A process for the preparation of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl) urea. The application comprises the following steps: S1. assembling a continuous tank reactor for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl) urea; S2. preparing a 3,5-dichlorophenyl isocyanate toluene solution and a sodium glycinate solution; S3. simultaneously feeding the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution prepared in step S2 into the continuous tank reactor for reaction; and S4. carrying out post-treatment on the liquid after reaction in the continuous tank reactor, and obtaining 1-carboxymethyl-3-(3,5-dichlorophenyl) urea. The application adopts a continuous flow mode to synthesize 1-carboxymethyl-3-(3,5-dichlorophenyl) urea in the continuous tank reactor, and the reaction period is shortened from 10 hours to 2 hours, so that the reaction efficiency is significantly improved. The whole reaction process is a continuous reaction, the process is simple, the reaction condition is accurately controlled, the equipment corrosion is small, the safety is high, and the frequent opening and closing of the tank and the temperature rising and falling are avoided.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea. Background Technology

[0002] 1-Carboxymethyl-3-(3,5-dichlorophenyl)urea is an intermediate in the preparation of isopyrenesin technical grade. The reaction for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea from 3,5-dichlorophenyl isocyanate, glycine, etc., is an addition reaction, which is an exothermic process and a relatively dangerous chemical process.

[0003] Currently, the domestic production process for 1-carboxymethyl-3-(3,5-dichlorophenyl)urea is mainly a batch process. First, caustic soda and water are added to a reactor. After the caustic soda dissolves, glycine is added. After the glycine dissolves, the temperature is raised to the operating temperature, and a toluene solution of 3,5-dichlorophenyl isocyanate is slowly added dropwise. After the reaction is complete, the product is obtained through separation processes such as adding water, layering, acidification, filtration, washing, filtration again, and drying. This reaction process is characterized by long cycle times, high production costs, frequent reactor opening and closing, and temperature adjustments, resulting in a low safety factor. Therefore, a simple, efficient, and continuous production method for 1-carboxymethyl-3-(3,5-dichlorophenyl)urea has attracted significant attention from enterprises. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing methods for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, such as long preparation cycle, frequent opening and closing of the reactor, and low preparation efficiency due to temperature fluctuations. This invention provides a method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea that has a short preparation cycle, can be continuously produced, and is highly efficient.

[0005] The technical solution adopted by this invention to solve its technical problem is: a method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, comprising the following steps:

[0006] S1. Assemble a continuous batch reactor for the preparation of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea;

[0007] S2. Prepare a toluene solution of 3,5-dichlorophenyl isocyanate and a sodium glycine solution;

[0008] S3. The sodium glycine solution and the 3,5-dichlorophenyl isocyanate toluene solution prepared in step S2 are simultaneously fed into the continuous batch reactor for reaction;

[0009] S4. After the reaction liquid enters and exits the continuous batch reactor, it is processed to obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea.

[0010] Preferably, the continuous batch reactor includes a stirred reaction vessel, a water addition vessel, an acidification vessel, a filter, and a toluene recovery vessel that are connected in sequence via liquid channels; the water addition vessel includes a first water addition vessel and a second water addition vessel that are both connected in liquid channels to the stirred reaction vessel and the acidification vessel.

[0011] Preferably, the sodium glycine solution and the 3,5-dichlorophenyl isocyanate toluene solution from step S3 are simultaneously added to the stirred reactor for reaction, and the reaction equation is as follows:

[0012]

[0013] The molar ratio of 3,5-dichlorophenyl isocyanate to glycine is 1:1.1 to 1.5.

[0014] Preferably, the sodium glycine solution and the 3,5-dichlorophenyl isocyanate toluene solution mentioned in step S3 are simultaneously fed into the continuous batch reactor for reaction, specifically including the following steps:

[0015] S31. A sodium glycinate solution and a toluene solution of 3,5-dichlorophenyl isocyanate are reacted to obtain a condensation reaction solution; that is, the sodium glycinate solution and the toluene solution of 3,5-dichlorophenyl isocyanate are reacted in the stirred reactor to obtain the condensation reaction solution;

[0016] S32. The condensation reaction solution is separated into layers; that is, after the reaction is completed in the stirred reaction vessel, the condensation reaction solution is continuously discharged into the first water addition vessel and / or the second water addition vessel, and water is added and the layers are separated alternately; after separation, the lower layer in the first water addition vessel and the second water addition vessel is an aqueous phase layer and the upper layer is a toluene phase layer;

[0017] S33. The aqueous phase layer and toluene phase layer in step S32 are processed separately; that is, the lower layer in the first water addition vessel and / or the second water addition vessel is discharged into the acidification vessel for acidification to obtain the acidified acidification reaction solution, and the upper layer in the first water addition vessel and / or the second water addition vessel is discharged into the toluene recovery vessel for toluene recovery;

[0018] S34. Obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea; that is, post-process the acidified reaction solution obtained above to obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea.

[0019] Preferably, the stratification temperature in both the first and second water-adding kettles in step S32 is 30-60℃.

[0020] Preferably, in step S32, the amount of water added alternately to the first and second water addition vessels is 0.1 to 1 times the weight of the reaction liquid collected in the corresponding first and / or second water addition vessels.

[0021] Preferably, the pH of the acidification process in the acidification reactor in step S33 is 1 to 5.

[0022] Preferably, the post-processing in step S34 includes a filtration process, a washing process, and a drying process arranged sequentially; the amount of water used for washing during the washing process is 0.1 to 1 times the total weight of the reaction liquid collected in the first and second water addition tanks.

[0023] Preferably, the sodium glycinate solution in step S2 comprises glycine, sodium hydroxide, and water, and the molar ratio of glycine, sodium hydroxide, and water is 1:(1.05-1.5):(10-100).

[0024] Preferably, the reaction time of the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution in step S3 in the stirred reactor is 1-5 hours, and the reaction temperature is 10-50°C.

[0025] The beneficial effects of the method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the present invention are:

[0026] This invention utilizes a continuous flow reactor in a continuous batch reactor to synthesize 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, reducing the reaction cycle from the traditional 10 hours to 2 hours, significantly improving reaction efficiency. Furthermore, the entire reaction process is continuous, simplifying the process, allowing for precise control of reaction conditions, minimizing equipment corrosion, and ensuring high safety, while avoiding frequent reactor opening and closing and temperature fluctuations. Using this method, the selectivity of the prepared product is significantly improved, with a marked reduction in the content of byproducts 3,5-dichloroaniline and the product formed by the combination of 3,5-dichloroaniline and 3,5-dichlorophenyl isocyanate. The reaction yield is increased to 95-98%, and the product purity is greater than 98%, achieving new heights in both yield and purity. The production cost of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea using this invention's continuous batch reactor is far lower than the production cost of existing batch processes. Attached Figure Description

[0027] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.

[0028] Figure 1 This is a process flow diagram of the preparation method of the present invention;

[0029] Figure 2 This is a schematic diagram of the connection of the continuous batch reactor in the preparation method of the present invention;

[0030] Figure 3 This is a flow chart of the reaction of sodium glycinate solution and 3,5-dichlorophenyl isocyanate toluene solution in the continuous batch reactor of the present invention.

[0031] In the diagram: 1. Stirred reaction vessel, 2. First water addition vessel, 3. Second water addition vessel, 4. Acidification vessel, 5. Filter. Detailed Implementation

[0032] The present invention will now be described in further detail with reference to the accompanying drawings. These drawings are simplified schematic diagrams, illustrating only the basic structure of the invention, and therefore only show the components relevant to the invention.

[0033] like Figures 1-3 A specific embodiment of the method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the present invention is shown, comprising the following steps:

[0034] S1. Assemble a continuous batch reactor for the preparation of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea;

[0035] S2. Prepare a toluene solution of 3,5-dichlorophenyl isocyanate and a sodium glycine solution;

[0036] S3. The sodium glycine solution and the 3,5-dichlorophenyl isocyanate toluene solution prepared in step S2 are simultaneously fed into the continuous batch reactor for reaction;

[0037] S4. After the reaction liquid enters and exits the continuous batch reactor, it is processed to obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea.

[0038] In this embodiment, the continuous reactor includes a stirred reaction vessel 1, a first water addition vessel 2, an acidification vessel 4, a filter 5, and a toluene recovery vessel, which are connected sequentially by liquid channels; a second water addition vessel 3 is also provided between the stirred reaction vessel 1 and the acidification vessel 4. (Refer to...) Figure 2A 3,5-dichlorophenyl isocyanate solution and a glycine solution are fed into a stirred reactor 1 at a specific molar ratio and feed flow rate. After the reaction in the stirred reactor 1 is completed, the mixture is continuously discharged into a first water addition reactor 2 and / or a second water addition reactor 3. Water is added alternately and the mixture separates into layers in the first and / or second water addition reactors 2 and 3, meaning that appropriate amounts of process water are added to both. The lower layer in the first and / or second water addition reactors 3 is the aqueous phase, which is discharged into an acidification reactor 4. An appropriate amount of hydrochloric acid is added to the acidification reactor 4. The acidified liquid from the acidification reactor 4 is then discharged into a filter 5 for filtration, washing, and drying to obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a purity of over 98%. The upper layer in the first and / or second water addition reactors 3 is the toluene phase, which is discharged into a toluene recovery reactor for toluene recovery. In this embodiment, 30% hydrochloric acid is used in acidification reactor 4. The highest content of commercially available hydrochloric acid is 30%. Using high-content hydrochloric acid for neutralization can reduce the amount of wastewater.

[0039] like Figure 3 As shown, in this embodiment, the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution mentioned in step S3 are simultaneously fed into the continuous batch reactor for reaction, specifically including the following steps:

[0040] S31. A sodium glycinate solution and a toluene solution of 3,5-dichlorophenyl isocyanate are reacted to obtain a condensation reaction solution; that is, the sodium glycinate solution and the toluene solution of 3,5-dichlorophenyl isocyanate are reacted in the stirred reactor 1 to obtain the condensation reaction solution. The reaction equation for the sodium glycinate solution and the toluene solution of 3,5-dichlorophenyl isocyanate in the stirred reactor 1 is as follows:

[0041]

[0042] It should be further noted that, in this embodiment, the molar ratio of 3,5-dichlorophenyl isocyanate solution to glycine solution added to stirred reactor 1 is 1:1.1 to 1.5. The reaction time of 3,5-dichlorophenyl isocyanate solution and glycine solution in stirred reactor 1 is 1 to 5 hours, and the reaction temperature is 10 to 50°C.

[0043] S32. The condensation reaction solution is separated into layers; that is, after the reaction is completed in the stirred reaction vessel 1, the condensation reaction solution is continuously discharged into the first water addition vessel 2 and / or the second water addition vessel 3, and water is added and the layers are separated alternately; after separation, the lower layer in the first water addition vessel 2 and the second water addition vessel 3 is an aqueous phase layer and the upper layer is a toluene phase layer; it is further noted that the separation temperature in the first water addition vessel 2 and the second water addition vessel 3 is 30-60℃.

[0044] S33. The aqueous phase and toluene phase layers from step S32 are processed separately; that is, the lower layer from the first water addition vessel 2 and / or the second water addition vessel 3 is discharged into the acidification vessel 4 for acidification to obtain an acidified reaction solution, and the upper layer from the first water addition vessel 2 and / or the second water addition vessel 3 is discharged into the toluene recovery vessel for toluene recovery. The pH of the acidification process in the acidification vessel 4 is 1-5.

[0045] S34. The solution A obtained above is post-processed to obtain 1-carboxymethyl-3-

[0046] (3,5-Dichlorophenyl)urea. The post-treatment includes a filtration step, a washing step, and a drying step arranged sequentially; the washing water volume during the washing process is 0.1 to 1 times the total weight of the reaction liquid collected in the first water addition vessel 2 and the second water addition vessel 3.

[0047] In this embodiment, the sodium glycinate solution prepared in step S2 includes glycine, sodium hydroxide, and water, and the molar ratio of glycine, sodium hydroxide, and water is 1:(1.05-1.5):(10-100). The 3,5-dichlorophenyl isocyanate toluene solution prepared has a 3,5-dichlorophenyl isocyanate toluene content of 12-16%. The preparation processes of both the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution employ relatively mature existing technologies, and will not be described in detail here.

[0048] The first example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0049] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0050] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the reaction residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the reaction was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0051] Finally, the acidified material was filtered through a sand core funnel in filter 5. The filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven to dry at 70℃, yielding 95.0g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a content of 98.1% and a target product yield of 95.15%.

[0052] A second example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0053] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 12% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.1:20.

[0054] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.51. The reaction temperature in the stirred reactor 1 was set to 25°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 733g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0055] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven to dry at 70℃, yielding 81.9g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a content of 98.5% and a target product yield of 96.08%.

[0056] Extensive data analysis revealed that setting the temperature in the reactor too low reduces the reaction rate or even halts the reaction altogether, resulting in noticeable solid precipitation. Conversely, setting the temperature too high accelerates side reactions and increases the amount of impurities in the product. Based on these considerations, the reaction temperature of this invention is set between 10 and 50°C.

[0057] A third example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0058] First press as follows Figure 2A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 16% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.37:87.60.

[0059] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.13. The reaction temperature in the stirred reactor 1 was set to 35°C, the pressure to atmospheric pressure, and the reaction residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 1323g of reaction solution was collected in the first water addition reactor 2, the reaction was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0060] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 109.0g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a content of 98.8% and a target product yield of 96.20%.

[0061] A fourth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0062] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0063] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set at 45°C, the pressure at atmospheric pressure, and the reaction residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the reaction was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0064] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 95.5g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a content of 99.2% and a target product yield of 96.71%.

[0065] A fifth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0066] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0067] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 60±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0068] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 98.1g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, with a content of 97.3% and a target product yield of 97.44%.

[0069] The sixth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0070] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0071] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 40±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0072] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 97.2g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, with a content of 97.8% and a target product yield of 97.05%.

[0073] Based on extensive experimental data and data from Examples 4 to 6, it was found that the higher the temperature during layering, the lower the product content and the higher the yield, indicating that excessively high temperatures during layering can lead to impurities entering the aqueous phase. To ensure both high product content and high yield while minimizing impurities entering the aqueous phase, the layering temperature was set at 30-35°C.

[0074] The seventh example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0075] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0076] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 20±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 2.

[0077] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 96.9g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, with a content of 98.3% and a target product yield of 97.25%.

[0078] As can be seen from the data in Examples 7 to 10, the yield slightly decreases when the pH value of the acidification vessel 4 increases; the yield also slightly decreases when the pH is too low. Furthermore, it should be noted that extensive experiments have shown that the yield begins to decrease significantly when the pH is greater than 5. Therefore, in the preparation method of this invention, the pH value of the acidification vessel 4 is set between 1 and 5.

[0079] The eighth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0080] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0081] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 3.

[0082] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 95.6g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea with a content of 98.0% and a target product yield of 95.65%.

[0083] The ninth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0084] First press as follows Figure 2A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0085] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the mixture was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 4.

[0086] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed three times, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 94.9g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, with a content of 98.3% and a target product yield of 95.24%.

[0087] The tenth example of preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to the above preparation method.

[0088] First press as follows Figure 2 A schematic diagram of the connection of a continuous batch reactor is shown. The continuous batch reactor is assembled. A toluene solution containing 14% 3,5-dichlorophenyl isocyanate is prepared. A sodium glycinate solution is prepared with a molar ratio of glycine to sodium hydroxide and water of 1:1.26:33.90.

[0089] The prepared solution was then fed with 3,5-dichlorophenyl isocyanate and glycine at a molar ratio of 1:1.29. The reaction temperature in the stirred reactor 1 was set to 30°C, the pressure to atmospheric pressure, and the reaction residence time in the stirred reactor 1 was 2 hours, yielding the reaction solution. The reaction solution was discharged into the first water addition reactor 2. When 855g of reaction solution was collected in the first water addition reactor 2, the reaction was switched to the second water addition reactor 3. 150g of process water was added to the first water addition reactor 2, and after stirring for 10 minutes, the mixture was allowed to separate into layers at 30±2°C. The lower layer was transferred to the acidification reactor 4, and the upper layer was placed in the toluene recovery reactor. The temperature was controlled at 30-35°C, and 30% hydrochloric acid was added to the acidification reactor 4 to adjust the pH to 1.

[0090] Finally, the acidified material was filtered through a sand core funnel, and the filtered material was washed twice, with 250g of washing water added each time. The washed material was then placed in an oven and dried at 70℃ to obtain 96.8g of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, with a content of 97.5% and a target product yield of 96.36%.

[0091] As can be seen from Examples 1 and 10, the more times the product is washed, the less the total amount of the target product is obtained, and the higher the content. In practical applications, the number of washing cycles can be adjusted as needed.

[0092] Comparative Example 1

[0093] 1-Carboxymethyl-3-(3,5-dichlorophenyl)urea was prepared using an existing batch process. Water and 70g of sodium hydroxide were added to a reaction vessel, the vessel was closed, and the mixture was stirred until dissolved. Then, glycine was added and stirred until dissolved. The mixture was heated to 28°C, and a toluene solution was added dropwise. After the addition was complete, the mixture was kept at this temperature for 30 minutes. After filtration, the mixture was allowed to stand and separate into layers. The aqueous layer was acidified and then filtered again. The resulting solid was dried, and the purity was 96.2%, with a yield of 87.9%.

[0094] Comparative Example 2

[0095] 1-Carboxymethyl-3-(3,5-dichlorophenyl)urea was prepared using an existing batch process. Water and 50g of sodium hydroxide were added to a reaction vessel, the reaction vessel was closed, and the mixture was stirred until dissolved. Then, glycine was added to the reaction vessel and stirred until dissolved. The temperature was raised to 30°C, and a toluene solution was added dropwise. After the addition was complete, the mixture was kept at this temperature for 30 minutes. After filtration, the mixture was allowed to stand and separate into layers. The aqueous layer was acidified and then filtered again. The obtained solid was dried, and the purity was 96.5%, with a yield of 89.6%.

[0096] Comparative Example 3

[0097] 1-Carboxymethyl-3-(3,5-dichlorophenyl)urea was prepared using an existing batch process. Water and 30g of sodium hydroxide were added to a reaction vessel, the vessel was closed, and the mixture was stirred until dissolved. Then, glycine was added and stirred until dissolved. The mixture was heated to 30°C, and a toluene solution was added dropwise. After the addition was complete, the mixture was kept at this temperature for 40 minutes. After filtration, the mixture was allowed to stand and separate into layers. The aqueous layer was acidified and then filtered again. The resulting solid was dried, and the purity was 97.0%, with a yield of 88.3%.

[0098] As can be seen from the content and yield of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea prepared by the preparation method of the present invention and 1-carboxymethyl-3-(3,5-dichlorophenyl)urea prepared by the batch process in the prior art, the 1-carboxymethyl-3-(3,5-dichlorophenyl)urea prepared by the preparation method of the present invention has fewer impurities, higher content, and higher yield. Moreover, the entire preparation process does not require frequent opening and closing of the reactor or heating and cooling, resulting in high safety and a simple process.

[0099] It should be understood that the specific embodiments described above are for illustrative purposes only and are not intended to limit the scope of the invention. Obvious variations or modifications derived from the spirit of the invention are still within the protection scope of the invention.

Claims

1. A method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea, characterized in that, Includes the following steps: S1. Assemble a continuous batch reactor for the preparation of 1-carboxymethyl-3-(3,5-dichlorophenyl)urea; S2. Prepare a toluene solution of 3,5-dichlorophenyl isocyanate and a sodium glycine solution; S3. The sodium glycine solution and the 3,5-dichlorophenyl isocyanate toluene solution prepared in step S2 are simultaneously fed into the continuous batch reactor for reaction; S4. After the liquid from the reaction in the continuous batch reactor is processed, 1-carboxymethyl-3-(3,5-dichlorophenyl)urea is obtained; The continuous batch reactor includes a stirred reaction vessel (1), a water addition vessel, an acidification vessel (4), a filter (5), and a toluene recovery vessel, which are connected in sequence by liquid channels; the water addition vessel includes a first water addition vessel (2) and a second water addition vessel (3), both of which are connected in liquid channels to the stirred reaction vessel (1) and the acidification vessel (4). In step S3, the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution are simultaneously fed into the continuous batch reactor for reaction, specifically including the following steps: S31. Sodium glycinate solution and 3,5-dichlorophenyl isocyanate toluene solution are reacted to obtain a condensation reaction solution; that is, the sodium glycinate solution and 3,5-dichlorophenyl isocyanate toluene solution are reacted in the stirred reactor (1) to obtain the condensation reaction solution; S32. The condensation reaction solution is divided into layers; that is, after the reaction is completed in the stirred reaction vessel (1), the condensation reaction solution is obtained and continuously discharged into the first water addition vessel (2) and / or the second water addition vessel (3), and water is added and the layers are divided alternately; after the layers are divided, the lower layer of the first water addition vessel (2) and the second water addition vessel (3) is an aqueous phase layer and the upper layer is a toluene phase layer; S33. The aqueous phase layer and toluene phase layer in step S32 are processed separately; that is, the lower layer in the first water addition vessel (2) and / or the second water addition vessel (3) is discharged into the acidification vessel (4) for acidification to obtain the acidified acidification reaction solution, and the upper layer in the first water addition vessel (2) and / or the second water addition vessel (3) is discharged into the toluene recovery vessel for toluene recovery; S34. Obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea; that is, post-process the acidified reaction solution obtained above to obtain 1-carboxymethyl-3-(3,5-dichlorophenyl)urea; The stratification temperature in both the first water addition vessel (2) and the second water addition vessel (3) in step S32 is 30-60℃; In step S32, the amount of water added alternately in the first water addition vessel (2) and the second water addition vessel (3) is 0.1 to 1 times the weight of the reaction liquid collected in the corresponding first water addition vessel (2) and / or second water addition vessel (3).

2. The method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to claim 1, characterized in that: In step S3, the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution are simultaneously added to the stirred reactor (1) for reaction. The reaction equation is as follows: ， The molar ratio of 3,5-dichlorophenyl isocyanate to glycine is 1:1.1 to 1.

5.

3. The method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to claim 1, characterized in that, The pH of the acidification process in the acidification vessel (4) described in step S33 is 1 to 5.

4. The method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to claim 1, characterized in that, The post-processing in step S34 includes a filtration process, a washing process, and a drying process arranged sequentially; the amount of water used for washing during the washing process is 0.1 to 1 times the total weight of the reaction liquid collected in the first water addition vessel (2) and the second water addition vessel (3).

5. The method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to claim 1, characterized in that, The sodium glycinate solution in step S2 includes glycine, sodium hydroxide, and water, and the molar ratio of glycine, sodium hydroxide, and water is 1:(1.05-1.5):(10-100).

6. A method for preparing 1-carboxymethyl-3-(3,5-dichlorophenyl)urea according to any one of claims 1-5, characterized in that, The reaction time of the sodium glycinate solution and the 3,5-dichlorophenyl isocyanate toluene solution in step S3 in the stirred reactor (1) is 1-5 h, and the reaction temperature is 10-50 °C.

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