阅读说明：本技术 一种含N-αβ不饱和酮化合物的制备方法及应用 (Preparation method and application of unsaturated ketone compound containing N-alpha beta ) 是由 于腾飞 王伟 崔宁宁 陈锦春 于 2020-12-08 设计创作，主要内容包括：本发明涉及一种含N-αβ不饱和酮化合物的制备方法,所述的制备方法为：(1)将和混合在一起,加热至回流；(2)加热回流至反应体系变黄,进行降温,析出固体；(3)使用甲基叔丁基醚进行打浆,得到黄色固体的产物所述含N-αβ不饱和酮化合物的制备方法无需使用反应溶剂,也无需使用催化剂和氧化剂,降低原料成本,而且后处理纯化简单,收率高,操作简单,降低制备成本。(The invention relates to a preparation method of an N-alpha-beta unsaturated ketone compound, which comprises the following steps: (1) will be provided with And mixing together, heating to reflux; (2) heating and refluxing until the reaction system turns yellow, cooling and separating out solids; (3) pulping with methyl tert-butyl ether to obtain yellow solid product The preparation method of the N-alpha-beta-containing unsaturated ketone compound does not need to use a transThe solvent is used, the catalyst and the oxidant are not needed, the raw material cost is reduced, the post-treatment and purification are simple, the yield is high, the operation is simple, and the preparation cost is reduced.)

1. A preparation method of an N-alpha beta unsaturated ketone compound is characterized by comprising the following steps:

(1) will be provided withMixing together, heating to reflux;

(2) heating and refluxing until the reaction system turns yellow, cooling and separating out solids;

(3) pulping with organic solvent to obtain yellow solid product

2. A process according to claim 1, wherein in step (1), said unsaturated ketone compound isIn a molar ratio of 1: 1 to 2.

3. The method according to claim 1, wherein the reflux time in step (2) is 10 to 60 min.

4. The process according to claim 1, wherein in the step (2), the temperature of the reaction system is lowered to a range of-5 to-15 ℃.

5. The process according to claim 1, wherein in the step (3), the organic solvent is methyl t-butyl ether.

6. Use of the N- α β -containing unsaturated ketone compound obtained by the production method according to any one of claims 1 to 5, wherein the N- α β -containing unsaturated ketone compound is used in an anti-inflammatory agent.

7. The use of an N- α β -unsaturated ketone-containing compound according to claim 6, wherein the N- α β -unsaturated ketone-containing compound is used in an anti-inflammatory agent for the treatment of peritonitis or sepsis.

Technical Field

The invention relates to a preparation method and application of an N-alpha-beta-containing unsaturated ketone compound, belonging to the technical field of drug synthesis.

Background

Compounds containing N- α β unsaturated ketones play a key role in a variety of inflammatory pathways, inhibiting the formation of such compounds, and can lead to systemic side effects. The N-alpha beta unsaturated ketone compound seems to be a good lead for drug development, and the N-alpha beta unsaturated ketone compound has better curative effect on peritonitis and sepsis and has no side effect. The N-alpha beta unsaturated ketone compound is an organic matter with multiple reaction sites, can generate a plurality of drug molecules with high biological activity by utilizing the characteristic that the multiple reaction sites participate in the reaction cooperatively, and is a very important compound in pharmacological research and a good lead for drug development.

In the technology disclosed in CN109796399A, the preparation of an unsaturated ketone compound containing N- α β requires reaction in an inert solvent under the action of a metal catalyst and an oxidant, and the crude product after the reaction requires chromatographic separation to obtain the product, which is complicated in process, high in production cost, difficult in purification and low in yield.

Disclosure of Invention

Aiming at the defects in the prior art, the invention provides a preparation method and application of an N-alpha beta-containing unsaturated ketone compound, and the preparation method has the advantages of simple post-treatment, high yield and low preparation cost.

The technical scheme for solving the technical problems is as follows: a preparation method of an N-alpha beta unsaturated ketone-containing compound comprises the following steps:

(1) will be provided withMixing together, heating to reflux;

(2) heating and refluxing until the reaction system turns yellow, cooling and separating out solids;

(3) use ofPulping with organic solvent to obtain yellow solid product

Further, in the step (1), theIn a molar ratio of 1: 1 to 2.

Preferably, in step (1), theIn a molar ratio of 1: 1.5.

further, in the step (2), the heating reflux time is 10-60 min.

Preferably, in the step (2), the heating reflux time is 20 min.

Further, in the step (2), the temperature of the reaction system is reduced to-5 to-15 ℃.

Preferably, in the step (2), the temperature of the reaction system is reduced to-10 ℃.

Further, in the step (3), the organic solvent is methyl tert-butyl ether.

The invention also discloses application of the N-alpha beta-containing unsaturated ketone compound, and the N-alpha beta-containing unsaturated ketone compound is applied to anti-inflammatory drugs.

Furthermore, the N-alpha-beta unsaturated ketone compound is applied to anti-inflammatory drugs for treating peritonitis or sepsis.

The invention has the beneficial effects that: the preparation method of the unsaturated ketone compound containing N-alpha beta does not need to use a reaction solvent, a catalyst and an oxidant, so that the raw material cost is reduced, the post-treatment and purification are simple, the yield is high, the operation is simple, and the preparation cost is reduced; the product containing the fragment can be rapidly synthesized by a two-step reaction.

Drawings

FIG. 1 is a nuclear magnetic spectrum of the product of example 1;

FIG. 2 is a nuclear magnetic spectrum of the product of example 2.

Detailed Description

The present invention will be described in detail with reference to the following embodiments in order to make the aforementioned objects, features and advantages of the invention more comprehensible. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

Example 1

(1)

Table 1 example 1 raw material table for step (1)

Material(s)	Feed amount	M	Number of moles	Molar feed ratio
					Acetophenone	50g	120.15	0.416mol	1
DMF-DMA	77.4g	119.2	0.649mol	1.5

Acetophenone and DMF-DMA are mixed together according to the feeding amount in Table 1, heated to the reflux point, the reaction system turns yellow after 20min, cooled to-10 ℃ to separate out the solid, and the methyl tert-butyl ether is pulped to obtain the pure yellow solid. The total amount of the product obtained after pulping is 50-60g, and the yield reaches more than 80%.

(2)

TABLE 2 raw material table for step (2) of example 1

According to the raw material dosage in table 2Adding water, adding nitroaniline, adding ferric chloride hydrate, stirring overnight, precipitating solid, adding water, quenching, extracting with EA, concentrating, passing through column, pulping with petroleum ether to obtain 3.5-4.5gThe product has yield of more than 50%, and the nuclear magnetic spectrum is shown in figure 1.

Example 2

(1)

TABLE 3 raw materials Table for step (1) of example 2

Material(s)	Feed amount	M	Number of moles	Molar feed ratio
					Acetophenone	50g	120.15	0.416mol	1
DMF-DMA	77.4g	119.2	0.649mol	1.5

Acetophenone and DMF-DMA are mixed together according to the feeding amount in Table 3, the mixture is heated to reach the reflux point, the reaction system turns yellow after 20min, the reaction system is cooled to-10 ℃, the Chinese is separated out, and the methyl tert-butyl ether is pulped to obtain the pure yellow solid. The total amount of the product obtained after pulping is 50-60g, and the yield reaches more than 80%.

(2)

TABLE 4 raw material table for step (2) of example 2

According to the raw material dosage in the table 4, theDissolving in water, adding aniline and ferric chloride hydrate, darkening color, stirring overnight, precipitating solid, adding water, quenching, extracting with EA, concentrating, passing through column, pulping with petroleum ether to obtain final productThe product is 3g-5g, the yield is more than 50%, and the nuclear magnetic spectrum is shown in figure 2.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.