Method for preparing 2-substituted benzothiazole derivative through light driving

Abstract

The invention discloses a method for preparing a 2-substituted benzothiazole derivative through light driving. Comprising the following steps: mixing an N-aryl thioamide compound, a photocatalyst and a solvent, reacting, removing the solvent, separating and purifying to obtain the 2-substituted benzothiazole derivative, the method has the advantages of high yield, high atom economy, cheap and easy-to-separate catalyst, mild reaction conditions, simple and convenient post-treatment, greenness, environmental protection and the like, and an economical, practical, green and environment-friendly new method is provided for preparation of the 2-substituted benzothiazole compound widely applied to the fields of medicines, luminescent materials, pesticides and the like.

Description

Technical Field

[0001] The present application relates to a method for light-driven preparation of 2-substituted benzothiazole derivatives, belonging to the field of photocatalysis. Background Art

[0002] Benzothiazole compounds are important nitrogen-containing and sulfur-containing heterocycles of a class, and are widely used in various fields such as medicine, agriculture and industry as important organic synthesis intermediates. In anti-tuberculosis, anti-tumor, antimalarial, anticonvulsant, antibacterial, anthelmintic, hypoglycemic, analgesic, anti-inflammatory and diuretic aspects, important pharmacological activities have been exerted, showing good drug activity. Meanwhile, due to the unique luminescent properties of the compound of benzothiazole parent, it has attracted much attention in the field of novel organic photoelectric materials. With the continuous progress and development of science and technology, the application of benzothiazole compounds is more and more extensive, and their synthetic methods have also attracted more and more attention. Over the years, synthetic chemists have invested a lot of energy in the efficient synthesis of the exploration of benzothiazole compounds. In the multiple synthetic routes of benzothiazole, the internal cyclization reaction based on thioamide is considered to have the advantages of wide substrate applicability, easy conversion, few by-products, and has been widely studied. For example, in 1886, Jacobson et al. reported the preparation of benzothiazole by intramolecular oxidation ring using N-phenylthiobenzamide as raw material in the presence of K3[Fe(CN)6] as catalyst and NaOH as base, so it is also called Jacobson cyclization method. In 2006, Bose et al. reported a method for synthesizing 2-arylbenzothiazole compounds by intramolecular cyclization at room temperature using thiobenzamide as raw material. Since then, the synthesis method of benzothiazole derivatives based on intramolecular cyclization has been widely studied.

[0003] In recent years, the light-driven preparation of 2-substituted benzothiazole derivatives has opened up a green and sustainable route. Due to the advantages of high energy utilization, mild reaction conditions and green chemistry concept, visible light photocatalysis has attracted great attention from researchers. In 2012, Li et al. reported a method for preparing 2-substituted benzothiazole derivatives by internal cyclization reaction catalyzed by Ru(bpy)3(PF6)2 under visible light drive (Org. Lett., 2012, 14, 98-101). In 2015, Lei et al. used Ru(bpy)3(PF6)2 and Co complex as a co-catalyst system to efficiently prepare a variety of 2-substituted benzothiazole derivatives and produce H2 under blue light irradiation (J.Am.Chem.Soc.2015, 137, 9273-9280). In 2024, Roy et al. reported the use of benzophenone-based organic photocatalysts to prepare 2-substituted benzothiazole derivatives and produce H2 by means of photoelectrocatalysis under mild conditions (ACS Catal. 2024, 14, 907-920). Although the photocatalytic synthesis of 2-substituted benzothiazole derivatives has made great progress, most methods have one or more disadvantages. For example, the use of other inorganic oxidants will lead to desulfurization of the thioamide substrate to form amide by-products, reducing the yield; the use of precious metal catalysts requires additional processing and costs; the use of homogeneous photocatalysts makes it difficult to separate the catalyst and difficult to recycle, which increases the cost of the reaction. Therefore, it is of great significance to develop reactions catalyzed by heterogeneous visible light photocatalysts. Summary of the invention

[0004] The present invention aims to solve the above shortcomings and deficiencies of the prior art and provide a method for preparing 2-substituted benzothiazole derivatives by using light as the driving force of the reaction. The method has easy separation of the reaction catalyst, high yield, wide substrate applicability, low cost and conforms to the concept of green chemistry.

[0005] According to one aspect of the present application, a method for preparing 2-substituted benzothiazole derivatives by light-driven method is provided, comprising the following steps:

[0006] The N-arylthioamide compound, the photocatalyst and the solvent are mixed, reacted under light-driven conditions, the reaction is tracked and detected by thin layer chromatography, the catalyst is removed by centrifugation, the organic solvent is removed by rotary evaporation with an organic solvent, the organic solvent is separated and purified to obtain a 2-substituted benzothiazole derivative;

[0007] Under light-driven conditions, bismuth vanadate catalyst oxidizes N-phenylthiobenzamide to produce thiol free radicals, followed by a free cyclization reaction, where the thiol free radicals attack the benzene ring to form phenyl free ions, which then lose hydrogen ions to form 2-substituted benzothiazoles and produce hydrogen. In the presence of oxygen, bismuth vanadate reduces oxygen to produce superoxide free radicals, which oxidize phenyl free ions to form 2-substituted benzothiazoles.

[0008] The N-arylthioamide compound has a structure shown in Formula I:

[0009]

[0010] The 2-substituted benzothiazole derivative has a structure shown in Formula II:

[0011]

[0012] Among them, R 1 , R 2 independently selected from hydrogen, methyl, methoxy, halogen, trifluoromethyl, cyano, alkyl, aryl, substituted C1C 10 At least one of the alkyl groups;

[0013] The substituted C1-C 10 The substituents in the alkyl group are selected from C6-C 10 The aromatic group;

[0014] The photocatalyst is selected from BiVO4 and / or Pt-loaded BiVO4.

[0015] The solvent is selected from at least one of cyclohexane, dichloromethane, ethyl acetate, acetone, acetonitrile, tetrahydrofuran and water.

[0016] The molar ratio of the photocatalyst, the N-arylthioamide compound and the solvent is 1:1 to 10:1 to 10000;

[0017] Optionally, the molar ratio of the photocatalyst, the N-arylthioamide compound, and the solvent is 1:1-4:1000-5000.

[0018] The reaction temperature is 20 to 50°C;

[0019] The reaction time is 2 to 20 hours;

[0020] The reaction atmosphere is selected from at least one of a pure oxygen atmosphere, an oxygen-containing atmosphere, a nitrogen atmosphere, and an inert gas atmosphere.

[0021] The catalyst was prepared by precipitation synthesis method. Bismuth nitrate (Bi(NO3)3·5H2O) and ammonium metavanadate (NH4VO3) were used to prepare BiVO4. Then Pt / BiVO4 was prepared by deposition method.

[0022] The beneficial effects of this application include:

[0023] (1) The synthesis method of the present application avoids the use of stoichiometric oxidants or precious metals. The preparation of 2-substituted benzothiazole derivatives is carried out under light-driven conditions at room temperature. This method has the advantages of easy catalytic separation, few by-products, mild conditions, safe operation, and simplicity.

[0024] (2) The method provided in the present application has the advantages of being green and environmentally friendly, having high atom economy, being simple and convenient for post-processing, and being suitable for large-scale production, which can make the preparation of 2-substituted benzothiazole derivatives greener and reduce the synthesis cost. DETAILED DESCRIPTION

[0025] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0026] Unless otherwise specified, the raw materials and catalysts in the examples of this application were purchased through commercial channels.

[0027] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0028] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0029] In the examples, a Varian I NOVA 400 MHz nuclear magnetic resonance spectrometer from Varian Corporation of the United States was used to perform qualitative analysis on the product.

[0030] The yield of the target product in this application is calculated using the following method:

[0031] Yield of target product = actual mass of target product obtained / theoretical mass of target product obtained × 100%.

[0032] Example 1

[0033] 2-Phenylbenzothiazole

[0034] This embodiment provides a method for preparing 2-phenylbenzothiazole, using N-phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0035]

[0036] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product as a white solid. The yield of the target product is 85%.

[0037] Example 2

[0038] 6-Methoxy-2-phenylbenzothiazole

[0039] This embodiment provides a method for preparing 6-methoxy-2-phenylbenzothiazole, using N-(p-methoxyphenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0040]

[0041] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(p-methoxyphenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product as a white solid. The yield of the target product is 91%.

[0042] Example 3

[0043] 6-Methyl-2-phenylbenzothiazole

[0044] This embodiment provides a method for preparing 6-methyl-2-phenylbenzothiazole, using N-(p-methylphenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0045]

[0046] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(p-methylphenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product as a white solid. The yield of the target product is 86%.

[0047] Example 4

[0048] 6-Trifluoromethyl-2-phenylbenzothiazole

[0049] This embodiment provides a method for preparing 6-trifluoromethyl-2-phenylbenzothiazole, using N-(4-trifluoromethylphenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0050]

[0051] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(4-trifluoromethylphenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product. The yield of the target product is 81%.

[0052] Example 5

[0053] 6-Fluoro-2-phenylbenzothiazole

[0054] This embodiment provides a method for preparing 6-fluoro-2-phenylbenzothiazole, using N-(4-fluorophenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0055]

[0056] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(4-fluorophenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product. The yield of the target product is 84%.

[0057] Example 6

[0058] 6-Bromo-2-phenylbenzothiazole

[0059] This embodiment provides a method for preparing 6-bromo-2-phenylbenzothiazole, using N-(4-bromophenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0060]

[0061] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(4-bromophenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product. The yield of the target product is 84%.

[0062] Example 7

[0063] 6-Chloro-2-phenylbenzothiazole

[0064] This embodiment provides a method for preparing 6-chloro-2-phenylbenzothiazole, using N-(4-chlorophenyl)phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0065]

[0066] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(4-chlorophenyl)phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product. The yield of the target product is 84%.

[0067] Example 8

[0068] 2-(4-Methoxyphenyl)benzothiazole

[0069] This embodiment provides a method for preparing 2-(4-methoxyphenyl)benzothiazole, using 4-methoxy-N-phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0070]

[0071] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate 4-methoxy-N-phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product. The yield of the target product is 87%.

[0072] Example 9

[0073] 2-(4-Chlorophenyl)benzothiazole

[0074] This embodiment provides a method for preparing 2-(4-chlorophenyl)benzothiazole, using 4-chloro-N-phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0075]

[0076] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate 4-chloro-N-phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product. The yield of the target product is 86%.

[0077] Example 10

[0078] 2-(4-Trifluoromethylphenyl)benzothiazole

[0079] This embodiment provides a method for preparing 2-(4-trifluoromethylphenyl)benzothiazole, using 4-trifluoromethyl-N-phenylthiobenzamide as a raw material and Pt / BiVO4 as a photocatalyst for the reaction, and the reaction equation is as follows:

[0080]

[0081] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate 4-trifluoromethyl-N-phenylthiobenzamide (0.2mmol) and 10mg Pt / BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product. The yield of the target product is 83%.

[0082] Embodiment 11

[0083] 2-Phenylbenzothiazole

[0084] This embodiment provides a method for preparing 2-phenylbenzothiazole, using N-phenylthiobenzamide as a raw material and BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0085]

[0086] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-phenylthiobenzamide (0.2mmol) and 10mg BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product as a white solid. The yield of the target product is 86%.

[0087] Example 12

[0088] 6-Methoxy-2-phenylbenzothiazole

[0089] This embodiment provides a method for preparing 6-methoxy-2-phenylbenzothiazole, using N-(p-methoxyphenyl)phenylthiobenzamide as a raw material and BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0090]

[0091] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(p-methoxyphenyl)phenylthiobenzamide (0.2mmol) and 10mg BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product as a white solid. The yield of the target product is 90%.

[0092] Example 13

[0093] 6-Trifluoromethyl-2-phenylbenzothiazole

[0094] This embodiment provides a method for preparing 6-trifluoromethyl-2-phenylbenzothiazole, using N-(4-trifluoromethylphenyl)phenylthiobenzamide as a raw material and BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0095]

[0096] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate N-(4-trifluoromethylphenyl)phenylthiobenzamide (0.2mmol) and 10mg BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by column chromatography on petroleum ether / ethyl acetate to obtain the desired product. The yield of the target product is 86%.

[0097] Embodiment 14

[0098] 2-(4-Methoxyphenyl)benzothiazole

[0099] This embodiment provides a method for preparing 2-(4-methoxyphenyl)benzothiazole, using 4-methoxy-N-phenylthiobenzamide as a raw material and BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0100]

[0101] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate 4-methoxy-N-phenylthiobenzamide (0.2mmol) and 10mg BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product. The yield of the target product is 89%.

[0102] Embodiment 15

[0103] 2-(4-Chlorophenyl)benzothiazole

[0104] This embodiment provides a method for preparing 2-(4-chlorophenyl)benzothiazole, using 4-chloro-N-phenylthiobenzamide as a raw material and BiVO4 as a photocatalyst for reaction, and the reaction equation is as follows:

[0105]

[0106] In a transparent quartz bottle with a rubber stopper and a magnetic stirring bar, the reaction substrate 4-chloro-N-phenylthiobenzamide (0.2mmol) and 10mg BiVO4 are added to the reaction solvent. Under light irradiation, the reaction mixture is stirred in an oxygen atmosphere at ambient temperature in a nitrogen atmosphere. During the reaction, the progress of the reaction can be monitored by GC or TLC. After the reaction is completed, the solvent is removed by vacuum or extraction, and the residue is purified by petroleum ether / ethyl acetate column chromatography to obtain the desired product. The yield of the target product is 88%.

[0107] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A method for preparing 2-substituted benzothiazole derivatives driven by light, characterized in that: The following steps are involved: The N-arylthioamide compound, the photocatalyst and the solvent are mixed, reacted, the solvent is removed, separated and purified to obtain a 2-substituted benzothiazole derivative; The N-arylthioamide compound has a structure shown in Formula I: The 2-substituted benzothiazole derivative has a structure shown in Formula II: Among them, R 1 , R 2 independently selected from hydrogen, methyl, methoxy, halogen, trifluoromethyl, cyano, alkyl, aryl, substituted C1C 10 At least one of the alkyl groups; The substituted C1-C 10 The substituents in the alkyl group are selected from C6-C 10 The aromatic group; The photocatalyst is selected from BiVO4 and / or Pt-loaded BiVO4.

2. The method according to claim 1, characterized in that The solvent is selected from at least one of cyclohexane, dichloromethane, ethyl acetate, acetone, acetonitrile, tetrahydrofuran and water.

3. The method according to claim 1, characterized in that The molar ratio of the photocatalyst, the N-arylthioamide compound and the solvent is 1:1 to 10:1 to 10000; Preferably, the molar ratio of the photocatalyst, the N-arylthioamide compound, and the solvent is 1:1-4:1000-5000.

4. The method according to claim 1, characterized in that: The reaction temperature is 20 to 50°C; The reaction time is 2 to 20 hours; The reaction atmosphere is selected from at least one of a pure oxygen atmosphere, an oxygen-containing atmosphere, a nitrogen atmosphere, and an inert gas atmosphere.

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