Method for continuously preparing m-trifluoromethyl acetophenone
By using m-trifluoromethyl benzoate as raw material, combined with the microchannel reactor and scraper film evaporator, the high cost and low yield problems of the existing m-trifluoromethylacetophenone synthesis method are solved, and efficient and low pollution continuous production is achieved.
Patent Information
- Application Number
- CN202510615334.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-14
- Publication Date
- 2025-08-19
AI Technical Summary
The existing synthesis method of trifluoromethylacetophenone has problems such as cumbersome reaction steps, many side reactions, high wastewater consumption, high production costs, expensive reagents and low yields, making it difficult to achieve large-scale industrial production.
Using methyl m-trifluoromethylbenzoate as the starting material, the condensation reaction with the acetate under the action of alkali, then the contact hydrolysis and decarboxylation reaction are carried out under the action of dilute acid, and efficient separation is performed using a micro-channel reactor and a scraper film evaporator to obtain high-purity m-trifluoromethylacetophenone.
It has achieved efficient and low-cost synthesis of intertrifluoromethylacetophenone, with a product yield of more than 90% and a purity of more than 99%, reducing the generation of three wastes, reducing production risks, and suitable for continuous production.
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Figure CN120504585A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for continuously preparing m-trifluoromethylacetophenone. Background Art
[0002] 3'-(Trifluoromethyl)acetophenone, with a molecular formula of C9H7F3O and a boiling point of 198-200°C, is a colorless or pale yellow liquid. It is a key intermediate in the synthesis of the methoxypropylene compound trifloxystrobin (trade name Flint) and an important raw material for the synthesis of pharmaceuticals and dyes.
[0003] Currently, there are several main methods for synthesizing m-trifluoromethylacetophenone: (1) Using m-trifluoromethylaniline as the starting material, m-trifluoromethylacetophenone is synthesized through diazotization, coupling reaction and hydrolysis. This is the mainstream route for industrial production. However, this route has complicated reaction steps, many side reactions, and wastewater consumption is as high as 30% or more. The production capacity is low and the production cost is high. (2) Using m-chlorotrifluorotoluene as the raw material, m-trifluoromethylacetophenone is synthesized by reacting it with acetonitrile after Grignard reaction. (3) Using trifluoromethylbenzene as the raw material, m-trifluoromethylacetophenone is synthesized by bromination, Grignard reaction and acetic anhydride after reaction. (4) Grignard reaction of m-trifluoromethylbenzonitrile with iodomethane. (5) Reaction of m-trifluoromethylbenzaldehyde with diazomethane. (6) Using ionic liquid as the reaction medium, m-trifluoromethyl halogenated benzene is reacted with vinyl ether compound (Heck reaction) in the presence of palladium catalyst, ligand and triethylamine to synthesize m-trifluoromethylacetophenone. Routes (2) to (6) all have the disadvantages of expensive reagents, high risk, and low yield, making them difficult to carry out large-scale industrial production.
[0004] Therefore, it is of great significance to provide a method for synthesizing m-trifluoromethylacetophenone oxime with low raw material consumption, small amount of three wastes generated, high production capacity and simple process route. Summary of the Invention
[0005] To solve the above problems, the present invention aims to provide a method for continuously preparing m-trifluoromethylacetophenone.
[0006] To achieve the above-mentioned purpose, the present invention is implemented through the following technical solutions:
[0007] The invention discloses a method for continuously preparing m-trifluoromethylacetophenone. The method comprises the following steps: using m-trifluoromethylbenzoic acid methyl ester as a starting material, condensing the methyl ester with acetate under the action of a base, and then synthesizing the m-trifluoromethylacetophenone under the action of a dilute acid.
[0008] The method for continuously preparing m-trifluoromethylacetophenone specifically comprises the following steps:
[0009] 1) Add a base to an alcohol solvent and acetate, heat to 40-60°C, stir for 15 minutes, and filter press to obtain reaction solution 1;
[0010] 2) injecting methyl m-trifluoromethylbenzoate and the reaction solution 1 prepared in step 1) into a microchannel reactor 1 via a metering pump, and carrying out a contact condensation reaction at 70-90° C. and 0.6-0.8 MPa for 6-10 seconds to obtain a reaction solution 2;
[0011] 3) The reaction solution 2 prepared in step 2) and the dilute acid are pumped into the microchannel reactor 2 via a metering pump, and a contact hydrolysis and decarboxylation reaction is carried out at 100-120° C. and 0.6-0.8 MPa for 6-10 seconds to obtain a reaction solution 3;
[0012] 4) passing the reaction solution 3 prepared in step 3) into a scraped film evaporator, setting the scraped film evaporator temperature to 110-120° C., to obtain an evaporated liquid;
[0013] 5) The evaporated liquid obtained in step 4) is transferred to a reaction kettle, and the organic solvent is removed by reduced pressure distillation at 40-60° C., and the aqueous phase is separated to obtain m-trifluoromethylacetophenone.
[0014] The alcohol solvent in step 1) is one or two of methanol, ethanol and isopropanol.
[0015] The acetate in step 1) is one or two of methyl acetate, ethyl acetate and isopropyl acetate.
[0016] The base in step 1) is one or two of sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide.
[0017] The molar ratio of the acetate in step 1), the base, the methyl m-trifluoromethylbenzoate in step 2), and the dilute acid in step 3) is 1.2-1.5:2.0-2.5:3.0-4.0:1.
[0018] The amount of the alcohol solvent used in step 1) is 2 to 3 times the mass of the methyl m-trifluoromethylbenzoate in step 2).
[0019] The dilute acid in step 3) is one or both of dilute hydrochloric acid and dilute sulfuric acid, and the mass concentration of the dilute acid is 8-10%.
[0020] Preferably, in step 1), the alcohol solvent is methanol, the acetate is methyl acetate, the base is sodium methoxide, and the dilute acid is dilute hydrochloric acid.
[0021] Preferably, the heating in step 1) is to 50-60°C.
[0022] Preferably, the contact condensation reaction in step 2) is carried out at 75-85° C. When the temperature is too low, the reaction is likely to be incomplete, and when the temperature is too high, more side reactions may occur.
[0023] Preferably, the contact hydrolysis and decarboxylation reaction in step 3) is carried out at 105-115° C. When the temperature is too low, the reaction is likely to be incomplete, and when the temperature is too high, more side reactions may occur.
[0024] The synthetic route of m-trifluoromethylacetophenone of the present invention is:
[0025]
[0026] Compared with the prior art, the present invention has the following advantages:
[0027] The method for continuously preparing m-trifluoromethylacetophenone of the present invention uses m-trifluoromethylbenzoic acid methyl ester as a raw material, and obtains m-trifluoromethylacetophenone through Clemmensen condensation and ketolysis. Methanol is used as a solvent, which increases the mixing of the two phases and the solubility of the base, while reducing the amount of acetate used and avoiding excessive acetic acid produced by hydrolysis. A microchannel reactor is used for the reaction. Due to its efficient mass transfer effect and the ability to achieve pressure reaction, the reaction temperature can be increased while retaining the alcohol solvent, avoiding the disadvantage of poor mixing in the two-phase reaction and greatly shortening the reaction time. The reaction liquid obtained from the microchannel reactor is passed into a scraped film evaporator, and the m-trifluoromethylacetophenone is directly distilled out by utilizing the characteristic that water can form an azeotrope with the m-trifluoromethylacetophenone. Finally, the distilled reaction liquid is subjected to reduced pressure distillation to remove the low-boiling point organic solvent, and the water phase is separated to obtain high-purity m-trifluoromethylacetophenone.
[0028] The reaction process of the invention is simple and efficient, the post-treatment is simple and easy to operate, the product yield is high, the production cost is low, the three wastes are less, the pollution is small, the production risk is low, the controllability is good, and continuous production can be achieved. The total yield of the prepared m-trifluoromethylacetophenone is above 90%, and the purity is above 99%. BRIEF DESCRIPTION OF THE DRAWINGS
[0029] Figure 1 The present invention is a process flow chart for the continuous preparation of m-trifluoromethylacetophenone. DETAILED DESCRIPTION
[0030] In order to better understand the technical solutions of the present invention, the following is a further detailed description of the above content of the present invention through specific implementation methods in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention.
[0031] Example 1
[0032] 43.24 g of sodium methoxide was added to 163.32 g of methanol and 35.56 g of methyl acetate, heated to 50° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 80° C. and 0.7 MPa for 8 s to obtain reaction solution 2; reaction solution 2 and 567.16 g of dilute hydrochloric acid with a mass concentration of 9% were pumped into the reaction solution 1 via a metering pump. The reaction mixture was added to a microchannel reactor 2, and catalytic hydrolysis and decarboxylation reactions were carried out at 110° C. and 0.7 MPa for 8 seconds to obtain a reaction solution 3. The reaction solution 3 was passed into a wiper film evaporator, and the temperature of the wiper film evaporator was set to 110° C. to obtain an evaporated liquid. The obtained evaporated liquid was transferred to a reactor, and the organic solvent was removed by reduced pressure distillation at 40° C., and the aqueous phase was separated to obtain 70.03 g of m-trifluoromethylacetophenone with a product purity of 99.69% and a yield of 93.05%.
[0033] Example 2
[0034] 62.61 g of sodium ethoxide was added to 204.15 g of ethanol and 45.82 g of ethyl acetate, heated to 45° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 75° C. and 0.6 MPa for 8 s to obtain reaction solution 2; reaction solution 2 and 1524.44 g of dilute sulfuric acid with a mass concentration of 9% were pumped into the reaction solution 1 via a metering pump. The reaction mixture was injected into microchannel reactor 2, and catalytic hydrolysis and decarboxylation reactions were carried out at 105°C and 0.6 MPa for 8 seconds to obtain reaction solution 3. The reaction solution 3 was passed into a scraped film evaporator, and the temperature of the scraped film evaporator was set to 115°C to obtain an evaporated liquid. The obtained evaporated liquid was transferred to a reactor, and the organic solvent was removed by reduced pressure distillation at 50°C. The aqueous phase was separated to obtain 69.83 g of m-trifluoromethylacetophenone with a product purity of 99.49% and a yield of 92.81%.
[0035] Example 3
[0036] 70.13 g of potassium methoxide was added to 244.98 g of isopropanol and 61.28 g of isopropyl acetate, heated to 60° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 90° C. and 0.8 MPa for 6 s to obtain reaction solution 2; reaction solution 2 and 583.36 g of dilute hydrochloric acid with a mass concentration of 10% were measured. The reaction mixture was pumped into microchannel reactor 2, where catalytic hydrolysis and decarboxylation reactions were carried out at 100° C. and 0.8 MPa for 6 seconds to obtain reaction solution 3. The reaction solution 3 was passed into a wiper film evaporator at a temperature of 120° C. to obtain an evaporated liquid. The evaporated liquid was transferred to a reactor, where the organic solvent was removed by reduced pressure distillation at 60° C., and the aqueous phase was separated to obtain 68.78 g of m-trifluoromethylacetophenone with a product purity of 99.33% and a yield of 91.39%.
[0037] Example 4
[0038] 74.06 g of potassium ethoxide was added to 244.98 g of methanol and 52.87 g of ethyl acetate, heated to 60° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 70° C. and 0.6 MPa for 10 s to obtain reaction solution 2; reaction solution 2 and 546.90 g of dilute hydrochloric acid with a mass concentration of 8% were pumped into the reaction solution 1 via a metering pump. The reaction mixture was added to microchannel reactor 2, and catalytic hydrolysis and decarboxylation reactions were carried out at 120° C. and 0.6 MPa for 10 s to obtain reaction solution 3. The reaction solution 3 was passed into a scraped film evaporator, and the temperature of the scraped film evaporator was set to 120° C. to obtain an evaporated liquid. The obtained evaporated liquid was transferred to a reactor, and the organic solvent was removed by reduced pressure distillation at 60° C., and the aqueous phase was separated to obtain 69.39 g of m-trifluoromethylacetophenone with a product purity of 99.61% and a yield of 92.20%.
[0039] Example 5
[0040] 43.24 g of sodium methoxide was added to 163.32 g of methanol and 42.30 g of ethyl acetate, heated to 50° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 70° C. and 0.6 MPa for 9 s to obtain reaction solution 2; reaction solution 2 and 546.90 g of dilute hydrochloric acid with a mass concentration of 8% were pumped into the reaction solution 1 via a metering pump. The reaction mixture was introduced into microchannel reactor 2, where catalytic hydrolysis and decarboxylation reactions were carried out at 100° C. and 0.6 MPa for 7 seconds to obtain reaction solution 3. The reaction solution 3 was introduced into a wiper film evaporator, and the temperature of the wiper film evaporator was set to 110° C. to obtain an evaporated liquid. The obtained evaporated liquid was transferred to a reactor, and the organic solvent was removed by reduced pressure distillation at 40° C. The aqueous phase was separated to obtain 69.04 g of m-trifluoromethylacetophenone with a product purity of 99.42% and a yield of 91.74%.
[0041] Example 6
[0042] 49.68 g of sodium methoxide was added to 200 g of methanol and 38.52 g of methyl acetate, heated to 55° C., stirred for 15 min, and filtered to obtain reaction solution 1; 81.66 g of methyl m-trifluoromethylbenzoate and reaction solution 1 were pumped into microchannel reactor 1 via a metering pump, and a contact condensation reaction was carried out at 85° C. and 0.7 MPa for 8 s to obtain reaction solution 2; reaction solution 2 and 567.16 g of dilute hydrochloric acid with a mass concentration of 9% were pumped into In microchannel reactor 2, a catalytic hydrolysis and decarboxylation reaction was carried out at 115° C. and 0.7 MPa for 8 seconds to obtain a reaction solution 3; the reaction solution 3 was passed into a scraped film evaporator, and the temperature of the scraped film evaporator was set to 115° C. to obtain an evaporated liquid; the obtained evaporated liquid was transferred to a reactor, and the organic solvent was removed by reduced pressure distillation at 50° C., and the aqueous phase was separated to obtain 69.90 g of m-trifluoromethylacetophenone with a product purity of 99.69% and a yield of 92.88%.
[0043] Although the above describes the specific implementation methods of the present invention, it does not limit the scope of protection of the present invention. Based on the technical solution of the present invention, various modifications or variations that can be made by those skilled in the art without creative work are still within the scope of protection of the present invention.
Claims
1. A method for continuously preparing m-trifluoromethylacetophenone, characterized in that: Methyl m-trifluoromethylbenzoate is used as the starting material, which undergoes condensation with acetate in the presence of a base, and then is synthesized in the presence of a dilute acid to form m-trifluoromethylacetophenone.
2. The method for continuously preparing m-trifluoromethylacetophenone according to claim 1, wherein: The specific steps include: 1) Add a base to an alcohol solvent and acetate, heat to 40-60°C, stir for 15 minutes, and filter press to obtain reaction solution 1; 2) injecting methyl m-trifluoromethylbenzoate and the reaction solution 1 prepared in step 1) into a microchannel reactor 1 via a metering pump, and carrying out a contact condensation reaction at 70-90° C. and 0.6-0.8 MPa for 6-10 seconds to obtain a reaction solution 2; 3) The reaction solution 2 prepared in step 2) and the dilute acid are pumped into the microchannel reactor 2 via a metering pump, and a contact hydrolysis and decarboxylation reaction is carried out at 100-120° C. and 0.6-0.8 MPa for 6-10 seconds to obtain a reaction solution 3; 4) passing the reaction solution 3 prepared in step 3) into a scraped film evaporator, setting the scraped film evaporator temperature to 110-120° C., to obtain an evaporated liquid; 5) The evaporated liquid obtained in step 4) is transferred to a reaction kettle, and the organic solvent is removed by reduced pressure distillation at 40-60° C., and the aqueous phase is separated to obtain m-trifluoromethylacetophenone.
3. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The alcohol solvent in step 1) is one or two of methanol, ethanol and isopropanol.
4. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The acetate in step 1) is one or two of methyl acetate, ethyl acetate and isopropyl acetate.
5. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The base in step 1) is one or two of sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide.
6. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The molar ratio of the acetate in step 1), the base, the methyl m-trifluoromethylbenzoate in step 2), and the dilute acid in step 3) is 1.2-1.5:2.0-2.5:3.0-4.0:
1.
7. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The amount of the alcohol solvent used in step 1) is 2 to 3 times the mass of the methyl m-trifluoromethylbenzoate in step 2).
8. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The dilute acid in step 3) is one or both of dilute hydrochloric acid and dilute sulfuric acid, and the mass concentration of the dilute acid is 8-10%.
9. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: In step 1), the alcohol solvent is methanol, the acetate is methyl acetate, the base is sodium methoxide, and the dilute acid is dilute hydrochloric acid; and in step 1), the temperature is heated to 50-60°C.
10. The method for continuously preparing m-trifluoromethylacetophenone according to claim 2, wherein: The contact condensation reaction in step 2) is carried out at 75-85° C.; and the contact hydrolysis and decarboxylation reaction in step 3) is carried out at 105-115° C.