A kind of hydroxy aromatic ketone and its synthesis method

Abstract

The invention discloses a hydroxy aromatic ketone and a synthesis method thereof. The synthesis method of the invention comprises reacting an alkylphenol or a halogenated phenol with an acylating agent in a solvent or non-solvent state under the action of a catalyst to obtain the hydroxy aromatic ketone, wherein the catalyst is an acid-modified organic metal framework material. The synthesis method of the invention has the characteristics of less esterification side reactions, high conversion rate of alkylphenol or halogenated phenol, high selectivity of hydroxy aromatic ketone, and easy separation and recovery of the catalyst.

Description

Technical Field

[0001] The invention relates to a hydroxy aromatic ketone and a synthesis method thereof. Background Art

[0002] Hydroxyaromatic ketone molecules contain hydroxyl and ketone groups on the benzene ring. They are very important fine chemicals and synthetic intermediates, and are widely used in the fields of medicine, cosmetics, food, synthetic materials, etc. Among them, p-hydroxyacetophenone is an example. It is a natural plant extract that naturally exists in the stems and leaves of the Asteraceae plant Artemisia scoparia, the roots of Artemisia capillaris, Asclepiadaceae plants, and Panax ginseng. It has important application value in the fields of medicine, dyes, cosmetics, liquid crystal materials, synthetic resins, etc. Ortho-hydroxyacetophenone is mainly used as a pharmaceutical intermediate and fragrance.

[0003] The synthesis methods of hydroxyacetophenone mainly include phenyl acetate method, p-aminoacetophenone method, photocatalytic method, etc., but the synthetic routes reported so far have the problems of long reaction process and complicated operation. Therefore, the research on the preparation method of hydroxyacetophenone directly synthesized by acylation of phenol is particularly important. However, there is an esterification competition reaction in the synthesis of phenol acylation catalyzed by trifluoromethanesulfonic acid, which generates phenyl acetate and / or phenyl trifluoromethanesulfonate, and trifluoromethanesulfonic acid is a homogeneous catalyst, which has the problem that the catalyst is difficult to separate and recover. Summary of the invention

[0004] Aiming at the problems in the prior art that esterification side reactions are prone to occur in the synthesis of hydroxy aromatic ketones by direct acylation of alkylphenol or halogenated phenol and the problem that catalysts are difficult to separate, the present invention provides a novel method for synthesizing hydroxy aromatic ketones, which has the characteristics of less esterification side reactions, high conversion rate of alkylphenol or halogenated phenol, high selectivity of hydroxy aromatic ketone and easy separation and recovery of catalysts.

[0005] The first aspect of the present invention provides a method for synthesizing hydroxyaromatic ketone, comprising reacting alkylphenol or halogenated phenol with an acylating agent in a solvent or non-solvent state in the presence of a catalyst to obtain hydroxyaromatic ketone, wherein the catalyst is an acid-modified organic metal framework material.

[0006] In the above technical solution, preferably, the method for preparing the acid-modified organic metal framework material comprises: mixing the organic metal framework material, an acid and a first solvent and performing a modification reaction.

[0007] In the above technical solution, preferably, the weight ratio of the organic metal framework material, the acid and the first solvent is 1:0.01-50:0.01-100, preferably 1:0.01-20:5-50.

[0008] In the above technical solution, preferably, the conditions of the modification reaction include: 10-200° C., and time of 0.1-48 h.

[0009] In the above technical solution, the first solvent is an inert solvent, including but not limited to one or more of chlorobenzene, nitrobenzene, toluene, nitromethane, acetonitrile and dichloromethane.

[0010] In the above technical solution, preferably, the acid is an organic acid and / or an inorganic acid; preferably one or more selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and trifluoromethanesulfonic anhydride.

[0011] In the above technical solution, preferably, the organic metal framework material is selected from one or more of IRMOF, ZIFs, PCP and MIL; preferably MIL; more preferably MIL-100(Cr) and / or MIL-101(Cr).

[0012] In the present invention, the organic metal framework material is preferably an organic metal framework material that has been dried.

[0013] In the above technical solution, preferably, the alkylphenol has a structural formula shown in chemical formula a and / or chemical formula b,

[0014] Chemical formula a,

[0015] Chemical formula b,

[0016] Wherein, R1, R2, and R3 are independently selected from H and C1-C6 alkyl.

[0017] In the above technical solution, preferably, the alkylphenol is selected from one of phenol, 2-methylphenol, 4-methylphenol, 2-ethylphenol, 4-ethylphenol and 2,5-dimethylphenol.

[0018] In the above technical solution, preferably, the halogenated phenol has a structural formula shown in chemical formula c,

[0019] Chemical formula c;

[0020] Wherein, X is selected from one selected from -F, -Cl, -Br and -I.

[0021] In the above technical solution, preferably, the halogenated phenol is selected from one of 2-chlorophenol, 4-chlorophenol and 2,5-dichlorophenol.

[0022] In the above technical solution, preferably, the acylating agent is selected from one or more of alkyl acyl chlorides, aryl acyl chlorides, acetic anhydride and alkyl carboxylic acids; preferably, the acylating agent is selected from one or more of glacial acetic acid, benzoyl chloride, acetyl chloride and acetic anhydride.

[0023] In the above technical solution, preferably, the solvent is selected from one or more of chlorobenzene, nitrobenzene, toluene, nitromethane, acetonitrile and dichloromethane.

[0024] In the above technical solution, preferably, the molar ratio of alkylphenol or halogenated phenol to acylating agent is 1:(0.01-10), preferably 1:(0.5-2).

[0025] In the above technical solution, preferably, the weight ratio of the alkylphenol or halogenated phenol and the acid-modified organic metal framework material is 1:(0-2), preferably 1:(0.05-0.8).

[0026] In the above technical solution, preferably, the reaction conditions include: a temperature of 20-200°C, preferably 20-100°C.

[0027] In the above technical solution, preferably, the reaction conditions include: pressure of 0.1 MPa-6 MPa, preferably 0.1 MPa-2 MPa.

[0028] In the above technical solution, preferably, the reaction conditions include: time is 0.1-10h, preferably 0.5-5h.

[0029] In the above technical solution, "under non-solvent state" refers to the condition where no solvent is used.

[0030] In the above technical scheme, preferably, the preparation method further comprises adding water and stirring, extracting with ethyl acetate, combining the organic phases, drying with anhydrous Na2SO4, filtering, and removing the solvent under reduced pressure.

[0031] The second aspect of the present invention provides a hydroxy aromatic ketone prepared by the above preparation method.

[0032] Beneficial effects of the present invention:

[0033] The synthesis method of the invention can effectively improve the conversion rate of alkylphenol or halogenated phenol and the selectivity of hydroxy aromatic ketone, and the catalyst can be easily separated and recovered. DETAILED DESCRIPTION

[0034] In order to make the present invention more easily understood, the present invention will be described in detail below in conjunction with embodiments. These embodiments are only for illustration and are not intended to limit the application scope of the present invention.

[0035] In the present invention,

[0036] The conversion rate of the raw material (alkylphenol or halogenated phenol) is calculated as follows: conversion rate = (amount of alkylphenol or halogenated phenol before reaction - amount of alkylphenol or halogenated phenol after reaction) / amount of alkylphenol or halogenated phenol before reaction × 100%.

[0037] The selectivity of the product (hydroxy aromatic ketone) is calculated as follows: selectivity of hydroxy aromatic ketone = amount of substance of hydroxy aromatic ketone / (amount of substance of alkylphenol or halogenated phenol before reaction - amount of substance of alkylphenol or halogenated phenol after reaction) × 100%.

[0038] The formula for calculating the selectivity of the by-product is selectivity of the by-product = amount of substance of the by-product / (amount of substance of the alkylphenol or halogenated phenol before the reaction - amount of substance of the alkylphenol or halogenated phenol after the reaction)×100%.

[0039] [Preparation Example 1]

[0040] The MIL-101(Cr) was dried in an oven at 150°C overnight.

[0041] 2g of dried MIL-101(Cr) and 25g of anhydrous toluene were added to a 50mL reaction bottle containing a cold finger (condenser) after drying, and the mixture was placed in an ice-water bath and stirred vigorously. 3.5g of trifluoromethanesulfonic anhydride was added dropwise. After the addition was completed, the mixture naturally returned to room temperature, and then heated to 80°C and maintained for 6 hours, and then naturally cooled to room temperature. Then, the mixture was filtered, and the filter cake was washed with anhydrous toluene. The solid was dried under vacuum at room temperature to obtain the catalyst MIL-101(Cr)-OTf, which was recorded as catalyst 1.

[0042] [Preparation Example 2-5]

[0043] According to the method of Preparation Example 1, the only difference is that the trifluoromethanesulfonic anhydride in Preparation Example 1 is replaced by trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid, and trifluoromethanesulfonic anhydride, respectively, to obtain Catalyst 2, Catalyst 3, Catalyst 4, and Catalyst 5, respectively.

[0044] [Preparation Example 6]

[0045] Catalyst 6 was obtained by following the method of Preparation Example 1, except that MIL-101(Cr) in Preparation Example 1 was replaced by MIL-100(Cr).

[0046] [Example 1]

[0047] In a 50mL flask, 4.1g phenol, 5mL glacial acetic acid and 0.4g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, and the solvent was removed under reduced pressure. The residue was analyzed by GC (Agilent, model 7890), and no key impurity trifluoromethanesulfonic acid phenol ester was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) were calculated, and the results are shown in Table 1.

[0048] [Example 2-6]

[0049] The method of Example 1 was followed, except that Catalyst 1 was replaced by Catalysts 2-6 prepared in Preparation Examples 2-6, respectively. The results of the conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) are shown in Table 1.

[0050] [Examples 7-9]

[0051] The method of Example 1 was followed, except that phenol was replaced by 2-methylphenol, 2,5-dimethylphenol, and 2-chlorophenol, respectively. The results of the conversion rate of the raw material, the selectivity of the product, and the selectivity of the by-product are shown in Table 1.

[0052] [Examples 10-12]

[0053] The method of Example 1 was followed, except that glacial acetic acid was replaced by benzoyl chloride, acetyl chloride, and acetic anhydride, respectively. The results of the conversion rate of the raw material, the selectivity of the product, and the selectivity of the by-product are shown in Table 1.

[0054] [Example 13]

[0055] In a 50mL flask, 4.1g phenol, 5mL glacial acetic acid and 3.28g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, extracted three times with ethyl acetate after sufficient stirring, the organic phase was merged, dried over anhydrous Na2SO4 and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonic acid phenol ester was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) were calculated, and the results are shown in Table 1.

[0056] [Example 14]

[0057] In a 50mL flask, 4.1g phenol, 5mL glacial acetic acid and 8.2g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonyl phenol was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonyl phenol) were calculated, and the results are shown in Table 1.

[0058] [Example 15]

[0059] In a 50mL flask, 4.1g phenol, 2mL glacial acetic acid and 0.4g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonyl phenol was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonyl phenol) were calculated, and the results are shown in Table 1.

[0060] [Example 16]

[0061] In a 50mL flask, 4.1g phenol, 8mL glacial acetic acid and 0.4g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonyl phenol was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonyl phenol) were calculated, and the results are shown in Table 1.

[0062] [Example 17]

[0063] In a 50mL flask, 4.1g phenol, 40mL glacial acetic acid and 0.4g catalyst 1 (obtained in Preparation Example 1) were added, the system was heated to 80°C for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonyl phenol was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonyl phenol) were calculated, and the results are shown in Table 1.

[0064] [Example 18]

[0065] In a 50mL flask, add 4.1g phenol, 5mL glacial acetic acid, 0.4g catalyst 1 (preparation example 1 obtains) and 10g acetonitrile, the system is heated to 80 ℃ and kept for 2 hours, and cooled to room temperature. The system is poured into 100mL ice water, fully stirred and extracted with ethyl acetate three times, the organic phase is merged, anhydrous Na2SO4 is dried and filtered, and the solvent is removed under reduced pressure. The residue is analyzed by GC detection, and no key impurity trifluoromethanesulfonic acid phenol ester is detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) are calculated, and the results are shown in Table 1.

[0066] [Example 19]

[0067] In a 50mL flask, 4.1g phenol, 5mL glacial acetic acid, 0.4g catalyst 1 (preparation example 1 obtained) and 10g nitrobenzene were added, the system was heated to 80 ℃ and kept for 2 hours, and cooled to room temperature. The system was poured into 100mL ice water, extracted three times with ethyl acetate after sufficient stirring, the organic phase was merged, anhydrous Na2SO4 was dried and filtered, and the solvent was removed under reduced pressure. The residue was analyzed by GC detection, and no key impurity trifluoromethanesulfonyl phenol was detected. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonyl phenol) were calculated, and the results are shown in Table 1.

[0068] [Examples 20-22]

[0069] The method of Example 1 was followed, except that 80° C. was replaced by 40° C., 60° C., and 100° C. The results of the conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone), and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) are shown in Table 1.

[0070] [Comparative Example 1]

[0071] 4.1 g of phenol, 5 mL of glacial acetic acid and 0.17 mL of trifluoromethanesulfonic anhydride were added to a 50 mL flask, the system was heated to 80 ° C for 2 hours, and then cooled to room temperature. The system was poured into 100 mL of ice water, fully stirred and extracted with ethyl acetate three times, the organic phases were combined, dried over anhydrous Na2SO4 and filtered, the solvent was removed under reduced pressure, and the residue was analyzed by GC. The conversion rate of the raw material (phenol), the selectivity of the product (hydroxyacetophenone) and the selectivity of the by-product (trifluoromethanesulfonic acid phenol ester) are shown in Table 1.

[0072] [Comparative Example 2]

[0073] The method of Example 1 is followed, except that the catalyst 1 obtained in Preparation Example 1 is replaced by MIL-101(Cr), that is, the catalyst is an organic metal framework material, not an acid-modified organic metal framework material.

[0074] Table 1

[0075] Example Conversion rate of raw materials (%) Selectivity of hydroxyacetophenone (%) Selectivity of by-products (%) Example 1 95.3 87.6 1.8 Example 2 77.8 77.1 18.2 Example 3 77.2 78.5 15.0 Example 4 79.8 80.1 14.8 Example 5 96.7 89.0 2.6 Example 6 94.8 86.2 2.1 Example 7 96.0 88.9 1.1 Example 8 98.2 90.2 0.7 Example 9 75.6 85.0 2.5 Example 10 86.2 88.5 1.2 Embodiment 11 93.5 86.2 3.7 Example 12 92.0 83.5 5.5 Embodiment 13 96.7 91.4 1.2 Embodiment 14 99.4 90.8 1.4 Embodiment 15 80.4 86.5 1.6 Example 16 96.0 88.2 1.9 Embodiment 17 96.9 79.8 5.6 Embodiment 18 86.3 81.4 3.8 Embodiment 19 92.3 87.4 1.5 Embodiment 20 66.3 75.1 14.3 Embodiment 21 89.0 84.9 2.6 Embodiment 22 96.2 82.4 3.7 Comparative Example 1 83.7 67.4 24.3 Comparative Example 2 77.8 4.5 86.9

[0076] It can be seen from Table 1 that the synthesis method of the present invention has few esterification side reactions, high conversion rate of alkylphenol or halogenated phenol, and high selectivity of hydroxy aromatic ketone. In addition, the catalyst of the present invention is easy to separate and recycle.

[0077] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this field, under the technical enlightenment provided by the present invention, as common knowledge in the field, other equivalent variations and improvements can also be made, which should also be regarded as the protection scope of the present invention.

Claims

1. A method for synthesizing a hydroxy aromatic ketone, comprising reacting phenol or alkylphenol or halogenated phenol with an acylating agent in a solvent or non-solvent state in the presence of a catalyst to obtain a hydroxy aromatic ketone, wherein: The catalyst is an acid-modified organic metal framework material; The acid is selected from one or more of hydrochloric acid, sulfuric acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and trifluoromethanesulfonic anhydride; The organic metal framework material is selected from one or more of IRMOF, ZIFs, PCP and MIL.

2. The synthesis method according to claim 1, characterized in that The method for preparing the acid-modified organic metal framework material comprises: mixing the organic metal framework material, an acid and a first solvent and performing a modification reaction.

3. The synthesis method according to claim 2, characterized in that The weight ratio of the organic metal framework material, the acid and the first solvent is 1:0.01-50:0.01-100; And / or, the conditions of the modification reaction include: temperature of 10-200° C. and time of 0.1-48 h.

4. The synthesis method according to claim 3, characterized in that The weight ratio of the organic metal framework material, the acid and the first solvent is 1:0.01-20:5-50.

5. The synthesis method according to claim 1, characterized in that The organic metal framework material is selected from MIL.

6. The synthesis method according to claim 5, characterized in that The organic metal framework material is selected from MIL-100 (Cr) and / or MIL-101 (Cr).

7. The synthesis method according to any one of claims 1 to 6, characterized in that The alkylphenol has a structural formula shown in chemical formula a and / or chemical formula b, Wherein, R1, R2, and R3 are independently selected from C1 to C6 alkyl groups.

8. The synthesis method according to claim 7, characterized in that The alkylphenol is selected from one of 2-methylphenol, 4-methylphenol, 2-ethylphenol, 4-ethylphenol and 2,5-dimethylphenol.

9. The synthesis method according to any one of claims 1 to 6, characterized in that The halogenated phenol has the structural formula shown in chemical formula c, Wherein, X is selected from one selected from -F, -Cl, -Br and -I.

10. The synthesis method according to any one of claims 1 to 6, characterized in that: The halogenated phenol is selected from one of 2-chlorophenol, 4-chlorophenol and 2,5-dichlorophenol.

11. The synthesis method according to any one of claims 1 to 6, characterized in that: The acylating agent is selected from one or more of alkyl acyl chlorides, aryl acyl chlorides, acetic anhydride and alkyl carboxylic acids; and / or, The solvent is selected from one or more of chlorobenzene, nitrobenzene, toluene, nitromethane, acetonitrile and dichloromethane.

12. The synthesis method according to claim 11, characterized in that The acylating agent is selected from one or more of glacial acetic acid, benzoyl chloride, acetyl chloride and acetic anhydride.

13. The synthesis method according to any one of claims 1 to 6, characterized in that: The molar ratio of phenol or alkylphenol or halogenated phenol to the acylating agent is 1:(0.01-10); and / or, The weight ratio of phenol or alkylphenol or halogenated phenol and acid-modified organic metal framework material is 1:(0.01-2).

14. The synthesis method according to claim 13, characterized in that: The molar ratio of phenol or alkylphenol or halogenated phenol to the acylating agent is 1:(0.5-2); and / or, The weight ratio of phenol or alkylphenol or halogenated phenol and acid-modified organic metal framework material is 1:(0.05-0.8).

15. The synthesis method according to any one of claims 1 to 6, characterized in that: The reaction conditions include: temperature of 20-200° C.; and / or pressure of 0.1 MPa-6 MPa; and time of 0.1-10 h.

16. The synthesis method according to claim 15, characterized in that: The reaction conditions include: temperature of 60-200° C.; and / or pressure of 0.1 MPa-2 MPa; and / or time of 0.5-5 h.

17. The synthesis method according to claim 16, characterized in that: The reaction conditions include: a temperature of 60-100°C.

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