CN102408384A - Improved synthesis method of quinocetone - Google Patents
Improved synthesis method of quinocetone Download PDFInfo
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- CN102408384A CN102408384A CN2011103278829A CN201110327882A CN102408384A CN 102408384 A CN102408384 A CN 102408384A CN 2011103278829 A CN2011103278829 A CN 2011103278829A CN 201110327882 A CN201110327882 A CN 201110327882A CN 102408384 A CN102408384 A CN 102408384A
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- quinocetone
- mequindox
- thanomin
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- phenyl aldehyde
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Abstract
The invention belongs to the technical field of veterinary medicine preparation, and particularly relates to an improved synthesis method of quinocetone. The method comprises the following steps of: (1) taking mequindox as a start raw material, adding mequindox and a proper amount of methanol into a round-bottomed flask and stirring uniformly; (2) adding benzaldehyde into the solution obtained by the step (1), then adding ethanolamine, reacting at 38-45 DEG C for 8-48 h, stopping the heating, cooling, and performing suction filtration to obtain a crude product of quinocetone; and (3) washing the crude product of quinocetone with methanol, and drying, wherein the obtained solid is a finished product of quinocetone; and the molar ratio of mequindox to benzaldehyde to ethanolamine is (2-6):6:(0.5-2.5). The method, provided by the invention, for preparing quinocetone has the advantages of low cost, high yield and high product purity and solves the problems existing in traditional quinocetone synthesis process.
Description
Technical field
The invention belongs to technical field of animal remedy preparation, be specifically related to a kind of improved Quinocetone compound method.
Background technology
Quinocetone, chemical name is: 3-methyl-2-phenylethylene keto-quinoxaline-1, the 4-dioxide, molecular formula is: C
8H
14N
2O
3, molecular weight is: 306.5, and structural formula is:
Quinocetone (Quinocetone) is the feed medicated premix as quinoxaline class upgrading, has has a broad antifungal spectrum, has no side effect, does not accumulate, noresidue, nothing three cause, and be safe in utilization efficient, and anti-microbial effect is strong, promote advantages such as the growth of animals or poultry effect is obvious.Through serial safety evaluation, feeding experiment and the compliance test result in 20 years, be widely used in the animal husbandry and aquaculture production.Quinocetone can promote animal bodies such as livestock and poultry, fish to grow, and promotes the protein assimilation, improves lean ratio and feed conversion rate, suppresses unwanted bacteria, and the protection profitable strain is a kind of new feed medicated premix that widespread use is worth that has.Absorb seldom in the body of the oral back of Quinocetone and metabolism very fast, most ofly discharge with original shape from digestive tube, bioavailability is lower.
Up to the present, mainly contain the method for following two kinds of synthetic Quinocetones:
First kind is, with benzo-2,1,3-oxadiazoles-1-oxide compound is a starting raw material, synthetic with benzene fork methyl ethyl diketone single step reaction.This synthetic route is brief, but reaction mixture needs the long time to carry out aging crystallization, and main reaction benzene feedstock fork methyl ethyl diketone does not have the off-the-shelf supply, and used propyl carbinol sodium catalyst costs an arm and a leg, character unstable, has corrodibility and toxicity.Therefore, this method only is suitable for prepared in laboratory, can not be converted into actual large-scale industrial production, and productive rate is about 85%.This compound method reaction formula is suc as formula shown in (1):
Second kind is, also is to be starting raw material with the benzo furazan, and respectively with 2, two-step reaction is synthetic altogether for 4-diacetylmethane (the first step) and phenyl aldehyde (second step).The used raw material of this synthetic route is easy to get, and can carry out large-scale industrial production, but used catalyzer is a sodium methylate; Inflammable, have corrodibility and toxicity, and price is higher; Sepn process difficulty after reaction finishes, the operability on historical facts or anecdotes border is not strong.In addition, reaction yield is lower, and about about 70%.This compound method reaction formula is suc as formula shown in (2):
Summary of the invention
The objective of the invention is to provides the compound method of the Quinocetone that a kind of cost is low, productive rate is high, purity is high to the above-mentioned defective that exists in the prior art.
The inventive method comprises the step of following order:
(1) with the mequindox is starting raw material, mequindox and amount of methanol are joined in the round-bottomed flask, stir;
(2) phenyl aldehyde is added in the solution of step (1) gained, add thanomin again, stop heating after 8～48 hours in reaction under 38～45 ℃, cooling, suction filtration obtains Quinocetone and gives bullion;
(3) Quinocetone is given bullion and use methanol wash, drying, the solid that obtains is the Quinocetone highly finished product;
Wherein, the mol ratio of said mequindox, phenyl aldehyde, thanomin is 2～6: 6: 0.5～2.5.
Reaction formula of the present invention is suc as formula shown in (3):
As further preferred version be: in the step (2), temperature of reaction is 40 ℃, and the reaction times is 24 hours; The mass ratio of said mequindox, phenyl aldehyde, thanomin is 4: 6: 1.
The present invention compares with the compound method of existing Quinocetone, is raw material with mequindox and phenyl aldehyde, makes solvent with methyl alcohol; Adopt thanomin as catalyzer; Condensation reaction takes place generate Quinocetone, not only productive rate is high, and degree of purity of production is better; Catalyzer also compares safety, cheapness, is convenient to separate better economy.Therefore, adopt the inventive method to prepare Quinocetone, cost is low, productive rate is high, purity is high, has solved the problem that exists in the present Quinocetone building-up process.
Embodiment
Below in conjunction with concrete experiment embodiment the present invention is described in further detail.
Embodiment 1:
A. get 8.72g (20mmol) mequindox and 30mL methyl alcohol, join in the exsiccant 100mL round-bottomed flask, stir.
B. 6.36g (30mmol) phenyl aldehyde, 2.18g (2.5mmol) thanomin are added in the above-mentioned solution, under agitation behind 40 ℃ of reactions of temperature 24h, stop heating, cooling, suction filtration gets the Quinocetone bullion.
C. use methyl alcohol (5mL) washing, drying, the solid that obtains is the Quinocetone highly finished product, and productive rate is 90%.
Embodiment 2:
A. get 13.08g (30mmol) mequindox and 30mL methyl alcohol, join in the exsiccant 100mL round-bottomed flask, stir.
B. 6.36g (30mmol) phenyl aldehyde, 1.74g (2.0mmol) thanomin are added in the above-mentioned solution, under agitation behind 45 ℃ of reactions of temperature 24h, stop heating, cooling, suction filtration gets the Quinocetone bullion.
C. use methyl alcohol (5mL) washing, drying, the solid that obtains is the Quinocetone highly finished product, and productive rate is 85%.
Embodiment 3:
A. get 6.54g (15mmol) mequindox and 30mL methyl alcohol, join in the exsiccant 100mL round-bottomed flask, stir.
B. 6.36g (30mmol) phenyl aldehyde, 3.92g (6.0mmol) thanomin are added in the above-mentioned solution, under agitation behind 38 ℃ of reactions of temperature 24h, stop heating, cooling, suction filtration gets the Quinocetone bullion.
C. use methyl alcohol (5mL) washing, drying, the solid that obtains is the Quinocetone highly finished product, and productive rate is 86%.
Claims (2)
1. improved Quinocetone compound method is characterized in that comprising the step of following order:
(1) with the mequindox is starting raw material, mequindox and amount of methanol are joined in the round-bottomed flask, stir;
(2) phenyl aldehyde is added in the solution of step (1) gained, add thanomin again, stop heating after 8～48 hours in reaction under 38～45 ℃, cooling, suction filtration obtains Quinocetone and gives bullion;
(3) Quinocetone is given bullion and use methanol wash, drying, the solid that obtains is the Quinocetone highly finished product;
Wherein, the mol ratio of said mequindox, phenyl aldehyde, thanomin is 2～6: 6: 0.5～2.5.
2. according to the said improved Quinocetone compound method of claim 1, it is characterized in that: in the step (2), temperature of reaction is 40 ℃, and the reaction times is 24 hours; The mass ratio of said mequindox, phenyl aldehyde, thanomin is 4: 6: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110327882.9A CN102408384B (en) | 2011-10-25 | 2011-10-25 | Improved synthesis method of quinocetone |
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| CN201110327882.9A CN102408384B (en) | 2011-10-25 | 2011-10-25 | Improved synthesis method of quinocetone |
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| CN102408384A true CN102408384A (en) | 2012-04-11 |
| CN102408384B CN102408384B (en) | 2014-03-05 |
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| CN201110327882.9A Expired - Fee Related CN102408384B (en) | 2011-10-25 | 2011-10-25 | Improved synthesis method of quinocetone |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104672155A (en) * | 2013-12-03 | 2015-06-03 | 中牧实业股份有限公司黄冈动物药品厂 | Synthetic method of improved quinocetone |
| CN104788392A (en) * | 2015-04-13 | 2015-07-22 | 浙江汇能动物药品有限公司 | Synthetic method for high-purity and high-yield quinocetone |
| CN105566234A (en) * | 2015-12-24 | 2016-05-11 | 南阳市天华制药有限公司 | Quinocetone preparation method |
| CN110003124A (en) * | 2019-03-22 | 2019-07-12 | 苏州华道生物药业股份有限公司 | A kind of synthetic method of quinocetone |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4373101A (en) * | 1980-06-03 | 1983-02-08 | Egyt Gyogyszervegyeszeti Gyar | Quinoxaline-2-yl ethenyl ketones |
| CN1197068A (en) * | 1997-04-21 | 1998-10-28 | 中国农业科学院中兽医研究所 | Compound and synthetic process of 3-methyl-2-phenylethylene keto-quinooxaline-1.4-dioxide |
| CN1785979A (en) * | 2004-12-07 | 2006-06-14 | 中国农业科学院兰州畜牧与兽药研究所 | Preparation method of 3-methyl-2-cinoamoyl-quinoxaline-1,4-dioxide |
| CN101402612A (en) * | 2008-11-14 | 2009-04-08 | 刘占领 | Synthesis of quinocetone |
-
2011
- 2011-10-25 CN CN201110327882.9A patent/CN102408384B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4373101A (en) * | 1980-06-03 | 1983-02-08 | Egyt Gyogyszervegyeszeti Gyar | Quinoxaline-2-yl ethenyl ketones |
| CN1197068A (en) * | 1997-04-21 | 1998-10-28 | 中国农业科学院中兽医研究所 | Compound and synthetic process of 3-methyl-2-phenylethylene keto-quinooxaline-1.4-dioxide |
| CN1785979A (en) * | 2004-12-07 | 2006-06-14 | 中国农业科学院兰州畜牧与兽药研究所 | Preparation method of 3-methyl-2-cinoamoyl-quinoxaline-1,4-dioxide |
| CN101402612A (en) * | 2008-11-14 | 2009-04-08 | 刘占领 | Synthesis of quinocetone |
Non-Patent Citations (1)
| Title |
|---|
| 赵晓丽等: "喹烯酮合成方法的研究", 《兽药与饲料添加剂》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104672155A (en) * | 2013-12-03 | 2015-06-03 | 中牧实业股份有限公司黄冈动物药品厂 | Synthetic method of improved quinocetone |
| CN104672155B (en) * | 2013-12-03 | 2017-11-07 | 中牧实业股份有限公司黄冈动物药品厂 | A kind of synthetic method for improving quinocetone |
| CN104788392A (en) * | 2015-04-13 | 2015-07-22 | 浙江汇能动物药品有限公司 | Synthetic method for high-purity and high-yield quinocetone |
| CN105566234A (en) * | 2015-12-24 | 2016-05-11 | 南阳市天华制药有限公司 | Quinocetone preparation method |
| CN110003124A (en) * | 2019-03-22 | 2019-07-12 | 苏州华道生物药业股份有限公司 | A kind of synthetic method of quinocetone |
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| CN102408384B (en) | 2014-03-05 |
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