阅读说明：本技术 一种活性苯丙烯酸/对氯苯甲酸蔗渣木聚糖双酯的合成方法 (Method for synthesizing active cinnamic acid/p-chlorobenzoic acid bagasse xylan diester ) 是由 李和平 杨锦武 葛文旭 李明坤 杨莹莹 张淑芬 郑光绿 耿恺 柴建啟 武晋雄 于 2019-10-22 设计创作，主要内容包括：本发明公开了一种活性苯丙烯酸/对氯苯甲酸蔗渣木聚糖双酯的合成方法。以蔗渣木聚糖为主要原料,苯丙烯酰氯为酯化剂,三乙胺为催化剂,首先在二氯甲烷溶剂中经酯化反应合成了蔗渣木聚糖苯丙烯酸酯；再以对氯苯甲酰氯为酯化剂,吡啶、732型强酸性阳离子交换树脂为复合催化剂,经过第二步强化酯化反应合成苯丙烯酸/对氯苯甲酸蔗渣木聚糖双酯。本发明通过两步酯化反应合成了最终产物苯丙烯酸/对氯苯甲酸蔗渣木聚糖双酯。所得目标产物不仅改善了原蔗渣木聚糖的理化性质,而且通过引入苯丙烯酸和对氯苯甲酸两种活性基团,大大增强了蔗渣木聚糖衍生物的抗HIV等活性。(The invention discloses a method for synthesizing active cinnamic acid/p-chlorobenzoic acid bagasse xylan diester. Bagasse xylan is used as a main raw material, phenyl acryloyl chloride is used as an esterifying agent, triethylamine is used as a catalyst, and bagasse xylan phenylacrylate is synthesized through an esterification reaction in a dichloromethane solvent; then takes p-chlorobenzoyl chloride as esterifying agent and pyridine, 732 type strong acid cation exchange resin as composite catalyst, and synthesizes cinnamic acid/p-chlorobenzoic acid bagasse xylan diester through the second step of intensified esterification reaction. The invention synthesizes the final product cinnamic acid/p-chlorobenzoic acid bagasse xylan diester through two esterification reactions. The obtained target product not only improves the physicochemical property of the original bagasse xylan, but also greatly enhances the anti-HIV activity of the bagasse xylan derivative by introducing two active groups, namely cinnamic acid and p-chlorobenzoic acid.)

1. A method for synthesizing active cinnamic acid/p-chlorobenzoic acid bagasse xylan diester is characterized by comprising the following steps:

(1) placing 15 ~ 20g of bagasse xylan into a vacuum constant-temperature drying oven at 50 ~ 60 ℃ for drying for 24 hours to obtain dry-based bagasse xylan;

(2) weighing 0.5 ~ 1.0.0 g of acryloyl chloride into a 50mL beaker, adding 15 ~ 30mL of analytically pure dichloromethane to obtain an esterifying agent solution, and pouring the esterifying agent solution into a 100mL constant-pressure dropping funnel for later use;

(3) weighing 2 ~ 5g of the dry bagasse xylan obtained in the step (1), placing the dry bagasse xylan into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, adding 20 ~ 30mL of analytically pure dichloromethane and 1 ~ 2mL of analytically pure triethylamine, and stirring at room temperature for 20 ~ 30 minutes to obtain a bagasse xylan activation solution;

(4) heating the system in the step (3) to 60 ~ 80 ℃, dropwise adding the esterifying agent solution obtained in the step (2) into a four-neck flask after the temperature is reached, controlling the dropwise adding time to be 10 ~ 30 minutes, continuously reacting for 1 ~ 2 hours after the dropwise adding of the esterifying agent solution is finished, and cooling the materials to room temperature;

(5) carrying out suction filtration on the material obtained in the step (4), sequentially washing and carrying out suction filtration by using 15 ~ 30mL of absolute ethyl alcohol, 30 ~ 40mL of analytically pure acetone and 20 ~ 30mL of deionized water respectively, and placing a filter cake in a constant-temperature vacuum drying oven at 50 ~ 60 ℃ for drying for 24 hours to obtain bagasse xylan phenylacrylate;

(6) sequentially adding 5 ~ 8g of p-chlorobenzoic acid and 20 ~ 40mL of 3% ~ 5% sodium hydroxide solution into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, and stirring at room temperature for 20 ~ 40 minutes to obtain a p-chlorobenzoic acid sodium salt solution;

(7) weighing 5 ~ 8g of bagasse xylan polyacrylate obtained in the step (5), adding the bagasse xylan polyacrylate into the p-chlorobenzoate solution system obtained in the step (6), stirring at room temperature for 30 ~ 60 minutes, adding 20 ~ 030mL of hydrochloric acid solution with the mass fraction of 3% and ~ 15% to adjust the pH of the reaction solution to 6 ~ 27, adding 1 ~ 1.5.5 mL of analytically pure pyridine and 0.2 ~ 0.4 and 0.4g of 732 type strongly acidic cation exchange resin, heating to 50 ~ 70 ℃, reacting under stirring for 5 ~ 7 hours, adjusting the pH of the system to 4 ~ 5 with 10 ~ 15mL of hydrochloric acid solution with the mass fraction of 3% and ~ 5% after the reaction is finished, cooling the material to room temperature, and continuing stirring for 30 ~ 60 minutes;

(8) pouring the material obtained in the step (7) into a 100mL beaker, adding 20 ~ 30mL of analytically pure absolute ethyl alcohol, precipitating for 30 ~ 40 minutes after uniformly stirring, filtering, washing with 10 ~ 15mL of deionized water and 10 ~ 15mL of analytically pure absolute ethyl alcohol respectively in sequence, performing suction filtration for 2 ~ 3 times, putting the filter cake into a watch glass, and drying in a vacuum constant-temperature drying oven at 50 ℃ for 24 hours to constant weight to obtain the product of the cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

Technical Field

The invention relates to the field of fine chemical engineering, in particular to a method for synthesizing active cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

Background

At present, the existence and development of human beings are seriously threatened by AIDS (HIV), and the solution is urgently needed. Domestic and foreign researches show that xylan is the main component of hemicellulose, has good biocompatibility and biodegradability, and also has immune stimulation behavior in the medical field. The xylan esterified derivative has obvious biological activities of inhibiting HIV, resisting virus, resisting blood coagulation and the like, and is a novel modified bioactive substance. Common esterification agents comprise organic acid, inorganic acid, acid anhydride, acyl chloride and the like, and the main products of research and synthesis comprise mono-esterified derivatives such as xylan sulfate, xylan benzoate, xylan caprate, xylan laurate and the like. Because the molecules of the xylan monoesterified derivative contain an anti-biological active group, the generated biological active effect is not ideal.

By carrying out two-step esterification modification on bagasse xylan, the xylan structurally has a phenylpropionate group and a parachlorobenzoate group at the same time, both groups have the effect of inhibiting the replication of viruses such as HIV (human immunodeficiency virus), and the obtained xylan diester derivative can greatly enhance the antiviral activity under the dual activity effect.

The method comprises the steps of taking bagasse xylan as a main raw material, phenyl acryloyl chloride as an esterifying agent and triethylamine as a catalyst, and synthesizing bagasse xylan phenylacrylate through esterification reaction in a dichloromethane solvent; then takes p-chlorobenzoyl chloride as esterifying agent and pyridine, 732 type strong acid cation exchange resin as composite catalyst, and synthesizes cinnamic acid/p-chlorobenzoic acid bagasse xylan diester through the second step of intensified esterification reaction.

Disclosure of Invention

The invention aims to enhance the biological activity of bagasse xylan, expand the application range of the bagasse xylan in the field of fine chemical engineering, and provide a method for synthesizing bagasse xylan cinnamic acid/p-chlorobenzoic acid diester with biological activity.

The method comprises the following specific steps:

(1) and (3) placing 15-20 g of bagasse xylan into a vacuum constant-temperature drying oven at 50-60 ℃ for drying for 24 hours to obtain the dry-based bagasse xylan.

(2) Weighing 0.5-1.0 g of acryloyl chloride into a 50mL beaker, adding 15-30 mL of analytically pure dichloromethane to obtain an esterifying agent solution, and pouring the esterifying agent solution into a 100mL constant-pressure dropping funnel for later use.

(3) Weighing 2-5 g of the dry bagasse xylan obtained in the step (1), placing the dry bagasse xylan into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, adding 20-30 mL of analytically pure dichloromethane and 1-2 mL of analytically pure triethylamine, and stirring at room temperature for 20-30 minutes to obtain the bagasse xylan activating solution.

(4) And (3) heating the system in the step (3) to 60-80 ℃, dropwise adding the esterifying agent solution obtained in the step (2) into a four-neck flask after the temperature is reached, and controlling the dropwise adding time to be 10-30 minutes. And after the esterification agent solution is dripped, continuously reacting for 1-2 hours, and cooling the material to room temperature.

(5) And (4) carrying out suction filtration on the material obtained in the step (4), and sequentially and respectively washing and carrying out suction filtration by using 15-30 mL of absolute ethyl alcohol, 30-40 mL of analytically pure acetone and 20-30 mL of deionized water. And (3) drying the filter cake in a constant-temperature vacuum drying oven at 50-60 ℃ for 24 hours to obtain the bagasse xylan phenylacrylate.

(6) Sequentially adding 5-8 g of p-chlorobenzoic acid and 20-40 mL of 3-5% sodium hydroxide solution by mass fraction into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, and stirring at room temperature for 20-40 minutes to obtain a p-chlorobenzoic sodium formate solution.

(7) And (3) weighing 5-8 g of bagasse xylan polyacrylate obtained in the step (5), adding the bagasse xylan polyacrylate into the p-chlorobenzoate sodium salt solution system obtained in the step (6), and stirring at room temperature for 30-60 minutes. Adding 20-30 mL of hydrochloric acid solution with the mass fraction of 3% -5% to adjust the pH of the reaction solution to 6-7, adding 1-1.5 mL of analytically pure pyridine and 0.2-0.4 g of 732 type strong-acid cation exchange resin, heating to 50-70 ℃, and reacting for 5-7 hours under stirring. And after the reaction is finished, adjusting the pH value of the system to 4-5 by using 10-15 mL of hydrochloric acid solution with the mass fraction of 3% -5%, cooling the material to room temperature, and continuously stirring for 30-60 minutes.

(8) And (3) pouring the material obtained in the step (7) into a 100mL beaker, adding 20-30 mL of analytically pure anhydrous ethanol, uniformly stirring, precipitating for 30-40 minutes, filtering, washing with 10-15 mL of deionized water and 10-15 mL of analytically pure anhydrous ethanol in sequence, and performing suction filtration for 2-3 times. Putting the filter cake into a watch glass, and sending the filter cake into a vacuum constant-temperature drying oven at 50 ℃ for drying for 24 hours until the weight is constant, thereby obtaining the product cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

(9) And (3) determining the esterification substitution degree of the cinnamic acid/p-chlorobenzoic acid bagasse xylan diester obtained in the step (8) by adopting an acid-base titration method, wherein the specific operation method comprises the following steps: accurately weighing 0.5g of product sample, putting the product sample into a 50mL conical flask, adding 5mL of deionized water, fully shaking the mixture, dripping 2 drops of phenolphthalein reagent, titrating the mixture to light red by using a 0.1mol/L NaOH standard solution, and maintaining the red color within 30 seconds without removing the red color; then, continuously adding 2.5mL of 0.5mol/L NaOH standard solution, after shaking and saponifying for 2 hours at room temperature, titrating by using 0.5mol/L hydrochloric acid standard solution until the solution system is colorless, and recording the volume of HCl standard solution consumed by titration as V₁. Under the same conditions, blank titration is carried out by using bagasse xylan before esterification, and the volume V of consumed hydrochloric acid standard solution with the concentration of 0.5mol/L is recorded₀. Degree of Substitution (DS) of target product by esterification_c) The calculation formula of (a) is as follows:

in the formula:

W_c-the mass fraction of ester carbonyl in cinnamic acid/p-chlorobenzoic acid bagasse xylan diester;

V₀titrating the volume of the hydrochloric acid standard solution consumed by the bagasse xylan in unit mL;

V₁titrating the volume of the hydrochloric acid standard solution consumed by the target product sample in mL;

C_HCl-hydrochloric acid standard solution concentration, in mol/L;

m is the mass of the product sample in g;

DS_c-degree of substitution by esterification of cinnamic acid/p-chlorobenzoic acid bagasse xylan diester;

m and 132-acyl group of Carboxylic acid esterifying agent and relative molecular mass of the bagasse xylan anhydroxylose unit.

The invention synthesizes the final product cinnamic acid/p-chlorobenzoic acid bagasse xylan diester through two esterification reactions. The obtained target product not only improves the physicochemical property of the original bagasse xylan, but also greatly enhances the anti-HIV activity of the bagasse xylan derivative by introducing two active groups, namely cinnamic acid and p-chlorobenzoic acid.

Drawings

FIG. 1 is an SEM photograph of raw bagasse xylan.

FIG. 2 is an SEM photograph of cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

FIG. 3 is an IR chart of raw bagasse xylan.

FIG. 4 is an IR chart of cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

Figure 5 is an XRD pattern of raw bagasse xylan.

FIG. 6 is an XRD pattern of cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

FIG. 7 shows TG and DTG curves of raw bagasse xylan.

FIG. 8 shows TG and DTG curves of cinnamic acid/p-chlorobenzoic acid bagasse xylan diester.

Detailed Description