阅读说明：本技术 甜菜碱型两性离子的合成方法 (Method for synthesizing betaine type zwitterion ) 是由 侯荣雪 武利斌 张民 郝俊 闫彩桥 葛建民 王军 于 2019-05-05 设计创作，主要内容包括：甜菜碱型两性离子的合成方法,属于化合物合成的技术领域,包括以下步骤：A、向反应器中加入甲基丙烯酸二甲氨乙酯或二甲胺基丙基丙烯酰胺,加入乙酸,冰浴降温滴加丙烯酸反应；B、氮气条件,向容器中加入乙二醇单甲醚、吡啶、二氯甲烷,冰浴下滴加甲烷磺酰氯反应；C、氮气条件,将钠加入到二氯甲烷中,加热至钠熔融,搅拌至室温,冰浴下加入2-二甲基氨基乙醇,常温反应,冰浴下滴加淡黄色透明液体,室温反应,制备无色液体；D、取无色液体与丙酮混合,得到混合物；E、搅拌条件,无色液体滴加到澄清黏稠液体中,常温搅拌,滴入混合物,搅拌,过滤,洗涤,干燥,得到甜菜碱型两性离子。本发明反应条件温和稳定,产品纯度高。(A synthesis method of betaine type zwitterion belongs to the technical field of compound synthesis, and comprises the following steps: A. adding dimethylaminoethyl methacrylate or dimethylamino propyl acrylamide into the reactor, adding acetic acid, cooling in an ice bath, and dropwise adding acrylic acid for reaction; B. under the condition of nitrogen, adding ethylene glycol monomethyl ether, pyridine and dichloromethane into a container, and dropwise adding methane sulfonyl chloride under ice bath for reaction; C. adding sodium into dichloromethane under the condition of nitrogen, heating until the sodium is molten, stirring to room temperature, adding 2-dimethylaminoethanol under ice bath, reacting at room temperature, dropwise adding a light yellow transparent liquid under ice bath, and reacting at room temperature to prepare a colorless liquid; D. mixing the colorless liquid with acetone to obtain a mixture; E. stirring, dropping colorless liquid into the clear viscous liquid, stirring at normal temperature, dropping the mixture, stirring, filtering, washing, and drying to obtain betaine type zwitterion. The invention has mild and stable reaction conditions and high product purity.)

1. The synthetic method of the betaine type zwitterion is characterized by comprising the following steps of:

A. adding dimethylaminoethyl methacrylate or dimethylaminopropyl acrylamide into a reactor, adding acetic acid into the reactor at the speed of (1-2) g/min, cooling to 0-15 ℃ in an ice bath, dropwise adding acrylic acid, completing dropwise adding within 30min, and stirring at normal temperature for 16-32h under the condition of keeping out of the sun to obtain clear viscous liquid for later use;

B. under the condition of nitrogen, adding ethylene glycol monomethyl ether, pyridine and dichloromethane into a container, dropwise adding methane sulfonyl chloride under ice bath, reacting for 8-12h, performing suction filtration, performing reduced pressure distillation on filtrate, and removing dichloromethane and excessive pyridine to obtain light yellow transparent liquid for later use;

C. adding sodium into dichloromethane under the condition of nitrogen, heating the oil bath until the sodium is molten, removing the oil bath, stirring to room temperature, then adding 2-dimethylaminoethanol at the speed of (0.5-0.6) ml/min under an ice bath, reacting at normal temperature for 20-30min after the dropwise addition is finished, then dropwise adding the light yellow transparent liquid obtained in the step B at the speed of (0.5-0.6) ml/min under the ice bath, reacting at room temperature for 16-18h, adding water, separating, washing and drying an organic phase, distilling under reduced pressure, and removing dichloromethane to obtain a colorless liquid for later use;

D. c, mixing the colorless liquid prepared in the step C with acetone according to the volume ratio of 1:2 to obtain a mixture;

E. and C, under the stirring condition, dropwise adding the colorless liquid prepared in the step C into the clear viscous liquid obtained in the step A to obtain a mixed liquid, wherein the dropwise adding time is 20-30min, then stirring at normal temperature for 30-40min, then dropwise adding the mixture into the mixed liquid within 0.5-1.5h, stirring for 20-30min, filtering and collecting white crystals, washing, and drying to obtain the betaine type zwitterion.

2. The method for synthesizing betaine type zwitterions according to claim 1, wherein the obtained betaine type zwitterions are dissolved in methanol, and the step E is repeated to obtain a refined betaine type zwitterion.

3. The method for synthesizing betaine type zwitterions according to claim 1, wherein the molar ratio of dimethylaminoethyl methacrylate or dimethylaminopropyl acrylamide to acrylic acid is 1: (0.8-1.2).

4. The method for synthesizing betaine type zwitterions according to claim 1, wherein the molar ratio of acetic acid to dimethylaminoethyl methacrylate or dimethylaminopropyl acrylamide is (0.8-1.2): 1.

5. the method for synthesizing betaine-type zwitterions according to claim 1, wherein in the step B, the mass ratio of ethylene glycol monomethyl ether to pyridine to methane sulfonyl chloride is 1: (1.1-1.2): (1.5-1.7).

6. The method for synthesizing betaine-type zwitterions according to claim 1, wherein in the step C, the mass ratio of sodium to 2-dimethylaminoethanol to the light yellow transparent liquid is 1: (3.5-4): (6-6.5).

7. The method for synthesizing betaine-type zwitterions according to claim 1, wherein the amount of the colorless liquid used in step E is 3.8 to 4.5 times by volume based on the mass of acetic acid.

8. The method for synthesizing betaine-type zwitterions according to claim 1, wherein in step E, the amount of the mixture is 16 to 20 times by volume based on the mass of acetic acid.

9. The method of claim 2, wherein the amount of methanol is 1.4-2 times the volume of the betaine type zwitterion.

Technical Field

The invention belongs to the technical field of compound synthesis, and particularly relates to a synthesis method of betaine type zwitterions.

Background

The biological pollution refers to the action that protein, bacteria, algae and the like are adsorbed and aggregated on the surface of the material to influence the performance of the material. The reduction of biological pollution is essential to the actual life. The U.S. naval research institute states that biofouling can increase the sailing resistance by more than 60% and reduce the sailing speed of ships by 10%, which for the U.S. naval means that additional billions of dollars will be required for unplanned fuel and maintenance; uremia patients need to regularly carry out hemodialysis, if proteins in blood adhere to a pipeline or a dialysis device in the process, the flux of the device is reduced, and the blood can be coagulated in vitro, so that the life safety of people is threatened; in addition, biological contamination such as contact lenses, medical implant devices, medical diagnostic devices, and the like can also have adverse effects on human life and physical health. These problems urgently require us to develop new materials or modify existing materials to prevent the occurrence of biological contamination.

At present, polyethylene glycol (PEG) and derivatives thereof are the most applied anti-biological pollution materials, but researches show that PEG is easily affected by oxidation and can be decomposed in the environment with oxygen and transition metal ions (namely most of solutions related to biochemistry); at 35 ℃, the protein adsorption resistance function of the PEG polymer brush disappears, and the long-term stability is poor. The betaine type zwitterion-based material discovered in recent years is widely applied to the fields of biomedical materials, petroleum industry, sewage treatment, textile printing and dyeing and the like by people by virtue of the characteristics of good chemical performance, strong biological pollution resistance, strong hydration capability, difficulty in being influenced by the pH value of a solution and the like, so that the development of life science, energy development and utilization and the like are rapidly realized. In particular, according to research, the polymerizable zwitterionic monomers 3- [ [2- (methacryloyloxy) ethyl ] dimethyl ammonium ] propionate and 3- [ (3-acrylamidopropyl) dimethyl ammonium ] propionate play a vital role in synthesizing the betaine polymer, and have extremely high application value. However, the conventional method has high cost to prepare the zwitterionic monomer, and limits the large-scale industrial application of the zwitterionic monomer, so that the method has extremely practical application value.

Disclosure of Invention

The invention aims to provide a synthesis method of betaine type zwitterion, which is simple, low in cost, mild and stable in reaction condition and high in product purity.

The technical scheme adopted by the invention for realizing the purpose is as follows:

the synthesis method of the betaine type zwitterion comprises the following steps:

A. adding dimethylaminoethyl methacrylate or dimethylaminopropyl acrylamide into a reactor, adding acetic acid into the reactor at the speed of (1-2) g/min, cooling to 0-15 ℃ in an ice bath, dropwise adding acrylic acid, completing dropwise adding within 30min, and stirring at normal temperature for 16-32h under the condition of keeping out of the sun to obtain clear viscous liquid for later use;

B. under the condition of nitrogen, adding ethylene glycol monomethyl ether, pyridine and dichloromethane into a container, dropwise adding methane sulfonyl chloride under ice bath, reacting for 8-12h, performing suction filtration, performing reduced pressure distillation on filtrate, and removing dichloromethane and excessive pyridine to obtain light yellow transparent liquid for later use;

C. adding sodium into dichloromethane under the condition of nitrogen, heating the oil bath until the sodium is molten, removing the oil bath, stirring to room temperature, then adding 2-dimethylaminoethanol at the speed of (0.5-0.6) ml/min under an ice bath, reacting at normal temperature for 20-30min after the dropwise addition is finished, then dropwise adding the light yellow transparent liquid obtained in the step B at the speed of (0.5-0.6) ml/min under the ice bath, reacting at room temperature for 16-18h, adding water, separating, washing and drying an organic phase, distilling under reduced pressure, and removing dichloromethane to obtain a colorless liquid for later use;

D. c, mixing the colorless liquid prepared in the step C with acetone according to the volume ratio of 1:2 to obtain a mixture;

E. and C, under the stirring condition, dropwise adding the colorless liquid prepared in the step C into the clear viscous liquid obtained in the step A to obtain a mixed liquid, wherein the dropwise adding time is 20-30min, then stirring at normal temperature for 30-40min, then dropwise adding the mixture into the mixed liquid within 0.5-1.5h, stirring for 20-30min, filtering and collecting white crystals, washing, and drying to obtain the betaine type zwitterion.

And E, dissolving the obtained betaine type zwitterion in methanol, and repeating the step E to obtain the refined betaine type zwitterion.

The mol ratio of the dimethylaminoethyl methacrylate or the dimethylaminopropyl acrylamide to the acrylic acid is 1: (0.8-1.2).

The molar ratio of the acetic acid to the dimethylaminoethyl methacrylate or dimethylaminopropyl acrylamide is (0.8-1.2): 1.

in the step B, the mass ratio of ethylene glycol monomethyl ether, pyridine and methane sulfonyl chloride is 1: (1.1-1.2): (1.5-1.7).

In the step C, the mass ratio of sodium to 2-dimethylaminoethanol to the light yellow transparent liquid is 1: (3.5-4): (6-6.5).

The amount of the colorless liquid used in step E is 3.8-4.5 times the volume of the acetic acid.

In step E, the amount of the mixture is 16 to 20 times by volume based on the mass of acetic acid.

The dosage of the methanol is 1.4-2 times of the volume of the betaine type zwitterion.

The invention has the beneficial effects that:

the raw materials used in the invention are cheap and easily available, the reaction conditions are mild and stable, and the product purity is high.

Drawings

FIG. 1 is a 1H diagram of the synthesis of 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate according to the invention.

FIG. 2 is a 13C diagram of the synthesis of 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate according to the invention.

FIG. 3 is a 1H map of the present invention for the synthesis of 3- [ (3-acrylamidopropyl) dimethylammonium ] propionate.

FIG. 4 is a 13C map of the synthesized 3- [ (3-acrylamidopropyl) dimethylammonium ] propionate of the present invention.

Detailed Description

The present invention will be further described with reference to the following examples.