阅读说明：本技术 一种芝麻酚的制备方法 (Preparation method of sesamol ) 是由 周石洋 陈本寿 于 2021-09-01 设计创作，主要内容包括：本发明属于化合物合成技术领域,具体涉及一种芝麻酚的制备方法,先以对二苯酚和氯气为原料制备2-氯-1,4-二苯酚,随后2-氯-1,4-二苯酚和氢氧化钠水溶液反应得到1,2,4-三苯酚,最后1,2,4-三苯酚和二氯甲烷反应制备得到芝麻酚。本发明提供了一种新的制备芝麻酚途径,并显著提高了芝麻酚的收率。(The invention belongs to the technical field of compound synthesis, and particularly relates to a preparation method of sesamol, which comprises the steps of firstly preparing 2-chloro-1, 4-diphenol by taking p-diphenol and chlorine as raw materials, then reacting the 2-chloro-1, 4-diphenol with an aqueous solution of sodium hydroxide to obtain 1,2, 4-triphenol, and finally reacting the 1,2, 4-triphenol with dichloromethane to prepare the sesamol. The invention provides a new route for preparing sesamol, and obviously improves the yield of sesamol.)

1. The preparation method of sesamol is characterized by firstly preparing 2-chloro-1, 4-diphenol by taking p-diphenol and chlorine as raw materials, then reacting the 2-chloro-1, 4-diphenol with an aqueous solution of sodium hydroxide to obtain 1,2, 4-triphenol, and finally reacting the 1,2, 4-triphenol with dichloromethane to prepare the sesamol.

2. The method according to claim 1, wherein the 2-chloro-1, 4-diphenol is prepared by:

heating p-diphenol and reducing iron powder to boiling in the presence of carbon tetrachloride, and introducing chlorine under the irradiation of an ultraviolet light source; after the chlorine gas is introduced, continuously performing reflux reaction for 1-10h, and after the reaction is finished, introducing nitrogen gas; filtering while hot, cooling, standing, filtering and recrystallizing the obtained filter residue.

3. The method according to claim 2, wherein the recrystallization is recrystallization from acetone.

4. The method of claim 2 or 3, wherein the molar ratio of chlorine to p-diphenol is from 2:1 to 5: 1.

5. The process according to any one of claims 1 to 4, wherein the 1,2, 4-trisphenol is prepared by a specific operation comprising: heating 2-chloro-1, 4-diphenol and sodium hydroxide aqueous solution to 40-100 ℃, and reacting for 1-16h at the temperature; after completion of the reaction, it was cooled, extracted with ethyl acetate, and the ethyl acetate extract was distilled under reduced pressure, followed by recrystallization.

6. The method of claim 5, wherein the molar ratio of 2-chloro-1, 4-diphenol to sodium hydroxide is from 1:1 to 1: 3.

7. The process according to any one of claims 1 to 6, wherein the reaction of 1,2, 4-trisphenol with dichloromethane to produce sesamol is carried out in the following manner: heating sodium hydroxide-dichloromethane-toluene to 80-100 ℃, adding a 1,2, 4-trisphenol-toluene mixture, reacting at 100-110 ℃ for 0.5-3h, cooling, filtering and recrystallizing the obtained filter residue.

8. The method according to claim 7, wherein the molar ratio of dichlorotoluene to 1,2, 4-trisphenol is from 1:1 to 1: 2.

9. The method according to claim 7, wherein the recrystallization is recrystallization from petroleum ether.

Technical Field

The invention belongs to the technical field of compound synthesis, and particularly relates to a preparation method of sesamol.

Background

Sesamol has chemical name of 3, 4-methylenedioxyphenol and molecular formula of C₇H₆O₃Structural formula isIs a natural fat-soluble lignan compound (Chenjinying, Luo faing. sesamol stability research [ J)]Food research and development 2015, 36(4): 14-18; state of the Art of lignans in Niger sesame [ J]Science and technology in food industry 2014, 35(1): 383-.

Sesamol is a main component of sesame oil, and is also a component that imparts a special flavor to sesame oil. The sesamol can enable the quality of the sesame oil to be more stable, and also has the effects of antibiosis, anti-inflammation, antioxidation, anti-melanin, anti-aging, anticancer, neuroprotection, weight loss and the like (Ma Su, xu Jiu, Sinkiao, Yan Bei, Yan Chen, Huang Qingde. the research progress of the bioactivity of the sesamol [ J ]. Chinese food and nutrition, 2019, 25(9): 62-65; Ma Su, xu Jiu, Xinjiang, Yang Bei, Huang Qingde. the research progress of the anti-inflammation mechanism of the sesamol [ J ]. Chinese grease, 2019, 44(9): 109-.

At present, sesamol is obtained in two ways, one is obtained by extracting and separating from sesame oil, and the other is obtained by synthesizing. However, sesamol is extracted from sesame oil, so that the solvent consumption is large and the cost is high.

The artificial synthesis method of sesamol mainly comprises two steps: the total synthesis is carried out by taking piperine as a raw material and the semi-synthesis is carried out by taking piperonal as a raw material (https:// www.yixue.com/% E8%, 8A%, 9D%, E9%, BA%, BB%, E9%, 85% 9A, medical encyclopedia, sesamol). However, the sesamol synthesized by the two methods has a low yield of about 60%.

Disclosure of Invention

In view of the above, the present invention aims to provide a method for preparing sesamol with high yield.

In order to achieve the purpose, the technical scheme of the invention is as follows:

the preparation method of sesamol is characterized by using p-diphenol and chlorine as raw materials to prepare 2-chloro-1, 4-diphenol.

Further, the preparation of the 2-chloro-1, 4-diphenol specifically comprises the following steps: heating p-diphenol and reducing iron powder to boiling in the presence of carbon tetrachloride, and introducing chlorine under the irradiation of an ultraviolet light source; after the chlorine gas is introduced, continuously performing reflux reaction for 1-10h, and after the reaction is finished, introducing nitrogen gas; filtering while hot, cooling, standing, filtering and recrystallizing the obtained filter residue.

Furthermore, the molar ratio of the chlorine to the p-diphenol is 2:1-5: 1.

Further, the recrystallization in the preparation process of 2-chloro-1, 4-diphenol means recrystallization with acetone.

Further, the preparation of the 1,2, 4-trisphenol specifically comprises the following steps: heating 2-chloro-1, 4-diphenol and sodium hydroxide aqueous solution to 40-100 ℃, and reacting for 1-16h at the temperature; after completion of the reaction, it was cooled, extracted with ethyl acetate, and the ethyl acetate extract was distilled under reduced pressure, followed by recrystallization.

Further, the molar ratio of the 2-chloro-1, 4-diphenol to the sodium hydroxide is 1:1 to 1: 3.

Further, the recrystallization in the preparation process of the 1,2, 4-trisphenol means recrystallization with diethyl ether.

Further, the reaction of 1,2, 4-trisphenol and dichloromethane to prepare sesamol is specifically as follows: heating sodium hydroxide-dichloromethane-toluene to 80-100 ℃, adding a 1,2, 4-trisphenol-toluene mixture, reacting at 100-110 ℃ for 0.5-3h, cooling, filtering and recrystallizing the obtained filter residue.

Further, the molar ratio of dichlorotoluene to 1,2, 4-trisphenol is 1:1 to 1: 2.

Further, the recrystallization in the process of preparing sesamol by reacting 1,2, 4-trisphenol with sodium hydroxide refers to recrystallization by using petroleum ether with a boiling range of 60-90 ℃.

The invention has the beneficial effects that:

the invention obviously improves the yield of sesamol.

The invention provides a new synthesis path of sesamol.

The invention has low cost of raw materials and simple process, and is beneficial to realizing pilot-scale production or industrial production.

Drawings

FIG. 1 is a schematic diagram of a process for preparing sesamol according to the present invention;

FIG. 2 shows sesamol obtained in example 1¹H nuclear magnetic resonance image, the abscissa is chemical shift;

FIG. 3 shows sesamol obtained in example 1¹³C nuclear magnetic resonance image, the abscissa is chemical shift.

Detailed Description

The examples are provided for better illustration of the present invention, but the present invention is not limited to the examples. Therefore, those skilled in the art should make insubstantial modifications and adaptations to the embodiments of the present invention in light of the above teachings and remain within the scope of the invention.

Example 1

The preparation method of sesamol comprises the following specific steps:

(1) synthesis of 2-chloro-1, 4-diphenol

Weighing 11.01g (0.10mol) of p-diphenol and 2.80g (0.05mol) of reducing iron powder, placing the p-diphenol and the 2.80g (0.05mol) of reducing iron powder into a 500mL round-bottom flask, adding 150mL of carbon tetrachloride into the round-bottom flask, and stirring by a magnetic force to fully dissolve the carbon tetrachloride; heating to boiling, and slowly introducing 0.40mL of chlorine gas at a constant speed under the irradiation of an ultraviolet light source; after the chlorine gas is introduced, continuing to perform magnetic stirring reflux reaction for 5 hours, and after the reaction is finished, introducing nitrogen gas; the mixture is filtered while hot, cooled and kept stand, white crystals are separated out, the mixture is filtered (carbon tetrachloride in the filtrate is recovered), filter residues are collected and recrystallized by acetone, and 13.54g of white crystals of 2-chloro-1, 4-diphenol is obtained, namely the yield of the 2-chloro-1, 4-diphenol is 93.6%.

(2) Synthesis of 1,2, 4-trisphenol

14.46g (0.10mol) of 2-chloro-1, 4-diphenol and 6.0g of sodium hydroxide solid (0.15mol) are weighed into a 500mL round-bottom flask, 150mL of distilled water are added into the flask, and the mixture is stirred by magnetic force to be fully miscible; heating to 80 ℃, and carrying out constant-temperature magnetic stirring reaction for 8 hours at the temperature; after completion of the reaction, it was cooled, extracted with ethyl acetate, the organic layer was collected, and the ethyl acetate extract was distilled under reduced pressure to give a crude product, which was recrystallized from ether to give 11.90g of 1,2, 4-trisphenol as a leaf crystal in a yield of 94.4% in this step.

(3) Synthesis of sesamol

Weighing 12.61g (0.10mol) of 1,2, 4-trisphenol and dissolving in 30mL of toluene to obtain a 1,2, 4-trisphenol-toluene solution;

placing 8.0g of sodium hydroxide solid (0.2mol) and 8.09mL (0.12mol) of dichloromethane in a 500mL round-bottom flask, adding 100mL of toluene into the round-bottom flask, heating, stirring by magnetic force, and slowly dropwise adding 1,2, 4-trisphenol-toluene solution when the temperature is raised to 90 ℃; controlling the dropping speed and the reaction temperature of the 1,2, 4-trisphenol-toluene solution, and dropping at the speed of 12 drops/min, wherein the reaction temperature is controlled at 95 ℃; after the dropwise addition, stirring and reacting for 1h at the constant temperature of 105 ℃; after the reaction is finished, cooling and filtering, collecting filter residues, and recovering toluene; the residue was recrystallized from petroleum ether with a boiling range of 60-90 deg.C to give sesamol as white needle crystals in an amount of 12.72g, and the yield of sesamol in this step was 92.1%.

In this example, the total yield of sesamol was 93.6% 94.4% 92.1% and 81.38%.

Performance detection

NMR of sesamol obtained in example 1¹H detection and nuclear magnetic resonance¹³C, detecting, wherein the result is shown in figure 1-2;

wherein the nuclear magnetic resonance¹H and nuclear magnetic resonance¹³C, the detection method comprises the following steps; with D₂And O is used as a solvent to prepare a polysaccharide solution of 50 mg/mL.¹H NMR and¹³c NMR spectra were recorded using Bruker AV III-600NMR spectra.

As can be seen from FIG. 1, NMR hydrogen spectrum data of sesamol¹H NMR(600MHz,DMSO-d₆)δ:5.90(2H,s,-CH₂-),6.20(1H,dd,J＝8.4,2.5Hz,Ph-H),6.39(1H,d,J＝2.4Hz,Ph-H),6.70(1H,d,J＝8.3Hz,Ph-H),9.12(1H,s,-OH)。

As can be seen from FIG. 2, NMR carbon spectrum data of sesamol¹³C NMR(100MHz,DMSO-d₆)δ:98.3,101.0,106.7,108.6,140.1,148.2,153.0。

Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.