CN110845308A - Preparation process of capsaicin - Google Patents
Preparation process of capsaicin Download PDFInfo
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- CN110845308A CN110845308A CN201911017367.3A CN201911017367A CN110845308A CN 110845308 A CN110845308 A CN 110845308A CN 201911017367 A CN201911017367 A CN 201911017367A CN 110845308 A CN110845308 A CN 110845308A
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- dihydroxybenzyl
- capsaicin
- chloride
- catechol
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- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 title claims abstract description 66
- 235000017663 capsaicin Nutrition 0.000 title claims abstract description 33
- 229960002504 capsaicin Drugs 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims abstract description 50
- NNVPWGAAGKAPKD-UHFFFAOYSA-N 4-(chloromethyl)benzene-1,2-diol Chemical compound OC1=CC=C(CCl)C=C1O NNVPWGAAGKAPKD-UHFFFAOYSA-N 0.000 claims abstract description 31
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 230000035484 reaction time Effects 0.000 claims abstract description 21
- 239000002841 Lewis acid Substances 0.000 claims abstract description 9
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 238000007146 photocatalysis Methods 0.000 claims abstract description 6
- 230000001699 photocatalysis Effects 0.000 claims abstract description 6
- SXQFCVDSOLSHOQ-UHFFFAOYSA-N lactamide Chemical compound CC(O)C(N)=O SXQFCVDSOLSHOQ-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- ZBCATMYQYDCTIZ-UHFFFAOYSA-N 4-methylcatechol Chemical compound CC1=CC=C(O)C(O)=C1 ZBCATMYQYDCTIZ-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- -1 3, 4-dihydroxybenzyl Chemical group 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 claims 1
- 229940050176 methyl chloride Drugs 0.000 claims 1
- 238000004064 recycling Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- HFLGBNBLMBSXEM-UHFFFAOYSA-N 4-Ethyl-1,2-benzenediol Chemical compound CCC1=CC=C(O)C(O)=C1 HFLGBNBLMBSXEM-UHFFFAOYSA-N 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- VZIIOZNXGMMAHC-UHFFFAOYSA-N N-[(3,4-dihydroxyphenyl)methyl]-2-hydroxypropanamide Chemical compound OC=1C=C(CNC(C(C)O)=O)C=CC=1O VZIIOZNXGMMAHC-UHFFFAOYSA-N 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000012805 post-processing Methods 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000012535 impurity Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 abstract 1
- 229940080818 propionamide Drugs 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 description 7
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 230000001376 precipitating effect Effects 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000590002 Helicobacter pylori Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940037467 helicobacter pylori Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 235000002566 Capsicum Nutrition 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000011587 gastric lymphoma Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000001589 lymphoproliferative effect Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- WRPWWVNUCXQDQV-UHFFFAOYSA-N vanillylamine Chemical compound COC1=CC(CN)=CC=C1O WRPWWVNUCXQDQV-UHFFFAOYSA-N 0.000 description 1
- 229940053939 vanillylamine Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
- C07C37/16—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by condensation involving hydroxy groups of phenols or alcohols or the ether or mineral ester group derived therefrom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及药物合成技术领域，尤其是一种合成工艺简单、产率高的辣椒素制备工艺；包括以下步骤：儿茶酚和一氯甲烷在路易斯酸的催化下进行Friedel‑Crafts烷基化反应得到3，4‑二羟基苯甲烷；3，4‑二羟基苯甲烷在光催化下与氯气发生反应得到3，4‑二羟基苄基氯；3，4‑二羟基苄基氯与2‑羟基丙酰胺反应，后处理后得到N‑（3，4‑二羟基苄基）‑2‑羟基丙酰胺；本发明中的辣椒素的制备工艺，原料简单易得，反应条件温和，反应时间短，只需要3.5h就可以完成反应，相比现有技术中10d，是显著缩短了反应时间；而且产率高达85.5%，现有技术中的收率仅有73%，同时，反应过程中产生的杂质少，后处理简单，产品纯度高，且未反应的物质可回用。The invention relates to the technical field of drug synthesis, in particular to a capsaicin preparation process with simple synthesis process and high yield; the invention comprises the following steps: carrying out Friedel-Crafts alkylation reaction of catechol and monochloromethane under the catalysis of Lewis acid Obtain 3,4-dihydroxybenzyl methane; 3,4-dihydroxybenzyl methane reacts with chlorine under photocatalysis to obtain 3,4-dihydroxybenzyl chloride; 3,4-dihydroxybenzyl chloride and 2-hydroxyl Propionamide reaction, after post-processing, N-(3,4-dihydroxybenzyl)-2-hydroxypropionamide is obtained; the preparation process of capsaicin in the present invention has simple and easy-to-obtain raw materials, mild reaction conditions, and short reaction time, It only takes 3.5h to complete the reaction, which significantly shortens the reaction time compared to 10d in the prior art; and the yield is as high as 85.5%, while the yield in the prior art is only 73%. Less impurities, simple post-processing, high product purity, and unreacted substances can be reused.
Description
技术领域technical field
本发明涉及药物合成技术领域，尤其是一种合成工艺简单、产率高的辣椒素制备工艺。The invention relates to the technical field of drug synthesis, in particular to a preparation process of capsaicin with simple synthesis process and high yield.
背景技术Background technique
辣椒素因为具有镇痛消炎、抗病菌、抗肿瘤、促进胃液分泌、增强食欲，促进血液循环、提高机体免疫力的功效，在欧美、日本、韩国等国家已经具有了广阔的市场，尤其在医药等领域，但由于其过高的提取成本、较低的产量限制了其推广应用。Capsaicin has a broad market in Europe, America, Japan, South Korea and other countries because of its analgesic and anti-inflammatory, anti-bacterial, anti-tumor, promoting gastric juice secretion, enhancing appetite, promoting blood circulation, and improving immunity. However, due to its high extraction cost and low yield, its popularization and application are limited.
辣椒素除了在农药、医药、轻工、食品添加剂等方便都具有较高的应用价值，还具有优异的抗菌效果。幽门螺旋菌是引起胃炎、消化道溃疡、淋巴增生性胃淋巴瘤等疾病的元凶，而辣椒素能够有效的抑制幽门螺旋菌的生长。In addition to its high application value in pesticides, medicine, light industry, and food additives, capsaicin also has excellent antibacterial effects. Helicobacter pylori is the culprit of gastritis, peptic ulcer, lymphoproliferative gastric lymphoma and other diseases, and capsaicin can effectively inhibit the growth of Helicobacter pylori.
目前，辣椒素的制取方法有天然提取法、生物细胞培养制取法和化学合成法。At present, the preparation methods of capsaicin include natural extraction method, biological cell culture preparation method and chemical synthesis method.
（1）天然提取法(1) Natural extraction method
从天然辣椒中提取辣椒素的方法是根据其溶解性的特点，先由有机溶剂浸出，然后层析分析，最后经有机溶剂低温下结晶而成。常见的方法有浸出-萃取法、离子交换法纯化和二氧化碳超临界萃取法。天然提取的方法提取的产物纯度不高，而且受限于产地、品种等因素。The method of extracting capsaicin from natural pepper is based on its solubility characteristics, firstly by leaching with organic solvent, then by chromatographic analysis, and finally by crystallization of organic solvent at low temperature. Common methods are leaching-extraction, ion exchange purification and carbon dioxide supercritical extraction. The purity of the product extracted by the natural extraction method is not high, and it is limited by factors such as origin and variety.
（2）生物细胞培养制取法(2) Biological cell culture preparation method
生物细胞配方法是通过细胞生物转化为辣椒素，但是对于细胞的培养、培养液的提取和分离的要求严格，不适合大规模生产。The biological cell preparation method is to convert capsaicin into capsaicin through the biotransformation of cells, but it has strict requirements for cell culture, extraction and separation of culture medium, and is not suitable for large-scale production.
（3）化学合成法(3) Chemical synthesis method
辣椒素从化学结构上看可以是香草基胺与脂肪酸形成的酰胺化合物，最初合成辣椒素的目的是为了证实天然辣椒素的化学结构。虽然利用化学合成法合成出了高纯度的辣椒素，但是目前化学合成法制得辣椒素的产率较低，反应时间长，需要10d，不适合大规模工业化生产。From the chemical structure, capsaicin can be an amide compound formed by vanillylamine and fatty acid. The original purpose of synthesizing capsaicin is to confirm the chemical structure of natural capsaicin. Although high-purity capsaicin has been synthesized by chemical synthesis, the yield of capsaicin obtained by chemical synthesis is low, the reaction time is long, and it takes 10 days, which is not suitable for large-scale industrial production.
发明内容SUMMARY OF THE INVENTION
本发明的目的是：克服现有技术中不足，提供一种工艺简单、反应时间短、生产效率高的辣椒素的制备工艺。The object of the present invention is to: overcome the deficiencies in the prior art, and provide a preparation process of capsaicin with simple process, short reaction time and high production efficiency.
为解决上述技术问题，本发明采用的技术方案如下：In order to solve the above-mentioned technical problems, the technical scheme adopted in the present invention is as follows:
一种辣椒素的制备工艺，化学反应式如下：
具体包括以下步骤：Specifically include the following steps:
（1）儿茶酚和一氯甲烷在路易斯酸的催化下进行反应得到3，4-二羟基苯甲烷，反应温度为40-45℃；(1) 3,4-dihydroxybenzenemethane is obtained by reacting catechol and monochloromethane under the catalysis of Lewis acid, and the reaction temperature is 40-45°C;
（2）步骤（1）中制得的3，4-二羟基苯甲烷在光催化下与氯气发生反应得到3，4-二羟基苄基氯，反应后用减压蒸馏或者柱层析分离得到3，4-二羟基苄基氯，(2) The 3,4-dihydroxybenzyl methane prepared in step (1) reacts with chlorine under photocatalysis to obtain 3,4-dihydroxybenzyl chloride, which is then separated by vacuum distillation or column chromatography to obtain 3,4-Dihydroxybenzyl chloride,
（3）步骤（2）中制得的3，4-二羟基苄基氯与2-羟基丙酰胺反应，后处理后得到N-（3，4-二羟基苄基）-2-羟基丙酰胺。(3) The 3,4-dihydroxybenzyl chloride obtained in step (2) is reacted with 2-hydroxypropionamide, and after post-treatment, N-(3,4-dihydroxybenzyl)-2-hydroxypropionamide is obtained .
进一步的，所述步骤（1）中儿茶酚和一氯甲烷之间的摩尔比为1:0.9～0.95，反应时间为1～2h。Further, in the step (1), the molar ratio between catechol and monochloromethane is 1:0.9-0.95, and the reaction time is 1-2h.
进一步的，所述步骤（2）的反应时间为20～30min。Further, the reaction time of the step (2) is 20-30 min.
进一步的，所述步骤（2）中3，4-二羟基苯甲烷循环使用。Further, in the step (2), 3,4-dihydroxybenzenemethane is recycled.
进一步的，所述步骤（2）中3，4-二羟基苯甲烷与氯气的摩尔比为1:0.3～0.5。Further, in the step (2), the molar ratio of 3,4-dihydroxybenzenemethane to chlorine is 1:0.3-0.5.
进一步的，所述步骤（3）中3，4-二羟基苄基氯与2-羟基丙酰胺的摩尔比为1:1。Further, in the step (3), the molar ratio of 3,4-dihydroxybenzyl chloride to 2-hydroxypropionamide is 1:1.
进一步的，所述步骤（3）中的反应时间为1～1.2h。Further, the reaction time in the step (3) is 1-1.2 h.
进一步的，所述步骤（3）中的溶剂选用氯仿、丙酮或者乙醇。Further, the solvent in the step (3) is selected from chloroform, acetone or ethanol.
进一步的，所述步骤（3）中的后处理包括加入乙醇和水的混合溶剂，加入碳酸钠或者碳酸氢钠溶液调节pH8～9，析出3，4-二羟基苄基氯与2-羟基丙酰胺，抽滤，重结晶得到3，4-二羟基苄基氯与2-羟基丙酰胺。Further, the post-treatment in the step (3) includes adding a mixed solvent of ethanol and water, adding sodium carbonate or sodium bicarbonate solution to adjust the pH to 8 to 9, and precipitating 3,4-dihydroxybenzyl chloride and 2-hydroxypropane. amide, suction filtration, and recrystallization to obtain 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide.
进一步的，所述步骤（1）中催化剂用量为儿茶酚质量的1%。Further, the catalyst dosage in the step (1) is 1% of the catechol mass.
采用本发明的技术方案的有益效果是：The beneficial effects of adopting the technical scheme of the present invention are:
本发明中的辣椒素的制备工艺，原料简单易得，反应条件温和，反应时间短，只需要3.5h就可以完成反应，相比现有技术中的10d，是显著缩短了反应时间；而且产率高达85.5%，现有技术中的收率仅有73%，同时，反应过程中产生的杂质少，后处理简单，产品纯度高。The preparation process of capsaicin in the present invention has simple and easy-to-obtain raw materials, mild reaction conditions, short reaction time, and only needs 3.5h to complete the reaction, which significantly shortens the reaction time compared to 10d in the prior art; The yield is as high as 85.5%, and the yield in the prior art is only 73%. At the same time, the impurities generated in the reaction process are few, the post-processing is simple, and the product purity is high.
本发明中通过控制3，4-二羟基苯甲烷和氯气的摩尔比，可以显著减少或避免多氯代产物的产生，而且，过量的、未反应的3，4-二羟基苯甲烷可以继续循环使用，从而使得3，4-二羟基苯甲烷的转化率达到100%。In the present invention, by controlling the molar ratio of 3,4-dihydroxybenzenemethane and chlorine, the generation of polychlorinated products can be significantly reduced or avoided, and the excess, unreacted 3,4-dihydroxybenzenemethane can continue to be circulated use, so that the conversion rate of 3,4-dihydroxybenzenemethane reaches 100%.
具体实施方式Detailed ways
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合具体实施方式对本发明作进一步详细的说明。In order to make the above objects, features and advantages of the present invention more clearly understood, the present invention will be described in further detail below with reference to specific embodiments.
此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。Reference herein to "one embodiment" or "an embodiment" refers to a particular feature, structure, or characteristic that may be included in at least one implementation of the present invention. The appearances of "in one embodiment" in various places in this specification are not all referring to the same embodiment, nor are they separate or selectively mutually exclusive from other embodiments.
本发明中的辣椒素的制备工艺的化学反应式如下：The chemical reaction formula of the preparation technology of capsaicin in the present invention is as follows:
实施例1Example 1
一种辣椒素的制备工艺，包括以下步骤：A preparation technology of capsaicin, comprising the following steps:
（1）儿茶酚和一氯甲烷在路易斯酸的催化下进行反应得到3，4-二羟基苯甲烷，儿茶酚和一氯甲烷的摩尔比为1:0.9，路易斯酸的添加量为儿茶酚质量的1%，儿茶酚11.01g，一氯甲烷4.54g，三氯化铝1.10g，反应时间为1h，得到3，4-二羟基苯甲烷11.17g，摩尔收率为90%以儿茶酚计，(1) 3,4-dihydroxyphenylmethane is obtained by reacting catechol and monochloromethane under the catalysis of Lewis acid, the molar ratio of catechol and monochloromethane is 1:0.9, and the amount of Lewis acid added is catechol 1% of the mass of tea phenol, catechol 11.01g, chloromethane 4.54g, aluminum trichloride 1.10g, the reaction time is 1h, and 11.17g of 3,4-dihydroxyphenylmethane is obtained, and the molar yield is more than 90%. Catechol Meter,
（2）步骤（1）中制得的3，4-二羟基苯甲烷在光催化下与氯气发生反应得到3，4-二羟基苄基氯；3，4-二羟基苯甲烷与氯气的摩尔比为1:0.3，反应时间为20min，未反应的3，4-二羟基苯甲烷循环使用，直至3，4-二羟基苯甲烷完全转化(2) The 3,4-dihydroxybenzylmethane prepared in step (1) reacts with chlorine gas under photocatalysis to obtain 3,4-dihydroxybenzyl chloride; moles of 3,4-dihydroxybenzylmethane and chlorine gas The ratio is 1:0.3, the reaction time is 20min, and the unreacted 3,4-dihydroxybenzenemethane is recycled until the 3,4-dihydroxybenzenemethane is completely converted
（3）步骤（2）中制得的3，4-二羟基苄基氯与2-羟基丙酰胺反应，后处理后得到N-（3，4-二羟基苄基）-2-羟基丙酰胺，3，4-二羟基苄基氯与2-羟基丙酰胺的摩尔比为1:1，3，4-二羟基苄基氯的质量为14.27g，2-羟基丙酰胺的质量为7.83g，反应时间为1h，溶剂选用氯仿，后处理包括加入乙醇和水的混合溶剂，加入碳酸钠或者碳酸氢钠溶液调节pH8～9，析出3，4-二羟基苄基氯与2-羟基丙酰胺，抽滤，重结晶得到3，4-二羟基苄基氯与2-羟基丙酰胺，重结晶采用乙醇作为溶剂，得到产品19.87g，摩尔收率为95%以儿茶酚计。(3) The 3,4-dihydroxybenzyl chloride obtained in step (2) is reacted with 2-hydroxypropionamide, and after post-treatment, N-(3,4-dihydroxybenzyl)-2-hydroxypropionamide is obtained , the molar ratio of 3,4-dihydroxybenzyl chloride to 2-hydroxypropionamide is 1:1, the mass of 3,4-dihydroxybenzyl chloride is 14.27g, the mass of 2-hydroxypropionamide is 7.83g, The reaction time is 1h, the solvent is chloroform, the post-treatment includes adding a mixed solvent of ethanol and water, adding sodium carbonate or sodium bicarbonate solution to adjust pH 8-9, and precipitating 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide, Suction filtration, recrystallization to obtain 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide, recrystallization using ethanol as a solvent to obtain 19.87 g of product, the molar yield is 95% in terms of catechol.
三步反应的总收率为85.5%，产品纯度为99.8%。The total yield of the three-step reaction was 85.5%, and the product purity was 99.8%.
实施例2Example 2
一种辣椒素的制备工艺，包括以下步骤：A preparation technology of capsaicin, comprising the following steps:
（1）儿茶酚和一氯甲烷在路易斯酸的催化下进行反应得到3，4-二羟基苯甲烷；儿茶酚和一氯甲烷的摩尔比为1:0.95，儿茶酚11.01g，一氯甲烷4.80g，三氯化铝1.10g，路易斯酸的添加量为儿茶酚质量的1%，反应时间为1.5h，得到3，4-二羟基苯甲烷11.29g，摩尔收率为91%以儿茶酚计，(1) 3,4-dihydroxyphenylmethane is obtained by reacting catechol and monochloromethane under the catalysis of Lewis acid; the molar ratio of catechol and monochloromethane is 1:0.95, catechol 11.01g, one 4.80 g of methyl chloride, 1.10 g of aluminum trichloride, the addition amount of Lewis acid is 1% of the mass of catechol, and the reaction time is 1.5 h to obtain 11.29 g of 3,4-dihydroxyphenylmethane with a molar yield of 91% In terms of catechol,
（2）步骤（1）中制得的3，4-二羟基苯甲烷在光催化下与氯气发生反应得到3，4-二羟基苄基氯；3，4-二羟基苯甲烷与氯气的摩尔比为1:0.4，反应时间为25min，未反应的3，4-二羟基苯甲烷循环使用，直至3，4-二羟基苯甲烷完全转化，(2) The 3,4-dihydroxybenzylmethane prepared in step (1) reacts with chlorine gas under photocatalysis to obtain 3,4-dihydroxybenzyl chloride; moles of 3,4-dihydroxybenzylmethane and chlorine gas The ratio is 1:0.4, the reaction time is 25min, and the unreacted 3,4-dihydroxybenzenemethane is recycled until the 3,4-dihydroxybenzenemethane is completely converted,
（3）步骤（2）中制得的3，4-二羟基苄基氯与2-羟基丙酰胺反应，后处理后得到N-（3，4-二羟基苄基）-2-羟基丙酰胺，3，4-二羟基苄基氯与2-羟基丙酰胺的摩尔比为1:1，3，4-二羟基苄基氯的质量为14.43g，2-羟基丙酰胺的质量为7.92g，反应时间为1.2h，溶剂选用丙酮，后处理包括加入乙醇和水的混合溶剂，加入碳酸钠或者碳酸氢钠溶液调节pH8～9，析出3，4-二羟基苄基氯与2-羟基丙酰胺，抽滤，重结晶得到3，4-二羟基苄基氯与2-羟基丙酰胺，重结晶采用乙醇作为溶剂，得到产品19.91g，摩尔收率为95.2%以儿茶酚计。(3) The 3,4-dihydroxybenzyl chloride obtained in step (2) is reacted with 2-hydroxypropionamide, and after post-treatment, N-(3,4-dihydroxybenzyl)-2-hydroxypropionamide is obtained , the molar ratio of 3,4-dihydroxybenzyl chloride to 2-hydroxypropionamide is 1:1, the mass of 3,4-dihydroxybenzyl chloride is 14.43g, the mass of 2-hydroxypropionamide is 7.92g, The reaction time is 1.2h, the solvent is acetone, the post-treatment includes adding a mixed solvent of ethanol and water, adding sodium carbonate or sodium bicarbonate solution to adjust the pH to 8-9, and precipitating 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide , suction filtration, and recrystallization to obtain 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide. The recrystallization adopts ethanol as a solvent to obtain 19.91 g of the product, and the molar yield is 95.2% in terms of catechol.
三步反应的总收率为86.45%，产品纯度为99.8%。The total yield of the three-step reaction was 86.45%, and the product purity was 99.8%.
实施例3Example 3
一种辣椒素的制备工艺，包括以下步骤：A preparation technology of capsaicin, comprising the following steps:
（1）儿茶酚和一氯甲烷在路易斯酸的催化下进行反应得到3，4-二羟基苯甲烷；儿茶酚和一氯甲烷的摩尔比为1:0.95，路易斯酸的添加量为儿茶酚质量的1%，儿茶酚11.01g，一氯甲烷4.80g，三氯化铝1.10g，反应时间为2h，得到3，4-二羟基苯甲烷11.42g，摩尔收率为92%以儿茶酚计，(1) 3,4-dihydroxybenzenemethane is obtained by reacting catechol and monochloromethane under the catalysis of Lewis acid; the molar ratio of catechol and monochloromethane is 1:0.95, and the amount of Lewis acid added is catechol 1% of the mass of tea phenol, 11.01g of catechol, 4.80g of monochloromethane, 1.10g of aluminum trichloride, the reaction time is 2h, and 11.42g of 3,4-dihydroxyphenylmethane is obtained, and the molar yield is 92% or more. Catechol Meter,
（2）步骤（1）中制得的3，4-二羟基苯甲烷在光催化下与氯气发生反应得到3，4-二羟基苄基氯，3，4-二羟基苯甲烷与氯气的摩尔比为1:0.5，反应时间为30min，，未反应的3，4-二羟基苯甲烷循环使用，直至3，4-二羟基苯甲烷完全转化，(2) The 3,4-dihydroxybenzylmethane prepared in step (1) reacts with chlorine gas under photocatalysis to obtain 3,4-dihydroxybenzyl chloride, moles of 3,4-dihydroxybenzylmethane and chlorine gas The ratio is 1:0.5, the reaction time is 30min, and the unreacted 3,4-dihydroxybenzenemethane is recycled until the 3,4-dihydroxybenzenemethane is completely converted,
（3）步骤（2）中制得的3，4-二羟基苄基氯与2-羟基丙酰胺反应，后处理后得到N-（3，4-二羟基苄基）-2-羟基丙酰胺，3，4-二羟基苄基氯与2-羟基丙酰胺的摩尔比为1:1，3，4-二羟基苄基氯的质量为14.59g，2-羟基丙酰胺的质量为8.00g，反应时间为1.2h，溶剂选用氯仿，后处理包括加入乙醇和水的混合溶剂，加入碳酸钠或者碳酸氢钠溶液调节pH8～9，析出3，4-二羟基苄基氯与2-羟基丙酰胺，抽滤，重结晶得到3，4-二羟基苄基氯与2-羟基丙酰胺，重结晶采用乙醇作为溶剂，得到产品19.93g，摩尔收率为95.3%以儿茶酚计。(3) The 3,4-dihydroxybenzyl chloride obtained in step (2) is reacted with 2-hydroxypropionamide, and after post-treatment, N-(3,4-dihydroxybenzyl)-2-hydroxypropionamide is obtained , the molar ratio of 3,4-dihydroxybenzyl chloride to 2-hydroxypropionamide is 1:1, the mass of 3,4-dihydroxybenzyl chloride is 14.59g, the mass of 2-hydroxypropionamide is 8.00g, The reaction time is 1.2h, the solvent is chloroform, and the post-treatment includes adding a mixed solvent of ethanol and water, adding sodium carbonate or sodium bicarbonate solution to adjust the pH to 8 to 9, and precipitating 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide. , suction filtration, and recrystallization to obtain 3,4-dihydroxybenzyl chloride and 2-hydroxypropionamide. The recrystallization adopts ethanol as a solvent to obtain 19.93 g of the product, and the molar yield is 95.3% in terms of catechol.
三步反应的总收率为87.68%，产品纯度为99.9%。The total yield of the three-step reaction was 87.68%, and the product purity was 99.9%.
以上述依据本发明的理想实施例为启示，通过上述的说明内容，相关工作人员完全可以在不偏离本项发明技术思想的范围内，进行多样的变更以及修改。凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。本项发明的技术性范围并不局限于说明书上的内容，必须要根据权利要求范围来确定其技术性范围。Taking the above ideal embodiments according to the present invention as inspiration, and through the above description, relevant personnel can make various changes and modifications without departing from the technical idea of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention. The technical scope of the present invention is not limited to the contents in the specification, and the technical scope must be determined according to the scope of the claims.
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