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CN-122010869-A - Dioxygen di-oxygen benzothiazepines Synthesis method of heptanone derivative

CN122010869ACN 122010869 ACN122010869 ACN 122010869ACN-122010869-A

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a dioxadibenzothiazepinone derivative. The invention discloses a method for carrying out intramolecular cyclization reaction on an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound serving as a substrate under the condition of visible light in the presence of CO 2 , alkali, a hydrogen atom transfer agent and a photocatalyst. The reaction synthesizes the dioxadibenzothiazepinone derivative in a medium yield under the condition of the temperature and the visible light. The method has the advantages of mild reaction conditions, good substrate compatibility, simple operation, low-cost and easily available raw materials, simple preparation, stable structure and the like.

Inventors

  • LIU CHENJIANG
  • ZHANG TAO
  • CHEN ZIREN
  • ZHANG YONGHONG

Assignees

  • 新疆大学

Dates

Publication Date
20260512
Application Date
20260126

Claims (10)

  1. 1. A synthesis method of a dioxadibenzothiazepinone derivative is characterized in that an N- (2-ethynylaryl) -N-alkylbenzene sulfonamide compound is used as a substrate, and the substrate is induced to synthesize the dioxadibenzothiazepinone derivative under the condition of visible light in the presence of a base, a hydrogen atom transfer agent and a photocatalyst under the atmosphere of CO 2 .
  2. 2. A process for the synthesis of a dioxabenzothiazepine derivative according to claim 1, Taking an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound as a substrate, wherein a compound generated by intramolecular cyclization is a dioxydibenzothiazepinone derivative (II); The preparation method comprises the steps of adding alkali, a hydrogen atom transfer agent and a photocatalyst into a solvent by using an N- (2-ethynylaryl) -N-alkylbenzene sulfonamide compound in a CO 2 atmosphere, and generating the dioxadibenzothiazepinone derivative (II) through a visible light induced reaction.
  3. 3. A process for the synthesis of a dioxadibenzothiazepinone derivative according to claim 1 or 2, The structure of the N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound is as follows: ; The structure of the dioxadibenzothiazepinone derivative is as follows: ; Substituent R 1 is H or halogen; The substituent R 2 is alkyl with 1-4 carbon atoms and cycloalkyl with 5,6 carbon atoms; The substituent R 3 is one or more than two of H, halogen, alkyl with 1-4 carbon atoms, alkoxy, phenyl and fluoroalkyl with 1 carbon atoms, and fluoroalkyl C n F m ; n is 1, m is 3, and halogen is one or more of F, cl and Br.
  4. 4. The method for synthesizing the dioxadibenzothiazepinone derivative according to claim 1 or 2, wherein the visible light is one or more of 1-18W white light (6500K), 1-18W purple light (400-405 nm), 1-18W blue light (460-465 nm), 1-18W green light (526-531 nm) and 1-18W red light (700-705 nm).
  5. 5. The method for synthesizing a dioxadibenzothiazepinone derivative according to claim 2, wherein the solvent is one or more of dichloromethane, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and dimethylsulfoxide, and 0.5 to 3 mL of the solvent is added per 0.1 mmolN- (2-ethynylaryl) -N-alkylbenzene sulfonamide compound.
  6. 6. The method for synthesizing a dioxadibenzothiazepinone derivative according to claim 1 or 2, wherein the base is any one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium t-butoxide, potassium formate, and 1, 8-diazabicyclo [5,4,0] undecene-7 (DBU), and the molar concentration of the base in the solvent is 0.01 to 0.1M.
  7. 7. The method for synthesizing a dioxabenzothiazepine derivative according to claim 1 or 2, wherein the photocatalyst is any one or more of fac-Ir (ppy) 3 (Shanghai, division of medical science and technology), 4CzIPN, 4CzIPN-CH 3 、4CzIPN-tBu、DCA、Ru(bpy)Cl 2 ·6H 2 O, and the molar concentration of the photocatalyst in the solvent is preferably 0.0005-0.0015M.
  8. 8. The method for synthesizing a dioxadibenzothiazepinone derivative according to claim 1 or 2, wherein the hydrogen atom transfer agent is one or more of p-MePhSH, DABCO, quinine, and p-BuPhSH, nBuSH, iPr 3 SiSH, and the molar concentration of the hydrogen atom transfer agent (HAT) in the solvent is 0.0005 to 0.005M.
  9. 9. The method for synthesizing a dioxabenzothiazepine derivative according to claim 1 or 2, wherein the molar ratio of the amount of CO 2 is 1 bar to 2 bar.
  10. 10. The method for synthesizing a dioxadibenzothiazepinone derivative according to claim 1 or 2, wherein the reaction time is 36 to 48 hours and the reaction temperature is 25 o C under a CO 2 atmosphere.

Description

Dioxygen di-oxygen benzothiazepines Synthesis method of heptanone derivative Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a dioxadibenzothiazepinone derivative. Background The benzazepine skeleton is formed by combining benzene rings and seven-membered nitrogen heterocycles, is an important nitrogen-containing heterocyclic structural unit and widely exists in a plurality of natural products and commercial drug molecules. For example, benazepril (Benazepril) has angiotensin converting enzyme inhibiting effects and is useful for treating hypertension and heart failure. Epinastine (EPINASTINE) is a high-efficiency histamine H1 receptor antagonist, can treat inflammation caused by allergy, and the tianestine (TIANEPTINE) is a medicament for treating mental disorder, has good antidepressant effect, and the sirolimus (Zepastine) is a bioactive compound and has good antihistamine effect. Based on the unique biological activity, the development of efficient and convenient synthesis methods for the benzothiazepine skeleton derivatives is attracting attention. Traditionally, lewis acid-promoted Friedel-Crafts cyclization or transition metal-catalyzed Heck-like coupling reactions have been employed to synthesize such framework compounds, however, such reactions often require strongly acidic or high temperature reaction environments, limiting the possibility of further large-scale application of these methods. No synthetic method under mild conditions has been reported for dioxadibenzothiazepinone derivatives. Therefore, the development of a synthetic method of the dioxadibenzothiazepinone derivative which is easy to obtain raw materials, simple and convenient to operate, mild in reaction conditions and environment-friendly is urgent to solve the technical problem of the technicians in the field. Disclosure of Invention In view of the above, the invention discloses a synthesis method of a dioxadibenzothiazepinone derivative, which is characterized in that the method is characterized in that raw materials are easy to obtain, the operation is simple and convenient, the reaction condition is mild, the method is environment-friendly, 4CzIPN is used as a photocatalyst, potassium carbonate is used as alkali, triisopropylsilicon mercaptan is used as a hydrogen atom transfer agent (HAT), acetonitrile is used as a solvent, and the intramolecular cyclization reaction is carried out, so that the dioxadibenzothiazepinone derivative is prepared. In order to achieve the above purpose, the present invention adopts the following technical scheme: The first technical object of the present invention is to provide a method for synthesizing a dioxadibenzothiazepinone derivative, comprising the steps of: Under the condition of visible light, the N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound (I) undergoes intramolecular cyclization reaction at room temperature (reaction formula 1), and after the reaction is finished, the product is separated and characterized according to a conventional separation and purification method, thus obtaining the corresponding dioxadibenzothiazepinone derivative (II). Reaction 1 The invention discloses a method for preparing a dioxydibenzothiazepinone derivative (II) by taking blue light as a light source under normal temperature and using an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound (I) as a substrate to realize visible light-induced intramolecular cyclization reaction at room temperature. Wherein the structure of the dioxadibenzothiazepinone derivative (II) is as follows: ; Substituent R 1 is H or halogen; The substituent R 2 is alkyl with 1-4 carbon atoms and cycloalkyl with 5,6 carbon atoms; The substituent R 3 is one or more than two of H, halogen, alkyl with 1-4 carbon atoms, alkoxy, phenyl and fluoroalkyl with 1 carbon atoms, and fluoroalkyl C nFm; n is 1, m is 3, and halogen is one or more of F, cl and Br. In the invention, the reaction is carried out under the irradiation of one or more than two of 1-18W white light (6500K), 1-18W purple light (400-405 nm), 1-18W blue light (460-465 nm), 1-18W green light (526-531 nm) and 1-18W red light (700-705 nm), and the optimal condition is 12W blue light (460-465 nm), and the reaction light source is 460-465 nm blue light. In the reaction, the solvent is one or more than two of dichloromethane, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide, the preferable solvent is acetonitrile, and 0.5-3 mL of the solvent is added to each 0.1 mmolN- (2-ethynylaryl) -N-alkylbenzene sulfonamide compound, and the optimal solvent dosage is 2 mL. In the invention, in the reaction, the alkali is any one or more than two of sodium carbonate, potassium carbonate, cesium carbonate, potassium tert-butoxide, potassium formate and 1, 8-diaza [5,4,0] undecene-7 (DBU), the preferable alka