WO2022061920A1 - Procédé de préparation de 3',5'-dichloro-2,2,2-trifluoroacétophénone - Google Patents

Procédé de préparation de 3',5'-dichloro-2,2,2-trifluoroacétophénone Download PDF

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WO2022061920A1
WO2022061920A1 PCT/CN2020/118513 CN2020118513W WO2022061920A1 WO 2022061920 A1 WO2022061920 A1 WO 2022061920A1 CN 2020118513 W CN2020118513 W CN 2020118513W WO 2022061920 A1 WO2022061920 A1 WO 2022061920A1
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acid
compound
trifluoroacetophenone
dichloro
reaction solution
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PCT/CN2020/118513
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Chinese (zh)
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蔡刚华
张凌霄
唐宏渊
程锦涛
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台州臻挚生物科技有限公司
浙江江北南海药业有限公司
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Priority to PCT/CN2020/118513 priority Critical patent/WO2022061920A1/fr
Publication of WO2022061920A1 publication Critical patent/WO2022061920A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
    • C07C245/20—Diazonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen

Definitions

  • the application relates to the technical field of chemical pharmacy, in particular to a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone.
  • 3',5'-dichloro-2,2,2-trifluoroacetophenone is an important intermediate for the synthesis of pesticides and veterinary drugs.
  • the synthetic method of 3',5'-dichloro-2,2,2-trifluoroacetophenone mainly includes the following:
  • the PCT patent of the application number WO2018009751 discloses a preparation method using 3,5-dichlorobromobenzene and methyl trifluoroacetate as starting materials, using tetrahydrofuran as a solvent, by mixing 3,5-dichlorobromobenzene React with isopropyl magnesium chloride-lithium chloride to prepare Grignard reagent and then react with methyl trifluoroacetate.
  • isopropyl magnesium chloride and tetrahydrofuran are relatively expensive and explosive, and the production cost in industrial production is higher and less economical.
  • Chinese invention patent with publication number CN107353189A discloses a kind of taking 3,5-dichlorobromobenzene as raw material, reacting with trifluoroacetyl compound under the effect of butyllithium to obtain 3,5-dichlorobromobenzene and The preparation method of methyl trifluoroacetate, in the same way, in this method, the price of tert-butyl lithium is high, the danger is high, and the whole reaction process needs to be carried out under the condition of -78 ° C, the industrial production cost is high, and the economic effect is poor.
  • the purpose of this application is to provide a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, using inexpensive raw materials and a relatively mild reaction conditions, to achieve the preparation of 3',5'-dichloro-2,2,2-trifluoroacetophenone, which has a good economic effect.
  • the present application provides a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, comprising the following steps:
  • step S2 The composition of compound II and compound III obtained in step S1 is subjected to a nitro reduction reaction to obtain a composition of compound IV and compound V;
  • step S3 The composition of compound IV and compound V obtained in step S2 is subjected to a chlorination reaction with a chlorinating reagent to obtain a composition of compound VI and compound VII;
  • step S4 carrying out a diazotization elimination reaction on the composition of compound VI and compound VII obtained in step S3 to obtain 3',5'-dichloro-2,2,2-trifluoroacetophenone;
  • the acid I is phosphoric acid, polyphosphoric acid, methanesulfonic acid, chlorosulfonic acid, trifluoromethanesulfonic acid, trifluoromethanesulfonic anhydride, acetic acid, acetic anhydride, boron trifluoride ether, perchloric acid, phosphorus One of molybdic acid, strong acid resin, fuming sulfuric acid and 80%-98% sulfuric acid, or a stable mixed system formed by any two or more of the above-mentioned acids; the nitrating reagent is nitric acid, fuming nitric acid, sodium nitrate, Any one or more of potassium nitrate, ammonium nitrate, lead nitrate, aluminum nitrate, barium nitrate, dinitrogen pentoxide and nitrogen dioxide; the reaction temperature during nitrification is 0 to 80°C;
  • step S3 select any one or more of chlorine, sulfonyl chloride, trichloroisocyanuric acid, and NCS for chlorination.
  • Compound I is a common chemical raw material, which is simple and easy to obtain, can be directly purchased, and is inexpensive. After the nitration of compound I, under the action of chloride ion substitution, two compounds, compound II and compound III, are produced, and compound II and compound III are directly put into the next reaction without separation.
  • step S2 after reducing the nitro group to an amino group, a mixture of compound IV and compound V is obtained, which can also be used in the next step without separation.
  • the amino group is a strong electron-donating group and has a good ortho-para-positioning effect, so both compound IV and compound V will only undergo halogenation reaction at the 5' position of the benzene ring during the chlorination process, And the reaction is easy to occur without harsh reaction conditions.
  • 3',5'-dichloro-2,2,2-trifluoroacetophenone can be obtained by removing the amino group through the diazotization reaction.
  • the whole reaction has no complicated process, and the raw materials are also simple and easy-to-obtain common chemical raw materials, so the production cost in the whole production process is low, and the economic effect is good.
  • Step S1 is as follows:
  • step S1-3 washing the organic phase I obtained in step S1-2 and removing the solvent to obtain a composition of compound II and compound III;
  • acid I is one of 80%-98% sulfuric acid or oleum
  • the nitrifying reagent is fuming nitric acid
  • Sulfuric acid is selected as the catalyst for nitration, and fuming nitric acid is selected.
  • sulfuric acid as an industrial raw material has a large supply and low price, and the degree of dissociation of sulfuric acid in the system has the characteristics of gradient, which can provide more stable in the reaction process.
  • the concentration of hydrogen ions makes the reaction process more controllable and helps save costs.
  • sulfuric acid is not easy to introduce other groups on the benzene ring, which helps to improve the purity of the target product.
  • the fuming nitric acid exists in a liquid state and has good reactivity, and no other solvent needs to be introduced during the reaction, which reduces the difficulty of post-processing and separation.
  • step S1-1 after compound I and acid I are mixed, the temperature is raised to 40-60° C., and then a nitration reagent is added dropwise for the reaction; in step S1-2, First, the intermediate reaction solution I was cooled to 0-10° C., the intermediate reaction solution I was added dropwise to ice water, and then the extractant I was added.
  • the temperature is first heated, and the reaction can be carried out quickly after the temperature is increased, and the site on the benzene ring is activated by the concentrated sulfuric acid by means of pre-heating, and the nitrated
  • the reagent is added dropwise to the above system, so that there is sufficient material in the system for nitrification.
  • the present application can be further configured as: in step S2, the nitro group is reduced by hydrogenation reduction under the action of catalyst I, and catalyst I is any one of platinum carbon, palladium carbon or Raney nickel. kind.
  • Step S2 is as follows:
  • step S2-1 The composition of compound II and compound III obtained in step S1 is dissolved in solvent I, a catalyst is added, and air is removed, then the temperature is raised to 40°C to 60°C and hydrogen is introduced, and the intermediate reaction is obtained after sufficient reaction.
  • solvent I a catalyst is added, and air is removed, then the temperature is raised to 40°C to 60°C and hydrogen is introduced, and the intermediate reaction is obtained after sufficient reaction.
  • step S2-2 cooling, filtering, and concentrating the intermediate reaction solution II obtained in step S2-1, and further purifying and drying by recrystallization to obtain the composition of compound IV and compound V;
  • solvent I is any one of the following substances, or a homogeneous mixed system formed by any of the following substances: methanol, ethanol, ethyl acetate, n-butyl acetate, isopropyl acetate, isopropanol and toluene.
  • the material after the reaction is purified and dried by the method of recrystallization, the operation is relatively simple, and the equipment maintenance components are low.
  • the solution obtained after recrystallization can be reused after treatment, which reduces the waste of materials, thereby helping to further reduce the production cost and improve the economic effect.
  • step S2-2 the details are as follows: the intermediate reaction solution II obtained in step S2-1 is cooled and filtered, then toluene is added and the temperature is raised to 40-50°C to fully dissolve After that, the temperature is lowered to -30 ⁇ -20°C, and the solid is precipitated by standing, and then filtered and dried to obtain the composition of compound IV and compound V.
  • step S2-1 Select toluene as a solvent to recrystallize the intermediate reaction solution II obtained in step S2-1, and make the solid material in the intermediate reaction solution II fully dissolve in the toluene by heating first, so that impurities are not easily adsorbed on the residual solid In the process, it is helpful to more fully remove the impurities in the intermediate reaction solution II and improve the purity of the final target product.
  • Step S3 is as follows:
  • step S3-2 cooling the intermediate reaction solution obtained in step S3-1 and adding water for extraction, and retaining the organic phase to obtain organic phase II;
  • step S4 the diazotization deamination reaction is directly carried out in the organic phase II;
  • the chlorination reagent is any one of chlorine, sulfonyl chloride, trichloroisocyanuric acid, and NCS, or a composition formed by any number of chlorine, sulfonyl chloride, trichloroisocyanuric acid, and NCS.
  • the solvent II is any one of toluene, dichloromethane, chloroform, acetonitrile, isopropanol, and ethanol, or a homogeneous system formed by mixing any of the above-mentioned solvents.
  • the organic phase II is directly put into the next step to carry out the reaction, which reduces the post-processing steps between the reactions, thereby reducing the technological steps of the reaction, and improving the reaction efficiency, thereby helping to further improve the economic effect.
  • Step S4 is as follows:
  • step S4-1 cooling the organic phase II obtained in step S3-2 to -10 ⁇ 0°C, and adding acid II dropwise to make it acidified, and fully reacted to obtain intermediate reaction solution IV;
  • acid II is any one in hydrochloric acid, hydrobromic acid, hydrofluoric acid, phosphoric acid, acetic acid or sulfuric acid;
  • nitrous acid reagent is sodium nitrite, potassium nitrite, calcium nitrite, barium nitrite, silver nitrite, Any of the C1-C6 alkyl nitrites.
  • step S3-2 the lead organic phase II in step S3-2 is directly introduced into step S4 for reaction, which reduces the separation process, thereby further reducing the process step flow and reducing the production cost.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone comprising the following steps:
  • step S2 The composition of compound II and compound III obtained in step S1 is subjected to a nitro reduction reaction to obtain a composition of compound IV and compound V;
  • step S3 The composition of compound IV and compound V obtained in step S2 is subjected to a chlorination reaction with a chlorinating reagent to obtain a composition of compound VI and compound VII;
  • step S4 carrying out a diazotization elimination reaction on the composition of compound VI and compound VII obtained in step S3 to obtain 3',5'-dichloro-2,2,2-trifluoroacetophenone;
  • Step S1 specifically includes the following sub-steps:
  • Step S2 specifically includes the following sub-steps:
  • step S2-1 Take 122.8 g (0.484 mol) of the composition of compound II and compound III obtained in step S1-3, add 300 mL of absolute ethanol as solvent I, and add 5.0 g of 5% platinum-carbon catalyst as catalyst I, Replace the air with nitrogen three times to remove the air, and then replace it with hydrogen three times to remove the nitrogen, introduce hydrogen to start stirring and react.
  • the hydrogen pressure is between 0.1 MPa, and the temperature is controlled at 50 ⁇ 10 ° C, and the intermediate reaction solution is obtained after the reaction for 1.5 hours. II;
  • Step S3 specifically includes the following sub-steps:
  • step S3-1 Take 44.7 g of the composition of compound IV and compound V obtained in step S2-2, add 200 mL of toluene (solvent II) and raise the temperature to 50°C. After fully dissolving, 33.7 g (0.25 g (0.25 g) mol) sulfonyl chloride as the chlorination reagent, followed by incubation for 8h to obtain intermediate reaction solution III;
  • Step S4 specifically includes the following sub-steps:
  • the intermediate reaction solution VI is statically layered, the organic layer is washed with 5% sodium bicarbonate solution, dried with sewage magnesium sulfate, and the solvent is distilled under reduced pressure to obtain a clear and transparent liquid that is 3',5'-dicarbonate Chloro-2,2,2-trifluoroacetophenone 41.2g, purity 99.3%, yield 89.1%.
  • step S1-1 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is: in step S1-1, acid I selects oleum (200g, 0.4mol).
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that: in step S1-1, acid I selects 80% sulfuric acid, and the reaction is kept warm The time is 2h and 1h respectively.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that: in step S1-1, acid I selects the same amount of trifluoroacetophenone. Fluoromethanesulfonic acid.
  • step S1-1 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is: in step S1-1, acid I selects acetic anhydride, and adds 100 mL Dichloromethane was used as solvent.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is: in step S1-1, the nitration reagent is selected from saturated aqueous sodium nitrate and The amount of nitrogen dioxide, the nitrifying agent, remains the same.
  • step S1-2 and step S1-3 are replaced by step S1-2' :
  • the intermediate reaction solution I after the reaction was naturally cooled to -5 ⁇ 5°C, and 500 mL of toluene was added and stirred for 30 min. After standing for stratification, the organic layer was retained, and 500 mL of 10% sodium carbonate aqueous solution was added to wash, and then washed with 500 mL of water. Toluene was distilled off under reduced pressure to obtain a composition of compound II and compound III.
  • step S1-1 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S1-1, compound I is mixed with 98% sulfuric acid After homogenization, 35.3 g of fuming nitric acid was added dropwise as a nitrifying reagent (0.55 mol) within 10 min, and then the temperature was raised to 60 °C, and the reaction was maintained for 1.5 h to obtain intermediate reaction solution I.
  • step S1-2 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S1-2, the intermediate reaction solution I after the reaction is added 1000 mL of dichloromethane was used as extractant I, and after fully stirring for 30 min, it was kept still and separated to obtain organic phase I.
  • step S2-1 Raney nickel is selected as catalyst I, solvent I
  • step S2-1 Raney nickel is selected as catalyst I
  • step S2-1 Raney nickel is selected as catalyst I
  • solvent I A homogeneous mixed system obtained by mixing ethanol and isopropanol at a volume of 1:1 was selected.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S2-1, the pressure of hydrogen is 1.0 MPa.
  • step S2-2 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S2-2, the amount of toluene added is 200 mL, and toluene is added Then, the temperature was raised to 50°C, fully dissolved and then cooled to -30°C, left standing overnight, filtered and dried to obtain the composition of compound IV and compound V.
  • step S3 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 18 is that in step S3, chlorine is selected as the chlorination reagent, and the specific steps are as follows:
  • step S3-1' take 44.7 g of the composition of compound IV and compound V obtained in step S2-2, add 500 mL of glacial acetic acid (solvent II) and heat up to 40°C, after fully dissolving, slowly pass chlorine gas 17.04 g in 3 h g (0.24mol), at the same time point plate tracking detection raw material, after the completion of the reaction, pass nitrogen gas to blow the hydrogen chloride and excess chlorine generated into the tail gas absorption device to obtain the intermediate reaction solution III';
  • step S4 the above-obtained composition of compound IV and compound V is added to toluene again to prepare organic phase II for reaction.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S4, acid II selects hydrochloric acid with a mass fraction of 30%, and hydrochloric acid is The add-on amount is 240g, and the nitrous acid reagent is selected as a saturated solution of potassium nitrite in the amount of the substance.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S4, 150g glacial acetic acid is selected for acid II, and nitrous acid reagent is selected, etc.
  • the amount of substance is a saturated solution of calcium nitrite.
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S4, the nitrous acid reagent selects nitrous acid in an equivalent amount methyl ester.
  • step S1 A preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that in step S1, it further comprises the following steps:
  • step S1-4 Add the composition of compound II and compound III obtained in step S1-3 into 330 mL of toluene, heat up to 40°C and dissolve it completely, then cool down to -20°C, stand overnight and filter to obtain a solid , which is compound compound III, and the remaining liquid is distilled under reduced pressure to remove toluene to obtain compound II.
  • step S2, S3 and S4 are carried out separately for compound II and compound III, and the finally obtained products are combined, namely 3',5'-dichloro-2,2,2-trifluoroacetophenone .
  • a preparation method of 3',5'-dichloro-2,2,2-trifluoroacetophenone, the difference from Example 1 is that the experimental conditions in Example 1 are amplified, wherein each material The addition amount of 10 times in Example 1, the reaction time and other reaction conditions remain unchanged.
  • Step 1 Under nitrogen protection, n-butyllithium (23.2 mmol was dissolved in 14.5 mL of n-hexane to prepare a 1.6 M solution) was uniformly added dropwise to compound VIII (5 g, 22.1 mmol) at -78°C within 30 min.
  • compound VIII 5 g, 22.1 mmol
  • the reaction was kept stirring for 1 h, and then trifluoroacetic anhydride (2.56 g, 23.2 mmol) was added dropwise to the above mixed solution, and the reaction was kept at -78 °C for 2 h. It was then warmed to room temperature and the reaction was continued at room temperature for 2.5 h.
  • Compound VIII was the same as that of Comparative Example 1 to obtain 2.28 g of 3',5'-dichloro-2,2,2-trifluoroacetophenone with a yield of 42.5% and a purity of 98.8%.
  • Example 3 sulfuric acid with a concentration of 80% was used for the reaction, and the yield still decreased under the conditions of prolonging the reaction time. Compared with Example 3, Example 4 shortens the reaction time, which further leads to the reduction of the yield in step S1.
  • Embodiment 5 and embodiment 6 select trifluoromethanesulfonic acid and acetic anhydride to replace 98% sulfuric acid respectively, all cause the reduction of yield, prove that 98% sulfuric acid and oleum have better reaction characteristics in many acid reagents .
  • Example 8 the nitration reagent was selected from saturated aqueous sodium nitrate solution, and in Example 9, the method of feeding nitrogen dioxide was selected to react. Wherein the purchase cost of the aqueous sodium nitrate solution is lower, but its reaction performance is less effective than the technical scheme of using fuming nitric acid in Example 1. The introduction of nitrogen dioxide requires additional equipment support.
  • the above solutions can be selected according to the conditions of the actual production line, and all have good industrial application value.
  • Example 11 the specific process steps in step S1 were adjusted, all of which resulted in a decrease in yield.
  • the intermediate reaction solution I was cooled by a natural cooling method, which took a long time, and the temperature of the system was still relatively high during the cooling process, which was easy to produce some side reactions, which reduced the yield of step S1.
  • Example 12 fuming nitric acid was added dropwise and then the system was heated up, which also had a certain adverse effect on the yield of step S1.
  • Example 13 the reacted material did not undergo ice-water quenching reaction, resulting in difficulties in the separation process, and impurities could not be fully separated from the organic phase during liquid separation, thereby causing the yield of step S1 to decrease, and finally The purity of the obtained product is somewhat reduced.
  • Example 14 to 17 adjusted the process parameters in step S2. It can be seen that the increase of hydrogen pressure helps to improve the yield of step S2, and the selection of Raney nickel and palladium carbon instead of platinum carbon both helps to improve the yield in S2. In Examples 18 and 19, some parameters in step S3 were adjusted, which had little effect on the final yield. In Examples 20 to 22, step S4 was adjusted to some extent. From the above data, it can be seen that the use of methyl nitrite has a higher yield in the production process than other nitrous acid reagents.
  • Example 23 after the completion of step S1, compound II and compound III were separated and the subsequent reaction was carried out. It can be seen that no matter whether compound II and compound III are separated or not, there is basically no obvious effect on the subsequent reaction. Therefore, in the actual production process, the process of separating compound II and compound III can be completely omitted, thereby reducing the production cost. The purpose of improving economic efficiency.
  • Example 24 is an experiment in which the solution in Example 1 is amplified. It can be seen that the technical solution in Example 1 can still achieve 3',5'-dichloro-2 , The production of 2,2-trifluoroacetophenone, and the yield and purity have no obvious change, which proves that the technical scheme in this application has the prospect of amplifying the reaction and applying it to large-scale production.

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Abstract

L'invention concerne un procédé de préparation de 3',5'-dichloro-2,2,2-trifluoroacétophénone. Le procédé consiste à soumettre de la 3'-chloro-2,2,2-trifluoroacétophénone en tant que matière première à quatre étapes, soit une nitrification, une réduction, une chloration et une désamination, de manière à préparer la 3',5'-dichloro-2,2,2-trifluoroacétophénone. Le procédé présente un coût de matière première réduit, des conditions de réaction douces et un processus de réaction simple et contribue à réduire le coût de production, outre un effet économique amélioré.
PCT/CN2020/118513 2020-09-28 2020-09-28 Procédé de préparation de 3',5'-dichloro-2,2,2-trifluoroacétophénone WO2022061920A1 (fr)

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