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CN-122010870-A - Ester group substitution dibenzothio of (C) Synthesis method of azepine derivative

CN122010870ACN 122010870 ACN122010870 ACN 122010870ACN-122010870-A

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an ester-substituted dibenzothiazepine derivative. The invention discloses a method for realizing intramolecular tandem aryl carboxylation cyclization reaction of an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound under the condition of visible light by taking the N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound as a substrate, sodium formate as a C1 source and alkali as an additive under the atmosphere of carbon dioxide (air and oxygen accounting for 21%). The reaction synthesizes the dibenzothiazepine derivative substituted by ester groups in medium yield under the conditions of high temperature and 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 (9)

  1. 1. The synthesis method of the ester-substituted dibenzothiazepine derivative is characterized in that an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound is used as a substrate, and under the atmosphere of carbon dioxide (air and oxygen accounting for 21%), alkali and formate are used for inducing the substrate to synthesize the ester-substituted dibenzothiazepine derivative under the condition of visible light.
  2. 2. The method for synthesizing the ester-substituted dibenzothiazepine derivative according to claim 1, wherein, N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound is taken as a substrate, and compound generated by intramolecular tandem aryl carboxylation cyclization is ester-substituted dibenzothiazepine derivative (II); in the specific preparation process, under the atmosphere of carbon dioxide (air exists and oxygen accounts for 21%), adding alkali and formate into a solvent by using an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound, and generating the ester-substituted dibenzothiazepine derivative (II) through a visible light induction reaction.
  3. 3. The method for synthesizing an ester-substituted dibenzothiazepine derivative according to claim 1 or 2, wherein, The structure of the N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound is as follows: ; The structure of the ester-substituted dibenzothiazepine derivative is as follows: ; The substituent R is alkyl with 1-4 carbon atoms; 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 and phenyl; halogen is one or more than two of F, cl and Br.
  4. 4. The method for synthesizing the ester-substituted dibenzothiazepine 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 (440-445 nm), 1-18W green light (526-531 nm) and 1-18W red light (700-705 nm).
  5. 5. The method for synthesizing the ester-substituted dibenzothiazepine 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 dimethyl sulfoxide, and 0.5-3 mL solvent is added to each 0.1 mmolN- (2-ethynylaryl) -N-alkylbenzene sulfonamide compound.
  6. 6. The method for synthesizing the ester-substituted dibenzothiazepine derivative according to claim 1 or 2, wherein the base is any one or more of sodium carbonate, potassium carbonate, cesium carbonate, 1, 4-diazabicyclo [2.2.2] octane (DABCO) and 1, 8-diazabicyclo [5,4,0] undecene-7 (DBU), and the molar concentration of the base in a solvent is 0.01-0.2M.
  7. 7. The method for synthesizing the ester-substituted dibenzothiazepine derivative according to claim 1 or 2, wherein formate is any one or more of sodium formate, potassium formate and cesium formate, and the molar concentration of formate in a solvent is 0.5-10M.
  8. 8. The method of synthesizing an ester-substituted dibenzothiazepine derivative according to claim 1 or 2 wherein CO 2 (air present, oxygen present at 21%) is used in a molar ratio of 1: 1 bar to 2: 2 bar.
  9. 9. The method for synthesizing the ester-substituted dibenzothiazepine derivative according to claim 1 or 2, wherein the reaction is carried out in the presence of CO 2 (air, oxygen accounting for 21%) for 18-30 hours at 25-35 o ℃.

Description

Ester group substitution dibenzothio of (C) Synthesis method of azepine derivative Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an ester-substituted dibenzothiazepine 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 tenecteplatine (TIANEPTINE) is a medicament for treating mental disorder and has good antidepressant effect. The construction of such frameworks has received considerable attention due to their unique structural features and broad spectrum of biological significance. 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. In recent years, due to the rapid development of the free radical chemistry field, a plurality of chemical bonds are constructed in one step with excellent atom economy in a green and mild catalytic system by utilizing a free radical-mediated serial cyclization strategy, so that the efficient synthesis of heterocyclic compounds with complex structures is realized, and the method gradually becomes a popular research field, and solves a plurality of problems in the traditional method. In view of this, in the past few years, a number of subject groups at home and abroad have utilized the strategy of radical tandem cyclization to achieve a number of very distinctive methods of synthesis of benzazepine backbone derivatives. In addition, carboxylic acid esters are important structural motifs that are widely present in biologically active compounds, natural products, agrochemicals, fragrances and flavors. They can also be used as universal pro-drug carriers for carboxyl and hydroxyl groups in pharmaceutical chemistry. At present, there is no related synthesis method for the dibenzothiazepine derivative substituted by ester groups, and the compound containing the ester can improve the modification and transformation of the dibenzothiazepine skeleton of the medicine. Therefore, the development of a synthetic method of the ester-substituted dibenzothiazepine derivative which has the advantages of readily available raw materials, simple and convenient operation, mild reaction conditions and environmental protection is urgently needed to be solved by the technicians in the field. Disclosure of Invention In view of the above, the invention discloses a synthesis method of an ester-substituted dibenzothiazepine derivative, which is an ester-substituted dibenzothiazepine derivative prepared by using an N- (2-ethynylaryl) -N-alkyl benzene sulfonamide compound which is easily available in raw materials, simple and convenient to operate, mild in reaction condition, environment-friendly, and cheap and easily available as a substrate, DBACO as a base, sodium formate as a C1 source and dimethyl sulfoxide as a solvent, and performing intramolecular serial aryl carboxylation cyclization reaction. In order to achieve the above purpose, the present invention adopts the following technical scheme: The first technical purpose of the invention is to provide a synthesis method of an ester-substituted dibenzothiazepine derivative, which comprises the following steps: Under the condition of visible light, the N- (2-ethynyl aryl) -N-alkyl benzene sulfonamide compound (I) is subjected to intramolecular serial aryl carboxylation cyclization reaction (reaction formula 1) at room temperature, and after the reaction is finished, the product is separated and characterized by a conventional separation and purification method, so that the corresponding ester-substituted dibenzothiazepine derivative (II) is obtained. Reaction 1 The invention discloses a method for preparing an ester group substituted dibenzothiazepine 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 induction and intramolecular serial aryl carboxylation cyclization reaction at room temperature. Wherein the structure of the ester group substituted dibenzothiazepine derivative (II) is as follows: ; The substituent R is alkyl with 1-4 carbon atoms; Substituent R 1 is H or halogen; the substituent R 2 is alkyl with 1-4 carbon atoms and cyc