A continuous process for the preparation of 3,4-difluorobenzonitrile

Abstract

This invention discloses a continuous preparation method for 3,4-difluorobenzonitrile, using 3,4-dichlorobenzonitrile and potassium fluoride as raw materials, and carrying out a fluorination reaction in the presence of an aprotic polar solvent, a dehydrating agent, and a phase transfer catalyst. The method is characterized by the following steps: S1: 3,4-dichlorobenzonitrile, an aprotic polar solvent, and a dehydrating agent are continuously added to the middle of a dehydration tower; potassium fluoride and a composite phase transfer catalyst are continuously added to the bottom of the dehydration tower; the dehydrating agent-water azeotrope distilled from the top of the dehydration tower is condensed and separated, with the aqueous phase discharged and the oil phase dehydrating agent returned to the tower; the bottom material undergoes a fluorination reaction. This invention employs a composite phase transfer catalyst system composed of a main catalyst and a co-catalyst. The main catalyst, N-bis(dimethylamino)-1,3-dimethylimidazoline, ensures the reaction activity, while the co-catalyst, tetraphenylphosphonium chloride or tetraphenylphosphonium bromide, enhances the thermal stability of the system. The synergistic effect of these two catalysts significantly improves the reaction efficiency, with a total yield exceeding 98.0%.

Description

Technical Field

[0001] This invention relates to the field of fine chemical intermediates synthesis technology, and in particular to a continuous preparation method for 3,4-difluorobenzonitrile. Background Technology

[0002] 3,4-Difluorobenzonitrile is an important fine chemical intermediate, widely used in the synthesis of the highly effective herbicide cyhalofop-butyl, pharmaceuticals, dyes, and fluorinated liquid crystal materials. Currently, the most economical industrial route for preparing 3,4-difluorobenzonitrile is to use inexpensive 3,4-dichlorobenzonitrile as a raw material, in a polar aprotic solvent, with potassium fluoride as the fluorinating agent, and in the presence of a phase transfer catalyst via a halogen exchange fluorination reaction.

[0003] Traditional production processes for this route are mostly batch operations. Batch operations have inherent drawbacks: low equipment utilization, poor batch-to-batch quality stability, high labor intensity, and high energy consumption due to repeated heating and cooling during the reaction. Especially in the later stages of the reaction, as the product concentration increases, prolonged residence at high temperatures can easily lead to side reactions such as polymerization, dehalogenation, and coking, limiting further yield improvements.

[0004] To address the shortcomings of batch processes, continuous production methods have emerged in recent years. For example, Chinese patent document CN117756671A (A Continuous Reaction and Separation Process for 3,4-Difluorobenzonitrile) discloses a continuous process that achieves continuous reaction and separation by connecting a dehydration tower, a dewatering agent tower, and a product removal tower in series, with a total yield that can be increased to up to 98%. This process represents a new direction in the technological development of this field, breaking the reaction equilibrium by continuously removing products and water, and significantly suppressing side reactions.

[0005] Although CN117756671A proposes a framework for continuous processes, there is still room for optimization in specific aspects such as reaction depth control, selective activation of the catalyst system, and synergistic control of multiple towers in series. In particular, how to accurately control the reaction progress to avoid over-reaction in the initial and middle stages of the reaction, and how to achieve efficient recycling of the catalyst system throughout the continuous process, are key to further improving process economy and product quality. Summary of the Invention

[0006] The purpose of this invention is to overcome the above-mentioned technical deficiencies and propose a continuous preparation method for 3,4-difluorobenzonitrile. Based on the existing continuous reactive distillation technology, this method achieves higher reaction efficiency and product purity by optimizing the catalyst system and reaction depth control strategy.

[0007] To achieve the above-mentioned technical objectives, in a first aspect, the present invention provides a continuous preparation method for 3,4-difluorobenzonitrile, using 3,4-dichlorobenzonitrile and potassium fluoride as raw materials, and carrying out a fluorination reaction in the presence of an aprotic polar solvent, a dehydrating agent, and a phase transfer catalyst, comprising the following steps:

[0008] S1: 3,4-Dichlorobenzonitrile, aprotic polar solvent and dehydrating agent are continuously added to the middle of the dehydration tower, and potassium fluoride and composite phase transfer catalyst are continuously added to the bottom of the dehydration tower; the dehydrating agent-water azeotrope distilled from the top of the dehydration tower is condensed and separated into phases, the aqueous phase is discharged, and the oil phase dehydrating agent is returned to the tower; the bottom material undergoes a fluorination reaction. S2: The material from the bottom of the tower in step S1 is continuously introduced into the middle of the dehydration agent tower, the dehydration agent is continuously collected from the top of the tower, and the material in the bottom of the tower continues to react. S3: The material from the bottom of the column in step S2 is continuously introduced into the middle of the product removal column, and crude 3,4-difluorobenzonitrile is continuously collected from the top of the column. The material in the bottom of the column continues to react. S4: After cooling the material in the bottom of the tower in step S3, perform solid-liquid separation, and return the filtrate to the dehydration tower for reuse. The composite phase transfer catalyst is composed of a main catalyst and a co-catalyst.

[0009] Preferably, the main catalyst is N-bis(dimethylamino)-1,3-dimethylimidazoline, and the co-catalyst is tetraphenylphosphonium chloride or tetraphenylphosphonium bromide.

[0010] Preferably, the molar ratio of the main catalyst to the co-catalyst is 1.0:0.1~0.5.

[0011] Preferably, in step S1, the reaction space velocity is controlled at 2~5 h⁻¹, and the water content in the bottom of the column is less than 20 ppm; in step S2, the reaction space velocity is controlled at 0.5~3.0 h⁻¹; and in step S3, the reaction space velocity is controlled at 0.3~1.0 h⁻¹.

[0012] Preferably, by controlling the reaction space velocity, the conversion rate of 3,4-dichlorobenzonitrile in the reboiler of step S1 is 60%~70%, the conversion rate in the reboiler of step S2 is 85%~95%, and the conversion rate in the reboiler of step S3 is above 98%.

[0013] Preferably, the aprotic polar solvent is 1,3-dimethyl-2-imidazolinone or sulfolane; the dehydrating agent is toluene or xylene.

[0014] Preferably, the molar ratio of 3,4-dichlorobenzonitrile to potassium fluoride is 1.0:1.5~2.2.

[0015] Preferably, the solid-liquid separation in step S4 is performed by continuous centrifugation or membrane separation.

[0016] Preferably, the crude 3,4-difluorobenzonitrile collected in step S3 is further purified by a distillation column to obtain a finished product with a purity of over 99.5%.

[0017] Secondly, the technical solution of the present invention provides a continuous preparation method for 3,4-difluorobenzonitrile, which is applied in the continuous production of 3,4-difluorobenzonitrile.

[0018] The beneficial effects of this invention include: 1. This invention employs a composite phase transfer catalyst system consisting of a main catalyst and a co-catalyst. The main catalyst, N-bis(dimethylamino)-1,3-dimethylimidazoline, ensures the reaction activity, while the co-catalyst, tetraphenylphosphonium chloride or tetraphenylphosphonium bromide, enhances the thermal stability of the system. The synergistic effect of the two significantly improves the reaction efficiency, with a total yield of over 98.0%.

[0019] 2. This invention precisely controls the reaction depth of each tower by connecting multiple towers in series and segmented space velocity control, avoiding prolonged residence of the product in the high-temperature zone, effectively suppressing side reactions such as polymerization, dehalogenation and coking, and achieving a product purity of over 99.7%. Detailed Implementation

[0020] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0021] The raw materials used in the embodiments of this invention are all commercially available industrial products.

[0022] Example 1 3,4-Difluorobenzonitrile was prepared according to the following steps: S1: 3,4-Dichlorobenzonitrile is continuously added to the middle of the dehydration tower (30 trays) at a flow rate of 10 kg / h, while DMI is added at a flow rate of 20 kg / h and toluene is added at a flow rate of 3 kg / h. Potassium fluoride (molar ratio to 3,4-dichlorobenzonitrile is 1.0:2.0) and a composite catalyst are continuously added to the bottom of the tower. The composite catalyst consists of the main catalyst N-bis(dimethylamino)-1,3-dimethylimidazoline and the co-catalyst tetraphenylphosphonium chloride at a molar ratio of 1.0:0.3.

[0023] The top temperature of the dehydration tower is controlled at 85-90℃, with a reflux ratio of 3:1. The azeotrope of toluene and water is distilled off. After condensation and phase separation, the aqueous phase is discharged, and the oil phase (toluene) is refluxed back into the tower. The bottom temperature is controlled at 180-190℃, with a water content <20ppm, and the reaction space velocity is controlled at 3h. -1 .

[0024] S2: The material from the bottom of the column in step S1 is continuously pumped into the middle of the dehydration agent column (20 trays). Toluene is continuously collected from the top of the column and returned to step S1 for reuse. The bottom temperature is controlled at 195-205℃, and the reaction space velocity is controlled at 1.5h. -1 The materials continue to react.

[0025] S3: Continuously pump the material from the bottom of the column in step S2 into the middle of the product removal column (15 trays). Crude 3,4-difluorobenzonitrile is continuously collected from the top of the column. The bottom temperature is controlled at 200-210℃, and the reaction space velocity is controlled at 0.5 h⁻¹. -1 The materials continue to react deeply, ensuring a conversion rate of over 98%.

[0026] S4: After cooling the material from the bottom of the column in step S3 to 80°C, it is fed into a continuous centrifuge for solid-liquid separation. The resulting filtrate (containing solvent and catalyst) is returned to the dehydration column for reuse. The filter cake is washed with toluene and dried to obtain potassium chloride as a byproduct. The crude product collected from the top of the column is further purified by a distillation column to obtain the finished product 3,4-difluorobenzonitrile.

[0027] The purity of the 3,4-difluorobenzonitrile product prepared in this embodiment was 99.6%, and the total yield was 97.5% (based on 3,4-dichlorobenzonitrile).

[0028] Example 2 The molar ratio of the main catalyst to the co-catalyst in the composite catalyst was adjusted to 1.0:0.5, and other conditions were the same as in Example 1.

[0029] Results: Product purity was 99.4%, and total yield was 97.0%.

[0030] Example 3 The conversion rate in the reboiler of column S1 is adjusted to approximately 65%, the conversion rate in column S2 to approximately 90%, and the conversion rate in column S3 to over 98.5%. This is achieved by adjusting the space velocity of each column; the space velocity in step S1 is 4 h⁻¹. -1 Step S2 airspeed 2.0h -1 S3 airspeed 0.8h -1 Other conditions are the same as in Example 1.

[0031] Results: Product purity was 99.7%, and total yield was 98.0%.

[0032] Example 4 The solvent was changed from DMI to sulfolane, and other conditions were the same as in Example 1.

[0033] Results: Product purity was 99.3%, and total yield was 96.5%.

[0034] Example 5 The water-removing agent was replaced with xylene, and other conditions were the same as in Example 1.

[0035] Results: Product purity was 99.4%, and total yield was 96.8%.

[0036] Example 6 The molar ratio of 3,4-dichlorobenzonitrile to potassium fluoride was adjusted to 1.0:1.5, and other conditions were the same as in Example 1.

[0037] Results: Product purity was 99.2%, and total yield was 96.0%.

[0038] Example 7 The molar ratio of 3,4-dichlorobenzonitrile to potassium fluoride was adjusted to 1.0:2.2, and other conditions were the same as in Example 1.

[0039] Results: Product purity was 99.5%, and total yield was 97.3%.

[0040] Example 8 The cocatalyst was replaced with tetraphenylphosphonium chloride, and other conditions were the same as in Example 1.

[0041] Results: Product purity was 99.5%, and total yield was 97.2%.

[0042] Comparative Example 1 The continuous reaction was carried out according to the method of Example 1 of CN117756671A, using a single catalyst N-bis(dimethylamino)-1,3-dimethylimidazoline, without adding a co-catalyst.

[0043] Results: Product purity was 99.0%, and total yield was 95.5%.

[0044] Comparative Example 2 Adjust the airspeed in step S1 to 1.5h. -1 This resulted in a high conversion rate of 85% in the reactor of step S1, and an increase in side reactions in step S1. Other conditions were the same as in Example 1.

[0045] Results: Product purity was 98.6%, and total yield was 93.8%.

[0046] Comparative Example 3 Adjust the airspeed in step S3 to 1.5h. -1 This resulted in a conversion rate of only 95% in the reactor of step S3, while other conditions were the same as in Example 1.

[0047] Results: Product purity was 98.8%, and total yield was 94.5%.

[0048] Comparison table of experimental data between the examples and comparative examples To more intuitively demonstrate the technical effects of the present invention, the key process parameters and results of the above embodiments and comparative examples are summarized in Table 1.

[0049] Table 1. Comparison of preparation effects of 3,4-difluorobenzonitrile under different process conditions

[0050] The following conclusions can be drawn from the data in Table 1: 1. Comparing Examples 1-2 with Comparative Example 1, it can be seen that the composite catalyst of the present invention improves product purity by 0.4-0.6 percentage points and overall yield by 1.5-2.0 percentage points compared with a single catalyst, indicating that the composite catalyst system can effectively suppress side reactions and improve reaction efficiency.

[0051] 2. Comparing Examples 1 and 3 with Comparative Examples 2 and 3, it can be seen that controlling the space velocity of each column within the preferred range of this invention can achieve precise control of the reaction depth. Too slow a space velocity leads to an increase in early-stage side reactions, resulting in a significant decrease in yield and purity; too fast a space velocity leads to incomplete reactions, also affecting product quality.

[0052] 3. Examples 4-8 show that the method of the present invention can maintain high purity and yield under different solvents, dehydrating agents, potassium fluoride ratios and types of co-catalysts, proving that the process of the present invention has good prospects for industrial application.

[0053] 4. In summary, Example 3 achieved the best technical results, with a product purity of 99.7% and a total yield of 98.0%.

[0054] The specific embodiments of the present invention described above do not constitute a limitation on the scope of protection of the present invention. Any other corresponding changes and modifications made in accordance with the technical concept of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A continuous preparation method for 3,4-difluorobenzonitrile, comprising using 3,4-dichlorobenzonitrile and potassium fluoride as raw materials, and carrying out a fluorination reaction in the presence of an aprotic polar solvent, a dehydrating agent, and a phase transfer catalyst, characterized in that, Includes the following steps: S1: 3,4-Dichlorobenzonitrile, aprotic polar solvent and dehydrating agent are continuously added to the middle of the dehydration tower, and potassium fluoride and composite phase transfer catalyst are continuously added to the bottom of the dehydration tower; the dehydrating agent-water azeotrope distilled from the top of the dehydration tower is condensed and separated into phases, the aqueous phase is discharged, and the oil phase dehydrating agent is returned to the tower; the bottom material undergoes a fluorination reaction. S2: The material from the bottom of the tower in step S1 is continuously introduced into the middle of the dehydration agent tower, the dehydration agent is continuously collected from the top of the tower, and the material in the bottom of the tower continues to react. S3: The material from the bottom of the column in step S2 is continuously introduced into the middle of the product removal column, and crude 3,4-difluorobenzonitrile is continuously collected from the top of the column. The material in the bottom of the column continues to react. S4: After cooling the material in the bottom of the tower in step S3, perform solid-liquid separation, and return the filtrate to the dehydration tower for reuse. The composite phase transfer catalyst is composed of a main catalyst and a co-catalyst.

2. The preparation method according to claim 1, characterized in that, The main catalyst is N-bis(dimethylamino)-1,3-dimethylimidazoline, and the co-catalyst is tetraphenylphosphonium chloride or tetraphenylphosphonium bromide.

3. The preparation method according to claim 2, characterized in that, The molar ratio of the main catalyst to the co-catalyst is 1.0:0.1~0.

5.

4. The preparation method according to claim 1, characterized in that, In step S1, the reaction space velocity is controlled at 2-5 h. -1 The water content in the reboiler is below 20 ppm; the reaction space velocity in step S2 is controlled at 0.5~3.0 h⁻¹. -1 In step S3, the reaction space velocity is controlled at 0.3~1.0 h⁻¹. -1 .

5. The preparation method according to claim 1, characterized in that, By controlling the reaction space velocity, the conversion rate of 3,4-dichlorobenzonitrile in the reboiler of step S1 is 60%~70%, the conversion rate in the reboiler of step S2 is 85%~95%, and the conversion rate in the reboiler of step S3 is above 98%.

6. The preparation method according to claim 1, characterized in that, The aprotic polar solvent is 1,3-dimethyl-2-imidazolinone or sulfolane; the dehydrating agent is toluene or xylene.

7. The preparation method according to claim 1, characterized in that, The molar ratio of 3,4-dichlorobenzonitrile to potassium fluoride is 1.0:1.5~2.

2.

8. The preparation method according to claim 1, characterized in that, The solid-liquid separation in step S4 is performed using continuous centrifugation or membrane separation.

9. The preparation method according to claim 1, characterized in that, The crude 3,4-difluorobenzonitrile collected in step S3 is further purified by a distillation column to obtain a finished product with a purity of over 99.5%.

10. The use of the method according to any one of claims 1-9 in the continuous production of 3,4-difluorobenzonitrile.

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