The Synthesis And Process Improvement Of The Intermediate Of Pranlukast

Pranlukast is the new anti-asthmatic drugs, it has good curative effect in asthma andallergic. As the key intermediate Pranlukast,2-hydroxy-3-amino acetophenone has importantresearch value, broad market and good development situation. In the paper, we researched andimproved the synthetic process of2-hydroxy-3-amino acetophenone. Using the cheapermaterial as the starting material, through esterification, Fries rearrangement, nitration andreduction four steps to preparation the target products each of the process conditions wasinvestigated and explored.We discussed and obtained the best mole ratio was1.2:1, the reaction temperature is120℃,the product yield is95.0%, the purity is99.11%; investigation the amount of anhydrousaluminium trichloride, the optimum amount is2equivalent of reactant, the product yield is95.7%, the purity is99.26%; in the process of nitration, The effects of molar excess, reactiontemperature and selection nitration reagent on the properties of product are investigated. Thebest process conditions are determined:the dilute nitric acid and acetic acid reaction system,nitric acid and5-chloro-2-hydroxy acetophenone of amount of molar ratio1.5, best reactiontemperature is30℃; the effect of the pressure, temperature, and applied base on catalytichydrogenation is investigated, the best technological conditions through the single factorexperiment and the orthogonal experiment for the pressure is0.5MPa, the optimum reactiontemperature is50to50℃, applied base agent is triethylamine, using methanol as solvent, whilepalladium carbon can be repeated paraphrasing secondary greatly reduces the production cost;Products in the total yield is69.2%, high performance liquid chromatography (HPLC) testingpurity of product is99.11%.Compared with the process reported in literatures, this paper design and improvement ofthe process has the following advantages: cheaper raw materials accessible, easy to operate,reduce the emissions of "three wastes"; improved the product yield, mild reaction conditions,the process is optimized, and reduces the production cost, the total yield is69.2%. Overall theprocess simple operation, through the material cost accounting, with strong market competitiveadvantage, and is more suitable for industrial production.