A method for highly efficient purification of 3-chloropropiophenone

Abstract

The present invention relates to the technical field of purification of m-chloropropiophenone, and particularly to a high-efficiency purification method for m-chloropropiophenone. The purification of m-chloropropiophenone is carried out by a coupled process of melt crystallization and rectification, which includes: S1, heating the crystallizer containing m-chloropropiophenone to melt it, then cooling it, filtering out the mother liquor after maintaining for 1-5 h; S2, raising the temperature to make the crystals melt and sweat, filtering out the sweating liquid at different temperature points, and collecting them as mother liquor according to the purity; S3, quickly heating the crystallizer to melt the crystals to obtain purified m-chloropropiophenone; S4, combining the mother liquor with an m-chloropropiophenone content of less than 50% for vacuum rectification, collecting the m-chloropropiophenone fraction, and when the m-chloropropiophenone content is higher than 80%, crystallizing the fraction and then carrying out melt crystallization operation. In the whole purification process, the combination of melt crystallization and rectification purification is adopted, so that the obtained m-chloropropiophenone has high purity, reduces the waste of m-chloropropiophenone, and improves the yield of m-chloropropiophenone.

Description

Technical Field

[0001] The present invention relates to the technical field of purification of m-chloropropiophenone, and particularly to a method for efficiently purifying m-chloropropiophenone. Background Art

[0002] Bupropion hydrochloride is a new type of antidepressant drug first marketed in the United States by a British company in 1989. Compared with irreversible monoamine oxidase inhibitors, it has the characteristics of rapid enzyme inhibition and quick recovery of MAO (monoamine oxidase type A) activity after drug withdrawal. It is suitable for patients who are not responsive to other antidepressants or cannot tolerate depression. At the same time, bupropion hydrochloride has a good effect on smoking cessation. In 1997, the US FDA approved it as the first non-nicotine smoking cessation drug and it has now been marketed in many countries.

[0003] The melting point of m-chloropropiophenone is 43 - 46 °C and the boiling point is 246 °C. It is an important intermediate of bupropion hydrochloride. Currently, the main industrial synthesis route is the reaction of propiophenone with chlorine gas to produce m-chloropropiophenone, and at the same time, impurities such as o-chloropropiophenone, p-chloropropiophenone, 3,4-dichloropropiophenone, and 3,5-dichloropropiophenone are generated. The properties of p-chloropropiophenone and o-chloropropiophenone are similar to those of m-chloropropiophenone and are likely to participate in the next reaction to produce impurities, making them difficult to separate. Therefore, the crude m-chloropropiophenone obtained from the reaction needs to be separated and purified to obtain a product with higher purity. In actual production, the content of p-chloropropiophenone and o-chloropropiophenone in m-chloropropiophenone needs to be controlled to be less than 0.1%.

[0004] The currently known purification method is to use the difference in boiling points between the product and the raw materials and by-products, and adopt conventional distillation methods for purification. The content of m-chloropropiophenone in the crude product is 80 - 85%, the content of o-chloropropiophenone is 15 - 18%, and the total content of impurities such as p-chloropropiophenone and 3,4-dichloropropiophenone is 2 - 5%. The boiling points of the impurities o-chloropropiophenone and p-chloropropiophenone are very close to that of the product. Although distillation can separate them, the theoretical number of plates in the laboratory distillation is greater than 50 and the reflux ratio is 5:1, and the yield of the pure product is only about 60%. However, in the actual distillation process in factories, a taller tower is required and the steam energy consumption is extremely large. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a method for efficiently purifying m-chloropropiophenone.

[0006] The method for efficiently purifying m-chloropropiophenone provided by the present invention adopts the following technical solution:

[0007] A method for efficiently purifying m-chloropropiophenone, which uses a coupled process of melt crystallization - distillation to purify m-chloropropiophenone, comprising the following steps:

[0008] S1. Rapidly heat the crystallizer containing the m-chloropropiophenone to be purified to above 48 °C to completely melt the m-chloropropiophenone, and then cool it down to 20 - 25 °C through the jacket to crystallize the m-chloropropiophenone. Keep it for 1 - 5 h and then filter out the mother liquor;

[0009] S2. After discharging the mother liquor, control the jacket temperature to raise the temperature to 45 - 47 °C and keep it for 30 - 60 min to partially melt and sweat the crystals. Filter out the sweating liquid at different temperature points and collect it as the mother liquor according to the purity of m-chloropropiophenone;

[0010] S3. Rapidly heat the crystallizer to above 48 °C to completely melt the m-chloropropiophenone crystals, and then the purified m-chloropropiophenone can be obtained;

[0011] S4. Combine the mother liquors with m-chloropropiophenone content less than 50% obtained in S1 and S2 for vacuum distillation. Collect the m-chloropropiophenone fraction from the bottom of the distillation column. When the m-chloropropiophenone content in this fraction is higher than 80%, crystallize this fraction and continue the operation of S1.

[0012] Preferably, when the m-chloropropiophenone content in the mother liquors filtered out in S1 and S2 is within the same range, the mother liquors are combined.

[0013] Preferably, the ranges of the content are respectively less than 50%, 50 - 80% and more than 80%.

[0014] Preferably, the mother liquor with m-chloropropiophenone content more than 80% is returned to S1 as the crystallization raw material for continued use.

[0015] Preferably, for the mother liquor with m-chloropropiophenone content between 50 - 80%, rapidly reduce the temperature to 10 - 15 °C and filter the uncrystallized mother liquor.

[0016] Preferably, the mother liquor with m-chloropropiophenone content less than 50% is subjected to the distillation operation in S4.

[0017] Preferably, in S1, the cooling rate is 1.0 - 5.0 °C / h and the heating rate is 1.0 - 3.0 °C / h.

[0018] Preferably, in S4, the number of theoretical plates of the distillation column is 15 - 30, the reflux ratio is 1 - 3, and the vacuum degree is controlled at 2 - 10 mmHg.

[0019] In summary, the present invention has the following beneficial technical effects:

[0020] 1. The innovation of this high-efficiency purification method of m-chloropropiophenone lies in: the coupled process of melt crystallization - distillation.

[0021] During the entire purification process, the combination of melt crystallization and rectification purification is adopted, resulting in high-purity m-chloropropiophenone, meeting the purity requirements in actual production, reducing the waste of m-chloropropiophenone, and increasing the yield of m-chloropropiophenone.

[0022] 2. The rectification column in this rectification process has fewer trays, lower tray resistance, lower energy consumption, and high separation efficiency.

[0023] 3. During the melt crystallization process, the mother liquor is divided into three types according to the purity range of m-chloropropiophenone, namely greater than 80%, 50 - 80%, and less than 50%. Different operations are carried out for purification respectively, with high purification efficiency, high raw material utilization rate, and low loss. Description of the Drawings

[0024] Figure 1 is the gas chromatogram of m-chloropropiophenone in the product obtained in Example 1;

[0025] Figure 2 is the gas chromatogram of the crude m-chloropropiophenone in Example 2;

[0026] Figure 3 is the gas chromatogram of m-chloropropiophenone with the mother liquor collected in the melt crystallization process in Example 4 as the raw material. Detailed Description of the Invention

[0027] Example 1

[0028] Take a certain amount of crude m-chloropropiophenone (main substance content: propiophenone 0.21%, m-chloropropiophenone 81.24%, o-chloropropiophenone 16.43%, p-chloropropiophenone 0.9%) and place it in a crystallizer with a glass jacket. The inner tube diameter of the crystallizer is 50 mm and the height is 800 mm. The jacket can be passed with heating or cooling water for temperature control. Heat the crystallizer to above 48°C until the crystals are completely melted, and then cool it at a rate of 1°C / h to 25°C and keep it warm for 5 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and then slowly heat and raise the temperature of the crystals through the jacket for sweating. The heating rate is 1.0°C / h, raise the temperature to 47°C, keep it warm for 60 min, end the sweating, discharge the sweat, collect the sweating liquid, and collect and combine them according to the content range of m-chloropropiophenone being greater than 80%, 50% - 80%, and greater than 80% respectively.

[0029] Put the purified product crystals into the crystallizer and quickly heat it to above 48°C to melt the crystals into a colorless and transparent liquid. The single-pass crystallization yield is 73.1%. After gas chromatographic analysis, referring to Figure 1 the gas chromatogram, the purity of m-chloropropiophenone in the product is 99.81%, and the content of single impurities is less than 0.1%.

[0030] Example 2

[0031] Take a certain amount of the initial product m-chloropropiophenone (refer to Figure 2 the gas chromatogram, the main substance contents are: propiophenone 0.17%, m-chloropropiophenone 80.35%, o-chloropropiophenone 17.23%, p-chloropropiophenone 1.2%) and place it in a crystallizer with a glass jacket (the crystallizer is the same as in Example 1).

[0032] Heat the crystallizer to above 48 °C until the crystals are completely melted, then cool it at a cooling rate of 5 °C / h to 20 °C and keep it warm for 1 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and then slowly heat the crystals through the jacket for sweating, with a heating rate of 3 °C / h, heat up to 47 °C, keep it warm for 30 min, end the sweating, discharge the sweat, collect the sweating liquid, and collect and combine it according to the content range of m-chloropropiophenone being greater than 80%, 50%-80% and greater than 80% respectively.

[0033] Put the purified product crystals into the crystallizer and quickly heat it to above 48 °C to melt the crystals to obtain a colorless transparent liquid, and the single-pass crystallization yield is 68.2%. After gas chromatographic analysis, the purity of m-chloropropiophenone in the product is 99.63%, and the content of single impurities is less than 0.1%.

[0034] Example 3

[0035] Take a certain amount of the enriched mother liquor m-chloropropiophenone (the main substance contents are: m-chloropropiophenone 70.45%, o-chloropropiophenone 26.81%, propiophenone 0.76%, p-chloropropiophenone 2.38%) and place it in a crystallizer with a glass jacket (the crystallizer is the same as in Example 1). Heat the crystallizer to above 48 °C until the crystals are completely melted, then cool it at a cooling rate of 5 °C / h to 10 °C and keep it warm for 3 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and then slowly heat the crystals through the jacket for sweating, with a heating rate of 3 °C / h, heat up to 45 °C, keep it warm for 50 min, end the sweating, discharge the sweat, collect the sweating liquid, and collect and combine it according to the content range of m-chloropropiophenone being greater than 80%, 50%-80% and greater than 80% respectively.

[0036] Put the purified product crystals into the crystallizer and quickly heat it to above 48 °C to melt the crystals to obtain a colorless transparent liquid, and the single-pass crystallization yield is 63.2%. After gas chromatographic analysis, the purity of m-chloropropiophenone in the product is 97.52%, and it can be used as a crystallization raw material to continue the above operation.

[0037] Example 4

[0038] Use the mother liquor collected from the melt crystallization process as the raw material for vacuum distillation experiment, refer to Figure 3The gas chromatogram shows that the mass contents of the main substances in the mother liquor are: 45.03% of m-chloropropiophenone, 0.69% of propiophenone, 48.98% of o-chloropropiophenone, 2.53% of p-chloropropiophenone, and 1.07% of others.

[0039] Take 1000 g of the above product in a three-necked flask and carry out rectification in a rectification column with a theoretical plate number of 15. The pressure during the rectification process is about 10 mmHg, and the reflux ratio is 3:1.

[0040] Finally, 500.2 g of the top fraction is collected. After analysis, the contents of the main substances in the collected fraction are: 19.37% of propiophenone, 77.33% of o-chloropropiophenone, 2.53% of m-chloropropiophenone, and 0.77% of p-chloropropiophenone. It can be used as the raw material for recycling propiophenone and obtaining the by-product o-chloropropiophenone.

[0041] The bottom fraction is 493.5 g, and the contents of the main substances are: 10.6% of o-chloropropiophenone, 85.11% of m-chloropropiophenone, 2.12% of p-chloropropiophenone, and 2.17% of others. It can be used as the raw material for further crystallization of m-chloropropiophenone.

[0042] Example 5

[0043] Using the mother liquor collected from the melt crystallization process as the raw material for a vacuum rectification experiment, the mass contents of the main substances in this product are: 49.16% of m-chloropropiophenone, 3.63% of propiophenone, 44.58% of o-chloropropiophenone, 1.68% of p-chloropropiophenone, and 0.95% of others.

[0044] Take 1000 g of the above product in a three-necked flask and carry out rectification in a rectification column with a theoretical plate number of 30. The pressure during the rectification process is about 2 mmHg, and the reflux ratio is 1:1.

[0045] Finally, 486.4 g of the top fraction is collected. After analysis, the contents of the main substances in the collected fraction are: 7.46% of propiophenone, 86.51% of o-chloropropiophenone, 4.85% of m-chloropropiophenone, and 1.18% of p-chloropropiophenone. It can be used as the raw material for recycling propiophenone and obtaining the by-product o-chloropropiophenone.

[0046] At the same time, 507.6 g of the bottom fraction can be obtained. The contents of the main substances are: 8.78% of o-chloropropiophenone, 87.3% of m-chloropropiophenone, 2.05% of p-chloropropiophenone, and 1.87% of others. It can be used as the raw material for further crystallization of m-chloropropiophenone.

[0047] The above are all the preferred embodiments of the present invention. The protection scope of the present invention is not limited thereby. Therefore, all equivalent changes made according to the structure, shape, and principle of the present invention shall be covered within the protection scope of the present invention.

Claims

1. A method for purifying m-chloropropiophenone, characterized in that: Purify m-chloropropiophenone by using a coupled process of melt crystallization and rectification, including the following steps: S1. Rapidly heat the crystallizer containing the m-chloropropiophenone to be purified to above 48 °C to completely melt the m-chloropropiophenone, and then cool it to 20 - 25 °C through the jacket to crystallize the m-chloropropiophenone. After maintaining for 1 - 5 h, filter out the mother liquor; S2. After discharging the mother liquor, control the jacket temperature to raise the temperature to 45 - 47 °C and maintain for 30 - 60 min to make the crystals melt and sweat. Filter out the sweating liquid at different temperature points, and collect the mother liquors with different m-chloropropiophenone purities respectively; S3. Rapidly heat the crystallizer to above 48 °C to completely melt the internal m-chloropropiophenone crystals, and then purified m-chloropropiophenone can be obtained; S4. Combine the mother liquors with m-chloropropiophenone content less than 50% obtained in S1 and S2 for vacuum rectification, collect the m-chloropropiophenone fraction from the bottom of the rectification column. When the m-chloropropiophenone content in this fraction is higher than 80%, crystallize this fraction and then continue the operation of S1; When the m-chloropropiophenone content in the mother liquors filtered out in S1 and S2 is within the same range, combine the mother liquors; The ranges of the said content are respectively less than 50%, 50 - 80% and more than 80%; The mother liquor with m-chloropropiophenone content more than 80% is returned to S1 as the crystallization raw material for continued use; For the mother liquor with m-chloropropiophenone content between 50 - 80%, rapidly reduce the temperature to 10 - 15 °C, and filter the uncrystallized mother liquor; The mother liquor with m-chloropropiophenone content less than 50% undergoes the rectification operation of S4.

2. The purification method of 3-chloropropiophenone according to claim 1, characterized in that: In the said S1, the cooling rate is 1.0 - 5.0 °C / h, and the heating rate is 1.0 - 3.0 °C / h.

3. A method for purifying m-chloropropiophenone according to claim 1, characterized in that: In S4, the theoretical number of plates of the rectification column is 15 - 30, the reflux ratio is 1 - 3, and the vacuum degree is controlled at 2 - 10 mmHg.

Images