Background and overview[1][2]
1-Chloromethyl-3-trifluoromethylbenzene is a pesticide and pharmaceutical intermediate, and there are some reports on the public technology at home and abroad. For example, m-trifluoromethylbenzene chloride is synthesized from trifluorotoluene, chloromethyl methyl ether and chlorosulfonic acid as raw materials. In this method, the raw material chloromethyl methyl ether is a strong carcinogen and chlorosulfonic acid is a highly corrosive and dangerous product, so it is not suitable for large-scale production. Meta-xylene can also be used as raw material, first chlorinated to synthesize а,а,а-trichloro m-xylene; then а,а,а-trichloro m-xylene can be reacted with hexachloroethane in a tetrachloroethylene solvent to synthesize а,а,а, à-Tetrachlorom-xylene is then fluorinated with hydrogen fluoride gas to synthesize m-trifluoromethyl chloride. This process contains a lot of toxic and harmful raw materials and solvents, which can easily cause serious environmental harm and is not conducive to large-scale production. In addition, there are reports on the synthesis of m-trifluoromethylbenzene chloride using trifluorotoluene, chlorosulfonic acid, paraformaldehyde raw materials, and inorganic acids (such as sulfuric acid) as catalysts. The raw material of this method, chlorosulfonic acid, is a highly corrosive and dangerous product, and the reaction process is difficult to control. At the same time, a large amount of waste sulfuric acid and fluorine-containing by-products will be produced. The reaction yield is low, and it is not suitable for the current requirements for safe and clean production.
Apply[3-4]
1-Chloromethyl-3-trifluoromethylbenzene is a pesticide and pharmaceutical intermediate. For example, it can be used to prepare m-trifluoromethylbenzeneacetonitrile. The specific steps are: convert 3-trifluoromethyl chloride into After benzyl is mixed with the phase transfer catalyst, the temperature is raised to 40~80°C. The sodium cyanide aqueous solution is added dropwise to the above mixed solution. The temperature is maintained at 40~80°C until the reaction is complete to obtain 3-trifluoromethyl. phenylacetonitrile.
1-Chloromethyl-3-trifluoromethylbenzene can also be used to prepare m-trifluoromethylbenzoic acid. m-Trifluoromethylbenzoic acid is a chemical intermediate for medicines and pesticides, and is widely used in medicine, pesticides and other fields. The preparation method is to use 1-chloromethyl-3-trifluoromethylbenzene as raw material, perform an oxidation reaction with nitric acid with a concentration of 60 to 70% by weight at 100 to 110°C, and then cool it. , filter to obtain m-trifluoromethylbenzoic acid product. The specific steps are as follows: reflux 194.5 grams of 1-chloromethyl-3-trifluoromethylbenzene and 700 grams of 65% nitric acid at 100-108°C for 20 hours, cool to room temperature, filter and dry. , 173 grams of m-trifluoromethylbenzoic acid was obtained, melting point: 100～103℃, yield: 91%.
In addition, 1-chloromethyl-3-trifluoromethylbenzene can also be used to prepare m-trifluoromethylbenzyl alcohol, which is a pharmaceutical and pesticide chemical intermediate. It has a very wide range of applications in other fields. The specific steps are: add 200g (2.44ml) of sodium acetate and 250ml of acetic acid to a 1L three-necked flask equipped with a stirrer, reflux condenser and thermometer, and heat to 80℃, gradually dripping Add 292 grams (1.5 ml) of 1-chloromethyl-3-trifluoromethylbenzene. After the addition is completed, continue to raise the temperature to 120°C and reflux for 8 hours until the reaction is complete. Acetic acid is recovered by distillation under reduced pressure. Then add 500ml of water layer, wash the organic matter with 4*100ml of water, and obtain 312 grams of organic matter, with a yield of 95.4%. The product is very pure and does not need purification. It can be directly used for the next step of hydrolysis reaction; install a stirrer and reflux. Add 218.12g (1.0m.) of the ester prepared above and 450g of 15% alkali solution (2.25ml) into the 1L three-necked flask of the condenser and thermometer. The mixture was refluxed for 3 hours, and plate chromatography was performed to check that the reaction was complete. Then cool to room temperature and acidify with 370ml 6N hydrochloric acid. The separated organic phase was washed with 4*8ml of water. The organic product was dried over anhydrous MgSO4, and then fractionated under reduced pressure to obtain 153 grams of (100-103°C/18mm) product, with a yield of 86.9% and a purity of 99.2 %. The two-step synthesis yield was: 82.9%.
Preparation[1][2]
Method 1: Cool the concentrated sulfuric acid to -5~5℃ and mix it with parformaldehyde, then add thionyl chloride dropwise to it, and after the dropwise addition is completed, wait at -5~5℃Incubate for 30-60 minutes and then add the catalyst; then add trifluoromethylbenzene dropwise to react to obtain 1-chloromethyl-3-trifluoromethylbenzene;
Method 2: A method for preparing 1-chloromethyl-3-trifluoromethylbenzene, which uses trifluorotoluene, paraformaldehyde, and sulfoxide chloride as raw materials, and uses sulfuric acid as the solvent to react to prepare 1 -Chloromethyl-3-trifluoromethylbenzene. The reaction formula is as follows:
The specific steps are as follows: add 73 grams (0.5 mol) of trifluorotoluene, 150 grams of 95% sulfuric acid and 15 grams (0.5 mol) of paraformaldehyde into the reaction bottle, stir, cool to 15 degrees, and then add dropwise for about 4 hours 30 grams (0.252 mol) of thionyl chloride, after the dropwise addition, continue the heat preservation reaction for 4 hours, separate into layers, the lower layer of sulfuric acid can be used for the next batch of reactions, the upper oil layer is subjected to vacuum distillation under a vacuum of 0.09 to 0.099MPa, and collected em>75-80℃Fraction, 76 grams of product 1-chloromethyl-3-trifluoromethylbenzene was obtained, yield: 78.1%.
Main reference materials
[1] CN106349006 Preparation method of 3-trifluoromethylphenylacetonitrile
[2] CN201410844330.9 Preparation method of 1-chloromethyl-3-trifluoromethylbenzene
[3] CN201310379816.5 Preparation method of m-trifluoromethylbenzoic acid
[4] CN03115231.7 Preparation method of m-trifluoromethylbenzyl alcohol
