阅读说明：本技术 N,n′-二丙烯酰赖氨酸化合物及其制备方法 (N, N' -diacryloyl lysine compound and preparation method thereof ) 是由 刘文广 吕远宁 杨建海 于 2019-09-25 设计创作，主要内容包括：本发明公开了一种N,N’-二丙烯酰赖氨酸及其制备方法,具体地说,是以赖氨酸和丙烯酰氯为原料,在一定的条件下反应生成N,N’-二丙烯酰赖氨酸。N,N’-二丙烯酰赖氨酸带有两个双键和一个羧基基团,两个双键可进行自由基聚合,从而可以作为交联剂使用,此外因携带羧基,所以参与聚合后得到的聚合物具备一定黏性,在生物医用粘附领域有着潜在的应用价值。(The invention discloses N, N '-diacryloyl lysine and a preparation method thereof, and particularly relates to N, N' -diacryloyl lysine which is prepared by reacting lysine and acryloyl chloride serving as raw materials under certain conditions. The N, N ' -diacryloyl lysine has two double bonds and a carboxyl group, the two double bonds can be subjected to free radical polymerization, so that the N, N ' -diacryloyl lysine can be used as a cross-linking agent, and in addition, the N, N ' -diacryloyl lysine carries carboxyl, so that the polymer obtained after the polymerization has certain viscosity, and has potential application value in the field of biomedical adhesion.)

1. An N, N' -diacryloyl lysine compound, characterized in that: having a molecular structure shown below

2. A method for preparing an N, N' -diacryloyl lysine compound is characterized in that: the method comprises the following steps: uniformly dispersing a lysine and potassium carbonate solution in a mixed solvent of water and an organic solvent, uniformly dispersing acryloyl chloride in the organic solvent, adding the acryloyl chloride solution into the mixed solution of lysine and potassium carbonate in an ice bath for reaction, so that an amino group of lysine reacts with a chloride ion of the acryloyl chloride to generate N, N' -diacryloyl lysine, wherein the molar ratio of lysine acryloyl chloride is 1: (2-3), the mass ratio of the solvent water to the lysine is (1-3) to 1, the volume ratio of the potassium carbonate solution to the solvent water is (4-8) to 1, and the mass fraction of the potassium carbonate solution is 15-20%.

3. The process for producing an N, N' -diacryloyl lysine compound according to claim 2, characterized in that: the volume ratio of the organic solvent to the water in the mixed solvent is (3-5):1, and the volume ratio of the organic solvent for diluting the acryloyl chloride to the acryloyl chloride is (1-2): 1.

4. The process for producing an N, N' -diacryloyl lysine compound according to claim 2, characterized in that: the organic solvent is dichloromethane, diethyl ether, petroleum ether, chloroform, tetrahydrofuran or toluene, preferably diethyl ether.

5. The process for producing an N, N' -diacryloyl lysine compound according to claim 2, characterized in that: and dropwise adding the acryloyl chloride solution into the mixed solution of the lysine and the potassium carbonate in an ice bath at 0-10 ℃, and reacting for 1-6h in the ice bath at 0-10 ℃.

6. The process for producing an N, N' -diacryloyl lysine compound according to claim 2, characterized in that: after the reaction is finished, adding a sodium hydroxide solution into the reaction system to adjust the pH value of a water layer to 9-10, then washing the water layer by using ethyl acetate, leaving a water phase, adding a hydrochloric acid solution into the water phase to adjust the pH value to 2-4, then extracting by using ethyl acetate, adding anhydrous magnesium sulfate into an extract liquid, drying overnight, filtering, and finally performing rotary evaporation on the filtrate.

7. The process for producing an N, N' -diacryloyl lysine compound according to claim 6, characterized in that: the concentration of the sodium hydroxide solution is 0.1-2 mol/L.

8. The process for producing an N, N' -diacryloyl lysine compound according to claim 6, characterized in that: the concentration of the hydrochloric acid solution is 1-6 mol/L.

9. The process for producing an N, N' -diacryloyl lysine compound according to claim 6, characterized in that: the volume ratio of the ethyl acetate extract to the solvent water in the reaction system is not less than 10: 1.

Technical Field

The invention relates to an N, N '-diacryloyl lysine compound and a preparation method thereof, in particular to a method for generating N, N' -diacryloyl lysine by utilizing the reaction between lysine and acryloyl chloride under certain conditions.

Background

The multiple double bond type chemical cross-linking agent contains two or more double bonds, and in free radical polymerization, a plurality of double bonds participate in polymerization at the same time to form a cross-linking network, which is a common cross-linking means for constructing a polymer system. Plays an important role in regulating and controlling the properties of three-dimensional structure such as formability, mechanical property, porosity and the like.

Lysine is an amino acid containing two amino groups, and a series of new monomers can be obtained by designing a reaction with the amino groups. The carboxyl group contained in itself can exhibit tackiness by interacting with a metal ion by chelation or hydrogen bonding, and can enhance the adhesion of the polymer.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides an N, N' -diacryloyl lysine compound and a preparation method thereof.

The technical purpose of the invention is realized by the following technical scheme.

The invention relates to an N, N' -diacryloyl lysine compound and a preparation method thereof, which are carried out according to the following steps:

uniformly dispersing a lysine and potassium carbonate solution in a mixed solvent of water and an organic solvent, uniformly dispersing acryloyl chloride in the organic solvent, adding the acryloyl chloride solution into the mixed solution of lysine and potassium carbonate in an ice bath for reaction, so that an amino group of lysine reacts with a chloride ion of the acryloyl chloride to generate N, N' -diacryloyl lysine, wherein the molar ratio of lysine acryloyl chloride is 1: (2-3), the mass ratio of the solvent water to the lysine is (1-3) to 1, the volume ratio of the potassium carbonate solution to the solvent water is (4-8) to 1, and the mass fraction of the potassium carbonate solution is 15-20%.

The volume ratio of the organic solvent to the water in the mixed solvent is (3-5):1, and the volume ratio of the organic solvent for diluting the acryloyl chloride to the acryloyl chloride is (1-2): 1.

The organic solvent is dichloromethane, diethyl ether, petroleum ether, chloroform, tetrahydrofuran or toluene, preferably diethyl ether.

And dropwise adding the acryloyl chloride solution into the mixed solution of the lysine and the potassium carbonate in an ice bath at 0-10 ℃, and reacting for 1-6h in the ice bath at 0-10 ℃.

After the reaction is finished, adding a sodium hydroxide solution into the reaction system to adjust the pH value of a water layer to 9-10, then washing the water layer by using ethyl acetate, leaving a water phase, adding a hydrochloric acid solution into the water phase to adjust the pH value to 2-4, then extracting by using ethyl acetate, adding anhydrous magnesium sulfate into an extract liquid, drying overnight, filtering, and finally performing rotary evaporation on the filtrate.

The concentration of the sodium hydroxide solution is 0.1-2 mol/L.

The concentration of the hydrochloric acid solution is 1-6 mol/L.

The volume ratio of the ethyl acetate extract to the solvent water in the reaction system is not less than 10: 1.

The chemical reactions involved in the present invention are carried out according to the following chemical reaction formulae.

Compared with the prior art, the invention has the beneficial effects that: according to the invention, lysine and acryloyl chloride are used as raw materials, and react at 0-10 ℃, and acryloyl chloride is disubstituted for two amino groups on the lysine to obtain a new monomer N, N' -diacryloyl lysine, wherein the monomer has two double bonds and can be used as a free radical polymerization cross-linking agent to enhance the mechanical strength of a polymer; in addition, the existence of carboxyl groups can enhance the viscosity of the polymer and broaden the application range, and the polymer obtained after polymerization has viscosity due to the carboxyl groups, so that the polymer can be used for enhancing the viscosity and the mechanical property of a medical adhesive material; the invention has the advantages of less synthesis byproducts, high yield, simple synthesis method, simple and efficient purification process and contribution to industrial mass production.

Drawings

FIG. 1 shows the preparation of N, N' -diacryloyl lysine according to the invention¹H-NMR spectrum.

Detailed Description

The following is a further description of the invention and is not intended to limit the scope of the invention.

Example 1

To a round-bottomed flask were added 3.75g of lysine and 5ml of water, and the reaction was stirred in an ice bath at 4 ℃. 7.5g of potassium carbonate solid is weighed, 40ml of water is weighed out and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask described above. 15ml of diethyl ether were measured and added to the system. To a constant pressure funnel was added 10ml of diethyl ether, 9ml of acryloyl chloride and added dropwise to the round bottom flask. After the addition, the reaction was carried out in ice bath for 4 hours. After the reaction, the pH of the reaction mixture was adjusted to 9 with 2mol/L NaOH solution. The ether and aqueous solutions were separated with a separatory funnel and the lower aqueous layer was collected. The aqueous solution obtained by the separation was washed three times with ethyl acetate. Subsequently, the reaction solution was adjusted to pH 2 by using a 2mol/L hydrochloric acid solution to adjust the pH of the reaction solution. Extracting with 500ml ethyl acetate for many times, spreading a layer of anhydrous magnesium sulfate solid in the obtained organic phase solution, standing overnight, then performing suction filtration, and rotating the filtrate at low temperature to obtain the final product.

Example 2

7.5g of lysine and 10ml of water were added to a round-bottomed flask, and the reaction was stirred in an ice bath at 4 ℃. 15g of potassium carbonate solid is weighed, 80ml of water is weighed out and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask described above. 30ml of diethyl ether was measured and added to the system. 30ml of diethyl ether, 18ml of acryloyl chloride were added to a constant pressure funnel and added dropwise to the round bottom flask. After the dropwise addition, the reaction was carried out in ice bath for 6 hours. After the reaction, the pH of the reaction mixture was adjusted to 10 with 2mol/L NaOH solution. The ether and aqueous solutions were separated with a separatory funnel and the lower aqueous layer was collected. The aqueous solution obtained by the separation was washed three times with ethyl acetate. Subsequently, the reaction solution was adjusted to pH 3 with 6mol/L hydrochloric acid solution. Extracting with 800ml ethyl acetate for multiple times, spreading a layer of anhydrous magnesium sulfate solid in the obtained organic phase solution, standing overnight, then performing suction filtration, and rotating the filtrate at low temperature to obtain the final product.

Example 3

7.5g of lysine and 15ml of water were added to a round-bottomed flask, and the reaction was stirred in an ice bath at 10 ℃. 15g of potassium carbonate solid is weighed, 80ml of water is weighed out and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask described above. 30ml of diethyl ether was measured and added to the system. 40ml of diethyl ether, 18ml of acryloyl chloride were added to a constant pressure funnel and added dropwise to the round bottom flask. After the addition, the reaction was carried out in ice bath for 3 hours. After the completion of the reaction, the pH of the reaction mixture was adjusted to 9 with 0.1mol/L NaOH solution. The ether and aqueous solutions were separated with a separatory funnel and the lower aqueous layer was collected. The aqueous solution obtained by the separation was washed three times with ethyl acetate. Subsequently, the reaction solution was adjusted to pH 4 with 1mol/L hydrochloric acid solution. Extracting with 800ml ethyl acetate for multiple times, spreading a layer of anhydrous magnesium sulfate solid in the obtained organic phase solution, standing overnight, then performing suction filtration, and rotating the filtrate at low temperature to obtain the final product.

By using¹The chemical structure of the N, N '-diacryloyl lysine prepared by the invention is characterized by H NMR, and absorption peaks at 6.27ppm, 6.10ppm and 5.88ppm of hydrogen atoms on double bonds on the N, N' -diacryloyl lysine, absorption peaks at 12.24ppm of carboxyl groups, absorption peaks at 8.31ppm and 8.05ppm of hydrogen atoms on amide groups, absorption peaks at 3.08ppm, 1.99ppm, 1.89ppm and 1.18ppm of hydrogen atoms on methylene groups and absorption peaks at 4.01ppm of hydrogen atoms on methine groups can be obviously observed from FIG. 1, thereby proving that the double bonds, the carboxyl groups, the two amide groups and the methylene methine groups do exist, and well characterizing the structure of the N, N '-diacryloyl lysine, and further proving that the N, N' -diacryloyl lysine is successfully synthesized.

The preparation of the N, N '-diacryloyl lysine can be realized by adjusting the process parameters according to the content of the invention, and the performance of the N, N' -diacryloyl lysine is basically consistent with the embodiment of the invention.

The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.