METHOD FOR THE ALKOXYCARBONYLATION OF ETHYLENICALLY UNSATURATED COMPOUNDS USING BENZOLE-BASED DIPHOSPHINLIGANDS AND ALUMINUM TRIFLATE

Description

[0001] The invention relates to a process for the alkoxycarbonylation of ethylene unsaturated compounds using benzene-based diphosphine ligands and aluminium triflate.

[0002] The alkoxycarbonylation of ethylene-unsaturated compounds is a process of increasing importance. Alkoxycarbonylation is the reaction of ethylene-unsaturated compounds (olefins) with carbon monoxide and alcohols in the presence of a metal-ligand complex to form the corresponding esters. Palladium is typically used as the metal. The following scheme shows the general reaction equation for an alkoxycarbonylation:

[0003] In Dong Kaiwu et al.: "Efficient Palladium-Catalyzed Alkoxycarbonylation of Bulk Industrial Olefins Using Ferrocenyl Phosphine Ligands" Angewandte Chemie International Edition 2017, Vol: 56, No: 19, Pages: 5267 - 5271, a process for the alkoxycarbonylation of olefins is described. The process is catalyzed by a palladium ligand complex.

[0004] EP 3 121 184 A2 describes a process for the alkoxycarbonylation of olefins using benzene-based diphosphine compounds. A Brønsted acid was added to the reaction in each case: para-toluenesulfonic acid (PTSA), trifluoromethanesulfonic acid, or sulfuric acid.

[0005] Sulfuric acid, however, causes severe corrosion on metallic surfaces. Another disadvantage of using sulfuric acid is that it requires extensive pretreatment / degassing.

[0006] Catalyst systems are often sensitive to oxygen. Contact with even trace amounts of oxygen leads to ligand oxidation, ultimately reducing the activity of the entire catalyst complex. Traces of oxygen can be introduced, for example, through the continuous addition of components.

[0007] The technical objective of the invention is to provide a new process that does not exhibit the drawbacks associated with the use of Brønsted acid, as described in the prior art. Furthermore, the process should deliver a high yield.

[0008] The problem is solved by a method according to claim 1.

[0009] The procedure encompasses the following procedural steps: a) Providing an ethylene unsaturated compound; b) Adding a ligand according to formula (I): where R1< and R3< each represent a -(C3-C20)-heteroaryl group, R2< and R4< each represent a -(C1-C12)-alkyl group, and a compound comprising Pd; c) pretreatment of aluminum triflate by applying a vacuum; d) addition of the pretreated aluminum triflate from c), wherein the ratio of aluminum triflate : ligand is in the range of 2 mol : 1 mol to 25 mol : 1 mol; e) addition of an alcohol; f) supply of CO; g) heating of the reaction mixture from a) to f), wherein the ethylene unsaturated compound is converted to an ester.

[0010] The substances can be added in any order. However, CO is usually added after the reactants have been added in steps a) to e). Furthermore, CO can also be added in several steps, for example, by first adding some CO, then heating it, and then adding another portion.

[0011] In the context of this invention, "vacuum" means a pressure of 100 mbar or less.

[0012] The pretreatment of the aluminium triflate can, for example, take place in a holding container.

[0013] The application of a vacuum can be repeated several times.

[0014] In one variant of the process, process step c) is carried out at least twice, and the applied vacuum is released by flooding with inert gas. For example, N₂, He, or Ar can be used as the inert gas.

[0015] The term (C1-C12)-alkyl includes straight-chain and branched alkyl groups with 1 to 12 carbon atoms. Preferably, these are (C1-C8)-alkyl groups, particularly preferably (C1-C6)-alkyl, and most preferably (C1-C4)-alkyl.

[0016] The term (C3-C20)-heteroaryl comprises mono- or polycyclic aromatic hydrocarbon residues with 3 to 20 carbon atoms, wherein one or more of the carbon atoms are replaced by heteroatoms. Preferred heteroatoms are N, O, and S. The (C3-C20)-heteroaryl groups have 3 to 20, preferably 6 to 14, and particularly preferably 6 to 10 ring atoms. Thus, for example, pyridyl is a C6 heterooaryl residue within the scope of this invention, and furyl is a C5 heterooaryl residue.

[0017] The ethylene-unsaturated compounds used as starting materials in the process according to the invention contain one or more carbon-carbon double bonds. These compounds are also known as olefins. The double bonds can be terminal or internal.

[0018] In one variant of the process, the ethylene unsaturated compound comprises no other functional groups besides carbon-carbon double bonds.

[0019] In the event that the catalyst in situ If the ligand is formed, it can be added in excess, so that unbound ligand is also present in the reaction mixture.

[0020] In a variant of the process, R 1<, R 3< R 1<, R 3< are each selected from furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, benzofuranyl, indolyl, isoindolyl, Benzimidazolyl, quinolyl, isoquinolyl.

[0021] In one variant of the procedure, R 2< and R 4< represent ter< Bu.

[0022] In one variant of the procedure, the ligand in process step b) has the formula (1):

[0023] In one variant of the process, the process includes the additional process step c'): c') dissolving the pretreated aluminium triflate from c) in a solvent.

[0024] By producing a solution from the pretreated aluminium triflate, it is possible to continuously add aluminium triflate to the process without introducing significant amounts of oxygen.

[0025] In one variant of the process, the solvent in process step c') is an alcohol.

[0026] In one variant of the process, the same alcohol is used as the solvent in process step c') as in process step e).

[0027] In one variant of the process, the compound in process step b), which comprises Pd, is selected from palladium dichloride, palladium(II) acetylacetonate, palladium(II) acetate, dichloro(1,5-cyclooctadiene)palladium(II), bis(dibenzylideneacetone)palladium, bis(acetonitrile)dichloropalladium(II), palladium(cinnamyl)dichloride.

[0028] Preferably, the compound comprising Pd is Pd(dba)₂, Pd(acac)₂, or Pd(OAc)₂. Pd(acac)₂ is particularly suitable.

[0029] The mass ratio of Pd to the ethylene unsaturated compound provided in step a) is preferably in the range of 0.001 to 0.5 wt.%, preferably from 0.01 to 0.1 wt.%, and particularly preferably from 0.01 to 0.05 wt.%.

[0030] The molar ratio of the ligand to Pd is preferably in the range of 0.1:1 to 400:1, more preferably from 0.5:1 to 400:1, particularly preferably from 1:1 to 100:1, most preferably from 2:1 to 50:1.

[0031] In one variant of the process, the alcohol in process 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.

[0032] In one variant of the process, the alcohol in process step e) is methanol.

[0033] In one variant of the process, the alcohol is used in excess in process step e).

[0034] In one variant of the process, the alcohol is used simultaneously as a solvent in process step e).

[0035] The molar ratio of the ethylene unsaturated compound presented in process step a) to the alcohol added in process step e) is preferably in the range of 1:1 to 1:20, more preferably from 1:2 to 1:10, and particularly preferably from 1:3 to 1:6.

[0036] In one variant of the process, the ratio of aluminium triflate : ligand in process step d) is in the range of 2.5 mol : 1 mol to 15 mol : 1 mol.

[0037] In process step f), CO is preferably supplied at a CO partial pressure in the range of 0.1 to 10 MPa (1 to 100 bar), preferably from 1 to 5 MPa (10 to 50 bar), and particularly preferably from 1 to 2 MPa (10 to 20 bar).

[0038] In process step g) of the process according to the invention, the reaction mixture is preferably heated to a temperature in the range of 30 °C to 150 °C, preferably from 40 °C to 140 °C, particularly preferably from 50 °C to 120 °C, in order to convert the ethylene unsaturated compound to an ester.

[0039] The invention will now be explained in more detail using exemplary embodiments. General work regulations

[0040] Unless otherwise specified, work is carried out under an argon atmosphere. Reaction vessels have been previously dried under the influence of temperature (80 °C) and oil pump vacuum.

[0041] Liquid substances (e.g. sulfuric acid (H 2 SO 4 )) are degassed for at least 15 minutes by bubbling in argon.

[0042] The aluminum trifold (Al(OTf)3) used, as well as other solid acids, were pretreated as follows: In the case of a solid acid, it is first weighed out and the vessel is sealed airtight using a crimped septum. Using a pierced cannula connected to an argon / vacuum distribution station (Schlenkline), the acid is first prepared oxygen-free by alternating three cycles of vacuum (50 mbar) and argon flooding. In the following steps, an argon atmosphere is maintained, and pressure equalization (adding solutions) is also possible.

[0043] As a ligand ( 1) 1,2-Bis((tert-butyl(pyridin-2-yl)phosphanyl)methyl)benzene is used. Palladium(II) bis(acetylacetonate) (Pd(acac)₂) is used as a precursor. Di-isobutene is a mixture consisting of the two C8 isomers 2,4,4-trimethylpent-1-ene and 2,4,4-trimethylpent-2-ene in a ratio of approximately 80:20. 0.5 mL of these samples are treated with isooctane as an internal standard, and the conversion and yield are determined by GC and GC-MS analysis. Analytics

[0044] GC analysis of di-isobutene and 1-octene: For GC analysis, an Agilent GC Agilent 7890A chromatograph with a 30 m HP5 column was used. Temperature profile: 35 °C, 10 min; 10 °C / min to 200 °C; the injection volume was 1 µl with a 50:1 split. Experiments Variation of Lewis acids (1-octenes)

[0045] Catalyst solution:

[0046] In a 10 mL Schlenk vessel, Pd(acac) 2 (8.53 mg) and (1 ) (35.42 mg) weighed out and dissolved in methanol (7 mL). Sulfuric acid solution:

[0047] H2SO4 (0.184 g) is weighed into a 15 mL Schlenk vessel and dissolved in methanol (10 mL).

[0048] The reaction is carried out in 10 mL glass vessels using magnetic stir bars. In the case of a solid acid, it is first weighed in (later ratio of acid : ( 1 ) should be 3 mol : 1 mol) and pretreated as previously described. In the case of salicyclic acid, for example, 10.76 mg, 0.156 mol%, are weighed out. The required amount of catalyst solution (0.75 mL) is added using a microliter syringe, resulting in a weight of Pd(acac)₂ (0.914 mg, 0.018 mol%) and ( 1) (3.795 mg, 0.052 mol%). For investigations with liquid acids, the required amount of acid solution is added. For example, for an H₂SO₄ ratio of 3:1, 0.14 mL (0.156 mol%) is added using a microliter syringe. Finally, methanol is added using a microliter syringe to achieve a total volume of 3.38 mL and a molar MeOH to substrate ratio of 5:1. In the example above, 2.3 mL are therefore added. Five of the prepared glass vessels are suspended in a 300 mL autoclave. Simultaneously, a separate line is inserted into each vessel, allowing for precise dosing of the substrate at reaction temperature. The autoclave is closed and purged three times with CO₂, then pressurized with CO₂ at 15 bar. The reaction solutions are then heated to the required temperature of 115 °C.After 20 minutes at constant temperature, the substrate is transferred to the reaction vessels using an HPLC pump (2.6 mL, 16.7 mmol). After 1 h, a sample is drawn off via the substrate line. 0.5 mL of this sample is mixed with isooctane as a standard, and the yield and n:iso ratios are determined by GC / GC-MS analysis. acid Yield (ester mixture) [%] n:iso [%] H₂SO₄ 78 68 Al(OTf) 3 * 92 67 Salicylic acid 1 68 B(OH) 3 4 68 BSA (0.156 mol%) 4 70 [B(OH) 3 ] / [Salicylic acid] 1:2 BSA (0.520 mol%) 6 70 [B(OH) 3 ] / [Salicylic acid] 1:2 BSA (1.040 mol%) 5 70 [B(OH) 3 ] / [Salicylic acid] 1:2 boric acid trimethyl ester 2 68 Boric acid methyl ester 3 67 2-Thienylboronic acid 2 68 Phenylboronic acid 2 68 Tris(pentafluorophenyl)borane 70 67 Ce(SO4)2 2 67 * embodiments according to the invention Aluminum or triflate compounds (di-iso-butene)

[0049] Catalyst solution:

[0050] In a 10 mL Schlenk vessel, Pd(acac) 2 (83.3 mg) and ( 1 ) (238.1 mg) weighed out and dissolved in methanol (7 mL). Sulfuric acid solution:

[0051] H2SO4 (0.386 g) is weighed into a 15 mL Schlenk vessel and dissolved in methanol (5 mL).

[0052] The reaction is carried out in 10 mL glass vessels using magnetic stir bars. In the case of a solid acid, it is first weighed out (4 mol%, molar ratio acid : ( 1 ) = 10:1) and pretreated as previously described. The required amount of catalyst solution (1 mL) is added using a µL syringe, resulting in a sample weight of Pd(acac)₂ (11.9 mg, 0.2 mol%) and ( 1) (34.01 mg, 0.4 mol%). For investigations with the liquid acid H₂SO₄, the required amount of acid solution, 1 mL (4 mol%), is added using a microliter syringe. Finally, methanol is added using a microliter syringe to achieve a total volume of 3.94 mL and a molar MeOH to substrate ratio of 5:1. Five of the prepared glass vessels are suspended in a 300 mL autoclave. Simultaneously, a separate line is inserted into each vessel, allowing for a defined dose of the substrate (3 mL, 19.4 mmol) at reaction temperature. The autoclave is closed and purged three times with CO₂, then pressurized with CO₂ at 15 bar. The reaction solutions are then heated to the required temperature of 115 °C. After 20 minutes at a constant temperature, the substrate is transferred to the reaction vessels using an HPLC pump (3 mL, 19.4 mmol). After 1 hour, a sample is taken via the substrate line.0.5 mL of this sample is mixed with isooctane as a standard, and the yield and n:iso ratios are determined by GC / GC-MS analysis. acid Yield (TMH-ME) [%] H₂SO₄ 87 Al(OTf) 3 * 94 Cu(OTf) 3 <1 Fe(OTf) 3 <1 Mg(OTf) 3 <1 Na(OTf) 3 <1 Zn(OTf) 3 <1 Al(H 2 PO 4 ) 3 3 Al 2 (SO 4 ) 3 8 Al(acac) 3 <1 * embodiments according to the invention Ligand variation (1-octene)

[0053] Catalyst solution:

[0054] In a 10 mL Schlenk vessel, Pd(acac) 2 (0.004 mol / L) and ligand (0.0116 mol / L) are weighed out to form 7 mL of methanol solution.

[0055] The reaction is carried out in 10 mL glass vessels using magnetic stir bars. In the case of a solid acid, it is first weighed out and pretreated as previously described. For the required ratio of 1 mol:1 mol, 4.13 mg of Al(OTf)₃ is weighed out. The required amount of catalyst solution (0.75 mL) is added using a microliter syringe, resulting in a weight of Pd(acac)₂ (0.914 mg, 0.018 mol%) and ( 1) (3.795 mg, 0.052 mol%). Finally, methanol is added via a microliter syringe to achieve a total volume of 3.38 mL and a molar MeOH to substrate ratio of 5:1. Five of the prepared glass vessels are suspended in a 300 mL autoclave. Simultaneously, a separate line is inserted into each vessel, allowing for controlled dosing of the substrate at reaction temperature. The autoclave is sealed and purged three times with CO₂, then pressurized with CO₂ at 15 bar. The reaction solutions are then heated to the required temperature of 115 °C. After 20 minutes at a constant temperature, the substrate is transferred into the reaction vessels using an HPLC pump (2.6 mL, 16.7 mmol). After 1 h, a sample is taken from each vessel via the substrate line. 0.5mL of this sample is mixed with isooctane as a standard and the yield and n:iso ratios are determined by GC / GCMS analysis. Ligand Acid: Ligand [mol]:[mol] Yield (ester mixture) [%] n:iso [%] 0,5 : 1 70 68 1 : 1 82 68 3 : 1* 92 68 5 : 1* 89 68 7 : 1 * 88 68 10 : 1* 88 68 3 : 1 19 92 5 : 1 17 92 10 : 1 15 92 15 : 1 17 92 1 : 1 9 72 3 : 1 10 72 5 : 1 10 72 7,5 : 1 11 72 1 : 1 54 69 3 : 1 65 67 5 : 1 76 68 7,5 : 1 76 68 * embodiments according to the invention Variation of acid equivalents (1-octene)

[0056] Catalyst solution:

[0057] In a 10 mL Schlenk vessel, Pd(acac) 2 (8.53 mg) and (1) (35.42 mg) are weighed and dissolved in methanol (7 mL). Sulfuric acid solution:

[0058] H2SO4 (0.184 g) is weighed into a 15 mL Schlenk vessel and dissolved in methanol (10 mL).

[0059] The reaction is carried out in 10 mL glass vessels using magnetic stir bars. In the case of a solid acid, it is first weighed out and pretreated as described previously. The required amount of catalyst solution (0.75 mL) is added using a microliter syringe, resulting in a sample weight of Pd(acac)₂ (0.914 mg, 0.018 mol%) and ( 1) (3.795 mg, 0.052 mol%). For investigations with liquid acids, the required amount of acid solution is added. For example, for an H₂SO₄ ratio of 4:1, 0.19 mL (0.21 mol%) is added using a microliter syringe. Finally, methanol is added using a microliter syringe to achieve a total volume of 3.38 mL and a molar MeOH to substrate ratio of 5:1. In the example above, 2.44 mL is added. Five of the prepared glass vessels are suspended in a 300 mL autoclave. Simultaneously, a separate line is inserted into each vessel, allowing for precise dosing of the substrate at reaction temperature. The autoclave is closed and purged three times with CO₂, then pressurized with CO₂ at 15 bar. The reaction solutions are then heated to the required temperature of 115 °C.After 20 minutes at constant temperature, the substrate is transferred to the reaction vessels using an HPLC pump (2.6 mL, 16.7 mmol). After 1 h, a sample is drawn off via the substrate line. 0.5 mL of this sample is mixed with isooctane as a standard, and the yield and n:iso ratios are determined by GC / GC-MS analysis. acid Acid :( 1 ) [mol:mol] Yield (ester mixture) [(%] H₂SO₄ 1 : 1 44 2 : 1 73 3 : 1 78 4 : 1 73 5 : 1 65 7 : 1 48 10 : 1 34 Al(OTf) 3 1 : 1 82 3 : 1* 92 5 : 1* 89 7 : 1 * 88 10 : 1* 88 * embodiments according to the invention Variation of acid equivalents (di-iso-butene)

[0060] Catalyst solution:

[0061] In a 10 mL Schlenk vessel, Pd(acac) 2 (83.3 mg) and ( 1 ) (238.1 mg) weighed out and dissolved in methanol (7 mL). Sulfuric acid solution:

[0062] H2SO4 (0.386 g) is weighed into a 15 mL Schlenk vessel and dissolved in methanol (5 mL).

[0063] The reaction is carried out in 10 mL glass vessels using magnetic stir bars. In the case of a solid acid, it is first weighed out and pretreated as described previously. The required amount of catalyst solution (1 mL) is added using a microliter syringe, resulting in a sample weight of Pd(acac)₂ (11.9 mg, 0.2 mol%) and ( 1) (34.01 mg, 0.4 mol%). For investigations with liquid acids, the required amount of acid solution is added. For example, for an H₂SO₄ ratio of 1:1, 0.1 mL (0.4 mol%) is added using a microliter syringe. Finally, methanol is added using a microliter syringe to achieve a total volume of 3.94 mL and a molar MeOH to substrate ratio of 5:1. In the example above, 2.8 mL is added. Five of the prepared glass vessels are suspended in a 300 mL autoclave. Simultaneously, a separate line is inserted into each vessel, allowing for a defined dose of the substrate (3 mL, 19.4 mmol) at reaction temperature. The autoclave is closed and purged three times with CO₂, then pressurized with CO₂ at 15 bar. The reaction solutions are then heated to the required temperature of 115 °C.After 20 minutes at constant temperature, the substrate is transferred to the reaction vessels using an HPLC pump (3 mL, 19.4 mmol). After 1 h, a sample is drawn off via the substrate line. 0.5 mL of this sample is mixed with isooctane as a standard, and the yield and n:iso ratios are determined by GC / GC-MS analysis. acid Acid :( 1 ) [mol:mol] Yield (TMH-ME) [%] H₂SO₄ 1 80 2,5 88 4 91 7 89 10 87 13 81 15 70 Al(OTf) 3 1 84 2,5 : 1* 92 4 : 1* 92 7 : 1* 95 10 : 1* 94 13 : 1* 92 15 : 1* 93 * embodiments according to the invention

Claims

1. Process comprising the process steps of: a) initially charging an ethylenically unsaturated compound; b) adding a ligand of formula (I): where R1 and R3 are each a -(C3-C20)-heteroaryl radical, R2 and R4 are each -(C1-C12)-alkyl, and a compound comprising Pd; c) pretreating aluminium triflate by applying reduced pressure; d) adding the pretreated aluminium triflate from c), where the ratio of aluminium triflate: ligand is in the range from 2 mol: 1 mol to 25 mol: 1 mol; e) adding an alcohol; f) supplying CO; g) heating the reaction mixture of a) to f), with conversion of the ethylenically unsaturated compound to an ester.

2. Process according to Claim 1, wherein process step c) is conducted at least twice, and the vacuum applied is broken by flooding with inert gas.

3. Process according to either of Claims 1 and 2, where R1, R3 are each selected from furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, benzofuranyl, indolyl, isoindolyl, benzimidazolyl, quinolyl, isoquinolyl.

4. Process according to any of Claims 1 to 3, where R2 and R4 are terBu.

5. Process according to any of Claims 1 to 4, wherein the ligand in process step b) has the formula (1):

6. Process according to any of Claims 1 to 5, wherein the process comprises the additional process step c'): c') dissolving the pretreated aluminium triflate from c) in a solvent.

7. Process according to Claim 6, wherein the solvent used in process step c') is the same alcohol as used in process step e).

8. Process according to any of Claims 1 to 7, wherein the compound in process step b) comprising Pd is selected from palladium dichloride, palladium(II) acetylacetonate, palladium(II) acetate, dichloro(1,5-cyclooctadiene)palladium(II), bis(dibenzylideneacetone)palladium, bis(acetonitrile)dichloropalladium(II), (cinnamyl)palladium dichloride.

9. Process according to any of Claims 1 to 8, wherein the alcohol in process 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. Process according to any of Claims 1 to 9, wherein the alcohol in process step e) is methanol.

11. Process according to any of Claims 1 to 10, where the ratio of aluminium triflate: ligand in process step d) is in the range from 2.5 mol: 1 mol to 15 mol: 1 mol.