Method for converting sulfanilamide into pyrrole compound and application thereof
By condensing sulfonamide compounds with ketodiketone compounds under the action of acid catalysts and further converting them under the action of visible light and photosensitizers, the problem of insufficient means of converting sulfonamide to pyrrole compounds is solved, and the high value conversion of sulfonamide and the improvement of corporate operating efficiency is achieved.
Patent Information
- Application Number
- CN202510298525.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-13
- Publication Date
- 2025-06-06
AI Technical Summary
The lack of means of converting sulfonamide into pyrrole compounds in the prior art, resulting in insufficient development and utilization of sulfonamide compounds and their waste materials, increasing the production costs and waste waste of enterprises.
By condensing the sulfonamide compound with the ketone-protected or unprotected diketone compound under the action of an acid catalyst, N-sulfonylpyrrole is obtained and further converted into a 2-sulfonylpyrrole compound or a dipyrrole compound under the action of visible light and photosensitizer.
The high value of sulfonamide is transformed into a rich new pyrrole compound, which reduces the production costs of the enterprise, improves the operating efficiency of the enterprise, and solves the problem of waste and waste of sulfonamide waste.
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Figure CN120097887A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for converting sulfonamide into pyrrole compounds and its application. Background Art
[0002] Sulfonamide has antibacterial activity. In order to expand the antibacterial spectrum of sulfonamide and enhance its antibacterial activity, a series of sulfonamide compounds have been developed. As basic antibacterial drugs, sulfonamide compounds are produced in large quantities, but the market conditions fluctuate at any time. The produced sulfonamides often increase the burden on companies due to their low prices and high inventory. Moreover, due to the high stability of the sulfonamide group, it is difficult for companies to convert sulfonamide compounds into high value-added products. In addition, the sulfonamide waste generated in the production process of the company will also cause waste.
[0003] Among the known aromatic nitrogen heterocycles, pyrrole is a special aromatic heterocycle that is widely present in biologically active molecules. The synthesis of new pyrrole compounds is beneficial to the screening of new biologically active molecules and even drug molecules. The current method for synthesizing substituted pyrroles usually directly utilizes commercialized pyrrole derivatives and modifies them through transition metal catalysis, organic small molecule catalysis, etc. Although this type of method can synthesize new pyrrole compounds, the synthesis cost is high and is not conducive to large-scale production by enterprises. If sulfonamide compounds and their waste materials can be converted into new pyrrole compounds with high value, the company's cheap inventory can be reduced and the company's operating efficiency can be improved. Summary of the invention
[0004] In view of this, the present application provides a method for converting sulfonamide into pyrrole compounds and its application, which are used to solve the technical problem that there is a lack of means for converting sulfonamide into pyrrole compounds in the prior art.
[0005] In a first aspect, the present application provides a method for converting sulfonamide into pyrrole compounds, the method comprising the steps of: condensing a sulfonamide compound and a diketone compound with protected or unprotected keto group under the action of an acid catalyst to obtain N-sulfonylpyrrole.
[0006] Preferably, the sulfonamide compound is selected from at least one of aromatic sulfonamides, alkyl sulfonamides and heterocyclic sulfonamides.
[0007] Preferably, the sulfonamide compound is selected from benzenesulfonamide.
[0008] Preferably, the diketone compound with a protected keto group is a ketal compound, which may be a monosubstituted ketal compound, a disubstituted ketal compound or a polysubstituted ketal compound;
[0009] The diketone compound whose keto group is not protected is a diketone compound, which can be a monosubstituted diketone compound, a disubstituted diketone compound or a polysubstituted diketone compound.
[0010] Preferably, the keto-protected diketone compound is selected from 4-phenyl-4-propanone-2,5-dioxolane;
[0011] The diketone compound with unprotected keto group is selected from 4-phenyl-1,4-butanedione.
[0012] Preferably, the acid catalyst is selected from Lewis acids and / or protonic acids.
[0013] Preferably, the Lewis acid is selected from scandium trifluoromethanesulfonate and / or copper trifluoromethanesulfonate;
[0014] The protonic acid is selected from at least one of p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid and sulfuric acid.
[0015] Preferably, the method for converting sulfonamide into pyrrole compounds further comprises the steps of: converting N-sulfonylpyrrole into 2-sulfonylpyrrole compound by breaking the NS bond under the action of visible light and a photosensitizer;
[0016] Or N-sulfonylpyrrole and unsaturated hydrocarbons are converted into dipyrrole compounds under the action of visible light and photosensitizer.
[0017] Preferably, the unsaturated hydrocarbon is selected from olefins and / or alkynes.
[0018] Preferably, the olefin is selected from at least one of styrene, diphenylethylene, acrylate, acrylamide and acrylonitrile;
[0019] The alkyne is selected from at least one of phenylacetylene, propiolonitrile and propiolate.
[0020] Preferably, the visible light is selected from full-wavelength visible light, which is at least one of red light, orange light, yellow light, green light, cyan light, blue light, purple light, and ultraviolet light;
[0021] The photosensitizer is selected from at least one of amine organic molecules, iridium metal complexes, and ruthenium metal complexes.
[0022] The second aspect of the present application provides the use of the pyrrole compounds obtained by the method for converting sulfonamide into pyrrole compounds described in the first aspect in the field of screening bioactive molecules / drug molecules.
[0023] Compared with the prior art, the method for converting sulfonamide into pyrrole compounds provided in the present application has at least the following beneficial effects:
[0024] 1. In a method for converting sulfonamide into pyrrole compounds provided in the present application, sulfonamide is reacted with a diketone compound with a protected or unprotected keto group under the action of an acid catalyst, and can be converted into abundant N-sulfonylpyrrole depending on the substituents of the diketone compound.
[0025] 2. In the method for converting sulfonamide into pyrrole compounds provided in the present application, N-sulfonylpyrrole can be further converted into complex pyrrole heterocyclic compounds such as 2-sulfonylpyrrole compounds and dipyrrole compounds under the action of visible light and photosensitizer, thereby providing abundant new pyrrole compounds.
[0026] 3. The present application provides a method for converting sulfonamide into pyrrole compounds. After sulfonamide is converted into novel pyrrole compounds, the novel pyrrole compounds can be used to screen biologically active molecules / drug molecules. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0028] Figure 1 Schematic diagram of the process for converting sulfonamide into pyrrole compounds provided in Examples 1-3 of the present application. DETAILED DESCRIPTION
[0029] The present application provides a method for converting sulfonamide into pyrrole compounds and its application, which are used to solve the technical problem that there is a lack of means for converting sulfonamide into pyrrole compounds in the prior art.
[0030] The technical solution of the present application will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present application.
[0031] In view of the fact that the development and utilization of sulfonamide compounds and their wastes are currently insufficient, and there is a lack of means to convert sulfonamide into high-value novel pyrrole compounds; the present application provides a method for converting sulfonamide into pyrrole compounds; the method comprises: firstly condensing a sulfonamide compound and a diketone compound with a protected or unprotected keto group under the action of an acid catalyst to obtain N-sulfonylpyrrole; then converting N-sulfonylpyrrole into a 2-sulfonylpyrrole compound or reacting with an unsaturated hydrocarbon to convert into a dipyrrole compound; the reaction process is shown in the following formula:
[0032] .
[0033] Among them, R 1 Can be selected from phenyl, R 2Can be selected from phenyl, R 3 can be selected from methyl; wherein the substituent R in the diketone compound 2 and R 3 In addition to phenyl and methyl, it can also be substituted with aryl, alkyl, hydroxyl, carboxyl, amino, nitro and other substituents, and can also be monosubstituted or trisubstituted. According to the different substituted diketone compounds, a rich variety of N-sulfonylpyrroles can be synthesized.
[0034] After obtaining a rich variety of N-sulfonylpyrroles, the NS bond of N-sulfonylpyrrole can be further broken to convert it into a variety of 2-sulfonylpyrrole compounds; or N-sulfonylpyrrole can be reacted with different unsaturated hydrocarbons such as olefins and / or alkynes to convert it into dipyrrole compounds; thus, the present application can synthesize a rich variety of pyrrole compounds and achieve high-value conversion of sulfonamides; it overcomes the current shortcomings of insufficient development and utilization of sulfonamide compounds and their waste materials and lack of means to convert sulfonamides into high-value new pyrrole compounds.
[0035] Example 1
[0036] Example 1 of the present application provides a method for converting sulfonamide into pyrrole compounds, and the preparation method includes the steps of converting into N-sulfonylpyrrole and converting into dipyrrole compounds.
[0037] The steps of converting to N-sulfonylpyrrole include: adding sulfonamide (3 mmol), diketone (3.6 mmol), p-toluenesulfonic acid (0.15 mmol), and toluene (10 mL) into a reaction bottle, stirring the reaction solution in an oil bath at 100 degrees for 3 hours; after the reaction, the solvent is dried by spin drying, and the product N-sulfonylpyrrole is separated by column chromatography with a yield of 85%. The reaction process is shown in the following formula:
[0038] .
[0039] The H NMR spectrum data, C NMR spectrum data and mass spectrum data of the product N-sulfonylpyrrole are as follows:
[0040]
[0041] The steps of converting to dipyrrole compounds include: adding N-sulfonylpyrrole (3 mmol), photosensitizer [Ir(dFCF 3 ppy) 2 (dtbpy)]PF 6(0.09mmol), acrylonitrile (1mmol). After the reaction bottle was sealed and replaced with vacuum-nitrogen three times, tert-butyl methyl ether (10mL) was added, and the reaction bottle was placed under 30-watt blue light for 24 hours; after the reaction, the solvent was dried and separated by column chromatography to obtain the product dipyrrole compound with a yield of 74%; the reaction process is shown in the following formula:
[0042] .
[0043] The H NMR spectrum data, C NMR spectrum data and mass spectrum data of the product dipyrrole compound are as follows:
[0044]
[0045] Example 2
[0046] Example 2 of the present application provides a method for converting sulfonamide into pyrrole compounds, and the preparation method includes the steps of converting into N-sulfonylpyrrole and converting into dipyrrole compounds.
[0047] The steps of converting to N-sulfonylpyrrole include: adding sulfonamide (3 mmol), diketone (3.6 mmol), p-toluenesulfonic acid (0.15 mmol), and toluene (10 mL) into a reaction bottle, stirring the reaction solution in an oil bath at 100 degrees for 3 hours; after the reaction, the solvent is dried by spin drying, and the product N-sulfonylpyrrole is separated by column chromatography; the reaction process is shown in the following formula:
[0048] .
[0049] The steps of converting to dipyrrole compounds include: adding N-sulfonylpyrrole (3 mmol), photosensitizer [Ir(dFCF 3 ppy) 2 (dtbpy)]PF 6 (0.09mmol), phenylacetylene (1mmol). After the reaction bottle was sealed and replaced with vacuum-nitrogen three times, tetrahydrofuran (10mL) was added and the reaction bottle was placed under 30W blue light for 24 hours. After the reaction, the solvent was dried and separated by column chromatography to obtain the product dipyrrole compound with a yield of 68%. The reaction process is shown in the following formula:
[0050] .
[0051] The H NMR spectrum data of the product dipyrrole compound are:
[0052] Example 3
[0053] Example 3 of the present application provides a method for converting sulfonamide into pyrrole compounds, and the preparation method includes the steps of converting into N-sulfonylpyrrole and converting into 2-sulfonylpyrrole compounds.
[0054] The steps of converting to N-sulfonylpyrrole include: adding sulfonamide (3 mmol), diketone (3.6 mmol), p-toluenesulfonic acid (0.15 mmol), and toluene (10 mL) into a reaction bottle, stirring the reaction solution in an oil bath at 100 degrees for 3 hours; after the reaction, the solvent is dried by spin drying, and the product N-sulfonylpyrrole is separated by column chromatography; the reaction process is shown in the following formula:
[0055] .
[0056] The step of converting into a 2-sulfonylpyrrole compound comprises: adding N-sulfonylpyrrole (3 mmol) and 10-phenylphenothiazine (0.09 mmol) into a reaction bottle, sealing the reaction bottle, vacuum-nitrogen replacement three times, adding acetonitrile (10 mL), placing the reaction bottle under a 30-watt 390-nanometer ultraviolet lamp for irradiation for 24 hours; after the reaction is completed, the solvent is dried by spin drying, and column chromatography is performed to separate the product 2-sulfonylpyrrole compound with a yield of 85%. The reaction process is shown in the following formula:
[0057] .
[0058] The H NMR spectrum data of the product 2-sulfonylpyrrole compound are:
[0059] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.
Claims
1. A method for converting sulfonamide into pyrrole compounds, characterized in that: The method comprises the steps of: condensing a sulfonamide compound and a diketone compound with protected or unprotected ketone group under the action of an acid catalyst to obtain N-sulfonylpyrrole.
2. The method for converting sulfonamide into pyrrole compounds according to claim 1, characterized in that: The sulfonamide compound is selected from at least one of aryl sulfonamides, alkyl sulfonamides and heterocyclic sulfonamides.
3. The method for converting sulfonamide into pyrrole compounds according to claim 1, characterized in that: The diketone compound with a protected keto group is selected from ketals; The diketone compound whose keto group is not protected is selected from diketones.
4. The method for converting sulfonamide into pyrrole compounds according to claim 1, characterized in that: The acid catalyst is selected from Lewis acids and / or protic acids.
5. The method for converting sulfonamide into pyrrole compounds according to claim 1, characterized in that: The method for converting sulfonamide into pyrrole compounds also includes the step of converting N-sulfonylpyrrole into 2-sulfonylpyrrole by breaking the NS bond under the action of visible light and a photosensitizer.
6. The method for converting sulfonamide into pyrrole compounds according to claim 1, characterized in that: The method for converting sulfonamide into pyrrole compounds also includes the step of converting N-sulfonylpyrrole and unsaturated hydrocarbon into dipyrrole compounds under the action of visible light and a photosensitizer.
7. The method for converting sulfonamide into pyrrole compounds according to claim 6, characterized in that: The unsaturated hydrocarbon is selected from olefins and / or alkynes.
8. The method for converting sulfonamide into pyrrole compounds according to claim 7, characterized in that: The olefin is selected from at least one of styrene, distilbenes, acrylates, acrylamide and acrylonitrile; The alkyne is selected from at least one of phenylacetylene, propiolonitrile and propiolate.
9. The method for converting sulfonamide into pyrrole compounds according to claim 5 or 6, characterized in that: The visible light is selected from full-wavelength visible light, which is at least one of red light, orange light, yellow light, green light, cyan light, blue light, purple light, and ultraviolet light; The photosensitizer is selected from at least one of amine organic molecules, iridium metal complexes, and ruthenium metal complexes.
10. Use of the pyrrole compounds obtained by the method for converting sulfonamide into pyrrole compounds according to any one of claims 1 to 9 in the field of screening bioactive molecules / drug molecules.