Crystallization method of DMBCP crude product and application thereof

Abstract

The invention relates to a DMBCP crude product crystallization method, through specific crystallization operation steps, a system is dissolved and clarified in the heating process, DMBCP crystals are fully separated out under the condition of staged slow cooling, the reaction yield and the product quality of DMBCP can be effectively improved, the production cost can be reduced, and the method has wide application prospects in industrial application.

Description

Technical Field

[0001] The present invention relates to the field of chemistry, and in particular to a crystallization method for improving the yield and purity of 5-(4-chlorobenzylidene)-2,2-dimethylcyclopentanone. Background Art

[0002] 5-(4-Chlorobenzylidene)-2,2-dimethylcyclopentanone, abbreviated as DMBCP, CAS No. 131984-21-9, is a chemical with important applications. EP0751111A discloses a synthesis method for this compound. However, the methylation step described in this document yields only 89%. Recovering as much of the target product as possible during purification is beneficial for reducing production costs.

[0003] Existing technical documents CN110204500A, CN114230531A, CN106045830B, CN104710372B, CN1454200A, CN103664561B, WO2012041871A1 and EP0751111A2 have disclosed methods for producing the compound, but there is still room for improvement in increasing the reaction yield and product purity.

[0004] Therefore, there is an urgent need for a crude DMBCP crystallization method to improve the purity and yield of the product as much as possible to further reduce production costs. Summary of the Invention

[0005] The present invention aims to provide a method for crystallizing a crude DMBCP product. By means of specific crystallization operation steps, the system is dissolved and cleared during the heating process, and DMBCP crystals are fully precipitated under the condition of slow temperature reduction in stages, thereby improving the reaction yield of DMBCP and the product quality.

[0006] To achieve the above-mentioned purpose, the present invention provides the following technical solutions:

[0007] A method for crystallizing a crude DMBCP product comprises the following steps:

[0008] a) distilling and removing the reaction solvent in the DMBCP reaction solution;

[0009] b) adding a crystallization organic solvent to the remaining reaction system, heating to a specific temperature and maintaining it for a period of time;

[0010] c) cooling the system until a large amount of solid precipitates;

[0011] d) growing the crystal and cooling it to the target temperature, maintaining it for a period of time, and filtering to obtain DMBCP crystals.

[0012] Wherein, in step a, the organic solvent is selected from polar solvents, selected from any one or more of toluene, benzene, and dichloromethane.

[0013] Wherein, in step b, the crystallization organic solvent is selected from any one or more of cyclohexane, petroleum ether, acetone, hexane, and pentane.

[0014] Wherein, in step b, the weight ratio of the DMBCP reaction solution to the crystallization organic solvent is 1:0.8-4, preferably 1:0.85-2.

[0015] Wherein, in step b, the reaction temperature is raised to 80-100°C.

[0016] Furthermore, in step c, the reaction system is first cooled rapidly and then slowly to promote crystallization and growth of crystals to obtain larger and more complete DMBCP crystals.

[0017] Furthermore, in step c, the temperature is lowered at 8-15°C / hour for 5-10 minutes, and then slowly lowered to 50-70°C at a cooling rate of 3-5°C / hour.

[0018] In step d, the system is returned to a temperature of 2-8°C, crystals are grown at this temperature for 1-3 hours, the temperature is lowered at 5-10°C / hour for 2 hours, and then the temperature is lowered to 15-30°C at 10-20°C / hour, kept warm for a period of time, and DMBCP crystals are obtained by filtration.

[0019] Furthermore, after step a is completed, the organic solvent content in the DMBCP reaction solution must be less than 5%, preferably less than 2%.

[0020] Furthermore, in steps b, c, and d, ultrasonic radiation can be used to excite the system to promote the dissolution of DMBCP in the organic solvent and accelerate the formation and precipitation of crystals after cooling, thereby obtaining more uniform and finer crystal particles.

[0021] Furthermore, after step d is completed, the crystallization organic solvent can be recycled.

[0022] On the other hand, the present invention also provides DMBCP crystals obtained using the above-mentioned crude DMBCP crystallization method.

[0023] On the other hand, the present invention also provides a method for preparing DMBCP, comprising:

[0024] a) synthesizing DMBCP;

[0025] b) carry out above-mentioned DMBCP crude product crystallization method.

[0026] In the prior art, 2-methylcyclopentanone, p-chlorobenzaldehyde, and methyl bromide react in a polar organic solvent. This reaction is carried out simultaneously in multiple steps within the same reactor, resulting in numerous side reactions and impurity levels exceeding 30% in the reaction solution, which are difficult to fully remove through a single crystallization. The inventors, through numerous experimental studies, have discovered that specific crystallization procedures can be employed, such as optimizing solvent selection and introducing ultrasonic-assisted crystallization to achieve clear dissolution during heating. Furthermore, DMBCP crystals can be fully precipitated under conditions of gradual, staged cooling, effectively removing various impurities from the product. These procedures can effectively improve the reaction yield and product purity of DMBCP.

[0027] Furthermore, the inventors unexpectedly discovered that residual organic solvent in the DMBCP synthesis reaction can affect DMBCP crystallization. Excessive residual polar solvent can introduce some of the polar solvent into the organic solvent used for recycling and crystallization, exacerbating product losses during crystallization and impacting the overall crystallization system.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] The crystallization process of the present invention is simple to operate and easy to control, and can not only solve the problem of low reaction yield in the DMBCP synthesis step in the prior art, but also provide an economical, efficient and feasible method for crystallizing a crude DMBCP product. The application of the obtained high-purity DMBCP crystals is conducive to reducing production costs and has broad application prospects in industrial applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the analysis spectrum of the condensation reaction liquid of Example 1 of the present invention

[0031] Figure 2 This is the product analysis spectrum of Example 1 of the present invention

[0032] Figure 3 Product analysis diagram of Comparative Example 1 of the present invention DETAILED DESCRIPTION

[0033] In order to better understand the essence of the present invention, the contents of the present invention are further illustrated in conjunction with the embodiments below, but they should not be regarded as limiting the present invention. The following description is only used to explain the present invention. Any modifications, replacements or improvements made without departing from the spirit and principles of the present invention are within the scope of protection claimed by the present invention.

[0034] Example 1

[0035] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0036] After the solvent is distilled, 2430 kg of DMBCP reaction liquid is obtained, 2700 kg of petroleum ether is added, the temperature is raised to 80-100 ° C to dissolve, and the temperature is kept for 1 hour. The temperature is lowered at 8-15 ° C / hour for 5-10 minutes, and then slowly cooled to 50-70 ° C at a cooling rate of 3-5 ° C / hour.

[0037] The system was returned to a temperature of 2-8°C and crystals were grown at this temperature for 1-3 hours. After the crystals were grown, the temperature was lowered at 5-10°C / hour for 2 hours, then lowered to 15-30°C at 10-20°C / hour, and kept at this temperature for 0.5 hours. A total of 1480 kg of DMBCP crystals were obtained by filtration. The yield of the first crystallization was 92.50% based on the finished product, the qualitative analysis of the crude DMBCP was 99.6%, and the total impurity content was less than 1%.

[0038] Example 2

[0039] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0040] After the solvent is distilled, 2430 kg of DMBCP reaction liquid is obtained, 2700 kg of petroleum ether is added, the temperature is raised to 80-100 ° C to dissolve, and the temperature is kept for 1 hour. The temperature is lowered at 8-15 ° C / hour for 5-10 minutes, and then slowly cooled to 50-70 ° C at a cooling rate of 3-5 ° C / hour.

[0041] The system was returned to a temperature of 2-8°C and crystals were grown at this temperature for 1-3 hours. After the crystals were grown, the temperature was lowered at 5-10°C / hour for 2 hours, then lowered to 15-30°C at 10-15°C / hour, and kept at this temperature for 0.5 hours. A total of 1450 kg of DMBCP crystals were obtained by filtration. The yield of the first crystallization was 90.63% based on the finished product, the qualitative analysis of the crude DMBCP was 98.2%, and the total impurity content could be controlled to be less than 1%.

[0042] Example 3

[0043] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0044] After the solvent is distilled, 2430 kg of DMBCP reaction liquid is obtained. 2700 kg of cyclohexane is added and the temperature is raised to 80-100 ° C to dissolve it. The temperature is kept for 1 hour, and the temperature is lowered at 8-15 ° C / hour for 5-10 minutes. Then, the temperature is slowly lowered to 50-70 ° C at a cooling rate of 3-5 ° C / hour.

[0045] The system was returned to a temperature of 2-8°C and crystals were grown at this temperature for 1-3 hours. After the crystals were grown, the temperature was lowered at 5-10°C / hour for 2 hours, then lowered to 15-25°C at 10-20°C / hour, and kept at this temperature for 0.5 hours. A total of 1461 kg of DMBCP crystals were obtained by filtration. The yield of the first crystallization was 91.32% based on the finished product, the qualitative analysis of the crude DMBCP was 98.6%, and the total impurity content could be controlled to be less than 1%.

[0046] Example 4

[0047] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0048] After the solvent is distilled, 2430 kg of DMBCP reaction liquid is obtained. 2300 kg of acetone is added and the temperature is raised to 80-100 ° C to dissolve it. The temperature is kept for 1 hour, and the temperature is lowered at 8-15 ° C / hour for 5-10 minutes. Then, the temperature is slowly lowered to 50-70 ° C at a cooling rate of 3-5 ° C / hour.

[0049] The system was returned to a temperature of 2-8°C and crystals were grown at this temperature for 1-3 hours. After the crystals were grown, the temperature was lowered at 5-10°C / hour for 2 hours, then lowered to 15-25°C at 10-20°C / hour, and kept at this temperature for 0.5 hours. A total of 1430 kg of DMBCP crystals were obtained by filtration. The yield of the first crystallization was 89.38% based on the finished product, the qualitative analysis of the crude DMBCP was 97.6%, and the total impurity content could be controlled to be less than 1%.

[0050] Comparative Example 1 Solvent Residue Too High

[0051] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system was completed, the system was transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent. The toluene content in the reaction solution was detected to be 6.4%.

[0052] After the solvent is distilled, 2430 kg of DMBCP reaction liquid is obtained, 2700 kg of petroleum ether is added, the temperature is raised to 80-100 ° C to dissolve, and the temperature is kept for 1 hour. The temperature is lowered at 8-15 ° C / hour for 5-10 minutes, and then slowly cooled to 50-70 ° C at a cooling rate of 3-5 ° C / hour.

[0053] The crystals were grown at a temperature of 50-70°C for 1-3 hours. After growing, the temperature was lowered at 5-10°C / hour for 2 hours, then lowered to 15-25°C at 10-20°C / hour, kept warm for 0.5 hours, and filtered to obtain a total of 1300 kg of crude DMBCP crystals. A secondary crystallization was performed. According to the finished product, the crystallization yield was 81.25%, the qualitative analysis of the crude DMBCP was 89.2%, the impurity content was 10.7%, and several impurities could not be removed.

[0054] The residual solvent toluene content in the reaction solution is too high, which affects the crystallization effect, resulting in low reaction yield, low product purity and high impurity content.

[0055] Comparative Example 2 Rapid and uniform cooling

[0056] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0057] After the solvent was distilled, 2430 kg of DMBCP reaction solution was obtained. 2700 kg of petroleum ether was added and the temperature was raised to 80-100 ° C to dissolve the clear solution. The temperature was kept for 1 hour, and the temperature was cooled to 50-70 ° C at a cooling rate of 10-20 ° C / hour for crystal growth. The temperature was kept for 1 hour and then cooled to 15-25 ° C at a cooling rate of 10-20 ° C / hour. The temperature was kept for 0.5 h and filtered to obtain a total of 1330 kg of crude DMBCP crystals. The yield of the first crystallization was 83.13% based on the finished product. The qualitative analysis of the crude DMBCP was 90.1%, and the total impurity content was 12.2%.

[0058] This method uses a uniform and rapid cooling method to obtain a crude DMBCP product, which has a low content of DMBCP and a high impurity content. Analysis shows that due to the excessively rapid cooling rate, DMBCP is not completely precipitated, resulting in a low yield and an inability to remove impurities, which is not conducive to industrial production.

[0059] Comparative Example 3: Slow and uniform cooling

[0060] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system is completed, the reaction mixture is transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent, and the toluene content in the reaction solution is controlled to be less than 5%.

[0061] After the solvent was distilled, 2430 kg of DMBCP reaction solution was obtained. 2700 kg of petroleum ether was added and the temperature was raised to 80-100 ° C to dissolve the clear solution. The temperature was kept for 1 hour, and the temperature was cooled to 50-70 ° C at a cooling rate of 3-5 ° C / hour for crystal growth. The temperature was kept for 1 hour and then cooled to 15-25 ° C at a cooling rate of 5-10 ° C / hour. The temperature was kept for 0.5 h and filtered to obtain a total of 1350 kg of crude DMBCP crystals. The yield of the first crystallization was 84.38% based on the finished product. The qualitative analysis of the crude DMBCP was 90.6%, and the total impurity content was 11.5%.

[0062] This method uses a uniform and slow cooling method to obtain a crude DMBCP product, which has a long reaction time, low efficiency, low crude product content, and high impurity content. Analysis shows that due to the slow cooling rate, DMBCP is not completely precipitated, resulting in a low yield and an inability to remove impurities, which is not conducive to industrial production.

[0063] Comparative Example 4CN110204500A

[0064] After the condensation of 2-methylcyclopentanone, p-chlorobenzaldehyde and methyl chloride in the toluene solvent system was completed, the system was transferred to a crude distillation kettle and distilled under reduced pressure to remove and recover the toluene solvent. The toluene content in the reaction solution was detected to be 6.0%.

[0065] After the solvent was distilled off, ethyl acetate was added to the remaining reaction solution and extracted three times. The organic phase was combined with saturated brine, washed, dried over anhydrous sodium sulfate, concentrated in vacuo, and recrystallized to obtain DMBCP. The crude DMBCP had a qualitative value of 78.3% and a total impurity content of 17.8%.

[0066] Table 1 Description of Examples 1-4 and Comparative Examples 1-3

[0067]

[0068]

[0069] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for crystallizing crude DMBCP, characterized in that: The following steps are involved: a) distilling off the reaction solvent in the DMBCP reaction solution; b) adding a crystallization organic solvent to the remaining reaction system, heating to a specific temperature and maintaining it for a period of time; c) cooling the system until a large amount of solid is precipitated; d) growing crystals and cooling to the target temperature, maintaining the temperature for a period of time, filtering, and obtaining DMBCP crystals.

2. The method according to claim 1, characterized in that In step a, the organic solvent is selected from polar solvents, selected from any one or more of toluene, benzene, and dichloromethane.

3. The method according to claim 1, characterized in that: In step b, the crystallization organic solvent is selected from any one or more of cyclohexane, petroleum ether, acetone, hexane, and pentane.

4. The method according to claim 1, characterized in that In step b, the weight ratio of the DMBCP reaction solution to the crystallization organic solvent is 1:0.8-4, preferably 1:0.85-2.

5. The method according to claim 1, characterized in that In step b, the reaction temperature is raised to 80-100°C.

6. The method according to claim 1, characterized in that In step c, the temperature is lowered at 8-15°C / hour for 5-10 minutes, and then slowly lowered to 50-70°C at a rate of 3-5°C / hour.

7. The method according to claim 1, characterized in that In step d, the system is heated to 2-8°C, the crystals are grown at this temperature for 1-3 hours, the temperature is lowered at 5-10°C / hour for 2 hours, and then the temperature is lowered to 15-30°C at 10-20°C / hour, the temperature is kept for a period of time, and DMBCP crystals are obtained by filtration.

8. The method according to claim 2, characterized in that: After step a is completed, the organic solvent content in the DMBCP reaction solution must be less than 5%, preferably less than 2%.

9. A DMBCP crystal obtained using the DMBCP crude product crystallization method described in claims 1-8.

10. A method for preparing DMBCP, comprising: a) Synthesis of DMBCP; B) carrying out the DMBCP crude product crystallization method according to claim 1-8.

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