4 - Aminopyridine Synthesis

4-aminopyridine is an important organic intermediate and has been widely used in pharmacy industry. For the passed decades, the synthesis of 4-aminopyridine has been performed by the preparation of pyridine-N-oxide from the oxidation of pyridine using H2O2 as oxidant in the presence of acetic acid, and then 4-nitropyridine-N-oxide using the concentrated sulfuric or nitric acid, followed by the reduction using iron powder in the solvent of acetic acid.This method is simple, however the use of concentrated sulfuric and nitric acid led to the severe pollution to the environment and dangerous to the workers. The most important task is how to decrease the pollution during the production of 4-aminopyridine.The present research focused on the preparation of some solid catalysts. Acetic acid was replaced by SiO2 supported phosphotungstic acid, one kind of heteropoly acid, in the oxidation of pyridine, solid superacid was used instead of concentrated sulfuric acid and Pd/C catalyst joined in the reduction of 4-nitro pyridine-N-oxide rather than iron powder. The result shows this is an environmentally friendly reaction.Phosphotungstic acid of the Keggin chemical structure exhibits higher acid strength and catalytic performance for the oxidation of pyridine than acetic acid in the presence of water. Phosphotungstic acid supported on SiO2 solves the problem of the separation of catalysts with reaction products. The yield of pyridine-N-oxide reached to 93% on the catalyst of 20wt.%PW12/SiO2 under the reaction conditions of 1:1.5 mole ratio of pyridine to water and 2 hours at 80°C of reaction temperature. The other result, the yield of 4-nitro pyridine-N-oxide was 70% in the present experiment using solid superacid ofSO42-/ZrO2 instead of concentrated sulfuric acid. The yield of 4-aminopyridine as the ultimate product was more than 85% by the addition of Pd/C catalyst in the presence of ethanol.The physicochemical properties of the catalysts have been characterized by specific surface area, infrared spectra and X-ray diffraction, respectively, and the reaction intermediates and products were detected by infrared spectra, NMR and mass spectroscopy.In conclusion, the synthesis of 4-amino pyridine by the use PW12/Si02, solid superacid and Pd/C catalysts in our research provides a simple process with less pollution to the environment.