Improved Synthesis Of Cetirizine Hydrochloride

Cetirizine hydrochloride is a second generation antihistamines without calming effect, it is a selective long-term oral potent anti allergy medicine with strong biological activity. This work is aimed at optimizing and improving the synthesis route of the product. The new synthesis route use chlorobenzene and benzoyl chloride as starting materials, through Friedel-crafts reaction, carbonyl reductive reaction, chlorination, nucleophilic substitution, obtained the product. Compared with the original synthesis route, this synthesis route shortened one reaction step, reduced the cost of raw materials, the total yield is increased from20.9%to24.87%. The structure of the product was characterized by IR,1H-NMR and MS.In the first step, chlorobenzene and benzoyl chloride was catalyzed by anhydrous aluminum chloride though Friedel-Crafts acylation to4-chlorobenzophenone. The optimal condition was got after several attempts and the crude product was recrystallized by alcohol.In the second step,4-chlorobenzophenone was reducted to4-chlorobenzohydrol with Zn/NaOH and NaBH4/CH3OH. The result showed that NaBH4/CH3OH was better, and after the attempt of a variety of the ratios, the best reaction condition was generated.In the third step,4-chlorobenzhydrylchloride was prepared by chlorination reaction of4-chlorobenzohydrolp-fluoroaniline with POCI3, HC1or SOCl2. The result showed that SOCl2was better and after the attempt of a variety of the ratios, the best reaction condition was generated.The step four was using4-chlorobenzhydrylchloride and N-hydroxyethyl piperazine to get2-[4-{4-chlorophenyl}phenylmethyl]-1-piperazinylethanoloxime by condensation reaction. The best reaction condition was generated after the attempt of a variety of the ratios.The step five was the reaction between2-[4-{4-chloropheny1}phenylmethyl]-1-pip-erazinylethanoloxime and sodium chloroacetate. The reaction used (CH3)3COK and K.OH respectively as the deacid reagent. The result showed KOH was better. Then the reaction condition was certificated and the crude product was purified.