CN-122010675-A - Method for synthesizing 1-bromo-2-styrene derivative by metal bromide catalysis

CN122010675ACN 122010675 ACN122010675 ACN 122010675ACN-122010675-A

Abstract

The invention discloses a method for synthesizing 1-bromo-2-styrene derivatives by metal bromide catalysis, which takes styryl sulfoxide compounds as substrates, takes metal bromide as a bromine source, and prepares brominated olefin derivatives efficiently by dissolving the metal bromide in a solvent and directly reacting at a certain temperature. Compared with the prior synthesis method, the method has the advantages that the reaction only needs one step, peroxide, strong alkali, transition metal or ligand and the like are not required to be used as catalysts or bromine sources, and the operation is simpler and safer. The method has good substrate applicability, and can be compatible with monosubstituted or polysubstituted phenyl alkenyl sulfoxide compounds containing electron withdrawing or electron donating groups. In particular, the strategy of synthesizing bromoolefin by using metal bromide such as CuBr2 and the like as a catalyst is not reported before, and under the optimized condition, the product separation yield can reach 92 percent at the highest.

Inventors

WANG MIN
YAN JIANWEI
WANG AIFANG
Tong Sudan
CHEN YANLING
ZENG YUTING

Assignees

杭州师范大学

Dates

Publication Date: 20260512
Application Date: 20251223

Claims (7)

1. A method for the catalytic synthesis of 1-bromo-2-styrene derivatives by metal bromide, characterized in that it comprises the following steps: the preparation method comprises the steps of taking a styryl sulfoxide compound as a substrate, taking a metal bromide as a bromine source, mixing and dissolving in a solvent, and preparing the 1-bromo-2-styrene derivative shown in a formula (1) at a certain temperature; The synthetic route is as follows: Wherein R is one of hydrogen, methyl, tertiary butyl, methoxy, benzyloxy, halogen, phenyl and naphthyl, and n is 1, 2 or 3.
2. The method of claim 1, wherein the molar ratio of the styryl sulfoxide compound to the metal bromide is 1:0.5-2.5.
3. The method of claim 1, wherein the metal bromide is one or more of copper bromide, iron bromide, manganese bromide, zinc bromide, magnesium bromide, lithium bromide, nickel bromide, cobalt bromide, cuprous bromide, ferrous bromide.
4. The method of claim 1, wherein the reaction temperature is 25-120 ℃.
5. The method of claim 1, wherein the reaction time is 3 to 48 hours.
6. The method according to claim 1, characterized in that the reaction further comprises a post-treatment, in particular: After the reaction, the system was cooled to room temperature, quenched with water, extracted with ethyl acetate, washed with water and saturated brine, and the obtained organic layer was dried, concentrated and purified by column chromatography to give a pure 1-bromo-2-styrene derivative.
7. The method of claim 1, wherein the reaction solvent is one or more of toluene, acetonitrile, acetone, methylene chloride, 1, 2-dichloroethane, tetrahydrofuran, absolute ethanol, isopropanol, 1, 4-dioxane, N-hexane, dimethyl sulfoxide, and N, N-dimethylformamide.

Description

Method for synthesizing 1-bromo-2-styrene derivative by metal bromide catalysis Technical Field The invention belongs to the technical field of synthesis research of chemical synthesis and high-activity biomedical intermediates, and particularly relates to a method for synthesizing a 1-bromo-2-styrene derivative by metal bromide catalysis. Background Halogenated olefins are a key intermediate in organic synthesis, and are widely applied due to high reactivity and conversion flexibility, for example, 1-bromo-2-styrene and derivatives thereof have been continuously paid attention to by researchers in recent years due to their unique reactivity and various functional potentials. The compound plays an important role in a plurality of fields such as medicine synthesis, agricultural chemicals, functional materials, liquid crystal molecule construction and the like. In the field of medicinal chemistry, the 1-bromo-2-styrene derivative can introduce different pharmacophores (such as amino, hydroxyl, halogen and the like) through structural modification, so that the biological activity and selectivity of the derivative are optimized, potential pharmacological activities of inhibiting tumor cell proliferation, regulating inflammatory reaction and the like are shown, and a valuable candidate skeleton is provided for research and development of new drugs. In the aspect of material science, the 1-bromo-2-styrene can be used as a functional monomer to participate in polymerization reaction, or the functional materials such as polymer, ion exchange resin, high molecular catalyst carrier and the like with stimulus response characteristics can be prepared through subsequent functionalization. In conclusion, 1-bromo-2-styrene and its derivatives have become important bridges for organic synthesis and leading-edge application research of connection bases by virtue of structural adjustability and reaction diversity, and have wide development prospects. In recent years, the synthetic method of bromoolefin is developed rapidly, and is continuously focused by chemists at home and abroad, and related research reports are increasing year by year. Although the reported synthetic routes exhibit some broad applicability to substrates, there are still a number of methodologically limitations. For example, nitin D Arote reports a method for synthesizing bromoolefins efficiently at room temperature for 0.5 hours using DMP/TEAB as a catalyst system and dichloroethane as a solvent. Although the reaction has the advantages of short time and high yield, the substrate source is difficult, DMP needs to be specially prepared, and TEAB has strong irritation to human body, so that the potential of the method in substrate expansion and practical application is limited. Andr BeB Charette developed a process for the conversion of benzyl bromide to bromoolefins in a one-pot process at-78℃using CH 2Br2 as bromine source and NaHMDS as base. The method avoids the use of a transition metal catalyst, has easily available substrate and good functional group compatibility, but has low reaction temperature and long reaction time, and needs to be further optimized. With the development of technology, some stereoselective synthesis methods for 1, 2-cis dibromoolefins are realized through an Ag/CH 3SO3 H co-catalytic system. However, the reaction uses terminal alkyne as a raw material and NBS as a bromine source, and has limited substrate applicability. In summary, the existing bromoolefin synthesis method generally depends on reagents such as peroxide, strong alkali, transition metal or special ligand, and the like, and is often accompanied with the problems of heavy environmental burden, large substrate limitation, complicated steps, multiple side reactions, harsh conditions and the like. Therefore, it is especially necessary to develop a simple and efficient new method for synthesizing bromoolefin. Disclosure of Invention The invention aims to provide a novel synthetic method of bromoolefin derivatives, aiming at the defects of the existing synthetic route. The method takes styryl sulfoxide compounds as substrates, metal bromide as bromine source, and the preparation of bromoolefin derivatives is efficiently and rapidly realized under mild conditions. The strategy has the remarkable advantages that the traditional necessary catalysts or bromine sources such as peroxide, strong alkali, transition metal or additional ligand are completely avoided, so that the reaction system is simplified, and the practicability and the environmental compatibility of the process are improved. Specifically, the method is to directly convert the styryl sulfoxide compound into the target bromoolefin compound in the presence of metal bromide. In order to achieve the above purpose, the present invention adopts the following technical scheme: The preparation method comprises the steps of taking a styryl sulfoxide compound as a substrate, taking a metal bromide as a bromine source, m