Method for synthesizing trifluoromethyl tertiary alcohol compound

Abstract

The invention provides a synthesis method of a trifluoromethyl tertiary alcohol compound, which comprises the following steps: (1) mixing a ketone compound, trifluoromethyl trimethylsilane and a carbonate catalyst for reaction to prepare an intermediate product; and (2) carrying out acidification reaction on the intermediate product prepared in the step (1) to prepare the trifluoromethyl tertiary alcohol compound. The method has the advantages of mild reaction conditions, simple operation, short reaction time, cheap and easily available catalyst, excellent catalytic effect, high product yield and few byproducts.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing trifluoromethyl tertiary alcohol compounds. Background Art

[0002] Currently, the most important and widely used method for preparing tertiary alcohol compounds is to use a Grignard reagent to perform a nucleophilic addition reaction on a ketone compound, and then acidify it under acidic conditions to obtain the product.

[0003] The structural formula of the Grignard reagent is R-Mg-X, in which the alkyl group and the magnesium atom are connected by a polar covalent bond. In R-Mg, the alkyl group is an electron-donating group and the carbon is the negative electron end. Therefore, the Grignard reagent is a very strong basic Lewis base that can react with water and oxygen. Therefore, the reaction conditions must be absolutely anhydrous, oxygen-free, and carbon dioxide-free, which greatly limits the use of the Grignard reagent. And because the Grignard reagent is highly alkaline, when the Grignard reagent and aldehyde and ketone compounds undergo addition reaction, ketone compounds containing α-H will undergo aldol condensation side reactions, and when the Grignard reagent contains β-H, the ketone compound will be reduced, thereby affecting the yield.

[0004] CN107936815A reports a synthetic method for preparing a tertiary alcohol compound, which uses trifluoromethyltrimethylsilane as a trifluoromethyl source and a fluoride salt as a catalyst, first preparing an addition product of trifluoromethyltrimethylsilane and a carbonyl group, and then acidifying and removing trimethylsilane to obtain a tertiary alcohol compound. The reaction requires high pressure and low temperature conditions, and the reaction time is long. Moreover, the catalyst used is a fluoride, such as cesium fluoride and potassium fluoride. The current market price of fluoride salt is about 20000 / t, the catalyst price is abnormally expensive, and the reaction yield is low, and the catalytic effect is poor.

[0005] Therefore, there is an urgent need to develop a method for synthesizing trifluoromethyl tertiary alcohol compounds with mild reaction conditions, simple operation, short reaction time, cheap and readily available catalysts, excellent catalytic effect, high product yield, and few by-products. Summary of the invention

[0006] In order to solve the problems existing in the prior art, the present invention uses trifluoromethyltrimethylsilane as a trifluoromethyl source and a reactant that attacks the carbonyl active site, and uses carbonate as a catalyst. Since carbonate is a bilateral catalysis and fluoride salt is a unilateral catalysis, compared with using fluoride salt as a catalyst, using carbonate as a catalyst has the advantages of good catalytic effect, fast reaction, high conversion rate, high yield, high catalytic activity, mild reaction, and greatly shortened total reaction time.

[0007] Specifically, the present invention provides a method for synthesizing trifluoromethyl tertiary alcohol compounds, the method comprising the following steps:

[0008] (1) mixing a ketone compound, trifluoromethyltrimethylsilane and a carbonate catalyst to react to obtain an intermediate product;

[0009] (2) subjecting the intermediate product obtained in step (1) to an acidification reaction to obtain a trifluoromethyl tertiary alcohol compound.

[0010] In one or more embodiments, in step (1), the reaction is carried out in a solvent; preferably, the solvent is selected from one or more of ethanol, toluene, N,N-dimethylformamide, 1,2-dichloroethane, acetonitrile, 1,4-dioxane, dimethyl sulfoxide, ethylene glycol and ethyl acetate; preferably, the mass ratio of the ketone compound to the solvent is 1:(1-10), preferably 1:(1-2).

[0011] In one or more embodiments, in step (1), the reaction is carried out in a protective atmosphere.

[0012] In one or more embodiments, in step (1), the carbonate catalyst is a metal carbonate; preferably, the metal carbonate is selected from one or more of potassium carbonate, sodium carbonate, magnesium carbonate and calcium carbonate.

[0013] In one or more embodiments, the ketone compound has a structure shown in Formula I:

[0014]

[0015] In Formula I, R 1 Each is independently selected from C1-C10 alkyl, C1-C10 alkoxy, hydroxy, nitro, aromatic heterocycle, phenoxy, carboxyl, amino and halogen, R 2 is an aromatic ring, n is an integer from 0 to a, a is R 2 The maximum number of substituents that can exist on the 3 It is a C1~C10 alkyl group.

[0016] In one or more embodiments, R 1 Each is independently selected from C1-C10 alkyl, hydroxyl and nitro.

[0017] In one or more embodiments, n is an integer from 0 to 2.

[0018] In one or more embodiments, R 2 For benzene ring, naphthalene ring, anthracene ring, ring, a perylene ring, a benzopyrene ring, a furan ring, a pyrrole ring, a thiophene ring, a thiazole ring, an imidazole ring, a pyrazole ring, an oxazole ring, a pyridine ring, a pyran ring, a pyridazine ring, a pyrimidine ring, an indole ring, a purine ring, a quinoline ring or an isoquinoline ring.

[0019] In one or more embodiments, in step (1), the molar ratio of the ketone compound to the trifluoromethyltrimethylsilane is 1:(1-10), preferably 1:(1-5), and more preferably 1:(1-2).

[0020] In one or more embodiments, in step (1), the molar ratio of the ketone compound to the carbonate catalyst is 1:(0.01-0.1), preferably 1:(0.02-0.05).

[0021] In one or more embodiments, in step (1), the reaction temperature is 20 to 100°C, preferably 20 to 60°C.

[0022] In one or more embodiments, in step (1), the reaction time is 2 to 10 hours, preferably 4 to 6 hours.

[0023] In one or more embodiments, in step (2), the acidification reaction is carried out in a solvent; preferably, the solvent is a non-polar solvent; preferably, the non-polar solvent is selected from one or more of ethyl acetate, butyl acetate, tetrahydrofuran, chloroform and carbon tetrachloride; preferably, the mass ratio of the intermediate product to the solvent is 1:(1-10), preferably 1:(1-5).

[0024] In one or more embodiments, in step (2), the acidification reaction is carried out in a protective atmosphere;

[0025] In one or more embodiments, in step (2), the acid used in the acidification reaction is an organic acid or an inorganic acid.

[0026] In one or more embodiments, the organic acid is selected from one or more of formic acid, acetic acid, methanesulfonic acid and malonic acid, and the inorganic acid is selected from one or more of hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid.

[0027] In one or more embodiments, in step (2), the molar ratio of the intermediate product to the acid used in the acidification reaction is 1:(1-2), preferably 1:(1-1.5).

[0028] In one or more embodiments, in step (2), the reaction temperature is 20 to 100°C, preferably 20 to 60°C.

[0029] In one or more embodiments, in step (2), the reaction time is 1 to 10 hours, preferably 2 to 5 hours. DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to understand the characteristics and effects of the present invention, the following is a general description and definition of the terms and expressions mentioned in the specification and claims. Unless otherwise specified, all technical and scientific terms used in the text are the common meanings understood by those skilled in the art for the present invention. In the event of a conflict, the definition in this specification shall prevail.

[0031] The theories or mechanisms described and disclosed herein, whether correct or incorrect, should not limit the scope of the present invention in any way, that is, the present invention can be implemented without being limited by any specific theory or mechanism.

[0032] Herein, “comprising”, “including”, “containing” and similar terms encompass the meanings of “consisting essentially of” and “consisting of”. For example, when “A comprises B and C” is disclosed herein, “A consists essentially of B and C” and “A consists of B and C” should be deemed to be disclosed herein.

[0033] In this article, all features such as values, quantities, contents and concentrations defined in the form of numerical ranges or percentage ranges are only for brevity and convenience. Accordingly, the description of numerical ranges or percentage ranges should be considered to have included and specifically disclosed all possible secondary ranges and individual values ​​within the range (including integers and fractions).

[0034] In this document, unless otherwise specified, percentage refers to mass percentage and ratio refers to mass ratio.

[0035] Herein, when describing embodiments or examples, it should be understood that they are not used to limit the present invention to these embodiments or examples. On the contrary, all substitutes, improvements and equivalents of the methods and materials described in the present invention can be included in the scope limited by the claims.

[0036] In this document, in order to make the description concise, not all possible combinations of various technical features in various embodiments or examples are described. Therefore, as long as there is no contradiction in the combination of these technical features, the various technical features in various embodiments or examples can be combined arbitrarily, and all possible combinations should be considered to be within the scope of this specification.

[0037] The present invention provides a method for synthesizing trifluoromethyl tertiary alcohol compounds, the method comprising the following steps:

[0038] (1) mixing a ketone compound, trifluoromethyltrimethylsilane and a carbonate catalyst to react to obtain an intermediate product;

[0039] (2) subjecting the intermediate product obtained in step (1) to an acidification reaction to obtain a trifluoromethyl tertiary alcohol compound.

[0040] In the present invention, trifluoromethyltrimethylsilane is used as a trifluoromethylating agent with strong nucleophilicity. Due to the strong electron-withdrawing effect of the trifluoromethyl group, CF 3 -Si have very small chemical bond energy. Through the action of carbonate catalyst, CF 3 -Si C-Si bond between the two is easily broken, CF 3 - It acts as an anionic nucleophilic group to attack the carbonyl group in ketone compounds, completes the transfer of trifluoromethyl, and then acidifies under acidic conditions to prepare tertiary alcohol. The reaction process is mild, the product yield is high, the atomic utilization rate is high, and it is economical and environmentally friendly.

[0041] In the present invention, the ketone compound has a structure shown in Formula I:

[0042]

[0043] In Formula I, R 1 Each is independently selected from C1-C10 alkyl, C1-C10 alkoxy, hydroxy, nitro, aromatic heterocycle, phenoxy, carboxyl, amino and halogen, R 2 is an aromatic ring, n is an integer from 0 to a, a is R 2 The maximum number of substituents that can exist on the 3 It is a C1~C10 alkyl group.

[0044] In the present invention, the aromatic ring refers to a cyclic organic group having 4m+2 (m is a natural number) delocalized π electrons.

[0045] In the present invention, the aromatic heterocycle refers to an aromatic ring whose ring atoms include at least one heteroatom selected from N, S and O.

[0046] Preferably, R 1 are each independently selected from C1-C10 alkyl, hydroxyl and nitro. 1 It is hydroxyl.

[0047] Preferably, n is an integer from 0 to 2. In some embodiments, n is 0 or 1.

[0048] Preferably, R 2 For benzene ring, naphthalene ring, anthracene ring, In some embodiments, R 2 is a benzene ring, a naphthalene ring, a pyridine ring, a thiophene ring or a furan ring. 2 It is a benzene ring or a naphthalene ring.

[0049] In some specific embodiments, the ketone compound is selected from the following compounds:

[0050]

[0051] In step (1), the reaction is carried out in a solvent. Preferably, the solvent can be selected from one or more of ethanol, toluene, N,N-dimethylformamide, 1,2-dichloroethane, acetonitrile, 1,4-dioxane, dimethyl sulfoxide, ethylene glycol and ethyl acetate. Preferably, the mass ratio of the ketone compound to the solvent can be 1:1 to 1:10, preferably 1:1 to 1:2, for example 1:1, 1:1.2, 1:1.4, 1:1.6, 1:1.8, 1:2.

[0052] In step (1), the reaction is carried out in a protective atmosphere (eg, a nitrogen atmosphere).

[0053] In step (1), the carbonate catalyst may be a metal carbonate. Preferably, the metal carbonate may be selected from one or more of potassium carbonate, sodium carbonate, magnesium carbonate and calcium carbonate. In the present invention, carbonate is a bilateral catalyst. Compared with fluoride salts, carbonate has the advantages of good catalytic effect, fast reaction, high conversion rate, high yield, high catalytic activity, mild reaction and greatly shortened total reaction time.

[0054] In step (1), the molar ratio of the ketone compound to trifluoromethyltrimethylsilane can be 1:(1-10), preferably 1:(1-5), more preferably 1:(1-2), such as 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9. Setting the feed ratio within a more preferred molar ratio range is conducive to shortening the total reaction time and improving the total yield.

[0055] In step (1), the molar ratio of the ketone compound to the carbonate catalyst can be 1:(0.01-0.1), preferably 1:(0.02-0.05), for example 1:0.025, 1:0.030, 1:0.035, 1:0.040, 1:045. Setting the feed ratio within the preferred molar ratio range is conducive to shortening the total reaction time and improving the total yield.

[0056] In step (1), the reaction temperature can be 20-100°C, preferably 20-60°C, for example 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C.

[0057] In step (1), the reaction time may be 2 to 10 h, preferably 4 to 6 h, for example 4 h, 4.5 h, 5 h, 5.5 h, 6 h.

[0058] In step (2), the acidification reaction is carried out in a solvent. Preferably, the solvent can be a non-polar solvent. Available non-polar solvents can be selected from one or more of ethyl acetate, butyl acetate, tetrahydrofuran, chloroform and carbon tetrachloride. Preferably, the mass ratio of the intermediate product to the solvent can be 1: (1 to 10), preferably 1: (1 to 5), for example 1: 1.5, 1: 2, 1: 2.5, 1: 3, 1: 3.5, 1: 4, 1: 4.5.

[0059] In step (2), the acidification reaction is carried out in a protective atmosphere (eg, a nitrogen atmosphere).

[0060] In step (2), the acid used in the acidification reaction may be an organic acid or an inorganic acid.

[0061] In step (2), the organic acid may be one or more selected from formic acid, acetic acid, methanesulfonic acid and malonic acid. The inorganic acid may be one or more selected from hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid.

[0062] In step (2), the molar ratio of the intermediate product to the acid used in the acidification reaction is 1:(1-2), preferably 1:(1-1.5), for example 1:1, 1:1.1, 1:1.2, 1:1.3, 1:4, 1:1.5.

[0063] In step (2), the reaction temperature can be 20-100°C, preferably 20-60°C, for example 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C.

[0064] In step (2), the reaction time may be 1 to 10 h, preferably 2 to 5 h, for example 2 h, 3 h, 4 h, or 5 h.

[0065] Compared with the prior art, the present invention has the following beneficial effects:

[0066] (1) In the present invention, carbonates are used as catalysts, which greatly reduces the cost due to the low price of carbonates;

[0067] (2) In the present invention, due to the excellent catalytic effect of carbonate, the activation energy required for the reaction is greatly reduced, so that the reaction can be carried out at room temperature, the process conditions are optimized, the reaction conditions are mild, the use conditions are wide, and the requirements for water and oxygen conditions are not harsh;

[0068] (3) In the present invention, the reaction rate is high and the reaction time is greatly shortened;

[0069] (4) In the present invention, the atomic utilization rate is high, the yield of the main product is high, and the side reactions are few;

[0070] (5) In the present invention, the reaction process is simple and can be industrially scaled up for production;

[0071] (6) The present invention avoids the side reactions caused by using Grignard reagent to prepare alcohol compounds.

[0072] The present invention will be described below in the form of specific examples. It should be understood that these examples are merely illustrative and are not intended to limit the scope of the present invention. The methods, reagents and materials used in the examples are, unless otherwise stated, conventional methods, reagents and materials in the art. The raw material compounds in the examples can all be purchased through commercial routes.

[0073] Example 1

[0074] (1)N 2 Under the atmosphere, 68.07g (0.5mol) of p-hydroxyacetophenone, 71.09g (0.5mol) of trifluoromethyltrimethylsilane, 1.73g (0.0125mol) of anhydrous potassium carbonate and 100g of N,N-dimethylformamide were added to a 250mL four-necked flask, and the reaction was stirred at 25°C. The progress of the reaction was monitored by thin layer chromatography (TLC), and the reaction was completed in 4h. After the reaction was completed, saturated brine (2×20mL) was added to the reactant system twice for salt washing, and then ethyl acetate (3×100mL) was used for liquid separation and extraction. The upper organic layer was collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 133.61g of light white solid, i.e., 4-(2,2,2-trifluoro-1-methyl-1-((trimethylsilyl)oxy)ethyl)phenol, with a yield of 96.0% and a purity of 97.0%.

[0075]

[0076] (2)N 2 Under the atmosphere, 25 g of hydrochloric acid and 250 g of ethyl acetate were added to the obtained 4-(2,2,2-trifluoro-1-methyl-1-((trimethylsilyl)oxy)ethyl)phenol, and stirred at 25°C for 2 h. After the reaction was completed, ethyl acetate (3×50 mL) was used for liquid extraction, and the organic phases were combined. The organic phases were first washed twice with water (2×50 mL), and then washed twice with 10% saturated sodium carbonate (2×20 mL) and saturated brine (2×20 mL), respectively. The organic phases were collected, dried over anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 93.02 g of white solid, i.e., 4-(1,1,1-trifluoro-2-hydroxypropane-2-yl)phenol, with a yield of 94% and a purity of 98%.

[0077]

[0078] Example 2

[0079] (1)N 2Under the atmosphere, 80.0g (0.47mol) 1-naphthone, 100.28g (0.71mol) trifluoromethyltrimethylsilane, 1.33g (0.0125mol) sodium carbonate and 120g dimethyl sulfoxide were added to a 250mL four-necked flask, stirred at 25°C, and the reaction progress was monitored by TLC. The reaction was completed in 6h. After the reaction was completed, saturated salt water (2×15mL) was added to the reactant system twice for salt washing, and then dichloromethane (3×150mL) was used for liquid separation and extraction. The upper organic layer was collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 128.8g of light yellow solid, i.e., 1-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]naphthalene, with a yield of 87.7% and a purity of 95.0%.

[0080]

[0081] (2)N 2 Under the atmosphere, 30g nitric acid and 300g tetrahydrofuran were added to the obtained 1-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]naphthalene, and stirred at 25°C for 4h. After the reaction was completed, tetrahydrofuran (3×100mL) was used for liquid separation and extraction, and the organic phases were combined, and the organic phases were first washed twice with water (2×50mL), and then washed twice with 10% saturated sodium carbonate (2×25mL) and saturated brine (3×20mL), respectively, and the organic phases were collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate was collected, and then the solvent was removed under reduced pressure to obtain 126.1g of yellow-white solid, i.e., α-methyl-α-trifluoromethyl-1-naphthylmethanol, with a yield of 97.9% and a purity of 96.2%.

[0082]

[0083] Comparative Example 1

[0084] (1)N 2Under the atmosphere, 68.09g (0.5mol) of p-hydroxyacetophenone, 71.10g (0.5mol) of trifluoromethyltrimethylsilane, 3.57g (0.0235mol) of cesium fluoride and 100g of N,N-dimethylformamide were added to a 250mL four-necked flask, and the reaction was stirred at 25°C. The progress of the reaction was monitored by TLC, and the reaction was completed after 35h. After the reaction was completed, saturated brine (2×20mL) was added to the reactant system twice for salt washing, and then separated and extracted with ethyl acetate (3×100mL). The upper organic layer was collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 86.29g of white solid, i.e., 4-(2,2,2-trifluoro-1-methyl-1-((trimethylsilyl)oxy)ethyl)phenol, with a yield of 62.1% and a purity of 93.9%.

[0085]

[0086] (2)N 2 Under the atmosphere, 22g of hydrochloric acid and 250g of ethyl acetate were added to the obtained 4-(2,2,2-trifluoro-1-methyl-1-((trimethylsilyl))oxy)ethyl)phenol, and stirred at 25°C for 2h. After the reaction was completed, ethyl acetate (3×50mL) was used for liquid extraction, and the organic phases were combined. The organic phases were first washed twice with water (2×50mL), and then washed twice with 10% saturated sodium carbonate (2×20mL) and saturated brine (2×20mL), respectively, and the organic phases were collected, dried over anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 83.02g of white solid, i.e., 4-(1,1,1-trifluoro-2-hydroxypropane-2-yl)phenol, with a yield of 96.22% and a purity of 95.6%.

[0087]

[0088] Comparative Example 2

[0089] (1)N 2Under the atmosphere, 80.0g (0.47mol) 1-naphthone, 100.25g (0.71mol) trifluoromethyltrimethylsilane, 1.37g (0.0235mol) potassium fluoride and 120g dimethyl sulfoxide were added to a 250mL four-necked flask, stirred at 25°C, and the reaction progress was monitored by TLC. The reaction was completed after 35h. After the reaction was completed, saturated brine (2×15mL) was added to the reactant system twice for salt washing, and then dichloromethane (3×150mL) was used for liquid separation and extraction. The upper organic layer was collected, dried with anhydrous magnesium sulfate, filtered, the filtrate was collected, and then the solvent was removed under reduced pressure to obtain 84.73g of yellow-white solid, i.e., 1-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]naphthalene, with a yield of 57.7% and a purity of 95%.

[0090]

[0091] (2)N 2 Under the atmosphere, 30g nitric acid and 300g tetrahydrofuran were added to the obtained 1-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]naphthalene, and stirred at 25°C for 5h. After the reaction was completed, tetrahydrofuran (3×100mL) was used for liquid extraction, and the organic phases were combined. The organic phases were first washed twice with water (2×50mL), and then washed twice with 10% saturated sodium carbonate (2×25mL) and saturated brine (3×20mL), respectively, and the organic phases were collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate was collected. Then, the solvent was removed under reduced pressure to obtain 82.1g of yellow-white solid, i.e., α-methyl-α-trifluoromethyl-1-naphthylmethanol, with a yield of 96.9% and a purity of 96.1%.

[0092]

[0093] After the reaction of Example 1-2 and Comparative Example 1-2 was completed, the remaining amount of the ketone compound was detected by gas phase.

[0094] Yield = actual amount of target product produced / theoretical amount of target product produced × 100%

[0095] Total yield = first step reaction yield × second step reaction yield

[0096] Conversion rate = (mass of ketone compound before reaction - mass of ketone compound after reaction) / mass of ketone compound before reaction × 100%

[0097] The experimental results of the total reaction time, total yield and conversion rate of the synthesis of trifluoromethyl tertiary alcohol compounds in Example 1-2 and Comparative Example 1-2 are summarized in Table 1.

[0098] Table 1: Experimental results of total reaction time, total yield and conversion rate of synthesis of trifluoromethyl tertiary alcohol compounds in Example 1-2 and Comparative Example 1-2

[0099] Catalyst type Total reaction time / h Total yield / % Conversion rate / % Example 1 Potassium carbonate 6 90.24 99.8 Example 2 Sodium carbonate 10 85.86 99.6 Comparative Example 1 Cesium fluoride 37 59.75 99.5 Comparative Example 2 Potassium fluoride 40 55.91 99.1

Claims

1. A method for synthesizing trifluoromethyl tertiary alcohol compounds, characterized in that: The method comprises the following steps: (1) mixing a ketone compound, trifluoromethyltrimethylsilane and a carbonate catalyst to react to obtain an intermediate product; (2) subjecting the intermediate product obtained in step (1) to an acidification reaction to obtain a trifluoromethyl tertiary alcohol compound.

2. The method according to claim 1, characterized in that The method has one or more of the following features: In step (1), the reaction is carried out in a solvent; preferably, the solvent is selected from one or more of ethanol, toluene, N,N-dimethylformamide, 1,2-dichloroethane, acetonitrile, 1,4-dioxane, dimethyl sulfoxide, ethylene glycol and ethyl acetate; preferably, the mass ratio of the ketone compound to the solvent is 1:(1-10), preferably 1:(1-2); In step (1), the reaction is carried out in a protective atmosphere; In step (1), the carbonate catalyst is a metal carbonate; preferably, the metal carbonate is selected from one or more of potassium carbonate, sodium carbonate, magnesium carbonate and calcium carbonate.

3. The method according to claim 1, characterized in that The ketone compound has a structure shown in Formula I: In Formula I, R1 is independently selected from C1-C10 alkyl, C1-C10 alkoxy, hydroxy, nitro, aromatic heterocycle, phenoxy, carboxyl, amino and halogen, R2 is an aromatic ring, n is an integer from 0 to a, a is the maximum number of substituents that can exist on R2, and R3 is a C1-C10 alkyl; Preferably, R1 is each independently selected from C1-C10 alkyl, hydroxyl and nitro; Preferably, n is an integer from 0 to 2; Preferably, R2 is a benzene ring, a naphthalene ring, an anthracene ring, ring, a perylene ring, a benzopyrene ring, a furan ring, a pyrrole ring, a thiophene ring, a thiazole ring, an imidazole ring, a pyrazole ring, an oxazole ring, a pyridine ring, a pyran ring, a pyridazine ring, a pyrimidine ring, an indole ring, a purine ring, a quinoline ring or an isoquinoline ring.

4. The method according to claim 1, characterized in that In step (1), the molar ratio of the ketone compound to the trifluoromethyltrimethylsilane is 1:(1-10), preferably 1:(1-5), more preferably 1:(1-2); and / or In step (1), the molar ratio of the ketone compound to the carbonate catalyst is 1:(0.01-0.1), preferably 1:(0.02-0.05).

5. The method according to claim 1, characterized in that In step (1), the reaction temperature is 20 to 100°C, preferably 20 to 60°C.

6. The method according to claim 1, characterized in that In step (1), the reaction time is 2 to 10 hours, preferably 4 to 6 hours.

7. The method according to claim 1, characterized in that The method has one or more of the following features: In step (2), the acidification reaction is carried out in a solvent; preferably, the solvent is a non-polar solvent; preferably, the non-polar solvent is selected from one or more of ethyl acetate, butyl acetate, tetrahydrofuran, chloroform and carbon tetrachloride; preferably, the mass ratio of the intermediate product to the solvent is 1:(1-10), preferably 1:(1-5); In step (2), the acidification reaction is carried out in a protective atmosphere; In step (2), the acid used in the acidification reaction is an organic acid or an inorganic acid.

8. The method according to claim 7, characterized in that The organic acid is selected from one or more of formic acid, acetic acid, methanesulfonic acid and malonic acid, and the inorganic acid is selected from one or more of hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid.

9. The method according to claim 1, characterized in that In step (2), the molar ratio of the intermediate product to the acid used in the acidification reaction is 1:(1-2), preferably 1:(1-1.5).

10. The method according to claim 1, characterized in that In step (2), the reaction temperature is 20 to 100°C, preferably 20 to 60°C; and / or In step (2), the reaction time is 1 to 10 hours, preferably 2 to 5 hours.

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