Composite catalyst, its preparation method and application

Abstract

This invention provides a composite catalyst, its preparation method, and its application. Belonging to the field of organic synthesis, the composite catalyst comprises an active component, a support, and an auxiliary agent. The active component is one or a combination of at least two of the following: chlorides, sulfates, nitrates, or acetates containing iron, nickel, copper, zinc, zirconium, or magnesium. The support is a metal-organic framework compound, and the auxiliary agent is an amino halide compound. This composite catalyst solves the problems of easy deactivation and inapplicability in existing technologies, while improving reaction selectivity and yield, thus facilitating the application of Friedel-Crafts acylation reactions in large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a composite catalyst, its preparation method and application, and particularly to a composite catalyst for Friedel-Crafts acylation reactions, its preparation method and application. Background Technology

[0002] The Friedel-Crafts reaction, or simply Friedel-Crafts reaction, is a class of aromatic electrophilic substitution reactions, discovered in 1877 by French chemist Charles Friedel and American chemist James Mason Crafts. This reaction is mainly divided into two categories: alkylation and acylation. The Friedel-Crafts acylation reaction, or Friedel-Crafts acylation reaction, is a type of Friedel-Crafts reaction. Catalyzed by protic acids or Lewis acids (such as aluminum trichloride), it is an electrophilic substitution reaction in which aromatic compounds react with acyl halides or acid anhydrides; it is a modified electrophilic substitution reaction.

[0003] Friedel-Crafts acylation is one of the most efficient methods for achieving carbon-carbon bonding and is an important means of preparing various aryl ketones and heterocyclic aromatic ketones. Therefore, it has very wide applications in the industrial production of pharmaceuticals, pesticides, dyes, and fragrances. Generally speaking, the catalysts used in Friedel-Crafts acylation reactions are Lewis acids, such as zinc chloride, aluminum chloride, ferric chloride, tin tetrachloride, and titanium tetrachloride, or strong protic acids, such as hydrofluoric acid and sulfuric acid. Lewis acids or protic acids have problems such as strong corrosiveness to equipment, non-recoverable catalysts, harsh reaction conditions, long reaction times, and the generation of harmful substances that pollute the environment during the production process.

[0004] Although Friedel-Crafts acylation reactions have been striving towards green chemistry over the past few decades, there is still a need to continuously develop more efficient catalysts or optimize reaction conditions to improve reaction efficiency and catalyst recycling. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a composite catalyst, its preparation method, and its application, particularly a composite catalyst for Friedel-Crafts acylation reactions, its preparation method, and its application. The composite catalyst of the present invention solves the problems of easy deactivation and inapplicability in existing technologies, while simultaneously improving reaction selectivity and yield, thus facilitating the application of Friedel-Crafts acylation reactions in large-scale industrial production.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] On one hand, the present invention provides a composite catalyst comprising an active component, a support, and an auxiliary agent. The active component is one or a combination of at least two of the following: chlorides, sulfates, nitrates, or acetates containing iron, nickel, copper, zinc, zirconium, or magnesium. The support is a metal-organic framework compound (MOF), and the auxiliary agent is an amino halide compound.

[0008] In this invention, the active component is selected from any one or a combination of at least two of MgSO4, CuSO4, Fe(NO3)3, Zn(OAc)2, ZrCl4, Ni(NO3)2, FeCl3 or their hydrates.

[0009] Preferably, the metal-organic framework compound is selected from the Uio series or the MIL series of metal-organic framework compounds.

[0010] Preferably, the Uio series metal-organic framework compounds include one or a combination of at least two of Uio-66, Uio-67, and Uio-68;

[0011] Preferably, the MIL series metal-organic framework compounds include one or a combination of at least two of MIL-101, MIL-53, MIL-47, and MIL-88A.

[0012] Preferably, the mass ratio of the metal element to the carrier in the active component is 0.01~0.09:1.0, such as 0.01:1.0, 0.03:1.0, 0.05:1.0, 0.07:1.0 or 0.09:1.0, etc., and preferably 0.05~0.07:1.0.

[0013] Preferably, the adjuvant is selected from one or a combination of at least two of the following: bis(2-chloroethyl)ammonium hydrochloride, 2-chloroethylamine hydrochloride, 3-chloropropylamine hydrochloride, 2-bromoethylamine hydrobromide, 3-bromopropylamine hydrobromide, 2-chloro-N,N-dimethylethylamine hydrochloride, 3-dimethylaminopropyl chloride hydrochloride, 2-chloro-N,N-dimethylethylamine hydrochloride, 3-dimethylaminopropyl chloride hydrochloride, 2-diethylaminochloroethane hydrochloride, 2-chloro-N,N-dimethylpropylamine hydrochloride, and 2-bromo-N,N-diethylethylamine hydrobromide; more preferably, it is selected from one or a combination of at least two of the following: bis(2-chloroethyl)ammonium hydrochloride, 3-chloropropylamine hydrochloride, 2-chloro-N,N-dimethylethylamine hydrochloride, 3-dimethylaminopropyl chloride hydrochloride, and 2-chloro-N,N-dimethylpropylamine hydrochloride.

[0014] Preferably, the mass ratio of the adjuvant to the carrier is 2 to 10:1.0, such as 2:1.0, 4:1.0, 6:1.0, 8:1.0 or 10:1.0, and more preferably 6 to 8:1.0.

[0015] On the other hand, the present invention provides a method for preparing the composite catalyst as described above, the method comprising the following steps:

[0016] (1) Modify the carrier using an auxiliary agent to obtain the modified carrier;

[0017] (2) Add the active component to the system obtained in step (1) and adsorb it to obtain a catalyst precursor suspension;

[0018] (3) The catalyst precursor suspension obtained in step (2) is subjected to solvent removal and drying treatment to obtain the composite catalyst.

[0019] Preferably, the modification in step (1) is carried out in a solvent, which is preferably capable of dispersing the additives and the carrier, and is selected from alcohols or water, with water being preferred.

[0020] Preferably, the modification temperature in step (1) is 80~160℃ (e.g., 80℃, 90℃, 100℃, 110℃, 120℃, 130℃, 140℃, 150℃ or 160℃, etc.), preferably 120~160℃.

[0021] Preferably, the modification time in step (1) is 2 to 6 hours (e.g., 2 hours, 3 hours, 4 hours, 5 hours or 6 hours, etc.), preferably 4 to 6 hours.

[0022] In this invention, the modified carrier suspension is obtained after the modification in step (1).

[0023] Preferably, the adsorption temperature in step (2) is 40~60℃ (e.g., 40℃, 45℃, 50℃, 55℃ or 60℃, etc.); the adsorption time is 2~4 hours (e.g., 2 hours, 2.5 hours, 3 hours, 3.5 hours or 4 hours, etc.).

[0024] On the other hand, the present invention provides a method for performing a Friedel-Crafts acylation reaction, the method comprising the following steps:

[0025] The reaction substrate shown in Formula I is reacted with an acylation reagent in the presence of the composite catalyst described above to undergo a Friedel-Crafts acylation reaction, yielding the product shown in Formula II, as shown in the following reaction formula:

[0026] ;

[0027] Wherein, R1 is selected from -H, alkyl of C1~C3 (e.g., C1, C2 or C3), alkoxy of C1~C3 (e.g., C1, C2 or C3) or -OH; and R is selected from methyl, ethyl or phenyl.

[0028] The acylation reagent is selected from one or a combination of at least two of the following: acid anhydrides, acyl chlorides, cyanuric chloride, and phthalic anhydride; specifically, it is selected from one or a combination of at least two of the following: propionic anhydride, acetic anhydride, acetic acid, propionyl chloride, acetyl chloride, benzoyl chloride, cyanuric chloride, and phthalic anhydride.

[0029] In this invention, the reaction utilizes the Friedel-Crafts reaction, or simply the Friedel-Crafts reaction.

[0030] Preferably, the reaction substrate is specifically selected from one or a combination of at least two of benzene, anisole, phenol, or piperine.

[0031] Preferably, the product can be acetophenone, benzophenone, p-methoxyacetophenone, p-methoxyacetophenone, p-hydroxyacetophenone, 2-(4-hydroxybenzoyl)benzoic acid, 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine, or 3,4-methylenedioxyacetophenone.

[0032] Preferably, the mass ratio of the composite catalyst to the reaction substrate is 0.03~0.09:1.0, such as 0.03:1.0, 0.045:1.0, 0.06:1.0, 0.075:1.0 or 0.09:1.0, and more preferably 0.05~0.07:1.0.

[0033] Preferably, the mass ratio of the reaction substrate to the acylation reagent is 1:1.0 to 2.0 (e.g., 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6 or 1:2, etc.); more preferably 1:1.0 to 1.4.

[0034] Preferably, the temperature of the Friedel-Crafts acylation reaction is 100~160℃ (e.g., 100℃, 105℃, 110℃, 115℃, 120℃, 125℃, 130℃, 135℃, 140℃ or 160℃, etc.), more preferably 100~120℃.

[0035] Preferably, the Friedel-Crafts acylation reaction takes 2 to 6 hours (e.g., 2 hours, 3 hours, 4 hours, 5 hours or 6 hours), more preferably 2 to 4 hours.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] The composite catalyst of this invention can replace traditional Lewis acid or protic acid catalysts, such as AlCl3, solving problems such as strong equipment corrosion, non-recoverable catalysts, harsh reaction conditions, long reaction time, and large amounts of waste. At the same time, it improves the selectivity and yield of the reaction, which is beneficial to the industrial application of Friedel-Crafts acylation reaction. Detailed Implementation

[0038] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0039] Unless otherwise specified, the test reagents used in the following examples are all conventional biochemical reagents; and the experimental methods described are all conventional methods unless otherwise specified.

[0040] Catalyst Example 1

[0041] At room temperature, 60.0 g of bis(2-chloroethyl)ammonium hydrochloride and 10.0 g of MIL-88A were added to 100 ml of deionized water. The mixture was stirred and heated to 120 °C. After stirring for 4 hours, the temperature was lowered to 40 °C, and 5.07 g of MgSO4•7H2O was added. The mixture was kept at this temperature and stirred for 2 hours. After cooling to room temperature, the mixture was filtered, and the resulting filter cake was dried to constant weight to obtain catalyst No. 1.

[0042] Catalyst Preparation Examples 2-6

[0043] Examples 2-6 of this catalyst preparation method provide a method for preparing a composite catalyst (catalyst 2-6). The only difference from Example 1 is that the MgSO4•7H2O metal salt in Example 1 is replaced with CuSO4·5H2O (1.96 g), Fe(NO3)3·9H2O (3.62 g), Zn(OAc)2·2H2O (1.68 g), ZrCl4 (1.28 g), and Ni(NO3)2·6H2O (2.48 g) respectively. The rest is the same as in Example 1.

[0044] Catalyst Preparation Examples 7-10

[0045] Examples 7-10 of this catalyst preparation method provide a method for preparing a composite catalyst (catalyst 7-10). The difference from Example 3 is that the Fe(NO3)3·9H2O metal salt in Example 3 is changed to FeCl3 and the loading of iron element (i.e. the mass ratio of iron element to support) is changed to 0.01, 0.03, 0.07 and 0.09 respectively, and the corresponding metal salt masses are 0.29 g, 0.87 g, 2.03 g and 2.61 g respectively. Other aspects are the same as in Example 3.

[0046] Catalyst Preparation Examples 11-16

[0047] Examples 11-16 of this catalyst preparation method provide a method for preparing a composite catalyst (catalyst 11-16). The difference from Example 3 is that the support MIL-88A in Example 1 is replaced sequentially with MIL-101, MIL-53, MIL-47, Uio-66, Uio-67, and Uio-68, while keeping the mass of the support unchanged. The rest is the same as in Example 3.

[0048] Catalyst Preparation Examples 17-26

[0049] Examples 17-26 of this catalyst preparation method provide a method for preparing a composite catalyst (catalyst 17-26). The difference from Example 3 is that the auxiliary agent bis(2-chloroethyl)ammonium hydrochloride in Example 3 is replaced sequentially with 2-chloroethylamine hydrochloride, 3-chloropropylamine hydrochloride, 2-bromoethylamine hydrobromide, 3-bromopropylamine hydrobromide, 2-chloro-N,N-dimethylethylamine hydrochloride, 3-dimethylaminopropylchlorohydrochloride, 3-dimethylaminopropylchlorohydrochloride, 2-diethylaminochloroethane hydrochloride, 2-chloro-N,N-dimethylpropylamine hydrochloride, and 2-bromo-N,N-diethylethylamine hydrobromide, while keeping the mass ratio of auxiliary agent and support unchanged. Other aspects are the same as in Example 3.

[0050] Catalyst Preparation Examples 27-30

[0051] Examples 27-30 of this catalyst preparation method provide a method for preparing a composite catalyst (catalyst 27-30). The difference from Example 1 is that the mass ratio of the support and the auxiliary agent in Example 3 is replaced by 1:2, 1:4, 1:8 and 1:10, respectively, and the corresponding amounts of the modifier are 20g, 40g, 80g and 100g, respectively. The rest is the same as in Example 3.

[0052] Catalyst Preparation Examples 31-40

[0053] Examples 31-40 provide a method for preparing a composite catalyst (catalyst 31-40). The difference from Example 3 is only in adjusting the temperature and time of the support modification and the temperature and time of the modified support adsorption, as shown in Table 1.

[0054] Table 1

[0055]

[0056] Comparative Example 1

[0057] At room temperature, 60.0 g of bis(2-chloroethyl)ammonium hydrochloride and 10.0 g of Al2O3 were added to 100 ml of deionized water. The mixture was stirred and heated to 120 °C. After stirring for 4 hours, the temperature was lowered to 40 °C, and 1.45 g of FeCl3 was added. The mixture was kept at this temperature and stirred for 2 hours. After cooling to room temperature, the mixture was filtered, and the resulting filter cake was dried to constant weight to obtain the catalyst of Comparative Example 1.

[0058] Comparative Example 2

[0059] At room temperature, 60.0 g of bis(2-chloroethyl)ammonium hydrochloride was added to 100 ml of deionized water, and then stirring was started. The temperature was raised to 120°C and stirred for 4 hours. Then the temperature was lowered to 40°C, and 1.45 g of FeCl3 was added. After stirring for 2 hours, the temperature was lowered to room temperature, and excess water was removed by rotary evaporation under reduced pressure to obtain a suspension, which is the catalyst of Comparative Example 2.

[0060] Comparative Example 3

[0061] At room temperature, 60.0 g of bis(2-chloroethyl)ammonium hydrochloride and 10.0 g of MIL-88A were added to 100 ml of deionized water. The mixture was stirred and heated to 120 °C. After stirring for 4 hours, the temperature was lowered to 40 °C. After stirring for 2 hours, the temperature was lowered to room temperature, filtered, and the resulting filter cake was dried to constant weight to obtain the catalyst of Comparative Example 3.

[0062] Comparative Example 4

[0063] At room temperature, 10.0 g of MIL-88A was added to 100 ml of deionized water, and then stirring was started. The temperature was raised to 120°C and heated and stirred for 4 hours. Then the temperature was lowered to 40°C, and 1.45 g of FeCl3 was added. After stirring and maintaining the temperature for 2 hours, the temperature was lowered to room temperature, filtered, and the resulting filter cake was dried to constant weight to obtain the catalyst of Comparative Example 4.

[0064] Application Example 1

[0065] In a reaction vessel, anisole (50.0 g, 0.462 mol), propionic anhydride (60.0 g, 0.461 mol), and 3.0 g of catalyst 3 (5.00%) were added. The mixture was stirred and heated to 120 °C, and the reaction was maintained at this temperature for 2 hours. After the reaction was completed, vacuum distillation was performed to obtain 74.59 g of p-methoxyphenylacetone product, with a separation yield of 98.53%.

[0066] Application Examples 2-4

[0067] The only difference between Application Examples 2-4 and Application Example 1 is that the concentration of the catalyst is changed to 3.0%, 7.0%, and 9.0% respectively, and the corresponding catalyst dosages are 1.8g, 4.2g, and 5.4g respectively. Everything else is the same as Application Example 1. The results are shown in Table 2.

[0068] Application Examples 5-9

[0069] The only difference between Application Examples 5-9 and Application Example 1 is the change in the mass ratio of anisole to propionic anhydride, which is 1:1.0, 1:1.4, 1:1.6, 1:1.8, and 1:2.0, respectively. The corresponding amounts of propionic anhydride used are 50 g (0.3842 mol), 70 g (0.5379 mol), 80 g (0.6147 mol), 90 g (0.6916 mol), and 100 g (0.7684 mol), respectively. Everything else is the same as in Application Example 1. The results are shown in Table 2.

[0070] Application Examples 10-15

[0071] The only difference between Application Examples 10-15 and Application Example 1 is the type of acylation reagent, which is propionyl chloride (60 g, 0.6485 mol), acetic anhydride (60 g, 0.5877 mol), acetyl chloride (60 g, 0.7643 mol), acetic acid (60 g, 0.9992 mol), phthalic anhydride (60 g, 0.4051 mol), and cyanuric chloride (60 g, 0.3254 mol). The corresponding products are p-methoxyacetophenone, p-methoxyacetophenone, p-methoxyacetophenone, 2-(4-hydroxybenzoyl)benzoic acid, and 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine, respectively. Everything else is the same as in Application Example 1. The results are shown in Table 2.

[0072] Application Examples 16-19

[0073] The difference between Application Examples 16-19 and Application Example 1 is that the substrates were replaced sequentially with benzene (50 g, 0.640 mol), benzene (50 g, 0.640 mol), phenol (50 g, 0.529 mol), and piperonyl ring (50 g, 0.409 mol); the acylation reagents were replaced sequentially with acetic anhydride (60 g, 0.5877 mol), benzoyl chloride (60 g, 0.4268 mol), acetic anhydride (60 g, 0.5877 mol), and acetic anhydride (60 g, 0.5877 mol). The corresponding products were acetophenone, benzophenone, p-hydroxyacetophenone, and 3,4-methylenedioxyacetophenone, respectively. Other aspects were the same as in Application Example 1. The results are shown in Table 2.

[0074] Application Examples 20-24

[0075] The only difference between Application Examples 20-24 and Application Example 1 is the change in reaction temperature and reaction time; otherwise, they are the same as Application Example 1. The temperatures for Application Examples 20, 21, and 22 are 100℃, 140℃, and 160℃, respectively; otherwise, they are the same as Application Example 1. The reaction times for Application Examples 23 and 24 are 4 hours and 6 hours, respectively; otherwise, they are the same as Application Example 1. The results are shown in Table 2.

[0076] Application Examples 25-64

[0077] Application Examples 25-64 provide a composite phase catalyst, which is the composite phase catalyst provided in Catalyst Examples 1-40 (except for Catalyst Example 3) and is used in the Friedel-Crafts acylation reaction of anisole and propionic anhydride, with other parameters the same as in Application Example 1. The results are shown in Table 2.

[0078] Table 2

[0079]

[0080] Catalyst Application Examples

[0081] After filtration, the catalyst from Application Example 1 was reused directly without further treatment. After five consecutive reuses, the reaction yield decreased. The inventors speculated that this might be because the waste material coated the catalyst, covering the active sites on the catalyst surface and leading to a decrease in reaction conversion and selectivity. Therefore, in the sixth reuse, the catalyst was washed 2-3 times with deionized water at 40°C, and the reuse experiment was conducted again. It was found that the catalyst activity and selectivity could be restored to the level of the first use. The reuse data are shown in Table 3.

[0082] Table 3

[0083]

[0084] The applicant declares that the present invention is illustrated by the above embodiments to demonstrate the composite catalyst, its preparation method, and its application. However, the present invention is not limited to the above embodiments, i.e., it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials in the product of the present invention, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A composite catalyst for Friedel-Crafts acylation reactions, characterized in that, The composite catalyst comprises an active component, a support, and an auxiliary agent. The active component is one or a combination of at least two of the following: chlorides, sulfates, nitrates, or acetates containing iron, nickel, copper, zinc, zirconium, or magnesium. The support is a metal-organic framework compound. The mass ratio of the metal element to the support in the active component is 0.01~0.09:1.0, and the mass ratio of the auxiliary agent to the support is 2~10:1.

0. The metal-organic framework compound is selected from the Uio series or the MIL series of metal-organic framework compounds; The adjuvant is selected from one or a combination of at least two of the following: bis(2-chloroethyl)ammonium hydrochloride, 2-chloroethylamine hydrochloride, 3-chloropropylamine hydrochloride, 2-bromoethylamine hydrobromide, 3-bromopropylamine hydrobromide, 2-chloro-N,N-dimethylethylamine hydrochloride, 3-dimethylaminopropylchlorohydrochloride, 2-diethylaminochloroethane hydrochloride, 2-chloro-N,N-dimethylpropylamine hydrochloride, and 2-bromo-N,N-diethylethylamine hydrobromide.

2. The composite catalyst according to claim 1, characterized in that, The active component is selected from any one or a combination of at least two of MgSO4, CuSO4, Fe(NO3)3, Zn(OAc)2, ZrCl4, Ni(NO3)2, FeCl3 or their hydrates.

3. The composite catalyst according to claim 1, characterized in that, The Uio series of metal-organic framework compounds include one or a combination of at least two of Uio-66, Uio-67, and Uio-68; The MIL series of metal-organic framework compounds include one or a combination of at least two of MIL-101, MIL-53, MIL-47, and MIL-88A.

4. The method for preparing the composite catalyst according to any one of claims 1-3, characterized in that, The preparation method includes the following steps: (1) Modify the carrier using an auxiliary agent to obtain the modified carrier; (2) Add the active component to the system obtained in step (1) for adsorption to obtain a catalyst precursor suspension; (3) The catalyst precursor suspension obtained in step (2) is subjected to solvent removal and drying treatment to obtain the composite catalyst.

5. The preparation method according to claim 4, characterized in that, The modification in step (1) is carried out in a solvent selected from alcohols or water; The modification temperature in step (1) is 80~160℃, and the modification time is 2~6 hours; The adsorption temperature in step (2) is 40~60℃; the adsorption time is 2~4 hours.

6. A method for performing a Friedel-Crafts acylation reaction, characterized in that, The method includes the following steps: The reaction substrate shown in Formula I is reacted with an acylation reagent in the presence of the composite catalyst described in any one of claims 1-3 to undergo a Friedel-Crafts acylation reaction, yielding the product shown in Formula II, as shown in the following reaction formula: ； Wherein, R1 is selected from -H, C1~C3 alkyl, C1~C3 alkoxy or -OH; and R is selected from methyl, ethyl or phenyl.

7. The method according to claim 6, characterized in that, The reaction substrate is selected from one or a combination of at least two of benzene, anisole, phenol, or piperon; The acylation reagent is selected from one or a combination of at least two of acid anhydrides, acyl chlorides, cyanuric chloride, and phthalic anhydride; The product is acetophenone, benzophenone, p-methoxyacetophenone, p-methoxyacetophenone, p-hydroxyacetophenone, 2-(4-hydroxybenzoyl)benzoic acid, 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine, or 3,4-methylenedioxyacetophenone.

8. The method according to claim 6, characterized in that, The acylation reagent is selected from one or a combination of at least two of propionic anhydride, acetic anhydride, acetic acid, propionyl chloride, acetyl chloride, benzoyl chloride, cyanuric chloride, or phthalic anhydride; The mass ratio of the composite catalyst to the reaction substrate is 0.03~0.09:1.0; The mass ratio of the reaction substrate to the acylation reagent is 1:1.0~2.0; The Friedel-Crafts acylation reaction is performed at a temperature of 100~160℃; The Friedel-Crafts acylation reaction takes 2 to 6 hours.

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