Preparation method of 2, 4-difluorobenzonitrile

Abstract

The invention relates to a preparation method of 2, 4-difluorobenzonitrile, which comprises the following steps: (1) mixing an aprotic polar solvent, toluene and potassium fluoride, heating and refluxing for dehydration and toluene removal; (2) adding 2, 4-dichlorobenzonitrile and a catalyst into the mixed solution obtained in the step (1), and reacting to obtain 2, 4-difluorobenzonitrile; the catalyst comprises any one or a combination of at least two of a pyridine catalyst, a crown ether catalyst and an imidazole catalyst. The preparation method provided by the invention has the advantages of low synthesis cost, simple synthesis process, high yield and high purity, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of organic compound synthesis, and in particular to a method for preparing 2,4-difluorobenzonitrile. Background Art

[0002] 2,4-Difluorobenzonitrile is an important intermediate for the synthesis of new fluorine-containing pesticides and medicines, and has broad market application prospects. Therefore, how to efficiently synthesize 2,4-difluorobenzonitrile has attracted widespread attention. At present, the main methods for the synthesis of 2,4-difluorobenzonitrile are as follows:

[0003] 1. Chinese patent CN108947868 discloses a preparation process of 2,4-difluorobenzonitrile, which uses 2,4-difluorobenzoic acid as a raw material, undergoes chlorination, aminolysis, and dehydration to obtain 2,4-difluorobenzonitrile, and the reaction route is:

[0004]

[0005] 2. Document DE2239799, reported in 1974, discloses that m-difluorobenzene is used as a raw material, and 2,4-difluorobenzonitrile is obtained by methylation and ammoxidation at 300°C. The reaction route is:

[0006]

[0007] 3. Chinese patent CN1962623A discloses a preparation process of 2,4-difluorobenzonitrile, which uses 2,4-difluorobromobenzene as a raw material and reacts with sodium cyanide at 100-150°C for 20-48 hours to obtain 2,4-difluorobenzonitrile. The reaction route is:

[0008]

[0009] Among the above-mentioned synthesis methods of 2,4-difluorobenzonitrile, Route 1 has relatively long steps and high costs; Route 2 involves an ammoxidation reaction at 300°C; and the synthesis process of Route 3 involves the use of the highly toxic substance sodium cyanide, all of which are not conducive to industrial production.

[0010] Therefore, it is of great significance to design an efficient and environmentally friendly preparation method of 2,4-difluorobenzonitrile that can meet the needs of industrial production. Summary of the invention

[0011] In order to solve the above technical problems, the purpose of the present invention is to provide a method for preparing 2,4-difluorobenzonitrile. Compared with the prior art, it only requires a one-step reaction, has a simple preparation process, a high yield, is environmentally friendly, and is easy to realize industrial production.

[0012] To achieve this object, the present invention adopts the following technical solutions:

[0013] In a first aspect, the present invention provides a method for preparing 2,4-difluorobenzonitrile, the preparation method comprising the following steps:

[0014] (1) mixing a non-protonic polar solvent, toluene and potassium fluoride, heating and refluxing to dehydrate and remove toluene;

[0015] (2) adding 2,4-dichlorobenzonitrile and a catalyst to the mixed solution obtained in step (1) to react to obtain 2,4-difluorobenzonitrile;

[0016] The catalyst includes any one of a pyridine catalyst, a crown ether catalyst or an imidazole catalyst, or a combination of at least two of them.

[0017] The relevant synthetic route of the preparation method of 2,4-difluorobenzonitrile provided by the present invention is as follows:

[0018]

[0019] Using 2,4-dichlorobenzonitrile as raw material and selecting a specific catalyst, the preparation of 2,4-difluorobenzonitrile can be achieved in a one-step reaction. The reaction raw materials are cheap and easily available, the preparation process is simple, the product has a high yield and high purity, and is easy to realize industrial production.

[0020] Preferably, the aprotic polar solvent comprises any one of N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone or sulfolane, or a combination of at least two thereof. Typical but non-limiting combinations include a combination of N,N-dimethylacetamide and dimethyl sulfoxide, a combination of N,N-dimethylacetamide and N-methylpyrrolidone, a combination of N,N-dimethylacetamide and 1,3-dimethyl-2-imidazolidinone, a combination of N,N-dimethylacetamide and sulfolane, a combination of dimethyl sulfoxide and N-methylpyrrolidone, a combination of dimethyl sulfoxide and 1,3-dimethyl-2-imidazolidinone, a combination of dimethyl sulfoxide and sulfolane. The combination of N-methylpyrrolidone and 1,3-dimethyl-2-imidazolidinone, the combination of N-methylpyrrolidone and sulfolane, the combination of N,N-dimethylacetamide, dimethyl sulfoxide and N-methylpyrrolidone, the combination of N,N-dimethylacetamide, dimethyl sulfoxide and 1,3-dimethyl-2-imidazolidinone, the combination of N,N-dimethylacetamide, dimethyl sulfoxide and sulfolane, the combination of dimethyl sulfoxide, N-methylpyrrolidone and 1,3-dimethyl-2-imidazolidinone, the combination of dimethyl sulfoxide, N-methylpyrrolidone and sulfolane, the combination of N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and sulfolane, and sulfolane is further preferred.

[0021] The aprotic polar solvent selected in the present invention has good solubility, which is conducive to the dispersion of the raw materials, and thus is conducive to increasing the reaction rate. Further, the present invention selects aprotic polar solvent sulfolane with good solubility, which has good dispersibility and is conducive to increasing the reaction rate; the boiling point is 285°C and the thermal stability is strong.

[0022] Preferably, the mass ratio of the aprotic polar solvent to 2,4-dichlorobenzonitrile is (3-6):1, for example, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1 or 6:1, etc.

[0023] Preferably, the mass ratio of potassium fluoride to 2,4-dichlorobenzonitrile is (1-5):1, for example, it can be 1.2:1, 1.5:1, 1.8:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1 or 4.5:1, etc.

[0024] Preferably, the mass ratio of toluene to 2,4-dichlorobenzonitrile is (4-8):1, for example, it can be 4.5:1, 5:1, 5.2:1, 5.5:1, 5.8:1, 6:1, 6.5:1, 7:1 or 7.5:1, etc., preferably (5-6):1.

[0025] Preferably, the pyridine catalyst includes N-ethylpyridine chloride and / or N-propylpyridine chloride.

[0026] Preferably, the crown ether catalyst includes 18-crown-6.

[0027] Preferably, the imidazole catalyst includes 1-methyl-3-butylimidazole hydrochloride and / or 1-butyl-3-methylimidazole tetrafluoroborate.

[0028] Preferably, the catalyst is an imidazole catalyst.

[0029] In the present invention, imidazole catalysts are used in the preparation of 2,4-difluorobenzonitrile, so that the entire synthesis reaction has the advantages of strong thermal stability, small catalyst dosage, high catalytic efficiency, high atom economy, and recyclability, which effectively reduces the generation of three wastes, achieves the purpose of environmentally friendly synthesis of 2,4-difluorobenzonitrile, and is easy to realize industrial production.

[0030] Preferably, the mass ratio of the catalyst to 2,4-dichlorobenzonitrile is (0.01-0.14):1, for example, it can be 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.08:1, 0.1:1 or 0.12:1, etc.

[0031] In the present invention, when the content of the catalyst is low, a good catalytic effect cannot be exerted, and when the content of the catalyst is high, it is easy to cause a waste of the catalyst.

[0032] Preferably, the mixing in step (1) is carried out under stirring.

[0033] Preferably, the heating in step (1) is to 120-150°C, for example, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C or 150°C, and the reflux time is 2-3h, for example, 2.1h, 2.2h, 2.3h, 2.4h, 2.5h, 2.6h, 2.7h, 2.8h or 2.9h, etc.

[0034] Preferably, the reaction in step (2) is first carried out at 180-200°C (for example, 180°C, 185°C, 190°C, 195°C or 200°C, etc.) for a first reaction for 10-20h (for example, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h or 19h, etc.), and then at 220-250°C (for example, 225°C, 230°C, 235°C, 240°C, 245°C or 250°C, etc.) for a second reaction for 3-5h (for example, 3.2h, 3.5h, 3.8h, 4h, 4.2h, 4.5h or 4.8h, etc.).

[0035] In the preparation method of the present invention, the reaction temperature is first controlled at 180-200°C for the first reaction for 10-20h. In this stage, due to steric hindrance and electronic effects, a lower temperature is conducive to controlling the single chlorine atom in 2,4-dichlorobenzonitrile to be replaced by a fluorine atom to obtain a monofluorinated intermediate. Then the reaction temperature is controlled at 220-250°C for a second reaction for 3-5h. Since fluorine is a passivating group, the activity of the monofluorinated intermediate to continue fluorinated substitution is reduced. Increasing the temperature is conducive to promoting the reaction, thereby obtaining a difluorinated target product. By performing two reactions in a staged temperature-controlled manner, the yield and purity of the target product 2,4-difluorobenzonitrile can be effectively improved. At the same time, if the temperature is raised to 220-250°C for the reaction, it is easier to produce a monofluorinated byproduct, and in actual production, the monofluorinated product is not easy to separate from the target product, thereby reducing the purity of the target product.

[0036] Preferably, the first reaction time is 12-16 h, for example, it can be 12.5 h, 13 h, 13.5 h, 14 h, 14.5 h, 15 h or 15.5 h.

[0037] Preferably, after the reaction is completed, a post-treatment step is further included.

[0038] Preferably, the post-treatment step comprises cooling, filtration and distillation.

[0039] Preferably, the cooling temperature is 20-30°C, for example, it can be 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C or 29°C.

[0040] Preferably, the distillation is vacuum distillation, and the vacuum degree of the vacuum distillation is -0.1 MPa.

[0041] Preferably, the distillation collects the fraction at 105-108° C. to obtain the 2,4-difluorobenzonitrile.

[0042] The present invention recovers the filter cake obtained by filtration in the post-treatment step to obtain relatively pure potassium fluoride, potassium chloride and a catalyst. The obtained potassium fluoride and catalyst can be used for the next production, thereby reducing the production cost and improving the economic value.

[0043] The recycling method illustratively includes:

[0044] a. Wash the fluorinated salt mixture with ethyl acetate, dissolve it in water, and separate the layers to obtain a lower aqueous phase and an upper organic phase;

[0045] b. The lower aqueous phase obtained in step a is crystallized, filtered, and evaporated under vacuum at -0.1 MPa and 50 ° C to obtain potassium chloride crystals and crystallization mother liquor;

[0046] c. drying the crystallization mother liquor of step b to obtain recovered potassium fluoride;

[0047] d. Dry the upper organic phase obtained in step a to remove ethyl acetate to obtain a catalyst.

[0048] Preferably, the preparation method of 2,4-difluorobenzonitrile specifically comprises the following steps:

[0049] (1) mixing a non-protonic polar solvent, toluene and potassium fluoride under stirring, heating to 120-150° C., and reflux for 2-3 hours to dehydrate and remove toluene;

[0050] (2) adding a catalyst and 2,4-dichlorobenzonitrile in a mass ratio of (0.01-0.14):1 to the mixed solution obtained in step (1), first controlling the reaction temperature to 180-200° C., carrying out a first reaction for 10-20 hours, and then controlling the reaction temperature to 220-250° C., carrying out a second reaction for 3-5 hours;

[0051] (3) The reaction solution obtained in step (2) is cooled to 20-30° C., filtered, and the filtrate is distilled under a vacuum degree of -0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0052] Compared with the prior art, the present invention has at least the following beneficial effects:

[0053] The present invention uses 2,4-dichlorobenzonitrile as a raw material, selects a specific catalyst, and combines a specific preparation method to realize the preparation of 2,4-difluorobenzonitrile in a one-step reaction. The reaction raw materials are cheap and easily available, the preparation process is simple, the product has a high yield and high purity, the post-processing method is simple, and industrial production can be easily realized. DETAILED DESCRIPTION

[0054] For the convenience of understanding the present invention, the present invention lists the following embodiments. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0055] Example 1

[0056] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0057] (1) 49 mL of sulfolane, 110 mL of toluene and 51.6 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C., and refluxed for detoxification for 1 h;

[0058] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 1 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 14 h, and then controlling the reaction temperature to 235° C., carrying out the second reaction for 4 h;

[0059] (3) The reaction solution obtained in step (2) is cooled to 25° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0060] The NMR characterization data of the compound 2,4-difluorobenzonitrile are as follows:

[0061] 1 H NMR (300MHz, DMSO-d6): δ7.46 (m, 1H, J = 15.9Hz), 7.04 (t, 1H, J = 15.2Hz), 6.66 (t, 1H, J = 15.1Hz).

[0062] Example 2

[0063] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0064] (1) 60 mL of sulfolane, 100 mL of toluene and 38 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C., refluxed for detoxification for 1 h;

[0065] (2) adding 15 g of 2,4-dichlorobenzonitrile and 2 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 180° C., carrying out the first reaction for 12 h, and then controlling the reaction temperature to 220° C., carrying out the second reaction for 3 h;

[0066] (3) The reaction solution obtained in step (2) is cooled to 20° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0067] Example 3

[0068] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0069] (1) 100 mL of sulfolane, 200 mL of toluene and 70 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1.5 h, and then continued to heat to 150° C., and refluxed for detoxification for 1.5 h;

[0070] (2) adding 34.4 g of 2,4-dichlorobenzonitrile and 4 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 200° C., carrying out the first reaction for 16 h, and then controlling the reaction temperature to 250° C., carrying out the second reaction for 5 h;

[0071] (3) The reaction solution obtained in step (2) is cooled to 30° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0072] Example 4

[0073] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0074] (1) 30 mL of sulfolane, 25 mL of dimethyl sulfoxide, 80 mL of toluene and 17.2 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C., refluxed for detoxification for 1 h;

[0075] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 0.2 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 10 h, and then controlling the reaction temperature to 225° C., carrying out the second reaction for 3.5 h;

[0076] (3) The reaction solution obtained in step (2) is cooled to 22° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0077] Example 5

[0078] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0079] (1) 30 mL of sulfolane, 41 mL of dimethyl sulfoxide, 110 mL of toluene and 52 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1.5 h, and then continued to heat to 150° C., refluxed for detoxification for 1 h;

[0080] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 0.5 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 11 h, and then controlling the reaction temperature to 235° C., carrying out the second reaction for 3 h;

[0081] (3) The reaction solution obtained in step (2) is cooled to 28° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0082] Example 6

[0083] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0084] (1) 40 mL of sulfolane, 26 mL of N-methylpyrrolidone, 138 mL of toluene and 69 g of potassium fluoride were mixed under stirring, heated to 125° C., refluxed for dehydration for 1.5 h, and then continued to heat to 145° C., refluxed for detoxification for 1 h;

[0085] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 1.2 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 18 h, and then controlling the reaction temperature to 245° C., carrying out the second reaction for 4 h;

[0086] (3) The reaction solution obtained in step (2) is cooled to 30° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0087] Example 7

[0088] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0089] (1) 40 mL of sulfolane, 45 mL of N-methylpyrrolidone, 158 mL of toluene and 86 g of potassium fluoride were mixed under stirring, heated to 130° C., refluxed for dehydration for 1.5 h, and then continued to heat to 145° C., and refluxed for detoxification for 1.5 h;

[0090] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 1.55 g of 1-methyl-3-butylimidazole hydrochloride to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 20 h, and then controlling the reaction temperature to 250° C., carrying out the second reaction for 4.5 h;

[0091] (3) The reaction solution obtained in step (2) is cooled to 30° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0092] Example 8

[0093] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0094] (1) 80 mL of sulfolane, 100 mL of toluene and 41 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C., refluxed for detoxification for 1 h;

[0095] (2) adding 17.2 g of 2,4-dichlorobenzonitrile and 1 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 14 h, and then controlling the reaction temperature to 235° C., carrying out the second reaction for 4 h;

[0096] (3) The reaction solution obtained in step (2) is cooled to 25° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0097] Example 9

[0098] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which differs from Example 8 only in that 1-butyl-3-methylimidazolium tetrafluoroborate is replaced with an equal mass of 1-methyl-3-butylimidazolium hydrochloride, and other raw materials and steps are the same as those in Example 8.

[0099] Example 10

[0100] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which differs from Embodiment 8 only in that 1-butyl-3-methylimidazolium tetrafluoroborate is replaced with an equal mass of N-ethylpyridine, and other raw materials and steps are the same as those in Embodiment 8.

[0101] Embodiment 11

[0102] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which differs from Embodiment 8 only in that 1-butyl-3-methylimidazolium tetrafluoroborate is replaced with an equal mass of 18-crown ether-6, and other raw materials and steps are the same as those in Embodiment 8.

[0103] Example 12

[0104] This embodiment provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0105] (1) 49 mL of sulfolane, 110 mL of toluene and 51.6 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C., and refluxed for detoxification for 1 h;

[0106] (2) Add 17.2 g of 2,4-dichlorobenzonitrile and 1 g of 1-butyl-3-methylimidazolium tetrafluoroborate to the mixed solution obtained in step (1), raise the temperature to 235° C., and keep the temperature for reaction for 15 h;

[0107] (3) The reaction solution obtained in step (2) is cooled to 25° C., filtered, and the filtrate is distilled under a vacuum degree of −0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

[0108] Comparative Example 1

[0109] This comparative example provides a method for preparing 2,4-difluorobenzonitrile, which differs from Example 1 only in that 1-butyl-3-methylimidazolium tetrafluoroborate is replaced by an equal mass of 2,3,3,3-tetrafluoro-2-(perfluoropropoxy)propionyl fluoride, and the other raw materials and steps are the same as those in Example 1.

[0110] Comparative Example 2

[0111] This comparative example provides a method for preparing 2,4-difluorobenzonitrile, which differs from Example 1 only in that 1-butyl-3-methylimidazolium tetrafluoroborate is replaced with an equal mass of tetraphenylphosphine chloride, and other raw materials and steps are the same as those in Example 1.

[0112] Comparative Example 3

[0113] This comparative example provides a method for preparing 2,4-difluorobenzonitrile, which comprises the following steps:

[0114] (1) 62 g of 1-butyl-3-methylimidazolium tetrafluoroborate, 110 mL of toluene and 51.6 g of potassium fluoride were mixed under stirring, heated to 120° C., refluxed for dehydration for 1 h, and then continued to heat to 150° C. and refluxed for detoxification for 1 h;

[0115] (2) adding 17.2 g of 2,4-dichlorobenzonitrile to the mixed solution obtained in step (1), first controlling the reaction temperature to 190° C., carrying out the first reaction for 14 h, and then controlling the reaction temperature to 235° C., carrying out the second reaction for 4 h;

[0116] (3) The reaction solution obtained in step (2) is cooled to 25° C., filtered, and the filtrate is distilled under a vacuum degree of -0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile. The yield and purity of the product 2,4-difluorobenzonitrile obtained in the above Examples 1-12 and Comparative Examples 1-3 are shown in Table 1.

[0117] Table 1

[0118] Test items Yield (%) purity(%) Example 1 93.5 99.5 Example 2 92.8 99.1 Example 3 87.4 98.7 Example 4 86.2 99.1 Example 5 83.4 98.0 Example 6 84.0 97.6 Example 7 86.1 98.2 Example 8 80.7 96.8 Example 9 78.6 98.4 Example 10 76.4 98.5 Embodiment 11 75.2 97.9 Example 12 86.7 98.8 Comparative Example 1 84.5 99.2 Comparative Example 2 80.7 98.4 Comparative Example 3 79.6 97.8

[0119] The test results show that:

[0120] (1) It can be seen from Examples 1-12 that the yield of 2,4-difluorobenzonitrile prepared by the specific preparation method of the present invention can reach 93.5%, and the purity is higher than 96%;

[0121] (2) By comparing Example 8 with Examples 9-11, it can be seen that the specific selection of the imidazole catalyst in the present invention can further improve the yield of the product;

[0122] (3) By comparing Example 1 with Example 12, it can be seen that the present invention can further improve the yield and purity of the product by controlling the setting of the staged reaction;

[0123] (4) By comparing Example 1 with Comparative Examples 1 and 2, it can be seen that the selection of a specific catalyst in the present invention is beneficial to improving the yield and purity of the product.

[0124] In summary, the present invention uses 2,4-dichlorobenzonitrile as a raw material, selects a specific catalyst, and combines a specific preparation method to realize the preparation of 2,4-difluorobenzonitrile in a one-step reaction. The reaction raw materials are cheap and easily available, the preparation process is simple, the product has a high yield and high purity, the post-treatment is simple, and it is easy to realize industrial production; and the yield of the prepared 2,4-difluorobenzonitrile can reach 93.5%, and the purity can reach 99.5%.

[0125] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing 2,4-difluorobenzonitrile, characterized in that: The preparation method comprises the following steps: (1) mixing a non-protonic polar solvent, toluene and potassium fluoride, heating and refluxing to dehydrate and remove toluene; (2) adding 2,4-dichlorobenzonitrile and a catalyst to the mixed solution obtained in step (1) to react to obtain 2,4-difluorobenzonitrile; The catalyst includes any one of a pyridine catalyst, a crown ether catalyst or an imidazole catalyst, or a combination of at least two of them.

2. The preparation method according to claim 1, characterized in that: The aprotic polar solvent includes any one or a combination of at least two of N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone or sulfolane, and sulfolane is more preferably; Preferably, the mass ratio of the aprotic polar solvent to 2,4-dichlorobenzonitrile is (3-6):

1.

3. The preparation method according to claim 1 or 2, characterized in that: The mass ratio of potassium fluoride to 2,4-dichlorobenzonitrile is (1-5):

1.

4. The preparation method according to any one of claims 1 to 3, characterized in that The mass ratio of toluene to 2,4-dichlorobenzonitrile is (4-8):1, preferably (5-6):

1.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The pyridine catalyst includes N-ethylpyridine chloride and / or N-propylpyridine chloride; Preferably, the crown ether catalyst includes 18-crown-6; Preferably, the imidazole catalyst includes 1-methyl-3-butyl imidazole hydrochloride and / or 1-butyl-3-methyl imidazole tetrafluoroborate; Preferably, the catalyst is an imidazole catalyst; Preferably, the mass ratio of the catalyst to 2,4-dichlorobenzonitrile is (0.01-0.14):

1.

6. The preparation method according to any one of claims 1 to 5, characterized in that: The mixing in step (1) is carried out under stirring; Preferably, the temperature in step (1) is raised to 120-150° C., and the reflux time is 2-3 h.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The reaction in step (2) is first carried out at 180-200° C. for 10-20 h, and then at 220-250° C. for 3-5 h. Preferably, the first reaction time is 12-16 hours.

8. The preparation method according to any one of claims 1 to 7, characterized in that: After the reaction is completed, a post-processing step is also included; Preferably, the post-treatment step comprises cooling, filtration and distillation.

9. The preparation method according to claim 8, characterized in that: The cooling temperature is 20-30°C; Preferably, the distillation is vacuum distillation, and the vacuum degree of the vacuum distillation is -0.1 MPa; Preferably, the distillation collects the fraction at 105-108° C. to obtain the 2,4-difluorobenzonitrile.

10. The preparation method according to any one of claims 1 to 9, characterized in that: The preparation method specifically comprises the following steps: (1) mixing a non-protonic polar solvent, toluene and potassium fluoride under stirring, heating to 120-150° C., and reflux for 2-3 hours to dehydrate and remove toluene; (2) adding a catalyst and 2,4-dichlorobenzonitrile in a mass ratio of (0.01-0.14):1 to the mixed solution obtained in step (1), first controlling the reaction temperature to 180-200° C., carrying out a first reaction for 10-20 hours, and then controlling the reaction temperature to 220-250° C., carrying out a second reaction for 3-5 hours; (3) The reaction solution obtained in step (2) is cooled to 20-30° C., filtered, and the filtrate is distilled under a vacuum degree of -0.1 MPa, and the fraction at 105-108° C. is collected to obtain the 2,4-difluorobenzonitrile.

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