Sulfonylated furan derivative and preparation method thereof

Abstract

The invention relates to the technical field of preparation of furan compounds, and provides a sulfonylated furan derivative and a preparation method thereof. The preparation method of the sulfonylated furan derivative comprises the step of carrying out common reaction on alpha-acyl ketene dithioacetal, terminal alkyne, sulfonyl methyl isocyanide, a palladium catalyst, a copper promoter, a ligand and alkali in a nitrogen atmosphere to prepare the sulfonylated furan derivative. According to the preparation method of the sulfonylated furan derivative, a cheap, simple and convenient synthesis method of the sulfonylated furan derivative can be provided, and a new thought is provided for research and development of new drugs and diagnosis and treatment of diseases.

Description

Technical Field

[0001] This application relates to the field of furan compound preparation technology, and in particular to a sulfonated furan derivative and its preparation method. Background Technology

[0002] The furan skeleton is often used as a beneficial pharmacological group in drug molecule design to improve the pharmacological activity of drug molecules. With further research, medicinal chemists have discovered that introducing different substituents into the furan unit can selectively enhance the biological activity of the parent drug.

[0003] On the other hand, sulfonyl groups, as bioisosteres of carbonyl, carboxyl, and phosphate groups, can enhance or inhibit the biological activity of small molecules; as hydrogen bond acceptors, they can increase the hydrogen bond interaction between drug molecules and target sites; their structural stability can prolong the metabolic time of drug molecules in the human body and improve drug efficacy; their strong electron-withdrawing properties can reduce the lipid solubility and basicity of drugs, thereby reducing the hERG toxicity of drugs.

[0004] Given the diverse pharmacological properties of furan skeletons and sulfonyl groups, researching and developing simple and efficient methods for synthesizing multifunctional sulfonated furan derivatives with potential applications from inexpensive and readily available raw materials is a key research focus in the field of synthetic methodology, and is of great significance for new drug development, disease diagnosis and treatment, and the discovery of novel materials. Summary of the Invention

[0005] In view of this, this application aims to propose a method for preparing sulfonated furan derivatives, so as to provide a low-cost and simple method for synthesizing sulfonated furan derivatives, and provide new ideas for new drug development and disease diagnosis and treatment.

[0006] To achieve the above objectives, the technical solution of this application is implemented as follows: A method for preparing a sulfonated furan derivative, the method comprising reacting α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand and base together under a nitrogen atmosphere to obtain the sulfonated furan derivative.

[0007] Furthermore, the reaction formula for the preparation method is as follows:

[0008] Wherein, in the reaction formula: R 1The group is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl group are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl-substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, benzyl. The heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl group is 1-5. R 2 The groups are selected from hydrogen atoms; C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; phenyl rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, C1-C6 hydrocarbon amide-substituted benzyl groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1 -C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)aryl group; (hetero)aryl ring with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid group, aldehyde group, C1-C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)arylformyl group; C Acyl groups of 0-C8 hydrocarbon groups; carboxyl groups; ester carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; amide carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano groups, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; and vinyl groups substituted with fluorine, chlorine, chlorine, methyl methacrylate ... Chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted ethynyl; double bonded with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted allyl; R 3The functional groups are selected from C1-C12 hydrocarbon groups; the benzene ring is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, acyl group of C1-C6 hydrocarbon group, alkoxycarbonyl group of C1-C6 hydrocarbon group, or amide-substituted benzyl group of C1-C6 hydrocarbon group; the double bond is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon group, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl group, or C1-C8 hydrocarbon group. Allyl groups substituted with hydrocarbon groups and (hetero)aryl amides or sulfonic acid groups; methylene groups substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amides; propargyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amides or sulfonic acid groups on a triple bond; R 4 The group is selected from C1-C12 hydrocarbon groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic carboxyl groups; C1-C8 hydrocarbon acyl groups; carboxyl groups; C1-C12 hydrocarbon groups and (hetero)aromatic substituted ester carbonyl groups; C1-C12 hydrocarbon groups and (hetero)aromatic substituted amide carbonyl groups; R 5 The group is selected from C1-C12 hydrocarbon groups; the heteroaryl ring is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, acyl group of C1-C6 hydrocarbon group, alkoxycarbonyl group of C1-C6 hydrocarbon group, or amide-substituted heteroaryl group of C1-C6 hydrocarbon group. The heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc., and the number of substituents on the heteroaryl group is 1-5.

[0009] Furthermore, the molar ratio of the α-acyl dithiocarbamate, the terminal alkyne, the sulfonyl methyl isocyanate, the palladium catalyst, the ligand, the copper co-catalyst, and the base satisfies the following: α-acyl dithiocarbamate: terminal alkyne: sulfonyl methyl isocyanate: palladium catalyst: ligand: copper co-catalyst: base is 1: (0.8-2.0): (0.8-2.0): (0.1%-5%): (0.2%-10%): (0.1-1): (0.1-1).

[0010] Furthermore, the α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand, and base react together under a nitrogen atmosphere to prepare the sulfonated furan derivative, comprising: Under a nitrogen atmosphere, the α-acyl dithiocarbamate, the terminal alkyne, the sulfonylmethyl isocyanate, the palladium catalyst, the ligand, the copper co-catalyst, and the base are added to the reaction solvent and mixed. The mixture is stirred at a preset temperature to carry out a heteroaromatic-sulfonation cascade reaction. After the reaction is complete, the solution is quenched in potassium chloride solution and then extracted with an extractant to obtain the extracted organic phase. The extracted organic phase was dried with a desiccant, and the solvent was recovered to obtain the crude product. The crude product was separated and purified by an eluent to obtain the sulfonated furan derivative.

[0011] Furthermore, the palladium catalyst is one or more of palladium chloride, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium bromide, palladium di(acetonitrile)dichloride, palladium di(triphenylphosphine)dichloride, carbon-supported palladium, tetra(triphenylphosphine)palladium, or tri(dibenzylacetone)dipalladium; and / or, The copper co-catalyst is one or more of cuprous chloride, cuprous iodide, cuprous bromide, cuprous thiophene-2-carboxylate, cuprous cyanide, cuprous thiocyanate, copper bromide, copper chloride, copper acetate, or copper trifluoromethanesulfonate.

[0012] Furthermore, the ligands are tri-tert-butylphosphine, triphenylphosphine, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-2',4',6'-tri-tert-butylbiphenyl, 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, bis(diphenylphosphine)methane, bis(diphenylphosphine)methane, bis(dicyclohexylphosphine)ethane, bis(cyclopentylphosphine)ethane, 1,2-bis(diphenylphosphine)ethane, 1,3 -One or more of the following: bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, bis(dicyclohexylphosphine)butane, 1,1'-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphinophenyl)ether, 4,5-bis(diphenylphosphine)xanthone, pyridine, 1,10-o-phenanthroline, 2,2'-bipyridine, bisoxazoline, or diimine; and / or, The alkali is one or more of the following: triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, pyridine, potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, calcium carbonate, potassium phosphate, sodium phosphate, dipotassium hydrogen phosphate, sodium hydroxide, potassium hydroxide, calcium hydroxide, and barium hydroxide.

[0013] Furthermore, the reaction solvent is one or more of toluene, xylene, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, anisole, chlorobenzene, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, 1,4-dioxane, butyronitrile, N-methylpyrrolidone, methyl tert-butyl ether, cyclohexanone, tetrahydrofuran, dichloroethane, or dichloromethane.

[0014] Furthermore, the reaction temperature of the heteroaromatization-sulfonation cascade reaction is between 25℃ and 110℃, and the reaction time is between 5h and 24h.

[0015] Furthermore, the extractant is one or more of ethyl acetate, dichloromethane, n-hexane, cyclohexane, acetone, diethyl ether, n-butyl ether, cyclohexanone, ethyl propionate, or butyl acetate; and / or, The desiccant is one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, calcium chloride, magnesium chloride, sodium carbonate, or calcium hydroxide; and / or, The eluent is one or more of petroleum ether, n-hexane, cyclohexane, acetone, acetonitrile, methanol, ethanol, acetic acid, ethyl acetate, toluene, benzene, triethylamine, dichloromethane, or chloroform.

[0016] The sulfonated furan derivatives are used in anticancer drugs, antispasmodic drugs, anti-HIV drugs, antifungal drugs, immunosuppressive drugs, or anti-inflammatory drugs.

[0017] Compared with the prior art, this application has the following advantages: This application employs a multi-component reaction that directly yields structurally complex target compounds without the need for intermediate separation. It boasts advantages such as simple operation, readily available raw materials, and environmental friendliness. Furthermore, this application designs a three-component [4+1] heteroaromatization-sulfonation cascade reaction involving α-acyl dithiocarbamate, terminal alkyne, and sulfonylmethyl isocyanate to prepare polysubstituted sulfonated furan derivatives. The synthesized sulfonated furan derivatives possess abundant functional groups that can be further modified. Therefore, this application provides a cost-effective, simple, and universal method for the synthesis of novel sulfonated furan derivatives with potential biological activity, offering new insights for drug development, disease diagnosis and treatment, and the discovery of novel materials.

[0018] This application also proposes a sulfonated furan derivative, which is prepared by the above-described method for preparing sulfonated furan derivatives. Attached Figure Description

[0019] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments and descriptions of this application are used to explain this application and do not constitute an undue limitation of this application. In the drawings: Figure 1The 1H NMR spectrum of 1-(2-methyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)ethane-1-one as described in Example 1 of this application; Figure 2 The carbon NMR spectrum of 1-(2-methyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)ethane-1-one as described in Example 1 of this application. Detailed Implementation

[0020] To make the technical solution and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0021] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other.

[0022] For items where specific conditions are not specified in this application, conventional conditions or conditions recommended by the manufacturer of the equipment used shall apply. For items where the manufacturer of the reagents or instruments used is not specified, conventional products that can be purchased commercially shall be used. As for the technical means or processes involved, if specific conditions are not specified, they shall be carried out in accordance with the existing methods in the relevant field.

[0023] The embodiments of the first aspect of this application provide a method for preparing sulfonated furan derivatives, which can provide a low-cost and simple method for synthesizing sulfonated furan derivatives, providing new ideas for new drug development and disease diagnosis and treatment.

[0024] In existing technologies, as the properties of sulfonated furan derivatives are gradually discovered, more and more research groups are showing great interest in these compounds. For example, Professor Zeng Qingle synthesized benzenesulfonylmethylfuran in 69% yield using benzaldehyde, sodium benzenesulfinate, and 2-methylfuran as raw materials, water as solvent, and sulfuric acid as Brønsted acid catalyst (Eur. J. Org. Chem., 2020, 4004-4008). Zhu Gangguo's research group synthesized a series of 2-amino-5-sulfonylmethylfuran derivatives using high-alkenylamide as raw material, sodium sulfinate as sulfone source, and PIFA as oxidant, under the catalysis of a catalyst (Org. Biomol. Chem., 2017, 15, 7204-7211). Wang Lei's research group synthesized multisubstituted furfural sulfone derivatives via a free radical tandem reaction of oxidative cyclization, using enynyl ketone as substrate, aryl sulfinic acid as sulfonating agent, air as oxidant, and water as solvent (Org. Lett. 2018, 20, 4430−4433).

[0025] The above preparation methods have problems such as complex synthesis steps, difficulty in obtaining reaction raw materials, and lack of economic applicability.

[0026] In view of this, in order to overcome the shortcomings of the prior art, the preparation method of the sulfonated furan derivative in this embodiment is designed to include the reaction of α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand and base under a nitrogen atmosphere to obtain the sulfonated furan derivative.

[0027] The preparation method of this embodiment involves a multi-component reaction of α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand, and base. This allows for the direct yield of structurally complex sulfonated furan derivatives without intermediate separation. The entire process is simple and has promising application prospects. Furthermore, the sulfonated furan derivatives synthesized in this embodiment possess abundant functional groups that can be further modified, providing a cost-effective, simple, and universal method for synthesizing novel sulfonated furan derivatives with potential biological activity.

[0028] It is worth noting that the reaction formula of the preparation method in this embodiment, as an exemplary implementation, can be as follows:

[0029] Specifically, in the above reaction formula: R 1 Preferred groups may be selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the heteroaryl group are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl-substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, and benzyl. The heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the heteroaryl group is 1-5. R 2Preferred groups may be selected from, for example, hydrogen atoms; C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; phenyl rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, C1-C6 hydrocarbon amide-substituted benzyl groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1 -C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)aryl group; (hetero)aryl ring with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid group, aldehyde group, C1-C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)arylformyl group; C Acyl groups of 0-C8 hydrocarbon groups; carboxyl groups; ester carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; amide carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano groups, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; and vinyl groups substituted with fluorine, chlorine, chlorine, methyl methacrylate ... Chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted ethynyl; double bonded with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted allyl; R 3 Preferred groups may be selected from C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, acyl groups of C1-C6 hydrocarbon groups, alkoxycarbonyl groups of C1-C6 hydrocarbon groups, and amide-substituted benzyl groups of C1-C6 hydrocarbon groups; double bonds may be selected from C1-C12 hydrocarbon groups, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon groups, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl groups, and C1-C12 hydrocarbon groups. -C8 hydrocarbon group and (hetero)aryl amide, sulfonic acid group substituted allyl group; methylene group substituted with nitro, cyano, sulfonic acid group, carboxyl group, C1-C8 hydrocarbon alkoxycarbonyl group, C1-C8 alkyl group and (hetero)aryl amide group; propargyl group substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon group, (hetero)aryl group, C1-C8 hydrocarbon alkoxycarbonyl group, C1-C8 hydrocarbon group and (hetero)aryl amide, sulfonic acid group substituted propargyl group; R 4Preferred groups may be selected from, for example, C1-C12 hydrocarbon groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic carboxyl groups; C1-C8 hydrocarbon acyl groups; carboxyl groups; C1-C12 hydrocarbon groups and (hetero)aromatic substituted ester carbonyl groups; and C1-C12 hydrocarbon groups and (hetero)aromatic substituted amide carbonyl groups. R 5 The preferred group can be selected from C1-C12 hydrocarbon groups; the heteroaryl ring is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, acyl group of C1-C6 hydrocarbon group, alkoxycarbonyl group of C1-C6 hydrocarbon group, or amide-substituted heteroaryl group of C1-C6 hydrocarbon group, etc., and the heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc., and the number of substituents on the heteroaryl group is 1-5.

[0030] In the preparation method of sulfonated furan derivatives in this embodiment, the molar ratio of α-acyl dithiocarbamate, terminal alkyne, sulfonyl methyl isocyanate, palladium catalyst, ligand, copper co-catalyst and base can be, for example, satisfying the following: α-acyl dithiocarbamate: terminal alkyne: sulfonyl methyl isocyanate: palladium catalyst: ligand: copper co-catalyst: base is 1: (0.8-2.0): (0.8-2.0): (0.1%-5%): (0.2%-10%): (0.1-1): (0.1-1).

[0031] Furthermore, in this embodiment, the preparation method involves the co-reaction of α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand, and base under a nitrogen atmosphere to obtain the sulfonated furan derivative. As an exemplary embodiment, this may include, for example, the following steps: Step S1: Under a nitrogen atmosphere, α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, ligand, copper co-catalyst and base are added to the reaction solvent and mixed. The mixture is stirred at a preset temperature to carry out the heteroaromatic-sulfonation cascade reaction.

[0032] In step S1 above, the palladium catalyst can preferably be one or more of palladium chloride, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium bromide, palladium di(acetonitrile) dichloride, palladium di(triphenylphosphine) dichloride, carbon-supported palladium, tetra(triphenylphosphine) palladium, or tri(dibenzylacetone) dipapadium.

[0033] The preferred copper co-catalyst may be one or more of cuprous chloride, cuprous iodide, cuprous bromide, cuprous thiophene-2-carboxylate, cuprous cyanide, cuprous thiocyanate, copper bromide, copper chloride, copper acetate, or copper trifluoromethanesulfonate.

[0034] Preferred ligands may include, for example, tri-tert-butylphosphine, triphenylphosphine, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-2',4',6'-tri-tert-butylbiphenyl, 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, bis(diphenylphosphine)methane, bis(diphenylphosphine)methane, bis(dicyclohexylphosphine)ethane, bis(cyclopentylphosphine)ethane, 1,2-bis(diphenylphosphine)ethane, 1,3 -One or more of the following: bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, bis(dicyclohexylphosphine)butane, 1,1'-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphinophenyl)ether, 4,5-bis(diphenylphosphine)xanthone, pyridine, 1,10-o-phenanthroline, 2,2'-bipyridine, bisoxazoline, or diimine; and / or, The preferred base may be one or more of the following: triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, pyridine, potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, calcium carbonate, potassium phosphate, sodium phosphate, dipotassium hydrogen phosphate, sodium hydroxide, potassium hydroxide, calcium hydroxide, and barium hydroxide.

[0035] The preferred reaction solvent may be one or more of toluene, xylene, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, anisole, chlorobenzene, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, 1,4-dioxane, butyronitrile, N-methylpyrrolidone, methyl tert-butyl ether, cyclohexanone, tetrahydrofuran, dichloroethane, or dichloromethane.

[0036] In the preparation method of this embodiment, the addition of palladium catalyst can accelerate the reaction process without affecting the final yield and improve the reaction efficiency; copper co-catalyst can improve the activity of palladium catalyst and play a synergistic role with the catalyst; by adding ligands to coordinate with metal ions / atoms, it serves as a core regulatory means for asymmetric catalysis and complex molecule construction in metal catalytic reactions; by adding reaction solvent and base, a reaction environment is provided for the reaction, dissolving the reactants and catalyst.

[0037] The synergistic effect of the above components makes the preparation method of this embodiment simpler and more efficient.

[0038] Furthermore, the heteroaromatic-sulfonation cascade reaction in step S1 above is preferably carried out at a reaction temperature between 25°C and 110°C and a reaction time between 5h and 24h.

[0039] Step S2: After the reaction is complete, the solution is quenched in potassium chloride solution and then extracted with an extractant to obtain the extracted organic phase.

[0040] The extractant in step S2 above is preferably one or more of ethyl acetate, dichloromethane, n-hexane, cyclohexane, acetone, diethyl ether, n-butyl ether, cyclohexanone, ethyl propionate, or butyl acetate.

[0041] Step S3: Dry the extracted organic phase with a desiccant and recover the solvent to obtain the crude product.

[0042] The desiccant used in step S3 above is preferably one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, calcium chloride, magnesium chloride, sodium carbonate, or calcium hydroxide.

[0043] Step S4: The crude product is separated and purified by an eluent to obtain the sulfonated furan derivative.

[0044] The eluent in step S4 above is preferably one or more of petroleum ether, n-hexane, cyclohexane, acetone, acetonitrile, methanol, ethanol, acetic acid, ethyl acetate, toluene, benzene, triethylamine, dichloromethane, or chloroform.

[0045] Based on the above introduction, the preparation method of sulfonated furan derivatives in this embodiment involves a three-component [4+1] heteroaromatization-sulfonation cascade reaction of α-acyl dithiocarbamate, terminal alkyne, and sulfonylmethyl isocyanate. The reaction efficiency is improved by utilizing the synergistic effect of palladium catalyst, ligand, copper co-catalyst, and base to prepare multi-substituted sulfonated furan derivatives. This provides a simple and universal method for the synthesis of novel sulfonated furan derivatives with potential biological activity.

[0046] An embodiment of the second aspect of this application provides a sulfonated furan derivative, which is prepared by the above-described method for preparing sulfonated furan derivatives.

[0047] By introducing different substituents into the furan unit, the biological activities of the parent drug, such as anticancer, antispasmodic, anti-HIV, antifungal, immunosuppressive, and anti-inflammatory effects, can be selectively enhanced. At the same time, the sulfonyl group has pharmacological properties such as enhancing or inhibiting the biological activity of small molecules, prolonging the metabolic time of drug molecules in the human body, and improving drug efficacy. Moreover, it is currently known that sulfonyl-substituted furan compounds and their derivatives have pharmacological activities for treating inflammatory or autoimmune diseases and can be applied to a variety of drug compositions. Therefore, the sulfonated furan derivatives of this application have potential application value in anticancer, antispasmodic, anti-HIV, antifungal, anti-inflammatory, and immunosuppressive drugs.

[0048] It is worth noting that, for the preferred embodiments of the sulfonated furan derivatives and their preparation methods in this example, the following preparation examples can be referred to in specific implementation.

[0049] Example 1 Example 1 describes the preparation of compound 1-(2-methyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)ethane-1-one, with the following reaction formula:

[0050] The specific preparation steps are as follows: Step S1: In a 25 mL three-necked flask containing a magnetic flask, add 0.5 mmol of 3-(bis(methylthio)methylene)pentane-2,4-dione, 0.55 mmol of p-toluenesulfonylmethylisocyanate, 0.025 mmol of Pd(PPh3)4, and 0.5 mmol of CuTc sequentially. Replace the air three times with nitrogen. Then, under a nitrogen atmosphere, add 5 mL of DMF, 0.55 mmol of phenylacetylene, and 0.5 mmol of Et3N, respectively. Heat and stir the system in an oil bath at 80 °C for 12 hours.

[0051] Step S2: Cool the system to room temperature, quench with saturated brine, and extract with ethyl acetate (2×15 mL).

[0052] Step S3: Dry the combined organic phases with anhydrous magnesium sulfate and concentrate to obtain the crude product.

[0053] Step S4: The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 10 / 1, v / v) to give a white solid 1-(2-methyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)ethane-1-one (0.207 g, 86%).

[0054] The proton, carbon, and mass spectrometry results of the compound 1-(2-methyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)ethane-1-one prepared in Example 1 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 6.0 Hz, 2H), 7.47 (d, J = 8.0 Hz,2H), 7.34 – 7.32 (m, 3H), 7.20 (d, J = 7.6 Hz, 2H), 5.98 (s, 1H), 2.62 (s, 3H), 2.60 (s, 3H), 2.40 (s, 3H), 2.13 (s, 3H). 13 C NMR(100 MHz, CDCl3) δ 194.6,160.1, 147.7, 144.9, 134.5, 130.5(2C), 130.2, 129.2 (2C), 129.12 (2C),129.07, 128.6 (2C), 123.6, 118.6, 67.6, 30.0, 21.6, 20.2, 15.1.HRMS(ESI-TOF)calcd for C 22 H 22 NaO4S2 + ([M + Na)) + ) 437.0852, found 437.0851. Example 2 Example 2 is for the preparation of compound 1-(2-ethyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)propane-1-one, the reaction formula is as follows:

[0055] The specific preparation steps are as follows: Step S1: In a 25 mL three-necked flask containing a magnetic flask, add 0.5 mmol of 3-(bis(methylthio)methylene)heptane-3,5-dione, 0.55 mmol of p-toluenesulfonylmethylisocyanate, 0.025 mmol of Pd(PPh3)2Cl2, and 0.5 mmol of CuBr sequentially. Replace the air three times with nitrogen. Then, under a nitrogen atmosphere, add 5 mL of DMF, 0.55 mmol of phenylacetylene, and 0.5 mmol of K2CO3, respectively. Heat and stir the system in an oil bath at 80 °C for 12 hours.

[0056] Step S2: Cool the system to room temperature, quench with saturated brine, and extract with ethyl acetate (2×15 mL).

[0057] Step S3: Dry the combined organic phases with anhydrous magnesium sulfate and concentrate to obtain the crude product.

[0058] Step S4: The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 10 / 1, v / v) to obtain a yellow oily liquid 1-(2-ethyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)propane-1-one (0.179 g, 81%).

[0059] The proton, carbon, and mass spectra of the compound 1-(2-ethyl-4-(methylthio)-5-(phenyl)(toluenesulfonyl)methyl)furan-3-yl)propane-1-one prepared in Example 2 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 6.8 Hz, 2H), 7.56 (d, J = 8.0 Hz,2H), 7.35 – 7.33 (m, 3H), 7.19 (d, J = 8.4 Hz, 2H), 5.99 (s, 1H), 3.03 – 2.92(m, 4H), 2.39 (s, 3H), 2.10 (s, 3H), 1.30 (t, J = 7.4 Hz, 3H), 1.12 (t, J = 7.2Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 198.0, 163.9, 147.7, 144.9, 134.5, 130.5(2C), 130.2, 129.2 (2C), 129.1 (3C), 128.5 (2C),122.5, 118.0, 67.7, 35.3,21.9, 21.6, 20.3, 12.1, 7.9.HRMS(ESI-TOF) calcd for C 24 H 26 NaO4S2 + ([M + Na)) + )465.1165, found 465.1167. Example 3 Example 3 describes the preparation of methyl 2-ethyl-4-(methylthio)-5-(phenyl(p-toluenesulfonyl)methyl)furan-3-carboxylate, using the following reaction formula:

[0060] The specific preparation steps are as follows: Step S1: In a 25 mL three-necked flask containing a magnetic flask, methyl 2-(bis(methylthio)methylene)-3-oxovalerate (0.5 mmol), p-toluenesulfonylmethyl isocyanate (0.55 mmol), Pd(PPh3)4 (0.025 mmol), and CuTc (0.5 mmol) were added sequentially. The air was purged three times with nitrogen, and DMF (5 mL), phenylacetylene (0.55 mmol), and Et3N (0.5 mmol) were added under a nitrogen atmosphere. The system was heated and stirred in an oil bath at 90 °C for 15 hours.

[0061] Step S2: Cool the system to room temperature, quench with saturated brine, and extract with ethyl acetate (2×15 mL).

[0062] Step S3: Dry the combined organic phases with anhydrous magnesium sulfate and concentrate to obtain the crude product.

[0063] Step S4: The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 10 / 1, v / v) to obtain a yellow oily liquid methyl 2-ethyl-4-(methylthio)-5-(phenyl(p-toluenesulfonyl)methyl)furan-3-carboxylate (0.189 g, 85%).

[0064] The proton, carbon, and mass spectra of methyl 2-ethyl-4-(methylthio)-5-(phenyl(p-toluenesulfonyl)methyl)furan-3-carboxylate prepared in Example 3 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.6 Hz, 2H), 7.48 (d, J = 8.0 Hz,2H), 7.36 – 7.34 (m, 3H), 7.20 (d, J = 8.0 Hz, 2H), 5.99 (s, 1H), 3.85 (s, 3H), 3.09 – 3.01 (m, 2H), 2.39 (s, 3H), 2.12 (s, 3H), 1.31 (t, J = 7.6 Hz, 3H). 13CNMR(100 MHz, CDCl3) δ 165.8, 163.3, 147.2, 144.8, 134.7, 130.6 (2C), 130.2,129.3 (2C), 129.1, 129.0 (2C), 128.6 (2C), 119.6, 114.5, 67.5, 51.5, 22.0,21.6, 19.2, 12.2.HRMS(ESI-TOF) calcd for C 23 H 24 NaO4S2 + ([M + Na)) + ) 451.1008, found 451.1006. Example 4 Example 4 describes the preparation of compound methyl 5-(cyclopropyl(p-toluenesulfonyl)methyl)-2-ethyl-4-(methylthio)furan-3-carboxylate, using the following reaction formula:

[0065] The specific preparation steps are as follows: Step S1: In a 25 mL three-necked flask containing a magnetic flask, methyl 2-(bis(methylthio)methylene)-3-oxovalerate (0.5 mmol), p-toluenesulfonylmethyl isocyanate (0.55 mmol), Pd(PPh3)4 (0.025 mmol), and CuTc (0.5 mmol) were added sequentially. The air was purged three times with nitrogen, and DMF (5 mL), phenylacetylene (0.55 mmol), and Et3N (0.5 mmol) were added under a nitrogen atmosphere. The system was heated and stirred in an oil bath at 70 °C for 20 hours.

[0066] Step S2: Cool the system to room temperature, quench with saturated brine, and extract with ethyl acetate (2×15 mL).

[0067] Step S3: Dry the combined organic phases with anhydrous magnesium sulfate and concentrate to obtain the crude product.

[0068] Step S4: The crude product was purified by column chromatography (petroleum ether / ethyl acetate: 10 / 1, v / v) to obtain a yellow oily methyl 5-(cyclopropyl(p-toluenesulfonyl)methyl)-2-ethyl-4-(methylthio)furan-3-carboxylate (0.108 g, 53%).

[0069] The proton, carbon, and mass spectrometry results of the compound methyl 5-(cyclopropyl(p-toluenesulfonyl)methyl)-2-ethyl-4-(methylthio)furan-3-carboxylate prepared in Example 4 are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 7.6 Hz, 2H), 4.11 (d, J = 10.4 Hz, 1H), 3.88 (s, 3H), 3.06 – 2.91 (m, 2H), 2.44 (s,3H), 2.17 (s,3H), 1.56 (m, 1H), 1.24 (t, J = 7.6 Hz, 3H), 0.81 (m, 1H), 0.61 –0.57 (m, 2H), 0.22 – 0.17 (m, 1H). 13 C NMR(100 MHz, CDCl3) δ 165.5, 163.5,148.5, 144.8, 135.6, 129.5 (2C), 129.0 (2C), 119.0, 114.6, 67.4, 51.5, 21.9,21.7, 19.4, 12.2, 9.1, 6.2, 3.8.HRMS(ESI-TOF) calcd for C 20 H 24 NaO5S2 + ([M + Na)) + )431.0957, found 431.0955. As can be seen from the above examples, the preparation method of the present invention has simple operation steps, readily available and economical raw materials, and the sulfonated furan derivatives prepared have multiple substituents. Therefore, they have abundant functional groups that can be further modified, which can provide a low-cost, simple and universal method for the synthesis of novel sulfonated furan derivatives with potential biological activity, and provide new ideas for new drug development and disease diagnosis and treatment.

[0070] The above descriptions are merely some embodiments of this application and are not intended to limit this application. The technical features or structures in the foregoing different embodiments can be arbitrarily combined to form other specific technical solutions as needed. For those skilled in the art, this application can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of the claims of this application.

Claims

1. A method for preparing a sulfonated furan derivative, characterized in that: The preparation method includes reacting α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand and base together under a nitrogen atmosphere to obtain the sulfonated furan derivative.

2. The method for preparing sulfonated furan derivatives according to claim 1, characterized in that, The reaction formula for the preparation method is as follows: Wherein, in the reaction formula: R 1 The group is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl group are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl-substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, benzyl. The heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl group is 1-5. R 2 The groups are selected from hydrogen atoms; C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; phenyl rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, C1-C6 hydrocarbon amide-substituted benzyl groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1 -C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)aryl group; (hetero)aryl ring with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid group, aldehyde group, C1-C8 hydrocarbon group, C1-C6 hydrocarbon group acyl group, C1-C6 hydrocarbon group alkoxycarbonyl group, C1-C6 hydrocarbon group amide-substituted (hetero)arylformyl group; C Acyl groups of 0-C8 hydrocarbon groups; carboxyl groups; ester carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; amide carbonyl groups substituted with C1-C12 hydrocarbon groups or (hetero)aryl groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; vinyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano groups, C1-C4 hydrocarbon groups, (hetero)aryl groups, C1-C8 hydrocarbon alkoxycarbonyl groups, C1-C8 hydrocarbon groups and (hetero)aryl amides, sulfonic acid groups; and vinyl groups substituted with fluorine, chlorine, chlorine, methyl methacrylate ... Chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted ethynyl; double bonded with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid-substituted allyl; R 3 The functional groups are selected from C1-C12 hydrocarbon groups; the benzene ring is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, acyl group of C1-C6 hydrocarbon group, alkoxycarbonyl group of C1-C6 hydrocarbon group, or amide-substituted benzyl group of C1-C6 hydrocarbon group; the double bond is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon group, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl group, or C1-C8 hydrocarbon group. Allyl groups substituted with hydrocarbon groups and (hetero)aryl amides or sulfonic acid groups; methylene groups substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amides; propargyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amides or sulfonic acid groups on a triple bond; R 4 The group is selected from C1-C12 hydrocarbon groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic groups; (hetero)aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon groups, C1-C6 hydrocarbon acyl groups, C1-C6 hydrocarbon alkoxycarbonyl groups, and C1-C6 hydrocarbon amide-substituted (hetero)aromatic carboxyl groups; C1-C8 hydrocarbon acyl groups; carboxyl groups; C1-C12 hydrocarbon groups and (hetero)aromatic substituted ester carbonyl groups; C1-C12 hydrocarbon groups and (hetero)aromatic substituted amide carbonyl groups; R 5 The group is selected from C1-C12 hydrocarbon groups; the heteroaryl ring is attached with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, acyl group of C1-C6 hydrocarbon group, alkoxycarbonyl group of C1-C6 hydrocarbon group, or amide-substituted heteroaryl group of C1-C6 hydrocarbon group. The heteroaryl group is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc., and the number of substituents on the heteroaryl group is 1-5.

3. The method for preparing sulfonated furan derivatives according to claim 1, characterized in that: The molar ratio of the α-acyl dithiocarbamate, the terminal alkyne, the sulfonyl methyl isocyanate, the palladium catalyst, the ligand, the copper co-catalyst, and the base satisfies the following: α-acyl dithiocarbamate: terminal alkyne: sulfonyl methyl isocyanate: palladium catalyst: ligand: copper co-catalyst: base is 1: (0.8-2.0): (0.8-2.0): (0.1%-5%): (0.2%-10%): (0.1-1): (0.1-1).

4. The method for preparing sulfonated furan derivatives according to claim 3, characterized in that, The α-acyl dithiocarbamate, terminal alkyne, sulfonylmethyl isocyanate, palladium catalyst, copper co-catalyst, ligand, and base react together under a nitrogen atmosphere to prepare the sulfonated furan derivative, comprising: Under a nitrogen atmosphere, the α-acyl dithiocarbamate, the terminal alkyne, the sulfonylmethyl isocyanate, the palladium catalyst, the ligand, the copper co-catalyst, and the base are added to the reaction solvent and mixed. The mixture is stirred at a preset temperature to carry out a heteroaromatic-sulfonation cascade reaction. After the reaction is complete, the solution is quenched in potassium chloride solution and then extracted with an extractant to obtain the extracted organic phase. The extracted organic phase was dried with a desiccant, and the solvent was recovered to obtain the crude product. The crude product was separated and purified by an eluent to obtain the sulfonated furan derivative.

5. The method for preparing sulfonated furan derivatives according to claim 4, characterized in that: The palladium catalyst is one or more of palladium chloride, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium bromide, palladium di(acetonitrile)dichloride, palladium di(triphenylphosphine)dichloride, carbon-supported palladium, tetra(triphenylphosphine)palladium, or tri(dibenzylacetone)dipalladium; and / or, The copper co-catalyst is one or more of cuprous chloride, cuprous iodide, cuprous bromide, cuprous thiophene-2-carboxylate, cuprous cyanide, cuprous thiocyanate, copper bromide, copper chloride, copper acetate, or copper trifluoromethanesulfonate.

6. The method for preparing the sulfonated furan derivative according to claim 4, characterized in that: The ligands are tri-tert-butylphosphine, triphenylphosphine, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-2',4',6'-tri-tert-butylbiphenyl, 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, bis(diphenylphosphine)methane, bis(diphenylphosphine)methane, bis(dicyclohexylphosphine)ethane, bis(cyclopentylphosphine)ethane, 1,2-bis(diphenylphosphine)ethane, 1,3 -One or more of the following: bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, bis(dicyclohexylphosphine)butane, 1,1'-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphinophenyl)ether, 4,5-bis(diphenylphosphine)xanthone, pyridine, 1,10-o-phenanthroline, 2,2'-bipyridine, bisoxazoline, or diimine; and / or, The alkali is one or more of the following: triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, pyridine, potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, calcium carbonate, potassium phosphate, sodium phosphate, dipotassium hydrogen phosphate, sodium hydroxide, potassium hydroxide, calcium hydroxide, and barium hydroxide.

7. The method for preparing sulfonated furan derivatives according to claim 4, characterized in that: The reaction solvent is one or more of toluene, xylene, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, anisole, chlorobenzene, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, 1,4-dioxane, butyronitrile, N-methylpyrrolidone, methyl tert-butyl ether, cyclohexanone, tetrahydrofuran, dichloroethane, or dichloromethane.

8. The method for preparing sulfonated furan derivatives according to claim 4, characterized in that: The reaction temperature of the heteroaromatization-sulfonation cascade reaction is between 25℃ and 110℃, and the reaction time is between 5h and 24h.

9. The method for preparing the sulfonated furan derivative according to claim 4, characterized in that: The extractant is one or more of ethyl acetate, dichloromethane, n-hexane, cyclohexane, acetone, diethyl ether, n-butyl ether, cyclohexanone, ethyl propionate, or butyl acetate; and / or, The desiccant is one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, calcium chloride, magnesium chloride, sodium carbonate, or calcium hydroxide; and / or, The eluent is one or more of petroleum ether, n-hexane, cyclohexane, acetone, acetonitrile, methanol, ethanol, acetic acid, ethyl acetate, toluene, benzene, triethylamine, dichloromethane, or chloroform.

10. A sulfonated furan derivative, characterized in that: The sulfonated furan derivative is prepared by the method for preparing sulfonated furan derivatives according to any one of claims 1 to 9.

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