A process for the preparation of 1,4-bis(chlorodifluoromethyl)benzene

Abstract

The application provides a preparation method of 1,4-bis(chlorodifluoromethyl)benzene, which comprises the following steps: (1) performing a chlorination reaction on terephthaldehyde, a chlorination reagent and a catalyst to obtain 1,4-bis(dichloromethyl)benzene; (2) performing a fluorine-chlorine displacement reaction on the 1,4-bis(dichloromethyl)benzene obtained in the step (1) and a fluorination reagent to obtain 1,4-bis(difluoromethyl)benzene; (3) performing a reaction on the 1,4-bis(difluoromethyl)benzene obtained in the step (2) and an electrophilic chlorination reagent to obtain the 1,4-bis(chlorodifluoromethyl)benzene. The preparation method has the advantages of simple operation, low toxicity of raw materials, high yield and high purity, solves the problems of difficult scale production, low yield and high toxicity and high cost of raw materials in the prior art, and has great industrial value.

Description

Technical Field

[0001] This invention belongs to the field of organic chemistry technology, specifically relating to a method for preparing 1,4-bis(chlorodifluoromethyl)benzene. Background Technology

[0002] Parylene HT powder possesses excellent insulation, stability, water resistance, mildew resistance, and salt spray resistance. It can withstand short-term temperatures up to 450℃ and long-term temperatures up to 350℃, and also exhibits strong UV resistance, biological stability, and good physical and mechanical properties. Parylene HT coating materials are widely used in aerospace, microelectronics, semiconductors, sensors, magnetic materials, medical devices, and cultural relic preservation.

[0003] Currently, the key raw material for preparing phenelzine HT powder is 1,4-bis(chlorodifluoromethyl)benzene. However, existing methods for preparing 1,4-bis(chlorodifluoromethyl)benzene involve highly corrosive chemicals such as thionyl chloride and highly toxic chlorine gas. The entire preparation and purification process is complex and unsuitable for large-scale production, severely limiting the application of phenelzine HT powder. Therefore, it is necessary to develop an economical and efficient method for preparing 1,4-bis(chlorodifluoromethyl)benzene that can be used for industrial production.

[0004] Dolbier William R et al. from the University of Florida invented a method for preparing 1,4-bis-(chlorodifluoromethyl)benzene ("Efficient synthesis of p-bis-(chlorodifluoromethyl)benzene.", Dolbier, et al., Journal of Fluorine Chemistry, 2007, 1091-1093.). This method utilizes cesium fluoride to prepare 1,4-bis-(difluoromethyl)benzene by melt reaction at 180 degrees Celsius. However, the reaction system is difficult to stir, and incomplete fluorine-halogen substitution leads to numerous impurities. Furthermore, many impurities have boiling points close to the target product, making purification extremely difficult and lacking the potential for large-scale industrial production.

[0005] US20050143608A1 discloses a method for preparing high-purity α,α,α',α'-tetrachloro-p-xylene. This method includes a first-stage reaction 2 involving a mixture of phenylenedialdehyde and thionyl chloride, followed by dimethylformamide (DMF) to obtain a mixture containing α,α,α',α'-tetrachloro-p-xylene as the main product and 4-dichloromethylbenzaldehyde as a byproduct; a second-stage reaction involving the addition of thionyl chloride; and the addition of the product mixture from the second-stage reaction to cold water to obtain a solid product of α,α,α',α'-tetrachloro-p-xylene with a purity of 90-99 mol%. Its disadvantages include the easy generation of incompletely chlorinated impurities, requiring repeated reaction with thionyl chloride to obtain relatively pure 1,4-bis(dichloromethyl)benzene, making the operation cumbersome and difficult to purify.

[0006] 1,4-bis(dichloromethyl)benzene can also be prepared by reacting p-xylene with chlorine under light ("Facile synthesis of hypercrosslinked resin via photochlorination of p-xylene and succedent alkylation polymerization." Ling, et al., Chinese Chemical Letters, 2011, 111-114.). However, incompletely substituted impurities are generated. The disadvantages are that separation and purification are difficult, the yield is low, and the process is complex.

[0007] Existing methods for preparing 1,4-bis(chlorodifluoromethyl)benzene suffer from drawbacks such as cumbersome operation, difficulty in purification, and lack of large-scale industrial production value. Therefore, developing a simple preparation method with low-toxicity raw materials, high yield and purity, and significant industrial value is an urgent problem to be solved in this field. Summary of the Invention

[0008] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing 1,4-bis(chlorodifluoromethyl)benzene. The preparation method, through the selection of raw materials and the optimization of the method, makes the preparation of 1,4-bis(chlorodifluoromethyl)benzene simple, with low toxicity of raw materials, high yield and purity, economic efficiency, and can be used for industrial production.

[0009] To achieve this objective, the present invention adopts the following technical solution:

[0010] This invention provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, the method comprising the following steps:

[0011] (1) Chlorination reaction of benzoxaldehyde, chlorination reagent and catalyst yields 1,4-bis(dichloromethyl)benzene;

[0012] (2) The 1,4-bis(dichloromethyl)benzene obtained in step (1) is subjected to a fluorine-chlorine substitution reaction with a fluorinating agent to obtain 1,4-bis(difluoromethyl)benzene;

[0013] (3) The 1,4-bis(difluoromethyl)benzene obtained in step (2) is reacted with an electrophilic chlorination reagent to obtain the 1,4-bis(chlorodifluoromethyl)benzene.

[0014] The process route for preparing 1,4-bis(chlorodifluoromethyl)benzene provided by this invention is as follows:

[0015]

[0016] The first step involves synthesizing 1,4-bis(dichloromethyl)benzene using terephthalaldehyde, a chlorinating reagent, and a catalyst. Recrystallization yields 1,4-bis(dichloromethyl)benzene with a purity ≥99% and a yield ≥87%. The second step utilizes a fluorinating reagent to perform a fluorine-chlorine substitution reaction with 1,4-bis(dichloromethyl)benzene. This method is simple to operate, yielding a product with a purity ≥98% and a yield ≥85%. The third step involves reacting 1,4-bis(difluoromethyl)benzene with an electrophilic chlorinating reagent, effectively overcoming the drawbacks of traditional chlorination reactions that rely on highly toxic chlorine gas. This process solves the problems of existing processes being difficult to scale up, having low yields, and using highly toxic and expensive raw materials, thus possessing significant industrial value.

[0017] Preferably, the chlorination reagent in step (1) is oxalyl chloride and / or 1,2-dichloroethane.

[0018] Preferably, the molar ratio of terephthalaldehyde to the chlorinated reagent in step (1) is 1:(2-5), for example, it can be 1:2, 1:2.6, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0019] Preferably, the chlorination reaction in step (1) is carried out in the presence of a solvent.

[0020] Preferably, the solvent includes 1,2-dichloroethane.

[0021] Preferably, the chlorination reagent in step (1) is oxalyl chloride, and the molar ratio of terephthalaldehyde to oxalyl chloride in step (1) is 1:(2-5), for example, it can be 1:1, 1:1.5, 1:2, 1:2.6, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0022] Preferably, the chlorination reagent in step (1) is oxalyl chloride, and the amount of 1,2-dichloroethane (solvent) added is 200-400 mL, for example, 200 mL, 250 mL, 300 mL, 350 mL, 400 mL, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0023] Preferably, the chlorination reagent in step (1) is 1,2-dichloroethane. Based on 100 mmol of terephthalaldehyde, the amount of 1,2-dichloroethane (as a solvent and chlorination reagent) added is 500-800 mL, for example, 500 mL, 550 mL, 600 mL, 650 mL, 700 mL, 750 mL, 800 mL, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0024] Preferably, the catalyst in step (1) is a combination of tetrabutylammonium iodide and triphenylphosphine or triphenylphosphine oxide.

[0025] Preferably, the molar ratio of terephthalaldehyde to catalyst in step (1) is 1:(0.01-5), for example, it can be 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.15, 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0026] Preferably, the catalyst in step (1) is triphenylphosphine oxide, and the molar ratio of terephthalaldehyde to triphenylphosphine oxide is 1:(0.01-1). For example, it can be 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.15, 1:0.2, 1:0.25, 1:0.3, 1:0.35, 1:0.4, 1:0.45, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0027] Preferably, the catalyst in step (1) is a combination of tetrabutylammonium iodide and triphenylphosphine, and the molar ratio of terephthalaldehyde to tetrabutylammonium iodide is 1:(1.5-3), for example, it can be 1:1.5, 1:1.7, 1:1.9, 1:2, 1:2.2, 1:2.4, 1:2.5, 1:2.8, 1:3, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0028] Preferably, the catalyst in step (1) is a combination of tetrabutylammonium iodide and triphenylphosphine, and the molar ratio of terephthalaldehyde to triphenylphosphine is 1:(1.5-3), for example, it can be 1:1.5, 1:1.7, 1:1.9, 1:2, 1:2.2, 1:2.5, 1:2.6, 1:2.8, 1:3, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0029] As a preferred embodiment of the present invention, the catalyst and the chlorination reagent form a highly active quaternary phosphonium salt chlorination reagent, which reacts with terephthalaldehyde to obtain high-purity 1,4-bis(dichloromethyl)benzene with a yield of 94%.

[0030] Preferably, the temperature of the chlorination reaction in step (1) is 10-100℃, for example, it can be 10℃, 20℃, 30℃, 40℃, 50℃, 60℃, 65℃, 70℃, 75℃, 80℃, 85℃, 90℃, 95℃, 100℃, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0031] Preferably, the chlorination reaction time in step (1) is 3-24 hours, for example, it can be 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0032] Preferably, after the chlorination reaction in step (1) is completed, a recrystallization step is also included.

[0033] Preferably, the recrystallization reagent is any one or a combination of at least two of petroleum ether, n-hexane, cyclohexane, heptane, isopropyl ether, methyl tert-butyl ether, ethyl acetate, or isopropyl acetate.

[0034] Preferably, the fluorinating agent in step (2) is tertiary amine hydrogen fluoride.

[0035] Preferably, the tertiary amine hydrogen fluoride includes any one or a combination of at least two of the following: pyridine hydrogen fluoride, triethylamine hydrogen fluoride, tripropylamine hydrogen fluoride, tributylamine hydrogen fluoride, or diisopropylethylamine.

[0036] Preferably, the molar ratio of the fluorinating agent to 1,4-bis(dichloromethyl)benzene in step (2) is (4-100):1, for example, it can be 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, 100:1, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0037] Preferably, the temperature of the fluorine-chlorine replacement reaction in step (2) is 10-100℃, for example, it can be 10℃, 20℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, 70℃, 80℃, 90℃, 100℃, and specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0038] Preferably, the fluorine-chlorine replacement reaction in step (2) is carried out in the presence of a solvent.

[0039] Preferably, the solvent is any one or a combination of at least two of the following: tetrahydrofuran, N,N-dimethylacetamide, N,N-dimethylformamide, dichloromethane, diethyl ether, ethylene glycol dimethyl ether, dimethyl sulfoxide, acetonitrile, sulfolane, dioxane, ethyl acetate, or isopropyl acetate.

[0040] Preferably, the time for the fluorine-chlorine replacement reaction in step (2) is 2-24 hours, for example, it can be 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0041] Preferably, the electrophilic chlorination reagent in step (3) is N-chlorosuccinimide.

[0042] Preferably, the molar ratio of the electrophilic chlorinating agent to 1,4-bis(difluoromethyl)benzene in step (3) is (1-5):1, for example, it can be 1:1, 2:1, 2.5:1, 3:1, 3.6:1, 4:1, 4.5:1, 5:1, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0043] Preferably, the reaction temperature in step (3) is 10-100℃, for example, it can be 10℃, 20℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, 70℃, 80℃, 90℃, 100℃, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0044] Preferably, the reaction in step (3) is carried out in the presence of a solvent.

[0045] Preferably, the solvent includes any one or a combination of at least two of carbon tetrachloride, chlorobenzene, 1,2-dichloroethane, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), or benzene.

[0046] Preferably, the reaction in step (3) is carried out under ultraviolet light irradiation or in the presence of an initiator.

[0047] Preferably, the initiator includes any one or a combination of at least two of azobisisobutyronitrile, azobisisoheptanenitrile, benzoyl peroxide, or tert-butyl hydroperoxide.

[0048] Preferably, the reaction time in step (3) is 1-20h, for example, it can be 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h, 20h, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0049] Preferably, the preparation method specifically includes the following steps:

[0050] (1) Terephthalaldehyde and chlorination reagent are chlorinated in the presence of a catalyst and a solvent to give 1,4-bis(dichloromethyl)benzene;

[0051] The chlorination reagent is oxalyl chloride and / or 1,2-dichloroethane, the catalyst is a combination of tetrabutylammonium iodide and triphenylphosphine or triphenylphosphine oxide, and the chlorination reaction is carried out at a temperature of 10-100℃ for 3-24 hours.

[0052] (2) The 1,4-bis(dichloromethyl)benzene obtained in step (1) is subjected to a fluorine-chlorine substitution reaction with a fluorinating agent to obtain 1,4-bis(difluoromethyl)benzene;

[0053] The fluorinating agent is tertiary amine hydrogen fluoride, and the temperature of the fluorine-chlorine replacement reaction is 10-100℃, and the time is 2-24h.

[0054] (3) The 1,4-bis(difluoromethyl)benzene obtained in step (2) is reacted with N-chlorosuccinimide to obtain the 1,4-bis(chlorodifluoromethyl)benzene;

[0055] The reaction is carried out at a temperature of 10-100℃ for 1-20 hours.

[0056] Compared with the prior art, the present invention has the following beneficial effects:

[0057] This invention provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene. The method uses terephthalaldehyde, a chlorinating reagent, and a catalyst as raw materials. High-purity 1,4-bis(dichloromethyl)benzene can be obtained by recrystallization. A fluorination reagent is used to perform a fluorine-chlorine substitution reaction with 1,4-bis(dichloromethyl)benzene, which is simple to operate and yields high purity and high efficiency. The use of an electrophilic chlorinating reagent effectively overcomes the drawback of traditional chlorination reactions relying on highly toxic chlorine gas. This method makes the preparation of 1,4-bis(chlorodifluoromethyl)benzene simple to operate, uses low-toxicity raw materials, achieves a maximum total yield of 82.1% in three steps, a purity of up to 99.8%, is economical and efficient, and can be used for industrial production. Attached Figure Description

[0058] Figure 1 The image shows the 1H NMR spectrum of 1,4-bis(dichloromethyl)benzene obtained in Synthesis Example 1.

[0059] Figure 2 The image shows the 1H NMR spectrum of 1,4-bis(difluoromethyl)benzene obtained in Synthesis Example 7.

[0060] Figure 3 The image shows the 1H NMR spectrum of 1,4-bis(chlorodifluoromethyl)benzene obtained in Example 1. Detailed Implementation

[0061] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0062] Synthesis example 1

[0063] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, the specific preparation method is as follows:

[0064]

[0065] In 1,2-dichloroethane (200 mL), terephthalaldehyde (100 mmol) and triphenylphosphine oxide (15 mmol) were added sequentially. Under stirring at 70 °C, a solution of oxalyl chloride (110 mL, 260 mmol) in 1,2-dichloroethane (100 mL) was added dropwise. After the addition was completed, the mixture was heated for 5 hours. After the reaction was completed, the solvent was removed under reduced pressure to obtain a crude solid product. The product was recrystallized in petroleum ether to give white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 90% and a purity of 99.5%.

[0066] The structure of the 1,4-bis(dichloromethyl)benzene provided in this synthetic example was characterized by NMR analysis using a Bruker 400MHz NMR spectrometer. Figure 1 As shown,

[0067] l ¹H NMR (400 MHz, CDCl₃): δ 7.65 (s, 4H), 6.75 (s, 2H), indicating that the product obtained is 1,4-bis(dichloromethyl)benzene.

[0068] Synthesis example 2

[0069] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, which differs from Synthetic Example 1 only in that 5 mmol of triphenylphosphine oxide is added to obtain white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 87% and a purity of 99.5%.

[0070] Synthesis example 3

[0071] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, which differs from Synthetic Example 1 only in that 35 mmol of triphenylphosphine oxide is added to obtain white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 91% and a purity of 99.5%.

[0072] Synthesis example 4

[0073] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, the specific preparation method is as follows:

[0074]

[0075] In 1,2-dichloroethane (500 mL), terephthalaldehyde (100 mmol), tetrabutylammonium iodide (200 mmol), and triphenylphosphine (250 mmol) were added sequentially. The mixture was stirred at 80 °C for 10 hours. The mixture was concentrated under reduced pressure to obtain a crude solid. 500 mL of petroleum ether and 100 mL of water were added, and the mixture was stirred and filtered to remove insoluble matter. The petroleum ether layer obtained by separation was concentrated to 100 mL, and then cooled to crystallize, yielding white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 94% and a purity of 99.4%.

[0076] The structure of the 1,4-bis(dichloromethyl)benzene provided in this synthetic example was characterized by NMR analysis using a Bruker 400MHz nuclear magnetic resonance spectrometer. l ¹H NMR (400 MHz, CDCl₃): δ 7.65 (s, 4H), 6.75 (s, 2H), indicating that the product obtained is 1,4-bis(dichloromethyl)benzene.

[0077] Synthesis example 5

[0078] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, which differs from synthetic example 4 only in that the reaction is stirred at 40°C for 21 hours to obtain white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 88% and a purity of 99.5%.

[0079] Synthesis example 6

[0080] This synthetic example provides a method for preparing 1,4-bis(dichloromethyl)benzene, which differs from synthetic example 4 only in that the amount of tetrabutylammonium iodide added is 300 mmol and the amount of triphenylphosphine added is 300 mmol, yielding white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 95% and a purity of 99.5%.

[0081] Synthesis Example 7

[0082] This synthetic example provides a method for preparing 1,4-bis(difluoromethyl)benzene, the specific preparation method is as follows:

[0083]

[0084] Add 0.16 mol (1 eq) of 1,4-bis(dichloromethyl)benzene obtained in Synthesis Example 6, 100 mL of dichloromethane, and 12.8 mol (80 eq) of a pyridine solution of 70% pyridine hydrogen fluoride to a 1 L reaction flask. Start heating and stirring, and react at 40 °C for 3 hours. Slowly pour the reaction solution into 1000 mL of ice water to quench it, then extract with petroleum ether. Combine the organic phases, wash with water, dry with anhydrous magnesium sulfate, filter, and remove the solvent from the filtrate by rotary evaporation to obtain a pale yellow liquid. Then, distill under reduced pressure and collect the fraction at 84 °C and 25 mmHg to obtain a colorless and transparent liquid 1,4-bis(difluoromethyl)benzene with a yield of 95% and a purity of 99.4%.

[0085] The structure of the 1,4-bis(difluoromethyl)benzene provided in this synthetic example was characterized by NMR analysis using a Bruker 400MHz NMR spectrometer. Figure 2 As shown, l H NMR (400MHz, CDCl3): δ7.63 (s, 4H), 6.71 (J F-H =40.78, t,2H), indicating that the product obtained is 1,4-bis(difluoromethyl)benzene.

[0086] Synthesis example 8

[0087] This synthetic example provides a method for preparing 1,4-bis(difluoromethyl)benzene, which differs from synthetic example 7 only in that a pyridine solution (3.2 mol, 20 eq) of 70% by mass of pyridine hydrogen fluoride is added to obtain a colorless and transparent liquid 1,4-bis(difluoromethyl)benzene with a yield of 87% and a purity of 99.1%.

[0088] Synthesis example 9

[0089] This synthetic example provides a method for preparing 1,4-bis(difluoromethyl)benzene, the specific preparation method is as follows:

[0090]

[0091] Add 0.16 mol (1 eq) of 1,4-bis(dichloromethyl)benzene obtained in Synthesis Example 6, 100 mL of diethyl ether, and 12.8 mol (80 eq) of triethylamine solution containing 37% triethylamine hydrogen fluoride to a 1 L reaction flask. Start heating and stirring, and react at 40 °C for 3 hours. Slowly pour the reaction solution into 1000 mL of ice water to quench it, then extract with petroleum ether. Combine the organic phases, wash with water, dry with anhydrous magnesium sulfate, filter, and remove the solvent from the filtrate by rotary evaporation to obtain a pale yellow liquid. Then, distill under reduced pressure and collect the fraction at 84 °C and 25 mmHg to obtain a colorless and transparent liquid 1,4-bis(difluoromethyl)benzene with a yield of 92% and a purity of 98.7%.

[0092] Synthesis example 10

[0093] This synthetic example provides a method for preparing 1,4-bis(difluoromethyl)benzene, which differs from synthetic example 9 only in that the reaction is carried out at 10°C for 24 h to obtain a colorless and transparent liquid 1,4-bis(difluoromethyl)benzene with a yield of 85% and a purity of 99.2%.

[0094] Synthesis example 11

[0095] This synthetic example provides a method for preparing 1,4-bis(difluoromethyl)benzene, which differs from synthetic example 9 only in that the reaction is carried out at 80°C for 2 hours to obtain a colorless and transparent liquid 1,4-bis(difluoromethyl)benzene with a yield of 93% and a purity of 99.1%.

[0096] Example 1

[0097] This embodiment provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, the specific preparation method is as follows:

[0098]

[0099] 1,4-bis(difluoromethyl)benzene (0.18 mol) obtained from Synthesis Example 7, N-chlorosuccinimide (NCS, 0.65 mol, 3.6 eq), and 250 mL of carbon tetrachloride were added to a 1 L three-necked flask. The reaction mixture was reacted at 35 °C under UV irradiation for 16 hours. After cooling and filtration, the solvent was removed from the filtrate under reduced pressure. The resulting liquid was then distilled under reduced pressure, and the fraction collected at 94 °C at 30 mmHg was obtained to give a colorless and transparent liquid, 1,4-bis(chlorodifluoromethyl)benzene, with a yield of 94% and a purity of 99.8%.

[0100] The structure of the 1,4-bis(chlorodifluoromethyl)benzene provided in this embodiment was characterized by proton NMR spectroscopy using a Bruker 400MHz nuclear magnetic resonance spectrometer. Figure 3 As shown, l ¹H NMR (400 MHz, CDCl₃): δ 7.77 (s, 4H), indicating that the product obtained is 1,4-bis(chlorodifluoromethyl)benzene.

[0101] Example 2

[0102] This embodiment provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, which differs from Example 1 only in that 0.35 mol of 1,4-bis(difluoromethyl)benzene obtained in Synthesis Example 7 is added to obtain a colorless and transparent liquid 1,4-bis(chlorodifluoromethyl)benzene with a yield of 86% and a purity of 99.8%.

[0103] Example 3

[0104] This embodiment provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, which differs from Example 1 only in that 0.13 mol of 1,4-bis(difluoromethyl)benzene obtained from Synthesis Example 7 is added to obtain a colorless and transparent liquid 1,4-bis(chlorodifluoromethyl)benzene with a yield of 95% and a purity of 99.8%.

[0105] Example 4

[0106] This embodiment provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, the specific preparation method is as follows:

[0107]

[0108] 1,4-bis(difluoromethyl)benzene (0.18 mol), N-chlorosuccinimide (NCS, 0.40 mol, 3.6 eq), azobisisobutyronitrile (AIBN, 0.018 mol), and 250 mL of carbon tetrachloride were added to a 1 L three-necked flask. The reaction mixture was stirred at 65 °C for 6 hours, cooled, and filtered. The solvent was removed from the filtrate under reduced pressure, and the resulting liquid was distilled under reduced pressure. The fraction collected at 94 °C and 30 mmHg was used to obtain a colorless and transparent liquid, 1,4-bis(chlorodifluoromethyl)benzene, with a yield of 90% and a purity of 99.5%.

[0109] Example 5

[0110] This embodiment provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, the specific preparation method is as follows:

[0111]

[0112] 1,4-bis(difluoromethyl)benzene (0.18 mol), N-chlorosuccinimide (NCS, 0.54 mol, 3.6 eq), benzoyl peroxide (0.1 eq, 0.018 mol), and 250 mL of chlorobenzene were added to a 1 L three-necked flask using the method described in Synthesis Example 7. The reaction mixture was stirred at 75 °C for 5 hours, cooled, and filtered. The filtrate was desolventized under reduced pressure, and the resulting liquid was distilled under reduced pressure. The fraction collected at 94 °C and 30 mmHg yielded a colorless, transparent liquid, 1,4-bis(chlorodifluoromethyl)benzene, with a yield of 92% and a purity of 99.8%.

[0113] Comparative Example 1

[0114] This comparative example provides a method for preparing 1,4-bis(dichloromethyl)benzene, the specific preparation method is as follows:

[0115]

[0116] 50 mmol of terephthalaldehyde was added to 100 mL of 1,2-dichloroethane. While stirring at 70 °C, a solution of 55 mL (130 mmol) of oxalyl chloride in 200 mL of 1,2-dichloroethane was added dropwise. After the addition was complete, the mixture was heated for another 5 hours. After the reaction was complete, the solvent was removed under reduced pressure to obtain a crude solid product. The product was recrystallized in petroleum ether to give white crystalline 1,4-bis(dichloromethyl)benzene with a yield of 45% and a purity of 99.3%.

[0117] Comparative Example 2

[0118] This comparative example provides a method for preparing 1,4-bis(dichloromethyl)benzene, the specific preparation method is as follows:

[0119]

[0120] At room temperature, terephthalaldehyde (150 mmol) and phenylphosphonic dichloride (3 eq, 450 mmol) were added sequentially to a 1 L three-necked flask, and the internal temperature was raised to 50 °C. Then, phosphorus pentachloride (750 mmol, 5 eq) was slowly added in portions. After the addition was complete, the temperature was raised to reflux for 10 hours. Phosphorus oxychloride generated in the reaction was first recovered by distillation, and then cooled to room temperature. While stirring, the cooled reaction solution was slowly poured into 500 mL of saturated sodium bicarbonate solution. After the liquid in the beaker cooled to room temperature, the precipitated solid was filtered, washed with water, and finally recrystallized with petroleum ether to obtain a white solid 1,4-bis(dichloromethyl)benzene with a yield of 72% and a purity of 98.5%.

[0121] Comparative Example 3

[0122] This comparative example provides a method for preparing 1,4-bis(difluoromethyl)benzene, the specific steps of which are as follows:

[0123] Potassium fluoride (8 eq, 0.40 mol) was placed in a 100 mL round-bottom flask and dried under reduced pressure at 200 °C for 2 hours. After cooling to room temperature, 1,4-bis(dichloromethyl)benzene (0.05 mol), xylene (20 mL), and tetraphenylphosphine chloride (0.005 mol) were added under nitrogen. The mixture was stirred and refluxed under nitrogen for 48 hours to obtain 1,4-bis(dichloromethyl)benzene with a purity of 95.5% and a yield of 50%.

[0124] Comparative Example 4

[0125] This comparative example provides a method for preparing 1,4-bis(chlorodifluoromethyl)benzene, the specific steps of which are as follows:

[0126] Chlorine gas was passed into a solution of 1,4-bis(difluoromethyl)benzene (74.8 mmol) in carbon tetrachloride (250 mL), and the mixture was irradiated with a sun lamp for 20 hours. The reaction mixture was slowly evaporated to remove carbon tetrachloride. The fraction collected under reduced pressure at 92-94 °C at 30 mmHg was obtained to yield 1,4-bis(chlorodifluoromethyl)benzene (60.6 mol), with a product yield of 81% and a purity of 98.2%.

[0127] In the preparation method of 1,4-bis(chlorodifluoromethyl)benzene provided by this invention, in the first step, the 1,4-bis(dichloromethyl)benzene obtained by Synthetic Examples 1-6 has higher purity (up to 99.5%) and higher yield (up to 95%) compared to the synthesis methods in Comparative Examples 1-2; in the second step, Synthetic Examples 7-11 utilize two different fluorinating agents (pyridine hydrogen fluoride and triethylamine hydrogen fluoride) to carry out a fluorine-chlorine substitution reaction with 1,4-bis(dichloromethyl)benzene, which is simpler to operate than Comparative Example 3, 1, The purity (up to 99.4%) and yield (up to 95%) of 4-bis(difluoromethyl)benzene are high. In the third step, Examples 1-3 utilize the reaction of N-chlorosuccinimide with 1,4-bis(difluoromethyl)benzene, which effectively overcomes the disadvantage of traditional chlorination reactions relying on highly toxic chlorine gas compared to Comparative Example 4. The preparation process of 1,4-bis(chlorodifluoromethyl)benzene is simple to operate, uses low-toxic raw materials, has a yield (up to 95%), high purity (up to 99.8%), is economical and efficient, and can be used for industrial production.

[0128] The applicant declares that this invention illustrates a method for preparing 1,4-bis(chlorodifluoromethyl)benzene through the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials for the product of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

Claims

1. A method for preparing 1,4-bis(chlorodifluoromethyl)benzene, characterized in that, The preparation method includes the following steps: (1) Chlorination reaction of phenylenedialdehyde, chlorination reagent and catalyst to obtain 1,4-bis(dichloromethyl)benzene; (2) The 1,4-bis(dichloromethyl)benzene obtained in step (1) is subjected to a fluorine-chlorine substitution reaction with a fluorinating agent to obtain 1,4-bis(difluoromethyl)benzene; (3) The 1,4-bis(difluoromethyl)benzene obtained in step (2) is reacted with an electrophilic chlorination reagent to obtain the 1,4-bis(chlorodifluoromethyl)benzene; The catalyst in step (1) is a combination of tetrabutylammonium iodide and triphenylphosphine; The chlorination reaction in step (1) is carried out at a temperature of 80-100℃; The fluorinating agent in step (2) is any one or a combination of at least two of the following: pyridine hydrogen fluoride, triethylamine hydrogen fluoride, tripropylamine hydrogen fluoride, tributylamine hydrogen fluoride, or diisopropylethylamine. The electrophilic chlorination reagent in step (3) is N-chlorosuccinimide; The molar ratio of the electrophilic chlorinating agent to 1,4-bis(difluoromethyl)benzene in step (3) is (2-5):1; The reaction described in step (3) is carried out in the presence of an initiator.

2. The preparation method according to claim 1, characterized in that, The chlorination reagent in step (1) is oxalyl chloride and / or 1,2-dichloroethane.

3. The preparation method according to claim 1, characterized in that, The molar ratio of terephthalaldehyde to chlorinated reagent in step (1) is 1:(2-5).

4. The preparation method according to claim 1, characterized in that, The molar ratio of terephthalaldehyde to catalyst in step (1) is 1:(0.01-5).

5. The preparation method according to claim 1, characterized in that... The chlorination reaction in step (1) is carried out in the presence of a solvent.

6. The preparation method according to claim 5, characterized in that, The solvent includes 1,2-dichloroethane.

7. The preparation method according to claim 1, characterized in that, The chlorination reaction in step (1) takes 3-24 hours.

8. The preparation method according to claim 1, characterized in that, The molar ratio of the fluorinating agent to 1,4-bis(dichloromethyl)benzene in step (2) is (4-100):

1.

9. The preparation method according to claim 1, characterized in that, The temperature of the fluorine-chlorine replacement reaction in step (2) is 10-100℃.

10. The preparation method according to claim 1, characterized in that... The fluorine-chlorine replacement reaction in step (2) is carried out in the presence of a solvent.

11. The preparation method according to claim 10, characterized in that, The solvent is any one or a combination of at least two of the following: tetrahydrofuran, N,N-dimethylacetamide, N,N-dimethylformamide, dichloromethane, diethyl ether, ethylene glycol dimethyl ether, dimethyl sulfoxide, acetonitrile, sulfolane, dioxane, ethyl acetate, or isopropyl acetate.

12. The preparation method according to claim 1, characterized in that, The time for the fluorine-chlorine replacement reaction in step (2) is 2-24 hours.

13. The preparation method according to claim 1, characterized in that, The reaction temperature in step (3) is 10-100℃.

14. The preparation method according to claim 1, characterized in that, The chlorination reaction in step (3) is carried out in the presence of a solvent.

15. The preparation method according to claim 14, characterized in that, The solvent includes any one or a combination of at least two of the following: carbon tetrachloride, chlorobenzene, 1,2-dichloroethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or benzene.

16. The preparation method according to claim 1, characterized in that, The initiator includes any one or a combination of at least two of azobisisobutyronitrile, azobisisoheptanenitrile, benzoyl peroxide, or tert-butyl hydroperoxide.

17. The preparation method according to claim 1, characterized in that, The reaction time in step (3) is 1-20 h.

18. The preparation method according to claim 1, characterized in that, The preparation method specifically includes the following steps: (1) Terephthalaldehyde and chlorination reagent are chlorinated in the presence of a catalyst and a solvent to give 1,4-bis(dichloromethyl)benzene; The chlorination reagent is oxalyl chloride and / or 1,2-dichloroethane, the catalyst is a combination of tetrabutylammonium iodide and triphenylphosphine, and the chlorination reaction is carried out at a temperature of 80-100℃ for 3-24 hours. (2) The 1,4-bis(dichloromethyl)benzene obtained in step (1) is subjected to a fluorine-chlorine substitution reaction with a fluorinating agent to obtain 1,4-bis(difluoromethyl)benzene; The fluorinating agent is any one or a combination of at least two of the following: pyridine hydrogen fluoride, triethylamine hydrogen fluoride, tripropylamine hydrogen fluoride, tributylamine hydrogen fluoride, or diisopropylethylamine. The temperature of the fluorine-chlorine replacement reaction is 10-100℃, and the time is 2-24 h. (3) The 1,4-bis(difluoromethyl)benzene obtained in step (2) is reacted with N-chlorosuccinimide to obtain the 1,4-bis(chlorodifluoromethyl)benzene; The reaction is carried out at a temperature of 10-100℃ for a time of 1-20 h in the presence of an initiator.

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