CN106632096B - A kind of synthetic method of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline - Google Patents
A kind of synthetic method of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline Download PDFInfo
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- CN106632096B CN106632096B CN201611203253.4A CN201611203253A CN106632096B CN 106632096 B CN106632096 B CN 106632096B CN 201611203253 A CN201611203253 A CN 201611203253A CN 106632096 B CN106632096 B CN 106632096B
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- methyl
- ethyl alcohol
- alcohol base
- base quinoxaline
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- 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
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
Abstract
The present invention provides a kind of synthetic methods of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline, mequindox, phase transfer catalyst and solvents tetrahydrofurane are added into reactor, single reducing agent is slowly added to after being stirred at room temperature, reaction 0.5-5 hours, obtains 3- methyl -2- ethyl alcohol base quinoxaline after post treatment after reaction.Reactions steps of this method is short, it is only necessary to which a step, easy to operate, high-efficient, the yield and purity of product are higher, and reaction condition is mild, are suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of preparation methods of Novel veterinary drug, more particularly, to a kind of antibacterial growth promotion animal specific medicine 3-
The synthetic method of methyl -2- ethyl alcohol base quinoxaline.
Background technique
Olaquindox is a kind of antivirus somatotropic agent, since its excess can remain in animal body, has apparent accumulation poison
Toxic side effects, the olaquindox itself such as property and DNA damage are unstable, can be metabolized in animal body, and its metabolite ---
3- methyl-quinoxaline -2- carboxylic acid is that United Nations Food and Agricultural Organization and World Health Organization food additives expert combine committee
The olaquindox residual marker that member can assert.
Quinoxaline class drug is that one kind of N4- dioxide basic structure is chemically synthesized with quinoxaline-N1 have it is anti-
The animal specific medicine of bacterium and growth promoting function mainly includes China's a kind of novel chiral synthon quinocetone with independent intellectual property rights, second
Acyl first quinoline etc..Currently, quinoxaline class Drug safety problem is the hot spot of food safety concern, the veterinary drug in animal product
Residual can lead to the harm to human health and generate direct obstacle to industry development.When studying the metabolic pathway of this kind of drug
It was found that this kind of drug can react in animal body generates 3- methyl -2- ethyl alcohol base quinoxaline.Therefore research 3- methyl -2- ethyl alcohol
The chemical preparation process of base quinoxaline seems particularly significant.
There are the document report of 3- methyl -2- ethyl alcohol base quinoxaline preparation method, such as Chinese patent in the prior art
201010230172.X, which reports mequindox, to carry out reduction reaction under Hydros and obtains 3- methyl -2- acequinoline, so
3- methyl -2- acequinoline carries out reduction reaction under potassium borohydride effect and obtains the 3- methyl -2- ethyl alcohol base quinoxaline afterwards,
, the party
Method need to carry out two-step reaction, and reaction process is complicated, and the reaction of every step is required to be post-processed, and the yield of simultaneous reactions is low, instead
Answer inefficient.
To solve the above-mentioned problems, it is an object of the invention to provide a kind of synthetic method of 3- methyl -2- ethyl alcohol base quinoxaline,
Reactions steps of this method is short, it is only necessary to and a step, easy to operate, high-efficient, the yield and purity of product are higher, and reaction condition is mild,
It is suitable for industrialized production.
The technical solution adopted by the present invention is that: a kind of synthetic method of 3- methyl -2- ethyl alcohol base quinoxaline, into reactor
Mequindox, phase transfer catalyst and solvents tetrahydrofurane is added, single reducing agent is slowly added to after being stirred at room temperature, reacts 0.5-
5 hours, obtain 3- methyl -2- ethyl alcohol base quinoxaline after post treatment after reaction.
Further, the single reducing agent is Lithium Aluminium Hydride.
Further, the phase transfer catalyst is tetrabutylammonium bromide, tetrabutylammonium chloride, benzyl trimethyl chlorination
The molar ratio of ammonium, phase transfer catalyst and mequindox is 0.1-1:1, preferably 0.2-0.3:1
Further, the molar ratio of the mequindox and Lithium Aluminium Hydride is 1:3-5, the mequindox and solvent
The mass volume ratio of tetrahydrofuran is 1:20 ~ 100g/ml, preferably 1:30-60 g/ml.
Further, the time of the reaction is 2-4 hours.
Further, the last handling process is to after reaction, saturated ammonium chloride is slowly added into reaction solution
Solution quenching reaction stirs 5 minutes, divides and goes water phase, and gained organic phase is washed with water respectively, saturated common salt is washed, anhydrous sodium sulfate
It is filtered after dry organic phase and obtains filtrate, rotary evaporation obtains 3- methyl -2- ethyl alcohol base quinoxaline crude product.Gained crude product is added
It into n-hexane, dissolves by heating, subsequent cooling and standings 3-6 hours, there is white crystal precipitation, filter, be dried to obtain in vacuum tank
Pure 3- methyl -2- ethyl alcohol base quinoxaline.
The utility model has the advantages that
The method provided by the invention for preparing 3- methyl -2- ethyl alcohol base quinoxaline, using completely new technique, using single
Catalyst complex phase transfer catalyst may be implemented efficiently to prepare 3- methyl -2- ethyl alcohol base quinoxaline from one step of mequindox, lead to
The nitrogen oxygen and carbonyl of mequindox, the party can be restored simultaneously by crossing initiative research discovery Lithium Aluminium Hydride and phase transfer catalyst
Method reaction step is short, it is only necessary to a step, easy to operate, enormously simplify cumbersome in the prior art operation and post-processing, reaction effect
Rate is high, and the yield and purity of product are also higher, and yield highest can achieve 84.9%, while the reaction condition is mild, is suitable for industry
Metaplasia produces.
Specific embodiment
The present invention is described in further details with reference to embodiments.
Embodiment 1
It is added in reactor into the three-necked flask equipped with blender and is separately added into 400ml tetrahydrofuran, 0.05mol acetyl
First quinoline (10.9g) and 0.01mol tetrabutylammonium chloride phase transfer catalyst, are slowly added to 0.18mol tetrahydro aluminium after being stirred at room temperature
Lithium reacts 2 hours, to after reaction, be slowly added to 200ml saturated ammonium chloride solution quenching reaction, stirring 5 into reaction solution
Minute, divide and go water phase, gained organic phase is washed with water respectively, saturated common salt is washed, and filters after the dry organic phase of anhydrous sodium sulfate
To filtrate, rotary evaporation obtains 3- methyl -2- ethyl alcohol base quinoxaline crude product.Gained crude product is added to proper amount of n-hexane
In, it is heated to just dissolving, subsequent cooling and standings 3-6 hours, there is white crystal precipitation, filter, be dried to obtain in vacuum tank
7.94g pure 3- methyl -2- ethyl alcohol base quinoxaline, yield 84.5%.
Embodiment 2
It is added in reactor into the three-necked flask equipped with blender and is separately added into 300ml tetrahydrofuran, 0.05mol acetyl
First quinoline (10.9g) and 0.015mol tetrabutylammonium bromide phase transfer catalyst, are slowly added to 0.15mol tetrahydro aluminium after being stirred at room temperature
Lithium reacts 2 hours, to after reaction, be slowly added to 200ml saturated ammonium chloride solution quenching reaction, stirring 5 into reaction solution
Minute, divide and go water phase, gained organic phase is washed with water respectively, saturated common salt is washed, and filters after the dry organic phase of anhydrous sodium sulfate
To filtrate, rotary evaporation obtains 3- methyl -2- ethyl alcohol base quinoxaline crude product.Gained crude product is added to proper amount of n-hexane
In, it is heated to just dissolving, subsequent cooling and standings 3-6 hours, there is white crystal precipitation, filter, be dried to obtain in vacuum tank
7.87g pure 3- methyl -2- ethyl alcohol base quinoxaline, yield 83.7%.
Embodiment 3
It is added in reactor into the three-necked flask equipped with blender and is separately added into 500ml tetrahydrofuran, 0.05mol acetyl
First quinoline (10.9g) and 0.015mol benzyltrimethylammonium chloride phase transfer catalyst, are slowly added to 0.2mol tetra- after being stirred at room temperature
Hydrogen aluminium lithium reacts 3 hours, to after reaction, be slowly added to 200ml saturated ammonium chloride solution quenching reaction into reaction solution,
Stirring 5 minutes divides and goes water phase, and gained organic phase is washed with water respectively, saturated common salt is washed, and takes out after the dry organic phase of anhydrous sodium sulfate
Filter obtains filtrate, and rotary evaporation obtains 3- methyl -2- ethyl alcohol base quinoxaline crude product.By gained crude product be added to it is proper amount of just oneself
It in alkane, is heated to just dissolving, subsequent cooling and standings 3-6 hours, there is white crystal precipitation, filter, be dried to obtain in vacuum tank
7.98g pure 3- methyl -2- ethyl alcohol base quinoxaline, yield 84.9%.
Above-described embodiment is not intended to limit the scope of the present invention.The technical staff of the industry is in this technology side
Under the inspiration of case, some deformations and modification can be made, according to the technical essence of the invention to made by above embodiment
Any modification, equivalent variations and modification, all of which are still within the scope of the technical scheme of the invention.
Claims (8)
1. a kind of synthetic method of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline, it is characterised in that: to anti-
It answers and solvents tetrahydrofurane, mequindox and phase transfer catalyst is added in device, single reducing agent is slowly added to after being stirred at room temperature, instead
It answers 0.5-5 hours, obtains 3- methyl -2- ethyl alcohol base quinoxaline after post treatment after reaction, the single reducing agent is
Lithium Aluminium Hydride, the phase transfer catalyst are tetrabutylammonium bromide, tetrabutylammonium chloride, one in benzyltrimethylammonium chloride
Kind is a variety of.
2. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as described in claim 1
Method, it is characterised in that: the molar ratio of the mequindox and Lithium Aluminium Hydride is 1:3-5.
3. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as described in claim 1
Method, it is characterised in that: the molar ratio of the phase transfer catalyst and mequindox is 0.1-1:1.
4. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as claimed in claim 3
Method, it is characterised in that: the molar ratio of the phase transfer catalyst and mequindox is 0.2-0.3:1.
5. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as described in claim 1
Method, it is characterised in that: the mass volume ratio of the mequindox and solvents tetrahydrofurane is 1:20 ~ 100g/ml.
6. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as claimed in claim 5
Method, it is characterised in that: the mass volume ratio of the mequindox and solvents tetrahydrofurane is 1:30-60 g/ml.
7. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as described in claim 1
Method, it is characterised in that: the time of the reaction is 2-4 hours.
8. a kind of synthesis side of antibacterial growth promotion animal specific medicine 3- methyl -2- ethyl alcohol base quinoxaline as described in claim 1
Method, it is characterised in that: the last handling process is to after reaction, saturated ammonium chloride solution is slowly added into reaction solution
Quenching reaction stirs 5-10 minutes, divides and goes water phase, and gained organic phase is washed with water respectively, saturated common salt is washed, and anhydrous sodium sulfate is dry
It is filtered after dry organic phase and obtains filtrate, rotary evaporation obtains 3- methyl -2- ethyl alcohol base quinoxaline crude product, gained crude product is added to
It in n-hexane, dissolves by heating, subsequent cooling and standings 3-6 hours, there is white crystal precipitation, filter, be dried to obtain 3- in vacuum tank
Methyl -2- ethyl alcohol base quinoxaline.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928252A (en) * | 2010-07-19 | 2010-12-29 | 中国农业大学 | Preparation method of 3-methyl-2-ethanol based quinoxaline |
| CN102070539A (en) * | 2010-12-31 | 2011-05-25 | 广州自远生物科技有限公司 | 1-oxo-2-methyl-3-(1-ethoxyl)-quinoxaline and preparation method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2282999B1 (en) * | 2008-03-04 | 2014-05-21 | Merck Sharp & Dohme Corp. | Amino-quinoxaline and amino-quinoline compounds for use as adenosine a2a receptor antagonists |
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- 2016-12-23 CN CN201611203253.4A patent/CN106632096B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928252A (en) * | 2010-07-19 | 2010-12-29 | 中国农业大学 | Preparation method of 3-methyl-2-ethanol based quinoxaline |
| CN102070539A (en) * | 2010-12-31 | 2011-05-25 | 广州自远生物科技有限公司 | 1-oxo-2-methyl-3-(1-ethoxyl)-quinoxaline and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| DERIVATIVES OF 5, 6, 11, 12-TETRAHYDRO DIBENZO [C, G][1, 2] DIAZOCINE;Charles Gansser;《European Journal of Medicinal Chemistry》;19751231;第10卷(第3期);第273-275页 * |
| Simultaneous determination of four synthesized metabolites of mequindox in urine samples using ultrasound-assisted dispersive liquid–liquid microextraction combined with high-performance liquid chromatography;Jiaheng Zhang et al.,;《Talanta》;20111118;第88卷;第330-337页 * |
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Effective date of registration: 20210716 Address after: 312000 room 506, 5 / F, building C, science and technology entrepreneurship center, No. 398, mahuan Road, Lihai Town, Binhai New Town, Shaoxing City, Zhejiang Province Patentee after: Zhejiang Hongsheng Biotechnology Co.,Ltd. Address before: 310018 Building 2, No. 452, No. 6 street, Baiyang street, Hangzhou Economic and Technological Development Zone, Zhejiang Province Patentee before: HANGZHOU HONGSHENG BIOTECHNOLOGY Co.,Ltd. Patentee before: Zhejiang University of Technology |
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