A method for synthesizing N-carboxy indole by copper-catalyzed cleavage of CC bonds of α,β-unsaturated ketones

Abstract

This invention proposes a copper-catalyzed method for the synthesis of N-carboxyindole from α,β-unsaturated ketones by C-C bond cleavage, belonging to the field of organic synthesis technology. The method involves reacting 4-(2-aminophenyl)-3-buten-2-one with CO2 under catalytic conditions to obtain... N α,β-Carboxyindole. This invention utilizes a developed Cu / Si catalytic system to achieve the synthesis of α,β-unsaturated ketones by C-C bond cleavage. N -Carboxyindole compounds.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a synthesis method for constructing N-carboxy indole by copper-catalyzed cleavage of CC bonds of α,β-unsaturated ketones. Background Art

[0002] N-carboxy indole compounds have a reduced electron cloud density in the five-membered ring, which makes them difficult to synthesize, especially the synthesis step of the indole ring. This special chemical structure makes N -Carboxy indole synthesis becomes complicated. Although, N The synthesis of N-carboxy indole can be achieved by capturing carbon dioxide with indole. However, this process often uses strong bases such as n-butyl lithium. This not only increases production costs, but also increases the complexity and safety risks of operations. In the process of introducing carboxyl groups, challenges such as reaction condition control, side reaction suppression, and product purification need to be faced. Existing synthesis methods are limited by technical implementation. These problems may lead to low efficiency and high cost of the synthesis of N-carboxy indole. Summary of the invention

[0003] The purpose of the present invention is to propose a copper-catalyzed α,β-unsaturated ketone CC bond cleavage to construct N-carboxy indole synthesis method, using the developed "Cu / Si" catalytic system to achieve α,β-unsaturated ketone CC bond cleavage synthesis N -Carboxy indole compounds.

[0004] The technical solution of the present invention is achieved in this way:

[0005] The present invention provides a copper-catalyzed α,β-unsaturated ketone CC bond cleavage construction method. N - A method for synthesizing carboxy indole, wherein 4-(2-aminophenyl)-3-butene-2-one is reacted with CO2 under catalyst conditions to obtain N -Carboxyindole.

[0006] As a further improvement of the present invention, the catalyst is a copper salt, a ligand, PhSiH3 and a base.

[0007] As a further improvement of the present invention, the molar ratio of the copper salt, the ligand, PhSiH3 and the base is 2-3:2.5-3.5:90-110:90-110.

[0008] As a further improvement of the present invention, the molar ratio of the copper salt, the ligand, PhSiH3 and the base is 2.5:3:100:100.

[0009] As a further improvement of the present invention, the reaction temperature is 75-85°C.

[0010] As a further improvement of the present invention, the reaction time is 20-28 hours.

[0011] As a further improvement of the present invention, the copper salt is copper chloride or copper sulfate.

[0012] As a further improvement of the present invention, the following steps are specifically included: transferring the reaction tube to a glove box, adding 4-(2-aminophenyl)-3-butene-2-one, copper salt, ligand, PhSiH3 and base, then removing the glove box and placing it in a CO2 environment, evacuating the reaction tube and filling it with CO2 three times, and then adding dry solvent to the reaction tube. Cover the reaction tube with a lid, stir at 75-85°C for 20-28h, and after the reaction is completed, carefully add HCl solution to quench the reaction, stir the reaction mixture at room temperature, then extract with EtOAc, concentrate the organic phase by air separation, and purify the crude material by silica gel flash column chromatography to obtain the target product.

[0013] The present invention further protects a compound obtained by the above-mentioned synthesis method. N -Carboxyindole.

[0014] The present invention has the following beneficial effects: The present invention utilizes the developed "Cu / Si" catalytic system to realize the synthesis of α,β-unsaturated ketone CC bond cleavage N -Carboxy indole compounds.

[0015] Innovations of this catalytic system:

[0016] 1. The indole ring is successfully closed by breaking the CC bond, avoiding the formation of by-products.

[0017] 2. Avoid using excessive amounts of strong base in the reaction system for synthesis N -Carboxyl compounds are conducive to industrial production.

[0018] 3. Realized the conversion from CO2 to high value-added chemicals. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0020] Figure 1 is the hydrogen spectrum of the target product in Example 1 of the present invention;

[0021] Figure 2 This is the carbon spectrum of the target product in Example 1 of the present invention. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0023] Example 1

[0024] Synthesis route:

[0025] .

[0026] Preparation method:

[0027] A magnetic stirring bar was added to a flame-dried 100 mL reaction tube. The reaction tube was then transferred to a glove box. 1a (4-(2-aminophenyl)-3-butene-2-one) (5 mmol), copper sulfate (0.25 mmol), ligand (0.3 mmol), PhSiH3 (10 mmol), and NaOH (10 mmol) were added to the tube, which was then removed from the glove box and placed in a CO2 environment. The reaction tube was evacuated and filled with CO2 three times, and then dry solvent (20 mL) was added to the reaction tube. The reaction tube was capped and stirred at 80 °C for 24 h. After the reaction was completed, 30 mL of 2 mol / L HCl solution was carefully added to quench the reaction. The reaction mixture was stirred at room temperature for 30 min and then extracted with EtOAc (4×20 mL). The organic phase was concentrated by air separation, and the crude material was purified by silica gel flash column chromatography (deactivated silica gel, PE / EA = 4 / 1, then 0.1% AcOH in PE / EA = 1 / 1) to obtain the target product. The hydrogen and carbon spectra of the product are shown in Figure 1 and 2 The results are as follows:

[0028] 1 H NMR (400 MHz, DMSO- d 6) δ 11.73 (s, 1H), 7.88 (d, J = 9.5 Hz, 1H),7.64 (dd, J = 7.9, 1.5 Hz, 1H), 7.48 (ddd, J = 8.5, 7.2, 1.5 Hz, 1H), 7.30(dd, J = 8.3, 1.1 Hz, 1H), 7.16 (ddd, J= 8.1, 7.2, 1.1 Hz, 1H), 6.49 (d, J =9.5 Hz, 1H).

[0029] 13 C NMR (101 MHz, DMSO- d 6) δ 162.4, 140.7, 139.4, 130.8, 128.3, 122.4,122.2, 119.6, 115.6.

[0030] Example 2

[0031] Preparation method:

[0032] A magnetic stirring bar was added to a flame-dried 100 mL reaction tube. The reaction tube was then transferred to a glove box. 1a (4-(2-aminophenyl)-3-butene-2-one) (5 mmol), copper chloride (0.3 mmol), ligand (0.35 mmol), PhSiH3 (11 mmol), and NaOH (11 mmol) were added to the tube, which was then removed from the glove box and placed in a CO2 environment. The reaction tube was evacuated and filled with CO2 three times, and then dry solvent (20 mL) was added to the reaction tube. The reaction tube was capped and stirred at 85 °C for 28 h. After the reaction was completed, 30 mL of 2 mol / L HCl solution was carefully added to quench the reaction. The reaction mixture was stirred at room temperature for 30 min and then extracted with EtOAc (4×20 mL). The organic phase was concentrated by air separation, and the crude material was purified by silica gel flash column chromatography (deactivated silica gel, PE / EA = 4 / 1, then 0.1% AcOH in PE / EA = 1 / 1) to obtain the target product.

[0033] Example 3

[0034] Preparation method:

[0035] A magnetic stirring bar was added to a flame-dried 100 mL reaction tube. The reaction tube was then transferred to a glove box. 1a (4-(2-aminophenyl)-3-butene-2-one) (5 mmol), copper sulfate (0.2 mmol), ligand (0.25 mmol), PhSiH3 (9 mmol), and KOH (9 mmol) were added to the tube, which was then removed from the glove box and placed in a CO2 environment. The reaction tube was evacuated and filled with CO2 three times, and then dry solvent (20 mL) was added to the reaction tube. The reaction tube was capped and stirred at 75 °C for 20 h. After the reaction was completed, 30 mL of 2 mol / L HCl solution was carefully added to quench the reaction. The reaction mixture was stirred at room temperature for 30 min and then extracted with EtOAc (4×20 mL). The organic phase was concentrated by air separation, and the crude material was purified by silica gel flash column chromatography (deactivated silica gel, PE / EA = 4 / 1, then 0.1% AcOH in PE / EA = 1 / 1) to obtain the target product.

[0036] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing N-carboxy indole by copper-catalyzed cleavage of the CC bond of α,β-unsaturated ketone, characterized in that: 4-(2-aminophenyl)-3-butene-2-one is reacted with CO2 under catalyst conditions to prepare N-carboxy indole, the catalyst is a copper salt, a ligand, PhSiH3 and a base, the molar ratio of the copper salt, the ligand, PhSiH3 and the base is 2-3:2.5-3.5:90-110:90-110, the copper salt is copper chloride or copper sulfate, and the ligand is 4,4'-di-tert-butyl-2,2'-bipyridine.

2. The synthesis method according to claim 1, characterized in that The molar ratio of the copper salt, the ligand, PhSiH3 and the base is 2.5:3:100:

100.

3. The synthesis method according to claim 1, characterized in that The temperature of the reaction is 75-85°C.

4. The synthesis method according to claim 1, characterized in that The reaction time is 20-28h.

5. The synthesis method according to any one of claims 1 to 4, characterized in that: The specific steps include: The reaction tube was transferred to a glove box, 4-(2-aminophenyl)-3-butene-2-one, copper salt, ligand, PhSiH3 and base were added, and then the glove box was removed and placed in a CO2 environment. The air was evacuated from the reaction tube and CO2 was filled into the reaction tube three times. Then, dry solvent was added to the reaction tube, and the lid of the reaction tube was closed. The reaction tube was stirred at 75-85°C for 20-28h. After the reaction was completed, HCl solution was added to quench the reaction. The reaction mixture was stirred at room temperature, and then extracted with EtOAc. The organic phase was concentrated, and the crude material was purified by silica gel flash column chromatography to obtain the target product.

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