CN112778126A - Method for synthesizing oak moss by catalysis of supported solid alkali - Google Patents
Method for synthesizing oak moss by catalysis of supported solid alkali Download PDFInfo
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- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
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- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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Abstract
The invention provides a method for synthesizing oak moss by using supported solid base as a raw material, which adopts supported methyl propionylacetate and methyl crotonate as raw materialsSolid base KF/gamma-Al2O3As a catalyst, preparing an important intermediate 4-hydroxy-3, 6-dimethyl-2-oxocyclohexyl-3-alkene methyl formate for synthesizing the main fragrance component of the oak moss, and finally obtaining a target product through aromatization reaction to synthesize the oak moss, namely 3, 6-dimethyl-beta-resorcylic acid methyl ester. The method solves the problem of difficult recovery of sodium methoxide. Solid base KF/gamma-Al2O3The utilization of the method not only realizes the high-efficiency recovery and cyclic utilization of the catalyst and reduces the process cost, but also inhibits the secondary addition side reaction in the Michael reaction and solves the problem of difficult separation of the target product 3, 6-dimethyl-beta-resorcylic acid methyl ester.
Description
Technical Field
The invention relates to the technical field of substance synthesis, in particular to a method for synthesizing oak moss by catalysis of supported solid alkali.
Background
Oak moss, a class of compounds commonly found in the fungus body of mountain forests in the temperate zone of the northern hemisphere. Oak moss is one of the most common natural fragrances, particularly in perfumes and aromatherapy. As essential base incense, the market demand is increasing, and the natural extraction of the oak moss is not in demand, so the market price is high. Meanwhile, the naturally extracted oak moss contains more allergic components and cannot be separated, so that a substance which has the unique smell of the natural oak moss and can be safely used by people is urgently needed in the market. The problem is solved by the appearance of the synthesized oak moss (3, 6-dimethyl-beta-methyl resorcinate), and the synthesized oak moss becomes a substitute of the oak moss.
The existing synthetic routes of the synthetic oak moss at home and abroad mainly comprise the following 4 types:
(1) the raw material 1, 3-dichloro-2, 5-dimethylbenzene (1) is hydrolyzed in a mixed solvent of water and a water-soluble organic solvent to obtain an intermediate 2, 5-dimethylresorcinol (2), and gaseous CO is used2And (3) methoxylating the intermediate 2 to obtain 2, 4-dihydroxy-3, 6-dimethylbenzoic acid (3), and finally selecting methyl iodide, dimethyl sulfate and the like as methylation reagents to obtain a target product 3, 6-dimethyl-beta-resorcylic acid methyl ester, which is shown in the formula I. The method has harsh technological conditions, the raw material 1, 3-dichloro-2, 5-dimethylbenzene is not commercialized, and the technological cost is high.
(2) Taking 5-methylresorcinol (5) as a raw material, protecting two hydroxyl groups through an ether forming reaction to generate an intermediate 3, 5-dimethoxytoluene (6), obtaining an intermediate 2, 6-dimethoxyphenyl lithium (7) through a metallization reaction, obtaining 2, 6-dimethoxy-4-methyltoluene (8) through a post reaction, finally deprotecting the hydroxyl groups to obtain a methylated product 2, 5-dimethylresorcinol (2), and obtaining a target product (4) (see formula II) through methoxylation and methylation reactions, wherein the methoxylation and methylation reactions of the intermediate 2 are discussed in the above text and are not repeated. During the first methylation step, although only C-2 is attached to a methyl group, in the actual methylation process, it is necessary to take into account competing reactions between carbon methylation and oxygen methylation that may occur. In order to reduce the occurrence of side reactions, the hydroxyl group needs to be protected before the methylation reaction, and in addition, the deprotection needs to be carried out after the methylation reaction is completed. This process increases the process difficulty and the cost of phenyllithium used to activate C-2 is high.
(3) Aromatizing 4-hydroxy-3, 6-dimethyl-2-oxocyclohex-3-ene methyl formate as a raw material to generate 2, 5-dimethyl resorcinol, and performing oxygen methylation and methylation to obtain a target product, namely 3, 6-dimethyl-beta-resorcin methyl ester (see formula III). Marmor reported that 2, 5-dimethyl-resorcinol was obtained from the intermediate 4-hydroxy-3, 6-dimethyl-2-oxocyclohex-3-enecarboxylic acid methyl ester through three-step reaction, and the reaction conditions were very harsh and had no industrial significance.
(4) Taking an acyclic compound as a raw material, and finally obtaining a target product of 3, 6-dimethyl-beta-resorcylic acid methyl ester through Michael addition, intramolecular condensation, oxidative dehydrogenation and other processes. In the process of preparing the target product by the route, the 4-hydroxy-3, 6-dimethyl-2-oxocyclohex-3-ene methyl formate is the key of the reaction. The key intermediate can be obtained by three methods, (a) Sonn et al report that ethyl acetoacetate (10) and methyl crotonate (11) can be cyclized to generate 4-hydroxy-6-methyl-2-oxocyclohex-3-enecarboxylic acid methyl ester (12), and then the key intermediate 4-hydroxy-3, 6-dimethyl-2-oxocyclohex-3-enecarboxylic acid methyl ester (9) is obtained through methylation reaction. (b) Pfau found that the key intermediate (9) was obtained in a higher yield by a one-step reaction with dimethyl malonate (14) and 4-hexen-3-one (15). The target product synthesized by aromatizing the intermediate is synthesized into the oak moss by a palladium catalytic dehydrogenation process, but the method has higher cost and is not easy to realize industrial production. Subsequent studies have found that an oxidation scheme of firstly halogenating and then removing hydrogen halide can be used by using a halogenating agent, and the method has higher yield of 3, 6-dimethyl-beta-resorcylic acid methyl ester. (c) There are reports that methyl propionylacetate (16) and methyl crotonate (11) are used as raw materials, sodium methoxide is used as a catalyst, a key intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-ene methyl formate (9) is obtained through Michael addition and intramolecular condensation reaction, and the intermediate (9) is subjected to aromatization to obtain a target product (4). The method can obtain oak moss with yield up to 85%, and has simple process.
The prior domestic main route for synthesizing 3, 6-dimethyl-beta-resorcylic acid methyl ester takes dimethyl malonate and 4-hexene-3-ketone as raw materials and sodium methoxide as alkali to synthesize a key intermediate 9, and a target product 4 is obtained by aromatizing anhydride acetic acid and hydrolyzing the alkali solution. The method has mild conditions and short reaction time, and the ester exchange reaction and the condensation reaction are combined and carried out in the same system, thereby simplifying the production process and realizing industrialization. However, the method has the defect that when 4-hexene-3-ketone is taken as a raw material to produce the oak moss, the raw material synthesis becomes a key restriction factor. In the process of synthesizing 4-hexene-3-ketone by the route of propylene and propionyl chloride, a large amount of three wastes are generated in the production process, and the environmental protection pressure is high. In the process of producing the intermediate 4-hexene-3-ketone by the Grignard and oxidation reaction of bromoethane and crotonaldehyde, a by-product of the 1, 4-addition reaction exists in the step of the Grignard reaction of the intermediate synthesis of the enols, and the product yield is low. The oxidation of alcoholic hydroxyl groups to carbonyl groups requires the use of dichromate oxidants and is also under environmental pressure. The first step reaction generates a key intermediate 9, sodium methoxide is used as an alkali reagent, and the subsequent washing with dilute hydrochloric acid is needed, so that waste liquid is generated, the requirement of green chemistry is not met, and the sodium methoxide meets water, and the humid air is inflammable, so that the storage and the industrial production are not facilitated.
Disclosure of Invention
The invention provides a method for catalytically synthesizing oak moss by using supported solid base, which takes methyl propionylacetate and methyl crotonate as raw materials and adopts supported solid base KF/gamma-Al2O3As a catalyst, preparing an important intermediate 4-hydroxy-3, 6-dimethyl-2-oxocyclohex-3-ene methyl formate for synthesizing the main fragrance component of the oak moss, and finally obtaining a target product synthetic oak moss (namely 3, 6-dimethyl-beta-resorcylic acid methyl ester) through aromatization reaction. The method solves the problem of sodium methoxideDifficult to recycle. Solid base KF/gamma-Al2O3The utilization of the method not only realizes the high-efficiency recovery and cyclic utilization of the catalyst and reduces the process cost, but also inhibits the secondary addition side reaction in the Michael reaction and solves the problem of difficult separation of the target product 3, 6-dimethyl-beta-resorcylic acid methyl ester.
The invention relates to an application of a solid base catalyst in the synthesis of rubber moss 3, 6-dimethyl-beta-resorcylic acid methyl ester. Takes methyl propionylacetate and methyl crotonate as raw materials and adopts the reaction at KF/gamma-Al2O3Under the action of the reaction, Michael reaction is carried out, and then intramolecular aldol condensation reaction is carried out to generate a key intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-methyl enoate; the intermediate is subjected to aromatization to obtain a target product, namely the synthetic oak moss. The synthetic route is shown in formula V:
KF/γ-Al2O3the multifunctional solid base has been widely used, has a basic catalytic center, and can avoid secondary addition side reaction in the catalytic Michael reaction. Meanwhile, KF/gamma-Al 2O3 is stable and easy to store, and the catalyst after repeated regeneration still has strong catalytic performance, thereby realizing the high-efficiency cyclic utilization of the catalyst.
The specific technical scheme of the invention is as follows:
a method for synthesizing oak moss by catalysis of supported solid alkali comprises the following steps:
step 1: synthesizing an intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-ene methyl formate:
dissolving methyl propionylacetate into a first organic solvent, and adding KF/gamma-Al2O3Uniformly stirring the catalyst to obtain a propionyl methyl acetate reaction solution; heating to 80-140 ℃, dissolving methyl crotonate in a second organic solvent, dropwise adding the methyl crotonate into the methyl propionylacetate reaction liquid, reacting for 3-48 hours (preferably 18-24 hours), filtering out the catalyst after the reaction is completed, removing the solvent by reduced pressure distillation, collectingWashing the separated white solid with water, washing with petroleum ether, and drying to obtain intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-cyclohex-3-ene methyl formate and catalyst KF/gamma-Al2O3Washing with ethanol, water and ethanol for 3 times, drying and recovering. The reaction is shown in formula six:
step 2: synthesis of target 3, 6-dimethyl-beta-resorcylic acid methyl ester: and (3) aromatizing the intermediate 4-hydroxy-3, 6-dimethyl-2-cyclohexene oxide-3-olefin methyl formate prepared in the step (1) to obtain the target 3, 6-dimethyl-beta-resorcin methyl ester. See formula seven for the reaction:
furthermore, the mass ratio of the methyl propionylacetate to the first organic solvent is 1 (3-50), and the mass ratio of the methyl crotonate to the second organic solvent is 1 (3-50).
Furthermore, the molar ratio of the methyl propionylacetate to the methyl crotonate is controlled to be 1 (1-3).
Further, the KF/gamma-Al2O3The mass ratio of the catalyst to the methyl propionylacetate is 1 (2-10).
Further, the first organic solvent and the second organic solvent are the same, and both the first organic solvent and the second organic solvent are aprotic solvents.
Further, the first organic solvent and the second organic solvent are acetonitrile, DMF, DMSO, THF, diethyl ether, or methyl tert-butyl ether; further, the first organic solvent and the second organic solvent are DMF, methyl tert-butyl ether or THF.
Further, the catalyst KF/gamma-Al2O3The preparation method comprises the following steps: dissolving potassium fluoride in deionized water to prepare potassium fluoride solution, weighing gamma-Al2O3The powder (as a carrier) is,mixing gamma-Al2O3Soaking the powder into potassium fluoride solution, stirring for 30min, vacuum drying, and activating at high temperature to obtain solid catalyst KF/gamma-Al2O3。
Further, the potassium fluoride and gamma-Al2O3The mass ratio of the powder is 1 (5-20).
Further, the activation temperature is 413K-513K.
Further, the step 2: the synthesis of the target 3, 6-dimethyl-beta-resorcylic acid methyl ester comprises the following steps: dissolving copper chloride dihydrate, NaCl and the intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-alkene methyl formate obtained in the step 1 into acetonitrile, reacting at 85 ℃ for 5 hours, removing the solvent acetonitrile after the reaction is finished, freezing and crystallizing the residue, filtering and separating to obtain a crude product of 3, 6-dimethyl-beta-resorcin methyl ester, dissolving the crude product with ethyl acetate, and recrystallizing to obtain a light yellow solid, namely the target 3, 6-dimethyl-beta-resorcin methyl ester.
According to the invention, potassium fluoride is loaded on the carrier, so that the condensation reaction selectivity can be improved, the byproduct production is reduced, the separation operation of 4-hydroxy-3, 6-dimethyl-2-cyclohexene oxide-3-alkene methyl formate is simplified, the generation of wastewater in the production process is reduced, and the discharge of three wastes is reduced. While KF/gamma-Al2O3The solid base catalyst is recycled by simple filtration, and the recycling and the high-efficiency recycling are realized, so that the service efficiency and the service life of the catalyst are improved. Solid base catalyst KF/gamma-Al2O3The catalyst is convenient to separate, and the separation efficiency is greatly improved.
Compared with the prior art, the invention has the following technical effects:
1. the invention adopts gamma-Al2O3The loaded KF is used as a catalyst for synthesizing a key intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-alkene methyl formate (9), so that the alkaline center required in the reaction is ensured, the side reaction of secondary Michael addition is avoided, and the yield of the key intermediate 9 is improved.
2. Gamma-Al used in the invention2O3Load KF solid alkali compares with traditional alkali sodium methoxide, and this solid alkali easily separates, and separation efficiency is high, just can used repeatedly through simple processing, has increased the availability factor of catalyst, greatly reduced manufacturing cost.
3. Catalyst KF/gamma-Al used in the invention2O3Can be recycled for multiple times, the catalytic efficiency is basically unchanged, the catalytic activity is stable, and the method is favorable for industrial practical application.
4. The method for synthesizing the 3, 6-dimethyl-beta-resorcylic acid methyl ester by adopting the route has the advantages of simple operation, mild condition, safety, controllability, good repeatability, environmental protection.
Detailed Description
The present invention will be further described with reference to the following embodiments.
Example 1
1. Catalyst KF/gamma-Al2O3Preparation of
Potassium fluoride (50g) was dissolved in 1000mL of deionized water to prepare a potassium fluoride solution. Then gamma-Al is added2O3(1000.0g) the powder was immersed in the potassium fluoride solution and sufficiently stirred for 30 minutes, followed by vacuum drying to remove water. Then activating the mixture at high temperature (513K) to obtain KF/gamma-Al with the mass ratio of 5 percent2O3A catalyst.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
20.3g of methyl crotonate (0.203mol) was dissolved in 100mL of DMSO to prepare a methyl crotonate solution; taking 3.2g of KF/gamma-Al with the mass ratio of 5%2O326.0g methyl propionylacetate (0.2mol) and 900mL DMSO were added in this order to a flask equipped with stirrer, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, stirring was turned on to allow the reactants to mix well. Heating to react to 80 ℃, and slowly dripping a methyl crotonate solution under a reflux state to react for 18 h. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is separated out from the solution, the solution is washed with water for three times, washed with petroleum ether for three times and dried to obtain the white solid with the yield of 42.4 percent. Nuclear magnetic data of such asThe following:1H NMR(600MHz,DMSO-d6):0.938(d, J＝8.4Hz,3H),1.544(s,3H),2.392(m,2H),2.463(m,1H),3.108(d,J＝11.2Hz,1H), 3.639(s,3H)。
3. synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
To a three-necked flask were added 40.0g of methyl 4-hydroxy-3, 6-dimethyl-2-oxido-cyclohex-3-enecarboxylate, 3.0g of copper chloride dihydrate, 1.0g of NaCl and 500mL of acetonitrile, and reacted at 85 ℃ for 5 hours. And after the reaction is finished, removing the solvent acetonitrile, freezing and crystallizing the residue, and filtering and separating to obtain a crude product of the 3, 6-dimethyl-beta-resorcylic acid methyl ester. The crude product was dissolved in 800mL ethyl acetate and recrystallized to give a pale yellow solid with 88.7% yield. The melting point is 128.6-130.8 ℃, and the nuclear magnetic data is as follows:
1H NMR(600MHz,DMSO-d6):1.939(s,3H),2.358(s,3H),3.843(s,3H), 6.279(s,1H),10.098(s,1H),11.637(s,1H).
13C NMR(600MHz,DMSO-d6):8.403,23.919,52.293,104.353,108.584, 110.575,110.966,139.216,160.477,162.237,172.307.
example 2
1. Catalyst KF/gamma-Al2O3Preparation of
100.0g of potassium fluoride was weighed by an electronic balance and dissolved in 1000mL of deionized water to prepare a potassium fluoride solution. 1000g of gamma-Al are weighed2O3Powder prepared by weighing gamma-Al by dipping method2O3The powder was immersed in the above potassium fluoride solution and sufficiently stirred for 30 min. Vacuum drying to remove water, and activating at 513K to obtain KF/gamma-Al with mass ratio of 10%2O3。
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
The intermediate 9 was synthesized by the same method as in example 1, except that 3.2g of KF/gamma-Al in an amount of 10% by mass was used as the solid base catalyst2O3The yield thereof was found to be 56.3%.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 3
1. Catalyst KF/gamma-Al2O3Preparation of
150g of potassium fluoride was dissolved in 1000mL of deionized water to prepare a potassium fluoride solution. 1000g of gamma-Al are weighed2O3Powder prepared by weighing gamma-Al by dipping method2O3Soaking the powder in the potassium fluoride solution, and stirring for 30 min. Vacuum drying to remove water, and activating at 413K to obtain KF/gamma-Al with mass ratio of 15%2O3。
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
The intermediate 9 was synthesized by the same method as in example 1, except that 3.2g of KF/gamma-Al was used as the solid base catalyst in an amount of 15% by mass2O3The yield thereof was found to be 44.1%.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 4
1. Catalyst KF/gamma-Al2O3Preparation of
20.0g of potassium fluoride was weighed using an electronic balance and dissolved in 100mL of deionized water to prepare a potassium fluoride solution. 100g of gamma-Al are weighed2O3Powder prepared by weighing gamma-Al by dipping method2O3Soaking the powder in the potassium fluoride solution, stirring for 30min, vacuum drying to remove water, and activating at 413K to obtain KF/gamma-Al with mass ratio of 20%2O3。
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
The intermediate 9 was synthesized by the same method as in example 1, except that 3.2g of 20% KF/γ -Al was used as the solid base catalyst2O3The yield thereof was found to be 35.7%.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 5
1. Catalyst KF/gamma-Al2O3Preparation of
KF/γ-Al2O3The same as in example 1.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
20.3g of methyl crotonate (0.203mol) was dissolved in 100mL of DMSO to prepare a methyl crotonate solution; 3.2g of KF/gamma-Al with the mass ratio of 5 percent are weighed2O326.0g methyl propionylacetate (0.2mol) and 1200mL DMSO were added in this order to a flask equipped with stirrer, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, stirring was turned on to allow the reactants to mix well. Heating to react to 100 ℃, slowly and dropwise adding a methyl crotonate solution under a reflux state, and reacting for 18 h. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is separated out from the solution, the solution is washed with water for three times, washed with petroleum ether for three times and dried to obtain the white solid with the yield of 77.8 percent.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 6
1. Catalyst KF/gamma-Al2O3Preparation of
KF/γ-Al2O3The same as in example 2.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
Dissolving 31.0g of methyl crotonate (0.31mol) in 100mL of DMF solution to obtain methyl crotonate solution; taking 6.4g of KF/gamma-Al with the mass ratio of 10%2O326.0g methyl propionylacetate (0.2mol) and 1100mL DMF were added in succession to a stirred, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, stirring was turned on to allow the reactants to mix well. Heating to react to 100 deg.C, slowly adding dropwise methyl crotonate solution under reflux state, and reactingAnd the time is 18 hours. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is separated out from the solution, the solution is washed with water for three times, washed with petroleum ether for three times and dried to obtain the white solid with the yield of 86.4 percent.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 7
1. Catalyst KF/gamma-Al2O3Preparation of
KF/γ-Al2O3The same as in example 2.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
Dissolving 31.0g of methyl crotonate (0.31mol) in 100mL of DMSO solution to obtain a methyl crotonate solution; taking 6.4g of KF/gamma-Al with the mass ratio of 10%2O326.0g methyl propionylacetate (0.2mol) and 900mL DMSO were added in this order to a flask equipped with stirrer, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, stirring was turned on to allow the reactants to mix well. Heating to react to 120 ℃, and slowly dropwise adding a methyl crotonate solution under a reflux state to react for 10 hours. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is separated out from the solution, the solution is washed with water for three times, washed with petroleum ether for three times and dried to obtain the white solid with the yield of 83.5 percent.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 8
1. Catalyst KF/gamma-Al2O3Preparation of
KF/γ-Al2O3The same as in example 2.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
31.0g of methyl crotonate (0.31mol) was dissolved in 100mL of DMF to obtain a solution of methyl crotonateLiquid; taking 6.4g of KF/gamma-Al with the mass ratio of 10%2O326.0g methyl propionylacetate (0.2mol) and 1000mL DMF were added in succession to a stirred flask, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, the stirring was turned on to mix the reactants uniformly. Heating to react to 100 ℃, slowly and dropwise adding a methyl crotonate solution under a reflux state, and reacting for 12 hours. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is separated out from the solution, the solution is washed with water for three times, washed with petroleum ether for three times and dried to obtain the white solid with the yield of 80.9 percent.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 9
1. Preparation of catalyst KF/gamma-Al 2O3
KF/γ -Al2O3 is the same as in example 2.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
Dissolving 31.0g of methyl crotonate (0.31mol) in 100mL of DMF solution to obtain methyl crotonate solution; taking 6.4g of KF/gamma-Al with the mass ratio of 10%2O326.0g methyl propionylacetate (0.2mol) and 800mL DMF were added in succession to a stirred, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, the stirring was turned on to mix the reactants uniformly. The reaction is heated to 140 ℃, and the methyl crotonate solution is slowly added dropwise under the reflux state to react for 18 h. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, after white solid is collected and separated out, the white solid is washed by water for three times, washed by petroleum ether for three times and dried to obtain the white solid with the yield of 72.5 percent.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
Example 10
1. Preparation of catalyst KF/gamma-Al 2O3
KF/γ -Al2O3 is the same as in example 2.
2. Synthesis of 4-hydroxy-3, 6-dimethyl-2-oxido-3-enecarboxylic acid methyl ester
Dissolving 31.0g of methyl crotonate (0.31mol) in 100mL of DMF solution to obtain methyl crotonate solution; taking 6.4g of KF/gamma-Al with the mass ratio of 10%2O326.0g methyl propionylacetate (0.2mol) and 1100mL DMF were added in succession to a stirred, thermometer, reflux condenser, dropping funnel and CaCl2In the reaction flask of the drying tube, the stirring was turned on to mix the reactants uniformly. Heating to react to 120 ℃, and slowly dropwise adding a methyl crotonate solution under a reflux state to react for 48 hours. After the reaction is finished, the catalyst is removed by suction filtration, the solvent is removed by reduced pressure distillation, the white solid is collected and precipitated, then the suction filtration is carried out again, and the white solid is obtained by washing with water for three times, washing with petroleum ether for three times and drying, wherein the yield is 63.9%.
3. Synthesis of 3, 6-dimethyl-beta-resorcylic acid methyl ester
The synthesis route of the target product 3, 6-dimethyl-beta-resorcin methyl ester is the same as that of example 1.
The above-mentioned embodiments are merely preferred embodiments of the present invention, which are merely illustrative and not restrictive, and it should be understood that various changes and modifications may be made by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. A method for synthesizing oak moss by catalysis of supported solid alkali is characterized by comprising the following steps:
step 1: synthesizing an intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-ene methyl formate:
dissolving methyl propionylacetate into a first organic solvent, and adding KF/gamma-Al2O3The catalyst is evenly stirred to obtain propionyl methyl acetate reaction liquid; heating to 80-140 ℃, and then adding crotonic acidDissolving methyl ester in a second organic solvent, dropwise adding the methyl ester into the methyl propionylacetate reaction liquid, reacting for 3-48 hours, filtering out the catalyst after the reaction is completed, removing the solvent by reduced pressure distillation, collecting the precipitated white solid, washing with water, washing with petroleum ether, and drying to obtain an intermediate 4-hydroxy-3, 6-dimethyl-2-cyclohexene oxide-3-methyl enoate;
step 2: synthesis of target 3, 6-dimethyl-beta-resorcylic acid methyl ester: and (3) aromatizing the intermediate 4-hydroxy-3, 6-dimethyl-2-cyclohexene oxide-3-olefin methyl formate prepared in the step (1) to obtain the target 3, 6-dimethyl-beta-resorcin methyl ester.
2. The method for synthesizing oak moss under the catalysis of the supported solid base according to claim 1, wherein the mass ratio of the methyl propionylacetate to the first organic solvent is 1 (3-50), and the mass ratio of the methyl crotonate to the second organic solvent is 1 (3-50).
3. The method for synthesizing oak moss by catalysis of the supported solid base, which is claimed in claim 1, wherein the molar ratio of methyl propionylacetate to methyl crotonate is controlled to be 1 (1-3).
4. The method for synthesizing oak moss by catalysis of supported solid base according to claim 1, wherein the KF/gamma-Al is2O3The mass ratio of the catalyst to the methyl propionylacetate is 1 (2-10).
5. The method for the supported solid base-catalyzed synthesis of oak moss according to claim 1, wherein the first organic solvent and the second organic solvent are the same and both the first organic solvent and the second organic solvent are aprotic solvents.
6. The method for the supported solid base-catalyzed synthesis of oak moss according to claim 1, wherein the first organic solvent and the second organic solvent are acetonitrile, DMF, DMSO, THF, diethyl ether or methyl tert-butyl ether.
7. The method for synthesizing oak moss by catalysis of supported solid base according to claim 1, wherein the catalyst KF/gamma-Al2O3The preparation method comprises the following steps: dissolving potassium fluoride in deionized water to prepare potassium fluoride solution, and weighing gamma-Al2O3Powder of gamma-Al2O3Soaking the powder into potassium fluoride solution, stirring for 30 minutes, drying in vacuum, and activating at high temperature to obtain the solid catalyst KF/gamma-Al2O3。
8. The method for synthesizing oak moss catalyzed by supported solid base according to claim 7, wherein the potassium fluoride is mixed with γ -Al2O3The mass ratio of the powder is 1 (5-20).
9. The method for synthesizing oak moss by catalysis of a supported solid base according to claim 7, wherein the activation temperature is 413K-513K.
10. The method for synthesizing oak moss by catalysis of the supported solid base according to claim 1, wherein the step 2: the synthesis of the target 3, 6-dimethyl-beta-resorcylic acid methyl ester comprises the following steps: dissolving copper chloride dihydrate, NaCl and the intermediate 4-hydroxy-3, 6-dimethyl-2-oxido-3-alkene methyl formate obtained in the step 1 into acetonitrile, reacting at 85 ℃ for 5 hours, removing the solvent acetonitrile after the reaction is finished, freezing and crystallizing residues, filtering and separating to obtain a crude product of 3, 6-dimethyl-beta-resorcin methyl ester, dissolving the crude product with ethyl acetate, and recrystallizing to obtain a light yellow solid, namely the target product of 3, 6-dimethyl-beta-resorcin methyl ester.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86100869A (en) * | 1986-01-10 | 1987-07-22 | 中国科学院上海有机化学研究所 | The chemosynthesis of the main essence of oak moss |
| US20180170824A1 (en) * | 2014-03-24 | 2018-06-21 | The Regents Of The University Of California | Methods for producing cyclic and acyclic ketones |
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2020
- 2020-12-31 CN CN202011638371.4A patent/CN112778126A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN86100869A (en) * | 1986-01-10 | 1987-07-22 | 中国科学院上海有机化学研究所 | The chemosynthesis of the main essence of oak moss |
| US20180170824A1 (en) * | 2014-03-24 | 2018-06-21 | The Regents Of The University Of California | Methods for producing cyclic and acyclic ketones |
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| 冯凌竹: "橡苔主香成分的合成与提纯工艺研究", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
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| 田丹碧等: "KF/Al_2O_3在Michael加成反应中的应用及其机理", 《南京工业大学学报(自然科学版)》 * |
| 胡泰山等: "负载型固体碱KF/Al2O3在有机合成中的应用", 《精细石油化工》 * |
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