CN-121990944-A - Method for preparing benzonitrile compound from aryl fluoride through C-F bond cleavage

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing benzonitrile compounds from aryl fluoride through C-F bond cleavage. Aiming at the challenges of high toxicity, difficulty in C-F bond activation, poor stability, low selectivity and the like of the traditional cyanide method in the water production environment, the hydrophobic microenvironment is constructed by introducing a copper-boron intercalated hydrotalcite catalyst, so that the problems of hydrolytic inactivation of a boron reagent and water interference of a catalytic active site are effectively solved, the efficient performance of C-F bond breakage and cyanide reaction is ensured, the high-selectivity synthesis of a target product is realized, the use of highly toxic cyanide is successfully avoided, and a novel clean production path with great prospect is provided for the efficient conversion of aryl fluoride in the fields of medicines, materials, fine chemicals and the like.

Inventors

• YU CHANGJIANG
• Bai Ruoshuang
• WANG YICHAO
• ZHAO QINGYING

Assignees

• 山东石油化工学院

Dates

Publication Date

20260508

Application Date

20260202

Claims (10)

1. 1. A method for preparing benzonitrile compounds from aryl fluorides through C-F bond cleavage, comprising the steps of: S1, dispersing magnesium aluminum carbonate type hydrotalcite powder in formamide solution, and carrying out ultrasonic treatment to obtain single-layer hydrotalcite colloid slurry; S2, adding copper triflate into the single-layer hydrotalcite colloid slurry, then adding boric acid, hydroxyl-terminated polydimethylsiloxane alcohol and tetraethoxysilane, and drying and granulating to obtain microspherical solid powder; s3, impregnating the bisboronic acid pinacol ester on the microspherical solid powder by adopting an isovolumetric impregnation method in an inert atmosphere to obtain a copper-boron intercalated hydrotalcite catalyst; S4, adding aryl fluoride as a substrate into a reaction container, adding a copper-boron intercalated hydrotalcite catalyst, a ligand, inorganic base and ammonium bicarbonate, and carrying out heating and stirring reaction under the Freon atmosphere to obtain the benzonitrile compound, wherein the reaction principle is as follows: 。
2. 2. The method according to claim 1, wherein the magnesium aluminum carbonate hydrotalcite powder, copper triflate, boric acid, ethyl orthosilicate, and pinacol biborate are used in a ratio of 8-12g:400-600mg:1.5-2.5g:0.8-1.2ml:4-6g.
3. 3. The method according to claim 1, wherein the power of the ultrasonic treatment in step S1 is 400-600W and the treatment time is 3-5h.
4. 4. The method according to claim 1, wherein the drying granulation in step S2 is spray drying, and the inlet air temperature is 140-160 ℃.
5. 5. The method according to claim 1, wherein the organic solvent for the heating and stirring reaction in step S4 is selected from one of N, N-dimethylformamide, dimethyl sulfoxide, acetonitrile, tetrahydrofuran, and 1, 4-dioxane.
6. 6. The method according to claim 1, wherein the reaction temperature in step S4 is 50-150 ℃ and the reaction time is 1-24h.
7. 7. The method of claim 1, wherein the molar ratio of ammonium bicarbonate to aryl fluoride in step S4 is 1:1-5:1 and the molar ratio of freon to aryl fluoride is 1:1-10:1.
8. 8. The method according to claim 1, wherein the catalyst is used in an amount of 10mol% based on the copper content in step S4, the ligand is 2,2' -bipyridine in an amount of 10mol%, the inorganic base is cesium carbonate in an amount of 5equiv.
9. 9. The method according to claim 1, wherein the separation and purification method in step S4 is a vacuum concentration followed by silica gel column flash chromatography, and the eluent is a mixture of ethyl acetate and petroleum ether in a volume ratio of 1:30.
10. 10. The method according to claim 1, characterized in that it is used for the preparation of pharmaceutical intermediates, liquid crystal materials or organic luminescent materials.

Description

Method for preparing benzonitrile compound from aryl fluoride through C-F bond cleavage Technical Field The invention relates to the technical field of organic synthesis, in particular to a method for preparing benzonitrile compounds from aryl fluoride through C-F bond cleavage. Background The aryl nitrile compound is an important organic synthesis intermediate and is widely applied to the fields of medicines, pesticides, dyes, high polymer materials, fine chemicals and the like. The traditional aryl nitrile preparation method introduces cyano through the reaction of aryl halide and highly toxic metal cyanide (such as NaCN and KCN), and has the prominent problems of high raw material toxicity, high operation risk, severe reaction conditions, serious environmental pollution and the like, so that the popularization and the application of the method in industrial production are severely restricted. In addition, the aryl nitrile is prepared by oxidative amination or dehydration of aromatic aldehyde or oxime, and the defects of poor raw material universality, multiple reaction steps, complex byproducts and the like are also present. Therefore, the development of a non-cyanide method for preparing the aryl nitrile compound, which is environment-friendly, safe, efficient and easy to operate, is always a hot spot and a difficult point of research in the chemical field. In recent years, carbon and nitrogen sources are utilized to replace traditional highly toxic cyanide, so that the cleavage of an aryl C-F bond (activation of the C-F bond) and the introduction of cyano are realized to synthesize aryl nitrile, and the toxicity of cyanide is avoided, and aryl fluoride is easy to introduce in synthesis, so that the aryl nitrile is widely focused by scientific researchers. The C-F bond is one of the highest energy, most stable chemical bonds of the carbon halogen bonds, and activation cleavage is challenging. Severe conditions such as strong bases, high temperatures, or transition metal catalysts are often required. At present, transition metal catalytic systems, particularly copper catalysts, are considered as potential alternatives to the traditional cyanide route due to their relatively low cost, low toxicity and efficient activation of the C-F bonds. However, existing copper catalytic systems still face a number of challenges in achieving C-F bond cleavage and cyanidation reactions. First, in non-cyanide cyanidation reactions, commonly used carbon and nitrogen sources (e.g., ammonium bicarbonate, formamide, etc.) may decompose or be present under the reaction conditions, thereby inevitably producing water. The presence of water presents a significant challenge for many transition metal catalysts, particularly for boron reagent catalytic systems. The water molecules easily cause the deactivation of the active site of the catalyst and the hydrolysis failure of the boron reagent, thereby seriously reducing the selectivity and the conversion rate of the reaction. For example, boron reagents, which act as important promoters or reducing agents, are highly susceptible to hydrolysis in hydrophilic environments, losing activity, resulting in an interruption of the catalytic cycle or a significant decrease in efficiency. This makes it particularly difficult to achieve efficient and stable C-F bond-activated cyanation reactions in aqueous systems. Secondly, many existing copper catalysts are easy to agglomerate or leach in the reaction cycle, so that the activity of the catalyst is lost, the service life of the catalyst is shortened, and the effective recovery and recycling are difficult to realize, thereby greatly increasing the production cost and generating secondary pollution. In order to improve the stability of the catalyst, researchers have attempted to load a homogeneous catalyst onto a heterogeneous carrier in order to achieve recovery and reuse of the catalyst. However, the conventional loading method often has problems of uneven dispersion of active components, limited loading capacity, or easy damage of active sites exposed to solvents. Furthermore, even if a supported catalyst is used, it is still a problem to be solved in a complex reaction system, especially when there are multiple active components (such as copper source, boron source, carbon-nitrogen source, etc.), how to precisely control the synergistic effect between these components, and avoid unnecessary side reactions (such as substrate dehalogenation, intermediate hydrolysis, cyano self-coupling, etc.), so as to realize selective synthesis of the target product. Homogeneous systems suffer from the lack of space constraints, and various active species are in disordered brownian motion, and highly active catalytic species are prone to side reactions, resulting in poor chemoselectivity. Therefore, how to achieve precise spatial isolation and regulation of reactants and catalyst active sites in the microstructure of heterogeneous catalysts to improve react