KR20070031345A - Alkoxycarbonylation of vinyl esters - Google Patents

Abstract

A process for the alkoxycarbonylation of vinyl esters is provided comprising reacting a vinyl ester with carbon monoxide in the presence of an alkanol and a catalyst system. The catalyst system used in the process comprises a) a Group VIIIB metal or a compound thereof; And b) it can be obtained by combining (bidentate ligand) of the formula (1).

<Formula 1>

의 3-히드록시 프로판오에이트 에스테르 또는 산을 제조하기 위해 수행된다. Wherein R is a covalent crosslinking group; R ¹ is a 2-Q ² -tricyclo [3.3.1.1 {3,7}] decyl group or derivative (2-PA) optionally substituted with Q ² bonded thereto; R ² and R ³ independently represent a monovalent radical of up to 20 atoms, or are linked to form a divalent radical of up to 20 atoms; Q ¹ and Q ² each independently represent phosphorus, arsenic or antimony. The method is represented by Formula 2

To prepare 3-hydroxy propanoate ester or acid.

The method may also be carried out to prepare lactate esters or acids of formula (3).

<Formula 3>

Description

Alkoxycarbonylation of vinyl esters

The present invention relates to a process for the alkoxycarbonylation of unsaturated esters, in particular vinyl acetate, and more particularly to the use of the alkoxycarbonylation process, in which methyl lactate and 3-hydroxymethyl propanoate are prepared. Provides steps, but is not limited to such.

Currently, methyl lactate is prepared by esterification of lactic acid, which is prepared by synthetic methods or fermentation.

The main synthetic route is based on the reaction of acetaldehyde. In one method, acetaldehyde is reacted with hydrogen cyanide to produce lactonitrile, which is then hydrolyzed. Alternatively, acetaldehyde may react with carbon monoxide and water in the presence of a nickel (II) iodide or sulfuric acid catalyst. The synthetic route produces a racemic mixture of lactic acid, resulting in methyl lactate output. Recently, fermentation methods have been improved, which has become a preferred route to lactic acid and its derivatives. Optically pure lactic acid can be prepared by fermenting sugars with carefully selected bacteria. Lactobacilli is heat resistant, so fermentation at approximately 50 ° C. inhibits secondary reactions. The reaction procedure is slow and pH, temperature and oxygen levels must be carefully observed, but lactic acid in both optically pure R and S forms can be prepared by selecting the appropriate bacterial culture.

Methyl lactate is used as a solvent having a high boiling point and exists in various forms of materials such as detergents, degreasing agents, cosmetics and food flavourings. It is biodegradable and therefore environmentally friendly.

Since there is currently no commercially viable route of diols, the route of 1,3-propanediol will be industrially advantageous. In the 1980s, Davy Process Technology discovered the route of 1,4-butanediol by forming diethyl maleate from butane under a solid acid catalyst and then dehydrogenating it to diol. 1,4-butanediol is currently widely used as a polymer component, also in the manufacture of fibers, and as a solvent having a high boiling point. Polyhydric alcohols are often used in the reaction with isocyanates for producing urethanes and with acids and acid anhydrides for producing (poly) esters. 1,3-propanediol is considered to have use as a polymer component and as a solvent having a high boiling point.

Carbon monoxide in the presence of a catalyst system comprising alcohol or water, and a Group VIB or Group VIII metal such as, for example, palladium, and, for example, alkyl phosphines, cycloalkyl phosphines, aryl phosphines, pyridyl phosphines or Carbonylation reactions of ethylenically unsaturated compounds using phosphine ligands such as bidentate phosphine are described, for example, in EP-A-0055875, EP-A-04489472, EP-A-0106379, EP-A- 0235864, EP-A-0274795, EP-A-0499329, EP-A-0386833, EP-A-0441447, EP-A-0489472, EP-A-0282142, EP-A-0227160, EP-A-0495547 and It has been described in a number of European patents and patent applications of EP-A-0495548. In particular, EP-A-0227160, EP-A-0495547 and EP-A-0495548 disclose that catalyst systems that allow bidentate phosphine ligands to achieve fast reaction rates.

WO 96/19434 describes certain groups of bidentate phosphine compounds that can provide an extremely stable catalyst that requires little or no replenishment; The use of such bidentate catalysts allows for much faster reaction rates than previously disclosed; It is disclosed that little or no impurities are produced at high conversions.

WO 01/68583 discloses the rate in the same method used for high carbon alkenes in the presence of externally added aprotic solvents.

EP 0495548B1 discloses an example of vinyl acetate carbonylation reaction using C3 crosslinked phosphine 1,3bis (di-tert-butylphosphino) propane. The quoted rates are 200 moles of product per mole of Pd and per hour, as a result of producing a 40:60 (straight chain: branched) ratio of 1 and 2-acetoxy methyl propanoate.

WO 98/42717 discloses a process for modifying bidentate phosphines used in EP 0495548, wherein one or two phosphorus atoms are optionally substituted 2-phospha-tricyclo [3.3.1.1 {3,7 }] The decyl group or one or more carbon atoms are incorporated into derivatives thereof ("2-PA" groups) substituted by heteroatoms. Examples include various alkoxycarbonylation reactions of ethene, propene and some high carbon number terminal and internal olefins. Also disclosed is the hydroformylation reaction of vinyl acetate to obtain a branched: straight product in a 10: 1 ratio. Notably, no alkoxycarbonylation reaction of vinyl acetate is disclosed.

WO 03/070370 expands the content of WO 98/42717 by disclosing bidentate phosphines having 1,2 substituted aryl crosslinking groups of the type disclosed in WO 96/19434. Suitable olefin supports disclosed include several types with various substituents. Notably, vinyl esters are not mentioned either generically or specifically.

Vinyl esters are known to readily hydrolyze to the corresponding acid or aldehyde. Therefore, exposure of vinyl esters to acids should be avoided. Although the alkoxycarbonylation reaction with the bidentate phosphine can proceed in the presence of Group VIB or Group VIII metals, such metals are used in the presence of an anion source derived from an acid having a pKa of 4 or less. Thus, the alkoxycarbonylation reaction may not be suitable as the carbonylation reaction of the vinyl ester.

According to a first aspect of the invention, there is provided a process for alkoxycarbonylation of a vinyl ester comprising reacting the vinyl ester with carbon monoxide in the presence of an alkanol and a catalyst system.

(a) a Group VIII metal or a compound thereof; And

(b) can be obtained by combining the bidentate ligands of formula (1):

Where

R is a covalent crosslinking group;

R ¹ is a 2-Q ² -tricyclo [3.3.1.1 {3,7}] decyl group optionally substituted with Q ² linked thereto, or a derivative thereof (2-PA);

R ² and R ³ independently represent a monovalent radical of up to 20 atoms, or are linked to form a divalent radical of up to 20 atoms;

Q ¹ and Q ² each independently represent phosphorus, arsenic or antimony.

Preferably, Q ² is phospha and also preferably Q ¹ is phospha.

Preferably, R ² represents CR ⁴ (R ⁵ ) (R ⁶ ), congressyl or adamantyl, or R ³ represents CR ⁷ (R ⁸ ) (R ⁹ ), soybean A 2-Q ¹ -tricyclo [3.3.1.1 {3,7}] decyl group, or a derivative thereof, indicating gresyl or adamantyl, or R ² and R ³ are optionally substituted with Q ¹ linked to them; To form.

Preferably, the bidentate ligand is a bidentate phosphine, arsine or stibine ligand, preferably a phosphine ligand.

In addition to a hydrogen atom, the adamantyl group is a lower alkyl group, -OR ¹⁹ , -OC (O) R ²⁰ , a halo group, a nitro group, -C (O) R ²¹ , -C (O) OR ²² , a cyano group, or an aryl group , -N (R ²³ ) R ²⁴ , -C (O) N (R ²⁵ ) R ²⁶ , -C (S) (R ²⁷ ) R ²⁸ , -CF ₃ , -P (R ⁵⁶ ) R ⁵⁷ , -PO (R ⁵⁸ ) (R ⁵⁹ ), -P0 ₃ H ₂ , -PO (OR ⁶⁰ ) (OR ⁶¹ ) or -SO ₃ R ⁶² may optionally include one or more substituents, wherein R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , lower alkyl group, cyano group and aryl group are as defined herein, and R ⁵⁶ to R ⁶² are each Independently, hydrogen, a lower alkyl group, an aryl group, or a hetero group is represented.

Preferably, the adamantyl group is substituted with one or more substituents as defined above, and very preferred substituents are unsubstituted C ₁ to C ₈ alkyl groups, -OR ¹⁹ , -OC (O) R ²⁰ , phenyl group, -C (O ) OR ²² , fluoro group, -S0 ₃ H, -N (R ²³ ) R ²⁴ , -P (R ⁵⁶ ) R ⁵⁷ , -C (O) N (R ²⁵ ) R ²⁶ and -PO (R ⁵⁸ ) (R ⁵⁹ ), -CF ₃ , wherein R ¹⁹ represents hydrogen, an unsubstituted C ₁ -C ₈ alkyl group or a phenyl group, and R ²⁰ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ are each independently hydrogen or non-substituted C ₁ -C ₈ alkyl group, R ⁵⁶ to R ⁵⁹ are, each independently, represent an unsubstituted C ₁ -C ₈ alkyl group or a phenyl group.

Preferably, the adamantyl group may comprise up to 10 substituents as defined above, in addition to a hydrogen atom, more preferably up to 5 substituents as defined above, even more preferably up to 3 said It may include a substituent defined in. Preferably, when the adamantyl group contains at least one substituent as defined above in addition to the hydrogen atom, each substituent is preferably the same. Preferred substituents are unsubstituted C ₁ -C ₈ alkyl groups and trifluoromethyl groups, in particular unsubstituted C ₁ -C ₈ alkyl groups such as methyl. A very preferred adamantyl group contains only a hydrogen atom, that is, an adamantyl group is not substituted.

Preferably, at least one adamantyl group is present in the compound of Formula 1 and each adamantyl group is identical.

2-Q ² (or Q ¹ ) -tricyclo [3.3.1.1 {3,7}] decyl group (hereinafter referred to as 2-metha-adamantyl group for convenience, where 2-metha-adamantyl is 2- 2-arsa-adamantyl and / or 2-stiba-adamantyl and / or 2-phospha-adamantyl, Preferably 2-phospha-adamantyl) may optionally include one or more substituents in addition to the hydrogen atom. Preferred substituents include substituents defined herein with respect to adamantyl groups. More preferred substituents include lower alkyl groups, in particular unsubstituted C ₁ -C ₈ alkyl groups, in particular methyl, trifluoromethyl, —OR ¹⁹ and 4-dodecylphenyl, wherein R ¹⁹ is used herein As defined and in particular unsubstituted C ₁ -C ₈ alkyl or aryl. When the 2-metha-adamantyl group contains one or more substituents, each substituent is preferably the same.

Preferably, the 2-metha-adamantyl group is substituted at one or more of the 1, 3, 5 or 7 positions with the substituents defined herein. More preferably, the 2-metha-adamantyl group is substituted at each 1, 3 or 5 position. Preferably, such an arrangement means that the Q atom of the 2-metha-adamantyl group is bonded to a carbon atom having no hydrogen atom in the adamantyl skeleton. More preferably, the 2-metha-adamantyl group is substituted at each 1, 3, 5 or 7 position. 2-metha-adamantyl groups include one or more substituents, preferably each substituent is the same. Especially preferred substituents are unsubstituted C ₁ -C ₈ alkyl group such as methyl, in particular methyl with unsubstituted C ₁ -C ₈ alkyl and trifluoromethyl.

Preferably, 2-metha-adamantyl is 2-metha-adamantyl or mixtures thereof substituted with unsubstituted 2-metha-adamantyl or one or more unsubstituted C ₁ -C ₈ alkyl substituents.

Preferably, the 2-metha-adamantyl group contains additional heteroatoms in the 2-metha-adamantyl backbone in addition to the 2-Q atom. Preferred further heteroatoms include oxygen and sulfur atoms, in particular oxygen atoms. More preferably, the 2-metha-adamantyl group comprises one or more additional heteroatoms at the 6, 9 and 10 positions. Even more preferably, the 2-metha-adamantyl group contains additional hetero atoms at the 6, 9 and 10 positions, respectively. Most preferably, where the 2-metha-adamantyl group has two or more additional heteroatoms in the 2-metha-adamantyl backbone, each additional heteroatom is identical. Particularly preferred 2-metha-adamantyl groups that may be optionally substituted with one or more substituents as defined herein include oxygen atoms at the respective 6, 9, and 10 positions in the 2-metha-adamantyl backbone.

Preferably, 2-metha-adamantyl includes one or more oxygen atoms in the 2-metha-adamantyl backbone.

Highly preferred 2-metha-adamantyl group as defined herein is a 2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxaadamantyl group (2-phospha-1 , 3,5,7-tetramethyl-6,9,10-trioxadamantyl group), 2-phospha-1,3,5-trimethyl-6,9,10-trioxaadamantyl group, 2-phospha-1 , 3,5,7-tetra (trifluoromethyl) -6,9,10-trioxaadamantyl group and 2-phospha-1,3,5-tri (trifluoromethyl) -6,9, 10-trioxadamantyl group. Most preferably, 2-phospha-adamantyl is a 2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxaadamantyl group or 2-phospha-1,3 , 5, -trimethyl-6,9,10-trioxadamantyl group.

Preferably, when two or more 2-metha-adamantyl groups are present in the compound of Formula 1, each 2-metha-adamantyl group is the same.

2-metha-adamantyl groups can be prepared by methods well known to those skilled in the art. Preferably, certain 2-phospha-adamantyl compounds can be obtained from Cytec Canada Inc. located at 901 Garner Road, Niagara Falls, Ontario, Canada L2E 6T4. Similarly, corresponding 2-metha-adamantyl compounds of formula (1) and the like can be obtained from the same source or prepared by similar methods.

Preferred Group VIIIB metals or compounds thereof that can be combined with a compound of Formula 1 include cobalt, nickel, palladium, rhodium and platinum. Preferably, the Group VIIIB metal is palladium or a compound thereof. Preferred compounds of such Group VIIIB metals are nitric acid; Sulfuric acid; Lower alkanoic acids such as acetic acid and propionic acid (up to C ₁₂ ); Sulfonic acids such as methane sulfonic acid, chlorosulfonic acid, fluorosulfonic acid, trifluoromethane sulfonic acid, benzene sulfonic acid, naphthalene sulfonic acid, for example toluene sulfonic acid such as p-toluene sulfonic acid, t-butyl sulfonic acid and 2-hydroxypropane sulfonic acid; Sulfonated ion exchange resins; Perhalogen acids, such as perchloric acid; Halogenated carboxylic acids such as trichloroacetic acid and trifluoroacetic acid; Orthophosphoric acid; Phosphonic acids such as benzenephosphonic acid; And salts of said metals with weakly coordinated bound anions derived from acids resulting from interactions between Lewis acids and Broensted acids or said metal compounds comprising said anions. Other sources that can provide a preferred anion include optionally halogenated tetraphenyl borate derivatives, for example perfluorotetraphenyl borate. In addition, zero valent palladium complexes, especially those having unstable ligands such as, for example, triphenylphosphine, or alkenes such as dibenzylideneacetone or styrene, or tri (dibenzylideneacetone) di Palladium can be used.

The anion is involved in the reaction as one or more acids having a pKa of 4 or less, more preferably 3 or less, measured in an 18 ° C. aqueous solution, for example metal salts or largely organic salts such as alkyl ammonium. Salts with cations that do not, and precursors such as esters that can break down under reaction conditions that produce anions in situ, or may be introduced as such. Preferred acids and salts include acids and salts other than the unsubstituted carboxylates listed above.

The content of anions present is not critical to the catalytic behavior of the catalyst system. The molar ratio of anion to palladium may be from 1: 1 to 500: 1, preferably from 2: 1 to 100: 1, especially from 3: 1 to 30: 1. If anions are provided by acids and salts, the relative ratios of acids and salts are not important. However, when the anion is provided by the acid, or partly by the acid, the ratio of acid to Group VIII metal is preferably from 1: 1 mol (H ⁺ ) / mol (C ^{2 +} ) to at least 5 : 1 mol (H ⁺ ) / mol (C ^{2 +} ), more preferably the ratio is from 2: 1 to at least 3: 1, most preferably approximately 2: 1 ratio. H ⁺ means the content of active acidic site: 1 mole of monobasic acid will have 1 mole of H ⁺ and 1 mole of dibasic acid is 2 moles Will have H ⁺ , and tribasic acid and the like can be understood as such. Similarly, C ^{2 +} 2 ⁺ ratio of the cationic charges to the bar, which means moles of metal having a metal cation in the M ⁺ ions are to be adjusted according to this. For example, M ⁺ cations should be considered to have 0.5 moles of C ^{2 +} per mole of M ⁺ .

Preferably, the ratio of the bidentate ligand to the acid is at least 1: 2 mol / mol (H ⁺ ), and preferably, the ratio of the bidentate ligand to the Group VIII metal is 1: 1 mol / mol ( C ^{2 +} ) or more. Preferably, the ligand is a large excess of metal ^{mol / mol (C 2 +)} , preferably acid and 1: 2 ratio or more mol / mol (H ^+). Excess ligand is preferred because the ligand itself acts as a base to buffer against acid levels in the reaction and can prevent degradation of vinyl esters. On the other hand, the presence of acid activates the reaction mixture and improves the overall reaction rate.

As mentioned above, the catalyst system of the present invention may be used homogeneously or heterogeneously. Preferably, the catalyst system is homogeneous.

Preferably, the catalyst system of the present invention is used in the alkoxycarbonylation reaction of vinyl esters to obtain predominantly straight chain products. This is a surprising result, since WO 98/42717 uses a 2-PA ligand with a propane bridge to hydroformylate vinyl acetate to obtain the predominantly branched product.

Thus, in a second aspect of the present invention, there is provided a process for the preparation of 3-hydroxy propanoate esters or acids of formula (2), wherein the vinyl esters together with carbon monoxide in the presence of alkanols and catalyst systems 3-hydroxy propanoate of formula (II) by carrying out a carbonation reaction and a treatment step on the linear (n) product 1-acetoxy CH ₂ CH ₂ C (O) OR ²⁸ obtained therefrom Obtaining an ester or acid, wherein the catalyst system comprises:

(a) a Group VIII metal or a compound thereof: and

(b) a combination of the bidentate ligands of formula (1) according to the first aspect of the invention as defined herein.

Wherein R ²⁸ is selected from H or a substituted or unsubstituted and C ₁ -C ₃₀ alkyl or aryl moiety which may be straight or branched.

The straight chain (n) and branched (iso) products of the alkoxycarbonylation reaction can be separated before or after the treatment step. Preferably, the product is separated from the reaction products by distillation.

According to a third aspect of the present invention, there is provided the use of any catalyst system defined in the first or second aspect of the invention, wherein the 3-hydroxy propanoate ester of formula (2) is prepared, preferably its commercial product. Use is provided in which the preparation method comprises alkoxycarbonylation of a vinyl ester followed by treatment of the linear (n) product of the alkoxycarbonylation.

However, notwithstanding the foregoing, the present invention does not exclude the possibility of using a branched product of the reaction.

Thus, according to a fourth aspect of the present invention, there is provided a process for the preparation of lactate esters or acids of formula (3), which method is a branched (iso) product 2-acetoxy (CH ₃ ) CHC (O) OR ²⁸ Alkoxycarbonylation of the vinyl ester with carbon monoxide in the presence of an alkanol and a catalyst system to produce a product comprising the same, and chemically treating the (iso) product obtained therefrom to a corresponding lactate of formula Or obtaining an acid, wherein the catalyst system

(a) a Group VIII metal or a compound thereof: and

(b) a combination of a bidentate ligand of formula (1), preferably a phosphine ligand, according to the first aspect of the invention as defined herein.

Wherein R ²⁸ is selected from H or a substituted or unsubstituted and C ₁ -C ₃₀ alkyl or aryl moiety which may be straight or branched.

The treatment or treatment step herein refers to conventional chemical treatments suitable for cleaving acetoxy groups to obtain hydroxy acids or esters, such as hydrolysis or transesterification on the acetoxy product of the alkoxycarbonylation reaction. Means to do.

The linear (n) and branched (iso) products of the carbonylation reaction can be separated before or after the treatment step. Preferably, the reaction products are separated by distillation. Since branched and straight chain products often have very different boiling points, distillation is an effective separation technique for the products of the reaction.

Preferably, the ratio of linear: branched product from the alkoxycarbonylation process is at least 1.5: 1, more preferably at least 2: 1 and most preferably at least 2.5: 1.

According to a fifth aspect of the present invention, there is provided a use of the catalyst system as defined in the first or second aspect of the invention, the method for producing a lactate ester or acid of formula (3), preferably in a commercial production process There is provided a process for preparing an alkoxycarbonylation reaction of a vinyl ester followed by treating a branched (iso) product of the alkoxycarbonylation reaction to obtain an ester or an acid.

Preferably, the lactate or 3-hydroxy propanoate ester or acid of the invention can be hydrogenated to produce 1,2 and 1,3 diols, respectively.

Preferably, the treatment is hydrolysis or transesterification and can be carried out by any suitable technique known to those skilled in the art. Such techniques are detailed, for example, in "Kirkothmer Encyclopaedia of Chemical Technology", Vol. 9, 4th edition, p. 783-"Hydrolysis of Organic Esters". Such methods include base hydrolysis, acid hydrolysis, steam hydrolysis and enzymic hydrolysis. Preferably, the hydrolysis is base hydrolysis, more preferably, the hydrolysis is carried out in excess base and then acidified to produce the acid product. Hydrogenation of the hydrolysis product can be carried out by any suitable method known to those skilled in the art. Preferably, vapor phase hydrogenation of the hydroxy alkanoate ester is carried out. Preferred techniques are illustrated in WO 01/70659 by Crabtree et al. Preferred experimental details are described in Examples 1-9 of the disclosure above, illustrating the route from 3-hydroxy propanoic esters to 1,3 propanediol. Preferably, the hydrogenation reaction is carried out in a hydrogenation zone comprising a heterogeneous hydrogenation catalyst. Preferred conditions and catalysts are described in WO 01/70659, as far as the hydrogenation of 3-hydroxy propanoic acid esters is concerned, the contents of which are incorporated herein by reference. However, for the purposes of the present application, such hydrogenation can also be applied to the hydrogenation of lactate esters to produce 1,2 propane diols. Preferably, transesterification is carried out with an alkanol corresponding to the alkyl group of the desired alkyl ester product, wherein methanol and acetoxy alkyl esters for converting acetoxy alkyl esters to hydroxy methyl esters are hydroxy. Examples, such as ethanol for conversion to ethyl ester, are mentioned. Preferably, this cleaves the acetoxy group but does not change the hydroxy alkyl alkanoate. Preferably, the transesterification reaction takes place in the presence of a suitable catalyst, for example methane sulfonic acid or p-toluene sulfonic acid.

The R group may represent an alkylene crosslinking group, preferably lower alkylene.

In one embodiment of the invention, the bridging group R may be defined as -A- (K, D) Ar (E, Z) -B-,

Where:

Ar is a bridging group comprising an optionally substituted aryl moiety linked to Q ¹ and Q ² atoms, preferably a phosphorus atom, to a bondable adjacent carbon atom;

A and B, each independently, represent lower alkylene;

K, D, E and Z are substituents of the aryl moiety (Ar), each independently hydrogen, lower alkyl, aryl, hetero, halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ or- JQ ³ (X ⁵ ) X ⁶ represents, and J represents a lower alkylene group; Or two adjacent groups selected from K, Z, D and E and the carbon atoms of the aryl groups to which they are linked form a phenyl ring, which is hydrogen, lower alkyl, halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ or C (O) Optionally substituted with one or more substituents selected from SR ²⁷ , or when Ar is a cyclopentadienyl group, Z can be represented by -M (L ₁ ) _n (L ₂ ) _m , and Z is also through a metal ligand bond Linked to a cyclopentadienyl group;

X ⁵ represents CR ¹³ (R ¹⁴ ) (R ¹⁵ ), congresyl or adamantyl, X ⁶ represents CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ), congresyl or adamantyl, or X ⁵ and X ⁶ together with Q ³ linked thereto form an optionally substituted 2-Q ³ -tricyclo [3.3.1.1 {3,7}] decyl group or derivative thereof;

Preferably, Q ³ is phospha.

Preferably, when K represents -A ₃ -Q ³ (X ⁵ ) X ⁶ in the compound of Formula 1 and E represents -A ₃ -Q ³ (X ⁵ ) X ⁶ , then D is -A _3- Q ³ (X ⁵ ) X ⁶ is represented.

The 2-metha-adamantyl group is a 2-Q ² -tricyclo [3.3.1.1. {3,7}] decyl group formed by combining R ¹ with Q ² linked thereto and R ² and R ³ linked thereto Q ¹ in combination with a 2-Q ¹ are formed with-tricyclo [. 3.3.1.1 {3,7}] decyl group, X ⁵ and X ⁶ is 2-Q ³ formed in combination with each of Q ³ is connected to these -Tricyclo [3.3.1.1 {3,7}] decyl group, wherein Q ¹ , Q ² and Q ³ constitute adamantyl while being at the 2-position of the adamantyl group and each Q ¹ , Q ² and Q ³ represent phosphorus, arsenic and / or antimony. Preferably, Q ¹ , Q ² and Q ³ represent phosphorus.

Preferred embodiments of the invention are:

R ² represents CR ⁴ (R ⁵ ) (R ⁶ ), R ³ represents CR ⁷ (R ⁸ ) (R ⁹ ), and R ¹ represents a 2-phospha-adamantyl group with Q ² linked thereto When forming;

R ² represents CR ⁴ (R ⁵ ) (R ⁶ ), R ³ represents adamantyl and R ¹ together with Q ² linked thereto form a 2-phospha-adamantyl group;

R ² represents CR ⁴ (R ⁵ ) (R ⁶ ), R ³ represents congresyl and R ¹ together with Q ² linked thereto form a 2-phospha-adamantyl group;

When R ² and R ³ independently represent adamantyl and R ¹ together with Q ² linked thereto form a 2-phospha-adamantyl group;

R ² and R ³ independently represent congresyl and R ¹ together with Q ² linked thereto form a 2-phospha-adamantyl group;

R ¹ forms a 2-phospha-adamantyl group with Q ² linked thereto, and R ² and R ³ together with Q ¹ linked thereto form a 2-phospha-adamantyl group;

Very preferred embodiments of the invention are:

R ¹ forms a 2-phospha-adamantyl group with Q ² linked thereto, and R ² and R ³ together with Q ¹ linked thereto form a 2-phospha-adamantyl group;

Preferably, in the compound of formula 1, R ² is the same as R ³ .

Preferably, in the compound of Formula 1, R ² and R ³ represent the same substituent, X ⁵ and X ⁶ (if present) represent the same substituent, more preferably R ² and R ³ , and X ⁵ And X ⁶ (if present) are combined in the same manner as R ¹ .

In the present invention, particularly preferred combinations include the following cases:

(1) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-phospha-adamantyl;

A and B are the same and represent -CH _2- ;

K, D and E are the same and represent hydrogen or unsubstituted C ₁ -C ₆ alkyl, in particular hydrogen;

Both Q ¹ and Q ² represent phosphorus.

(2) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

K represents -CH ₂ -Q ³ (X ⁵ ) X ⁶ , wherein X ⁵ and X ⁶ together with Q ³ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

Q ¹ , Q ² and Q ³ each represent phosphorus;

D and E are the same and represent hydrogen or unsubstituted C ₁ -C ₆ alkyl, in particular hydrogen.

(3) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

K represents -CH ₂ -Q ³ (X ⁵ ) X ⁶ , wherein X ⁵ and X ⁶ together with Q ³ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

Q ¹ , Q ² and Q ³ each represent phosphorus.

(4) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

Both Q ¹ and Q ² represent phosphorus;

K represents hydrogen or unsubstituted C ₁ -C ₆ alkyl, in particular hydrogen;

D and E together with the carbon atoms of the cyclopentadienyl ring linked thereto form an unsubstituted phenyl ring;

M represents Fe;

and n = _1, L 1 is a cyclopentadienyl, particularly represents unsubstituted cyclopentadienyl, m = 0.

(5) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

K, D and E are the same and represent hydrogen or unsubstituted C ₁ -C ₆ alkyl, in particular hydrogen;

Both Q ¹ and Q ² represent phosphorus;

M represents Fe;

n = 1, L ₁ represents cyclopentadienyl, in particular unsubstituted cyclopentadienyl, m = 0.

(6) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

K represents -CH ₂ -Q ³ (X ⁵ ) X ⁶ , wherein X ⁵ and X ⁶ together with Q ³ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

Q ¹ , Q ² and Q ³ each represent phosphorus;

D and E are the same and represent hydrogen or unsubstituted C ₁ -C ₆ alkyl, in particular hydrogen;

M represents Fe;

and n = _1, L 1 is a cyclopentadienyl, particularly represents unsubstituted cyclopentadienyl, m = 0.

(7) R ¹ represents 2-metha-adamantyl with Q ² linked thereto;

R ² and R ³ together with Q ¹ linked to them represent 2-metha-adamantyl;

K represents -CH ₂ -Q ³ (X ⁵ ) X ⁶ , wherein X ⁵ and X ⁶ together with Q ³ linked to them represent 2-metha-adamantyl;

A and B are the same and represent -CH _2- ;

Q ¹ , Q ² and Q ³ each represent phosphorus;

D and E together with the carbon atoms of the cyclopentadienyl ring linked thereto form an unsubstituted phenyl ring;

M represents Fe;

and n = _1, L 1 is a cyclopentadienyl, particularly represents unsubstituted cyclopentadienyl, m = 0.

R ⁴ to R ⁹ and R ¹³ to R ¹⁸ each independently represent a lower alkyl group, an aryl group, or a hetero group;

R ¹⁹ to R ²⁷ each independently represent hydrogen, a lower alkyl group, an aryl group or a hetero group;

M represents a Group VIB or Group VIII metal or metal cation thereof;

L ₁ represents a cyclopentadienyl group, indenyl group or aryl group, each of which is hydrogen, lower alkyl group, halo group, cyano group, nitro group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , Optional with one or more substituents selected from C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ or ferrocenyl groups Substituted with;

L ₂ represents at least one ligand, each ligand is independently selected from hydrogen, lower alkyl group, alkylaryl group, halo group, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ ;

R ⁴³ to R ⁴⁸ each independently represent hydrogen, a lower alkyl group, an aryl group, or a hetero group;

n = 0 or 1;

And m = 0-5;

Provided that when n = 1, m is 0 and when n is 0, m is not 0;

Q ³ (if present) represents phosphorus, arsenic or antimony.

Preferably, the Group VIIIB metal is palladium.

Preferably, when K, D, E or Z represents -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ), each K, D, E or Z is If A or B is on an aryl carbon adjacent to the linked aryl carbon, or if it is not so contiguous, then itself is -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ) adjacent to the remaining K, D, E or Z groups.

For convenience, any one or more of the five aspects of the present invention may be referred to herein as the method of the present invention.

Preferably, the process of the invention can be used to catalyze the reaction of carbonylating vinyl esters in the presence of carbon monoxide and hydroxyl group containing compounds, i.e., the process of the invention is the corresponding acetoxy carboxyl. It can catalyze the conversion of vinyl esters to ric esters. Conveniently, the methods of the present invention can utilize compounds that are very stable under conventional carbonylation reaction conditions, such as those requiring little or no replenishment. Conveniently, the process of the invention has a fast carbonylation reaction rate of vinyl esters. Conveniently, the process of the present invention can promote high conversion rates of vinyl esters, thereby obtaining desired products in high yields with little or no impurities. As a result, the commercial applicability of carbonylation methods, such as the carbonylation reaction of vinyl esters, can be increased by using the process of the invention.

As used herein, the term "Ar" or "aryl" refers to a 5-10 membered ring, preferably 6-10 membered carbocyclic aromatic or pseudoaromatic, such as phenyl, ferrocenyl and naphthyl. aromatic) groups, wherein the groups include, in addition to K, D, E or Z, an aryl group, a lower alkyl group (the alkyl group itself may be optionally substituted or terminated as defined herein below), hetero Group, halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ^Is optionally substituted with one or more substituents selected from ²⁷ , C (O) SR ²⁷ or C (S) NR ²⁵ R ²⁶ , wherein R ¹⁹ to R ²⁷ are each independently hydrogen, an aryl group or a lower alkyl group (alkyl group itself May optionally be substituted or terminated as defined herein below).

Preferably, Ar or aryl is cyclopentadienyl and when D and E together with the carbon atoms of the cyclopentadienyl ring linked thereto form a phenyl ring, the metal M or its cation is connected to the indenyl ring system do. In a preferred embodiment of the invention, Ar represents phenyl or naphthyl, more preferably phenyl, in both cases which may be optionally substituted as described in the preceding paragraphs.

In the compound of Formula 1, a metal such as Cr, Mo, W, Fe, Co, Ni, Ru, Rh, Os, Ir, Pt, and Pd is represented by the expression "M represents a Group VIB or Group VIII metal". Include. Preferably, the metal is selected from Cr, Mo, W, Fe, Co, Ni, Ru and Rh. For the avoidance of misunderstanding, the Group VIB or Group VIII metals herein should be understood to include Groups 6, 8, 9 and 10 of the modern periodic table nomenclature.

We mean by the term “the metal cation” that the Group VIB or Group VIII metal (M) in the compound of Formula 1 as defined herein has a positive charge. Preferably, the metal cation is in the form of a salt, or halo group, nitric acid; Sulfuric acid; Lower (up to C ₁₂ ) alkanoic acids such as acetic acid and propionic acid; Methane sulfonic acid, chlorosulfonic acid, fluorosulfonic acid, trifluoromethane sulfonic acid, benzene sulfonic acid, naphthalene sulfonic acid, for example sulfonic acids such as p-toluene sulfonic acid, toluene sulfonic acid such as t-butyl sulfonic acid and 2-hydroxypropane sulfonic acid; Sulfonated ion exchange resins; Perhalic acid, such as perchloric acid; Perfluorinated carboxylic acids such as trichloroacetic acid and trifluoroacetic acid; Orthophosphoric acid; Phosphonic acids such as benzene phosphonic acid; And weakly coordinated anions derived from acids due to the interaction between Lewis acid and Broensted acid. Other sources capable of providing the preferred anions include tetraphenyl borate derivatives.

Preferably, M represents a Group VIB or Group VIIIB metal. In other words, the total electron count for metal M is 18.

As L ₂ can represent, halo groups which can substitute or terminate the above-mentioned groups include fluoro groups, chloro groups, bromo groups and iodo groups.

Preferably, if A represents cyclopentadienyl and n = 1, then the compound of formula 1 is composed of two cyclopentadienyl rings, two indenyl rings or one indenyl and one cyclopentadienyl ring ( Each ring system may be optionally substituted as described herein). Such compounds may be referred to as "sandwich compounds" because metal M or its metal cations are sandwiched by two ring systems. Each cyclopentadienyl and / or indenyl ring system may be substantially coplanar with one another, or they may be inclined with respect to one another (commonly referred to as inclined metallocene).

Alternatively, when n = 1, the compound of the invention is one of one cyclopentadienyl or one indenyl ring (each ring system may be optionally substituted as defined herein), and It may include one aryl ring (ie, L ₁ represents aryl) which may be optionally substituted as defined herein. Preferably, when n = 1 and L ₁ represents aryl, the metal M of the compound of formula 1 as defined herein is typically in the form of a metal cation.

Preferably, when n = 0, the compounds of the present invention comprise only one cyclopentadienyl or indenyl ring (each ring system may be optionally substituted as defined herein). Such compounds may be referred to as "half sandwich compounds". Preferably, when n = 0, m represents 1 to 5 so that the metal M of the compound of formula 1 has 18 electron counts. In other words, when the metal M of the compound of formula 1 is iron, the total number of electrons provided by the ligand L ₂ is typically 5.

Preferably, the metal M, or metal cation thereof, in the cyclopentadienyl compound of Formula 1 is typically bonded to the cyclopentadienyl ring (s) or cyclopentadienyl moiety of the indenyl ring (s). Typically, the cyclopentadienyl ring (s) or cyclopentadienyl moieties of indenyl ring (s) exhibit a pentahapto bonding mode with the metal; However, other modes of bonding between cyclopentadienyl ring (s) or cyclopentadienyl moieties and metals of indenyl ring (s), such as trihapto coordination, are also included within the scope of the present invention.

Preferably, in the compound of Formula 1, Ar is cyclopentadienyl and M represents Cr, Mo, Fe, Co or Ru, or a metal cation thereof. More preferably, M represents Cr, Fe, Co or Ru, or represents its metal cation. Most preferably, M is selected from Group VIIIB metals or metal cations thereof. Particularly preferred Group VIII metal (M) is Fe. The metal M as defined herein may be in cationic form, preferably the metal essentially retains the residual charge due to coordinating bonds with L ₁ and / or L _{2 as} defined herein. (Essentially not involved at all).

Preferably, when n = 1 in the compound of Formula 1, L ₁ represents cyclopentadienyl, indenyl or aryl, each ring being hydrogen, lower alkyl group, halo group, cyano group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , SR ²⁷ or ferrocenyl, which is a cyclopentadienyl, indenyl or aryl ring which L ₁ may represent as a metallocenyl group It is optionally substituted with one or more substituents selected from (i.e., directly attached to the cyclopentadienyl ring). More preferably, if the cyclopentadienyl, indenyl or aryl ring which L ₁ can represent is substituted, it is preferably C ₁ -C ₆ alkyl group, halo group, cyano group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ are substituted with one or more substituents, wherein R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ and R ²⁴ are each Independently, hydrogen or a C ₁ -C ₆ alkyl _group .

Preferably, when n = 1, L ₁ represents optionally substituted cyclopentadienyl, indenyl, phenyl or naphthyl. Preferably, the cyclopentadienyl, indenyl, phenyl or naphthyl group is unsubstituted. More preferably, L ₁ represents cyclopentadienyl, indenyl or phenyl, each ring being unsubstituted. Most preferably, L ₁ represents unsubstituted cyclopentadienyl.

In one particularly preferred embodiment of the invention, for compounds of formula 1, n = 1, L ₁ is as defined herein and m = 0.

Alternatively, in compounds of Formula 1, when n is 0 and m is not 0, L ₂ represents at least one ligand, and each ligand is independently a lower alkyl group, halo group, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ . More preferably, L ₂ represents one or more ligands, each ligand independently representing a C ₁ to C ₄ alkyl group, a halo group, in particular a chloro group, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ Wherein R ⁴³ to R ⁴⁸ are independently selected from hydrogen or aryl such as a C ₁ -C ₆ alkyl group or a phenyl group.

In another particularly preferred embodiment of the invention, for compounds of formula 1, n = 0 and L ₂ is as defined herein and m = 3 or 4, in particular 3.

M represents a metal selected from Cr, Mo, Fe, Co or Ru, or a metal cation thereof;

L ₁ represents cyclopentadienyl, indenyl, naphthyl or phenyl, each ring being C ₁ -C ₆ alkyl group, halo group, cyano group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , Optionally substituted with one or more substituents selected from C (O) OR ²² , NR ²³ R ²⁴ ;

L ₂ represents one or more ligands, wherein each ligand is independently selected from C ₁ -C ₆ alkyl groups, halo groups, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ ;

n = 0 or 1;

And m = 0 to 4;

However, if n = 1, m = 0, and if m is not 0, n = 0.

More preferred compounds of formula (I) include the following cases:

M represents iron or a cation thereof;

L ₁ represents a cyclopentadienyl, indenyl or phenyl group, each group being C ₁ -C ₆ alkyl group, halo group, cyano group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O Optionally substituted with one or more substituents selected from OR ²² ;

L ₂ represents at least one ligand, each ligand is independently selected from C ₁ -C ₆ alkyl group, halo group, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ , wherein R ⁴³ to R ⁴⁸ are Independently hydrogen, C ₁ -C ₆ alkyl group or phenyl group;

n = 0 or 1; And m = 0-4.

Even more preferred compounds of formula (I) include the following cases:

L ₁ represents unsubstituted cyclopentadienyl, indenyl or phenyl, in particular unsubstituted cyclopentadienyl; And n = 1 and m = 0.

Optionally preferred compounds of formula (I) include the following cases:

n = 0;

L ₂ represents at least one ligand, each ligand is independently selected from C ₁ -C ₆ alkyl group, halo group, CO, PR ⁴³ R ⁴⁴ R ⁴⁵ or NR ⁴⁶ R ⁴⁷ R ⁴⁸ , wherein R ⁴³ to R ⁴⁸ are Independently hydrogen, C ₁ -C ₆ alkyl group or phenyl group; And m = 1 to 4, in particular 3 or 4. For example, when m = 3, the three ligands that L ₂ can represent are (CO) ₂ halo groups, (PR ⁴³ R ⁴⁴ R ⁴⁵ ) ₂ halo groups or (NR ⁴⁶ R ⁴⁷ R ⁴⁸ ) ₂ halo groups Include.

References herein to vinyl esters include those compounds represented by substituted or unsubstituted vinyl acetate of formula 4:

Wherein R ²⁹ is hydrogen, lower alkyl group, aryl group, hetero group, halo group, cyano group, nitro group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁹ , wherein R ¹⁹ to R ²⁷ are defined herein. As shown.

Preferably, R ²⁹ is selected from hydrogen, lower alkyl, phenyl or lower alkylphenyl. More preferably hydrogen, phenyl, C ₁ -C ₆ alkylphenyl or C ₁ -C ₆ alkyl such as methyl, ethyl, propyl, butyl, pentyl and hexyl, even more preferably C ₁ -C ₆ Alkyl, especially methyl.

Preferably, R ³⁰ -R ³² each independently represent a hydrogen, lower alkyl, aryl or hetero group as defined herein. Most preferably, R ³⁰ -R ³² represent hydrogen. As mentioned above, R ²⁸ is preferably a lower alkyl group, aryl group, hetero group, halo group, cyano group, nitro group, OR ¹⁹ , OC (O) R ²⁰ , as defined herein. One or more selected from C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ or C (O) SR ²⁷ May be optionally substituted with a substituent.

R ²⁸ is most preferably from C ₁ -C ₈ alkanols such as methanol, ethanol, propanol, iso-propanol, iso-butanol, t-butyl alcohol, n-butanol, phenol and chlorocapryl alcohol Derived alkyl / aryl groups. Most preferred groups are methyl and ethyl and particularly preferred groups are methyl

The term "hetero group" as used herein includes a 4- to 12-membered ring, preferably a 4- to 10-membered ring system, wherein the ring is selected from nitrogen, oxygen, sulfur and mixtures thereof. It contains one or more hetero atoms, and the ring may comprise one or more double bonds, or its properties are non-aromatic, partially aromatic, or wholly aromatic. The ring system can be monocyclic, bicyclic or fused. Each " hetero group &quot;, as defined herein, is a halo group, cyano group, nitro group, oxo, lower alkyl (alkyl group itself may be optionally substituted or terminated as defined herein below) OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ or C (S) Optionally substituted with one or more substituents selected from R ²⁵ R ²⁶ , wherein R ¹⁹ to R ²⁷ are each independently hydrogen, an aryl group or a lower alkyl group (the alkyl group itself being optionally substituted as defined herein below or Can be terminated). Thus, the term "hetero group" refers to optionally substituted azetidinyl, pyrrolidinyl, imidazolyl, indolyl, furanyl, oxazolyl, isoxazolyl, isoxadiazolyl, thiazolyl, thia Such as diazolyl, triazolyl, oxatriazolyl, tithiazolyl, pyridazinyl, morpholinyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl, piperidinyl, pyrazolyl and piperazinyl Contains groups. Substitution in the hetero group may be at the carbon of the hetero ring, or if appropriate, at one or more hetero atoms.

"Hetero" groups may also be in the form of N oxides.

As used herein, the term "lower alkyl" refers to C ₁ to C ₁₀ alkyl and includes methyl, ethyl, propyl, butyl, pentyl, hexyl and heptyl groups. Unless otherwise specified, an alkyl group can be straight or branched, saturated or unsaturated, cyclic, acyclic or partially cyclic / acyclic if there are a sufficient number of carbon atoms, and / or halo Group, cyano group, nitro group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ²⁷ , C May be substituted or terminated with one or more substituents selected from (O) SR ²⁷ , C (S) R ²⁵ R ²⁶ , aryl or hetero group, wherein R ¹⁹ to R ²⁷ are each independently hydrogen, aryl group or Lower alkyl groups and / or may be interrupted by one or more oxygen or sulfur atoms or silano or dialkylsilicon groups.

R ^l , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , R ²⁹ , R ³⁰ , R ³¹ , R ³² , K, D, Lower alkyl groups or alkyl groups, which can be represented by E and Z, thereby substituting aryl and hetero groups, may be straight or branched, saturated or unsaturated, cyclic, acyclic or May be partially cyclic / acyclic, and / or may be interrupted by one or more oxygen or sulfur atoms or silano or dialkylsilicon groups, and / or halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ , C (S) R ²⁵ may be substituted with one or more substituents selected from R ²⁶ , aryl or a hetero group, wherein R ¹⁹ to R ²⁷ are each independently , Hydrogen, an aryl group or a lower alkyl group.

Similarly, the term "lower alkylene" represented by R, A, B and J (if present) in the compound of Formula 1, when used herein, is to be bonded at two positions in a group And C ₁ to C ₁₀ groups which may be defined and otherwise defined in the same manner as in "lower alkyl".

Halo groups in which the above-mentioned groups may be substituted or terminated include fluoro groups, chloro groups, bromo groups and iodo groups.

When the compounds of the formula (eg, formulas 1 to 4) of the invention comprise alkenyl groups, cis (E) and trans (Z) isomerism may also occur. The present invention includes the individual stereoisomers of the compounds of any formula as defined herein, and, if appropriate, the individual tautomeric forms with the mixture. Separation of diastereoisomers or cis and trans isomers is a common technique, e.g., fractional crystallisation, chromatographic methods, for stereoisomeric mixtures of compounds of one of the above formulae or suitable salts or derivatives thereof. Or by performing HPLC. Individual optical enantiomers of compounds of one of the above formulas are also prepared from the corresponding optically pure intermediates, or HPLC of the corresponding racemate using the appropriate chiral support. Or by resolution such as fractional crystallization of diastereomeric salts prepared by reacting the corresponding racemate with a suitable optically active acid or base.

All stereoisomers are included within the scope of the present invention.

Those skilled in the art will understand that compound (b) of formula (1) can act as a ligand that coordinates with Group VIII metal or compound (a) to form a compound that can be used in the present invention. Typically, the Group VIIIB metal or compound (a) is coordinated to one or more phosphorus, arsenic and / or antimony atoms of the compound of formula (I).

Preferably, R ⁴ to R ⁹ , R ¹³ to R ^18, and R ²⁸ each independently represent a lower alkyl group or an aryl group. More preferably, R ⁴ to R ⁹ , R ¹³ to R ¹⁸ and R ²⁸ are each independently C ₁ to C ₆ alkyl, C ₁ -C ₆ alkyl phenyl (where the phenyl group is as defined herein) Optionally substituted) or phenyl, wherein the phenyl group is optionally substituted as defined herein. Even more preferably, R ⁴ to R ⁹ , R ¹³ to R ¹⁸ and R ²⁸ each independently represent a C ₁ to C ₆ alkyl group optionally substituted as defined herein. Most preferably, R ⁴ to R ⁹ , R ¹³ to R ¹⁸ and R ²⁸ are methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, hexyl and Non-substituted C ₁ to C ₆ alkyl groups such as cyclohexyl.

Alternatively, or in addition, each group of R ⁴ to R ⁶ , R ⁷ to R ⁹ , R ¹³ to R ^15, or R ¹⁶ to R ¹⁸ may be independently independently 1-norbornyl or 1-novo. Cyclic structures such as 1 -norbornadienyl. Other examples of complex groups include cyclic structures formed between R ⁴ -R ⁹ and R ¹³ -R ¹⁸ . Alternatively, one or more groups represent the solid phase to which the ligand is linked.

In a particularly preferred embodiment of the invention, R ⁴ , R ⁷ , R ¹³ and R ¹⁶ each represent the same lower alkyl, aryl or hetero group moiety as defined herein and R ⁵ , R ⁸ , R ¹⁴ And R ¹⁷ each represent the same lower alkyl, aryl or hetero group moiety as defined herein, and R ⁶ , R ⁹ , R ¹⁵ and R ¹⁸ are each the same lower alkyl, as defined herein; Aryl or hetero moiety. More preferably, R ⁴ , R ⁷ and R ¹⁶ are each the same C ₁ -C ₆ alkyl group, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl , Non-substituted C ₁ -C ₆ alkyl groups such as hexyl or cyclohexyl; R ⁵ , R ⁸ , R ¹⁴ and R ¹⁷ each independently represent the same C ₁ -C ₆ alkyl group as defined above; And R ⁶ , R ⁹ , R ¹⁵ and R ¹⁸ each independently represent the same C ₁ -C ₆ alkyl as defined above. For example: R ⁴ , R ⁷ , R ¹⁵ and R ¹⁶ each independently represent methyl; R ⁵ , R ⁸ , R ¹⁴ and R ¹⁷ each independently represent ethyl; And R ⁶ , R ⁹ , R ¹⁵ and R ¹⁸ each independently represent n-butyl or n-pentyl.

In a particularly preferred embodiment of the invention, each R ⁴ to R ⁹ , R ¹³ to R ¹⁸ and R ²⁸ group represents the same lower alkyl, aryl or hetero group moiety as defined herein. Preferably, in the case of alkyl groups, each of R ⁴ to R ⁹ , R ¹³ to R ¹⁸ is the same C ₁ to C ₆ alkyl group, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso- Non-substituted C ₁ -C ₆ alkyl groups such as butyl, tert-butyl, pentyl, hexyl or cyclohexyl. Most preferably, each of R ⁴ to R ⁹ , R ¹³ to R ¹⁸ and R ²⁸ represents methyl.

In the compound of formula 1, preferably each Q ¹ , Q ² and Q ³ (if present) are the same. Most preferably, each Q ¹ , Q ² and Q ³ (if present) is phosphorus.

Preferably, in the compound of Formula 1, R (if alkylene), A, B and J (if present) are each independently, as defined herein, for example lower alkyl groups Optionally substituted C ₁ to C ₆ alkylene groups. Preferably, the lower alkylene group represented by R (if alkylene), A, B and J (if present) is non-substituted. Particularly preferred lower alkylene groups which A, B and J can represent independently are -CH ₂ -or -C ₂ H _4- . Most preferably, each of A, B and J (if present) is the same lower alkylene group as defined herein, in particular -CH _2- . Particularly preferred lower alkylene groups represented by R can be selected from ethylene (-C ₂ H _4- ), propylene (-C ₄ H _6- ) and butylene (-C ₄ H _8- ), more preferably ethylene Or propylene, most preferably propylene.

Preferably, in the compound of Formula 1, when K, D, E or Z does not represent -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ), K, D, E or Z represents hydrogen, lower alkyl group, phenyl group or lower alkylphenyl group. More preferably, K, D, E or Z represent hydrogen, phenyl, C _l -C ₆ alkyl represents a phenyl group or a methyl, ethyl, propyl, butyl, pentyl and hexyl as C _l -C ₆ alkyl group. Most preferably, K, D, E or Z represents hydrogen.

Preferably, in the compounds of Formula 1, when K, D, E and Z do not form a phenyl ring with the carbon atoms of the aryl ring linked thereto, K, D, E and Z are each independently hydrogen, lower An alkyl group, a phenyl group, or a lower alkylphenyl group is represented. More preferably, K, D, E and Z are, each independently, hydrogen, phenyl, C _l -C ₆ alkyl group or a methyl, ethyl, propyl, butyl, pentyl and hexyl C _l -C ₆ shows such alkilgieul . Even more preferably, K, D, E and Z are the same substituent. Most preferably they are hydrogen.

Preferably, in the compound of Formula 1, K, D, E or Z does not represent -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ) and K, D When, and E and Z do not form a phenyl ring with the carbon atoms of the aryl ring linked thereto, each of K, D, E and Z is the same hydrogen, lower alkyl group, aryl group, or hetero group as defined herein A group selected from; In particular, it is hydrogen or a C ₁ -C ₆ alkyl group (more particularly an unsubstituted C ₁ -C ₆ alkyl group), in particular hydrogen.

Preferably, in the compound of Formula 1, when two of K, D, E and Z together with the carbon atoms of the aryl ring linked thereto form a phenyl ring, the phenyl ring is an aryl group, a lower alkyl group (the alkyl group itself is Optionally substituted or terminated as defined herein), hetero group, halo group, cyano group, nitro group, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ or C (S) R ²⁵ R ²⁶ optionally substituted with one or more substituents, wherein R ¹⁹ to R ²⁷ each independently represents hydrogen or a lower alkyl group, wherein the alkyl group itself may be optionally substituted or terminated as defined herein.

Preferred compounds of formula (I) include the following cases:

A and B each independently represent an unsubstituted C ₁ to C ₆ alkylene group;

K, D, Z and E are each independently hydrogen, a C ₁ -C ₆ alkyl group, a phenyl group, a C ₁ -C ₆ alkylphenyl group or -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ ( R ¹⁷ ) (R ¹⁸ ), wherein J represents an unsubstituted C ₁ to C ₆ alkylene group; Or two of K, D, Z and E together with the carbon atoms of the aryl ring linked thereto form a phenyl ring optionally substituted with one or more substituents selected from lower alkyl, phenyl or lower alkylphenyl groups.

R ⁴ to R ⁹ and R ¹³ to R ¹⁸ each independently represent a C ₁ to C ₆ alkyl group, a phenyl group or a C ₁ to C ₆ alkylphenyl group.

More preferred Formula 1 includes the following cases:

Both A and B represent —CH ₂ — or C ₂ H ₄ , in particular CH ₂ ;

K, D, Z and E are each independently hydrogen, a C ₁ -C ₆ alkyl phenyl group or a C ₁ -C ₆ alkyl group or -JQ ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ (R ¹⁸ ), where J is the same as A; Or two of K, D, E and Z together with the carbon atoms of the aryl ring linked thereto form an unsubstituted phenyl ring;

R ⁴ to R ⁹ and R ¹³ to R ¹⁸ each independently represent a C ₁ to C ₆ alkyl group;

Even more preferred compounds of formula (I) include the following cases:

R ⁴ to R ⁹ and R ¹³ to R ¹⁸ are alkylene groups and are the same, and each represent a C ₁ to C ₆ alkyl group, especially methyl.

Even more preferred compounds of formula (I) include the following cases:

K, D, Z and E are each independently selected from the group consisting of hydrogen or C ₁ to C ₆ alkyl groups, in particular each K, D, Z and E is the same group, in particular each K, D, Z and E represent hydrogen; or

K represents -CH ₂ -Q ³ (CR ¹³ (R ¹⁴ ) (R ¹⁵ )) CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ), and D, Z and E each independently represent hydrogen or C ₁ to C ₆ alkyl groups, in particular, both D and E are the same group, in particular D, Z and E represent hydrogen.

Particularly preferred particular compounds of formula (I) include the following cases:

Each of R ₄ to R ₉ is the same and represents methyl;

A and B are the same and represent -CH _2- ;

K, D, Z and E are the same and represent hydrogen.

The present invention provides a method of carbonylating a vinyl ester comprising contacting the vinyl ester with carbon monoxide in the presence of an alkanol and a catalytic compound as defined herein.

Preferably, the alkanols comprise organic molecules having hydroxyl functional groups. Preferably, the organic molecules having hydroxyl functional groups may be branched or straight-chain, and include alkanols including arylalkanols, in particular C ₁ -C ₃₀ alkanols, as defined herein Lower alkyl, aryl, hetero, halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O ) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ or C (O) SR ²⁷ may be optionally substituted with one or more substituents. Highly preferred alkanols are C ₁ -C ₈ alkanols such as methanol, ethanol, propanol, iso-propanol, iso-butanol, t-butyl alcohol, n-butanol, phenol and chlorocapryl alcohol. Although monoalkanol is most preferred, poly-alkanols preferably selected from di-octaols such as diols, triols, tetra-ols and sugars can also be used. Typically, such polyalkanols are 1,2-ethanediol, 1,3-propanediol, glycerol, 1,2,4 butanetriol, 2- (hydroxymethyl) -1,3-propanediol, 1, 2,6 trihydroxyhexane, pentaerythritol, 1,1,1tri (hydroxymethyl) ethane, nannose, sorbase, galactose and other sugars. Preferred sugars include sucrose, fructose and glucose. Particularly preferred alkanols are methanol and ethanol. Most preferred alkanols are methanol.

The content of alcohol is not important. Generally, it is used in an amount exceeding the content of the vinyl ester compound to be carbonylated. Thus, the alcohols may also be used as reaction solvents, but separate solvents may also be used if desired.

It will be appreciated that at least some of the final product of the reaction is determined by the source of alkanol used. Methanol is conveniently used to prepare 2-acetoxymethyl propanoate or 3-acetoxymethyl propanoate.

According to the invention, carbon monoxide may be used in a pure state or diluted with an inert gas such as a noble gas such as nitrogen, carbon dioxide or argon. Small amounts, typically less than 5% by volume of hydrogen, may also be present.

The ratio (volume / volume) of vinyl esters to alkanols can vary over a wide range, suitably in the range of 1: 0.1 to 1:10, preferably 2: 1 to 1: 2, alkanols also being If used as a reaction solvent, excess excess alkanol may be used, and may be excess alkanol up to 50: 1.

The catalyst content of the invention used in the carbonylation process of vinyl esters is not critical. Preferably, ⅧB-group metal content in this case in the range of 10 ^-7 to 10 ^-1 mole per mole of the vinyl ester, more preferably per mole of ester ^10-6 to 10 ^- 10 ^-5 to ² moles, most wind straight In the case of from 10 ^{to 2} moles, excellent results can be obtained. Preferably, the content of the by-den lactate compounds of the formula I for the unsaturated compound is a vinyl ester ^10-7 mol to ^10-1 mol, more preferably ^10-6 to ^10-2 mol, and most preferably from 10 ^-5 to 10 ^- in the range of ² molar.

Preferably, although it may not be an important part of the invention, the carbonylation reaction of the vinyl esters as defined herein may be carried out in one or more aprotic solvents. Suitable solvents include, for example, ketones such as methylbutyl ketone; For example anisole (methyl phenyl ether), 2,5,8-trioxanonane (diglyme), diethyl ethir, Ethers such as dimethyl ether, tetrahydrofuran, diphenyl ether, diisopropyl ether and dimethyl ether of di-ethylene-glycol; Esters such as, for example, methyl acetate, dimethyladipate methyl benzoate, dimethyl phthalate and butyrolactam; Amides such as dimethylacetamide, N-methylpyrrolidone and dimethyl formamide; Dimethylsulfoxide, di-isopropylsulfone, sulfolane (tetrahydrothiophene-2,2-dioxide), 2-methylsulforan, diethyl sulfone, tetrahydrothiophene 1,1-dioxide and 2-methyl-4 Sulfoxides and sulfones, such as ethyl sulfolane; Aromatic compounds comprising variants of halo groups such as, for example, benzene, toluene, ethyl benzene o-xylene, m-xylene, p-xylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene: for example hexane Alkanes including modifications of halo groups such as heptane, 2,2,3-trimethylpentane, methylene chloride and carbon tetrachloride; Nitriles such as, for example, benzonitrile and acetonitrile.

Very preferred are aprotic solvents having a dielectric constant in the range of 298.15 K and 1 × 10 ⁵ Nm ^{−2 up} to 50, more preferably in the range from 3 to 8. In this specification, the dielectric constant for a given solvent is used as a general meaning representing the ratio of the capacity of a capacitor having a material as the dielectric to the capacity of the same capacitor having a vacuum as the dielectric. Dielectric constant values of common organic solvents can be found in general references such as Handbook of Chemistry and Physics, 76 edition, edited by David R. Lide et al., 1995, published by CRC press, and generally at about 20 ° C or 25 ° C, That is, about 293.15K or 298.15K and atmospheric pressure, ie about 1 × 10 ⁵ Nm ⁻² , or can be readily converted to the corresponding temperature and pressure using the quoted conversion factors. In the absence of literature data for a particular compound, the dielectric constant can be readily determined using validated physico-chemical methods.

For example, the dielectric constant of anisole is 4.3 (at 294.2 K), diethyl ether is 4.3 (at 293.2 K), sulfolane is 43.4 (at 303.2 K), and methylpentanoate is 5.0 (293.2 K). ), Diphenylether is 3.7 (at 283.2 K), dimethyladipate is 6.8 (at 293.2 K), tetrahydrofuran is 7.5 (at 295.2 K), and methylnonanoate is 3.9 (at 293.2 K). )to be. Preferred solvent is anisole.

Due to the alkanols, an aprotic solvent will be produced by this reaction, since the ester carbonylation reaction products of vinyl esters, carbon monoxide and alkanols are aprotic solvents.

The reaction can be carried out in an excess of aprotic solvent, ie, the ratio (v / v) of aprotic solvent to alkanol of at least 1: 1. Preferably, this ratio is in the range of 1: 1 to 10: 1, more preferably 1: 1 to 5: 1. Most preferably, the ratio (v / v) is in the range of 1.5: 1 to 3: 1.

Notwithstanding the foregoing, the reaction is preferably carried out without an aprotic solvent added from the outside, i.e., an aprotic solvent not generated from the reaction itself.

Catalysts of the compounds of the present invention may act as "heterogeneous" catalysts or "homogeneous" catalysts.

The term “homogeneous” catalyst, together with the reactants of the carbonylation reaction (eg, vinyl esters, hydroxyl containing compounds and carbon monoxide), preferably in a suitable solvent as described herein, By catalyst, it is simply supported or formed in-situ, ie the compound of the invention.

The term "heterogeneous" catalyst means a catalyst carried on a carrier, ie a compound of the invention.

Accordingly, according to another aspect of the present invention, there is provided a process for carbonylating a vinyl ester as defined herein, the process comprising a catalyst comprising a support, preferably an insoluble carrier. Characterized in that it is performed.

Preferably, the carrier is a polystyrene copolymer such as polyolefin, polystyrene or divinylbenzene copolymer or other suitable polymer or copolymer known to those skilled in the art; Silicone derivatives, such as functionalized silica, silicone or silicone rubber; Or other porous particulate matter, for example inorganic oxides and inorganic chlorides.

Preferably, the carrier material is porous silica, which has a surface area in the range of 10 to 700 m ² / g, the total pore volume is in the range of 0.1 to 4.0 cc / g, and the average particle size is in the range of 10 to 500 μm. More preferably, the surface area is 50 to 500 m ² / g, the pore volume is in the range of 0.5 to 2.5 cc / g, and the average particle size is in the range of 20 to 200 μm. Most preferably, the surface area is in the range of 100 to 400 m ² / g, the pore volume is in the range of 0.8 to 3.0 cc / g, and the average particle size is in the range of 30 to 100 μm. The average pore size of conventional porous carrier materials ranges from 10 to 1000 mm 3. Preferably, a carrier material having an average pore diameter of 50 to 500 mm 3, most preferably 75 to 350 mm 3 is used. It may be particularly desirable to dehydrate the silica for a temperature of 100 ° C. to 800 ° C. for 3 to 24 hours.

Preferably, the carrier may be a soft or hard carrier and the insoluble carrier may be coated and / or impregnated with the compounds of the process of the invention by methods known to those skilled in the art.

Alternatively, the compounds of the method of the present invention are immobilized to the surface of the insoluble carrier, optionally via covalent bonds, the arrangement optionally including a bifunctional spacer molecule, with a gap between the insoluble carrier and the compound.

The compounds of the present invention are complementary reactive groups which are present on or in advance of the substituents K, D, Z and E of the functional groups present in the compound of formula 1, for example the aryl moiety It can be fixed to the surface of the insoluble carrier by promoting the reaction with. Combination of reactive groups of the carrier with complementary substituents of the compounds of the invention provides heterogeneous catalysts in which the compounds of the invention and the carrier are linked via linking groups such as ethers, esters, amides, amines, ureas, keto groups.

The choice of reaction conditions for linking the compounds of the process of the invention to the carrier depends on the group of vinyl esters and the carrier. For example, the use of reagents such as carbodiimide, 1,1-carbonyldiimidazole and mixed anhydrides, methods such as reductive amination This can be used.

According to another aspect of the invention, the invention provides the use of the method of any aspect of the invention, wherein the catalyst is attached to a carrier.

Complex groups in which the organic groups R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ or R ¹³ -R ¹⁸ , in conjunction with their respective carbon atoms, have at least sterically hindering such as t-butyl It is especially preferable to form a composite group. Steric hindrance is as discussed herein in C Masters, "Homogenous Transition Metal Catalysis-A Gentle Art," published in 1981 by Chapman and Hall (et seq.). Such steric groups may be cyclic, part-cyclic or acyclic. If cyclic or partially cyclic, the group may be substituted or unsubstituted, or saturated or unsaturated. Cyclic or partially cyclic groups contain tertiary carbons within their cyclic structure, such as C ₄ -C ₃₀ , more preferably C ₆ -C ₂₀ , most preferably C ₁₀ -C ₁₅ It may include a carbon atom of. The cyclic structure is halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ , C (S) NR ²⁵ R ²⁶ , may be substituted with one or more substituents selected from aryl or hetero groups, wherein R ¹⁹ to R ²⁷ are each independently hydrogen , An aryl group or lower alkyl group, and / or may be interrupted by one or more oxygen or sulfur atoms, or by silano or dialkylsilicon groups.

The bridging group Ar is an aryl moiety, for example a phenyl group which may be optionally substituted, provided that two phosphorus atoms are connected to the carbon at the 1 and 2 positions of the adjacent carbon, for example phenyl. The aryl moiety may also be a fused polycyclic group, for example naphthalene, biphenylene or indene.

Examples of suitable bidentate ligands include l, 2-bis (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) ferrocene, 1, 2-bis (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) benzene, 1,2,3-tris- (di- 2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) ferrocene; 1- (2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantyl} phosphinomethyl) -2- (di-t-butylphosphinomethyl) benzene; 1- (2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantyl} phosphinomethyl) -2- (diamantylphosphinomethyl) benzene; 1,2bis (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) naphthalene; 1,2-P, P'-di (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo- {3.3.1.1 [3.7]} decyl) ethane ( DPA2); 1,3-P, P'-di (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]}-decyl) propane ( DPA3); 1,2-P, P'-di-perfluoro (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]}- Decyl) ethane; 1,3-P, P'-di-perfluoro (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]} decyl ) -Propane; 1,2-P, P'-di- (2-phospha-1,3,5,7-tetra (trifluoro-methyl) -6,9,10-trioxatricyclo {3.3.1.1 [3.7 ]} Decyl) ethane and 1,3-P, P'-di- (2-phospha-1,3,5,7-tetra (trifluoro-methyl) -6,9,10-trioxatricyclo {3.3.1.1 [3.7]}} decyl) propane, with DPA3 being most preferred.

In addition, the bidentate phosphine may be bonded to a suitable polymeric support through at least one of the crosslinking group Ar, the linking group A or the linking group B, for example, bis (di-2 {1,3,5,7- Tetramethyl-6,9,10-trioxa-adamantylphosphino})-o-xylene can be bonded to polystyrene via a xylene group to obtain a fixed heteromobile (immobile).

The content of the bidentate ligands used can vary over a wide range. Preferably, the bidentate ligand is present at such an amount that the ratio of the number of moles of the present bidentate ligand to the number of moles of Group VIIIB metal present is 1 to 50, for example 1 to 10 per mole of metal, Especially 1 to 5 mol. More preferably, the molar: molar range of Formula 1: Group VIIIB metal is in the range of 1: 1 to 3: 1, most preferably in the range of 1: 1 to 1.5: 1. For convenience, it is desirable to apply such low molar ratios, which avoids the use of excess compounds of formula 1 and thus minimizes the consumption of these compounds, which are generally expensive. Preferably, the catalyst of the invention is prepared in a separate step prior to the use of in-situ in the carbonylation reaction of the vinyl esters.

Conveniently, the process of the present invention comprises a group VIIIB metal or a compound thereof, as defined herein, as described above with alkanols or aprotic solvents (particularly preferred solvents are esters or acid products of certain carbonylation reactions, for example For example, methyl lactate in vinyl acetate carbonylation).

Carbon monoxide can be used in the presence of other gases that are inert to the reaction. Examples of such gases include rare gases such as hydrogen, nitrogen, carbon dioxide and argon.

The molar ratio of the content of vinyl esters used in the reaction to the content of alkanols is not critical and can vary over a wide range, for example 0.001: 1 to 100: 1 moles / mole.

The reaction product can be separated from the other components by any suitable method. However, it is an advantage of the process of the present invention that significantly less byproducts are formed, thus reducing the need for further purification after the initial separation of the product, which can generally be demonstrated with a fairly high selectivity. Another advantage of the present invention is the other components, including the catalyst system, which can then be recycled and / or reused in the reaction, with minimal supplementation of fresh catalyst.

Preferably, the carbonylation reaction is carried out at a temperature of -10 ° C to 150 ° C, more preferably 0 ° C to 140 ° C, most preferably 20 ° C to 120 ° C. Particularly preferred temperatures are temperatures selected from 80 ° C to 120 ° C. Preferably, the carbonylation reaction is particularly preferred if it can be carried out at moderate temperatures and the reaction can be carried out at room temperature (20 ° C.).

Preferably, when operating the low temperature carbonylation reaction, the carbonylation reaction is -30 ° C to 49 ° C, more preferably -10 ° C to 45 ° C, even more preferably 0 ° C to 45 ° C, most preferably Preferably at 10 ° C to 45 ° C. The range of 10 degreeC-35 degreeC is especially preferable.

Preferably, 0.80 × 10 ⁵ Nm ⁻² to 90 × 10 ⁵ Nm ⁻² , more preferably 1 × 10 ⁵ Nm ⁻² to 65 × 10 ⁵ Nm ⁻² , most preferably 1-30 × 10 ⁵ The carbonylation reaction is carried out at a CO partial pressure of Nm ^-2 . Particular preference is given to a CO partial pressure of 20 × 10 ⁵ Nm ⁻² .

Preferably, low pressure carbonylation reactions are also contemplated. Preferably, the low-pressure carbonate When operating the carbonylation reaction, from 0.1 to ⁵ × 10 5 Nm ^-2, more preferably from 0.2 to 2 × 10 ⁵ Nm ^-2, most preferably from 0.5 to 1.5 × 10 ⁵ Nm ^{- The} carbonylation reaction is carried out at a CO partial pressure of ² .

The catalyst system of the present invention may be formed in a liquid phase, which may preferably be formed by one or more reactants or by the use of a suitable solvent.

As mentioned above, vinyl acetate may be substituted or non-substituted. However, vinyl acetate is preferably unsubstituted.

Using a stabilizing compound in conjunction with the catalyst system is also advantageous for improving the recovery of lost metal from the catalyst system. If a catalyst system is used in the liquid reaction medium, such stabilizing compounds can assist in the recovery of Group VIII metals.

Thus, preferably, the catalyst system comprises a polymeric dispersant dissolved in a liquid carrier in the liquid reaction medium, wherein the polymeric dispersant is a colloidal suspension of Group VIIIB metal or metal compound particles of the catalyst system in the liquid carrier. ) Can be stabilized.

The liquid reaction medium may be a reaction solvent or may include one or more reactants or the reaction product itself. Liquid reactants and reaction products may be miscible with solvents or liquid diluents or may be dissolved in solvents or liquid diluents.

The polymeric dispersant dissolves in the liquid reaction medium but should not seriously increase the viscosity of the reaction medium to the extent that it is detrimental to the reaction kinetics or heat transfer. The solubility of the dispersant in the liquid medium under reaction conditions of temperature and pressure should not be so great as to seriously hinder the adsorption of the dispersant molecules onto the metal particles.

The polymeric dispersant can stabilize the colloidal suspension of the Group VIII metal or metal compound particles in the liquid reaction medium so that the metal particles formed as a result of catalyst degradation are fixed as a suspension in the liquid reaction medium and regenerated ( Reclamation and selective re-use are withdrawn from the reactor together with the liquid for further production of the catalyst. The metal particles are usually colloidal in size, although in some cases larger particles may be formed, but for example have an average particle size in the range of 5-100 nm. Some of the polymeric dispersant is adsorbed onto the surface of the metal particles, while the remainder of these dispersant molecules is at least partially solvated by the liquid reaction medium, and the dispersed Group VIII metal particles are in this way on the walls of the reactor or It is stabilized from solidification by eventually settling into the dead space of the reactor or by forming agglomerates of metal particles that can be enlarged by particle collisions. Some agglomerates of the particles may occur even in the presence of a suitable dispersant, but if the type and concentration of the dispersant is optimal, such agglomerates will be relatively low and the agglomerates will form loosely, so they will be broken up by stirring and redispersed into particles. Can be.

Polymeric dispersants may include copolymers including polymers such as homopolymers or graft copolymers or star polymers.

Preferably, the polymeric dispersant has sufficiently acidic or basic functionality to substantially stabilize the colloidal suspension of the Group VIIIB metal or metal compound.

Substantially stabilizing means that precipitation of Group VIII metals in the solution phase is substantially avoided.

Particularly preferred dispersants for this purpose are acidic or basic polymers comprising carboxylic acids, sulfonic acids, amines and amides, such as polyacrylates, or substituted polys such as heterocycles, in particular nitrogen heterocycles, polyvinyl pyrrolidones. Vinyl polymers or copolymers thereof.

Examples of such polymeric dispersants include polyvinylpyrrolidone, polyacrylamide, polyacrylonitrile, polyethyleneimine, polyglycine, polyacrylic acid, polymethacrylic acid, poly (3-hydroxybutyl acid), poly-L- Leucine, poly-L-methionine, poly-L-proline, poly-L-serine, poly-L-tyrosine, poly (vinylbenzenesulfonic acid) and poly (vinylsulfonic acid).

Preferably, the polymeric dispersant incorporates an acidic or basic moiety into the pendant or polymer back bone. Preferably, the acidic moiety has _a dissociation constant (pK _a ) of 6.0 or less, more preferably 5.0 or less and most preferably 4.5 or less. Preferably, the basic moiety has a base dissociation constant (pK _b ) of 6.0 or less, more preferably 5.0 or less, most preferably 4.5 or less, and pK _b is measured in a 25 ° C. dilute aqueous solution.

Suitable polymeric dispersants not only dissolve in the reaction medium under reaction conditions, but also include one or more of an acidic or basic moiety, either as a polymer backbone or as a pendant group. The inventors have found that polymers incorporating acid and amide moieties such as polyacrylates such as polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) are particularly suitable. The molecular weight of a polymer suitable for use in the present invention depends on the nature of the reaction medium and the solubility of the polymer therein. We have found that the average molecular weight is usually 100,000 or less. Preferably, the molecular weight is in the range of 1,000-200,000, more preferably 5,000-100,000, most preferably 10,000-40,000, for example when using PVP, Mw is preferably 10,000-80,000, More preferably, it is in the range of 20,000-60,000, and in the case of PAA, about 1,000-10,000.

The effective concentration of dispersant in the reaction medium must be determined for each reaction / catalyst system used.

The dispersed Group VIIIB metal may be recovered from the liquid stream removed from the reactor, for example by filtration, and then disposed of or treated for re-use as a catalyst or other use. In a continuous process, the liquid stream may be circulated through an external heat-exchanger, in which case it may be convenient to mount a filter for palladium particles in the circulation apparatus.

Preferably, the mass ratio (g / g) of polymer to metal is 1: 1 to 1000: 1, more preferably 1: 1 and 400: 1, most preferably 1: 1 to 200: 1. Preferably, the mass ratio (g / g) of polymer to metal is 1000 or less, more preferably 400 or less, most preferably 200 or less.

1,2- Vis -(D- (1,3,5,7- Tetramethyl -6,9,10- Trioxa -2- Phospha - Adamantylmethyl )) Ferrocene  Produce

1,3,5,7-tetramethyl-2,4,8-trioxa-6-phospha-adamantane (obtained from Cytec, 14.0 g, 0.066 mol) was added 1,3 g, in acetic anhydride (100 ml) To a solution of 2-bis (dimethylaminomethyl) ferrocene (Example 1, 10 g, 0.033 mol) was added under nitrogen and the resulting mixture was stirred at 80 ° C. for 72 hours. Acetic anhydride was removed in vacuo at approximately 70 ° C. to give the crude title product as an orange / yellow solid. It was washed with hot methanol to give the product as an isomer mixture of orange solids. (12.0 g, 58%).

¹ H NMR (250 MHz; CDC1 ₃ ): δ 4.25-3.95 (8H, br, m); 3.46 (4H, broad singlet); 1.57-2.0 (8H, br, m); 1.43-1.23 (24H, broad multiplet).

31 P NMR (101 MHz; CDC1 ₃ ): δ-27.41 (br),-29.01 (s),-33.9 (br) ppm.

Elemental Analysis: Found: C: 57.80%; H: 7.35% calculated: C: 57.87%; H: 7.40%

1,2-P, P ' -D (2- Phospha -1,3,5,7- Tetramethyl Synthesis of -6,9,10-trioxatricyclo [3.3.1.1 [3.7] decyl) -methylene-benzene

Synthesis Step 1:

2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo [3.3.1.1 {3.7}] decane hydrate (H-PA) in tetrahydrofuran (40 ml) (13 g , 60 mmol) was added a solution of 1 M boron trihydride (73 mmol) in tetrahydrofuran at 0 ° C. over 5 minutes. After stirring for 4 hours at room temperature (20 ° C.), the solvent was removed and the crude product was recrystallized from a minimum volume of hot tetrahydrofuran (20 ml) and washed with hexane (2 × 5 ml) to give colorless crystals. 2-Phospa-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo [3.3.1.1 [3.7] decan borane (H-PA.BH ₃ ) was obtained. The filtrate from hot tetrahydrofuran (7 ml) was recrystallized to give a secondary product. The yield of H-PA.BH ₃ was 86% compared to H-PA.

Synthesis Step 2:

To a solution of H-PA.BH ₃ (3.67 g, 16 mmol) in tetrahydrofuran (40 ml) was added hexyllithium (6.4 ml (2.5 M), 16 mmol) at −75 ° C. After stirring for 1 hour, α, α'-dibromo-o-xylene (2.1 g, 8 mmol) in tetrahydrofuran (20 ml) was added at -75 ° C and the reaction temperature was raised to room temperature. After 3 hours, diethylamine (3 ml, 28 mmol) was added and the reaction was refluxed for 2 hours. After cooling, the solvent was removed and the crude product was dissolved in toluene (60 ml) and washed with water (4 × 40 ml). The solvent was removed to afford 1,2-P, P ¹ -di (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo [3.3.1.1 {as white solid. 3.7}] decyl) -methylene-benzene (3.9 g, 91%) was obtained (see Robert Pugh's paper on NMR characterization, submitted to the University of Bristol in April 2000). The diphosphine could be further purified by recrystallization from methanol.

Vinyl acetate carbonylation reaction

1,2-bis (di-2 {1,3,5- Trimethyl -6,9,10- Trioxa - Adamantylphosphinomethyl }) Ferrocene  ( FePA ) (metal: Ligand Ratio of acid (M: L: A ratio) = 1: 1.25: 2)

Standard conditions are: Pd (OAc) ₂ (134.7 mg, 0.6 mmol Pd) and 1,2-bis (di-2 {1,3,5-trimethyl) in an oxygen free (<10 ppm 0 ₂ ) environment -6,9,10-trioxa-adamantylphosphinomethyl}) ferrocene (492.3 mg, 0.75 mmol) was quantified in a 500 ml round bottom flask. To this, under a nitrogen protective atmosphere, 300 ml of degassed methanol was added and the solution was stirred for one hour. Methane sulfonic acid (77.9 ul, 1.2 mmol) was then added and 50 ml of degassed vinyl acetate (VAM) was added. This solution was placed in an autoclave under vacuum, heated to 60 ° C. with the addition of 10 bar of CO and the solution was allowed to react for 3 hours. The solution was then cooled and the pressure dropped to empty the autoclave. Analytical GC samples were taken.

Count Ligand Straight: Branched Ratio % Conversion to product % Conversion of VAM to product One FePA 5.99 56.63 56.33 2 FePA 5.87 64.75 64.07 3 FePA 5.93 60.38 60.00

1,2-bis (di-2 {1,3,5- Trimethyl -6,9,10- Trioxa - Adamantylphosphinomethyl Benzene (XylyPA) (M: L: A ratio = 1: 1.25: 2)

Standard conditions are: Pd (OAc) ₂ (134.7 mg, 0.6 mmol Pd) and 1,2-bis (di-2 {1,3,5-trimethyl) in an oxygen free (<10 ppm 0 ₂ ) environment -6,9,10-trioxa-adamantylphosphinomethyl}) benzene (411.4 mg, 0.75 mmol) was quantified in a 500 ml round bottom flask. To this, under a nitrogen protective atmosphere, 300 ml of degassed methanol was added and the solution was stirred for one hour. Methane sulfonic acid (77.9 ul, 1.2 mmol) was then added and 50 ml of degassed vinyl acetate (VAM) was added. This solution was placed in an autoclave under vacuum, heated to 60 ° C. with the addition of 10 bar of CO and the solution was allowed to react for 3 hours. The solution was then cooled and the pressure dropped to empty the autoclave. Analytical GC samples were taken.

Count Ligand Straight: Branched Ratio % Conversion to product % Conversion of VAM to product One XylyPA 6.16 62.07 61.83

After distillation of the carbonylation reaction product, 2-acetoxy methyl propionate and 3-acetoxy methyl propionate were collected as other distillates.

Lactate  And preparation of 3-hydroxy esters

3 Of hydroxymethylpropionate  Produce

To 25 g 3 acetoxy methyl propionate (0.171 mol) was added 25 g MeOH (0.78 mol) with 1% w / w methane sulfonic acid. The solution was stirred at 60 ° C. for 6 hours and then cooled to room temperature. As a result of analyzing the sample by GC, the peak corresponding to 3 acetoxy methylpropionate disappeared completely and was replaced by the peak corresponding to 3 hydroxymethylpropionate.

2- Of hydroxymethylpropionate  Produce

To 25 g 2 acetoxy methylpropionate (0.171 mol) was added 25 g MeOH (0.78 mol) with 1% w / w methane sulfonic acid. The solution was stirred at 60 ° C. for 6 hours and then cooled to room temperature. As a result of analyzing the sample by GC, the peak corresponding to 2 acetoxy methylpropionate disappeared completely and was replaced by the peak corresponding to 2 hydroxymethylpropionate.

Preparation of 2 Hydroxy Propionic Acid (Lactic Acid)

To 25 g 2 acetoxy methyl propionate (0.171 mol) was added 25 g MeOH. To this stirred solution was added 20 g of sodium hydroxide (0.5 mol) dissolved in 20 ml of water. The solution was stirred at 50 ° C. for one hour and then cooled to room temperature. The pH of the solution was then adjusted to pH 3.0 by the slow addition of HCl and the sample was stirred for 1 hour. As a result of analyzing the sample by GC, the peak corresponding to 2 acetoxy methyl propionate disappeared completely and was replaced by the peak corresponding to 2 hydroxy propionic acid.

Preparation of 3 hydroxy propionic acid

To 25 g 3 acetoxy methyl propionate (0.171 mol) was added 25 g MeOH. To this stirred solution was added 20 g of sodium hydroxide (0.5 mol) dissolved in 20 ml of water. The solution was stirred at 50 ° C. for one hour and then cooled to room temperature. The pH of the solution was then adjusted to pH 3.0 by the slow addition of HCl and the sample was stirred for 1 hour. As a result of analyzing the sample by GC, the peak corresponding to 3 acetoxy methyl propionate disappeared completely and was replaced by the peak corresponding to 3 hydroxy propionic acid.

All papers and documents submitted concurrently with or prior to this specification as disclosed in connection with this application and published with this application will be carefully reviewed, and the contents of all such papers and documents are incorporated by reference herein. do.

All features disclosed herein (including any of the appended claims, summaries, and drawings) and / or any steps of any method or process disclosed as such are at least some such features and / or steps Except in the case of mutually exclusive combinations, they can be combined in any combination.

Each feature disclosed in this specification (including any of the appended claims, summary and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

The invention is not limited to the details of the foregoing embodiment (s). The present invention is any novel one or any novel combination of the features disclosed herein (including any of the appended claims, summary and drawings), or any novel of the steps of any disclosed method or process. The scope of the invention extends to one or new combinations.

Claims (19)

A process for the alkoxycarbonylation of vinyl esters comprising reacting a vinyl ester with carbon monoxide in the presence of an alkanol and a catalyst system, the catalyst system comprising (c) a Group VIII metal or a compound thereof; And (d) alkoxycarbonylation method of vinyl ester, characterized in that obtained by combining (bidentate ligand) of the general formula (1): <Formula 1>

Where R is a covalent crosslinking group; R ¹ is a 2-Q ² -tricyclo [3.3.1.1 {3,7}] decyl group optionally substituted with Q ² linked thereto, or a derivative thereof (2-PA); R ² and R ³ independently represent a monovalent radical of up to 20 atoms, or are linked to form a divalent radical of up to 20 atoms; Q ¹ and Q ² each independently represent phosphorus, arsenic or antimony. As a process for preparing 3-hydroxy propanoate ester or acid of formula (2), The process involves alkoxycarbonylation of vinyl esters with carbon monoxide in the presence of alkanols and catalyst systems and treatment on the straight (n) product 1-acetoxy CH ₂ CH ₂ C (O) OR ²⁸ obtained therefrom. Performing a step to obtain 3-hydroxy propanoate ester or acid of formula (2), The catalyst system, (a) a Group VIII metal or a compound thereof; And (b) a method of producing the combination of the bidentate ligands of formula (1) according to claim 1; <Formula 2>

Wherein R ²⁸ is selected from H or substituted or unsubstituted and straight or branched C ₁ -C ₃₀ alkyl or aryl moieties. As a method for preparing a lactate ester or acid of formula (3), The process involves the alkoxycarbonylation of vinyl esters with carbon monoxide in the presence of alkanols and catalyst systems to produce products comprising branched (iso) product 2-acetoxy (CH ₃ ) CHC (O) OR ²⁸ And chemically treating the branched (iso) product to obtain a corresponding lactate or acid of formula The catalyst system is: (a) a Group VIII metal or a compound thereof; And (b) a method of obtaining a combination of the bidentate ligands of formula 1 in claim 1 <Formula 3>

Wherein R ²⁸ is selected from H or a substituted or unsubstituted and straight or branched C ₁ -C ₃₀ alkyl or aryl moiety. The method of any one of claims 1 to 3, wherein Q ² is phosphorous. 5. The compound of claim 1, wherein R ² represents CR ⁴ (R ⁵ ) (R ⁶ ), congresyl or adamantyl, or R ³ represents CR ⁷ (R ⁸ ) (R ⁹ ), 2-Q ¹ -tricyclo [3.3.1.1 {3,7} representing congresyl or adamantyl, or optionally substituted with Q ¹ linked to them ² and R ^3; ] The method of forming a decyl group or its derivative (s). The lower adamantyl group according to any one of claims 1 to 5, wherein in addition to a hydrogen atom, a lower alkyl group, OR ¹⁹ , -OC (O) R ²⁰ , a halo group, a nitro group, -C (O) R ²¹ , -C (O) OR ²² , cyano group, aryl group, -NR ²³ R ²⁴ , -C (O) NR ²⁵ R ²⁶ , -CS (R ²⁷ ) R ²⁸ , -CF ₃ , -P (R ⁵⁶ ) Optionally comprises one or more substituents selected from R ⁵⁷ , -PO (R ⁵⁸ ) (R ⁵⁹ ), -P0 ₃ H ₂ , -PO (OR ⁶⁰ ) (OR ⁶¹ ) or -S0 ₃ R ⁶² , wherein R is ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , lower alkyl groups, cyano groups and aryl groups are as defined herein and R ⁵⁶ to R ⁶² Each independently represents a hydrogen, a lower alkyl group, an aryl group or a hetero group. The method according to claim 1 to 5, wherein the 2-Q ² (or Q ¹ ) -tricyclo [3.3.1.1 {3,7}] decyl group (hereinafter referred to as 2-meth-adamantyl group for convenience) Wherein 2-metha-adamantyl is 2-arsa-adamantyl and / or 2-stiba-adamantyl and / or 2-phospha- Wherein adamantyl (referring to 2-phospha-adamantyl) optionally comprises at least one said adamantyl substituent as defined in claim 6 in addition to a hydrogen atom. 8. The method of claim 7, wherein said 2-metha-adamantyl group contains additional heteroatoms in the 2-metha-adamantyl backbone in addition to the 2-Q atom. 9. The 2-metha-adamantyl group of claim 1, wherein the 2-metha-adamantyl group is a 2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxadamantyl group. (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxadamantyl group), 2-phospha-1,3,5-trimethyl-6,9,10-trioxadamantyl group, 2-phospha-1,3,5,7-tetra (trifluoromethyl) -6,9,10-trioxadamantyl group and 2-phospha-1,3,5-tri (trifluoromethyl ), 6,9,10-trioxaadamantyl group.  10. The method of any one of claims 1 to 9, wherein the preferred Group VIIIB metal or compound thereof, which can be combined with the compound of Formula 1, comprises cobalt, nickel, palladium, rhodium and platinum. The process according to claim 1, wherein the ratio of linear: branched product from the alkoxycarbonylation method is at least 1.5: 1. The bidentate ligand according to any one of claims 1 to 11, wherein the bidentate ligand is l, 2-bis (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa- Adamantylphosphinomethyl}) ferrocene, 1,2-bis (di-2 {1,3,5,7-tetramethyl-6,9,1O-trioxa-adamantylphosphinomethyl}) benzene, 1,2,3-tris- (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) ferrocene; 1- (2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantyl} phosphinomethyl) -2- (di-t-butylphosphinomethyl) benzene; 1- (2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantyl} phosphinomethyl) -2- (diamantylphosphinomethyl) benzene; 1,2bis (di-2 {1,3,5,7-tetramethyl-6,9,10-trioxa-adamantylphosphinomethyl}) naphthalene; 1,2-P, P'-di (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo- {3.3.1.1 [3.7]} decyl) ethane ( DPA2); 1,3-P, P'-di (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]}-decyl) propane ( DPA3); 1,2-P, P'-di-perfluoro (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]}- Decyl) ethane; 1,3-P, P'-di-perfluoro (2-phospha-1,3,5,7-tetramethyl-6,9,10-trioxatricyclo {3.3.1.1 [3.7]} decyl ) -Propane; 1,2-P, P'-di- (2-phospha-1,3,5,7-tetra (trifluoro-methyl) -6,9,10-trioxatricyclo {3.3.1.1 [3.7 ]} Decyl) ethane and 1,3-P, P'-di- (2-phospha-1,3,5,7-tetra (trifluoro-methyl) -6,9,10-trioxatricyclo {3.3.1.1 [3.7]}} decyl) propane, or Wherein said bidentate ligand is bound to a suitable polymeric support through one or more of a crosslinking group, such as Ar, linking group A or linking group B. The process according to claim 1, wherein the carbonylation reaction is carried out at a temperature of −10 to 150 ° C. 13. The process according to claim 1, wherein the carbonylation reaction is carried out at a CO partial pressure of 0.80 × 10 ⁵ Nm ⁻² to 90 × 10 ⁵ Nm ⁻² . The method according to any one of claims 1 to 14, wherein the R group represents an alkylene crosslinking group. The compound according to claim 1, wherein the bridging group R is defined as -A- (K, D) Ar (E, Z) -B-, wherein: Ar is a bridging group comprising an optionally substituted aryl moiety linked to Q ¹ and Q ² atoms to an available adjacent carbon atom; A and B, each independently, represent a lower alkylene group; K, D, E and Z are substituents of the aryl moiety (Ar), each independently hydrogen, lower alkyl, aryl, hetero, halo, cyano, nitro, OR ¹⁹ , OC (O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ , C (O) SR ²⁷ or- JQ ³ (X ⁵ ) X ⁶ represents, and J represents a lower alkylene group; Or two adjacent groups selected from K, Z, D and E together with the carbon atoms of the aryl groups to which they are linked form a phenyl ring, which is hydrogen, lower alkyl, halo, cyano, nitro, OR ¹⁹ , OC ( O) R ²⁰ , C (O) R ²¹ , C (O) OR ²² , NR ²³ R ²⁴ , C (O) NR ²⁵ R ²⁶ , C (S) R ²⁵ R ²⁶ , SR ²⁷ or C (O) SR Optionally substituted with one or more substituents selected from ²⁷ , or when Ar is a cyclopentadienyl group, Z may be represented by -M (L ₁ ) _n (L ₂ ) _m , and Z is bonded to a cyclopentadienyl group Linked via a metal ligand; X ⁵ represents CR ¹³ (R ¹⁴ ) (R ¹⁵ ), congresyl or adamantyl, X ⁶ represents CR ¹⁶ (R ¹⁷ ) (R ¹⁸ ), congresyl or adamantyl, or And X ⁵ and X ⁶ together with Q ³ linked thereto form an optionally substituted 2-Q ³ -tricyclo [3.3.1.1 {3,7}] decyl group or derivative thereof. Alkoxycarbonylation of vinyl esters as described in connection with the above embodiments herein. Process for preparing 3-hydroxy propanoate ester or acid of formula (2) as described in connection with the examples herein: <Formula 2>

Wherein R ²⁸ is selected from H or substituted or unsubstituted and straight or branched C ₁ -C ₃₀ alkyl or aryl moieties. A process for preparing a lactate ester or acid of formula (3) as described in connection with the examples herein: <Formula 3>

Wherein R ²⁸ is selected from H or a substituted or unsubstituted and straight or branched C ₁ -C ₃₀ alkyl or aryl moiety.