CN-121974879-A - Synthesis method of imino spiro benzofuran compound

CN121974879ACN 121974879 ACN121974879 ACN 121974879ACN-121974879-A

Abstract

The invention belongs to the technical field of synthesis of medical intermediates, and particularly relates to a synthesis method of an imino spiro benzofuran compound. According to the invention, an iminobenzofuran derivative and MBH carbonic ester undergo [3+2] cycloaddition reaction under the action of a phosphine catalyst under the heating condition to obtain an iminospiro benzofuran compound. The method has the advantages of simple and efficient synthetic route and mild reaction conditions, and the synthesized iminospiro benzofuran compound has excellent antibacterial activity on gram-positive bacteria including staphylococcus aureus and bacillus subtilis.

Inventors

LIU XIUZHENG
LIU WANXING
CHEN WENWEN
XIE LEI
WU LINGANG
LIU WEIYE

Assignees

聊城金歌合成材料有限公司

Dates

Publication Date: 20260505
Application Date: 20260128
Priority Date: 20250221

Claims (5)

1. The synthesis method of the iminospiro benzofuran compound comprises the following steps of carrying out [3+2] cycloaddition reaction on an iminobenzofuran derivative and MBH carbonate under the action of a phosphine catalyst under the heating condition to obtain the iminospiro benzofuran compound.
2. The method according to claim 1, wherein the temperature is 30-120 ℃ and the time is 6-24 hours in the synthesis reaction of the iminospiro benzofuran compound.
3. The method of claim 1, wherein in the synthesis of the iminospirobenzofuran compound, the phosphine catalyst is one of diphenylcyclohexylphosphine, ethyldiphenylphosphine, and tri-p-tolylphosphine.
4. The method of claim 1, wherein the solvent in the synthesis of the iminospirobenzofuran compound is one of toluene, benzene, fluorobenzene, and bromobenzene.
5. The method according to claim 1, wherein the iminobenzofuran derivative, MBH carbonate and phosphine catalyst are present in a molar ratio of 1 (1-1.5): 0.05-0.3 in the synthesis of iminospiro benzofuran compounds.

Description

Synthesis method of imino spiro benzofuran compound Technical Field The invention belongs to the technical field of synthesis of medical intermediates, and particularly relates to a synthesis method of an imino spiro benzofuran compound. Background The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art. The spiro compounds have unique three-dimensional structures and rigid frameworks, which can significantly enhance their interactions with receptor binding sites, thereby consolidating their importance in the drug discovery process. Spiro benzofurans are widely found in various natural products, bioactive molecules and drugs as a common building block. As shown in figure 1, laurentristich-4-ol, which is a natural product and a drug molecule containing a spiro benzofuran structure, has been established as an anticancer agent, spiroapplanatumine K and Q isolated from ganoderma lucidum have inhibitory activity on JAK3 kinase, involucratustone B collected from rhizomes of Stahlianthus involucratus have excellent anticancer effect in cytotoxicity detection of U-2OS and SMMC-7721, and Ganoleucin D has been found to have good inhibitory effect on HMG-CoA reductase. However, the existing methods for synthesizing these complex compounds have low efficiency and selectivity and severe reaction conditions, so that development of a highly efficient and concise method for synthesizing such spiro compounds is needed. Disclosure of Invention Based on the wide application of spiro benzofuran compounds in pharmaceutical chemistry, and in order to solve the defects of the prior art, the invention aims to provide a synthesis method of imino spiro benzofuran compounds. The invention provides a novel method based on phosphine-catalyzed [3+2] cycloaddition reaction, through which imino spiro benzofuran compounds can be efficiently synthesized. The method uses Morita-Baylis-Hillman (MBH) carbonic ester and an iminobenzofuran derivative to react under the catalysis of a phosphine catalyst, so that the iminospiro benzofuran compound can be obtained under mild reaction conditions. In order to achieve the above object, the present invention is realized by the following technical scheme: a method for synthesizing an iminospiro benzofuran compound, comprising the following: Under the heating condition, the imino benzofuran derivative and MBH carbonic ester undergo [3+2] cycloaddition reaction under the action of a phosphine catalyst to obtain an imino spiro benzofuran compound, wherein the reaction equation is as follows: Preferably, in the synthesis reaction of the iminospiro benzofuran compound, the temperature is 30-120 ℃ and the time is 6-24 hours. Preferably, in the synthesis reaction of the iminospiro benzofuran compound, the phosphine catalyst is at least one of diphenyl cyclohexyl phosphine, ethyl diphenyl phosphine and tri-p-tolyl phosphine. Preferably, in the synthesis reaction of the iminospiro benzofuran compound, the solvent comprises at least one of toluene, benzene, fluorobenzene and bromobenzene. Preferably, in the synthesis reaction of the iminospiro benzofuran compound, the molar ratio of the iminobenzofuran derivative to the MBH carbonate to the phosphine catalyst is 1 (1-1.5) (0.05-0.3). The beneficial effects obtained by one or more of the technical schemes of the invention are as follows: According to the invention, an iminobenzofuran derivative and MBH carbonic ester undergo [3+2] cycloaddition reaction under the heating condition and under the action of a phosphine catalyst to obtain an iminospiro benzofuran compound. The method has the advantages of simple and efficient synthetic route and mild reaction conditions, and the synthesized iminospiro benzofuran compound has excellent antibacterial activity on gram-positive bacteria including staphylococcus aureus and bacillus subtilis. Drawings The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention. FIG. 1 shows natural products and drug molecules containing spiro benzofuran structures. FIG. 2 nuclear magnetic resonance spectrum of iminospiro benzofuran compounds Detailed Description In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail with reference to specific embodiments. Example 1: 50 mL toluene, iminobenzofuran derivatives (3.75 g,10 mmol) and MBH carbonate (4.5 g,12 mmol) were added to the reaction flask under nitrogen protection, diphenyl cyclohexylphosphine (0.54