Optimization For The Synthetic Process Of O-nitrobenzaldehvde

o-Nitrobenzaldehyde is used as an important intermediate for the synthesis ofpharmaceuticals, which especially is the key intermediate of expectorant ambroxol hydrochlorideand cardiovascular disease medicines such as nifedipine, nisoldipine, encainide. In this paper,o-nitrobenzaldehyde was prepared from o-nitrotoluene through three steps which werebromination, hydrolysis and oxidation. The optimal reaction conditions of bromination andhydrolysis were achieved by experiments. The oxidation conditions were also studied andoptimized. The products of hydrolysis and oxidation were indentified by1HNMR, IR, GC-MSetc.The experimental results show as follows. First, in the bromination step, under the optimalconditions (n(o-nitrotoluene):n(bromine) of1:0.45, m(o-nitrotoluene): m(catalyst):m(water) of1:0.103:0.86, m(benzoyl peroxide): m(azobisisobutyronitrile) of1:1, and in the absence ofsolvent,45～50°C),the yield of the bromination was73.1%. Second, in the hydrolysis step,under the optimal conditions(80°C, n(o-nitrobenzyl bromide):n(anhydrous sodium carbonate) of0.56:1, the alkali concentration of15%and the amount of phase transfer catalyst tetrabutylammonium bromide of1%,5h), the yield of the hydrolysis was99.3%based on the o-nitrobenzyl bromide.Third, in the oxidation step, under the optimal conditions(50°C, n(o-nitrobenzylalcohol):n(48%hydrobromic acid):(27.5%hydrogen peroxide): n(dioxane) of1:0.5:6.0:3.59,18h), the yield of the oxidation was70.5%, and the final yield of o-nitrobenzaldehyde was46.8%based on o-nitrotoluene.The bromination and hydrolysis were carried out in water instead of any other organicsolvent, which had some advantages such as saving the cost, improving the work environment.The new technology of oxidation with hydrogen peroxide was used instead of the old nitric acidoxidation technology which may corrode the equipment and pollute the environment. Theoxidation process with hydrogen peroxide was environmental-friendly, production safety andoperationally mild.