CN112778119A - Green aqueous phase solvent-free high-purity synthesis method of palmitoylethanolamide - Google Patents
Green aqueous phase solvent-free high-purity synthesis method of palmitoylethanolamide Download PDFInfo
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- 229950007031 palmidrol Drugs 0.000 title claims abstract description 56
- HXYVTAGFYLMHSO-UHFFFAOYSA-N palmitoyl ethanolamide Chemical compound CCCCCCCCCCCCCCCC(=O)NCCO HXYVTAGFYLMHSO-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 239000008346 aqueous phase Substances 0.000 title claims description 7
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims abstract description 76
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 43
- 235000021314 Palmitic acid Nutrition 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims abstract description 38
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims abstract description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 230000007062 hydrolysis Effects 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 21
- 238000005917 acylation reaction Methods 0.000 claims abstract description 20
- 239000000126 substance Substances 0.000 claims abstract description 18
- 235000019482 Palm oil Nutrition 0.000 claims abstract description 15
- 239000002540 palm oil Substances 0.000 claims abstract description 15
- 239000000413 hydrolysate Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 108010009736 Protein Hydrolysates Proteins 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000012071 phase Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 239000008234 soft water Substances 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- JDMJOWWQRDWAAG-UHFFFAOYSA-N ethanol;hexadecan-1-amine Chemical compound CCO.CCCCCCCCCCCCCCCCN JDMJOWWQRDWAAG-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 8
- 239000000047 product Substances 0.000 abstract description 8
- 239000006227 byproduct Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 5
- 238000007086 side reaction Methods 0.000 abstract description 4
- 239000007858 starting material Substances 0.000 abstract description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000012467 final product Substances 0.000 description 7
- 102000001390 Fructose-Bisphosphate Aldolase Human genes 0.000 description 4
- 108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 description 4
- SVIHWMDRHOLWGJ-UHFFFAOYSA-N ethanol hexadecanamide Chemical compound C(CCCCCCCCCCCCCCC)(=O)N.C(C)O SVIHWMDRHOLWGJ-UHFFFAOYSA-N 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 240000004713 Pisum sativum Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
- C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a green water-phase solvent-free high-purity synthesis method of palmitoylethanolamide, which adopts food-grade palm oil as an initial raw material, performs high-pressure catalyst-free continuous hydrolysis reaction on the initial raw material in a high-temperature high-pressure hydrolysis tower to obtain a hydrolysate, then rectifies the hydrolysate to obtain a high-purity compound palmitic acid A, and performs acylation reaction on the high-purity compound palmitic acid A and monoethanolamine to obtain the high-purity palmitoylethanolamide. The invention uses food-grade palm oil which is more healthy and friendly to human bodies as a starting material, adopts a green water-phase solvent-free preparation method, reduces side reactions and byproducts, greatly improves the product purity, does not use any chemical solvent in the whole reaction section, ensures that the produced palmitoylethanolamide has no solvent residue, and is a low-cost preparation method suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of organic chemistry, in particular to a green aqueous phase solvent-free high-purity synthetic method of palmitoylethanolamide.
Background
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, belonging to nuclear factor agonists. Palmitoylethanolamide has been one of the well-known food ingredients in european countries for more than 50 years. More than 500 efficacy reports of the product are reported in domestic and foreign authoritative journal. According to these official literature reports, palmitoylethanolamide is one of the very important endogenous analgesic and anti-inflammatory compounds and has been shown to be effective both in acute and in chronic pain. Palmitoylethanolamide is synthesized and metabolized in animals by different animal cell types, while it is also naturally present in many plants, for example: tomato, soybean, pea, etc. Palmitoylethanolamide has been identified as a therapeutic substance with potent anti-inflammatory properties in the last 50 centuries. Developed countries such as europe, usa, australia, canada, etc. have been widely used.
At present, the synthesis method of palmitoylethanolamide at home and abroad is commonly used as follows:
1) the hexadecanamide ethanol is synthesized by ethanolamine and palmitic acid, the reaction route uses chemical solvents of benzene and ethanol, although the yield can reach 99%, the content of the final product of the hexadecanamide ethanol is only 95-98%, and the hexadecanamide ethanol contains the residue of the solvent benzene which is extremely harmful to human bodies.
2) The palmitoylethanolamide is synthesized by ethanolamine and palmitoyl chloride, and the reaction route uses a chemical solvent n-hexane as a reaction solvent, so that the final product palmitoylethanolamide also contains solvent residues of the n-hexane. The hazards to humans of n-hexane are also well known.
3) Under the action of aldolase, ethanolamine and palmitic acid are used for synthesizing palmitoylethanolamide, the reaction route does not use any chemical solvent, has no chemical solvent residue, has high product purity and is friendly to human bodies, but aldolase is very expensive and is not suitable for industrial production.
In summary, in the 3 methods for synthesizing palmitoylethanolamide, which are commonly used at present, some reaction routes have toxic and harmful residual solvents and low product purity, and some reaction routes have the disadvantages of very high cost and incapability of realizing industrial production. This makes palmitoylethanolamide, prepared by the methods described in the prior documents, potentially harmful to the health of the human body when used as a food additive and a dietary supplement for applications requiring high quality, high purity and low solvent residue.
Disclosure of Invention
The invention provides a green water-phase solvent-free preparation method, which aims to solve the problems that a large amount of chemical solvents are used in the existing preparation method of palmitoylethanolamide, byproducts are more in the production process, the purity of finished products is low, toxic and harmful solvent residual benzene, n-hexane and the like are potentially harmful to human bodies, or aldolase with very high price is used, and the green water-phase solvent-free preparation method is adopted, so that side reactions and byproducts are reduced, the purity of the products is greatly improved, meanwhile, no chemical solvent is used in the whole reaction section, the cost is low, the produced palmitoylethanolamide has no solvent residue, and the green water-phase solvent-free high-purity synthesis method of palmitoylethanolamide is suitable for industrial production.
In order to achieve the purpose, the invention adopts the following technical scheme: a green water-phase solvent-free high-purity synthetic method of palmitoylethanolamide comprises the steps of adopting food-grade palm oil as an initial raw material, carrying out high-pressure catalyst-free continuous hydrolysis reaction on the initial raw material in a high-temperature high-pressure hydrolysis tower to obtain a hydrolysate, then rectifying the hydrolysate to obtain a high-purity compound palmitic acid A, and carrying out acylation reaction on the high-purity compound palmitic acid A and monoethanolamine to obtain high-purity palmitoylethanolamide;
wherein the chemical structural formula of the compound palmitic acid A is as follows:
the chemical structural formula of monoethanolamine is:
the chemical structural formula of the palmitoylethanolamide is as follows:
comprises the following synthesis steps: 1) adding food-grade palm oil into a high-temperature high-pressure hydrolysis tower, and adding soft water for hydrolysis reaction, wherein the mass ratio of the palm oil to the volume of the soft water is 100 Kg: 65L, controlling the hydrolysis temperature of the hydrolysis reaction to be 240-270 ℃, controlling the hydrolysis pressure to be 510-615 MPa, carrying out automatic reaction in a high-temperature high-pressure hydrolysis tower for 4-6 hours, and obtaining a hydrolysate solution after the hydrolysis reaction is finished; 2) rectifying the hydrolysate solution obtained in the step 1) in a rectifying tower, wherein the pressure intensity at the top of the rectifying tower is controlled to be 0.15Kpa-0.45Kpa during rectification, and the temperature of collected fraction is 175-190 ℃, so as to obtain a high-purity compound palmitic acid A; 3) adding the high-purity compound palmitic acid A obtained in the step 2) into a reaction kettle, adding deionized water, wherein the mass ratio of the high-purity compound palmitic acid A to the deionized water is 1:1, stirring a mixture of a high-purity compound palmitic acid A and deionized water in a reaction kettle, uniformly heating to 100 ℃ within 1 hour, keeping the temperature constant for 1 hour, dropwise adding a quantitative monoethanolamine solution into the reaction kettle at a constant speed for 2 hours, the mole number of the quantitative monoethanolamine solution is 1.0-1.2 times of that of the high-purity compound palmitic acid A, then heating up the reaction kettle and controlling the temperature of the acylation reaction to be 150-200 ℃ and stirring the mixture for 20 hours, after the acylation reaction is finished, and (3) keeping the temperature of 100-115 ℃ and standing for 0.5-1.5 hours, removing the bottom water phase of the reaction kettle, quickly centrifuging and cooling the upper layer liquid of the reaction liquid in the reaction kettle until a flaky solid is separated out, and drying to obtain flaky palmitoylethanolamide.
Preferably, in the step 1), the hydrolysis temperature of the hydrolysis reaction is controlled to be 260-265 ℃, the hydrolysis pressure is controlled to be 510MPa, and the automatic reaction time is 5 hours.
Preferably, in the step 2), the pressure at the top of the rectifying tower is controlled to be 0.4Kpa during rectification, and the temperature of the collected fraction is 180-183 ℃.
Preferably, the purity of the high-purity compound palmitic acid A obtained in the step 2) is 99.5% or more.
Preferably, in the step 3), the mole number of the quantitative monoethanolamine solution is 1.06 times of that of the high-purity compound palmitic acid A. In order to improve the efficiency of acylation reaction, the method gradually drops 1.06 equivalent of monoethanolamine and a certain amount of water into a reaction kettle at a certain temperature, the carboxylic acid group of palmitic acid preferentially reacts with the amino end of ethanolamine to generate amide, so that after the reaction is finished, the ethanolamine, water and the final product of the reaction, namely the Palmitoylethanolamide (PEA), are layered quickly under the condition of heat preservation, and the ethanolamine slightly excessive is distributed at the bottom of a water phase, thereby greatly improving the efficiency of acylation reaction, greatly reducing reaction byproducts and improving the purity of the final product, namely the palmitoylethanolamide.
Preferably, in the step 3), the acylation reaction temperature is controlled to be 155-165 ℃, and the standing time is 1 hour after the temperature is kept at 100-115 ℃.
Preferably, in the step 3), the purity of the flaked palmitoylethanolamide obtained by drying is higher than 99%, and the yield of the flaked palmitoylethanolamide is higher than 98%.
In order to solve the problem that a large amount of chemical solvents are used in the existing preparation method of palmitoylethanolamide to generate toxic and harmful solvent residues and avoid using aldolase with very high price, the technical scheme is a green water-phase solvent-free synthesis method, Malaysia food-grade palm oil is used as an initial raw material, the initial raw material palm oil is directly subjected to high-pressure catalyst-free continuous hydrolysis reaction in a high-temperature high-pressure hydrolysis tower, then a hydrolysis product is rectified to obtain a high-purity compound palmitic acid A, then the palmitic acid A and monoethanolamine are subjected to acylation reaction, and in the last step of acylation reaction, a mode of dripping monoethanolamine at a certain temperature is adopted, so that side reactions are greatly reduced, the acylation yield is greatly improved, and the Palmitoylethanolamide (PEA) with the purity of more than 99% is obtained. In addition, the whole reaction process is a water-phase reaction, and no chemical solvent is used, so that the potential hazard of the chemical solvent residue to the human body when the final product of the Palmitoylethanolamide (PEA) is used as a food additive and a dietary supplement is greatly reduced, and the human body use safety of the final product of the Palmitoylethanolamide (PEA) is improved.
Therefore, the invention has the following beneficial effects: the method has the advantages that food-grade palm oil which is healthier and more friendly to human bodies is used as a starting material, a green water-phase solvent-free preparation method is adopted, side reactions and byproducts are reduced, the product purity is greatly improved, meanwhile, no chemical solvent is used in the whole reaction section, so that the produced palmitoylethanolamide has no solvent residue, and the method is a low-cost preparation method of Palmitoylethanolamide (PEA) suitable for industrial production.
Drawings
FIG. 1 is a schematic diagram of the synthesis process of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by those skilled in the art without any inventive work based on the embodiments of the present invention belong to the protection scope of the present invention.
As shown in fig. 1, the present invention provides a technical solution:
a green water-phase solvent-free high-purity synthetic method of palmitoylethanolamide comprises the steps of adopting food-grade palm oil as an initial raw material, carrying out high-pressure catalyst-free continuous hydrolysis reaction on the initial raw material in a high-temperature high-pressure hydrolysis tower to obtain a hydrolysate, then rectifying the hydrolysate to obtain a high-purity compound palmitic acid A, and carrying out acylation reaction on the palmitic acid A and monoethanolamine to obtain high-purity palmitoylethanolamide;
comprises the following synthesis steps: 1) adding food-grade palm oil into a high-temperature high-pressure hydrolysis tower, and adding soft water for hydrolysis reaction, wherein the mass ratio of the palm oil to the volume of the soft water is 100 Kg: 65L, controlling the hydrolysis temperature of the hydrolysis reaction to be 240-270 ℃, controlling the hydrolysis pressure to be 510-615 MPa, carrying out automatic reaction in a high-temperature high-pressure hydrolysis tower for 4-6 hours, and obtaining a hydrolysate solution after the hydrolysis reaction is finished; 2) rectifying the hydrolysate solution obtained in the step 1) in a rectifying tower, wherein the pressure intensity at the top of the rectifying tower is controlled to be 0.15Kpa-0.45Kpa during rectification, and the temperature of collected fraction is 175-190 ℃, so as to obtain a high-purity compound palmitic acid A; 3) adding the high-purity compound palmitic acid A obtained in the step 2) into a reaction kettle, adding deionized water, wherein the mass ratio of the high-purity compound palmitic acid A to the deionized water is 1:1, stirring a mixture of the high-purity compound palmitic acid A and the deionized water in the reaction kettle, uniformly heating to 100 ℃ within 1 hour, keeping the temperature constant for 1 hour, dropwise adding a quantitative monoethanolamine solution into the reaction kettle at a constant speed, dropwise adding the ethanolamine solution for 2 hours, wherein the mole number of the quantitative monoethanolamine solution is 1.0-1.2 times of that of the high-purity compound palmitic acid A, heating in the reaction kettle, controlling the acylation reaction temperature to be 150-200 ℃, stirring for 20 hours, after the acylation reaction is finished, keeping the temperature and standing for 0.5-1.5 hours at 100-115 ℃, placing a bottom water phase of the reaction kettle, quickly centrifuging and cooling an upper layer liquid of a reaction liquid in the reaction kettle until a flaky solid is separated out, drying to obtain the flaky hexadecylamide ethanol.
The specific implementation process is that 1000Kg of food-grade palm oil is injected into the top of the high-temperature high-pressure hydrolysis tower, 650L of process water (soft water) is injected upwards from the bottom, the operation condition is that the hydrolysis temperature is controlled between 240 ℃ and 270 ℃, preferably between 260 ℃ and 265 ℃, the hydrolysis pressure is controlled between 510MPa and 615MPa, preferably between 600MPa, and the automatic reaction is carried out in the high-temperature high-pressure hydrolysis tower for 4 to 6 hours, preferably for 5 hours;
rectifying the obtained hydrolysate solution in a rectifying tower, wherein the pressure at the top of the rectifying tower is set to be 0.15Kpa-0.45Kpa, preferably 0.4Kpa, the temperature of collected fractions is 175-190 ℃, preferably 180-183 ℃, and the compound palmitic acid A with the purity of more than 99.5% is obtained;
adding 1280Kg of the obtained high-purity compound palmitic acid A into a reaction kettle, adding 1280Kg of deionized water, uniformly heating to 100 ℃ within 1 hour under a stirring state, keeping the temperature stable for 1 hour, then gradually dripping 1.0-1.2 times, preferably 1.06 times, of monoethanolamine solution of the mole number of the high-purity compound palmitic acid A into the reaction kettle, controlling the dripping speed, dripping all the monoethanolamine solution within 2 hours, heating, controlling the acylation reaction temperature to be 150-200 ℃, preferably 155-165 ℃, stirring for 20 hours, keeping the temperature of 100-115 ℃ and standing for 0.5-1.5 hours, preferably 1 hour after the acylation reaction is finished, removing a bottom water phase, quickly centrifugally cooling the upper layer liquid of the reaction liquid to precipitate a flaky solid, and drying to obtain 1470Kg of flaky Palmitoylethanolamide (PEA);
the purity of the compound A palmitic acid obtained by hydrolysis reaction and rectification in the scheme can reach more than 99.5%. The yield in the acylation reaction can reach 98.2 percent at most, and the purity of the final product, namely the Palmitoylethanolamide (PEA), can reach more than 99 percent.
Claims (7)
1. A green water-phase solvent-free high-purity synthesis method of palmitoylethanolamide is characterized in that food-grade palm oil is used as an initial raw material, high-pressure catalyst-free continuous hydrolysis reaction is carried out on the initial raw material in a high-temperature high-pressure hydrolysis tower to obtain a hydrolysate, then the hydrolysate is rectified to obtain a high-purity compound palmitic acid A, and the high-purity compound palmitic acid A and monoethanolamine are subjected to acylation reaction to obtain high-purity palmitoylethanolamide;
wherein the chemical structural formula of the compound palmitic acid A is as follows:
the chemical structural formula of monoethanolamine is:
the chemical structural formula of the palmitoylethanolamide is as follows:
comprises the following synthesis steps:
1) adding food-grade palm oil into a high-temperature high-pressure hydrolysis tower, and adding soft water for hydrolysis reaction, wherein the mass ratio of the palm oil to the volume of the soft water is 100 Kg: 65L, controlling the hydrolysis temperature of the hydrolysis reaction to be 240-270 ℃, controlling the hydrolysis pressure to be 510-615 MPa, carrying out automatic reaction in a high-temperature high-pressure hydrolysis tower for 4-6 hours, and obtaining a hydrolysate solution after the hydrolysis reaction is finished;
2) rectifying the hydrolysate solution obtained in the step 1) in a rectifying tower, wherein the pressure intensity at the top of the rectifying tower is controlled to be 0.15Kpa-0.45Kpa during rectification, and the temperature of collected fraction is 175-190 ℃, so as to obtain a high-purity compound palmitic acid A;
3) adding the high-purity compound palmitic acid A obtained in the step 2) into a reaction kettle, adding deionized water, wherein the mass ratio of the high-purity compound palmitic acid A to the deionized water is 1:1, stirring a mixture of the high-purity compound palmitic acid A and the deionized water in the reaction kettle, uniformly heating to 100 ℃ within 1 hour, keeping the temperature constant for 1 hour, dropwise adding a quantitative monoethanolamine solution into the reaction kettle at a constant speed, dropwise adding the ethanolamine solution for 2 hours, wherein the mole number of the quantitative monoethanolamine solution is 1.0-1.2 times of that of the high-purity compound palmitic acid A, heating in the reaction kettle, controlling the acylation reaction temperature to be 150-200 ℃, stirring for 20 hours, after the acylation reaction is finished, keeping the temperature and standing for 0.5-1.5 hours at 100-115 ℃, placing a bottom water phase of the reaction kettle, quickly centrifuging and cooling an upper layer liquid of a reaction liquid in the reaction kettle until a flaky solid is separated out, drying to obtain the flaky hexadecylamide ethanol.
2. The process of claim 1, wherein in step 1), the hydrolysis temperature of hydrolysis reaction is controlled to 260-265 ℃, the hydrolysis pressure is controlled to 510MPa, and the automatic reaction time is 5 hours.
3. The method for the green aqueous phase solvent-free high-purity synthesis of palmitoylethanolamide according to claim 1, characterized in that in the step 2), the pressure at the top of the rectifying tower is controlled to be 0.4Kpa during rectification, and the temperature of the collected fraction is 180-183 ℃.
4. The method for the green aqueous phase solvent-free high-purity synthesis of palmitoylethanolamide according to claim 1, characterized in that the purity of the high-purity compound palmitic acid A obtained in step 2) is more than 99.5%.
5. The method for the green aqueous phase solvent-free high-purity synthesis of palmitoylethanolamide according to claim 1, characterized in that in step 3), the mole number of the quantitative monoethanolamine solution is 1.06 times that of the high-purity compound palmitic acid A.
6. The method for synthesizing palmitoylethanolamide in a green water phase and without solvent and with high purity as recited in claim 1, wherein in said step 3), said acylation reaction temperature is controlled at 155-165 ℃, and said temperature of 100-115 ℃ is maintained for 1 hour.
7. The method for synthesizing palmitoylethanolamide in a green aqueous phase and without solvent and with high purity as claimed in claim 1, characterized in that in said step 3), the purity of palmitoylethanolamide in the form of sheets obtained by drying is higher than 99%, and the yield of palmitoylethanolamide in the form of sheets is higher than 98%.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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