Process for the alkoxycarbonylation of ethylenically unsaturated compounds with monophosphine ligands

Abstract

The invention relates to a process comprising the following process steps: a) introducing an ethylenically unsaturated compound; b) adding a monophosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and a monophosphine ligand; c) adding an aliphatic alcohol; d) supplying CO; e) heating the reaction mixture, the ethylenically unsaturated compound being reacted to form an ester;
where the monophosphine ligand is a compound of formula (I) ##STR00001##
where
R.sup.1 is selected from (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, O(C.sub.6-C.sub.20)-aryl, (C.sub.6-C.sub.20)-aryl, (C.sub.3-C.sub.12)-cycloalkyl, (C.sub.3-C.sub.12)-heterocycloalkyl, (C.sub.3-C.sub.20)-heteroaryl;
R.sup.2 is selected from (C.sub.6-C.sub.20)-aryl, (C.sub.3-C.sub.12)-cycloalkyl, (C.sub.3-C.sub.12)-heterocycloalkyl, (C.sub.3-C.sub.20)-heteroaryl;
R.sup.3 is (C.sub.3-C.sub.20)-heteroaryl;
and R.sup.1, R.sup.2 and R.sup.3 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 regioselective process for preparing an ester comprising the following process steps: a) introducing an ethylenieally unsaturated compound having 8 to 12 carbon atoms, forming a reaction mixture; b) adding a monophosphine ligand and a compound which comprises Pd, or adding a complex comprising Pd and a monophosphine ligand; c) adding an aliphatic alcohol; d) supplying CO; e) heating the reaction mixture, the ethylenically unsaturated compound being reacted with the epithelium CO and aliphatic alcohol to form the ester; where the monophosphine ligand is ##STR00019##

2. The process according to claim 1, wherein the ethylenically unsaturated compound is selected from the group consisting of ethene, propene, 1-butene, 2-butene, isobutene, 1,3-butadiene, 1-pentene, 2-pentene, 2-methyl-1-butene, 3-methyl-1-butene, 2-methyl-2-butene, hexene, tetramethylethylene, heptene, 1-octene, 2-octene, di-n-butene, and mixtures thereof.

3. The process according to claim 1, wherein the compound comprising Pd in process step b) is selected from the group consisting of palladium dichloride, palladium(II) acetylacetonate, palladium(II) acetate, dichloro(1,5-cyclooctadiene)palladium(II), bis(dibenzylideneacetone)palladium, bis(acetonitrile)dichloro-palladium(II), and palladium(cinnamyl) dichloride.

4. The process according to claim 1, wherein the 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.

5. The process according to claim 1, wherein the alcohol in process step c) is selected from the group consisting of methanol and ethanol.

Description

EXAMPLES

(1) The examples which follow illustrate the invention.

General Procedures

(2) 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).

(3) 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 () 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).

(4) 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)

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

(6) ##STR00006##

(7) 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. Thereafter, 953.5 l (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 l 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%).

(8) Analytical data: .sup.1H NMR (300 MHz, C.sub.6D.sub.6): 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).

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

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

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

Preparation of Compound 1

(12) ##STR00007##

(13) 0.78 g (9.5 mmol) of 1-methylimidazole are weighed out under argon in a 50 ml three-neck flask with thermometer and dropping funnel, and dissolved in 10 ml of THF. Then 1.6 ml of TMEDA are added to the solution. The mixture is then cooled down to 78 C. Thereafter 6 ml of 1,6 N n-butyllithium in hexane are added dropwise via dropping funnel. The 50 ml flask with the reaction mixture is stirred at room temperature for 30 minutes. Then 1.5 g of tert-butyldichlorophosphine are dissolved in 20 ml of THF. The 1-methylimidazole/BuLi mixture is then added dropwise at 78 C. to the tert-butyldichiorophosphine. This is followed by heating to room temperature. A product is precipitated. The suspension is filtered and the residue is dissolved in water and then washed three times with dichloromethane. The organic phase is dried over Na.sub.2SO.sub.4 and the solvent is then removed under reduced pressure. The residue is dissolved using 5 ml of dichloromethane and overlaid with 20 ml of diethyl ether. The product is crystallized. The product was obtained in 0.8 g.

(14) Purity (NMR)=98%,

(15) .sup.31P NMR (CD.sub.2Cl.sub.2, 121 MHz)=32.25 ppm,

(16) .sup.13C NMR (CD.sub.2Cl.sub.2, 75 MHz)=144 s, 130.2 d (J.sub.PC=3.7 Hz), 123.8 s, 34.2 d, (J.sub.PC=11.7 Hz), 25.9 d, (J.sub.PC=14.3 Hz)

(17) .sup.1H NMR (CD.sub.2Cl.sub.2, 300 MHz,): 7.04, d, (J=1 Hz, 1H), 6.94 dd (J=1 Hz, J=1.5 Hz, 1H), 3.4 s (6H), 1.2 d (J=14.6 Hz, 9H)

(18) HRMS: calculated for C.sub.12H.sub.19N.sub.4P: 251.14201. found: 251.14206.

Preparation of 2-(tert-butyl(phenyl)phosphino)pyridine (Compound 2)

(19) ##STR00008##

(20) 3.4 g (16.8 mmol) of 2-(tert-butylchlorophosphino)pyridine are dissolved under argon in 50 ml of absolute diethyl ether in a 100 ml three-neck flask equipped with low-temperature thermometer and magnetic stirrer. Cooling takes place to 78 C. At this temperature, over the course of 10 minutes, 10 ml of a 1.8 N phenyllithium solution (in dibutyl ether) are added by means of a dropping funnel. Stirring takes place at this temperature for 10 minutes, followed by warming to room temperature and stirring for a further half-hour. This solution is washed three times with 10 ml of degassed water. The organic phase is then distilled under a fine vacuum of 10.sup.1 torr. Under this pressure, the product is obtained at 130 C. as a clear liquid in high purity of more than 97% (NMR). The yield is 3.85 g (93%).

(21) Analysis:

(22) .sup.31P (acetone-d.sub.6, 121 MHz), 16.31 s,

(23) .sup.13C (75 MHz, acetone-d.sub.6, 165.1 (d, J.sub.PC=10.5 Hz), 150.3 (d, J.sub.PC=5 Hz), 137.3 s, 137.0 s, 136.7 s, 135.9 d, 135.9 (d, J.sub.PC=7.6 Hz), 131.1 s, 130.6 s, 130.2 s, 128.9 (d, J.sub.PC=8 Hz), 122.9 s, 32.1 (d, J.sub.PC=13.1 Hz), 28.5 (d, J.sub.PC=13.7 Hz),

(24) .sup.1H (acetone-d.sub.6, 300 MHz):

(25) 8.74 (dm, J=4.7 Hz), 7.7-7.6 m (2 H), 7.4-7.3 (m, 3 H), 7.28-7.23 (m, 1 H), 1.2 (d, J=12.6 Hz, 9 H)

(26) MS (EI, 70 eV): m/z (%), 243 (M+, 17), 203 (65), 187 (78), 156 (6), 126(8), 109(100), 78(11), 57(11), HRMS(EI), calculated for C15H18N1P1: 243.11714. found: 243.11753.

(27) Further Ligands

(28) The following compounds are commercially available and/or preparable by a known pathway.

(29) TABLE-US-00001 3 (CE) 0 7 8 Cf. A Zapf, M. Sundermeier, R. Jackstell, M. Beller, T. Riermeier, A. Monsees, U. Dingerdissen (Degussa AG); Nitrogen-containing monodentate phosphines and their use in catalysis; DE 103 22 408 A1. F. Rataboul, A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A. Monsees, U. Dingerdissen, M. Beller, Chem. Eur. J. 2004, 10, 12, 2983-2990, New Ligands for a General Palladium-Catalyzed Amination of Aryl and Heteroaryl Chlorides. 9 10 (CE) 11 See remark for compound 8 12 13 14 CE: comparative example
Alkoxycarbonylation Experiments
General Experiment Description for Reactions in Batchwise Mode

(30) The appropriate amounts of substrate, palladium salt, acid and alcohol are mixed under argon in a 50 ml Schlenk vessel while stirring with a magnetic stirrer.

(31) A 100 ml steel autoclave from Parr provided with a gas inlet and a gas outlet valve, a digital pressure transducer, a temperature sensor and a ball valve, and an installed capillary for sampling, is freed of oxygen by means of vacuum and argon purging three times. Subsequently, the reaction solution from the Schlenk vessel is introduced by means of a capillary into the autoclave in an argon counterflow through the ball valve. Subsequently, either the appropriate amount of CO is injected at room temperature and then the autoclave is heated up to reaction temperature (reactions that are not run under constant pressure) or the autoclave is first heated up to reaction temperature and then the CO is injected by means of a burette connected to the autoclave by means of a pressure reducer. This burette is then filled with CO to about 100 bar and, during the reaction, supplies the CO required at a constant pressure. This burette has a dead volume of about 30 ml and is provided with a digital pressure transducer. Then the reaction is conducted at the required temperature for the required time while stirring. In the course of this, by means of software (Specview from SpecView Corporation) and a Parr 4870 process controller and a 4875 power controller, data for the pressure variation in the autoclave and in the gas burette are recorded. If required, via the capillary, the GC samples are collected and analysed. For this purpose, a suitable exact amount (2-10 ml) of isooctane as internal standard is also added to the Schlenk vessel before the reaction. These also give information about the course of the reaction. At the end of the reaction, the autoclave is cooled down to room temperature, the pressure is cautiously released, isooctane is added if necessary as internal standard, and a GC analysis or, in the case of new products, a GC-MS analysis is conducted.

(32) General Experimental Method for Autoclave Experiments in Glass Vials

(33) A 300 ml Parr reactor is used. Matched to this is an aluminium block of corresponding dimensions which has been manufactured in-house and which is suitable for heating by means of a conventional magnetic stirrer, for example from Heidolph. For the inside of the autoclave, a round metal plate of thickness about 1.5 cm was manufactured, containing 6 holes corresponding to the external diameter of the glass vials. Matching these glass vials, they are equipped with small magnetic stirrers. These glass vials are provided with screw caps and suitable septa and charged, using a special apparatus manufactured by glass blowers, under argon with the appropriate reactants, solvents and catalysts and additives. For this purpose, 6 vessels are filled at the same time; this enables the performance of 6 reactions at the same temperature and the same pressure in one experiment. Then these glass vessels are closed with screw caps and septa, and a small syringe cannula of suitable size is used to puncture each of the septa. This enables gas exchange later in the reaction. These vials are then placed in the metal plate and these are transferred into the autoclave under argon. The autoclave is purged with CO and filled at room temperature with the CO pressure intended. Then, by means of the magnetic stirrer, under magnetic stirring, the autoclave is heated to reaction temperature and the reaction is conducted for the appropriate period. Subsequently, the autoclave is cooled down to room temperature and the pressure is slowly released. Subsequently, the autoclave is purged with nitrogen. The vials are taken from the autoclave, and a defined amount of a suitable standard is added. A GC analysis is effected, the results of which are used to determine yields and selectivities.

(34) Analysis:

(35) Methanol Analysis

(36) Methanol was pretreated in a solvent drying unit: Pure Solv MD-/Solvent purification system, Innovative Technology Inc. One Industrial Way, Amesbury MA 01013

(37) Water Values:

(38) Determined by Karl Fischer Titration: TitraLab 580-TIM580, Radiometer Analytical SAS (Karl-Fischer Titration), water content: measuring ranges, 0.1-100% w/w, measured water content: 0.13889%

(39) The following were used:

(40) Technical methanol Applichem: No. A2954,5000, batch number LOT: 3L005446 water content max. 1%

(41) Methanol Acros Organics (over molecular sieve): water content 0.005%, code number: 364390010, batch number: LOT 1370321

(42) Methoxycarbonylation of Ethene

(43) A 50 ml Schlenk vessel was charged with Pd(acac).sub.2 (6.53 mg, 0.04 mol %), ligand (0.16 mol %), ethene (1.5 g, 53 mmol), 20 ml of methanol and para-toluenesulphonic acid (PTSA, 61 mg, 0.6 mol %). The reaction mixture was transferred by means of a capillary in an argon counter-current into a 100 ml steel autoclave as described above. The CO pressure was adjusted to 40 bar. The reaction ran at 80 C. for 3 hours. After the end of the reaction, the autoclave was cooled to room temperature and cautiously decompressed. Isooctane (100 l) was added as internal GC standard. Yield and regioselectivity were determined by means of GC.

(44) The results are shown in the table below.

(45) TABLE-US-00002 Ligand Yield 1 30% 2 14% 3 (CE) 3% 7 18% 10 (CE) 0% CE: comparative example

(46) The ligands 1, 2 and 7 according to the invention achieve much better yields in the methoxycarbonylation of ethene than do the comparative ligands 3 and 10.

(47) Isomerizing Regioselective Methoxycarbonylation of 1-octene

(48) ##STR00018##

(49) The iso/n ratio reported below indicates the ratio of olefins reacted internally to form esters to olefins reacted terminally to form esters.

(50) Variant a)

(51) A 4 ml vial was charged with PdCl.sub.2 (1.77 mg, 1.0 mol %) and ligand (4.0 mol %) and a magnetic stirrer bar was added. Then toluene (2 ml), 1-octene (157 l, 1 mmol) and MeOH (40.5 l, 1 mmol) were injected via a syringe. The vial was placed on a sample holder, which was inserted in turn under argon atmosphere into a 300 ml Parr autoclave. After threefold purging of the autoclave with nitrogen, the CO pressure was adjusted to 40 bar. The reaction ran at 120 C. for 20 hours. After the end of the reaction, the autoclave was cooled to room temperature and cautiously decompressed. Isooctane (100 l) was added as internal GC standard. Yield and regioselectivity were determined by means of GC.

(52) The results are shown in the table below.

(53) TABLE-US-00003 Ligand Yield iso/n 2 75% 28/72 3 (CE) 87% 55/45 8 66% 36/64 9 49% 79/21 10 (CE) 10% 45/55 11 30% 75/25 12 49% 82/18 13 74% 86/14 14 22% 90/10 CE: comparative example

(54) The ligands according to the invention are notable for high yields and either high iso/n selectivity (ligands 9, 11 to 14) or high n/iso selectivity (ligands 2 and 8). Conversely, the prior-art ligand 10 achieves only a low yield and, furthermore, is not regioselective. Comparative ligand 3 does achieve a high yield, but is likewise not regioselective.

(55) Variant b)

(56) A 25 ml Schlenk vessel was charged with [Pd(acac).sub.2] (1.95 mg, 0.04 mol %), p-toluenesulphonic acid (PTSA) (18.24 l, 0.6 mol %) and MeOH (10 ml). A 4 ml vial was charged with the ligand (0.16 mol %), and a magnetic stirrer bar was added. Thereafter, 1.25 ml of the clear yellow solution from the Schlenk vessel and 1-octene (315 l, 2 mmol) were added with a syringe. The vial was placed into a sample holder which was in turn inserted into a 300 ml Parr autoclave under an argon atmosphere. After the autoclave had been purged three times with nitrogen, the CO pressure was adjusted to 40 bar. The reaction proceeded at 120 C. for 20 hours. On conclusion of the reaction, the autoclave was cooled down to room temperature and cautiously decompressed. Isooctane (100 l) was added as internal GC standard. Yield and regioselectivity were determined by means of GC.

(57) The results are shown in the table below.

(58) TABLE-US-00004 Ligand Yield iso/n 2 26% 74/26 3 (CE) 16% 77/23 7 20% 74/26 10 (CE) 0% N/A CE: comparative example

(59) Here again, the ligands 2 and 7 of the invention exhibit a high iso/n selectivity and a higher yield than the comparative ligands 3 and 10.