Application and production method of Ethyl acetoacetate

                                    Application and production method of ethyl acetoacetate

Application

Ethyl acetoacetate has a wide range of applications in organic synthesis. For example, it can be used to synthesize heterocyclic compounds such as pyridine, pyrrole, pyrazolone, pyrimidine, purine, and cyclic lactones. It is also widely used in drug synthesis, for example, the cyclization of ethyl acetoacetate with resorcinol yields 4-methyl-7-hydroxycoumarin, which is an intermediate for anti allergic drug scaling. Ethyl acetoacetate is condensed with benzyl chloride to obtain ethyl α - acetylphenylpropionate, which is an intermediate of cough suppressant cough ketone. Acetoacetate ethyl ester is condensed with benzoyl chloride to obtain benzoyl acetate ethyl ester, which is an intermediate of the central excitatory drug scopolamine hydrochloride. Ethyl acetate is cyclized with thiourea to produce the antithyroid drug trimethoprim, which is an intermediate of the coronary vasodilator persantine. The particularity of EAA structure determines that it has both ketone like properties and enol like reaction characteristics, and its chemical properties are very active. It is widely used in medicine, dyes, pesticides and other fields, as well as in food additives and essence. The biggest use of EAA in China is for the synthesis of pharmaceuticals and their intermediates, mainly for the synthesis of gamma acetyl butyrolactone (an important intermediate for vitamin B), 4-methyl-7-hydroxycoumarin (an intermediate for anti allergic drugs), etc; It is also used to prepare intermediates for dyes such as acetylaceto-chloroaniline (intermediate for synthesizing 1,3, Chemical book 5-pyrazolone, and Hansha yellow lake) and acetylaceto-methylaniline (intermediate for synthesizing organic yellow dye packaging efficiency pigment yellow); In addition, EAA is also used to produce pesticides such as methyl pyrimidine phosphate, pyrimidine phosphate, etc. It has also been applied in unsaturated polyester co promoters and synthetic fragrances such as linalool, ionone, and macrocyclic fragrances abroad. Ethyl acetoacetate is also used to synthesize 4-hydroxycoumarin, which is then used to manufacture new anticoagulant drugs. Ethyl acetoacetate was cyclized with 1,3-bromochloropropane to obtain 2-methyl-3-ethoxycarbonyl-5,6-dihydropyran. This is an intermediate of the vasodilator theobromine. Ethyl acetoacetate is also used in the synthesis of sodium dichlorobenzylpenicillin, amoxicillin, selective coronary vasodilator Yantongxin, and zolpidem. Ethyl acetoacetate is condensed with aniline to obtain 4-hydroxyquinazoline. Used for the production of disinfectant and preservative drug Chloramphenicol. The intermediate of pyrazolone derivatives and dyes formed by the condensation of ethyl acetoacetate and phenylhydrazine. It also has important applications in pesticides, fragrances, photo chemicals, polymerization catalysts, and other fields. Ethyl acetoacetate is also used as a food flavoring agent. Ethyl acetoacetate is also used as a solvent and as a reagent for detecting thallium, calcium oxide, calcium hydroxide, and copper

production method

The commonly used preparation method in industry is esterification of diketone and anhydrous ethanol under concentrated sulfuric acid catalysis to obtain crude ethyl acetate, which is then subjected to vacuum distillation to obtain the final product. Add ethanol and sulfuric acid in the esterification pot according to the ratio, stir and heat. When the temperature rises to 82 ℃, start adding diketone dropwise. The esterification temperature should not exceed 130 ℃. Continue to reflux until the reaction temperature no longer changes and the esterification solution is free of diketone, and end the reaction. Reduce the temperature of the feed liquid to below 120 ℃ and remove low boiling materials under the condition of controlling the reflux ratio of 1:1. When the low boiling materials are no longer distilled, increase the vacuum degree to 86.6kPa and continue to remove them. When the top temperature of the tower rises above 100 ℃, increase the vacuum degree to 97.3kPa and distill the finished product of Chemical Book with a content greater than 97%. Ethyl acetate self condensation reaction can also be used. 2CH3COOC3H5 [Na] → CH3COCH2COOC2H5 Add 250g of metallic sodium to 4240mL of ethyl acetate. The reaction starts slowly and needs to be warmed in a water bath. Once the reaction starts, it becomes very intense and needs to be cooled. After reflux reaction, recover ethyl acetate by distillation. Add 1375mL of 56% acetic acid solution and stir to reflux. Add 250g of salt and separate the oil. Extract with ether and recover ether from the extract. Wash with 10% sodium bicarbonate solution until no acidity is present. After drying with calcium chloride and vacuum distillation, the finished product is obtained by collecting the 76-78 ℃/2.4kPa fraction, with a yield of nearly 30%.