CN-121990875-A - Synthetic method of chlorohydrin compound

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a chlorohydrin compound. The method comprises the steps of adding acetonitrile solution of a compound 1 into 1, 2-tetrachloroethane under nitrogen atmosphere, then adding tert-butyl hydroperoxide, alkali and trimethylcyano silane, stirring at room temperature, heating and stirring for reaction, removing a solvent under reduced pressure after the reaction is completed, and then carrying out silica gel column chromatography on a crude product to obtain a chlorohydrin compound. The synthesis method of the invention effectively improves the yield of chlorohydrin compounds, improves the atom economy, efficiently utilizes the raw materials and reduces the emission of waste by regulating and controlling the reaction conditions and optimizing the raw material selection.

Inventors

• ZHANG JIANTAO
• SU RENHUA
• JIANG YANFU
• LIU WEIBING

Assignees

• 广东石油化工学院

Dates

Publication Date

20260508

Application Date

20260128

Claims (9)

1. 1. The synthesis method of the chlorohydrin compound is characterized by comprising the following steps of: Adding acetonitrile solution of a compound 1 into 1, 2-tetrachloroethane, then adding tert-butyl hydroperoxide, alkali and trimethylcyano silane, stirring at room temperature, heating and stirring for reaction, removing a solvent under reduced pressure after the reaction is completed, and then carrying out silica gel column chromatography on the crude product to obtain a product, namely the chlorohydrin compound.
2. 2. The method for synthesizing chlorohydrin compound according to claim 1, wherein the compound 1 is any one of the following structural formulas: 。
3. 3. The method for synthesizing a chlorohydrin compound according to claim 1, wherein the molar ratio of the compound 1 to t-butyl hydroperoxide to the base to the trimethylcyano silane is 1:2-6:4:3-5.
4. 4. The method for synthesizing chlorohydrin according to claim 3, wherein the molar ratio of the compound 1, t-butyl hydroperoxide, base and trimethylcyano silane is 1:6:4:4.
5. 5. The method for synthesizing chlorohydrin according to claim 1, wherein the base is any one of triethylamine, diethylamine, diisopropylethylamine, DBU, and triethylenediamine.
6. 6. The method for synthesizing chlorohydrin according to claim 5, wherein the base is triethylamine or diethylamine.
7. 7. The method for synthesizing chlorohydrin according to claim 1, wherein the tert-butyl hydroperoxide is a 70% aqueous solution.
8. 8. The method for synthesizing chlorohydrin according to claim 1, wherein the temperature of the heating and stirring reaction is 60 ℃.
9. 9. The method for synthesizing a chlorohydrin compound according to claim 1, wherein the heating and stirring reaction time is 24 hours.

Description

Synthetic method of chlorohydrin compound Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a chlorohydrin compound. Background Chlorohydrin is taken as an organic compound containing hydroxyl (-OH) and chlorine (-Cl) in the molecular structure, and plays a very important role in the chemical field. The unique structure of the novel composite material endows the novel composite material with various chemical properties, so that the novel composite material becomes a key raw material in a plurality of fields such as medicine, agriculture, synthetic methodologies and the like. In the pharmaceutical field, chlorohydrins play an essential role. The synthesis of many drugs relies on chlorohydrins as key intermediates, for example in the preparation of the non-steroidal anti-inflammatory drug fenoprofen calcium, which is converted to nitrile compounds by nucleophilic substitution reactions, thereby building up the drug core skeleton. In addition, chlorohydrin derivatives such as alpha-chlorohydrin are also used for preparing rodenticides, and the aim of controlling rodenticides is achieved by destroying the coagulation mechanism and endocrine system of mice. Although the toxicity is higher, the application is strictly regulated, but in the fields of agriculture and public health, the method is still an effective biological control means, and the importance of chlorohydrin in the aspects of protecting human health and environmental safety is reflected. In the agricultural field, chlorohydrins are also widely used. In addition to being a core component of rodenticides, chlorohydrins also play an important role in the synthesis of pesticides. With the increasing demand of agriculture for efficient and low-toxicity pesticides, chlorohydrin is used as an intermediate to provide powerful support for the development of novel pesticides. For example, certain chlorohydrin derivatives are useful for the synthesis of pesticides with specific biological activity that are capable of targeted pest control while reducing environmental and non-target organisms. The application of chlorohydrin not only improves the efficiency of agricultural production, but also promotes the sustainable development of agriculture. At the level of synthetic methodology, the preparation of chlorohydrins is a paradigm of classical organic synthesis, and its research has driven the development of green chemistry. The chloroethanol method which takes ethylene as raw material generates chloroethanol through the addition reaction of chlorine and water, and then the chloroethanol is closed loop through alkali treatment to form ethylene oxide, and the technology has lower atom utilization rate, but provides historic reference for the modern catalytic oxidation method (such as silver-catalyzed ethylene direct oxidation). The molecular weight calculation of chlorohydrins is based on the combination of the alcohol skeleton and chlorine atoms, and is realized through atomic mass accumulation, and the basic skill is important to understand the physical and chemical properties of the chlorohydrins. In addition, the synthesis of chlorohydrins involves green chemical concepts such as atomic economy, which underscores the importance of efficient utilization of raw materials and reduction of waste emissions. In summary, chlorohydrin is not only a catalyst for innovations of medicine and agriculture, but also a reduction of the progress of synthetic chemistry, the importance of which spans laboratory researches to industrial production, and the progress of science is continuously promoted, however, how to synthesize chlorohydrin compounds by regulating reaction conditions and optimizing raw material selection so as to improve the yield and the atomic utilization rate thereof and reduce the emission of waste is still a technical problem to be solved urgently. ‌ A Disclosure of Invention In order to overcome the defects in the prior art, the invention provides a method for synthesizing chlorohydrin compounds. The method comprises the steps of adding acetonitrile solution of a compound 1 into 1, 2-tetrachloroethane under nitrogen atmosphere, then adding tert-butyl hydroperoxide, alkali and trimethylcyano silane, stirring at room temperature, heating and stirring for reaction, removing a solvent under reduced pressure after the reaction is completed, and then carrying out silica gel column chromatography on a crude product to obtain a chlorohydrin compound. The synthesis method of the invention effectively improves the yield of chlorohydrin compounds, improves the atom economy, efficiently utilizes the raw materials and reduces the emission of waste by regulating and controlling the reaction conditions and optimizing the raw material selection. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: the invention provides a method for synthesizi