阅读说明：本技术 高纯度合成辣椒素的精制方法 (Refining method of high-purity synthetic capsaicin ) 是由 孔令航 马家松 孔晓伟 贾帮乐 孙徽 于 2019-10-29 设计创作，主要内容包括：本发明公开了一种高纯度合成辣椒素的精制方法,通过羟醛缩合、傅克反应、醚化和磺化合成了一种具有识别(反式)8-甲基-N-香草基-6-壬烯酰胺分子能力的杯芳烃；杯芳烃通过超分子作用,与合成辣椒素中的(反式)8-甲基-N-香草基-6-壬烯酰胺形成(反式)8-甲基-N-香草基-6-壬烯酰胺-杯芳烃主客体识别超分子,分离沉淀,得到正-壬酸香草酰胺溶液,蒸发脱溶结晶后得含量高于99.8%的正-壬酸香草酰胺精品。本发明所用的提纯方法,绿色环保,杯芳烃循环重复性能良好,原子经济性高。(The invention discloses a refining method for synthesizing capsaicin with high purity, which synthesizes calixarene with the ability of identifying (trans) 8-methyl-N-vanillyl-6-nonenamide molecules through aldol condensation, Friedel-crafts reaction, etherification and sulfonation; the calixarene and (trans) 8-methyl-N-vanillyl-6-nonenamide in the synthesized capsaicin form (trans) 8-methyl-N-vanillyl-6-nonenamide-calixarene host-guest recognition supermolecules through supermolecule action, the precipitate is separated to obtain N-nonanoic acid vanillimide solution, and the N-nonanoic acid vanillimide refined product with the content higher than 99.8 percent is obtained after evaporation, desolvation and crystallization. The purification method provided by the invention is green and environment-friendly, and has good calixarene recycling and repeating performance and high atom economy.)

1. A refining method of high-purity synthetic capsaicin is characterized by comprising the following steps:

synthesizing calixarene with the capability of identifying (trans) 8-methyl-N-vanillyl-6-nonenamide molecules through aldol condensation, Friedel-crafts reaction, etherification and sulfonation; calixarene forms (trans) 8-methyl-N-vanillyl-6-nonenamide with (trans) 8-methyl-N-vanillyl-6-nonenamide in the synthesized capsaicin through the action of supramolecules, a calixarene host object is identified with supramolecules, precipitates are separated to obtain a N-nonanoic acid vanillimide solution, and a N-nonanoic acid vanillimide refined product with the content higher than 99.8 percent is obtained after evaporation, desolvation and crystallization;

the specific process is as follows:

2. the process for refining high purity synthetic capsaicin according to claim 1, comprising the steps of:

(1) adding synthetic capsaicin and calixarene into a reactor according to the molar ratio of (trans) 8-methyl-N-vanillyl-6-nonenamide to calixarene of 1:1, wherein the content of ((trans) 8-methyl-N-vanillyl-6-nonenamide in the synthetic capsaicin is about 2%, adding dichloromethane which is 1-3 times of the mass of the synthetic capsaicin, stirring and reacting at room temperature for 6-8 hours;

(2) after the solution is changed from green to red, evaporating dichloromethane under the conditions of 30 ℃ and-0.01 MPa, adding diethyl ether with the mass 1-3 times of that of the synthesized capsaicin, stirring for a period of time at-5 ℃ to 5 ℃, filtering to obtain a n-nonanoic acid vanillimide solution, and evaporating, desolventizing and crystallizing to obtain a refined n-nonanoic acid vanillimide with the content higher than 99.8%.

3. The method of refining a high purity synthetic capsaicin according to claim 1, wherein:

the content of ((trans) 8-methyl-N-vanillyl-6-nonenamide) in the capsaicin synthesized in the step (1) is measured by an external standard method, and standard samples used for measuring the external standard are purchased from sigma company;

the filter residue in the step (2) is calixarene- (trans) 8-methyl-N-vanillyl-6-nonenamide complex, the calixarene- (trans) 8-methyl-N-vanillyl-6-nonenamide complex is dissolved in methanol at the temperature of 60 ℃, and the solution is cooled to room temperature to obtain calixarene precipitate and (trans) 8-methyl-N-vanillyl-6-nonenamide methanol solution, and the calixarene is filtered and recovered for reuse;

(trans) 8-methyl-N-vanillyl-6-nonenamide methanol solution when (trans) 8-methyl-N-vanillyl-6-nonenamide is enriched to a higher concentration, (trans) 8-methyl-N-vanillyl-6-nonenamide can be isolated by evaporative crystallization.

4. The refining method of high-purity synthesized capsaicin according to claim 1, wherein the synthesis method of calixarene is described in the report of Qinhain and the like (construction and functions of amphiphilic sulfonated calixarene nano supermolecule assembly), and the reaction equation is as follows:

Technical Field

The invention relates to the technical field of medicines, in particular to a refining method of high-purity synthesized capsaicin.

Background

High-purity capsaicin is a novel environment-friendly fine chemical and is widely applied to the fields of medical treatment, materials, war industry, biochemistry and the like. The purity of capsaicin is closely related to the indexes such as melting point, processing window, biological toxicity, pungency and the like. The high-purity capsaicin can be applied to top-end products of various industries, has high economic benefit, but is difficult to purify. The existing purification method is mainly recrystallization, and the refining process has no obvious refining effect on the (trans) 8-methyl-N-vanillyl-6-nonenamide impurity, so that the content of capsaicin is difficult to reach more than 99.2 percent.

The current method of controlling (trans) 8-methyl-N-vanillyl-6-nonenamide is mainly to remove (trans) 8-methyl-6-nonenoic acid as an impurity in nonanoic acid by rectification. The method has the advantages of high energy consumption, low efficiency and greatly increased cost, and is not suitable for industrial production. The removal of 8-methyl-N-vanillyl-6-nonenamide from synthetic capsaicin is a major bottleneck in increasing the purity of capsaicin.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a high-purity synthetic capsaicin refining method, which precisely removes (trans) 8-methyl-N-vanillyl-6-nonenamide by using different interactions between (trans) 8-methyl-N-vanillyl-6-nonenamide and nonanoic vanillyl amide and a special supramolecular ligand to achieve the aim of improving the content of nonanoic vanillyl amide.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows:

a refining method of high-purity synthetic capsaicin is characterized by comprising the following steps:

synthesizing calixarene with the capability of identifying (trans) 8-methyl-N-vanillyl-6-nonenamide molecules through aldol condensation, Friedel-crafts reaction, etherification and sulfonation; calixarene forms (trans) 8-methyl-N-vanillyl-6-nonenamide with (trans) 8-methyl-N-vanillyl-6-nonenamide in the synthesized capsaicin through the action of supramolecules, a calixarene host object is identified with supramolecules, precipitates are separated to obtain a N-nonanoic acid vanillimide solution, and a N-nonanoic acid vanillimide refined product with the content higher than 99.8 percent is obtained after evaporation, desolvation and crystallization;

the specific process is as follows:

the refining method of the high-purity synthetic capsaicin is characterized by comprising the following steps:

(1) adding synthetic capsaicin and calixarene into a reactor according to the molar ratio of (trans) 8-methyl-N-vanillyl-6-nonenamide to calixarene of 1:1, wherein the content of ((trans) 8-methyl-N-vanillyl-6-nonenamide in the synthetic capsaicin is about 2%, adding dichloromethane which is 1-3 times of the mass of the synthetic capsaicin, stirring and reacting at room temperature for 6-8 hours;

(2) after the solution is changed from green to red, evaporating dichloromethane under the conditions of 30 ℃ and-0.01 MPa, adding diethyl ether with the mass being 1-3 times that of the synthesized capsaicin, stirring for a period of time at-5 ℃, filtering to obtain a n-nonanoic acid vanillimide solution, and evaporating, desolventizing and crystallizing to obtain a refined n-nonanoic acid vanillimide with the content higher than 99.8%;

the content of ((trans) 8-methyl-N-vanillyl-6-nonenamide) in the capsaicin synthesized in the step (1) is measured by an external standard method, and standard samples used for measuring the external standard are purchased from sigma company;

the filter residue in the step (2) is calixarene- (trans) 8-methyl-N-vanillyl-6-nonenamide complex, the calixarene- (trans) 8-methyl-N-vanillyl-6-nonenamide complex is dissolved in methanol at the temperature of 60 ℃, and the solution is cooled to room temperature to obtain calixarene precipitate and (trans) 8-methyl-N-vanillyl-6-nonenamide methanol solution, and the calixarene is filtered and recovered for reuse;

(trans) 8-methyl-N-vanillyl-6-nonenamide methanol solution when (trans) 8-methyl-N-vanillyl-6-nonenamide is enriched to a higher concentration, (trans) 8-methyl-N-vanillyl-6-nonenamide can be isolated by evaporative crystallization.

The refining method for synthesizing the high-purity capsaicin is characterized in that the synthesis method of the calixarene refers to reports (construction and functions of an amphiphilic sulfonated calixarene nano supermolecule assembly) of Qinhen bin and the like, and a reaction equation is as follows:

the invention has the beneficial effects that:

1. according to the method for preparing the high-purity capsaicin, the purity of the obtained refined capsaicin can reach 99.8%.

2. The purification method provided by the invention is green and environment-friendly, and has good calixarene recycling and repeating performance and high atom economy.

3. The method can enrich and produce the byproduct (trans) -8-methyl-N-vanillyl-6-nonenamide, and generate certain economic benefit.

4. According to the method, the reaction condition can be judged by naked eyes, and the separation process is finished when the solution color is changed from green to red.

Detailed Description

The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:

preparation of MHZ001-1

A250 ml three-necked flask was charged with 23ml of 37% formaldehyde solution, 36.8g of p-hydroxybenzoic acid and 4.6g of caustic soda flakes. Heating to 110 ℃ by using a heating sleeve under the condition of magnetic stirring, evaporating water until the system in the bottle is purple jelly, standing and cooling to room temperature. 40ml of diphenyl ether was added, the temperature was raised to 170 ℃, argon gas was bubbled until the solution became dark green, and after refluxing for two hours, the solution was left to cool to room temperature. 50ml of ethyl acetate was added thereto, and stirred for 30 minutes to crystallize. Suction filtration, filter cake pulping with water and rinsing to obtain MHZ001-1 as white solid 2.00 g.

Preparation of MHZ001

To a 50ml three-necked flask, MHZ 001-10.5 g, 4-bromo-7-tetraphenylethylenebenzothiadiazole 10.64g, and DMF20ml were added, and stirred at room temperature for 15 minutes, and sodium hydride 1.23g was added in 5 portions, and then the mixture was allowed to stand at room temperature overnight. The reaction solution was poured into 50ml of ice water, extracted with 30ml of dichloromethane, and evaporated to dryness to obtain calixarene (MHZ001) as a white solid (8 g).