Synthesis method of 2-nitro-4-substituted phenylacetic acid

Abstract

The invention discloses an improved synthesis method of 2-nitro-4-substituted phenylacetic acid. The synthesis method is characterized by comprising the steps of: nitrifying 4-substituted halogeno benzene used as a raw material in a polar solvent by using a mixed acid of concentrated nitric acid and concentrated sulfuric acid to obtain 2-X-5-substituted nitrobenzene; carrying out substitution with excess malonic methyl ester nitrile or ethyl cyanoacetate on an alkaline condition; then reacting with excess concentrated hydrochloric acid to obtain 2-nitro-4-substituted benzyl cyanide; and finally hydrolyzing in a strong acid or strong alkaline aqueous solution to obtain the 2-nitro-4-substituted phenylacetic acid. Compared with the prior art, the synthesis method has the advantages of simple synthesis, no special demands on synthesis condition, high raw material convention rate, high overall yield of 40%-70%, no raw material surplus or generated needless by-products, no needs of additional operation process for removing raw material residual after reaction and separation by-products, no need of anhydrous solvents or equipment and no need of highly toxic substances; in addition, the synthesis method only needs to adopt filtering, extracting and other simpler separation processes for post-purification; and therefore, the synthesis method is quite suitable for industrialized production.

Description

technical field [0001] The invention is an improvement to the synthesis method of 2-nitro-4-substituted phenylacetic acid, in particular to a new process for synthesizing 2-nitro-4-substituted phenylacetic acid with 4-substituted halobenzene as the starting material. Background technique [0002] 2-nitro-4-substituted phenylacetic acid (4-Bromo-2-nitrophenylacetic Acid, molecular formula C 8 h 6 BrNO 4 , CAS Registry No. 6127-11-3) is an important chemical intermediate, one of which can be used as a raw material for the synthesis of 6-substituted indolinones, and also has many applications in the production of medicine, pesticides, spices and other fields. At home and abroad, the methods for synthesizing 2-nitro-4-substituted phenylacetic acid mainly contain the following: [0003] (1) "Bioorganic and Medicinal Chemistry Letters", 200616, 421-426 reported that 4-substituted toluene was used as raw material, and 2-nitro-4-substituted toluene was obtained after mixed acid n...

AI Technical Summary

Problems solved by technology

[0005] The shortcoming of this synthetic route is: with NBS bromination 2-nitro-4 bromotoluene, it is difficult to control the addition of equivalents, so it is inevitable that there will be troubles that the raw materials cannot be completely reacted, or dibromo by-products are generated, resulting in the purification of the product 2- Nitro-4-substituted benzyl bromide is complex; and this route requires the use of a highly toxic compound-sodium cyanide, which has potential safety hazards in the production process and requires high production equipment, resulting in large investment in equipment

[0011] This route requires anhydrous conditions when using sodium phenate, which requires high production equipment and is not suitable for industrial production.

Images