CN109942382B - Method for synthesizing vanillyl alcohol ether - Google Patents
Method for synthesizing vanillyl alcohol ether Download PDFInfo
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- CN109942382B CN109942382B CN201910331904.5A CN201910331904A CN109942382B CN 109942382 B CN109942382 B CN 109942382B CN 201910331904 A CN201910331904 A CN 201910331904A CN 109942382 B CN109942382 B CN 109942382B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a method for synthesizing vanillyl alcohol ether, belonging to the technical field of fine chemical engineering. The synthesis method comprises the following steps: dissolving vanillin in a solvent, adding a metal complex hydride and an alkylating reagent after uniformly stirring, reacting for 3-4 hours at 30-40 ℃ to obtain a vanillin alcohol ether solution, and separating and purifying the vanillin alcohol ether solution to obtain vanillin alcohol ether. The synthesis method adopts a one-pot method to prepare the vanillyl alcohol ether, has simple operation, mild reaction conditions, easily controlled reaction process, low production cost and less three wastes, and the vanillyl alcohol ether prepared by the synthesis method has high yield and high purity and is easy to realize industrial production.
Description
Technical Field
The invention relates to the technical field of fine chemical engineering, and particularly relates to a method for synthesizing vanillyl alcohol ether.
Background
The vanillyl alcohol ether is an oil-soluble thermal inductance agent, can quickly generate mild and lasting heat source effect after acting on the skin, effectively stimulates the metabolism of subcutaneous fat and promotes blood circulation. The structure of the fragrant and sweet aromatic compound is similar to that of most of thermal sensing agents, but compared with other thermal sensing agents, the fragrant and sweet aromatic compound has the advantages of low irritation, high thermal sensing degree, long thermal sensing time and capability of obtaining strong thermal sensing at an extremely low dosage, and meanwhile, the fragrant and sweet aromatic compound is stable and safe in property, has pleasant vanilla flavor, can be compounded with most of cosmetic ingredients for use, so that the fragrant and sweet aromatic compound is more and more favored by the cosmetic industry, and particularly, the fragrant and sweet aromatic compound is most widely applied to the fields of food, cosmetics and the like. However, in recent years, a method for synthesizing vanillyl butyl ether has been reported. At present, the synthesis of vanillyl butyl ether is mainly obtained by dehydrating and condensing vanillyl alcohol and n-butyl alcohol under an acid catalyst, but the yield of the method is low mainly because water generated by the reaction can inhibit the etherification reaction, and the common acid catalyst such as AlCl is used3、FeCl3It is easy to hydrolyze in the presence of water and lose its catalytic action. Later, it was reported that some acidic catalysts were cured on materials such as molecular sievesThe solid acid catalyst can improve the yield of the system, but the catalyst is not easy to obtain, has difficult preparation and high cost, is difficult to apply to large-scale production, and has high cost due to taking the vanillyl alcohol as a raw material.
Therefore, it is necessary to develop a method for synthesizing vanillyl alcohol ether, which has the advantages of simple operation, mild reaction conditions, high yield and low cost.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the method for synthesizing the vanillyl alcohol ether.
In order to solve the problems, the technical scheme adopted by the invention is as follows:
a method for synthesizing vanillyl alcohol ether, comprising the following steps: dissolving vanillin in a solvent, uniformly stirring, adding a metal complex hydride and an alkylating reagent, and reacting at 30-40 ℃ for 3-4 hours to obtain a vanillin alcohol ether solution.
In a preferred embodiment of the present invention, the molar ratio of vanillin, metal complex hydride and alkylating agent is 1: 0.8-1.2: 1 to 1.5.
In a preferred embodiment of the present invention, the molar ratio of vanillin to solvent is 3 to 6: 1.
in a preferred embodiment of the present invention, the solvent is one or a mixture of two or more of methanol, ethanol, propanol, n-butanol, ethyl acetate, and dichloromethane.
In a preferred embodiment of the present invention, the metal double hydride is one or a mixture of two or more of potassium borohydride, sodium borohydride, lithium aluminum hydride, sodium thioborohydride and sodium cyanoborohydride.
In a preferred embodiment of the present invention, the alkylating agent is one or a mixture of two or more of ethyl chloride, ethyl bromide, butyl chloride, butyl bromide and n-butyl chloride.
As a preferred embodiment of the present invention, the vanillin is vanillin or ethyl vanillin.
As a preferred embodiment of the present invention, the solvent is ethyl acetate, and the metal double hydride is potassium borohydride; the mole ratio of the vanillin to the metal complex hydride to the alkylating reagent is 1: 0.8: 1.2.
as a preferred embodiment of the present invention, the synthesis method of the present invention further comprises a step of separating and purifying the vanillin alcohol ether solution, specifically as follows: filtering the vanillyl alcohol ether solution, and carrying out vacuum rectification on the filtrate to obtain the vanillyl alcohol ether.
In a preferred embodiment of the present invention, the temperature of the vacuum distillation is 140 to 180 ℃.
Compared with the prior art, the invention has the beneficial effects that:
the synthesis method of the invention takes vanillin as raw material, takes metal complex hydride as reducing agent, takes halogenated alkane as alkylating reagent, and takes oxidation product of metal complex hydride as alkaline catalyst to prepare the vanillyl alcohol ether by adopting one-pot method, the preparation steps are simple to operate, the reaction condition is mild, the reaction process is easy to control, the production cost is low, the three wastes are less, the vanillyl alcohol ether prepared by the synthesis method of the invention has high yield and high purity, is easy to realize industrial production, has higher economic benefit, and has excellent popularization and application value in the fields of medicine, food, cosmetics and the like.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments.
A method for synthesizing vanillyl alcohol ether, comprising the following steps: dissolving vanillin in a solvent, uniformly stirring, adding a metal complex hydride and an alkylating reagent, and reacting at 30-40 ℃ for 3-4 hours to obtain a vanillin alcohol ether solution; filtering the vanillyl alcohol ether solution, washing filter residues, combining a washing solution with a filtrate, and then carrying out vacuum rectification at 140-180 ℃ to obtain the vanillyl alcohol ether.
In the above synthesis method, the mole ratio of vanillin, metal complex hydride and alkylating reagent is 1: 0.8-1.2: 1 to 1.5, and the preferable molar ratio is 1: 0.8: 1.2. the molar ratio of vanillin to solvent is 3-6: 1. the solvent is one or a mixture of more than two of methanol, ethanol, propanol, n-butanol, ethyl acetate and dichloromethane, and preferably ethyl acetate. The metal complex hydride is one or the mixture of more than two of potassium borohydride, sodium borohydride, lithium aluminum hydride, sodium sulfoborohydride and sodium cyanoborohydride, and preferably potassium borohydride. The alkylating reagent is one or the mixture of more than two of chloroethane, bromoethane, chlorobutane, bromobutane and chlorohexane. The vanillin is vanillin or ethyl vanillin.
Example 1: preparation of vanillyl butyl ether
Dissolving 100.00g of vanillin in 231.65g of ethyl acetate, stirring and dissolving, adding 28.36g of potassium borohydride and 90.06g of bromobutane, and reacting for 4 hours at 30-40 ℃. Cooling to room temperature, filtering to remove solid in the reaction solution, washing filter residue, combining washing liquid and filtrate, and distilling the mixed liquid under reduced pressure to obtain a colorless liquid crude product. Vacuum rectifying at 165 deg.c to obtain vanillyl butyl ether 131.57g, yield 95.20% and purity over 99%.
Example 2: preparation of vanillyl butyl ether
Dissolving 100.00g of vanillin in 231.65g of ethyl acetate, stirring and dissolving, adding 28.36g of potassium borohydride and 108.07g of bromobutane, and reacting for 3 hours at 30-40 ℃. Cooling to normal temperature, filtering to remove solid in the reaction solution, washing filter residue, combining the washing solution and the filtrate, and distilling the mixed solution under reduced pressure to obtain a colorless liquid crude product. Vacuum rectifying at 165 deg.c to obtain vanillyl butyl ether 135.62g with yield 98.13% and purity over 99%.
This example differs from example 1 in that: the reaction time was 3 hours, the molar ratio of vanillin to bromobutane was different from 1: 1.2, the rest being the same as in example 1.
Example 3: preparation of vanillyl butyl ether
Dissolving 100.00g of vanillin in 231.65g of ethyl acetate, stirring and dissolving, adding 28.36g of potassium borohydride and 60.85g of chlorobutane, and reacting for 4 hours at 30-40 ℃. Cooling to normal temperature, filtering to remove solid in the reaction solution, washing filter residue, combining the washing solution and the filtrate, and distilling the mixed solution under reduced pressure to obtain a colorless liquid crude product. Vacuum rectifying at 165 deg.c to obtain vanillyl butyl ether 125.09g with yield 90.51% and purity over 99%.
This example differs from example 1 in that: the alkylating agent was chlorobutane, the remainder being the same as in example 1.
Example 4: preparation of vanillyl ether
Dissolving 100.00g of vanillin in 223.29g of dichloromethane, stirring and dissolving, adding 28.36g of potassium borohydride and 85.94g of ethyl bromide, and reacting for 3 hours at 30-40 ℃. Cooling to normal temperature, filtering to remove solid in the reaction solution, washing filter residue, combining the washing solution and the filtrate, and distilling the mixed solution under reduced pressure to obtain a colorless liquid crude product. Vacuum rectifying at 165 deg.C to obtain vanillyl ether 115.23g, yield 96.21%, purity > 99%.
This example differs from example 2 in that: the reaction solvent is dichloromethane, the alkylating agent is ethyl bromide, and the mixture ratio, the reaction temperature, the reaction time and the like of other related materials are the same as those in the example 2.
Example 5: preparation of vanillyl ether
Dissolving 100.00g of vanillin in 90.84g of ethanol, stirring and dissolving, adding 86.65g of sodium borohydride and 63.61g of chloroethane, and reacting for 4 hours at 30-40 ℃. Cooling to room temperature, filtering to remove solid in the reaction solution, washing filter residue, combining washing liquid and filtrate, and distilling the mixed liquid under reduced pressure to obtain a colorless liquid crude product. Vacuum rectification is carried out at 165 ℃ to obtain 118.05g of vanillyl ether, the yield is 98.56%, and the purity is more than 99%.
This example differs from example 4 in that: the metal double hydride is sodium thioborohydride and the alkylating agent is ethyl chloride, all the other being the same as in example 4.
Comparative example 1: preparation of vanillyl ether
100.00g of vanillyl alcohol is dissolved in 179.29g of ethanol, stirred and dissolved, 12.99g of ferric chloride hexahydrate is added, and the mixture reacts for 12 hours at the temperature of 60-70 ℃. Cooling to room temperature, filtering to remove solid in the reaction solution, washing filter residue, combining washing liquid and filtrate, and distilling the mixed liquid under reduced pressure to obtain a yellow liquid crude product. Washing with 100g of water, separating the liquid, and then carrying out vacuum rectification on the organic phase at 165 ℃ to obtain 77.07g of vanillyl ether, wherein the yield is 65.21%, and the purity is more than 98%.
The comparative example uses expensive vanillyl alcohol as raw material and FeCl3The catalyst is an acidic catalyst, and compared with the preparation method of the invention, the catalyst has the advantages of high raw material cost, higher reaction temperature, long reaction time and low yield.
Comparative example 2: preparation of vanillyl butyl ether
Dissolving 100.00g of vanillin in 243.59g of n-butanol, stirring for dissolving, adding 2.97g of a metal catalyst Pb-C, filling 1.8MPa of hydrogen, heating to 60-70 ℃ for reacting for 8 hours, detecting complete reaction of vanillin, stopping heating, filtering after reaction liquid is cooled, recovering the metal catalyst Pb-C, adding filtrate into a reaction tank, adding 14.87g of aluminum trichloride, heating to 60-70 ℃ and reacting for 12 hours. Cooling to room temperature, filtering to remove solid in the reaction solution, washing filter residue, combining washing liquid and filtrate, and distilling the mixed liquid under reduced pressure to obtain a colorless liquid crude product. Washing with 100g of water, separating the liquid, taking an organic phase, and performing vacuum rectification at 165 ℃ to obtain 94.74g of vanillyl butyl ether, wherein the yield is 68.55%, and the purity is more than 98%.
The comparative example uses vanillin with low price as raw material and AlCl3The catalyst is an acidic catalyst, but the vanillyl butyl ether can be synthesized only by two steps of reduction and etherification, and the reduction needs pressure catalytic hydrogenation.
Compared with the preparation method in the prior art, the synthesis method has the advantages of simple preparation step operation, mild reaction conditions, easy control of reaction process, low production cost and less three wastes.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (7)
1. A method for synthesizing vanillyl alcohol ether is characterized by comprising the following steps: the synthesis method comprises the following steps: dissolving vanillin in a solvent, uniformly stirring, adding a metal complex hydride and an alkylating reagent, and reacting at 30-40 ℃ for 3-4 hours to obtain a vanillin alcohol ether solution; wherein the mole ratio of the vanillin to the metal complex hydride to the alkylating agent is 1: 0.8-1.2: 1 to 1.5; the alkylation reagent is one or the mixture of more than two of chloroethane, bromoethane, chlorobutane, bromobutane and chlorohexane; the solvent is one or a mixture of ethyl acetate and dichloromethane.
2. The method of synthesizing a vanillyl alcohol ether according to claim 1, wherein: the molar ratio of the vanillin to the solvent is 3-6: 1.
3. a method of synthesizing a vanillyl alcohol ether according to claim 1 or 2, characterized in that: the metal complex hydride is one or the mixture of more than two of potassium borohydride, sodium borohydride, lithium aluminum hydride, sodium sulfoborohydride and sodium cyanoborohydride.
4. A method of synthesizing a vanillyl alcohol ether according to claim 1 or 2, characterized in that: the vanillin is vanillin or ethyl vanillin.
5. A method of synthesizing a vanillyl alcohol ether according to claim 1 or 2, characterized in that: the solvent is ethyl acetate, and the metal complex hydride is potassium borohydride; the mole ratio of the vanillin to the metal complex hydride to the alkylating reagent is 1: 0.8: 1.2.
6. a method of synthesizing a vanillyl alcohol ether according to claim 1 or 2, characterized in that: the method also comprises the steps of separating and purifying the vanillyl alcohol ether solution, which specifically comprises the following steps: filtering the vanillyl alcohol ether solution, and carrying out vacuum rectification on the filtrate to obtain the vanillyl alcohol ether.
7. The method of synthesizing a vanillyl alcohol ether according to claim 6, wherein: the temperature of the vacuum rectification is 140-180 ℃.
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| CN201910331904.5A CN109942382B (en) | 2019-04-24 | 2019-04-24 | Method for synthesizing vanillyl alcohol ether |
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Citations (4)
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| CN101208082A (en) * | 2005-06-28 | 2008-06-25 | 默克公司 | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
| CN101970420A (en) * | 2007-10-04 | 2011-02-09 | 默克雪兰诺有限公司 | Oxadiazole derivatives |
| CN101987813A (en) * | 2009-08-07 | 2011-03-23 | 中国科学院海洋研究所 | Chemical total synthesis method for type II anti-diabetic medicament hypnopyrine |
| WO2017045893A1 (en) * | 2015-09-18 | 2017-03-23 | Henkel Ag & Co. Kgaa | Release of odoriferous substances from microcapsules |
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Patent Citations (4)
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| CN101208082A (en) * | 2005-06-28 | 2008-06-25 | 默克公司 | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
| CN101970420A (en) * | 2007-10-04 | 2011-02-09 | 默克雪兰诺有限公司 | Oxadiazole derivatives |
| CN101987813A (en) * | 2009-08-07 | 2011-03-23 | 中国科学院海洋研究所 | Chemical total synthesis method for type II anti-diabetic medicament hypnopyrine |
| WO2017045893A1 (en) * | 2015-09-18 | 2017-03-23 | Henkel Ag & Co. Kgaa | Release of odoriferous substances from microcapsules |
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| CN113563166A (en) | 2021-10-29 |
| CN113563166B (en) | 2023-08-01 |
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