Phenyl hydrazine and substituted phenyl hydrazine continuous flow synthesis process

Abstract

The invention provides a phenyl hydrazine and substituted phenyl hydrazine continuous flow synthesis process. Three-step reactions of diazotization, reduction and acidolysis salt formation are creatively and organically integrated; phenylamine or substituted phenylamine acid material liquid, diazotization reagents, reducing agents and acid are used as raw materials to be subjected to three-step reaction of diazotization, reduction and acidolysis salt formation to obtain phenyl hydrazine derivative salts. The synthesis process is performed in an integral reactor, and belongs to an integrated solution. The reaction raw materials are continuously added through a feeding opening of the integral reactor; the reactions of diazotization, reduction and acidolysis salt formation are continuously performed in the integral reactor; the phenyl hydrazine derivative salts are continuously obtained in the integral reactor; the total reaction time is less than or equal to 20min. Compared with a conventional production process, the continuous flow synthesis process has the advantages that the total reaction time is greatly shortened; the safety is greatly improved; no reaction byproducts (such as diazoamino compounds and reduction reaction midbodies) are included in the reaction process and the reaction products; the continuous flow process can prepare the high-purity products with the purity as high as 99 percent or higher without the additional purification steps.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a continuous flow synthesis process for phenylhydrazine salts. Background technique [0002] Phenylhydrazine was first synthesized by Hermann-Emil Fischer in 1875 as the first synthesized hydrazine derivative. With the in-depth study of heterocyclic compounds and the continuous expansion of applications, substituted phenylhydrazine compounds have a wide range of applications. In medicine, they can synthesize new antibacterial drugs, treat diabetes, anticancer drugs, antiviral drugs, antihypertensive drugs, etc. , In terms of pesticides, it can synthesize insecticides, fungicides and herbicides, etc. It is also widely used in the fuel industry, charge transport materials, polymers and other industries. [0003] The production process of substituted phenylhydrazine series compounds is similar, mainly the diazotization reaction of aromatic amines, and then various substituted phenylhydrazi...

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Problems solved by technology

[0016] Chinese patent CN106316879A discloses a method for preparing phenylhydrazine hydrochloride in a continuous reactor-type operation mode that can be used in industrial production. Although the diazotization stage is a continuous operation, the reactor is still used in the reduction stage and the acidolysis stage. The two-step process is still intermittent, and the whole process flow of synthesizing phenylhydrazine hydrochloride is still a batch reaction process in essence.

Although the diazotization stage is a continuous operation, which partially solves the safety risks faced by the diazotization reaction, on the one hand, the reduction step and the acid hydrolysis step of the method need a total of several hours, resulting in a longer total reaction time in the process; On the one hand, after acid analysis, it needs to go through purification steps such as neutralization and distillation

Therefore, this process is a batch reaction process, and it cannot fundamentally solve the problems of long reaction time, low production efficiency, low product purity after acid analysis, high production energy consumption and high cost.

[0017] The paper Org.Process Res.Dev.2015,19,892 and Chinese patent CN104744295A disclose a method for preparing o-ethylphenylhydrazine hydrochloride in a pipeline continuous adding reactor type operation mode that can be used in industrial production, although diazotization and The reduction stage is a continuous operation, but there are still the following problems: 1) the acidolysis stage of the above method still relies on the reactor (acidification kettle); Including the time required for hydrolysis will exceed 2 hours; 3) After the completion of hydrolysis, purification steps are still required, and organic solvent extraction is used, which has potential environmental pollution and environmental risks

[0019] 1. The existing synthesis processes of phenylhydrazine salts and substituted phenylhydrazine salts contain multiple or one batch steps, which cannot be a fully continuous process. In addition, the reduction step and the acid hydrolysis salt formation step are usually carried out at 100°C, and the reaction rate Slow, resulting in a long reaction time of the whole process, reducing production efficiency and increasing energy consumption and cost of the production process

[0020] 2. Due to the long reaction time and many by-products in the existing process, the purity of the product phenylhydrazine salt and substituted phenylhydrazine salt after acid hydrolysis into salt is not high, generally around 90%

Though product purity after purification also can reach more than 98%, this has further reduced product yield (being about 80% usually) and production efficiency again, has increased production cost

[0021] 3. In the prior art, it has not been seen that a single reactor can be used to complete the production of different phenylhydrazine salts and substituted phenylhydrazine salts under the condition of ensuring high purity, high yield and high production efficiency of the product.

[0026] In the prior art, under the condition of ensuring the high purity and high yield of phenylhydrazine salt and substituted phenylhydrazine salt products, it has not been developed to solve the problems of continuous process of the whole process, long process time and low production efficiency, and also take into account different The synthesis of phenylhydrazine salts and substituted phenylhydrazine salts involves differences in physical properties (such as melting and boiling points, thermal conductivity, heat capacity, solubility, etc.) and reactivity of materials (raw materials, reaction intermediates and products), to solve process selectivity and The problem of flexibility leads to high reaction efficiency (rapid reaction, high yield of target product), good equipment universality (using the same reactor to produce products with different types of substituents and substitution positions with high efficiency), safe process, easy operation and Ease of large-scale industrial production

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