Method for refining valerolactam crystal

Abstract

The invention discloses a valerolactam crystal refining method, which comprises the following steps: distilling an alcohol-valerolactam crude product to remove alcohol and low-boiling-point impurities, adding an extraction solvent, fully stirring, and standing to separate out high-boiling-point impurities, so as to obtain an upper solution which is a valerolactam crude solution; the valerolactam crude liquid is evaporated to remove an extraction solvent, then a non-benign solvent is added for recrystallization and filtration, the valerolactam crystal is obtained, the method is short in preparation process and low in energy consumption, and the obtained product valerolactam is few in heavy component residue and high in quality.

Description

Technical Field

[0001] The invention relates to a method for crystallization and purification of organic compounds, in particular to a method for crystallization and purification of valerolactam, and belongs to the technical field of organic chemical synthesis. Background Art

[0002] Valerolactam, also known as 2-piperidone, is a cyclic compound formed by the loss of a molecule of water between the amino group and the carboxyl group in the amino acid molecule. It has pharmacological activity, especially as an intermediate in the synthesis of various antibiotics such as penicillin.

[0003] In the synthesis of valerolactam, there were many studies from the mid-1960s to the early 1970s, and the industrial production in Japan was relatively mature. Valerolactam can be synthesized by reacting cyclopentanolactone and ammonia under high temperature and high pressure conditions, but because of its harsh conditions and low yield, this method of synthesizing valerolactam is not very good. There is also a method of synthesizing valerolactam by carboxylic acid amine, but the reaction route is too long and was abandoned. Later, someone used a rearrangement reaction to synthesize it through cyclopentanone. Using NH 4 HSO 4 It is used as a catalyst in Beckmann reaction with a yield of 90%, and is used to prepare valerolactam after synthesizing cyclopentanone oxime.

[0004] During the rearrangement process, heavy impurities with complex components are generated. Refining and purification are required to remove them. The conventional refining and purification process requires extraction, back extraction, distillation and other processes, which have problems such as long process, complex process, high solvent distillation consumption, and heavy component residue. In order to solve the above problems, it is necessary to improve and optimize the refining process of valerolactam. Summary of the invention

[0005] In order to solve the problems existing in the prior art, the purpose of the present invention is to provide a method for refining valerolactam with short process, low energy consumption, less residual heavy components in the product and high purity.

[0006] In order to achieve the above technical purpose, the present invention provides a method for crystallizing and refining valerolactam, which comprises the following steps: removing alcohol and low-boiling-point impurities from a crude alcohol-valerolactam product by distillation, adding an extraction solvent and stirring the product sufficiently, and then standing the product to precipitate high-boiling-point impurities, wherein the upper layer solution is a crude valerolactam liquid; removing the extraction solvent from the crude valerolactam liquid by evaporation, and then adding a non-benign solvent to perform recrystallization and filtration to obtain valerolactam crystals.

[0007] In the technical scheme of the present invention, the alcohol-valerolactam solution obtained by gas phase rearrangement of cyclopentanone oxime is evaporated to remove the low-boiling alcohol solvent, and the remaining solution contains a high-boiling solvent in addition to valerolactam. If distillation is performed at this time, valerolactam will form an azeotrope with the high-boiling solvent due to its high boiling point (256° C.), causing it to be distilled out simultaneously with part of the high-boiling solvent, making it difficult to separate. The extraction solvent used in the present invention extracts valerolactam using the principle of like dissolves like, thereby removing high-boiling impurities (i.e., heavy component impurities) by liquid separation. The extraction solvent can be removed by rotary evaporation afterwards. Although the purity of the valerolactam obtained at this time is greater than 90%, some impurities are still present in the valerolactam. The key to the present invention is to add a non-benign solvent. At room temperature, the non-benign solvent is difficult to dissolve valerolactam but has good solubility for impurities. However, under appropriate heating conditions, valerolactam and impurities can be dissolved together in the non-benign solvent. On this basis, by utilizing the characteristic that the solubility of valerolactam in the non-benign solvent decreases significantly as the temperature decreases, valerolactam crystals can be precipitated by cooling to obtain high-purity valerolactam. The inventors have found that if a benign solvent is added, the crystallization efficiency of valerolactam is greatly reduced due to excessive solubility, and impurities remain.

[0008] As a preferred solution, the extraction solvent includes at least one of isopropyl ether, n-butyl ether, methyl tert-butyl ether, benzene and toluene. The preferred extraction solvent is miscible with valerolactam, but has poor solubility for high boiling point impurities in valerolactam, thereby utilizing the poor solubility of high boiling point impurities with the extraction solvent and the high specific gravity to achieve separation of high boiling point impurities.

[0009] As a preferred solution, the volume ratio of the extraction solvent to the crude alcohol-valerolactam product is 1:(1.5-3).

[0010] As a preferred solution, the temperature of the solution system is controlled at 25-70° C. during the stirring process. Stirring can promote rapid dissolution equilibrium of valerolactam in the extraction solvent and the crude product, improve the extraction efficiency, and achieve full extraction.

[0011] As a preferred solution, the alcohol mass percentage of the crude alcohol-valerolactam product is 40-50wt%, the low boiling point impurities mass percentage is 4-6wt%, the high boiling point impurities mass percentage is 4-6wt%, and the rest is valerolactam.

[0012] As a preferred solution, the distillation temperature is 80-110°C and the pressure is normal pressure. The distillation temperature range selected in the present invention is the boiling point range of the alcohol solvent used in the crude product.

[0013] As a preferred solution, the non-benign solvent includes at least one of methylcyclohexane, cyclohexane, n-hexane, n-octane, n-heptane and methylcyclopentane. The preferred non-benign solvents of the present invention are difficult to dissolve valerolactam at room temperature but have good solubility for impurities. Therefore, the solubility of valerolactam in non-benign solvents decreases significantly with decreasing temperature, and valerolactam crystals can be precipitated by cooling to obtain high-purity valerolactam.

[0014] As a preferred solution, the volume ratio of the non-benign solvent to the crude valerolactam solution is 1:(1-3). Controlling the ratio of the non-benign solvent to the crude valerolactam solution within an appropriate range is beneficial for efficient separation of valerolactam from the crude valerolactam solution.

[0015] As a preferred solution, during the recrystallization process, valerolactam is first fully dissolved in a non-benign solvent to form a solution, the solution is heated to 25-35°C at a heating rate of 5-20°C / min, and kept warm for 0.5-2.5h to generate crystal nuclei, and then cooled at a rate of 2-4°C / h to allow crystal growth for 1.5-6h. The purpose of the recrystallization process of the present invention being divided into two stages is that, first, crystal nuclei with higher purity can be generated at a higher temperature, which can promote the crystallization rate on the one hand, and on the other hand, the crystal nucleus induction is combined with low temperature to quickly form valerolactam crystals with high purity.

[0016] As a preferred solution, the crystallization mother liquor is returned to the crystallization for repeated use.

[0017] As a preferred solution, the filtration is centrifugal filtration or vacuum filtration.

[0018] As a preferred solution, the valerolactam crystals are dried to obtain valerolactam solid particles.

[0019] As a preferred solution, the drying temperature is 25-50°C.

[0020] Compared with the prior art, the technical solution of the present invention has the following beneficial technical effects:

[0021] 1) The present invention adopts crystallization, extraction distillation separation and other technologies to replace the traditional amide benzene extraction, water extraction, hydrogenation and other processes, greatly shortening the process and reducing material consumption and energy consumption.

[0022] 2) The solid valerolactam product obtained by the method of the present invention has excellent quality and is stable and easy to store.

[0023] 3) The present invention removes low-boiling alcohol solvents by distillation, and then separates high-boiling impurities and valerolactam by adding an extraction solvent. The high-boiling impurities (i.e., heavy component impurities) can be removed by liquid separation to obtain valerolactam with higher purity.

[0024] 4) The present invention adds a non-benign solvent before recrystallization, and utilizes the difference in solubility of valerolactam in the non-benign solvent at different temperatures to achieve rapid crystallization of valerolactam, and the purity of the obtained valerolactam is as high as 99.9%. DETAILED DESCRIPTION

[0025] In order to facilitate the understanding of the present invention, the present invention will be described in more comprehensive and detailed manner in conjunction with preferred embodiments below, but the protection scope of the present invention is not limited to the following specific embodiments.

[0026] Unless otherwise defined, all the professional terms used below have the same meanings as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0027] Unless otherwise specified, all reagents and raw materials used in the present invention are commercially available products or products that can be prepared by known methods.

[0028] In the embodiments of the present invention and the comparative embodiments, the alcohol content in the alcohol-valerolactam solution is 50wt%, the mass percentage content of low boiling point impurities (mainly including high temperature decomposition products) is 6wt%, the mass percentage content of high boiling point impurities (mainly including high temperature polycondensates) is 4wt%, and the rest is valerolactam.

[0029] Example 1

[0030] (1) Removal of rearrangement solvent from crude product

[0031] The alcohol-valerolactam solution obtained by gas phase rearrangement of cyclopentanone oxime is distilled at a temperature of 80° C. and a pressure of normal pressure to remove low boiling point solvents and impurities.

[0032] (2) Valerolactam solvent extraction

[0033] Add isopropyl ether as an extraction solvent to the crude valerolactam obtained in step (1) (the volume ratio of isopropyl ether as the extraction solvent to the crude alcohol-valerolactam product is 1:1.5), and stir and stand for stratification at a temperature of 25° C. to obtain a crude valerolactam solution from which insoluble heavy component impurities are removed.

[0034] (3) Crystallization of valerolactam by cooling

[0035] The crude valerolactam solution obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother solution is heated and dissolved in methylcyclohexane (the volume ratio of methylcyclohexane to the crude valerolactam solution is 1:2), and the temperature of the crystallization mother solution is raised to 25°C at a heating rate of 5°C / min, and the temperature is continuously stirred and kept constant, and the crystal layer is allowed to grow for 0.5h, and then the crystal layer is allowed to grow for another 1.5h at a cooling rate of 2°C / h. Valerolactam crystals are obtained.

[0036] (4) Treatment of valerolactam crystals

[0037] The valerolactam crystal solution obtained in step (3) is centrifuged and filtered, and the valerolactam solid particles are dried at 25° C. to obtain valerolactam crystals with a purity of 99.0%. The crystallization mother liquor is returned to step (3).

[0038] Example 2

[0039] (1) Removal of rearrangement solvent from crude product

[0040] The alcohol-valerolactam solution obtained by gas phase rearrangement of cyclopentanone oxime is distilled at a temperature of 100° C. and a pressure of normal pressure to remove low boiling point solvents and impurities.

[0041] (2) Valerolactam solvent extraction

[0042] The crude valerolactam obtained in step (1) is added with an extraction solvent of n-butyl ether (the volume ratio of the extraction solvent of isopropyl ether to the crude alcohol-valerolactam product is 1:2), and the mixture is stirred and allowed to stand for stratification at a temperature of 25° C. to obtain a crude valerolactam solution from which insoluble heavy impurities are removed.

[0043] (3) Crystallization of valerolactam by cooling

[0044] The crude valerolactam solution obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother solution is heated and dissolved in cyclohexane (the volume ratio of cyclohexane to the crude valerolactam solution is 1:1.5), and the temperature of the crystallization mother solution is raised to 35°C at a rate of 15°C / min, and the temperature is continuously stirred and kept constant, and the crystal layer is allowed to grow for 1.5 hours, and then the crystal layer is allowed to grow for another 3 hours at a cooling rate of 2°C / h. Valerolactam crystals are obtained.

[0045] (4) Treatment of valerolactam crystals

[0046] The valerolactam crystal solution obtained in step (3) is centrifuged and filtered for separation, and the valerolactam solid particles are dried at 30° C. to obtain valerolactam crystals with a purity of 98.5%. The crystallization mother liquor is returned to step (3).

[0047] Example 3

[0048] (1) Removal of rearrangement solvent from crude product

[0049] The alcohol-valerolactam solution obtained by gas phase rearrangement of cyclopentanone oxime is distilled at a temperature of 110° C. and a pressure of normal pressure to remove low boiling point solvents and impurities.

[0050] (2) Valerolactam solvent extraction

[0051] A mixed solution of isopropyl ether and methyl tert-butyl ether (the volume ratio of isopropyl ether to methyl tert-butyl ether is 1:1, and the volume ratio of the mixed solution to the crude alcohol-valerolactam product is 1:2.5) is added to the crude valerolactam obtained in step (1), and the mixture is stirred and allowed to stand for stratification at a temperature of 25° C. to obtain a crude valerolactam solution from which insoluble heavy component impurities are removed.

[0052] (3) Crystallization of valerolactam by cooling

[0053] The crude valerolactam solution obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother solution is heated and dissolved in n-hexane (the volume ratio of n-hexane to the crude valerolactam solution is 1:3), and the temperature of the crystallization mother solution is raised to 35°C at a rate of 5°C / min, and the temperature is continuously stirred and kept constant, and the crystal layer is allowed to grow for 1.5h, and then the crystal layer is allowed to grow for another 2.5h at a cooling rate of 4°C / h. Valerolactam crystals are obtained.

[0054] (4) Treatment of valerolactam crystals

[0055] The valerolactam crystal solution obtained in step (3) is separated by vacuum filtration, and the valerolactam solid particles are dried at 35° C. to obtain valerolactam crystals with a purity of 99.9%. The crystallization mother liquor is returned to step (3).

[0056] Example 4

[0057] (1) Removal of rearrangement solvent from crude product

[0058] The alcohol-valerolactam solution obtained by gas phase rearrangement of cyclopentanone oxime is distilled at a temperature of 90° C. and a pressure of normal pressure to remove low boiling point solvents and impurities.

[0059] (2) Valerolactam solvent extraction

[0060] A mixed solution of benzene and toluene (the volume ratio of benzene to toluene is 1:0.5, and the volume ratio of the mixed solution to the crude alcohol-valerolactam product is 1:1.5) is added to the crude valerolactam obtained in step (1), and the mixture is stirred and allowed to stand for stratification at a temperature of 25° C. to obtain a crude valerolactam solution from which insoluble heavy component impurities are removed.

[0061] (3) Crystallization of valerolactam by cooling

[0062] The crude valerolactam solution obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother solution is heated and dissolved in methylcyclopentane (the volume ratio of methylcyclopentane to the crude valerolactam solution is 1:2.5), and the temperature of the crystallization mother solution is raised to 35°C at a heating rate of 20°C / min, and the temperature is continuously stirred and kept constant, and the crystal layer is allowed to grow for 1 hour, and then the crystal layer is allowed to grow for another 2 hours at a cooling rate of 4°C / h. Valerolactam crystals are obtained.

[0063] (4) Treatment of valerolactam crystals

[0064] The valerolactam crystal solution obtained in step (3) is separated by vacuum filtration, and the valerolactam solid particles are dried at 40° C. to obtain valerolactam crystals with a purity of 99.0%. The crystallization mother liquor is returned to step (3).

[0065] Comparative Example 1

[0066] (1) Removal of rearrangement solvent from crude product and (2) valerolactam solvent extraction are the same as in Example 1;

[0067] (3) Crystallization of valerolactam by cooling

[0068] The valerolactam extract obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother liquor is heated and dissolved in a benign solvent benzene (the volume ratio of benzene to valerolactam crude liquid is 1:2), and the crystallization mother liquor is heated to 30°C at a heating rate of 5°C / min, and the temperature is continuously stirred and kept constant, and the crystal layer is allowed to grow for 1h, and then the crystal layer is allowed to grow for another 1.5h at a cooling rate of 2°C / h. The obtained valerolactam crystals are not easy to form, and the crystal nucleus grows slowly. The purity of valerolactam is 95%.

[0069] Comparative Example 2:

[0070] (1) Removal of rearrangement solvent from crude product and (2) valerolactam solvent extraction are the same as in Example 3;

[0071] (3) Crystallization of valerolactam by cooling

[0072] The valerolactam extract obtained in step (2) is subjected to rotary evaporation to remove the extraction solvent. At this time, the purity of valerolactam is greater than 90%. The obtained crystallization mother liquor is dissolved in n-hexane at room temperature (the volume ratio of n-hexane to the valerolactam crude liquid is the same as in Example 3), and no valerolactam crystals can be obtained by continuous stirring. Under this operating condition, the growth of valerolactam crystals is limited and is in a co-solvent system with the solvent.

Claims

1. A method for crystallizing and refining valerolactam, characterized in that: The crude alcohol-valerolactam product is subjected to distillation to remove alcohol and low-boiling impurities, and then an extraction solvent is added to fully stir the product, and then the product is allowed to stand to precipitate high-boiling impurities. The upper layer of the solution is the crude valerolactam solution. The crude valerolactam solution is subjected to evaporation to remove the extraction solvent, and then a non-benign solvent is added to perform recrystallization and filtration to obtain valerolactam crystals.

2. A method for crystallizing and refining valerolactam according to claim 1, characterized in that: The extraction solvent includes at least one of isopropyl ether, n-butyl ether, methyl tert-butyl ether, benzene and toluene.

3. A method for crystallizing and refining valerolactam according to claim 2, characterized in that: The volume ratio of the extraction solvent to the crude alcohol-valerolactam product is 1:(1.5-3).

4. A method for crystallizing and refining valerolactam according to any one of claims 1 to 3, characterized in that: During the stirring process, the temperature of the system is controlled at 25-70°C.

5. A method for crystallizing and refining valerolactam according to claim 1, characterized in that: The alcohol-valerolactam crude product has an alcohol content of 40-50wt%, a low-boiling-point impurity content of 4-6wt%, a high-boiling-point impurity content of 4-6wt%, and the rest is valerolactam.

6. A method for crystallizing and refining valerolactam according to claim 1, characterized in that: The distillation temperature is 80-110° C. and the pressure is normal pressure.

7. A method for crystallizing and refining valerolactam according to claim 1, characterized in that: The non-benign solvent includes at least one of methylcyclohexane, cyclohexane, n-hexane, n-octane, n-heptane, and methylcyclopentane.

8. A method for crystallizing and refining valerolactam according to claim 7, characterized in that: The volume ratio of the non-benign solvent to the crude valerolactam solution is 1:(1-3).

9. A method for crystallizing and purifying valerolactam according to any one of claims 5 to 8, characterized in that: During the recrystallization process, valerolactam is first fully dissolved in a non-benign solvent to form a solution, the solution is heated to 25-35°C at a heating rate of 5-20°C / min, and kept warm for 0.5-2.5h to generate crystal nuclei, and then cooled at a rate of 2-4°C / h to allow crystals to grow for 1.5-6h.