阅读说明：本技术 丙烯酰-n-甲基取代甘氨酰胺单体及其制备方法 (acryloyl-N-methyl substituted glycinamide monomer and preparation method thereof ) 是由 刘文广 张卓丹 杨建海 于 2019-09-26 设计创作，主要内容包括：本发明公开了一种丙烯酰-N-甲基取代甘氨酰胺单体及其制备方法。具体地说,是以N-甲基甘氨酰胺盐酸盐或N,N-二甲基甘酰胺盐酸盐和丙烯酰氯为原料,在一定的条件下反应生成丙烯酰-N-甲基甘氨酰胺或丙烯酰-N,N-二甲基甘氨酰胺。丙烯酰-N-甲基甘氨酰胺和丙烯酰-N,N-二甲基甘氨酰胺同时带有双键和两个酰胺基团。双键可进行自由基聚合,酰胺基团可以形成氢键,因此合成的单体可以聚合形成多重氢键交联的聚合物,从而获得新型的聚合物材料,在生物工程领域有着潜在的应用价值。(The invention discloses an acryloyl-N-methyl substituted glycinamide monomer and a preparation method thereof. Specifically, N-methylglycinamide hydrochloride or N, N-dimethylglycinamide hydrochloride and acryloyl chloride are used as raw materials and react under certain conditions to generate acryloyl-N-methylglycinamide or acryloyl-N, N-dimethylglycinamide. acryloyl-N-methylglycinamides and acryloyl-N, N-dimethylglycinamides bear both a double bond and two amide groups. The double bonds can be subjected to free radical polymerization, and the amide groups can form hydrogen bonds, so that the synthesized monomer can be polymerized to form a polymer crosslinked by multiple hydrogen bonds, thereby obtaining a novel polymer material, and having potential application value in the field of bioengineering.)

1. An acryloyl-N-methyl substituted glycinamide monomer, which is characterized in that: having a molecular structure shown below

Wherein R is-CH₃R' is H or-CH₃。

2. A preparation method of an acryloyl-N-methyl substituted glycinamide monomer is characterized by comprising the following steps: the method comprises the following steps:

adding N-methylglycinamide hydrochloride or N, N-dimethylglycinamide hydrochloride into water, adding a potassium carbonate solution and diethyl ether, adding an ethyl ether solution of acryloyl chloride into the mixed solution under the ice bath condition, and continuously stirring in the ice bath to enable an amino group of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride to react with chloride ions of the acryloyl chloride to generate acryloyl chloride-N-methyl substituted glycinamide, wherein the molar ratio of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride, the potassium carbonate and the acryloyl chloride is 1: (1-1.5): (1-1.5).

3. The process for preparing an acryloyl-N-methyl substituted glycinamide monomer according to claim 2, characterized in that: in the mixed solution of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride, the potassium carbonate and the diethyl ether, the volume ratio of the solvent water to the potassium carbonate solution to the diethyl ether is 3:20: 18; the concentration of the potassium carbonate solution was 20 wt%.

4. The process for preparing an acryloyl-N-methyl substituted glycinamide monomer according to claim 2, characterized in that: in the acryloyl chloride solution, the volume ratio of acryloyl chloride to diethyl ether is 11: 48.

5. The process for preparing an acryloyl-N-methyl substituted glycinamide monomer according to claim 2, characterized in that: the reaction system is reacted for 3 to 5 hours, preferably 4 hours under the ice bath condition of 0 to 5 ℃.

6. The process for preparing an acryloyl-N-methyl substituted glycinamide monomer according to claim 2, characterized in that: after the reaction is finished, adding a hydrochloric acid solution to adjust the pH of the water layer to acidity, then washing the water layer by using ether, then adding a sodium hydroxide solution to adjust the pH of the solution to neutrality, and freeze-drying; and fully dissolving the solid obtained by freeze-drying in a mixed solvent of ethanol and methanol, carrying out suction filtration, carrying out rotary evaporation on the concentrated filtrate, cooling and recrystallizing the concentrated solution, carrying out suction filtration, and drying the solid to obtain the final product.

7. The process for preparing an acryloyl-N-methyl-substituted glycinamide monomer according to claim 6, characterized in that: after the reaction, hydrochloric acid solution was added to adjust the pH of the aqueous layer to 2.

8. The process for preparing an acryloyl-N-methyl-substituted glycinamide monomer according to claim 6, characterized in that: and in the mixed solvent of the ethanol and the methanol, the volume ratio of the ethanol to the methanol is 4:1, and the solid obtained by freeze-drying is dissolved in the mixed solvent of the ethanol and the methanol and stirred for 3-5 h.

9. The process for preparing an acryloyl-N-methyl-substituted glycinamide monomer according to claim 6, characterized in that: and (3) after cooling and recrystallization, carrying out suction filtration to obtain a solid, and drying in a constant-temperature drying oven at 37 ℃.

Technical Field

The invention relates to an acryloyl-N-methyl substituted glycinamide monomer and a preparation method thereof, in particular to acryloyl-N-methyl glycinamide or acryloyl-N, N-dimethyl glycinamide generated by the reaction between N-methyl glycinamide hydrochloride or N, N-dimethyl glycinamide hydrochloride and acryloyl chloride under certain conditions.

Background

N-acryloyl glycinamide (NAGA) is a novel monomer, which can be prepared by a one-step reaction of glycyl amine hydrochloride and acryloyl chloride. One NAGA molecule contains two amide groups, which are easy to form hydrogen bonds between molecules. High strength poly (N-acryloyl glycinamide) hydrogels can be prepared by simple free radical reactions in aqueous solution without additional addition of other cross-linking agents. The side chain of the poly (N-acryloyl glycinamide) molecular chain is provided with two amide groups, and multiple hydrogen bonds exist between molecules and in molecules, so that the physical crosslinking hydrogel is formed. The poly (N-acryloyl glycinamide) hydrogel has thermoplasticity at high temperature and higher mechanical strength due to reversibility of multiple hydrogen bond actions, and has great application potential in the field of materials.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides an acryloyl-N-methyl substituted glycinamide monomer and a preparation method thereof.

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

The invention relates to an acryloyl-N-methyl substituted glycinamide monomer and a preparation method thereof, which are carried out according to the following steps:

adding N-methylglycinamide hydrochloride or N, N-dimethylglycinamide hydrochloride into water, adding a potassium carbonate solution and diethyl ether, adding an ethyl ether solution of acryloyl chloride into the mixed solution under the ice bath condition, and continuously stirring in the ice bath to enable an amino group of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride to react with chloride ions of the acryloyl chloride to generate acryloyl chloride-N-methyl substituted glycinamide, wherein the molar ratio of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride, the potassium carbonate and the acryloyl chloride is 1: (1-1.5): (1-1.5).

In the mixed solution of the N-methylglycinamide hydrochloride or the N, N-dimethylglycinamide hydrochloride, the potassium carbonate and the diethyl ether, the volume ratio of the solvent water to the potassium carbonate solution to the diethyl ether is 3:20: 18; the concentration of the potassium carbonate solution was 20 wt%.

In the acryloyl chloride solution, the volume ratio of acryloyl chloride to diethyl ether is 11: 48.

The reaction system is reacted for 3 to 5 hours, preferably 4 hours under the ice bath condition of 0 to 5 ℃.

After the reaction is finished, adding a hydrochloric acid solution to adjust the pH of the water layer to acidity, then washing the water layer by using ether, then adding a sodium hydroxide solution to adjust the pH of the solution to neutrality, and freeze-drying; and fully dissolving the solid obtained by freeze-drying in a mixed solvent of ethanol and methanol, carrying out suction filtration, carrying out rotary evaporation on the concentrated filtrate, cooling and recrystallizing the concentrated solution, carrying out suction filtration, and drying the solid to obtain the final product.

After the reaction, hydrochloric acid solution was added to adjust the pH of the aqueous layer to 2.

And in the mixed solvent of the ethanol and the methanol, the volume ratio of the ethanol to the methanol is 4:1, and the solid obtained by freeze-drying is dissolved in the mixed solvent of the ethanol and the methanol and stirred for 3-5 h.

And (3) after cooling and recrystallization, carrying out suction filtration to obtain a solid, and drying in a constant-temperature drying oven at 37 ℃.

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

The invention has the beneficial effects that: the invention relates to an acryloyl-N-methyl substituted glycinamide monomer and a preparation method thereof, which takes N-methyl glycinamide hydrochloride or N, N-dimethyl glycinamide hydrochloride and acryloyl chloride as raw materials, and reacts under certain conditions to generate acryloyl-N-methyl glycinamide or acryloyl-N, N-dimethyl glycinamide, namely acryloyl-N-methyl substituted glycinamide, wherein the newly generated acryloyl-N-methyl substituted glycinamide monomer carries out methyl mono-substitution or di-substitution on a nitrogen atom at the tail end of N-acryloyl glycinamide (NAGA), and the monomer has double bonds so as to carry out free radical polymerization; meanwhile, the newly generated acryloyl-N-methyl substituted glycinamide monomer has two amide groups and can provide a double hydrogen bond structure, and the double hydrogen bond structure enables multiple hydrogen bond actions among and in polymer molecules; in addition, the existence of one or two methyl groups on the side chain can influence the structure and the strength of hydrogen bonds of the polymer, further influence various properties of the polymer hydrogel, and have great potential in the field of biomedical materials.

Drawings

FIG. 1 shows the preparation of acryloyl-N-methylglycinamide 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

Step 1, preparing the instruments needed by the experiment, cleaning a round-bottom flask, a beaker and magnetons used for reaction, and drying in an oven. A100 ml measuring cylinder and a glass vial were washed and dried in the same manner. A round bottom flask was charged with 12.5g N-methylglycinamide hydrochloride, 12ml water.

And 2, preparing the crushed ice in advance, putting the crushed ice into an aluminum basin, adding a proper amount of water, and using the mixture as an ice bath reaction. 20g of potassium carbonate solid was weighed on a tray balance and poured into a beaker. 80ml of water is weighed out, poured into the weighed potassium carbonate solid and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask and stirred well. 72ml of diethyl ether was measured and added to the system, and the mixture was subjected to ice-bath.

Step 3, adding 48ml of diethyl ether and 11ml of acryloyl chloride into a constant pressure funnel, and dropwise adding into a round-bottom flask. After the addition, the reaction was carried out in an ice bath for 4 hours. .

And 4, after the reaction is finished, adjusting the pH value of the reaction solution by using 6mol/L HCl so as to enable the pH value to be 2.

And 5, separating the ether from the aqueous solution by using a separating funnel, and collecting the aqueous solution at the lower layer. The aqueous solution obtained by separation was washed three times with ether. Subsequently, the reaction solution was adjusted to pH 7 with NaOH solution. Lyophilization afforded a white solid.

And 6, dissolving the solid obtained after the solution obtained in the last week is freeze-dried in 500ml of mixed solution of ethanol and methanol. Wherein the volume ratio of ethanol to methanol is 4:1, stirring for 3 to 5 hours.

And 7, carrying out suction filtration to remove inorganic salts which are insoluble in the mixed solution of ethanol and methanol. And (4) adopting a vacuum rotary evaporator, removing most of the solvent by rotary evaporation, pouring the remaining solution into a dry beaker, sealing, putting into a refrigerator, and cooling and recrystallizing.

And 8, when a large amount of precipitated solids appear in the beaker, performing suction filtration to separate white solids, and placing the white solids in a constant-temperature drying oven at 37 ℃ for drying to obtain a final product.

Example 2

Step 1, preparing the instruments needed by the experiment, cleaning a round-bottom flask, a beaker and magnetons used for reaction, and drying in an oven. A100 ml measuring cylinder and a glass vial were washed and dried in the same manner. 6.3g N-methylglycinamide hydrochloride, 6ml of water were added to the round bottom flask.

And 2, preparing the crushed ice in advance, putting the crushed ice into an aluminum basin, adding a proper amount of water, and using the mixture as an ice bath reaction. 10g of potassium carbonate solid was weighed on a tray balance and poured into a beaker. 40ml of water are weighed out and poured into the weighed potassium carbonate solid, and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask and stirred well. 36ml of diethyl ether was measured and added to the above system, and the mixture was subjected to ice-bath.

Step 3, add 24ml of ether, 5.5ml of acryloyl chloride to the constant pressure funnel and add dropwise to the round bottom flask. After the addition, the reaction was carried out in an ice bath for 4 hours. .

And 4, after the reaction is finished, adjusting the pH value of the reaction solution by using 6mol/L HCl so as to enable the pH value to be 2.

And 5, separating the ether from the aqueous solution by using a separating funnel, and collecting the aqueous solution at the lower layer. The aqueous solution obtained by separation was washed three times with ether. Subsequently, the reaction solution was adjusted to pH 7 with NaOH solution. Lyophilization afforded a white solid.

And 6, dissolving the solid obtained after the solution obtained in the last week is freeze-dried in 250ml of mixed solution of ethanol and methanol. Wherein the volume ratio of ethanol to methanol is 4:1, stirring for 3 to 5 hours.

And 7, carrying out suction filtration to remove inorganic salts which are insoluble in the mixed solution of ethanol and methanol. And (4) adopting a vacuum rotary evaporator, removing most of the solvent by rotary evaporation, pouring the remaining solution into a dry beaker, sealing, putting into a refrigerator, and cooling and recrystallizing.

And 8, when a large amount of precipitated solids appear in the beaker, performing suction filtration to separate white solids, and placing the white solids in a constant-temperature drying oven at 37 ℃ for drying to obtain a final product.

Example 3

Step 1, preparing the instruments needed by the experiment, cleaning a round-bottom flask, a beaker and magnetons used for reaction, and drying in an oven. A100 ml measuring cylinder and a glass vial were washed and dried in the same manner. A round bottom flask was charged with 25g N-methylglycinamide hydrochloride, 24ml water.

And 2, preparing the crushed ice in advance, putting the crushed ice into an aluminum basin, adding a proper amount of water, and using the mixture as an ice bath reaction. 40g of potassium carbonate solid was weighed on a tray balance and poured into a beaker. 160ml of water is measured and poured into the weighed solid potassium carbonate, and the mixture is stirred until the mixture is dissolved. The potassium carbonate solution was poured into the round bottom flask and stirred well. 144ml of diethyl ether was measured and added to the system and subjected to ice-bath.

Step 3, adding 96ml of diethyl ether and 22ml of acryloyl chloride into a constant pressure funnel, and dropwise adding into a round-bottom flask. After the addition, the reaction was carried out in an ice bath for 4 hours. .

And 4, after the reaction is finished, adjusting the pH value of the reaction solution by using 6mol/L HCl so as to enable the pH value to be 2.

And 5, separating the ether from the aqueous solution by using a separating funnel, and collecting the aqueous solution at the lower layer. The aqueous solution obtained by separation was washed three times with ether. Subsequently, the reaction solution was adjusted to pH 7 with NaOH solution. Lyophilization afforded a white solid.

And 6, dissolving the solid obtained after the solution obtained in the last week is freeze-dried in 1000ml of mixed solution of ethanol and methanol. Wherein the volume ratio of ethanol to methanol is 4:1, stirring for 3 to 5 hours.

And 7, carrying out suction filtration to remove inorganic salts which are insoluble in the mixed solution of ethanol and methanol. And (4) adopting a vacuum rotary evaporator, removing most of the solvent by rotary evaporation, pouring the remaining solution into a dry beaker, sealing, putting into a refrigerator, and cooling and recrystallizing.

And 8, when a large amount of precipitated solids appear in the beaker, performing suction filtration to separate white solids, and placing the white solids in a constant-temperature drying oven at 37 ℃ for drying to obtain a final product.

Example 4

Step 1, preparing the instruments needed by the experiment, cleaning a round-bottom flask, a beaker and magnetons used for reaction, and drying in an oven. A100 ml measuring cylinder and a glass vial were washed and dried in the same manner. 13.9g N, N-dimethylglycinamide hydrochloride and 12ml of water were added to the round bottom flask.

And 2, preparing the crushed ice in advance, putting the crushed ice into an aluminum basin, adding a proper amount of water, and using the mixture as an ice bath reaction. 20g of potassium carbonate solid was weighed on a tray balance and poured into a beaker. 80ml of water is weighed out, poured into the weighed potassium carbonate solid and stirred until dissolved. The potassium carbonate solution was poured into the round bottom flask and stirred well. 72ml of diethyl ether was measured and added to the system, and the mixture was subjected to ice-bath.

Step 3, adding 48ml of diethyl ether and 11ml of acryloyl chloride into a constant pressure funnel, and dropwise adding into a round-bottom flask. After the addition, the reaction was carried out in an ice bath for 4 hours. .

And 4, after the reaction is finished, adjusting the pH value of the reaction solution by using 6mol/L HCl so as to enable the pH value to be 2.

And 5, separating the ether from the aqueous solution by using a separating funnel, and collecting the aqueous solution at the lower layer. The aqueous solution obtained by separation was washed three times with ether. Subsequently, the reaction solution was adjusted to pH 7 with NaOH solution. Lyophilization afforded a white solid.

And 6, dissolving the solid obtained after the solution obtained in the last week is freeze-dried in 500ml of mixed solution of ethanol and methanol. Wherein the volume ratio of ethanol to methanol is 4:1, stirring for 3 to 5 hours.

And 7, carrying out suction filtration to remove inorganic salts which are insoluble in the mixed solution of ethanol and methanol. And (4) adopting a vacuum rotary evaporator, removing most of the solvent by rotary evaporation, pouring the remaining solution into a dry beaker, sealing, putting into a refrigerator, and cooling and recrystallizing.

And 8, when a large amount of precipitated solids appear in the beaker, performing suction filtration to separate white solids, and placing the white solids in a constant-temperature drying oven at 37 ℃ for drying to obtain a final product.

By using¹The chemical structure of acryloyl-N-methylglycinamide prepared in the examples of the present invention was characterized by H NMR, and it is apparent from FIG. 1 that absorption peaks at 6.24ppm, 6.02ppm and 5.54ppm of hydrogen atoms on the double bond of acryloyl-N-methylglycinamide, absorption peaks at 8.39ppm and 7.86ppm of hydrogen atoms on the amide group, an absorption peak at 2.50ppm of hydrogen atoms on the methyl group and an absorption peak at 3.67ppm of hydrogen atoms on the methine group are observed, thereby proving that two amide groups, a double bond and a methyl group are indeed present, well characterizing the structure of acryloyl-N-methylglycinamide, thereby proving that acryloyl-N-methylglycinamide is successfully synthesized.

The preparation of the acryloyl-N-methyl substituted glycinamide monomer can be realized by adjusting the process parameters according to the content of the invention, and the performance basically consistent with the embodiment of the invention is shown.

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.