Synthesis method of raspberry ketone and catalyst thereof

Abstract

The application belongs to the field of organic synthesis, and discloses a raspberry ketone synthesis method and a catalyst thereof, which comprises the following steps: carrying out a Friedel-Crafts alkylation reaction on butanone alcohol, phenol and a solvent under the catalysis of a composite catalyst to obtain raspberry ketone; the composite catalyst comprises an active component, a carrier and an additive; the active component is a transition metal salt; the carrier is a molecular sieve; and the additive is a crown ether. The application replaces an organic acid catalyst with a new composite catalyst, reduces the use of the additive crown ether, has high reaction selectivity and yield, reduces the feeding amount of phenol, saves raw material recovery energy consumption, and is beneficial to the industrialized mass production of raspberry ketone.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing raspberry ketones and its catalyst. Background Technology

[0002] Raspberry ketone, chemically known as 4-p-hydroxyphenyl-2-butanone, is the main aroma component of raspberry fruit, possessing a characteristic sweet fruity aroma and flavor. Raspberry ketone is an internationally recognized safe and widely used synthetic flavoring agent, possessing an elegant fruity aroma and enhancing sweetness. The latest version of my country's Food Additives Hygiene Standard (GB2760-2014) stipulates that raspberry ketone is a permitted edible flavoring agent (FEMA code: 2588). Raspberry ketone is used to formulate flavorings of raspberry, grape, pineapple, peach, plum, strawberry, raspberry, jasmine, gardenia, tuberose, etc., and can retain aroma for a long time. It is widely used as a modifier or fixative in daily fragrances, food flavorings, cosmetic flavorings, and tobacco flavorings. Raspberry ketone has certain whitening and anti-inflammatory effects and is widely used in cosmetic formulations. Raspberry ketone acetate is used in agriculture as a highly effective insect attractant (fly attractant). Furthermore, raspberry ketones possess α-glucosidase inhibitory activity and PPAR-α agonist activity, demonstrating their promising application prospects in the treatment of metabolic diseases. Therefore, raspberry ketones are a high-value-added fine chemical with significant development potential.

[0003] In recent years, the synthesis of raspberry ketones has been mainly divided into natural synthesis and chemical synthesis. At the same time, with the application of biosynthesis technology, researchers at home and abroad have synthesized raspberry ketones from the perspective of biosynthesis. At present, the main chemical synthesis routes of raspberry ketones are as follows: (1) p-hydroxybenzaldehyde and acetone are used as raw materials. In an alkaline system, such as NaOH, KOH and other alkaline liquid phase systems, Claisen-Schmidt condensation is carried out, and then catalytic hydrogenation is performed to synthesize raspberry ketones. This method can obtain a high raspberry yield, but the amount of alkaline waste liquid is large. (2) p-chlorophenol and 3-hydroxybutene are used to catalyze the synthesis of raspberry ketones. This method requires the use of precious metal catalysts, which makes the reaction cost high. (3) The synthesis of raspberry ketones from phenol and butanone alcohol is the most economical route. It has the advantages of readily available raw materials, low cost, simple equipment and convenient operation. Usually, catalysts such as H2SO4 and AlCl3 are used to catalyze this reaction. However, there are many problems such as equipment corrosion, environmental pollution, many side reactions and complicated post-treatment.

[0004] Patent CN113214059B discloses the reaction of phenol and butanone alcohol to obtain raspberry ketone under the action of an organic acid catalyst and a crown ether co-catalyst. Although this method achieves a high yield of raspberry ketone and significantly reduces the amount of acid catalyst used, the amount of crown ether used exceeds 10% of the mass of the substrate phenol, which is a relatively large amount. Furthermore, the excessive amount of phenol and the resulting wasteful recovery of raw materials lead to energy consumption. Therefore, there is room for improvement in this process. Thus, further development and improvement of a green and efficient new method for the synthesis of raspberry ketone have significant practical application value. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method and catalyst for the synthesis of raspberry ketone from phenol and butanone. This method solves numerous problems in the raspberry ketone preparation process, such as equipment corrosion, environmental pollution, numerous side reactions, and complex post-processing. The composite catalyst provided by this invention replaces organic acid catalysts, reduces the use of crown ether additives, and exhibits high reaction selectivity and yield. It also reduces the amount of phenol required, saves energy consumption for raw material recovery, and is beneficial for the large-scale industrial production of raspberry ketone.

[0006] The first aspect of this invention provides a method for preparing raspberry ketone: butanone alcohol and phenol undergo a Friedel-Crafts alkylation reaction under the catalysis of a composite catalyst to obtain raspberry ketone;

[0007] The composite catalyst includes an active component, a support, and an additive;

[0008] The active component is a transition metal salt;

[0009] The carrier is a molecular sieve;

[0010] The adjuvant is a crown ether.

[0011]

[0012] The mass ratio of phenol to butanone is 1~3:1, preferably 1.5~1.8:1.

[0013] The Friedel-Crafts alkylation reaction is carried out with or without a solvent; if a solvent is available, non-toxic and harmless solvents such as ethanol and water are preferred.

[0014] The mass ratio of butanone alcohol to solvent is 1:1~3, preferably 1:1.5~2.0.

[0015] The Friedel-Crafts alkylation reaction is carried out at a temperature of 60°C to 120°C, preferably 80°C to 100°C.

[0016] The active components are selected from chlorides, nitrates, sulfates and their aqueous compounds containing iron, zinc, copper and manganese.

[0017] The carrier is selected from one or more of Hβ, H-ZSM-5, HY, β / ZSM-5, SAPO-11, 5A molecular sieve, and MCM-41.

[0018] The adjuvant is selected from one or more of dibenzo-18-crown-6, dicyclohexano-24-crown-8, 18-crown-6, dibenzo-30-crown-10, benzo-15-crown-5, and dibenzo-27-crown-9.

[0019] The mass ratio of the metal in the active component (calculated as the metal) to the carrier is 0.03~0.09:1, preferably 0.05~0.07:1.

[0020] The mass ratio of the active component (in terms of the amount of salt) to the adjuvant is 1:1.0~8.0, preferably 1:4.0~6.0.

[0021] Preferably, the Friedel-Crafts alkylation reaction is carried out in a fixed-bed reactor, the composite catalyst is supported in the fixed-bed reactor, and the butanone alcohol, phenol and solvent are mixed and then introduced into the fixed-bed reactor.

[0022] The feeding rate is 0.2g~0.8g / min; preferably 0.4~0.6g / min.

[0023] Preferably, the composite catalyst is prepared by the following method:

[0024] (1) Add a transition metal salt to deionized water, dissolve it, and obtain a mixture;

[0025] (2) Add the carrier to the above mixture and stir to load it;

[0026] (3) Add the additive to the above mixture for further modification, and filter to obtain the catalyst precursor;

[0027] (4) The obtained catalyst precursor is processed to obtain the catalyst for later use.

[0028] In step (2), the load temperature is 20℃~60℃; the load time is 2 hours~6 hours.

[0029] In step (3), the modification temperature is 60℃~100℃; the modification time is 2 hours~6 hours.

[0030] In step (4), the treatment is to dry at a constant temperature of 80°C until constant weight.

[0031] A second aspect of the present invention provides a composite catalyst for the preparation of raspberry ketones by Friedel-Crafts alkylation reaction, the composite catalyst comprising an active component, a support, and an auxiliary agent;

[0032] The active component is a transition metal salt;

[0033] The carrier is a molecular sieve;

[0034] The adjuvant is a crown ether;

[0035] It was prepared using the following method:

[0036] (1) Add a transition metal salt to deionized water, dissolve it, and obtain a mixture;

[0037] (2) Add the carrier to the above mixture and stir to load it;

[0038] (3) Add the additive to the above mixture for further modification, and filter to obtain the catalyst precursor;

[0039] (4) The obtained catalyst precursor is processed to obtain the composite catalyst.

[0040] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0041] This invention provides a method for preparing raspberry ketones, using a composite catalyst instead of traditional organic acid catalysts. This composite catalyst can be reused multiple times, solving the problem of large amounts of waste, effectively improving reaction yield, and reducing production costs. Furthermore, the use of a fixed-bed reactor enables continuous production, simplifies the production process, improves production efficiency, and facilitates the large-scale industrial production of raspberry ketones. Attached Figure Description

[0042] Figure 1 The gas phase spectrum of the reaction liquid in Example 1 of catalyst application;

[0043] Figure 2 The gas phase spectrum of the pure product obtained after separation in Example 1 of catalyst application;

[0044] Figure 3 The mass spectrum of the product in Catalyst Application Example 1 is compared with that of a standard library. The upper image is the mass spectrum of the product, and the lower image is the mass spectrum of the standard library. Detailed Implementation

[0045] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0046] Gas phase detection conditions:

[0047] Chromatographic column: SE-30, 30m*0.25mm*0.25µm. Detection instrument: Fuli 9790plus.

[0048] Temperature conditions:

[0049] (1) Reaction conditions: Column oven 100℃, hold for 4 min; increase to 220℃ at 40℃ / min, hold for 15 min;

[0050] (2) Finished product conditions: constant temperature of 220℃. Inlet: 260℃; Detector: 260℃.

[0051] Injection volume: 0.2 µl. Column inlet pressure: 0.10 MPa. Split ratio: 1 / 60. Carrier gas: High-purity nitrogen; content results are obtained using the area normalization method.

[0052] Catalyst Preparation Example 1

[0053] At room temperature, 2.420 g of FeCl3·6H2O was added to 30 ml of deionized water and stirred until completely dissolved. 10 g of β / ZSM-5 support was added to the above solution, and the temperature was controlled at 40 °C for 4 hours to obtain a suspension. 14.52 g of dibenzo-18-crown-6 adjuvant was added to the above suspension, and the temperature was controlled at 80 °C for 4 hours to modify. The mixture was filtered, and the filter cake was dried at a constant temperature of 80 °C to obtain catalyst 1 with an active component loading of 5%, which was then set aside.

[0054] Catalyst Preparation Examples 2-4

[0055] Examples 2-4 of this catalyst preparation provide a method for preparing a composite catalyst. The only difference from Example 1 is that the FeCl3·6H2O metal salt in Example 1 is replaced with Zn(OAc)2·2H2O (1.678 g), CuSO4·5H2O (1.966 g), and Mn(NO3)2·4H2O (2.284 g), respectively. The corresponding amounts of the auxiliary agent dibenzo-18-crown-6 are 10.07 g, 11.80 g, and 13.71 g, respectively. The rest is the same as in Example 1.

[0056] Catalyst Preparation Examples 5-7

[0057] Examples 5-7 of this catalyst preparation provide a method for preparing a composite catalyst. The only difference from Example 1 is that the loading of FeCl3·6H2O in Example 1 is adjusted to 3%, 7%, and 9%, respectively, with corresponding amounts of FeCl3·6H2O of 1.452 g, 3.388 g, and 4.356 g; and the corresponding amounts of the auxiliary agent dibenzo-18-crown-6 of 8.71 g, 20.33 g, and 26.13 g; otherwise, it is the same as Example 1.

[0058] Catalyst Preparation Examples 8-13

[0059] Examples 8-13 of this catalyst preparation method provide a method for preparing a composite catalyst. The difference from Example 1 is that the support β / ZSM-5 in Example 1 is replaced with Hβ, H-ZSM-5, HY, SAPO-11, 5A molecular sieve, and MCM-41 in sequence, while keeping the amount of support unchanged. The rest is the same as in Example 1.

[0060] Catalyst Preparation Examples 14-18

[0061] Examples 14-18 of this catalyst preparation method provide a method for preparing a composite catalyst. The difference from Example 1 is that the auxiliary agent dibenzo-18-crown-6 in Example 1 is replaced sequentially with dicyclohexano-24-crown-8, 18-crown-6, dibenzo-30-crown-10, benzo-15-crown-5, and dibenzo-27-crown-9, while keeping the amount of auxiliary agent unchanged. The rest is the same as in Example 1.

[0062] Catalyst Preparation Examples 19-21

[0063] Examples 19-21 of this catalyst preparation method provide a method for preparing a composite catalyst. The only difference from Example 1 is that the mass ratio of FeCl3·6H2O and dibenzo-18-crown-6 in Example 1 is adjusted from 1:6 to 1:1, 1:4, and 1:8, with corresponding masses of 2.42 g, 9.68 g, and 19.36 g, respectively. The rest is the same as in Example 1.

[0064] Comparative Example 1

[0065] At room temperature, 2.420 g of FeCl3·6H2O was added to 30 ml of deionized water and stirred until completely dissolved; 10 g of β / ZSM-5 support was added to the above solution, and the temperature was controlled at 40℃ for 4 hours to obtain a suspension; the suspension was filtered, and the filter cake was dried at 80℃ to obtain comparative catalyst 1 for later use.

[0066] Catalyst Application

[0067] Application Example 1

[0068] To save raw materials and time, a batch reaction method was used for catalyst screening.

[0069] 10g phenol, 5.6g butanone alcohol, 0.5g catalyst 1, and 8.3g ethanol were added to the reaction apparatus. Stirring was started, and the temperature was raised to 80℃. The reaction was maintained at this temperature for 2 hours. Gas chromatography analysis of the reaction solution showed that the butanone alcohol content was ≤0.2%. At the end of the reaction, the butanone alcohol content was 93.63%, the by-product was 3.47%, and the remainder was the for-product. The calculated butanone alcohol selectivity was 96.42%. The catalyst was recovered by filtration, the solvent was recovered by vacuum distillation, and the product was obtained by fractional distillation with a purity of 100%. The gas chromatography and mass spectra are shown below. Figure 2 and Figure 3 .

[0070] Application Examples 2-21

[0071] Application Examples 2-21 were prepared sequentially using the catalysts described above to create the composite catalysts provided in Examples 2-21. These catalysts were used in ethanol solvent for the synthesis of raspberry ketone from phenol and butanone alcohol, with other conditions the same as in Application Example 1. The results are shown in Table 1.

[0072] Application Example 22

[0073] Catalyst 1 was selected, and 10.0 g of deionized water was used instead of ethanol in Application Example 1. All other conditions were the same as in Application Example 1. The results are shown in Table 1.

[0074] Application Example 23

[0075] Catalyst 1 was selected, and no solvent was used. Other procedures were the same as in Application Example 1. The results are shown in Table 1.

[0076] Application Comparative Example 1

[0077] The composite catalyst provided in Comparative Example 1 was used in the reaction of phenol and butanone alcohol to synthesize raspberry ketone in ethanol solvent, with other conditions the same as in Application Example 1. The results are shown in Table 1.

[0078] Table 1

[0079]

[0080] Fixed-bed continuous reaction

[0081] Based on the results of the batch reaction experiment, catalyst 1 was selected for fixed-bed continuous reaction to verify the optimal reaction conditions and catalyst stability, providing a reference for production scale-up.

[0082] 10g of catalyst was packed into a fixed bed (Φ10mm×10cm), with glass spring packing at both ends. The fixed bed was heated to 60℃~120℃ to activate the catalyst. In a flask, 100g of a mixture of phenol, butanone, and ethanol was pumped from the top to the fixed bed reactor in a ratio of phenol:butanone:ethanol = 1~3:1:1~5. The temperature of the fixed bed reactor was controlled at 60℃~120℃, and the flow rate was adjusted to 0.2g~0.8g / min. The reaction liquid flowing out of the fixed bed reactor entered a receiving flask. The composition of the reaction liquid was analyzed using gas chromatography, and the conversion and selectivity based on butanone were calculated.

[0083] Application Example 24

[0084] 10g of catalyst 1 was packed into a fixed bed (Φ10mm×10cm) using glass spring packing at both ends. The fixed bed was heated to 120℃ and held for 1 hour to activate the catalyst. 100g of a mixture of phenol, butanone, and ethanol (phenol:butanone:ethanol = 1.8:1:1.5) was pumped from the top of the fixed bed reactor into a flask using a peristaltic pump. The temperature of the fixed bed reactor was controlled at 80℃, and the flow rate was adjusted to 0.6g / min. The reaction liquid flowing out of the fixed bed reactor entered a receiving flask. The composition of the reaction liquid was analyzed using gas chromatography. Based on butanone, the butanone conversion rate was 45.8%, and the selectivity was 95.6%.

[0085] Application Examples 25-27

[0086] Application Examples 25-27 show the results of changing the feed rate to 0.2 g / min, 0.4 g / min, and 0.8 g / min respectively, as shown in Table 2.

[0087] Application Examples 28-31

[0088] Application Examples 28-31 show the results of changing the mass ratio of butanone alcohol and phenol to 1:1.0, 1:1.5, 1:2, and 1:3, as shown in Table 2.

[0089] Application Examples 32-34

[0090] Application Examples 32-34 show the results of changing the mass ratio of butanone alcohol and solvent to 1:1.0, 1:2.0, and 1:3.0, as shown in Table 2.

[0091] Application Examples 35-37

[0092] Application Examples 35-37 show the reaction temperatures changed to 60℃, 100℃, and 120℃ respectively, and the results are shown in Table 2.

[0093] Table 2

[0094]

[0095] Catalyst stability study

[0096] 10g of catalyst 1 was packed into a fixed bed (Φ10mm×10cm) using glass spring packing at both ends. The fixed bed was heated to 120℃ and held for 1 hour to activate the catalyst. 2000g of a mixture of phenol, butanone, and ethanol (phenol:butanone:ethanol = 1.8:1:1.5) was pumped from the top of the fixed bed reactor into a flask using a peristaltic pump. The temperature of the fixed bed reactor was controlled at 80℃, and the flow rate was adjusted to 0.6g / min. The reaction liquid flowing out of the fixed bed reactor entered a receiving flask. Gas chromatography was used to analyze the composition of the reaction liquid. Based on butanone, the conversion rate was 41.2%, and the selectivity was 93.7%. This indicates that catalyst 1 has good stability and can be reliably reused.

[0097] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for preparing raspberry ketone, characterized in that, include: Butanone and phenol undergo a Friedel-Crafts alkylation reaction catalyzed by a composite catalyst to yield raspberry ketone; The composite catalyst includes an active component, a support, and an additive; The active component is a transition metal salt; The carrier is a molecular sieve; The adjuvant is a crown ether; The Friedel-Crafts alkylation reaction is carried out under solvent or solvent-free conditions; The solvent is ethanol or water; The mass ratio of butanone alcohol to solvent is 1:1~3; The Friedel-Crafts alkylation reaction is carried out in a fixed-bed reactor; The composite catalyst is loaded in the fixed-bed reactor, and the butanone alcohol, phenol and solvent are mixed to form a mixture, which is then introduced into the fixed-bed reactor for reaction. The feed rate of the mixture is 0.2 g to 0.8 g / min; The composite catalyst was prepared using the following method: (1) Add a transition metal salt to deionized water, dissolve it, and obtain a mixture; (2) Add the carrier to the above mixture and stir to load it; (3) Add the additive to the above mixture for further modification, and filter to obtain the catalyst precursor; (4) The obtained catalyst precursor is processed to obtain the composite catalyst; The transition metal salts are selected from chlorides, nitrates, sulfates and their hydrated compounds containing iron, zinc, copper and manganese. The molecules are selected from one or more of Hβ, H-ZSM-5, HY, β / ZSM-5, SAPO-11, 5A molecular sieve, and MCM-41; The mass ratio of the metal in the active component to the carrier is 0.03~0.09:1; The crown ether is selected from one or more of dibenzo-18-crown-6, dicyclohexano-24-crown-8, 18-crown-6, dibenzo-30-crown-10, benzo-15-crown-5, and dibenzo-27-crown-9; The mass ratio of the active component to the auxiliary agent is 1:1.0~8.

0.

2. The method for preparing raspberry ketone according to claim 1, characterized in that, The mass ratio of phenol to butanone is 1 to 3:

1.

3. The method for preparing raspberry ketone according to claim 1, characterized in that, The Friedel-Crafts alkylation reaction is carried out at a temperature of 60°C to 120°C.

4. The method for preparing raspberry ketone according to claim 1, characterized in that, In step (2), the load temperature is 20℃~60℃, and the load time is 2 hours~6 hours; In step (3), the modification temperature is 60℃~100℃, and the modification time is 2 hours~6 hours; In step (4), the treatment is to dry at a constant temperature of 70~90℃ until constant weight.

5. A composite catalyst for the preparation method of raspberry ketone according to any one of claims 1 to 4, characterized in that, The composite catalyst includes an active component, a support, and an additive; The active component is a transition metal salt; The carrier is a molecular sieve; The adjuvant is a crown ether; It was prepared using the following method: (1) Add a transition metal salt to deionized water, dissolve it, and obtain a mixture; (2) Add the carrier to the above mixture and stir to load it; (3) Add the additive to the above mixture for further modification, and filter to obtain the catalyst precursor; (4) The obtained catalyst precursor is processed to obtain the composite catalyst; The transition metal salts are selected from chlorides, nitrates, sulfates and their hydrated compounds containing iron, zinc, copper and manganese. The molecules are selected from one or more of Hβ, H-ZSM-5, HY, β / ZSM-5, SAPO-11, 5A molecular sieve, and MCM-41; The mass ratio of the metal in the active component to the carrier is 0.03~0.09:1; The crown ether is selected from one or more of dibenzo-18-crown-6, dicyclohexano-24-crown-8, 18-crown-6, dibenzo-30-crown-10, benzo-15-crown-5, and dibenzo-27-crown-9; The mass ratio of the active component to the auxiliary agent is 1:1.0~8.0.

Images