阅读说明：本技术 一类n-羟甲基酰胺类抗菌剂及其制备方法 (N-hydroxymethyl amide antibacterial agent and preparation method thereof ) 是由 欧光南 于 2019-10-09 设计创作，主要内容包括：本发明公开了一类N-羟甲基酰胺类抗菌剂及其制备方法,一类N-羟甲基酰胺类抗菌剂,其具有以下通式,<Image he="411" wi="582" file="DDA0002227129670000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明首先合成N-羟甲基酰胺,酰胺在碱催化剂作用下与过量的甲醛反应生成N-羟甲基酰胺,然后过混合阴、阳离子交换柱除去离子杂质,所得的中性流出液旋转蒸发蒸去过量的甲醛和水分,真空干燥得到N-羟甲基酰胺,经生物学活性实验证实该类化合物具有显著的抗菌作用,可用于制备新的抗菌药物,工艺简便,原料价廉易得,且产品纯度高,产率高,适合工业化生产。(The invention discloses a N-hydroxymethyl amide antibacterial agent and a preparation method thereof, wherein the N-hydroxymethyl amide antibacterial agent has the following general formula, the invention firstly synthesizes N-hydroxymethyl amide, the amide reacts with excessive formaldehyde under the action of an alkali catalyst to generate N-hydroxymethyl amide, then the N-hydroxymethyl amide passes through a mixed anion and cation exchange column to remove ionic impurities, the obtained neutral effluent liquid is subjected to rotary evaporation to remove excessive formaldehyde and moisture, and the N-hydroxymethyl amide is obtained by vacuum dryingThe hydroxymethyl amide is proved to have remarkable antibacterial effect through biological activity experiments, can be used for preparing novel antibacterial drugs, has simple and convenient process, cheap and easily obtained raw materials, high product purity and high yield, and is suitable for industrial production.)

1. A N-hydroxymethyl amide antibacterial agent has the following general formula,

2. the preparation method of the N-hydroxymethyl amide antibacterial agent is characterized by comprising the following steps:

s1, adding amide, an alkali catalyst and water into a round-bottom flask, stirring to dissolve, adjusting the pH to 9-10, and cooling to below 5 ℃ by using ice water;

s2, dripping a formaldehyde solution into the ice water bath while stirring, and maintaining the reaction temperature below 10 ℃;

s3, removing the ice water bath after the dropwise addition, continuously stirring at room temperature for 18-24h, and controlling the pH value to be 9-10 during the reaction period to prepare the N-hydroxymethyl amide aqueous solution;

s4, passing the N-hydroxymethyl amide aqueous solution obtained in the step S1-S3 through a mixed anion and cation exchange column, and controlling the flow rate to be 5-40BV h ^-1And 1 cubic meter of the solution per cubic meter of resin. The obtained neutral effluent liquid is subjected to rotary evaporation to remove excessive formaldehyde and moisture;

s5, vacuum drying at 60 ℃ to obtain the N-hydroxymethyl amide.

3. The method for preparing N-hydroxymethyl amide antibacterial agents according to claim 2, wherein the N-hydroxymethyl amide antibacterial agents comprise: the ratio of the amounts of the amide and the formaldehyde in the steps S1-S3 is 1:1.1-1: 1.5.

4. The method for preparing N-hydroxymethyl amide antibacterial agents according to claim 2, wherein the N-hydroxymethyl amide antibacterial agents comprise: the alkali catalyst in the steps S1-S3 is NaOH, KOH or Na ₂CO ₃And K ₂CO ₃One of them, in an amount 1/100-3/100 of the substance of amide.

5. The method for preparing N-hydroxymethyl amide antibacterial agents according to claim 2, wherein the N-hydroxymethyl amide antibacterial agents comprise: the ratio of the anion exchange resin to the cation exchange resin in the steps S4 to S5 is 1:1.1-1: 1.5; the column height of the ion exchange column is 700-1000mm, and the flow rate is controlled to be 5-40BV h ^-1。

6. Use of a compound according to claim 1 or a compound prepared by a process according to any one of claims 2 to 5 as an antibacterial agent.

7. The preparation method of N-hydroxymethyl amide antibacterial agents according to claim 2, wherein the general formula of the synthetic route of the N-hydroxymethyl amide is as follows:

Technical Field

The invention relates to the technical field of antibiosis, in particular to an N-hydroxymethyl amide antibacterial agent and a preparation method thereof.

Background

Various pathogenic microorganisms are widely distributed in nature and grow and reproduce under certain conditions, which not only can cause decomposition, deterioration and putrefaction of various articles, but also threatens human health. At present, in addition to strict regulation of the use of antibacterial drugs and avoidance of the excessive generation of drug resistance by bacteria, the development of some novel antibacterial drugs is urgently needed. Amides are the fastest growing group of the antimicrobial market. The molecular structure of the prior amide antibacterial agent is characterized in that: containing an amide bond; the acyl end is connected with an aromatic ring and/or a hydrogen bond acceptor; the amino end is connected with an aromatic ring, and an auxiliary group is arranged at the ortho position of the aromatic amino, such as furametpyr, boscalid, fluxapyroxad, bixafen, penthiopyrad, isopyrazam and the like. The amide antibacterial agent has a complex molecular structure, a long synthetic route, is insoluble in water and has certain toxic and side effects. Therefore, research and development of novel low-toxicity hydrophilic antibacterial agents with high efficiency, short synthetic route, simple process, low raw material cost and environmental friendliness are imperative, and therefore, a class of N-hydroxymethyl amide antibacterial agents and a preparation method thereof are provided to solve the problems.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides an N-hydroxymethyl amide antibacterial agent and a preparation method thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

a N-hydroxymethyl amide antibacterial agent has the following general formula,

a preparation method of N-hydroxymethyl amide antibacterial agents comprises the following steps:

s1, adding amide, an alkali catalyst and water into a round-bottom flask, stirring to dissolve, adjusting the pH to 9-10, and cooling to below 5 ℃ by using ice water;

s2, dripping a formaldehyde solution into the ice water bath while stirring, and maintaining the reaction temperature below 10 ℃;

s3, removing the ice water bath after the dropwise addition, continuously stirring at room temperature for 18-24h, and controlling the pH value to be 9-10 during the reaction period to prepare the N-hydroxymethyl amide aqueous solution;

s4, passing the N-hydroxymethyl amide aqueous solution obtained in the step S1-S3 through a mixed anion and cation exchange column, and controlling the flow rate to be 5-40BV h ^-1The obtained neutral effluent liquid is subjected to rotary evaporation to remove excessive formaldehyde and moisture;

s5, vacuum drying at 60 ℃ to obtain the N-hydroxymethyl amide.

Preferably, the ratio of the amounts of the substances of amide and formaldehyde in the steps S1-S3 is 1:1.1-1: 1.5.

Preferably, the alkali catalyst in the steps S1-S3 is NaOH, KOH, Na ₂CO ₃And K ₂CO ₃One of them, in an amount 1/100-3/100 of the substance of amide.

Preferably, the ratio of the anion exchange resin to the cation exchange resin in the steps S4-S5 is 1:1.1-1: 1.5; the column height of the ion exchange column is 700-1000mm, and the flow rate is controlled to be 5-40BV h ^-1。

Preferably, the use of the compounds as antibacterial agents.

Preferably, the synthetic route of the N-hydroxymethyl amide is represented by the general formula:

the invention firstly synthesizes N-hydroxymethyl amide, the amide reacts with excessive formaldehyde under the action of an alkali catalyst to generate N-hydroxymethyl amide, then the N-hydroxymethyl amide is passed through a mixed anion and cation exchange column to remove ionic impurities, the obtained neutral effluent liquid is subjected to rotary evaporation to remove excessive formaldehyde and moisture, and vacuum drying is carried out to obtain the N-hydroxymethyl amide.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments.