the reaction mixture should be quenched if necessary. Suitable reaction times include, for example, 3–24 hours, such as 10–15 hours, or longer when carried out on a large industrial scale. Generally, the reaction can continue for any suitable time, as indicated by the methods used to measure the reaction progress and completion. Furthermore, carbonylation reactions can be carried out as part of either a batch or continuous process.

[0030] A. Ester starting materials and reaction products The disclosed methods can be used to carbonylate various esters. In one aspect, the esters have a structure represented by formula (I): , Where R 1 It is a hydrocarbon group.

[0031] R 1 The hydrocarbon group can be C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl, whether straight-chain or branched, as defined above. The hydrocarbon group can optionally be substituted as defined above, wherein at least one hydrogen atom of the hydrocarbon group is replaced by a non-hydrogen group, such as halide groups, hydroxyl groups, ether groups, thiol groups, thioether groups, carboxylic acid groups, carboxylic acid ester groups, phosphate groups, phosphate ester groups, sulfonic acid groups, sulfonate groups, nitro groups, cyano groups, cycloalkyl groups, cycloalkenyl groups, cycloalkynyl groups, aryl groups, heteroaryl groups, etc.

[0032] In one respect, R 1 The hydrocarbon group can be an alkyl ester, i.e., a branched or unbranched saturated hydrocarbon containing 1 to 24 carbon atoms (excluding any carbon atoms present on optional substituents). Alkyl esters can be substituted or unsubstituted. For example, in some aspects, alkyl esters can be substituted with one or more groups, including but not limited to alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxyl, nitro, silyl, sulfo-oxo, or thiol groups. Alkyl esters can be completely acyclic or contain one or more cyclic groups.

[0033] In one respect, R 1 The hydrocarbon group at the position can be C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, etc., and at most includes C1-C24 alkyl. When R 1 When it contains more than two carbon atoms, R 1 It can be branched or unbranched, such as branched or unbranched C3-C4 alkyl, branched or unbranched C3-C5 alkyl, branched or unbranched C3-C6 alkyl, branched or unbranched C3-C7 alkyl, branched or unbranched C3-C8 alkyl, branched or unbranched C3-C9 alkyl, branched or unbranched C3-C10 alkyl, etc., and at most including branched or unbranched C3-C24 alkyl. In some specific aspects, R 1 It is a C1-C20 alkyl, C1-C10 alkyl, or C2-C3 alkyl.

[0034] R 1 Non-limiting examples of hydrocarbon groups include methyl, ethyl, and... Primary propyl, isopropyl, Primary Butyl, isobutyl, Secondary Butyl,Tertiary Butyl, Primary pentyl, isopentyl, Secondary Pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, etc. In one specific aspect, R 1 It can be methyl, ethyl, or isopropyl. Therefore, specific alkyl ester starting materials include, but are not limited to, methyl acetate, methyl propionate, methyl butyrate, and methyl isobutyrate.

[0035] The ester can be carbonylated in its pure form or with the addition of a suitable solvent, such as an organic solvent. The solvent can be readily determined by those skilled in the art.

[0036] Esters of formula (I), such as alkyl esters, can be converted into a variety of reaction products, typically including anhydrides that primarily correspond to formula (IP): , Where R 1 As defined above with reference to formula (I) as the starting material for the ester. Other carboxylic acids and acetates may also be formed. For example, when methyl propionate is carbonylated, the main reaction products include acetic propionic anhydride in addition to the symmetrical anhydride (propionic anhydride), acetic acid, and methyl acetate. As those skilled in the art will understand, the properties of the reaction product mixture generally depend on the starting ester of formula (I).

[0037] B. Carbon monoxide and its sources In one aspect, the reactor includes carbon monoxide or a source thereof. In another aspect, carbon monoxide is present in a syngas composition containing hydrogen. Alternatively, any suitable source of carbon monoxide gas can be used, including precursor materials that can form carbon monoxide in the reactor, for example, under increased pressure. Examples of precursor materials that can form carbon monoxide in situ include carbon dioxide, metal carbonyls, formic acid derivatives, and methanol. These carbon monoxide sources may be desirable for minimizing any toxicity and transport problems arising from gaseous carbon monoxide.

[0038] Typically, carbon monoxide in the reactor is pressurized. For example, in one aspect, carbon monoxide is present in the reactor at a partial pressure of at least 20 bar. In another aspect, carbon monoxide is present in the reactor at a partial pressure of 20 to 50 bar. In some aspects, the carbon monoxide or its source, or the reactor, is substantially anhydrous, or in some aspects, it is anhydrous.

[0039] III. Catalyst system Catalyst systems typically include (i) a ligand precursor salt; (ii) a Group 8, 9, or 10 transition metal compound; and (iii) a halide source. The transition metal compound can be any suitable transition metal compound, such as those containing a Group 8, 9, or 10 transition metal. In some aspects, the transition metal includes nickel, rhodium, or iridium. Non-limiting examples include NiI₂, NiCl₂, Ni(OAc)₂, (Ni(OAc)₂-4H₂O), IrI₃, IrCl₃, Ir(OAc)₃, RhI₃, RhCl₃, and Rh(OAc)₃.

[0040] A. Ligand precursor salts The ligand precursor salt has a structure represented by formula (II): , The dashed lines (----) represent optional covalent bonds; where R 2 and R 3 Independently selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclocycloalkyl, or bicycloheteroalkyl; wherein R 4 For (i) hydrogen, (ii) –C(R) 5-7 ), where R 5 To R 7 Each of them is independently hydrogen or an unsubstituted C1-C4 alkyl group, or (iii) –C(=R) 8 (R) 7 ), where R 7 It is hydrogen or an unsubstituted C1-C4 alkyl group, wherein R is hydrogen or an unsubstituted C1-C4 alkyl group. 8 It is –CH2 or an unsubstituted C2-C4 alkyl group; and X is a halide, BF4 or PF6.

[0041] In some respects, the dashed line (----) represents a solid line indicating a covalent bond, and R 2 and R 3 Independently, it can be C1-C4 alkyl, aryl, or heteroaryl. On the other hand, the dashed line (----) represents a solid line indicating a covalent bond, and R... 2 and R 3 Independently methyl, ethyl, propyl, or butyl; in some respects, R 2 and R 3 Containing the same alkyl group, for example, both groups are methyl, ethyl, propyl, or butyl. On the other hand, the dashed line (----) represents a solid line indicating a covalent bond, R. 2 It is ethyl, and R 3 For methyl. On the other hand, the dashed line (----) is a solid line representing a covalent bond, and R 2 and R 3Independently benzyl, 1,3-diisopropylbenzyl, or mesitylene. In any of these aspects, R 4 It can be, for example, (i) hydrogen, (ii) –C(R) 5-7 ), where R 5 To R 7 Each of them is independently hydrogen or an unsubstituted C1-C4 alkyl group, or (iii) –C(=R) 8 (R) 7 ), where R 7 It is hydrogen or an unsubstituted C1-C4 alkyl group, wherein R is hydrogen or an unsubstituted C1-C4 alkyl group. 8 It is –CH2 or unsubstituted C2-C4 alkyl. In another specific aspect, R 4 The ligand precursor salts can be hydrogen, methyl, ethyl, propyl, butyl, or pentyl. Any of these specific ligand precursor salts can be present in the catalyst along with a suitable transition metal compound, such as a nickel compound, for example, Ni(OAc)2.

[0042] One advantage of the disclosed catalytic method is that it requires less catalyst to achieve commercially viable turnover numbers (TONs) and reaction yields. Therefore, in one aspect, prior to carbonylation, the ester and transition metal compound are present in the reactor at a molar ratio ranging from 100:1 to 10,000:1 (ester:transition metal compound). In another aspect, prior to carbonylation, the ester and transition metal compound are present in the reactor at a molar ratio ranging from 250:1 to 10,000:1 (ester:transition metal compound). In yet another aspect, prior to carbonylation, the ester and transition metal compound are present in the reactor at a molar ratio ranging from 500:1 to 10,000:1 (ester:transition metal compound). In yet another aspect, prior to carbonylation, the ester and transition metal compound are present in the reactor at a molar ratio ranging from 750:1 to 10,000:1 (ester:transition metal compound). On the other hand, prior to carbonylation, the ester and transition metal compound are present in the reactor in a molar ratio ranging from 1,000:1 to 10,000:1 (ester:transition metal compound). Alternatively, prior to carbonylation, the ligand precursor salt and transition compound are present in the reactor in a molar ratio ranging from 1:1 to 10:1 (salt:transition metal compound).

[0043] B. Halide promoters and other optional additives Catalyst systems typically include at least one halide source that can be used as a halide promoter. Suitable examples are iodomethane, LiI, or... N-Methylpyridinium iodide. In some aspects, prior to carbonylation, the alkyl halide used as a halide promoter may be present in the catalyst system at a molar ratio of 100:1 relative to the transition metal compound. In other aspects, prior to carbonylation, the alkyl source used as a halide promoter may be present in the catalyst system at a molar ratio of 1:1 to 200:1 relative to the catalyst precursor or transition metal compound component that also contains a carbene ligand or its salt; in other words, about 1 to 200 equivalents of halide source relative to the carbene complex or transition metal compound.

[0044] In some respects, other additives may also be present in the catalyst system. Examples include various halide salts other than another halide source, such as lithium iodide or lithium acetate. Such additives may be present in the catalyst system prior to carbonylation at a molar ratio of 1:1 to 200:1 relative to the transition metal compound; in other words, additives (such as LiI) at approximately 1 to 200 equivalents relative to the metal compound.

[0045] Example The following examples further illustrate this disclosure. The scope of this disclosure and the claims is not limited to the scope of the following examples.

[0046] The catalytic reaction was carried out using a steel pressure reactor with a glass liner. Reaction conditions were set at 0.025 mmol or 0.075 mmol Ni(OAc)₂. The mixture consisted of 4H2O (NHC ligands are shown in Table 1), 0.15 mmol imidazolyl, 7.5 mmol iodomethane and 208 mmol (20 mL) methyl propionate, and was heated to 200 °C at 50 bar CO for 15 hours.

[0047] Table 1. Ligands The catalytic reaction is shown in Scheme 1.

[0048] Option 1. Carbonylation of methyl propionate Table 2 summarizes the reaction yields and turnover numbers (TON) of the transition metal-catalyzed carbonylation of methyl esters. Comparative examples of the activities of free N-heterocyclic carbene and protonated imidazolium salts are included. The N-heterocyclic methylimidazolium ligand exhibits high activity at low catalyst loadings and is comparable to that of the N-heterocyclic carbene ligand. The catalytic activity remains stable over 15 hours, consistent with the fact that the alkylating agent is an effective catalyst promoter.

[0049] Table 2. Reaction Yields and Turnover (TON) The features and advantages of this disclosure are apparent from the detailed description, and the claims cover all such features and advantages. Many variations will occur to those skilled in the art, and any variations equivalent to those described herein fall within the scope of this disclosure. Those skilled in the art will understand that the concepts upon which this disclosure is based can serve as the basis for designing other compositions and methods for achieving some of the objectives of this disclosure. Therefore, the claims should not be construed as limiting to the description or examples.

Claims

1. A method comprising carbonylating an ester in a reactor containing carbon monoxide or a source thereof in the presence of a catalyst system; The ester described herein has a structure represented by formula (I): ， Where R 1 It is a hydrocarbon group; The catalyst system includes: Ligand precursor salts having the structure represented by formula (II): ， The dashed lines (----) represent optional covalent bonds; Where R 2 and R 3 Independently selected from C1-C4 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclocycloalkyl, or bicycloheterocycloalkyl; Where R 4 for hydrogen, –C(R 5-7 ), where R 5 To R 7 Each of them is independently hydrogen or an unsubstituted C1-C4 alkyl group, or –C(=R 8 (R) 7 ), where R 7 It is hydrogen or an unsubstituted C1-C4 alkyl group, wherein R is hydrogen or an unsubstituted C1-C4 alkyl group. 8 It is –CH2 or unsubstituted C2-C4 alkyl; Where X is a halide, BF4, or PF6; Group 8, 9, or 10 transition metal compounds; and Halogen source.

2. The method of claim 1, wherein the carbon monoxide is present in a syngas composition containing hydrogen.

3. The method according to claim 1 or 2, wherein the carbon monoxide is present in the reactor at a partial pressure of at least 20 bar.

4. The method according to any of the preceding claims, wherein the carbon monoxide is present in the reactor at a partial pressure of 20 to 50 bar.

5. The method according to any of the preceding claims, wherein R 1 It is a C1-C20 alkyl group.

6. The method according to any of the preceding claims, wherein R 1 It is a C1-C10 alkyl group.

7. The method according to any of the preceding claims, wherein R 1 It is a C2-C3 alkyl group.

8. The method according to any of the preceding claims, wherein the ester is methyl acetate, methyl propionate, methyl butyrate or methyl isobutyrate.

9. The method according to any of the preceding claims, wherein the carbonylation is carried out at a temperature of at least 50°C.

10. The method according to any of the preceding claims, wherein the carbonylation is carried out at a temperature of at least 180°C.

11. The method according to any of the preceding claims, wherein the carbonylation is carried out at a temperature of at least 200°C.

12. The method according to any of the preceding claims, wherein the transition metal compound comprises nickel, rhodium, or iridium.

13. The method according to any of the preceding claims, wherein the transition metal compound is nickel acetate (Ni(OAc)2-4H2O) or NiI2.

14. The method according to any of the preceding claims, wherein prior to carbonylation, the ligand precursor salt and the transition metal compound are present in the reactor in a molar ratio ranging from 1:1 to 10:

1.

15. The method according to any of the preceding claims, wherein R 2 and R 3 It can be independently aryl or heteroaryl.

16. The method according to any of the preceding claims, wherein R 2 and R 3 Each is 1,3-diisopropylphenyl.

17. The method according to any of the preceding claims, wherein R 4 It can be methyl, ethyl, isopropyl or propenyl.

18. The method according to any of the preceding claims, wherein R 4 It is a methyl group.

19. The method according to any preceding claim, wherein the halide source is iodomethane, LiI, or... N -Methylpyridinium iodide.

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