Nitrogen heterocyclic carbene oxazoline palladium catalyst, preparation method and catalytic application thereof

Abstract

The present invention belongs to the technical field of transition metal organic catalyst preparation, and is particularly related to the design and preparation method of a class of nitrogen heterocyclic carbene oxazoline palladium ring catalysts. The object of the present invention is to design and synthesize a class of novel nitrogen heterocyclic carbene oxazoline palladium ring catalysts with high catalytic activity. Its specific synthesis steps are to react the corresponding nitrogen heterocyclic carbene and oxazoline palladium ring dimer in dichloromethane, and after column chromatography separation and purification, vacuum drying to obtain the corresponding novel nitrogen heterocyclic carbene oxazoline palladium ring catalyst. The nitrogen heterocyclic carbene oxazoline palladium ring catalyst has high catalytic activity for catalyzing Buchwald-Hartwig amination reaction.

Description

Technical Field

[0001] The invention belongs to the technical field of transition metal organic catalyst preparation, and particularly relates to the preparation of a type of nitrogen heterocyclic carbene oxazoline palladium ring catalyst. Background Art

[0002] Nitrogen heterocyclic carbene (NHC) and its coordinated metal organic compounds have always been one of the hot research directions in the field of synthetic chemistry, especially in the field of metal organic chemistry. The main reasons are: 1) the preparation of nitrogen heterocyclic carbene is relatively simple, and the carbon-metal bond in its coordinated metal organic compound is very stable to air, water and high temperature; 2) nitrogen heterocyclic carbene as a ligand has strong σ electron donor properties and weak π electron acceptor properties, which further increases the electron density of the metal center, not only effectively stabilizing the nitrogen heterocyclic carbene carbon-metal bond (C NHC -M) and enhance the catalytic activity of organometallic catalysts. Over the past few decades, particularly since the 2010 Nobel Prize in Chemistry was awarded "for studies on palladium-catalyzed coupling reactions in organic synthesis," the research and preparation of nitrogen heterocyclic carbenes and their organometallic catalysts has advanced significantly. To further enhance the catalytic activity and substrate compatibility of these catalysts in coupling reactions, scientists have meticulously designed and prepared a variety of highly active nitrogen heterocyclic carbene organometallic catalysts.

[0003] Palladacycles are metallocyclic organometallic compounds that contain at least one carbon-palladium (C-Pd) bond in their molecular chemical formula, with nitrogen (N) atoms being common coordinating atoms. Since the 1960s, scientists have synthesized many types of palladacycles. For example, nitrogen heterocyclic carbene palladacycles. Due to the presence of a carbon-palladium chemical bond, nitrogen heterocyclic carbene palladacycles exhibit excellent stability and demonstrate very high catalytic activity in a range of organic catalytic reactions, such as α-arylation and amination of ketones, and Suzuki coupling reactions of arylboronic acids and aryl halides. In addition, oxazoline, a class of organic compounds containing nitrogen atoms, is widely used as a nitrogen ligand in the synthesis of oxazoline palladacycles and exhibits excellent catalytic activity in transition metal-catalyzed reactions.

[0004] Therefore, combining the oxazoline palladium skeleton with the nitrogen heterocyclic carbene ligand can regulate the electronic and steric properties of the metal catalytic center of the nitrogen heterocyclic carbene palladium catalyst and construct a series of highly catalytically active nitrogen heterocyclic carbene oxazoline palladium catalysts. Summary of the Invention

[0005] The purpose of the present invention is to design and synthesize a class of highly catalytically active nitrogen heterocyclic carbene oxazoline palladium ring catalysts, and to further demonstrate the high catalytic activity of the catalyst itself by the amination reaction of a heterocyclic substrate. The present invention designs and prepares a class of nitrogen heterocyclic carbene oxazoline palladium ring catalysts, the specific structure of which is shown below:

[0006]

[0007] R 1 =H,Me,iPr;R 2 =H,Me,iPr;

[0008] Wherein: Me is methyl, iPr is isopropyl.

[0009] The invention is to react different types of nitrogen heterocyclic carbenes with corresponding oxazoline palladium ring dimers in a dry solvent of dichloromethane, separate by column chromatography, and then vacuum dry to obtain the corresponding nitrogen heterocyclic carbene oxazoline palladium ring catalyst.

[0010] The synthesis method of the nitrogen heterocyclic carbene oxazoline palladium catalyst designed by the present invention is as follows:

[0011] Under a nitrogen atmosphere, a bromine-bridged oxazoline palladium ring dimer (0.5 mmol), a nitrogen heterocyclic carbene (1.05 mmol), and a dry solvent, dichloromethane (DCM, 10 mL), were added to a Schlenk reaction flask in sequence. The reaction was stirred at 30°C for 24 hours. After the reaction was completed, the solvent was directly removed under reduced pressure. After column chromatography separation and purification, the corresponding nitrogen heterocyclic carbene oxazoline palladium ring catalyst was obtained by vacuum drying. The reaction formula is as follows:

[0012]

[0013] The nitrogen heterocyclic carbene oxazoline palladium ring catalyst designed and synthesized by this invention was used to catalyze the Buchwald-Hartwig amination reaction, further demonstrating the high catalytic activity of the catalyst itself. The specific operation process of the Buchwald-Hartwig amination reaction is as follows:

[0014] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with an azocaproic acid (Cat., 2 mol%), 3-aminopyridine (1.2 mmol), 2-chlorothiazole (1.0 mmol), sodium tert-butoxide (tBuONa, 2.0 mmol), and the dry solvent, ethylene glycol dimethyl ether (DME, 3 mL). The reaction was allowed to proceed at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the target product of the amination reaction was isolated and purified by column chromatography and then dried under vacuum to obtain an off-white solid powder. The reaction formula is as follows:

[0015] BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a high-resolution mass spectrometric analysis of the nitrogen heterocyclic carbene oxazoline palladium catalyst 1 prepared in Example 1.

[0017] Figure 2 This is a high-resolution mass spectrometric analysis of the nitrogen heterocyclic carbene oxazoline palladium catalyst 2 prepared in Example 2.

[0018] Figure 3 This is a high-resolution mass spectrometric analysis of the nitrogen heterocyclic carbene oxazoline palladium catalyst 3 prepared in Example 3. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below by way of examples, but the present invention is not limited to the following examples.

[0020] Example 1: Preparation of nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat.1):

[0021]

[0022] Under a nitrogen atmosphere, a Schlenk reaction flask was charged with the bromine-bridged oxazoline palladium ring dimer OxaPd-dimer 1 (0.5 mmol, 0.411 g), acenaphthenoimidazole nitrogen heterocyclic carbene (1.05 mmol, 0.538 g), and dry dichloromethane (DCM, 10 mL). The reaction was stirred at 30°C for 24 hours. After the reaction, the solvent was removed under reduced pressure. After column chromatography and other purification operations, the corresponding nitrogen heterocyclic carbene oxazoline palladium ring catalyst 1 (Cat. 1) was dried under vacuum to obtain the corresponding catalyst. Yield: 0.534 g, 58%.

[0023] NMR analysis: 1H NMR (CDCl3, 600MHz, 298K): δ=7.75 (d, J=8.3Hz, 2H), 7.60 (d, J=8.0Hz, 1H), 7.51-7.47 (m, 3H), 7.38-7.30 (m, 4H), 7.23-7. 21 (m, 2H), 7.13-7.08 (m, 1H), 76.85-6.82 (dd, J=7.0Hz, J=8.2Hz, 2H), 6.66 (d, J=8.2Hz, 1H), 6.59-6.56 (m, 1H), 4.14 (d, J= 3.9Hz, 2H), 3.75-3.65 (m, 2H), 3.03-2.97 (m, 2H), 1.52 (s, 5H), 1.50 (s, 1H), 1.44 (dd, J=6.6Hz, J=7.9Hz, 6H), 0.72 (d, J=6. 8Hz, 5H), 0.68 (d, J=6.8Hz, 1H), 0.64 (d, J=6.8Hz, 1H), 0.52 (d, J=6.8Hz, 5H), 0.21 (d, J=6.7Hz, 5H), 0.14 (d, J=6.7Hz, 1H).

[0024] Example 2: Preparation of nitrogen heterocyclic carbene oxazoline palladium catalyst 2 (Cat.2):

[0025]

[0026] Under a nitrogen atmosphere, a Schlenk reaction flask was charged with the bromine-bridged oxazoline palladium ring dimer OxaPd-dimer 2 (0.5 mmol, 0.361 g), acenaphthenoimidazole nitrogen heterocyclic carbene (1.05 mmol, 0.538 g), and dry dichloromethane (DCM, 10 mL). The reaction was stirred at 30°C for 24 hours. After the reaction, the solvent was directly removed under reduced pressure. After column chromatography and other purification operations, the corresponding nitrogen heterocyclic carbene oxazoline palladium ring catalyst 2 (Cat. 2) was dried under vacuum. Yield: 0.560 g, 64%.

[0027] NMR analysis: 1H NMR (CDCl3, 600MHz, 298K): δ=7.72 (dd, J=4.4Hz, J=8.2Hz, 2H), 7.53 (t, J=7.7Hz, 2H), 7.39-7.34 (m, 4H), 7. 32 (dd, J=7.8Hz, J=1.4Hz, 2H), 7.13-7.08 (m, 1H), 6.97-6.90 (m, 2H), 6.84 (d, J=7.1Hz, 2H) 6.79 (d, J=7.4Hz , 1H), 4.12 (d, J=4.2Hz, 2H), 3.61-3.48 (m, 2H), 3.24-3.10 (m, 2H), 1.47 (d, J=6.5Hz, 6H), 1.47 (s, 6H), 1.12 (d, J=6.8Hz, 1H), 1.08 (d, J=6.8Hz, 5H), 0.64 (d, J=6.8Hz, 5H), 0.50 (d, J=6.6Hz, 1H), 0.46 (d, J=6.6Hz, 5H).

[0028] Example 3: Preparation of nitrogen heterocyclic carbene oxazoline palladium catalyst 3 (Cat.3):

[0029]

[0030] Under a nitrogen atmosphere, a Schlenk reaction flask was charged with the bromine-bridged oxazoline palladium ring dimer OxaPd-dimer 1 (0.5 mmol, 0.411 g), an imidazole nitrogen heterocyclic carbene (1.05 mmol, 0.408 g), and a dry solvent, dichloromethane (DCM, 10 mL). The reaction was stirred at 30°C for 24 hours. After completion of the reaction, the solvent was directly removed under reduced pressure. After column chromatography and other purification operations, the corresponding nitrogen heterocyclic carbene oxazoline palladium ring catalyst 3 (Cat. 3) was obtained by vacuum drying. Yield: 0.494 g, 61%.

[0031] NMR analysis: 1H NMR (CDCl3, 600MHz, 298K): δ=7.65 (q, J=8.1Hz, 1H), 7.52 (d, J=8.2Hz, 1H), 7.36 (q, J=6. 9, 3H), 7.32 (s, 2H), 7.25-7.27 (m, 3H), 7.09-7.12 (m, 1H), 7.07 (q, J=3.0Hz, 2H), 6.37 (d , J=8.7, 1H), 4.10 (s, 2H), 3.54-3.61 (m, 2H), 2.91-2.98 (m, 2H), 1.50 (s, 6H), 1.43 (d, J= 6.6Hz, 6H), 1.09 (dd, J=6.8Hz, J=6.9, 6H), 0.73 (d, J=6.8Hz, 6H), 0.24 (d, J=6.7Hz, 6H).

[0032] Example 4: Nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat.1) is used to catalyze the Buchwald-Hartwig amination reaction:

[0033]

[0034] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with a nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat. 1, 0.018 g, 2 mol%), 3-aminopyridine (0.132 g, 1.4 mmol), 2-chlorothiazole (0.119 g, 1.0 mmol), sodium tert-butoxide (tBuONa, 0.192 g, 2.0 mmol), and ethylene glycol dimethyl ether (DME, 3 mL). The reaction was allowed to proceed at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the target product of the amination reaction was isolated and purified by column chromatography and then dried under vacuum to obtain an off-white solid powder. Yield: 0.145 g, 82%.

[0035] NMR analysis: 1 H NMR (CDCl3, 600MHz, 298K): δ=8.61 (d, J=2.7Hz, 1H), 8.30 (dd, J=4.7, 1.1Hz, 1H ), 8.01 (ddd, J=8.3, 2.7, 1.3Hz, 1H), 7.35-7.27 (m, 2H), 6.71 (d, J=3.6Hz, 1H); 13 C NMR (600MHz, DMSO-d6, 298K): δ=163.5, 141.9, 138.9, 138.8, 138.1, 123.8, 123.1, 109.4.

[0036] Example 5: Nitrogen heterocyclic carbene oxazoline palladium catalyst 2 (Cat. 2) is used to catalyze the Buchwald-Hartwig amination reaction:

[0037]

[0038] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with a nitrogen heterocyclic carbene oxazoline palladium catalyst 2 (Cat. 2, 0.018 g, 2 mol%), 3-aminopyridine (0.132 g, 1.4 mmol), 2-chlorothiazole (0.119 g, 1.0 mmol), sodium tert-butoxide (tBuONa, 0.192 g, 2.0 mmol), and ethylene glycol dimethyl ether (DME, 3 mL). The reaction was allowed to proceed at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the target product of the amination reaction was isolated and purified by column chromatography and then dried under vacuum to obtain an off-white solid powder. Yield: 0.119 g, 67%.

[0039] NMR analysis: 1 H NMR (CDCl3, 600MHz, 298K): δ=8.61 (d, J=2.7Hz, 1H), 8.30 (dd, J=4.7, 1.1Hz, 1H ), 8.01 (ddd, J=8.3, 2.7, 1.3Hz, 1H), 7.35-7.27 (m, 2H), 6.71 (d, J=3.6Hz, 1H); 13 C NMR (600MHz, DMSO-d6, 298K): δ=163.5, 141.9, 138.9, 138.8, 138.1, 123.8, 123.1, 109.4.

[0040] Example 6: Nitrogen heterocyclic carbene oxazoline palladium catalyst 3 (Cat. 3) is used to catalyze the Buchwald-Hartwig amination reaction:

[0041]

[0042] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with a nitrogen heterocyclic carbene oxazoline palladium catalyst 3 (Cat. 3, 0.016 g, 2 mol%), 3-aminopyridine (0.132 g, 1.4 mmol), 2-chlorothiazole (0.119 g, 1.0 mmol), sodium tert-butoxide (tBuONa, 0.192 g, 2.0 mmol), and ethylene glycol dimethyl ether (DME, 3 mL). The reaction was allowed to proceed at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the target product of the amination reaction was isolated and purified by column chromatography and then dried under vacuum to obtain an off-white solid powder. Yield: 0.119 g, 67%.

[0043] NMR analysis: 1 H NMR (CDCl3, 600MHz, 298K): δ=8.61 (d, J=2.7Hz, 1H), 8.30 (dd, J=4.7, 1.1Hz, 1H ), 8.01 (ddd, J=8.3, 2.7, 1.3Hz, 1H), 7.35-7.27 (m, 2H), 6.71 (d, J=3.6Hz, 1H); 13 C NMR (600MHz, DMSO-d6, 298K): δ=163.5, 141.9, 138.9, 138.8, 138.1, 123.8, 123.1, 109.4.

[0044] Example 7: Nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat.1) is used to catalyze the Buchwald-Hartwig amination reaction:

[0045]

[0046] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat. 1, 0.018 g, 2 mol%), 2-aminoquinoline (0.202 g, 1.4 mmol), 2-chlorobenzothiazole (0.170 g, 1.0 mmol), sodium tert-butoxide (tBuONa, 0.192 g, 2.0 mmol), and ethylene glycol dimethyl ether (DME, 3 mL). The reaction was allowed to proceed at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the target product of the amination reaction was isolated and purified by column chromatography and then dried under vacuum to obtain a white solid. Yield: 0.250 g, 90%.

[0047] NMR analysis: 1 H NMR (600MHz, DMSO-d6, 298K): δ=11.93 (s, 1H), 8.28 (d, J=8.6Hz, 1H), 7.98 (d, J=7.6Hz, 1H), 7.92 (d, J=8.2Hz, 1H), 7.87 (d, J=7.7Hz, 1H) , 7.73 (t, J=7.3Hz, 1H), 7.68 (d, J=7.9Hz, 1H), 7.45 (t, J=7.2Hz, 1H), 7.41 (t, J=7.5Hz, 1H), 7.31 (d, J=8.7Hz, 1H), 7.25 (t, J=7.4Hz, 1H).

[0048] Example 8: Nitrogen heterocyclic carbene oxazoline palladium catalyst 1 (Cat.1) is used to catalyze the Buchwald-Hartwig amination reaction:

[0049]

[0050] Under a nitrogen atmosphere, a 25 mL Schlenk reaction tube was charged with azacyclic carbene palladium catalyst 1 (Cat1, 0.018 g, 2 mol%), 5-amino-1,3-dimethylpyrazole (0.156 g, 1.4 mmol), 2-chlorobenzothiazole (0.170 g, 1.0 mmol), sodium tert-butoxide (tBuONa, 0.192 g, 2.0 mmol), and ethylene glycol dimethyl ether (DME, 3 mL). The reaction was continued at 40°C for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the desired product was isolated and purified by column chromatography and dried under vacuum to obtain the amination reaction product as a white solid. Yield: 0.227 g, 93%.

[0051] NMR analysis: 1 H NMR (CDCl3, 600MHz, 298K): δ = 10.35 (s, 1H), 7.74 (s, 1H), 7.45 (s, 1H), 7.31 (t , J=7.1Hz, 1H), 7.13 (t, J=7.0Hz, 1H), 6.18 (s, 1H), 3.63 (s, 3H), 2.13 (s, 3H).

Claims

1. A nitrogen heterocyclic carbene oxazoline palladium catalyst, characterized in that, The specific structure of the catalyst is shown below: R 1 =H,Me,iPr;R 2 =H,Me,iPr; Wherein: Me is methyl, iPr is isopropyl.

2. Use of the nitrogen heterocyclic carbene oxazoline palladium ring catalyst according to claim 1 in a Buchwald-Hartwig amination reaction.

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