Method using one-step method to synthesize 2-amino-5-chloropyridine in high-selectivity manner

Abstract

The invention belongs to the technical field of intermediate synthesis and particularly relates to a method using a one-step method to synthesize 2-amino-5-chloropyridine in a high-selectivity manner.The method includes: adding 2-aminopyridine serving as the raw material into an organic solvent, dropwise adding bromine to serve as the catalyst under the irradiation of a blue LED lamp, and feedingchlorine after solution fading to perform chlorination reaction; subjecting obtained reaction liquid to reduced pressure distillation to obtain a crude product, and performing further recrystallization to obtain high-purity 2-amino-5-chloropyridine. The method has the advantages that the bromine is used as the catalyst, the bromine is irradiated by the blue light LED lamp to generate bromine freeradicals combining with the 5 site of a 2-aminopyridine ring, then chlorination is performed, product 2-amino-5-chloropyridine cascade reaction, which generates polychloro compounds, caused by directchlorination is avoided, good chlorination selectivity is achieved, and the high-content 2-amino-5-chloropyridine is obtained; compared with the prior art, the method is simplified in production process, mild in reaction condition, high in product purity, low in production cost and low in wastewater quantity.

Description

technical field [0001] The invention belongs to the technical field of synthesis of intermediates, and in particular relates to a method for synthesizing 2-amino-5-chloropyridine with high efficiency and high selectivity in one step. Background technique [0002] 2-Amino-5-chloropyridine is an important chemical intermediate widely used in the fields of medicine, pesticides and dyes. Many kinds of substances can be synthesized by using 2-amino-5-chloropyridine, such as sedative and hypnotic drug zopiclone, new anticoagulant drug edoxaban, etc. Parasite drugs. At present, domestic and foreign markets are in great demand, but there are not many reports on its synthesis in China. [0003] The synthetic method about this compound mainly takes 2-aminopyridine as raw material, and following several synthetic routes are arranged: [0004] (1) Thomas et al. proposed in their patent US3985759 that 2-aminopyridine was dissolved in a strong acid solvent, and chlorine gas was introdu...

AI Technical Summary

Problems solved by technology

Although this method has a high yield, the reaction conditions are harsh and the equipment requirements are high, and it must be carried out at -20 ° C and strong acid medium conditions.

[0005] (2) 2-aminopyridine prepares the target product 2-amino-5-chloropyridine through nitration, acylation, reduction, chlorination and hydrolysis reactions. Although the reaction conditions of this process are mild, the operation steps are complicated and are not suitable for industrial production

[0006] (3) N-chlorosuccinimide (NCS) is the synthetic product 2-amino-5-chloropyridine of chlorination agent, and the yield of this method can reach 90%, but the more expensive chlorination reagent NCS is used , and dichlorides are inevitably produced in the reaction, and the separation and purification of the product is more difficult

This method has better selectivity, but it cannot avoid the generation of dichlorides. At the same time, the addition of oxidant will cause the oxidation of part of the raw material 2-aminopyridine and the product 2-amino-5-chloropyridine, resulting in the loss of materials and products and the waste water production. bigger

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