Method for synthesizing aryl amide by light / nickel synergistic catalysis of aryl halide

Abstract

The invention discloses a method for synthesizing aryl amide by light / nickel concerted catalysis of aryl halide. Compared with the prior art, after the phenyl aryl benzoate product is obtained, treatment is not needed, and amine is directly added to obtain amide. The preparation method provided by the invention has the advantages of simple operation steps, good substrate universality, coverage of polycyclic and heterocyclic substituted aryl phenyl benzoate, wide functionality tolerance, mild reaction conditions and high yield, and is a green chemical synthesis method with good application prospects.

Description

Technical Field

[0001] The invention relates to a mild and efficient method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis. Background Art

[0002] As one of the most fundamental and important functional groups in organic chemistry, the amide bond (-C(O)NR1R2) is widely present in numerous high-value-added fine chemicals, particularly in pharmaceuticals (such as β-lactam antibiotics and lipid-lowering drugs), pesticides (such as herbicides and insecticides), high-performance polymers (such as nylon and aramid), surfactants, and natural products. Therefore, the development of efficient, economical, and environmentally friendly amide synthesis processes is a key technological challenge that continues to attract attention in the chemical industry.

[0003] In traditional chemical production, the aminolysis of esters involves reacting carboxylic acid esters with ammonia or amines. Although esters are relatively readily available, the reaction typically requires an excess of amine (often gaseous ammonia or low-boiling-point amines, which are inconvenient to operate and difficult to recycle) or a metal catalyst (such as alkoxytitanium or aluminum compounds), and is often carried out at high temperatures and high pressures. This poses challenges in catalyst cost, deactivation, and metal residue, and places significant pressure on the equipment. Against this backdrop, one-step modification of esters can yield amides. Using inexpensive and readily available photocatalysts under light induction, the conversion of abundant, inexpensive chemical raw materials into high-value-added compounds holds great promise for future applications. Summary of the Invention

[0004] Purpose of the invention: In order to break the limitations of the existing technical methods and as a supplement to the existing research on the conversion of esters into amides, the present invention provides a mild and efficient method for synthesizing aryl amides from aryl halides using photo / nickel synergistic catalysis.

[0005] In order to solve the above technical problems, the present invention provides the following technical solutions.

[0006] One of the technical solutions of the present invention is a method for synthesizing aryl amides from aryl halides catalyzed by light / nickel, the structural formula of which is:

[0007]

[0008] Here, R1 is any one of a trifluoromethyl group, an ester group, a cyano group, a methoxy group, a halogen atom, a polycyclic aromatic group, a heterocyclic group, and the like.

[0009] A second technical solution of the present invention provides a method for synthesizing aryl amides from aryl halides using the above-mentioned light / nickel synergistic catalysis, comprising the following steps:

[0010]

[0011] Among them, R2 and R3 are hydrogen, methoxy, alkyl, etc.

[0012] The aryl bromobenzene shown in Formula 1, the phenyl formate shown in Formula 2, and the reducing agent are dissolved in an organic solvent, and the reaction is carried out at room temperature for 16 hours under 456nm blue light irradiation. After the reaction is completed, amine is added to the reaction system, and the reaction is carried out at 80°C for 10 hours to synthesize the amide shown in Formula 3 and its derivatives. The target product is obtained by separation and purification, that is, the target product Formula 3 is synthesized.

[0013] The photocatalyst is 4CzIPN, 3DPAFIPN and the like.

[0014] The reducing agent is quinuclidine.

[0015] The metal catalysts are NiCl2·glyme, Ni(OTf)2, Ni(OAc)2·4H2O and Ni(COD)2.

[0016] The amines are primary amines, secondary amines and tertiary amines.

[0017] The inorganic base is sodium bicarbonate, cesium fluoride, tripotassium phosphate, triethylamine, and N,N-diisopropylethylamine.

[0018] The organic solvent is N,N-dimethylformamide, acetonitrile, toluene, 1,4-dioxane, N,N-dimethylacetamide, and tetrahydrofuran.

[0019] The visible light is blue light with a wavelength of 456nm.

[0020] The molar ratio of the compound represented by Formula 1 to the compound represented by Formula 2 may be 1:1.5.

[0021] The molar ratio of the compound represented by Formula 1 to the photocatalyst is 1:0.01.

[0022] The reaction is carried out under an inert gas environment, and the inert gas atmosphere can be nitrogen.

[0023] In the eluent, the volume ratio of petroleum ether to ethyl acetate is 1000:1 to 5:1.

[0024] The progress of the reaction can be monitored by conventional monitoring methods in the art (such as TLC).

[0025] The steps of separating and purifying the reaction system of the reaction are as follows: the reaction system is directly concentrated under reduced pressure, the obtained concentrate is separated and purified by column chromatography on silica gel, the eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate, the eluate is collected and the solvent is evaporated to obtain the target product.

[0026] In one embodiment of the present invention, the amidation product shown in Formula 3 includes but is not limited to any of the following structures:

[0027]

[0028] The beneficial effects of the present invention are: the present invention provides a mild and efficient method for synthesizing aromatic amides from aromatic halides through light / nickel synergistic catalysis, the raw materials are stable and easy to prepare, the reaction conditions are mild, the experimental operation is simple, the production capacity is high, the functional group tolerance is wide, and the chemical selectivity is good. It is a green chemical synthesis method with good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0030] Figure 1 is the reaction formula of aryl bromobenzene, phenyl formate and amine;

[0031] Figure 2 This is the H NMR spectrum of compound 3a prepared in Example;

[0032] Figure 3 This is the H NMR spectrum of compound 3b prepared in Example;

[0033] Figure 4 This is the H NMR spectrum of compound 3d prepared in Example;

[0034] Figure 5 This is the H NMR spectrum of compound 3e prepared in Example; DETAILED DESCRIPTION

[0035] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0036] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0037] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0038] Example 1: Preparation of morpholino (4- (trifluoromethyl) phenyl) ketone 3a, the formula is as follows:

[0039]

[0040] In a nitrogen-filled glove box, 1-bromo-4-(trifluoromethyl)benzene (0.3 mmol, 1.0 equiv), phenyl formate (0.45 mmol, 1.5 equiv), NiCl2·glyme (0.03 mmol, 10%), 4CzIPN (0.003 mmol, 1%), L1 (0.045 mmol, 15%), NaHCO3 (0.45 mmol, 1.5 equiv), and 3 mL of DMF were added to a 25 mL oven-dried Schlenk tube. Finally, the reaction mixture was stirred at room temperature for 16 h in a sealed tube under continuous light irradiation from a 40 W blue LED (λ = 456 nm). After completion of the reaction, morpholine (0.45 mmol, 1.5 equiv) was added to the reaction system and the mixture was reacted at 80°C for 10 h. The target product (Formula 3) was then isolated and purified. The system was concentrated under reduced pressure and the solvent was removed to obtain a crude product, which was then purified by column chromatography using petroleum ether as eluent to obtain 55.9 mg of the product with a yield of 70%.

[0041] NMR analysis: 1 H NMR (400MHz, CDCl3) δ7.73-7.67(m, 2H), 7.57-7.50(m, 2H), 3.80(s, 4H), 3.63(s, 2H), 3.41(s, 2H).

[0042] Example 2: Preparation of N-methoxy-N-methyl-4-trifluoromethylbenzamide 3b. The same method as Example 1 was used, except that morpholine in Example 1 was replaced with N,O-dimethylhydroxylamine hydrochloride, to obtain 46.1 mg of the target compound in a yield of 66%.

[0043] NMR analysis: 1 H NMR (400MHz, CDCl3) δ7.81-7.78(m, 2H), 7.69-7.66(m, 2H), 3.53(s, 3H), 3.38(s, 3H).

[0044] Example 3: Preparation of p-trifluoromethylbenzamide 3d. The same method as in Example 1 was used except that the morpholine in Example 1 was replaced with an equal molar amount of ammonia in dioxane solution to obtain 27 mg of the target compound in a yield of 65%.

[0045] NMR analysis: 1 H NMR (400MHz, DMSO) δ8.21 (s, 1H), 8.09-8.05 (m, 3H), 7.87-7.83 (m, 3H), 7.64 (s, 1H).

[0046] Example 4: Preparation of 4-chloro-7-methoxyquinoline-6-carboxamide 3e. The same procedure as in Example 1 was followed, except that 1-bromo-4-(trifluoromethyl)benzene in Example 1 was replaced with an equal molar amount of 4-chloro-7-methoxyquinoline-6-carboxamide, and morpholine in Example 1 was replaced with an equal molar amount of ammonia in dioxane solution. 55.4 mg of the target compound was obtained in a yield of 59%.

[0047] NMR analysis: 1 H NMR (400MHz, CDCl3) δ9.14 (s, 1H), 8.77 (d, J = 4.8Hz, 1H), 7.76 (s, 1H), 7.58 (s, 1H), 7.43 (d, J = 4.7Hz, 1H), 6.03 (s, 1H), 4.13 (s, 3H).

[0048] Example 5:

[0049] The above embodiments are only used to help understand the method and core concept of the present invention. It should be noted that any modifications, equivalent substitutions and improvements made by those skilled in the art without departing from the principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for synthesizing aryl amides from aryl halides using photocatalytic / nickel catalysis, characterized in that Bromobenzene represented by Formula 1, phenyl formate represented by Formula 2, a base, a reducing agent, and a photocatalyst are dissolved in an organic solvent and reacted at room temperature for 16 hours under visible light irradiation. After the reaction, amine is added to the reaction system and reacted at 80°C for 10 hours to synthesize amides represented by Formula 3 and their derivatives. The reaction formula is as follows:

2. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The photocatalysts include 4CzIPN, 3DPAFIPN, etc.

3. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The metal catalysts are NiCl2·glyme, Ni(OTf)2, Ni(OAc)2·4H2O and Ni(COD)2.

4. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The amines are primary amines, secondary amines and tertiary amines.

5. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The base is sodium bicarbonate, cesium fluoride, tripotassium phosphate, triethylamine, and N,N-diisopropylethylamine.

6. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The organic solvent is N,N-dimethylformamide, acetonitrile, toluene, 1,4-dioxane, N,N-dimethylacetamide, and tetrahydrofuran.

7. The method of synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The visible light is blue light.

8. The method of synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The ligands are 4,4′-di-tert-butyl-2,2′-bipyridine, 2,2′-bipyridine, and 5,5′-dimethyl-2,2′-bipyridine.

9. The method of synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The reaction is preferably carried out under an inert atmosphere, which may be nitrogen.

10. The method for synthesizing aryl amide from aryl halide by light / nickel synergistic catalysis according to claim 1, characterized in that The steps of separating and purifying the reaction system are as follows: the reaction system is directly concentrated under reduced pressure, the obtained concentrate is separated and purified by column chromatography on silica gel, the eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate, the eluate is collected and the solvent is evaporated to obtain the target product.

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