CN116003276A - Method for synthesizing capsaicin by utilizing micro-reaction chip - Google Patents
Method for synthesizing capsaicin by utilizing micro-reaction chip Download PDFInfo
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 126
- 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 101
- 229960002504 capsaicin Drugs 0.000 title claims abstract description 48
- 235000017663 capsaicin Nutrition 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 16
- 229940053939 vanillylamine Drugs 0.000 claims abstract description 24
- WRPWWVNUCXQDQV-UHFFFAOYSA-N vanillylamine Chemical compound COC1=CC(CN)=CC=C1O WRPWWVNUCXQDQV-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 19
- 239000011230 binding agent Substances 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 14
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000005643 Pelargonic acid Substances 0.000 claims abstract description 3
- 239000003513 alkali Substances 0.000 claims abstract description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
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- 239000007788 liquid Substances 0.000 claims description 21
- NTQYXUJLILNTFH-UHFFFAOYSA-N nonanoyl chloride Chemical compound CCCCCCCCC(Cl)=O NTQYXUJLILNTFH-UHFFFAOYSA-N 0.000 claims description 21
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- 238000002156 mixing Methods 0.000 claims description 15
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
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- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
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- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 235000009499 Vanilla fragrans Nutrition 0.000 description 8
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- 150000001412 amines Chemical class 0.000 description 7
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- 150000004665 fatty acids Chemical class 0.000 description 6
- ZENOXNGFMSCLLL-UHFFFAOYSA-N vanillyl alcohol Chemical compound COC1=CC(CO)=CC=C1O ZENOXNGFMSCLLL-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- -1 nonanoyl vanillylamine Chemical compound 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- 235000019633 pungent taste Nutrition 0.000 description 2
- TZZAKSLHHIJRLL-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1O TZZAKSLHHIJRLL-UHFFFAOYSA-N 0.000 description 1
- OCALSPDXYQHUHA-FNORWQNLSA-N 8-Methyl-6-nonenoic acid Chemical compound CC(C)\C=C\CCCCC(O)=O OCALSPDXYQHUHA-FNORWQNLSA-N 0.000 description 1
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- 240000008574 Capsicum frutescens Species 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing capsaicin by utilizing a micro-reaction chip, which takes vanillylamine and pelargonic acid as raw materials and organic alkali as an acid binding agent, and the capsaicin is generated by reaction in the micro-reaction chip, wherein the micro-reaction chip is a single-channel micro-reaction chip similar to a Tesla valve structure or a multi-channel micro-reaction chip similar to the Tesla valve structure. Compared with the prior art, the invention has the advantages of rapidness, high efficiency, safety, low amplification effect and the like, and simultaneously, the micro-reaction system has better sealing, can effectively prevent capsaicin from volatilizing, and avoid physical injury caused by contact of operators.
Description
Technical Field
The invention relates to the field of fine chemical engineering, in particular to a method for synthesizing nonanoyl vanillylamine (capsaicin) by utilizing a micro-reaction chip and utilizing a Tesla valve with high circulation performance.
Background
N-Vanillyl-N-nonanamide (nonanoyl vanillylamine) (English name: nonylic acid Vanillylamide) has the most intense pungent taste and very intense irritation in capsaicin, and can be extracted from natural capsicum or synthesized by chemical method. Because the synthesized capsaicin has absolute advantages in price and pungency compared with natural capsaicin, the synthesized capsaicin is deeply adopted and favored by wide users at home and abroad. The structure is as follows:
physical and chemical properties: white or off-white solids; mp:56-58 ℃; the solubility in water was 27ppm at 25 ℃. Acute toxicity data for the product: the oral LD50 of the rat is 5110mg/Kg.
Capsaicin can be seen chemically as an amide compound formed from fatty acids and vanillyl amines, and therefore its chemical synthesis and biosynthesis have striking similarities. The primary synthesis of capsaicin aims to verify the chemical structure of natural capsaicin, and Ernst Spth et al uses isobutyl zinc and 1, 6-ethyl-hexanoate monoacyl chloride as raw materials, and obtains 8-methyl-6-nonenoic acid through a series of chemical synthesis, and then obtains capsaicin through acyl chlorination (namely, fatty acid and coenzyme A (COA) form an activated form of fatty acid-COA in biosynthesis discovered after substitution), and then reacts with vanillylamine. This method is a classical method for capsaicin synthesis, and the latter synthesis method is only related to the difference in synthesis or sources of the raw material fatty acid and vanillyl amine. Hideshi Fujiwake et al synthesized vanillylamide from catechol, and then synthesized a series of capsaicin compounds by enzyme catalysis, thereby initiating the biomimetic synthesis of capsaicin.
Capsaicinoid-like Substances (Capsaicinoid-like substrates), namely Capsaicinoid esters (capsates), have the structure that esters formed by vanillyl alcohol and fatty acids of corresponding capsaicinoids are synthesized by the reaction of fatty acids with vanillyl alcohol after acyl chlorination, and stability of the Capsaicinoid esters and derivatives in different solvents is studied; then, a series of similar compounds including capsaicin esters are synthesized by using commercial enzyme as a catalyst and reacting fatty acid with vanillyl alcohol, and the yield reaches 64% -86%.
Because capsaicin has strong irritation, the volatilization of reaction liquid in the intermittent synthesis process is extremely easy to cause discomfort of operators, the conventional protective equipment cannot play a protective role, the overall sealability and the automation rate of the equipment are improved, the investment of production equipment is increased by 2-3 times, the cost increment can greatly offset project profit, and the project economic benefit is low.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for synthesizing capsaicin by utilizing a micro-reaction chip, which is quick, efficient, low in cost and easy for industrial amplification.
The aim of the invention can be achieved by the following technical scheme: a method for synthesizing capsaicin by utilizing a micro-reaction chip takes vanillylamine and pelargonic acid as raw materials and organic base as an acid binding agent, and is characterized in that capsaicin is generated by reaction in the micro-reaction chip.
Further, the micro-reaction chip is a single-channel micro-reaction chip similar to a Tesla valve structure or a multi-channel micro-reaction chip similar to a Tesla valve structure.
Further, the single-channel micro-reaction chip is formed by serially connecting microstructures with one or more similar tesla valves inside;
the multichannel micro-reaction chip is formed by connecting two or more single-channel micro-reaction chips in parallel.
Further, the micro-reaction chip is made of one of glass, stainless steel, ABS plastic, PLA plastic, PMMA, ceramic and resin.
Further, the micro-reaction chip is formed by fixing after being processed by 3D printing integral forming processing or laser inner carving integral forming processing or being divided into an upper block and a lower block respectively.
Further, the micro-reaction chip comprises a surface layer and a main body, wherein an upper heat conduction channel and a lower heat conduction channel are arranged between the surface layer and the main body, and the width and the length of the heat conduction channels are the same as the size of the chip inside the micro-reaction chip.
Further, the method comprises the following steps:
s1, raw material mixing section
Dissolving and mixing the vanillyl amine and the acid binding agent in a solvent to obtain a material A, wherein the dosage of the solvent is 3-5 times of the total mass of the vanillyl amine and the acid binding agent;
dissolving the nonanoyl chloride into a solvent to obtain a material B, wherein the dosage of the solvent is 3-5 times of the mass of the nonanoyl chloride;
the temperature of the raw material mixing section is 0-30 ℃, and the system pressure is 0.2-0.8 Mpa;
the mass ratio of the raw material feed materials is n (vanillylamine): n (nonanoyl chloride): n (acid binding agent) =1.0:1.0-1.5:1.1-1.8;
s2, reaction section
The material A and the material B are premixed (the premixing is carried out in a preheating chip, the structure of the preheating chip is the same as that of the micro-reaction chip, the preheating temperature is 20-30 ℃) and then enter the micro-reaction chip, the temperature is increased for reaction, the reaction temperature is controlled to be 20-60 ℃, and the residence time is 30-180 seconds.
S3, cooling section
The reaction product flows into a cooling chip to be cooled to 20-30 ℃, the cooled material and washing water (namely pure water, the consumption of the washing water is 0-1.0 equivalent of the total volume of the material) are mixed and washed in another group of cooling chips, then the mixture flows into a liquid separation device to carry out continuous liquid separation, an organic phase is subjected to continuous distillation, a crude product is obtained, and the crude product is further recrystallized on line to obtain a high-purity product. The cooling chip has the same structure as the micro-reaction chip.
Further, the acid binding agent is one of triethylamine, ammonia water, liquid alkali, sodium carbonate solution and potassium carbonate solution.
Further, the solvent is one of benzene, toluene, o-xylene, m-xylene and xylene mixed solvent.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention utilizes a micro-reaction chip with a tesla-like valve structure to prepare nonanoyl vanilla (capsaicin), and the method comprises the following steps: the invention adopts a micro-reaction chip with a similar Tesla valve structure, when fluid passes through the Tesla valve in the forward direction, the fluid is divided into two paths at each loop port, and then the two paths of fluid are converged at the next intersection port, thereby realizing acceleration. Conversely, if the fluid flows reversely into the tesla valve, the fluid is divided into two paths at the first junction and is converged again at the second junction, except that the flow directions of the two paths of fluid are opposite at this time, so that a great resistance is formed, and therefore, the tesla valve can only pass forward and is difficult to reverse flow. Because the Tesla valve structure can accelerate the forward flow of fluid, the internal pressure can be effectively reduced, and the overall pressure of the reaction system is reduced. The back pressure valve is connected behind the reaction chip to control the system pressure, the pressure range is 0.2 MPa-0.8 MPa, forward flow is promoted, internal flow is divided and mixed, the reaction time is shortened to be within 180 seconds, and the reaction liquid is continuously washed and concentrated on line to obtain a crude product. If further purification is needed, the recrystallization solvent can be supplemented after concentration, online continuous filtration and freeze-drying are performed, the whole process material quantity is controllable, the equipment tightness is good, the volatilization is difficult, and the injury to operators due to the volatilization of capsaicin is greatly reduced.
2. The invention aims to provide a novel method for producing nonanoyl vanilla (capsaicin) in an industrial scale-up way, which is fast, efficient, safe and low in comprehensive equipment cost, wherein the adopted reaction chip is a reaction chip with a tesla-like valve microstructure, and the reaction chip can adopt a plurality of single-channel reaction chips connected in series with the tesla-like valve microstructure according to parameters such as flow, flux and the like, and also can adopt a plurality of multi-channel reaction chips connected in parallel with the single-channel reaction chips.
3. The micro-structure of the Tesla-like valve in the reaction chip can be adjusted according to actual needs, and the reaction chip module is easy to clean and long in service life.
Drawings
FIG. 1 is a single tesla-like valve microstructure;
FIG. 2 is a cross-sectional view of a single-channel microreaction chip with multiple tesla-like valve microstructures in series;
FIG. 3 is a cross-sectional view of a multi-channel micro-reaction chip formed by connecting a plurality of Tesla-like valve microstructures in series and then connecting the valve microstructures in parallel;
FIG. 4 is a side elevational cross-sectional view of a microreaction chip;
fig. 5 is a schematic illustration of fluid flow within a tesla valve microstructure.
Detailed Description
The invention will now be described in detail with reference to the drawings and specific examples.
The procedure for synthesis of nonanoyl vanillylamine (capsaicin) using a tesla-like valve microreaction chip is as follows:
s1, raw material mixing section
Dissolving and mixing the vanillyl amine and the acid binding agent in a solvent to obtain a material A, wherein the dosage of the solvent is 3-5 times of the total mass of the vanillyl amine and the acid binding agent;
dissolving the nonanoyl chloride into a solvent to obtain a material B, wherein the dosage of the solvent is 3-5 times of the total mass of the nonanoyl chloride material;
the temperature of the raw material mixing section is 0-30 ℃, and the system pressure is 0.2-0.8 Mpa;
the mass ratio of the raw material feed materials is n (vanillylamine): n (nonanoyl chloride): n (acid binding agent) =1.0:1.0-1.5:1.1-1.8;
s2, reaction section
The material A and the material B are respectively pumped into a preheating chip for premixing (the structure of the preheating chip is the same as that of the micro-reaction chip, the preheating temperature is 20-30 ℃) and then enter the micro-reaction chip, the temperature is increased for reaction, the reaction temperature is controlled to be 20-60 ℃, and the residence time is 30-180 seconds.
S3, cooling section
The reaction product flows into a cooling chip to be cooled to 20-30 ℃, the cooled material and washing water (namely pure water, the consumption of the washing water is 0-1.0 equivalent of the total volume of the material) are mixed and washed in another group of cooling chips, then the mixture flows into a liquid separation device to carry out continuous liquid separation, an organic phase is subjected to continuous distillation, a crude product is obtained, and the crude product is further recrystallized on line to obtain a high-purity product. The cooling chip has the same structure as the micro-reaction chip.
Specific examples of synthesis of nonanoyl vanillylamine (capsaicin) using the microstructure reaction chip described above are as follows:
example 1
The system pressure is controlled to be 0.2MPa, triethylamine is selected as an acid binding agent, the mole ratio of vanillylamine to n-nonanoyl chloride to triethylamine is 1.0:1.2:1.25, toluene is adopted as a solvent, the vanillylamine/triethylamine/toluene solution and the n-nonanoyl chloride/toluene solution are pumped into a preheating chip at the same time, the preheating section temperature is 25 ℃, the reaction temperature is 45 ℃, the residence time is 120 seconds, the reaction enters a cooling chip after the reaction is completed, the cooling temperature is 25 ℃, the reaction liquid and one quarter volume of washing water of the reaction liquid are pumped into a mixing chip for mixing and washing at the same time, the mixture flows into a liquid separation device for continuous liquid separation, and an organic phase is continuously concentrated to obtain a capsaicin crude product, the capsaicin yield is 89.4%, and the purity is 96.3%.
In this embodiment, the micro-reaction chip is fabricated as follows: the single-channel micro-reaction chip shown in fig. 1 is prepared by integrally processing high-temperature-resistant glass serving as a material through laser internal engraving, the micro-reaction chip is formed by connecting 8 micro-structures of similar tesla valves in series (shown in fig. 2), and the size of each similar tesla valve is as follows: 3 cm long, 2 cm wide and 2 cm high, and the microstructure direct connection channel L is 1 cm long. The external dimensions of the single-channel micro-reaction chip are as follows: the length is 35 cm, the width is 3.4 cm, and the height is 3.4 cm. The flow of fluid within the microreaction chip is shown in FIG. 5.
The preheating chip, the micro-reaction chip and the cooling chip have the same structure and are respectively soaked in solvents with different temperatures.
Example 2
The system pressure is controlled to be 0.5MPa, an acid binding agent is 20% sodium carbonate solution, the mole ratio of the vanilla amine to the n-nonanoyl chloride to the sodium carbonate is 1.0:1.15:1.1, the solvent is m-xylene, the vanilla amine/sodium carbonate solution/m-xylene solution and the n-nonanoyl chloride/m-xylene solution are pumped into a preheating chip at the same time, the temperature of the preheating section is 20 ℃, the reaction is carried out in a micro-reaction chip, the reaction temperature is 60 ℃, the residence time is 150 seconds, the reaction is finished, the reaction liquid enters a cooling chip, the cooling temperature is 20 ℃, the reaction liquid directly flows into a liquid separation device for continuous liquid separation after cooling, the organic phase is continuously concentrated, the capsaicin crude product is obtained, the capsaicin yield is 93.2%, and the purity is 95.8%.
In this embodiment, the micro-reaction chip is fabricated as follows: with stainless steel as the material, adopt the slotting mode of machining, process the module that has 10 class tesla valve structures series connection in corrosion resistant plate one side, adopt the screw to fix two blocks of processed, symmetrical steel sheets into a single channel micro-reaction chip that contains 10 class tesla valve structures series connection inside, single class tesla valve size is: 3 cm long, 2 cm wide and 2 cm high, and the microstructure is directly connected with the channel length of 1 cm. The external dimensions of the single-channel reaction chip are as follows: the micro-reaction chip made of stainless steel has the advantages of 35 cm long, 3 cm wide and 3 cm high, high compressive strength, relatively thin wall thickness and more contribution to heat transfer.
The preheating chip, the micro-reaction chip and the cooling chip have the same structure and are respectively soaked in solvents with different temperatures.
Example 3
The system pressure is controlled to be 0.6MPa, triethylamine, vanillylamine, n-nonanoyl chloride and triethylamine are selected as acid binding agents, the molar ratio of the vanillylamine to the n-nonanoyl chloride to the triethylamine is 1.0:1.2:1.25, the solvent is m-xylene, the vanillylamine/triethylamine/m-xylene solution and the n-nonanoyl chloride/m-xylene solution, two materials are pumped into a preheating chip at the same time, the preheating section temperature is 30 ℃, the materials enter a micro-reaction chip to react, the reaction temperature is 60 ℃, the residence time is 180 seconds, the materials enter a cooling chip after the reaction is finished, the cooling temperature is 20 ℃, the reaction liquid and one quarter of washing water of the reaction liquid are pumped into a mixing chip to be mixed and washed at the same time, the mixture is fed into a liquid separation device to be continuously separated, and an organic phase is continuously concentrated, so that a capsaicin crude product is obtained, the capsaicin yield is 96.8%, and the purity is 95.9%.
The preheating chip, the reaction chip and the cooling chip used in this example were the same as those in example 1. Example 4
The system pressure is controlled to be 0.5MPa, 35% potassium carbonate solution is selected as acid binding agent, the mol ratio of vanilla amine to n-nonanoyl chloride to potassium carbonate is 1.0:1.2:1.1, toluene is adopted as solvent, the vanilla amine/potassium carbonate/toluene solution and the n-nonanoyl chloride/toluene solution are pumped into a preheating chip at the same time, the preheating section temperature is 30 ℃, the reaction is carried out in a micro-reaction chip, the reaction temperature is 45 ℃, the retention time is 150s, the reaction chip is cooled after the reaction is completed, the cooling temperature is 25 ℃, the reaction liquid directly flows into liquid separation equipment for continuous liquid separation after cooling, the organic phase is continuously concentrated, and the capsaicin crude product is obtained, the capsaicin yield is 92.4%, and the purity is 95.3%.
In this embodiment, the micro-reaction chip is fabricated as follows:
PMMA is used as a material, 3D printing is adopted for integrated processing to prepare a single-channel micro-reaction chip shown in figure 1, the reaction chip is formed by serially connecting 8 micro-structures of Tesla-like valves, and the size of each Tesla-like valve is as follows: 3 cm long, 2 cm wide and 2 cm high, and the microstructure is directly connected with the channel length of 1 cm. The external dimensions of the single-channel reaction chip are as follows: the length is 35 cm, the width is 3.4 cm, and the height is 3.4 cm. And the PMMA material is low in processing difficulty, a 3D printing mode is adopted, large-scale preparation is facilitated, and the comprehensive cost is low.
The preheating chip, the reaction chip and the cooling chip have the same structure and are respectively soaked in solvents with different temperatures.
Example 5
The system pressure is controlled to be 0.2MPa, 20% caustic soda liquid is selected as the acid binding agent, the mole ratio of the vanilla amine to the n-nonanoyl chloride to the caustic soda liquid is 1.0:1.2:1.2, the solvent is o-xylene, the vanilla amine/caustic soda liquid/o-xylene solution and the n-nonanoyl chloride/o-xylene solution are pumped into a preheating chip at the same time, the preheating section temperature is 20 ℃, the reaction is carried out in a micro-reaction chip, the reaction temperature is 45 ℃ and the residence time is 120 seconds, the reaction enters a cooling chip after the reaction is finished, the cooling temperature is 25 ℃, the reaction liquid directly flows into a liquid separation device for continuous liquid separation after the cooling, the organic phase is continuously concentrated, the capsaicin crude product is obtained, the capsaicin yield is 87.4%, and the purity is 96.7%.
In this embodiment, the micro-reaction chip is fabricated as follows: the method is characterized in that ABS plastic is used as a material, 3D printing is adopted to integrally form and process the ABS plastic, a multi-channel micro-reaction chip shown in figures 3-4 is prepared, the interior of the micro-reaction chip is formed by connecting 3 single-channel micro-reaction chips in parallel, and each single-channel micro-reaction chip is formed by connecting 6 Tesla-like valve microstructures in series. Fig. 4 is a cross-sectional side view of a micro-reaction chip, wherein the micro-reaction chip comprises a surface layer 2 and a main body 1, an upper heat conduction channel 3 and a lower heat conduction channel 3 are arranged between the surface layer 2 and the main body 1, the width and the length of the heat conduction channel 3 are the same as the size of the chip inside the micro-reaction chip, and materials enter and exit from a chip inlet and outlet 4.
The preheating chip, the micro-reaction chip and the cooling chip have the same structure and are respectively soaked in solvents with different temperatures.
Example 6
The system pressure is controlled to be 0.3MPa, triethylamine is selected as an acid binding agent, the mole ratio of vanillylamine to n-nonanoyl chloride to triethylamine is 1.0:1.2:1.25, toluene is adopted as a solvent, the vanillylamine/triethylamine/toluene solution and the n-nonanoyl chloride/toluene solution are pumped into a preheating chip at the same time, the preheating section temperature is 25 ℃, the reaction temperature is 60 ℃, the residence time is 120 seconds, the reaction is completed, the reaction enters a cooling chip, the cooling temperature is 25 ℃, the reaction liquid and one quarter volume of washing water of the reaction liquid are pumped into a mixing chip for mixing and washing at the same time after cooling, the mixture flows into a liquid separation device for continuous liquid separation, and an organic phase is continuously concentrated to obtain a capsaicin crude product, the capsaicin yield is 94.4%, and the purity is 95.3%.
The preheating chip, the reaction chip and the cooling chip used in this example were the same as those in example 1.
Claims (10)
1. A method for synthesizing capsaicin by utilizing a micro-reaction chip takes vanillylamine and pelargonic acid as raw materials and organic base as an acid binding agent, and is characterized in that capsaicin is generated by reaction in the micro-reaction chip.
2. The method for synthesizing capsaicin with a micro-reaction chip according to claim 1, wherein the micro-reaction chip is a single-channel micro-reaction chip similar to a tesla valve structure or a multi-channel micro-reaction chip similar to a tesla valve structure.
3. The method for synthesizing capsaicin with a micro-reaction chip according to claim 2, wherein the single-channel micro-reaction chip is a microstructure series containing one or more tesla-like valves inside;
the multichannel micro-reaction chip is formed by connecting two or more single-channel micro-reaction chips in parallel.
4. The method for synthesizing capsaicin with a micro-reaction chip according to claim 2, wherein the micro-reaction chip is made of one of glass, stainless steel, ABS plastic, PLA plastic, PMMA, ceramic and resin.
5. The method for synthesizing capsaicin with the micro-reaction chip according to claim 2, wherein the micro-reaction chip is formed by 3D printing integral forming processing or laser engraving integral forming processing or fixing after being divided into an upper piece and a lower piece which are respectively processed.
6. The method for synthesizing capsaicin with a micro-reaction chip according to claim 1 or 2, wherein the micro-reaction chip comprises a surface layer and a main body, wherein an upper heat conducting channel and a lower heat conducting channel are arranged between the surface layer and the main body, and the width and the length of the heat conducting channels are the same as the size of the chip inside the micro-reaction chip.
7. The method for synthesizing capsaicin with a micro-reaction chip according to claim 1, comprising the steps of:
s1, raw material mixing section
Dissolving and mixing vanillylamine and an acid binding agent in a solvent to obtain a material A; dissolving nonanoyl chloride in a solvent to obtain a material B;
s2, reaction section
Premixing the material A and the material B, then entering a micro-reaction chip, and heating for reaction;
s3, cooling section
And (3) cooling the reaction product flowing into a cooling chip, mixing and washing the cooled material with washing water again in another group of cooling chips, and then continuously separating liquid and distilling to obtain the product.
8. The method for synthesizing capsaicin with a micro-reaction chip according to claim 7, wherein the temperature of the raw material mixing section is 0-30 ℃ and the system pressure is 0.2-0.8 Mpa;
the mass ratio of the raw material feed materials is n (vanillylamine): n (nonanoyl chloride): n (acid binding agent) =1.0:1.0-1.5:1.1-1.8;
the temperature of the reaction section is controlled to be 20-60 ℃ and the residence time is 30-180 s.
9. The method for synthesizing capsaicin with a micro-reaction chip according to claim 1, wherein the acid binding agent is one of triethylamine, ammonia water, liquid alkali, sodium carbonate solution and potassium carbonate solution.
10. The method for synthesizing capsaicin with a micro-reaction chip according to claim 1, wherein the solvent is one of benzene, toluene, o-xylene, m-xylene and xylene mixed solvent.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117323879A (en) * | 2023-11-30 | 2024-01-02 | 中国科学院精密测量科学与技术创新研究院 | Multistage split micromixer and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010144055A1 (en) * | 2009-06-08 | 2010-12-16 | Nanyang Polytechnic | Novel compounds and uses thereof |
| CN102001958A (en) * | 2010-10-12 | 2011-04-06 | 浙江大学 | Method for synthesizing N-(3,4-dimethoxybenzyl)amide capsaicine homologous compounds |
| CN105646266A (en) * | 2016-02-03 | 2016-06-08 | 桐庐雷泰生物科技有限公司 | Method for synthesizing N-vanillylnonanamide |
| CN105859572A (en) * | 2016-04-28 | 2016-08-17 | 刘学娟 | New synthesis method of capsaicin |
| US20170174618A1 (en) * | 2014-03-27 | 2017-06-22 | Organofuel Sweden Ab | Efficient synthesis of amines and amides from alcohols and aldehydes by using cascade catalysis |
| CN112827407A (en) * | 2021-03-05 | 2021-05-25 | 锦州镁赫化学科技有限公司 | Continuous flow micro mixer |
-
2022
- 2022-12-22 CN CN202211656579.8A patent/CN116003276A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010144055A1 (en) * | 2009-06-08 | 2010-12-16 | Nanyang Polytechnic | Novel compounds and uses thereof |
| CN102001958A (en) * | 2010-10-12 | 2011-04-06 | 浙江大学 | Method for synthesizing N-(3,4-dimethoxybenzyl)amide capsaicine homologous compounds |
| US20170174618A1 (en) * | 2014-03-27 | 2017-06-22 | Organofuel Sweden Ab | Efficient synthesis of amines and amides from alcohols and aldehydes by using cascade catalysis |
| CN105646266A (en) * | 2016-02-03 | 2016-06-08 | 桐庐雷泰生物科技有限公司 | Method for synthesizing N-vanillylnonanamide |
| CN105859572A (en) * | 2016-04-28 | 2016-08-17 | 刘学娟 | New synthesis method of capsaicin |
| CN112827407A (en) * | 2021-03-05 | 2021-05-25 | 锦州镁赫化学科技有限公司 | Continuous flow micro mixer |
Non-Patent Citations (1)
| Title |
|---|
| 张龙等: "《绿色化学》", vol. 2, 31 August 2014, 华中科技大学出版社, pages: 358 - 360 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117323879A (en) * | 2023-11-30 | 2024-01-02 | 中国科学院精密测量科学与技术创新研究院 | Multistage split micromixer and application thereof |
| CN117323879B (en) * | 2023-11-30 | 2024-02-27 | 中国科学院精密测量科学与技术创新研究院 | Multistage split micromixer and application thereof |
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