Process for the alkoxycarbonylation of alcohols

Abstract

The invention relates to a process comprising the following process steps: a) introducing a first alcohol, the first alcohol having 2 to 30 carbon atoms; b) adding a phosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and a phosphine ligand; c) adding a second alcohol; d) supplying CO; e) heating the reaction mixture, the first alcohol reacting with CO and the second alcohol to form an ester;
where the phosphine ligand is a compound of formula (I) ##STR00001##
where m and n are each independently 0 or 1; R.sup.1, R.sup.2, R.sup.3, R.sup.4 are each independently selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl, —(C.sub.6-C.sub.20)-aryl, —(C.sub.3-C.sub.20)-heteroaryl; at least one of the R.sup.1, R.sup.2, R.sup.3, R.sup.4 radicals is a —(C.sub.3-C.sub.20)-heteroaryl radical; and R.sup.1, R.sup.2, R.sup.3, R.sup.4, if they are —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl, —(C.sub.6-C.sub.20)-aryl or —(C.sub.3-C.sub.20)-heteroaryl, may each independently be substituted by one or more substituents selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl-(C.sub.6-C.sub.20)-aryl, —O—(C.sub.3-C.sub.12)-cycloalkyl, —S—(C.sub.1-C.sub.12)-alkyl, —S—(C.sub.3-C.sub.12)-cycloalkyl, —COO—(C.sub.1-C.sub.12)-alkyl, —COO—(C.sub.3-C.sub.12)-cycloalkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.3-C.sub.12)-cycloalkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.3-C.sub.12)-cycloalkyl, —N—[(C.sub.1-C.sub.12)-alkyl].sub.2, —(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl-(C.sub.1-C.sub.12)-alkyl, —(C.sub.6-C.sub.20)-aryl-O—(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.20)-heteroaryl, —(C.sub.3-C.sub.20)-heteroaryl-(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.20)-heteroaryl-O—(C.sub.1-C.sub.12)-alkyl, —COOH, —OH, —SO.sub.3H, —NH.sub.2, halogen.

Claims

1. A process for forming an ester mixture product having n- and iso-ester components from a corresponding first alcohol substrate and CO and a second alcohol comprising the following process steps: a) introducing the first alcohol selected from a secondary or tertiary alcohol, having 2 to 30 carbon atoms, to form a reaction mixture; b) adding a phosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and the phosphine ligand; c) adding the second alcohol; d) supplying CO; e) heating the reaction mixture, the first alcohol reacting with CO and then the second alcohol to form the ester mixture with the iso- and n-products; where the phosphine ligand is a compound of formula (I) ##STR00012## where m and n are each independently 0 or 1; R.sup.1, R.sup.2, R.sup.3, R.sup.4 are each independently selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl, —(C.sub.6-C.sub.20)-aryl or —(C.sub.3-C.sub.20)-heteroaryl, where each is substituted or unsubstituted; and at least one of the R.sup.1, R.sup.2, R.sup.3, R.sup.4 radicals is a —(C.sub.3-C.sub.20)-heteroaryl radical; wherein the substituents are selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl-(C.sub.6-C.sub.20)-aryl, —O—(C.sub.3-C.sub.12)-cycloalkyl, —S—(C.sub.1-C.sub.12)-alkyl, —S—(C.sub.3-C.sub.12)-cycloalkyl, —COO—(C.sub.1-C.sub.12)-alkyl, —COO—(C.sub.3-C.sub.12)-cycloalkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.3-C.sub.12)-cycloalkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.3-C.sub.12)-cycloalkyl, —N—[(C.sub.1-C.sub.12)-alkyl].sub.2, —(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl-(C.sub.1-C.sub.12)-alkyl, —(C.sub.6-C.sub.20)-aryl-O—(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.20)-heteroaryl, —(C.sub.3-C.sub.20)-heteroaryl-(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.20)-heteroaryl-O—(C.sub.1-C.sub.12)-alkyl, —COOH, —OH, —SO.sub.3H, —NH.sub.2 or halogen.

2. The process according to claim 1, where the phosphine ligand is a compound of one of the formulae (II) and (III) ##STR00013##

3. The process according to claim 1, where at least two of the R.sup.1, R.sup.2, R.sup.3, R.sup.4 radicals are a —(C.sub.3-C.sub.20)-heteroaryl radical.

4. The process according to claim 1, where the R.sup.1 and R.sup.3 radicals are each a —(C.sub.3-C.sub.20)-heteroaryl radical.

5. The process according to claim 1, where the R.sup.1 and R.sup.3 radicals are each a —(C.sub.3-C.sub.20)-heteroaryl radical; and R.sup.2 and R.sup.4 are each independently selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl, —(C.sub.3-C.sub.12)-heterocycloalkyl or —(C.sub.6-C.sub.20)-aryl.

6. The process according to claim 1, where the R.sup.1 and R.sup.3 radicals are each a —(C.sub.3-C.sub.20)-heteroaryl radical; and R.sup.2 and R.sup.4 are each independently selected from —(C.sub.1-C.sub.12)-alkyl.

7. The process according to claim 1, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, if they are a heteroaryl radical, are each independently selected from furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, benzofuranyl, indolyl, isoindolyl, benzimidazolyl, quinolyl or isoquinolyl.

8. The process according to claim 1, wherein the first alcohol in process step a) is a compound of formula (IV) ##STR00014## where R.sup.5 is selected from —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl or —(C.sub.6-C.sub.20)-aryl; and R.sup.6 and R.sup.7 are each independently selected from —H, —(C.sub.1-C.sub.12)-alkyl, —(C.sub.3-C.sub.12)-cycloalkyl or —(C.sub.6-C.sub.20)-aryl and wherein not more than one of the radicals R.sup.6 and R.sup.7.

9. The process according to claim 8, wherein R.sup.5 is —(C.sub.1-C.sub.12)-alkyl.

10. The process according to claim 8, where R.sup.6 and R.sup.7 are each independently selected from —H, —(C.sub.1-C.sub.12)-alkyl or —(C.sub.6-C.sub.20)-aryl.

11. The process according to claim 1, wherein the compound comprising Pd in process step b) is selected from palladium dichloride, palladium(II) acetylacetonate, palladium(II) acetate, dichloro(1,5-cyclooctadiene)palla dium(II), bis(dibenzylideneacetone)palladium, bis(acetonitrile)dichloropalladium(II) or palladium(cinnamyl) dichloride.

12. The process according to claim 1, wherein the second alcohol in process step c) is selected from the group consisting of methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 2-propanol, tert-butanol, 3-pentanol, cyclohexanol, and mixtures thereof.

13. The process according to claim 1, wherein the second alcohol in process step c) is a primary alcohol.

14. A process for forming an ester mixture product having n- and iso-ester components from a corresponding first alcohol substrate and CO and a second alcohol comprising the following process steps: a) introducing the first alcohol selected from a secondary or tertiary alcohol, having 2 to 30 carbon atoms, to form a reaction mixture; b) adding a phosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and the phosphine ligand; c) adding the second alcohol; d) supplying CO; e) heating the reaction mixture, the first alcohol reacting with CO and then the second alcohol to form the ester mixture with the iso- and n-products; where the phosphine ligand is a compound of formula (1) ##STR00015##

15. A process for forming an ester mixture product having n- and iso-ester components from a corresponding first alcohol substrate and CO and a second alcohol comprising the following process steps: a) introducing the first alcohol selected from a secondary or tertiary alcohol, having 2 to 30 carbon atoms, to form a reaction mixture; b) adding a phosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and the phosphine ligand; c) adding the second alcohol; d) supplying CO; e) heating the reaction mixture, the first alcohol reacting with CO and then the second alcohol to form the ester mixture with the iso- and n-products; where the phosphine ligand is (α, α′-bis(2-pyridyl)(t-butyl)phosphino)o-xylene and the first alcohol is 3,3-dimethylbutan-2-ol.

Description

EXAMPLES

(1) The examples which follow illustrate the invention.

(2) General Procedures

(3) All the preparations which follow were carried out under protective gas using standard Schlenk techniques. The solvents were dried over suitable desiccants before use (Purification of Laboratory Chemicals, W. L. F. Armarego (Author), Christina Chai (Author). Butterworth Heinemann (Elsevier), 6th edition, Oxford 2009).

(4) Phosphorus trichloride (Aldrich) was distilled under argon before use. All preparative operations were effected in baked-out vessels. The products were characterized by means of NMR spectroscopy. Chemical shifts (δ) are reported in ppm. The .sup.31P NMR signals were referenced as follows: SR.sub.31p═SR.sub.1H*(BF.sub.31p/BF.sub.1H) ═SR.sub.1H*0.4048. (Robin K. Harris, Edwin D. Becker, Sonia M. Cabral de Menezes, Robin Goodfellow, and Pierre Granger, Pure Appl. Chem., 2001, 73, 1795-1818; Robin K. Harris, Edwin D. Becker, Sonia M. Cabral de Menezes, Pierre Granger, Roy E. Hoffman and Kurt W. Zilm, Pure Appl. Chem., 2008, 80, 59-84).

(5) The recording of nuclear resonance spectra was effected on Bruker Avance 300 or Bruker Avance 400, gas chromatography analysis on Agilent GC 7890A, elemental analysis on Leco TruSpec CHNS and Varian ICP-OES 715, and ESI-TOF mass spectrometry on Thermo Electron Finnigan MAT 95-XP and Agilent 6890 N/5973 instruments.

Preparation of chloro-2-pyridyl-tert-butylphosphine (Precursor A)

(6) The Grignard for the synthesis of chloro-2-pyridyl-t-butylphosphine is prepared by the “Knochel method” with isopropylmagnesiurn chloride (Angew. Chem. 2004, 43, 2222-2226). The workup is effected according to the method of Budzelaar (Organometallics 1990, 9, 1222-1227).

(7) ##STR00007##

(8) 8.07 ml of a 1.3 M isopropylmagnesium chloride solution (Knochel's reagent) are introduced into a 50 ml round-bottom flask with magnetic stirrer and septum, and cooled to −15° C.

(9) Thereafter, 953.5 μl (10 mmol) of 2-bromopyridine are rapidly added dropwise. The solution immediately turns yellow. It is allowed to warm up to −10° C. The conversion of the reaction is determined as follows: about 100 μl solution are taken and introduced into 1 ml of a saturated ammonium chloride solution. If the solution “bubbles”, not much Grignard has formed yet. The aqueous solution is extracted with a pipette of ether and the organic phase is dried over Na.sub.2SO.sub.4. A GC of the ethereal solution is recorded. When a large amount of pyridine has formed compared to 2-bromopyridine, conversions are high. At −10° C., there has been little conversion. After warming up to room temperature and stirring for 1-2 hours, the reaction solution turns brown-yellow. A GC test shows complete conversion, Now the Grignard solution can be slowly added dropwise with a syringe pump to a solution of 1.748 g (11 mmol) of dichloro.tert-butylphosphine in 10 ml of THF which has been cooled to −15° C. beforehand. It is important that the dichloro-tert-butylphosphine solution is cooled. At room temperature, considerable amounts of dipyridyl-tert-butylphosphine would be obtained. A clear yellow solution is initially formed, which then turns cloudy. The mixture is left to warm up to room temperature and to stir overnight, According to GC-MS, a large amount of product has formed. The solvent is removed under high vacuum and a whitish solid which is brown in places is obtained. The solid is suspended with 20 ml of heptane and the solid is comminuted in an ultrasound bath. After allowing the white solid to settle out, the solution is decanted. The operation is repeated twice with 10-20 ml each time of heptane, After concentration of the heptane solution under high vacuum, it is distilled under reduced pressure. At 4.6 mbar, oil bath 120° C. and distillation temperature 98° C., the product can be distilled. 1.08 g of a colourless oil are obtained. (50%).

(10) Analytical data: .sup.1H NMR (300 MHz, C.sub.6D.sub.6): δ 8.36 (m, 1H, Py), 7.67 (m, 1H, Py), 7.03-6.93(m, 1H, Py), 6.55-6.46 (m, 1H, Py), 1.07 (d, J=13.3 Hz, 9H, t-Bu).

(11) .sup.13C NMR (75 MHz, C.sub.6D.sub.6): δ 162.9, 162.6, 148.8, 135.5, 125.8, 125.7, 122.8, 35.3, 34.8, 25.9 and 25.8.

(12) .sup.31P NMR (121 MHz, C.sub.6D.sub.6) δ 97.9.

(13) MS (EI) m:z (relative intensity) 201 (M.sup.+, 2), 147(32), 145 (100), 109 (17), 78 (8), 57.1 (17).

Preparation of Ligand 1 (α,α′-bis(2-pyridyl(t-butyl)phosphino)o-xylene)

(14) ##STR00008##

(15) 675 mg (27.8 mmol, 4 eq) of Mg powder are weighed out in a glovebox in a 250 ml round-bottom flask with a nitrogen tap and magnetic stirrer bar, and the flask is sealed with a septum. High vacuum is applied to the round-bottom flask (about 5×10.sup.−2 mbar) and it is heated to 90° C. for 45 minutes. After cooling down to room temperature, 2 grains of iodine are added and the mixture is dissolved in 20 ml of THF. The suspension is stirred for about 10 minutes until the yellow colour of the iodine has disappeared. After the magnesium powder has settled out, the cloudy THF solution is decanted and the activated magnesium powder is washed twice with 1-2 ml of THF. Then another 20 ml of fresh THE are added. At room temperature, a solution of 1.21 g (6.9 mmol) of α,α′-dichloro-o-xylene in 70 ml of THF is slowly added dropwise with a syringe pump. The THF solution gradually turns a darker colour. The next day, the THF suspension is filtered to remove the unconverted magnesium powder and the content of Grignard compound is determined as follows:

(16) 1 ml of Grignard solution is quenched in a saturated aqueous solution of NH.sub.4Cl and extracted with ether. After drying over Na.sub.2SO.sub.4, a GC of the ether solution is recorded. In qualitative terms, it is observed that exclusively o-xylene has formed.

(17) Quantitative determination of the content of the Grignard solution:

(18) 1 ml of Grignard solution is quenched with 2 ml of 0.1 M HCl and the excess acid is titrated with 0.1 M NaOH. A suitable indicator is an aqueous 0,04% brornocresol solution. The colour change goes from yellow to blue. 0.74 ml of 0.1 M NaOH has been consumed. 2 ml−0.74 ml=1.26 ml, corresponding to 0.126 mmol of Grignard compound, Since a di-Grignard is present, the Grignard solution is 0.063 M. This is a yield exceeding 90%.

(19) In a 250 ml three-neck flask with reflux condenser and magnetic stirrer, under argon, 1.8 g (8.66 mmol) of chlorophosphine (2-Py(tBu)PCI) are dissolved in 10 ml of THF and cooled to −60° C. Then 55 ml of the above-stipulated Grignard solution (0.063 M, 3.46 mmol) are slowly added dropwise at this temperature with a syringe pump. The solution at first remains clear and then turns intense yellow. After 1.5 hours, the solution turns cloudy. The mixture is left to warm up to room temperature overnight and a clear yellow solution is obtained. To complete the reaction, the mixture is heated under reflux for 1 hour. After cooling, 1 ml of H.sub.2O is added and the solution loses colour and turns milky white. After removing THF under high vacuum, a stringy, pale yellow solid is obtained. 10 ml of water and 10 ml of ether are added thereto, and two homogeneous clear phases are obtained, which have good separability. The aqueous phase is extracted twice with ether. After the organic phase has been dried with Na.sub.2SO.sub.4, the ether is removed under high vacuum and a stringy, almost colourless solid is obtained. The latter is dissolved in 5 ml of MeOH while heating on a water bath and filtered through Celite. At −28° C., 772 mg of product are obtained in the form of white crystals overnight. (51%), After concentration, it was possible to isolate another 100 mg from the mother solution. The overall yield is 57.6%.

(20) .sup.1H NMR (300 MHz, C.sub.6D.sub.6): δ 8.58 (m, 2H, Py), 7.31-7.30 (m, 2H, benzene), 7.30-7.22 (m, 2H, Py), 6.85-6.77 (m, 2H, Py), 6.73 (m, 2H, benzene), 6.57-6.50 (m, 2H, py), 4.33 (dd, J=13.3 and 4.3 Hz, 2H, CH.sub.2), 3.72-3.62 (m, 2H, CH.sub.2), 121(d, J=11.8 Hz, 18H, tBu),

(21) .sup.13C NMR (75 MHz, C.sub.6D.sub.6): δ 161.3, 161.1, 149.6, 137.8, 137.7, 134.5, 133.3, 132.7, 131.4, 131.3, 125.7, 122.9, 30.7, 30.5, 28.2, 28.0, 26.5, 26.4, 26.2, and 26.1.

(22) .sup.31P NMR (121 MHz, C.sub.6D.sub.6) δ 8.8, EA calculated for C.sub.26H.sub.34N.sub.2P.sub.2; C, 71,54: H, 7.85; N, 6.56; P,14.35, found: C, 71.21; H, 7.55; N, 6.56; P, 14.35.

(23) Comparative Ligand

(24) The comparative ligand used in the following examples is 1,2-bis(di-tert-butylphosphino-methyl)benzene (DTBMB, ligand 3).

(25) ##STR00009##

Methoxycarbonylation of tert-butanol

(26) ##STR00010##

1) Without Ligand (Comparative Example)

(27) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), PTSA (28.5 mg, 7.5 mol %) and a magnetic stirrer. Then, under argon, MeOH (2 ml) and tert-butanol (0.2 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours. After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (0% yield of methyl 3-methylbutanoate).

2) Ligand 3 (Comparative Example)

(28) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 3 (15.8 mg, 2 mol %), PTSA (28.5 mg, 7.5 mol %) and a magnetic stirrer. Then, under argon, MeOH (2 ml) and tert-butanol (0.2 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours, After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (0% yield of methyl 3-methylbutanoate).

3) Ligand 1

(29) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 1 (17.5 mg. 2 mol %), PTSA (28.5 mg. 7.5 mol %) and a magnetic stirrer. Then, under argon, MeOH (2 ml) and tert-butanol (0.2 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours, After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (99% yield of methyl 3-methylbutanoate).

(30) The results are summarized in the following table:

(31) TABLE-US-00001 Example Ligand Yield of methyl 3-methylbutanoate (%) 1 (CE) none 0 2* 3 0 3 (CE) 1 99 CE: comparative example *inventive example

Methoxycarbonylation of 1-phenylethanol

(32) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), PTSA (28.5 mg, 7 mol %), ligand 1 (8.7 mg, 1 mol %) and a magnetic stirrer. Then, under argon, MeOH (2 ml) and 2 mmol of 1-phenylethanol are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours. After cooling down to room temperature, the autoclave is cautiously decompressed. The product obtained was a mixture of methyl 3-phenylpropanoate (n product) and methyl 2-phenylpropanoate (iso product). The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (40% overall yield, n/iso ratio 70/30).

Methoxycarbonylation of 3,3-dimethylbutan-2-ol

(33) ##STR00011##

Example 1

Ligand 3

(34) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 3 (15.8 mg, 2 mol %), CF.sub.3SO.sub.2OH (48.0 mg, 16 mol %) and a magnetic stirrer. Then, under argon, toluene (2 ml) and 3,3-dimethylbutan-2-ol (0.25 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three limes with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours, After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (0% yield).

Example 2

Ligand 3 with 4 Å Molecular Sieve

(35) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 3 (15.8 mg, 2 mol %), CF.sub.3SO.sub.2OH (48.0 mg, 16 mol %), 4 Å zeolite molecular sieve (4 Å MS, 20 mg) and a magnetic stirrer. Then, under argon, toluene (2 ml) and 3,3-dimethylbutan-2-ol (0.25 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours. After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (0% yield).

Example 3

Ligand 1

(36) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 1 (17.5 mg, 2 mol %), CF.sub.3SO.sub.2OH (48.0 mg, 16 mol %) and a magnetic stirrer. Then, under argon, toluene (2 ml) and 3,3-dimethylbutan-2-ol (0.25 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours. After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (10% yield).

Example 4

Ligand 1 with 4 Å Molecular Sieve

(37) A 4 ml glass reaction vessel (vial) is charged under argon with Pd(acac).sub.2 (3.1 mg, 0.5 mol %), 1 (17.5 mg, 2 mol %), CF.sub.3SO.sub.2OH (48.0 mg, 16 mol %), 4 Å MS (20 mg) and a magnetic stirrer. Then, under argon, toluene (2 ml) and 3,3-dimethylbutan-2-ol (0.25 ml, 2 mmol) are added. This vial is placed in a metal plate fabricated for this purpose, and the plate with vial is transferred to a 300 ml autoclave from Parr Instruments. The autoclave is purged three times with CO and then charged with 50 bar of CO at room temperature. The reaction is carried out with magnetic stirring at 120° C. for 20 hours. After cooling down to room temperature, the autoclave is cautiously decompressed. The yield was carried out by means of GC analysis with isooctane (200 μl) as internal standard (20% yield).

(38) The results are summarized in the following table:

(39) TABLE-US-00002 Example Ligand Additive Yield n/iso ratio 1 (CE) 3 0% — 2 (CE) 3 4 Å MS 0% — 3* 1 10% 75/25 4* 1 4 Å MS 20% 74/26 CE: comparative examples *inventive examples

(40) The above experiments show that by means of the process of the invention, using the ligands according to the invention, a series of structurally different alcohols can be reacted as substrate in an alkoxycarbonylation reaction with CO and a further alcohol to form esters, Conversely, the ligand known from the prior art is not suitable for the reaction of alcohols in an alkoxycarbonylation reaction.