Method and system for synthesizing amide compounds from nitrile compounds

Abstract

The present application discloses a method and system for synthesizing amide compounds from nitrile compounds. The method for synthesizing amide compounds from nitrile compounds of the present application comprises dispersing nitrile compounds, photocatalysts and organic base additives in a mixed solvent of water and organic solvents, and performing a photocatalytic reaction under light in an atmosphere of oxygen or oxygen-containing atmosphere to generate amide compounds. The method for synthesizing amide compounds from nitrile compounds of the present application only requires adding a small amount of photocatalyst and using cheap and readily available oxygen as a reactant to efficiently obtain amide compounds; the reaction conditions are simple and mild, green and environmentally friendly, and easy to operate. The method of the present application can be applied to various nitrile compounds including aromatic nitriles, alkyl nitriles, and heterocyclic nitriles, and has strong applicability; moreover, it can be applied to microchannel reactors to meet the needs of large-scale industrial production.

Description

Technical Field

[0001] The present application relates to the technical field of amide compound synthesis, and in particular to a method and system for synthesizing amide compounds from nitrile compounds. Background Art

[0002] Organic synthesis refers to the process of synthesizing organic compounds from simpler compounds or elements through chemical reactions. It sometimes also includes the degradation of complex raw materials into simpler compounds. As the foundation of organic chemistry, organic synthesis is the primary means and tool for creating new molecules. A core aspect of organic synthesis is the synthesis of a wide variety of chemical molecules, such as natural products, pharmaceuticals, functional molecules, and materials.

[0003] Amide compounds (amides, abbreviated as amides) are organic compounds containing an amide group in their molecular structure. Amide groups are important functional groups in organic synthesis and serve as the fundamental structural units of peptides, enzymes, and proteins. They are widely found in pharmaceuticals, pesticides, and natural products. Furthermore, amides serve as important chemical raw materials in applications such as lubricants, plastics, and detergents.

[0004] Amides are typically prepared by reacting carboxylic acids and their derivatives, such as anhydrides, esters, and halides, with amines. However, these common methods often have limitations. For example, the reaction of carboxylic acids and amines to prepare amides requires the addition of a stoichiometric amount or even more of a base as an activating agent, which becomes a byproduct after the reaction. This results in low atom efficiency and is inconsistent with the concept of green chemistry.

[0005] Nitriles, a class of compounds containing a cyano group, can react with both nucleophiles and electrophiles to form new carbon-carbon and carbon-heteroatom bonds. For example, cyclization reactions can be used to prepare polycyclic quinolines, which can then react with amines to form amides. Similarly, this reaction requires the addition of a stoichiometric or even larger amount of base as an activating agent, which becomes a byproduct after the reaction, resulting in low atom efficiency and inconsistent with the concept of green chemistry.

[0006] In addition, various catalytic systems have been developed, such as transition metal complexes, metal cations, metal nanoparticles, ionic liquids, and others. These systems have optimized the conditions for nitrile hydration to varying degrees, such as reducing catalyst usage and shortening reaction times.

[0007] Throughout the hydration reaction of nitrile compounds, different catalysts have different catalytic mechanisms, but most of them promote the reaction in two ways: (1) interacting with the cyanide group to activate the cyanide group, making it more likely to participate in the reaction; and (2) enhancing the nucleophilicity of the nucleophilic reagent and promoting the nucleophilic attack process. For example, after the metal center of the metal complex catalyst is coordinated with the cyanide group, the catalyst ligand reacts with the water molecule to form hydrogen bonds, thereby enhancing the nucleophilicity of the oxygen atom in the water molecule. Metal nanoparticle catalysts can promote the reaction by dissociating water molecules into hydroxyl groups with stronger nucleophilic ability through the surface oxygen atoms. The development and continuous development of these catalytic systems have provided a rich strategy for the hydration reaction of nitrile compounds to form amides.

[0008] Although significant progress has been made in the study of hydration reactions of nitrile compounds, many unresolved issues and challenges remain. For example, (1) most catalytic systems involve the use of precious metals and organic solvents, such as palladium, ruthenium, rhodium, and platinum. The catalysts are difficult to recover and reuse after the reaction, and issues such as cost and environmental pollution still need to be improved. (2) The substrate range is relatively limited. For example, in many reactions, when electron-withdrawing groups or nitriles with large steric hindrance are used as substrates, the corresponding amide yields are slightly low. Heteroaromatic nitriles and alkyl nitriles also have low conversion rates due to the inability to form intermediates.

[0009] Photocatalytic technology is a new technology that converts solar energy into chemical energy. It has the characteristics of mild conditions, green environmental protection and sustainable utilization. It is an effective way to solve the current energy and clean production problems. As a clean energy source, light has the advantages of being easily accessible, simple to use and naturally abundant, and has long attracted attention. Compared with traditional synthesis methods that are difficult to control, have high energy consumption and cause certain pollution to the environment, photocatalytic reactions have gradually become a green organic synthesis method that is highly valued due to their mild conditions, good functional group compatibility, controllable product selectivity, low environmental pollution and low energy consumption. Faced with the problems of catalyst poisoning, harsh reaction conditions and high material costs in the hydration reaction of nitrile compounds, exploring and developing green synthesis methods involving photochemistry and further exploring better and more universal catalytic systems are the focus and difficulty of current researchers. Summary of the Invention

[0010] The purpose of this application is to provide a new method and system for synthesizing amide compounds from nitrile compounds.

[0011] This application adopts the following technical solutions:

[0012] One aspect of the present application discloses a method for synthesizing an amide compound from a nitrile compound, comprising dispersing a nitrile compound, a photocatalyst, and an organic base additive in a mixed solvent of water and an organic solvent, and performing a photocatalytic reaction under light in an atmosphere of oxygen or oxygen-containing atmosphere to generate an amide compound.

[0013] It should be noted that the present application creatively uses photocatalytic reactions for the synthesis of amide compounds from nitrile compounds. The novel photocatalytic method for generating amides from nitrile compounds developed by the present application only requires the addition of a small amount of photocatalyst, such as 1 mol% of terpyridine ruthenium chloride hexahydrate ([Ru(bpy)3Cl2]·6H2O), and the use of cheap and readily available oxygen as a reactant to efficiently obtain amide compounds. Compared with existing methods, the method of the present application has simple and mild reaction conditions, is green and environmentally friendly, and is easy to operate. In one implementation of the present application, the method of the present application was used to convert 48 different nitrile compounds into amide compounds, including aromatic nitriles, alkyl nitriles, and heterocyclic nitriles. It can be seen that the method of the present application has very wide applicability. Moreover, in one implementation of the present application, the method for synthesizing amide compounds of the present application can also be applied to microchannel reactors and can adapt to large-scale industrial production.

[0014] In one implementation of the present application, the nitrile compound is an aromatic nitrile compound, an alkyl nitrile compound or a heterocyclic nitrile compound.

[0015] It should be noted that the key to this application lies in the development of a new method for synthesizing amide compounds using photocatalytic nitrile compounds. As for the specific nitrile compounds, it can be determined according to the amide compounds synthesized, including but not limited to aromatic nitrile compounds, alkyl nitrile compounds or heterocyclic nitrile compounds.

[0016] In one implementation of the present application, the nitrile compounds specifically include benzonitrile, 4-ethynylbenzonitrile, 2-naphthocyanin, 1-cyclopenteneacetonitrile, 2-cyanothiophene, terephthalonitrile, 4-nitrobenzonitrile, quinoline-6-carbonitrile, 3-phenylacrylonitrile, quinoline-4-carbonitrile, 2-bromobenzonitrile, 4-methoxybenzonitrile, 1,3-benzodicyclopentacyclo-5-carbonitrile, α-methylbenzeneacetonitrile, 3-methoxyisonicotinonitrile, 2-iodobenzonitrile, 4-morpholinebenzonitrile, n-octanonitrile, 1-phenyl-1-cyclopropylcarbonitrile, 2-cyano-5-fluoropyridine, 2-methylbenzonitrile, 4-aminobenzonitrile, cyclopentanecarbonitrile, 1-phenyl-1-cyclobutylcarbonitrile, 6-methyl-2-pyridinecarbonitrile, 2-ethoxybenzonitrile , p-phenylbenzonitrile, cyclohexanecarbonitrile, 1-phenyl-1-cyclopentylcarbonitrile, 2-methoxy-5-cyanopyridine, 2-nitrobenzonitrile, 4-tert-butylbenzonitrile, 4-phenylbutyronitrile, 5-methyl-1,3-benzenedicarbonitrile, 2,6-pyridinedicarbonitrile, 3-morpholinebenzonitrile, 3-fluoro-4-aminobenzonitrile, 2-phenoxyacetonitrile, 3-cyanopyridine, chromone-3-carbonitrile, 4-fluorobenzonitrile, isophthalonitrile, 4-bromophenylacetonitrile, 5-cyanopyridine, 4-chlorobenzonitrile, 2-methylterephthalonitrile, 1,2-benzenedicarbonitrile, 2-cyanofuran; the amide compounds synthesized in sequence from the above nitrile compounds include benzamide, 4-ethynylbenzamide, 2-naphthamide , 1-cyclopentenyl acetamide, 2-thiophenecarboxamide, terephthalamide, 4-nitrobenzamide, quinoline-6-carboxamide, 3-phenylacrylamide, quinoline-4-carboxamide, 2-bromobenzamide, 4-methoxybenzamide, 1,3-benzodicyclopentazoline-5-carboxamide, α-methylphenylacetamide, 3-methoxypyridine-4-carboxamide, 2-iodobenzamide, 4-morpholinobenzamide, n-octanamide, 1-phenyl-1-cyclopropylcarboxamide, 5-fluoropyridine-2-carboxamide, 2-methylbenzamide, 4-aminobenzamide, cyclopentanecarboxamide, 1-phenyl-1-cyclobutylcarboxamide, 6-methylpicolinamide, 2-ethoxybenzamide, p-phenylenediamine Amine, cyclohexanecarboxamide, 1-phenyl-1-cyclopentylcarboxamide, 6-methoxy-3-pyridinecarboxamide, 2-nitrobenzamide, 4-tert-butylbenzamide, 4-phenylbutanamide, 2-(3-(2-cyanopropan-2-yl)-5-methylphenyl)-2-methylpropionamide, pyridine-2,6-dicarboxamide, 3-morpholinobenzamide, 3-fluoro-4-aminobenzamide, 2-phenoxyacetamide, 3-pyridinecarboxamide, chromone-3-carboxamide, 4-fluorobenzamide, isophthalic acid amide, 4-bromophenylacetamide, pyrimidine-5-carboxamide, 4-chlorobenzamide, 3-methyl-4-cyanobenzamide, 1,2-benzenediacetamide, 2-furancarboxamide.

[0017] It should be noted that the 48 nitrile compounds and their corresponding amide compounds listed in this application are merely one implementation of this application, and specific experiments have verified that the amide compounds and nitrile compounds can be synthesized using the method of this application. It is understood that under the inventive concept of this application, the nitrile compounds that can be used include but are not limited to these 48; of course, the amide compounds that can be synthesized also include but are not limited to these 48; therefore, under the inventive concept of this application, it is not ruled out that other similar nitrile compounds can also be used to synthesize the corresponding amide compounds.

[0018] In one implementation of the present application, the photocatalyst is terpyridine ruthenium chloride or terpyridine ruthenium chloride hexahydrate.

[0019] In one implementation of the present application, the organic base additive is at least one of 1,8-diazobispiro[5.4.0]undec-7-ene, 7-methyl-1,5,7-triazabicyclo[4.4.0]quinacridone-5-ene, 2-tert-butyl-1,1,3,3-tetramethylguanidine, diisopropylamine, triethylamine, and N,N-diisopropylethylamine.

[0020] It should be noted that different organic base additives will affect the yield of amide compounds. In one implementation of the present application, 12 different organic base additives were tried to react with nitrile compounds to form amides. The results showed that only 1,8-diazobispiro[5.4.0]undec-7-ene, 7-methyl-1,5,7-triazabicyclo[4.4.0]quinone-5-ene, 2-tert-butyl-1,1,3,3-tetramethylguanidine, diisopropylamine, triethylamine, and N,N-diisopropylethylamine can obtain products. Taking into account the controllability and economy of the reaction, the preferred organic base additive is N,N-diisopropylethylamine (DIPEA).

[0021] In one implementation of the present application, the organic solvent is acetonitrile and / or methanol.

[0022] In one implementation of the present application, the mixed solvent consists of water, acetonitrile and methanol.

[0023] In one implementation of the present application, in the mixed solvent, the volume ratio of acetonitrile:methanol:water is 1:2:3.

[0024] In one implementation of the present application, the wavelength of the light is 400-480 nm.

[0025] In one implementation of the present application, the method of the present application further includes adding a metal salt additive to the photocatalytic reaction.

[0026] In one implementation of the present application, the metal salt additive is at least one of sodium acetate, sodium bicarbonate, sodium carbonate, cesium carbonate, cesium acetate, potassium fluoride, potassium carbonate, potassium phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate.

[0027] It should be noted that in the photocatalytic reaction of nitrile compounds to synthesize amide compounds in the present application, photocatalysts, organic base additives, water and oxygen, as well as light are necessary conditions; as for metal salt additives, they can be added according to the specific nitrile compounds used, and different metal salt additives will directly affect the yield of amide compounds. For example, in benzonitrile substrates, the yield of amide compounds is the highest when dipotassium hydrogen phosphate (K2HPO4) is used as a metal salt additive.

[0028] In one implementation of the present application, in the photocatalytic reaction, the concentration of the nitrile compound is 0.04-0.2 mmol / mL, the amount of the photocatalyst is 1-4 mol%, the amount of the organic base additive is 2-3.5 equivalents, and the amount of the metal salt additive is 0.5-1.5 equivalents.

[0029] Another aspect of the present application discloses a system for synthesizing amide compounds from nitrile compounds, comprising a microchannel reaction device and a light source; the microchannel reaction device comprises a material flow path, a gas path, and a light-transmitting microchannel chip; the material flow path is used to provide reaction raw materials to form a reaction liquid; the gas path is used to provide the gas required for the reaction; the microchannel chip is used to carry out a gas-liquid two-phase reaction, and the gas cuts the reaction liquid into microdroplets or forms a gas-liquid two-phase flow state in which a gas column and a liquid column alternately appear; the gas is oxygen or a gas containing oxygen, and the reaction liquid is the reaction solution of the photocatalytic reaction in the method of the present application; the light source is used to provide illumination for the gas-liquid two-phase reaction carried out in the microchannel chip to achieve a photocatalytic reaction.

[0030] It should be noted that the system for synthesizing amide compounds from nitrile compounds of the present application is actually a method for synthesizing amide compounds from nitrile compounds of the present application using a microchannel reaction device, so that the amide compound synthesis method of the present application can better meet the needs of large-scale industrial production. It can be understood that by controlling the alternating input of gas and reaction liquid into the microchannel chip, a gas-liquid two-phase flow state can be formed in which a gas column and a liquid column alternately appear; as for the gas cutting the reaction liquid into microdroplets, the reaction liquid can be atomized by referring to an existing atomization device or a similar method, so that the microdroplets of the reaction liquid are dispersed in the gas to form a gas-liquid segment flow.

[0031] The beneficial effects of this application are:

[0032] The method for synthesizing amide compounds from nitrile compounds disclosed herein requires only the addition of a small amount of photocatalyst and uses inexpensive and readily available oxygen as a reactant to efficiently obtain amide compounds. The reaction conditions are simple, mild, environmentally friendly, and easy to operate. The method disclosed herein is applicable to a variety of nitrile compounds, including aromatic nitriles, alkyl nitriles, and heterocyclic nitriles, and exhibits strong applicability. Furthermore, the method can be used in microchannel reactors to meet the needs of large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Schematic diagram of the structure of the microchannel reactor in the embodiment of the present application;

[0034] Figure 2 This is a physical photo of the microchannel chip in the embodiment of the present application;

[0035] Figures 3 to 12 These are 48 amide compounds synthesized from the 48 nitrile compounds in the examples of this application. DETAILED DESCRIPTION

[0036] Although photocatalytic technology has been used in chemical synthesis reactions, there is currently no research on using photocatalytic technology to synthesize amide compounds from nitrile compounds. Faced with the problems of catalyst poisoning, harsh reaction conditions, and high material costs in the existing synthesis of amide compounds from nitrile compounds, this application creatively proposes to use photocatalytic reactions to synthesize amide compounds from nitrile compounds; and develops a specific photocatalytic reaction system and conditions. Specifically, the method of the present application includes dispersing a nitrile compound, a photocatalyst, and an organic base additive in a mixed solvent of water and an organic solvent, and performing a photocatalytic reaction under light in oxygen or an atmosphere containing oxygen to generate an amide compound.

[0037] The method of the present application solves the problems of catalyst poisoning, harsh reaction conditions, and high material costs in the existing synthesis of amide compounds from nitrile compounds. Only a small amount of photocatalyst is needed and oxygen is used as a raw material to realize the synthesis of amide compounds from nitrile compounds. No precious metals are required and the amount of organic solvents used is also reduced. In one implementation of the present application, oxygen ( 18 The researchers used a photocatalytic method to track the role of oxygen in the reaction, using a nitrile (O2) solution. The results showed that all oxygen atoms in the synthesized amide compounds came from oxygen. This indicates that oxygen is indeed a raw material in the photocatalytic reaction of nitrile compounds to amide compounds. Furthermore, the method is generally applicable to aromatic nitriles, alkyl nitriles, and heterocyclic nitriles, allowing for a wide range of substrate options.

[0038] In addition, the method of the present application can also be applied to existing microchannel reactors to form a system for synthesizing amide compounds from nitrile compounds of the present application.

[0039] It should be noted that the microchannel reaction device of the present application, i.e., a microchannel reactor, is usually characterized by narrow and well-defined pipes with internal dimensions of 10 to 104 μm and internal volumes ranging from a few microliters to tens of milliliters. It can be divided into small-scale and medium-scale continuous flow reactors according to their respective inner diameters and volumes. The surface area / volume ratio of the microreactor tube is large. Compared with the traditional batch reaction process, the continuous flow system has many advantages, mainly including: ① Faster reaction rate: efficient mass and heat transfer and high pressure performance can increase the reaction rate; ② Higher safety: flow chemistry only produces a small amount of harmful intermediates, and the high surface area / volume can well control the release of heat; ③ Enhanced control of experimental variables and improved reproducibility: Compared with batch processes, flow chemistry is easier to establish and monitor reaction parameters such as temperature, pressure and flow rate, resulting in a more reliable and reproducible process; ④ Easy to separate target products and by-products: Traditional independent multi-step reactions can be integrated into a more automated and systematic single-step reaction; ⑤ Easy process scale-up with almost no scale-up effect; ⑥ Simpler automation control: Unmanned online monitoring and analysis can be performed; ⑦ Adjustable reaction volume to achieve flexible on-demand production.

[0040] In summary, the photocatalytic method of the present invention for generating amides from nitrile compounds can be applied to microchannel flow chemical reactors and has important significance and application value for the synthesis of amide compounds.

[0041] The explanations of some professional terms in this application are as follows:

[0042] Organic synthesis chemistry refers to the process of synthesizing organic compounds from simpler compounds or elements through chemical reactions. Sometimes it also includes the process of degrading complex raw materials into simpler compounds.

[0043] Flow chemistry, also known as continuous flow chemistry or microchannel chemistry, refers to the continuous flow of chemical reagents, including reagent addition, mixing, reaction, separation, and purification. This process is performed continuously, distinguishing it from batch chemistry. Flow chemistry typically uses microchannel chips, coils, and packed beds as reactors.

[0044] Gas-liquid segmented flow: refers to the gas-liquid two-phase flow state in a pipeline where a gas column and a liquid column alternate; or, a gas-liquid segmented flow formed by the gas cutting the reaction liquid into microdroplets.

[0045] Photocatalysis: Photocatalysis is the intersection of photochemistry and catalysis science, and generally refers to photochemical reactions with the participation of catalysts.

[0046] Nitrile compounds (nitriles): refers to organic compounds containing a nitrile group (-C≡N) in their molecular structure.

[0047] Amide compounds (amides): refers to compounds containing amide groups in their molecular structure of organic compounds.

[0048] The present invention is further described in detail below through specific examples. The following examples are only used to further illustrate the present invention and should not be construed as limiting the present invention.

[0049] Example 1

[0050] In this example, terephthalonitrile is used to synthesize an amide compound through a photocatalytic reaction.

[0051] The details are as follows:

[0052] 0.1 mmol of a terephthalonitrile substrate was placed in a transparent glass reaction bottle, and 1 mol% of a photocatalyst [Ru(bpy)3Cl2]·6H2O was added; 2 eq. (equivalent) of an organic base additive N,N-diisopropylethylamine (DIPEA) was added; 1 eq. (equivalent) of a metal salt additive dipotassium hydrogen phosphate (K2HPO4) was added; an oxygen environment at normal pressure was added; a mixed solvent of acetonitrile:methanol:water in a volume ratio of 1:2:3 (reaction substrate concentration was 0.08 mmol / mL) was used; and irradiation was performed using a 5-watt LED lamp with a wavelength of 400 nm. The reaction was carried out at room temperature for 20 hours to obtain an amide compound.

[0053] The photocatalytic reaction formula in this example is as follows:

[0054]

[0055] The structural formula of the photocatalyst [Ru(bpy)3Cl2]·6H2O is as follows:

[0056]

[0057] The yield of the reaction product was measured using gas chromatography-mass spectrometry (GCMS). The results showed that the yield of the amide compound product prepared in this example was 84%. The yield refers to the ratio of the actual amide compound obtained to the amide compound theoretically obtained using an equal amount of nitrile compound.

[0058] Example 2

[0059] This example is based on Example 1, and the amount of photocatalyst used, the amount of organic base additive used, the composition and ratio of the mixed solvent, whether oxygen was added, and whether light was irradiated were tested. The rest of the test conditions are the same as in Example 1. The specific experimental conditions are shown in Table 1.

[0060] Table 1 Photocatalytic reaction condition design

[0061] serial number Photocatalyst dosage DIPEA Methanol:water atmospheric pressure gas illumination Reaction time Yield 1 1 mol% 3.5eq. 1:1 <![CDATA[O2]]> 400nm 24h >95％ 2 4 mol% 3.5eq. 1:1 <![CDATA[O2]]> 400nm 24h 80％ 3 / 3.5eq. 1:1 <![CDATA[O2]]> 400nm 24h nd 4 2.5 mol% 2.5eq. 1:1 <![CDATA[O2]]> 400nm 24h 75％ 5 2.5 mol% / 1:1 <![CDATA[O2]]> 400nm 24h nd 6 2.5 mol% 3.5eq. 1:0 <![CDATA[O2]]> 400nm 24h <5％ 7 2.5 mol% 3.5eq. 0:1 <![CDATA[O2]]> 400nm 24h 32％ 8 2.5 mol% 3.5eq. 1:1 <![CDATA[N2]]> 400nm 24h nd 9 2.5 mol% 3.5eq. 1:1 <![CDATA[O2]]> darkroom 24h nd

[0062] In Table 1, the photocatalyst is the same as in Example 1, i.e., [Ru(bpy)3Cl2]·6H2O, methanol:water is the volume ratio, the illumination is the same as in Example 1, the reaction time is 24 h at room temperature, and the yield "nd" indicates that no product is generated.

[0063] The results in Table 1 show that in the photocatalytic reaction of nitrile compounds to amide compounds, the addition of a photocatalyst, an organic base additive, water, and oxygen, as well as illumination conditions, are all essential. A photocatalyst dosage of 1-4 mol% achieves a good yield; the organic base additive dosage is 2-3.5 equivalents; water is essential in the mixed solvent, and a mixture of acetonitrile, methanol, and water or a mixture of methanol and water can be used. Using water alone as a solvent also allows for the photocatalytic reaction, but the yield is lower, and using methanol alone results in a yield of less than 5%. Oxygen is a required reaction raw material; when nitrogen is used to replace oxygen, no amide compound product is produced. Similarly, illumination is also essential; no product is produced without illumination.

[0064] Further, in this example, according to the experiment No. 1, an equal amount of benzonitrile was used to replace terephthalonitrile, and by using oxygen ( 18 O2), and all the amide products labeled with oxygen-18 were obtained. The experimental reaction formula is as follows:

[0065]

[0066] It can be seen from this that in the method of photocatalytically generating amides from nitrile compounds, the oxygen atom of the amide product comes from oxygen.

[0067] Example 3

[0068] In this example, based on Example 1, different nitrile compounds were used to replace terephthalonitrile to prepare amide compounds, and the rest were the same as in Example 1.

[0069] The photocatalytic reaction formula in this example is as follows:

[0070]

[0071] The different nitrile compounds used in this example include 23 different aromatic nitrile compounds, 14 different alkyl nitrile compounds, and 11 different heterocyclic nitrile compounds. The same method as in Example 1 was used to test the yield of the amide compound.

[0072] 23 different aromatic nitrile compounds and their yields are as follows:

[0073]

[0074] For example, in “2, R=4-CN, 85%”, 2 refers to the test number, R=4-CN means that the R substituent is “4-CN”, and 85% refers to the yield of the amide compound.

[0075] Tests 2 to 25 have the same general structural formula, namely

[0076] Here, for example, "26, 52%" refers to the test number, and 52% is the yield of the amide compound.

[0077] 14 different alkyl nitrile compounds and their yields are as follows:

[0078]

[0079] Here, for example, "37, 83%" refers to the test number, and 83% is the yield of the amide compound.

[0080] 11 different heterocyclic nitrile compounds and their yields are as follows:

[0081]

[0082] Among them, for example, "46, 93%", 46 refers to the test number, and 93% is the yield of the amide compound. The 48 nitrile compounds used in this example and the amide compounds synthesized therefrom are as follows: Figures 3 to 12 shown.

[0083] It can be seen that the photocatalytic method of generating amides from nitrile compounds in this example has a wide substrate adaptability range. Through this method, 48 different nitrile substrates were successfully converted into corresponding amide compounds with good yields.

[0084] Example 4

[0085] This example is based on Example 1, and a microchannel reactor is used to synthesize amide compounds from nitrile compounds, that is, a system for synthesizing amide compounds from nitrile compounds, such as Figure 1As shown, it includes a microchannel reaction device and a light source 2; the microchannel reaction device includes a material flow path 11, a gas path 12 and a light-transmissive microchannel chip 13; the material flow path 11 is used to provide reaction raw materials to form a reaction liquid; the gas path 12 is used to provide the gas required for the reaction; the microchannel chip 13, as shown Figure 2 As shown, it is used to carry out a gas-liquid two-phase reaction; the gas is oxygen or a gas containing oxygen, and the reaction liquid is the reaction solution of the photocatalytic reaction in the method of Example 1; the light source 2, that is, a 5-watt LED lamp bead with a wavelength of 400nm, is used to provide light for the gas-liquid two-phase reaction carried out in the microchannel chip to achieve a photocatalytic reaction.

[0086] In this example, the system Figure 1 As shown, the reactants, after being dissolved in a mixed solvent, are introduced into a microchannel glass chip via a syringe pump. Simultaneously, an oxygen cylinder enters the microchannel glass chip via a gas flow controller. By adjusting the oxygen flow rate, the reactant solution is divided into microdroplets within the microchannel, forming a gas-liquid segmented flow. The oxygen-separated microdroplets then enter a glass chip placed in a light jacket. LED light beads illuminate the glass chip, allowing the gas-liquid reaction to proceed efficiently during the flow, continuously producing the amide product.

[0087] In addition, based on Example 1, this example applies the method of photocatalytically generating amides from nitrile compounds to a photocatalytic flow reactor produced by Corning Incorporated. When 1 mol% of the photocatalyst terpyridine ruthenium chloride hexahydrate ([Ru(bpy)3Cl2]·6H2O), 2.0 eq. of the organic base additive N,N-diisopropylethylamine, and 1 eq. of dipotassium hydrogen phosphate are added, in a mixed solvent of acetonitrile / methanol / water in a volume ratio of 2:1:1, oxygen is introduced, and 400 nm light is irradiated. When the flow rates of the materials and oxygen are adjusted so that they pass through the reactor flow path for 8 minutes, the terephthalonitrile substrate yields an amide product at a yield of 75%. Under the above conditions, the terephthalonitrile substrate can produce an amide product at an efficiency of 164 mg per hour through the Corning photoreactor.

[0088] Example 5

[0089] This example is based on Example 1, using benzonitrile as a substrate and using different photocatalysts to synthesize amide compounds from nitrile compounds.

[0090] Reaction conditions: 1 mol% photocatalyst was added to 0.1 mmol of benzonitrile; 2 eq. (equivalent) of N,N-diisopropylethylamine (DIPEA) as an organic base additive; 1 eq. (equivalent) of dipotassium hydrogen phosphate (K2HPO4) as a metal salt additive; atmospheric pressure, oxygen atmosphere; a mixed solvent of acetonitrile:methanol:water (1:2:3 by volume) (substrate concentration 0.08 mmol / mL); illumination with a 5-watt LED lamp at a wavelength of 400 nm; reaction at room temperature for 20 hours to obtain the amide compound. The yield of the reaction product was determined by GCMS.

[0091] Different photocatalysts and their yields are as follows:

[0092]

[0093] in, Indicates the test number, "CAS: 7220-79-3" is the number of "methylene blue", and the corresponding "no product generated" means that no amide compound is generated when "methylene blue" is used as a photocatalyst.

[0094] The results showed that only when terpyridine ruthenium chloride and terpyridine ruthenium chloride hexahydrate were used as catalysts could the amide product be obtained under the reaction conditions, among which terpyridine ruthenium chloride hexahydrate [Ru(bpy)3Cl2]·6H2O was proved to be the catalyst with the highest yield.

[0095] Example 6

[0096] In this example, based on Example 1, benzonitrile was used as a substrate, and 12 organic base additives were used to synthesize amide compounds from nitrile compounds.

[0097] Reaction conditions: 1 mol% of the photocatalyst [Ru(bpy)3Cl2]·6H2O was added to 0.1 mmol of benzonitrile; 2 eq. (equivalent) of an organic base additive; and 1 eq. (equivalent) of a metal salt additive, dipotassium hydrogen phosphate (K2HPO4). The reaction was carried out under normal pressure in an oxygen atmosphere using a 1:2:3 (volume) mixture of acetonitrile, methanol, and water (substrate concentration 0.08 mmol / mL). Irradiation was performed using a 5-watt LED with a wavelength of 400 nm. The reaction was allowed to proceed at room temperature for 20 hours to yield the amide compound. The yield of the product was determined by GCMS.

[0098] Different organic base additives and their yields are as follows:

[0099]

[0100] in, Indicates the test number. "CAS: 108-48-5" is the number of "2,6-lutidine". The corresponding "no product is generated" means that no amide compound is generated when "2,6-lutidine" is used as the organic base additive.

[0101] Results showed that 12 different organic base additives had different effects on the amide formation reaction of nitrile compounds. Of these, only six produced products: 1,8-diazobispiro[5.4.0]undec-7-ene, 7-methyl-1,5,7-triazabicyclo[4.4.0]quinacridone-5-ene, 2-tert-butyl-1,1,3,3-tetramethylguanidine, diisopropylamine, triethylamine, and N,N-diisopropylethylamine. Although 1,8-diazobispiro[5.4.0]undec-7-ene as the organic base additive produced the highest yield of amide compounds, N,N-diisopropylethylamine (DIPEA) was ultimately determined to be the optimal organic base based on a comprehensive consideration of reaction controllability and economic efficiency.

[0102] Example 7

[0103] This example, based on Example 1, uses benzonitrile as a substrate and 10 metal salt additives to conduct experiments to synthesize amide compounds from nitrile compounds.

[0104] Reaction conditions: 1 mol% of the photocatalyst [Ru(bpy)3Cl2]·6H2O was added to 0.1 mmol of benzonitrile; 2 eq. (equivalent) of the organic base additive N,N-diisopropylethylamine (DIPEA) was added; and 1 eq. (equivalent) of the metal salt additive was added. The reaction was carried out under atmospheric pressure in an oxygen atmosphere using a mixed solvent of acetonitrile:methanol:water (1:2:3 by volume) (substrate concentration 0.08 mmol / mL). Illumination was achieved using a 5-W LED with a wavelength of 400 nm. The reaction was allowed to proceed at room temperature for 20 hours to yield the amide compound. The yield of the product was determined by GCMS.

[0105] The metal salt additives used in this example include: sodium acetate (NaOAc), sodium bicarbonate (NaHCO3), sodium carbonate (Na2CO3), cesium carbonate (Cs2CO3), cesium acetate (CsOAc), potassium fluoride (KF), potassium carbonate (K2CO3), potassium phosphate (K3PO4), potassium dihydrogen phosphate (KH2PO4), and dipotassium hydrogen phosphate (K2HPO4).

[0106] The results showed that the 10 different metal salt additives had different effects on the amide-forming reaction of nitrile compounds. The amide yield of sodium acetate (NaOAc) was 56%, that of sodium bicarbonate (NaHCO3) was 65%, that of sodium carbonate (Na2CO3) was 57%, that of cesium carbonate (Cs2CO3) was 55%, that of cesium acetate (CsOAc) was 62%, that of potassium fluoride (KF) was 50%, that of potassium carbonate (K2CO3) was 74%, that of potassium phosphate (K3PO4) was 78%, that of potassium dihydrogen phosphate (KH2PO4) was 80%, and that of dipotassium hydrogen phosphate (K2HPO4) was 92%. Therefore, dipotassium hydrogen phosphate (K2HPO4) was identified as the optimal metal salt additive.

[0107] The above content is a further detailed description of the present application in conjunction with specific implementation methods, and it cannot be considered that the specific implementation of the present application is limited to these descriptions. For ordinary technicians in the technical field to which the present application belongs, they can make several simple deductions or substitutions without departing from the concept of the present application, which should be considered to fall within the scope of protection of the present application.

Claims

1. A method for synthesizing an amide compound from a nitrile compound, characterized in that: The method comprises dispersing a nitrile compound, a photocatalyst and an organic base additive in a mixed solvent of water and an organic solvent, and performing a photocatalytic reaction under light in an atmosphere containing oxygen to generate an amide compound; The photocatalyst is terpyridyl ruthenium chloride or terpyridyl ruthenium chloride hexahydrate; The organic base additive is at least one of 1,8-diazobispiro[5.4.0]undec-7-ene, 7-methyl-1,5,7-triazabicyclo[4.4.0]quinone-5-ene, 2-tert-butyl-1,1,3,3-tetramethylguanidine, diisopropylamine, triethylamine, and N,N-diisopropylethylamine; The organic solvent is methanol, or methanol and acetonitrile; It also includes adding a metal salt additive into the photocatalytic reaction, wherein the metal salt additive is at least one of sodium acetate, sodium bicarbonate, sodium carbonate, cesium carbonate, cesium acetate, potassium fluoride, potassium carbonate, potassium phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate.

2. The method according to claim 1, wherein: The nitrile compound is an aromatic nitrile compound, an alkyl nitrile compound or a heterocyclic nitrile compound.

3. The method according to claim 1, wherein: The nitrile compounds include benzonitrile, 4-ethynylbenzonitrile, 2-naphthylcarbonitrile, 1-cyclopenteneacetonitrile, 2-cyanothiophene, terephthalonitrile, 4-nitrobenzonitrile, quinoline-6-carbonitrile, 3-phenylacrylonitrile, quinoline-4-carbonitrile, 2-bromobenzonitrile, 4-methoxybenzonitrile, 1,3-benzodicyclopentacyclo-5-carbonitrile, α-methylphenylacetonitrile, 3-methoxyisonicotinonitrile, 2-iodobenzonitrile, 4-morpholinebenzonitrile, n-octanonitrile, 1-phenyl-1-cyclopropylcarbonitrile, 2-cyano-5-fluoropyridine, 2-methylbenzonitrile, 4-aminobenzonitrile, cyclopentanecarbonitrile, 1-phenyl-1-cyclobutylcarbonitrile, 6-methyl 2-Methyl-2-pyridinecarbonitrile, 2-ethoxybenzonitrile, p-phenylbenzonitrile, cyclohexanecarbonitrile, 1-phenyl-1-cyclopentylcarbonitrile, 2-methoxy-5-cyanopyridine, 2-nitrobenzonitrile, 4-tert-butylbenzonitrile, 4-phenylbutyronitrile, 5-methyl-1,3-phenylenedicarbonitrile, 2,6-pyridinedicarbonitrile, 3-morpholinobenzonitrile, 3-fluoro-4-aminobenzonitrile, 2-phenoxyacetonitrile, 3-cyanopyridine, chromone-3-carbonitrile, 4-fluorobenzonitrile, isophthalonitrile, 4-bromophenylacetonitrile, 5-cyanopyridine, 4-chlorobenzonitrile, 2-methylterephthalonitrile, 1,2-phenylenedicarbonitrile, 2-cyanofuran; The amide compounds synthesized in sequence from the above nitrile compounds include benzamide, 4-ethynylbenzamide, 2-naphthylcarboxamide, 1-cyclopenteneacetamide, 2-thiophenecarboxamide, terephthalamide, 4-nitrobenzamide, quinoline-6-carboxamide, 3-phenylacrylamide, quinoline-4-carboxamide, 2-bromobenzamide, 4-methoxybenzamide, 1,3-benzodicyclopentazoline-5-carboxamide, α-methylphenylacetamide, 3-methoxypyridine-4-carboxamide, 2-iodobenzamide, 4-morpholinobenzamide, n-octanamide, 1-phenyl-1-cyclopropylcarboxamide, 5-fluoropyridine-2-carboxamide, 2-methylbenzamide, 4-aminobenzamide, cyclopentanecarboxamide, 1-phenyl-1-cyclobutylcarboxamide, 6-methylbenzamide, 2-Methyl-1-pyridinecarboxamide, 2-ethoxybenzamide, p-phenylbenzamide, cyclohexanecarboxamide, 1-phenyl-1-cyclopentylcarboxamide, 6-methoxy-3-pyridinecarboxamide, 2-nitrobenzamide, 4-tert-butylbenzamide, 4-phenylbutyramide, 2-(3-(2-cyanoprop-2-yl)-5-methylphenyl)-2-methylpropionamide, pyridine-2,6-dicarboxamide, 3-morpholinobenzamide, 3-fluoro-4-aminobenzamide, 2-phenoxyacetamide, 3-pyridinecarboxamide, chromone-3-carboxamide, 4-fluorobenzamide, isophthalic acid amide, 4-bromophenylacetamide, pyrimidine-5-carboxamide, 4-chlorobenzamide, 3-methyl-4-cyanobenzamide, 1,2-benzenediacetamide, 2-furancarboxamide.

4. The method according to claim 1, wherein: The mixed solvent consists of water, acetonitrile and methanol.

5. The method according to claim 4, characterized in that: In the mixed solvent, the volume ratio of acetonitrile:methanol:water is 1:2:

3.

6. The method according to claim 1, wherein: The wavelength of the light is 400-480nm.

7. The method according to claim 1, wherein: In the photocatalytic reaction, the concentration of the nitrile compound is 0.04-0.2 mmol / mL, the amount of the photocatalyst is 1-4 mol%, the amount of the organic base additive is 2-3.5 equivalents, and the amount of the metal salt additive is 0.5-1.5 equivalents.

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