Synthesis Of Methyl2-methoxy-3-nitrobenzoate

Methyl2-methoxy-3-nitrobenzoate is an important intermediate in drug and fine chemical synthesis. It can simplify the synthesis of antibiotics A3by using this intermediate. In this dissertation, two new routes were designed and carried out to synthesize methyl2-methoxy-3-nitrobenzoate.In the first route, methyl salicylate was selected as the original substrate and it was firstly sulfonated by concentrated sulfuric acid to afford methyl5-sulfosalicylate. Then it was directly nitrated by nitric acid in one pot. After that, desulfonation was successively carried out, which followed by esterification. Finally, methyl2-methoxy-3-nitrobenzoate was prepared using dimethyl carbonate (DMC) or methyl iodide as the O-methylation reagent. The overall yield can be53.0%. The target products were characterized by ’H-NMR,13C-NMR and MS. In addition, a one-pot reaction was used in the two steps of sulfonation and nitration, which reduced the amount of reagent, reaction time and the loss of the intermediate product. It is worth noting that sulfonic group was chosen as the regioselective protection group for the orthzo-nitration in this method. There are some advantages in this novel synthetic method, such as low cost, high availability of substrates and reagents and simple work-up, which could be more suitable for industrial production.In the second route, methyl salicylate was also selected as the original substrate. Firstly, methyl salicylate was to be alkylated with the tert-butanol, then was nitrated with mixed acid. Secondly,3-nitrosalicylic acid was prepared via the retro-Friedel-Crafts reaction. Thirdly, the O-methylation was consistent with the first route. The intermediate products were identified by’H-NMR and13C-NMR. The most important is that the alkylation and nitration, were used as a one-pot reaction, which reduced the loss of the alkylation product and simplified the operation. Moreover, the tert-butyl group was chosen as the regioseletive protection group for the ortho-nitration in this method. This route is a supplement of orthzo-regioselectivity route in nitration, which has never been reported either.