A method for preparing trifluoromethyl aromatic compounds

Abstract

The present invention relates to the technical field of fluorinated aromatic compounds, and provides a method for preparing a trifluoromethyl aromatic compound. The present invention mixes a trichloromethyl aromatic compound and an organic base hydrofluoride to carry out a fluorination reaction, performs solid-liquid separation on the obtained reaction liquid, and obtains a wet product of an organic base hydrochloride and a filtrate; the wet product of the organic base hydrochloride is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensate; the filtrate and the condensate are distilled and purified to obtain a trifluoromethyl aromatic compound. The preparation method of the trifluoromethyl aromatic compound provided by the present invention has an effective conversion rate of more than 95%, a comprehensive molar yield of more than 95%, and the by-product hydrochloride produced is of excellent quality, meets industry standards, and can be sold as an industrial by-product, so the method almost does not produce "three wastes". Therefore, the present invention is an efficient, economical, green and environmentally friendly preparation method.

Description

Technical Field

[0001] The invention relates to the technical field of trifluoromethyl compounds, and in particular to a method for preparing a trifluoromethyl aromatic compound. Background Art

[0002] The trifluoromethyl group has strong electron-attracting and lipophilic properties, and the CF bond in it is very stable. Introducing it into organic compounds can change the polarity and stability of the compounds. Aromatic compounds containing trifluoromethyl are widely used in the fields of medicine, pesticides, etc.

[0003] Trifluoromethylbenzene compounds and trifluoromethylpyridine compounds are two common trifluoromethyl aromatic compounds. Both are important intermediates for fluorine-containing pesticides, dyes and medicines. Most of them are also used as excellent solvents in chemical organic synthesis and have extremely wide applications.

[0004] At present, trifluoromethyl aromatic compounds are usually prepared by using trichloromethyl aromatic compounds as starting materials, and synthesized by using hydrogen fluoride as fluorinating agent. For example, a preparation method of 2-fluoro-5-trifluoromethyl pyridine is provided in the Chinese patent application with publication number CN106866509A, using 3-picoline as raw material, firstly obtaining 2-chloro-5-trichloromethyl pyridine by chlorination, and then using anhydrous hydrogen fluoride as fluorinating agent, obtaining 2-fluoro-5-trifluoromethyl pyridine by fluorination reaction. A synthetic method of o-trifluoromethyl benzoyl chloride is disclosed in the Chinese patent application with publication number CN114195635A, first obtaining 1-(dichloromethyl)-2-(trichloromethyl) benzene by chlorination reaction, then preparing 1-(dichloromethyl)-2-(trifluoromethyl) benzene by using hydrogen fluoride as fluorinating agent, and then preparing target product by hydrolysis and chlorination.

[0005] In summary, the current preparation of trifluoromethyl aromatic compounds mostly uses hydrogen fluoride as a fluorination agent. 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; and 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 the environmental protection cost. Summary of the invention

[0006] In view of this, the present invention provides a method for preparing a trifluoromethyl aromatic compound. The present invention uses an organic base hydrofluoride as a fluorination reagent, does not require high pressure conditions, has good safety, stable product quality, and the generated organic base hydrochloride can be sold as a by-product, with significant economic benefits.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] A method for preparing a trifluoromethyl aromatic compound comprises the following steps:

[0009] The trichloromethyl aromatic compound and the organic base hydrofluoride are mixed to carry out a fluorination reaction to obtain a reaction solution;

[0010] 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;

[0011] The filtrate and the condensed product are subjected to rectification and purification to obtain a trifluoromethyl aromatic compound.

[0012] Preferably, the trichloromethyl aromatic compound comprises 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;

[0013]

[0014] In Formula I: R 1 is halogen, R 2 For-No 2 ; In formula II: R is halogen.

[0015] Preferably, the organic base hydrofluoride comprises an organic amine hydrofluoride.

[0016] Preferably, the organic amine hydrofluoride includes one or more of pyridine hydrofluoride, triethylamine hydrofluoride, diethylamine hydrofluoride, trimethylamine hydrofluoride, dimethylamine hydrofluoride and monomethylamine hydrofluoride.

[0017] Preferably, the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride is 1:(1-3).

[0018] Preferably, the temperature of the fluorination reaction is 80° C. to 140° C., and the reaction time is 5 to 20 hours.

[0019] Preferably, the drying is vacuum drying, the drying temperature is 70°C to 80°C, the time is 10 to 16 hours, and the vacuum degree is -0.09 to 0.095 MPa.

[0020] Preferably, the drying obtains an organic base hydrochloride; the organic base hydrochloride is neutralized by adding liquid alkali, and then distilled and dehydrated to obtain a free organic base.

[0021] 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.

[0022] Preferably, when the still residue obtained from the distillation includes trichloromethyl aromatic compounds and one or more of their mono- and di-fluoro substitutions, the method further comprises: returning the still residue obtained from the distillation to the fluorination reaction step for application.

[0023] 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 an organic base hydrochloride wet product and a filtrate; drying the organic base hydrochloride wet product, condensing and recovering the gas generated during the drying process to obtain a condensate product; purifying the filtrate and the condensate product to obtain a 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 low in price, 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.

[0024] In addition, 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 in the drying process is condensed and recovered, thereby further improving the yield of the trifluoromethyl aromatic compound; and at the same time, residual fluoride ions in the by-product hydrochloride can be avoided, thereby improving the quality of the by-product hydrochloride.

[0025] 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.

[0026] In summary, the preparation method of trifluoromethyl aromatic compounds provided by the present invention has an effective conversion rate of more than 95%, a comprehensive molar yield of more than 95%, and the by-product hydrochloride produced is freed by liquid alkali, 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, green and environmentally friendly preparation method. DETAILED DESCRIPTION

[0027] The present invention provides a method for preparing a trifluoromethyl aromatic compound, comprising the following steps:

[0028] The trichloromethyl aromatic compound and the organic base hydrofluoride are mixed to carry out a fluorination reaction to obtain a reaction solution;

[0029] 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;

[0030] The filtrate and the condensed product are subjected to rectification and purification to obtain a trifluoromethyl aromatic compound.

[0031] 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;

[0032]

[0033] In Formula I: R 1 is halogen, R 2 For-No 2 ; In formula II: R is halogen.

[0034] In the present invention, R in Formula I 1 is a meta-substituent of trichloromethyl, preferably Cl or Br, more preferably Cl; R in Formula I 2 It is a nitro group, and its position is the ortho, meta or para position of the trichloromethyl group, and more preferably 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 of the N atom, and R is preferably in the ortho, meta or para position of 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]

[0038] In formula III: R 1 is halogen, R 2 For-No 2 ; In formula IV: R is halogen.

[0039] In the present invention, R in Formula III 1 and R 2 The type and position of R in Formula IV are the same as those in Formula II and are not repeated here.

[0040] 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.

[0041] 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:

[0042]

[0043] 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:

[0044]

[0045] 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).

[0046] 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 under normal pressure without additional control of the reaction pressure; the fluorination is preferably carried out under stirring conditions. In a specific embodiment of the present invention, it is preferred to first add the trichloromethyl aromatic compound and the organic base hydrofluoride to the reaction vessel, heat it to the temperature of the fluorination reaction under stirring conditions, and react under insulation conditions; after the reaction is completed, cool it to room temperature.

[0047] 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 solid-liquid separation method 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 16h, more preferably 12 to 14h, and the vacuum degree is preferably -0.09 to -0.095MPa; during the drying process, the trifluoromethyl aromatic compound forms a gaseous state, and the present invention recovers it by condensation to further improve the product yield, reduce the fluorine content in the organic base hydrochloride, and improve the quality of the by-product.

[0048] In the present invention, the organic base hydrochloride is obtained after the drying; the organic base hydrochloride is preferably added with liquid alkali for neutralization and liberation, and then distilled and dehydrated to obtain the corresponding organic base.

[0049] 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 substitution and difluoro substitution, the present invention preferably returns the still residue to the fluorination reaction step for application, which can improve the utilization rate of the raw materials and the product yield.

[0050] 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 described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0051] Example 1

[0052] To a three-necked flask, add 275g of 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0mol) and 136g of triethylamine hydrofluoride (MW121.2, 1.1mol) in sequence, start stirring, heat to 100°C-110°C, keep the reaction for 15h, cool and filter to obtain a wet product of triethylamine hydrochloride and a filtrate. The wet product of triethylamine hydrochloride is vacuum dried for 14h at a drying temperature of 80°C and a vacuum degree of -0.095MPa to obtain 135g of by-product triethylamine hydrochloride. During the drying process, the evaporated gas is condensed to obtain recovered 2-trifluoromethyl-4-nitrochlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitrochlorobenzene are combined and rectified by a rectification column, the pressure is controlled within 200 Pa, the top temperature is 65°C-75°C, and the normal boiling temperature is collected to obtain 215g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.6%; the contents of 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene and 2-trifluoromethyl-4-nitrochlorobenzene in the still residue after the rectification are 33wt%, 56wt% and 8.5wt% respectively, and the still residue is returned to the fluorination reaction step for application; the average molar yield of the product after the still residue is applied is 95%.

[0053] Example 2

[0054] To a three-necked flask, 231 g of 3-trichloromethyl-6-chloropyridine (MW 230.9, 1.0 mol) and 148.6 g of pyridine hydrofluoride (MW 99.1, 1.5 mol) were added in sequence. The mixture was stirred and heated to 110°C-120°C. The reaction was kept warm for 12 h. The temperature was 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 h 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 the recovered 2-trifluoromethyl-6-chloropyridine were combined and rectified by a rectification column. The pressure was controlled within 200 Pa and the top temperature was 80°C to 90°C. The normal boiling temperature was collected to obtain 175g of 3-trifluoromethyl-6-chloropyridine with a purity of 99.4%. The contents of 3-monofluoromethyl-6-chloropyridine, 3-difluoromethyl-6-chloropyridine and 3-trifluoromethyl-6-chloropyridine in the still residue were 29.8%, 51% and 10.6% respectively. The still residue was returned to the fluorination reaction step for application. The average molar yield of the product after the still residue was applied was 96.6%.

[0055] Example 3

[0056] 275g 2-trichloromethyl-4-nitrochlorobenzene (MW274.9, 1.0mol) and 70g dimethylamine hydrofluoride were added to a three-necked flask in sequence, stirred, heated to 100°C-110°C, kept warm for 15h, cooled and filtered to obtain a wet product of dimethylamine hydrochloride and a filtrate. The wet product of dimethylamine hydrochloride was vacuum dried for 14h at 75°C and a vacuum degree of -0.095MPa to obtain 79g of by-product dimethylamine hydrochloride. During the drying process, the evaporated gas was condensed to obtain recovered 2-trifluoromethyl-4-nitrochlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitrochlorobenzene were combined and rectified through a rectifying column, the pressure was controlled within 200Pa, the top temperature was 65°C-75°C, and the normal boiling was collected to obtain 213g 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.7%. The contents of 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene and 2-trifluoromethyl-4-nitrochlorobenzene in the still residue after distillation are 32%, 57% and 8.7% respectively. The still residue is returned to the fluorination reaction step for application; the average molar yield of the product after the still residue is applied is 94.8%.

[0057] Example 4

[0058] To a three-necked flask, 275 g of 2-trichloromethyl-4-nitrochlorobenzene (MW 274.9, 1.0 mol) and 95 g of trimethylamine hydrofluoride (MW 79.1, 1.2 mol) were added in sequence, and the mixture was stirred and heated to 100° C. to 110° C. The mixture was kept warm for 15 hours, and the temperature was 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 hours 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 the recovered 2-trifluoromethyl-4-nitrochlorobenzene are combined, and distilled through a distillation column, the pressure is controlled within 200 Pa, the top temperature is 65°C to 75°C, and the normal boiling is collected to obtain 210g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.5%. The contents of 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene and 2-trifluoromethyl-4-nitrochlorobenzene in the still residue of the distillation are 29.8%, 59% and 9.6% respectively. The still residue is returned to the fluorination reaction step for application; the average molar yield of the product after the still residue is applied is 94.5%.

[0059] Comparative Example 1

[0060] To a three-necked flask, 275 g of 2-trichloromethyl-4-nitrochlorobenzene (MW 274.9, 1.0 mol) and 136 g of triethylamine hydrofluoride (MW 121.2, 1.1 mol) were added in sequence, and the mixture was stirred and heated to 100°C-110°C. The mixture was kept warm for 15 h, and the temperature was 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 there was too much residual 2-trifluoromethyl-4-nitrochlorobenzene to be dried). During the drying process, 2-trifluoromethyl-4-nitrochlorobenzene was recovered by evaporation and condensation. The filtrate and the recovered 2-trifluoromethyl-4-nitrochlorobenzene are combined and rectified by a rectification column, the pressure is controlled within 200 Pa, the top temperature is 65°C-75°C, and the normal boiling temperature is collected to obtain 186g of 2-trifluoromethyl-4-nitrochlorobenzene with a purity of 99.6%; the contents of 2-monofluoromethyl-4-nitrochlorobenzene, 2-difluoromethyl-4-nitrochlorobenzene and 2-trifluoromethyl-4-nitrochlorobenzene in the still residue remaining after the rectification are 30wt%, 58wt% and 9.0wt%, respectively, and the still residue is returned to the fluorination reaction step for application; the average molar yield of the product after the still residue is applied is 78% (the yield is low).

[0061] 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 principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a trifluoromethyl aromatic compound, characterized in that: The following steps are involved: A trichloromethyl aromatic compound and an organic base hydrofluoride are mixed for fluorination reaction to obtain a reaction solution; the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride is 1:(1-3); 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; The filtrate and the condensed product are subjected to rectification and purification to obtain a trifluoromethyl aromatic compound; 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; In formula I: R1 is halogen, R2 is -NO2; in formula II: R is halogen; When the still residue obtained from the distillation comprises trichloromethyl aromatic compounds and one or more of their mono- and di-fluoro substitutions, the method further comprises: returning the still residue obtained from the distillation to the fluorination reaction step for application.

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

3. The preparation method according to claim 2, 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.

4. The preparation method according to claim 1 or 3, characterized in that: The temperature of the fluorination reaction is 80° C. to 140° C., and the reaction time is 5 to 20 hours.

5. The preparation method according to claim 1, characterized in that: 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.

6. The preparation method according to claim 1, characterized in that: The drying obtains an organic base hydrochloride; the organic base hydrochloride is neutralized with liquid alkali, and then distilled and dehydrated to obtain a free organic base.

7. The preparation method according to claim 1, characterized in that: 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.

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