Novel diphosphine ligand taking bisphenol A as skeleton as well as synthesis method and application of novel diphosphine ligand

Abstract

The invention discloses a novel diphosphine ligand taking bisphenol A as a skeleton, and a synthesis method and application thereof, and particularly relates to a bisphenol A skeleton (such as a compound as shown in a formula II) obtained by taking substituted phenol as a starting material and carrying out reactions such as acid catalysis and hydroxyl alkylation. Carrying out substitution reaction on the bisphenol A skeleton and disubstituted phosphonium chloride to obtain a diphosphine ligand (a compound as shown in a formula I) taking bisphenol A as the skeleton; the invention also discloses an application of the novel diphosphine ligand taking bisphenol A as the skeleton in olefin hydroformylation reaction after the novel diphosphine ligand taking bisphenol A as the skeleton is matched with active metal, for example, a rhodium complex obtained by complexing the novel diphosphine ligand taking bisphenol A as the skeleton with rhodium salt shows excellent activity, selectivity and stability in hydroformylation reaction of 1-octene, 1-decene and dicyclopentadiene.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing a novel bisphosphine ligand with bisphenol A as a skeleton, and application of the novel bisphosphine ligand with bisphenol A as a skeleton in olefin hydroformylation reaction after coordination with an active metal, especially application in 1-octene, 1-decene and dicyclopentadiene hydroformylation reaction. Background Art

[0002] The hydroformylation reaction was discovered by Roelen in 1938. It is a reaction that uses olefins and synthesis gas (carbon monoxide and hydrogen) as raw materials to synthesize aldehydes. Transition metal-catalyzed olefin hydroformylation is a key technology for the production of high-value aldehydes, carboxylic acids, amines and other bulk fine chemicals. Catalysts are the key to controlling the activity and regioselectivity of the reaction. At present, the olefin hydroformylation reaction has developed into the largest homogeneous catalytic reaction in industrial application, with an annual output of more than 10 million tons of high-value-added aldehydes. It is the core technology for the production of fine chemicals such as detergents (annual output value exceeds 46.2 billion US dollars) and plasticizers (annual output value exceeds 13.9 billion US dollars). For a long time, European and American chemical giants, such as Eastman, Dow, DuPont, BASF, Mitsubishi, Shell, etc., have core catalysts and production technologies.

[0003] The linear selective hydroformylation reaction of α-olefins is an industrial production technology for synthesizing butyraldehyde, valeraldehyde, heptanal, octanal, nonanal and their derived alcohol ester products. At present, it is recognized at home and abroad that four generations of linear hydroformylation catalysts have been developed in this field, mainly phosphine ligand-cobalt or rhodium complexes. The first generation catalyst is cobalt without added ligands, and the catalytic reaction conditions are harsh (temperature 110-180℃, pressure 200-300 atmospheres), with high operating costs and safety hazards. There are very few cobalt-based hydroformylation reaction devices still in operation. The second generation catalyst is a cobalt complex with added electrophilic monophosphine ligands, which has improved selectivity and milder reaction conditions (temperature 160-200℃, pressure 50-100 atmospheres). It was developed by Shell in the Netherlands, and the core catalytic technology information has never been disclosed to the public. The third generation catalyst uses rhodium-monodentate organophosphine ligand (triphenylphosphine) as a catalyst, developed by DuPont in the United States, BASF in Germany and Mitsubishi in Japan, etc. It can convert α-olefins into aldehydes at relatively low pressure (<50 atmospheres), relying on the addition of ligands that are dozens of times the amount of metal to stabilize the dominant complex and obtain a more general selectivity. The fourth generation catalyst was developed by Ruhrchemie-Rhonepoulenc and is a rhodium-water-soluble monodentate phosphine ligand (TPPTS) complex. Because it is a two-phase catalytic reaction system, it is also called heterogeneous catalytic technology, but it is only applicable to the hydroformylation of propylene and 1-butene, and on a smaller scale.

[0004] The bidentate phosphine ligand-rhodium catalyst is an improved third-generation catalyst and is the focus of current research. This ligand has a stronger chelating effect and can significantly inhibit the formation of low-selectivity monophosphine-coordinated tricarbonyl rhodium species under synthesis gas conditions, so the linear selectivity is extremely well controlled, and there is no need to add dozens of times the equivalent of ligand. In 1987, Eastman reported the highly linearly selective bidentate phosphine ligand Bisbi. This catalyst can be used continuously for more than two years and is industrially applied to the linear hydroformylation reaction of propylene and 1-hexene, etc., to obtain more than 96% of normal aldehydes to produce plasticizers and polyols. In 2001, Beller and Eastman reported the NaPhos series of ligands with biphenyl structure replaced by binaphthyl and linear selectivity maintained. Based on Casey's preliminary study on the relationship between the natural angle of P-Rh-P and linear selectivity, van Leeuwen and Shell reported the Xantphos series of ligands. Theoretical calculations and experimental studies have shown that the Xantphos ligand has a natural bite angle of 102-121°, which can stabilize the equatorial-equatorial configuration of diphosphine-coordinated dicarbonyl rhodium active species HRh(PP)(CO)2, which is the key to high linear selectivity, with a positive-iso ratio (n / i) as high as 70, but the activity is not high, and it is usually used as a reference ligand. In addition, Union Carbide (now Dow) reported an extremely active and linearly selective electron-deficient bidentate phosphite ligand Biphephos, in the hydroformylation reaction of 1-nonene, the positive-iso ratio reached 99. In 2001, Borner reported a similar electron-deficient Acylphosphite ligand.

[0005] In recent years, the hydroformylation of 1,1-disubstituted olefins to synthesize key monomers of polymer materials has attracted much attention. Dicyclopentadiene (DCPD) is one of the most important components in the C5 fraction of naphtha and fuel oil cracking steam, with a global annual production capacity of more than 200,000 tons. DCPD can be converted into tricyclodecane dicarboxaldehyde (TCDDA) with broad application prospects through hydroformylation, and can be further converted into corresponding alcohols and amine compounds through reduction or amination for the synthesis of pesticides, medicines, lubricants and fragrances. However, due to the presence of two unsaturated double bonds with different activities at the 3,4-position and 8,9-position in its molecular structure, the products of DCPD hydroformylation reaction are usually very complex. In the past few decades, researchers have successively developed catalytic systems with high conversion and high selectivity for this purpose. However, the reaction conditions are relatively harsh, especially for the synthesis of dialdehyde TCDDA, which usually requires high reaction temperature and reaction pressure as well as a large amount of catalyst. The research team of Chen Hua, Wang Lailai and others developed monodentate phosphite ligands and bidentate phosphite amide ligands with 2”-binaphthyl skeleton, biphenyl skeleton, pyridine Pincer skeleton and biindole skeleton. The selectivity of dialdehyde TCDDA can reach 98%, but the corresponding ligands contain unstable phosphite amide or phosphite, which is unlikely to be used in continuous production processes (Catal. Commun. 2014, 50, 29-33; RSC Adv. 2016, 6, 107305-107309; Chin. J. Catal. 2018, 39, 1646-1652; J. Catal. 2023, 422, 77-85; Catal. Today, 2015, 258, 64-69, etc.).

[0006] The novel bisphosphine ligand with bisphenol A as the skeleton developed in the present invention can not only form a natural bite angle similar to the Xantphos series ligands after being coordinated with an active metal, but also has the advantages of cheap and readily available raw materials, easy synthesis, high yield, and suitability for industrial production, and the like. In addition, the catalytic complex obtained after the bisphosphine ligand is coordinated with the active metal has the characteristics of good reaction activity, high selectivity for dialdehyde TCDDA, extremely stable to water and oxygen, and not easy to decompose, and has great practical value. Summary of the invention

[0007] In view of the problems existing in the prior art, the present invention aims to provide a novel bisphosphine ligand with bisphenol A as the skeleton, and a synthesis method and application thereof. The synthesis method has the advantages of cheap and readily available raw materials, short synthesis steps, high yield, simple post-treatment, and suitability for industrial production; and the catalytic complex obtained after the bisphosphine ligand is coordinated with the active metal has the characteristics of good reaction activity, high selectivity for dialdehyde TCDDA, extremely stable to water and oxygen, and not easy to decompose, and has great practical value.

[0008] In order to achieve the above objectives and the above technical effects, the present invention adopts the following technical solutions:

[0009] In a first aspect, the present invention provides a novel bisphosphine ligand with bisphenol A as a skeleton, wherein the bisphosphine ligand has a structure as shown in Formula I:

[0010]

[0011] in:

[0012] R 1 are independently alkyl or alkoxy;

[0013] R 2 are independently alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

[0014] R 3 are independently alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

[0015] R 4 are independently aryl, substituted aryl, heteroaryl or substituted heteroaryl.

[0016] In a preferred embodiment of the present invention,

[0017] R 1 are independently C1-C6 alkyl or C1-C6 alkoxy;

[0018] R 2 are independently C1-C6 alkyl, substituted C1-C6 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl;

[0019] R 3 are independently C1-C6 alkyl, substituted C1-C6 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl;

[0020] R 4 Independently C6-C 10 Aryl, substituted C6-C 10 aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl.

[0021] In a preferred embodiment of the present invention,

[0022] R 1 are independently C1-C4 alkyl or C1-C4 alkoxy;

[0023] R 2 are independently C1-C4 alkyl, substituted C1-C4 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl;

[0024] R 3 are independently C1-C4 alkyl, substituted C1-C4 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl;

[0025] R 4 Independently C6-C 10 Aryl, substituted C6-C 10 aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl.

[0026] In a preferred embodiment of the present invention,

[0027] R 1 are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy or tert-butyloxy;

[0028] R 2 are independently methyl, ethyl, n-propyl, isopropyl,

[0029] R 3 are independently methyl, ethyl, n-propyl, isopropyl,

[0030] R 4 Independently

[0031] In a preferred embodiment of the present invention,

[0032] R 1 are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl;

[0033] R 2 are independently methyl, ethyl, n-propyl or isopropyl;

[0034] R3 are independently methyl, ethyl, n-propyl or isopropyl;

[0035] R 4 Independently

[0036] In a preferred embodiment of the present invention, the bisphosphine ligand has a structure as shown in Formula I':

[0037]

[0038] Among them, R 4 Independently

[0039] In a second aspect, the present invention provides a method for synthesizing a bisphosphine ligand as shown in formula I, the method comprising:

[0040] (1) Under a nitrogen atmosphere, compound V and compound IV react under the catalysis of H2SO4 to obtain compound III, and the reaction formula is:

[0041]

[0042] (2) Under nitrogen atmosphere, compound III and R 3 Y undergoes hydroxyalkylation reaction under the action of K2CO3 to obtain compound II, and the reaction formula is:

[0043]

[0044] wherein Y is F, Cl, Br or I;

[0045] (3) Under nitrogen atmosphere, compound II is ortho-lithiated in n-hexane under the conditions of n-butyl lithium and tetramethylethylenediamine, and then reacted with disubstituted phosphorus chloride to obtain compound I, the reaction formula of which is:

[0046]

[0047] In a preferred embodiment of the present invention,

[0048] In step (1), compound IV is slowly added to a mixture of compound V and H2SO4 at 0°C, and the temperature is raised to 35°C for reaction for 1 to 5 hours. The reaction solution is poured into cold water and stirred for 30 minutes. The precipitate is filtered and washed with cold water to ensure that the filtrate is no longer acidic. The precipitate is dissolved in ethanol and recrystallized to obtain compound III.

[0049] In step (2), compound III and K2CO3 are added to DMF, and R 3 Y is added dropwise to the above solution, and the temperature is raised to 80°C for reaction for 12 to 36 hours after the addition. After cooling to room temperature, the reaction solution is diluted with ethyl acetate, and aqueous hydrochloric acid is added for quenching, extraction, washing, drying, concentration, and purification by column chromatography to obtain compound II; and / or

[0050] In step (3), tetramethylethylenediamine is added to n-butyllithium at room temperature and stirred for 5 minutes, then the above solution is added dropwise to the n-hexane solution of compound II, the temperature is raised to 35°C and stirred for 4.5 hours, and the n-hexane solution of disubstituted phosphorus chloride is added dropwise to the above solution within 10 minutes, the reaction is reacted for 1 to 5 hours, the reaction solution is concentrated, dichloromethane is added to dilute, extraction and washing are performed, the organic phases are combined, filtered with zeolite, the organic phases are concentrated, vacuum dried, left to stand overnight under a nitrogen environment, an appropriate amount of methanol is added to obtain a white precipitate, the white precipitate is filtered, washed with methanol and dried to obtain compound I.

[0051] In a preferred embodiment of the present invention, in step (1), the molar ratio of compound IV to compound V is 1:2-4, preferably 1:2.0-2.5, more preferably 1:2.0;

[0052] In step (2), compound III and R 3 The molar ratio of Y is 1:3 to 10, preferably 1:3 to 5, more preferably 1:4; and / or

[0053] The molar ratio of compound III to K2CO3 is 1:3-10, preferably 1:3-5, and more preferably 1:4.

[0054] In a preferred embodiment of the present invention, in step (3), the molar ratio of compound II to n-butyl lithium is 1:2.0-5.0, preferably 1:2.2-3.0, more preferably 1:2.5;

[0055] The molar ratio of compound II to tetramethylethylenediamine is 1:2.0-5.0, preferably 1:2.2-3.0, more preferably 1:2.5; and / or

[0056] The molar ratio of compound II to disubstituted phosphorus chloride is 1:2.0-5.0, preferably 1:2.2-3.0, and more preferably 1:2.5.

[0057] In a third aspect, the present invention provides the use of a bisphosphine ligand as shown in formula I in an olefin hydroformylation reaction.

[0058] In a preferred embodiment of the present invention, in the olefin hydroformylation reaction, the bisphosphine ligand is used in combination with an active metal to catalyze olefins, carbon monoxide and hydrogen to prepare aldehydes, comprising the following steps:

[0059] Step 1: In a reaction kettle equipped with a stirring and heating device, under the protection of an inert gas, the diphosphine ligand and the active metal are added in sequence, and then a solvent is added, and the complexation is stirred at room temperature for 0.5 to 1 hour;

[0060] Step 2: Under the protection of inert gas, add olefin into the reaction kettle and stir at room temperature for 5 to 10 minutes;

[0061] Step 3: Fill the reactor with carbon monoxide and hydrogen, and react at the reaction pressure and reaction temperature.

[0062] In a preferred embodiment of the present invention, the olefin is C6-C 10 One or more of α-olefins, dicyclopentadiene; preferably, the olefin is 1-octene, 1-decene or dicyclopentadiene;

[0063] The active metal is one or more of rhodium, palladium, cobalt, platinum, and nickel; preferably, the active metal is a salt compound of the active metal, preferably one or more of acetylacetonate, acetate, trifluoroacetate, sulfonate, perchlorate, nitrate, sulfate, phosphate, and halide of the active metal;

[0064] The solvent is one or more of toluene, xylene, dichloromethane, 1,4-dioxane, tetrahydrofuran, ether, methanol, ethanol, and isopropanol, preferably toluene, xylene, or dichloromethane;

[0065] The molar ratio of the bisphosphine ligand to the active metal is 1 to 20:1, preferably 1 to 10:1, more preferably 10:1;

[0066] The molar ratio of the olefin to the active metal is 200 to 10000:1, preferably 200 to 2000:1, more preferably 400 to 600:1, particularly preferably 400:1, 500:1 or 600:1;

[0067] The molar ratio of carbon monoxide to hydrogen is 1 to 3:1, preferably 1:1;

[0068] The reaction pressure of step 3 is 1.0-5.0 MPa, preferably 2.0-4.0 MPa, more preferably 2.0 MPa, 3.0 MPa or 4.0 MPa;

[0069] The reaction temperature of step 3 is 30-100°C, preferably 60-100°C, more preferably 60°C, 70°C, 80°C, 90°C or 100°C; and / or

[0070] The reaction time of step 3 is 1 to 24 hours, preferably 1 to 12 hours, more preferably 1 to 5 hours, particularly preferably 2 hours, 3 hours, 4 hours or 5 hours.

[0071] Compared with the prior art, the technical solution of the present invention has the following positive effects:

[0072] 1. The bisphosphine ligand is a novel bisphosphine ligand with low cost, and its synthesis method has the advantages of cheap and readily available raw materials, short synthesis steps, high yield, simple post-treatment and suitability for industrial production;

[0073] 2. The catalytic complex obtained by combining the diphosphine ligand with the active metal has the characteristics of good reaction activity, high selectivity for dialdehyde TCDDA, extremely stable to water and oxygen, and not easy to decompose, and has great practical value.

[0074] Definitions and general terms

[0075] In general, the term "substituted" means that one or more hydrogen atoms in a given structure or group are replaced by a specific substituent. Unless otherwise indicated, a substituent can be substituted at each reasonable position of the group. When more than one position in the given structural formula can be substituted by one or more specific substituents selected, the substituents can be substituted at each reasonable position in the structural formula in the same or different manner. The substituents described in the present invention include, but are not limited to, D, F, Cl, Br, I, N3, -CN, -NO2, -NH2, -OH, -SH, -COOH, -CONH2, -C(=O)NHCH3, -C(=O)N(CH3)2, alkyl, alkoxy, aryl, heteroaryl, etc.

[0076] In addition, it should be noted that, unless explicitly stated otherwise, the description methods used in the present invention, "each... is independently" and "... are each independently" and "... are independently" can be interchanged and should be understood in a broad sense, which can mean that in different groups, the specific options expressed by the same symbols do not affect each other, or that in the same group, the specific options expressed by the same symbols do not affect each other.

[0077] The term "alkyl" as used herein refers to a saturated, straight-chain or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms, wherein the alkyl group may be optionally substituted with one or more substituents described herein. In one embodiment, the alkyl group contains 1 to 6 carbon atoms; in another embodiment, the alkyl group contains 1 to 4 carbon atoms; in another embodiment, the alkyl group contains 1 to 3 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), and the like.

[0078] The term "alkoxy" means an alkyl group attached to the rest of the molecule via an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy group contains 1-12 carbon atoms. In one embodiment, the alkoxy group contains 1-6 carbon atoms; in another embodiment, the alkoxy group contains 1-4 carbon atoms; in yet another embodiment, the alkoxy group contains 1-3 carbon atoms. The alkoxy group may be optionally substituted with one or more substituents as described herein. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH3), ethoxy (EtO, -OCH2CH3), 1-propoxy (n-propyloxy, n-PrO, n-propoxy, -OCH2CH2CH3), 2-propoxy (isopropyloxy, i-PrO, i-propoxy, -OCH(CH3)2), 1-butoxy (n-BuO, n-butoxy, -OCH2CH2CH2CH3), 2-methyl-1-propoxy (i-BuO, i-butoxy, -OCH2CH(CH3)2), 2-butoxy (s-BuO, s-butoxy, -OCH(CH3)CH2CH3), 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC(CH3)3), and the like.

[0079] The term "aryl" refers to a monocyclic, bicyclic and tricyclic carbocyclic ring system containing 6-14 ring atoms, or 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring system is aromatic, and wherein each ring system comprises a ring consisting of 3-7 atoms. The aryl group is usually, but not necessarily, connected to the parent molecule through the aromatic ring of the aryl group. The aryl group is optionally substituted by one or more substituents described in the present invention. Examples of aryl groups can include, but are not limited to, phenyl, indenyl, naphthyl and anthracenyl.

[0080] The term "heteroaryl" refers to monocyclic, bicyclic and tricyclic ring systems containing 5-12 ring atoms, or 5-10 ring atoms, or 5-6 ring atoms, wherein at least one ring system is aromatic, and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring consisting of 5-7 atoms. The heteroaryl group is usually, but not necessarily, connected to the parent molecule through the aromatic ring of the heteroaryl group. The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, the heteroaryl consisting of 5-10 atoms contains 1,2,3 or 4 heteroatoms independently selected from O, S and N. Examples of heteroaryl groups include, but are not limited to, 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-thienyl, 3-thienyl, pyrazolyl (e.g., 2-pyrazolyl), and the like.

[0081] The term "jk-membered", where j and k are integers greater than 0, and k is greater than j, typically describes the number of ring atoms in the molecule. For example, 5-10 membered heteroaryl means a heteroaryl consisting of 5, 6, 7, 8, 9 or 10 ring atoms. For another example, pyridyl is a 6-membered heteroaryl.

[0082] The term "inert gas" refers to helium, neon, argon, krypton, xenon, radon. DETAILED DESCRIPTION

[0083] The above technical scheme of the present invention is specifically described below by way of examples. It is necessary to point out that the present examples are only used to further illustrate the present invention, but do not constitute any limitation to the present invention. Those skilled in the art may make some non-essential improvements and adjustments based on the content of the present invention.

[0084] Further, specifically, the synthesis method of the novel bisphosphine ligand with bisphenol A as the skeleton involved in the present invention is specifically described as follows:

[0085] Example 1: Preparation of (propane-2,2-diylbis(5-(tert-butyl)-6-methoxy-3,1-phenylene))bis(diphenylphosphine) (L1)

[0086] Step 1) Preparation of 4,4'-(propane-2,2-diyl)bis(2-(tert-butyl)phenol) (Compound 1a)

[0087]

[0088] Under a nitrogen atmosphere, acetone (2.32 mL, 40 mmol) was slowly dripped into a mixture of 2-tert-butylphenol (12 mL, 80 mmol) and H2SO4 (98%, 3 mL), and stirred continuously under an ice bath. After addition, the ice bath was removed and the mixture was stirred at 35 ° C for 2 hours. The mixture was then poured into 40 mL of cold water and stirred for 30 minutes. The precipitate was filtered and washed with cold water to ensure that the filtrate was no longer acidic. The precipitate was dissolved by heating in 20 mL of ethanol and recrystallized at room temperature to obtain 2,2-bis(4-hydroxy-3-tert-butylphenyl)propane (Compound 1a) (white solid, 10.9 g, yield 80%).

[0089] 1 H NMR (400MHz, CDCl3) δ (ppm): 7.12 (d, J = 2.4Hz, 2H, H 3 ),6.90-6.93(dd,2H,J=2.4Hz,H 2 ),6.55(d,J=8Hz,2H,H 1 ),4.78(br s,2H,-OH(H 4 )),1.64(s,6H,C( CH3 )2(H 6 )),1.36(s,18H,C( CH3 )3(H 5 )).

[0090]

[0091] Step 2) Preparation of 4,4'-(propane-2,2-diyl)bis(2-(tert-butyl)-1-methoxybenzene) (Compound 2a)

[0092]

[0093] Under nitrogen atmosphere, 2,2-bis(4-hydroxy-3-tert-butylphenyl)propane (1a, 10 g, 29.4 mmol) and K2CO3 (16.235 g, 117.5 mmol) were added to DMF (50 mL) in sequence, and then CH3I (17 g, 117.5 mmol) was added dropwise to the above solution at 0°C, and stirring was continued at 80°C for 15 hours. After cooling to room temperature, the reaction mixture was diluted with 50 mL of ethyl acetate and quenched with 1M HCl (150 mL). The organic phase and the aqueous phase were collected separately, and the aqueous phase was extracted three times with 100 mL of ethyl acetate. The combined organic phase was washed with saturated brine (350 mL), dried over sodium sulfate, and the solvent was removed by rotary evaporator to obtain a crude mixture, which was separated and purified by column chromatography (petroleum ether: ethyl acetate (V: V) = 20: 1) to obtain the title compound (8.3 g, yield 76%).

[0094] 1H NMR(400MHz,CDCl3)δ(ppm):7.14(d,J=2.8Hz,2H,H 3 ),7.02-7.05(dd,2H,J=2.4Hz,H 2 ),6.76(d,J=8.4Hz,2H,H 1 ),3.80(s,6H,-OCH3(H 4 )),1.65(s,6H,C( CH3 )2(H 6 )),1.31(s,18H,C( CH3 )3(H 5 ));

[0095]

[0096] 13 C NMR(101MHz,CDCl3)δ(ppm):156.28(C4),142.42(C1),137.18(d)(C5),125.53(d)(C3),124.88(d)(C2),110.80(C6),55.05(-OCH3(C11)),42.10( C (CH3)2(C9)),35.02(C( CH3 )2(C10)),31.29( C (CH3)3)(C7),29.87(C( CH3 )3)(C8).

[0097]

[0098] Step 3) (Propane-2,2-diylbis(5-(tert-butyl)-6-methoxy-3,1-phenylene))bis(diphenylphosphine) Preparation of (L1)

[0099]

[0100] Under nitrogen atmosphere, tetramethylethylenediamine (TMEDA, 10.2 mL, 67.8 mmol) was added to n-butyllithium (n-BuLi, 2.5 M in hexane, 27.1 mL, 67.8 mmol) at room temperature and stirred for 5 minutes. This solution was then added dropwise to 2,2-bis(3-tert-butyl-4-methoxyphenyl)propane (2a, 10 g, 27.1 mmol) in 200 mL of n-hexane and stirred at 35 °C for 4.5 hours under nitrogen atmosphere to obtain a yellow suspension. ClPPh2 (12.2 mL, 67.8 mmol) in 30 mL of n-hexane was added dropwise to the above solution within 10 minutes and stirred for 1 hour. The solvent was removed under vacuum, and then dichloromethane (200 mL) and saturated brine (200 mL) were added, and the organic phase and aqueous phase were collected separately, and the aqueous phase was extracted three times with 150 mL of dichloromethane. The combined organic phases were filtered through zeolite, the solvent was removed in a rotary evaporator and dried in vacuo, and the resulting paste compound was left to stand overnight under a nitrogen atmosphere. Methanol (100 mL) was added to obtain a slightly orange solution and a white precipitate. The white solid was filtered, washed with methanol and dried to obtain the title compound (white solid, 8.2 g, 41% yield).

[0101] 1 H NMR(400MHz, CDCl3)δ(ppm):7.21-7.27(m,12H,Ph),7.14-7.18(td,8H,Ph,J 1 =2Hz,J 2 =1.2Hz,J 3 =1.6Hz),6.94-6.95(d,J=2.4Hz,2H,H 1 ),6.48-6.50(q,J=2.4Hz,2H,H 2 ),3.87(s,6H,-OCH3(H 3 )),1.29(s,18H,C( CH3 )3(H 4 )),1.17(s,6H,C( CH3 )2(H 5 ));

[0102]

[0103] 13C NMR(101MHz, CDCl3)δ(ppm):160.73(d)(C4),145.43(C1),141.68(d)(C5),137.76(d)(C12),133.77(d)(C13), 133.56(C6),131.44(C3),129.99(d)(C2),128.51-128.31(C14),127.51(C15),63.39(d,-OCH3(C11)),42.48( C (CH3)2(C9)),35.31(d, C (CH3)3(C7)),31.16(C( CH3 )3)(C8),30.08(C( CH3 )2)(C10);

[0104]

[0105] 31 P NMR (162MHz, CDCl3) δ (ppm): -14.407.

[0106] Further, specifically, the present invention compares and tests the reaction effects of the commercial ligand Xantphos and the novel bisphosphine ligands L1, L2, L3, L4, L5, and L6 (structures shown below) with bisphenol A as the skeleton in the olefin hydroformylation reaction under the same reaction conditions. The test olefins used include 1-octene, 1-decene, and dicyclopentadiene.

[0107]

[0108] Comparative Example 1 :

[0109] Under argon atmosphere, Rh(acac)(CO)2 (10.7 μmol) and ligand Xantphos or L1-6 (107 μmol) were added to a stainless steel reactor, and dichloromethane (1 mL) was added and stirred for 30 minutes to form a catalytic complex of rhodium and ligand. Subsequently, 1-octene (1 mL, 6.4 mmol) or 1-decene (1.25 mL, 6.4 mmol) was added, and after connecting the gas line and fully replacing, a mixture of carbon monoxide and hydrogen (1:1) was filled into the reactor until the total pressure was 2 MPa. The reactor was heated to 60°C. After reacting for 2 hours, the reactor was cooled to room temperature, and samples were taken to determine the substrate conversion rate and product selectivity using a gas chromatograph (GC). The results are shown in Tables 1 and 2:

[0110] Table 1

[0111] serial number Catalytic complex Solvents Conversion rate (%) Aldehyde selectivity (%) <![CDATA[1 a ]]> Rh-X DCM 43.5 92.3 <![CDATA[2 a ]]> Rh-L1 DCM 96.8 97.8 <![CDATA[3 a ]]> Rh-L2 DCM 96.0 98 <![CDATA[4 a ]]> Rh-L3 DCM 96.3 97.0 <![CDATA[5 a ]]> Rh-L4 DCM 96.6 97.5 <![CDATA[6 a ]]> Rh-L5 DCM 96.3 97.1 <![CDATA[7 a ]]> Rh-L6 DCM 96.7 97.3

[0112] a Reaction conditions: S / C = 600 / 1, Rh / L = 1 / 10, CO / H2 (20 bar), 60°C, 2h; dodecane was added as internal standard; X = Xantphos.

[0113] Table 2

[0114] serial number Catalytic complex Solvents Conversion rate (%) Aldehyde selectivity (%) <![CDATA[1 a ]]> Rh-X DCM 32.1 86.6 <![CDATA[2 a ]]> Rh-L1 DCM 63.3 96.5

[0115] a Reaction conditions: S / C = 600 / 1, Rh / L = 1 / 10, CO / H2 (20 bar), 60°C, 2h; dodecane was added as internal standard; X = Xantphos.

[0116] Taking 1-octene as an example (see Table 1), under 20 bar synthesis gas conditions, dichloromethane as solvent, at 60°C, Rh / L molar ratio of 1 / 10, substrate to catalyst (S / C) molar ratio of 600 / 1, it was observed that the new bisphosphine ligand L1-6 with bisphenol A as the skeleton has good chemical selectivity, and the aldehyde selectivity is greater than 97%. At the same time, the activity of the new ligand L1-6 is relatively high, and the activity of the new ligand L1-6 is more than twice that of the standard ligand Xantphos (X).

[0117] Taking 1-decene as an example (see Table 2), under 20 bar synthesis gas conditions, dichloromethane as solvent, at 60°C, Rh / L molar ratio of 1 / 10, substrate to catalyst (S / C) molar ratio of 600 / 1, it was observed that the new bisphosphine ligand L1 with bisphenol A as the skeleton had good chemical selectivity, with an aldehyde selectivity of 96.5%. At the same time, consistent with 1-octene, the activity of the new ligand L1 is about twice that of the standard ligand Xantphos (X).

[0118] Comparative Example 2 :

[0119] Under argon atmosphere, Rh(acac)(CO)2 (10.7 μmol) and ligand Xantphos or L1 (107 μmol) were added to a stainless steel reactor, and o-xylene (1 mL) was added and stirred for 30 minutes to form a catalytic complex of rhodium and ligand. Subsequently, dicyclopentadiene (0.72 mL, 5.3 mmol) was added, and after connecting the gas line and fully replacing, a mixture of carbon monoxide and hydrogen (1:1) was filled into the reactor until the total pressure was 3 MPa. The reactor was heated to 80 ° C. After reacting for 5 or 24 hours, the reactor was cooled to room temperature, and samples were taken to determine the substrate conversion rate and product selectivity using a gas chromatograph (GC). The results are shown in Table 3:

[0120] Table 3

[0121] serial number Catalytic complex Conversion rate (%) Monoaldehyde(%) Dialdehyde(%) <![CDATA[1 a ]]> Rh-X 78.3 60.1 - <![CDATA[2 a ]]> Rh-L1 100 48.5 47.9 <![CDATA[3 b ]]> Rh-X 100 70.5 6.1 <![CDATA[4 b ]]> Rh-L1 100 14.6 80.9

[0122] a Reaction conditions: S / C = 500 / 1, Rh / L = 1 / 10, CO / H2 (30 bar), 80°C, 5 hours; dodecane was added as internal standard; X = Xantphos; b The reaction was continued for 24 hours; - indicates no product was detected.

[0123] Taking dicyclopentadiene as an example (see Table 3), under 30 bar synthesis gas conditions, with dichloromethane as solvent, at 80°C, the Rh / L molar ratio is 1 / 10, and the substrate to catalyst (S / C) molar ratio is 500 / 1, it is observed that the new bisphosphine ligand with bisphenol A as the skeleton has good chemical selectivity. More importantly, when the reaction time is 5 hours, no dialdehyde TCDDA product is observed for the standard ligand Xantphos (X), and the chemical selectivity of the new ligand L1 to generate dialdehyde TCDDA is significantly improved to 47.9%. When the reaction time is increased to 24 hours, the chemical selectivity of the standard ligand Xantphos (X) to generate dialdehyde TCDDA product is 6.1%, and the chemical selectivity of the new ligand L1 to generate dialdehyde TCDDA is further improved to 80.9%, which is much higher than the standard ligand Xantphos (X).

[0124] The above description is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept, which all belong to the protection scope of the present invention.

Claims

1. A novel bisphosphine ligand with bisphenol A as the skeleton, characterized in that: The bisphosphine ligand has a structure as shown in Formula I: in: R 1 are independently C1-C6 alkyl or C1-C6 alkoxy; R 2 are independently C1-C6 alkyl, substituted C1-C6 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl; R 3 are independently C1-C6 alkyl, substituted C1-C6 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl; R 4 Independently C6-C 10 Aryl, substituted C6-C 10 aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl.

2. The bisphosphine ligand according to claim 1, characterized in that: R 1 are independently C1-C4 alkyl or C1-C4 alkoxy; R 2 are independently C1-C4 alkyl, substituted C1-C4 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl; R 3 are independently C1-C4 alkyl, substituted C1-C4 alkyl, C6-C 10 Aryl, substituted C6-C 10 Aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl; R 4 Independently C6-C 10 Aryl, substituted C6-C 10 aryl, 5-10 membered heteroaryl or substituted 5-10 membered heteroaryl.

3. The bisphosphine ligand according to claim 1, characterized in that: R 1 are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy or tert-butyloxy; R 2 are independently methyl, ethyl, n-propyl, isopropyl, R 3 are independently methyl, ethyl, n-propyl, isopropyl, R 4 Independently 4. A method for synthesizing a bisphosphine ligand as claimed in any one of claims 1 to 3, characterized in that: The synthesis method comprises: (1) Under a nitrogen atmosphere, compound V and compound IV react under the catalysis of H2SO4 to obtain compound III, and the reaction formula is: (2) Under nitrogen atmosphere, compound III and R 3 Y undergoes hydroxyalkylation reaction under the action of K2CO3 to obtain compound II, and the reaction formula is: wherein Y is F, Cl, Br or I; (3) Under nitrogen atmosphere, compound II is ortho-lithiated in n-hexane under the conditions of n-butyl lithium and tetramethylethylenediamine, and then reacted with disubstituted phosphorus chloride to obtain compound I, the reaction formula of which is:

5. The method for synthesizing a bisphosphine ligand according to claim 4, characterized in that: In step (1), compound IV is slowly added to a mixture of compound V and H2SO4 at 0°C, and the temperature is raised to 35°C for reaction for 1 to 5 hours. The reaction solution is poured into cold water and stirred for 30 minutes. The precipitate is filtered and washed with cold water to ensure that the filtrate is no longer acidic. The precipitate is dissolved in ethanol and recrystallized to obtain compound III. In step (2), compound III and K2CO3 are added to DMF, and R 3 Y is added dropwise to the above solution, and the temperature is raised to 80°C for reaction for 12 to 36 hours after the addition. After cooling to room temperature, the reaction solution is diluted with ethyl acetate, and aqueous hydrochloric acid is added for quenching, extraction, washing, drying, concentration, and purification by column chromatography to obtain compound II; and / or In step (3), tetramethylethylenediamine is added to n-butyllithium at room temperature and stirred for 5 minutes, then the above solution is added dropwise to the n-hexane solution of compound II, the temperature is raised to 35°C and stirred for 4.5 hours, and the n-hexane solution of disubstituted phosphorus chloride is added dropwise to the above solution within 10 minutes, the reaction is carried out for 1 to 5 hours, the reaction solution is concentrated, dichloromethane is added to dilute, extraction and washing are performed, the organic phases are combined, filtered with zeolite, the organic phases are concentrated, vacuum dried, left to stand overnight under a nitrogen environment, an appropriate amount of methanol is added to obtain a white precipitate, the white precipitate is filtered, washed with methanol and dried to obtain compound I.

6. The method for synthesizing a bisphosphine ligand according to claim 4, characterized in that: In step (1), the molar ratio of compound IV to compound V is 1:2-4, preferably 1:2.0-2.5, more preferably 1:2.0; In step (2), compound III and R 3 The molar ratio of Y is 1:3 to 10, preferably 1:3 to 5, more preferably 1:4; and / or The molar ratio of compound III to K2CO3 is 1:3-10, preferably 1:3-5, and more preferably 1:

4.

7. The method for synthesizing a bisphosphine ligand according to claim 4, characterized in that: In step (3), the molar ratio of compound II to n-butyl lithium is 1:2.0-5.0, preferably 1:2.2-3.0, more preferably 1:2.5; The molar ratio of compound II to tetramethylethylenediamine is 1:2.0-5.0, preferably 1:2.2-3.0, more preferably 1:2.5; and / or The molar ratio of compound II to disubstituted phosphorus chloride is 1:2.0-5.0, preferably 1:2.2-3.0, and more preferably 1:2.

5.

8. Use of the bisphosphine ligand according to any one of claims 1 to 3 or the bisphosphine ligand prepared by the synthesis method according to any one of claims 4 to 7 in olefin hydroformylation reaction.

9. The use according to claim 8, characterized in that: In the olefin hydroformylation reaction, the diphosphine ligand is used in combination with an active metal to catalyze olefins, carbon monoxide and hydrogen to prepare aldehydes, comprising the following steps: Step 1: In a reaction kettle equipped with a stirring and heating device, under the protection of an inert gas, the diphosphine ligand and the active metal are added in sequence, and then a solvent is added, and the complexation is stirred at room temperature for 0.5 to 1 hour; Step 2: Under the protection of inert gas, add olefin into the reaction kettle and stir at room temperature for 5 to 10 minutes; Step 3: Fill the reactor with carbon monoxide and hydrogen, and react at the reaction pressure and reaction temperature.

10. The use according to claim 9, characterized in that: The olefin is C6-C 10 One or more of α-olefins, dicyclopentadiene; preferably, the olefin is 1-octene, 1-decene or dicyclopentadiene; The active metal is one or more of rhodium, palladium, cobalt, platinum, and nickel; preferably, the active metal is a salt compound of the active metal, preferably one or more of acetylacetonate, acetate, trifluoroacetate, sulfonate, perchlorate, nitrate, sulfate, phosphate, and halide of the active metal; The solvent is one or more of toluene, xylene, dichloromethane, 1,4-dioxane, tetrahydrofuran, ether, methanol, ethanol, and isopropanol, preferably toluene, xylene, or dichloromethane; The molar ratio of the bisphosphine ligand to the active metal is 1 to 20:1, preferably 1 to 10:1, more preferably 10:1; The molar ratio of the olefin to the active metal is 200 to 10000:1, preferably 200 to 2000:1, more preferably 400 to 600:1, particularly preferably 400:1, 500:1 or 600:1; The molar ratio of carbon monoxide to hydrogen is 1 to 3:1, preferably 1:1; The reaction pressure of step 3 is 1.0-5.0 MPa, preferably 2.0-4.0 MPa, more preferably 2.0 MPa, 3.0 MPa or 4.0 MPa; The reaction temperature of step 3 is 30-100°C, preferably 60-100°C, more preferably 60°C, 70°C, 80°C, 90°C or 100°C; and / or The reaction time of step 3 is 1 to 24 h, preferably 1 to 12 h, more preferably 1 to 5 h, particularly preferably 2 h, 3 h, 4 h or 5 h.

Images