Process for the alkoxycarbonylation of olefinically unsaturated compounds using benzene-based diphosphine ligands and aluminium triflate

Abstract

Disclosed is a method for the alkoxycarbonylation of olefinically unsaturated compounds using a benzene-based diphosphine ligand and aluminum triflate.

Description

Technical Field

[0001] This invention relates to a method for alkoxycarbonylation of olefinic unsaturated compounds using benzene-based diphosphine ligands and aluminum trifluoromethanesulfonate. Background Technology

[0002] Alkoxycarbonylation of olefins is an increasingly important method. Alkoxycarbonylation should be understood as the reaction of an olefin (alkene) with carbon monoxide and an alcohol in the presence of a metal-ligand complex to yield the corresponding ester. Palladium is commonly used as the metal. The following scheme shows the general reaction equation for alkoxycarbonylation:

[0003]

[0004] EP 3 121 184 A2 describes a method for the alkoxycarbonylation of alkenes using benzene-based diphosphine compounds. In each case, a Brønsted acid is added to the reaction: p-toluenesulfonic acid (PTSA), trifluoromethanesulfonic acid, or sulfuric acid.

[0005] However, sulfuric acid causes severe corrosion on metal surfaces. Another drawback of using sulfuric acid is that it must be pretreated / degassed in a complex and expensive manner.

[0006] Catalytic systems are typically sensitive to oxygen. Even contact with trace amounts of oxygen can lead to the oxidation of the ligands, ultimately resulting in a decrease in the activity of the entire catalyst complex. Trace amounts of oxygen can be introduced through entrainment, for example, via the sequential introduction of components. Summary of the Invention

[0007] The technical problem to be solved by this invention is to provide a new method that does not have the disadvantages associated with Brønsted acids known in the prior art. Furthermore, the method should provide good yields.

[0008] The aforementioned technical problem is solved by the method according to the present invention.

[0009] This method includes the following steps:

[0010] a) Initial feeding of an olefinic unsaturated compound;

[0011] b) Additive (I) ligands and compounds containing Pd:

[0012] (I)

[0013] in

[0014] R 1 and R 3Each is -(C3-C 20 )-Heteroaryl group,

[0015] R 2 and R 4 Each is -(C1-C 12 )-alkyl;

[0016] c) Pretreatment of aluminum trifluoromethanesulfonate by applying a vacuum;

[0017] d) Adding pretreated aluminum trifluoromethanesulfonate obtained from c), wherein the ratio of aluminum trifluoromethanesulfonate to ligand is in the range of 2 mol : 1 mol to 25 mol : 1 mol;

[0018] e) Add alcohol;

[0019] f) Input CO;

[0020] g) Heating the reaction mixture obtained from a) to f), wherein the olefinic unsaturated compound is converted into an ester.

[0021] The substances can be added in any order. However, CO is typically added after the co-reactants have been initially added in steps a) through e). Alternatively, CO can be introduced in two or more steps, such that, for example, a portion of the CO is introduced first, the mixture is then heated, and then another portion of CO is introduced.

[0022] The term “vacuum” in connection with this invention should be understood to mean a pressure of 100 millibars or lower.

[0023] The aluminum trifluoromethanesulfonate can be pretreated, for example, in a storage container.

[0024] The application of vacuum can be repeated multiple times.

[0025] In a variation of the method, step c) is performed at least twice, and the applied vacuum is interrupted by purging with an inert gas. The inert gas used may be, for example, N2, He, or Ar.

[0026] The expression "(C1-C 12 "(C1-C8)-alkyl" includes straight-chain and branched alkyl groups having 1 to 12 carbon atoms. These are preferably (C1-C8)-alkyl groups, more preferably (C1-C6)-alkyl, and most preferably (C1-C4)-alkyl.

[0027] The expression "(C3-C 20 "(C3-C-heteroaryl)" comprises a monocyclic or polycyclic aromatic hydrocarbon group having 3 to 20 carbon atoms, wherein one or more of the carbon atoms are replaced by heteroatoms. Preferred heteroatoms are N, O, and S.20 The )-heteroaryl group has 3 to 20, preferably 6 to 14, and more preferably 6 to 10 ring atoms. Thus, for example, within the scope of the invention, pyridyl is a C6-heteroaryl group; furanyl is a C5-heteroaryl group.

[0028] The olefinic unsaturated compounds used as reactants in the method according to the invention contain one or more carbon-carbon double bonds. These compounds are also known as alkenes. The double bonds can be terminal or internal.

[0029] In a variation of the method, the olefinic unsaturated compound does not contain any functional groups other than carbon-carbon double bonds.

[0030] When the catalyst is formed in situ, the ligand can be added in excess, so that unbonded ligands are still present in the reaction mixture.

[0031] In a variation of the method, R 1 R 3 Each is selected from furanyl, thiophene, pyrrole, azole group, iso Azolyl, thiazolyl, isothiazolyl, imidazole, pyrazolyl, furazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, benzofuranyl, indolyl, isoindolyl, benzimidazolyl, quinolinyl, isoquinolinyl.

[0032] In a variation of the method, R 2 and R 4 It is tert-butyl ( ter Bu).

[0033] In a variation of the method, the ligand in step b) of the method has the formula (1):

[0034] (1)

[0035] In a variation of the method, the method includes an additional method step c').

[0036] c') The pretreated aluminum trifluoromethanesulfonate obtained from c) is dissolved in a solvent.

[0037] The preparation of the solution from the pretreated aluminum trifluoromethanesulfonate allows for continuous metering of aluminum trifluoromethanesulfonate into the method without introducing a significant amount of oxygen by entrainment.

[0038] In a variation of the method, the solvent in step c') is an alcohol.

[0039] In a variation of the method, the solvent used in step c') is the same alcohol as in step e).

[0040] In a variation of the method, the Pd-containing compound in step b) is selected from palladium dichloride, palladium(II) acetylacetone, palladium(II) acetate, palladium(II) dichloro(1,5-cyclooctadiene)palladium(II), bis(dibenzylpyridinylacetone)palladium, bis(acetonitrile)palladium(II) dichloro(II), and (cinnamyl)palladium dichloride.

[0041] Preferably, the Pd-containing compound is Pd(dba)2, Pd(acac)2, or Pd(OAc)2. Pd(acac)2 is particularly suitable.

[0042] The mass ratio of Pd to the olefinic unsaturated compound initially added in step a) is preferably from 0.001% to 0.5% by weight, more preferably from 0.01% to 0.1% by weight, and particularly preferably from 0.01% to 0.05% by weight.

[0043] The molar ratio of the ligand to Pd is preferably from 0.1:1 to 400:1, more preferably from 0.5:1 to 400:1, more preferably from 1:1 to 100:1, and most preferably from 2:1 to 50:1.

[0044] In a variation of the method, the alcohol in step e) is selected from methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 2-propanol, tert-butanol, 3-pentanol, cyclohexanol, phenol, or mixtures thereof.

[0045] In a variation of the method, the alcohol in step e) is methanol.

[0046] In a variation of the method, the alcohol used in step e) is in excess.

[0047] In a variation of the method, the alcohol in step e) is also used as a solvent.

[0048] The molar ratio of the olefinic unsaturated compound initially added in step a) to the alcohol added in step e) is preferably in the range of 1:1 to 1:20, more preferably 1:2 to 1:10, and even more preferably 1:3 to 1:6.

[0049] In a variation of the method, in step d), the ratio of aluminum trifluoromethanesulfonate to ligand is in the range of 2.5 mol: 1 mol to 15 mol: 1 mol.

[0050] In step f), CO is preferably introduced when the partial pressure of CO is in the range of 0.1 to 10 MPa (1 to 100 bar), more preferably in the range of 1 to 5 MPa (10 to 50 bar), and even more preferably in the range of 1 to 2 MPa (10 to 20 bar).

[0051] In step g) of the method according to the invention, the reaction mixture is preferably heated to a temperature in the range of 30°C to 150°C, more preferably 40°C to 140°C, and more preferably 50°C to 120°C, thereby converting the olefinic unsaturated compound into an ester. Detailed Implementation

[0052] The present invention will be described in detail below with reference to the embodiments.

[0053] General Operating Procedures

[0054] Unless otherwise specified, operate under an argon atmosphere. The reaction vessel has been pre-dried at 80°C under vacuum from an oil pump.

[0055] Liquid substances (such as sulfuric acid (H2SO4)) are degassed by purging argon gas for at least 15 minutes.

[0056] The pretreatment of aluminum trifluoromethanesulfonate (Al(OTf)3) and other solid acids used is as follows: In the case of solid acids, they are first weighed and the container is hermetically sealed using a septum mounted on a flange. The acid is then pre-prepared in an oxygen-free manner by alternatingly applying a vacuum (50 mbar) and purging with argon three times using a through-tube connected to an argon / vacuum distribution station (Schlenk technique). Furthermore, an argon atmosphere is maintained in subsequent steps, with the possibility of pressure equilibration (addition of solution).

[0057] The ligand (1) used was 1,2-bis((tert-butyl(pyridin-2-yl)phosphanyl)methyl)benzene. The precursor used was bis(acetylacetone)palladium(II) (Pd(acac)2). Diisobutylene was a mixture of two C8 isomers, “2,4,4-trimethylpent-1-ene” and “2,4,4-trimethylpent-2-ene”, in a ratio of approximately 80:20. Isooctane was added to 0.5 mL of these samples as an internal standard, and the conversion and yield were determined by GC and GCMS analysis.

[0058] analyze

[0059] GC analysis of diisobutylene and 1-octene: For the GC analysis, an Agilent 7890A GC chromatograph with a 30 m HP5 column was used. Temperature distribution: 35 °C for 10 min; 10 °C / min to 200 °C; injection volume 1 µL with a split ratio of 50:1.

[0060] experiment

[0061] Modify Lewis acid (1-octene)

[0062]

[0063] Catalyst solution:

[0064] Weigh Pd(acac)2 (8.53 mg) and (1) (35.42 mg) into a 10 mL Schlenk container and dissolve them in methanol (7 mL).

[0065] Sulfuric acid solution:

[0066] Weigh 0.184 g of H2SO4 into a 15 mL Schlenk container and dissolve it in 10 mL of methanol.

[0067] The reaction was carried out in a 10 mL glass container with a magnetic stir bar. In the case of a solid acid, it was first weighed in (the subsequent ratio of acid to (1) should be 3 mol: 1 mol) and pretreated as described above. For example, in the case of salicylic acid, 10.76 mg, 0.156 mol%. The required amount of catalyst solution (0.75 mL) was added by means of a µL syringe, so that the initial weights of Pd(acac)2 (0.914 mg, 0.018 mol%) and (1) (3.795 mg, 0.052 mol%) were obtained. In order to study with a liquid acid, the required amount of acid solution was added. For example, for a 3:1 H2SO4 ratio, 0.14 mL (0.156 mol%) was added by means of a µL syringe. Finally, methanol was added by means of a µL syringe, resulting in a total volume of 3.38 mL and a molar ratio of MeOH to substrate of 5:1. In the example above, therefore 2.3 mL was added. Five pre-prepared glass containers were suspended in a 300 mL autoclave. Separate lines were connected to each container, allowing for metered addition of the substrate at the specified reaction temperature. The autoclave was shut off and purged three times with CO, followed by CO injection to 15 bar. The reaction solution was then heated to the desired temperature of 115 °C. After 20 minutes at constant temperature, the substrate was transferred to the reaction vessel (2.6 mL, 16.7 mmol) using an HPLC pump. Samples were taken from each container via the substrate line after 1 hour. Isooctane was added to 0.5 mL of this sample as a standard, and the yield and n:iso ratio were determined by GC and GCMS analysis.

[0068]

[0069] Embodiments of the present invention

[0070] Aluminum or trifluoromethanesulfonate compounds (diisobutylene)

[0071]

[0072] Catalyst solution:

[0073] Weigh Pd(acac)2 (83.3 mg) and (1) (238.1 mg) into a 10 mL Schlenk container and dissolve them in methanol (7 mL).

[0074] Sulfuric acid solution:

[0075] Weigh 0.386 g of H2SO4 into a 15 mL Schlenk container and dissolve it in 5 mL of methanol.

[0076] The reaction was carried out in a 10 mL glass container equipped with a magnetic stir bar. In the case of a solid acid, it was first weighed in (4 mol%; the molar ratio of acid to (1) = 10:1) and pretreated as described above. The required amount of catalyst solution (1 mL) was added by means of a µL syringe, so as to obtain the initial weights of Pd(acac)2 (11.9 mg, 0.2 mol%) and (1) (34.01 mg, 0.4 mol%). For the study with liquid acid H2SO4, the required amount of acid solution, 1 mL (4 mol%), was added by means of a µL syringe. Finally, methanol was added by means of a µL syringe, so that the total volume was 3.94 mL and the molar ratio of MeOH to substrate was 5:1. Five pre-prepared glass containers were suspended in a 300 mL autoclave. At the same time, separate tubing was led to each container, which allowed for the metered addition of substrate (3 mL, 19.4 mmol) at a specific temperature. The autoclave was shut off and purged three times with CO, followed by CO injection to 15 bar. The reaction solution was then heated to the desired temperature of 115 °C. After 20 minutes at constant temperature, the substrate was transferred to the reaction vessel (3 mL, 19.4 mmol) using an HPLC pump. After 1 hour, samples were taken individually via the substrate lines. Isooctane was added to 0.5 mL of this sample as a standard, and the yield and normal:isomer ratio were determined by GC and GC-MS analysis.

[0077]

[0078] Embodiments of the present invention

[0079] Change the ligand (1-octene)

[0080]

[0081] Catalyst solution:

[0082] For a 7 mL methanol solution, weigh Pd(acac)2 (0.004 mol / L) and the ligand (0.0116 mol / L) into a 10 mL Schlenk container.

[0083] The reaction was carried out in a 10 mL glass container equipped with a magnetic stir bar. In the case of a solid acid, it was first weighed in and pretreated as described above. In the example where the desired ratio was 1 mol: 1 mol, 4.13 mg of Al(OTf)3 was weighed in. The desired amount of catalyst solution (0.75 mL) was added using a µL syringe, resulting in the initial weights of Pd(acac)2 (0.914 mg, 0.018 mol%) and (1) (3.795 mg, 0.052 mol%). Finally, methanol was added using a µL syringe, resulting in a total volume of 3.38 mL and a molar ratio of MeOH to substrate of 5:1. Five pre-prepared glass containers were suspended in a 300 mL autoclave. Separate lines were connected to each container, allowing for metered addition of the substrate at a defined reaction temperature. The autoclave was shut off and purged three times with CO, and then CO was injected to 15 bar. The reaction solution was then heated to the desired temperature of 115 °C. After 20 minutes at a constant temperature, the substrate was transferred to the reaction vessel (2.6 mL, 16.7 mmol) using an HPLC pump. After 1 hour, samples were taken individually via the substrate lines. Isooctane was added to 0.5 mL of this sample as a standard, and the yield and normal:isomer ratio were determined by GC and GCMS analysis.

[0084]

[0085] Embodiments of the present invention

[0086] Change the acid equivalent (1-octene)

[0087]

[0088] Catalyst solution:

[0089] Weigh Pd(acac)2 (8.53 mg) and (1) (35.42 mg) into a 10 mL Schlenk container and dissolve them in methanol (7 mL).

[0090] Sulfuric acid solution:

[0091] Weigh 0.184 g of H2SO4 into a 15 mL Schlenk container and dissolve it in 10 mL of methanol.

[0092] The reaction was carried out in a 10 mL glass container equipped with a magnetic stir bar. In the case of a solid acid, it was first weighed and pretreated as described above. The required amount of catalyst solution (0.75 mL) was added using a µL syringe, resulting in the initial weights of Pd(acac)₂ (0.914 mg, 0.018 mol%) and (1) (3.795 mg, 0.052 mol%). For the purpose of studying with a liquid acid, the required amount of acid solution was added. For example, for a 4:1 H₂SO₄ ratio, 0.19 mL (0.21 mol%) was added using a µL syringe. Finally, methanol was added using a µL syringe, resulting in a total volume of 3.38 mL and a molar ratio of MeOH to substrate of 5:1. In the above example, therefore 2.44 mL was added. Five pre-prepared glass containers were suspended in a 300 mL autoclave. Separate tubing was connected to each container, which allowed for metered addition of the substrate at a defined reaction temperature. The autoclave was shut off and purged three times with CO, followed by CO injection to 15 bar. The reaction solution was then heated to the desired temperature of 115 °C. After 20 minutes at constant temperature, the substrate was transferred to the reaction vessel (2.6 mL, 16.7 mmol) using an HPLC pump. After 1 hour, samples were taken individually via the substrate lines. Isooctane was added to 0.5 mL of this sample as a standard, and the yield and normal:isomer ratio were determined by GC and GCMS analysis.

[0093]

[0094] Embodiments of the present invention

[0095] Change the acid equivalent (diisobutylene)

[0096]

[0097] Catalyst solution:

[0098] Weigh Pd(acac)2 (83.3 mg) and (1) (238.1 mg) into a 10 mL Schlenk container and dissolve them in methanol (7 mL).

[0099] Sulfuric acid solution:

[0100] Weigh 0.386 g of H2SO4 into a 15 mL Schlenk container and dissolve it in 5 mL of methanol.

[0101] The reaction was carried out in a 10 mL glass container equipped with a magnetic stir bar. In the case of a solid acid, it was first weighed and pretreated as described above. The required amount of catalyst solution (1 mL) was added using a µL syringe, resulting in the initial weights of Pd(acac)₂ (11.9 mg, 0.2 mol%) and (1) (34.01 mg, 0.4 mol%). For the study with a liquid acid, the required amount of acid solution was added. For example, for a 1:1 H₂SO₄ ratio, 0.1 mL (0.4 mol%) was added using a µL syringe. Finally, methanol was added using a µL syringe, resulting in a total volume of 3.94 mL and a molar ratio of MeOH to substrate of 5:1. In the example above, 2.8 mL was therefore added. Five pre-prepared glass containers were suspended in a 300 mL autoclave. Separate tubing was connected to each container, allowing for the metered addition of substrate (3 mL, 19.4 mmol) at a specific temperature. The autoclave was shut off and purged three times with CO, followed by CO injection to 15 bar. The reaction solution was then heated to the desired temperature of 115 °C. After 20 minutes at constant temperature, the substrate was transferred to the reaction vessel (3 mL, 19.4 mmol) using an HPLC pump. After 1 hour, samples were taken individually via the substrate line. Isooctane was added to 0.5 mL of this sample as a standard, and the yield and normal:isomer ratio were determined by GC and GCMS analysis.

[0102]

[0103] Embodiments of the present invention.

Claims

1. A method for alkoxycarbonylating an alkene unsaturated compound, comprising the following steps: a) Initial feeding of an olefinic unsaturated compound; b) Additive (I) ligands and compounds containing Pd: （I） in R 1 and R 3 Each is -(C3-C 20 )-Heteroaryl group, R 2 and R 4 Each is -(C1-C 12 )-alkyl; c) Pretreatment of aluminum trifluoromethanesulfonate by applying a vacuum with a pressure of 100 mbar or lower; d) Adding pretreated aluminum trifluoromethanesulfonate obtained from c), wherein the ratio of aluminum trifluoromethanesulfonate to ligand is in the range of 2.5 mol : 1 mol to 15 mol : 1 mol; e) Add alcohol; f) Input CO; g) Heating the reaction mixture obtained from a) to f), wherein the olefinic unsaturated compound is converted into an ester.

2. The method of claim 1, wherein step c) is performed at least twice, and the applied vacuum is interrupted by filling with inert gas.

3. The method according to any one of claims 1 and 2, wherein R 1 R 3 Each is selected from furanyl, thiophene, pyrrole, azole group, iso Azolyl, thiazolyl, isothiazolyl, imidazole, pyrazolyl, furazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, benzofuranyl, indolyl, isoindolyl, benzimidazolyl, quinolinyl, isoquinolinyl.

4. The method according to claim 1 or 2, wherein R 2 and R 4 It is tert-butyl.

5. The method according to claim 1 or 2, wherein the ligand in step b) of the method has formula (1): （1）。 6. The method of claim 1 or 2, wherein the method includes an additional method step c'). c') The pretreated aluminum trifluoromethanesulfonate obtained from c) is dissolved in a solvent.

7. The method according to claim 6, wherein the solvent used in method step c') is the same alcohol as in method step e).

8. The method according to claim 1 or 2, wherein the Pd-containing compound in step b) is selected from palladium dichloride, palladium acetylacetonate (II), palladium acetate (II), palladium dichloro(1,5-cyclooctadiene) (II), bis(dibenzylpyridinylacetone) (II), bis(acetonitrile) (II), and palladium dichloride (cinnamyl) (II).

9. The method according to claim 1 or 2, wherein the alcohol in step e) is selected from methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 2-propanol, tert-butanol, 3-pentanol, cyclohexanol, phenol, or mixtures thereof.

10. The method according to claim 1 or 2, wherein the alcohol in step e) of the method is methanol.

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