GB2529007A - Process for making esters - Google Patents

Abstract

A process for preparing an alkyl alkanoate, comprising contacting a an alkene, carbon monoxide (CO), an alcohol, a catalyst and a co-catalyst comprising a Bronsted acid, under alkoxycarbonylation conditions to produce an alkyl alkanoate, wherein the catalyst comprises a metal-organophosphorous ligand complex comprising a ligand of the following formula: wherein X1 X8 are independently, H, R, Ar, substituted Ar, OR, OAr, CO2R, SiR3, SO3R, SO3H, or fluoro; where R is alkyl or substituted alkyl; where Ar is aryl; where X4 and X5 optionally may be linked to form a cyclic structure; where Y1 Y4 are independently Ar or substituted Ar; where the Y1 Y4 groups that are bound to the same P atom may also be linked with a carbon to carbon bond, CH2, NH, NR, NAr, or O; and where n is 0 or 1.

Description

Intellectual Property Office Application No. GB1503203.0 RTTVI Date:3 December 2015 The following terms are registered trade marks and should be read as such wherever they occur in this document: Gilson (page 15) Intellectual Property Office is an operating name of the Patent Office www.gov.uk/ipo

PROCESS FOR MAKING ESTERS

BACKGROUND OF THE INVENTION

This invention relates to a process for the alkoxycarbonylation of olefins to carboxylic acid esters.

US 6,348,621, US 7,485,739 and US 5,679,831 disclose catalyst systems for alkoxycarbonylation. However, those systems rely on the use of phosphine ligands containing sterically demanding, basic substituents, such as r-butyl, adamantyl and o-tolyl, which decrease the oxidative stability of the resulting catalyst. It would be advantageous to have a alkoxycarbonylation catalyst that would be less sensitive to oxygen and that would not require the use of ligands with substituents exhibiting high basicity and steric bulk.

SUMMARY OF THE INVENTION

The invention employs such a catalyst in a process comprising contacting an alkene, CO, an alkanol, a catalyst and a co-catalyst under alkoxycarbonylation reaction conditions to produce an alkyl alkanoate, wherein the co-catalyst comprises a Bronsted acid, and the catalyst comprises a metal-organophosphorous ligand complex catalyst comprising a ligand of the formula: x2 X4 x5 Y4 x6 x8 x7 where Xl -X8 are independently, H, R, Ar, substituted Ar, OR, OAr, CO2R, SiR3, SO3R, SO3H, or fluoro; where R is alkyl or substituted alkyl; where Ar is aryl; where X4 and X5 optionally may be linked to form a cyclic structure; where Y 1 -Y4 are independently Ar or substituted Ar; where the Yl -Y4 groups that are bound to the same P atom may also be linked with a carbon to carbon bond, CH2, NH, NB, NAr, or 0; and where n is 0 or 1.

Surprisingly, the ligands of the invention can be employed in the preparation of remarkably active and selective alkoxycarbonylation catalysts without the use of extremely bulky, basic phosphine substituents.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a schematic of a continuous process where distillation is conducted outside the reactor.

Figure 2 is a schematic of a continuous process where distillation is conducted in the reactor.

DETAILED DESCRIPTION OF TIlE INVENTION

The disclosed process comprises contacting an alkene, CO. an alkanol, a catalyst and a co-catalyst under alkoxyoxycarbonylation reaction conditions to produce an alkyl alkanoate, wherein the co-catalyst comprises a Bronsted acid, and the catalyst comprises a metal-organophosphorous ligand complex catalyst comprising a ligand of the formula shown hereinabove, All references to the Periodic Table of the Elements and the various groups therein are to the version published in the CRC Handbook of Chemistry and Physics, 72nd Ed. (1991- 1992) CRC Press, at page I-lU.

As used herein, "a," "an," "the," "at least one," and "one or more" are used interchangeably. The terms "comprises," "includes," and variations thereof do not have a limiting meaning where these tenns appear in the description and claims. Thus, for example, an aqueous composition that includes particles of "a" hydrophobic polymer can be interpreted to mean that the composition includes particles of "one or more" hydrophobic polymers, Also herein, the recitations of numerical ranges by endpoints include all numbers subsumed in that range (e.g., ito 5 includes 1, 1.5,2, 2.75, 3, 3.80, 4, 5, etc.). For the purposes of the invention, it is to be understood, consistent with what one of ordinary skill in the art would understand, that a numerical range is intended to include and support all possible subranges that are included in that nmge. For example, the range from I to 100 is intended to convey from 1,01 to 100, from ito 99,99, from 1,01 to 99,99, from 40 to 60, from ito 55, etc. Also herein, the recitations of numerical ranges and/or numerical values, including such recitations in the claims, can be read to include the term "about." In such instances the term "about" refers to numerical ranges and/or numerical values that are substantially the same as those recited herein.

The term "complex" as used herein and in the claims means a coordination compound formed by the union of one or more electronically rich molecules or atoms with one or more electronically poor molecules or atoms. For example, the organophosphorous ligands employable herein may possess four or more phosphorus donor atoms, each having one available or unshared pair of electrons that are each capable of forming a coordinate bond independently or possibly in concert (e.g., via chelation) with the metal. Carbon monoxide (which is also properly classified as a ligand) can also be present and coordinated to the metal.

The ultimate composition of the complex catalyst may also contain an additional ligand, e.g., hydrogen or an anion satisfying the coordination sites or nuclear charge of the metal.

Illustrative additional ligands include, for example, halogen (Cl, Br, I), alkyl, aryl, substituted aryl, acyl, CF3. C2 F5, CN, (Z)2P0 and ZP(O)(OH)O (wherein each Z is the same or different and is a substituted or unsubstituted hydrocarbon radical, e.g., the alkyl or aryl), acetate, acetylacetonate, SO4, PF4, PF6, NO2, NO6, CH6, CH2CHCH2, CHICHCHCH2, C6HSCN, CH3CN, NH1, pyridine, (C2H5)6N, mono-olefins, diolefins and triolefins, tetrahydrofliran, and the like, It is to be understood that the complex species are preferably free of any additional organic ligand or anion that might poison the catalyst or have an undue adverse effect on catalyst performance. It is preferred in the metal-organophosphine ligand complex catalyzed alkoxycarbonylation reactions that the active catalysts be free of sulfur directly bonded to the metal, although such may not be absolutely necessaly.

As used herein, the term "substituted" is contemplated to include all permissible substituents of organic compounds unless otherwise indicated. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds, Illustrative substituents include, for example, alkyl, alkyloxy, aryl, aryloxy, hydroxyalkyl, aminoalkyl, or fluoroalkyl, in which the number of carbons can range from I to 20 or more, preferably from I to 12, as well as silyl, sulfonyl, hydroxy, fluoro and amino. The permissible substituents can be one or more and the same or different for appropriate organic compounds. This invention is not intended to be limited in any manner by the pennissible substituents of organic compounds.

Unless stated to the contrary, or implicit from the context, all parts and percentages are based on weight and all test methods are current as of the filing date of this application. For purposes of United States patent practice, the contents of any referenced patent, patent application or publication are incorporated by reference in their entirety (or its equivalent US version is so incorporated by reference) especially with respect to the disclosure of definitions (to the extent not inconsistent with any definitions specifically provided in this disclosure) and general knowledge in the art, Carbon monoxide may be obtained from any suitable source, including petroleum cracking and refinery operations. Tnert gases such as, for example, nitrogen, and the noble gases, such as argon, may be present during the reaction.

Similarly, the alkene may be obtained from any suitable source. The alkene can be a substituted or unsubstituted olefinic unsaturated reactant containing from 2 to 40, preferably 2 to 20, carbon atoms. Such olefinic unsaturated compounds can be terminally or internally unsaturated and be of straight-chain, branched chain or cyclic structures, as well as olefin mixtures, such as obtained from the oligomerization of ethylene, propene, butene, isobutene, etc. (such as so called dimeric, trimeric or tetrameric propylene and the like, as disclosed, for example, in US 4,518,809 and US 4,528,403), The alkene preferably comprises ethylene. The molar ratio of the alkene to carbon monoxide in the gaseous phase is advantageously from 0.5:1 to 50:1, preferably at least 0,8:1 to 5:1, more preferably from 0,9:1 to 1,5:1 and most preferably in the range from 0,95:1 to 1.05:1. Tn one embodiment of the invention, this ratio is about 1:1.

Suitable alkanols include C10 alkanols, optionally substituted with one or more substituents such as cyano, carbonyl, alkoxy or aryl groups. Examples of suitable alkanols include methanol, ethanol, propanol, 2-propanol, 2-butanol, and t-butyl alcohol, Methanol and ethanol are particularly useful. Methanol is the preferred alkanol. Mixtures of alkanols can be employed.

The catalyst is formed when a ligand structure of Formula 1 is combined with a suitable metal source and a Brønsted acid co-catalyst. X4 X5 Y4 X5 X8 x7

Formula I where Xl -X8 are independently, H, R, Ar, substituted Ar, OR, OAr, CO2R, SiR3, SO3R, SO3H, or fluoro; where R is alkyl or substituted alkyl; where Ar is aryl; where X4 and X5 optionally may be linked to form a cyclic structure; where Yl -Y4 are independently Ar or substituted Ar; where the Yl -Y4 groups that are bound to the same P atom may also be linked with a carbon to carbon bond, CH2, NH, NB, NAr, or 0; and where n is 0 or 1 The ligand of FormUla 1 includes molecules where the X4 and X5 groups are connected to form a cyclic structure, Advantageously, X4 and X5 when linked form a ring comprising at least 5 atoms, which comprise 0, C and/or N atoms. Preferably, X4 and X5 when linked form a ring comprising from 5 to to atoms, including the 4 relevant carbon atoms shown in Formula 1. In one embodiment of the invention, X4 and X5 are linked with an ether or diether linkage.

The ligand is known to those skilled in the art and can be prepared according to known methods. See, for example, US 2013/0184479. Mixtures of ligands may be employed in the metal-organophosphorous ligand complex catalyst and/or free ligand, The metal source provides the catalytic metal to the catalyst, The catalytic metal can include Group 8, 9 and 10 metals selected from rhodium (Rh), cobalt (Co), iridium (Tr), ruthenium (Ru), iron (Fe), nickel (Ni), palladium (Pd), platinum (Pt), osmium (Os) and mixtures thereof, preferably palladium or rhodium, and most preferably palladium, Examples of effective metal sources, using Pd as an exemplary metal, include Pd(dba)2 (where dba = dibenzylideneacetone), Pd(acac)2 (where acac = acetylacetonato), and bis- (acetonitrile) palladium dichloride. Additional suitable compounds of palladium include salts of palladium with, or compounds comprising weakly coordinated anions derived from the following: nitric acid; sulphuric acid; lower alkanoic (up to Cu) acids such as acetic acid and propionic acid including halogenated carboxylic acids such as trifluoroacetic acid and trichloroacetic acid; suiphonic acids such as methanesuiphonic acid, chlorosuiphonic acid, fluorosuiphonic acid, trifluoromethanesuiphonic acid, benzenesulphonic acid, naphthalenesulphonic acid, toluenesuiphonic acids, e.g., p-toluenesulphonic acid, t-butylsulphonic acid, and 2-hydroxypropanesulphonic acid; sulphonated ion exchange resins; perhalic acids such as perchioric acid; halogenated carboxylic acids such as trichioroacetic acid and trifluoroacetic acid; orthophosphoric acid; phosphonic acids such as benzenephosphonic acid; and acids derived from interactions between Lewis acids and Bronsted acids. Other sources that may provide suitable anions include the optionally halogenated tetraphenylborate derivatives, e.g., perfluorotetraphenyl borate, Additionally, zero-valent palladium complexes, particularly those with labile ligands, e.g., alkenes such as dibenzylideneacetone or styrene, may be used.

Tn general, the catalyst may be preformed or formed in situ and comprises a metal in complex combination with one or more organophosphorous ligands as well as other ligands that may be present in the reaction mixture. The other ligands may include organic or inorganic anions added to the reaction mixture along with the metal source, electrically neutral ligands added to the reaction mixture along with the metal source, organic anions or neutral species produced in the reaction, the substrate olefin, the reactant alkanol, carbon monoxide and hydride, The ligand complex species may be present in mononuclear, dinuclear and/or higher nuclearity forms, The exact structure of the catalyst present during the reaction depends on the reaction conditions as well as the identity of the reactants and generally is not known.

The catalyst is preferably present as part of the liquid phase, which may be formed by one or more of the reactants and/or by the use of a suitable, optional, solvent, A Bronsted acid is employed as a co-catalyst, Bronsted acids are well known to those skilled in the art. In one embodiment of the invention, Bronsted acids of varying strength, ranging from acetic acid to trifluoromethanesulfonic acid, can be employed to produce a highly efficient catalyst system. Examples of suitable Bronsted acids include, sulfuric acid; phosphoric acid; nitric acid; phosphoric acid esters such as binapthyl hydrogenphosphate and BTNOL hydrogenphosphate; carboxylic acids such trifluoroacetic acid, acetic acid and propionic acid; sulfonic acids such as trifluoromethanesulfonic acid, methanesulfonic acid, benzenesulfonic acid, toluene sulfonic acid and propanesulfonic acid; and sulfoniniide acids such as bis(trifluoromethane)sulfonimide and 4,4,5,5,6,6-hexafluoro-1,3,2-dithiazinane 1,1,3,3-tetraoxide, Acids possessing weakly coordinating or non-coordinating counter anions are preferred. The preferred acid and proton to metal catalyst ratio varies according to the electronic and geometric structure of the ligand employed, metal source used and the identity of the nucleophile. The Bronsted acid advantageously has a pKa measured in aqueous solution of less than 4, more preferably less than 1. The Bronsted acid is employed in an amount suitable to facilitate the reaction. Advantageously, the molar ratio of Bronsted acid to catalytic metal may be from 1:1 to 1000:1, preferably from 2:1 to 500:1 andmore preferably from 3:1 to 100:1. Preferably, the catalyst system is capable of achieving > 99 % selectivity for methyl propionate at rates of greater than 1 mol/liter/hi.

A solvent is optionally employed. Suitable solvents that may be used in conjunction with the catalyst include one or more aprotic solvents, such as ethers, e.g., diethyl ether, dimethyl ether of diethylene glycol, anisole and diphenyl ether; aromatic compounds, e.g., benzene, toluene, ethyl benzene, o-xylene, m-xylene, p-xylene; alkanes, including halo variants of such compounds, e.g., hexane, heptane, 2,2,3-trimethylpentane, methylene chloride and carbon tetrachloride; nitriles, e.g., benzonitrile and acetonitrile; esters, e.g., methyl benzoate, methyl acetate, methyl propionate and dimethyl phthalate; sulphones, e.g., diethyl sulphone and tetrahydrothiophene 1,1-dioxide; and carboxylic acids, e.g., propionic acid, Particularly suitable solvents are the reactants and products of the reaction. For example, in the methoxycarbonylation of ethylene with carbon monoxide in the presence of methanol to form methyl propionate, the preferred solvents are methyl propionate and methanol.

In one embodiment of the invention, the catalyst is employed in a process comprising: a) supplying a first feed stream comprising carbon monoxide and ethylene in the gas phase to a reactor; b) supplying a second feed stream comprising methanol to the reactor; c) reacting together the reactants of the first and second feed streams in the reactor in the presence of a alkoxycarbonylation catalyst, which catalyzes the reaction between methanol, carbon monoxide and ethylene, to form a product comprising methyl propionate; d) removing a product- containing stream from the reactor; e) separating a product-containing stream from a catalyst-containing stream by a separation process such as distillation; and 0 optionally recycling the catalyst-containing stream to the reactor. In another embodiment of the invention, the catalyst is used in a process comprising: a) supplying a first feed stream comprising carbon monoxide and ethylene in the gas phase to a reactor; b) supplying a second feed stream comprising methanol to the reactor; c) reacting together the reactants of the first and second feed streams in the reactor in the presence of a alkoxycarbonylation catalyst, which catalyzes the reaction between methanol, carbon monoxide and ethylene, to form a product comprising methyl propionate; d) removing a product-containing stream from the reactor by distillation leaving a catalyst-containing liquid in the reactor.

The reaction conditions of the alkoxycarbonylation process may include any suitable alkoxycarbonylation conditions for producing esters. For instance, the total gas pressure of carbon monoxide and alkene starting compound of the alkoxycarbonylation process may range from I to 69,000 kPa (0. 14 to 10,000 psig). In general, however, it is preferred that the process be operated at a total gas pressure of carbon monoxide and alkene starting compound of from 276 to 6,900 kPa (40 to 1,000 psig) and more preferably from 552 to 2,068 kPa (80 to 300 psig). The minimum total pressure is limited predominantly by the amount of reactants necessary to obtain a desired rate of reaction. More specifically, the carbon monoxide partial pressure of the alkoxycarbonylation process is preferably from 1 to 14,000 kPa, and more preferably from 21 to 5,000 kPa. in general, the molar ratio of gaseous ethylene:CO may range from 1:lOto 100:1 orhigher, preferablyfrom 1:lOto 10:1.

Tn general, the alkoxycarbonylation process may be conducted at any operable reaction temperature. Advantageously, the process is conducted at a reaction temperature from 0°C to 200°C, preferably from 50°C to 120°C, and more preferably from 70°C to 100°C.

The alkoxvcarbonylation process may be carried out using one or more suitable reactors such as, for example, a continuous stirred tank reactor (CSTR). The reaction zone employed may be a single vessel or may comprise two or more discrete vessels. The separation zone employed may be a single vessel or may comprise two or more discrete vessels. The reaction zone(s) and separation zone(s) employed herein may exist in the same vessel or in different vessels. For example, reactive separation techniques such as reactive distillation, reactive membrane separation, and the like, may occur in the reaction zone(s). The reaction is preferably operated as a continuous process, however batch or semi-batch operation are also possible.

The alkoxycarbonylation process can be conducted with recycle of unconsumed starting materials if desired. The reaction can be conducted in a single reaction zone or in a plurality of reaction zones, and in series or in parallel. When complete conversion is not desired or not obtainable, the starting materials can be separated from the product, for example by distillation, and the starting materials then recycled back into the reaction zone.

The alkoxycarbonylation process may be conducted in glass lined, stainless steel, HastalloyTM or similar type reaction equipment. The reaction zone may be fitted with one or more internal and/or external heat exchanger(s) in order to control undue temperature fluctuations, or to prevent any possible "runaway" reaction temperatures.

The alkoxycarbonylation process of this invention may be conducted in one or more steps or stages. The exact number of reaction steps or stages will be governed by the best compromise between capital costs and achieving high catalyst selectivity, activity, lifetime and ease of operability, as well as the intrinsic reactivity of the starting materials in question and the stability of the starting materials and the desired reaction product to the reaction conditions.

The alkoxvcarbonylation processes of this invention may be conducted continuously in a CSTR (11) configured as shown in Figure 1, with ethylene feed (12), CO feed (13) and methanol feed (14) . With the reactor in this configuration, methanol is fed to the bottom of the reactor at the desired rate, Ethylene and carbon monoxide enter the reactor through a sparger at a rate great enough to assure that the head space vent rate is sufficient to allow effective pressure control, The vent stream (15) passes through a condenser (16) to condense any product that conies overhead with the vapor. Catalyst, dissolved in methanol and methyl propionate, is initially charged to the reactor, and subsequently is recycled to the reactor via stream (1 9). Ethylene, carbon monoxide and methanol react in the reactor to give methyl propionate. As material is added to the reactor, liquid in the reactor overflows through a stand pipe (20) and goes to the vaporizer (21), where it separates into a product stream (22) and a catalyst-containing stream (19). The product distills out of the vaporizer, and the catalyst returns to the reactor via a liquid catalyst recycle stream (19).

The alkoxycarbonylation processes of this invention may alternatively be conducted continuously in a CS TR (1) configured as shown in Figure 2, with ethylene feed (2), CO feed (3) and methanol feed (4). In this configuration, the product distills overhead from the reactor in the vapor phase. Ethylene and carbon monoxide are fed to the CSTR through a sparger at an operator-determined, desired feed rate. Methanol is fed to the reactor at a rate controlled by the control system to maintain the operator-determined, desired reactor level. A differential pressure cell (not shown) determines the reactor level and the methanol feed rate is adjusted accordingly in order to maintain a constant liquid level in the reactor. The reactor head space contains methanol and methyl propionate at the vapor pressure of the materials at the reaction temperature. Unreacted ethylene and carbon monoxide exit the reactor through the head space via the reactor vent (5), carrying methanol and methyl propionate out of the reactor. The vapor passes through a high efficiency condenser (6) that condenses the methanol and methyl propionate, allowing the bulk of the uncondensed excess ethylene and carbon monoxide to vent via line (7) to a hood, The condensed liquid stream (8), comprising product methyl propionate, unreacted methanol and a small amount of dissolved ethylene and carbon monoxide, goes to product recovery, The alkyl alkanoate, e.g., methyl propionate, product may be obtained from the product stream by a separation method, such as distillation, via various recovery schemes known to those skilled in the art; see, e.g., US 6,476,255.

SPECIFIC EMBODIMENTS OF THE [NVENTION The following examples are given to illustrate the invention and should not be construed as limiting its scope.

Example 1. Methoxycarbonylation using 4,4',6,6'-tetramethoxy-[1,1 -biphenyl]-2,2'-diyl)bis(bis(3,5-bis(trifluoromethyl)phenyl)phosphine (hereinafter Ligand 1), palladium dibenzylideneacetone (hereinafter Pd(dba)2) and trifluoromethanesulfonic acid.

PdUdba)2) (0.0468g, 0.08 14 mmol) and Ligand 1(0.1001 g, 0.0844 mmol) are added to a mixture of methanol (20 mL, 0.49 mol) and p-dioxane (17 mL, 0.20 mol) in a 100 mL volumetric flask to prepare a solution. The solution is diluted to the mark using methyl butyrate. A stirbar is added to the resulting solution, which is stirred for 2 days to form a precatalyst stock solution, An aliquot of the precatalyst stock solution (20 mL) is transferred to a 20 mL scintillation vial, Trifluoromethanesulfonic acid (HOTf) (0,0420 mL, 0,47 mmol) is added to the vial to form a catalyst stock solution, and the catalyst stock solution is allowed to stir for 20 nunules. An aliquol of the catalyst stock solution (5 niL) is added In a parallel pressure reactor glass liner and loaded into a 20 mL reactor. The reactor is charged to 65 psig with 1:1 C2H4:CO, heated to 100°C and pressurized to 120 psig with 1: I C2H4:CO, After two hours, the reactor is cooled to 40°C and vented, By gas chromatographic (GC) analysis, 0,45 g of unreacted methanol is recovered, and 0.75 g methyl propionate (34 % yield) is found. The turnover frequency (TOF) in moles methyl propionate per moles Pd per hour is 1.0 x 1 3 h'.

-ID-

For the purposes of the invention, the term "yield" means the moles of product produced divided by the moles of methanol charged to the reactor.

Example 2, Methoxycarbonylation using Ligand 1 and Pd(dba)2 with different acids.

The procedure of Example 1 is repeated, except that 0.47 mmol of the desired acid is added to the vial in place of HOTf. By OC analysis, the product mixture consists of methanol, methyl propionate and propionic acid. Table 1 summarizes the results for a variety of acids.

For the purposes of the invention, the term "selectivity" means the moles of a given product or by-product produced divided by the total moles of products and by-products produced, Rate constants are obtained by fitting the gas uptake data in Microsoft Excel using the assumptions and rationale that follow, The kinetics are expected to be first order in active catalyst concentration, Under a constant gas headspace pressure, the kinetics can appear to be zeroth order with respect to methanol as observed from a constant gas uptake rate as the methanol is depleted. A slight deviation from zeroth order is seen in some experiments, This deviation is corrected for by fitting a first order decay, with rate constant kd, of the zeroth order rate constant, k. The overall reaction rate is expressed as: rate = lc*(et) The data presented here include only the zeroth other rate constant, k, because the decay rate is very small and can be neglected over the time frame of the experiments. The ethylene partial pressure and the CO partial pressure are included in the observed k, so this rate constant is valid only for the conditions of the experiment, Changes in liquid volume are neglected for the purposes of calculating rate constants.

For the purposes of the invention, the capitalized term "Rate Constant" means the rate constant calculated as described above as measured under the conditions of Example 1, Tn various embodiments of the invention, the Rate Constant is at least 350, at least 800, or at least 1100.

-II -

Table I: Sunimarv of results for various sulfonic and carboxylic acids g gMethyl % Acid Methanol Propionate Yield Selectivity k, (mol/hr/mol Pd) Trifluorornethanesulfonic acid 0.45 0.75 34% 99% 1.4 x io Benzenesulfonic acid 0.68 (325 12% 100% 3,1 x 102 Methanesulfonic acid 0.72 0,13 6,1% 100% 1,5 x 102 Trifluoroacetic Acid 0.73 0.00 0.00% 100% 0.0 Example 3. Methoxycarbonylation using diphenyl-1,1 -biphenyl (hereinafter Ligand 2), Pd(dba)2 and benzenesulfonic acid.

The procedure of Example 1 is followed except that Ligand 2 (0.0467 g, 0,0894 mmol) and bezenesulfonic acid (BSA) (0.0420 mL, 0.47 rnrnol) are used. By GC analysis, 0.73 g of unreacted methanol is recovered and 0.060 g methyl propionate (2.7% yield) is found. The TOF in moles methyl propionate per moles Pd per hour is 82 h1, k = 90 mol/hr/mol Pd, Example 4, Methoxycarbonylation using bis(diphenylphosphino)biphenvl and derivatives (Ligands 3 to 7), Pd(dba)2) and an acid co-catalyst.

The procedure of Example 1 is used, except as noted. A variety bis(diphenylphosphino)-I,i -biphenyl ligands (Ligands 3 through 7, shown in Table 2) possessing phenyl substituents of varying steric and electronic characteristics are explored, Tn Table 2, in terms of Formula 1, each Xis H and the column labeled "Y" indicates that each Y substituent of the ligand has the structure shown. All ligands are used in a 1.1 molar ratio with respect to Pd(dba)2. Four acid co-catalysts (30 equivalents oFBSA, trifluoromethanesulfonic acid (HOTO, methanesulfonic acid (MSA) and trifluoroacetic acid (IFA)) are investigated independently with each ligand/Pd combination, and the optimal acid varies with the identity of the ligand. A summary of results is displayed in Table 3, showing the results only for the best co-catalyst for a given ligand. Unless otherwise indicated, the ligands have the general form: OC H3 4OCH3 HscotFi OC H3 Table 2: Effect of ligand substituent on selectivity and yield 0/ /0 % Propionate Propionate R Ligand Acid Yield Selectivity.4, (moles/hr/moles Pd) OF3 1 HOTf 32% 99% 1.4x 1O CE3 3 TFA 1.5% 100% 43 OH3 OH3 4 TFA 129% 100% 36 OH3 TFA 0.93% 100% 38 OCH3 \CH. 6 ALL ND 0 0 7 ALL ND 0 0 * ND = none detected.

Example 5. Methoxycarbonylation using bis(diphenylphosphinomethyl) biphenyl (hereinafter Ligand 9) and derivatives (Ligands 10-16), Pd(dba)7) and an acid co-catalyst.

Reactions carried out as in Example 1, except that the ligands used are bis(diphenylphosphinomethyl) biphenyl and derivatives. The acid co-catalyst used is indicated in the table, Unless otherwise indicated, the ligands have the general form:

Table 3 k

Propionate moles/hours/Moles Structure Ligand Acid EQ yield Pd) 8 BSA 30 21% 94x 10' Q 9 MSA 30 14% 2,Sx BSA 30 69% 2,3 x io AqCF3 11 HOTf 30 1.4% 5.3 x 10' CF3 ________ ________ _______ __________ _______________ 12 BSA 30 3.8% 9.2 x l0 H3 _______ _______ ______ _________ ______________ 13 BSA 30 2.8% 2.8 H3C ________ _______ ______ _________ ______________ 13 HOTf 30 2.8% 3,2 x 102 H3C ________ _______ ______ _________ ______________ CH3 14 BSA 30 2.3% 1.2 x 102 H3CCH3 _______ _______ ______ _________ ______________ CH3 14 HOTf 30 1.4% 3.9 x 101 H3CCH3 _______ _______ ______ _________ ______________ CH3 14 MSA 30 2.4% 6.6 x 101 H3CCH3 _______ _______ ______ _________ ______________ CH3 I 14 TFA 30 12% 27x 102 H3O OH3 _______ _______ ______ ________ _____________ MSA 30 13.1% 3.2 x 102 OH3 _______ _______ ______ _________ ______________ 16 BSA 30 12% 5.3 x 102 OH3 ________ ________ _______ __________ _______________ This ligand class is highly selective. The only product detected in all cases is methyl propionate.

Example 6: Continuous methoxycarbonylation in which reaction and catalyst separation take place in a single vessel.

The reaction is run continuously as described above in a CSTR (1) configured as shown in Figure 2, A solution of Pd(AcAc)2, Ligand 10 and methanol (degassed) and/or methyl propionate is stirred in a glove box for 2 hours, At that time, the co-catalyst, benzenesulfonic acid, is added to the solution and the solution is stirred for 30 minutes, The reactor is filled halfway with a 10-50 wt% solution of methanol in methyl propionate. The reactor is heated to the desired reaction temperature. The pre-made catalyst charge solution is staged air free into a pressure cylinder to feed the reactor through a Gilson 5SC piston, CO and ethylene gas feeds are started at about 50 SLPH each, The reactor pressure increases to the desired reaction pressure (300 psig). The catalyst charge is fed to the reactor at about 1.7-4m1/min. As the reaction begins to take up gas, the gas feeds are increased to maintain a blow off gas rate of about 100-400 SLPH. Once the desired amount of catalyst is added, the catalyst addition is stopped and the methanol feed to the reactor is started. The methanol feed is kept under manual control at a feed rate of at least 20g/hr methanol until the reaction stabilizes. The level is controlled where the level stabilizes. The material from the overhead collection tank is collected in 5-gallon plastic containers, Under the reaction conditions, which are shown in Table 4, the methyl propionate production rate after three hours is 1,8 mol/liter/hr,

-IS-

Table 4: Reaction Conditions for ExampleS, MeOH feed rate 75 g/hr Ethylene feed rate 150 SLPH CO feed rate 250 SLPH Reactor temperature 100°C Reactor pressure 300 psi Pd concentration 100 ppm Lig:Pd 2 BSA:Pd 30 SLPH = standard lilers per hour.