CN110317178A - A kind of mequindox novel method for synthesizing - Google Patents
A kind of mequindox novel method for synthesizing Download PDFInfo
- Publication number
- CN110317178A CN110317178A CN201910661417.5A CN201910661417A CN110317178A CN 110317178 A CN110317178 A CN 110317178A CN 201910661417 A CN201910661417 A CN 201910661417A CN 110317178 A CN110317178 A CN 110317178A
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- CN
- China
- Prior art keywords
- potassium acetate
- mequindox
- novel method
- organic solvent
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- CUJMCPPBTUATEJ-UHFFFAOYSA-N 1-(3-methyl-4-oxido-1-oxoquinoxalin-1-ium-2-yl)ethanone Chemical compound C1=CC=C2[N+](=O)C(C(=O)C)=C(C)N([O-])C2=C1 CUJMCPPBTUATEJ-UHFFFAOYSA-N 0.000 title claims description 20
- 238000000034 method Methods 0.000 title claims description 17
- 230000002194 synthesizing effect Effects 0.000 title claims description 13
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 44
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 28
- 235000011056 potassium acetate Nutrition 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000003960 organic solvent Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000005605 benzo group Chemical group 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000012065 filter cake Substances 0.000 claims description 5
- 238000009413 insulation Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- -1 benzo oxygen Chemical compound 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 238000007259 addition reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
- C07D241/52—Oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of mequindox novel method for synthesizing, include the following steps: that (1) weighs the amyl- N- oxide of benzo oxa- phenodiazine, organic solvent is put into reaction kettle, start to stir, it is heated to 55 DEG C, (2) acetylacetone,2,4-pentanedione is weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C, (3) weighed potassium acetate is added several times, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours, it is cooled to 20 ~ 25 degrees Celsius, it is separated with centrifuge, filter cake is cleaned with organic solvent, obtains mequindox crude product after dry.The beneficial effects of the present invention are: using potassium acetate as catalyst, since potassium acetate dissolves fastly in methanol or ethyl alcohol, improve catalytic efficiency, the alkalinity of potassium acetate is weaker than soda ash, react easily controllable, experimental data shows that selecting potassium acetate to do catalyst prod yield improves 13%, and the reaction time foreshortens to 2 ~ 3 hours.
Description
Technical field
The present invention relates to organic chemical synthesis field more particularly to a kind of mequindox novel method for synthesizing.
Background technique
Soda ash or anhydrous sodium acetate, and soda ash and anhydrous sodium acetate all indissolubles are used in existing mequindox synthesis process
In ethyl alcohol and methanol, reaction speed is slower, and activity is too strong after soda ash dissolution, it is difficult to control, be also easy to produce side reaction, to acetyl
The rate of recovery of first quinoline influences very big, it is therefore desirable to which new catalyst replaces soda ash or anhydrous sodium acetate.
Summary of the invention
It is an object of the invention to overcome problem above of the existing technology, a kind of novel synthesis side of mequindox is provided
Method makees catalyst using potassium acetate, improves catalytic efficiency.
To realize above-mentioned technical purpose and the technique effect, the invention is realized by the following technical scheme:
A kind of mequindox novel method for synthesizing, includes the following steps:
(1) weigh the amyl- N- oxide of benzo oxa- phenodiazine, organic solvent investment reaction kettle in, start to stir, be heated to 55 DEG C,
(2) acetylacetone,2,4-pentanedione is weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C,
(3) weighed potassium acetate is added several times, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours, be cooled to 20 ~ 25 degrees Celsius, with from
Scheming separation, filter cake are cleaned with organic solvent, obtain mequindox crude product after dry.
Further, the organic solvent is methanol or ethyl alcohol.
Further, the acetylacetone,2,4-pentanedione: the amyl- N- oxide of benzo oxa- phenodiazine: organic solvent: potassium acetate=11.5:
16.5:15:5.5。
Further, the potassium acetate is divided into five addition reaction kettles, and each additional amount is identical.
Further, the potassium acetate is potassium acetate powder.
Further, dry to be pressed dry using centrifuge drying or filter press.
The beneficial effects of the present invention are: using potassium acetate as catalyst, since potassium acetate dissolves in methanol or ethyl alcohol
Fastly, catalytic efficiency is improved, the alkalinity of potassium acetate is weaker than soda ash, reacts easily controllable, and experimental data shows that potassium acetate is selected to do
Catalyst prod yield improves 13%, and the reaction time foreshortens to 2 ~ 3 hours.
Specific embodiment
Below in conjunction with embodiment, next the present invention will be described in detail.
A kind of mequindox novel method for synthesizing, includes the following steps:
(1) weigh the amyl- N- oxide of benzo oxa- phenodiazine, organic solvent investment reaction kettle in, start to stir, be heated to 55 DEG C,
(2) acetylacetone,2,4-pentanedione is weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C,
(3) weighed potassium acetate is added several times, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours, be cooled to 20 ~ 25 degrees Celsius, with from
Scheming separation, filter cake are cleaned with organic solvent, obtain mequindox crude product after dry.
Preferably, organic solvent is methanol or ethyl alcohol.
Preferably, acetylacetone,2,4-pentanedione: the amyl- N- oxide of benzo oxa- phenodiazine: organic solvent: potassium acetate=11.5:16.5:
15:5.5。
Preferably, potassium acetate is divided into five addition reaction kettles, each additional amount is identical.
Preferably, potassium acetate is potassium acetate powder.
Preferably, dry pressed dry using centrifuge drying or filter press.
Embodiment one: a kind of mequindox novel method for synthesizing includes the following steps:
(1) it weighs the amyl- N- oxide of 1650 grams of benzo oxa- phenodiazines, in 1500 grams of ethyl alcohol investment reaction kettles, starts to stir, heat
To 55 DEG C,
(2) 1150 grams of acetylacetone,2,4-pentanediones are weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C,
(3) divide 5 times and weighed 55 grams of potassium acetates be added, 11 grams of potassium acetates are once added, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours,
20 ~ 25 degrees Celsius are cooled to, is separated with centrifuge, filter cake is cleaned with organic solvent, with obtaining after centrifuge centrifugal drying
Mequindox crude product.
A kind of embodiment two, mequindox novel method for synthesizing, includes the following steps:
(1) it weighs the amyl- N- oxide of 1650 grams of benzo oxa- phenodiazines, in 1500 grams of methanol investment reaction kettles, starts to stir, heat
To 55 DEG C,
(2) 1150 grams of acetylacetone,2,4-pentanediones are weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C,
(3) divide 5 times and weighed 55 grams of potassium acetates be added, 11 grams of potassium acetates are once added, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours,
20 ~ 25 degrees Celsius are cooled to, is separated with centrifuge, filter cake is cleaned with organic solvent, with obtaining after filter press pressure-filteration drying
Mequindox crude product.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.
Claims (6)
1. a kind of mequindox novel method for synthesizing, which comprises the steps of:
(1) weigh the amyl- N- oxide of benzo oxa- phenodiazine, organic solvent investment reaction kettle in, start to stir, be heated to 55 DEG C,
(2) acetylacetone,2,4-pentanedione is weighed to be added in reaction kettle, temperature control keeps the temperature 2 hours at 55 ~ 62 DEG C,
(3) weighed potassium acetate is added several times, 60 ~ 65 DEG C insulation reaction 2 ~ 3 hours, be cooled to 20 ~ 25 degrees Celsius, with from
Scheming separation, filter cake are cleaned with organic solvent, obtain mequindox crude product after dry.
2. mequindox novel method for synthesizing according to claim 1, it is characterised in that: the organic solvent be methanol or
Ethyl alcohol.
3. mequindox novel method for synthesizing according to claim 1, it is characterised in that: the acetylacetone,2,4-pentanedione: benzo oxygen
The miscellaneous amyl- N- oxide of phenodiazine: organic solvent: potassium acetate=11.5:16.5:15:5.5.
4. mequindox novel method for synthesizing according to claim 1, it is characterised in that: the potassium acetate is divided into five times and adds
Enter in reaction kettle, each additional amount is identical.
5. mequindox novel method for synthesizing according to claim 1, it is characterised in that: the potassium acetate is potassium acetate powder
End.
6. mequindox novel method for synthesizing according to claim 1, it is characterised in that: it is dry using centrifuge drying or
Filter press press dry.
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|---|---|---|---|
| CN201910661417.5A CN110317178A (en) | 2019-07-22 | 2019-07-22 | A kind of mequindox novel method for synthesizing |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910661417.5A CN110317178A (en) | 2019-07-22 | 2019-07-22 | A kind of mequindox novel method for synthesizing |
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| Publication Number | Publication Date |
|---|---|
| CN110317178A true CN110317178A (en) | 2019-10-11 |
Family
ID=68124248
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|---|---|---|---|
| CN201910661417.5A Pending CN110317178A (en) | 2019-07-22 | 2019-07-22 | A kind of mequindox novel method for synthesizing |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5789427A (en) * | 1994-03-07 | 1998-08-04 | Sugen, Inc. | Methods and compositions for inhibiting cell proliferative disorders |
| CN102329272A (en) * | 2011-11-01 | 2012-01-25 | 荆州市新元生物科技有限公司 | Method for preparing quinocetone |
| CN102442956A (en) * | 2011-11-21 | 2012-05-09 | 衢州伟荣药化有限公司 | Synthetic method of mequindox |
| CN102796051A (en) * | 2012-09-11 | 2012-11-28 | 湖北中牧安达药业有限公司 | Preparation method of mequindox |
| CN103787994A (en) * | 2013-12-13 | 2014-05-14 | 河北美荷药业有限公司 | 3-methyl-(P-sodium benzenesulfonate)-2-allyl quinoxaline di-nitrogen oxide and preparation method and application thereof |
| CN107793372A (en) * | 2017-06-22 | 2018-03-13 | 北京立时达药业有限公司 | A kind of synthetic method of mequindox |
| CN109251178A (en) * | 2018-11-23 | 2019-01-22 | 河北美荷药业有限公司 | A kind of preparation method of mequindox |
-
2019
- 2019-07-22 CN CN201910661417.5A patent/CN110317178A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5789427A (en) * | 1994-03-07 | 1998-08-04 | Sugen, Inc. | Methods and compositions for inhibiting cell proliferative disorders |
| CN102329272A (en) * | 2011-11-01 | 2012-01-25 | 荆州市新元生物科技有限公司 | Method for preparing quinocetone |
| CN102442956A (en) * | 2011-11-21 | 2012-05-09 | 衢州伟荣药化有限公司 | Synthetic method of mequindox |
| CN102796051A (en) * | 2012-09-11 | 2012-11-28 | 湖北中牧安达药业有限公司 | Preparation method of mequindox |
| CN103787994A (en) * | 2013-12-13 | 2014-05-14 | 河北美荷药业有限公司 | 3-methyl-(P-sodium benzenesulfonate)-2-allyl quinoxaline di-nitrogen oxide and preparation method and application thereof |
| CN107793372A (en) * | 2017-06-22 | 2018-03-13 | 北京立时达药业有限公司 | A kind of synthetic method of mequindox |
| CN109251178A (en) * | 2018-11-23 | 2019-01-22 | 河北美荷药业有限公司 | A kind of preparation method of mequindox |
Non-Patent Citations (7)
| Title |
|---|
| COSTAS H. ISSIDORIDES,ET AL.: "Benzofurazan Oxide. II. Reactions with Enolate Anions", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| ZHANG, JH，ET AL.: "Synthesis, mass spectral characterization, NMR analyses, and DFT calculations of 1-desoxymaquindox and 4-desoxymaquindox", 《JOURNAL OF MOLECULAR STRUCTURE》 * |
| 北京化工厂: "《化学试剂生产技术资料》", 31 December 1959, 化学工业出版社 * |
| 唐树和等: "喹烯酮合成工艺的改进", 《化学通报》 * |
| 林树坤等: "十一种2，3-二取代喹喔啉-1，4-二氧化物抗菌剂的合成与谱学研究", 《应用化学》 * |
| 林树坤等: "取代喹喔啉-1，4-二氧化物合成方法的改进", 《有机化学》 * |
| 赵荣材等: "MAQO和MCEQO抑菌活性及其毒性的初步观察", 《中兽医医药杂志》 * |
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Application publication date: 20191011 |
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