CN111362902A - Preparation method of heliotropin - Google Patents
Preparation method of heliotropin Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
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Abstract
The invention discloses a preparation method of heliotropin, which adopts safrole as a raw material and can obtain high-quality heliotropin through isomerization, oxidation, reduction, neutralization, rectification and crystallization. The isomerization reaction time is short; the ozonization reaction is basically kept at room temperature for reaction, and a water solvent is directly adopted, so that the reaction time is short; the concentration of the reducing agent is low, the dosage is less, and the temperature of the reduction reaction is reduced; the concentration of the sodium carbonate solution used in the neutralization step is low, and the rectification treatment can be directly carried out without a complex post-treatment process after neutralization; the rectification step is carried out in high vacuum, and heating is carried out in a falling film evaporation mode; a combination of dynamic crystallization and static crystallization is used. Under the process conditions of the invention, the conditions of all the steps are mild, the side reaction can be well controlled, the post-treatment difficulty is reduced, the process yield and the process safety are improved, the purity and the quality of the product are ensured, and the production cost is also reduced.
Description
Technical Field
The invention relates to the field of heliotropin production, and particularly relates to a preparation method of heliotropin.
Background
Heliotropin (Heliotropine), Piperonal (Piperonal), heliotropin, 3,4-methylenedioxybenzaldehyde (3,4-methylenedioxybenzaldehyde) as white or yellowish crystal with melting point of 37 deg.C, boiling point of 263 deg.C and molecular formula of C8H6O3Relative molecular mass: 150.13, is easily soluble in diethyl ether, ethanol and benzyl benzoate, is soluble in propylene glycol, is insoluble in glycerol and water, is stable in weak base or weak acid, but is easy to color, has fragrance type of bean fragrance, has fragrance similar to sunflower and cherry, has strong sweet flower fragrance, is spicy and slightly bitter, and has the following structural formula:
as early as the beginning of the nineteenth century, in the process of researching the structure of piperine, namely black pepper alkaloid, a substance with the fragrance of almond is discovered when the piperine is oxidized by nitric acid, and then the structure of piperonal is determined. The presence of heliotropin was also found later in the essential oils of flowers of right camphor trees, spiraea ulmaria, pimento, acacia flowers, robinia orange leaves, pimento grass, vanilla, cymbidium indicum, violet, cinnamomum leaves and cocklebur cress.
Heliotropin has sweet heliotropin fragrance, light and slightly sweet cherry and sunflower fragrance, weak spicy fragrance and long fragrance-retaining time, is one of the most main and attractive fragrances in the world, and is widely applied to edible essences, tobacco essences, soaps and daily cosmetic essences.
In the perfume industry, the using amount of the heliotropin can reach 1-10%, a small amount of heliotropin can be emitted in the residual fragrance, and a large amount of heliotropin can be emitted in the top fragrance; it is applied to various fragrant essences such as sunflower, lily, violet, lily of the valley, sweet osmanthus and the like; can be blended with anisic aldehyde, vanillin, Moschus, lemon oil, etc., and has fragrance fixing effect.
In the pharmaceutical industry, heliotropin is also an important pharmaceutical intermediate, can be used as a raw material for synthesizing pharmaceutical raw materials and intermediates such as berberine, antiepileptic drug, sesamol, fasidox, piperonal and the like, and is also a main raw material for synthesizing alkaloid; in addition, heliotropin can also be used as an insect repellent for food, a brightening agent in the electroplating industry, and the like.
Heliotropin, as an important monomer synthetic perfume raw material, has been developed for a long time in its production process. In the sixth and seventies of the last century, heliotropin production areas were concentrated in europe and america countries such as japan, usa and germany, and main manufacturers thereof were: japan high sand flavor industry Co Ltd (TAKASAGO), Hammen Reimer company, Germany (Haarmann & Reimer), Bush Boake Allen, British, and BBA company etc.. After the nineties, the transition to developing countries began, and manufacturers focused on china, brazil, spain, etc. After this century, major manufacturers focused on china and india.
The industrial synthesis method of the heliotropin mainly comprises a semi-synthesis method and a total synthesis method, wherein the semi-synthesis method generally adopts safrole in safrole oil as a raw material and obtains a product through two-step chemical reaction; the total synthesis is generally to obtain the product by a series of chemical reactions with pyrocatechol or piperonyl and the like as raw materials.
The semi-synthesis process adopts safrole as raw material, which is natural vegetable oil extracted from natural plant such as safrole, and other plant containing safrole such as eucalyptus, laurel, etc. The cinnamomum camphora tree is rich in resources, and is planted in large quantities in provinces such as Sichuan, Yunnan, Hunan, Jiangxi, Guangxi and the like, wherein the region with the most abundant resources is a Sichuan yibin region, and the yield reaches about 1000 tons/year when the highest; secondly, Yunnan province, the yield is about 200 tons each year. The countries with rich safrole resources in the world also include Vietnam, Laos, Burma, Brazil, India and other countries. Southeast Asian countries may also provide safrole oil as a supplement to the market.
The two-step chemical reaction in the semi-synthesis process is as follows: firstly, carrying out isomerization reaction on safrole, and then oxidizing the safrole to prepare heliotropin:
the two-step process has several different process technologies:
(1) isomerization reaction of safrole
A. The traditional safrole isomerization process is that safrole and 50% KOH solution are mixed according to the weight ratio of 20: 1, refluxing at 170-190 ℃ under reduced pressure for about 6 hours, determining a reaction end point by measuring refractive index, washing reactants to be neutral, and evaporating to remove water to obtain the isosafrole, wherein the yield can reach 90%.
In the 60's of the B.20 th century, G.Riezehos et al proposed that a cis-trans isomeric mixture of isosafrole could be obtained by isomerization reaction of iron pentacarbonyl with NaOH, which could reduce environmental pollution, but due to the problems of catalyst and low reaction yield, it only stayed in the laboratory research stage and could not be applied in large-scale production in industry.
(2) Oxidation of isosafrole
The oxidation process of isosafrole includes traditional chemical oxidation, ozone oxidation and electrochemical oxidation developed recently.
A. Dichromate oxidation method:
with sodium dichromate (Na)2Cr2O7) Adding sulfanilic acid or p-amino group as oxidantBenzoic acid (to avoid deep oxidation of aldehyde groups) to improve yield. The reaction is generally carried out at about 60 ℃, and the yield can reach 75-83%. As early as 50 s in the last century in China, flavor factories such as Tianjin and Shanghai began to produce heliotropin by using the process, but the method can generate a large amount of chromium-containing wastewater, is difficult to treat and has serious pollution to the environment, so the method is gradually eliminated.
In addition to the above two methods, there are potassium permanganate oxidation, lead tetraacetate oxidation, CrO3 catalytic oxidation, and the like, and these methods have environmental problems and low yield, and are mostly in the laboratory stage.
B. An ozone oxidation method:
dissolving isosafrole in solvent, introducing ozone or 2-3% mixed gas of ozone and air at low temperature for oxidation reaction, and using sodium pyrosulfite (Na) as ozonide2S2O5) Or sodium bisulfite (NaHSO)3) The solution is reduced and decomposed, and the piperonal is obtained after acidification, and the yield can reach 85 percent.
C. Electrochemical oxidation process
The oxidation directly carried out on the surface of the electrode is called as a direct oxidation method, Japanese Sigeru et al firstly put forward a method for synthesizing the heliotropin by two-step electrooxidation of isosafrole as early as 1984, but the staged oxidation process is complex, the yield of the electrooxidation is low, Chinese Fang faiian and the like preliminarily explore the possibility of synthesizing the heliotropin by directly electrooxidizing the isosafrole.
The second phase of the document "optimization of reaction for producing piperonal by ozone method" of Guangzhou chemical industry 1991 reports a method for producing piperonal by ozone method:
the method comprises the steps of taking isosafrole as a basic raw material, wherein the content of the isosafrole is 98.14%, the test dosage is 30g each time, putting the isosafrole and a mixed solvent into a glass specimen cylinder, introducing oxygen containing ozone to control the ventilation speed, regarding the tail gas as a reaction end point when the tail gas is potassium iodide acidic solution changed to yellowish, and then carrying out reduction reaction; the reduction reaction is carried out in a three-neck flask, the ozonization reaction is dropwise added into the prepared sodium sulfate solution under the condition of continuous stirring, the temperature of the decomposition reaction solution is increased, the temperature is kept for a certain time at a certain temperature after the addition is finished, then the mixture is kept still for layering, the oil phase is washed by water to be neutral, the heliotropin content is measured by using a gas chromatography, and the yield is calculated.
According to the experimental process, the optimal process conditions are as follows: the mixed solvent is a combination of polar and nonpolar solvents, the composition of related solvents is not reported in the literature, according to the introduction of other literatures, the polar solvent generally adopts water, ethanol, methanol and the like, and the nonpolar solvent generally adopts benzene and more toluene; the weight ratio of the mixed solvent to the isosafrole is 5: 1; the ratio of polar to non-polar solvents in the mixed solvent is 3: 1; the molar ratio of the reducing agent sodium sulfite to the isosafrole is 1.1-1.2: 1, the concentration of sodium sulfite is 10 percent; the ozonization reaction time is 20min, and the reaction temperature is 0 ℃.
The reported isosafrole is synthesized into piperonal by ozonization, the process yield is high, but the following problems exist: a. the reaction temperature is low, the process time is long and the yield is reduced after the process is amplified to industrialization; b. the reducing agent has higher concentration and larger dosage, which can cause the yield to be reduced after amplification and increase the difficulty of wastewater treatment; c. the washing of the crude product can cause a large amount of waste water, and simultaneously, the product yield is reduced; d. the use of mixed solvents can ensure high yields, but the use of large amounts of organic solvents can greatly increase the safety risk due to the poor stability of the ozonized intermediate.
Therefore, the synthesis process of heliotropin still needs to be further improved.
Disclosure of Invention
The invention mainly solves the technical problem of providing a preparation method of piperonal, which can perfectly solve some main problems of the traditional semi-synthesis piperonal process from a plurality of process steps, so that the product yield is higher, the cost is greatly reduced, and the product quality is good.
In order to solve the technical problems, the invention adopts a technical scheme that:
the preparation method of the heliotropin is characterized by comprising the steps of ozonization: at room temperature, isosafrole is mixed with water and ozone is introduced for reaction.
Further, the isosafrole: the mass ratio of water is 1: (2-5), preferably 1: 3.
Further, the room temperature is 20-35 ℃, and preferably 25-30 ℃.
In the existing heliotropin production process, an ozonization reaction is usually carried out at a low temperature, and is dissolved by an organic solvent, so that the energy consumption is high, the safety cannot be guaranteed, and more side reactions can be caused due to long reaction time.
The ozonization process temperature is normal temperature, heating or refrigeration is not needed in the production process, and the materials can be completely reacted only about 2 hours after being mixed, so that the production energy consumption is reduced, the production efficiency is improved, the side reaction is reduced, and the yield is improved.
Further, in the preparation method of the heliotropin, after the ozonization step, a reduction step is also included: mixing the ozonized product of the isosafrole with a sodium metabisulfite aqueous solution with the mass concentration of 3-6% to perform reduction reaction at the temperature of 70-85 ℃; the mass consumption of the sodium metabisulfite aqueous solution is 1.2-1.8 times of the mass of the isosafrole.
Further, the mass concentration of the sodium metabisulfite aqueous solution is 5 percent; the mass consumption of the sodium metabisulfite aqueous solution is 1.4-1.6 times of the mass of the isosafrole.
Further, the reaction temperature was 80 ℃.
In the existing heliotropin production process, the concentration of the used reducing agent solution is higher, usually 10%, the using amount is also higher, the reduction temperature is also higher, side reactions are increased, the yield of products is reduced, and the difficulty in treating wastewater is also higher.
In the invention, the reducing agent used in the reduction process has low concentration and lower reduction temperature, so that the occurrence of side reactions can be well reduced, and the yield is improved.
Further, an aqueous solution of sodium metabisulfite is added in portions to the ozonide of isosafrole.
Further, in the preparation method of the heliotropin, the step of neutralizing the isosafrole after ozonization and reduction comprises the following steps: mixing a system obtained after reduction of an ozonide of isosafrole with a sodium carbonate aqueous solution with the mass concentration of 3-6% for neutralization; the mass consumption of the sodium carbonate aqueous solution is 3-3.6 times of that of the isosafrole;
further, the mass concentration of the sodium carbonate aqueous solution is 5 percent; the mass consumption of the sodium carbonate aqueous solution is 3.3-3.5 times of that of the isosafrole;
the invention adopts low-concentration sodium carbonate solution to neutralize at normal temperature, solves the problem that oil-water two phases are not separated by solution in the prior art, and simultaneously ensures that the materials can not generate side reactions such as polymerization, oxidation and the like in the rectification process by a large margin due to alkalescence.
Furthermore, the sodium carbonate aqueous solution is added into the system after the reduction of the ozonide of the isosafrole in batches.
The term "batchwise addition" as used herein means that the entire amount of the material is not added at once, and the batchwise addition may be divided into several portions at a predetermined time interval, or may be continued at a predetermined rate.
In a particular embodiment of the invention, both the reducing agent solution and the sodium carbonate solution used for neutralization are added dropwise.
Further, in the preparation method of the heliotropin, the distillation step is also included after the isosafrole is subjected to ozonization, reduction and neutralization: heating the neutralized crude aldehyde in a falling film evaporation mode, and rectifying under the condition that the vacuum degree is less than or equal to 500 Pa.
Further, in the preparation method of the heliotropin, the isosafrole is subjected to ozonization, reduction, neutralization and rectification, and then the crystallization step is included: mixing the rectified aldehyde with ethanol, and performing dynamic crystallization; then dissolving the crystal obtained by dynamic crystallization in ethanol for static crystallization;
the temperature of the dynamic crystallization and the static crystallization is-10-0 ℃, and is preferably-5 ℃.
Further, in the dynamic crystallization, the ratio of refined aldehyde: the mass ratio of the ethanol is (3-0.5) to 1, preferably 1: 1;
in static crystallization, crystals obtained by dynamic crystallization: the mass ratio of ethanol is (3-0.5): 1, preferably 1: 1.
Further, the dynamic crystallization time is 5-10 h; preferably 8 h.
In the traditional preparation process and documents, static crystallization is generally adopted, or the use amount of solvent alcohol is increased to improve the purity of crystals, or the crystallization frequency is increased to improve the purity, but the problem that materials such as solvents, impurities and the like are hidden in the crystals is difficult to solve by the static crystallization. Therefore, the traditional crystallization method uses a large amount of solvent, and needs repeated rectification, purification and recovery, or repeated crystallization, which causes the problems of low process efficiency, low product yield, high process cost and the like.
The crystallization process combines dynamic crystallization and static crystallization phases, not only ensures the purity of the material and well solves the problems, but also ensures that various physical and chemical indexes of the material are excellent, and simultaneously has simple process and high yield.
Further, the preparation method of the heliotropin also comprises the following steps of: mixing safrole with a KOH aqueous solution with the mass concentration of 40-60%, and carrying out isomerization reaction at 160-200 ℃, wherein the content of the safrole: the mass ratio of the KOH aqueous solution is 1: 0.04.
Further, the mass concentration of the KOH aqueous solution was 50%, and the isomerization reaction temperature was 180 ℃.
In the prior art, the isomerization process of safrole is usually carried out under reduced pressure, the isomerization process of the invention is normal pressure, the required reaction time is short, the process is simpler, and the energy consumption is reduced.
The invention has the beneficial effects that:
(1) the reaction temperature of the ozonization step is 25-30 ℃, the reaction is basically kept at room temperature, and the energy consumption is obviously reduced; secondly, the ozonization directly adopts a water solvent, so that the stability of an ozonized intermediate can be kept, the safety of the process is greatly improved, and the stability of the system temperature is favorably kept; the present invention has short ozonization reaction time, well controlled side reaction and high technological yield.
(2) The concentration of the reducing agent used in the reduction step is greatly reduced compared with the prior art, the using amount of the reducing agent is less, on one hand, the side reaction is well controlled, on the other hand, the difficulty of wastewater treatment is reduced, and simultaneously, the temperature of the reduction reaction is reduced, thereby being beneficial to improving the yield of the product.
(3) The concentration of the sodium carbonate solution used in the neutralization step is greatly reduced compared with the prior art, so that the method is beneficial to the oil-water phase separation of materials, the yield is better improved, and the problem of increased wastewater treatment difficulty caused by factors such as suspension of products in wastewater is reduced; on the other hand, after the concentration of the sodium carbonate is reduced, the crude aldehyde is alkalescent, and can be directly rectified without a complex post-treatment process, so that the post-treatment difficulty of the crude aldehyde is greatly reduced, and the yield of the refined aldehyde is also improved.
(4) The rectification step of the invention adopts a falling film evaporation mode for heating, and adopts high vacuum for rectification, thus ensuring the thermal stability of the material.
(5) The crystallization step of the invention adopts a mode of two-time crystallization, namely one-time dynamic crystallization and one-time static crystallization; dynamic crystallization ensures that part of impurities in the material are not easily occluded in crystals in the crystallization process, thereby ensuring the purity of the material; the static crystallization ensures that the physical indexes of the product, such as crystal form, color, aroma and the like, are qualified.
(6) The isomerization reaction for preparing the isosafrole has the advantages that the isomerization process time is only 2 hours, the raw material conversion rate and the intermediate yield are high, and the yield is basically equivalent to or higher than the optimal yield in the prior art; the data in the invention are data of large-scale industrial production, the yield reported in the prior art is basically small trial production rate, amplification effects such as yield reduction, reaction time extension and the like usually exist after amplification, and a plurality of unknown factors also exist.
(7) The method for preparing the heliotropin has high yield, the total yield can reach 77 percent by taking the safrole as a raw material for production, the conditions are mild, the post-treatment is simple, various problems in the prior art can be solved, the production cost is reduced, and the prepared heliotropin has excellent quality.
Detailed Description
The technical solutions of the present invention are described clearly and completely below, and it is obvious that the described embodiments are some, not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The volume fraction of ethanol in the edible alcohol used in the examples of the present invention was 95%.
Example 1
(1) Isomerization reaction of safrole
5.2kg of clear water and 5.2kg of potassium hydroxide were added to the catalyst preparation tank, and then dissolved with stirring.
Then 260kg of sassafras oil (the content of safrole is 95.2%) is added into a 300L stainless steel heterogeneous reaction kettle, a gas bubbler is started, 10.4kg of prepared 50% potassium hydroxide is added, then a condenser is started to cool water, stirring is started, a jacket is started to perform steam heating, the temperature is increased to 180 ℃, and the reaction is performed for 2 hours in a timing manner. Sampling at the later stage of the reaction, and detecting the reaction end point by chromatographic analysis.
After the reaction is finished, starting a vacuum pump, adjusting an air inlet valve, slowly increasing the vacuum degree of the system, and starting to distill the isosafrole. 5.0g of water is discharged at the early stage, then 248.8kg of vacuum positive material is continuously discharged, the purity analysis is 97.2 percent (the yield is 97.7 percent), after the distillation is finished, the vacuum pump is closed, and the temperature is reduced.
When the temperature of the distillation kettle is reduced to below 80 ℃, 65kg of clear water is added, the kettle is washed for 15min under stirring, 78.4kg of kettle washing water is discharged when the kettle is hot, 68.5kg of water phase, 9.9kg of solid phase and 3.2kg of material loss are separated after standing.
(2) Ozonization reaction
50kg (the purity is 97.2%) of isosafrole with good isomerism and 150kg of water are added into a 300L stainless steel ozonization reaction tower, then the ozonization reaction tower is connected with an ozone tail gas absorption tower, 50kg of isosafrole and 150kg of water are also filled into the absorption tower so as to absorb the ozone tail gas which does not participate in the reaction tower, the concentration of ozone in the tail gas is reduced, the raw materials are fully utilized, and the absorbed tail gas is connected with a packed tower for treating the tail gas. Then connecting with an air inlet pipe of the ozone generator. After the materials are prepared, starting an ozone generator, controlling the reaction temperature to be 25-30 ℃ by using jacket cooling water, starting an ozone inlet pipe valve, adding 16.0kg of ozone to start an ozonization reaction, and controlling the system temperature. And determining the ozonization reaction end point according to the reaction time or the detected ozone content in the tail gas. After the reaction, the materials were immediately transferred to a clarifying kettle, 72.5kg of oil phase at the bottom was separated, and pumped to a reduction reaction kettle by vacuum, and 140.3kg of water phase was separated to a wastewater storage tank. The material loss was 3.2 kg.
(3) Reductive decomposition reaction
3.75kg of sodium metabisulfite and 71.25kg of water were completely dissolved with stirring to prepare a reducing agent solution.
After the ozonization reaction is finished, the material enters a clarifying kettle to be subjected to phase splitting, and 72.5kg of oil phase is pumped into a 250L glass lining reduction reaction kettle by vacuum pumping; stirring, heating with jacket steam, slowly adding sodium pyrosulfite solution dropwise, controlling reaction temperature at about 80 deg.C, and reacting for 1 hr. After the reaction, the stirring is stopped, the heating is stopped, the materials are kept stand for 30min, 46.5kg of oil phase at the bottom is separated out, the oil phase is pumped into a neutralization reaction kettle by vacuum, 100.9kg of water phase at the upper layer is separated out to enter a wastewater storage tank, and the material loss is 0.1 kg.
(4) Neutralization reaction
8.3kg of sodium carbonate and 158.7kg of water were thoroughly dissolved with stirring. And then sucking 46.5kg of the reduced oil phase into a 250L glass lining neutralization reaction kettle by using vacuum, starting stirring, slowly dropwise adding a sodium carbonate solution, and continuing to react for 30min after the addition is finished. After the neutralization reaction is finished, stirring is stopped, the materials are kept stand for 30min, then 45.5kg of oil phase (crude piperonal, the purity is 92.6 percent, and the yield is 93.66 percent) at the bottom is separated out to be prepared to enter a rectification process, 166.5kg of water phase enters a wastewater storage tank, and the material loss is 1.5 kg.
(5) Rectification
100kg of crude piperonal (purity 92.6%) is added into a 200L stainless steel rectifying still, then a vacuum pump is started, a condenser is started to cool water, a rectifying still jacket is started to heat by steam, and temperature rise is started. When the temperature reaches a certain value, the reflux begins to appear, and the material is kept to be refluxed for 1 hour. Then 7.5kg (60%) of the forward run was withdrawn at a certain reflux ratio. After the front distillation is finished, ensuring that the vacuum of the system is less than 500Pa, and starting to perform reaction according to a reflux ratio of 4: a86.5 kg positive material (98.1% purity) is discharged from the reactor.
When the temperature in the rectifying still had risen to a certain value, the receiver was switched to the back-distilled 2.0kg (purity 85%). After the rectification is finished, the vacuum is closed, the heating is stopped, and 2.0kg of residue in the kettle is discharged after the materials in the kettle are cooled to a certain temperature. The material loss was 2.0 kg.
The front distillation and the back distillation are continuously carried out for rectification separation, the front distillation obtains 1.58kg of the positive material (the purity is 98.1 percent), the back distillation obtains 0.51kg of the positive material (the purity is 98.1 percent), and the total amount of the positive material is 88.59kg (the purity is 98.1 percent, and the yield is 93.85 percent).
(6) Crystallization of
Putting 259.4kg of rectified aldehyde into a dynamic crystallization kettle, adding 259.4kg of edible alcohol according to the proportion (alcohol: heliotropin is 1:1), then heating to 50 ℃ under stirring to dissolve and mix the materials uniformly, then starting a program to cool, continuing to stir and cool for crystallization for 8h after reaching the end temperature of-5 ℃, then discharging the materials into a fully-closed centrifuge, and recovering alcohol and crude aldehyde from the thrown mother liquor; 272kg of crystals are added with 272kg of edible alcohol according to the ratio of 1:1, the crystals are dissolved completely in a melting pot, then the crystals are placed in 10L stainless steel basins in batches and are placed in a cold storage, the cold storage freezing program is set for cooling, and when the temperature is reduced to about minus 5 ℃, the crystals continue to crystallize for 12 hours. Pouring out the frozen crystal piperonal, crushing, adding into a fully-closed centrifuge, performing centrifugal separation for 15min to obtain 286kg of mother liquor, and collecting and entering an auxiliary process for treatment. 255.0kg of crystals are poured out and enter a drying procedure, and 3kg of materials are lost.
(7) Drying by baking
And (3) pouring 255.0kg of crystalline piperonal finally obtained in the step (6) into a stainless steel drying tray, uniformly distributing, then starting a drying hot air blower, adjusting the air speed, sealing a drying room, leading out dried tail gas through an air guide pipe, then cooling and collecting 18.8kg of alcohol in the crystalline piperonal through a condenser, keeping the temperature at about 30 ℃, and drying for 24h to obtain 228.3kg of product piperonal, wherein the purity is more than 99.0%. The material loss is 7.9kg, and then the physicochemical indexes of the product piperonal are analyzed, the chromatographic content is more than 99.0 percent, and the freezing point is more than 35.0 ℃. And packaging as a finished product after the product is qualified.
Based on safrole, the total yield of the product is 77.01%, and the unit consumption is 1.298.
Example 2
(1) Isomerization reaction of safrole
5.0kg of clear water and 7.5kg of potassium hydroxide were added to the catalyst preparation tank, followed by dissolution with stirring.
Then 312.5kg of sassafras oil (the sassafras oil content is 95.2%) is added into a stainless steel isomerization reaction kettle, a gas bubbler is started, 12.5kg of prepared 60% potassium hydroxide is added, then a condenser is started to cool water, stirring is started, a jacket is started to perform steam heating, the temperature is raised to 160 ℃, and the reaction is performed for 2 hours in a timing manner. Sampling at the later stage of the reaction, and detecting the reaction end point by chromatographic analysis.
After the reaction is finished, starting a vacuum pump, adjusting an air inlet valve, slowly increasing the vacuum degree of the system, and starting to distill the isosafrole. 4.8g of water is discharged at the early stage, then the vacuum is continuously improved to discharge 298.7kg of the positive material, the purity analysis is 97.3 percent (the yield is 97.7 percent), after the distillation is finished, the vacuum pump is closed, and the temperature is reduced.
When the temperature of the distillation kettle is reduced to below 80 ℃, 65kg of clear water is added, the kettle is washed for 15min under stirring, 83.4kg of kettle washing water is discharged when the kettle is hot, and after standing, 70.5kg of water phase, 12.9kg of solid phase and 3.1kg of material loss are separated.
(2) Ozonization reaction
50kg (the purity is 97.3%) of isosafrole with good isomerism and 100kg of water are added into a 300L stainless steel ozonization reaction tower, then the ozonization reaction tower is connected with an ozone tail gas absorption tower, 50kg of isosafrole and 100kg of water are also filled into the absorption tower so as to absorb the ozone tail gas which does not participate in the reaction tower, reduce the concentration of ozone in the tail gas, fully utilize the raw materials, and the absorbed tail gas is connected with a packed tower for treating the tail gas. Then connecting with an air inlet pipe of the ozone generator. After the materials are prepared, starting an ozone generator, controlling the reaction temperature to be 25-30 ℃ by using jacket cooling water, starting an ozone inlet pipe valve, adding 16.0kg of ozone to start an ozonization reaction, and controlling the system temperature. And determining the ozonization reaction end point according to the reaction time or the detected ozone content in the tail gas. After the reaction, the materials were immediately transferred to a clarifying kettle, 72.6kg of oil phase at the bottom was separated, and pumped to a reduction reaction kettle by vacuum, and 90.2kg of water phase was separated to a wastewater storage tank. The material loss was 3.2 kg.
(3) Reductive decomposition reaction
3.60kg of sodium metabisulfite and 56.40kg of water were completely dissolved with stirring to prepare a reducing agent solution.
After the ozonization reaction is finished, the material enters a clarifying kettle to be subjected to phase splitting, and 72.6kg of oil phase is pumped into a glass lining reduction reaction kettle by utilizing vacuum; stirring, heating with jacket steam, slowly adding sodium pyrosulfite solution dropwise, controlling reaction temperature at about 70 deg.C, and reacting for 1 hr. After the reaction, the stirring is stopped, the heating is stopped, the materials are kept stand for 30min, 46.6kg of oil phase at the bottom is separated out, the oil phase is pumped into a neutralization reaction kettle by vacuum, 85.9kg of water phase at the upper layer is separated out to enter a wastewater storage tank, and the material loss is 0.1 kg.
(4) Neutralization reaction
9.0kg of sodium carbonate and 141.0kg of water were thoroughly dissolved with stirring. And then sucking 46.6kg of the reduced oil phase into a glass lining neutralization reaction kettle by utilizing vacuum, starting stirring, slowly dropwise adding a sodium carbonate solution, and continuing to react for 30min after the addition is finished. After the neutralization reaction, the stirring is stopped, the materials are kept stand for 30min, then 45.6kg of oil phase (crude piperonal, the purity is 92.4 percent, and the yield is 93.63 percent) at the bottom is separated out to be prepared to enter a rectification process, 149.5kg of water phase enters a wastewater storage tank, and the material loss is 1.5 kg.
(5) Rectification
100kg of crude piperonal (purity 92.4%) is added into a 200L stainless steel rectifying still, then a vacuum pump is started, a condenser is started to cool water, a rectifying still jacket is started to heat by steam, and temperature rise is started. When the temperature reaches a certain value, the reflux begins to appear, and the material is kept to be refluxed for 1 hour. Then 7.8kg (60%) of the forward run was withdrawn at a certain reflux ratio. After the front distillation is finished, ensuring that the vacuum of the system is less than 500Pa, and starting to perform reaction according to a reflux ratio of 4: a86.2 kg positive material (98.1% purity) is discharged from the reactor.
When the temperature in the rectifying still had risen to a certain value, the receiver was switched to the back-distilled 1.8kg (purity 85%). After the rectification is finished, the vacuum is closed, the heating is stopped, and 2.2kg of residue in the kettle is discharged after the materials in the kettle are cooled to a certain temperature. The material loss was 2 kg.
The front distillation and the back distillation can be continued to carry out rectification separation, the front distillation can obtain 1.6kg of the positive material (the purity is 98.1 percent), the back distillation can obtain 0.48kg of the positive material (the purity is 98.1 percent), and the total amount of the positive material is 88.28kg (the purity is 98.1 percent, and the yield is 93.73 percent).
(6) Crystallization of
Adding 300kg (purity 98.1%) of rectified refined aldehyde into a dynamic crystallization kettle, adding 100kg of edible alcohol according to the proportion (alcohol: heliotropin is 1:3), heating to 50 ℃ under stirring to dissolve and mix the materials uniformly, starting a program to cool, continuing to stir and cool for crystallization for 8h after reaching the end temperature of 0 ℃, discharging the materials into a fully-closed centrifuge, and recovering alcohol and crude aldehyde from the thrown mother liquor; adding 107kg of edible alcohol (alcohol: aldehyde is 1:3) into 321kg of crystals, dissolving completely in a melting pot, putting the crystals in 10L stainless steel basins in batches, putting the crystals in a cold storage, setting a cold storage freezing program to reduce the temperature, and continuing crystallizing for 12 hours when the temperature is reduced to about 0 ℃. And pouring out the frozen crystal piperonal, crushing, adding into a fully-closed centrifuge, performing centrifugal separation for 15min to obtain 130kg of mother liquor, and collecting and performing auxiliary process treatment. Pouring 295kg of crystals out, and then entering a drying process. The material loss was 3 kg.
(7) Drying by baking
295kg of crystalline heliotropin finally obtained in the step (6) is poured into a stainless steel drying disc, after the crystalline heliotropin is uniformly distributed, a drying hot air blower is started, the air speed is adjusted, a drying room is closed, the dried tail gas is led out through an air guide pipe, 23.7kg of alcohol in the crystalline heliotropin is collected through cooling of a condenser, the temperature is kept at about 30 ℃, and drying is carried out for 24 hours, so that 263.4kg of heliotropin is obtained, wherein the purity is higher than 99.0%. The material loss is 7.9kg, and then the physicochemical indexes of the product piperonal are analyzed, the chromatographic content is more than 99.0 percent, and the freezing point is more than 35.0 ℃. And packaging as a finished product after the product is qualified.
Based on safrole, the total yield of the product is 76.74 percent, and the unit consumption is 1.303.
Example 3
(1) Isomerization reaction of safrole
In the catalyst preparation tank, 6.24kg of clean water and 4.16kg of potassium hydroxide were added and then dissolved with stirring.
Then 260kg of sassafras oil (the content of safrole is 95.2%) is added into a 300L stainless steel heterogeneous reaction kettle, a gas bubbler is started, 10.4kg of prepared 40% potassium hydroxide is added, then a condenser is started to cool water, stirring is started, a jacket is started to perform steam heating, the temperature is increased to 180 ℃, and the reaction is performed for 2 hours in a timing manner. Sampling at the later stage of the reaction, and detecting the reaction end point by chromatographic analysis.
After the reaction is finished, starting a vacuum pump, adjusting an air inlet valve, slowly increasing the vacuum degree of the system, and starting to distill the isosafrole. 6.1g of water is discharged at the early stage, then the vacuum is continuously improved to discharge 248.7kg of the positive material, the purity analysis is 97.1 percent (the yield is 97.56 percent), after the distillation is finished, the vacuum pump is closed, and the temperature is reduced.
When the temperature of the distillation kettle is reduced to below 80 ℃, 65kg of clear water is added, the kettle is washed for 15min under stirring, 78.4kg of kettle washing water is discharged when the kettle is hot, and after standing, 70.5kg of water phase, 7.9kg of solid phase and 2.2kg of material loss are separated.
(2) Ozonization reaction
50kg (the purity is 97.1%) of isosafrole with good isomerism and 250kg of water are added into a stainless steel ozonization reaction tower and then connected with an ozone tail gas absorption tower, 50kg of isosafrole and 250kg of water are filled into the absorption tower so as to absorb the ozone tail gas which does not participate in the reaction tower, reduce the concentration of ozone in the tail gas, fully utilize the raw materials, and the absorbed tail gas is connected with a packed tower for treating the tail gas. Then connecting with an air inlet pipe of the ozone generator. After the materials are prepared, starting an ozone generator, controlling the reaction temperature to be 25-30 ℃ by using jacket cooling water, starting an ozone inlet pipe valve, adding 16.0kg of ozone to start an ozonization reaction, and controlling the system temperature. And determining the ozonization reaction end point according to the reaction time or the detected ozone content in the tail gas. After the reaction, the materials were immediately transferred to a clarifying kettle, 72.3kg of oil phase at the bottom was separated, and pumped to a reduction reaction kettle by vacuum, and 240.4kg of water phase was separated to a wastewater storage tank. The material loss was 3.3 kg.
(3) Reductive decomposition reaction
3.70kg of sodium metabisulfite and 86.30kg of water were completely dissolved with stirring to prepare a reducing agent solution.
After the ozonization reaction is finished, the material enters a clarifying kettle to be subjected to phase splitting, and 72.3kg of oil phase is pumped into a glass lining reduction reaction kettle by utilizing vacuum; stirring, heating with jacket steam, slowly adding sodium pyrosulfite solution dropwise, controlling reaction temperature at about 70 deg.C, and reacting for 1 hr. After the reaction, the stirring is stopped, the heating is stopped, the materials are kept stand for 30min, 46.4kg of oil phase at the bottom is separated out, the oil phase is pumped into a neutralization reaction kettle by vacuum, 115.8kg of water phase at the upper layer is separated out to enter a wastewater storage tank, and the material loss is 0.1 kg.
(4) Neutralization reaction
5.4kg of sodium carbonate and 174.6kg of water were thoroughly dissolved with stirring. And then sucking 46.4kg of the reduced oil phase into a glass lining neutralization reaction kettle by utilizing vacuum, starting stirring, slowly dropwise adding a sodium carbonate solution, and continuing to react for 30min after the addition is finished. After the neutralization reaction, the stirring is stopped, the materials are kept stand for 30min, then 45.5kg of oil phase (crude piperonal, the purity is 92.5 percent, and the yield is 93.62 percent) at the bottom is separated out to be prepared to enter a rectification process, 179.3kg of water phase enters a wastewater storage tank, and the material loss is 1.6 kg.
(5) Rectification
100kg of crude piperonal (purity 92.5%) is added into a 200L stainless steel rectifying still, then a vacuum pump is started, a condenser is started to cool water, a rectifying still jacket is started to heat by steam, and temperature rise is started. When the temperature reaches a certain value, the reflux begins to appear, and the material is kept to be refluxed for 1 hour. Then 7.7kg (60%) of the forward run was withdrawn at a certain reflux ratio. After the front distillation is finished, ensuring that the vacuum of the system is less than 500Pa, and starting to perform reaction according to a reflux ratio of 4: a86.3 kg positive material (98.1% purity) is discharged from the reactor.
When the temperature in the rectifying still had risen to a certain value, the receiver was switched to the back-distilled 1.9kg (purity 85%). After the rectification is finished, the vacuum is closed, the heating is stopped, and 2.0kg of residue in the kettle is discharged after the materials in the kettle are cooled to a certain temperature. The material loss was 2.1 kg.
The front distillation and the back distillation can be carried out for further rectification separation, the front distillation can obtain 1.6kg of the positive material (the purity is 98.1 percent), the back distillation can obtain 0.5kg of the positive material (the purity is 98.1 percent), and the total amount of the positive material is 88.5kg (the purity is 98.1 percent, and the yield is 93.75 percent).
(6) Crystallization of
Putting 200kg of rectified aldehyde into a dynamic crystallization kettle, adding 100kg of edible alcohol according to the proportion (alcohol: heliotropin is 1:0.5), heating to 50 ℃ under stirring to dissolve and mix the materials uniformly, starting a program to cool, continuing stirring and cooling to crystallize for 8 hours after reaching the end temperature of 0 ℃, discharging the materials into a fully-closed centrifuge, and recovering alcohol and crude aldehyde from the thrown mother liquor; adding 420kg of edible alcohol (alcohol: aldehyde is 1:0.5) into 210kg of crystals, dissolving completely in a melting pot, putting the crystals in 10L stainless steel basins in batches, putting the stainless steel basins into a cold storage, setting a cold storage freezing program to reduce the temperature, and continuing crystallizing for 12 hours when the temperature is reduced to about-10 ℃. And pouring out the frozen crystal piperonal, crushing, adding into a fully-closed centrifuge, performing centrifugal separation for 15min to obtain 430kg of mother liquor, and collecting and entering an auxiliary process for treatment. Pouring out 195kg of crystals and then entering a drying process. The material loss was 5 kg.
(7) Drying by baking
And (3) pouring 195kg of crystalline piperonal finally obtained in the step (6) into a stainless steel drying tray, uniformly distributing, starting a drying hot air blower, adjusting the air speed, sealing a drying room, leading out dried tail gas through an air guide pipe, cooling and collecting 10.9kg of alcohol in the crystalline piperonal through a condenser, keeping the temperature at about 30 ℃, and drying for 24h to obtain 176.3kg of the product piperonal, wherein the purity is more than 99.0%. The material loss is 7.8kg, and then the physicochemical indexes of the product piperonal are analyzed, the chromatographic content is more than 99.0 percent, and the freezing point is more than 35.0 ℃. And packaging as a finished product after the product is qualified.
The total yield of the product is 76.94 percent and the unit consumption is 1.3 percent based on safrole.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. The preparation method of the heliotropin is characterized by comprising the steps of ozonization: at room temperature, isosafrole is mixed with water and ozone is introduced for reaction.
2. The method of claim 1, wherein the ratio of isosafrole: the mass ratio of water is 1: (2-5), preferably 1: 3.
3. The method of claim 1, wherein the room temperature is 20 to 35 ℃, preferably 25 to 30 ℃.
4. The method of claim 1, further comprising, after the ozonation step, a reduction step of: mixing the ozonized product of the isosafrole with a sodium metabisulfite aqueous solution with the mass concentration of 3-6% to perform reduction reaction at the temperature of 70-85 ℃; the mass consumption of the sodium metabisulfite aqueous solution is 1.2-1.8 times of that of the isosafrole;
further, the mass concentration of the sodium metabisulfite aqueous solution is 5 percent; the mass consumption of the sodium metabisulfite aqueous solution is 1.4-1.6 times of that of the isosafrole;
further, the reaction temperature was 80 ℃;
further, an aqueous solution of sodium metabisulfite is added in portions to the ozonide of isosafrole.
5. The method according to any one of claims 1 to 4, wherein the method further comprises a neutralization step after the isosafrole is ozonized and reduced: mixing a system obtained after reduction of an ozonide of isosafrole with a sodium carbonate aqueous solution with the mass concentration of 3-6% for neutralization; the mass consumption of the sodium carbonate aqueous solution is 3-3.6 times of that of the isosafrole;
further, the mass concentration of the sodium carbonate aqueous solution is 5 percent; the mass consumption of the sodium carbonate aqueous solution is 3.3-3.5 times of that of the isosafrole;
furthermore, the sodium carbonate aqueous solution is added into the system after the reduction of the ozonide of the isosafrole in batches.
6. The preparation method according to any one of claims 1 to 5, wherein the isosafrole is subjected to ozonization, reduction and neutralization, and then further comprises a rectification step: heating the neutralized crude aldehyde in a falling film evaporation mode, and rectifying under the condition that the vacuum degree is less than or equal to 500 Pa.
7. The preparation method according to any one of claims 1 to 6, wherein the isosafrole after ozonization, reduction, neutralization and rectification further comprises a crystallization step: mixing the rectified aldehyde with ethanol, and performing dynamic crystallization; then dissolving the crystal obtained by dynamic crystallization in ethanol for static crystallization;
the temperature of the dynamic crystallization and the static crystallization is-10-0 ℃, and is preferably-5 ℃.
8. The process according to claim 7, wherein in the dynamic crystallization, the ratio of refined aldehyde: the mass ratio of the ethanol is (3-0.5) to 1, preferably 1: 1;
in static crystallization, crystals obtained by dynamic crystallization: the mass ratio of ethanol is (3-0.5): 1, preferably 1: 1.
9. The preparation method according to claim 7, wherein the time for dynamic crystallization is 5 to 10 hours; preferably 8 h.
10. The preparation method according to any one of claims 1 to 4, further comprising the step of preparing isosafrole: mixing safrole with a KOH aqueous solution with the mass concentration of 40-60%, and carrying out isomerization reaction at 160-200 ℃, wherein the content of the safrole: the mass ratio of the KOH aqueous solution is 1: 0.04;
further, the mass concentration of the KOH aqueous solution was 50%, and the isomerization reaction temperature was 180 ℃.
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