An azidodifluorinated imidazole salt compound, a preparation method and use thereof

Abstract

The application discloses an azido difluoro imidazole salt compound and a preparation method and application thereof, relates to the fields of organic synthesis and application, and provides an azido difluoro imidazole salt compound, wherein the azido difluoro imidazole salt compound has a structure shown in formula (I). 2 and R 3 together with carbon atoms connected therewith form a benzene ring; or R 2 , R 3 are each independently selected from one or a combination of H, C1-10 alkyl, phenyl, heteroaryl and aryl; R 1 is selected from one or a combination of H, C1-10 alkyl, phenyl, heteroaryl and aryl; and R 4 represents an alkyl group.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and application, and in particular to an azide difluoroimidazolium salt compound, its preparation method, and its uses. Background Technology

[0002] In organic synthesis and medicinal chemistry, photocatalyst-generated free radicals exhibit excellent reactivity and substrate applicability, demonstrating a wide variety of addition reactions with free radical acceptors such as alkenes, alkynes, and aromatic compounds. As a green and efficient synthetic method, photocatalysis is widely used in many industrial production and drug development processes, avoiding environmental pollution and reaction system interference caused by large amounts of oxidizing and reducing agents and metal reagents. It is particularly suitable for the synthesis of sensitive molecules with multiple functional groups. Developing novel photocatalytic free radical reagents has extremely high application value. Summary of the Invention

[0003] (a) Technical problems to be solved In view of this, one of the main objectives of the present invention is to provide an azide difluoroimidazolium salt compound that not only has the advantages of chemical stability, low cost, easy purification and high yield, but also can adapt to various free radical reactions due to the introduction of an organic ionic salt structure; by modifying the imidazolium structure, it can selectively generate various nitrogen free radicals, and the generated free radicals have good reactivity and substrate applicability, and can have a wide variety of synthetic reactions with free radical acceptors such as alkenes, alkynes and aromatic compounds.

[0004] (II) Technical Solution To achieve the above objectives, the present invention provides an azide difluoroimidazolium salt compound having the structure shown in formula (I); Formula (I), Among them, R 2 and R 3 Together with the carbon atom it is attached to, they form a benzene ring; or R 3 R 4 Each and every one of H, C1-10 alkyl, phenyl, heteroaryl and aryl, or a combination thereof, is independently selected. R 1 Selected from one or a combination of H, C1-10 alkyl, phenyl, heteroaryl and aryl; R 4 Indicates alkyl group.

[0005] In one embodiment, any position of the C1-10 alkyl or phenyl group is substituted with one or more of halogen, nitro, methoxy, alkyl, aliphatic, nitrile, and trifluoromethyl groups.

[0006] In one embodiment, the number of substituents on the phenyl group is 0-5.

[0007] In one embodiment, the azidodifluoroimidazole salt compound further includes one or a combination of pharmaceutically acceptable esters, hydrates, solvates, metabolites, prodrugs, stereoisomers, tautomers, polymorphs, and isotopic derivatives.

[0008] In one embodiment, the azide difluoroimidazole salt compound is .

[0009] In one embodiment, the azide difluoroimidazole salt compound is .

[0010] In another aspect, the present invention also provides a method for preparing the above-mentioned difluoroimidazole salt compound, comprising: S1: Imidazole compounds are dissolved in a solvent, and then sodium hydride and difluorodibromomethane are added to react and obtain difluorobromoimidazole compounds; S2: Dissolve the difluorobromoimidazole compound in a solvent, then add azide trimethylsilane, tetrabutylammonium fluoride and potassium fluoride to react and obtain the azide difluoroimidazole compound; S3: Dissolve the azidodifluoroimidazole compound in a solvent, and then add alkyl trifluoromethanesulfonate to react and obtain the azidodifluoroimidazole salt compound.

[0011] In one embodiment, step S1 further includes dissolving an imidazole compound in a solvent, adding sodium hydride to react, and then adding difluorodibromomethane to react and obtain a difluorobromoimidazole compound.

[0012] In one embodiment, the preparation method specifically includes: S1: Imidazole compounds are dissolved in a solvent, sodium hydride is added to react, and then difluorodibromomethane is added to react to obtain difluorobromoimidazole compounds; S2: Dissolve the difluorobromoimidazole compound in a solvent, then add azide trimethylsilane, tetrabutylammonium fluoride and potassium fluoride to react and obtain the azide difluoroimidazole compound; S3: Dissolve the azidodifluoroimidazole compound in a solvent, and then add alkyl trifluoromethanesulfonate to react and obtain the azidodifluoroimidazole salt compound.

[0013] In one embodiment, the molar ratio of imidazole compound: sodium hydride: difluorodibromomethane in S1 is 1:(1.1-1.5):(1.5-3.5).

[0014] In one embodiment, the preparation method specifically includes: the molar ratio of imidazole compound: sodium hydride: difluorodibromomethane in S1 is 1:1.1:1.7.

[0015] In one embodiment, the molar ratio of imidazole compound: azidotrimethylsilane: tetrabutylammonium fluoride: potassium fluoride in S2 is 1:(1.0-3.5):(0.5-3.5):(0.5-2.5).

[0016] In one embodiment, the molar ratio of imidazole compound: azidotrimethylsilane: tetrabutylammonium fluoride: potassium fluoride in S2 is 1:1.5:0.5:1.

[0017] In one embodiment, the molar ratio of imidazole compound to alkyl trifluoromethanesulfonate in S3 is 1:(0.5-3.5).

[0018] In one embodiment, the molar ratio of imidazole compound to alkyl trifluoromethanesulfonate in S3 is 1:0.525.

[0019] In one embodiment, the preparation method specifically includes: S1: Dissolve imidazole compounds in a solvent, add sodium hydride according to the molar ratio of imidazole compounds: sodium hydride: difluorodibromomethane of 1:(1.1-1.5):(1.5-3.5) to react, and then add difluorodibromomethane to react to obtain difluorobromoimidazole compounds; S2: The difluorobromoimidazole compound is dissolved in a solvent, and the imidazole compound, azidotrimethylsilane, tetrabutylammonium fluoride and potassium fluoride are added in a molar ratio of 1:(1.0-3.5):(0.5-3.5):(0.5-2.5) to obtain the difluoroimidazole compound; S3: Dissolve the azidodifluoroimidazole compound in a solvent, and add alkyl trifluoromethanesulfonate at a molar ratio of imidazole compound to alkyl trifluoromethanesulfonate of 1:(0.5-3.5) to obtain the azidodifluoroimidazole salt compound.

[0020] In one embodiment, the preparation method specifically includes: S1: Dissolve imidazole compounds in a solvent, add sodium hydride according to the molar ratio of imidazole compounds: sodium hydride: difluorodibromomethane of 1:1.1:1.7 to react, and then add difluorodibromomethane to react to obtain difluorobromoimidazole compounds; S2: Dissolve the difluorobromoimidazole compound in a solvent, and add azide, trimethylsilane, tetrabutylammonium fluoride and potassium fluoride in a molar ratio of imidazole compound: trimethylsilane: tetrabutylammonium fluoride: potassium fluoride of 1:1.5:0.5:1 to react and obtain the difluoroimidazole compound. S3: Dissolve the azidodifluoroimidazole compound in a solvent, and add alkyl trifluoromethanesulfonate according to the molar ratio of imidazole compound to alkyl trifluoromethanesulfonate of 1:0.525 to react and obtain the azidodifluoroimidazole salt compound.

[0021] In one embodiment, the solvent in S1 is N,N-dimethylformamide.

[0022] In one embodiment, the solvent in S2 is dimethyl sulfoxide.

[0023] In one embodiment, the solvent in S3 is methyl tert-butyl ether.

[0024] In one embodiment, the preparation method specifically includes: S1: Imidazole compounds are dissolved in N,N-dimethylformamide. Sodium hydride is added according to the molar ratio of imidazole compound:sodium hydride:difluorodibromomethane of 1:1.1:1.7 to carry out the reaction. Then, difluorodibromomethane is added to carry out the reaction to obtain difluorobromoimidazole compound. S2: The difluorobromoimidazole compound is dissolved in dimethyl sulfoxide, and the imidazole compound, azidotrimethylsilane, tetrabutylammonium fluoride and potassium fluoride are added in a molar ratio of 1:1.5:0.5:1 to obtain the difluoroimidazole compound. S3: The azidodifluoroimidazolium compound is dissolved in methyl tert-butyl ether, and alkyl trifluoromethanesulfonate is added according to the molar ratio of imidazolium compound to alkyl trifluoromethanesulfonate of 1:0.525 to react and obtain the azidodifluoroimidazolium salt compound.

[0025] In one embodiment, the preparation method specifically includes: (1) Dissolve imidazole compounds in N,N-dimethylformamide, then add sodium hydride and difluorodibromomethane, and stir to react; (2) After the reaction in step (1) is completed, the solvent is removed and extracted. The organic phase is dried, subjected to reduced pressure, and separated by column chromatography to obtain the difluorobromoimidazole compound. Then, the difluorobromoimidazole compound is dissolved in dimethyl sulfoxide, and azide-trimethylsilane, tetrabutylammonium fluoride and potassium fluoride are added and stirred to react.

[0026] (3) After the reaction in step (2) is completed, the solvent is removed and the mixture is extracted. The organic phase is dried, subjected to reduced pressure, and separated by column chromatography to obtain the difluoroimidazole azido compound. Then, the difluorobromoimidazole compound is dissolved in methyl tert-butyl ether, and alkyl trifluoromethanesulfonate is added. The reaction yields the crude product of the difluoroimidazole azido salt. After washing, the pure difluoroimidazole azido salt compound is obtained.

[0027] In one embodiment, the preparation method specifically includes: (1) Dissolve imidazole compounds in N,N-dimethylformamide, then add sodium hydride and difluorodibromomethane, and stir to react; (2) After the reaction in step (1) is completed, the solvent is removed and extracted. The organic phase is dried, subjected to reduced pressure, and separated by column chromatography to obtain the difluorobromoimidazole compound. Then, the difluorobromoimidazole compound is dissolved in dimethyl sulfoxide, and azide-trimethylsilane, tetrabutylammonium fluoride and potassium fluoride are added and stirred to react.

[0028] (3) After the reaction in step (2) is completed, the solvent is removed and the mixture is extracted. The organic phase is dried, subjected to reduced pressure, and separated by column chromatography to obtain the difluoroimidazole azido compound. Then, the difluorobromoimidazole compound is dissolved in methyl tert-butyl ether, and alkyl trifluoromethanesulfonate is added. The reaction yields the crude product of the difluoroimidazole azido salt. After washing, the pure difluoroimidazole azido salt compound is obtained.

[0029] In one embodiment, step (1) involves dissolving an imidazole compound in a round-bottom flask containing N,N-dimethylformamide solvent to form an organic solution containing the imidazole compound, and then adding sodium hydride and difluorodibromomethane. Preferably, sodium hydride is added first and the mixture is stirred at 0°C before difluorodibromomethane is added and stirred at 50°C. Preferably, the molar ratio of the imidazole compound, sodium hydride, and difluorodibromomethane is 1:(1.1-1.5):(1.5-3.5). In one embodiment, in step (2), the solvent is removed by vacuum distillation; extraction is performed using ethyl acetate; the organic phase is dried using anhydrous sodium sulfate; the difluorobromoimidazole compound is dissolved in a round-bottom flask containing dimethyl sulfoxide solvent to form an organic solution containing the difluorobromoimidazole compound, and azidotrimethylsilane, tetrabutylammonium fluoride and potassium fluoride are added to it; preferably, the reaction temperature is 50°C; preferably, the molar ratio of imidazole compound, azidotrimethylsilane, tetrabutylammonium fluoride and potassium fluoride is 1:(1.0-3.5):(0.5-3.5):(0.5-2.5); In one embodiment, in step (3), the solvent is removed by vacuum distillation; the organic phase is extracted with ethyl acetate; the organic phase is dried with anhydrous sodium sulfate; the reaction time with alkyl trifluoromethanesulfonate is 8-12 h; the crude product of difluoroimidazolium salt is washed with methyl tert-butyl ether; wherein the molar ratio of imidazole compound to alkyl trifluoromethanesulfonate is 1:(0.5-3.5).

[0030] In one embodiment, the reaction conditions for step (1) are as follows: under an argon atmosphere, sodium hydride is first added and stirred at 0°C for 30 min, and then difluorodibromomethane is added and stirred at 50°C for 8-12 h.

[0031] In one embodiment, in step (1), the ratio of imidazole compound to N,N-dimethylformamide is 1 mmol: 3 mL.

[0032] In one embodiment, in step (2), the reaction is carried out at 50°C for 8-12 hours under an argon atmosphere.

[0033] In one embodiment, in step (2), the ratio of difluorobromoimidazole compound to dimethyl sulfoxide is 1 mmol: 5 mL.

[0034] In one embodiment, in step (3), the product is washed with methyl tert-butyl ether, and after washing 1-2 times, an azide difluoroimidazolium salt compound is obtained; wherein the ratio of methyl tert-butyl ether to the azide difluoroimidazolium salt compound is 2 mL: 1 mmol.

[0035] In one embodiment, the imidazole compound is selected from: , , , , , , .

[0036] In another aspect, the present invention also provides an azide difluoroimidazole salt compound, which is prepared by the above-described preparation method.

[0037] In another aspect, the present invention also provides the application of the above-mentioned azidodifluoroimidazolium salt compound in the preparation of photocatalytic free radical reagents.

[0038] In one embodiment, the reagent catalyzes the nitrogen difluorochloro and nitrogen trifluoromethylation reaction.

[0039] (III) Beneficial Effects This invention provides an azide difluoroimidazole salt compound.

[0040] Compared with existing technologies, it has the following beneficial effects: 1. It has stable chemical properties, low cost, is easy to purify, and has a high yield.

[0041] 2. Due to the introduction of organic ionic salt structures, it can adapt to various free radical reactions; by modifying the pyridine and quinoline structures, it can selectively generate various carbon free radicals, and the generated free radicals have good reactivity and substrate applicability, and can have very diverse synthetic reactions with free radical acceptors such as alkenes, alkynes, and aromatic compounds. Attached Figure Description

[0042] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0043] Figure 1 This is the hydrogen NMR spectrum of D1.

[0044] Figure 2 This is the carbon NMR spectrum of D1.

[0045] Figure 3 It's D1. 19 F NMR spectrum.

[0046] Figure 4 This is the hydrogen NMR spectrum of D2.

[0047] Figure 5 This is the carbon NMR spectrum of D2.

[0048] Figure 6 It's D2. 19 F NMR spectrum.

[0049] Figure 7 This is the hydrogen NMR spectrum of A-1.

[0050] Figure 8 This is the carbon NMR spectrum of A-1.

[0051] Figure 9 It is A-1 19 F NMR spectrum.

[0052] Figure 10 This is the hydrogen NMR spectrum of B-1.

[0053] Figure 11 This is the carbon NMR spectrum of B-1.

[0054] Figure 12 It's B-1. 19F NMR spectrum.

[0055] Figure 13 This is the hydrogen nuclear magnetic resonance spectrum of C-1.

[0056] Figure 14 This is the carbon NMR spectrum of C-1.

[0057] Figure 15 It is C-1. 19 F NMR spectrum.

[0058] Figure 16 This is a general chemical reaction diagram of azide difluoroimidazolium salt compounds. Detailed Implementation

[0059] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0060] As used herein, the term "stereoisomer" refers to an isomer formed due to at least one asymmetric center. In compounds having one or more (e.g., one, two, three, or four) asymmetric centers, racemic mixtures, single enantiomers, diastereomer mixtures, and single diastereomers can be produced. Specific individual molecules may also exist as geometric isomers (cis / trans).

[0061] Pharmaceutically acceptable salts of the compounds disclosed in this invention include their acid addition salts and base addition salts.

[0062] The compounds disclosed in this invention form pharmaceutically acceptable acid or base addition salts with a variety of organic and inorganic acids and bases, including physiologically acceptable salts commonly used in medicinal chemistry, which are also part of this invention. Typical inorganic acids used to form such salts include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, diphosphonic acid, etc. Salts derived from aliphatic and dicarboxylic acids, phenyl-substituted alkanes, hydroxyalkanes and hydroxyalkanediacids, aromatic acids, and aliphatic and aromatic sulfonic acids may also be used. Therefore, pharmaceutically acceptable salts include acetates, phenylacetates, trifluoroacetates, acrylates, ascorbic acid salts, benzoates, chlorobenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, methylbenzoates, o-acetoxybenzoates, naphthalene-2-benzoates, isobutyrate, phenylbutyrate, β-hydroxybutyrate, butyn-1,4-diacid, hexyn-1,4-diacid, decanoate, octanoate, cinnamate, citrate, formate, fumarate, glycolate, heptanoate, hippurate, lactate, maleate, malate, and hydroxymethylbenzoate. Salts include malonates, mandelates, methanesulfonates, nicotinates, isonicotinates, nitrates, oxalates, phthalates, terephthalates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, propynates, propionates, phenylpropionates, salicylates, sebates, succinates, octanoates, sulfates, hydrogen sulfates, pyrosulfites, sulfites, bisulfites, sulfonates, benzenesulfonates, p-bromobenzenesulfonates, chlorobenzenesulfonates, ethanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, p-toluenesulfonates, xylenesulfonates, tartrates, etc. Preferred salts are hydrochlorides, hydrobromides, citrates, and oxalates.

[0063] Typical bases used to form pharmaceutically acceptable addition salts can be inorganic bases, such as those of sodium, potassium, lithium, calcium, aluminum, ammonium, barium, zinc, magnesium, etc. Alternatively, organic bases can be used to form salts, such as N-N'-dibenzylethylenediamine, choline, diethanolamine, ethylenediamine, N-methylglucosamine, triethylamine, dimethylamine, procaine salts, etc. Salts of amino acids, such as arginine salts, are also included.

[0064] Pharmaceutically acceptable acid or base salts are typically formed by reacting a compound of formula (I) with an equimolar or excess amount of acid or base in a net solvent or a suitable inert solvent. The resulting salt is further processed and purified by known methods.

[0065] As used herein, the term "ester" means an ester derived from the various general formula compounds of this application, including physiologically hydrolyzable esters (the compounds of this invention that can be hydrolyzed under physiological conditions to release free acids or alcohols). The compounds disclosed in this invention may themselves be esters.

[0066] The compounds disclosed in this invention can exist as solvates (preferably hydrates), wherein the compounds of this invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the compound's crystal lattice. The amount of the polar solvent, particularly water, can be stoichiometric or non-stoichiometric.

[0067] The scope of this invention also includes metabolites of the compounds disclosed herein, i.e., substances formed in the body upon administration of the compounds disclosed herein. Such products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, defatting, enzymatic hydrolysis, etc., of the administered compound. Therefore, this invention includes metabolites of the compounds of this invention, including compounds obtained by methods that expose the compounds of this invention to mammals for a time sufficient to produce their metabolites.

[0068] The compounds disclosed in this invention can be in the form of prodrugs. Prodrugs are typically pharmacologically inactive derivatives of parent drug molecules that require spontaneous or enzymatic conversion in vivo to release the active drug, and possess pharmacokinetic properties superior to those of the parent drug molecule. Therefore, prodrugs of compounds of formula (I) have chemically cleavable or metabolically cleavable groups, readily undergoing chemical changes under physiological conditions to provide compounds of formula (I) in vivo. Prodrugs include conjugates obtained by combining a compound of formula (I) and a sugar moiety with the addition of a suitable spacer group, alkyl esters obtained by reacting a parent acidic compound with a suitable alcohol, or amides obtained by reacting a parent acidic compound with a suitable amine.

[0069] As used herein, the term “derivative” can include any salt, hydrate, and solvate prepared by commonly used methods.

[0070] As used herein, the term "isotope derivative" means that which is identical to the compounds disclosed herein, except that one or more atoms are replaced by atoms having the same atomic number but a different atomic mass or mass number than the dominant atomic mass or mass number found in nature. Examples of isotopes suitable for inclusion in the compounds of this invention include (but are not limited to) isotopes of hydrogen (e.g., deuterium (D, 2H), tritium (T, 3H); isotopes of carbon (e.g., 11C, 13C, and 14C); isotopes of chlorine (e.g., 36Cl); isotopes of fluorine (e.g., 18F); isotopes of iodine (e.g., 123I and 125I); isotopes of nitrogen (e.g., 13N and 15N); isotopes of oxygen (e.g., 15O, 17O, and 18O); isotopes of phosphorus (e.g., 32P); and isotopes of sulfur (e.g., 35S). Certain isotopically labeled compounds of this invention may be used in pharmaceutical and / or substrate tissue distribution studies (e.g., analysis).

[0071] Those skilled in the art are familiar with various methods for detecting labeled compounds. For example, magnetic resonance imaging (MRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT) can be used to detect radiolabeled compounds. The labeling introduced into the compound will depend on the desired detection method.

[0072] As used in this article, “containing,” “having,” or “including” includes “containing,” “mainly composed of,” “substantially composed of,” and “composed of”; “mainly composed of,” “substantially composed of,” and “composed of” are subordinate concepts of “containing,” “having,” or “including.”

[0073] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the reagents, methods and equipment used are conventional reagents, methods and equipment in this technical field.

[0074] Example 1 Synthesis of D1: (1) such as Figure 16 The general reaction formula was used for the synthesis reaction. 10 mmol of imidazole compound (A1) was dissolved in a round-bottom flask containing 36 mL of N,N-dimethylformamide solvent to form an organic solution containing imidazole compound (A1). 11 mmol of sodium hydride was added to the solution, and the mixture was stirred at 0 °C for 0.5 h. 17 mmol of difluorodibromomethane was then added, and the mixture was reacted at 50 °C for 8-12 h. (2) After the reaction was completed, the solvent was removed under reduced pressure, and then extracted with ethyl acetate multiple times. The organic phase was dried with anhydrous sodium sulfate, filtered, and separated by column chromatography to obtain difluorobromoimidazole compound (B1). Then it was dissolved in 30 mL of dimethyl sulfoxide to form an organic solution containing difluorobromoimidazole compound (B1). 5 mmol of tetrabutylammonium fluoride, 15 mmol of trimethylsilane azide, and 10 mmol of potassium fluoride were added to it, and the reaction was carried out at 50 °C for 8-12 h. (3) After the reaction was completed, the solvent was removed by vacuum distillation, and then extracted multiple times with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate, filtered, and separated by column chromatography to obtain the azidodifluoroimidazolium compound (C1). It was dissolved in 10 mL of methyl tert-butyl ether, and 5.25 mmol of trifluoromethanesulfonate was added. The reaction was carried out for 8-12 h to obtain the crude product of the azidodifluoroimidazolium salt. Finally, it was washed with 10 mL of methyl tert-butyl ether to obtain the pure azidodifluoroimidazolium salt compound (D1). The yield of the product azidodifluoroimidazolium salt (D1) was 96%, and it was a white solid.

[0075] The structural formula of the obtained difluoroimidazole salt compound D1 is as follows: like Figures 1-3 The product's 1H NMR spectrum data are shown below: 1 H NMR (400 MHz, CDCl3δ 7.93 – 7.85 (m, 1H), 7.83 – 7.76 (m, 1H), 7.71– 7.62 (m, 2H), 4.11 (s, 3H), 3.11 (t, J = 1.7 Hz, 3H); The product's carbon NMR spectrum data: 13 C NMR (101 MHz, CDCl3) δ 152.5, 131.6, 128.6, 128.4, 127.9, 120.6,(q, J = 322.2 Hz) 118.6 (t, J = 269.5 Hz), 114.4 (t, J = 5.4 Hz), 113.6, 33.0, 13.3(t, J = 4.0 Hz); Products 19 F NMR data: 19 F NMR (377 MHz, CDCl3) δ -54.2 (s, 2F), -78.7 (s, 3F); High-resolution mass spectrometry data of the product: HRMS(ESI): caled for C 10 H 10 F2N5[(M - OTf) + ] 238.0899, found 238.0898.

[0076] Example 2: Synthesis of D2: (1) Dissolve 50 mmol of imidazole compound (A2) in a round-bottom flask containing 180 mL of N,N-dimethylformamide solvent to form an organic solution containing imidazole compound (A2). Add 55 mmol of sodium hydride and stir at 0 °C for 0.5 h. Add 85 mmol of difluorodibromomethane and react at 50 °C for 8-12 h. (2) After the reaction was completed, the solvent was removed by vacuum distillation, and then extracted with ethyl acetate multiple times. The organic phase was dried with anhydrous sodium sulfate, filtered, and separated by column chromatography to obtain difluorobromoimidazole compound (B2). It was then dissolved in 180 mL of dimethyl sulfoxide to form an organic solution containing difluorobromoimidazole compound (B2). 30 mmol tetrabutylammonium fluoride, 90 mmol trimethyl azidosilane, and 60 mmol potassium fluoride were added to it, and the reaction was carried out at 50 °C for 8-12 h. (3) After the reaction was completed, the solvent was removed by vacuum distillation, and then extracted multiple times with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate, filtered, and separated by column chromatography to obtain the azidodifluoroimidazolium compound (C2). It was dissolved in 60 mL of methyl tert-butyl ether, and 30 mmol of trifluoromethanesulfonate was added. The reaction was carried out for 8-12 h to obtain the crude azidodifluoroimidazolium salt product. Finally, it was washed with 20 mL of methyl tert-butyl ether to obtain the pure azidodifluoroimidazolium salt compound (D2). The yield of the product azidodifluoroimidazolium salt (D2) was 95%, and it was a white solid.

[0077] The structural formula of the obtained difluoroimidazole salt compound D2 is as follows: like Figures 4-6 The product's 1H NMR spectrum data are shown below: 1 H NMR (400 MHz, CDCl3) δ 7.98 – 7.91 (m, 1H), 7.89 – 7.80 (m, 3H), 7.78 – 7.62 (m, 5H), 3.88 (s, 3H); The product's carbon NMR spectrum data: 13 C NMR (101 MHz, CDCl3) δ 150.4, 133.6, 131.9, 130.2, 129.6, 129.2,128.8, 128.4, 121.0, 120.5 (q, J = 320.7 Hz), δ 118.2 (t, J = 270.2 Hz), 114.7(t, J = 5.0 Hz), 114.5, 33.8; Products 19 F NMR data: 19 F NMR (377 MHz, CDCl3) δ -52.3 (s, 2F), -78.7 (s, 3F); High-resolution mass spectrometry data of the product: HRMS(ESI): caled for C 15 H 12 F2N5[(M - OTf) + ] 300.1055, found 300.1056.

[0078] Example 3: Photocatalytic synthesis of A-1: The application of D2 in generating free radicals and catalyzing other reactions under photocatalytic conditions is as follows: The yield of compound A to compound A-1 was 72%. like Figures 7-9 The following is the 1H NMR spectrum data for compound A-1: 1 H NMR (400 MHz, CDCl3) δ 8.52 (dd, J = 8.1, 1.3 Hz, 1H), 7.72 – 7.64(m, 1H), 7.58 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 7.50 – 7.45 (m, 2H), 7.42 (d, J =7.9 Hz, 1H), 7.39 – 7.33 (m, 2H), 7.23 (s, 1H); Carbon NMR data of compound A-1: 13 C NMR (126 MHz, CDCl3) δ 159.8, 135.7, 134.6, 134.1, 133.9, 131.3,129.2, 129.0, 128.4, 126.4, 125.1, 122.0 (t, J = 293.3 Hz). δ 121.8 (t, J = 8.0Hz), 120.0; Compound A-1 19 F NMR data: 19 F NMR (377 MHz, CDCl3) δ -40.11 (s, 2F); High-resolution mass spectrometry data of compound A-1: HRMS(ESI): caled for C 16 H10 Cl2F2NO [(M + H) + ] 340.0102, found 340.0109.

[0079] Example 4: Photocatalytic synthesis of B-1: The application of D2 in generating free radicals and catalyzing other reactions under photocatalytic conditions is as follows: The yield of compound B to compound B-1 was 52%. like Figures 10-12 The following is the 1H NMR spectrum data for compound B-1: 1 H NMR (400 MHz, CDCl3) δ 8.52 (dd, J = 8.1, 1.4 Hz, 1H), 7.68 (ddd, J =8.3, 7.2, 1.5 Hz, 1H), 7.57 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 7.53 – 7.38 (m,6H), 7.20 (s, 1H); Carbon NMR data of compound B-1: 13 C NMR (126 MHz, CDCl3) δ 160.2, 136.3, 135.4, 134.0, 130.0, 129.0,128.9, 128.5, 128.2, 126.3, 125.5, 122.0 (q, J = 4.8 Hz), 121.0, 119.9 (q, J =268.4 Hz); Compound B-1 19 F NMR data: 19 F NMR (377 MHz, CDCl3) δ -59.91 (s, 3F); High-resolution mass spectrometry data of compound B-1: HRMS(ESI): caled for C 16 H 11 F3NO [(M + H) + ]290.0788, found 290.0792.

[0080] Example 5: Photocatalytic synthesis of C-1: The application of D2 in generating free radicals and catalyzing other reactions under photocatalytic conditions is as follows: The yield of compound C to compound C-1 was 81%. like Figures 13-15 The following is the 1H NMR spectrum data for compound C-1: 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.39 (m, 2H), 7.34 – 7.18 (m, 8H), 7.17 (s, 1H), 3.67 (t, J = 4.9 Hz, 4H), 3.39 (t, J = 4.9 Hz, 4H); Carbon NMR data of compound C-1: 13 C NMR (126 MHz, CDCl3) δ 146.7 (d, J = 315.0 Hz), 142.6, 139.2, 132.5,131.0, 128.5, 128.2, 127.6 (d, J = 21.7 Hz), 127.5, 126.7, 126.6, 66.3, 45.1(d, J = 1.7 Hz); Compound C-1 19 F NMR data: 19 F NMR (377 MHz, CDCl3) δ -63.90 (s, 1F); High-resolution mass spectrometry data of compound C-1: HRMS(ESI): caled for C 19 H 20 FN2O [(M + H) + ]311.1555, found 311.1550.

[0081] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0082] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A difluoroimidazole salt compound, characterized in that, The azide difluoroimidazolium salt compound has the structure shown in formula (I); Formula (I), Among them, R 2 and R 3 Together with the carbon atom it is attached to, they form a benzene ring; or R 2 R 3 Each and every one of H, C1-10 alkyl, phenyl, heteroaryl and aryl, or a combination thereof, is independently selected. R 1 Selected from one or a combination of H, C1-10 alkyl, phenyl, heteroaryl and aryl; R 4 Indicates alkyl group.

2. The azide difluoroimidazolium salt compound according to claim 1, characterized in that, The C1-10 alkyl or phenyl group is substituted at any position with one or more of halogen, nitro, methoxy, alkyl, aliphatic, nitrile and trifluoromethyl groups.

3. The azide difluoroimidazolium salt compound according to claim 1 or 2, characterized in that, The azidodifluoroimidazole salt compound also includes one or a combination of its pharmaceutically acceptable esters, hydrates, solvates, metabolites, prodrugs, stereoisomers, tautomers, polymorphs, and isotopic derivatives.

4. The azide difluoroimidazolium salt compound according to claim 3, characterized in that, It includes: ; and / or 。 5. A method for preparing the azide difluoroimidazolium salt compound according to any one of claims 1-4, characterized in that, The preparation method includes: S1: Imidazole compounds are dissolved in a solvent, and then sodium hydride and difluorodibromomethane are added to react and obtain difluorobromoimidazole compounds; S2: Dissolve the difluorobromoimidazole compound in a solvent, then add azide trimethylsilane, tetrabutylammonium fluoride and potassium fluoride to react and obtain the azide difluoroimidazole compound; S3: Dissolve the azidodifluoroimidazole compound in a solvent, and then add alkyl trifluoromethanesulfonate to react and obtain the azidodifluoroimidazole salt compound.

6. The preparation method according to claim 5, characterized in that, S1 further includes dissolving an imidazole compound in a solvent, adding sodium hydride to react, and then adding difluorodibromomethane to react and obtain a difluorobromoimidazole compound.

7. The preparation method according to claim 6, characterized in that, The molar ratio of imidazole compounds, sodium hydride, and difluorodibromomethane in S1 is 1:(1.1-1.5):(1.5-3.5). The molar ratio of imidazole compounds, azidotrimethylsilane, tetrabutylammonium fluoride, and potassium fluoride in S2 is 1:(1.0-3.5):(0.5-3.5):(0.5-2.5). The molar ratio of imidazole compounds to alkyl trifluoromethanesulfonate in S3 is 1:(0.5-3.5).

8. A difluoroimidazole salt compound, characterized in that, It is prepared by the preparation method described in any one of claims 5-7.

9. The use of the azide difluoroimidazolium salt compound according to any one of claims 1-4 or claim 8 in the preparation of photocatalytic free radical reagents.

10. The application according to claim 9, characterized in that, The reagent catalyzes the nitrogen difluorochloride and nitrogen trifluoromethylation reactions.

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