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CN-116730948-B - Method for synthesizing N-cyclohexyl-2-benzothiazole

CN116730948BCN 116730948 BCN116730948 BCN 116730948BCN-116730948-B

Abstract

The invention provides a method for synthesizing N-cyclohexyl-2-benzothiazole, which comprises the following steps of reacting cyclohexylamine and 2-halogenated benzothiazole in an alcohol solvent at 60-80 ℃ in the presence of a deacidification agent to generate N-cyclohexyl-2-benzothiazole. The method has the advantages of simple operation, easily obtained raw materials, no halogen-containing catalyst, less pollution, higher product purity and yield, no use of DMSO as solvent, and solves the problem of difficult recovery and purification of DMSO.

Inventors

  • ZHOU XIAOYIN
  • GUO XIANGYUN
  • LI QINGHUA
  • TANG ZHIMIN

Assignees

  • 圣奥化学科技有限公司

Dates

Publication Date
20260505
Application Date
20220302

Claims (14)

  1. 1. A method of synthesizing N-cyclohexyl-2-benzothiazole, the method comprising: Reacting cyclohexylamine and 2-halogenated benzothiazole in an alcohol solvent at 70-75 ℃ in the presence of a deacidification agent to produce N-cyclohexyl-2-benzothiazole; The 2-halogenated benzothiazole is selected from one or more of 2-chlorobenzothiazole, 2-bromobenzothiazole and 2-iodobenzothiazole; the deacidification agent is selected from one or more of sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate; The alcohol solvent is selected from C1-C4 alcohols; The boiling point of the alcohol solvent is less than or equal to 120 ℃.
  2. 2. The method of claim 1, wherein the alcoholic solvent is selected from one or more of ethanol, n-propanol, isopropanol, and n-butanol.
  3. 3. The method of claim 1, wherein the alcoholic solvent is ethanol.
  4. 4. The method of claim 1, wherein the 2-halobenzothiazole is 2-chlorobenzothiazole.
  5. 5. The method of claim 1, wherein the reaction time is from 4 to 8 hours.
  6. 6. The process according to claim 1, wherein the molar ratio of cyclohexylamine to 2-halobenzothiazole is from 1 to 1.5:1.
  7. 7. The process according to claim 1, wherein the molar ratio of cyclohexylamine to 2-halobenzothiazole is (1-1.2): 1.
  8. 8. The method of claim 1, wherein the molar ratio of deacidification agent to 2-halobenzothiazole is (1-3): 1.
  9. 9. The process according to claim 1, wherein the alcohol solvent is used in an amount of 3 to 8 times the total mass of cyclohexylamine and 2-halobenzothiazole.
  10. 10. The process according to claim 1, wherein the process comprises heating the mixture of cyclohexylamine, deacidification agent and alcohol solvent to 60-80℃and then adding 2-halobenzothiazole dropwise thereto to react at 60-80 ℃.
  11. 11. The method of claim 10, wherein the 2-halobenzothiazole has a drip rate of less than or equal to 0.2mol/h.
  12. 12. The method of claim 10, wherein the 2-halobenzothiazole has a drip rate of less than or equal to 0.1mol/h.
  13. 13. The method of claim 10, wherein the 2-halobenzothiazole has a drip rate of 0.05 to 0.1mol/h.
  14. 14. The method according to claim 1, further comprising filtering inorganic salt in the reaction system while the solution is hot after the reaction is completed, recovering the solvent under reduced pressure, cooling to normal temperature, filtering, washing and drying the filter cake to obtain the N-cyclohexyl-2-benzothiazole.

Description

Method for synthesizing N-cyclohexyl-2-benzothiazole Technical Field The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of N-cyclohexyl-2-benzothiazole. Background Benzothiazole compounds have been widely used in the fields of agricultural chemicals, medicines and the like since synthesis, and are industrially useful as rubber accelerators, vulcanizing agents, fibers, plastic colorants, agricultural antibacterial agents, pesticides, fungicides and the like, and pharmaceutical agents for antiparasitic agents, anticancer agents and the like. The modification of benzothiazole mainly comprises the introduction of different substituents on benzene ring and the introduction of different active groups on 2-position, wherein the 2-position active groups have the greatest influence on the activity. Amino derivatives are introduced into the 2-position of benzothiazole, so that Schiff base properties can be obtained, and various biological activities are shown, when the Schiff base is combined with metal ions through N, S atoms to form heterocyclic metal complexes, the antibacterial activity on fungi and bacteria microorganisms can be greatly enhanced, and cytotoxicity of human cancer cells can be detected. As a benzothiazole compound with amino derivatives introduced at the 2-position, the N-cyclohexyl-2-benzothiazole has the structural formula: At present, the method for synthesizing N-cyclohexyl-2-benzothiazole mainly comprises the steps of (1) synthesizing N-cyclohexyl-2-benzothiazole by phenyl 2-iodo-isothiocyanato and cyclohexylamine under the catalysis of tetrabutyl phosphonium bromide, (2) synthesizing N-cyclohexyl-2-benzothiazole by heating cyclohexyl-isothiocyanato and 2-mercaptoaniline in water or dimethyl sulfoxide (DMSO), and (3) deacidifying chloro-benzothiazole and cyclohexylamine in DMSO by adopting K 2CO3 and CuI as a catalyst to synthesize the N-cyclohexyl-2-benzothiazole. Visekhonuo Kuotsu et al (An environmentally benign synthesis of Tetrabutylphosphonium tribromide(TBPTB)–a versatile and efficient phase transfer reagent for organic transformations[J].Green Chemistry Letters and Reviews,2021,14(2):424-433) use of phenyl 2-iodo-isothiocyanato with cyclohexylamine under the catalysis of tetrabutylphosphonium bromide gave N-cyclohexyl-2-benzothiazole in 80% yield. The yield of the method is not very high, the sources of raw materials and catalysts are not wide, and halogen-containing catalysts are easy to cause pollution. RITIKA SHARMA et al (Water-mediated synthesis of benzazole and thiourea motifs by reacting naturally occurring isothiocyanate with amines[J].Synthetic Communications,2015,45:2106-2114) synthesized N-cyclohexyl-2-benzothiazole by reaction of cyclohexyl isothiocyanato with 2-mercaptoaniline at 120℃for 48h in 56% yield. The method has low yield, complex operation process, long time consumption and low raw material source. Ste phanie Toulot et al (Convenient and Reliable Routes Towards 2-Aminothiazoles:Palladium-Catalyzed versus Copper-Catalyzed Aminations of Halothiazoles[J].Advanced Synthesis&Catalysis,2013,355(16):3263-3272) reacted with cyclohexylamine in DMSO using K 2CO3 deacidification under the catalysis of CuI to give N-cyclohexyl-2-benzothiazole. The method uses DMSO as a solvent, the post-treatment and the recovery are difficult, and the halogen-containing catalyst is easy to cause environmental pollution. Therefore, the existing method for synthesizing the N-cyclohexyl-2-benzothiazole has the problems of low yield, low sources of raw materials and catalysts, easy environmental pollution caused by the catalysts, complex operation, difficult post-treatment and recovery of solvents and the like. There is a need in the art for a simple and environmentally friendly method for synthesizing N-cyclohexyl-2-benzothiazole. Disclosure of Invention Aiming at the defects of the synthesis method, the invention provides a novel synthesis method of N-cyclohexyl-2-benzothiazole, which takes cyclohexylamine and 2-halogenated benzothiazole as raw materials and adopts alcohol solvents as solvents to directly synthesize target products at 60-80 ℃. The method has the advantages of simple operation, easily obtained raw materials, no halogen-containing catalyst, less pollution, higher product purity and yield, no use of DMSO as solvent, and solves the problem of difficult recovery and purification of DMSO. Specifically, the method for synthesizing the N-cyclohexyl-2-benzothiazole comprises the following steps: reacting cyclohexylamine and 2-halogenated benzothiazole in alcohol solvent at 60-80 ℃ in the presence of deacidification agent to generate N-cyclohexyl-2-benzothiazole. In one or more embodiments, the deacidification agent is selected from one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate. In one or more embodiments, the alcoholic solvent is a low boiling alcoholic solvent, preferably having