A method for recycling and treating phloroglucinol mother liquor

Abstract

The present invention discloses a method for recycling and treating phloroglucinol mother liquor. The steps are as follows: after adding alkali treatment to the phloroglucinol black mother liquor, it is successively subjected to atmospheric pressure filtration through silica gel and acidic alumina to remove most of the polymers and a small part of the chlorides, obtaining a yellow mother liquor; adding activated carbon, heating and stirring under the protection of an inert atmosphere, and filtering to remove most of the chlorides, obtaining a relatively pure mother liquor; treating with concentrated hydrochloric acid, cooling and crystallizing, filtering and drying to obtain phloroglucinol fine product and the mother liquor that cannot crystallize; the mother liquor that cannot crystallize is used for quenching treatment in the phloroglucinol synthesis reaction, and the obtained mother liquor repeats the above steps. The present invention solves the problem of difficult treatment of phloroglucinol mother liquor, reduces environmental pollution, and has simple operation; realizes the closed-loop recycling of phloroglucinol mother liquor, reduces the re-generation of wastewater, is green and environmentally friendly, maximally recovers and utilizes materials, and at the same time improves the reaction yield of phloroglucinol.

Description

Technical Field

[0001] The present invention belongs to the recycling of mother liquor in drug synthesis, and particularly relates to a cyclic treatment method for phloroglucinol mother liquor. Technical Background

[0002] Phloroglucinol, chemical name: 1,3,5-trihydroxybenzene, CAS No.: 6099-90-7, molecular formula: C6H6O3·2H2O. Phloroglucinol belongs to the category of chemical drugs. Phloroglucinol can directly act on the smooth muscles of the gastrointestinal tract and urogenital tract, and is a myotropic, non-atropine, non-papaverine smooth muscle spasmolytic. Compared with other smooth muscle spasmolytics, its characteristic is that it does not have an anticholinergic effect. While relieving smooth muscle spasm, it will not produce a series of anticholinergic side effects, will not cause symptoms such as hypotension, increased heart rate, and arrhythmia, and has no effect on cardiovascular function. Its indications mainly include acute spastic pain caused by digestive system and biliary tract dysfunction; acute spastic urethral, bladder, and renal colic; gynecological spastic pain.

[0003] Currently, in the synthesis of phloroglucinol, a large amount of water is required for post-reaction treatment to quench the reaction and refine the crude product. Due to the water solubility of phloroglucinol, the yield of the finished product is extremely low, and the content of phloroglucinol in the mother liquor is relatively high. The mother liquor also contains a large amount of polymers and chlorides, resulting in poor crystallization of the mother liquor, and the mother liquor is strongly acidic. In industrial production, the mother liquor is generally directly treated as waste, causing a large amount of material loss, seriously polluting the environment, and having a high treatment cost.

[0004] Summary of the Invention

[0005] The purpose of the present invention is to provide a treatment method for phloroglucinol mother liquor, which solves the problem of difficult treatment of phloroglucinol mother liquor, reduces environmental pollution, and has simple operation; realizes the closed-loop recycling of phloroglucinol mother liquor, reduces the re-generation of wastewater, is green and environmentally friendly, maximally recycles materials, and at the same time improves the reaction yield of phloroglucinol.

[0006] In order to achieve the above purpose, the present invention adopts the following technical solutions:

[0007] Provide a cyclic treatment method for phloroglucinol mother liquor, including the following steps:

[0008] 1) Removal of polymers: After adding alkali treatment to the phloroglucinol black mother liquor obtained during the synthesis of phloroglucinol, it is successively subjected to normal pressure filtration through silica gel and acidic alumina to remove most of the polymers and a small part of chlorides, obtaining a yellow mother liquor; wherein the phloroglucinol black mother liquor includes phloroglucinol, polymers, and chlorides;

[0009] 2) Removal of chlorides: Activated carbon is added to the yellow mother liquor obtained in step 1), and it is heated and stirred under the protection of an inert atmosphere, then filtered to remove most of the chlorides, obtaining a relatively pure mother liquor substance;

[0010] 3) Refining: The mother liquor substance obtained in step 2) is treated with concentrated hydrochloric acid, then cooled to crystallize, and filtered and dried to obtain high-quality phloroglucinol and the mother liquor substance that cannot crystallize;

[0011] 4) Recycling: The mother liquor substance that cannot crystallize in step 3) is used for quenching treatment in the phloroglucinol synthesis reaction, and the mother liquor substance generated by the reaction is recycled in steps 1)-3).

[0012] According to the above scheme, in step 1), the phloroglucinol black mother liquor substance is generated during the preparation of phloroglucinol by reflux reaction with chlorophenol as the raw material. Specifically, for example, it is obtained during the preparation of phloroglucinol by reflux reaction with 2,6-dichlorophenol as the raw material.

[0013] According to the above scheme, in step 1), the pH of the phloroglucinol black mother liquor substance is ≤3.

[0014] According to the above scheme, in step 1), in the phloroglucinol black mother liquor substance, calculated by mass percentage based on solvent-free, phloroglucinol: 40–50%, polymer: 10–30%, chloride: 30–40%.

[0015] Preferably, the structural formula of the polymer is ; the structural formula of the chloride is .

[0016] According to the above scheme, in step 1), the pH range of the phloroglucinol black mother liquor substance after alkali treatment is 5.5-6.5. Preferably, the alkali is flake soda. By adding alkali to neutralize the acidity to increase the pH, the adsorption effect of the adsorbent is avoided from being affected.

[0017] According to the above scheme, in step 1), the silica gel includes two mesh sizes of 300-400 meshes and 1000 meshes. Among them, the upper layer is 1000-mesh silica gel, and the lower layer is 300-400-mesh silica gel. The use of two different mesh sizes of silica gel together has a better effect. Preferably, the thickness ratio of 1000-mesh silica gel to 300-400-mesh silica gel is 1.25-1.75:1. The phloroglucinol mother liquor to be treated in the present invention is acidic, and a relatively acidic, polar adsorbent silica gel and acidic alumina are selected to be used together. Among them: the silica gel is mainly used to adsorb the phloroglucinol polymer with a relatively large polarity, and the acidic alumina can effectively remove a small amount of chloride ions in the system and at the same time play a role in decolorization.

[0018] According to the above solution, in step 1), the mesh number of the acidic alumina is 100 - 200 meshes. Preferably, the thickness ratio of 1000-mesh silica gel to acidic alumina is 2.5 - 3.5:1.

[0019] According to the above solution, in step 2), the molar ratio of activated carbon to the untreated phloroglucinol black mother liquor in step 1) is 0.3 - 0.5:1.

[0020] According to the above solution, in step 2), when heating and stirring, the heating temperature is 60 - 80 °C, and the stirring time is 1 - 2 h.

[0021] According to the above solution, in step 2), the activated carbon is 100-mesh medicinal activated carbon.

[0022] According to the above solution, in step 3), after the mother liquor is treated with concentrated hydrochloric acid, the pH range is 1 - 2, the temperature for cooling and crystallization is 0 - 5 °C, the crystallization time is 2 - 3 h, the drying temperature is 40 - 50 °C, and the drying duration is 12 - 15 h.

[0023] According to the above solution, in the mother liquor that cannot crystallize in step 3), based on solvent-free basis, the mass percentage of phloroglucinol is 30 - 40%.

[0024] A method for synthesizing phloroglucinol is provided. The specific operation steps are as follows: Using chlorophenol as a raw material, adding a strong base, and refluxing to react to prepare phloroglucinol. After the reaction is completed, the mother liquor that cannot crystallize obtained in step 3) of the above-mentioned cyclic treatment method of the phloroglucinol mother liquor is used to quench the reaction. After liquid separation, the aqueous phase is acidified with concentrated hydrochloric acid, and the temperature is lowered for crystallization to obtain phloroglucinol.

[0025] According to the above solution, the addition amount of the mother liquor that cannot crystallize is 4 - 5 times the mass of chlorophenol.

[0026] The beneficial effects of the present invention are as follows:

[0027] 1. The present invention utilizes the adsorption properties of silica gel, alumina, and activated carbon to adsorb and remove different impurities in the phloroglucinol mother liquor, ultimately improving the purity of the mother liquor, realizing the re-crystallization of the mother liquor to recover the product, and the remaining mother liquor that cannot crystallize can be repeatedly used for quenching treatment in the phloroglucinol synthesis reaction system. The obtained mother liquor can be treated again according to the method of the present invention. Thus, while improving the product yield, the recycling of the mother liquor is also realized; the purity of the phloroglucinol recovered by crystallization in the present invention is as high as over 99.5%, and after the mother liquor is reused in the reaction system, the product yield can be further increased by about 10 - 15%.

[0028] 2. The present invention solves the problem of difficult treatment of phloroglucinol mother liquor, reduces environmental pollution, and has simple operation; realizes the closed-loop recycling of phloroglucinol mother liquor, reduces the re-generation of wastewater, and is green and environmentally friendly; through repeated extraction, basically realizes the maximum material recovery and utilization, and further improves the reaction yield of phloroglucinol. Detailed implementation manners

[0029] The following further explains and illustrates the present invention through specific embodiments.

[0030] Example 1

[0031] A cyclic treatment method for phloroglucinol mother liquor includes the following steps:

[0032] (1) Take the black mother liquor obtained during the high-temperature synthesis of phloroglucinol using 2,6-dichlorophenol as the raw material. After removing the solvent, it is about 500 g, containing 43% phloroglucinol, 26% polymer, 31% chloride, and the pH is 2.0. Slowly add 62 g of flake caustic soda to the mother liquor to adjust the pH to 5.5.

[0033] The loading height of the filter medium in the filter is 0.55 m. The lower layer is loaded with 100 - 200 mesh acidic alumina, the middle layer is loaded with 300 - 400 mesh silica gel, and the upper layer is loaded with 1000 mesh silica gel. After compaction, the thickness ratio from top to bottom is 2.5:2:1 in turn. Pass the above-treated mother liquor through this filter for normal pressure filtration to remove most of the polymer and a small part of the chloride, and obtain a yellow mother liquor.

[0034] (2) Add 150 g of 100-mesh medicinal activated carbon to the yellow mother liquor in step (1), heat to 60 °C under nitrogen protection, keep warm and stir for 1 h, and filter while it is hot to obtain a mother liquor with a lighter color.

[0035] (3) Adjust the pH of the mother liquor in step (2) to 2.0 with 52 ml of concentrated hydrochloric acid, then place it in an ice bath at 0 °C for 2 h for cooling and crystallization, filter, and dry the filter cake in a vacuum oven at 40 °C for 15 h. After drying and discharging for inspection, 120 g of high-purity phloroglucinol fine product is obtained, and the HPLC purity is 99.8%.

[0036] (4) In the mother liquor that cannot be crystallized obtained by filtration in step (3), calculated on a solvent-free basis, the mass percentage content of phloroglucinol is 33%.

[0037] (5) Dissolve 500 g of 2,6-dichlorophenol in 5 L of toluene, add 100 g of sodium hydroxide, heat to 110 °C for reflux reaction. After the reaction is completed, add 2000 g of the mother liquor that cannot be crystallized in step (4) to quench the reaction. After liquid-liquid extraction, adjust the pH of the aqueous phase to 2 with about 215 ml of concentrated hydrochloric acid, then cool to 0 °C for 2 h for crystallization, and filter to obtain 300 g of qualified phloroglucinol.

[0038] Example 2

[0039] A method for recycling and treating phloroglucinol mother liquor, comprising the following steps:

[0040] (1) Take about 500 g of the black mother liquor obtained during the high-temperature synthesis of phloroglucinol using 2,6-dichlorophenol as the raw material, and remove the solvent. It contains 48% phloroglucinol, 18% polymer, 34% chloride, and the pH is 1.0. Slowly add 80 g of caustic soda to the mother liquor and adjust the pH to 6.5.

[0041] The loading height of the filter medium in the filter is 0.65 m. The lower layer is loaded with 100 - 200 mesh acidic alumina, the middle layer is loaded with 300 - 400 mesh silica gel, and the upper layer is loaded with 1000 mesh silica gel. After compaction, the thickness ratio from top to bottom is 3.5:2:1. Pass the above-treated mother liquor through this filter for normal pressure filtration to remove most of the polymer and a small part of the chloride, obtaining a yellow mother liquor.

[0042] (2) Add 250 g of 100-mesh medicinal activated carbon to the yellow mother liquor in step (1), heat to 80 °C under nitrogen protection, keep warm and stir for 2 h, and filter while it is hot to obtain a mother liquor with a lighter color.

[0043] (3) Adjust the pH of the mother liquor in step (2) to 2.0 with 70 ml of concentrated hydrochloric acid, then place it in a 5 °C water bath to cool and crystallize for 3 h, filter, and dry the filter cake in a 50 °C vacuum oven for 12 h. After drying and discharging for inspection, 108 g of high-purity phloroglucinol fine product is obtained, and the HPLC purity is 99.6%.

[0044] (4) In the mother liquor that cannot crystallize obtained by filtering in step (3), calculated on a solvent-free basis, the mass percentage of phloroglucinol is 38%.

[0045] (5) Dissolve 500 g of 2,6-dichlorophenol in 5 L of toluene, add 100 g of sodium hydroxide, heat to 110 °C for reflux reaction. After the reaction is completed, add 2000 g of the mother liquor that cannot crystallize in step (4) to quench the reaction. After liquid-liquid extraction, adjust the pH of the aqueous phase to 1 with about 208 ml of concentrated hydrochloric acid, then cool to 5 °C to crystallize for 3 h, and filter to obtain 314 g of qualified phloroglucinol.

[0046] Comparative Example ①

[0047] Dissolve 500 g of 2,6-dichlorophenol in 5 L of toluene, add 100 g of sodium hydroxide, heat the reaction to 110 °C for reflux reaction. After the reaction is completed, add 2000 g of cold water to quench the reaction. After liquid-liquid extraction, adjust the pH of the aqueous phase to 1 with about 230 ml of concentrated hydrochloric acid, then cool to 5 °C to crystallize for 3 h, and filter to obtain 273 g of qualified phloroglucinol.

[0048] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for recycling and treating phloroglucinol mother liquor, characterized in that, It includes the following steps: 1) Removal of polymers: After adding alkali treatment to the phloroglucinol black mother liquor obtained during the synthesis of phloroglucinol, it is successively filtered under normal pressure through silica gel and acidic alumina to remove most of the polymers and a small amount of chlorides, obtaining a yellow mother liquor; the phloroglucinol black mother liquor includes phloroglucinol, polymers, and chlorides; the structural formula of the polymer is , and the structural formula of the chloride is ; 2) Removal of chlorides: Activated carbon is added to the yellow mother liquor obtained in step 1), heated and stirred under an inert atmosphere protection, and most of the chlorides are removed by filtration to obtain a relatively pure mother liquor substance; 3) Refining: The mother liquor substance obtained in step 2) is treated with concentrated hydrochloric acid, cooled and crystallized, and filtered and dried to obtain high-quality phloroglucinol and the mother liquor substance that cannot crystallize; 4) Recycling: The mother liquor substance that cannot crystallize in step 3) is used for quenching treatment in the phloroglucinol synthesis reaction, and the mother liquor substance generated by the reaction repeats steps 1)-3).

2. The recycling treatment method of phloroglucinol mother liquor according to claim 1, wherein In the said step 1), the pH range of the phloroglucinol black mother liquor substance after alkali treatment is 5.5 - 6.

5.

3. The recycling treatment method of phloroglucinol mother liquor according to claim 1, characterized in that, In the said step 1), in the phloroglucinol black mother liquor substance, calculated by mass percentage based on solvent-free, phloroglucinol: 40–50%, polymer: 10–30%, chloride: 30–40%.

4. The recycling treatment method of phloroglucinol mother liquor according to claim 1, characterized in that, In the said step 1), the silica gel includes two mesh sizes of 300 - 400 mesh and 1000 mesh, where the upper layer is 1000-mesh silica gel and the lower layer is 300 - 400-mesh silica gel; the mesh size of the acidic alumina is 100 - 200 mesh.

5. The recycling treatment method of phloroglucinol mother liquor according to claim 1, characterized in that, In the said step 2), the mass ratio of the activated carbon to the untreated phloroglucinol black mother liquor substance in step 1) is 0.3 - 0.5:

1.

6. The recycling treatment method of phloroglucinol mother liquor according to claim 1, characterized in that, In the said step 2), when heating and stirring, the heating temperature is 60 - 80 °C, and the stirring time is 1 - 2 h.

7. The method for recycling and treating the phloroglucinol mother liquor according to claim 1, characterized in that In the said step 3), after the mother liquor is treated with concentrated hydrochloric acid, the pH range is 1 - 2, the cooling crystallization temperature is 0 - 5 °C, the crystallization time is 2 - 3 h, the drying temperature is 40 - 50 °C, and the drying duration is 12 - 15 h.

8. A method for synthesizing phloroglucinol, characterized in that, The specific operation steps are as follows: Using chlorophenol as a raw material, adding a strong base, refluxing to prepare phloroglucinol. After the reaction is completed, the non-crystallizable mother liquor obtained in step 3) of the cyclic treatment method of the phloroglucinol mother liquor described in claim 1 is used to quench the reaction. After stratification, the aqueous phase is acidified with concentrated hydrochloric acid, cooled and crystallized to obtain phloroglucinol.

9. The synthesis method according to claim 8, characterized in that, The addition amount of the non-crystallizable mother liquor is 4 - 5 times the mass of the chlorophenol.

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