Synthesis Of Isosorbide 5-Mononitrate

Isosorbide 5-mononitrate is a new long-term anti-angina cardiovascular drug used for clinical treatment of angor pectoris.5-ISMN is an in vivo metabolite of isosorbide dinitrate, did not show the first pass effect of hepar. This thesis studied a new synthetic process of isosorbide 5-mononitrate.The starting material sorbitol was dehydrated to obtain isosorbide. The isosorbide obtained was purified by the activated carbon filtration, then treated with nitration, neutralization, de-salting and hydrolysis to obtain isosorbide 5-mononitrate with the overall yield of 18%.The dehydration was completed under vacuum condition using p-toluene sulfuric acid as catalyst. The reaction mixture was neutralized and purified by activated carbon filtration. The filtered product was directly used with the vacuum distillation. The vacuum distillation operation under high temperature was avoided. In the nitration process, PhMe-AcOH-Ac20 mixture was used as the soluvent, while the 95% fuming nitric acid was used as the nitrification reagent. The reaction mixture was treated by adding sodium hydroxide to form the white solid. Finally, isosorbide 5-mononitrate was obtained by neutralizing precipitation.The structure of the intermediates and isosorbide 5-mononitrate were confirmed by MS, 'H-NMR,13C-NMR and IR. Better technical parameters of synthesizing isosorbide 5-mononitrate were obtained from the discussion of factors of affecting the reactions above.