CN111892541A - Recovery and purification method of imidocarb - Google Patents
Recovery and purification method of imidocarb Download PDFInfo
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- CN111892541A CN111892541A CN202010893610.4A CN202010893610A CN111892541A CN 111892541 A CN111892541 A CN 111892541A CN 202010893610 A CN202010893610 A CN 202010893610A CN 111892541 A CN111892541 A CN 111892541A
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- CN
- China
- Prior art keywords
- imidocarb
- phenylurea
- imidazole
- purifying
- recovering
- Prior art date
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- SCEVFJUWLLRELN-UHFFFAOYSA-N imidocarb Chemical compound C=1C=CC(C=2NCCN=2)=CC=1NC(=O)NC(C=1)=CC=CC=1C1=NCCN1 SCEVFJUWLLRELN-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 229960004683 imidocarb Drugs 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000000746 purification Methods 0.000 title description 4
- 238000011084 recovery Methods 0.000 title description 2
- ROYGEONSPSZKNF-UHFFFAOYSA-N N1C=NC=C1.C1(=CC=CC=C1)NC(=O)N Chemical compound N1C=NC=C1.C1(=CC=CC=C1)NC(=O)N ROYGEONSPSZKNF-UHFFFAOYSA-N 0.000 claims abstract description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- 238000003756 stirring Methods 0.000 claims abstract description 18
- BXBHZLHTTHMUTG-UHFFFAOYSA-N methyl 1h-pyrrolo[3,2-b]pyridine-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OC)=CC2=N1 BXBHZLHTTHMUTG-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229940113484 imidocarb dipropionate Drugs 0.000 claims abstract description 14
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims abstract description 12
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012452 mother liquor Substances 0.000 claims abstract description 6
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- 238000002425 crystallisation Methods 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 10
- 238000007670 refining Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 239000002699 waste material Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000001035 drying Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 description 1
- HSLPBCRWOIMTGS-UHFFFAOYSA-N 1H-benzimidazol-4-ylurea Chemical compound N1=CNC2=C1C=CC=C2NC(=O)N HSLPBCRWOIMTGS-UHFFFAOYSA-N 0.000 description 1
- HKLBMYTZBSUBCS-UHFFFAOYSA-N C(CC)(=O)O.C(CC)(=O)O.C1(=CC=CC=C1)NC(=O)N.N1C=NC=C1 Chemical compound C(CC)(=O)O.C(CC)(=O)O.C1(=CC=CC=C1)NC(=O)N.N1C=NC=C1 HKLBMYTZBSUBCS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- 241000231139 Pyricularia Species 0.000 description 1
- 208000001117 Theileriasis Diseases 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 201000008680 babesiosis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 201000002311 trypanosomiasis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/24—Radicals substituted by nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for recovering and purifying imidocarb. The method for collecting and purifying comprises the following steps: adding softened water and butyl acetate into the mother liquor concentrated residue after synthesizing imidocarb dipropionate, stirring to fully dissolve, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, and stirring and crystallizing to obtain a crude imidazole phenylurea product. According to the method for recovering and purifying the imidazole phenylurea, the residual imidazole phenylurea is extracted and purified by researching the imidazole phenylurea waste residue, so that the utilization rate of the waste residue is improved, and the production cost of the imidazole phenylurea is greatly reduced.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for recovering and purifying compound imidazole phenylurea.
Background
The summary of imidazophenylurea is as follows:
the chemical formula is as follows: c19H20N6O；
The chemical name is N, N' -bis (3- (4, 5-dihydro-1H-imidazole-2-yl) phenyl) urea;
structural formula (xvi):
the application is as follows: the imidazole phenylurea belongs to the derivative of the sym-diphenylurea, and is a novel antiprotozoal chemical drug special for animals. The dipropionate or the double hydrochloride of the compound is generally prepared into a preparation clinically and is used for treating and preventing various babesiosis, pyricularia, trypanosomiasis, eperythrozoonosis, marginalis, theileriosis and the like by intramuscular or subcutaneous injection.
Patent CN105949127A discloses a purification method of imidocarb, which specifically comprises adding a surfactant into an imidocarb feed liquid, stirring for reaction, cooling for crystallization, and drying. Dissolving imidazole phenylurea in an organic solvent, adding water, adjusting the pH value with propionic acid, stirring for crystallization, and drying to obtain the imidazole phenylurea dipropionate. The method is a synthesis and purification method of imidocarb dipropionate, and the target product is used for preparing imidocarb dipropionate salt.
Chinese patent CN103896843A, CN1850805A, CN101348465A and US3338917 report various synthesis methods of imidocarb dipropionate, but the residual imidocarb in the salification mother liquor of imidocarb dipropionate is not recycled and researched, so that waste residue containing an imidocarb plate directly enters an environment-friendly treatment system, great waste is generated, and the cost of the product is increased.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for recovering and purifying imidocarb.
The invention is realized by the following technical scheme:
the method for recovering and purifying the imidocarb comprises the following steps:
adding softened water and butyl acetate into the mother liquor residue after synthesizing imidocarb dipropionate, stirring to fully dissolve, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, and stirring and crystallizing to obtain a crude imidazole phenylurea product.
In the method for recovering and purifying the imidazole phenylurea, the mass ratio of the imidazole phenylurea to the softened water and the butyl acetate is 1:4-8: 0.5-1.5.
Preferably, in the above method for recovering and purifying imidocarb, the mass ratio of imidocarb to demineralized water and butyl acetate is 1:6: 1.
In the method for recovering and purifying the imidazole phenylurea, the crude imidazole phenylurea also comprises a refining step. The refining step comprises the following steps: and dissolving the crude imidazole phenylurea with toluene, and adding the dissolved crude imidazole phenylurea into acetone for crystallization to obtain a pure imidazole phenylurea product.
In the method for recovering and purifying the imidazole phenylurea, the dosage of the toluene is 2-3 times of the weight of the crude imidazole phenylurea.
Preferably, in the above method for recovering and purifying imidocarb, the amount of toluene is 2.5 times of the weight of the crude imidocarb. In the method for recovering and purifying the imidazole phenylurea, the using amount of the acetone is 5-7 times of the weight of the crude imidazole phenylurea.
Preferably, in the above method for recovering and purifying imidocarb, the amount of acetone is 6 times of the weight of the crude imidocarb.
The invention has the beneficial effects that:
according to the method for recovering and purifying the imidazole phenylurea, the residual imidazole phenylurea is extracted and purified by researching the imidazole phenylurea waste residue, so that the utilization rate of the waste residue is improved, and the production cost of the imidazole phenylurea is greatly reduced.
Detailed Description
The present invention will be further described with reference to specific examples so that those skilled in the art may better understand the present invention, but the present invention is not limited thereto.
The residue in the embodiment of the invention is the mother liquor residue after synthesizing the imidocarb dipropionate, is the mother liquor residue generated in the process of producing the imidocarb dipropionate by the company, and about 100kg of residue is generated every 135kg of finished product of the imidocarb dipropionate
Example 1
Adding 600kg of softened water and 100kg of butyl acetate into 100kg of residue (about 100kg of residue is generated in the production of 135kg of finished product of imidocarb dipropionate), stirring for 1.5-2h, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, stirring and crystallizing, centrifuging to obtain a crude imidazole phenylurea product, and drying to obtain 53 kg. After dissolving the crude imidazole phenylurea with 132.5kg of toluene, adding the dissolved crude imidazole phenylurea into 318kg of acetone for crystallization for 16h, centrifuging, and obtaining 35.46kg of dried pure imidazole phenylurea. The HPLC purity of the pure imidazole phenylurea is 99.72%.
Example 2
Adding 600kg of softened water and 100kg of butyl acetate into 100kg of residue (about 100kg of residue is generated in the production of 135kg of finished product of imidocarb dipropionate), stirring for 1.5-2h, and separating out a water layer; adjusting pH of water layer with sodium hydroxide =9.5-10.5, stirring for crystallization, centrifuging to obtain crude imidazole phenylurea, and oven drying to obtain 53.5 kg. After the crude imidazole phenylurea is dissolved by 133.75kg of toluene, the crude imidazole phenylurea is added into 321kg of acetone for crystallization for 16h, and then the mixture is centrifuged, and 36.26kg of dried pure imidazole phenylurea is obtained. The HPLC purity of the pure product of the imidazole phenylurea is 99.56 percent.
Example 3
Adding 600kg of softened water and 100kg of butyl acetate into 100kg of residue (about 100kg of residue is generated in the production of 135kg of finished product of imidocarb dipropionate), stirring for 1.5-2h, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, stirring and crystallizing, centrifuging to obtain a crude imidazole phenylurea product, and drying to obtain 51.6 kg. After the crude imidazole phenylurea is dissolved by 154.8kg of toluene, the crude imidazole phenylurea is added into 258kg of acetone for crystallization for 16h, and then the mixture is centrifuged, and 34.85kg of dried imidazole phenylurea pure product is obtained. The HPLC purity of the pure product of the imidazole phenylurea is 99.13 percent.
Example 4
Adding 400kg of softened water and 50kg of butyl acetate into 100kg of residue (about 100kg of residue is generated in the production of 135kg of finished product of imidocarb dipropionate), stirring for 0.5-2h, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, stirring and crystallizing, centrifuging to obtain a crude imidazole phenylurea product, and drying to obtain 50.8k imidazole phenylurea. After dissolving the crude imidazole phenylurea by 150kg of toluene, adding the dissolved crude imidazole phenylurea into 300kg of acetone for crystallization for 16h, centrifuging, and obtaining 30.23kg of dried imidazole phenylurea pure product. The HPLC purity of the pure product of the imidazole phenylurea is 98.95 percent.
Example 5
Adding 400kg of softened water and 50kg of butyl acetate into 100kg of residue (about 100kg of residue is generated in the production of 135kg of finished product of imidocarb dipropionate), stirring for 0.5-2h, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, stirring and crystallizing, centrifuging to obtain a crude imidazole phenylurea product, and drying to obtain 52.6 k. Dissolving crude imidazole phenylurea with 120kg of toluene, adding into 315kg of acetone for crystallization for 16h, centrifuging, and drying 35.88kg of pure imidazole phenylurea. The HPLC purity of the pure product of the imidazole phenylurea is 99.02 percent.
Claims (9)
1. The method for recovering and purifying the imidocarb comprises the following steps:
adding softened water and butyl acetate into the mother liquor residue after synthesizing imidocarb dipropionate, stirring to fully dissolve, and separating out a water layer; adjusting the pH of the water layer to be 9.5-10.5 by using sodium hydroxide, and stirring and crystallizing to obtain a crude imidazole phenylurea product.
2. The method for recovering and purifying imidocarb according to claim 1, wherein the mass ratio of imidocarb to demineralized water and butyl acetate is 1:4-8: 0.5-1.5.
3. The method for recovering and purifying imidocarb according to claim 1, wherein the mass ratio of imidocarb to demineralized water to butyl acetate is 1:6: 1.
4. The method for recovering and purifying imidocarb according to claim 1, wherein the crude imidocarb further comprises a refining step.
5. The method for recovering and purifying imidocarb according to claim 4, wherein the refining step comprises the steps of: and dissolving the crude imidazole phenylurea with toluene, and adding the dissolved crude imidazole phenylurea into acetone for crystallization to obtain a pure imidazole phenylurea product.
6. The method for recovering and purifying imidocarb according to claim 5, wherein the amount of toluene is 2-4 times of the weight of crude imidocarb.
7. The method for recovering and purifying imidocarb according to claim 6, wherein the amount of toluene is 2.5 times of the weight of crude imidocarb.
8. The method for recovering and purifying imidocarb according to claim 5, wherein the amount of acetone is 5-7 times of the crude imidocarb.
9. The method for recovering and purifying imidocarb according to claim 8, wherein the amount of acetone is 6 times the weight of crude imidocarb.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010893610.4A CN111892541A (en) | 2020-08-31 | 2020-08-31 | Recovery and purification method of imidocarb |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010893610.4A CN111892541A (en) | 2020-08-31 | 2020-08-31 | Recovery and purification method of imidocarb |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112521337A (en) * | 2020-12-15 | 2021-03-19 | 河北威远药业有限公司 | Preparation method of imidocarb dipropionate sterile bulk drug |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574455A (en) * | 2020-05-15 | 2020-08-25 | 山东省药学科学院 | Preparation method of imidocarb dipropionate and intermediate thereof |
-
2020
- 2020-08-31 CN CN202010893610.4A patent/CN111892541A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574455A (en) * | 2020-05-15 | 2020-08-25 | 山东省药学科学院 | Preparation method of imidocarb dipropionate and intermediate thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李光壁: "一种抗梨形虫药物咪唑苯脲及其盐的合成研究", 《山东大学硕士学位论文》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112521337A (en) * | 2020-12-15 | 2021-03-19 | 河北威远药业有限公司 | Preparation method of imidocarb dipropionate sterile bulk drug |
| CN112521337B (en) * | 2020-12-15 | 2022-08-05 | 河北威远药业有限公司 | Preparation method of imidocarb dipropionate sterile bulk drug |
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