4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol_Industrial additive

[Background and Overview]^[1]

Pyrethroid insecticides were put on the market in the 1990s and caused a sensation at the time due to their excellent properties. In the past four decades, pyrethroid insecticides have developed rapidly and still occupy a very important position in the pesticide market. Calcium-zinc heat stabilizers have now become the next most popular pesticide after organochlorines, organophosphorus, and amino acids. Formic ester insecticides are another series of insecticides, accounting for more than 70% of the active ingredients used in sanitary insecticides. As household insecticides, they are widely used to control mosquitoes, flies, mantises, and livestock parasites. Pyrethroids are an important class of synthetic insecticides, including allethrin, tefluthrin, propargylthrin, pentythrin, metofluthrin and many other varieties, with high efficiency, broad spectrum, It has the advantages of low toxicity, biodegradability, and environmental friendliness. There are nearly 3 varieties of pyrethroids commercialized so far, accounting for more than 19% of the world’s insecticide sales. Pyrethroids are mainly used in agriculture, such as controlling crop pests, and their usage accounts for the largest share of total sales. It is predicted that the domestic demand for hygienic pyrethroids will also be in a golden cycle of accelerated growth in the next year. At present, the problem of pyrethroid resistance has restricted the further development of this class of insecticides and has attracted widespread attention. Methoxyfluthrin synthesized in recent years is a new type of pyrethroid. It is a new milestone in the research and development of pyrethroid insecticides and promotes the further development of pyrethroid synthesis technology. It can be seen from the development history of pyrethrins that it has gone through the process of extracting and isolating active ingredients from natural products with insecticidal activity to identifying the structure, then synthesizing its analogs, studying the relationship between chemical structure and biological activity, and exploring the synthesis of active ingredients that are better than natural ones. Better simulation compounds and a series of biomimetic pesticide research processes.

4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol, English name 4-Methoxymethyl-2,3,5,6-tetraFluoro benzenemethanol, Chinese alias 4-methoxymethyl-2 , 3,5,6-tetrafluorobenzyl alcohol, 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol, tetrafluoro-p-methoxymethylbenzyl alcohol, 4-methoxymethyl Base-2,3,5,6-tetrafluorobenzyl alcohol, 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl alcohol, CAS number is 83282-91-1, molecular formula is C₉H₈F₄O₂, molecular weight 224.15200; PSA: 29.46000; LogP: 1.88170. Density 1.407, boiling point 214ºC, flash point 107ºC, refractive index 1.464. 4-Methoxy-2,3,5,6-tetrafluorobenzyl alcohol can be used as a synthetic insecticide metofluthrin, a powerful of new synthetic pyrethroids with high vapor activity against mosquitoes.

[Structure]^[1]

【Synthesis】^[3]

Method 1: Use 1,2,4,5-tetrafluorobenzene as the starting material to react to generate 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol:

Method 2: Production of 4-methoxymethyl-2,3,5,6- by selective methylation of 2,3,5,6-tetrafluoro-1,4-benzenedimethanol Tetrafluorobenzyl alcohol, the specific steps are as follows:

1) Reaction of 2,3,5,6-tetrafluoro-1,4-benzenedimethanol with an inorganic base in water and a water-immiscible organic solvent selected from hydrocarbons and ethers,

2) Add dimethyl sulfate and optional water-immiscible organic solvent to the reaction mixture to obtain the target compound 4-methoxy-2,3,5,6-tetrafluorobenzyl alcohol. In 2), the reaction must be carried out in water and a water-immiscible organic solvent selected from hydrocarbons and ethers. Examples of water-immiscible organic solvents include aromatic hydrocarbons such as toluene and xylene, aliphatic hydrocarbons such as hexane and heptane and others such as tert-butyl methyl ether.

[Application]

4-Methoxy-2,3,5,6-tetrafluorobenzyl alcohol is a pesticide intermediate that can be used to synthesize the pesticide metofluthrin. Examples of its application are as follows:

1. Quotation of propane carboxylic acid or 2,2-dimethyl-3-(1-propenyl) cyclopropane acid chloride based on 2,2-dimethyl-3-(1-propenyl) cyclopvc resin powder Methoxyfluthrin was synthesized in tetrahydrofuran with 4-methoxy-2,3,5,6-tetrafluorobenzyl alcohol as raw material, pyridine as acid binding agent, and the yield was 88%, and it was discovered that The compound has extremely high mosquito-killing properties, but the price of pyridine is high, and column chromatography is used in the post-processing, which makes the operation complex and the production cost high. The reaction process is as follows:

2. Metofluthrin was synthesized through transesterification reaction. The reaction process is as follows:

3. Using the first chrysanthemic acid as raw material, in order to avoid the first chrysanthemic acid being oxidized to generate peroxyacid and reducing the yield during ozone oxidation, the carboxyl group is first protected by methyl esterification, and the first chrysanthemic acid methyl ester undergoes ozone After oxidation, methyl aldehyde is generated, which is converted into methyl metachrysanthemate through Witting reaction, and then hydrolyzed to generate metachrysanthemum acid. Finally, metachrysanthemum acid is acyl chlorinated to generate metachrysanthemum acid chloride, which is then combined with 4- The esterification reaction of methoxy-2,3,5,6-tetrafluorobenzyl alcohol produces metofluthrin. The reaction process is as follows:

[References]

[1] Cao Changhui. Research on the synthesis of metofluthrin[D]. Zhejiang University, 2011.

[3] Hirose Taro; SendaZai .Production method of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol. CN00132454.3, application date 2000-11-21