CN113214059B - Preparation method of raspberry ketone - Google Patents
Preparation method of raspberry ketone Download PDFInfo
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- CN113214059B CN113214059B CN202110174121.8A CN202110174121A CN113214059B CN 113214059 B CN113214059 B CN 113214059B CN 202110174121 A CN202110174121 A CN 202110174121A CN 113214059 B CN113214059 B CN 113214059B
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- 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
- C07C45/67—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 isomerisation; by change of size of the carbon skeleton
- C07C45/68—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 isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
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Abstract
The invention relates to a preparation method of raspberry ketone, which comprises the following steps: under the action of an organic acid catalyst and a crown ether cocatalyst, phenol reacts with butanone alcohol to obtain a target product raspberry ketone. The raspberry ketone prepared by the method has high yield which can reach 91.96% (calculated by the mol number of butanone alcohol consumption), and meanwhile, the dosage of the organic acid catalyst in the preparation method is small, so that the generation of three wastes can be effectively reduced, and the method has great economic benefit and environmental protection benefit.
Description
Technical Field
The invention relates to the technical field of organic synthesis, and particularly relates to a method for preparing raspberry ketone.
Background
Raspberry ketone is also called rubusflavone, is a white needle-shaped crystal or fine granular solid in appearance, is an essence and spice with elegant fruity flavor widely applied at home and abroad, and is widely used for blending edible essence and essence for cosmetics.
The conventional raspberry ketone preparation method mainly comprises the following 2 routes:
(1) Synthetic route to Claisen-Schmidt condensation of p-hydroxybenzaldehyde with acetone followed by hydrogenation reduction:
the process route takes p-hydroxybenzaldehyde and acetone as starting materials, 4- (4-hydroxyphenyl) -3-butene-2 ketone is generated through one-step condensation reaction, and then the raspberry ketone with ideal purity is obtained through the post-treatment of selective hydrogenation, reduced pressure distillation, recrystallization and the like of the 4- (4-hydroxyphenyl) -3-butene-2 ketone. Although the synthesis method has high product yield, the raw material p-hydroxybenzaldehyde has high cost and rare sources, so that the whole production process has no advantages in cost and small profit margin. In addition, the selective hydrogenation process easily generates by-product 4- (4-hydroxyphenyl) -2-butanol, and the substance is difficult to completely separate from the target product raspberry ketone, thereby influencing the quality of the product.
(2) Synthetic route to phenol and Ding Tongchun:
the synthesis route takes phenol and Ding Tongchun (4-hydroxy-2-butanone) as initial raw materials, and the raspberry ketone is generated by one step of Friedel-crafts alkylation reaction under the acidic condition. The yield of the process is not high, the yield of the traditional process is 45-62% by using water-soluble acid as a catalyst, and the yield of the traditional process is 67-70% by using cation exchange resin as the catalyst, but the price of the raw materials is relatively low, and the raspberry ketone prepared by the process has pure fragrance, so the process draws extensive attention and research of researchers at home and abroad.
In the patent document DE2145308, butanone alcohol and phenol are used as raw materials, concentrated sulfuric acid is used as a catalyst to perform Friedel-crafts reaction, the mole yield can reach 51% by Ding Tongchun, the yield is low, the amount of waste acid is large, and the environment friendliness is poor.
Patent document CN108530280a uses phenol and Ding Tongchun as starting materials, and obtains raspberry ketone by preparation at 40-50 ℃ under the condition of using acidic immobilized ionic liquid as a catalyst. The preparation process of the acidic immobilized ionic liquid is complex and long in period, and the obtained raspberry ketone finished product has low content and low yield.
Patent document US8471068B2 discloses a method for preparing a solid acid catalyst by using hydrochloric acid activated montmorillonite, and the solid acid catalyst is applied to friedel-crafts alkylation reaction of phenol and Ding Tongchun, wherein the conversion rate of raw materials of the reaction is only 35-55%, and the selectivity of raspberry ketone is 75-81%.
Patent document GB2080284B discloses a method for preparing raspberry ketone by catalyzing phenol and butanone alcohol to perform Friedel-crafts alkylation reaction by using sulfuric acid activated acidic cationic resin. The yield of the raspberry ketone obtained by the method is 69%, and is low.
Disclosure of Invention
Accordingly, there is a need to provide an efficient and economical method for preparing raspberry ketone, which has high raspberry ketone yield and low acid catalyst consumption.
In order to achieve the purpose, the invention provides a preparation method of raspberry ketone, which comprises the following steps: reacting phenol with butanone alcohol under the action of an organic acid catalyst and a crown ether cocatalyst to obtain the raspberry ketone.
In one or more embodiments, the crown ether co-catalyst comprises one or more of 18-crown-6, dibenzo-18-crown-6, 4-nitrobenz-15-crown-5, dicyclohexyl-24-crown-8, benzo-15-crown-5, dibenzo-21-crown-7, dibenzo-24-crown-8, dibenzo-27-crown-9, dibenzo-30-crown-10, oxadiazole macrocyclic crown ethers, preferably dicyclohexyl-24-crown-8, oxadiazole macrocyclic crown ethers, benzo-15-crown-5.
The crown ether cocatalyst, also called macrocyclic ether, adopted by the invention is a macrocyclic compound containing a plurality of oxygen atoms, and the molecular structure of the macrocyclic ether cocatalyst has a hydrophobic external framework and a hydrophilic inner cavity. Crown ethers can form stable complexes with various metal salts, ammonium salts, organic cationic compounds, and the like. The coordination can be carried out in two ways: one way is that crown ether and various metal ions form a host-guest complex (crown ether compound is used as a host, and other groups are used as guests) with certain stability through dipole-ion action; the other way is that the host molecule and the guest molecule generate a complex through hydrogen bonds, and the effect is mostly generated between crown ether and ammonium ions and organic molecules.
In the present invention, the oxygen atom in the crown ether forms a hydrogen bond with the hydroxyl hydrogen in phenol. The molecular volume of the crown ether is large, and a large ortho steric hindrance effect can be generated, so that a Friedel-crafts alkylation reaction is difficult to occur at ortho positions, the selectivity of a para Friedel-crafts alkylation product is improved, and the yield of the raspberry ketone is improved.
In one or more embodiments, the organic acid catalyst comprises one or more of methanesulfonic acid, trichloroacetic acid, benzenesulfonic acid, picric acid, mellitic acid, trinitrobenzenesulfonic acid, preferably methanesulfonic acid, trichloroacetic acid, benzenesulfonic acid.
In one or more embodiments, the mass ratio of Ding Tongchun to crown ether is 1.01 to 1:5, preferably 1.05 to 1:2.
In one or more embodiments, the mass ratio of Ding Tongchun to organic acid is 3:1-10, preferably 6:1-8:1.
In one or more embodiments, the Ding Tongchun to phenol mass ratio is 1:2 to 1:9, preferably 1:4 to 1:7. The excessive phenol is added, so that the concentration of the phenol can be improved, the excessive phenol can also be used as a solvent to reduce the concentration of the butyl ketol, and the stability of the butyl ketol is facilitated.
Specifically, the preparation method of raspberry ketone comprises the following steps:
s1, preheating after mixing phenol, an organic acid catalyst and a crown ether cocatalyst;
s2, adding butanone alcohol into the preheated mixture obtained in the step S1, and continuously heating to react to obtain a product mixture;
and S3, separating the raspberry ketone from the product mixture in the step S2.
In one or more embodiments, to avoid oxidation of phenol, nitrogen or an inert gas is introduced into the reaction apparatus and the air therein is replaced before step S2.
In one or more embodiments, the Ding Tongchun is added dropwise, butanone alcohol is poor in stability, the concentration of Ding Tongchun in the reaction system is reduced by the dropwise addition, and the dropwise addition time is 0.5-5h, preferably 1-1.5h.
In one or more embodiments, the heating temperature of step S1 is 50 to 100 ℃, preferably 70 to 80 ℃; in order to finish the conversion of the butanone alcohol as soon as possible, the temperature is continuously increased after the dropwise addition of the butanone alcohol, and the reaction temperature in the step S2 is 80-115 ℃, preferably 90-105 ℃.
In one or more embodiments, the reaction time of step S2 is 1 to 5 hours, preferably 2 to 4 hours.
Specifically, the raspberry ketone is obtained by carrying out reduced pressure distillation and recrystallization on the product mixture in the step S2. Specifically, the process of reduced pressure distillation and recrystallization comprises the following steps: cooling the product mixture, distilling the product mixture under reduced pressure by a circulating water type multi-purpose vacuum pump, recovering phenol, and distilling the kettle liquid under reduced pressure by a rotary vane type vacuum pump to obtain crude raspberry ketone and kettle liquid. Recrystallizing the crude raspberry ketone to obtain a finished raspberry ketone product with the purity of 99.99%, wherein the organic solvent for recrystallization is one or more of toluene, methanol, ethanol, isopropanol, acetone, ethyl acetate, tetrahydrofuran, methyl tetrahydrofuran and 1,4-dioxane.
Specifically, when the boiling point of the organic acid and/or the crown ether used in the step S1 is lower than that of the raspberry ketone as the target product, the organic acid and/or the crown ether can be recycled and reused by distillation, when the boiling point of the organic acid and/or the crown ether used in the step S2 is higher than that of the raspberry ketone as the target product, the organic acid and/or the crown ether remain in the kettle liquid, the kettle liquid can be directly recycled, and the organic acid and the crown ether recycled and reused still maintain good catalyst activity.
Compared with the prior art, the invention has the following advantages:
(1) The macrocyclic crown ether cocatalyst is adopted in the reaction system for preparing raspberry ketone by reacting phenol with butanone alcohol, so that the probability of phenol ortho-alkylation is reduced, the generation of byproducts is reduced, the selectivity of target products is improved, and the reaction yield is improved.
(2) In the traditional process, sulfuric acid or hydrochloric acid with the mass being several times that of the butyl ketone alcohol is used as a catalyst, and after crown ether is used, the acid content of the organic acid can be reduced to 10-33% of the mass of the butyl ketone alcohol, so that the using amount of the organic acid is greatly reduced, the cost is saved, and the generation of three wastes is reduced.
(3) The organic acid catalyst and the crown ether in the reaction system can be used circularly and the good catalytic activity is kept.
Detailed Description
In order to describe the invention in further detail, the invention will now be described more fully with reference to specific examples.
Example 1
267g of phenol, 25g of 18-crown-6 and 8.3g of benzenesulfonic acid are added into a reaction device to form a mixture, nitrogen is introduced to replace air in the reaction device, 50g of Ding Tongchun is dropwise added into a mixture reaction system when the mixture is heated to 72 ℃, the dropwise addition time is 1.5 hours, and after the dropwise addition is finished, the temperature is raised to 100 ℃ and the temperature is kept for 3.5 hours. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure with a circulating water type multipurpose vacuum pump to obtain 8.3g benzenesulfonic acid and 205g phenol, respectively, and then distilled under reduced pressure with a rotary vane vacuum pump to obtain 25g 18-crown-6, 82.5g crude raspberry ketone, and 0.8g residue, respectively.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is toluene), 79.8g of qualified finished product (with the GC content of 99.99%) is finally obtained, and the molar yield of the target raspberry ketone is 85.63% (calculated by the consumption molar number of butanone alcohol) and 73.77% (calculated by the consumption molar number of phenol).
Example 2
Adding 270g of phenol, 75g of dibenzo-18-crown-6 and 6.5g of picric acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, starting to dropwise add 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 72 ℃, wherein the dropwise adding time is 1.5h, raising the temperature to 100 ℃ after the dropwise adding is finished, and keeping the temperature for 3h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure with a circulating water type multipurpose vacuum pump to recover 210g of phenol, and then distilled under reduced pressure with a rotary vane type vacuum pump to obtain 86.0g of crude raspberry ketone, and 83.5g of residue.
The crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate) to finally obtain 83.6g (the GC content is 99.99 percent) of qualified finished product, and the molar yield of the target raspberry ketone is 89.71 percent (calculated by the consumption molar number of butanone alcohol) and 79.85 percent (calculated by the consumption molar number of phenol).
Example 3
Adding 345g of phenol, 90g of dicyclohexyl-24-crown-8 and 6.5g of methanesulfonic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, starting to dropwise add 50g of Ding Tongchun into the mixture reaction system when the mixture is heated to 76 ℃, wherein the dropwise adding time is 1h, raising the temperature to 100 ℃ after the dropwise adding is finished, and keeping the temperature for 4h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure by a circulating water type multipurpose vacuum pump to recover 287g of phenol, and then distilled under reduced pressure by a rotary vane vacuum pump to obtain 6.5g of methanesulfonic acid, 90.3g of crude raspberry ketone, and 91.0g of residue, respectively.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethanol), qualified finished products of 84.90g (the GC content is 99.99 percent) are finally obtained, and the molar yield of the target raspberry ketone is 91.10 percent (calculated by the consumption mole number of butanone alcohol) and 83.89 percent (calculated by the consumption mole number of phenol).
Comparative example 1: without addition of crown ethers, using catalytic amounts of organic acids alone
Adding 345g of phenol and 6.5g of methanesulfonic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, starting to dropwise add 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 76 ℃, wherein the dropwise adding time is 1h, raising the temperature to 100 ℃ after the dropwise adding is finished, and keeping the temperature for 4h. And (3) gas phase detection of Ding Tongchun content not more than 0.5%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure by a circulating water type multipurpose vacuum pump to recover 311g of phenol, and then distilled under reduced pressure by a rotary vane type vacuum pump to obtain 6.5g of methanesulfonic acid, 32.50g of crude raspberry ketone, and 1.1g of the residue, respectively.
The crude raspberry ketone product is recrystallized for three times (the crystallization solvent is ethyl acetate), and qualified finished products of 30.22g (with the GC content of 99.99 percent) and 50.95 percent (with the consumption mol number of phenol) are finally obtained, wherein the mol yield of the target product raspberry ketone is 32.43 percent (with the consumption mol number of butanone alcohol).
Comparative example 2: the dosage of organic acid is increased without adding crown ether
Adding 345g of phenol 3 and 150g of methane sulfonic acid into a reaction device to form a mixture, introducing nitrogen to replace the air in the reaction device, starting to dropwise add 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 76 ℃, wherein the dropwise adding time is 1h, raising the temperature to 100 ℃ after the dropwise adding is finished, and keeping the temperature for 4h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture is subjected to reduced pressure distillation by a circulating water type multi-purpose vacuum pump to recover 280g of phenol, and then is subjected to reduced pressure distillation by a rotary vane type vacuum pump to respectively obtain 150g of methane sulfonic acid, 72.54g of crude raspberry ketone and 0.9g of kettle liquid.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate), 68.18g of qualified finished product (with the GC content of 99.99%) is finally obtained, and the molar yield of the target product raspberry ketone is 73.17% (calculated by the consumption molar number of butanone alcohol) and 60.12% (calculated by the consumption molar number of phenol).
Example 4
Adding 345g of phenol, 110g of dibenzo-30-crown-10 and 7.0g of trinitrobenzenesulfonic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, dropwise adding 50g of Ding Tongchun into the mixture reaction system when the mixture is heated to 72 ℃, wherein the dropwise adding time is 1h, raising the temperature to 90 ℃ after the dropwise adding is finished, and keeping the temperature for 4h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. And distilling the product mixture by a circulating water type multi-purpose vacuum pump under reduced pressure to recover 285g of phenol, and distilling by a rotary vane type vacuum pump under reduced pressure to obtain 88.6g of crude raspberry ketone and 118.2g of kettle liquid.
The crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate) to finally obtain 82.5g of qualified finished product (the GC content is 99.99 percent), and the molar yield of the target raspberry ketone is 88.53 percent (calculated by the consumption molar number of butanone alcohol) and 78.80 percent (calculated by the consumption molar number of phenol).
Example 5
Adding 345g of phenol, 95g of dibenzo-27-crown-9 and 8.0g of trichloroacetic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, dropwise adding 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 75 ℃, wherein the dropwise adding time is 1.5h, raising the temperature to 100 ℃ after the dropwise adding is finished, and keeping the temperature for 3h. Gas phase detection Ding Tongchun content less than or equal to 0.2%, ending the reaction, and cooling the product mixture. And carrying out reduced pressure distillation on the product mixture by using a circulating water type multi-purpose vacuum pump, respectively recovering 8.0g of trichloroacetic acid and 286g of phenol, and carrying out reduced pressure distillation by using a rotary vane type vacuum pump to obtain 89.80g of crude raspberry ketone and 96.0g of kettle liquid.
The crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate) to finally obtain a qualified finished product of 84.30g (with the GC content of 99.99 percent), and the molar yield of the target product raspberry ketone is 90.46 percent (calculated by the consumption molar number of butanone alcohol) and 81.89 percent (calculated by the consumption molar number of phenol).
Example 6
Adding 100g of phenol, 0.5g of 4-nitrobenzo-15-crown-5 and 16.7g of mellitic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, starting dropwise adding 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 50 ℃, wherein the dropwise adding time is 0.5h, raising the temperature to 80 ℃ after the dropwise adding is finished, and keeping the temperature for 5h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. And distilling the product mixture by a circulating water type multi-purpose vacuum pump under reduced pressure to recover 42g of phenol, and distilling by a rotary vane type vacuum pump under reduced pressure to obtain 89.42g of crude raspberry ketone and 18.3g of kettle liquid.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is methyl tetrahydrofuran), a qualified finished product of 81.80g (with the GC content of 99.99%) is finally obtained, and the molar yield of the target raspberry ketone is 87.78% (calculated by the consumption molar number of butanone alcohol) and 80.83% (calculated by the consumption molar number of phenol).
Example 7
Adding 200g of phenol, 2.5g of benzo-15-crown-5 and 8.3g of trinitrobenzenesulfonic acid into a reaction device to form a mixture, introducing nitrogen to replace air in the reaction device, starting to dropwise add 50g of Ding Tongchun into the mixture reaction system when the mixture is heated to 70 ℃, wherein the dropwise adding time is 1h, raising the temperature to 90 ℃ after the dropwise adding is finished, and keeping the temperature for 4h. Gas phase detection Ding Tongchun content less than or equal to 0.2%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure by a circulating water type multipurpose vacuum pump to recover 140g of phenol, and then distilled under reduced pressure by a rotary vane vacuum pump to obtain 92.43g of crude raspberry ketone and 11.8g of residue.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is 1,4-dioxane), a qualified finished product 85.30g (with the GC content of 99.99%) is finally obtained, and the molar yield of the raspberry ketone target product is 91.53% (calculated by the consumption molar number of butanone alcohol) and 81.48% (calculated by the consumption molar number of phenol).
Example 8
350g of phenol, 100g of dibenzo-21-crown-7 and 6.3g of methanesulfonic acid are added into a reaction device, nitrogen is introduced to replace air in the reaction device, 50g of Ding Tongchun is dropwise added into a mixture reaction system when the mixture is heated to 80 ℃, the dropwise adding time is 1.5h, the temperature is raised to 105 ℃ after the dropwise adding is finished, and the temperature is kept for 2h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture was distilled under reduced pressure by means of a circulating water type multipurpose vacuum pump to recover 292g of phenol, and then distilled under reduced pressure by means of a rotary-vane vacuum pump to obtain 6.3g of methanesulfonic acid, 91.2g of crude raspberry ketone, and 101.2g of the residue, respectively.
The crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethanol) to finally obtain a qualified finished product of 84.20g (the GC content is 99.99 percent), and the molar yield of the target raspberry ketone is 90.35 percent (calculated by the consumption molar number of butanone alcohol) and 83.20 percent (calculated by the consumption molar number of phenol).
Example 9
Adding 450g of phenol, 250g of dibenzo-24-crown-8 and 5.0g of methanesulfonic acid into a reaction device, introducing nitrogen to replace air in the reaction device, dropwise adding 50g of butanone alcohol into a mixture reaction system for 5 hours when the mixture is heated to 100 ℃, heating to 115 ℃ after dropwise adding, and keeping the temperature for 1 hour. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture is subjected to reduced pressure distillation by a circulating water type multi-purpose vacuum pump to recover 385g of phenol, and then is subjected to reduced pressure distillation by a rotary-vane vacuum pump to respectively obtain 5.0g of methane sulfonic acid, 88.30g of crude raspberry ketone and 251.1g of kettle liquid.
The crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate) to finally obtain a qualified finished product of 81.90g (the GC content is 99.99 percent), and the molar yield of the target raspberry ketone is 87.88 percent (calculated by the consumption molar number of butanone alcohol) and 72.21 percent (calculated by the consumption molar number of phenol).
Example 10
Adding 150g of phenol, 150g of oxadiazole macrocyclic crown ether and 10.0g of methanesulfonic acid into a reaction device, introducing nitrogen to replace air in the reaction device, dropwise adding 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 90 ℃, wherein the dropwise adding time is 3h, heating to 110 ℃ after the dropwise adding is finished, and keeping the temperature for 1h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. The product mixture is decompressed and distilled by a circulating water type multi-purpose vacuum pump to recover 87g of phenol, and then decompressed and distilled by a rotary vane type vacuum pump to respectively obtain 9.99g of methane sulfonic acid, 86.10g of crude raspberry ketone and 138.9g of kettle liquid, which are applied to the next batch.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate), qualified finished products of 80.20g (the GC content is 99.99 percent) are finally obtained, and the molar yield of the target raspberry ketone is 86.06 percent (calculated by the consumption mole number of butanone alcohol) and 72.96 percent (calculated by the consumption mole number of phenol).
Example 11
Adding 250g of phenol, 5.0g of oxadiazole macrocyclic crown ether and 7.1g of methanesulfonic acid into a reaction device, introducing nitrogen to replace air in the reaction device, dropwise adding 50g of Ding Tongchun into a mixture reaction system when the mixture is heated to 78 ℃, wherein the dropwise adding time is 1h, heating to 105 ℃ after the dropwise adding is finished, and keeping the temperature for 2h. And (3) gas phase detection of Ding Tongchun content not more than 0.2%, ending the reaction, and cooling the product mixture. And distilling the product mixture by a circulating water type multi-purpose vacuum pump under reduced pressure to recover 190g of phenol, and distilling by a rotary-vane vacuum pump under reduced pressure to respectively obtain 7.1g of methane sulfonic acid, 92.10g of crude raspberry ketone and 150.9g of kettle liquid, wherein the methane sulfonic acid, the crude raspberry ketone and the kettle liquid are applied to the next batch.
After the crude raspberry ketone is recrystallized for three times (the crystallization solvent is ethyl acetate), qualified finished products of 85.70g (the GC content is 99.99%) are finally obtained, and the molar yield of the target raspberry ketone is 91.96% (calculated by the consumption molar number of butanone alcohol) and 81.86% (calculated by the consumption molar number of phenol).
The residue and the recovered methanesulfonic acid in example 11 were subjected to a loop experiment, and the data are shown in table 1. The experimental procedure was as in example 11.
TABLE 1 catalyst application data
Finally, supplementary explanation: although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art may still modify the technical solutions described in the embodiments or make equivalents to some of the techniques. Any modification, replacement or the like which comes within the technical core and principle of the invention shall fall within the scope of the invention.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (8)
1. A preparation method of raspberry ketone is characterized in that under the action of an organic acid catalyst and a crown ether cocatalyst, phenol and butanone alcohol react to obtain raspberry ketone;
the crown ether cocatalyst is one or more of 18-crown-6, dibenzo-18-crown-6, 4-nitrobenzo-15-crown-5, bicyclohexano-24-crown-8, benzo-15-crown-5, dibenzo-21-crown-7, dibenzo-24-crown-8, dibenzo-27-crown-9, dibenzo-30-crown-10, oxadiazole macrocyclic crown ethers;
the organic acid catalyst comprises one or more of methane sulfonic acid, trichloroacetic acid, benzene sulfonic acid, picric acid, mellitic acid and trinitrobenzene sulfonic acid;
the mass ratio of Ding Tongchun to phenol is 1:2-1:9.
2. The process of making raspberry ketone of claim 1, wherein said crown ether promoter is one or more of bicyclohexano-24-crown-8, oxadiazole macrocyclic crown ethers, benzo-15-crown-5.
3. The method for preparing raspberry ketone of claim 1, wherein the mass ratio of Ding Tongchun to crown ether is 1.
4. The method for preparing raspberry ketone of claim 1, wherein the mass ratio of Ding Tongchun to organic acid is 3:1-10.
5. A process for the preparation of raspberry ketone of claims 1-4, comprising:
s1, preheating after mixing phenol, an organic acid catalyst and a crown ether cocatalyst;
s2, adding butanone alcohol into the preheated mixture obtained in the step S1, and continuously heating to react to obtain a product mixture;
and S3, separating the raspberry ketone from the product mixture in the step S2.
6. The method for preparing raspberry ketone of claim 5, wherein the Ding Tongchun is added dropwise for 0.5-5h.
7. The process for preparing raspberry ketone of claim 5, wherein the preheating temperature in step S1 is 50-100 ℃.
8. The method for preparing raspberry ketone of claim 5, wherein the temperature of step S2 is 80-115 ℃ and the reaction time is 1-5 hours.
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| JPH03109342A (en) * | 1989-09-22 | 1991-05-09 | Mitsubishi Petrochem Co Ltd | Production of 4,4'-dihydroxydiphenylmethane |
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| CN112225646A (en) * | 2020-09-16 | 2021-01-15 | 万华化学集团股份有限公司 | Preparation method of bisphenol TMC |
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| US5019656A (en) * | 1989-03-04 | 1991-05-28 | Mitsubishi Petrochemical Co., Ltd. | Process for preparing p-hydroxybenzyl alcohol |
| JPH03109342A (en) * | 1989-09-22 | 1991-05-09 | Mitsubishi Petrochem Co Ltd | Production of 4,4'-dihydroxydiphenylmethane |
| CN106916059A (en) * | 2015-12-25 | 2017-07-04 | 上虞新和成生物化工有限公司 | A kind of method that multi-sulfonic catalysis of functional ionic liquid prepares raspberry ketone |
| CN112225646A (en) * | 2020-09-16 | 2021-01-15 | 万华化学集团股份有限公司 | Preparation method of bisphenol TMC |
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