CN105949127B - A kind of method of purification of imidazophenylurea - Google Patents
A kind of method of purification of imidazophenylurea Download PDFInfo
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- CN105949127B CN105949127B CN201610313072.0A CN201610313072A CN105949127B CN 105949127 B CN105949127 B CN 105949127B CN 201610313072 A CN201610313072 A CN 201610313072A CN 105949127 B CN105949127 B CN 105949127B
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- imidazophenylurea
- surfactant
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- purification
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- 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
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of methods of purification of imidazophenylurea, and surfactant specially is added in the feed liquid of imidazophenylurea, is stirred to react, and cool down crystallization, dry.Then plus water imidazophenylurea is dissolved in organic solvent, adjusts PH with propionic acid, stirring and crystallizing, dry imidocard dipropionate.This method is easy to operate, is easy to industrial operation, at low cost, and imidocard dipropionate product content can reach 99.9% or more.
Description
Technical field
The invention belongs to the purifying crystal technical field of chemicals more particularly to a kind of purifying crystal sides of imidazophenylurea
Method.
Background technique
Imidazophenylurea is chemical synthesis bulk pharmaceutical chemicals for animals, as anti-piroplasmosis drug object hexichol class diamidine derivative, is had wide
Compose, have a wide range of application, long action time, small dosage the advantages that, have to domestic animal piroplasmosis, anaplasmosis etc. and control well
Treatment effect, it may have good prevention effect.Imidazophenylurea is white or off-white powder, odorless, tasteless, is insoluble in water, is made
For anti-piroplasmosis drug object hexichol class diamidine derivative, it generally clinically is made into preparation with its dipropionate or dihydrochloride, wherein
Imidocard dipropionate is most commonly seen.
Have a large amount of report to the synthesis technology of imidazophenylurea in recent years, is passed through using nitro compound as raw material
Cyclization, nitro reduction, amidation and etc., imidazophenylurea, such as Chinese patent CN103896843A is prepared,
CN1850805A, CN101348465A, United States Patent (USP) US3338917.The impurity generated during synthesis of imidoearb at present is outstanding
Nitro compound between it is not reacted completely has larger toxic side effect to animal, due to existing side although content is few
The imidazophenylurea purity of method preparation can reach 98% or more, so, mesh very big for the difficulty of impurity a small amount of in feed liquid removal
The preceding impurity effectively removed in imidazophenylurea feed liquid not yet, especially between nitro compound method.With dipropyl imidazole acid
Phenylurea is found new clinical application, and demand is more and more, and use is more and more extensive, and client is to imidazophenylurea and its propionate
Quality requirements it is also higher and higher, the client of especially some foreign countries is stringenter to imidazophenylurea purity requirement, thus be badly in need of
A kind of method that imidazophenylurea feed liquid can be further purified.
Summary of the invention
The purpose of the present invention is to solve the above-mentioned problems, provides a kind of method of purification of imidazophenylurea.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of method of purification of imidazophenylurea, is added surfactant in the feed liquid of imidazophenylurea, is stirred to react, cooling
Crystallization, it is dry.
The advantages of surfactant is added is that surfactant forms micella in feed liquid, in conjunction with nitro compound,
The solubility for improving a nitro compound makes it be not easy to be precipitated in the crystallization process of imidazophenylurea, to improve product
Purity.
It is preferred that: the surfactant is polysorbate, sucrose fatty ester etc..
It is preferred that: the surfactant and the mass ratio of feed liquid are 1:200-1:100.
It is preferred that: the purified reaction temperature is 35-50 DEG C.
It is preferred that: the purified reaction time is 2-3 hours.
It is preferred that: the crystallization temperature is 10-15 DEG C.
A kind of method for crystallising of imidocard dipropionate, steps are as follows:
(1) surfactant is added in the feed liquid of imidazophenylurea, is stirred to react, cool down crystallization, dry imidazophenylurea；
Then plus water (2) imidazophenylurea is dissolved in organic solvent, adjusts PH with propionic acid, stirring and crystallizing, dry dipropionic acid
Imidazophenylurea.
It is preferred that: the organic solvent is that acetone, isopropanol, ethyl alcohol, methanol etc. are one or more.
It is preferred that: the imidazophenylurea: organic solvent=1:1-3 (mass volume ratio).
It is preferred that: the water: organic solvent=1:2-3 (volume ratio).
It is preferred that: the PH=5-6.
Beneficial effects of the present invention:
Surfactant has good solubilizing effect: surfactant (especially polysorbate, sucrose fatty ester)
Micella is formed in feed liquid, in conjunction with nitro compound, the selective nitro compound between improving impurity in crystallization process
The solubility of object makes it be not easy to be precipitated in imidazophenylurea crystallization process, improves imidazophenylurea product content.This method operation letter
Just, economize on resources that low energy consumption, easy to industrialized production without increasing professional equipment, imidazophenylurea product content 99.8% with
On, imidazophenylurea propionate content reaches 99.9% or more, meets industry to the requirement of imidazophenylurea high-quality.
Specific embodiment
Below with reference to embodiment, the invention will be further described.
Embodiment 1
0.41g sucrose fat is added in the feed liquid 81.94g (the theoretical amount 14.10g containing imidazophenylurea) containing imidazophenylurea
Acid esters, 35 DEG C are stirred 2 hours, and 12 DEG C of stirring and crystallizings are then cooled to, and are filtered, dry imidazophenylurea 12.83g, content
99.82%, white powder.
12.83g imidazophenylurea is dissolved in 26ml acetone, then plus water 13ml is stirred and analysed with propionic acid adjusting PH=5.0
Crystalline substance, filtering, dry imidocard dipropionate 17.92g, content 99.90%, white powder.
Embodiment 2
The poly- sorb of 0.42g is added in the feed liquid 83.51g (the theoretical amount 13.81g containing imidazophenylurea) containing imidazophenylurea
Ester, 45 DEG C are stirred 3 hours, and 10 DEG C of stirring and crystallizings are then cooled to, and are filtered, dry imidazophenylurea 12.71g, content
99.84%, white powder.
12.71g imidazophenylurea is dissolved in 35ml acetone, then plus water 15ml is stirred and analysed with propionic acid adjusting PH=5.5
Crystalline substance, filtering, dry imidocard dipropionate 17.85g, content 99.92%, white powder.
Embodiment 3
0.54g sucrose fat is added in the feed liquid 82.00g (the theoretical amount 14.27g containing imidazophenylurea) containing imidazophenylurea
Acid esters, 50 DEG C are stirred 2 hours, and 15 DEG C of stirring and crystallizings are then cooled to, and are filtered, dry imidazophenylurea 12.74g, content
99.83%, white powder.
12.74g imidazophenylurea is dissolved in 36ml ethyl alcohol, then plus water 18ml is stirred and analysed with propionic acid adjusting PH=6.0
Crystalline substance, filtering, dry imidocard dipropionate 17.85g, content 99.90%, white powder.
Embodiment 4
The poly- sorb of 0.53g is added in the feed liquid 84.11g (the theoretical amount 14.29g containing imidazophenylurea) containing imidazophenylurea
Ester, 40 DEG C are stirred 3 hours, and 10 DEG C of stirring and crystallizings are then cooled to, and are filtered, dry imidazophenylurea 13.07g, content
99.84%, white powder.
13.07g imidazophenylurea is dissolved in 40ml ethyl alcohol, then plus water 20ml is stirred and analysed with propionic acid adjusting PH=5.0
Crystalline substance, filtering, dry imidocard dipropionate 18.32g, content 99.92%, white powder.
Embodiment 5
0.55g polysorbate is added in the feed liquid 81.9g (the theoretical amount 14.0g containing imidazophenylurea) containing imidazophenylurea,
45 DEG C are stirred 2 hours, and 12 DEG C of stirring and crystallizings are then cooled to, and are filtered, dry that imidazophenylurea 12.88g, content 99.85% are white
Color powder.
12.88g imidazophenylurea is dissolved in 30ml methanol, then plus water 10ml is stirred and analysed with propionic acid adjusting PH=5.4
Crystalline substance, filtering, dry imidocard dipropionate 18.04g, content 99.95%, white powder.
Above-mentioned, although specific embodiments of the present invention have been described, not to the limit of the scope of the present invention
System, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art do not need to pay
The various modifications or changes that creative work can be made out are still within protection scope of the present invention.
Claims (8)
1. a kind of method of purification of imidazophenylurea, it is characterized in that: surfactant is added in the feed liquid of imidazophenylurea, stirring is anti-
It answers, cool down crystallization, dry；The surfactant and the mass ratio of feed liquid are 1:200-1:100, the surfactant
For polysorbate or sucrose fatty ester.
2. method of purification as described in claim 1, it is characterized in that: the purified reaction temperature is 35-50 DEG C.
3. method of purification as described in claim 1, it is characterized in that: the purified reaction time is 2-3 hours.
4. a kind of method for crystallising of imidocard dipropionate, it is characterized in that: steps are as follows:
(1) surfactant will be added in the feed liquid of imidazophenylurea, is stirred to react, cool down crystallization, dry imidazophenylurea；It is described
Surfactant is polysorbate or sucrose fatty ester；
Then plus water (2) imidazophenylurea is dissolved in organic solvent, adjusts PH with propionic acid, stirring and crystallizing, dry dipropyl imidazole acid
Phenylurea.
5. method for crystallising as claimed in claim 4, it is characterized in that: the organic solvent is acetone, isopropanol, ethyl alcohol, methanol
In more than one.
6. method for crystallising as claimed in claim 4, it is characterized in that: the imidazophenylurea: organic solvent=1:1-3, mass body
Product ratio.
7. method for crystallising as claimed in claim 4, it is characterized in that: the PH=5-6.
8. the application of polysorbate or sucrose fatty ester in imidazophenylurea removal of impurities.
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| CN201610313072.0A CN105949127B (en) | 2016-05-12 | 2016-05-12 | A kind of method of purification of imidazophenylurea |
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| CN201610313072.0A CN105949127B (en) | 2016-05-12 | 2016-05-12 | A kind of method of purification of imidazophenylurea |
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| CN105949127A CN105949127A (en) | 2016-09-21 |
| CN105949127B true CN105949127B (en) | 2018-12-21 |
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| 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850805A (en) * | 2006-06-05 | 2006-10-25 | 吴汝林 | Method for preparing imidazophenylurea hydrochloride |
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- 2016-05-12 CN CN201610313072.0A patent/CN105949127B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850805A (en) * | 2006-06-05 | 2006-10-25 | 吴汝林 | Method for preparing imidazophenylurea hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| 表面活性剂对结晶过程影响的研究进展;杨宗璐;《云南化工》;19940930(第3期);第28页第4.1节 * |
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Denomination of invention: A Purification Method for Imidazole Benzurea Effective date of registration: 20230625 Granted publication date: 20181221 Pledgee: Qilu Bank Co.,Ltd. Dezhou Qihe sub branch Pledgor: SHANDONG JIULONG HISINCE PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980045334 |