Method for preparing trifluoromethyl aromatic compounds
The use of organic base hydrofluoride salts for fluorination reactions in trifluoromethyl aromatic compound synthesis addresses safety and stability issues, achieving high yields and reducing environmental impact.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- JINGDEZHEN FUXIANG LIFE TECHNOLOGY CO LTD
- Filing Date
- 2024-03-07
- Publication Date
- 2026-06-26
Smart Images
Figure 0007880975000001 
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Abstract
Description
Technical Field
[0001] (Cross - reference to related applications) This application claims the priority of a Chinese patent application with application number CN202410102233.6 and invention title "Method for Preparing Trifluoromethyl - group Aromatic Compounds" filed with the China National Intellectual Property Administration on January 24, 2024, and all of its contents are incorporated herein by reference.
[0002] The present invention relates to the technical field of trifluoromethyl - group compounds, and particularly to a method for preparing trifluoromethyl - group aromatic compounds.
Background Art
[0003] The trifluoromethyl group has strong electron - attracting ability and lipophilicity, and its C - F bond is very stable. Therefore, by introducing it into organic compounds, the polarity and stability of the compounds can be changed. Aromatic compounds containing trifluoromethyl groups are widely used in fields such as pharmaceuticals and pesticides.
[0004] Trifluoromethylbenzene compounds and trifluoromethylpyridine compounds are two common trifluoromethyl - group aromatic compounds. Both are important intermediates for fluorine - containing pesticides, dyes, and pharmaceuticals. At the same time, most of them are also used as excellent solvents for organic chemical synthesis and have very wide applications.
[0005] Currently, trifluoromethyl aromatic compounds are typically synthesized using trichloromethyl aromatic compounds as starting materials and hydrogen fluoride as the fluorinating agent. For example, a Chinese patent application with publication number CN106866509A provides a method for preparing 2-fluoro-5-trifluoromethyl pyridine, using 3-methyl pyridine as a starting material, first obtaining 2-chloro-5-trichloromethyl pyridine by chlorination, and then obtaining 2-fluoro-5-trifluoromethyl pyridine by a fluorination reaction using anhydrous hydrogen fluoride as the fluorinating agent. Another Chinese patent application with publication number CN114195635A discloses a method for synthesizing o-trifluoromethyl benzoyl chloride, in which 1-(dichloromethyl group)-2-(trichloromethyl group)benzene is first obtained by a chlorination reaction, then 1-(dichloromethyl group)-2-(trifluoromethyl group)benzene is prepared using hydrogen fluoride as the fluorinating agent, and then the desired product is prepared by hydrolysis and chloride acylation.
[0006] In summary, current preparations of trifluoromethyl aromatic compounds often use hydrogen fluoride as the fluorinating agent. Because hydrogen fluoride is used, most reactions must be carried out under high pressure, posing significant safety risks. Furthermore, the difficulty in controlling side reactions leads to unstable product quality. Additionally, residual fluoride ions in the by-product hydrochloric acid are difficult to remove, limiting the application range of the by-product hydrochloric acid and unknowingly increasing environmental protection costs. [Overview of the Initiative] [Problems that the invention aims to solve]
[0007] In view of this, the present invention provides a method for preparing trifluoromethyl aromatic compounds. Since the present invention uses an organic base hydrofluoride as the fluorinating reagent, it does not require high pressure conditions, is highly safe, has stable product quality, and the generated organic base hydrochloride can be sold as a by-product, thus offering significant economic advantages. [Means for solving the problem]
[0008] To achieve the above-mentioned objectives of the present invention, the present invention provides the following technical solutions. A method for preparing trifluoromethyl aromatic compounds, The process involves mixing a trichloromethyl aromatic compound with an organic base hydrofluoride salt to carry out a fluorination reaction and obtain a reaction solution. The above reaction solution is subjected to solid-liquid separation to obtain an organic base hydrochloride wet product and a filtrate, the organic base hydrochloride wet product is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensate product. The process includes the step of rectifying and purifying the above filtrate and the above condensate to obtain a trifluoromethyl aromatic compound.
[0009] Preferably, the trichloromethyl aromatic compound includes a trichloromethyl benzene compound or a trichloromethyl pyridine compound, the structure of the trichloromethyl benzene compound is as shown in formula I, and the structural formula of the trichloromethyl pyridine compound is as shown in formula II.
[0010] [ka]
[0011] [ka]
[0012] In Equation I, R1 is a halogen element and R2 is -NO2, and in Equation II, R is a halogen element.
[0013] Preferably, the above-mentioned organic base hydrofluoric acid salt includes an organic amine hydrofluoric acid salt.
[0014] Preferably, the above organic amine hydrofluoric acid salts include one or more of pyridine hydrofluoric acid, triethylamine hydrofluoric acid, diethylamine hydrofluoric acid, trimethylamine hydrofluoric acid, dimethylamine hydrofluoric acid, and monomethylamine hydrofluoric acid.
[0015] Preferably, the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride salt is 1:(1~3).
[0016] Preferably, the temperature of the fluorination reaction is 80°C to 140°C, and the reaction time is 5 to 20 hours.
[0017] Preferably, the drying is performed under vacuum, the drying temperature is 70°C to 80°C, the drying time is 10 to 16 hours, and the vacuum level is -0.09 to -0.095 MPa.
[0018] Preferably, the above drying yields an organic base hydrochloride, and the above preparation method further includes neutralizing the organic base hydrochloride by adding it to sodium hydroxide, and then distilling and dehydrating it to obtain a free organic base.
[0019] Preferably, the vacuum level for the rectification and purification is 100 to 200 Pa, and the temperature at the top of the rectification column is 80°C to 100°C, which is below the boiling point of the target product.
[0020] Preferably, if the residue obtained by rectification contains one or more trichloromethyl aromatic compounds and their monofluoro substituents and difluoro substituents, the process further includes the step of carrying out a fluorination reaction using the residue obtained by rectification.
[0021] (Effects of the invention) The present invention provides a method for preparing trifluoromethyl group aromatic compounds, which includes the steps of mixing a trichloromethyl group aromatic compound and an organic base hydrogen fluoride salt to carry out a fluorination reaction to obtain a reaction solution; performing solid-liquid separation on the reaction solution to obtain a wet organic base hydrochloride and a filtrate, drying the wet organic base hydrochloride, and condensing and recovering the gas generated during the drying process to obtain a condensation product; and purifying the filtrate and the condensation product to obtain a trifluoromethyl group aromatic compound. Since the present invention uses an organic base hydrogen fluoride salt as a fluorination reagent, the fluorination reaction does not require high-pressure conditions, the reaction conditions are mild, the safety is high, the product quality is stable, and the organic base hydrogen fluoride salt is inexpensive, which is advantageous for reducing the production cost. In addition, the organic base hydrochloride generated by the reaction can be sold as a by-product, so great economic benefits can be obtained.
[0022] Moreover, the present invention utilizes the large difference in boiling points between the trifluoromethyl group aromatic compound and the organic base hydrochloride to condense and recover the trifluoromethyl group aromatic compound generated during the drying process when drying the wet organic base hydrochloride, so that the production rate of the trifluoromethyl group aromatic compound can be further improved. At the same time, the residual of fluoride ions in the by-product hydrochloride can be avoided, and the quality of the by-product hydrochloride can be improved.
[0023] Furthermore, the present invention returns the bottom residue remaining after rectification to the fluorination reaction step to continuously participate in the reaction. The main components of the bottom residue remaining after rectification are a trichloromethyl group aromatic compound and its mono-fluoro substitution product and di-fluoro substitution product. The present invention returns it to the fluorination reaction step, and can further increase the utilization rate of raw materials and the yield of products.
[0024] To sum up, the preparation method of trifluoromethyl group aromatic compounds provided by the present invention has an effective conversion rate reaching over 95% and a comprehensive molar yield that can reach over 95%. The generated by-product hydrochloride is liberated by sodium hydroxide, and the by-product organic base obtained after distillation and dehydration drying meets the industry standard and can be sold as an industrial by-product. Therefore, this method generates little wastewater and no other hazardous waste. Thus, the present invention is an efficient, economical, green and environmentally friendly preparation method.
Embodiments for Carrying out the Invention
[0025] The present invention provides a method for preparing trifluoromethyl group aromatic compounds, mixing a trichloromethyl group aromatic compound with an organic base hydrogen fluoride salt to carry out a fluorination reaction to obtain a reaction solution, solid-liquid separating the above reaction solution to obtain a wet organic base hydrochloride and a filtrate, drying the wet organic base hydrochloride, and condensing and recovering the gas generated during the drying process to obtain a condensation product, and rectifying and purifying the above filtrate and the above condensation product to obtain a trifluoromethyl group aromatic compound.
[0026] The present invention mixes a trichloromethyl group aromatic compound with an organic base hydrogen fluoride salt to carry out a fluorination reaction to obtain a reaction solution. In the present invention, the trichloromethyl group aromatic compound includes a trichloromethyl group benzene compound or a trichloromethyl group pyridine compound. The structure of the trichloromethyl group benzene compound is as shown in Formula I, and the structural formula of the trichloromethyl group pyridine compound is as shown in Formula II.
[0027]
Chemical formula
[0028]
Chemical formula
[0029] In Equation I, R1 is a halogen element and R2 is -NO2, and in Equation II, R is a halogen element.
[0030] In the present invention, R1 in the above formula I is a meta substituent of the trichloromethyl group, preferably Cl or Br, more preferably Cl, and R2 in the above formula I is a nitro group, located at the ortho, meta, or para position of the trichloromethyl group, and more preferably at the meta position of the trichloromethyl group.
[0031] In the present invention, R in formula II is preferably Cl or Br, more preferably Cl, the trichloromethyl group in formula II is preferably located at the ortho, meta, or para position of the N atom, and R is preferably located at the ortho, meta, or para position of the trichloromethyl group.
[0032] In the present invention, the above trifluoromethyl aromatic compound is preferably a trifluoromethyl benzene compound or a trifluoromethyl pyridine compound, the structural formula of the above trifluoromethyl benzene compound is as shown in Formula III, and the structural formula of the above trifluoromethyl pyridine compound is as shown in Formula IV.
[0033] [ka]
[0034] [ka]
[0035] In equation III, R1 is a halogen element and R2 is -NO2, and in equation IV, R is a halogen element.
[0036] In this invention, the types and positions of R1 and R2 in Equation III are the same as those in Equation I, so a further explanation is omitted here. The types and positions of R in Equation IV are the same as those in Equation II, so a further explanation is omitted here.
[0037] In the present invention, the above trichloromethyl aromatic compound preferably includes 2-trichloromethyl-4-nitro-chlorobenzene or 3-trichloromethyl-6-chloropyridine, and the above trifluoromethyl aromatic compound preferably includes 2-trifluoromethyl-4-nitro-chlorobenzene or 3-trifluoromethyl-6-chloropyridine.
[0038] In this invention, when the trichloromethyl aromatic compound is a trichloromethyl benzene compound, the final product obtained is a trifluoromethyl benzene compound, and the reaction equation is as shown in formula A.
[0039] [ka]
[0040] In this invention, when the trichloromethyl aromatic compound is a trichloromethyl pyridine compound, the final product obtained is a trifluoromethyl pyridine compound, and the reaction formula is as shown in formula B.
[0041] [ka]
[0042] In the present invention, the above organic base hydrofluoric acid preferably includes an organic amine hydrofluoric acid, and the above organic amine hydrofluoric acid preferably includes one or more of pyridine hydrofluoric acid, triethylamine hydrofluoric acid, diethylamine hydrofluoric acid, trimethylamine hydrofluoric acid, dimethylamine hydrofluoric acid, and monomethylamine hydrofluoric acid, and the molar ratio of the above trichloromethyl group aromatic compound to the organic base hydrofluoric acid is preferably 1:(1~3), and 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, the reaction time is preferably 5 to 20 hours, more preferably 10 to 15 hours, and in specific embodiments of the present invention, it is sufficient for the fluorination reaction to be carried out at atmospheric pressure, there is no need to separately control the reaction pressure, and the fluorination is carried out under stirring conditions. In specific embodiments of the present invention, it is preferable to first add a trichloromethyl aromatic compound and an organic base hydrofluoride salt to a reaction vessel, raise the temperature to the temperature of the fluorination reaction under stirring conditions, carry out the reaction under heat retention conditions, and after the reaction is completed, cool to room temperature.
[0044] After obtaining the reaction solution, the present invention separates the reaction solution into solid and liquid to obtain an organic base hydrochloride wet product and a filtrate, dries the organic base hydrochloride wet product, and recovers the gas generated during the drying process by condensation to obtain a condensate product. In the present invention, the solid and liquid separation method is preferably filtration or centrifugal separation, 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 level is preferably -0.09 to -0.095 MPa. In the drying process, the trifluoromethyl aromatic compound forms a gaseous state, and the present invention recovers this gas by condensation, thereby further increasing the yield of the product, reducing the fluorine content in the organic base hydrochloride, and improving the quality of the by-product.
[0045] In the present invention, an organic base hydrochloride salt is obtained after the above drying. Preferably, the organic base hydrochloride salt is neutralized and liberated by adding it to sodium hydroxide, and then distilled and dehydrated to obtain the corresponding organic base.
[0046] After obtaining the filtrate and the condensed trifluoromethyl aromatic compound, the present invention purifies the filtrate and the condensed product to obtain the trifluoromethyl aromatic compound. In the present invention, preferably, the filtrate and the condensed product are combined and then purified, the purification method is preferably rectification, the apparatus used for rectification is preferably a rectification column, the vacuum level for rectification is preferably 100 to 200 Pa, the top temperature of the rectification column is preferably determined according to the boiling point of the target product, specifically 80 to 100°C lower than the boiling point of the target product, in the present invention, the product is collected at the top of the rectification apparatus, and in specific examples of the present invention, if the residue remaining after rectification contains one or more of the trichloromethyl aromatic compound and its monofluorosubstituted and difluorosubstituted products, the present invention preferably follows the step of performing a fluorination reaction using the residue, thereby improving the utilization rate of the raw materials and the yield of the product.
[0047] The technical solutions of the present invention will be described clearly and completely below in relation to the embodiments of the present invention, but it is clear that the embodiments described are only a part of the embodiments of the present invention, and not all of them. All other embodiments that can be obtained by those skilled in the art without creative effort based on the embodiments of the present invention are included within the scope of protection of the present invention.
[0048] (Example 1) 275 g of 2-trichloromethyl-4-nitro group chlorobenzene (MW 274.9, 1.0 mol) and 136 g of triethylamine hydrofluoride (MW 121.2, 1.1 mol) were sequentially added to a three-necked flask, stirring was started, and the mixture was heated to 100°C to 110°C and incubated for 15 hours. After cooling and filtering, a wet triethylamine hydrochloride product and a filtrate were obtained. The wet triethylamine hydrochloride product was vacuum-dried for 14 hours at a drying temperature of 80°C and a vacuum of -0.095 MPa, yielding 135 g of triethylamine hydrochloride as a by-product. The gas evaporated during the drying process was condensed to obtain the recovered 2-trifluoromethyl-4-nitro group chlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitro chlorobenzene were combined and rectified in a rectification column, with the pressure controlled to within 200 Pa and the column top temperature to 65°C-75°C. The fraction was collected to obtain 215 g of 99.6% pure 2-trifluoromethyl-4-nitro chlorobenzene. The content of 2-monofluoromethyl-4-nitro chlorobenzene, 2-difluoromethyl-4-nitro chlorobenzene, and 2-trifluoromethyl-4-nitro chlorobenzene in the residue remaining after rectification was 33% by weight, 56% by weight, and 8.5% by weight, respectively. The fluorination reaction step was followed using the residue, and the average molar yield of the product after the residue was 95%.
[0049] (Example 2) 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 sequentially added to a three-necked flask, stirring was started, and the mixture was heated to 110°C to 120°C and incubated for 12 hours. The mixture was then cooled and filtered to obtain a pyridine hydrochloride wet product and a filtrate. The pyridine hydrochloride wet product was vacuum-dried for 14 hours at a drying temperature of 80°C and a vacuum of -0.095 MPa, yielding 110 g of pyridine hydrochloride as a by-product. The gas evaporated during the drying process was condensed to recover 2-trifluoromethyl-6-chloropyridine. The filtrate and the recovered 2-trifluoromethyl-6-chloropyridine were combined and rectified in a rectification column, with the pressure controlled to within 200 Pa and the column top temperature to 80°C-90°C. The fraction was collected to obtain 175 g of 3-trifluoromethyl-6-chloropyridine with a purity of 99.4%. The content of 3-monofluoromethyl-6-chloropyridine, 3-difluoromethyl-6-chloropyridine, and 3-trifluoromethyl-6-chloropyridine in the residue remaining after rectification was 29.8%, 51%, and 10.6%, respectively. The fluorination reaction step was followed using the residue, and the average molar yield of the product after the residue was 96.6%.
[0050] (Example 3) 275 g of 2-trichloromethyl-4-nitro chlorobenzene (MW274.9, 1.0 mol) and 70 g of dimethylamine hydrofluoride were sequentially added to a three-necked flask, stirring was started, and the mixture was heated to 100°C to 110°C and incubated for 15 hours. After cooling and filtering, the mixture was obtained as a wet dimethylamine hydrochloride product and a filtrate. The wet dimethylamine hydrochloride product was vacuum-dried for 14 hours at a drying temperature of 75°C and a vacuum of -0.095 MPa, yielding 79 g of dimethylamine hydrochloride as a by-product. The gas evaporated during the drying process condensed to obtain the recovered 2-trifluoromethyl-4-nitro chlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitro chlorobenzene were combined and rectified using a rectification column, with the pressure controlled to within 200 Pa and the column top temperature controlled to 65°C to 75°C. The fraction was collected to obtain 213 g of 99.7% pure 2-trifluoromethyl-4-nitro chlorobenzene. In the rectification residue, the content of 2-monofluoromethyl-4-nitro group chlorobenzene, 2-difluoromethyl-4-nitro group chlorobenzene, and 2-trifluoromethyl-4-nitro group chlorobenzene was 32%, 57%, and 8.7%, respectively. The fluorination reaction was carried out using the rectification residue, and the average molar yield of the product after the residue was used was 94.8%.
[0051] (Example 4) 275 g (MW 274.9, 1.0 mol) of 2-trichloromethyl-4-nitro group chlorobenzene and 95 g (MW 79.1, 1.2 mol) of trimethylamine hydrofluoride were sequentially added to a three-necked flask, stirring was started, and the mixture was heated to 100°C to 110°C and incubated for 15 hours. After cooling and filtering, a wet trimethylamine hydrochloride product and a filtrate were obtained. The wet trimethylamine hydrochloride product was vacuum-dried for 14 hours at a drying temperature of 75°C and a vacuum of -0.095 MPa, yielding 110 g of trimethylamine hydrochloride as a by-product. The gas evaporated during the drying process was condensed to obtain the recovered 2-trifluoromethyl-4-nitro group chlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitro chlorobenzene were combined and rectified in a rectification column, with the pressure controlled to within 200 Pa and the column top temperature to 65°C-75°C. The fraction was collected to obtain 210 g of 99.5% pure 2-trifluoromethyl-4-nitro chlorobenzene. The content of 2-monofluoromethyl-4-nitro chlorobenzene, 2-difluoromethyl-4-nitro chlorobenzene, and 2-trifluoromethyl-4-nitro chlorobenzene in the residue remaining after rectification was 29.8%, 59%, and 9.6%, respectively. The fluorination reaction step was followed using the residue, and the average molar yield of the product after the residue was 94.5%.
[0052] (Comparative Example 1) 275 g (MW 274.9, 1.0 mol) of 2-trichloromethyl-4-nitro group chlorobenzene and 136 g (MW 121.2, 1.1 mol) of triethylamine hydrofluoride were sequentially added to a three-necked flask, stirring was started, and the mixture was heated to 100°C to 110°C and incubated for 15 hours. After cooling and filtering, a wet triethylamine hydrochloride product and a filtrate were obtained. The wet triethylamine hydrochloride product was vacuum-dried for 14 hours at a drying temperature of 50°C and a vacuum of -0.08 MPa, yielding 196 g of by-product triethylamine hydrochloride (due to the low drying temperature and the excessive amount of residual 2-trifluoromethyl-4-nitro group chlorobenzene, drying was not possible). The gas evaporated during the drying process condensed to obtain the recovered 2-trifluoromethyl-4-nitro group chlorobenzene. The filtrate and the recovered 2-trifluoromethyl-4-nitro chlorobenzene were combined and rectified in a rectification column, with the pressure controlled to within 200 Pa and the column top temperature to 65°C-75°C. The fraction was collected to obtain 186 g of 2-trifluoromethyl-4-nitro chlorobenzene with a purity of 99.6%. The content of 2-monofluoromethyl-4-nitro chlorobenzene, 2-difluoromethyl-4-nitro chlorobenzene, and 2-trifluoromethyl-4-nitro chlorobenzene in the residue remaining after rectification was 30% by weight, 58% by weight, and 9.0% by weight, respectively. The fluorination reaction step was followed using the residue, and the average molar yield of the product after the residue was 78% (low yield).
[0053] It should be noted that the above are merely preferred embodiments of the present invention, and those skilled in the art can make many improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing trifluoromethyl aromatic compounds, A step of mixing a trichloromethyl aromatic compound with an organic base hydrofluoride salt to carry out a fluorination reaction and obtain a reaction solution, wherein the molar ratio of the trichloromethyl aromatic compound to the organic base hydrofluoride salt salt is 1:(1-3), The reaction solution is subjected to solid-liquid separation to obtain an organic base hydrochloride wet product and a filtrate, the organic base hydrochloride wet product is dried, and the gas generated during the drying process is condensed and recovered to obtain a condensate product. A step of obtaining a trifluoromethyl aromatic compound by rectifying and purifying the filtrate and the condensed product, The aforementioned trichloromethyl aromatic compound includes trichloromethyl benzene compounds or trichloromethyl pyridine compounds. The structure of the trichloromethylbenzene compound is as shown in formula I, The structural formula of the aforementioned trichloromethyl pyridine compound is shown in formula II. 【Chemistry 1】 【Chemistry 2】 In equation I, R 1 It is a halogen element, R 2 teeth - NO 2 And, In formula II, R is a halogen element and includes, If the residue obtained by rectification contains one or more of trichloromethyl aromatic compounds and their monofluorosubstituted and difluorosubstituted compounds, further, The step includes following the step of carrying out the fluorination reaction using the residue obtained by the rectification, The aforementioned drying is vacuum drying, with a drying temperature of 70°C to 80°C, a drying time of 10 to 16 hours, and a vacuum level of -0.09 to -0.095 MPa. The preparation method is characterized in that the aforementioned organic base hydrofluoric acid salt is an organic amine hydrofluoric acid salt containing 1 mol of hydrogen fluoride per 1 mol of organic base.
2. The preparation method according to claim 1, characterized in that the aforementioned organic base hydrofluoric acid salt includes an organic amine hydrofluoric acid salt.
3. The preparation method according to claim 2, characterized in that the organic amine hydrofluoric acid salt includes one or more of pyridine hydrofluoric acid salt, triethylamine hydrofluoric acid salt, diethylamine hydrofluoric acid salt, trimethylamine hydrofluoric acid salt, dimethylamine hydrofluoric acid salt, and monomethylamine hydrofluoric acid salt.
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 an organic base hydrochloride salt is obtained by the aforementioned drying, the organic base hydrochloride salt is neutralized with sodium hydroxide, and then distilled and dehydrated to obtain a free organic base.
6. The vacuum level for the aforementioned rectification and purification is 100 to 200 Pa. The preparation method according to claim 1, characterized in that the top temperature of the rectification column is 80°C to 100°C lower than the boiling point of the target product.