Rubusoside and a method for preparing the same

Abstract

The present disclosure relates to the technical field of organic synthesis, and particularly relates to raspberry ketone and a preparation method thereof. The preparation method of the raspberry ketone comprises the following steps: reacting 4-hydroxy-2-butanone and phenol under the condition of a solvent and a bimetallic catalyst to generate the raspberry ketone; the bimetallic catalyst comprises an alumina carrier and nickel oxide and copper oxide loaded on the alumina carrier. The present disclosure uses NiO-CuO / Al2O3 to catalyze the aldol condensation reaction of 4-hydroxy-2-butanone and phenol, and the conversion rate and selectivity of the raspberry ketone are high, and the product purity is also high.

Description

Technical Field

[0001] This disclosure relates to the field of organic synthesis technology, and in particular to raspberry ketones and their preparation methods. Background Technology

[0002] Raspberry ketone, chemically known as 4-(4-hydroxyphenyl)-2-butanone, is one of the main aroma components naturally found in red raspberries. As an important flavor compound and food additive, raspberry ketone is widely used in the food, cosmetics, and perfume industries due to its unique and sweet fruity aroma. Given its potential applications in the food, flavor, and health product industries, and considering the extremely low content of raspberry ketone in natural raspberry fruits and the high cost of direct extraction from plant materials, it is necessary to adopt artificial synthesis methods to achieve its industrial-scale production.

[0003] In the traditional route, phenol and 4-hydroxy-2-butanone undergo an aldol condensation reaction under the action of a catalyst to obtain raspberry ketone, typically using a large amount of water-soluble strong acids (such as sulfuric acid and hydrochloric acid) as catalysts. However, this process has significant drawbacks: the reaction generates large amounts of acidic wastewater and waste salts, resulting in high costs for waste treatment; the catalyst is difficult to recover and recycle, placing a heavy burden on the environment; at the same time, the strong acid system severely corrodes production equipment, posing safety hazards and hindering the green and sustainable industrial development of this route. Summary of the Invention

[0004] Based on this, the first aspect of this disclosure provides a method for preparing raspberry ketone, the technical solution of which is as follows: A method for preparing raspberry ketone includes the following steps: Under the conditions of solvent and bimetallic catalyst, 4-hydroxy-2-butanone and phenol are reacted to generate the raspberry ketone; The bimetallic catalyst comprises an alumina support and nickel oxide and copper oxide supported on the alumina support.

[0005] The reaction route of the above implementation method is as follows: .

[0006] The main mechanisms of action of NiO-CuO / Al2O3 mentioned above, without being limited to any particular theory, may include: (1) Both Lewis acid sites and weakly basic sites exist on the surface of NiO-CuO / Al2O3. The acid sites provided by the Al2O3 support are the key active centers; the introduction of NiO and CuO may adjust the density and strength of acid centers on the catalyst surface by forming Ni-Cu-Al composite oxides or generating oxygen vacancies.

[0007] (2) The 4-hydroxy-2-butanone molecule is first adsorbed on the acid center of NiO-CuO / Al2O3 and undergoes a dehydration reaction under heating conditions to generate active α,β-unsaturated ketones (such as 3-buten-2-one (methyl vinyl ketone)) or corresponding conjugated carbocations in situ.

[0008] (3) The generated α,β-unsaturated ketones or carbocations act as electrophiles, attacking the ortho or para positions of the hydroxyl group on the aromatic ring of phenol. Furthermore, since the hydroxyl group is a strongly activating group, the electrophilic substitution reaction mainly occurs at the para position.

[0009] (4) The intermediate rapidly loses a proton on the surface of NiO-CuO / Al2O3, and after intramolecular rearrangement, restores the aromatic structure of the benzene ring, completes electrophilic substitution, and generates raspberry ketone.

[0010] In some embodiments, the nickel oxide is loaded in the bimetallic catalyst at an amount of 0.5% to 5%.

[0011] In some embodiments, the nickel oxide is loaded in the bimetallic catalyst at an amount of 0.5% to 2%.

[0012] In some embodiments, the copper oxide is loaded in the bimetallic catalyst at an amount of 0.5% to 5%.

[0013] In some embodiments, the copper oxide is loaded at a rate of 3% to 4% in the bimetallic catalyst.

[0014] In some embodiments, the preparation method of the bimetallic catalyst includes the following steps: Mix nickel salt, copper salt, aluminum oxide and water, stir and let stand to obtain a mixture; The mixture is subjected to dehydration treatment to obtain a catalyst precursor; The catalyst precursor is calcined.

[0015] In some embodiments, the nickel salt includes nickel nitrate.

[0016] In some embodiments, the copper salt includes copper nitrate.

[0017] In some embodiments, the stirring temperature is 50°C to 70°C.

[0018] In some implementations, the settling time is 20h to 30h.

[0019] In some embodiments, the calcination temperature is 500°C to 600°C.

[0020] In some implementations, the roasting time is 2 to 4 hours.

[0021] In some embodiments, the mass ratio of the bimetallic catalyst to the 4-hydroxy-2-butanone is (0.01~1):1.

[0022] In some embodiments, the molar ratio of the 4-hydroxy-2-butanone to the phenol is 1:(2~5).

[0023] In some embodiments, the temperature at which 4-hydroxy-2-butanone and phenol react is 50°C to 100°C.

[0024] In some embodiments, the solvent is selected from methanol.

[0025] In some embodiments, after the reaction is complete, the following steps are also included: solid-liquid separation to collect the filtrate, and crystallization of the solid from the filtrate.

[0026] A second aspect of this disclosure provides a raspberry ketone prepared by the preparation method described above.

[0027] Compared with traditional solutions, this disclosure has the following advantages: The method for preparing raspberry ketone disclosed herein uses a bimetallic catalyst (NiO-CuO / Al2O3) to catalyze the aldol condensation reaction of 4-hydroxy-2-butanone and phenol. Compared to using a large amount of water-soluble strong acid as a catalyst, the cost of waste treatment is low. Furthermore, NiO-CuO / Al2O3 is a solid, making it easy to recover and recycle, resulting in minimal environmental pollution. It also avoids corrosion of production equipment, showing promising prospects for industrial application. Importantly, the use of NiO-CuO / Al2O3 catalysis leads to high conversion and selectivity of raspberry ketone, as well as high product purity. Detailed Implementation

[0028] The present disclosure will be further described in detail below with reference to specific embodiments. The present disclosure can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and complete understanding of the disclosure.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of this disclosure.

[0030] In the traditional route, phenol and 4-hydroxy-2-butanone undergo an aldol condensation reaction under the action of a catalyst to obtain raspberry ketone, typically using a large amount of water-soluble strong acids (such as sulfuric acid and hydrochloric acid) as catalysts. However, this process has significant drawbacks: the reaction generates large amounts of acidic wastewater and waste salts, resulting in high costs for waste treatment; the catalyst is difficult to recover and recycle, placing a heavy burden on the environment; at the same time, the strong acid system severely corrodes production equipment, posing safety hazards and hindering the green and sustainable industrial development of this route.

[0031] Based on this, the first aspect of this disclosure provides a method for preparing raspberry ketone. In one embodiment, the method for preparing raspberry ketone includes the following steps: Under the conditions of solvent and bimetallic catalyst, 4-hydroxy-2-butanone and phenol react to generate raspberry ketone; The bimetallic catalyst (NiO-CuO / Al2O3) includes an alumina (Al2O3) support and nickel oxide (NiO) and copper oxide (CuO) supported on the Al2O3 support.

[0032] The reaction route of the above implementation method is as follows: .

[0033] The main mechanisms of action of NiO-CuO / Al2O3 mentioned above, without being limited to any particular theory, may include: (1) Both Lewis acid sites and weakly basic sites exist on the surface of NiO-CuO / Al2O3. The acid sites provided by the Al2O3 support are the key active centers; the introduction of NiO and CuO may adjust the density and strength of acid centers on the catalyst surface by forming Ni-Cu-Al composite oxides or generating oxygen vacancies.

[0034] (2) The 4-hydroxy-2-butanone molecule is first adsorbed on the acid center of NiO-CuO / Al2O3 and undergoes a dehydration reaction under heating conditions to generate active α,β-unsaturated ketones (such as 3-buten-2-one (methyl vinyl ketone)) or corresponding conjugated carbocations in situ.

[0035] (3) The generated α,β-unsaturated ketones or carbocations act as electrophiles, attacking the ortho or para positions of the hydroxyl group on the aromatic ring of phenol. Furthermore, since the hydroxyl group is a strongly activating group, the electrophilic substitution reaction mainly occurs at the para position.

[0036] (4) The intermediate rapidly loses a proton on the surface of NiO-CuO / Al2O3, and after intramolecular rearrangement, restores the aromatic structure of the benzene ring, completes electrophilic substitution, and generates raspberry ketone.

[0037] The method for preparing raspberry ketone provided in the above embodiments involves the aldol condensation reaction of 4-hydroxy-2-butanone and phenol catalyzed by NiO-CuO / Al2O3. Compared to using a large amount of water-soluble strong acid as a catalyst, the cost of waste treatment is low. Furthermore, NiO-CuO / Al2O3 is a solid, making it easy to recover and recycle, resulting in minimal environmental pollution. It also avoids corrosion of production equipment, showing good prospects for industrial application. Importantly, the use of NiO-CuO / Al2O3 catalysis results in high conversion rate and selectivity of raspberry ketone, as well as high product purity.

[0038] In addition to the aforementioned use of water-soluble strong acids as catalysts, there are reports of using acidic supported ionic liquids as catalysts for the alkylation reaction of phenol and butanone to prepare raspberry ketones. However, ionic liquids are generally expensive, and problems such as dissolution of active components and insufficient catalytic stability during use limit the large-scale industrial application of this method. There are also reports of using D218 type resin as a catalyst, which is a sulfonic acid-based cation exchange resin, to prepare raspberry ketones in a reactor and fluidized bed external reflux device. Sulfonic acid-based cation exchange resins are easy to separate and recover from the reaction system. However, sulfonic acid-based cation exchange resins still have shortcomings in actual reactions: as the reaction proceeds, hydrogen ions are gradually lost, catalytic activity continuously decreases, and catalyst life is short. Furthermore, in its original form, sulfonic acid-based cation exchange resins have limited acid strength, poor thermal stability, poor hydrophobic properties, and the pores are prone to blockage during the reaction, affecting mass transfer and catalytic efficiency. Other reports describe a continuous process using a fixed-bed reactor, where phenol, butanone, and solvent are mixed and pumped into the fixed bed. An alkylation reaction occurs under the action of an alkylating resin, allowing for the continuous production of raspberry ketones. However, this method uses a large amount of phenol, requiring subsequent distillation and crystallization to obtain the product. This results in high energy consumption and a product yield of only about 80%, leading to low economic efficiency and hindering industrial production.

[0039] Unlike the methods reported above, this embodiment provides a novel catalyst for the synthesis of raspberry ketones, using NiO-CuO / Al2O3 to catalyze the alkylation reaction of 4-hydroxy-2-butanone and phenol. Compared to ionic liquids, this method is less expensive. Furthermore, the operation of this embodiment is simple, achieving a reaction conversion rate of 99.6%, a selectivity of 98.7%, and a purity of 99.5%.

[0040] Optionally, the loading of NiO in NiO-CuO / Al2O3 is 0.5% to 5%. For example, the loading of NiO in NiO-CuO / Al2O3 is 0.5%, 1%, 2%, 3%, 4%, or 5%. Preferably, the loading of NiO in NiO-CuO / Al2O3 is 0.5% to 2%.

[0041] Optionally, the loading of CuO in NiO-CuO / Al2O3 is 0.5% to 5%. For example, the loading of CuO in NiO-CuO / Al2O3 is 0.5%, 1%, 2%, 3%, 4%, or 5%. Preferably, the loading of CuO in NiO-CuO / Al2O3 is 3% to 4%.

[0042] The loading of NiO and CuO in NiO-CuO / Al2O3 affects the catalytic effect. Experiments have shown that when the loading of NiO in NiO-CuO / Al2O3 is 0.5%~2% and the loading of CuO in NiO-CuO / Al2O3 is 3%~4%, the catalytic effect is good, the conversion rate of raspberry ketone is high, the selectivity is good, and the purity is good.

[0043] Optionally, the preparation method of NiO-CuO / Al2O3 includes the following steps: Mix nickel salt (Ni salt), copper salt (Cu salt), Al2O3 and water, stir and let stand to obtain a mixed solution; The mixture was subjected to dehydration treatment to obtain the catalyst precursor; Calcined catalyst precursor.

[0044] Optionally, the Ni salt is a water-soluble Ni salt. For example, the Ni salt includes nickel nitrate (Ni(NO3)2), such as Ni(NO3)2·6H2O. Optionally, the Cu salt is a water-soluble Cu salt. For example, the Cu salt is selected from copper nitrate (Cu(NO3)2), such as Cu(NO3)2·3H2O.

[0045] Al2O3 can be Al2O3 powder, which serves as a carrier in NiO-CuO / Al2O3.

[0046] After mixing Ni salt, Cu salt, Al₂O₃, and water, the mixture is stirred. Optionally, the stirring temperature is 50℃~70℃. For example, the stirring temperature is 50℃, 60℃, or 70℃. After stirring, the mixture is allowed to stand for 20h~30h. For example, it is allowed to stand for 20h, 25h, or 30h. During this process, the Ni salt and Cu salt are fully loaded on the Al₂O₃, resulting in a mixed solution.

[0047] The dehydration treatment of the mixture includes the following steps: vacuum evaporation and drying of the mixture. The vacuum evaporation temperature is 88℃~95℃. For example, the vacuum evaporation temperatures are 88℃, 90℃, and 95℃. The drying temperature is 120℃~140℃. For example, the drying temperatures are 120℃, 130℃, and 140℃.

[0048] After calcination, the Ni salt is converted to NiO in situ, and the Cu salt is converted to CuO in situ. Optionally, the calcination temperature is 500℃~600℃. For example, the calcination temperature is 500℃, 550℃, or 600℃. Optionally, the calcination time is 2h~4h. For example, the calcination time is 2h, 3h, or 4h.

[0049] The aforementioned NiO-CuO / Al2O3, with NiO and CuO supported on an Al2O3 support, serves as a catalyst for the aldol condensation reaction of 4-hydroxy-2-butanone and phenol. Optionally, the mass ratio of NiO-CuO / Al2O3 to 4-hydroxy-2-butanone is (0.01~1):1. For example, the mass ratios of NiO-CuO / Al2O3 to 4-hydroxy-2-butanone are 0.01:1, 0.05:1, 0.1:1, 0.5:1, and 1:1.

[0050] Optionally, the molar ratio of 4-hydroxy-2-butanone to phenol is 1:(2~5). For example, the molar ratio of 4-hydroxy-2-butanone to phenol is 1:2, 1:3, 1:4, or 1:5. Preferably, the molar ratio of 4-hydroxy-2-butanone to phenol is 1:(2~3).

[0051] Optionally, the solvent is selected from methanol. NiO-CuO / Al2O3 is insoluble in methanol, and can be subsequently recovered through solid-liquid separation.

[0052] Optionally, the reaction temperature between 4-hydroxy-2-butanone and phenol is 50°C to 100°C. For example, the reaction temperatures are 50°C, 60°C, 70°C, 80°C, 90°C, and 100°C. Preferably, the reaction temperature is 70°C to 80°C. These reaction conditions are relatively mild and simple to operate.

[0053] Optionally, after the reaction is complete, the method further includes the following steps: solid-liquid separation to collect the filtrate, and crystallizing the solid from the filtrate. Optionally, crystallizing the solid from the filtrate includes the following steps: adding a crystallization solvent to the filtrate and cooling to crystallize. Optionally, the mass ratio of the crystallization solvent to the solvent is (0.1~1):1. For example, the mass ratio of the crystallization solvent to the solvent is 0.1:1, 0.4:1, 0.6:1, or 1:1. The crystallization solvent is selected from water.

[0054] The above preparation method utilizes NiO-CuO / Al2O3 catalysis to induce an aldol condensation reaction between 4-hydroxy-2-butanone and phenol. The reaction conditions are mild and the operation is simple, making it suitable for industrial production. Furthermore, it yields high raspberry ketone conversion and selectivity, as well as high product purity.

[0055] A second aspect of this disclosure provides a raspberry ketone prepared by the preparation method described above.

[0056] The following description is further illustrated with specific embodiments and comparative examples. Unless otherwise specified, the raw materials involved in the following specific embodiments and comparative examples are all commercially available; the instruments used are all commercially available unless otherwise specified; and the processes involved are conventionally selected by those skilled in the art unless otherwise specified.

[0057] Gas chromatography analysis conditions: Online analysis was performed using an Agilent HP-5 polysiloxane column with a two-stage temperature program: initial temperature 70℃, held for 4.5 minutes, then increased to 200℃ at a rate of 30℃ / min; held for 5 minutes. High-purity N2 was used as the carrier gas with a split ratio of 30:1. The injection temperature was 250℃, and the detector was an FID detector at 250℃. The injection volume was 0.3 μL.

[0058] Example 1 This embodiment provides a raspberry ketone and its preparation method, the steps of which are as follows: Step 1: Preparation of 2% NiO-4% CuO / Al2O3 catalyst: Weigh 7.80g of Ni(NO3)2·6H2O, 12.15g of Cu(NO3)2·3H2O, and 100g of Al2O3 powder, add 2L of deionized water to prepare a mixed solution, stir in a constant temperature water bath at 60℃ for 3h until homogeneous, let stand in air for 26h, place in a rotary evaporator and vacuum evaporate at 90℃ until the water evaporates to dryness, dry in an electric heating blast drying oven at 130℃ for 1h to obtain the catalyst precursor.

[0059] The catalyst precursor was calcined in a muffle furnace at 580℃ for 2 hours to decompose nitrates and generate a mixed oxide active component of NiO and CuO, thus preparing NiO-CuO / Al2O3. Spectroscopic analysis showed that the loading of NiO was 2% and the loading of CuO was 4%.

[0060] Step 2, Preparation of raspberry ketone: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (94.1 g, 1 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected. NiO-CuO / Al2O3 (4.4 g, with a mass ratio of 0.1:1 to 4-hydroxy-2-butanone) was added. The mixture was magnetically stirred at 800 rpm and heated to 80 °C. The reaction was continued until the 4-hydroxy-2-butanone content was <0.5% (monitored by gas chromatography). The mixture was cooled to room temperature, filtered, and the filter residue was washed with 10 g of methanol to recover the catalyst. The filtrate was collected, and a sample was taken for gas chromatography analysis. The reaction conversion rate was 99.6%, and the selectivity was 98.7%.

[0061] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 76.5g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 99.5%, with a separation yield of 94.3%.

[0062] The product, raspberry ketone, was analyzed by NMR using a Bruker-400MHz resonator with deuterated chloroform as the solvent. The reference value for the solvent in the 1H NMR spectrum was δ = 7.26 ppm (CDCl3). The test results are as follows: 1H NMR (500 MHz, CDCl3) 7.00 (d, J = 8.5 Hz, 3H), 6.76 (d, J = 8.5Hz, 2H), 2.81 (t, J = 7.0 Hz, 2H), 2.73 (t, J = 7.0 Hz, 2H), 2.13 (s, 3H). 13C NMR (125 MHz, CDCl3) δ = 210.1, 154.3, 132.3, 129.3, 115.5, 45.5,30.1, 29.0. Example 2 This embodiment provides a raspberry ketone and its preparation method, the steps of which are as follows: Step 1: Preparation of 0.5% NiO-3% CuO / Al2O3 catalyst: Weigh 1.95 g of Ni(NO3)2·6H2O, 9.11 g of Cu(NO3)2·3H2O, and 100 g of Al2O3 powder, and add them to 2 L of deionized water to prepare a mixed solution. Stir the solution in a constant temperature water bath at 60 °C for 3 h until homogeneous. Let it stand in air for 26 h, then place it in a rotary evaporator and evaporate it under vacuum at 90 °C until the water content is reduced to dryness. Finally, dry it in an electric heating drying oven at 130 °C for 1 h to obtain the catalyst precursor.

[0063] The catalyst precursor was calcined in a muffle furnace at 580℃ for 2 hours to decompose nitrates and generate a mixed oxide active component of NiO and CuO, thus preparing NiO-CuO / Al2O3. Spectroscopic analysis showed that the loading of NiO was 0.5% and the loading of CuO was 3%.

[0064] Step 2, Preparation of raspberry ketone: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (94.1 g, 1 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected. NiO-CuO / Al2O3 (4.4 g, with a mass ratio of 0.1:1 to 4-hydroxy-2-butanone) was added. The mixture was magnetically stirred at 800 rpm and heated to 80 °C. The reaction was continued until the 4-hydroxy-2-butanone content was <1% (monitored by gas chromatography). The mixture was cooled to room temperature, filtered, and the filter residue was washed with 10 g of methanol to recover the catalyst. The filtrate was collected, and a sample was taken for gas chromatography analysis. The reaction conversion rate was 99.1%, and the selectivity was 94.2%.

[0065] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 71.4g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 99.2% with a separation yield of 92.4%.

[0066] Example 3 This embodiment provides a raspberry ketone and its preparation method, the steps of which are as follows: Step 1: Preparation of 4% NiO-5% CuO / Al2O3 catalyst: Weigh 15.58 g of Ni(NO3)2·6H2O, 15.19 g of Cu(NO3)2·3H2O, and 100 g of Al2O3 powder, and add them to 2 L of deionized water to prepare a mixed solution. Stir the solution in a constant temperature water bath at 60 °C for 3 h until homogeneous. Let it stand in air for 26 h, then place it in a rotary evaporator and evaporate it under vacuum at 90 °C until the water content is reduced to dryness. Finally, dry it in an electric heating drying oven at 130 °C for 1 h to obtain the catalyst precursor.

[0067] The catalyst precursor was calcined in a muffle furnace at 580℃ for 2 hours to decompose nitrates and generate a mixed oxide active component of NiO and CuO, thus preparing NiO-CuO / Al2O3. Spectroscopic analysis showed that the loading of NiO was 4% and the loading of CuO was 5%.

[0068] Step 2 is the same as in Example 1, with a reaction conversion rate of 98.2% and a selectivity of 90.5%.

[0069] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 66.0g of white crystalline raspberry ketone. Take a sample for gas chromatography detection, and the purity is 99.0%, with a separation yield of 89.5%.

[0070] Example 4 This embodiment provides a raspberry ketone and its preparation method, which is basically the same as that in Example 1, the main difference being that the mass ratio of NiO-CuO / Al2O3 to 4-hydroxy-2-butanone is 1:0.5. The steps are as follows: Step 1 is the same as in Example 1.

[0071] Step 2, Preparation of raspberry ketone: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (94.1 g, 1 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected. 22 g of the above-mentioned NiO-CuO / Al2O3 (mass ratio of 0.5:1 to 4-hydroxy-2-butanone) was added. The mixture was magnetically stirred at 800 rpm and heated to 80 °C. The reaction was continued until the 4-hydroxy-2-butanone content was <0.5% (monitored by gas chromatography). The mixture was cooled to room temperature, filtered, and the filter residue was washed with 10 g of methanol to recover the catalyst. The filtrate was collected, and a sample was taken for gas chromatography analysis. The reaction conversion rate was 99.2%, and the selectivity was 97.8%.

[0072] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 74.6g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 99.4%, with a separation yield of 93.2%.

[0073] Example 5 This embodiment provides a raspberry ketone and its preparation method, which is basically the same as that in Example 1, the main difference being that the reaction temperature is 50℃. The steps are as follows: Step 1 is the same as in Example 1.

[0074] Step 2, Preparation of raspberry ketone: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (94.1 g, 1 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected. NiO-CuO / Al2O3 (4.4 g, with a mass ratio of 0.1:1 to 4-hydroxy-2-butanone) was added. The mixture was magnetically stirred at 800 rpm and heated to 50 °C. The reaction was continued until the 4-hydroxy-2-butanone content was <5% (monitored by gas chromatography). The mixture was cooled to room temperature, filtered, and the filter residue was washed with 10 g of methanol to recover the catalyst. The filtrate was collected, and a sample was taken for gas chromatography analysis. The reaction conversion rate was 95.3%, and the selectivity was 97.4%.

[0075] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 71.6g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 97.2%, with a separation yield of 91.4%.

[0076] Example 6 This embodiment provides a raspberry ketone and its preparation method, which is basically the same as that in Example 1, the main difference being that the molar ratio of 4-hydroxy-2-butanone to phenol is 1:4. The steps are as follows: Step 1 is the same as in Example 1.

[0077] Step 2, Preparation of raspberry ketone: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (188.2 g, 2 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected. NiO-CuO / Al2O3 (4.4 g, with a mass ratio of 0.1:1 to 4-hydroxy-2-butanone) was added. The mixture was magnetically stirred at 800 rpm and heated to 80 °C. The reaction was continued until the 4-hydroxy-2-butanone content was <0.5% (monitored by gas chromatography). The mixture was cooled to room temperature, filtered, and the filter residue was washed with 10 g of methanol to recover the catalyst. The filtrate was collected, and a sample was taken for gas chromatography analysis. The reaction conversion rate was 99.4%, and the selectivity was 98.4%.

[0078] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 76.1g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 97.2%, with a separation yield of 92.1%.

[0079] Comparative Example 1 This comparative example provides a raspberry ketone and its preparation method, which is basically the same as that in Example 1, the main difference being that no catalyst was added. The steps are as follows: 4-Hydroxy-2-butanone (44.0 g, 0.5 mol), phenol (94.1 g, 1 mol), and 100 g of methanol were added to a 500 mL three-necked flask. A short-path distillation head and a condenser were connected, and the mixture was magnetically stirred at 800 rpm and heated to 80 °C. Gas chromatography analysis showed no formation of raspberry ketone.

[0080] Comparative Example 2 This comparative example provides a raspberry ketone and its preparation method, which is basically the same as that in Example 1, the main difference being that the catalyst is 2% ZnO-4% CuO / Al2O3. The steps are as follows: Step 1: Preparation of 2%ZnO-4%CuO / Al2O3 catalyst Weigh 7.31 g of Zn(NO3)2·6H2O, 12.15 g of Cu(NO3)2·3H2O, and 100 g of Al2O3 powder, and add them to 2 L of deionized water to prepare a mixed solution. Stir the solution in a constant temperature water bath at 60°C for 3 hours until homogeneous. Let it stand in air for 26 hours, then place it in a rotary evaporator and evaporate it under vacuum at 90°C until the water content is reduced to dryness. Finally, dry it in an electric heating oven at 130°C for 1 hour to obtain the catalyst precursor.

[0081] The catalyst precursor was calcined in a muffle furnace at 580℃ for 2 hours to decompose nitrates and generate a mixed oxide active component of ZnO and CuO, thus preparing ZnO-CuO / Al2O3. Spectroscopic analysis showed that the loading of ZnO was 2% and the loading of CuO was 4%.

[0082] Step 2, same as in Example 1, with a reaction conversion rate of 24.2% and a selectivity of 74.2%.

[0083] Add 44g of pure water to the filtrate, cool to 0℃, and crystallize to obtain 9.5g of white raspberry ketone crystals. Take a sample for gas chromatography detection, and the purity is 84.2%, with a separation yield of 54.4%.

[0084] Based on the above embodiments and comparative examples, it can be seen that: Compared to Comparative Example 1, the NiO-CuO / Al2O3 in each embodiment can catalyze the alkylation reaction of 4-hydroxy-2-butanone and phenol with higher conversion and selectivity. After the reaction, NiO-CuO / Al2O3 can be recovered by solid-liquid separation. The filtrate can be crystallized to obtain a high-purity product with a high separation yield. In Example 1, 2% NiO-4% CuO / Al2O3 was used as a bimetallic catalyst. Under optimized conditions of 80°C and a mass ratio of NiO-CuO / Al2O3 to 4-hydroxy-2-butanone of 0.1:1, the catalytic condensation reaction performance was excellent, with a conversion rate of 99.6%, a selectivity of 98.7%, a product purity of 99.5%, and a separation yield of 94.3%.

[0085] Combining Examples 1, 2, and 3, the loading amounts of NiO and CuO in NiO-CuO / Al2O3 affect the catalytic effect. In Examples 1 and 2, the loading amounts of NiO in NiO-CuO / Al2O3 were 0.5%–2%, and the loading amounts of CuO were 3%–4%. The reaction conversion rates of 4-hydroxy-2-butanone and phenol were 99.1%–99.6%, and the selectivity was 94.2%–98.7%. After crystallization, the separation yield was 92.4%–94.3%. Compared to Example 3, where the loading amounts of NiO in NiO-CuO / Al2O3 were 4% and the loading amounts of CuO were 5%, the reaction conversion rate, selectivity, and separation yield were all higher. This indicates that there is an effective window for the loading amounts of NiO and CuO, and more is not necessarily better.

[0086] Combining Examples 1 and 4, Example 4, using less NiO-CuO / Al2O3, slightly affected the reaction selectivity. Combining Examples 1 and 5, a decrease in reaction temperature led to a decrease in conversion, indicating that the reaction requires a certain activation energy. Combining Examples 1 and 6, using more phenol resulted in a similar catalytic effect to Example 1, indicating that excess phenol has a limited promoting effect on the reaction.

[0087] Combining Example 1 and Comparative Example 1, it can be seen that the combination of NiO and CuO is the key to the efficient catalysis of the reaction between 4-hydroxy-2-butanone and phenol. The combination of ZnO and CuO will cause a significant decrease in conversion and selectivity, proving that ZnO cannot replace NiO in the catalytic reaction between 4-hydroxy-2-butanone and phenol.

[0088] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0089] The embodiments described above are merely examples of several implementation methods of this disclosure, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this disclosure, and these all fall within the protection scope of this disclosure.

Claims

1. A method for preparing raspberry ketone, characterized in that, Includes the following steps: Under the conditions of solvent and bimetallic catalyst, 4-hydroxy-2-butanone and phenol are reacted to generate the raspberry ketone; The bimetallic catalyst comprises an alumina support and nickel oxide and copper oxide supported on the alumina support; The nickel oxide is loaded at a rate of 0.5% to 5% in the bimetallic catalyst; The copper oxide loading in the bimetallic catalyst is 0.5% to 5%; The preparation method of the bimetallic catalyst includes the following steps: Mix nickel salt, copper salt, aluminum oxide and water, stir and let stand to obtain a mixture; The mixture is subjected to dehydration treatment to obtain a catalyst precursor; The catalyst precursor is calcined.

2. The method for preparing raspberry ketone according to claim 1, characterized in that, The nickel oxide is loaded at a rate of 0.5% to 2% in the bimetallic catalyst.

3. The method for preparing raspberry ketone according to claim 1, characterized in that, The copper oxide loading in the bimetallic catalyst is 3% to 4%.

4. The method for preparing raspberry ketone according to claim 1, characterized in that, Includes at least one of the following features: (1) The nickel salt includes nickel nitrate; (2) The copper salts include copper nitrate.

5. The method for preparing raspberry ketone according to claim 1, characterized in that, Includes at least one of the following features: (1) The stirring temperature is 50℃~70℃; (2) The settling time is 20h~30h; (3) The roasting temperature is 500℃~600℃; (4) The roasting time is 2h~4h.

6. The method for preparing raspberry ketone according to claim 1, characterized in that, The mass ratio of the bimetallic catalyst to the 4-hydroxy-2-butanone is (0.01~1):

1.

7. The method for preparing raspberry ketone according to any one of claims 1 to 6, characterized in that, The molar ratio of 4-hydroxy-2-butanone to phenol is 1:(2~5).

8. The method for preparing raspberry ketone according to any one of claims 1 to 6, characterized in that, The reaction temperature between 4-hydroxy-2-butanone and phenol is 50℃~100℃.

9. The method for preparing raspberry ketone according to any one of claims 1 to 6, characterized in that, The solvent is selected from methanol.

10. The method for preparing raspberry ketone according to any one of claims 1 to 6, characterized in that, After the reaction is complete, the following steps are also included: solid-liquid separation to collect the filtrate, and crystallization of the solid from the filtrate.