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CN-121991000-A - Synthesis method of oxazole derivative

CN121991000ACN 121991000 ACN121991000 ACN 121991000ACN-121991000-A

Abstract

The invention discloses a synthetic method of an oxazole derivative, and belongs to the technical field of chemical synthesis. The oxazole derivative is synthesized by a ketone ester compound and thiourea in one pot, the required raw materials are cheap and easy to obtain, the experimental operation is simple, the reaction condition is mild, metal catalysts and other reagents are not needed, the defects of the metal catalysis synthesis method are avoided, for example, the catalyst is high in price, the reaction synthesis route is multiple in steps, the reaction rate is low, the intermediate is unstable, the yield is low, and the like, most of synthesis steps of the metal-free catalysis synthesis method are bypassed, and a simple, efficient, green and environment-friendly way for synthesizing the oxazole derivative is developed. Under mild conditions, the ketoester substrates with different substituents have strong compatibility, and a new green synthesis way is provided for synthesizing the substituted oxazole.

Inventors

  • CHEN XIULING
  • LI WENSHOU

Assignees

  • 广东石油化工学院

Dates

Publication Date
20260508
Application Date
20260123

Claims (10)

  1. 1. An oxazole derivative is characterized by being synthesized by a one-pot reaction of a ketoester compound and thiourea.
  2. 2. The oxazole derivative according to claim 1, wherein the substituted oxazole compound has the structural formula: The structural general formula of the ketoester compound is as follows: ; Wherein R 1 is one of-H, methyl, methoxy, halogen, hydroxyl, -NO 2 、-CF 3 , phenyl and thienyl, and R 2 is one of-H, methyl, ethyl, isopropyl, tertiary butyl, methoxy, phenyl, methyl substituted phenyl, nitro substituted phenyl, halogen substituted phenyl, naphthyl and indolyl.
  3. 3. The oxazole derivative of claim 1 wherein the structural formula of the oxazole derivative comprises: 。
  4. 4. The oxazole derivative according to claim 1, characterized in that the ketoester compound is synthesized as follows: 。
  5. 5. an oxazole derivative according to any of claims 1 to 3, characterized in that the oxazole derivative is synthesised as follows: 。
  6. 6. a process for the preparation of an oxazole derivative as claimed in any of claims 1 to 3 comprising the steps of: The ketone ester compound and thiourea are added into a solvent, and the mixture is heated and reacted in a schlenk reaction tube in nitrogen atmosphere, and then the oxazole derivative is obtained through post-treatment.
  7. 7. The method of claim 6, wherein the molar ratio of the ketoester compound to the thiourea is 1:2-3.
  8. 8. The method according to claim 6, wherein the solvent is one of 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, and ethyl acetate.
  9. 9. The method of claim 6, wherein the heating reaction temperature is 150-180deg.C.
  10. 10. The method according to claim 9, wherein the heating reaction temperature is 160 ℃.

Description

Synthesis method of oxazole derivative Technical Field The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of an oxazole derivative. Background Oxazole is a critical five-membered heterocyclic compound, mainly in natural products and bioactive molecules. By virtue of the unique five-membered ring structure containing nitrogen and oxygen, the oxazole has become a core component in organic synthesis, medicine research and development and material science, and particularly in the field of medicine, the oxazole derivative has attracted great interest due to various biological characteristics. Many compounds containing oxazole structures have been developed as therapeutic agents for the treatment of various diseases such as anti-inflammatory, antibacterial, antidiabetic, antiviral, anticancer and antitubercular. In addition, oxazole plays an important role in polymer materials, fluorescent dyes, and as a catalyst ligand, and various methods for synthesizing oxazole have been developed due to the wide application of oxazole. The synthesis of the oxazole compound is mainly obtained by synthesizing metal catalysts such as Pd, ru, rh, cu, co, ag and the like, but the frequent use of the oxazole compound possibly causes environmental and health hazards due to the toxicity of the metal and the complex thereof, and the residue of trace transition metal in the synthesis of the medicine has certain hazard to the medicine property and human health. In addition, the synthesis method using metal catalysis has certain defects, such as complicated synthesis steps, expensive catalyst, unstable intermediates, low yield, troublesome post-treatment and the like. Therefore, it is important to explore a simple, efficient, green and environment-friendly way for synthesizing the oxazole compounds. Disclosure of Invention The invention mainly aims to provide a method for synthesizing an oxazole derivative under the condition of no metal catalysis. In order to achieve the aim, the invention provides an oxazole derivative, which is synthesized by a one-pot reaction of a ketoester compound and thiourea. The structural general formula of the substituted oxazole compound is as follows:; the structural general formula of the ketoester compound is as follows: ; Wherein R 1 is one of-H, methyl, methoxy, halogen, hydroxyl, -NO 2、-CF3, phenyl and thienyl, and R 2 is one of-H, methyl, isopropyl, tertiary butyl, methoxy, phenyl, methyl substituted phenyl, nitro substituted phenyl, halogen substituted phenyl, naphthyl and indolyl. Preferably, the structural formula of the oxazole derivative includes: 。 Preferably, the synthetic route of the oxazole derivative is as follows: 。 the invention provides a synthesis method of the oxazole derivative, which comprises the following steps: The ketone ester compound and thiourea are added into a solvent, and the mixture is heated and reacted in a schlenk reaction tube in nitrogen atmosphere, and then the oxazole derivative is obtained through post-treatment. The synthetic route of the ketoester compound is as follows: the molar ratio of the ketone ester compound to the thiourea is 1:2-3, the solvent is one of 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide and ethyl acetate, and more preferably, the solvent is 1, 4-dioxane. The heating reaction temperature is 150-180 ℃, and more preferably, the heating reaction temperature is 160 ℃. Compared with the prior art, the invention has the beneficial effects that: The invention provides a method for synthesizing an oxazole derivative under a metal-free catalysis condition, which comprises the steps of synthesizing the oxazole derivative by a ketone ester compound and thiourea one-pot method, has the advantages of cheap and easily available raw materials, simple experimental operation, mild reaction conditions, no need of other additional additives and the like, avoids the defects of high price of a catalyst, troublesome post-treatment and the like existing in the metal-catalyzed synthesis method, and develops a simple, efficient and environment-friendly way for synthesizing the oxazole derivative. Under mild conditions, the ketoesters with different substituents have strong applicability to the reaction, and a new green synthesis way is provided for synthesizing the substituted oxazole. Detailed Description For the sake of brevity, the articles used in the examples below are commercially available products unless specifically stated otherwise, and the methods used are conventional methods unless specifically stated otherwise, and the reagents used are commercial reagents unless specifically stated otherwise and do not require purification treatment. The instrument characterization includes that the used instruments are liquid chromatography-mass spectrometry (LC-MS) islands 804 and 5975, a Gas Chromatograph (GC) 7820A and a nuclear magnetic instrument model Bruker-AV (400 and 100 MHz). 1 H NMR and 13 CNMR, r