Method for preparing trifluoromethyl aromatic compound

Abstract

A method for preparing a trifluoromethyl aromatic compound, comprising: mixing a trichloromethyl aromatic compound and an organic alkali hydrofluoride for a fluorination reaction and carrying out solid-liquid separation on the resulting reaction solution to obtain a wet organic alkali hydrochloride product and a filtrate; drying the wet organic alkali hydrochloride product and condensing a gas generated in the drying process for recovery to obtain a condensation product; and carrying out rectification purification on the filtrate and the condensation product to obtain the trifluoromethyl aromatic compound. The preparation method can achieve an effective conversion rate of 95% or more and an overall molar yield of 95% or more, produce a hydrochloride byproduct which has excellent quality, meets industry standards, and can be sold externally as an industrial byproduct, generate almost no "waste gas, waste water, and waste residue", and is thus an efficient, economical, and environmentally friendly preparation method.

Description

Preparation method of trifluoromethyl aromatic compound

[0001] This application claims priority to the Chinese patent application filed with the Patent Office of China on January 24, 2024, with application number CN202410102233.6 and invention name “A method for preparing trifluoromethyl aromatic compounds”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present invention relates to the technical field of trifluoromethyl compounds, in particular to a method for preparing a trifluoromethyl aromatic compound. Background Art

[0003] The trifluoromethyl group has strong electron-attracting and lipophilic properties, and its C-F bond is very stable. Introducing it into organic compounds can change the polarity and stability of the compound. Aromatic compounds containing trifluoromethyl groups are widely used in medicine, pesticides and other fields.

[0004] Trifluoromethylbenzene compounds and trifluoromethylpyridine compounds are two common trifluoromethyl aromatic compounds. Both are important intermediates for fluorine-containing pesticides, dyes and pharmaceuticals. Most of them are also used as excellent solvents in chemical organic synthesis and have extremely wide applications.

[0005] At present, trifluoromethyl aromatic compound, when preparing, usually adopts trichloromethyl aromatic compound as starting raw material, synthesizes with hydrogen fluoride as fluorinating agent.For example, publication number is that a kind of preparation method of 2-fluoro-5-trifluoromethyl pyridine is provided in the Chinese patent application of CN106866509A, with 3-picoline as raw material, first obtains 2-chloro-5-trichloromethyl pyridine by chlorination, then takes anhydrous hydrogen fluoride as fluorinating agent, obtains 2-fluoro-5-trifluoromethyl pyridine by fluorination reaction.Publication number is that a kind of synthetic method of o-trifluoromethyl benzoyl chloride is announced in the Chinese patent application of CN114195635A, first obtains 1-(dichloromethyl)-2-(trichloromethyl) benzene by chlorination reaction, then takes hydrogen fluoride as fluorinating agent and prepares 1-(dichloromethyl)-2-(trifluoromethyl) benzene, and follow-up prepares target product by hydrolysis and chlorination again.

[0006] In summary, the current preparation of trifluoromethyl aromatic compounds mostly uses hydrogen fluoride as the fluorination reagent. Due to the use of hydrogen fluoride, most reactions need to be carried out under high pressure, which not only has high safety risks but also makes side reactions difficult to control, resulting in unstable product quality. In addition, the residual fluoride ions in the by-product hydrochloric acid are difficult to remove, resulting in a limited application range of the by-product hydrochloric acid, which invisibly increases environmental protection costs.

[0007] Summary of the Invention

[0008] In view of this, the present invention provides a method for preparing trifluoromethyl aromatic compounds. The method uses an organic base hydrofluoride as a fluorination reagent, does not require high pressure conditions, has good safety, and produces stable product quality. The organic base hydrochloride produced can be sold as a by-product, resulting in significant economic benefits.

[0009] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0010] A method for preparing a trifluoromethyl aromatic compound comprises the following steps:

[0011] mixing a trichloromethyl aromatic compound and an organic base hydrofluoride to carry out a fluorination reaction to obtain a reaction solution;

[0012] The reaction liquid is subjected to solid-liquid separation to obtain a wet product of organic base hydrochloride and a filtrate; the wet product of organic base hydrochloride is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensed product;

[0013] The filtrate and the condensed product are subjected to rectification and purification to obtain a trifluoromethyl aromatic compound.

[0014] Preferably, the trichloromethyl aromatic compound includes a trichloromethyl benzene compound or a trichloromethyl pyridine compound; the structure of the trichloromethyl benzene compound is shown in Formula I; the structure of the trichloromethyl pyridine compound is shown in Formula II;

[0015] In formula I: R1 is halogen, R2 is -NO2; in formula II: R is halogen.

[0016] Preferably, the organic base hydrofluoride comprises an organic amine hydrofluoride.

[0017] Preferably, the organic amine hydrofluoride includes one or more of pyridine hydrofluoride, triethylamine hydrofluoride, diethylamine hydrofluoride, trimethylamine hydrofluoride, dimethylamine hydrofluoride and monomethylamine hydrofluoride.

[0018] Preferably, the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride is 1:(1-3).

[0019] Preferably, the temperature of the fluorination reaction is 80° C. to 140° C., and the reaction time is 5 to 20 hours.

[0020] Preferably, the drying is vacuum drying, the drying temperature is 70° C. to 80° C., the drying time is 10 to 16 hours, and the vacuum degree is -0.09 to 0.095 MPa.

[0021] Preferably, the drying obtains an organic base hydrochloride; the preparation method further comprises: adding the organic base hydrochloride to liquid alkali for neutralization, and then distilling and dehydrating to obtain a free organic base.

[0022] Preferably, the vacuum degree of the distillation purification is 100-200 Pa, and the top temperature of the distillation is 80° C.-100° C. below the boiling point of the target product.

[0023] Preferably, when the still residue obtained from the distillation comprises one or more of trichloromethyl aromatic compounds and mono- and di-fluoro aromatic compounds thereof, the method further comprises: returning the still residue obtained from the distillation to the fluorination reaction step for reuse.

[0024] The present invention provides a method for preparing a trifluoromethyl aromatic compound, comprising the following steps: mixing a trichloromethyl aromatic compound and an organic base hydrofluoride to carry out a fluorination reaction to obtain a reaction solution; performing solid-liquid separation on the reaction solution to obtain a wet product of an organic base hydrochloride and a filtrate; drying the wet product of the organic base hydrochloride, condensing and recovering gas generated during the drying process to obtain a condensate; purifying the filtrate and the condensate to obtain the trifluoromethyl aromatic compound. The present invention uses an organic base hydrofluoride as a fluorination reagent, the fluorination reaction does not require high pressure conditions, the reaction conditions are mild, the safety is good, the product quality is stable, and the organic base hydrofluoride is inexpensive, which is conducive to reducing production costs; and the organic base hydrofluoride produced by the reaction can be sold as a by-product, with significant economic benefits.

[0025] Furthermore, the present invention utilizes the large difference in boiling points between the trifluoromethyl aromatic compound and the organic base hydrochloride. When the wet organic base hydrochloride product is dried, the trifluoromethyl aromatic compound produced during the drying process is condensed and recovered, thereby further improving the yield of the trifluoromethyl aromatic compound. At the same time, residual fluoride ions in the by-product hydrochloride can be avoided, thereby improving the quality of the by-product hydrochloride.

[0026] Furthermore, the present invention returns the remaining still residue from the distillation to the fluorination reaction step to continue participating in the reaction. The main components of the remaining still residue from the distillation are trichloromethyl aromatic compounds and their mono- and di-fluoro substitutes. The present invention returns them to the fluorination reaction step, which can further improve the utilization rate of the raw materials and the yield of the product.

[0027] In summary, the method for preparing trifluoromethyl aromatic compounds provided by the present invention has an effective conversion rate of over 95%, a comprehensive molar yield of over 95%, and the by-product hydrochloride is liberated by liquid caustic soda, and the by-product organic base obtained after distillation, dehydration, and drying meets industry standards and can be sold as an industrial by-product. Therefore, this method produces no other hazardous waste except a small amount of wastewater. Therefore, the present invention is an efficient, economical, and environmentally friendly preparation method. DETAILED DESCRIPTION

[0028] The present invention provides a method for preparing a trifluoromethyl aromatic compound, comprising the following steps:

[0029] mixing a trichloromethyl aromatic compound and an organic base hydrofluoride to carry out a fluorination reaction to obtain a reaction solution;

[0030] The reaction liquid is subjected to solid-liquid separation to obtain a wet product of organic base hydrochloride and a filtrate; the wet product of organic base hydrochloride is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensed product;

[0031] The filtrate and the condensed product are subjected to rectification and purification to obtain a trifluoromethyl aromatic compound.

[0032] The present invention mixes a trichloromethyl aromatic compound and an organic base hydrofluoride to carry out a fluorination reaction to obtain a reaction solution. In the present invention, the trichloromethyl aromatic compound includes a trichloromethyl benzene compound or a trichloromethyl pyridine compound; the structure of the trichloromethyl benzene compound is shown in Formula I; the structure of the trichloromethyl pyridine compound is shown in Formula II;

[0033] In formula I: R1 is halogen, R2 is -NO2; in formula II: R is halogen.

[0034] In the present invention, R1 in the formula I is a meta-substituent of the trichloromethyl group, preferably Cl or Br, more preferably Cl; R2 in the formula I is a nitro group, which is located at the ortho, meta or para position of the trichloromethyl group, and more preferably at the meta position of the trichloromethyl group.

[0035] In the present invention, R in formula II is preferably Cl or Br, more preferably Cl; the trichloromethyl group in formula II is preferably in the ortho, meta or para position to the N atom, and R is preferably in the ortho, meta or para position to the trichloromethyl group.

[0036] In the present invention, the trifluoromethyl aromatic compound is preferably a trifluoromethyl benzene compound or a trifluoromethyl pyridine compound; the structural formula of the trifluoromethyl benzene compound is shown in Formula III, and the structural formula of the trifluoromethyl pyridine compound is shown in Formula IV;

[0037] In formula III: R1 is halogen, R2 is -NO2; in formula IV: R is halogen.

[0038] In the present invention, the types and positions of R1 and R2 in Formula III are the same as those in Formula I and are not repeated here; the types and positions of R in Formula IV are the same as those in Formula II and are not repeated here.

[0039] In the present invention, the trichloromethyl aromatic compound preferably includes 2-trichloromethyl-4-nitrochlorobenzene or 3-trichloromethyl-6-chloropyridine; the trifluoromethyl aromatic compound preferably includes 2-trifluoromethyl-4-nitrochlorobenzene or 3-trifluoromethyl-6-chloropyridine.

[0040] In the present invention, when the trichloromethyl aromatic compound is a trichloromethyl benzene compound, the final product is a trifluoromethyl benzene compound, and the reaction formula is shown in Formula A:

[0041] In the present invention, when the trichloromethyl aromatic compound is a trichloromethyl pyridine compound, the final product is a trifluoromethyl pyridine compound, and the reaction formula is shown in Formula B:

[0042] In the present invention, the organic base hydrofluoride preferably includes organic amine hydrofluoride; the organic amine hydrofluoride preferably includes one or more of pyridine hydrofluoride, triethylamine hydrofluoride, diethylamine hydrofluoride, trimethylamine hydrofluoride, dimethylamine hydrofluoride and monomethylamine hydrofluoride; the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride is preferably 1:(1-3), more preferably 1:(1-1.5).

[0043] In the present invention, the temperature of the fluorination reaction is preferably 80°C to 140°C, more preferably 100°C to 120°C, and the reaction time is preferably 5 to 20 hours, more preferably 10 to 15 hours. In a specific embodiment of the present invention, the fluorination reaction can be carried out at normal pressure without the need for additional control of the reaction pressure. The fluorination is preferably carried out under stirring. In a specific embodiment of the present invention, it is preferred to first add the trichloromethyl aromatic compound and the organic base hydrofluoride to a reaction vessel, raise the temperature to the fluorination reaction temperature under stirring, and react under insulation conditions; after the reaction is completed, cool to room temperature.

[0044] After obtaining the reaction liquid, the present invention performs solid-liquid separation on the reaction liquid to obtain a wet product of organic base hydrochloride and a filtrate; the wet product of organic base hydrochloride is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensed product. In the present invention, the method of solid-liquid separation is preferably filtration or centrifugation; the drying is preferably vacuum drying; the drying temperature is preferably 70°C to 80°C, more preferably 75°C to 80°C, the time is preferably 10 to 16 hours, more preferably 12 to 14 hours, and the vacuum degree is preferably -0.09 to -0.095MPa; during the drying process, the trifluoromethyl aromatic compound forms a gaseous state, which is recovered by condensation in the present invention to further improve the product yield, reduce the fluorine content in the organic base hydrochloride, and improve the quality of the by-product.

[0045] In the present invention, the organic base hydrochloride is obtained after drying; the organic base hydrochloride is preferably added with liquid alkali for neutralization and release, and then distilled and dehydrated to obtain the corresponding organic base.

[0046] After obtaining the filtrate and the trifluoromethyl aromatic compound recovered by condensation, the present invention purifies the filtrate and the condensate to obtain the trifluoromethyl aromatic compound. In the present invention, the filtrate and the condensate are preferably combined and then purified; the purification method is preferably distillation; the device used for the distillation is preferably a distillation column; the vacuum degree of the distillation is preferably 100-200 Pa, and the top temperature of the distillation is preferably determined according to the boiling point of the target product, specifically 80°C to 100°C below the boiling point of the target product; the present invention collects the product at the top of the distillation device; in a specific embodiment of the present invention, when the still residue remaining in the distillation includes one or more of the trichloromethyl aromatic compound and its monofluoro-substituted and difluoro-substituted products, the present invention preferably returns the still residue to the fluorination reaction step for reuse, which can improve the utilization rate of the raw materials and the product yield.

[0047] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0048] Example 1

[0049] To a three-necked flask, 275 g of 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0 mol) and 136 g of triethylamine hydrofluoride (MW121.2, 1.1 mol) were added in sequence. The mixture was stirred and heated to 100°C to 110°C. The reaction was kept warm for 15 h, and the temperature was lowered and filtered to obtain a wet product of triethylamine hydrochloride and a filtrate. The wet product of triethylamine hydrochloride was vacuum dried for 14 h at a drying temperature of 80°C and a vacuum degree of -0.095 MPa to obtain 135 g of by-product triethylamine hydrochloride. During the drying process, the evaporated gas was condensed to obtain recovered 2-trifluoromethyl-4-nitrochlorobenzene. The filtrate and recovered 2-trifluoromethyl-4-nitrochlorobenzene are combined and rectified in a distillation column under a pressure controlled within 200 Pa and a top temperature of 65°C to 75°C. The boiling liquid is collected to obtain 215 g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.6%. The still residue remaining after the rectification contains 33 wt% of 2-monofluoromethyl-4-nitrochlorobenzene, 56 wt% of 2-difluoromethyl-4-nitrochlorobenzene, and 8.5 wt% of 2-trifluoromethyl-4-nitrochlorobenzene, respectively. The still residue is returned to the fluorination reaction step for reuse. The average molar yield of the product after reuse of the still residue is 95%.

[0050] Example 2

[0051] To a three-necked flask, 231 g of 3-trichloromethyl-6-chloropyridine (MW230.9, 1.0 mol) and 148.6 g of pyridine hydrofluoride (MW99.1, 1.5 mol) were added in sequence, stirred, heated to 110°C to 120°C, kept warm for 12 hours, cooled and filtered to obtain a wet product of pyridine hydrochloride and a filtrate. The wet product of pyridine hydrochloride was vacuum dried for 14 hours at a drying temperature of 80°C and a vacuum degree of -0.095 MPa to obtain 110 g of by-product pyridine hydrochloride. During the drying process, the evaporated gas was condensed to obtain recovered 2-trifluoromethyl-6-chloropyridine. The filtrate and recovered 2-trifluoromethyl-6-chloropyridine were combined and rectified in a distillation column under a pressure controlled within 200 Pa and a top temperature of 80°C to 90°C. The normal boiling point was collected to yield 175 g of 3-trifluoromethyl-6-chloropyridine with a purity of 99.4%. The remaining still residue contained 29.8%, 51%, and 10.6% 3-monofluoromethyl-6-chloropyridine, 3-difluoromethyl-6-chloropyridine, and 3-trifluoromethyl-6-chloropyridine, respectively. The still residue was returned to the fluorination reaction step for further use; the average molar yield of the product after this still residue application was 96.6%.

[0052] Example 3

[0053] 275g 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0mol) and 70g dimethylamine hydrofluoride were added to a three-necked flask, stirred, heated to 100°C-110°C, and the reaction was incubated for 15h. The reaction was cooled and filtered to obtain a wet dimethylamine hydrochloride product and a filtrate. The wet dimethylamine hydrochloride product was vacuum dried for 14h at 75°C under a vacuum of -0.095MPa to obtain 79g of by-product dimethylamine hydrochloride. During the drying process, the evaporated gas was condensed to obtain the recovered 2-trifluoromethyl-4-nitrochlorobenzene. The combined filtrate and the recovered 2-trifluoromethyl-4-nitrochlorobenzene were rectified on a rectifying column under a controlled pressure of 200Pa or less and a top temperature of 65°C-75°C. The product was then boiled to obtain 213g 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.7%. The still residue remaining after distillation contained 32%, 57%, and 8.7% 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene, and 8.7% 2-trifluoromethyl-4-nitrochlorobenzene, respectively. The still residue was recycled to the fluorination step; the average molar yield of the product after recycling the still residue was 94.8%.

[0054] Example 4

[0055] To a three-necked flask, 275 g of 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0 mol) and 95 g of trimethylamine hydrofluoride (MW79.1, 1.2 mol) were added sequentially, stirred, heated to 100° C. to 110° C., kept warm for 15 hours, cooled and filtered to obtain a wet product of trimethylamine hydrochloride and a filtrate. The wet product of trimethylamine hydrochloride was vacuum dried for 14 h at a drying temperature of 75° C. and a vacuum degree of -0.095 MPa to obtain 110 g of by-product trimethylamine hydrochloride. During the drying process, the evaporated gas was condensed to obtain recovered 2-trifluoromethyl-4-nitrochlorobenzene. The filtrate and recovered 2-trifluoromethyl-4-nitrochlorobenzene were combined and rectified in a distillation column under a pressure controlled within 200 Pa and a top temperature of 65°C to 75°C. The boiling liquid was collected to obtain 210 g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.5%. The remaining still residue contained 29.8%, 59%, and 9.6% 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene, and 2-trifluoromethyl-4-nitrochlorobenzene, respectively. The still residue was returned to the fluorination reaction step for further use; the average molar yield of the product after this still residue was 94.5%.

[0056] Comparative Example 1

[0057] To a three-necked flask, 275 g of 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0 mol) and 136 g of triethylamine hydrofluoride (MW121.2, 1.1 mol) were added in sequence, stirred, heated to 100° C. to 110° C., kept warm for 15 h, cooled and filtered to obtain a wet product of triethylamine hydrochloride and a filtrate. The wet product of triethylamine hydrochloride was vacuum dried for 14 h at a drying temperature of 50° C. and a vacuum degree of -0.08 MPa to obtain 196 g of by-product triethylamine hydrochloride (the drying temperature was low, and the residual 2-trifluoromethyl-4-nitrochlorobenzene was too much to be dried). During the drying process, evaporation and condensation were performed to obtain recovered 2-trifluoromethyl-4-nitrochlorobenzene. The filtrate and recovered 2-trifluoromethyl-4-nitrochlorobenzene were combined and rectified in a distillation column under a pressure controlled within 200 Pa and a top temperature of 65°C to 75°C. The boiling liquid was collected to obtain 186 g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.6%. The still residue remaining after the rectification had 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene, and 2-trifluoromethyl-4-nitrochlorobenzene in contents of 30 wt %, 58 wt % and 9.0 wt %, respectively. The still residue was returned to the fluorination reaction step for reuse. The average molar yield of the product after reuse of the still residue was 78% (a relatively low yield).

[0058] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing a trifluoromethyl aromatic compound, characterized in that, It includes the following steps: Mix a trichloromethyl aromatic compound and an organic base hydrofluoride for a fluorination reaction to obtain a reaction solution; Perform solid-liquid separation on the reaction solution to obtain a wet product of the organic base hydrochloride and a filtrate; dry the wet product of the organic base hydrochloride, and condense and recover the gas generated during the drying process to obtain a condensation product; Perform rectification and purification on the filtrate and the condensation product to obtain a trifluoromethyl aromatic compound.

2. The preparation method according to claim 1, wherein, The trichloromethyl aromatic compound includes trichloromethyl benzene compounds or trichloromethyl pyridine compounds; the structure of the trichloromethyl benzene compounds is shown in Formula I; the structural formula of the trichloromethyl pyridine compounds is shown in Formula II; In formula I: R1 is a halogen, and R2 is -NO2; in formula II: R is a halogen.

3. The preparation method according to claim 2, wherein The trichloromethyl aromatic compound includes 2-trichloromethyl-4-nitrochlorobenzene or 3-trichloromethyl-6-chloropyridine.

4. The preparation method according to claim 1, characterized in that, The organic base hydrofluoride includes an organic amine hydrofluoride.

5. The preparation method according to claim 4, characterized in that, The organic amine hydrofluoride includes one or more of pyridine hydrofluoride, triethylamine hydrofluoride, diethylamine hydrofluoride, trimethylamine hydrofluoride, dimethylamine hydrofluoride, and monomethylamine hydrofluoride.

6. The preparation method according to claim 1, wherein The molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride is 1:(1 - 3).

7. The preparation method according to claim 1 or 6, characterized in that, The temperature of the fluorination reaction is 80°C - 140°C, and the reaction time is 5 - 20 h.

8. The preparation method according to claim 1, characterized in that The fluorination reaction is carried out under normal pressure.

9. The preparation method according to claim 1, characterized in that, The drying is vacuum drying, the temperature of the drying is 70°C - 80°C, the time is 10 - 16 h, and the vacuum degree is -0.09 - -0.095 MPa.

10. The preparation method according to claim 1, characterized in that, The drying obtains the organic base hydrochloride; the preparation method further includes: neutralizing the organic base hydrochloride with liquid alkali, and then performing distillation and dehydration drying to obtain the free organic base.

11. The preparation method according to claim 1, characterized in that, The vacuum degree of the rectification and purification is 100 - 200 Pa, and the top temperature of the rectification is 80°C - 100°C below the boiling point of the target product.

12. The preparation method according to claim 11, characterized in that, When the still residue obtained by rectification includes one or more of the trichloromethyl aromatic compound and its mono-fluorinated and di-fluorinated derivatives, it further includes: returning the still residue obtained by rectification to the fluorination reaction step for reuse.

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