A bisphosphine ligand containing an indole group, and its preparation method and application

Abstract

The present invention relates to the field of catalytic technology, and in particular to an indole-containing bisphosphine ligand, its preparation method, and application. The present invention provides an indole-containing bisphosphine ligand having a structure as shown in formula (I): wherein R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, alkoxy, hydrocarbon, substituted or unsubstituted aryl, and heterocyclic rings; and Ar is selected from any one of substituted or unsubstituted aryl and aromatic heterocyclic rings. The present invention introduces an indole group by designing the structure of the bisphosphine ligand, thereby improving its stability. As a catalyst for the carbonyl esterification reaction of olefins, the bisphosphine ligand improves olefin conversion, product yield, and product regioselectivity.

Description

Technical Field

[0001] The present invention relates to the field of catalysis technology, in particular to an indole-containing bisphosphine ligand and a preparation method and application thereof. Background Art

[0002] Bidentate phosphine ligands, particularly 1,2-bis(di-tert-butylphosphinomethyl)benzene (DTPBX), are considered among the best ligands for the carbonyl esterification of a range of unsaturated hydrocarbons. These ligands, when used in conjunction with palladium catalysts, provide the basis for the commercial production of methyl methacrylate (MMA) and exhibit high selectivity for the esterification of terminal or internal double bonds.

[0003] In 1976, Shaw first synthesized the bisphosphine ligand DTPBX by reacting o-dibenzyl bromide with di-tert-butylphosphine, followed by base treatment of the reaction mixture to obtain the target product. In 1999, Eastham, Thorpe, and others proposed a method for preparing the bisphosphine ligand DTPBX. This method was improved by Tooze and others in 2002, enabling the commercial synthesis of DTPBX. This method primarily involves the reaction of iodine-activated magnesium powder with o-dibenzyl chloride to prepare a difunctionalized Grignard reagent, which is then reacted with di-tert-butylphosphonium chloride to obtain the target product. This method requires an increased ratio of di-tert-butylphosphonium chloride to the difunctionalized Grignard reagent to obtain DTPBX in a 58% yield.

[0004] To further enhance the branched-chain selectivity of olefin carbonyl esterification, a series of alkyl-containing bisphosphine ligands have been designed and have shown promising applications. In 2017, Meurs et al. designed and synthesized the bisphosphine ligand 1,2-bis(4-phosphino)xylene (BPX), demonstrating high selectivity for olefin carbonyl esterification across a broad substrate range. Furthermore, Beller et al. designed and synthesized a bisphosphine ligand with a tert-butylpyridine functional group, which yielded high yields and linear selectivity for tetramethylethylene.

[0005] Although a variety of bisphosphine ligands have been designed and synthesized and widely used in the carbonyl esterification reaction of olefins, there are still characteristics such as poor selectivity of the catalytic esterification reaction, single ligand structure and poor stability, which limit industrial application. Therefore, the design and synthesis of bisphosphine ligands for carbonyl esterification reaction is of great significance.

[0006] In view of this, this invention is proposed. Summary of the Invention

[0007] The first object of the present invention is to provide a bisphosphine ligand containing an indole group. By designing the structure of the bisphosphine ligand, the indole group is used as an electron-rich and sterically hindered functional group to improve the activation ability for CO and the coordination ability of phosphine with metals. The bisphosphine ligand is used as a catalyst for the carbonyl esterification reaction of olefins, and has good stability, thereby improving the conversion rate of olefins and the regioselectivity of the product.

[0008] The second object of the present invention is to provide a method for preparing an indole-containing bisphosphine ligand, which has simple steps and high yield.

[0009] The third object of the present invention is to provide a method for preparing ester compounds by carbonyl esterification of olefins, which greatly improves the conversion rate of raw materials, the yield of products and the regioselectivity of products in the carbonyl esterification reaction.

[0010] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are adopted:

[0011] The present invention provides an indole-containing bisphosphine ligand having a structure as shown in formula (I):

[0012] In the formula, R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, alkoxy, hydrocarbon, substituted or unsubstituted aryl, and heterocyclic ring; Ar is selected from any one of substituted or unsubstituted aryl and aromatic heterocyclic ring.

[0013] Furthermore, R1 is selected from any one of hydrogen, halogen, C1-C5 branched or straight-chain alkoxy, C1-C5 branched or straight-chain hydrocarbon; Ar is selected from any one of phenyl, naphthyl, pyridyl, pyrazinyl and quinoxaline groups.

[0014] The present invention also provides a method for preparing the above-mentioned indole-containing bisphosphine ligand, comprising the following steps:

[0015] S1, compound A, tert-butylphosphonium dichloride and a hydrogen extraction agent are reacted in an organic solvent to obtain compound II;

[0016] S2, compound B, n-butyl lithium, sodium tert-butoxide and tetramethylethylenediamine are subjected to a second reaction in an organic solvent to obtain a reaction solution; the reaction solution is subjected to a third reaction with the compound II to obtain the indole-containing bisphosphine ligand;

[0017] Wherein, the structural formula of the compound A is: The structural formula of the compound B is The structural formula of the compound II is: In the formula, R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, alkoxy, hydrocarbon, substituted or unsubstituted aryl, and heterocyclic ring; Ar is selected from any one of substituted or unsubstituted aryl and aromatic heterocyclic ring.

[0018] Furthermore, in step S1, the hydrogen removal reagent includes n-butyl lithium and / or sodium hydride.

[0019] Furthermore, in step S1, the molar ratio of the compound A, the tert-butyl phosphorus dichloride and the hydrogenation reagent is 1:(1.05-3):(1.1-3).

[0020] Furthermore, in step S1, the temperature of the first reaction is -80°C to 50°C, and the time of the first reaction is 3 to 48 hours.

[0021] Furthermore, in step S2, the molar ratio of the compound B, the sodium tert-butoxide, the tetramethylethylenediamine and the n-butyllithium is 1:(2-5):(3-5):(2-5);

[0022] And / or, the molar ratio of the compound B to the compound II is 1:(2-5).

[0023] Furthermore, in step S2, the temperature of the second reaction is -80°C to 80°C, and the time of the second reaction is 3 to 36 hours;

[0024] And / or, the temperature of the third reaction is -30 to 50° C., and the time of the third reaction is 12 to 48 hours.

[0025] The present invention also provides a method for preparing ester compounds by carbonyl esterification of olefins, which uses the above-mentioned indole-containing bisphosphine ligand.

[0026] Furthermore, the method for preparing ester compounds by carbonyl esterification of olefins comprises the following steps:

[0027] The olefin, carbon monoxide, a hydroxy compound, a metal catalyst, the indole-containing bisphosphine ligand and an acid react to obtain the ester compound.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The indole-containing bisphosphine ligand provided by the present invention is designed by introducing indole as an electron-rich and sterically hindered functional group, thereby improving the activation ability for CO and the coordination ability of phosphine with metals, and having good stability. The bisphosphine ligand is applied to the carbonyl esterification reaction of olefins involving CO, and is coordinated with a metal catalyst to serve as a catalyst for the reaction, thereby improving the conversion rate of olefins, the yield of the product, and the regioselectivity of the product. DETAILED DESCRIPTION

[0030] The technical scheme of the present invention will be clearly and completely described below in conjunction with specific embodiments, but it will be understood by those skilled in the art that the following described embodiments are part of embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work premise belong to the scope of protection of the present invention. Those who do not specify specific conditions in the embodiments are carried out according to normal conditions or the conditions recommended by the manufacturer. Those whose reagents or instruments are not specified by the manufacturer are conventional products that can be purchased commercially.

[0031] In some embodiments of the present invention, an indole-containing bisphosphine ligand is provided, having a structure as shown in formula (I):

[0032] In the formula, R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, alkoxy, hydrocarbon, substituted or unsubstituted aryl, and heterocyclic ring; Ar is selected from any one of substituted or unsubstituted aryl and aromatic heterocyclic ring.

[0033] The indole-containing bisphosphine ligand provided by the present invention is designed by introducing indole as an electron-rich and sterically hindered functional group to improve the activation ability for CO and the coordination ability of phosphine with metals. The indole-containing bisphosphine ligand has good stability. When applied to the carbonyl esterification reaction of olefins, the conversion rate of olefins and the regioselectivity of the products are improved.

[0034] In some embodiments of the present invention, the alkoxy group includes a C1 to C20 branched or straight chain alkoxy group; for example, methoxy, ethoxy, propoxy; preferably, the alkoxy group includes a C1 to C10 branched or straight chain alkoxy group; more preferably, the alkoxy group includes a C1 to C5 branched or straight chain alkoxy group; more preferably, the alkoxy group is selected from methoxy or ethoxy.

[0035] In some embodiments of the present invention, the hydrocarbon group includes a branched or straight-chain hydrocarbon group of C1 to C20; for example: methyl, ethyl, allyl, isopropyl, tert-butyl, adamantane; preferably, the hydrocarbon group includes a branched or straight-chain hydrocarbon group of C1 to C10; more preferably, the hydrocarbon group includes a branched or straight-chain hydrocarbon group of C1 to C5; more preferably, the hydrocarbon group is selected from any one of methyl, ethyl and isopropyl.

[0036] In some embodiments of the present invention, the substituted or unsubstituted aryl group includes a substituted or unsubstituted aryl group of C1 to C24; for example, phenyl, benzyl, naphthyl, biphenyl, indenyl, 4-methoxyphenyl, 4-methylphenyl, 3,5-dimethylphenyl; preferably, the substituted or unsubstituted aryl group includes a substituted or unsubstituted phenyl group of C1 to C24; more preferably, the substituted or unsubstituted aryl group includes a substituted or unsubstituted phenyl group of C5 to C8; more preferably, the substituted or unsubstituted aryl group is selected from any one of phenyl, benzyl, naphthyl, biphenyl, 4-methoxyphenyl and 4-methylphenyl.

[0037] In some embodiments of the present invention, the aromatic heterocyclic group includes an aromatic heterocycle containing at least one heteroatom of N, O and S; for example, a thiophene group, a furan group, a pyrrole group, a pyrazole group, a pyridine group, a pyrazine group, an indole group, a benzofuran group, a benzothiophene group, a pyrimidine group, a quinoxaline group; preferably, the aromatic heterocyclic group is selected from at least one of a thiophene group, a furan group, a pyrrole group, an indole group and a quinoxaline group.

[0038] In some embodiments of the present invention, R1 is selected from any one of hydrogen, halogen, C1-C5 branched or straight-chain alkoxy, C1-C5 branched or straight-chain hydrocarbon; Ar is selected from any one of phenyl, naphthyl, pyridyl, pyrazinyl and quinoxaline groups.

[0039] In some embodiments of the present invention, the indole-containing bisphosphine ligand mainly includes at least one of the following compounds, and can also be prepared by combining other indole-containing bisphosphine ligands containing o-dimethyl substituted or unsubstituted aromatic groups, aromatic heterocyclic groups and indole-containing phosphine chloride reagents.

[0040]

[0041]

[0042] In some embodiments of the present invention, a method for preparing the above-mentioned indole-containing bisphosphine ligand is also provided, comprising the following steps:

[0043] S1, compound A, tert-butylphosphonium dichloride and a hydrogen extraction agent are reacted in an organic solvent to obtain compound II;

[0044] S2, compound B, n-butyl lithium, sodium tert-butoxide and tetramethylethylenediamine are subjected to a second reaction in an organic solvent to obtain a reaction solution; the reaction solution is subjected to a third reaction with compound II to obtain an indole-containing bisphosphine ligand;

[0045] Wherein, the structural formula of compound A is: The structural formula of compound B is The structural formula of compound II is: In the formula, R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, alkoxy, hydrocarbon, substituted or unsubstituted aryl, and heterocyclic ring; Ar is selected from any one of substituted or unsubstituted aryl and aromatic heterocyclic ring.

[0046] In some embodiments of the present invention, in step S1, the hydrogen withdrawal reagent includes n-butyllithium (n-BuLi) and / or sodium hydride (NaH).

[0047] The preparation method of the indole-containing bisphosphine ligand of the present invention is as follows:

[0048]

[0049]

[0050] The preparation method of the indole-containing bisphosphine ligand of the present invention has simple steps, wide sources of raw materials, high selectivity, and can prepare the indole-containing bisphosphine ligand in high yield.

[0051] In some embodiments of the present invention, in step S1, the molar ratio of compound A to tert-butyl phosphorus dichloride is 1:(1.05-3); typically but not limiting, for example, the molar ratio of compound A to tert-butyl phosphorus dichloride can be 1:1.05, 1:1.5, 1:2, 1:2.5, 1:3 or a range of any two thereof; preferably 1:(1.3-1.8).

[0052] In some embodiments of the present invention, in step S1, the molar ratio of compound A to the hydrogenation agent is 1:(1.1-3); typically but not limiting, for example, the molar ratio of compound A to the hydrogenation agent can be 1:1.1, 1:1.5, 1:2, 1:2.5, 1:3 or a range of any two thereof; preferably 1:(1.1-1.5).

[0053] In some embodiments of the present invention, in step S1, the organic solvent includes at least one of diethyl ether, tetrahydrofuran, n-hexane and toluene; preferably n-hexane.

[0054] In some embodiments of the present invention, in step S1, the temperature of the first reaction is -80°C to 50°C, and the time of the first reaction is 3 to 48 hours; typically but not limitatively, for example, the temperature of the first reaction can be -80°C, -60°C, -40°C, -20°C, 0°C, 20°C, 40°C, 50°C or a range consisting of any two thereof, preferably -40°C to 30°C; the time of the first reaction can be 3h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, 48h or a range consisting of any two thereof; preferably 10 to 30h.

[0055] In some embodiments of the present invention, in step S1, after the first reaction, the process further includes successively drying the organic solvent (ie, removing the organic solvent using a rotary evaporator) and distilling under reduced pressure.

[0056] In some embodiments of the present invention, in step S2, the molar ratio of compound B, sodium tert-butoxide (t-BuONa), tetramethylethylenediamine (TMEDA) and n-butyllithium (n-BuLi) is 1:(2-5):(3-5):(2-5).

[0057] In some embodiments of the present invention, in step S2, the molar ratio of compound B to compound II is 1:(2-5); typically but not limitatively, for example, in step S2, the molar ratio of compound B to compound II can be 1:2, 1:3, 1:4, 1:5 or a range of any two thereof.

[0058] In some embodiments of the present invention, in step S2, the organic solvent includes at least one of diethyl ether, tetrahydrofuran and n-hexane; preferably n-hexane.

[0059] In some embodiments of the present invention, in step S2, the temperature of the second reaction is -80°C to 80°C, and the time of the second reaction is 3 to 36 hours; typically but not limitatively, for example, the temperature of the second reaction can be -80°C, -50°C, -20°C, 0°C, 20°C, 50°C, 80°C or a range consisting of any two thereof, preferably 50 to 70°C; the time of the second reaction can be 3 hours, 10 hours, 15 hours, 20 hours, 25 hours, 30 hours, 36 hours or a range consisting of any two thereof, preferably 3 to 10 hours.

[0060] In some embodiments of the present invention, in step S2, the temperature of the third reaction is -30 to 50°C, and the time of the third reaction is 12 to 48 hours; the temperature of the third reaction can be -30°C, -20°C, 0°C, 20°C, 50°C or a range consisting of any two thereof, preferably 10 to 30°C; the time of the third reaction can be 12h, 15h, 20h, 25h, 30h, 35h, 40h, 48h or a range consisting of any two thereof, preferably 20 to 30h.

[0061] In some embodiments of the present invention, after the third reaction is completed, water is added to quench the reaction, and then the organic phase is separated to obtain an organic phase. Anhydrous sodium sulfate is added to the organic phase for drying, the organic solvent is spin-dried, and recrystallization is performed to obtain an indole-containing bisphosphine ligand; preferably, the recrystallization includes adding methanol for recrystallization.

[0062] In some embodiments of the present invention, a catalyst for olefin carbonyl esterification reaction is also provided, comprising the above-mentioned indole-containing bisphosphine ligand.

[0063] In some embodiments of the present invention, the catalyst for the olefin carbonyl esterification reaction comprises a metal catalyst and an indole-containing bisphosphine ligand; preferably, the metal catalyst comprises a palladium catalyst.

[0064] In some embodiments of the present invention, a method for preparing ester compounds by carbonyl esterification of olefins is also provided, using the above-mentioned indole-containing bisphosphine ligand.

[0065] In some embodiments of the present invention, the method for preparing an ester compound by carbonyl esterification of olefins comprises the following steps:

[0066] Olefins, carbon monoxide, hydroxy compounds, metal catalysts, indole-containing bisphosphine ligands and acids react to obtain ester compounds.

[0067] The indole-containing bisphosphine ligand of the present invention has good stability. When used in the carbonyl esterification reaction of olefins with the participation of CO to prepare ester compounds, it is combined with a metal catalyst to serve as a catalyst for the reaction, thereby significantly improving the olefin conversion rate, product yield and regioselectivity.

[0068] In some embodiments of the present invention, the olefin includes C2 to C20 olefins; preferably, the olefin includes any one of ethylene, propylene, butene and C8 olefins; more preferably, ethylene.

[0069] In some embodiments of the present invention, the hydroxy compound includes any one of methanol, ethanol, isopropanol, n-butanol, tert-butanol, phenol and naphthol; preferably methanol.

[0070] In some embodiments of the present invention, the molar ratio of olefin to carbon monoxide is 1:(1-20); preferably 1:(2-5).

[0071] In some embodiments of the present invention, the molar ratio of the olefin to the hydroxy compound is 1:(2-50); preferably 1:(5-10).

[0072] In some embodiments of the present invention, the metal catalyst comprises a palladium catalyst; preferably, the palladium catalyst comprises at least one of palladium chloride, palladium acetate, palladium acetylacetonate, palladium trifluoroacetate, bis(acetonitrile)palladium dichloride and bisdibenzylideneacetonepalladium.

[0073] In some embodiments of the present invention, the molar ratio of olefin to metal catalyst is 1:(0.01-0.2).

[0074] In some embodiments of the present invention, the molar ratio of the indole-containing bisphosphine ligand to the metal catalyst is (1-5):1.

[0075] In some embodiments of the present invention, the acid comprises at least one of acetic acid, benzoic acid, p-toluenesulfonic acid, pivalic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, and methanesulfonic acid.

[0076] In some embodiments of the present invention, the molar ratio of the acid to the metal catalyst is (10-50):1.

[0077] In some embodiments of the present invention, in the method for preparing ester compounds by carbonyl esterification of olefins, the reaction temperature is 50-150°C.

[0078] In some embodiments of the present invention, in the method for preparing ester compounds by carbonyl esterification of olefins, the reaction time is 12 to 48 hours.

[0079] In some embodiments of the present invention, in the method for preparing ester compounds by carbonyl esterification of olefins, the reaction pressure is 2 to 10 MPa.

[0080] In some embodiments of the present invention, in the method for preparing ester compounds by carbonyl esterification of olefins, the conversion rate of olefins is 70% to 99%, the yield of ester compounds is 75% to 95%, and the regioselectivity of ester compounds is 60% to 93%.

[0081] Example 1

[0082] The preparation method of 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)benzene provided in this embodiment has a synthetic route as follows:

[0083]

[0084] The specific steps include:

[0085] S1. Indole (23.4 g, 200 mmol) and n-hexane (300 mL) were added sequentially to a reaction flask. After completion of the addition, nitrogen was fully replaced three times. The mixture was thoroughly stirred at -30 °C, and n-butyl lithium (added as a 2.5 M n-butyl lithium n-hexane solution, 96 mL, 240 mmol) was added dropwise. After the reaction was continued for 1 h, tert-butyl phosphorus dichloride (47.4 g, 300 mmol) was added dropwise. After completion of the addition, the temperature was slowly raised to 25 °C, and the reaction was continued for 18 h. After complete conversion of indole by TLC, the organic solvent was spin-dried and distilled under reduced pressure to give 31.4 g of light yellow 1-(tert-butylchlorophosphino)-1H-indole in a yield of 66%.

[0086] S2. Add o-xylene (5.33 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) to the reaction flask, stir evenly and fully replace nitrogen, add n-butyl lithium (added in the form of 2.5 M n-butyl lithium n-hexane solution, 50 mL, 125 mmol) dropwise in a low-temperature bath at -30 ° C. After the addition is completed, heat to 60 ° C and react for 5 h. After the reaction is completed, , obtaining a reaction solution; the reaction solution was cooled to -30°C, 1-(tert-butylchlorophosphino)-1H-indole (23.9 g, 100 mmol) was added dropwise, and the temperature was raised to 25°C for reaction for 24 h; after the reaction, water was added to quench the reaction, and the organic phase was obtained by separation, and anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added to recrystallize to obtain a light yellow solid, which is the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)benzene (Ia), with a yield of 61%.

[0087] The H NMR spectrum results of the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0088] 1 H NMR (400MHz, C6D6): δ8.00-7.92(m,4H),7.71-7.68(m,2H),7.41-7.38(m,2H),7 .10-7.14(m,4H),7.00-6.96(m,2H),6.31-6.28(m,2H),3.1(s,4H),1.5(s,18H).

[0089] The high-resolution mass spectrometry results of the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0090] HRMS (APCI): calcd for C 32 H 39 N2P2[M+H] + 513.2500; found 513.2508.

[0091] Example 2

[0092] The preparation method of 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline provided in this embodiment has a synthetic route as follows:

[0093]

[0094] The specific steps include:

[0095] 2,3-Dimethylquinoxaline (7.9 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) were added to the reaction flask and stirred evenly, and then nitrogen was fully replaced. n-Butyl lithium (added in the form of 2.5 M n-Butyl lithium in n-hexane, 50 mL, 125 mmol) was added dropwise in a low-temperature bath at -30 ° C. After the addition was completed, the temperature was raised to 60 ° C for 5 h. After the reaction was completed, the product was obtained. reaction solution; the reaction solution was cooled to -30 ° C, 1-(tert-butylchlorophosphino)-1H-indole (23.9 g, 100 mmol) prepared in Example 1 was added dropwise, and the temperature was raised to 25 ° C for reaction for 36 h; after the reaction, water was added to quench the reaction, and the organic phase was obtained by separation, and anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added to recrystallize to obtain a yellow solid, which is the product 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline (Ib) in a yield of 41%.

[0096] The H NMR spectrum results of the product 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline are as follows:

[0097] 1 H NMR (400MHz, C6D6): δ8.01-7.93(m,6H),7.81-7.75(m,2H),7.67-7.60(m,2H),7. 40-7.33(m,2H),6.91-6.88(m,2H),6.41-6.36(m,2H),2.77(s,4H),1.21(s,18H).

[0098] The high-resolution mass spectrometry results of the product 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline are as follows:

[0099] HRMS (APCI): calcd for C 34 H 39 N4P2[M+H] + 565.2645; found 565.2650.

[0100] Example 3

[0101] The preparation method of 1,1'-((pyridine-2,3-diylmethylene)bis(tert-butylphosphinomethylene))bis(5-methyl-1H-indole) provided in this embodiment has a synthetic route as follows:

[0102]

[0103] The specific steps include:

[0104] S1, in reaction flask, add 5-methyl indole (26.2g, 200mmol) and normal hexane (300mL) successively, fully replace nitrogen three times after adding, at-30 DEG C, fully stir, dropwise add n-butyl lithium (add as the form of 2.5M n-butyl lithium n-hexane solution, 96mL, 240mmol).After sustained reaction 1h, dropwise add tert-butyl phosphorus dichloride (47.4g, 300mmol), after dropping and finishing, slowly warming up to 25 DEG C, react 21h, detect by TLC, after 5-methyl indole is converted completely, be spin-dried for organic solvent, underpressure distillation, obtain 27.8g faint yellow 1-(tert-butyl chlorophosphino)-5-methyl-1H-indole, yield is 58%.

[0105] S2. Add 2,3-dimethylpyridine (5.35 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) into the reaction flask, stir evenly and fully replace nitrogen, add n-butyl lithium dropwise in a low-temperature bath at -30°C (added in the form of 2.5 M n-butyl lithium n-hexane solution, 50 mL, 125 mmol), after the addition is completed, heat to 60°C and react for 5 h. After the reaction is completed, obtain a reaction solution; The reaction mixture was cooled to -30°C, 1-(tert-butylchlorophosphino)-5-methyl-1H-indole (25.3 g, 100 mmol) was added dropwise, and the temperature was raised to 25°C for 30 h. After the reaction, water was added to quench the reaction, and the organic phase was obtained by separation. Anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added for recrystallization to obtain a light yellow solid, which was the product 1,1'-((pyridine-2,3-diylmethylene)bis(tert-butylphosphinomethylene))bis(5-methyl-1H-indole) (Ic) in a yield of 46%.

[0106] The H NMR spectrum results of the product 1,1'-((pyridine-2,3-diylmethylene)bis(tert-butylphosphinomethylene))bis(5-methyl-1H-indole) are as follows:

[0107] 1 H NMR (400MHz, C6D6): δ9.20-9.01(m,2H),8.51-8.49(m,1H),8.01-7.96(m,2H),7.72-7.67(m,2H),7.56-7.54(m,1 H),7.38-7.32(m,2H),7.01-6.98(m,1H),6.36-6.32(m,2H),3.30(s,2H),2.91(s,2H),2.35(s,6H),1.23(s,18H).

[0108] The high-resolution mass spectrometry results of the product 1,1'-((pyridine-2,3-diylmethylene)bis(tert-butylphosphinomethylene))bis(5-methyl-1H-indole) are as follows:

[0109] HRMS (APCI): calcd for C 33 H 42 N3P2[M+H] + 542.2800; found 542.2803.

[0110] Example 4

[0111] The preparation method of 1,2-bis((tert-butyl(5-methoxy-1H-indol-1-yl)phosphino)methyl)benzene provided in this embodiment has a synthetic route as follows:

[0112]

[0113]

[0114] The specific steps include:

[0115] S1, in reaction flask, add 5-methoxy indole (29.4g, 200mmol) and n-hexane (300mL) successively, fully replace nitrogen three times after adding, at-30 DEG C, fully stir, dropwise add n-butyl lithium (add as the form of 2.5M n-butyl lithium n-hexane solution, 96mL, 240mmol).After sustained reaction 1h, dropwise add tert-butyl phosphorus dichloride (47.4g, 300mmol), after dropping and finishing, slowly warming up to 25 DEG C, react 16h, detect by TLC, after 5-methoxy indole is fully converted, be spin-dried for organic solvent, underpressure distillation, obtain 32.8g faint yellow 1-(tert-butyl chlorophosphino)-5-methoxy-1H-indole, yield is 61%.

[0116] S2. Add o-xylene (5.33 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) to the reaction flask, stir evenly and fully replace nitrogen, add n-butyl lithium dropwise in a low-temperature bath at -30 ° C (added in the form of 2.5 M n-butyl lithium n-hexane solution, 50 mL, 125 mmol), after the addition is completed, heat to 60 ° C and react for 5 h. After the reaction is completed, the reaction solution is obtained. The reaction solution was cooled to -30°C, 1-(tert-butylchlorophosphino)-5-methoxy-1H-indole (26.9 g, 100 mmol) was added dropwise, and the temperature was raised to 25°C for 20 h. After the reaction, water was added to quench the reaction, and the organic phase was obtained by separation. Anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added for recrystallization to obtain a light yellow solid, which was the product 1,2-bis((tert-butyl(5-methoxy-1H-indol-1-yl)phosphino)methyl)benzene (Id), with a yield of 53%.

[0117] The H NMR spectrum results of the product 1,2-bis((tert-butyl(5-methoxy-1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0118] 1 H NMR (400MHz, C6D6): δ7.96-7.92(m,4H),7.70-7.65(m,2H),7.10-7.15(m,4H) ),6.65-6.62(m,2H),6.39-6.33(m,2H),3.9(s,6H),2.7(s,4H),1.3(s,18H).

[0119] The high-resolution mass spectrometry results of the product 1,2-bis((tert-butyl(5-methoxy-1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0120] HRMS (APCI): calcd for C 34 H 43 N2O2P2[M+H] + 573.2795;found573.2802.

[0121] Example 5

[0122] The preparation method of 1,2-bis((tert-butyl(5-chloro-1H-indol-1-yl)phosphino)methyl)benzene provided in this embodiment has a synthetic route as follows:

[0123]

[0124] The specific steps include:

[0125] S1, in reaction flask, add 5-chloroindole (30.2g, 200mmol) and normal hexane (300mL) successively, fully replace nitrogen three times after adding, at-30 ℃, fully stir, dropwise add n-Butyl Lithium (add with the form of 2.5M n-Butyl Lithium n-hexane solution, 96mL, 240mmol).After sustained reaction 1h, dropwise add tert-butyl phosphorus dichloride (47.4g, 300mmol), after dripping and finishing, slowly be warming up to 25 ℃, react 30h, detect by TLC, after 5-chloroindole is converted completely, be spin-dried for organic solvent, underpressure distillation, obtain 30.6g faint yellow 1-(tert-butyl chlorophosphino)-5-chloro-1H-indole, yield is 56%.

[0126] S2. Add o-xylene (5.33 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) to the reaction flask, stir evenly and fully replace nitrogen, add n-butyl lithium dropwise in a low-temperature bath at -30 ° C (added in the form of 2.5 M n-butyl lithium in n-hexane solution, 50 mL, 125 mmol), after the addition is completed, heat to 60 ° C and react for 5 h. After the reaction is completed, the reaction mixture is obtained. The reaction solution was cooled to -30 ° C, 1-(tert-butylchlorophosphino)-5-chloro-1H-indole (27.3 g, 100 mmol) was added dropwise, and the temperature was raised to 25 ° C for 24 h; after the reaction, water was added to quench the reaction, and the organic phase was obtained by separation, and anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added to recrystallize to obtain a light yellow solid, which is the product 1,2-bis((tert-butyl(5-chloro-1H-indol-1-yl)phosphino)methyl)benzene (Ie) in a yield of 41%.

[0127] The H NMR spectrum results of the product 1,2-bis((tert-butyl(5-chloro-1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0128] 1 H NMR (400MHz, C6D6): δ8.11-8.08(m,2H),8.00-7.96(m,2H),7.70-7.65(m,2H),7.15-7.08(m,6H),6.40-6.35(m,2H),2.8(s,4H),1.3(s,18H).

[0129] The high-resolution mass spectrometry results of the product 1,2-bis((tert-butyl(5-chloro-1H-indol-1-yl)phosphino)methyl)benzene are as follows:

[0130] HRMS (APCI): calcd for C 32 H 37 Cl2N2P2[M+H]+ 581.1804;found581.1821.

[0131] Example 6

[0132] The preparation method of 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)naphthalene provided in this embodiment has a synthetic route as follows:

[0133]

[0134] The specific steps include:

[0135] 2,3-Dimethylnaphthalene (7.8 g, 50 mmol), sodium tert-butoxide (14.4 g, 150 mmol), tetramethylethylenediamine (23 mL, 150 mmol) and n-hexane (60 mL) were added to the reaction flask and stirred evenly, and then nitrogen was fully replaced. n-Butyl lithium (added in the form of 2.5 M n-Butyl lithium in n-hexane, 50 mL, 125 mmol) was added dropwise in a low-temperature bath at -30 ° C. After the addition was completed, the temperature was raised to 60 ° C for 5 h. After the reaction was completed, the reaction product was obtained. The reaction solution was cooled to -30 ° C, 1-(tert-butylchlorophosphino)-1H-indole (23.9 g, 100 mmol) prepared in Example 1 was added dropwise, and the temperature was raised to 25 ° C for 30 h; after the reaction, water was added to quench the reaction, and the organic phase was obtained by separation, and anhydrous sodium sulfate was added to dry the organic solvent, and methanol was added to recrystallize to obtain a light yellow solid, which is the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)naphthalene (If), and the yield was 55%.

[0136] The H NMR spectrum results of the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)naphthalene are as follows:

[0137] 1 H NMR (400MHz, C6D6): δ7.95-7.83(m,6H),7.68-7.64(m,2H),7.45-7.33(m,6H),6.88-6.85(m,2H),6.39-6.35(m,2H),2.8(s,4H),1.2(s,18H).

[0138] The high-resolution mass spectrometry results of the product 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)naphthalene are as follows:

[0139] HRMS (APCI): calcd for C 36 H 41 N2P2[M+H] + 563.2740; found 563.2727.

[0140] Example 7

[0141] The method for preparing methyl propionate by carbonyl esterification of ethylene provided in this embodiment has a synthetic route as follows:

[0142]

[0143] The specific steps include:

[0144] Under nitrogen protection, palladium acetate (1.12 g, 5 mmol), 1,2-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)benzene (3.98 g, 10 mmol) in Example 1, methanesulfonic acid (1.92 g, 20 mmol), methanol (240 g, 7.5 mol), dodecane (internal standard, 1.7 g, 10 mmol) and ethylene (14 g, 500 mmol) were added to the autoclave in sequence, and carbon monoxide was introduced to a pressure of 6 MPa. The temperature was raised to 100 ° C and the reaction was carried out for 36 h to obtain methyl propionate.

[0145] After the reaction was completed, the reaction solution was cooled to room temperature, diluted, and sampled for GC-MS analysis. The GC-MS results showed that the conversion rate of ethylene was 97.3%, and the yield of methyl propionate was 91.2%.

[0146] Example 8

[0147] The method for preparing n-butyl butyrate by carbonyl esterification of propylene provided in this embodiment has a synthetic route as follows:

[0148]

[0149] The specific steps include:

[0150] Under nitrogen protection, bis(acetylacetonate)palladium (1.52 g, 5 mmol), 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline (4.5 g, 10 mmol) in Example 3, p-toluenesulfonic acid monohydrate (3.8 g, 20 mmol), n-butanol (555 g, 7.5 mol), dodecane (internal standard, 1.7 g, 10 mmol) and propylene (21 g, 500 mmol) were added to the autoclave in sequence, and carbon monoxide was introduced to a pressure of 8 MPa. The temperature was raised to 120 ° C and the reaction was carried out for 30 h to obtain n-butyl butyrate.

[0151] After the reaction, the reaction solution was cooled to room temperature, diluted, and sampled for GC-MS analysis. The GC-MS results showed that the conversion of propylene was 95.6%, the yield of n-butyl butyrate was 90.1%, and the regioselectivity of n-butyl butyrate was 88.2%.

[0152] Example 9

[0153] The method for preparing methyl valerate by carbonyl esterification of butene provided in this embodiment has the following synthetic route:

[0154]

[0155] The specific steps include:

[0156] Under nitrogen protection, bisdibenzylideneacetone palladium (2.88 g, 5 mmol), 1,1'-((pyridine-2,3-diylmethylene)bis(tert-butylphosphinomethylene))bis(5-methyl-1H-indole) (4.27 g, 10 mmol) in Example 2, methanesulfonic acid (1.92 g, 20 mmol), methanol (240 g, 7.5 mol), dodecane (internal standard, 1.7 g, 10 mmol) and butene (28 g, 500 mmol) were added to the autoclave in sequence, and carbon monoxide was introduced to a pressure of 5 MPa. The temperature was raised to 110 ° C and the reaction was carried out for 48 h to obtain methyl valerate.

[0157] After the reaction, the reaction solution was cooled to room temperature, diluted, and sampled for GC-MS analysis. The GC-MS results showed that the conversion of butene was 97.1%, the yield of methyl valerate was 88.2%, and the regioselectivity of methyl valerate was 78.2%.

[0158] Example 10

[0159] The method for preparing methyl nonanoate by carbonyl esterification of octene provided in this embodiment has a synthetic route as follows:

[0160]

[0161] The specific steps include:

[0162] Under nitrogen protection, bis(acetylacetonate)palladium (1.52 g, 5 mmol), 2,3-bis((tert-butyl(1H-indol-1-yl)phosphino)methyl)quinoxaline (4.5 g, 10 mmol) in Example 3, p-toluenesulfonic acid monohydrate (3.8 g, 20 mmol), methanol (240 g, 7.5 mol), dodecane (internal standard, 1.7 g, 10 mmol) and propylene (56 g, 500 mmol) were added to the autoclave in sequence, and carbon monoxide was introduced to a pressure of 6 MPa. The temperature was raised to 120 ° C and the reaction was carried out for 40 h to obtain methyl nonanoate.

[0163] After the reaction, the reaction solution was cooled to room temperature, diluted, and sampled for GC-MS analysis. The GC-MS results showed that the conversion rate of octene was 97.1%, the yield of methyl nonanoate was 93.5%, and the regioselectivity of methyl nonanoate was 81.2%.

[0164] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An indole-containing bisphosphine ligand, characterized in that: It has a structure as shown in formula (I): (I); wherein R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, C1-C20 branched or straight-chain alkoxy, C1-C20 branched or straight-chain hydrocarbon, phenyl, benzyl, naphthyl, biphenyl, indenyl, 4-methoxyphenyl, 4-methylphenyl, and 3,5-dimethylphenyl; and Ar is selected from any one of phenyl, naphthyl, pyridyl, pyrazinyl, and quinoxaline groups.

2. The indole-containing bisphosphine ligand according to claim 1, characterized in that R1 is selected from any one of hydrogen, halogen, C1-C5 branched or straight chain alkoxy, and C1-C5 branched or straight chain hydrocarbon.

3. The method for preparing the indole-containing bisphosphine ligand according to claim 1 or 2, characterized in that: The steps include: S1, compound A, tert-butylphosphonium dichloride and a hydrogen extraction agent are reacted in an organic solvent to obtain compound II; S2, compound B, n-butyl lithium, sodium tert-butoxide and tetramethylethylenediamine are subjected to a second reaction in an organic solvent to obtain a reaction solution; the reaction solution and the compound II are subjected to a third reaction to obtain the indole-containing bisphosphine ligand; Wherein, the structural formula of the compound A is: ; The structural formula of the compound B is ; The structural formula of the compound II is: wherein R1 is selected from any one of hydrogen, halogen, nitro, trifluoromethyl, C1~C20 branched or straight-chain alkoxy, C1~C20 branched or straight-chain hydrocarbon, phenyl, benzyl, naphthyl, biphenyl, indenyl, 4-methoxyphenyl, 4-methylphenyl, 3,5-dimethylphenyl; and Ar is selected from any one of phenyl, naphthyl, pyridyl, pyrazinyl and quinoxaline groups.

4. The method for preparing an indole-containing bisphosphine ligand according to claim 3, wherein: In step S1, the hydrogen removal reagent includes n-butyl lithium and / or sodium hydride.

5. The method for preparing the indole-containing bisphosphine ligand according to claim 3, wherein: In step S1, the molar ratio of the compound A, the tert-butyl phosphorus dichloride and the hydrogenation reagent is 1: (1.05-3): (1.1-3).

6. The method for preparing an indole-containing bisphosphine ligand according to claim 3, wherein: In step S1, the temperature of the first reaction is -80°C to 50°C, and the time of the first reaction is 3 to 48 hours.

7. The method for preparing an indole-containing bisphosphine ligand according to claim 3, wherein: In step S2, the molar ratio of the compound B, the sodium tert-butoxide, the tetramethylethylenediamine and the n-butyllithium is 1:(2-5):(3-5):(2-5); And / or, the molar ratio of the compound B to the compound II is 1:(2-5).

8. The method for preparing an indole-containing bisphosphine ligand according to claim 3, wherein: In step S2, the temperature of the second reaction is -80°C to 80°C, and the time of the second reaction is 3 to 36 hours; And / or, the temperature of the third reaction is -30~50°C, and the time of the third reaction is 12~48h.

9. A method for preparing ester compounds by carbonyl esterification of olefins, characterized in that: The indole-containing bisphosphine ligand according to claim 1 or 2 is used.

10. The method for preparing ester compounds by carbonyl esterification of olefins according to claim 9, characterized in that: The steps include: The olefin, carbon monoxide, a hydroxy compound, a metal catalyst, the indole-containing bisphosphine ligand and an acid react to obtain the ester compound.

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