CN106699664A - Synthetic process of 4-ampyrone product - Google Patents
Synthetic process of 4-ampyrone product Download PDFInfo
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- CN106699664A CN106699664A CN201611083425.9A CN201611083425A CN106699664A CN 106699664 A CN106699664 A CN 106699664A CN 201611083425 A CN201611083425 A CN 201611083425A CN 106699664 A CN106699664 A CN 106699664A
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- solution
- antipyrine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthetic process of a 4-ampyrone product, which comprises the following steps of: preparing antipyrine and sulfuric acid with concentration of 40 to 60% into solution; enabling the solution and sodium nitrite solution to simultaneously flow into a nitrosation reactor, controlling flow rates of the solution and the sodium nitrite solution, and controlling a reaction temperature to be 45 to 50 DEG C; performing a reaction with stirring; testing a reaction endpoint by iodine powder and starch test paper to regulate a water flow rate; enabling nitroso antipyrine generated by nitrosation to immediately flow into a reducing pot to react with a reducing agent ammonium hydrogen sulfite prepared in the pot and aqueous solution of ammonium sulfite; carrying out sampling and measuring a pH value and a reduction degree; heating to a temperature of 90 to 100 DEG C; after hydrolysis, cooling to a temperature of 80 to 85 DEG C; neutralizing to pH of 7 to 7.5 by liquid ammonia; carrying out standing and layering. The process provided by the invention is simple, convenient to operate and high in yield.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, more particularly to a kind of synthesis technique of 4-AA product.
Background technology
At present, antipyrine Chinese nickname：Antipyrine, antipyrine, 1,5- dimethyl -2- phenyl -3- pyrazolines
Ketone, phenazone, phenopyrine；Color crystal or white crystalline powder.Benzene, ethanol, water, chloroform are dissolved in, are slightly soluble in
Ether；Odorless, there is slight bitter taste；Solubility in water:1000 g/l (20°C)；It is mainly used as the analysis examination of nitric acid, nitrous acid and iodine
Agent.Measure can form the element (such as bismuth, tin, antimony and mercury) of complex cation.Weight analysis determining titanium；Colourless crystallization or white
Crystalline powder, odorless, mildly bitter flavor；Soluble in water, ethanol, chloroform is slightly soluble in ether.It is made with other analgesic-antipyretic more multiple
Square preparation application, its tablet has been washed in a pan；Toxicity is larger, and fash easily occurs, and cyanosis, indigestion, insomnia, collapse and granulocyte are reduced
Deng.It is used to determine alcohol and phenol and amine and its homologue, chromatographic determination alkylphenol；Determining phenol, alcohol, amine as photometry has
The developer of machine thing.And as the reagent of polarography determination phenolic compound.But, existing 4-AA product
There is complex process in synthesis technique, operation is inconvenient, the problem of method of purification effect difference,
Therefore, invent a kind of synthesis technique of 4-AA product and seem very necessary.
The content of the invention
In order to solve the above-mentioned technical problem, the present invention provides a kind of synthesis technique of 4-AA product.
A kind of synthesis technique of 4-AA product of the present invention, step is as follows：
（1）By antipyrine and 40-60% sulfuric acid wiring solution-formings；
（2）Above-mentioned solution and sodium nitrite solution are flowed into the flow of both nitrosation reactor, control, control reaction temperature simultaneously
45-50 DEG C of degree, the lower reaction of stirring, and reaction end is surveyed with regulating water flow with iodine powder starch paper；
（3）The nitroso antipyrine that nitrosation is generated is flowed into reductive jar immediately, it is anti-with the reducing agent aqueous solution for preparing in tank
Should；
（4）PH value is surveyed in sampling, and reduction terminates when pH value is between 5.4-5.8, and pH value is adjusted to 5.8-6.0, is warming up to 98-
100 DEG C, 2.5-3.5h is hydrolyzed, be cooled to 80-85 DEG C, pH7-7.5, stratification are neutralized to liquefied ammonia；
（5）Divide and remove waste water, obtain 4-AA oil, be pressed into crystallizing tank, stirring, crystallisation by cooling and filtering obtain 4- ammonia
Base antipyrine.
Preferably, described step（1）In, solution is with the weight ratio of sulfuric acid containing antipyrine（3-4）:1.
Preferably, described step（3）In, described reducing agent is any one in ammonium bisulfite and ammonium sulfite
Or the mixture of two kinds of any ratio.
Compared with prior art, the present invention has the advantages that：A kind of 4-AA product of the invention
Synthesis technique, process is simple is easy to operate, by antipyrine through natrium nitrosum nitrosation, through ammonium bisulfite and sulfurous
Sour ammonium reduction, through sulphuric acid hydrolysis, is finally neutralized with liquefied ammonia, obtains 4-AA, is advantageously used as medicine analgin
Intermediate, for examining and determine alcohol and amine, surveys phenolic compound in air and water so that the synthesis work of 4-AA product
Skill is easy and effective, and yield is high.
Specific embodiment
Embodiment 1：
A kind of synthesis technique of 4-AA product of the present invention, step is as follows：
1) by antipyrine and 50% sulfuric acid wiring solution-forming.
2) solution and sodium nitrite solution are flowed into the flow of both nitrosation reactor, control, control reaction temperature simultaneously
45-50 DEG C of degree, the lower reaction of stirring, and reaction end is surveyed with regulating water flow with iodine powder starch paper.
3) the nitroso antipyrine that nitrosation is generated is flowed into reductive jar immediately, with the reducing agent aqueous solution for preparing in tank
Reaction.
4) pH value is surveyed in sampling, and reduction terminates when pH value is between 5.4-5.8, and pH value is adjusted to 5.8-6.0, is warming up to
100 DEG C, 3h is hydrolyzed, be cooled to 80 DEG C, pH7-7.5, stratification are neutralized to liquefied ammonia.
5) divide and remove waste water, obtain 4-AA oil, be pressed into crystallizing tank, stirring, crystallisation by cooling and filtering obtain 4-
Amino-antipyrine.
Described step（1）In, solution is 3.5 with the weight ratio of sulfuric acid containing antipyrine:1.
Described step（3）In, described reducing agent is ammonium bisulfite.
The yield of the 4-AA is 96.0%.
Embodiment 2：
A kind of synthesis technique of 4-AA product of the present invention, step is as follows：
1) by antipyrine and 60% sulfuric acid wiring solution-forming.
2) solution and sodium nitrite solution are flowed into the flow of both nitrosation reactor, control, control reaction temperature simultaneously
45-50 DEG C of degree, the lower reaction of stirring, and reaction end is surveyed with regulating water flow with iodine powder starch paper.
3) the nitroso antipyrine that nitrosation is generated is flowed into reductive jar immediately, with the reducing agent aqueous solution for preparing in tank
Reaction.
4) pH value is surveyed in sampling, and reduction terminates when pH value is between 5.4-5.8, and pH value is adjusted to 5.8-6.0, is warming up to 98
DEG C, 3.5h is hydrolyzed, 82 DEG C are cooled to, it is neutralized to pH7-7.5, stratification with liquefied ammonia.
5) divide and remove waste water, obtain 4-AA oil, be pressed into crystallizing tank, stirring, crystallisation by cooling and filtering obtain 4-
Amino-antipyrine.
Described step（1）In, solution is 3 with the weight ratio of sulfuric acid containing antipyrine:1.
Described step（3）In, described reducing agent is ammonium sulfite.
The yield of the 4-AA is 95.5%.
Embodiment 3：
A kind of synthesis technique of 4-AA product of the present invention, step is as follows：
1) by antipyrine and 40% sulfuric acid wiring solution-forming.
2) solution and sodium nitrite solution are flowed into the flow of both nitrosation reactor, control, control reaction temperature simultaneously
45-50 DEG C of degree, the lower reaction of stirring, and reaction end is surveyed with regulating water flow with iodine powder starch paper.
3) the nitroso antipyrine that nitrosation is generated is flowed into reductive jar immediately, with the reducing agent aqueous solution for preparing in tank
Reaction.
4) pH value is surveyed in sampling, and reduction terminates when pH value is between 5.4-5.8, and pH value is adjusted to 5.8-6.0, is warming up to 99
DEG C, 2.5h is hydrolyzed, 85 DEG C are cooled to, it is neutralized to pH7-7.5, stratification with liquefied ammonia.
5) divide and remove waste water, obtain 4-AA oil, be pressed into crystallizing tank, stirring, crystallisation by cooling and filtering obtain 4-
Amino-antipyrine.
Described step（1）In, solution is 4 with the weight ratio of sulfuric acid containing antipyrine:1.
Described step（3）In, described reducing agent is ammonium bisulfite and the mixture of ammonium sulfite, two kinds of materials
Mol ratio is 1:1.
The yield of the 4-AA is 95.2%.
The above, the only present invention preferably specific embodiment, but protection scope of the present invention is not limited thereto,
Any one skilled in the art the invention discloses technical scope in, technology according to the present invention scheme and its
Inventive concept is subject to equivalent or change, should all be included within the scope of the present invention.
Claims (3)
1. a kind of synthesis technique of 4-AA product, it is characterised in that comprise the following steps：
（1）By antipyrine and 40-60% sulfuric acid wiring solution-formings；
（2）Above-mentioned solution and sodium nitrite solution are flowed into the flow of both nitrosation reactor, control, control reaction temperature simultaneously
45-50 DEG C of degree, the lower reaction of stirring, and reaction end is surveyed with regulating water flow with iodine powder starch paper；
（3）The nitroso antipyrine that nitrosation is generated is flowed into reductive jar immediately, it is anti-with the reducing agent aqueous solution for preparing in tank
Should；
（4）PH value is surveyed in sampling, and reduction terminates when pH value is between 5.4-5.8, and pH value is adjusted to 5.8-6.0, is warming up to 98-
100 DEG C, 2.5-3.5h is hydrolyzed, be cooled to 80-85 DEG C, pH7-7.5, stratification are neutralized to liquefied ammonia；
（5）Divide and remove waste water, obtain 4-AA oil, be pressed into crystallizing tank, stirring, crystallisation by cooling and filtering obtain 4- ammonia
Base antipyrine.
2. the synthesis technique of 4-AA product as claimed in claim 1, it is characterised in that described step（1）
In, solution is with the weight ratio of sulfuric acid containing antipyrine（3-4）:1.
3. the synthesis technique of 4-AA product as claimed in claim 1, it is characterised in that described step（3）
In, described reducing agent is any one in ammonium bisulfite and ammonium sulfite or the mixture of two kinds of any ratio.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611083425.9A CN106699664A (en) | 2016-11-30 | 2016-11-30 | Synthetic process of 4-ampyrone product |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611083425.9A CN106699664A (en) | 2016-11-30 | 2016-11-30 | Synthetic process of 4-ampyrone product |
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| CN106699664A true CN106699664A (en) | 2017-05-24 |
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| CN201611083425.9A Pending CN106699664A (en) | 2016-11-30 | 2016-11-30 | Synthetic process of 4-ampyrone product |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110526869A (en) * | 2019-08-29 | 2019-12-03 | 青岛科技大学 | A kind of continuous production system of 4-AA |
| CN110624495A (en) * | 2019-11-04 | 2019-12-31 | 锦益创典(天津)科技有限责任公司 | Nitrosation continuous reaction device and method |
| CN113058529A (en) * | 2021-03-30 | 2021-07-02 | 河北冀衡药业股份有限公司 | Continuous preparation method of 4-nitrosoantipyrine |
| CN113200917A (en) * | 2021-05-21 | 2021-08-03 | 河北冀衡药业股份有限公司 | Purification method of 4-aminoantipyrine |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101357903A (en) * | 2008-09-05 | 2009-02-04 | 山东新华制药股份有限公司 | Novel technique for preparing 4-formyl amino antipyrine |
| CN101891683A (en) * | 2010-07-22 | 2010-11-24 | 河北冀衡（集团）药业有限公司 | Aminopyrine production method |
| CN102584707A (en) * | 2012-01-18 | 2012-07-18 | 河北冀衡（集团）药业有限公司 | Production method of analgin bulk drug |
| CN103613544A (en) * | 2013-12-09 | 2014-03-05 | 山东新华制药股份有限公司 | 4-aminoantipyrene production technology and device thereof |
| CN106632049A (en) * | 2016-11-21 | 2017-05-10 | 江苏仁航药业股份有限公司 | Synthesis process of 4-amino antipyrine product and preparation method of synthesis process of 4-amino antipyrine product and preparation method |
-
2016
- 2016-11-30 CN CN201611083425.9A patent/CN106699664A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101357903A (en) * | 2008-09-05 | 2009-02-04 | 山东新华制药股份有限公司 | Novel technique for preparing 4-formyl amino antipyrine |
| CN101891683A (en) * | 2010-07-22 | 2010-11-24 | 河北冀衡（集团）药业有限公司 | Aminopyrine production method |
| CN102584707A (en) * | 2012-01-18 | 2012-07-18 | 河北冀衡（集团）药业有限公司 | Production method of analgin bulk drug |
| CN103613544A (en) * | 2013-12-09 | 2014-03-05 | 山东新华制药股份有限公司 | 4-aminoantipyrene production technology and device thereof |
| CN106632049A (en) * | 2016-11-21 | 2017-05-10 | 江苏仁航药业股份有限公司 | Synthesis process of 4-amino antipyrine product and preparation method of synthesis process of 4-amino antipyrine product and preparation method |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110526869A (en) * | 2019-08-29 | 2019-12-03 | 青岛科技大学 | A kind of continuous production system of 4-AA |
| CN110526869B (en) * | 2019-08-29 | 2022-06-28 | 青岛科技大学 | Continuous production system of 4-aminoantipyrine |
| CN110624495A (en) * | 2019-11-04 | 2019-12-31 | 锦益创典(天津)科技有限责任公司 | Nitrosation continuous reaction device and method |
| CN113058529A (en) * | 2021-03-30 | 2021-07-02 | 河北冀衡药业股份有限公司 | Continuous preparation method of 4-nitrosoantipyrine |
| CN113200917A (en) * | 2021-05-21 | 2021-08-03 | 河北冀衡药业股份有限公司 | Purification method of 4-aminoantipyrine |
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Application publication date: 20170524 |