Phosphine Ligands for Palladium-Catalyzed Synthesis of δ-Caprolactone from 1,3-Butadiene

Abstract

The present invention relates to a phosphine ligand, which is a compound having at least one hydroxyl group on at least one benzene ring in a triphenylphosphine molecule. The phosphine ligand can be used for palladium-catalyzed synthesis of delta-caprolactone from 1,3-butadiene.

Description

Technical Field

[0001] The invention belongs to the field of metal organic synthesis, and particularly relates to a hydroxyl-containing phosphine ligand and an application thereof in palladium-catalyzed synthesis of delta-caprolactone from 1,3-butadiene. Background Art

[0002] The telomerization of 1,3-butadiene is an important catalytic reaction with widespread applications, achieving 100% atomic efficiency, and offering both economic and ecological benefits. Waste gas carbon dioxide can also be used as a C1 chemical raw material. The availability of inexpensive, readily available, bulk raw materials like 1,3-butadiene and carbon dioxide increases the added value of the reaction. The catalytic reaction of 1,3-butadiene and carbon dioxide was first discovered by Inoue and Musco et al. in the 1970s. The reaction produces numerous products, including lactones, carboxylic acids, and butadiene polymers.

[0003] Behr et al. conducted extensive research on catalysts for this reaction and demonstrated that systems based on phosphine ligands offer the best selectivity for the valuable lactone 3-vinyl-6-vinyltetrahydro-2h-pyran-2-one (δ-lactone). This lactone has numerous synthetic applications, including hydroformylation, hydroamination, hydroaminomethylation, and hydrogenation. These reactions yield a variety of products, including saturated and unsaturated diols and unsaturated hydroxy acids, which are useful as monomers in the polymer industry.

[0004] The ratio of the amount of substrate to the amount of catalyst is called the Catalytic Cycle Number (TON), an important indicator of catalytic efficiency. It is reported that no catalytic reaction system to date can achieve a TON of more than 4,000 without any additives. Summary of the Invention

[0005] To address the aforementioned issues in the prior art telomerization reaction of 1,3-butadiene with carbon dioxide, the present invention provides the design, synthesis, and application of a hydroxyl-containing phosphine ligand. This ligand has the advantage of enabling the palladium-catalyzed synthesis of δ-caprolactone from 1,3-butadiene with carbon dioxide in an additive-free reaction system, thereby enhancing the catalytic activity. Specifically, the present invention includes the following technical solutions.

[0006] A phosphine ligand is a compound having at least one hydroxyl group (phenolic hydroxyl group) on at least one benzene ring in a triphenylphosphine molecule.

[0007] Furthermore, the phosphine ligand is a compound having a hydroxyl group on a benzene ring in a triphenylphosphine molecule.

[0008] Furthermore, at least one phenyl ring in the triphenylphosphine molecule has at least one alkyl group, wherein the alkyl group is a C1-C4 alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and tert-butyl. Preferably, the alkyl group is methyl or ethyl, more preferably methyl. The hydroxyl group and the alkyl group are located on the same phenyl ring or on different phenyl rings.

[0009] Preferably, one of the benzene rings in the triphenylphosphine molecule has an alkyl group, such as a methyl group.

[0010] In a preferred embodiment, the phosphine ligand is selected from the group consisting of compounds I-1, I-2, I-3, I-4 and I-5:

[0011]

[0012] Preferably, the phosphine ligand is a compound represented by formula I-1:

[0013]

[0014] It is a compound having a para-hydroxyl group (phenolic hydroxyl group) on one benzene ring in the triphenylphosphine molecule.

[0015] A second aspect of the present invention provides a method for preparing phosphine ligands I-1, I-2, I-3 and I-4, comprising the following steps:

[0016] The phenol compounds iodinated at the ortho, meta, and para positions are reacted with diphenylphosphine hydrogen HPPh2, palladium acetate Pd(OAc)2, and potassium acetate KOAc to obtain compounds represented by formulas I-1, I-2, I-3, and I-4:

[0017]

[0018] Specifically, the reaction steps are: adding an ortho-, meta- or para-iodinated phenol compound to anhydrous DMAC in an inert gas atmosphere (such as nitrogen or argon) with diphenylphosphine hydrogen HPPh2, palladium acetate Pd(OAc)2, and potassium acetate KOAC, respectively, and reacting the mixed liquid at 100-150° C., preferably 130° C., for 1-5 hours, for example, 3 hours. The reaction system is cooled to room temperature and a small amount of water is added to quench the reaction to obtain compounds represented by Formulas I-1, I-2, I-3, and I-4.

[0019] Preferably, the above method further comprises the following post-processing steps: extraction, washing, drying, and column chromatography separation to obtain a pure compound.

[0020] The column chromatography condition may be eluent EA:PE=1:10-30:1.

[0021] The third aspect of the present invention provides the use of the above-mentioned phosphine ligand in the palladium-catalyzed reaction of 1,3-butadiene and carbon dioxide to produce δ-caprolactone.

[0022] In one embodiment, the phosphine ligand in the above application is selected from compounds I-1, I-2, I-3, I-4, and I-5.

[0023] The phosphine ligand of the present invention can be used in the palladium-catalyzed reaction of 1,3-butadiene and carbon dioxide to synthesize δ-caprolactone. Without the need to add other co-catalysts such as protonic acids, the reaction activity can be significantly improved, and the TON is increased to above 4600. Another important indicator, TOF (turnover frequency, the number of reactant molecules converted at each active center per unit time), is also improved to above 550, thus having potential prospects for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of compound I-1 of the present invention.

[0025] Figure 2 is the nuclear magnetic resonance phosphorus spectrum of compound I-1 of the present invention.

[0026] Figure 3 It is the hydrogen nuclear magnetic resonance spectrum of compound I-2 of the present invention.

[0027] Figure 4 It is the nuclear magnetic resonance phosphorus spectrum of compound I-2 of the present invention.

[0028] Figure 5 It is the hydrogen nuclear magnetic resonance spectrum of compound I-3 of the present invention.

[0029] Figure 6 It is the nuclear magnetic resonance phosphorus spectrum of compound I-3 of the present invention.

[0030] Figure 7 is the hydrogen nuclear magnetic resonance spectrum of compound I-4 of the present invention.

[0031] Figure 8 is the nuclear magnetic resonance phosphorus spectrum of compound I-4 of the present invention.

[0032] Figure 9 is the hydrogen nuclear magnetic resonance spectrum of compound (c) in Example 5 of the present invention.

[0033] Figure 10 This is the nuclear magnetic resonance phosphorus spectrum of compound (c) in Example 5 of the present invention.

[0034] Figure 11 It is the hydrogen nuclear magnetic resonance spectrum of compound I-5 of the present invention.

[0035] Figure 12 It is the nuclear magnetic resonance phosphorus spectrum of compound I-5 of the present invention.

[0036] Figure 13 This is the nuclear magnetic resonance phosphorus spectrum of the δ-lactone compound prepared in Example 6 of the present invention. DETAILED DESCRIPTION

[0037] In our research on the palladium-catalyzed polymerization of 1,3-butadiene with carbon dioxide, we focused on the ligands of the primary catalyst, the palladium salt. In telomerization, the ligands of palladium salts typically include monophosphine and bisphosphine ligands. For triphenylphosphine, a monophosphine ligand, we conducted various modifications, including substituting various polar and nonpolar groups on one, two, or three benzene rings. Ultimately, we discovered that the presence of polar phenolic hydroxyl groups significantly altered the ligand's activity and allowed the coexistence of nonpolar short-chain alkyl groups, such as methyl, within the triphenylphosphine molecule.

[0038] When the triphenylphosphine derivative compounds I-1, I-2, I-3, I-4 and I-5 containing phenolic hydroxyl groups of the present invention are used as catalyst ligands to participate in the palladium-catalyzed reaction of 1,3-butadiene and carbon dioxide to produce δ-caprolactone, high chemical selectivity and good reaction activity can be obtained.

[0039] Herein, the term "compound represented by formula X" is sometimes expressed as "compound X", which is understandable to those skilled in the art. For example, the compound represented by formula I and compound I both refer to the same compound.

[0040] In the embodiments of the present invention for synthesizing compounds I-1, I-2, I-3, I-4 and I-5, after the reaction of each step is completed, purification operations such as filtration, washing, and drying can be performed according to common knowledge in the art.

[0041] The present invention is further described below by way of examples. It should be understood that these examples are intended for illustrative purposes only and are not intended to limit the present invention. Various changes or adjustments made by those skilled in the art based on the present invention are intended to fall within the scope of the present invention.

[0042] This article involves the addition amount, content and concentration of various substances, and the percentages mentioned therein, unless otherwise specified, refer to the percentage by mass.

[0043] In the examples herein, if no specific description is given for the reaction temperature or the operating temperature, the temperature generally refers to room temperature (15-30° C.).

[0044] Example

[0045] Reagents: The reactants and catalysts used in the examples of the present invention were all chemically pure and used directly or after simple purification as needed; organic solvents and other materials were all analytically pure and used directly. All reagents were purchased from China National Pharmaceutical (Group) Shanghai Chemical Reagent Company.

[0046] Testing instruments:

[0047] NMR instrument models: Bruker avance HD 600 MHz, Bruker avance III 500 MHz;

[0048] Mass spectrometer (liquid chromatography-mass spectrometry (LCMS)), model: Agilent 6120B, detector: DAD.

[0049] High performance liquid chromatography, model: Shimadzu 20, A detector is ultraviolet absorption detector.

[0050] Gas chromatograph, model: Shimadzu 2030, detector: FID detector.

[0051] Example 1: Preparation of Compound I-1

[0052]

[0053] Weigh p-iodophenol (1.1 g, 5.0 mmol, 1.0 eq) and palladium acetate (11.2 mg, 0.05 mmol, 0.01 eq) into a 100 mL sealed tube, add 10 mL of N,N-dimethylformamide, and degas the resulting suspension in vacuo. Add diphenylphosphine (0.931 g, 5.0 mmol, 1.0 eq) and heat the mixture for 8 hours. 31 The reaction was monitored by P NMR until the phosphorus NMR spectrum 31 The peaks of diphenylphosphine in the P NMR spectrum disappeared completely. The reaction mixture was poured into 40 ml of water, and the isolated product was dissolved in 30 ml of CH2Cl2. The mixture was washed with CH2Cl2 solution (3 × 10 ml), dried over Na2SO4, and evaporated in vacuo to yield a red oily liquid. The crude product was passed through a silica gel column (PE, EA:PE = 1:10) to obtain 932 mg (67% yield) of a white solid. This white solid was confirmed by NMR to be the target compound I-1.

[0054] The H NMR spectrum of compound I-1 is as follows Figure 1 As shown, the phosphorus spectrum is Figure 2 As shown, the NMR data are as follows:

[0055] 1H NMR(500MHz, CDCl3)δ:7.35-7.32(m,6H),7.31-7.26(m,4H),7.25–7.21(m,2H),6.86–6.80(m,2H),5.19(s,1H).

[0056] 31 P NMR (203 MHz, CDCl3) δ-6.93.

[0057] Example 2: Preparation of Compound I-2

[0058]

[0059] Meta-iodophenol (1.1 g, 5.0 mmol, 1.0 eq) and palladium acetate (11.2 mg, 0.05 mmol, 0.01 eq) were weighed into a 100 mL sealed tube, 10 mL of N,N-dimethylformamide was added, and the resulting suspension was degassed in vacuo. Diphenylphosphine (0.93 g, 5.0 mmol, 1.0 eq) was added and the mixture was heated for 8 hours. During the reaction, the reaction was characterized by nuclear magnetic resonance phosphorus spectroscopy. 31 The reaction was monitored by P NMR until 31 The peaks of diphenylphosphine in the P NMR spectrum disappeared completely. The reaction mixture was poured into 40 ml of water, and the isolated product was dissolved in 30 ml of CH2Cl2. The mixture was washed with CH2Cl2 solution (3 × 10 ml), dried over Na2SO4, and evaporated in vacuo to yield a red oily liquid. The crude product was purified by silica gel chromatography (PE, EA:PE = 1:10) to obtain 1.13 g (81% yield) of a white solid. This white solid was confirmed by NMR to be the target compound I-2.

[0060] The H NMR spectrum of compound I-2 is as follows Figure 3 As shown, the phosphorus spectrum is Figure 4 The NMR data are as follows:

[0061] 1 H NMR(500MHz, CDCl3)δ:7.36-7.28(m,10H),7.22(td,J=7.8,1.9Hz,1H),6.90(t, 1H), 6.81 (dd, J=8.2, 2.6Hz, 1H), 6.71 (ddd, J=7.6, 2.6, 1.3Hz, 1H), 4.83 (s, 1H).

[0062] 31 P NMR (203 MHz, CDCl3) δ-5.11.

[0063] Example 3: Preparation of Compound I-3

[0064]

[0065] o-Iodophenol (1.1 g, 5.0 mmol, 1.0 eq) and palladium acetate (11.2 mg, 0.05 mmol, 0.01 eq) were weighed into a 100 mL sealed tube, 10 mL of N,N-dimethylformamide was added, and the resulting suspension was degassed in vacuo. Diphenylphosphine (0.93 g, 5.0 mmol, 1.0 eq) was added and the mixture was heated for 8 hours. 31 The reaction was monitored by P NMR until 31 The peaks of diphenylphosphine in the P NMR spectrum disappeared completely. The reaction mixture was poured into 40 ml of water, and the isolated product was dissolved in 30 ml of CH2Cl2. The mixture was washed with CH2Cl2 solution (3 × 10 ml), dried over Na2SO4, and evaporated in vacuo to yield a red oily liquid. The crude product was purified by silica gel chromatography (PE, EA:PE = 1:10) to obtain 1.015 g (73% yield) of a white solid. This white solid was confirmed by NMR to be the target compound I-3.

[0066] The H NMR spectrum of compound I-3 is as follows Figure 5 As shown, the phosphorus spectrum is Figure 6 As shown, the NMR data are as follows:

[0067] 1 H NMR (500MHz, DMSO-d6) δ: 9.74 (d, J = 2.5Hz, 1H), 7.33-7.26 (m, 6H), 7.15-7.08 (m, 5H), 6.77 (m, 1H), 6.80-6.75 (t, J = 7.5Hz, 1H), 6.42-6.36 (m, 1H).

[0068] 31 P NMR(203MHz,DMSO-d6)δ-17.04.

[0069] Example 4: Preparation of Compound I-4

[0070]

[0071] 4-Iodo-3-methylphenol (1.17 g, 5.0 mmol, 1.0 eq) and palladium acetate (11.2 mg, 0.05 mmol, 0.01 eq) were weighed into a 100 mL sealed tube and 10 mL of N,N-dimethylformamide was added. The resulting suspension was degassed in vacuo. Diphenylphosphine (0.93 g, 5.0 mmol, 1.0 eq) was added and the mixture was heated for 8 hours. 31 The reaction was monitored by PNMR until31 The peaks of diphenylphosphine in the P NMR spectrum disappeared completely. The reaction mixture was poured into 40 ml of water, and the isolated product was dissolved in 30 ml of CH2Cl2. The mixture was washed with CH2Cl2 solution (3 × 10 ml), dried over Na2SO4, and evaporated in vacuo to yield a red oily liquid. The crude product was purified by silica gel chromatography (PE, EA:PE = 1:10) to obtain 375 mg (25.6% yield) of a white solid. This white solid was confirmed by NMR to be the target compound I-4.

[0072] The H NMR spectrum of compound I-4 is as follows Figure 7 As shown, the phosphorus spectrum is Figure 8 As shown, the NMR data are as follows:

[0073] 1 H NMR(500MHz, CDCl3)δ:7.35-7.30(m,6H),7.28–7.22(m,4H),6.74–6.69(m,1H),6 .66(dd,J=8.3,4.3Hz,1H),6.57(dd,J=8.3,2.6Hz,1H),5.04(s,1H),2.37(s,3H).

[0074] 31 P NMR (203MHz, CDCl3) δ-15.11.

[0075] Example 5: Preparation of Compound I-5

[0076]

[0077] The synthesis method of the hydroxyl-containing phosphine ligand I-5 comprises the following steps:

[0078] 1. Using phenylphosphonium dichloride as raw material, c was synthesized from a and b in one pot. The reaction equation is as follows.

[0079]

[0080] Diethylamine (1.21 g, 16.5 mmol) was added dropwise to a solution of dichlorophenylphosphine (1.477 g, 8.25 mmol) in tetrahydrofuran (40 mL) at -78°C. After the addition was complete, the reaction mixture was warmed to room temperature, stirred for 3 hours, and then filtered to remove the precipitated diethylammonium chloride salt. The solvent was removed under reduced pressure to obtain a pale yellow oil, which was compound (a). o-Tolylmagnesium bromide (8.25 mL, 2 mol / L) was then added at 0°C. After a two-hour reaction, ethereal hydrochloric acid (16.5 mL, 2 mol / L) was added at 0°C. After the addition was complete, the reaction mixture was warmed to room temperature, stirred for 3 hours, and then filtered to remove the precipitate. The solvent was removed under reduced pressure to obtain a colorless oil, which was compound (b). 50 mL of tetrahydrofuran was then added, and p-methoxyphenylmagnesium bromide was added at 0°C. After the addition was complete, the reaction mixture was warmed to room temperature and stirred for 2 hours. Water was added to quench the reaction, and the mixture was extracted three times with diethyl ether. The mixture was then dried over anhydrous sodium sulfate and evaporated in vacuo to yield an oily liquid. The crude product was purified by silica gel chromatography (PE, EA:PE = 1:20) to obtain 1.338 g (53% yield) of a white solid. Nuclear magnetic resonance (NMR) confirmed that this white solid was the intermediate compound (c).

[0081] The H NMR spectrum of compound (c) is as follows Figure 9 As shown, the phosphorus spectrum is Figure 10 As shown, the NMR data are as follows:

[0082] 1 H NMR(600MHz, CDCl3)δ:7.37–7.34(m,3H),7.34–7.20(m,6H),7.14–7.09(m,1H),6.95–6.91(m,2H),6.83–6.78(m,1H),3.84(s,3H),2.41(m,3H).

[0083] 31 P NMR (243MHz, CDCl3) δ-14.92.

[0084] 2. Using compound c as the raw material, the target compound I-5 was synthesized in one step. The reaction equation is as follows.

[0085]

[0086] Compound (c) (1.338 g, 4.3 mmol) obtained in the previous step was added to a 48% aqueous HBr solution (50 mL) and refluxed for 24 h. After cooling to room temperature, the mixture was extracted three times with 50 mL of diethyl ether, dried over Na₂SO₄, and evaporated in vacuo to yield an oily liquid. The crude product was purified by silica gel chromatography (PE, EA:PE = 1:10) to afford 600 mg (47.7% yield) of a white solid. Nuclear magnetic resonance (NMR) confirmed this white solid to be the target compound I-5.

[0087] The H NMR spectrum of compound I-5 is as follows Figure 11 As shown, the phosphorus spectrum is Figure 12 As shown, the NMR data are as follows:

[0088] 1 H NMR(600MHz, CDCl3)δ:7.38–7.35(m,3H),7.32–7.26(m,3H),7.25–7.19(m,3H),7 .15–7.11(m,1H),6.90–6.84(m,2H),6.84–6.79(m,1H),5.62(s,1H),2.40(s,3H).

[0089] 31 P NMR (243MHz, CDCl3) δ-14.82.

[0090] The hydroxyl-containing phosphine ligands prepared in Examples 1-5 can all be used as catalyst ligands for the telomerization reaction of 1,3-butadiene and carbon dioxide. For example, the hydroxyl-containing phosphine ligand I-2 prepared in Example 2 was used as a palladium catalyst ligand to catalyze the reaction of 1,3-butadiene and carbon dioxide to produce δ-lactone.

[0091] Example 6: Application example of compound I-2

[0092]

[0093] A 125 mL stainless steel autoclave was charged with Pd catalyst Pd2(dba)3 (9.2 mg, 0.01 mmol), compound I-2 (0.06 mmol), and a PTFE-coated magnetic stir bar. The autoclave was purged with argon, and MeCN (10 mL) was placed inside to maintain the argon flow. The autoclave was then cooled in an ethyl acetate / liquid nitrogen bath. 1,3-Butadiene (6.0 g, 0.11 mol), pre-purified using two columns filled with P2O5 and a CaO / CaCl2 mixture, was then added to the autoclave via cryogenic liquefaction. The butadiene temperature was below its boiling point (<-4°C). The amount of 1,3-Butadiene added was 6.5 g. The reaction was then filled with 20 bar of carbon dioxide and allowed to react at 80°C for 8 h. After the reaction, isooctane was added as an internal standard. The TON and TOF, as well as the regioselectivity and chemoselectivity of the telomerization product were determined by GC analysis. Gas phase analysis showed that the TON reached 4640, the TOF was 580, the chemical selectivity was 95%, and the regioselectivity was 89%. The H NMR spectrum of the product δ-lactone is as follows: Figure 13 As shown, the NMR data are as follows:

[0094] 1 H NMR(600MHz, CDCl3)δ:7.06–6.99(qt,J=7.3,2.5Hz,1H),5.84–5.74(ddd,J=17.2,10.7,5.4H z,1H),5.28–5.23(dt,J=17.2,1.4Hz,1H),5.16–5.07(dd,J=10.7,1.4Hz,1H),4.72–4.66(ddd t,J=9.7,5.7,3.0,1.5Hz,1H),2.54–2.47(dddd,J=16.3,5.3,3.5,1.8Hz,1H),2.40–2.31(ddd t,J=14.3,10.2,5.9,2.1Hz,1H),2.01–1.94(dtd,J=13.9,5.4,2.8Hz,1H),1.76–1.61(m,4H).

[0095] The above embodiments are merely exemplary embodiments of the present invention, and the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. Use of a phosphine ligand selected from the following compounds I-1, I-2, I-4, and I-5 in the palladium-catalyzed reaction of 1,3-butadiene with carbon dioxide to produce δ-caprolactone:

2. The use according to claim 1, characterized in that The phosphine ligand is compound I-1.

3. The use according to claim 1, characterized in that The preparation method of the compounds I-1, I-2 and I-4 comprises the following steps: The meta- and para-iodinated phenol compounds react with diphenylphosphine hydrogen HPPh2, palladium acetate Pd(OAc)2, and potassium acetate KOAc to obtain compounds represented by formulas I-1, I-2, and I-4, respectively:

4. The use according to claim 3, characterized in that The steps are as follows: adding a meta- or para-iodinated phenol compound, diphenylphosphine hydrogen HPPh2, palladium acetate Pd(OAc)2, and potassium acetate KOAC to anhydrous DMAC in an inert gas atmosphere, reacting the mixed liquid at 100-150° C. for 1-5 hours, cooling the reaction system to room temperature, and quenching the reaction with water to obtain compounds represented by formulas I-1, I-2, and I-4.

5. The use according to claim 4, characterized in that The method further comprises the following post-processing steps: extraction, washing, drying, and column chromatography separation to obtain a pure compound.

6. The use according to claim 5, characterized in that The column chromatography condition is that the eluent EA:PE=1:10-30:1.

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