Method for synthesizing N-monosubstituted piperazine-2,3-dione

Abstract

The invention discloses a method for synthesizing N-monosubstituted piperazine-2,3-dione. The method comprises the following steps of: performing cyclization reaction on a starting material of ethylenediamine by using a cyclizing reagent to obtain an intermediate product of piperazine-2,3-dione; and performing substitution reaction on the intermediate product serving as a raw material by using a substituting reagent to obtain the target product of N-monosubstituted piperazine-2,3-dione. In the reaction process, the intermediate product of piperazine-2,3-dione obtained in the first step can be not required to be separated and directly undergo the substitution reaction in the second step. The synthesis method has the advantages of high yield, mild conditions, simple equipment, simple posttreatment, stable product quality, high efficiency, low energy consumption, environment friendliness and the like, and has great industrialization prospect and promotion value.

Description

technical field [0001] The invention relates to a synthesis method of N-monosubstituted piperazine-2,3-dione, which belongs to the technical field of organic synthesis. Background technique [0002] N-monosubstituted piperazine-2,3-dione is used to prepare penicillin antibiotics such as piperacillin, etc.; cephalosporin antibiotics such as cefoperazone, cefoperazone, etc.; Amidinophenoxy)propyl]piperazine-2,3-dione-N'-acetic acid, N-[4-(4-amidinophenoxy)butyl]piperazine-2,3-dione -N'-acetic acid, etc.; plant growth regulators such as N,N'-bis(phosphonophenylmethine)piperazine-2,3-dione, etc.; and important intermediates of other types of compounds, which are widely used. Its structural formula is as follows. [0003] [0004] Among them, R can be: alkyl: such as methyl, ethyl, propyl, butyl, isopropyl, etc.; substituted alkyl: such as carboxymethyl, alkoxycarboxymethyl, benzyl, substituted benzyl, benzene Oxymethyl, 2-phenoxyethyl, 3-phenoxypropyl, 3-(4-amidinophenoxy)...

AI Technical Summary

Problems solved by technology

[0007] Although the above synthetic route has a simple reaction principle and fewer synthetic steps, the preparation of the intermediate product N-monosubstituted ethylenediamine is very difficult, and its shortcomings are mainly reflected in: 1) low yield (ranging from 40% to 75%), side effects There are many products (N, N′-disubstituted and polysubstituted ethylenediamine are generated at the same time), and the intermediate product N-monosubstituted ethylenediamine must be fully separated from the raw materials and by-products, otherwise it will seriously affect the second step of the ring closure reaction. Yield; 2) post-treatment separation energy consumption is large, the cycle is long, and the production efficiency is low. Separation can only be achieved through long-term (>30h), high-energy-consuming (110°C-190°C) unit operations such as rectification; 3) Equipment investment and maintenance costs are high, resulting in high production costs, which is not conducive to industrialization

[0008] Although there are some improved research reports (US 4217308, GB 2082172, GB 2051040, GB 2013180A, CA 47779, CA 1120059, GB 1007343, DE 2900060, DE 3128810, DD 259846, DD 286348, US 5001267, CN 1438993, J.Am.Chem.Soc., 1941,63,852, J.Am.Chem.Soc., 1951,73,1370-1371, J.Org.Chem.,1957,22( 5): 538, J.Org. Chem., 1992,57, 6257-6265, etc.), but all failed to fundamentally overcome the defects of low synthesis yield, difficult separation and high cost of N-monosubstituted ethylenediamine

[0009] It can be seen that the existing synthesis method of N-monosubstituted piperazine-2,3-dione is not perfect, and cannot adapt to the economic development mode of low-carbon environmental protection, energy saving and consumption reduction advocated by the world.

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