Synthesis Of 2-chloro-5-nitropyridine And 4-amino-2-chloropyridine

2-Chloro-5-Nitropyridine and 4-Amino-2-Chloropyridine are two important pyridine derivatives, which are developed and applied as fungicides, plant growth regulators, as well as pharmaceutical intermediates. Therefore, researching on the synthesis of 2-Chloro-5-Nitropyridine and 4-Amino-2-Chloro- pyridine is of great practical value.According to the referrence and mechanism analysis, several possible synthesis methods were designed in this dissertation. After a full evaluation, a best synthetic route was determined: Started from 2-Aminopyridine, which was nitrified by mixed acid of HNO₃ and H₂SO₄, 2-Amino-5-Nitropyrodine was prepared. Then, under the acidic condition, as a result of diazotization and hydrolysis reaction, 2-Hydroxy-5-Nitropyridine was prepared. At last, 2-Hydroxy-5-Nitropyridine was chlorinated by PCl₅/ POCl₃ to be 2-Chloro-5-Nitropyridine. The total yield of 2-Chloro-5-Nitro-pyridine is 41.1 %. Started from 2-Chloropyridine and hydrogen peroxide, N-oxidation reaction carried out and 2-Chloropyridine-N-oxide was prepared. Then, 2-Chloro-4-Nitropyridine-N-oxide was prepared through nitrition by mixed acid of HNO₃ and H₂SO₄. Finally, 2-Chloro-4- Nitropyridine-N-oxide was reduced and 4-Amino-2-Chloropyridine obtained. The total yield of 4-Amino-2-Chloropyridine is 69 %. In this dissertation, reaction mechanisms of each step were also discussed while the single factor and orthogonal experiments were carried out to determine the optimum reaction conditions.The structures of the synthetic products were characterized by Melting Point (MP), Infrared Spectoscopy (IR), Mass Spectra (MS) and ¹H Nuclear Magnetic Resonance (¹H-NMR). It proved that the synthetic route was feasible and the products satisfied the design requirements.