Catalytic carbonylation of esters

Abstract

Catalytic carbonylation method using catalyst systems having a ligand salt which is a precursor to a carbene ligand and a transition metal compound.

Description

Attorney Docket No.37676.0004P1 CATALYTIC CARBONYLATION OF ESTERS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No.63 / 531,226, filed August 7, 2023, which is incorporated into this application by reference. BACKGROUND

[0002] Catalytic carbonylation refers to 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 anhydrides, carboxylic acids, and esters. To achieve desirable yields using inexpensive metal catalysts, however, the required catalyst loading is typically high. Commonly used transition-metal catalysts can be very expensive and undergo sudden and steep price surges based on availability and demand.

[0003] Common catalysts for carbonylation of esters are phosphine-based transition metal catalysts, such as catalysts including one or more triphenylphosphine ligands. Triphenylphosphine transition-metal catalysts routinely achieve sub-optimal turnover numbers such that the amount of ligand or metal used is relatively high. This makes such catalysts unattractive alternatives to more commonly used, yet highly expensive, transition metal complexes. Accordingly, there is a need in the art for improved catalytic methods for carbonylating substrates such as esters. These needs and others are met by the present disclosure. SUMMARY

[0004] In one aspect, disclosed is a method comprising carbonylating an ester in a reactor comprising carbon monoxide or a source thereof in the presence of a catalyst system; wherein the ester has a structure represented by Formula (I): O R1 O(I), wherein R1is hydrocarbyl; wherein the catalyst system comprises: a) a ligand precursor salt having a structure represented by Formula (II):Attorney Docket No.37676.0004P1, wherein the dashed line (----) represents an optional covalent bond; wherein R2and R3are independently selected from C1-C4 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, or bicyclic heterocycloalkyl; wherein R4is i) hydrogen, ii) –C(R5-7), wherein each of R5-R7is independently hydrogen or unsubstituted C1-C4 alkyl, or iii) –C(=R8)(R7), wherein R7is hydrogen of unsubstituted C1-C4 alkyl, and wherein R8is –CH2 or unsubstituted C2-C4 alkyl; wherein X is a halide, BF4, or PF6; b) a Group 8, 9, or 10 transition metal compound; and c) a halide source. DETAILED DESCRIPTION I. Definitions

[0005] “Carbonylation” means a reaction in which carbon monoxide is introduced into an organic substrate, either 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 acetic propionic anhydride along with other reaction products including acetic acid and methyl acetate.

[0006] “Hydrocarbyl” encompasses C1-C24 alkyl, C2-C24 alkenyl, and C2-C24 alkynyl, whether linear or branched. A hydrocarbyl can be optionally substituted, in which at least one hydrogen of the hydrocarbyl has been replaced with a group that is not hydrogen, such as halide groups, hydroxyl groups, ether groups, thiol groups, thiol ether groups, carboxylic acid groups, carboxylic acid ester groups, phosphoric acid groups, phosphoric acid ester groups, sulfonic acid groups, sulfonic acid ester groups, nitro groups, cyano groups, cycloalkyl groups, cycloalkenyl groups, cycloalkynyl groups, aryl groups, heteroaryl groups, among others.Attorney Docket No.37676.0004P1

[0007] “Alkyl” means a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n- pentyl, isopentyl, s-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, hydroxy, nitro, silyl, sulfo-oxo, or thiol, 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 a C1-C24 alkyl.

[0008] “Cycloalkyl” means a non-aromatic carbon-based ring composed 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, where 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. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol.

[0009] “Bicyclic cycloalkyl” or “bicyclic heterocycloalkyl” refers to a compound in which two or more cycloalkyl or heterocycloalkyl groups are fused together. Non-limiting examples of bicyclic cycloalkyl groups include without limitation (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 without limitation 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 from 2 to 24 carbons with a structural formula containing at least one carbon-carbon double bond. Asymmetric structures such as (AA)C=C(AA) are intended to include both the E and Z isomers. The alkenyl group can

[0011] be substituted with one or more groups including alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylicAttorney Docket No.37676.0004P1 acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, among others.

[0012] “Cycloalkenyl” means a non-aromatic carbon-based ring composed of at least three carbon atoms and containing at least one carbon-carbon double bound, i.e., C=C. Examples of cycloalkenyl groups include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornenyl, among others. The term “heterocycloalkenyl” is a type of cycloalkenyl group and is included within the meaning of the term “cycloalkenyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as nitrogen, oxygen, sulfur, or phosphorus. The cycloalkenyl group and heterocycloalkenyl group can be substituted or unsubstituted. The cycloalkenyl group and heterocycloalkenyl group 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, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, among others.

[0013] “Alkynyl” means a hydrocarbon group of 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon triple bond. The alkynyl group 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, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, among others.

[0014] “Cycloalkynyl” means a non-aromatic carbon-based ring composed of at least seven carbon atoms and containing at least one carbon-carbon triple bound. Examples of cycloalkynyl groups include cycloheptynyl, cyclooctynyl, cyclononynyl, and the like. The term “heterocycloalkynyl” is a type of cycloalkenyl group and is included within the meaning of the term “cycloalkynyl,” where 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. The cycloalkynyl group and heterocycloalkynyl group can be substituted or unsubstituted. The cycloalkynyl group and heterocycloalkynyl group 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, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, among others.

[0015] “Aryl” means a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or moreAttorney Docket No.37676.0004P1 groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, ─NH2, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond. For example, aryl can include biaryl in which two aryl groups are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl.

[0016] “Heteroaryl” means an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further non-limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl.

[0017] “Halide” means F, Cl, Br, or I.

[0018] “Transition metal” can refer to the IUPAC definition, which defines a transition metal as an element whose atom has a partially filed d sub-shell, or which can give rise to cations with an incomplete d sub-shell. Alternatively, “transition metal” can refer to any element in the d-block of the periodic table, which includes Group 3-12 metals. In one aspect, “transition metal” can be a Group 8, 9, or 10 element, such as nickel, rhodium, or iridium.

[0019] “Carbene” means a molecule containing a neutral carbon atom with a valence of two and two unshared valence electron, i.e., a “-C:”-containing molecule. A “carbene salt” or “salt of a carbene” refers to a compound in which the carbene has been converted to salt withAttorney Docket No.37676.0004P1 a positively charged atom and a negatively charged counterion.

[0020] “Syngas” means a gaseous mixture comprising carbon monoxide, hydrogen, and in some instances carbon dioxide.

[0021] “Reactor” means any suitable vessel useful for performing the catalytic reaction methods. The reactor can be a smaller, lab-scale reactor, or a larger commercial scale reactor. Smaller reactors include, without limitation, steel pressure reactors containing glass or TEFLON (PTFE) liners. In other aspects, the reactor can be a Hastelloy autoclave having a suitable volume. In some aspects, the reactor can be equipped with an infrared spectroscopy probe for in situ monitoring of the reaction mixture.

[0022] “Molar ratio” means the moles of one substance relative to the moles of another substance.

[0023] “Turnover number” or “TON” means the moles of a reaction product divided by the moles of a precatalyst or catalyst added to the reactor.

[0024] “Partial pressure” means the pressure of a constituent gas in the atmosphere of the reaction medium, which is the notional pressure of that constituent gas if that gas occupied the entire volume of the original mixture at the same temperature. Partial pressures of a gas in a reactor can be measured according to methods known in the art. II. Catalytic Carbonylation

[0025] Previous research 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 metal are required, which defeats the purpose of moving to a low-cost metal. The present methods feature catalysts or precatalyst systems comprising carbene ligands, such as N-heterocyclic carbene (NHC) ligands. Such catalyst systems exhibit higher activity at lower catalyst loadings, showing promise for the development of a process that could compete with industry-standard catalysts. The homogeneous nature of these catalysts lends itself well for rapid implementation into the existing infrastructure for large-scale carbonylation processes.

[0026] The selectivity of the catalysts for carbonylation (vs. hydrogenation) also optionally allows for the use of syngas with hydrogen gas present along with carbon monoxide. The large number of available carbene (e.g., NHC) ligands and precursors to these ligands provides a convenient method to tune reactivity. One advantage of the disclosed catalytic methods is that the ligands can be used in conjunction with simple transition metalAttorney Docket No.37676.0004P1 salts or compounds. The described methods are useful for carbonylation reactions used in the synthesis of various carboxylic acids, anhydrides, esters, alkyl acetates, and other large-scale commodity chemicals.

[0027] In general, the carbonylation reaction converts esters such as alkyl esters to anhydrides (with other products such as acetic acid and acetyl esters) under an atmosphere of carbon monoxide. In one aspect, the method comprises carbonylating an ester in a reactor comprising carbon monoxide or a source thereof in the presence of a catalyst system. The catalyst system generally comprises a catalyst system which includes a ligand or a ligand precursor salt, a Group 8, 9, or 10 transition metal compound, and a halide source. Thus, the method allows for catalytic precursors (e.g., salts of carbene ligands) that allow for the formation of the carbene catalyst in situ.

[0028] When ligand precursor salts are used, they can be present in the catalyst system in an amount equal to or in excess of the transition metal compound. In some aspects, for example, the salt can be present in the catalyst system in a 1:1-10:1 molar ratio relative to the transition metal compound. For example, the salt can be present in the catalyst system in a 2:1, 5:1, or 10:1 molar ratio relative to the transition metal compound, or in other words, two, five, or ten equivalents of ligand precursor salt relative to the transition metal compound.

[0029] The catalytic reactions can be carried out at a variety of suitable temperatures. In one aspect, carbonylation is carried out at a temperature of at least 50°C. In a further aspect, carbonylation is carried out at a temperature of at least 180°C, e.g., 180°C-200°C. In a further aspect, carbonylation is carried out at a temperature of at least 200°C, e.g., 200°C-220°C.

[0030] Carbonylation can generally be carried out at a suitable time which can depend on a variety of factors. Reaction products, however, can be monitored to determine when the reaction mixture should be quenched if necessary. Suitable reaction times include for example 3-24 hours, e.g., 10-15 hours, or much longer times when carried out on large industrial scales. In general, the reaction can be carried out for any suitable time as indicated by methods for measuring reaction progress and completion. In addition, the carbonylation reaction can be implemented as part of a batch or continuous process. A. Ester Starting Materials and Reaction Products

[0031] A variety of esters can be carbonylated using the disclosed methods. In one aspect, the ester has a structure represented by Formula (I):Attorney Docket No.37676.0004P1, wherein R1is hydrocarbyl.

[0032] The hydrocarbyl group at R1can be C1-C24 alkyl, C2-C24 alkenyl, and C2-C24 alkynyl, whether linear or branched, as defined above. The hydrocarbyl group can be optionally substituted as defined above, in which at least one hydrogen of the hydrocarbyl has been replaced with a group that is not hydrogen, such as halide groups, hydroxyl groups, ether groups, thiol groups, thiol ether groups, carboxylic acid groups, carboxylic acid ester groups, phosphoric acid groups, phosphoric acid ester groups, sulfonic acid groups, sulfonic acid ester groups, nitro groups, cyano groups, cycloalkyl groups, cycloalkenyl groups, cycloalkynyl groups, aryl groups, heteroaryl groups, among others.

[0033] In one aspect, the hydrocarbyl group at R1can be an alkyl ester, i.e., a branched or unbranched saturated hydrocarbon comprising 1-24 carbon atoms, not including any carbon atoms present on optional substituents. The alkyl ester can be substituted or unsubstituted. For example, in some aspects, the alkyl ester can be substituted with one or more groups including but not limited to alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol. The alkyl ester can be entirely acyclic or comprise one or more cyclic groups.

[0034] In one aspect, the hydrocarbyl at R1can 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, and the like up to and including a C1-C24 alkyl. When R1comprises more than two carbon atoms, R1can be branched or unbranched, for example 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, and the like up to and including branched or unbranched C3-C24 alkyl. In certain specific aspects, R1is C1-C20 alkyl, C1-C10 alkyl, or C2-C3 alkyl.

[0035] Non-limiting examples of hydrocarbyl groups at R1include methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. In one specific aspect, R1is methyl, ethyl, or isopropyl. Thus, specific alkyl ester starting materials include without limitation methyl acetate, methyl propionate, methyl butyrate, and methyl isobutyrate.Attorney Docket No.37676.0004P1

[0036] The ester can be carbonylated in neat form or with the addition of a suitable solvent, such as an organic solvent. Solvents can be readily determined by one skilled in the art.

[0037] Esters of Formula (I), such as alkyl esters, can be converted to a variety of reaction products, typically including a predominance of an anhydride corresponding to Formula (I-P):(I-P) , where R1is defined above with reference to the ester starting material of Formula (I). In addition, other carboxylic acids and acetates can also form. For example, when carbonylating methyl propionate, major reaction products include acetic propionic anhydride, in addition to the symmetric anhydride (propionic anhydride), acetic acid, and methyl acetate. As one of skill in the art will appreciate, the nature of the reaction product mixture depends generally on the starting ester of Formula (I). B. Carbon Monoxide and Sources Thereof

[0038] In one aspect, the reactor comprises carbon monoxide or a source thereof. In a further aspect, the carbon monoxide is present in a syngas composition comprising hydrogen gas. In addition, 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, among others. These sources of carbon monoxide can be desirable for minimizing any toxicity and transportation problems resulting from gaseous carbon monoxide.

[0039] In general, the carbon monoxide in the reactor will be pressurized. For example, in one aspect, the carbon monoxide is present in the reactor at a partial pressure of at least 20 bar. In a further aspect, the carbon monoxide is present in the reactor at a partial pressure of 20-50 bar. In some aspects, the carbon monoxide or source thereof, or reactor, is substantially free of water, or in some aspects, free of water. III. Catalyst Systems

[0040] The catalyst system generally comprises (i) a ligand precursor salt; (ii) a Group 8, 9, or 10 transition metal compound; (iii) a halide source. The transition metal compound canAttorney Docket No.37676.0004P1 be any suitable transition metal compound such as a compound comprising a Group 8, 9, or 10 transition metal. In some aspects, the transition metal comprises 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. A. Ligand Precursor Salts

[0041] The ligand precursor salts have a structure represented by Formula (II):, wherein the dashed line (----) represents an optional covalent bond; wherein R2and R3are independently selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, or bicyclic heterocycloalkyl; wherein R4is (i) hydrogen, (ii) –C(R5-7), wherein each of R5-R7is independently hydrogen or unsubstituted C1-C4 alkyl, or (iii) –C(=R8)(R7), wherein R7is hydrogen of unsubstituted C1-C4 alkyl, and wherein R8is –CH2 or unsubstituted C2-C4 alkyl; and wherein X is a halide, BF4, or PF6.

[0042] In some aspects, the dashed line (----) is a solid line, representative of a covalent bond, and R2and R3are independently C1-C4 alkyl, aryl or heteroaryl. In a further aspect, the dashed line (----) is a solid line, representative of a covalent bond, and R2and R3are independently methyl, ethyl, propyl, or butyl; in some aspects R2and R3comprise the same alkyl group, e.g., both groups are each methyl, ethyl, propyl, or butyl. In a further aspect, the dashed line (----) is a solid line, representative of a covalent bond, R2is ethyl, and R3is methyl. In a further aspect, the dashed line (----) is a solid line, representative of a covalent bond, and R2and R3are independently benzyl, 1,3-diisopropylbenzyl, or mesitylenyl. In any of these described aspects, R4can be, for example, (i) hydrogen, (ii) –C(R5-7), wherein each of R5-R7is independently hydrogen or unsubstituted C1-C4 alkyl, or (iii) –C(=R8)(R7), wherein R7is hydrogen of unsubstituted C1-C4 alkyl, and wherein R8is –CH2or unsubstituted C2-C4 alkyl. In a further specific aspect, R4is hydrogen, methyl, ethyl, propyl, butyl, or pentyl. Any of these specific ligand precursor salts can be in the catalyst with a suitable transition metal compound such as a compound of nickel, e.g., Ni(OAc)2.

[0043] One advantage of the disclosed catalytic methods is that less catalyst is required to achieve commercially viable turnover numbers (TONs) and reaction yields. Thus, in one aspect, prior to carbonylation, the ester and the transition metal compound are present in theAttorney Docket No.37676.0004P1 reactor at a molar ratio ranging from 100:1 to 10,000:1 (ester: transition metal compound). In a further aspect, prior to carbonylation, the ester and the 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 a further aspect, prior to carbonylation, the ester and the 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 a further aspect, prior to carbonylation, the ester and the transition metal compound are present in the reactor at a molar ratio ranging from 750:1 to 10,000:1 (ester: transition metal compound). In a further aspect, prior to carbonylation, the ester and the transition metal compound are present in the reactor at a molar ratio ranging from 1,000:1 to 10,000:1 (ester: transition metal compound). In a further aspect, prior to carbonylation, the ligand precursor salt and the transition compound are present in the reactor at a molar ratio ranging from 1:1 to 10:1 (salt: transition metal compound). B. Halide Promoters and Other Optional Additives

[0044] The catalyst system in general comprises at least one halide source which can serve as a halide promoter. A suitable example is methyl iodide, LiI, or N-methyl-pyridinium iodide. The alkyl halide serving as the halide promoter can in some aspects be present in the catalyst system prior to carbonylation at a 100:1 molar ratio relative to the transition metal compound. In other aspects, the alkyl source serving as the halide promoter can be present in the catalyst system prior to carbonylation at a 1:1-200:1 molar ratio relative to the catalyst or transition metal compound component of the catalyst precursor that also comprises the carbene ligand or a salt thereof, in other words, about 1-200 equivalents of the halide source relative to the carbene complex or transition metal compound.

[0001] Other additives can in some aspects also be present in the catalyst system. Examples include various halide salts such as lithium iodide or lithium acetate in addition to another halide source. Such additives can be present in the catalyst system prior to carbonylation at a 1:1-200:1 molar ratio relative to the transition metal compound, in other words, about 1-200 equivalents of additive such as LiI relative to the metal compound. EXAMPLES

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

[0046] Catalytic reactions were conducted using steel pressure reactors containing glass liners. Reaction conditions consisted of 0.025 mmol or 0.075 mmol Ni(OAc)2•4H2O (NHCAttorney Docket No.37676.0004P1 ligands are shown in Table 1), 0.15 mmol imidazolium, 7.5 mmol methyl iodide, and 208 mmol (20 mL) methyl propionate heated to 200°C under 50 bar CO for 15 hours. Table 1. Ligands

[0002] The catalytic reaction is shown in Scheme 1.Attorney Docket No.37676.0004P1 Scheme 1. Carbonylation of Methyl Propionate

[0047] Table 2 shows a summary of reaction yields and turnover numbers (TONs) for transition metal-catalyzed methyl ester carbonylation reactions. Comparative examples of activity with free N-heterocyclic carbene and pronated imidazolium salts are included. The N-heterocyclic methylimidazolium ligands exhibited higher activity at low catalyst loadings and comparable activity to N-heterocyclic carbene ligands. The catalytic activity remains steady over the 15 hours, which is consistent with alkylated species being competent catalytic promoters. Table 2. Reaction Yields and Turnover Number (TON) EntryImidazoliumAnhydride AcOH MeOAc Total Total (moles) (mmol) (mmol) (mmol) Acetyls Acetyls TON Yield 0.9 6.6 1247 15.0%0.6 9.2 1116 13.4%[IPr-Me-d3][I] 3 (0.075 mmol) (avg. of 2 38.9 1.05 5.6 607 22.0% experiments) 4 IPr (0.025) 24.5 1.6 11.7 1509 18.2% IPr1.2 13.0 685 24.8% experiments) IPr•HCl0 14.4 754 27.3% experiments)0.7 0.7 44 1.6%Attorney Docket No.37676.0004P1 8 MeIm•HCl 2.7 0.3 0.5 47 1.7%2.6 28. 856 30.9%10 Me2-IMes•HCl 30.1 1.6 8.6 537 19.4%

[0048] Features and advantages of this disclosure are apparent from the detailed specification, and the claims cover all such features and advantages. Numerous variations will occur to those skilled in the art, and any variations equivalent to those described in this disclosure fall within the scope of this disclosure. Those skilled in the art will appreciate that the conception upon which this disclosure is based may be used as a basis for designing other compositions and methods for carrying out the several purposes of this disclosure. As a result, the claims should not be considered as limited by the description or examples.

Claims

Attorney Docket No.37676.0004P1 CLAIMS What is claimed is:

1. A method comprising carbonylating an ester in a reactor comprising carbon monoxide or a source thereof in the presence of a catalyst system; wherein the ester has a structure represented by Formula (I):, wherein R1is hydrocarbyl; wherein the catalyst system comprises: a) a ligand precursor salt having a structure represented by Formula (II):, wherein the dashed line (----) represents an optional covalent bond; wherein R2and R3are independently selected from C1-C4 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, or bicyclic heterocycloalkyl; wherein R4is iv) hydrogen, v) –C(R5-7), wherein each of R5-R7is independently hydrogen or unsubstituted C1-C4 alkyl, or vi) –C(=R8)(R7), wherein R7is hydrogen of unsubstituted C1-C4 alkyl, and wherein R8is –CH2or unsubstituted C2-C4 alkyl; wherein X is a halide, BF4, or PF6; b) a Group 8, 9, or 10 transition metal compound; and c) a halide source.

2. The method of claim 1, wherein the carbon monoxide is present in a syngas composition comprising hydrogen gas.Attorney Docket No.37676.0004P1 3. The method of 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 of any preceding claim, wherein the carbon monoxide is present in the reactor at a partial pressure of 20-50 bar.

5. The method of any preceding claim, wherein R1is C1-C20 alkyl.

6. The method of any preceding claim, wherein R1is C1-C10 alkyl.

7. The method of any preceding claim, wherein R1is C2-C3 alkyl.

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

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

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

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

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

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

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

1.

15. The method of any preceding claim, wherein R2and R3are independently aryl or heteroaryl.

16. The method of any preceding claim, wherein R2and R3are each 1,3-diisopropylphenyl.

17. The method of any preceding claim, wherein R4is methyl, ethyl, isopropyl, or propenyl.Attorney Docket No.37676.0004P1 18. The method of any preceding claim, wherein R4is methyl.

19. The method of any preceding claim, wherein the halide source is methyl iodide, LiI, or N- methyl-pyridinium iodide.

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