Aryl ¦Á-keto Ester Synthesis And Restores

Aromaticα-keto esters have more lively two-functional groups, it is an important organic synthetic intermediates , which have very important applications in pharmaceutical, pesticide etc. It can be converted into many compounds with important functional groups, such as it can be reduced to aromaticα-hydroxy esters (mandelic acid esters structure), and with reduction and amination it can form amino (amine) acids esters structure, which can also form the other useful structure by reaction with carbon anion groups. The studies of synthesis and reduction of aromaticα-keto esters have more important theoretical and practical value.In the paper, the process of the synthesis of aromaticα-keto esters is described, and the higher aromaticα-keto esters were prepared from simple and easy methyl phenylglyoxylate or ethyl phenylglyoxylate by transesterification, and the reduction of aromaticα-keto esters were studied, which were used to synthesize Cyclandelate (cardiovascular and cerebrovascular drug) and Pemo1ine (central nervous system stimulant Pemoline).First of all, aromaticα-keto esters were prepared by oxalyl chloride ester by reacting with anhydrous alcohol. at low temperature, the production were distillated by vacuum, the best condition was studied.Aromaticα-keto esters were prepared from aromatics by Friedel-Crafts reaction with methyl oxalylchloride or ethyl oxalylchloride under the catalyst of aluminum trichloride. In order to determine better reaction condition, we measured the impact of temperature, time and solvent in the Friedel-Crafts reaction. The better reaction condition as follow: temperature 0℃, time 3~6h, solvent CH2Cl2.Series of aromaticα-hydroxy esters were prepared from aromaticα-keto esters via transesterification reaction with primary, secondary alcohols and phenols, and we futher study the reaction of transesterification by primary, secondary, tertiary alcohols or phenols. The reaction was investigated in detail, the appropriate catalyst and solvent.The reaction of reducing aromaticα-keto esters to aromaticα-hydroxy esters by NaBH4 and ethanol, Pd / C and H2, Zn / HCOONH4 etc was investigated. We measured the impact of different reducing agent, and further optimum the reaction condition, Zn / HCOONH4 is the best system. With the optimal conditions established, a series of different aromaticα-hydroxy esters was then synthesized.Cyclandelate was prepared from ethyl benzoylformate by transesterification with 3,3,5-trimethyl cyclohexanol under the catalyst of sodium methoxide to give benzoylformate 3,3,5-trimethyl cyclohexanol ester, which were reduced by zinc dust and ammonium formate with an overall yield of 59.6%. The process of preparing the 2-imino-5-phenyl-4- oxazolone (Pemoline) was described. Ethyl mandelate was was obtained through the reduction of ethyl benzoylformate and further react with guanidine nitrate via replacing reaction, removing ammonia and hydrolysis reaction to give Pemoline, yield 56.5%. 4-Methoxyphenylacetic acid was prepared from anisole by Friedel-Crafts reaction with ethyl oxalylchloride under the catalyst of aluminum trichloride to give ethyl 4-methoxybenzoylformate, which were subjected to reduction by Wolff-Kishner-Huang reaction with hydrazine hydrate with an overall yield of 55.1%.In the paper, the target compounds and intermediates were qualitatively confirmed by IR,1H NMR,13C NMR and MS.