Preparation
Synthesis of 2-methoxy-5-sulfamoyl benzoic Acid: In the amination reaction of 2-methoxyl-5-amino-sulfonyl benzoic acid, the main influence factors were mainly ammonia concentration, reaction temperature and reaction time. Firstly, we investigated two approaches of animation reaction: ventilation with ammonia in solvent and ammonium hydroxide as amino-reactant and solvent. In this section, the way of ventilation with ammonia in methyl alcohol and tetrahydrofuran would cause the rapid reaction, resulting to the incomplete reaction of 2-methoxy-5-sulfamoylbenzoic acid owing to the formation of 2-methoxy-5-sulfamoyl benzoic acid coated on the surface of the reaction. On the contrary, the lab test indicated that the way of ammonium hydroxide as amino-reactant and solvent can provide better experimental results. Secondly, the reactive temperature was the more important factor. The optimized amination temperature was to 30 °C. The low temperature would result to the long amination time, whereas high temperature can result to the generation of by-product owing to the hydrolysis of sulfonyl chloride. Finally, we evaluated the effect of reaction time. The optimized reaction time was to 5 hours. The extended reaction time can’t cause the significant improvement of yield. As a consequence, the best reactive temperature was to 30 °C and the best mole ratio between 2-methoxy-5-sulfonylchlorobenzoic acid and ammonium hydroxide was to 1:20 and the best reactive time was to 5 hours. Under the best conditions, the yield can reach to 75.8%.
