Studies On The Synthetic Process Of Substituted Phenylacetic Acid

Mesitylacetic acid and 2,4-dichlorophenylacetic acid is the key intermediates of Spiromesifen and Spirodiclofen, which are novel insecticide/acaricide discovered and developed by Bayer. Based on the reported literatures, this paper has overviewed their synthesis and application of substituted phenylacetic acid. And then, the optimization on the synthesis process of the mesitylacetic acid and 2,4-dichlorophenylacetic acid were studied in detail.A reasonable synthesis of mesitylacetic acid was obtained from chloromethylation, cyanidation and basic hydrolysis reaction through mesitylene, the yield and purity of the product was≥78% and≥99%, respectively. However, there is not industrialization production in our country now.In this paper, the deficiencies in the synthetic process of mesitylacetic acid were improved via large quantity of exploratory and parallel experiments. During the process of preparingα1-chloroisodurene, the process was simplified and the cost was reduced by using concentrated hydrochloric acid to replace the gas of hydrogen chloride. And then, various reaction conditions, such as material ratio, temperature, amount of concentrated hydrochloric acid and so on, were discussed to reduce the binary substituted by-products, so the process of separation and purity could be avoided. On the other hand, the reaction’s selectivity and yield was greatly improved. The selectivity and total yield of the product were more than 96% and 88%, respectively. During the process of preparing 2,4,6-dichlorophenylacetonitrile, the amount of sodium cyanide was reduced from 1.74 to 1.15 equiv by adding phase-transfer catalyst, which greatly reduced the amount of cyanide in the waste stream and resolved the key problem on color of the product. Certainly, the cost was also reduced. And also target compound was synthesized from mesitylacetonitrile in alkaline system to avoid producing hydrocyanic acid from acid hydrolysis during the process of preparing mesitylacetic acid. After this, the yield was improved by 11% as compared with the value reported by references. From the above mentioned of improved synthesis, the total yield increased about 36%.The synthesis of 2,4-dichlorophenylacetic acid was also got from cyanidation and basic hydrolysis through 2,4-dichlorobenzylchloride. From this, the purity of the product was more than 99% and two step yields were 84.8%. However, the by-product of 2,3-bis (2,4-dichlorophenyl) propane-nitrile was inevitably generated during the reaction of cyanidation. So the reaction parameters, such as temperature, solvent, amount of water and so on, were optimizated to control the by-product≤4%. And also the molar ratio, solvents, temperature and phase-transfer catalyst were also discussed in preparing of 2,4-dichlorophenylacetic acid.Additionally, the mechanism of related reactions was also studied. The by-products and important intermediates were separated, and then characterized by NMR and MS. It’s found that the structures of target product and important intermediates were confirmed.