阅读说明：本技术 一种3,4-二氢嘧啶-2(1h)-酮类化合物的制备方法 (Preparation method of 3, 4-dihydropyrimidine-2 (1H) -ketone compound ) 是由 刘万毅 吴志强 王刚 刘睿波 段斌 相庆雨 王旭军 陈小燕 于 2020-06-19 设计创作，主要内容包括：本发明公开了一种3,4-二氢嘧啶-2(1H)-酮类化合物的制备方法,包括以下步骤：(1)将反应底物原料芳香醛类、1,3-二酮酯、尿素和微量的水分别加入到反应器内；(2)在密闭状态下加热到110-160℃,保持一定的时间；(3)停止加热,使反应器冷却到室温至40℃,加入有机溶剂冲洗物料到收集槽中；(4)进行固液分离、洗涤和再结晶操作,获得目标产物3,4-二氢嘧啶-2(1H))酮类化合物；(5)溶剂母液收集并回收产物、回收溶剂套用。本发明与现有技术相比的优点在于：成本低、环保。(The invention discloses a preparation method of 3, 4-dihydropyrimidine-2 (1H) -ketone compounds, which comprises the following steps: (1) adding aromatic aldehydes, 1, 3-diketone ester, urea and trace water serving as reaction substrate raw materials into a reactor respectively; (2) heating to 110-160 ℃ in a sealed state, and keeping for a certain time; (3) stopping heating, cooling the reactor to room temperature to 40 ℃, and adding an organic solvent to flush the material into a collection tank; (4) carrying out solid-liquid separation, washing and recrystallization to obtain a target product 3, 4-dihydropyrimidine-2 (1H)) ketone compound; (5) collecting the solvent mother liquor, recovering the product, and recovering the solvent for reuse. Compared with the prior art, the invention has the advantages that: low cost and environmental protection.)

1. A preparation method of 3, 4-dihydropyrimidine-2 (1H) -ketone compounds is characterized by comprising the following steps:

(1) adding aromatic aldehydes, 1, 3-diketone ester, urea and trace water serving as reaction substrate raw materials into a reactor respectively;

(2) heating to 110-160 ℃ in a sealed state, and keeping for a certain time;

(3) stopping heating, cooling the reactor to room temperature to 40 ℃, and adding an organic solvent to flush the material into a collection tank;

(4) carrying out solid-liquid separation, washing and recrystallization to obtain a target product 3, 4-dihydropyrimidine-2 (1H)) ketone compound;

(5) collecting the solvent mother liquor, recovering the product, and recovering the solvent for reuse.

2. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: in the step (1), the feeding proportion of the reaction substrate raw materials, namely aromatic aldehydes, 1, 3-diketone ester and urea is 1: 1.5-4 mol.

3. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: the 1, 3-diketone ester in the step (1) can be replaced by ethyl acetoacetate or methyl acetoacetate, and the urea can be replaced by thiourea.

4. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: the catalyst used in the step (1) is water generated by reaction and fresh water added, and the amount of the fresh water is 0.16-1.9 mol% of the reaction substrate raw material.

5. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: the reaction pressure in the step (2) is 1 to 6 atmospheres.

6. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: the reaction time in the step (2) is 20 to 90 minutes.

7. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: and (3) measuring the temperature distribution of the reaction device by using an infrared measuring instrument.

8. The process for preparing 3, 4-dihydropyrimidin-2 (1H) -ones according to claim 1, characterized in that: the organic solvent of the washing material added in the step (3) is one of polar solvents or a mixed solvent with any proportion.

Technical Field

The invention relates to the technical field of ketone compounds, in particular to a preparation method of a 3, 4-dihydropyrimidine-2 (1H) -ketone compound.

Background

The 3, 4-dihydropyrimidine-2 (1H)) -ketone compound belongs to heterocyclic derivatives of thiourea or urea, has wide biological activity and pharmacological activity such as anti-HIV, antiviral, antibacterial and analgesic properties and the like, and has very important application. The catalyst is usually obtained by mixing the catalyst with a multi-component reaction substrate 1, 3-diketo ester (methyl or ethyl acetoacetate), aromatic aldehydes and urea (such as urea, thiourea) and carrying out a multi-stage reaction in an open vessel (Biginelli reaction). Wherein the catalyst comprises acidic catalysts such as protonic acid, Lewis acid-surfactant, solid acid and the like; such as HCl, SnCl₄·5H₂O, PGO, lactic acid, PANI-FeCl₃，FeCl₃/H₂O, CSA, graphene oxide-chitosan nano catalyst and the like, and the adopted solvent is acetonitrile, methanol/ethanol, benzene, toluene and the like, or the water phase system of water and a surfactant is subjected to synthetic reaction; or an excess of 1, 3-diketonate is used as the reaction solvent. The methods generally have the defects that the catalyst is difficult to recycle, and more acidic wastewater is generated by post-treatment; or the catalyst is complex to prepare and high in cost; or in the aqueous phase in lewis acid-surfactant combination (LASCs) catalyst systems, but produce large amounts of toxic metal and surfactant-containing organic waste streams due to demulsification and washing, especially toxic waste streams containing large amounts of surfactant sodium lauryl sulfate, and the like. Generally, the yield of various catalytic reactions is not ideal, the generation amount of subsequent purification wastes is large, and a large amount of waste liquid is generated due to the fact that a large amount of organic solvents participate in the reactions, and the whole process has poor atom economy, high cost and serious pollution, so that the industrial large-scale application is difficult; in addition, stirring is required to avoid local overheating carbonization and the like caused by uneven mass transfer of the reaction. It is therefore an object of the present invention to overcome or solve the above problems and to provide a catalyst-free and almost organic solvent-free catalystAn effective, clean and green new synthesis technical method.

Disclosure of Invention

The invention aims to overcome the technical defects and provide a preparation method of a 3, 4-dihydropyrimidine-2 (1H) -ketone compound, which is low in cost and environment-friendly.

In order to solve the technical problems, the technical scheme provided by the invention is as follows: a preparation method of 3, 4-dihydropyrimidine-2 (1H) -ketone compounds comprises the following steps:

(1) adding aromatic aldehydes, 1, 3-diketone ester, urea and trace water serving as reaction substrate raw materials into a reactor respectively;

(2) heating to 110-160 ℃ in a sealed state, and keeping for a certain time;

(3) stopping heating, cooling the reactor to room temperature to 40 ℃, and adding an organic solvent to flush the material into a collection tank;

(4) carrying out solid-liquid separation, washing and recrystallization to obtain a target product 3, 4-dihydropyrimidine-2 (1H)) ketone compound;

(5) collecting the solvent mother liquor, recovering the product, and recovering the solvent for reuse.

Compared with the prior art, the invention has the advantages that: the preparation method of the 3, 4-dihydropyrimidine-2 (1H) -ketone compound does not need other catalysts for reaction when in use, only needs water generated by the reaction and fresh water added, can eliminate the use of the catalyst in the preparation reaction process, saves a large amount of resources, reduces the use cost, can reduce the pollution of a solvent in the preparation reaction process through the high-efficiency mass transfer of a reaction system and the thermal catalytic effect of an autolysate, realizes the high-efficiency and clean production of the 3, 4-dihydropyrimidine-2 (1H)) -ketone compound, does not have the phenomena that the catalyst is difficult to recycle and pollutes the environment, and is more environment-friendly.

As an improvement, the feeding proportion of the aromatic aldehydes, the 1, 3-diketone ester and the urea which are used as the raw materials of the reaction substrate in the step (1) is 1: 1.5-4 mol.

As an improvement, the 1, 3-diketone ester in the step (1) can be replaced by ethyl acetoacetate or methyl acetoacetate, and the urea can be replaced by thiourea.

As an improvement, the catalyst used in the step (1) is water generated by reaction and fresh water added, and the amount of the fresh water is 0.16-1.9 mol% of the reaction substrate raw material.

As a modification, the reaction pressure in the step (2) is 1 to 6 atmospheres.

As a modification, the reaction time in the above (2) is 20 to 90 minutes.

As a modification, the temperature distribution of the reaction apparatus in (3) is measured by using an infrared measuring instrument.

As an improvement, the organic solvent of the washing material added in the step (3) is one of polar solvents or a mixed solvent with any proportion.

Detailed Description

The present invention is further described in the following by specific examples, which are illustrative only and not limiting, and should not be construed as limiting the scope of the present invention.

The reaction scheme of the invention is as follows: