CN118063340A - Purification method for synthesizing capsaicin - Google Patents
Purification method for synthesizing capsaicin Download PDFInfo
- Publication number
- CN118063340A CN118063340A CN202410234153.6A CN202410234153A CN118063340A CN 118063340 A CN118063340 A CN 118063340A CN 202410234153 A CN202410234153 A CN 202410234153A CN 118063340 A CN118063340 A CN 118063340A
- Authority
- CN
- China
- Prior art keywords
- solid
- capsaicin
- alcohol
- synthetic capsaicin
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 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 46
- 238000000034 method Methods 0.000 title claims abstract description 37
- 229960002504 capsaicin Drugs 0.000 title claims abstract description 22
- 235000017663 capsaicin Nutrition 0.000 title claims abstract description 22
- 238000000746 purification Methods 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 43
- 239000007787 solid Substances 0.000 claims abstract description 39
- 238000003756 stirring Methods 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001035 drying Methods 0.000 claims abstract description 17
- 239000012535 impurity Substances 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 14
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 7
- 238000002386 leaching Methods 0.000 claims abstract description 6
- 239000012043 crude product Substances 0.000 claims abstract description 5
- 238000004090 dissolution Methods 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- RGOVYLWUIBMPGK-UHFFFAOYSA-N nonivamide Chemical compound CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 RGOVYLWUIBMPGK-UHFFFAOYSA-N 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 3
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 239000000047 product Substances 0.000 abstract description 32
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000002425 crystallisation Methods 0.000 abstract description 6
- 230000008025 crystallization Effects 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 description 18
- 239000012065 filter cake Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 10
- 238000004811 liquid chromatography Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- TZZAKSLHHIJRLL-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1O TZZAKSLHHIJRLL-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000003373 anti-fouling effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- 239000003973 paint Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000002519 antifouling agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- -1 tincture Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a purification method for synthesizing capsaicin. The method of the invention comprises the following steps: dissolving the synthesized capsaicin crude product in 3-7 times of first alcohol; cooling the solution obtained after full dissolution to-5 ℃ to 30 ℃, then adding 1 equivalent of alkali in batches, preserving heat and stirring for 2-3 hours after the addition, and filtering to obtain a solid; and (3) leaching the obtained solid by adopting a second alcohol, adding water with the mass which is 2-4 times that of the solid, mixing and stirring, then dripping an acid solution to adjust the pH value to 7-8, and filtering and drying the precipitated solid to obtain the solid. The method has the advantages of simple process, low production cost and high yield; can solve the problem that the existing crude synthesized capsaicin purification method needs multiple crystallization to meet the product purity requirement; and the purity of the prepared synthesized capsaicin is not lower than 99.9%, and the maximum content of single impurity is not higher than 0.03%.
Description
Technical Field
The invention relates to the technical field of preparation of synthetic capsaicin, in particular to a purification method of synthetic capsaicin.
Background
The synthesized capsaicin, also called n-nonanoic acid vanillamide, is a natural capsaicin analog, is white or light yellow solid, has CAS registration number of 2444-46-4, molecular formula of C 17H27NO3, molecular weight of 293.4, melting point of 56-58 ℃, decomposition temperature of 340 ℃ and water solubility of 27ppm at 25 ℃. The structural formula is as follows:
Synthetic capsaicin has a chemical structure and biological activity similar to those of natural capsaicin compounds, and has wide application, and can replace natural capsaicin. Such as: in the field of medicine, the external preparation can be used for non-addiction pain relieving, bacteria and fungi inhibiting, blood circulation promoting, and can be made into liniment, tincture, cream, patch, fever patch, etc. In the field of rat-proof cables: the rat-proof additive used as the plastic sheath of the cable is used for preventing animals from being chewed and cut, and can be used in the cable and optical cable industry. The biological antifouling agent is used in the field of ship antifouling paint, is coated on the parts of ships and offshore structures, which are contacted with seawater, prevents the attachment of marine organisms such as algae, shellfish, mollusks and the like, can achieve the aim of preventing the aggregation of the aquatic organisms on the ship hulls, and replaces the organotin antifouling paint.
Chinese patent documents such as CN111875514A, CN113105354 and CN107793325A respectively disclose various synthesis methods for synthesizing capsaicin, which respectively adopt crystallization purification of ethyl acetate, petroleum ether, toluene and the like, and the obtained synthesized capsaicin has higher purity but does not give the content of single impurity. Because the pharmaceutical grade product has high requirements on the purity of the product and the single impurity, especially the content of the single impurity in the product is required to be less than 0.05 percent, the crystallization and purification of the ethyl acetate, the petroleum ether, the toluene and the like are adopted, and at least 3 to 4 times of crystallization are required to meet the purity requirements, especially the purity requirements of the single impurity, so that the problems of complex process, low yield, high production cost and the like can be caused.
CN1852707a discloses the preparation and purification of a synthetic capsaicin, wherein the purification process is specifically to dissolve the crude synthetic capsaicin product in a mixture of diethyl ether/hexane, and heat the mixture to 40-45 ℃, then cool the mixture to room temperature or below; filtering the mixture to provide a purified synthetic capsaicin product; the synthetic capsaicin product can be further purified using semi-preparative HPLC to yield a high purity capsaicin product. But also cannot achieve control over the maximum content of a single impurity.
Therefore, the development of a convenient and efficient purification method for synthesizing capsaicin, which can realize the control of the maximum content of single impurity and has low production cost, has important significance.
Disclosure of Invention
The invention aims to solve the technical problems in the prior art and provides a purification method for synthesizing capsaicin, which has the advantages of simple process, low production cost and no more than 0.03 percent of single impurity in the purified product.
In order to solve the technical problems, the invention adopts the following technical scheme:
The invention provides a purification method of synthetic capsaicin, which comprises the following steps:
(1) Dissolving the synthesized capsaicin crude product in 3-7 times of first alcohol;
(2) Cooling the solution obtained after full dissolution to-5 ℃ to 30 ℃, then adding 1 molar equivalent of alkali in batches, preserving heat and stirring for 2-3 hours after the addition is finished, and filtering to obtain a solid; the addition in batches can avoid the temperature rise caused by heat release;
(3) And (3) leaching the solid obtained in the step (2) by adopting a second alcohol, adding water with the mass which is 2-4 times that of the solid, mixing and stirring, then dripping an acid solution to adjust the pH value to 7-8, and filtering and drying the precipitated solid to obtain the solid.
Further, the first alcohol in the step (1) is any one of methanol, ethanol and isopropanol. Isopropyl alcohol is preferred.
Further, the second glycol used for leaching in the step (3) is any one of methanol, ethanol and isopropanol.
Preferably, for ease of solvent recovery, the first alcohol of step (1) is the same as the second alcohol used for the rinsing of step (3).
Further, the alkali added in the step (2) is any one of sodium hydroxide, potassium hydroxide, sodium methoxide, potassium tert-butoxide or sodium methoxide in methanol.
Preferably, the base added in step (2) is 28% strength by mass sodium methoxide in methanol.
Further, the temperature of the heat preservation stirring after the alkali is added in the step (2) is 0-5 ℃.
Further, the acid solution for adjusting the pH in the step (3) is hydrochloric acid or sulfuric acid.
Further, step (3) further comprises washing the filtered solid with water.
Further, the drying mode of the step (3) is reduced pressure drying, and the drying temperature is 35-45 ℃.
Further, the purity of the synthesized capsaicin prepared by the purification method is not lower than 99.9 percent and the content of single impurity is not higher than 0.03 percent through HPLC test.
The invention has the beneficial effects that:
1. The method provided by the invention has the advantages of simple process, low production cost and high yield; the sodium salt forming step can effectively remove impurities through simple leaching, and can solve the problems of complex process, low yield and high production cost caused by the fact that the existing crude synthesized capsaicin purification method needs 3-4 times of crystallization to meet the product purity requirement.
2. The purity of the synthesized capsaicin prepared by the method is not lower than 99.9%, the maximum content of single impurity is not higher than 0.05%, the high requirements of high purity of medical grade products and less than 0.05% of single impurity can be met, and the application prospect of the products is improved.
Drawings
FIG. 1 is a diagram showing the nuclear magnetic resonance spectrum of 1 HNMR of the product obtained in the example of the present invention. The abscissa in the figure is chemical shift; the ordinate is the absorption peak intensity.
Detailed Description
The term as used herein:
"prepared from … …" is synonymous with "comprising". The terms "comprising," "including," "having," "containing," or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.
When an equivalent, concentration, or other value or parameter is expressed as a range, preferred range, or a range bounded by a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when ranges of "1 to 5" are disclosed, the described ranges should be construed to include ranges of "1 to 4", "1 to 3", "1 to 2 and 4 to 5", "1 to 3 and 5", and the like. When a numerical range is described herein, unless otherwise indicated, the range is intended to include its endpoints and all integers and fractions within the range.
In these examples, the parts and percentages are by mass unless otherwise indicated.
"Parts by weight"/"parts by mass" means a basic unit of measurement indicating a mass ratio relationship of a plurality of components, and 1 part may indicate an arbitrary unit mass, for example, 1g may be indicated, 2g may be indicated, or the like. If we say that the mass part of the a component is a part and the mass part of the B component is B part, the ratio a of the mass of the a component to the mass of the B component is represented as: b. or the mass of the A component is aK, the mass of the B component is bK (K is any number and represents a multiple factor). It is not misunderstood that the sum of the parts by mass of all the components is not limited to 100 parts, unlike the parts by mass.
"And/or" is used to indicate that one or both of the illustrated cases may occur, e.g., a and/or B include (a and B) and (a or B).
In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The embodiment of the invention provides a purification method for synthesizing capsaicin, which comprises the following steps:
(1) Dissolving the synthesized capsaicin crude product in 3-7 times of first alcohol; as a preferred embodiment, the first alcohol is selected from any one of methanol, ethanol and isopropanol, and more preferably isopropanol.
(2) The solution obtained after full dissolution is cooled to-5 ℃ to 30 ℃, and then 1 molar equivalent of alkali is added in batches, so that the severe temperature rise caused by heat release can be avoided; after the addition, preserving heat at 0-5 ℃ and stirring for 2-3 hours, and filtering to obtain solid; as a preferred embodiment, the base added is any one of sodium hydroxide, potassium hydroxide, sodium methoxide, potassium tert-butoxide or sodium methoxide in methanol. More preferably 28% by mass sodium methoxide in methanol.
(3) And (3) leaching the solid obtained in the step (2) by adopting a second alcohol with the mass 1-1.5 times of that of the crude product, adding water with the mass 2-4 times of that of the solid, mixing, stirring, dissolving and dispersing the salt of the product, then dripping an acid solution to adjust the pH value to 7-8, and filtering, washing and drying the precipitated solid to obtain the solid. As a preferred embodiment, the second alcohol is selected from any one of methanol, isopropanol or ethanol. The first alcohol is selected from the same alcohol as the second. The acid solution for adjusting the pH is hydrochloric acid or sulfuric acid, more preferably hydrochloric acid. The drying mode adopts decompression drying, and the drying temperature is 35-45 ℃.
The following is described by way of specific examples:
Example 1
(1) 100 G of crude synthetic capsaicin (97.7% pure) are dissolved in 500 g (5 times mass) of isopropanol.
(2) The temperature is reduced to 0 ℃ by stirring, 66 g (1 mol equivalent) of 28% sodium methoxide methanol solution is added dropwise, and the mixture is kept at 0-5 ℃ and stirred for 2 hours and filtered.
(3) After washing the cake with cold 100g (1 time mass) of isopropanol, 300 g of water (3 times mass) was then added to the resulting solid, which was cooled to 10 ℃ with stirring, and 37% concentrated hydrochloric acid was slowly added dropwise to adjust the pH to 7-8, and stirred for 2-3 hours until the pH stabilized at 7-8. The solid was separated out, filtered, the filter cake was washed with water and dried under reduced pressure at 40℃to give 91 g of the product, designated sample Y1.
Example 2
(1) 25 G of crude synthetic capsaicin (97.7% purity) is dissolved in 100 g (4 times mass) ethanol.
(2) Stirring and cooling to 0 ℃, and adding 3.4 g (1 equivalent) of sodium hydroxide solid; after the addition, the mixture is stirred for 2 hours at the temperature of between 0 and 5 ℃ and filtered.
(3) After washing the filter cake with 25g of cold ethanol, 100 g of water (4 times of mass) is then added to the obtained solid, the mixture is cooled to 10 ℃ under stirring, 37% concentrated hydrochloric acid is slowly added dropwise to adjust the pH value to 7-8, and the mixture is stirred for 2-3 hours until the pH value is stabilized at 7-8. Separating out and filtering solid, washing filter cake with water, decompressing and drying at 40 ℃ to obtain 23g of product which is marked as sample Y2.
Example 3
(1) 25 Kg of crude synthetic capsaicin (purity 97.2%) are dissolved in 125 kg (4 times mass) of isopropanol.
(2) Stirring and cooling to 0 ℃, and dropwise adding 16.5 kg of 28% sodium methoxide methanol solution; after the addition, the mixture is stirred for 2 hours at the temperature of between 0 and 5 ℃ and filtered.
(3) After washing the filter cake with 25 kg of cold isopropanol, 75 kg of water is added to the obtained solid, the solid is cooled to 10 ℃ under stirring, 37% of concentrated hydrochloric acid is slowly added dropwise to adjust the pH value to 7-8, and the mixture is stirred for 2-3 hours until the pH value is stabilized at 7-8. Separating out solid, centrifugally filtering, washing a filter cake with water, and drying under reduced pressure at 40 ℃ to obtain 23.25 kg of a product, which is marked as a sample Y3.
Example 4
(1) 250 G of crude synthetic capsaicin (97.2% purity) is dissolved in 750 g (3 times mass) isopropanol.
(2) Stirring and cooling to 0 ℃, and dropwise adding 165 g of 28% sodium methoxide methanol solution; after the addition, the mixture is stirred for 2 hours at the temperature of between 0 and 5 ℃ and filtered.
(3) After the filter cake is washed with 250 g of cold isopropanol, 750 g of water is added to the obtained solid, the solid is cooled to 10 ℃ under stirring, 37% of concentrated hydrochloric acid is slowly added dropwise to adjust the pH value to 7-8, and the mixture is stirred for 2-3 hours until the pH value is stabilized at 7-8. Separating out solid, centrifugally filtering, washing a filter cake with water, and drying under reduced pressure at the temperature of 40 ℃ to obtain 225 g of product which is marked as a sample Y4.
Example 5
(1) 250 G of crude synthetic capsaicin (97.2% purity) is dissolved in 1750 g (7 times mass) isopropanol.
(2) Stirring and cooling to 0 ℃, and dropwise adding 165 g of 28% sodium methoxide methanol solution; after the addition, the mixture is stirred for 2 hours at the temperature of between 0 and 5 ℃ and filtered.
(3) After the filter cake is washed with 250 g of cold isopropanol, 750 g of water is added to the obtained solid, the solid is cooled to 10 ℃ under stirring, 37% of concentrated hydrochloric acid is slowly added dropwise to adjust the pH value to 7-8, and the mixture is stirred for 2-3 hours until the pH value is stabilized at 7-8. Separating out solid, centrifugally filtering, washing a filter cake with water, and drying under reduced pressure at the temperature of 40 ℃ to obtain 215 g of product which is marked as a sample Y5.
Comparative example 1 (pH change vs. example 4)
(1) 250 G of crude synthetic capsaicin (97.2% purity) is dissolved in 1000 g (4 times mass) of isopropanol.
(2) Stirring and cooling to 0 ℃, and dropwise adding 165 g of 28% sodium methoxide methanol solution; after the addition, the mixture is stirred for 2 hours at the temperature of between 0 and 5 ℃ and filtered.
(3) After the filter cake is washed with 250 g of cold isopropanol, 750 g of water is added to the obtained solid, the solid is cooled to 10 ℃ under stirring, 37% of concentrated hydrochloric acid is slowly added dropwise to adjust the pH value to 8-9, and the mixture is stirred for 2-3 hours until the pH value is stabilized at 8-9. Separating out solid, centrifugally filtering, washing a filter cake with water, and drying under reduced pressure at the temperature of 40 ℃ to obtain 220 g of product which is marked as sample Y6.
In order to verify the feasibility and effectiveness of the present invention, the samples Y1 to Y6 prepared in the above examples were subjected to the following experimental verification:
1. product purity detection
The liquid chromatography (HPLC) method is adopted to detect each product sample, and the specific method is as follows: the chromatographic column adopts a C-18 column (4.6 mm. Times.250 mm,5 μm); the mobile phase is acetonitrile: water (0.1% sodium dodecyl sulfate, 0.1% triethylamine, pH adjusted with phosphoric acid to 3.8) =42:58, flow rate to 1.0 mL/min, detection wavelength to 215nm, sample injection amount to 20 μl; column temperature 25 ℃.
The liquid chromatography data of each example and comparative example are shown in tables 1 to 6 below.
TABLE 1 liquid chromatography data for the product of example 1
TABLE 2 liquid chromatography data for the product of example 2
TABLE 3 liquid chromatography data for the product of example 3
TABLE 4 liquid chromatography data for the product of example 4
TABLE 5 liquid chromatography data for the product of example 5
TABLE 6 liquid chromatography data for the product of comparative example 1
The liquid chromatography detection results of each product are shown in the following table 7:
TABLE 7 comparison of product yields, purities and maximum impurity levels for the examples and comparative examples
2. 1 HNMR structural characterization
The product samples obtained in each example and comparative example were subjected to 1 HNMR structural characterization, and the results are shown in FIG. 1. The specific characterization results are as follows:
1HNMR(500MHz,CDCl3)：δ6.85ppm(dd,1H,ArH);δ6.80ppm(s,1H,ArH);δ6.75ppm(dd,1H,ArH);δ5.73ppm(bs,1H,PhOH);δ4.35ppm(d,2H,Ar-CH2-N);δ3.87ppm(s,3H,-OCH3);δ2.19ppm(m,2H,N-CH2-C);δ1.67ppm(m,2H,-CH2-);δ1.29ppm(m,10H,-(CH2)5-);δ0.87ppm(m,3H,-CH3).
In conclusion, the purification method provided by the invention has simple process, can realize the high purity requirement of the synthesized capsaicin (the purity of the synthesized capsaicin is not lower than 99.9 percent, and the maximum content of single impurity is not higher than 0.03 percent) without repeated crystallization for many times, and can meet the high purity of medical grade products; low production cost and high yield.
The foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for purifying synthetic capsaicin, comprising the steps of:
(1) Dissolving the synthesized capsaicin crude product in 3-7 times of first alcohol;
(2) Cooling the solution obtained after full dissolution to-5 ℃ to 30 ℃, then adding 1 molar equivalent of alkali in batches, preserving heat and stirring for 2-3 hours after the addition is finished, and filtering to obtain a solid;
(3) And (3) leaching the solid obtained in the step (2) by adopting a second alcohol, adding water with the mass which is 2-4 times that of the solid, mixing and stirring, then dripping an acid solution to adjust the pH value to 7-8, and filtering and drying the precipitated solid to obtain the solid.
2. The method for purifying synthetic capsaicin according to claim 1, wherein the first alcohol in step (1) is any one of methanol, ethanol and isopropanol.
3. The method for purifying synthetic capsaicin according to claim 1, wherein the second alcohol used in the rinsing in step (3) is any one of methanol, ethanol and isopropanol.
4. The method of purifying synthetic capsaicin according to claim 1, wherein the first alcohol of step (1) is the same as the second alcohol used in the rinsing of step (3).
5. The method for purifying synthetic capsaicin according to claim 1, wherein the base added in step (2) is any one of sodium hydroxide, potassium hydroxide, sodium methoxide, potassium tert-butoxide or sodium methoxide in methanol.
6. The method for purifying synthetic capsaicin according to claim 5, wherein the alkali added in the step (2) is 28% sodium methoxide methanol solution.
7. The method for purifying synthetic capsaicin according to claim 1, wherein the temperature of the heat-preserving stirring after the alkali is added dropwise in the step (2) is 0-5 ℃.
8. The method for purifying synthetic capsaicin according to claim 5, wherein the pH-adjusted acid solution in step (3) is hydrochloric acid or sulfuric acid.
9. The method for purifying synthetic capsaicin according to claim 1, wherein the drying mode in step (3) is reduced pressure drying at 35-45 ℃.
10. A method for purifying synthetic capsaicin according to any one of claims 1-9, wherein the synthetic capsaicin obtained by the purification method has a purity of not less than 99.9% and a single impurity content of not more than 0.03% as measured by HPLC.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410234153.6A CN118063340A (en) | 2024-03-01 | 2024-03-01 | Purification method for synthesizing capsaicin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410234153.6A CN118063340A (en) | 2024-03-01 | 2024-03-01 | Purification method for synthesizing capsaicin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118063340A true CN118063340A (en) | 2024-05-24 |
Family
ID=91103746
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410234153.6A Pending CN118063340A (en) | 2024-03-01 | 2024-03-01 | Purification method for synthesizing capsaicin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118063340A (en) |
-
2024
- 2024-03-01 CN CN202410234153.6A patent/CN118063340A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100418950C (en) | Process for the manufacture of quinoline derivatives | |
| CN107216289A (en) | A kind of preparation method of Edaravone | |
| DE2210563A1 (en) | Process for the separation of a diastereo isomer mixture from zearalanol | |
| DE69502572T2 (en) | Process for the preparation of geranylgeraniol | |
| CN118063340A (en) | Purification method for synthesizing capsaicin | |
| JPH08134055A (en) | Production of 3-o-substituted-ascorbic acid | |
| EP3580199A1 (en) | Method for the one-pot production of organo-iodinated compounds | |
| DE60102763T2 (en) | Process for the preparation of dihydroperimidine squaraine compounds | |
| JPS584785A (en) | Manufacture of isosorbide-2-nitrate | |
| RU2184119C2 (en) | Method of synthesis of ruthenium (iii) carboxylate | |
| US6297396B1 (en) | Method of crystallizing and purifying alkyl gallates | |
| CN114195720A (en) | Etomidate purification method | |
| US5310915A (en) | Process for the purification of 7-chloroquinoline-8-carboxylic acids | |
| FR2512042A1 (en) | NOVEL AZOIC COMPOUNDS USEFUL AS PIGMENTS | |
| CN106588633A (en) | Crystal of fumarate of salmeterol intermediate and preparation process thereof | |
| CN115677456B (en) | Preparation method of cannabidiol | |
| EP0985658B1 (en) | Process for producing l-valine benzyl ester p-toluenesulfonate | |
| CH432542A (en) | Process for the preparation of new hydrazides | |
| CN109836322B (en) | Preparation method of royal jelly acid | |
| CH616410A5 (en) | ||
| CN105985305B (en) | The preparation method of Simvastatin | |
| US6355836B1 (en) | Process for the preparation of cis 5-fluoro-2-methyl-1[p-(methylthio)benzyliden]-inden-3-acetic acid | |
| JP2531660B2 (en) | Method for purifying bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate | |
| EP0688763A1 (en) | Process for preparing anilides of hydroxycarboxylic acids | |
| DE69010686T2 (en) | METHOD FOR PRODUCING D-PROPOXYPHEN. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |