PROCESS FOR ALKOXYCARBONYLATION OF ETHYLENICALLY UNSATURATED COMPOUNDS USING BENZENE-BASED DIPHOSPHINE LIGANDS AND ALUMINIUM TRIFLATE

Abstract

Process for alkoxycarbonylation of ethylenically unsaturated compounds using benzene-based diphosphine ligands and aluminium triflate.

Claims

1. Process comprising the process steps of: a) initially charging an ethylenically unsaturated compound; b) adding a ligand of formula (I): ##STR00013## where R.sup.1 and R.sup.3 are each a —(C.sub.3-C.sub.20)-heteroaryl radical, R.sup.2 and R.sup.4 are each —(C.sub.1-C.sub.12)-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) feeding in CO; g) heating the reaction mixture from 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 claim 2, where R.sup.1, R.sup.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.

4. Process according to claim 1, where R.sup.2 and R.sup.4 are .sup.terBu.

5. Process according to claim 1, wherein the ligand in process step b) has the formula (1): ##STR00014##

6. Process according to claim 1, 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 in process step e).

8. Process according to claim 1, 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 claim 1, 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 claim 1, wherein the alcohol in process step e) is methanol.

11. Process according to claim 1, wherein 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.

Description

[0051] The invention is to be described in detail hereinbelow with reference to working examples,

General Procedural Methods

[0052] Unless stated otherwise, an argon atmosphere is employed. Reaction vessels have been dried beforehand at high temperature (80° C.) and under oil-pump vacuum.

[0053] Liquid substances (e.g. sulfuric acid (H.sub.2SO.sub.4)) are degassed by bubbling in argon for at least 15 minutes.

[0054] The aluminium triflate (Al(OTf):.sub.3) used, and also other solid acids, were pretreated as follows: In the case of a solid acid, this is first weighed out and the vessel is sealed airtight by means of a crimp-fitted septum. By means of a penetrating cannula connected to an argon/reduced pressure distributor station (Schlenk line), this acid is prepared in an oxygen-free manner first by alternately applying reduced pressure (50 mbar) and flooding with argon three times. In addition, argon atmosphere is guaranteed in the subsequent steps, and it is additionally possible to balance the pressure (addition of solutions).

[0055] The ligand (1) used is 1,2-bis((tert-butyl(pyridin-2-yl)phosphanyl)methyl)benzere. The precursor used is palladium(II) bis(acetylacetonate) (Pd(acac).sub.2), Di-iso-butene is a mixture consisting of the two C8 isomers 2,4,4-trimethylpent-1-ene and 2,4,4-trimethylpent-2-ene in ratios of about 80:20. 0.5 ml of these samples is spiked with isooctane as internal standard, and conversion and yield are determined by means of GC and GC-MS analysis.

Analysis

[0056] GC analysis of diisobutene and 1-octene: For the GC analysis, an Agilent 7890A gas chromatograph having a 30 m HP5 column is used. Temperature profile: 35° C., 10 min; 10° C./min to 200° C.; the injection volume is 1 μl with a split of 50:1.

Experiments

[0057] Variation of the Lewis Acids (1-octenes)

##STR00004##

Catalyst solution:
Pd(acac).sub.2 (8.53 mg) and (1) (35.42 mg) are weighed out in a 10 ml Schlenk vessel and dissolved in methanol (7 ml).
Sulfuric acid solution:
H.sub.2SO.sub.4 (0.184 mg) is weighed out in a 15 ml Schlenk vessel and dissolved in methanol (10 ml).

[0058] The reaction is conducted in 10 ml glass vessels with magnetic stirrer bars. In the case of a solid acid, it is first weighed out (later ratio of acid:(1) should be 3 mol:1 mol) and pretreated as described above. In the case of salicylic acid, for example, 10.76 mg, 0.156 mol %, is weighed out. The amount of catalyst solution required (0.75 ml) is added by means of a μl syringe, so as to result in a starting weight of Pd(acac)2 (0.914 mg, 0.018 mol %) and (1) (3.795 mg, 0.052 mol %). For studies with liquid acids, the amount of acid solution required is added. For example, for an H.sub.2SO.sub.4 ratio of 3:1, 0.14 ml (0.156 mol %) is added by means of a μl syringe. Finally, methanol is added by means of a syringe, resulting in a total volume of 3.38 ml and a molar MeOH to substrate ratio of 5:1. In the aforementioned example, 2.3 ml is accordingly added. Five of the glass vessels prepared are hung up in a 300 ml autoclave. At the same time, a separate line is guided into each vessel, which enables defined dosage of the substrate at reaction temperature. The autoclave is closed and purged three times with CO, and then CO is injected to 15 bar. The reaction solutions are then heated up to the required temperature of 115° C. After 20 minutes at constant temperature, the substrate is transferred into the reaction vessels (2.6 ml, 16.7 mmol) by means of an HPLC pump. After 1 h, a sample was taken via each substrate line. 0.5 ml of this sample is spiked with isooctane as standard, and yield and n:iso ratios are determined by means of GC and GC-MS analysis.

TABLE-US-00001 Acid Yield (ester mixture) [%] n:iso [%] H.sub.2SO.sub.4 78 68 Al(OTf).sub.3* 92 67 Salicylic acid 1 68 B(OH).sub.3 4 68 SA (0.156 mol %) 4 70 [B(OH).sub.3]/[salicylic acid] 1:2 SA (0.520 mol %) 6 70 [B(OH).sub.3]/[salicylic acid] 1:2 SA (1.040 mol %) 5 70 [B(OH).sub.3]/[salicylic acid] 1:2 Trimethyl borate 2 68 Methyl borate 3 67 2-Thienylboronic acid 2 68 Phenylboronic acid 2 68 Tris(pentafluorophenyl)borane 70 67 Ce(SO.sub.4).sub.2 2 67 *inventive working examples

Aluminium Triflate Compounds (Diisobutene)

[0059] ##STR00005##

Catalyst solution:
Pd(acac).sub.2 (83.3 mg) and (1) (238.1 mg) are weighed out in a 10 ml Schlenk vessel and dissolved in methanol (7 ml).
Sulfuric acid solution:
H.sub.2SO.sub.4 (0.386 mg) is weighed out in a 15 ml Schlenk vessel and dissolved in methanol (5 ml).

[0060] The reaction is conducted in 10 ml glass vessels with magnetic stirrer bars. In the case of a solid acid, it is first weighed out (4 mol %; molar ratio of acid:(1)=10:1) and pretreated as described above. The amount of catalyst solution required (1 ml) is added by means of a μl syringe, so as to result in a starting weight of Pd(acac).sub.2 (11.9 mg, 0.2 mol %) and (1) (34.01 mg, 0.4 mol %). For studies with the liquid acid H.sub.2SO.sub.4, the amount of acid solution required, 1 ml (4 mol %), is added by means of a pi syringe. Finally, methanol is added by means of a μl syringe, resulting in a total volume of 3.94 ml and a molar MeOH to substrate ratio of 5:1. Five of the glass vessels prepared are hung up in a 300 ml autoclave. At the same time, a separate line is guided into each vessel, which enables defined dosage of the substrate (3 ml, 19.4 mmol) at reaction temperature. The autoclave is closed and purged three times with CO, and then CO is injected to 15 bar. The reaction solutions are then heated up to the required temperature of 115° C. After 20 minutes at constant temperature, the substrate is transferred into the reaction vessels (3 ml, 19.4 mmol) by means of an HPLC pump. After 1 h, a sample was taken via each substrate line. 0.5 ml of this sample is spiked with isooctane as standard, and yield and n:iso ratios are determined by means of GC and GC-MS analysis.

TABLE-US-00002 Acid Yield (MTMH) [%] H.sub.2SO.sub.4 87 Al(OTf).sub.3* 94 Cu(OTf).sub.3 <1 Fe(OTf).sub.3 <1 Mg(OTf).sub.3 <1 Na(OTf).sub.3 <1 Zn(OTf).sub.3 <1 Al(H.sub.2PO.sub.4).sub.3 3 Al.sub.2(SO.sub.4).sub.3 8 Al(acac).sub.3 <1 *inventive working examples
Variation of the Ligand (1-octenes)

##STR00006##

Catalyst solution:
Pd(acac).sub.2 (0.004 mol/l) and (ligand) (0.0116 mol/l) are weighed out in a 10 ml Schlenk vessel for 7 ml of methanol solution.

[0061] The reaction is conducted in 10 ml glass vessels with magnetic stirrer bars. In the case of a solid acid, it is first weighed out and pretreated as described above. In the example of the required ratio of 1 mol:1 mol, 4.13 mg Al(OTf).sub.3 is weighed out. The amount of catalyst solution required (0.75 ml) is added by means of a μl syringe, so as to result in a starting weight of Pd(acac).sub.2 (0.914 mg, 0.018 mol %) and (1) (3.795 mg, 0.052 mol %). Finally, methanol is added by means of a syringe, resulting in a total volume of 3.38 ml and a molar MeOH to substrate ratio of 5:1. Five of the glass vessels prepared are hung up in a 300 ml autoclave. At the same time, a separate line is guided into each vessel, which enables defined dosage of the substrate at reaction temperature. The autoclave is closed arid purged three times with CO, and then CO is injected to 15 bar. The reaction solutions are then heated up to the required temperature of 115° C. After 20 minutes at constant temperature, the substrate is transferred into the reaction vessels (2.6 ml, 16.7 mmol) by means of an HPLC pump. After 1 h, a sample was taken via each substrate line. 0.5 ml of this sample is spiked with isooctane as standard, and yield and n:iso ratios are determined by means of GC and GC-MS analysis.

TABLE-US-00003 Yield Acid:ligand (ester mixture) Ligand [mol]:[mol] [%] n:iso [% ] [00007] 0.5:1   1:1  3:1*  5:1*  7:1* 10:1  70 82 92 89 88 88 68 68 68 68 68 68 [00008] 3:1 5:1 10:1  15:1  19 17 15 17 92 92 92 92 [00009] 1:1 3:1 5:1 7.5:1   9 10 10 11 72 72 72 72 [00010] 1:1 3:1 5:1 7.5:1   54 65 76 76 69 67 68 68 *inventive working examples
Variation of the Acid Equivalents (1-octanes)

##STR00011##

Catalyst solution:
Pd(acac).sub.2 (8.53 mg) and (1) (35.42 mg) are weighed out in a 10 ml Schlenk vessel and dissolved in methanol (7 ml).
Sulfuric acid solution:
H.sub.2SO.sub.4 (0.184 mg) is weighed out in a 15 ml Schlenk vessel and dissolved in methanol (10 ml).

[0062] The reaction is conducted in 10 ml glass vessels with magnetic stirrer bars. In the case of a solid acid, it is first weighed out and pretreated as described above. The amount of catalyst solution required (0.75 ml) is added by means of a μl syringe, so as to result in a starting weight of Pd(acac).sub.2 (0.914 mg, 0.018 mol %) and (1) (3.795 mg, 0.052 mol %). For studies with liquid acids, the amount of acid solution required is added. For example, for an H.sub.2SO.sub.4 ratio of 4:1, 0.19 ml (0.21 mol %) is added by means of a μl syringe. Finally, methanol is added by means of a syringe, resulting in a total volume of 3.38 ml and a molar MeOH to substrate ratio of 5:1. In the aforementioned example, 2.44 ml is accordingly added. Five of the glass vessels prepared are hung up in a 300 ml autoclave. At the same time, a separate line is guided into each vessel, which enables defined dosage of the substrate at reaction temperature. The autoclave is closed and purged three times with CO, and then CO is injected to 15 bar. The reaction solutions are then heated up to the required temperature of 115° C. After 20 minutes at constant temperature, the substrate is transferred into the reaction vessels (2.6 ml, 16.7 mmol) by means of an HPLC pump. After 1 h, a sample was taken via each substrate line. 0.5 ml of this sample is spiked with isooctane as standard, and yield and n:iso ratios are determined by means of GC and GC-MS analysis.

TABLE-US-00004 Acid:(1) Yield Acid [mol:mol] (ester mixture) [%] H.sub.2SO.sub.4 1:1 44 2:1 73 3:1 78 4:1 73 5:1 65 7:1 48 10:1  34 Al(OTf).sub.3 1:1 82  3:1* 92  5:1* 89  7:1* 88 10:1* 88 *inventive working examples

Variation of the Acid Equivalents (Diisobutene)

[0063] ##STR00012##

Catalyst solution:
Pd(acac).sub.2 (83.3 mg) and (1) (238.1 mg) are weighed out in a 10 ml Schlenk vessel and dissolved in methanol (7 ml)
Sulfuric acid solution:
H.sub.2SO.sub.4 (0.386 mg) is weighed out in a 15 ml Schlenk vessel and dissolved in methanol (5 ml),

[0064] The reaction is conducted in 10 ml glass vessels with magnetic stirrer bars. In the case of a solid acid, it is first weighed out and pretreated as described above. The amount of catalyst solution required (1 ml) is added by means of a μl syringe, so as to result in a starting weight of Pd(acac).sub.2 (11.9 mg, 0.2 mol %) and (1) (34.01 mg, 0.4 mol %). For studies with liquid acids, the amount of acid solution required is added. For example, for an H.sub.2SO.sub.4 ratio of 1:1, 0.1 ml (0.4 mol %) is added by means of a pi syringe. Finally, methanol is added by means of a syringe, resulting in a total volume of 3.94 ml and a molar MeOH to substrate ratio of 5:1. In the aforementioned example, 2.8 ml is accordingly added. Five of the glass vessels prepared are hung up in a 300 ml autoclave. At the same time, a separate line is guided into each vessel, which enables defined dosage of the substrate (3 ml, 19.4 mmol) at reaction temperature. The autoclave is closed and purged three times with CO, and then CO is injected to 15 bar. The reaction solutions are then heated up to the required temperature of 115° C. After 20 minutes at constant temperature, the substrate is transferred into the reaction vessels (3 ml, 19.4 mmol) by means of an HPLC pump. After 1 h, a sample was taken via each substrate line. 0.5 ml of this sample is spiked with isooctane as standard, and yield and n:iso ratios are determined by means of GC and GC-MS analysis.

TABLE-US-00005 Acid:(1) Yield (MTMH) Acid [mol:mol] [%] H.sub.2SO.sub.4 1 80 2.5 88 4 91 7 89 10 87 13 81 15 70 Al(OTf).sub.3 1 84 2.5:1*  92  4:1* 92  7:1* 95 10:1* 94 13:1* 92 15:1* 93 *inventive working examples