A method for preparing an NHC-PdCl2-3-chloropyridine complex

Abstract

The application relates to a preparation method of an NHC-PdCl2-3-chloropyridine complex, which comprises the following steps: reacting 2,6-diisopropylaniline, glyoxal and acetic acid in an ethanol solvent for 2-4 days to obtain glyoxal-bis-(2,6-diisopropylphenyl) imine; stirring and reacting a mixed solution of the glyoxal-bis-(2,6-diisopropylphenyl) imine, chloromethyl ether, tetrahydrofuran and water at 30-50 DEG C for 10-20 hours to obtain 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride, and the molar ratio of the glyoxal-bis-(2,6-diisopropylphenyl) imine to water is 1:2%-10%; reacting 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride, palladium chloride, cesium carbonate and 3-chloropyridine at 60-100 DEG C for 10-20 hours to obtain [1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene](3-chloropyridyl) palladium (II) dichloride, the method has the advantages of easy raw material acquisition, simple operation, mild and easy-to-control reaction conditions and convenience in industrial large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of metal-organic palladium catalyst preparation technology, specifically relating to a method for preparing an NHC-PdCl2-3-chloropyridine complex. Background Technology

[0002] Palladium catalysts are various catalysts made with metallic palladium as the main active component, using palladium black or palladium salts supported on alumina, zeolites, etc., and sodium, cadmium, lead, etc., as co-catalysts. They are frequently used in chemical and chemical reaction processes. Some traditional catalysts, such as palladium acetate and tetra(triphenylphosphine)palladium, are sensitive to air and moisture, have low catalytic efficiency, and their applications are somewhat limited. In contrast, the organometallic complex PEPPSI-IPr catalyst NHC-PdCl2-3-chloropyridine complex, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridinyl)palladium(II) dichloride, is a highly efficient catalyst that is very stable to air and humidity. It can catalyze a variety of coupling reactions at room temperature and does not require additional ligands. It has wide applications in reactions such as Negishi coupling, Suzuki coupling, Buchwald-Hartwig amination, and Kumada coupling. However, existing preparation methods for this catalyst suffer from problems such as harsh preparation conditions and low yields. Among them, the most important step affecting the yield of PEPPSI-IPr catalyst is the preparation of N-heterocyclic imidazolium salt. In the existing technology, for aromatic amines with large steric hindrance, the synthesis steps of their related onium salts are as follows: First, the amine reacts with glyoxal to obtain a Schiff base, and then the ring is closed with chloromethyl ethyl ether or triethyl orthoformate to obtain the N-heterocyclic imidazolium salt product (Arduengo IIIA.J., Krafczyk R., Schmutzler R., Imidazolylidenes, imidazolinylidenes and imidazolidines. Tetrahedron, 1999, 55, 14523-14534.). This reaction needs to be carried out under a dry nitrogen atmosphere, in a vacuum drying oven, or under Schlenk technology that can provide an inert environment and vacuum conditions. The experimental requirements are relatively strict. In the existing technology, the preparation conditions of NHC-PdCl2-3-chloropyridine complex are harsh and the yield is low, making it impossible to prepare in large quantities. This results in the high price of the catalyst, which limits its large-scale preparation. Summary of the Invention

[0003] The technical problem solved by this invention is to provide a method for preparing NHC-PdCl2-3-chloropyridine complexes, thereby solving the problems of harsh preparation conditions and low yield in the prior art, and thus achieving large-dose preparation.

[0004] The specific solution provided by this invention is as follows:

[0005] This invention provides a method for preparing an NHC-PdCl2-3-chloropyridine complex, comprising the following steps:

[0006] Step 1: React 2,6-diisopropylaniline (as shown in Formula a), glyoxal and acetic acid in ethanol solvent at 15-40°C for 2-4 days to obtain glyoxal-bis-(2,6-diisopropylphenyl)imine (as shown in Formula b);

[0007] Step 2: In air, a mixture of glyoxal-bis-(2,6-diisopropylphenyl)imine, chloromethyl ethyl ether, tetrahydrofuran, and water is stirred and reacted at 30-50°C for 10-20 hours to obtain 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt (as shown in Formula c), wherein the molar ratio of glyoxal-bis-(2,6-diisopropylphenyl)imine to water is 1:(2%-10%).

[0008] Step 3: React 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, palladium chloride, cesium carbonate and 3-chloropyridine at 60-100℃ for 10-20 hours to obtain [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylyl](3-chloropyridyl)palladium dichloride (II) (as shown in Formula d).

[0009]

[0010]

[0011] The method of the present invention has the following beneficial technical effects:

[0012] (1) Compared with traditional synthesis methods, the method based on the present invention does not require strict control of anhydrous and oxygen-free conditions in the synthesis of (1,3-bis(2,6-diisopropylphenyl)imidazolium chloride. The preparation of the above-mentioned imidazolium chloride can be achieved in air. The yield is high, the starting materials are cheap and readily available, the reaction conditions are mild, the reaction conditions are easy to control, and the operation is simple. This facilitates the large-scale preparation of (1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, and finally realizes the large-scale preparation of NHC-PdCl2-3-chloropyridine complex ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl subunit](3-chloropyridinyl)palladium dichloride(II)), reducing the synthesis cost of the above-mentioned palladium catalyst.

[0013] (2) In step three, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, palladium chloride, and 3-chloropyridine are used as raw materials to react with cesium carbonate. The reaction is relatively complete, with high yield, and the operation is simple, the reaction conditions are mild, and it is easy to carry out industrial production. This makes it easy to synthesize NHC-PdCl2-3-chloropyridine complex ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl subunit](3-chloropyridinyl)palladium dichloride (II) in large quantities.

[0014] (3) Based on the method of the present invention, adding a small amount of water to the reaction solution in step two can significantly increase the yield of 1,3-bis(2,6-diisopropylphenyl)chlorinated imidazolium salt.

[0015] Based on the above solution, the present invention can be further improved as follows:

[0016] Furthermore, in step one, the molar ratio of 2,6-diisopropylaniline (a), glyoxal, and acetic acid is (2-3):1:(0.1-0.3).

[0017] Furthermore, in step three, the molar ratio of 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt (c), palladium chloride, cesium carbonate and 3-chloropyridine is 1:1:5:(40-100).

[0018] Under the above ratio conditions, Schiff bases glyoxal-bis-(2,6-diisopropylphenyl)imine (b) and [1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl imide](3-chloropyridinyl)palladium dichloride (II) can be obtained with higher yields and higher purity.

[0019] Furthermore, step one is performed at room temperature.

[0020] The above reaction can be carried out at room temperature, reducing production costs.

[0021] Furthermore, after reacting for 2-4 days in step one, the reaction is quenched with saturated sodium bicarbonate solution, the reaction solution is filtered, and the precipitate is dried under vacuum to obtain the Schiff base glyoxal-bis-(2,6-diisopropylphenyl)imine (b).

[0022] Further, after reacting for 10-20 hours in step two, the reaction solution is filtered, the precipitate is washed with n-pentane, and dried under vacuum to obtain the 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt (c).

[0023] The control of the above-mentioned quenching reaction, washing, drying and other conditions is to obtain intermediate and final products with higher product purity and higher yield.

[0024] Further, after reacting for 10-20 hours in step three, the reaction solution is diluted with dichloromethane, then filtered, concentrated and dried to obtain the [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylyl](3-chloropyridinyl)palladium dichloride(II).

[0025] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0026] Figure 1 This is the [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridyl)palladium(II) dichloride synthesized in Example 1 of this invention. 1 H NMR characterization spectrum.

[0027] Figure 2 This is the [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridyl)palladium(II) dichloride synthesized in Example 1 of this invention. 13 C10 NMR characterization spectrum. Detailed Implementation

[0028] The embodiments of the present invention are described in detail below. These embodiments are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0029] Example 1

[0030] Step 1: Synthesis of Schiff base glyoxal-bis-(2,6-diisopropylphenyl)imine:

[0031]

[0032] In air, 500 mmol of 2,6-diisopropylaniline, 250 mmol of glyoxal, and 50 mmol of acetic acid were added to a reaction flask, followed by 250 mL of ethanol. The mixture was reacted at room temperature for three days. After the reaction was completed, the precipitate was filtered and dried under vacuum to obtain the Schiff base glyoxal-bis-(2,6-diisopropylphenyl)imine (yellow solid) with a yield of 88%.

[0033] Step 2: Synthesis of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride:

[0034]

[0035] In air, glyoxal-bis-(2,6-diisopropylphenyl)imine (250 mmol), tetrahydrofuran (500 mL), and a small amount of water (0.225 mL, i.e., the molar ratio of glyoxal-bis-(2,6-diisopropylphenyl)imine to water was 1:5%) were added to a reaction flask, followed by chloromethyl ethyl ether (250 mmol). The mixture was stirred at 40 °C for 16 hours. After the reaction was completed, the precipitate was filtered and thoroughly washed with n-pentane, and dried under vacuum to obtain 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt (white solid) with a yield of 65%.

[0036] Step 3: Synthesis of the NHC-PdCl2-3-chloropyridine complex ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridinyl)palladium(II) dichloride):

[0037]

[0038] In air, palladium chloride (53 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (59 mmol), cesium carbonate (267 mmol), and 3-chloropyridine (2239 mmol) were added to a reaction flask. The mixture was stirred at 90 °C for 16 hours. After the reaction was completed, the mixture was cooled to room temperature, diluted with dichloromethane, filtered to remove the precipitate, washed thoroughly with dichloromethane, concentrated the filtrate, and dried under vacuum to obtain a yellow solid NHC-PdCl2-3-chloropyridine complex ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridyl)palladium dichloride(II)), with a yield of 91%.

[0039] Figure 1 It is a synthetic [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridyl)palladium(II) dichloride 1 H NMR characterization spectrum: 1 H NMR (400MHz, CDCl3): δ (ppm) 8.52 (s, 1H), 8.45 (d, J = 4.0Hz, 1H), 7.49-7.41 (m, 3H), 7.28 (d, J = 4.0Hz, 4 H),7.07-6.98(m,3H),3.64(s,1H),3.12-3.05(m,4H),1.41(d,J=8.0Hz,12H),1.05(d,J=8.0Hz,12H).

[0040] Figure 2 It is a synthetic [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylylene](3-chloropyridyl)palladium(II) dichloride 13 C NMR characterization spectrum: 13C NMR (100MHz, CDCl3): δ (ppm) 150.4, 149.4, 146.6, 134.9, 131.9, 130.3, 125.1, 124.3, 124.0, 28.7, 26.3, 23.2.

[0041] Example 2

[0042] Steps one, two, and three are the same as in Example 1, except that in step two, the molar ratio of glyoxal-bis-(2,6-diisopropylphenyl)imine to water is 1:2%, and the yield of 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt in step two is 60%.

[0043] Example 3

[0044] Steps 1, 2 and 3 are the same as in Example 1, except that in step 2, the molar ratio of glyoxal-bis-(2,6-diisopropylphenyl)imine to water is 1:10%, and the yield of 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt in step 2 is 63%.

[0045] Comparative Example 1

[0046] Steps one, two, and three are the same as in Example 1, except that no water is added in step two, and the yield of 1,3-bis(2,6-diisopropylphenyl)chloroimidazolium salt in step two is 20%.

[0047] All the raw materials listed in this invention, as well as the upper and lower limits and ranges of the raw materials and the upper and lower limits and ranges of the process parameters (such as temperature, time, etc.), can realize this invention. Examples are not listed one by one here.

[0048] Although embodiments of the present invention have been described in detail above, those skilled in the art will understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the claims and their equivalents.

Claims

1. A process for the preparation of a NHC-PdCl2-3-chloropyridine complex, characterized in that, The process comprises the following steps: Step one, reacting 2,6-diisopropylaniline, glyoxal and acetic acid in ethanol solvent at 15-40°C for 3 days in air to obtain glyoxal-bis-(2,6-diisopropylphenyl) imine; Step two, stirring the mixture of glyoxal-bis-(2,6-diisopropylphenyl) imine, chloromethyl ether, tetrahydrofuran and water at 40°C for 16 hours in air to obtain 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride, the molar ratio of glyoxal-bis-(2,6-diisopropylphenyl) imine to water being 1:(2%-10%); Step three, reacting 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride, palladium chloride, cesium carbonate and 3-chloropyridine at 90°C for 16 hours in air to obtain [1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride; The step one is carried out at room temperature.

2. The process for the preparation of the NHC-PdCl2-3-chloropyridine complex according to claim 1, characterized in that, The molar ratio of 2,6-diisopropylaniline (II), glyoxal and acetic acid in step one is (2-3):1:(0.1-0.3).

3. The process for the preparation of NHC-PdCl2-3-chloropyridine complex as claimed in claim 1, wherein, The molar ratio of 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride, palladium chloride, cesium carbonate and 3-chloropyridine in step three is 1:1:5:(40-100).

4. The process for the preparation of NHC-PdCl2-3-chloropyridine complex as claimed in claim 1, wherein, After reacting for 2-4 days in step one, the reaction is quenched with saturated sodium bicarbonate solution, the reaction solution is filtered, and the precipitate is vacuum dried to obtain the Schiff base glyoxal-bis-(2,6-diisopropylphenyl) imine.

5. The process for the preparation of NHC-PdCl2-3-chloropyridine complex as claimed in claim 1, wherein, After reacting for 10-20 hours in step two, the reaction solution is filtered, the precipitate is washed with n-pentane, and vacuum dried to obtain the 1,3-bis(2,6-diisopropylphenyl) imidazolium chloride.

6. The process for the preparation of NHC-PdCl2-3-chloropyridine complex as claimed in claim 1, wherein, After reacting for 10-20 hours in step three, the reaction solution is diluted with dichloromethane, then the reaction solution is filtered, the filtrate is concentrated and dried to obtain the [1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride.

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