Rel-(2S, 3R)-2, 3-diisopropyl-2-cyano diethyl succinate compound as well as preparation method and application thereof

Abstract

The invention belongs to the field of catalyst preparation, and relates to a rel-(2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester compound as well as a preparation method and application of the rel-(2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester compound. The compound has a structure as shown in a formula (I), is a pure raceme, has an impurity content of less than 0.1%, and has a nuclear magnetic hydrogen spectrogram basically consistent with a figure 5. The invention provides a pure rel-(2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester compound and a preparation method thereof, and completes the identification of the relative configuration of the rel-(2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester compound. The preparation method is suitable for industrial large-scale production of pure (2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester, and the pure (2S, 3R)-2, 3-diisopropyl-2-cyanosuccinic acid diethyl ester is used as an internal electron donor for preparation of a Ziegler-Natta polypropylene catalyst.

Description

Technical Field

[0001] The present invention belongs to the field of catalyst preparation. Specifically, it relates to rel-(2S,3R)-2,3-diisopropyl-2-cyanobutanedioic acid diethyl ester compound, its preparation method and application. Background Art

[0002] As is well known, internal electron donors are the core components of Ziegler-Natta polypropylene catalysts, which are metaphorically called the DNA of polypropylene catalysts by international scholars. To a great extent, they determine the activity, hydrogen regulation performance and stereospecific ability of the catalysts, and thus determine the microstructure, mechanical properties and processing properties of the resins. The exploration and research of new internal electron donors have always been the basis and important direction for the development of polypropylene catalyst technology. 2,3-Diisopropyl-2-cyanobutanedioic acid diethyl ester is a new type of internal electron donor. Compared with the phthalate internal electron donors used in traditional fourth-generation Z-N catalysts, it not only avoids the use of phthalates (plasticizers), but also endows the catalysts with different properties. The catalysts using this compound as an internal electron donor have excellent comprehensive performance, and the polymers prepared have characteristics such as a wide molecular weight distribution (MWD>12).

[0003] As an excellent new type of internal electron donor, the preparation method of 2,3-diisopropyl-2-cyanobutanedioic acid diethyl ester has always been a research hotspot. Chinese patents CN101811983B, CN101811982B, CN106608935B and WO2010094211 disclose the synthesis methods of this kind of compound and its derivatives and their applications in the preparation of Z-N catalysts. There are two chiral carbon atoms in the 2,3-diisopropyl-2-cyanobutanedioic acid diethyl ester compound, so there are four optically active isomers, and its structure is as Figure 1as shown by A, B, C, and D therein. Among them, compound A and B are enantiomers; compound C and D are enantiomers. Except for the difference in optical rotation performance, the physical and chemical properties of enantiomers are the same. Therefore, their retention times in the achiral capillary column of gas chromatography are the same, and the peak emergence times are the same. Therefore, diethyl 2,3-diisopropyl-2-cyanobutanedioate shows two chromatographic peaks in the achiral capillary column of gas chromatography. In Patent CN106608935B, the one with a shorter retention time is defined as component a, and the one with a longer retention time is defined as component b. Both component a and component b are racemates. Component a may be either the racemate of compound A and B or the racemate of C and D, and it is also uncertain which racemate component b is. A and C or D are diastereomers of each other, and B and C or D are diastereomers of each other. As known from stereochemistry knowledge, diastereomers not only have different optical rotation abilities but also many different physical and chemical properties. This difference in chemical properties has been confirmed in the application of Patent CN106608935B. Due to technical limitations, Patent CN106608935B cannot obtain pure racemic components a and b. The patent prepared a polypropylene catalyst using a mixture of two racemates of component a and component b in different proportions. Experiments have shown that the higher the proportion of component a (whose relative configuration cannot be determined) in the two racemic mixtures, the more it will affect the hydrogen regulation sensitivity of the polypropylene catalyst and the narrower the molecular weight distribution of the prepared polyolefin. The higher the proportion of component b (whose relative configuration cannot be determined), the higher the activity of the prepared catalyst, the better the orientation ability (the higher the isotactic index of the prepared polyolefin), the less sensitive to hydrogen (the lower the melt index of the prepared polyolefin), and the wider the molecular weight distribution of the prepared polymer, which is beneficial to preparing a better catalyst for pipes.

[0004] Due to technical limitations, the preparation methods reported in current patents and literature can only obtain a mixture composed of two racemates of component a and component b, cannot obtain pure racemates, and there is no literature report that can identify the relative configuration of component a or component b. Summary of the Invention

[0005] In view of the limitations of the prior art, the present invention creatively obtains one of the pure racemates of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate, namely the compound rel-(2S,3R)-diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate, and its preparation method. The identification of the relative structure of this racemate is completed, and it is determined that rel-(2S,3R)-diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate is component a in the mixture of two racemates of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate reported in CN106608935B. Moreover, this method has low requirements for equipment, mild reaction conditions, simple operation and is easy to scale up, is environmentally friendly, can efficiently resolve the two racemates, and simultaneously obtain racemates with high purity.

[0006] The first aspect of the present invention provides a rel-(2S,3R)-diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate compound having the structure shown in formula (Ⅰ):

[0007]

[0008] The compound is a pure racemate with an impurity content of less than 0.1%, and has a nuclear magnetic resonance hydrogen spectrum Figure 5 substantially consistent with...

[0009] The second aspect of the present invention provides a preparation method of the above - mentioned compound, including Method 1 or Method 2:

[0010] Method 1 includes the following steps:

[0011] Mix metal alkoxide, aprotic solvent, and ethyl 3 - methyl - 2 - cyanobutyrate to react to form a salt; add ethyl 2 - bromoisovalerate and continue the reaction to form diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate, then filter, remove the solvent, extract, wash, and dry to obtain the crude reaction product; carry out rectification and purification of the crude reaction product in a rectification column, and collect the light distillate at the top of the column; further purify and separate the crude product obtained by rectification using methods such as column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain the pure rel-(2S,3R)-diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate compound; the operating temperature of the rectification column is 60 - 260 °C, the operating pressure is 0.1 - 2800 Pa, and the reflux ratio of rectification is controlled such that the draw ratio to reflux is 1:50 - 10:1;

[0012] Method 2 includes the following steps:

[0013] (i) Mix a metal alkoxide, an aprotic solvent, and ethyl cyanoacetate to react and form a salt; add an alkali metal salt and ethyl 2-bromo-3-methylbutyrate and continue to react to form diethyl 2-cyano-3-isopropylsuccinate; then filter, remove the solvent, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column to obtain diethyl 2-cyano-3-isopropylsuccinate;

[0014] (ii) Mix a metal alkoxide, an aprotic solvent, and diethyl 2-cyano-3-isopropylsuccinate to react and form a salt, add an alkali metal salt and 2-bromopropane and continue to react to form diethyl 2,3-diisopropyl-2-cyanosuccinate; then filter, remove the solvent, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column and collect the light distillate at the top of the column; further purify and separate the rectified crude product by using methods such as column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain the pure product rel-(2S,3R)-2,3-diisopropyl-2-cyanosuccinate compound; the operating temperature of the rectification column is 60 - 260 °C, the operating pressure is 0.1 - 2800 Pa, and the reflux ratio of the rectification is controlled such that the take-off ratio to the reflux is 1:50 - 10:1.

[0015] The third aspect of the present invention provides the use of the above compound in the preparation of a solid catalyst component for olefin polymerization, wherein the compound is used as at least a part of the internal electron donor.

[0016] The present invention provides a pure rel-(2S,3R)-2,3-diisopropyl-2-cyanosuccinate compound and its preparation method, and has completed the identification of its relative configuration. This preparation method is not only applicable to the industrial-scale production of pure (2S,3R)-2,3-diisopropyl-2-cyanosuccinate, enabling it to be used independently as an internal electron donor in the preparation of Ziegler-Natta polypropylene catalysts. It can also be used in the preparation of Ziegler-Natta polypropylene catalysts by mixing the pure rel-(2S,3R)-2,3-diisopropyl-2-cyanosuccinate with a mixture of two racemates of rel-(2S,3R)-2,3-diisopropyl-2-cyanosuccinate or 2,3-diisopropyl-2-cyanosuccinate prepared by the prior art in a certain proportion to prepare two racemic mixtures with different proportions as electron donors with different functions.

[0017] Other features and advantages of the present invention will be described in detail in the following specific implementation section. Brief Description of the Drawings

[0018] The exemplary embodiments of the present invention will be described in more detail by combining with the drawings.

[0019] Figure 1 Shows the structures of four optically active isomers of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate.

[0020] Figure 2 Shows the gas chromatography results of the product after the first rectification in Example 1.

[0021] Figure 3 Shows the gas chromatography results of the product after the second rectification in Example 1.

[0022] Figure 4 Shows the gas chromatography results of the purified product in Example 1.

[0023] Figure 5 Shows the ¹H - NMR results of the purified product in Example 1.

[0024] Figure 6 Shows the ¹³C - NMR results of the purified product in Example 1.

[0025] Figure 7 Shows the HMBC results of the purified product in Example 1.

[0026] Figure 8 Shows the NOESY structure of the purified product in Example 1.

[0027] Figure 9 Shows the gas chromatography results of the product after the first rectification in Example 5.

[0028] Figure 10 Shows the gas chromatography results of the product after the second rectification in Example 5.

[0029] Figure 11 Shows the gas chromatography results of the product after the first rectification in Comparative Example 1. Detailed Description of the Invention

[0030] The following provides a detailed description of the specific embodiments of the present invention. It should be understood that the specific embodiments described herein are only for the purpose of illustrating and explaining the present invention and are not intended to limit the present invention.

[0031] The present invention provides a rel - (2S,3R) - diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate compound having the structure shown in Formula (I):

[0032]

[0033] The compound is a pure racemate, i.e., a mixture of (2S,3R)-diisopropyl 2-cyanobutanedioate and (2R,3S)-diisopropyl 2-cyanobutanedioate in equal proportions, with an impurity content of less than 0.1%, and has a nuclear magnetic resonance hydrogen spectrum Figure 5 substantially consistent with

[0034] Specifically, the characteristic nuclear magnetic resonance hydrogen spectrum of the compound is as follows: 1 1H-NMR(CDCl3 / TMS,500MHz)(δppm): 0.983–0.996(d,3H,CH(CH3)2), 1.008-1.022(d,6H,CH(CH3)2), 1.121–1.134(d,3H,CH(CH3)2), 1.291–1.320(t,3H,CH2CH3), 1.331–1.360(t,3H,CH2CH3), 2.114–2.210(m,1H,CH(CH3)2), 2.238–2.293(m,1H,CH(CH3)2), 2.965–2.980(d,1H,O=CCHCH(CH3)2), 4.173-4.324(m,4H,2OCH2CH3). It can be confirmed that the compound is the rel-(2S,3R)-diisopropyl 2-cyanobutanedioate compound with the structure shown in formula (Ⅰ).

[0035] There are two preparation methods for this compound:

[0036] Method 1 includes the following steps:

[0037] React metal alkoxide, aprotic solvent, and ethyl 3-methyl-2-cyanobutyrate to form a salt; add ethyl 2-bromo-3-methylbutanoate and continue the reaction to form diisopropyl 2-cyanobutanedioate, then filter, remove the solvent, extract, wash, and dry to obtain the crude reaction product; purify the crude reaction product in a distillation column, collect the light fractions at the top of the column; further purify and separate the crude product obtained by distillation (i.e., the light fractions) using methods such as column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain the pure rel-(2S,3R)-diisopropyl 2-cyanobutanedioate compound; the operating temperature of the distillation column is 60-260 °C, the operating pressure is 0.1-2800 Pa, and the reflux ratio of the distillation is controlled such that the take-off ratio to the reflux is 1:50-10:1.

[0038] Method 2 includes the following steps:

[0039] (i) Mix a metal alkoxide, an aprotic solvent, and ethyl cyanoacetate to react and form a salt; add an alkali metal salt and ethyl 2-bromo-3-methylbutyrate and continue the reaction to form diethyl 2-cyano-3-isopropylsuccinate; then filter, remove the solvent, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column to obtain diethyl 2-cyano-3-isopropylsuccinate;

[0040] (ii) Mix a metal alkoxide, an aprotic solvent, and diethyl 2-cyano-3-isopropylsuccinate to react and form a salt; add an alkali metal salt and 2-bromopropane and continue the reaction to form diethyl 2,3-diisopropyl-2-cyanosuccinate; then filter, remove the solvent, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column and collect the light distillate at the top of the column; further purify and separate the rectified crude product (i.e., the light distillate) by using column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain the pure product rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanosuccinate compound; the operating temperature of the rectification column is 60 - 260 °C, the operating pressure is 0.1 - 2800 Pa, and the reflux ratio of rectification is controlled such that the draw ratio to reflux is 1:50 - 10:1.

[0041] In Method 1 and Method 2, the aprotic solvent can be selected from one or more of tetrahydrofuran, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and acetonitrile.

[0042] In Method 1 and Method 2, the metal alkoxide can be an alkali metal alkoxide, preferably selected from one or more of potassium methoxide, potassium ethoxide, potassium n-propoxide, potassium isopropoxide, potassium n-butoxide, potassium isobutoxide, potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium n-propoxide, sodium isopropoxide, sodium n-butoxide, sodium isobutoxide, and sodium tert-butoxide.

[0043] In Method 1, the preferred amounts of each component are as follows: the molar ratio of the metal alkoxide to ethyl 3-methyl-2-cyanobutyrate is 1:0.5 - 2; relative to each gram of ethyl 3-methyl-2-cyanobutyrate, the amount of the aprotic solvent used is 1 - 50 mL; the molar ratio of the raw material ethyl 3-methyl-2-cyanobutyrate to ethyl 2-bromo-3-methylbutyrate is 1:0.5 - 3.

[0044] In Method 1, the temperature of the mixing reaction and the continuing reaction can each independently be 10 - 150 °C, preferably 20 - 120 °C; the pressure of the mixing reaction and the continuing reaction can each independently be 0.8 - 20 atmospheres, preferably 0.8 - 2 atmospheres.

[0045] In Method 1, the number of trays in the rectification column can be 1 - 150, preferably 1 - 60.

[0046] The operating temperature of the rectification column is preferably 100 - 240 °C, for example, it can be 100 °C, 110 °C, 120 °C, 130 °C, 140 °C, 150 °C, 160 °C, 170 °C, 180 °C, 190 °C, 200 °C, 210 °C, 220 °C, 230 °C, 240 °C, and the values between any two of the above numerical points. More preferably, it is 150 - 210 °C.

[0047] In the present invention, a higher vacuum degree than conventional rectification is adopted, and better separation effect can be obtained. The operating pressure of the rectification column is preferably 10 - 2000 Pa, more preferably 50 - 1500 Pa. For example, it can be 50 Pa, 60 Pa, 70 Pa, 80 Pa, 90 Pa, 100 Pa, 200 Pa, 300 Pa, 400 Pa, 500 Pa, 600 Pa, 700 Pa, 800 Pa, 900 Pa, 1000 Pa, 1100 Pa, 1200 Pa, 1300 Pa, 1400 Pa, 1500 Pa, and the values between any two of the above numerical points.

[0048] The reflux ratio of the rectification column is also a control condition. Different from the higher extraction amount in conventional rectification, the reflux ratio in the present invention is preferably controlled such that the extraction - to - reflux ratio is 5:1 - 1:45. Specifically, the extraction - to - reflux ratio can be 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, and the values between any two of the above ratios. Preferably, the extraction - to - reflux ratio is controlled to be 1:2 - 1:40, and more preferably, the extraction - to - reflux ratio is controlled to be 1:10 - 1:30.

[0049] In Method 2, the alkali metal salt is preferably an alkali metal halide, and more preferably one or more of potassium iodide, sodium iodide, and lithium iodide.

[0050] In Method 2, the dosages of each component are preferably as follows: in step (i), the molar ratio of the metal alkoxide to ethyl cyanoacetate is 1:0.5 - 2; for every gram of ethyl cyanoacetate, the dosage of the aprotic solvent is 1 - 50 mL; the molar ratio of the raw material ethyl cyanoacetate to ethyl 2-bromoisovalerate is 1:0.6 - 2; in step (ii), the molar ratio of the metal alkoxide to diethyl 2-cyano-3-isopropylsuccinate is 1:0.5 - 3; for every gram of diethyl 2-cyano-3-isopropylsuccinate, the dosage of the aprotic solvent is 1 - 50 mL; the molar ratio of diethyl 2-cyano-3-isopropylsuccinate to 2-bromopropane is 1:0.8 - 3.

[0051] In step (i) of Method 2, the temperatures of the mixing reaction and the continuous reaction can each independently be 10 - 150 °C, preferably 20 - 120 °C; the pressures of the mixing reaction and the continuous reaction can each independently be 0.8 - 20 atmospheres, preferably 0.8 - 2 atmospheres; in step (ii) of Method 2, the temperature of the mixing reaction can be 20 - 120 °C, the pressure is 0.8 - 20 atmospheres, the temperature of the continuous reaction can be 60 - 120 °C, and the pressure is 0.8 - 20 atmospheres.

[0052] In step (i) of Method 2, the number of trays in the distillation column can be 1 - 150, preferably 1 - 60; the temperature at the bottom of the column can be 120 - 170 °C; the operating pressure can be 0.1 - 3000 Pa, preferably 500 - 2000 Pa; the reflux ratio is controlled such that the ratio of the distillate to the reflux is 1:30 - 30:1, preferably 1:25 - 25:1, and more preferably 1:1 - 10:1.

[0053] In step (ii) of Method 2, the number of trays in the distillation column can be 1 - 150, preferably 1 - 60.

[0054] Similarly to the aforementioned Method 1, the operating temperature of the distillation column is preferably 100 - 240 °C, for example, it can be 100 °C, 110 °C, 120 °C, 130 °C, 140 °C, 150 °C, 160 °C, 170 °C, 180 °C, 190 °C, 200 °C, 210 °C, 220 °C, 230 °C, 240 °C, and the values between any two of the above numerical points, and more preferably 150 - 210 °C.

[0055] The operating pressure of the rectification column is preferably 10 - 2000 Pa, more preferably 50 - 1500 Pa. For example, it can be 50 Pa, 60 Pa, 70 Pa, 80 Pa, 90 Pa, 100 Pa, 200 Pa, 300 Pa, 400 Pa, 500 Pa, 600 Pa, 700 Pa, 800 Pa, 900 Pa, 1000 Pa, 1100 Pa, 1200 Pa, 1300 Pa, 1400 Pa, 1500 Pa, and the values between any two of the above numerical points.

[0056] The reflux ratio of the rectification column is preferably controlled such that the draw ratio to reflux is 5:1 - 1:45. Specifically, it can be 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, and the values between any two of the above ratios; the draw ratio to reflux is further preferably 1:2 - 1:40, and more preferably 1:10 - 1:30.

[0057] According to a specific embodiment of the present invention, in each method and each step, after the product is rectified, column chromatography is further used for purification. In the column chromatography method after rectification, the packing used in the chromatography column is one or more of silica gel, alumina, silica - magnesium adsorbent, C18 packing, and ion - exchange column, and the developing agent used is one or more combinations of petroleum ether, n - hexane, benzene, ether, tetrahydrofuran, ethyl acetate, chloroform, dichloromethane, toluene, xylene, isopropanol, n - butanol, acetonitrile, acetone, ethanol, methanol, and water.

[0058] According to another specific embodiment of the present invention, in each method and each step, after the product is rectified, recrystallization is further used for purification. In the recrystallization method after rectification, the recrystallization solvent is selected from one or more combinations of petroleum ether, n - hexane, benzene, ether, tetrahydrofuran, ethyl acetate, chloroform, dichloromethane, toluene, xylene, isopropanol, n - butanol, acetonitrile, acetone, ethanol, methanol, and water; the recrystallization temperature is - 30°C to 45°C, and the ratio of solute to solvent is 1:0.1 - 10.

[0059] The further purification of the product can also be achieved by combining column chromatography and recrystallization, and the specific conditions of the column chromatography and recrystallization are as described above.

[0060] The above-mentioned compound of the present invention can be used as an internal electron donor in the preparation of solid catalyst components for olefin polymerization, and the solid catalyst components can further be used to prepare Ziegler-Natta polypropylene catalysts.

[0061] There are two chiral carbons in the structure of diethyl 2,3-diisopropyl-2-cyanobutanedioate, so there are four optical isomers. The structures of the optical isomers are as shown by Compounds A, B, C, and D in Figure 1 In the figure, Compound A and Compound B in Component i are enantiomers; Compound C and Compound D in Component ii are enantiomers. The compound with the structure of rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate prepared by the inventor was identified as Component ii through structure identification. The specific rotation of it was tested, and the specific rotation was zero, indicating that Component ii is a racemate.

[0062] The rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate compound prepared by using the synthesis technology of the present invention was subjected to analytical tests such as gas chromatography, 1H NMR, 13C NMR, HMBC NMR, and NOESY NMR, and it was determined that the prepared target compound is a pure rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate compound.

[0063] The diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate prepared by the current process is a mixture of two racemates, showing two chromatographic peaks in a gas chromatographic achiral capillary column, with each peak corresponding to one racemate. Under the same gas chromatographic conditions as in CN106608935A, the gas chromatographic detection of pure rel-(2S,3R)-2,3 - diisopropyl - 2 - cyanobutanedioate racemate was carried out separately. Compared with the gas chromatogram of the mixture of two racemates of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate, it was found that the retention time of the peak of rel-(2S,3R)-2,3 - diisopropyl - 2 - cyanobutanedioate was relatively short, which was the a component in the mixture of two racemates of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate reported in patent CN106608935A. CN106608935A reported that when the content of component a (whose relative configuration could not be determined) was higher, it would affect the hydrogen response sensitivity of the polypropylene catalyst, and the molecular weight distribution of the prepared polyolefin was narrower. The inventor creatively prepared pure rel-(2S,3R)-2,3 - diisopropyl - 2 - cyanobutanedioate, which is not only suitable for industrial scale - up production of pure (2S,3R)-2,3 - diisopropyl - 2 - cyanobutanedioate as an internal electron donor for the preparation of Ziegler - Natta polypropylene catalysts. It can also be mixed in proportion with another racemate rel-(2S,3S)-2,3 - diisopropyl - 2 - cyanobutanedioate or a mixture of two racemates of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate prepared by the prior art to prepare two racemic mixtures with different ratios, which are used as electron donors with different functions for the preparation of Ziegler - Natta polypropylene catalysts.

[0064] The present invention will be further described below in conjunction with embodiments, but the scope of the present invention is not limited to these embodiments.

[0065] Example 1

[0066] Prepare rel-(2S,3R)-2,3 - diisopropyl - 2 - cyanobutanedioate.

[0067] Add 500 g of tetrahydrofuran into a 2-L three-necked flask. Under stirring conditions, add 143.2 g of potassium ethoxide, and then add 264 g of ethyl 3-methyl-2-cyanobutyrate into the reaction flask. Stir at room temperature and atmospheric pressure for 30 min, then add 355.6 g of ethyl 2-bromoisovalerate. Control the reaction temperature at 30 °C and the reaction pressure at atmospheric pressure. React for 8 h. After the reaction is completed, filter, remove the solvent, wash with 100 mL of water, and then extract three times with 300 mL of ether. Collect the organic phase and wash it twice with 100 mL of saturated aqueous sodium bicarbonate solution until the organic phase is neutral. Dry the organic phase, and the crude product after concentrating and removing ether is 567.3 g.

[0068] Add 300 g of the crude product into a 500-mL high-efficiency rectifying column with 35 theoretical plates. Rectify the product under the conditions that the column bottom temperature is 190 °C, the vacuum degree is 800 Pa, and the reflux ratio is controlled such that the take-off ratio to reflux is 1:20. Collect the light fractions at the top of the column and analyze them using gas chromatography. The results are shown in Figure 2 . After deducting the dilution solvent, the purity of diethyl 2,3-diisopropyl-2-cyanobutanedioate is 96.51%. Among them, the content of the racemate with a shorter retention time for peak emergence is 87.428%, and the content of the racemate with a longer retention time for peak emergence is 9.082%. Conduct secondary rectification on it, control the reflux ratio such that the take-off ratio to reflux is 1:20, collect the pre-fractions at the top of the column, and conduct chromatographic analysis. The results are shown in Figure 3 , after deducting the dilution solvent used for chromatography, the purity of diethyl 2,3-diisopropyl-2-cyanobutanedioate is 99.50%, and it is a mixture of two racemates. Among them, the content of the racemate with a shorter retention time for peak emergence is 91.281%, and the content of the racemate with a longer retention time for peak emergence is 8.219%. Then use column chromatography for separation and purification. The stationary phase is silica gel, and the mobile phase is ethyl acetate and petroleum ether with a ratio of 1:9. Obtain the compound with a shorter retention time for peak emergence in gas chromatography and conduct chromatographic analysis on it. The results are shown in Figure 4 , its purity is greater than 99.9%. Identify its structure through 1H NMR. The 1H NMR spectrum is: 11H-NMR (CDCl3 / TMS, 500 MHz) (δ ppm): 0.983–0.996 (d, 3H, CH(CH3)2), 1.008 - 1.022 (d, 6H, CH(CH3)2), 1.121–1.134 (d, 3H, CH(CH3)2), 1.291–1.320 (t, 3H, CH2CH3), 1.331–1.360 (t, 3H, CH2CH3), 2.114–2.210 (m, 1H, CH(CH3)2), 2.238–2.293 (m, 1H, CH(CH3)2), 2.965–2.980 (d, 1H, O=CCHCH(CH3)2), 4.173 - 4.324 (m, 4H, 2OCH2CH3). See the 1H NMR spectrum in Figure 5 。

[0069] The relative configuration was identified and analyzed by 13C NMR, HMBC, and NOESY methods, and its relative structure was determined to be rel-(2S,3R)-diisopropyl 2-cyanobutanedioate. See the test results in Figures 6 - 8 。

[0070] Example 2

[0071] Preparation of rel-(2S,3R)-diisopropyl 2-cyanobutanedioate.

[0072] Take 20 g of the crude product prepared in Example 1, use 15 g of petroleum ether as the recrystallization solvent, and recrystallize it at 25 °C - 8 °C to obtain 3.3 g of pure racemic rel-(2S,3R)-diisopropyl 2-cyanobutanedioate. Its relative configuration was identified by gas chromatography, 1H NMR, 13C NMR, HMBC, and NOESY methods, and the structure was consistent with that of Example 1.

[0073] Example 3

[0074] Method 2: Preparation of rel-(2S,3R)-diisopropyl 2-cyanobutanedioate.

[0075] In a 2000 mL round-bottom flask, 269.3 g of potassium tert-butoxide was dissolved in 600 mL of N,N'-dimethylformamide, and the temperature was maintained at 30 °C. Then, 271.5 g of ethyl cyanoacetate was added dropwise. The reaction was carried out at room temperature and atmospheric pressure for 2 hours. After that, 31.4 g of potassium iodide was added, and the temperature was raised to 65 °C. At this temperature, 596.9 g of ethyl 2-bromoisovalerate was added dropwise. After the addition was complete, the reaction was carried out at atmospheric pressure for 10 hours. The reaction was stopped and cooled, and the solid inorganic salts and solvents were removed. It was washed with 200 mL of water, and then extracted three times with 600 mL of ether. The organic phase was collected and washed twice with 200 mL of saturated aqueous sodium bicarbonate solution until the organic phase was neutral. The organic phase was dried, and the ether was removed by concentration to obtain 579.5 g of the crude product. In a high-efficiency rectification column with 35 theoretical plates, under the conditions of a column bottom temperature of 150 °C, a vacuum degree of 800 Pa, and a reflux ratio controlled such that the take-off ratio to reflux was 4:1, the product was subjected to vacuum rectification to obtain 463.6 g of diethyl 2-cyano-3-isopropylsuccinate with a purity of 97.3%.

[0076] Add 139.7 g of potassium tert-butoxide to a 2000 mL round-bottom flask, and then add 380 mL of DMF. After complete dissolution, add 300 g of diethyl 2-cyano-3-isopropylsuccinate while stirring, and react at room temperature and normal pressure for 1 h. Then add 12.5 g of potassium iodide. Subsequently, heat to 80 °C and dropwise add 152.9 g of 2-bromopropane. After the addition is complete, react at 80 °C and normal pressure for 10 hours, cool, filter, and remove the solvent. Wash with 100 mL of water, and then extract three times with 300 mL of ether in portions. Collect the organic phase and wash it twice with 100 mL of saturated aqueous sodium bicarbonate solution until the organic phase is neutral. Dry the organic phase, concentrate and remove the ether to obtain 350.7 g of the crude product. Add 350.7 g of the crude product to a 500 mL high-efficiency rectification column with 35 theoretical plates. Rectify the product under the conditions of a column bottom temperature of 190 °C, a vacuum degree of 800 Pa, and a reflux ratio controlled such that the take-off ratio to reflux is 1:20. Collect the light fractions at the top of the column and perform chromatographic analysis on the fractions. The purity of diethyl 2,3-diisopropyl-2-cyanosuccinate is 95.430%, among which the content of the racemate with a shorter peak retention time is 88.724%, and the content of the racemate with a longer peak retention time is 6.706%. Perform secondary rectification on the rectified fractions. Similarly, control the reflux ratio such that the take-off ratio to reflux is 1:20, collect the light fractions at the top of the column, and perform chromatographic analysis. After deducting the dilution solvent used for chromatography, the purity of diethyl 2,3-diisopropyl-2-cyanosuccinate is 97.335%, which is a mixture of two racemates. Among them, the content of the racemate with a shorter peak retention time is 92.382%, and the content of the racemate with a longer peak retention time is 4.953%. Then use column chromatography for separation and purification. The stationary phase is silica gel, and the mobile phase is ethyl acetate and petroleum ether in a ratio of 1:9 to obtain the compound with a shorter peak retention time, whose purity is greater than 99.9%. Identify its relative configuration by gas chromatography, 1H NMR, 13C NMR, HMBC NMR, and NOESY analysis methods. Its relative structure is rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanosuccinate, which is consistent with Example 1.

[0077] Example 4

[0078] Prepare rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanosuccinate.

[0079] Take 20 g of the crude product prepared in Example 3 and use 15 g of petroleum ether as the recrystallization solvent to recrystallize at 25 °C - 8 °C to obtain 4 g of pure rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanosuccinate. Identify its relative configuration by gas chromatography, 1H NMR, 13C NMR, HMBC NMR, and NOESY analysis methods. The product structure is consistent with Example 1.

[0080] Example 5

[0081] The synthesis method and rectification steps of Example 1 are adopted, with the difference that the reflux ratio in the rectification step is controlled such that the draw ratio to reflux is 6:1.

[0082] The crude product is prepared using the synthesis method of Example 1. 300 g of the crude product is added to a 500 mL high-efficiency rectification column with 35 plates. The product is rectified under the conditions that the temperature of the column kettle is 190 °C, the vacuum degree is 800 Pa, and the reflux ratio is controlled such that the draw ratio to reflux is 6:1. The light fractions at the top of the column are collected and analyzed using gas chromatography. The results are shown in Figure 9 .. The purity of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate is 95.414%. Among them, the content of the racemate with a shorter peak retention time is 74.910%, and the content of the racemate with a longer peak retention time is 20.504%. It is subjected to secondary rectification. Similarly, the reflux ratio is controlled such that the draw ratio to reflux is 6:1. The light fractions at the top of the column are collected and subjected to chromatographic analysis. The results are shown in Figure 10 , and after deducting the dilution solvent used for chromatography, the purity of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate is 97.030%. It is a mixture of two racemates. Among them, the content of the racemate with a shorter peak retention time is 81.365%, and the content of the racemate with a longer peak retention time is 15.665%.

[0083] It can be found by comparing Example 5 with Example 1 that when the reflux ratio is controlled such that the draw ratio to reflux is 1:20, the purity of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate after rectification is 99.50%, which is higher than the purity of 97.030% of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate when the reflux ratio is controlled such that the draw ratio to reflux is 6:1. Moreover, when the reflux ratio is controlled such that the draw ratio to reflux is 1:20, the ratio of the racemate with a shorter peak retention time to the racemate with a longer peak retention time in the rectified diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate is 11.11:1, which is higher than the ratio of 5.19:1 of the racemate with a shorter peak retention time to the racemate with a longer peak retention time in diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate when the reflux ratio is controlled such that the draw ratio to reflux is 6:1. This shows that using a reflux ratio controlled such that the draw ratio to reflux is 1:20 can not only improve the purity of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate, but also increase the ratio of the two racemates, facilitating the further separation of the two racemates.

[0084] Comparative Example 1

[0085] The synthesis method and rectification steps of Example 1 are adopted, with the difference that the vacuum degree used in the rectification step is 3000 Pa, and the corresponding temperature inside the rectification kettle is 270 °C.

[0086] The crude product was prepared using the synthesis method of Example 1. 300 g of the crude product was added to a 500 mL high-efficiency rectification column with 35 theoretical plates. The product was rectified under the conditions of a column bottom temperature of 270 °C, a vacuum degree of 3000 Pa, and a reflux ratio controlled such that the take-off ratio to reflux was 1:20. The light fractions at the top of the column were collected and analyzed using gas chromatography. The results are shown in Figure 11 . The purity of diethyl 2,3 - diisopropyl - 2 - cyanobutanedioate was 88.294%. The content of the racemate with a shorter peak retention time was 75.652%, and the content of the racemate with a longer peak retention time was 12.642%.

[0087] It can be seen that the vacuum degree used in the rectification step was 3000 Pa, and the temperature in the rectification kettle was 270 °C. After one rectification, obvious thermal decomposition of the product occurred, generating more by - products, which seriously affected the further separation and yield of the product.

[0088] The various embodiments of the present invention have been described above. The above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations are obvious to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.

[0089] The endpoints and any values disclosed herein are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

Claims

1. A rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate compound having the structure shown in formula (I): The compound is a pure racemate with an impurity content of less than 0.1%, and has a proton nuclear magnetic resonance spectrum substantially consistent with that of Figure 5.

2. The compound according to claim 1, wherein The characteristic 1H-NMR spectrum of the said compound is as follows: 1 1H-NMR(CDCl3 / TMS,500MHz)(δppm): 0.983–0.996(d, 3H, CH(CH3)2), 1.008-1.022(d, 6H, CH(CH3)2), 1.121–1.134(d, 3H, CH(CH3)2), 1.291–1.320(t, 3H, CH2CH3), 1.331–1.360(t, 3H, CH2CH3), 2.114–2.210(m, 1H, CH(CH3)2), 2.238–2.293(m, 1H, CH(CH3)2), 2.965–2.980(d, 1H, O=CCHCH(CH3)2), 4.173-4.324(m, 4H, 2OCH2CH3).

3. A method for preparing the compound according to claim 1 or 2, comprising Method 1 or Method 2: Method 1 includes the following steps: React metal alkoxide, aprotic solvent, and ethyl 3-methyl-2-cyanobutyrate to form a salt; add ethyl 2-bromo-3-methylbutanoate and continue the reaction to form diethyl 2,3-diisopropyl-2-cyanobutanedioate, then filter, desolventize, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column, and collect the light distillate at the top of the column; further purify and separate the crude product obtained by rectification using column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain a pure rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate compound; the operating temperature of the rectification column is 60-260 °C, the operating pressure is 0.1-2800 Pa, and the reflux ratio of rectification is controlled such that the draw ratio to reflux is 1:50-10:1; Method 2 includes the following steps: (i) React metal alkoxide, aprotic solvent, and ethyl cyanoacetate to form a salt; add an alkali metal salt and ethyl 2-bromo-3-methylbutanoate and continue the reaction to form diethyl 2-cyano-3-isopropylbutanedioate; then filter, desolventize, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column to obtain diethyl 2-cyano-3-isopropylbutanedioate; (ii) React metal alkoxide, aprotic solvent, and diethyl 2-cyano-3-isopropylbutanedioate to form a salt, add an alkali metal salt and 2-bromopropane and continue the reaction to form diethyl 2,3-diisopropyl-2-cyanobutanedioate; then filter, desolventize, extract, wash, and dry to obtain a crude reaction product; subject the crude reaction product to rectification purification in a rectification column, and collect the light distillate at the top of the column; further purify and separate the crude product obtained by rectification using column chromatography, recrystallization, or a combination of column chromatography and recrystallization to finally obtain a pure rel-(2S,3R)-diethyl 2,3-diisopropyl-2-cyanobutanedioate compound; the operating temperature of the rectification column is 60-260 °C, the operating pressure is 0.1-2800 Pa, and the reflux ratio of rectification is controlled such that the draw ratio to reflux is 1:50-10:

1.

4. The preparation method according to claim 3, wherein, The aprotic solvent is one or more of tetrahydrofuran, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and acetonitrile.

5. The preparation method according to claim 3, wherein, The metal alkoxide is an alkali metal alkoxide, preferably selected from one or more of potassium methoxide, potassium ethoxide, potassium n-propoxide, potassium isopropoxide, potassium n-butoxide, potassium isobutoxide, potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium n-propoxide, sodium isopropoxide, sodium n-butoxide, sodium isobutoxide, and sodium tert-butoxide.

6. The preparation method according to claim 3, wherein, In Method 1, the molar ratio of the metal alkoxide to ethyl 3-methyl-2-cyanobutyrate is 1:0.5 - 2; for every gram of ethyl 3-methyl-2-cyanobutyrate, the amount of the aprotic solvent used is 1 - 50 mL; the molar ratio of the raw material ethyl 3-methyl-2-cyanobutyrate to ethyl 2-bromoisovalerate is 1:0.5 - 3.

7. The preparation method according to claim 3, wherein, In Method 1, the temperatures of the mixing reaction and the continuous reaction are each independently 10 - 150 °C, preferably 20 - 120 °C; the pressures of the mixing reaction and the continuous reaction are each independently 0.8 - 20 atmospheres, preferably 0.8 - 2 atmospheres.

8. The preparation method according to claim 3, wherein, In Method 1, the number of trays of the distillation column is 1 - 150, preferably 1 - 60; the operating temperature is 100 - 240 °C, preferably 150 - 210 °C; the operating pressure is 10 - 2000 Pa, preferably 50 - 1500 Pa; the reflux ratio is controlled such that the take-off ratio to the reflux is 5:1 - 1:45, preferably 1:2 - 1:40, more preferably 1:10 - 1:

30.

9. The preparation method according to claim 3, wherein, In Method 2, the alkali metal salt is an alkali metal halide, preferably one or more of potassium iodide, sodium iodide, and lithium iodide.

10. The preparation method according to claim 3, wherein In step (i) of Method 2, the molar ratio of the metal alkoxide to ethyl cyanoacetate is 1:0.5 - 2; for every gram of ethyl cyanoacetate, the amount of the aprotic solvent used is 1 - 50 mL; the molar ratio of the raw material ethyl cyanoacetate to ethyl 2-bromoisovalerate is 1:0.6 - 2; In step (ii) of Method 2, the molar ratio of the metal alkoxide to diethyl 2-cyano-3-isopropylbutanedioate is 1:0.5 - 3; for every gram of diethyl 2-cyano-3-isopropylbutanedioate, the amount of the aprotic solvent used is 1 - 50 mL; the molar ratio of diethyl 2-cyano-3-isopropylbutanedioate to 2-bromopropane is 1:0.8 - 3.

11. The preparation method according to claim 3, wherein, In step (i) of Method 2, the temperatures of the mixing reaction and the continuous reaction are each independently 10 - 150 °C, preferably 20 - 120 °C; the pressures of the mixing reaction and the continuous reaction are each independently 0.8 - 20 atmospheres, preferably 0.8 - 2 atmospheres; In step (ii) of Method 2, the temperature of the mixing reaction is 20 - 120 °C, the pressure is 0.8 - 20 atmospheres, the temperature of the continuous reaction is 60 - 120 °C, and the pressure is 0.8 - 20 atmospheres.

12. The preparation method according to claim 3, wherein, In step (i) of Method 2, the number of trays of the distillation column is 1 - 150, preferably 1 - 60; the bottom temperature of the column is 120 - 170 °C; the operating pressure is 0.1 - 3000 Pa, preferably 500 - 2000 Pa; the reflux ratio is controlled such that the take-off ratio to the reflux is 1:30 - 30:1, preferably 1:25 - 25:1, more preferably 1:1 - 10:1; In step (ii) of Method 2, the number of trays in the distillation column is 1 - 150, preferably 1 - 60; the operating temperature is 100 - 240 °C, preferably 150 - 210 °C; the operating pressure is 10 - 2000 Pa, preferably 50 - 1500 Pa; the reflux ratio is controlled such that the ratio of distillate to reflux is 5:1 - 1:45, preferably 1:2 - 1:40, more preferably 1:10 - 1:

30.

13. The preparation method according to claim 3, wherein, In the column chromatography method after distillation, the packing used in the chromatography column is one or more of silica gel, alumina, silica-magnesia adsorbent, C18 packing, and ion exchange column, and the developing agent used is one or more combinations of petroleum ether, n-hexane, benzene, diethyl ether, tetrahydrofuran, ethyl acetate, chloroform, dichloromethane, toluene, xylene, isopropanol, n-butanol, acetonitrile, acetone, ethanol, methanol, and water.

14. The preparation method according to claim 3, wherein In the recrystallization method after distillation, the solvent for recrystallization is selected from one or more combinations of petroleum ether, n-hexane, benzene, diethyl ether, tetrahydrofuran, ethyl acetate, chloroform, dichloromethane, toluene, xylene, isopropanol, n-butanol, acetonitrile, acetone, ethanol, methanol, and water; the recrystallization temperature is -30 °C to 45 °C, and the ratio of solute to solvent is 1:0.1 - 10.

15. Use of the compound according to claim 1 or 2 in the preparation of a solid catalyst component for olefin polymerization, wherein, The compound serves as at least a partial internal electron donor.

16. The application according to claim 15, wherein, The internal electron donor further includes a mixture of two racemates of diethyl 2,3-diisopropyl-2-cyanosuccinate.

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