Bipyridine diamine ligands and methods for their preparation
By optimizing the preparation method of bispyridine diamine ligands, the reaction of Grignard reagents with pyridine-2-carboxaldehyde derivatives to generate haloalkanes, combined with anhydrous acetonitrile reaction, solved the problems of low yield and difficult purification in the existing technology, and realized the efficient and environmentally friendly synthesis of bispyridine diamine ligands.
Patent Information
- Application Number
- CN202311003057.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-08-10
- Publication Date
- 2026-02-06
- Estimated Expiration
- 2043-08-10
AI Technical Summary
Existing processes for preparing bispyridine diamine ligands suffer from low yields, high purification difficulty, and environmental unfriendliness. In particular, the small polarity difference makes it difficult to purify intermediates and products, and the introduction of N-containing 1,2-cyclohexanediamine further reduces the yield.
An improved preparation method was adopted, in which a pyridine-2-methanol derivative was generated by reacting a Grignard reagent with a pyridine-2-carboxaldehyde derivative, which was then reacted with thionyl chloride to generate a haloalkane, and finally reacted with a diamine compound in anhydrous acetonitrile. The solvent and reaction conditions were optimized to increase the polarity difference and simplify the post-processing.
It significantly improved the product yield, with an overall yield of 88%, simplified the separation process, reduced environmental impact, and provided a new synthetic approach for bispyridine diamine ligands.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of heterocyclic compound preparation, and particularly relates to a bispyridyl diamine ligand and a preparation method thereof. BACKGROUND
[0002] The bispyridyl diamine ligand is a tetrazine ligand, and a complex formed by coordination of the tetrazine ligand with metal salts such as manganese, zinc and iron has wide application in the fields of organic synthesis and catalysis. Some complexes have certain biomimetic properties, such as non-hematin tetrazine manganese complexes and non-hematin tetrazine iron complexes. These complexes have been widely used in the fields of asymmetric epoxidation of olefins, catalytic oxidation of alcohols, catalytic conversion of carbon dioxide and the like. The complexes containing the bispyridyl diamine tetrazine ligand have high catalytic performance in catalytic reactions, and therefore, synthesis of the bispyridyl diamine ligand has attracted wide attention from researchers.
[0003] In the prior art, a bispyridyl diamine ligand, N,N'-dimethyl-N,N'-bis(phenylpyridine-2-methyl)cyclohexane-1,2-diamine (I-3), is disclosed, and a synthesis route thereof is as follows:
[0004]
[0005] The preparation route of the above ligand includes three steps. Although the yield of the first step is high, the purification of the product is difficult due to the remaining of raw materials and the instability of the generated Schiff base. In addition, the yields of the second step and the third step are low due to the quaternary ammonium of nitrogen. Furthermore, the preparation process introduces 1,2-cyclohexane diamine containing N from the first step, which results in large polarity of the intermediates and the product, and the difference in polarity is small, which further increases the difficulty of purification of the intermediates and the product, and results in a low total yield of the final product, generally less than 30%.
[0006] In view of the good application prospect of the bispyridyl diamine complex in the fields of organic synthesis and catalysis, it is of great practical significance to develop a synthesis method of a bispyridyl diamine ligand with low cost, high yield, small purification difficulty and environmental friendliness. SUMMARY
[0007] In order to solve the above technical problems, the application provides a bispyridyl diamine ligand and a preparation method thereof.
[0008] The bispyridyl diamine ligand provided by the application includes the following structural types of formula I, II, III and IV:
[0009]
[0010] wherein, R 1It is any one of pyrene, phenanthrene, naphthyl, phenyl, and alkyl;
[0011] R 2 It can be any one of fluorine, chlorine, bromine, hydrogen, alkyl, alkoxy, or amino atoms.
[0012] Furthermore, the method for preparing the bispyridine diamine ligands having the above-described I-IV structures provided by the present invention includes the following steps:
[0013] S1: Grignard reagent R 1 Preparation of MgX;
[0014] S2: A tetrahydrofuran solution of pyridine-2-carboxaldehyde derivative is added dropwise to the Grignard reagent system prepared in S1, and the reaction is carried out at -50 to 50 °C. After the reaction is completed, a pyridine-2-methanol derivative is obtained, with the structure shown in formula V below:
[0015]
[0016] Among them, R 1 It is any one of pyrene, phenanthrene, naphthyl, phenyl, and alkyl;
[0017] R 2 It can be any one of fluorine atom, chlorine atom, bromine atom, hydrogen atom, alkyl, alkoxy, and amino;
[0018] S3: The pyridine-2-methanol derivative obtained in S2 was dissolved in dichloromethane, and sulfoxide was added dropwise. The reaction was carried out at -10 to 30 °C. After the reaction was completed, the corresponding haloalkane was obtained, with the structure shown in Formula VI below:
[0019]
[0020] Among them, R 1 It is any one of pyrene, phenanthrene, naphthyl, phenyl, and alkyl;
[0021] R 2 It can be any one of fluorine atom, chlorine atom, bromine atom, hydrogen atom, alkyl, alkoxy, and amino;
[0022] S4: Under argon atmosphere, the haloalkanes synthesized in S3 are dissolved in anhydrous acetonitrile, and tetrabutylammonium bromide, Na2CO3, and diamine compounds are added sequentially. The mixture is reacted at 60–100 °C for 12–72 h. After the reaction is complete, the mixture is extracted with dichloromethane, and the organic phases are combined, dried, and subjected to column chromatography to obtain bispyridine diamine ligands with structures I–IV. The diamine compounds are selected from any one of N,N'-dimethyl-1,2-cyclohexanediamine, N,N'-dimethyl-1,2-diphenylamine, N,N'-dimethyl-1,2-cyclopentanediamine, and 2,2'-bipyrrolidine.
[0023] In the above steps:
[0024] In S1, Grignard reagent R 1 Preparation of MgX: Put magnesium metal, iodine element into a reaction bottle, replace the reaction system with argon, and add anhydrous tetrahydrofuran (THF) with a syringe under argon atmosphere. Add compound R 1 X, after the dropwise addition is completed, monitor the raw material point with thin layer chromatography until the raw material point disappears, wherein the volume mass ratio of THF to compound R 1 X is 1-100 mL: 1 g, and the molar ratio of metal Mg to compound R 1 X is 1-5: 1.
[0025] Preferably, in S1, wherein the volume mass ratio of THF to compound R 1 X is 1-60 mL: 1 g, and the molar ratio of metal Mg to compound R 1 X is 1-3: 1, and the reaction temperature is -15-25°C.
[0026] Preferably, in S1, wherein the volume mass ratio of THF to compound R 1 X is 1-20 mL: 1 g, and the molar ratio of metal Mg to compound R 1 X is 1: 1, and the reaction temperature is 0°C.
[0027] In S2, the molar ratio of the Grignard reagent to the pyridine-2-formaldehyde derivative is 1-5: 1, and the reaction temperature is -10-30°C.
[0028] Preferably, in S2, the molar ratio of the Grignard reagent to the pyridine-2-formaldehyde derivative is 1-3: 1, and the reaction temperature is -10-10°C.
[0029] Preferably, in S2, the reaction temperature is 0°C.
[0030] In S3, the volume mass ratio of the solvent dichloromethane to the pyridine-2-methanol derivative is 1-12 mL: 1 g, and the molar ratio of dichlorosulfoxide to the pyridine-2-methanol derivative is 1-10: 1.
[0031] Preferably, in S3, the volume mass ratio of the solvent dichloromethane to the pyridine-2-methanol derivative is 3-9 mL: 1 g, and the molar ratio of dichlorosulfoxide to the pyridine-2-methanol derivative is 1-5: 1.
[0032] Preferably, in S3, the volume-mass ratio of the solvent dichloromethane to pyridine-2-methanol derivative is 7-9 mL:1 g, and the molar ratio of dichlorosulfoxide to pyridine-2-methanol derivative is 1-2:1.
[0033] In S4, the volume-mass ratio of the solvent anhydrous acetonitrile to halogenated hydrocarbon is 1-10 mL:1 g, the molar ratio of halogenated hydrocarbon to diamine compound is 2-5:1, and the reaction temperature is 60-100 DEG C.
[0034] Preferably, in S4, the volume-mass ratio of the solvent anhydrous acetonitrile to halogenated hydrocarbon is 5-10 mL:1 g.
[0035] Preferably, in S4, the volume-mass ratio of the solvent anhydrous acetonitrile to halogenated hydrocarbon is 7-9 mL:1 g.
[0036] The present application has the following advantages:
[0037] (1) The present application improves the preparation process of the bipyridine diamine ligand, i.e. introducing a N-containing group in the last step of the reaction, which reduces the polarity of the products of the first two steps, and increases the polarity difference between the halogenated hydrocarbon and the product in the third step, and most of the diamine compound raw materials are soluble in water, which can be removed by washing with brine in the post-processing, thus the improved process has the advantages of simple synthesis method, easy product separation, etc.
[0038] (2) After improving the preparation process of the bipyridine diamine ligand, the yield of the product is significantly improved. Specifically, the yield of the first and second steps in the method of the present application is very high, and the yield of the intermediate product in the second step is close to 100%. In the third step, the halogenated hydrocarbon is more sterically hindered than the iodomethane in the traditional method, which can effectively inhibit the generation of quaternary ammonium salt and is conducive to improving the yield of the product. The total yield of the target product is as high as 88%.
[0039] (3) In the present application, bipyridine diamine ligands other than I-3, including I-1, I-2, and I, II, III, IV structures, are synthesized for the first time, which provides a new idea for the development and application of bipyridine diamine ligands. BRIEF DESCRIPTION OF DRAWINGS
[0040] Figure 1 The preparation principle diagram of the bipyridine diamine ligand provided by the present application;
[0041] Figure 2 The nuclear magnetic resonance hydrogen spectrum of the product I-1 in Example 1 of the present application;
[0042] Figure 3NMR chart of hydrogen spectrum of product I-1 in Example 1 of the present application;
[0043] Figure 4 NMR chart of hydrogen spectrum of product I-2 in Example 2 of the present application;
[0044] Figure 5 NMR chart of carbon spectrum of product I-2 in Example 2 of the present application;
[0045] Figure 6 NMR chart of hydrogen spectrum of product I-3 in Example 3 of the present application;
[0046] Figure 7 NMR chart of carbon spectrum of product I-3 in Example 3 of the present application; DETAILED DESCRIPTION
[0047] In order to enable a person skilled in the art to better understand the present application, the present application will be further described in conjunction with specific embodiments.
[0048] The principle of the preparation method of the bipyridine diamine ligand provided by the present application is shown in the accompanying Figure 1
[0049] Example 1
[0050] The synthesis method of compound I-1 is as follows:
[0051]
[0052] First, place elemental iodine and 0.24 g of magnesium metal (about 10 mmol) in a Schlenk flask, replace argon, and add 15 mL of anhydrous THF using a syringe. Then, dissolve 2.57 g of 9-bromophenanthrene (about 10 mmol) in 5 mL of anhydrous THF to prepare a THF solution of 9-bromophenanthrene, and add the THF solution of 9-bromophenanthrene dropwise into the above system at 0°C using a syringe. After the dropwise addition is completed, react for 1 h.
[0053] Next, dissolve 1.07 g of pyridine-2-carboxaldehyde (about 10 mmol) in 5 mL of anhydrous THF at 0°C, and add the THF solution of pyridine-2-carboxaldehyde dropwise into the above Schlenk flask using a syringe. After the dropwise addition is completed, react for 1 h, then quench with a saturated ammonium chloride solution, extract three times with dichloromethane (3 x 20 mL), combine the organic phases, and dry with anhydrous sodium sulfate. Column chromatography (petroleum ether: ethyl acetate = 2:1) is performed to obtain 2.66 g of compound V-1 (about 9.3 mmol), with a yield of about 93%.
[0054] The obtained compound V-1 (2.66 g, 9.3 mmol) was dissolved in 20 mL of dichloromethane, 1.79 g of SOCl2 (about 15 mmol) was added dropwise to the system at 0°C, and after the dropwise addition was completed, the reaction was carried out for 30 min. After the reaction was completed, saturated NaHCO3 was added dropwise to the system until no gas bubbles were generated, and extraction was carried out three times with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography (petroleum ether: ethyl acetate = 2:1) was performed to obtain 2.82 g of compound VI-1 (about 9.2 mmol), with a yield of about 98%.
[0055] The obtained compound VI-1 (2.82 g, 9.2 mmol) was added to 20 mL of anhydrous acetonitrile, and 0.15 g of TBAB (0.46 mmol), 2.12 g of Na2CO3 (about 20 mmol), and 0.57 g of N,N'-dimethyl-1,2-cyclohexanediamine (about 4 mmol) were sequentially added, and then the reaction system was placed in a 90°C refluxing reactor for 24 h.
[0056] After the reaction was completed, extraction was carried out three times with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography (petroleum ether: ethyl acetate: triethylamine = 4:1:0.1) was performed to obtain 2.17 g of the target compound I-1, with a yield of 80% and a purity of 99%.
[0057] The compound I-1 was detected by nuclear magnetic resonance hydrogen spectrum, and the detection conditions were as follows: 15 mg of the target compound I-1 was placed in a nuclear magnetic tube, about 0.5 mL of deuterated chloroform was added to dissolve the sample, and the nuclear magnetic resonance instrument was used for testing at room temperature.
[0058] The nuclear magnetic resonance hydrogen spectrum is shown in FIG. 1, and the nuclear magnetic resonance carbon spectrum is shown in FIG. 2. Figure 2 Figure 3
[0059] 1 H NMR (400 MHz, Chloroform-d) δ 8.93 (s, 2H), 8.72 (dd, J = 7.8, 1.8 Hz, 2H), 8.66 (dd, J = 8.2, 1.2 Hz, 2H), 8.57 (t, J = 4.9 Hz, 4H), 7.91 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 7.9 Hz, 2H), 7.63 - 7.47 (m, 10H), 7.15 - 7.07 (m, 2H), 5.96 (s, 2H), 3.07 - 2.92 (m, 2H), 2.12 (s, 6H), 2.08 (d, J = 11.2 Hz, 2H), 1.52 (d, J = 9.1 Hz, 2H), 1.26 - 1.13 (m, 2H), 0.81 (t, J = 10.0 Hz, 2H).
[0060] 13 C NMR(101MHz,Chloroform-d)δ162.91,148.73,136.48,136.31,131.81,130.96,130.02,128.93,127.44,12 6.60,126.55,126.36,126.02,124.88,123.80,123.12,122.49,121.91,69.94,61.45,34.95,25.57,24.83.
[0061] Example 2
[0062] A method for synthesizing compound I-2, with the following reaction equation:
[0063]
[0064] First, place elemental iodine and metallic magnesium (0.24 g, 10 mmol) in a Shrek flask, replace with argon gas, and add anhydrous THF (15 mL) using a syringe. Dissolve 1-bromonaphthalene (2.07 g, 10 mmol) in 5 mL of anhydrous THF. At 0 °C, add 1-bromonaphthalene dropwise to the above system using a syringe. After the addition is complete, react for 1 h.
[0065] Next, at 0°C, pyridine-2-carboxaldehyde (1.07 g, 10 mmol) was dissolved in 5 mL of anhydrous THF. The THF solution of pyridine-2-carboxaldehyde was added dropwise to the Shrek flask using a syringe. After the addition was complete, the reaction was carried out for 1 h. The reaction was quenched with saturated ammonium chloride solution and extracted three times with dichloromethane (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and subjected to column chromatography (petroleum ether: ethyl acetate = 2:1) to give 2.23 g of compound V-2, with a yield of approximately 95%.
[0066] The obtained compound V-2 (2.23 g, 9.5 mmol) was dissolved in 20 mL of dichloromethane. SOCl2 (1.79 g, 15 mmol) was added dropwise to the system at 0 °C. After the addition was complete, the reaction was allowed to proceed for 30 min. Once the reaction was complete, saturated NaHCO3 was added dropwise until no more bubbles were produced. The mixture was extracted three times with dichloromethane (3 × 20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and subjected to column chromatography (petroleum ether: ethyl acetate = 2:1) to give 2.39 g of compound VI-2, with a yield of approximately 99%.
[0067] The obtained compound VI-2 (2.39 g, 9.4 mmol) was added into anhydrous acetonitrile (20 mL), and TBAB (0.15 g, 0.47 mmol), 2.12 g of Na2CO3 (about 20 mmol), N, N'-dimethyl-1,2-cyclohexanediamine (0.57 g, 4 mol) were added in sequence, and the reaction system was placed under reflux at 90°C for 24 h. After the reaction was completed, extraction was performed with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography (petroleum ether: ethyl acetate: triethylamine = 4:1:0.1) was performed to obtain 1.96 g of the target compound I-2, with a product yield of about 85% and a purity of 99%.
[0068] The compound I-2 was detected by nuclear magnetic resonance hydrogen spectrum, and the detection method was the same as in Example 1. The nuclear magnetic resonance hydrogen spectrum is shown in FIG. 2, and the nuclear magnetic resonance carbon spectrum is shown in FIG. 3. Figure 4 Figure 5
[0069] 1 H NMR (400 MHz, Chloroform-d) δ 8.61-8.44 (m, 6H), 7.81 (d, J = 8.0 Hz, 4H), 7.76-7.61 (m, 4H), 7.51-7.38 (m, 6H), 7.10 (ddd, J = 7.4, 5.0, 1.1 Hz, 2H), 5.93 (s, 2H), 2.72 (d, J = 9.0 Hz, 2H), 2.08 (s, 6H), 1.91 (s, 2H), 1.46 (d, J = 7.3 Hz, 2H), 1.15 (s, 2H), 0.71 (q, J = 9.9 Hz, 2H).
[0070] 13 C NMR (101 MHz, Chloroform-d) δ 148.61, 138.11, 136.43, 133.85, 131.83, 128.78, 127.53, 126.92, 125.97, 125.66, 125.25, 123.86, 123.45, 121.76, 69.22, 60.33, 35.45, 25.40, 24.59.
[0071] Example 3
[0072] A method for synthesizing compound I-3, the reaction equation is as follows:
[0073]
[0074] In this embodiment, first, magnesium metal (0.24 g, 10 mmol) and iodine were placed in a Schlenk flask, argon was replaced, anhydrous THF (15 mL) was added by a syringe, and bromobenzene (1.57 g, 10 mmol) was dissolved in 5 mL of anhydrous THF. At 0°C, the bromobenzene THF solution was added dropwise into the above system by a syringe. After the addition was completed, the reaction was carried out for 1 h.
[0075] Then, at 0°C, pyridine-2-carboxaldehyde (1.07 g, 10 mmol) was dissolved in 5 mL of anhydrous THF, and the pyridine-2-carboxaldehyde THF solution was added dropwise into the above Schlenk flask by a syringe. After the addition was completed, the reaction was carried out for 1 h. The reaction was quenched with saturated ammonium chloride solution, extracted with dichloromethane (3 x 20 mL) three times, and the organic phases were combined and dried over anhydrous sodium sulfate. Column chromatography (petroleum ether: ethyl acetate = 2:1) was performed to obtain 1.80 g of the alcohol compound V-3, with a yield of about 97%.
[0076] The obtained alcohol compound V-3 (1.80 g, 9.7 mmol) was dissolved in 20 mL of dichloromethane, and SOCl2 (1.79 g, 15 mmol) was added dropwise into the system at 0°C. After the addition was completed, the reaction was carried out for 30 min. The reaction was quenched by adding saturated NaHCO3 dropwise until no gas bubbles were generated. The reaction was extracted with dichloromethane (3 x 20 mL) three times, and the organic phases were combined and dried over anhydrous sodium sulfate. Column chromatography (petroleum ether: ethyl acetate = 2:1) was performed to obtain 1.97 g of the compound VI-3, with a yield close to 100%.
[0077] The obtained compound VI-3 (1.97 g, 9.7 mmol) was added to anhydrous acetonitrile (20 mL), and TBAB (0.15 g, 0.48 mmol), 2.12 g of Na2CO3 (about 20 mmol), and N,N'-dimethyl-1,2-cyclohexanediamine (0.57 g, 4 mmol) were sequentially added. The reaction system was placed in a 90°C water bath and refluxed for 24 h.
[0078] After the reaction was completed, the reaction was extracted with dichloromethane (3 x 20 mL), and the organic phases were combined and dried over anhydrous sodium sulfate. Column chromatography (petroleum ether: ethyl acetate: triethylamine = 4:1:0.1) was performed to obtain 1.68 g of the target compound I-3, with a yield of about 88% and a purity of 99%.
[0079] The compound I-3 was detected by nuclear magnetic resonance hydrogen spectrum, and the detection method was the same as in Example 1. The nuclear magnetic resonance hydrogen spectrum is shown in FIG. 1, and the nuclear magnetic resonance carbon spectrum is shown in FIG. 2. Figure 6 The nuclear magnetic resonance hydrogen spectrum is shown in FIG. 1, and the nuclear magnetic resonance carbon spectrum is shown in FIG. 2. Figure 7 The nuclear magnetic resonance hydrogen spectrum is shown in FIG. 1, and the nuclear magnetic resonance carbon spectrum is shown in FIG. 2.
[0080] 1H NMR (400 MHz, Chloroform-d) δ 8.49 (t, J = 4.7 Hz, 2H), 7.90 (d, J = 7.9 Hz, 1H), 7.75 (td, J = 7.7, 1.8 Hz, 1H), 7.65 - 7.51 (m, 4H), 7.48 (d, J = 7.0 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.24 (d, J = 7.9 Hz, 3H), 7.20 (dt, J = 8.5, 2.0 Hz, 1H), 7.16 - 7.04 (m, 2H), 5.05 (d, J = 52.9 Hz, 2H), 2.60 - 2.44 (m, 2H), 2.17 (d, J = 5.0 Hz, 6H), 1.88 (dd, J = 70.0, 13.1 Hz, 2H), 1.53 (s, 2H), 1.04 (t, J = 7.1 Hz, 2H), 0.78 (t, J = 10.3 Hz, 2H).
[0081] 13 C NMR (101 MHz, Chloroform-d) δ 148.95, 148.74, 136.74, 136.27, 129.11, 128.47, 128.41, 128.31, 127.25, 126.99, 123.38, 122.33, 121.85, 75.19, 74.74, 60.36, 59.93, 34.53, 34.37, 25.66, 25.40, 25.05, 24.51.
[0082] Example 4
[0083] The synthesis method of compound I-1 is different from that of Example 1, and the parameters of the reaction process are different. The specific parameter settings are as follows:
[0084] The preparation method of Grignard reagent is the same as that of Example 1.
[0085] Then, 10 mmol of pyridine-2-carboxaldehyde was dissolved in 5 mL of anhydrous THF at 0°C, and the THF solution of pyridine-2-carboxaldehyde was added dropwise into the Schlenk flask containing 30 mmol of Grignard reagent with a syringe, and after the dropwise addition was completed, the reaction was carried out for 1.5 h, then quenched with saturated ammonium chloride solution, extracted with dichloromethane (3 x 20 mL) three times, combined the organic phase, and dried with anhydrous sodium sulfate, and column chromatography to obtain 2.71 g of compound V-1 (about 9.5 mmol), the yield is about 95%.
[0086] The obtained compound V-1 was dissolved in 20 mL of dichloromethane, 80 mmol of SOCl2 was added dropwise into the system at 0°C, and after the dropwise addition was completed, the reaction was carried out for 30 min, and after the reaction was completed, saturated NaHCO3 was added dropwise into the system until no gas bubbles were generated, and extraction was carried out three times with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography was performed to obtain 2.89 g of compound VI-2 (about 9.4 mmol), and the yield was about 99%.
[0087] The obtained compound VI-1 was added into 20 mL of anhydrous acetonitrile, 0.15 g of TBAB (0.47 mmol), 2.12 g of Na2CO3 (about 20 mmol), and 2 mmol of N,N'-dimethyl-1,2-cyclohexanediamine were sequentially added, and then the reaction system was placed under reflux at 85°C for 36 h.
[0088] After the reaction was completed, extraction was carried out three times with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography was performed to obtain 1.15 g of the target compound I-1 (about 1.7 mmol), and the yield was about 85%.
[0089] Comparative Example 1
[0090] The reactant I-3 was prepared by using a traditional three-step method, and the reaction equation is as follows:
[0091]
[0092] The ratio of each raw material was the same as in Example 1.
[0093] As a result, the yield of the product I-3 was only 20%, and the purity was 98%.
[0094] Comparative Example 2
[0095] On the basis of Example 1, only the reaction temperature of the third step was changed, and the specific operation was as follows:
[0096] Compound VI-1 (9.4 mmol) was added into 20 mL of anhydrous acetonitrile, 0.15 g of TBAB (0.47 mmol), 2.12 g of Na2CO3 (about 20 mmol), and 4 mmol of N,N'-dimethyl-1,2-cyclohexanediamine were sequentially added, and then the reaction system was placed under reflux at room temperature for 36 h.
[0097] After the reaction was completed, extraction was carried out three times with dichloromethane (3 x 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography was performed to obtain 0.13 g of the target compound I-1 (about 0.20 mmol), and the yield was only 5%.
[0098] Comparative Example 3
[0099] Different from example 1, the reaction time of the third step is set to 3h, and the specific operation is as follows:
[0100] Compound VI-1 (9.4mmol) is added to 20mL of anhydrous acetonitrile, 0.15g of TBAB (0.47mmol), 2.12g of Na2CO3 (about 20mmol), 4mmol of N,N'-dimethyl-1,2-cyclohexanediamine are sequentially added, and then the reaction system is placed in a 90℃ reflux reactor for 3h.
[0101] After the reaction is completed, it is extracted with dichloromethane (3x20mL), the organic phases are combined, dried with anhydrous sodium sulfate, and column chromatography is performed to obtain 0.29g of the target compound I-1 (about 0.43mmol) with a yield of only 11%.
Claims
1. A method for preparing bispyridine diamine ligands, characterized in that, The steps include the following: S1: Grignard reagent R 1 Preparation of MgX; S2: Add a tetrahydrofuran solution of a pyridine-2-carboxaldehyde derivative to the Grignard reagent system prepared in S1. Grignard reagent R 1 The molar ratio of MgX to pyridine-2-carboxaldehyde derivative is 1~5:1, and the reaction is carried out at -10~30℃. After the reaction is completed, pyridine-2-methanol derivative is obtained. S3: Dissolve the pyridine-2-methanol derivative obtained in S2 in dichloromethane, and add sulfoxide dropwise to react. The volume-to-mass ratio of dichloromethane to pyridine-2-methanol derivative is 1~12 mL:1 g, and the molar ratio of sulfoxide to pyridine-2-methanol derivative is 1~10:
1. After the reaction is complete, the corresponding haloalkanes are obtained. S4: Under argon atmosphere, the haloalkanes synthesized in S3 were dissolved in anhydrous acetonitrile, and tetrabutylammonium bromide, Na2CO3, the compound, and the diamine compound were added sequentially. The reaction was carried out at 60-100℃ for 12-72 h. After the reaction was completed, the mixture was extracted with dichloromethane, and the organic phases were combined, dried, and subjected to column chromatography to obtain bispyridine diamine ligands. The volume-to-mass ratio of anhydrous acetonitrile to haloalkanes was 1-10 mL:1 g, and the molar ratio of haloalkanes to diamine compounds was 2-5:
1. During column chromatography, the ratio of petroleum ether:ethyl acetate:triethylamine was 4:1:0.
1. The bispyridine diamine ligands described herein have the following structural type: ； Among them, R 1 It is any one of phenanthrene, naphthyl, and phenyl; R 2 It is a hydrogen atom; The reaction principle of the preparation method is as follows: 。