CN112939782B - Preparation method of fluorine-containing aryl compound - Google Patents

Preparation method of fluorine-containing aryl compound Download PDF

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CN112939782B
CN112939782B CN201911268253.6A CN201911268253A CN112939782B CN 112939782 B CN112939782 B CN 112939782B CN 201911268253 A CN201911268253 A CN 201911268253A CN 112939782 B CN112939782 B CN 112939782B
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cyano
nitro
acyl
formula
fluoride
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CN112939782A (en
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曾原
赵子强
李桂云
华立新
何立
袁云龙
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Lanzhou Kangpeng Technology Co.,Ltd.
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Lanzhou Kangpengweier Chemical Co ltd
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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
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/58—Preparation of carboxylic acid halides

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Abstract

The invention relates to the field of organic synthesis, in particular to a preparation method of a fluorine-containing aryl compound. The present invention provides a process for preparing a compound of formula 1, comprising: fluorination reaction: the compound of formula 2 is reacted with an alkali metal fluoride in the presence of a phase transfer catalyst to obtain the compound of formula 1. According to the preparation method of the fluorine-containing aryl compound, a reaction system does not include a solvent, the boiling point of the phase transfer catalyst is higher, no solvent interference exists during rectification or short steaming after the reaction is finished, the distillation yield is high, and the product purity is good.

Description

Preparation method of fluorine-containing aryl compound
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of a fluorine-containing aryl compound.
Background
The fluorine-containing aryl compound is an important intermediate of compounds such as pesticides, medicines and materials. After fluorine atoms are introduced into aromatic compounds, the physical and chemical properties of the compounds can be obviously changed, and even the aromatic compounds can generate a plurality of new and special functions, for example, after fluorine atoms are introduced into active intermediates of pesticides, medicines and the like, the drug effect of the compounds can be obviously enhanced, and the action time is longer.
There are several methods for fluorine-containing aromatic compounds: 1) direct fluorine substitution reaction. In general, fluorine gas is diluted with nitrogen or argon gas and introduced into an inert solvent for aromatic hydrocarbons at a relatively low temperature to carry out a reaction. Because the activity of fluorine gas is very high, the direct fluorination reaction is not easy to control, side reactions are more, and the reaction conditions and the requirements on reaction equipment are harsh, the application of fluorine gas direct fluorination reaction for preparing fluorine-containing aromatic compounds is not much. 2) Balz-Schiemann diazotization. The method uses aromatic primary amine as raw material, diazotizes the aromatic primary amine by nitrous acid to generate arylamine diazonium salt, and then the diazonium salt and HBF 2 The reaction generates insoluble fluoboric acid diazonium salt, and the fluoboric acid diazonium salt is dried to remove water and is heated to decompose to generate the fluorine-containing aromatic compound. When the method is used for heating the diazonium salt, a large amount of toxic gas is generated through decomposition, and the risk of violent heat release exists during decomposition, so that the application of the method is greatly limited. 3) Halogen exchange fluorination. The method is to use alkali metal fluoride (such as KF, NaF, CsF) and other halogens (chlorine, bromine, iodine) on the benzene ring for halogen exchange. In the method, high-boiling-point solvents such as DMF, DMSO, NMP and sulfolane are generally used as reaction solvents, the boiling points of the solvents are often close to that of target products, the products and the solvents are not easy to separate during rectification separation of the products in actual production, the product purity is difficult to improve, the yield is low, and the recovery and the reuse of the solvents have certain difficulty.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, it is an object of the present invention to provide a method for preparing a fluoroaryl compound, which solves the problems of the prior art.
To achieve the above and other related objects, the present invention provides a method for preparing a compound of formula 1, comprising:
fluorination reaction: the compound of formula 1 is prepared by reacting a compound of formula 2 with an alkali metal fluoride in the presence of a phase transfer catalyst, and the reaction equation is as follows:
Figure BDA0002313463680000021
in the formula 1, R 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from nitro, cyano, acyl fluoride, H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from nitro, cyano, acyl fluoride, H, F;
R 5 selected from nitro, cyano, acyl fluoride, H, F;
and R is 1 、R 2 、R 3 、R 4 、R 5 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl and Br;
R 1 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 2 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 3 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 4 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 5 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
and R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 At least one group in the formula is nitryl, cyano, acyl chloride and acyl fluoride;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl or Br, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from the group consisting of acid chlorides, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from acyl fluorides;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from nitro, cyano, acyl fluoride, H, F, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Remain unchanged.
In some embodiments of the invention, R in formula 1 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from H, F;
R 5 selected from nitre H, F;
and R is 1 、R 3 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl;
R 1 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 2 ' is selected from H, Cl, F;
R 3 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 4 ' is selected from H, Cl, F;
R 5 ' is selected from H, Cl, F;
and R is 1 ’、R 3 At least one group is nitro, cyano or acyl chloride;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' each is independently selected fromWhen acyl chloride, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from acyl fluorides;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from nitro, cyano, H, F, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Remain unchanged.
In some embodiments of the invention, the reaction is carried out in the absence of a solvent.
In some embodiments of the invention, the alkali metal fluoride is selected from potassium fluoride and/or sodium fluoride.
In some embodiments of the present invention, the molar ratio of alkali metal fluoride to compound of formula 2 is 1 to 8: 1.
in some embodiments of the invention, the phase transfer catalyst is selected from crown ethers, preferably from a combination of one or more of 18-crown-6, 15-crown-5.
In some embodiments of the invention, the weight ratio of the phase transfer catalyst to the compound of formula 2 is 0.1 to 3: 1.
in some embodiments of the invention, the reaction is carried out under anhydrous conditions.
In some embodiments of the invention, the reaction temperature is 70 to 180 ℃.
In some embodiments of the invention, the post-treatment of the reaction comprises: pulping, carrying out solid-liquid separation, and purifying the obtained liquid phase substance to obtain the compound shown in the formula 1.
In some embodiments of the invention, the method of purification specifically comprises recrystallization and/or rectification.
In some embodiments of the invention, at least a portion of the liquid phase is purified to provide a residue that is used as a phase transfer catalyst in fluorination reactions.
In some embodiments of the invention, the solid phase from the solid-liquid separation comprises an alkali metal halide.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments, and other advantages and effects of the present invention will be apparent to those skilled in the art from the disclosure of the present specification.
The present invention provides a method for preparing a compound of formula 1, which may comprise: the compound of formula 1 is prepared by reacting a compound of formula 2 with an alkali metal fluoride in the presence of a phase transfer catalyst, and the reaction equation is as follows:
Figure BDA0002313463680000041
in the formula 1, R 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from nitro, cyano, acyl fluoride, H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from nitro, cyano, acyl fluoride, H, F;
R 5 selected from nitro, cyano, acyl fluoride, H, F;
and R is 1 、R 2 、R 3 、R 4 、R 5 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl and Br;
R 1 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 2 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 3 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 4 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 5 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
and R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 At least thereinOne group is nitro, cyano, acyl chloride, acyl fluoride.
In the method for preparing the compound of formula 1 provided by the present invention, the reaction is typically a fluorination reaction, and the group X on the aromatic ring of the compound of formula 2 is converted to F in the fluorination reaction, thereby providing the compound of formula 1. In the above fluorination reaction, R in the compound of the formula 2 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' the site of the group is usually separately reacted with R in the reaction product of the compound of formula 1 1 、R 2 、R 3 、R 4 、R 5 The position of the group corresponds to the position of the group. When R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl or Br, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F; when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from acyl chlorides, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from acyl fluorides; when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from nitro, cyano, acyl fluoride, H, F, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Remain unchanged.
In a preferred embodiment of the present invention, in formula 1, R 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from H, F;
R 5 selected from nitre H, F;
and R is 1 、R 3 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl;
R 1 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 2 ' is selected from H, Cl, F;
R 3 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 4 ' is selected from H, Cl, F;
R 5 ' is selected from H, Cl, F;
and R is 1 ’、R 3 At least one group is nitro, cyano or acyl chloride;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F; when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from the group consisting of acid chlorides, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from acyl fluorides; when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from nitro, cyano, H, F, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Remain unchanged.
In the method for preparing the compound of formula 1 provided by the present invention, the reaction can be usually carried out in the absence of a solvent, i.e., the reaction system does not substantially contain other solvents for dispersing the compound of formula 2, the alkali metal fluoride and the phase transfer catalyst, except for the compound of formula 2, the alkali metal fluoride and the phase transfer catalyst. The preparation method of the compound shown in the formula 1 takes aryl halide as a raw material to react with alkali metal fluoride in the presence of a phase transfer catalyst to prepare the corresponding fluorine-containing aryl compound. After the reaction is finished, the reaction product can be treated by post-treatment methods such as solvent pulping, solid-liquid separation and the like, the obtained solid phase substance can comprise alkali metal halide (such as potassium chloride, sodium chloride and the like), so that a byproduct alkali metal halide can be recycled, the obtained liquid phase substance can be further purified to prepare the compound shown in the formula 1, the obtained caldron residue can be directly applied to the fluorination reaction for catalysis in the purification process, and the reaction speed is not obviously changed.
In the preparation method of the compound of formula 1 provided by the present invention, the alkali metal fluoride may be selected from potassium fluoride and/or sodium fluoride, and the amount of the alkali metal fluoride is generally related to the number of halogen atoms of the substrate, for example, the amount of the alkali metal fluoride is generally substantially equal to or excessive with respect to the compound of formula 2, and for example, the molar ratio of the alkali metal fluoride to the compound of formula 2 may be 1 to 8: 1. 1-2: 1. 2-3: 1. 3-4: 1. 4-5: 1. 5-6: 1. 6-7: 1. or 7-8: 1.
in the preparation method of the compound of formula 1 provided by the present invention, the phase transfer catalyst generally has a suitable melting point, so that the phase transfer catalyst can be melted into a liquid in the reaction, and on one hand, the phase transfer catalyst can be phase-transferred and can also be a solvent of the system to have a good solubilizing effect, for example, the melting point of the phase transfer catalyst is generally less than the reaction temperature of the reaction system, and further, for example, the melting point of the phase transfer catalyst can be generally less than or equal to 50 ℃. Of course, at this temperature, the phase transfer catalyst still has relatively good stability. The phase transfer catalyst generally has a suitable boiling point so as to avoid interference during rectification or short steaming after the reaction is completed, and thus, the product yield and the product purity are improved, for example, the boiling point of the phase transfer catalyst is generally higher than that of the target product, and for example, the boiling point of the phase transfer catalyst may be 110 ℃ or higher, or 115 ℃ or higher. In a particular embodiment of the invention, the phase transfer catalyst may be selected from crown ethers and the like, in particular 18-crown-6, 15-crown-5. The crown ether has better thermal stability relatively, does not need to be supplemented in the whole reaction process, and has a proper melting point to assist dissolution. In addition, the crown ether has moderate boiling point, and can be separated from the product by rectification with good distinction, and can be recovered by reduced pressure distillation. The amount of the phase transfer catalyst used can be adjusted by those skilled in the art, for example, the weight ratio of the phase transfer catalyst to the compound of formula 2 can be 0.1 to 3: 1. 0.1-0.3: 1. 0.3-0.5: 1. 0.5-1: 1. 1-1.5: 1. 1.5-2: 1. 2-2.5: 1. or 2.5-3: 1, preferably 0.5 to 1: 1.
in the preparation method of the compound of formula 1 provided by the present invention, the fluorination reaction can be generally carried out under anhydrous conditions, which generally means that the reaction system contains substantially no water. One skilled in the art can select a suitable method to provide an anhydrous reaction system, for example, a solvent reflux method with water can be used to qualify the water content in the reaction system, and for example, the solvent used in the reflux method with water can be one or more combinations of benzene solvents, alkane solvents, and the like, and specifically can be one or more combinations of benzene, toluene, xylene, cyclohexane, hexane, heptane, petroleum ether, and the like.
In the preparation method of the compound of formula 1 provided by the present invention, the fluorination reaction can be usually performed under heating conditions, specifically, the temperature can be 70-180 ℃, 70-90 ℃, 90-110 ℃, 110-130 ℃, 130-150 ℃, or 150-180 ℃, and preferably, 130-150 ℃. The reaction time can be appropriately adjusted by those skilled in the art according to the progress of the reaction, and methods for monitoring the progress of the reaction are known to those skilled in the art, and may be, for example, analytical methods such as chromatography, nuclear magnetic resonance method, or the like, and generally, the end point of the reaction may be substantially disappearance of the raw material substrate, and the specific reaction time may be 3 to 10 hours.
In the preparation method of the compound of formula 1 provided by the invention, the post-treatment of the reaction comprises: after the reaction is finished, pulping, carrying out solid-liquid separation, and purifying the obtained liquid phase substance to obtain the compound shown in the formula 1. The product obtained from the reaction can be subjected to a pulping treatment by selecting a suitable solvent by those skilled in the art, for example, the solvent used in the pulping process can be one or more combinations of benzene-based solvents, alkane-based solvents, halogenated alkane-based solvents, and the like, and specifically can be one or more combinations of benzene, toluene, xylene, cyclohexane, hexane, heptane, petroleum ether, dichloromethane, dichloroethane, and the like.
During the post-treatment, the solid phase obtained by solid-liquid separation may generally include an alkali metal halide, which generally corresponds to the alkali metal fluoride as the reaction raw material, and since X is selected from Cl and Br, the alkali metal halide is generally an alkali metal chloride and an alkali metal bromide, further, when the alkali metal fluoride is selected from potassium fluoride and sodium fluoride, the alkali metal halide generated generally corresponds to a potassium halide and a sodium halide, and for example, the alkali metal halide may specifically be a combination of one or more of potassium chloride, potassium bromide, sodium chloride, sodium bromide and the like.
In the post-treatment process, the method for purifying the liquid phase obtained by solid-liquid separation may specifically include recrystallization and/or rectification. Before purification, the solvent may be removed, and the amount of the solvent to be removed may be usually an appropriate amount or completely removed, so as to facilitate the subsequent purification treatment. In the rectification process, the target product can be obtained by collecting at a proper fraction temperature, the residual substance usually comprises a phase transfer catalyst, and at least part of the residual substance can be used as the phase transfer catalyst in the fluorination reaction, so that the phase transfer catalyst can be recycled and reused. In the recrystallization, the liquid phase obtained by the solid-liquid separation may be recrystallized using a suitable solvent, for example, an alkane solvent, an alcohol solvent, an aromatic hydrocarbon solvent, a ketone solvent, an ester solvent, an ether solvent, water, and the like, more specifically, a solvent such as hexane, ethanol, methanol, isopropanol, heptane, toluene, acetone, water, ethyl acetate, methyl tert-butyl ether, tetrahydrofuran, methyl tetrahydrofuran, and the like, and after the recrystallization to separate the solid phase, the remaining residue usually includes a phase transfer catalyst, and at least a part of the residue may be used as a phase transfer catalyst in the fluorination reaction, thereby realizing recovery and reuse of the phase transfer catalyst. The number of times of applying at least part of the residue obtained by purifying the liquid phase as a phase transfer catalyst in the fluorination reaction may be generally multiple times, and specifically may be 5 to 12 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, or 12 times.
The post-treatment process may further comprise purifying at least a part of the residue obtained by the liquid phase purification to recover the phase transfer catalyst. One skilled in the art can select a suitable method to recover the phase transfer catalyst in the residue obtained by purifying the liquid phase after multiple uses (e.g., the residue left after rectification, the residue left after recrystallization, etc.), for example, the phase transfer catalyst can be recovered by distillation, so that the recycling of the phase transfer catalyst is realized, and the unit consumption is low.
According to the preparation method of the fluorine-containing aryl compound, a reaction system does not include a solvent, the boiling point of the phase transfer catalyst is higher, no solvent interference exists during rectification or short steaming after the reaction is finished, the distillation yield is high, and the product purity is good. In addition, the phase transfer catalyst can not only play a role of catalysis, but also disperse raw materials in a reaction system, so that the reaction speed of the fluorination reaction can be effectively improved, and compared with the conventional tetraphenylphosphonium bromide, tetramethylammonium chloride and other phase transfer catalysts, the reaction speed is improved by more than 5 times, and the unit productivity is greatly improved; meanwhile, the phase transfer catalyst (such as crown ether) has good thermal stability, and side reactions such as degradation and the like can not occur at high temperature, and the phase transfer catalyst does not need to be added through a normally open kettle to promote the reaction. In addition, the preparation method has the advantages of high reaction speed and low tar content of the system, purer byproducts such as potassium chloride or sodium chloride can be obtained through pulping and filtering after the reaction is finished, the potassium chloride or the sodium chloride can be recycled by professional recycling companies, the byproducts obtained by the traditional process contain more tar and are difficult to recycle, the solid waste output is greatly reduced, crown ether is mainly used in the kettle residue after distillation and recrystallization, the crown ether can be directly reused in the fluorination reaction for many times, the raw material cost and the three-waste output of the reaction are greatly reduced, the crown ether can be recycled through short distillation after the repeated reuse, the cyclic reuse of the crown ether is realized, and the unit consumption is low. Meanwhile, the crown ether has a higher boiling point, has better discrimination with a target product than a conventional fluorinated solvent (NMP, sulfolane and the like), can be conveniently separated from a product in the rectification operation, and greatly improves the purity and the separation yield of the product.
The invention of the present application is further illustrated by the following examples, which are not intended to limit the scope of the present application.
Example 1
Preparation of 2,4, 5-trifluoronitrobenzene:
adding 350.0g of 2, 4-dichloro-5-fluoronitrobenzene, 175.0g of 18-crown-6 and 242.0g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 140-150 ℃ for reaction for 5-10 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using toluene, combining organic phases, recovering toluene by short steaming at a vacuum degree of-0.095 Mpa, collecting fractions at a top temperature of 90-110 ℃ to obtain 250.7g of a product, wherein the HPLC purity is 99.0%, and the yield is 85.0%.
Mechanically applying the kettle residues: and carrying out short steaming to obtain 208g of kettle residue, adding 350.0g of 2, 4-dichloro-5-fluoro-nitrobenzene and 242.0g of anhydrous potassium fluoride, heating to 140-150 ℃ for reaction for 5-10 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using methylbenzene, combining organic phases, carrying out short steaming to recover methylbenzene, keeping the vacuum degree at-0.095 Mpa, collecting fractions with the top temperature of 90-110 ℃ to obtain 295.5g of a product, wherein the HPLC purity is 99.1%, and the yield is 88.0%.
The residue was repeatedly used in the fluorination reaction for seven times, and the yield and purity of the product were shown in table 1.
TABLE 1
Number of times of application Yield of Purity of
1 92.2％ 99.0％
2 90.1％ 98.9％
3 91.2％ 99.3％
4 88.8％ 99.0％
5 88.3％ 98.6％
6 87.8％ 99.0％
7 86.9％ 98.7％
Recovering crown ether in the kettle residue: distilling the residue after being repeatedly applied under the vacuum degree of 2-3 mmHg, and collecting the fraction with the top temperature of 130-140 ℃ to obtain 151.6g of 18-crown-6 with the purity of 97.2% and the recovery rate of 86.3%.
Figure BDA0002313463680000081
Example 2
Preparation of 2,4, 5-trifluorophenylnitrile:
adding 380.0g of 2, 4-dichloro-5-fluorobenzonitrile, 95.0g of 18-crown-6 and 290.5g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 120-130 ℃ for reaction for 5-10 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using dimethylbenzene, combining organic phases, recovering dimethylbenzene 3 by short steaming, keeping the vacuum degree at-0.095 Mpa, collecting fractions with the top temperature of 80-95 ℃ to obtain 289.0g of product, wherein the HPLC purity is 99.2%, and the yield is 92.0%. 206g of residue. H 1 NMR(400MHz,CDCl 3 ):δ6.75-6.82(m,1H),δ7.18-7.28(m,1H)。
The recycling scheme and recycling scheme of the kettle residues can be carried out according to example 1, the kettle residues can be recycled for ten times, and the product yield and the product purity of the relevant recycled kettle residues are shown in table 2.
TABLE 2
Number of times of application Yield of the product Purity of
1 94.2％ 98.7％
2 90.1％ 99.4％
3 90.2％ 98.8％
4 88.5％ 99.0％
5 88.9％ 98.6％
6 88.8％ 99.2％
7 87.9％ 98.7％
8 88.0％ 98.5％
9 87.7％ 98.8％
10 85.4％ 98.9％
Recovering crown ether in the kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-685.0 g with the purity of 96.1% and the recovery rate of 90.0%.
Figure BDA0002313463680000091
Example 3
Preparation of 2,4, 6-trifluorobenzoyl fluoride:
adding 965.0g of 2,4, 6-trichlorobenzoyl chloride, 2895.0g of 18-crown-6 and 1380.4g of anhydrous potassium fluoride into a 10L reaction bottle, heating to 110-120 ℃ for reaction for 10-15 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using dichloromethane, combining organic phases, recovering dichloromethane by short evaporation, rectifying under the vacuum degree of 45-50 mmHg, and collecting a fraction with the top temperature of 85-90 ℃ to obtain 634.1g of a product, wherein the HPLC purity is 98.5%, and the yield is 90.0%. 2936.5g of residue. H 1 NMR(400MHz,CDCl 3 ):δ6.48-6.62(m,2H)。
The recycling scheme and recycling scheme of the kettle residues can be carried out according to example 1, eight times of recycling can be carried out totally, and the yield and purity of the related recycled products are shown in table 3.
TABLE 3
Number of times of application Yield of Purity of
1 93.2％ 98.7％
2 92.1％ 99.4％
3 93.2％ 98.8％
4 88.5％ 98.5％
5 88.9％ 98.6％
6 86.7％ 99.2％
7 86.9％ 98.7％
8 87.0％ 99.2％
Recovering crown ether in the kettle residue: distilling the residue after being applied for many times under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-62547.6 g with the recovery rate of 88.0%.
Figure BDA0002313463680000101
Example 4
Preparation of 4-fluoronitrobenzene:
adding 360.0g of 4-chloronitrobenzene, 36.0g of 18-crown-6 and 172.6g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 140-150 ℃ for reaction for 3-5 hours, cooling after the middle control reaction is completed, filtering, pulping filter cakes by dichloroethane, combining organic phases, recovering dichloroethane by short distillation, distilling at a vacuum degree of 45-50 mmHg, collecting fractions at an overhead temperature of 75-80 ℃ to obtain 293.4g of a product with the yield of 91.0%, the HPLC purity of 98.8% and the residue of 38.6 g.
The recycling scheme and the recycling scheme of the kettle residues can be carried out according to the example 1, eight times of recycling can be carried out totally, the yield and the purity of the related recycled products are shown in the table 4,
TABLE 4
Number of times of application Yield of Purity of
1 93.8％ 98.7％
2 93.1％ 99.4％
3 93.2％ 98.4％
4 89.5％ 99.3％
5 88.9％ 99.6％
6 86.6％ 99.2％
7 87.5％ 98.7％
8 87.0％ 99.0％
Recovering crown ether in the kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-629.6 g with the recovery rate of 82.2%.
Figure BDA0002313463680000111
Example 5
Preparation of 2, 4-difluoronitrobenzene:
adding 360.0g of 2-fluoro-4-bromonitrobenzene, 360.0g of 15-crown-5 and 123.6g of anhydrous sodium fluoride into a 1L reaction bottle, heating to 150-160 ℃, reacting for 3-5 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using cyclohexane, combining organic phases, recovering cyclohexane by short steaming, distilling under the vacuum degree of 45-50 mmHg, and collecting distillate with the top temperature of 70-75 ℃ to obtain 234.3g of product, wherein the yield is 90.0% and the HPLC purity is 99.2%. 386.1g of kettle residue.
The recycling scheme and recycling scheme of the kettle residues can be carried out according to example 1, eight times of recycling can be carried out totally, and the yield and purity of the related recycled products are shown in table 5.
TABLE 5
Figure BDA0002313463680000112
Figure BDA0002313463680000121
Recovering crown ether in kettle residue: distilling the residue after being applied for many times under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 110-120 ℃, and recovering 15-crown-5315.0 g with the recovery rate of 87.5%.
Figure BDA0002313463680000122
Example 6
Preparation of 2,4, 6-trifluorobenzoyl fluoride:
adding 500.0g of 2, 4-difluoro-6-chlorobenzoyl fluoride, 150.0g of 18-crown-6 and 194.1g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 70-90 ℃ for reaction for 3-5 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using toluene, combining organic phases, recovering toluene by short distillation, rectifying under the vacuum degree of 45-50 mmHg, and collecting fractions with the top temperature of 85-90 ℃ to obtain 422.0g of a product, wherein the yield is 92.2 percent and the HPLC purity is 98.6 percent. 168.2g of residue.
The recycling scheme and recycling scheme of the kettle residues can be performed according to example 1, the kettle residues can be recycled for twelve times, and the product yield and the product purity of the relevant recycled kettle residues are shown in table 6.
TABLE 6
Number of times of application Yield of the product Purity of
1 93.8％ 99.0％
2 93.0％ 99.4％
3 91.2％ 98.8％
4 88.9％ 98.3％
5 88.9％ 98.6％
6 88.6％ 98.2％
7 88.5％ 99.7％
8 85.0％ 98.3％
9 87.6％ 98.8％
10 88.5％ 98.4％
11 85.0％ 98.6％
12 85.4％ 98.4％
Recovering crown ether in kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting the fraction with the top temperature of 130-140 ℃, and recovering 18-crown-6140.0 g with the recovery rate of 93.3%.
Figure BDA0002313463680000131
Example 7
Preparation of pentafluorophenylnitrile:
adding 500.0g of pentachlorobenzonitrile, 1500.0g of 18-crown-6 and 633.0g of anhydrous potassium fluoride into a 3L reaction bottle, heating to 160-180 ℃ for reaction for 15-20 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using toluene, combining organic phases, recovering toluene by short evaporation, rectifying under a vacuum degree of 45-50 mmHg, collecting a fraction with a top temperature of 100-110 ℃ to obtain 298.2g of product, wherein the yield is 85.0%, and the HPLC purity is 99.0%. 1560.2g of residue.
The recycling scheme of the kettle residue can be performed according to example 1, and can be recycled for ten times, and the yield and the purity of the related recycled products are shown in table 7.
TABLE 7
Number of times of application Yield of Purity of
1 88.8％ 99.2％
2 87.0％ 99.0％
3 87.2％ 98.8％
4 88.0％ 98.8％
5 86.9％ 98.6％
6 86.6％ 98.5％
7 85.5％ 98.7％
8 86.0％ 98.3％
9 87.6％ 98.8％
10 83.5％ 97.9％
Recovering crown ether in kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-61350.0 g with the recovery rate of 90.0%.
Figure BDA0002313463680000141
Example 8
Preparation of 2, 4-difluoro-5-nitrobenzonitrile:
adding 400.0g of 2-fluoro-4-chloro-5-nitrobenzonitrile, 400.0g of 18-crown-6 and 194.1g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 70-85 ℃, reacting for 5-8 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using dichloromethane, combining organic phases, and recovering two phases by short steamingMethyl chloride is rectified under the vacuum degree of 45-50 mmHg, fractions with the top temperature of 125-130 ℃ are collected to obtain 316.5g of products, the yield is 86.2%, and the HPLC purity is 99.0%. 268.2g of residue. H 1 NMR(400MHz,CDCl 3 ):δ7.10-7.22(m,2H),δ8.45-8.53(m,2H)。
The recycling scheme and recycling scheme of the kettle residues can be performed according to example 1, the recycling scheme can be performed for seven times, and the product yield and the product purity of the related recycling scheme are shown in table 8.
TABLE 8
Number of times of application Yield of Purity of
1 85.8％ 98.9％
2 91.1％ 99.4％
3 92.2％ 98.4％
4 88.5％ 99.0％
5 88.9％ 98.6％
6 85.6％ 99.2％
7 83.5％ 99.1％
Recovering crown ether in the kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-6350.0 g with the recovery rate of 87.5%.
Figure BDA0002313463680000142
Example 9
Preparation of 4, 5-difluorophthaloyl fluoride:
adding 360.0g of 4, 5-dichlorophthaloyl chloride, 100.0g of 15-crown-5 and 384.6g of anhydrous sodium fluoride into a 1L reaction bottle, heating to 110-130 ℃ for reaction for 6-15 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using hexane, combining organic phases, recovering hexane by short steaming, distilling under the vacuum degree of 25-30 mmHg, and collecting the fraction with the top temperature of 85-95 ℃ to obtain 221.6g of product, wherein the yield is 81.2% and the HPLC purity is 99.0%. 113.6g of a residue. H 1 NMR(400MHz,CDCl 3 ):δ7.98-8.12(m,2H)。
The recycling scheme and recycling scheme of the kettle residue can be performed according to example 1, nine times of recycling can be performed totally, and the yield and purity of the related recycled products are shown in table 9.
TABLE 9
Number of times of application Yield of Purity of
1 80.2％ 99.3％
2 87.1％ 99.2％
3 86.2％ 98.8％
4 87.5％ 99.0％
5 86.9％ 98.6％
6 85.8％ 98.2％
7 83.9％ 98.7％
8 80.0％ 98.8％
9 78.4％ 98.0％
Recovering crown ether in the kettle residue: distilling the residue after being applied for many times under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 110-120 ℃, and recovering 15-crown-587.0 g with the recovery rate of 87.0%.
Figure BDA0002313463680000151
Example 10
Preparation of 2, 4-difluoro-5-nitrobenzoyl fluoride:
adding 400.0g of 2-chloro-4-bromo-5-nitrobenzoyl chloride, 200.0g of 18-crown-6 and 311.0g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 130-150 ℃ for reacting for 6-8 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using toluene, combining organic phases, recovering toluene by short evaporation, rectifying under the vacuum degree of 25-30 mmHg, and collecting fractions with the top temperature of 90-95 ℃ to obtain 226.7g of a product, wherein the yield is 82.6% and the HPLC purity is 99.0%. 223.1g of residue. H 1 NMR(400MHz,CDCl 3 ):δ7.18-7.28(m,1H),δ8.75-8.82(m,1H)。
The recycling scheme and recycling scheme of the kettle residues can be carried out according to example 1, the recycling scheme can be carried out for six times, and the product yield and the product purity of related recycling are shown in table 10.
Watch 10
Number of times of application Yield of Purity of
1 86.2％ 99.0％
2 86.1％ 98.9％
3 85.2％ 98.6％
4 86.8％ 99.0％
5 83.3％ 98.6％
6 80.8％ 98.0％
Recovering crown ether in the kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-6187.0 g with the recovery rate of 93.5%.
Figure BDA0002313463680000161
Example 11
Preparation of 2, 3-difluoro-6-nitrobenzonitrile:
adding 360.0g of 2-fluoro-3-chloro-6-nitrobenzonitrile, 400.0g of 18-crown-6 and 125.2g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 100-105 ℃, reacting for 5-8 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake with heptane, combining organic phases, recovering heptane by short steaming at a vacuum degree of 15 ℃Distilling at 20mmHg, collecting distillate with the top temperature of 95-100 ℃ to obtain 268.3g of product, wherein the yield is 81.2%, and the HPLC purity is 99.0%. 436.6g of residue. H 1 NMR(400MHz,CDCl 3 ):δ7.78-7.88(m,1H),δ8.26-8.38(m,1H)。
The recycling scheme of the kettle residue can be performed according to example 1, six times of recycling can be performed, and the yield and purity of the related recycled product are shown in table 11.
TABLE 11
Figure BDA0002313463680000162
Figure BDA0002313463680000171
Recovering crown ether in kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-6387.0 g with the recovery rate of 96.5%.
Figure BDA0002313463680000172
Example 12
Preparation of 2, 4-difluoro-1, 3, 5-trinitrobenzene:
adding 282.0g of 2, 4-dichloro-1, 3, 5-trinitrobenzene, 282.0g of 18-crown-6 and 133.6g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 70-75 ℃ for reaction for 5-8 hours, cooling after the middle control reaction is completed, filtering, pulping a filter cake by using toluene, combining organic phases, recovering toluene by short steaming, and recrystallizing the obtained kettle residue by using ethanol to obtain 186.8g of a product, wherein the yield is 75.1%, and the HPLC purity is 98.0%. The mother liquid was concentrated to obtain 302.9g of residue. H 1 NMR(400MHz,CDCl 3 ):δ9.50-9.62(m,1H)。
The recycling scheme and recovery scheme of the kettle residue can be performed according to example 1, the recycling scheme can be performed for five times, and the product yield and the product purity of the related recycling scheme are shown in table 12.
TABLE 12
Number of times of application Yield of Purity of
1 76.2％ 98.0％
2 86.1％ 98.9％
3 85.2％ 98.6％
4 86.8％ 99.0％
5 83.3％ 97.6％
Recovering crown ether in kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-6241.0 g with the recovery rate of 85.5%.
Figure BDA0002313463680000173
Example 13
Preparation of 2, 4-difluoro-1, 5-dinitrobenzene:
adding 300.0g of 2-fluoro-4-chloro-1, 3, 5-trinitrobenzene, 300.0g of 18-crown-6 and 102.7g of anhydrous potassium fluoride into a 1L reaction bottle, heating to 100-105 ℃, reacting for 3-6 hours, cooling after the middle control reaction is completed, filtering, pulping by using toluene to obtain a filter cake, combining organic phases, recovering toluene by short steaming, distilling at a vacuum degree of 2-3 mmHg, collecting distillate with a top temperature of 90-100 ℃ to obtain 221.0g of product, wherein the yield is 79.6%, and the HPLC purity is 99.0%. 316.4g of residue. H 1 NMR(400MHz,CDCl 3 ):δ7.28-7.38(m,1H),δ8.86-8.98(m,1H)。
The recycling scheme and recovery scheme of the kettle residue can be performed according to example 1, the recycling scheme can be performed for five times, and the product yield and the product purity of the related recycling scheme are shown in table 13.
Watch 13
Number of times of application Yield of the product Purity of
1 85.2％ 99.0％
2 85.1％ 98.7％
3 85.2％ 99.3％
4 84.8％ 99.0％
5 80.3％ 98.6％
6 77.8％ 98.8％
Recovering crown ether in the kettle residue: distilling the residue after being applied repeatedly under the vacuum degree of 2-3 mmHg, collecting distillate with the top temperature of 130-140 ℃, and recovering 18-crown-6261.0 g with the recovery rate of 87.0%.
Figure BDA0002313463680000181
Example 14
Preparation of 2,4, 5-trifluoronitrobenzene:
adding 350.0g of 2, 4-dichloro-5-fluoronitrobenzene, 700.0g of sulfolane and 242.0g of anhydrous potassium fluoride into a 2L reaction bottle, heating to 140-150 ℃ for reaction, opening a bottle plug every three hours, adding 3.5g of tetramethylammonium chloride, performing gas chromatography controlled reaction, and using 38.5g of tetramethylammonium chloride together when the reaction end point is reached within about 30 hours. And (3) short steaming to remove the product and the sulfolane mixed solvent, wherein the kettle residue is mixed solid of potassium chloride, potassium fluoride and tar, and the color is black and gray, and the mixed solid is treated as solid waste. And purifying the short distillation fraction by using a rectifying tower to obtain 200.7g of a product with the purity of 97.4 percent and the yield of 68.1 percent.
This example is a control reaction of example 1, conducted using a conventional fluorination process, i.e., a fluorination reaction using sulfolane as the reaction solvent and tetramethylammonium chloride as the phase transfer catalyst. In the reaction, the cover is opened for multiple times to supplement the phase transfer catalyst, and because the product is difficult to separate from the sulfolane, the purity and the yield of the product are both obviously reduced, and simultaneously, a large amount of inorganic salt and tar mixed solid waste generated in the reaction can not be recycled.
In conclusion, the present invention effectively overcomes various disadvantages of the prior art and has high industrial utilization value.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Those skilled in the art can modify or change the above-described embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which may be made by those skilled in the art without departing from the spirit and scope of the present invention as defined in the appended claims.

Claims (6)

1. A process for preparing a compound of formula 1, comprising:
fluorination reaction: the compound of formula 1 is prepared by reacting a compound of formula 2 with an alkali metal fluoride in the presence of a phase transfer catalyst, and the reaction equation is as follows:
Figure FDA0003785899340000011
in the formula 1, R 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from nitro, cyano, acyl fluoride, H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from nitro, cyano, acyl fluoride, H, F;
R 5 selected from nitro, cyano, acyl fluoride, H, F;
and R is 1 、R 2 、R 3 、R 4 、R 5 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl and Br;
R 1 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 2 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 3 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 4 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
R 5 ' is selected from nitro, cyano, acyl chloride, acyl fluoride, H, Cl, Br, F;
and R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 At least one group in the formula is nitryl, cyano, acyl chloride and acyl fluoride;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl or Br, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from the group consisting of acid chlorides, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from acyl fluorides;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from nitro, cyano, acyl fluoride, H, F, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Keeping the same;
the weight ratio of the phase transfer catalyst to the compound of the formula 2 is 0.1-3: 1;
the phase transfer catalyst is selected from one or more of 18-crown-6 and 15-crown-5;
the reaction is carried out in the absence of a solvent, the reaction temperature is 70-180 ℃, and the reaction time is 3-10 hours;
the alkali metal fluoride is selected from potassium fluoride and/or sodium fluoride;
the post-treatment of the reaction includes: pulping, carrying out solid-liquid separation, and purifying the obtained liquid phase substance to obtain the compound shown in the formula 1;
at least part of residues obtained by purifying the liquid phase substance are used as phase transfer catalysts in the fluorination reaction, and the number of times of applying the residues as the phase transfer catalysts in the fluorination reaction is 5-12.
2. A process for the preparation of a compound of formula 1 as claimed in claim 1, wherein in formula 1, R is 1 Selected from nitro, cyano, acyl fluoride, H, F;
R 2 selected from H, F;
R 3 selected from nitro, cyano, acyl fluoride, H, F;
R 4 selected from H, F;
R 5 selected from H, F;
and R is 1 、R 3 Wherein at least one group is nitro, cyano or acyl fluoride;
in the formula 2, X is selected from Cl;
R 1 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 2 ' is selected from H, Cl, F;
R 3 ' is selected from nitro, cyano, acyl chloride, H, Cl, F;
R 4 ' is selected from H, Cl, F;
R 5 ' is selected from H, Cl, F;
and R is 1 ’、R 3 At least one group is nitro, cyano or acyl chloride;
when R is 1 ’、R 2 ’、R 3 ’、R 4 ’、R 5 ' when each is independently selected from Cl, R corresponding thereto 1 、R 2 、R 3 、R 4 、R 5 Each independently selected from F;
when R is 1 ’、R 3 ' when each is independently selected from acyl chlorides, R corresponding thereto 1 、R 3 Each independently selected from acyl fluorides;
when R is 1 ’、R 3 ' when each is independently selected from nitro, cyano, H, F, R corresponding thereto 1 、R 3 Keeping the same;
when R is 2 ’、R 4 ’、R 5 ' when each is independently selected from H, F, R corresponding thereto 2 、R 4 、R 5 Remain unchanged.
3. The process for preparing a compound of formula 1 according to claim 1, wherein the molar ratio of the alkali metal fluoride to the compound of formula 2 is 1 to 8: 1.
4. a process for the preparation of a compound of formula 1 according to claim 1, wherein the reaction is carried out under anhydrous conditions.
5. The process for the preparation of the compound of formula 1 according to claim 4, characterized in that the purification process comprises in particular recrystallization and/or rectification.
6. The process of claim 5 for preparing a compound of formula 1, wherein the solid phase from the solid-liquid separation comprises an alkali metal halide.
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