CN101007786B - 2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method - Google Patents
2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method Download PDFInfo
- Publication number
- CN101007786B CN101007786B CN2007100513708A CN200710051370A CN101007786B CN 101007786 B CN101007786 B CN 101007786B CN 2007100513708 A CN2007100513708 A CN 2007100513708A CN 200710051370 A CN200710051370 A CN 200710051370A CN 101007786 B CN101007786 B CN 101007786B
- Authority
- CN
- China
- Prior art keywords
- methyl
- quinoxaline
- phenyl
- ethanoyl
- reaction
- 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.)
- Expired - Fee Related
Links
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to field of chemical preparation, which in detail relates to a chemical method for preparing metabolite of quinoxaline 2 [(3- phenyl) ally acetone] - 3- methyl quinoxaline. The method comprises following steps: producing 1, 4- dioxide- 3- methyl- 2- acetyl quinoxaline by reacting with acetylacetone under catalyzing action of organic alkali and by taking benzofuran as raw material, getting 3- methyl- 2- acetyl quinoxaline through reducing reaction by using natrium hyposulfidum, and obtaining final product through condensation reaction with benzaldehyde. The invention is characterized in that it takes normal solution as reaction medium, the reaction condition is temperate, the product purity is high, and it not only provides metabolite standard product for ketenes residual, but also provides method for the synthesis of metabolite of the same kind.
Description
Technical field
The invention belongs to chemical technology field, be specifically related to quinoxaline compound Quinocetone meta-bolites 2-[(3-phenyl in animal body) acrylketone]-synthetic method of 3-methyl-quinoxaline.
Background technology
Quinoxaline-N, N-dioxy compounds is the animal specific medicine with broad-spectrum antimicrobial and promotes growth double effects, is widely used in aquaculture, represents kind that carbadox and olaquindox are arranged.In recent years, big quantity research has confirmed that carbadox has extremely strong cytogenetic toxicity, has been under an embargo as fodder additives; Then because of having serious cumulative toxicity, poultry is particularly responsive to it for olaquindox, and China has forbidden that it is applied to poultry.
Quinocetone belongs to the quinoxaline new variety, and chemical structure and olaquindox, carbadox are similar.Be the new veterinary drug of a class that China has independent intellectual property right, livestock and poultry are had tangible promotes growth and anti-microbial effect.When in animal body pathways metabolism of research Quinocetone, find that Quinocetone generates the 2-[(3-phenyl by reduction reaction) acrylketone]-the 3-methyl-quinoxaline.In order further to confirm metabolite 2-[(3-phenyl) acrylketone]-generation of 3-methyl-quinoxaline, and study its toxic side effect, this patent adopts chemical synthesis process to prepare the 2-[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline.The chemosynthesis of this material simultaneously not only can provide standard substance for residual, the metabolism research of Quinocetone, and provides reference for synthetic with metabolite.
At present also do not have Quinocetone to take off the patent of titanium dioxide compound synthetic method both at home and abroad, bibliographical information also seldom.The synthetic route of having reported is as follows: be raw material with the Quinocetone; Trichloromethane, water and tetrahydrofuran (THF) mixing solutions are solvent; Vat powder (Na
2S
2O
4) be that (Zhang Lifang etc., the synthetic of dioxy Quinocetone, chemistry world, 2006 (5): 269-270) are taken off in the tlc monitoring to reductive agent by the reduction reaction preparation.
The advantage of this method is that the productive rate of gained target product is higher.But, be that the raw material cost is higher with the Quinocetone because the used tetrahydrofuran (THF) of its reaction is a highly toxic substance; To add Sodium Hydrosulphite (Na repeatedly in the reaction process
2S
2O
4), complex operation.These all make it be restricted in concrete synthesizing.
Summary of the invention
The object of the present invention is to provide a kind of suitable 2-[(3-phenyl) acrylketone]-synthetic method of 3-methyl-quinoxaline, thus Quinocetone metabolite standard substance are provided.
The present invention is achieved through the following technical solutions:
The method of a kind of Synthetic 2-[(3-phenyl) acrylketone]-3-methyl-quinoxaline is characterized in that comprising the steps:
1) in reactor, (for example adopt the 500ml four-hole bottle) and add benzo furazan, Virahol, methyl ethyl diketone successively, (their molecular volume ratio is respectively and is 1mol: 1000ml: 1mol: 1mol Tri N-Propyl Amine.), (preferably, the reaction times is that 4～8h) back distillations remove solvent to back flow reaction 2～10h, and the gained solid is 1 with methyl alcohol or ethyl alcohol recrystallization, gained yellow crystals, 4-dioxy-3-methyl-2-ethanoyl quinoxaline (C
11H
10N
2O
3).；
2) with step 1) products therefrom 1,4-dioxy-3-methyl-2-ethanoyl quinoxaline and concentration are that the ethanol 100～300ml of 40～100% (preferably, concentration is 60～95%) joins in the reactor, add Na after the stirring and dissolving
2S
2O
4Wherein 1; 4-dioxy-3-methyl-2-ethanoyl quinoxaline is 0.01: 250～0.05: 250 (being preferably 0.05: 250) with ethanol molecular volume ratio; (preferably, the reflection time is 4～8h) and cools off back adding distilled water back flow reaction 2～10h, with trichloromethane or ethyl acetate 600ml extraction; merge organic phase; with anhydrous magnesium sulfate drying, filtration, precipitation, gained resistates low-carbon alcohol recrystallization, getting faint yellow needle-like crystal is 3-methyl-2-ethanoyl quinoxaline (C
11H
10N
2O);
3) with step 2) products therefrom 3-methyl-2-ethanoyl quinoxaline, phenyl aldehyde, 2N sodium hydroxide (3-methyl-2-ethanoyl quinoxaline; the mass volume ratio of phenyl aldehyde and 2N sodium hydroxide is 4.7g: 2.7g: 10ml) join in the reactor successively; stirring reaction 1～9h (reaction times 2～7h) after-filtration preferably, light yellow crystal is the 2[(3-phenyl) acrylketone]-3-methyl-quinoxaline (C
18H
14N
2O).
Synthetic route of the present invention is as follows:
Technological line of the present invention has the following advantages
1. raw material is easy to get: raw material used in the present invention and reagent benzo furazan, Virahol, methyl ethyl diketone, Tri N-Propyl Amine, dehydrated alcohol, trichloromethane, anhydrous magnesium sulfate etc. all are raw material commonly used and reagent, obtain easily.
2. conversion unit, operational condition etc. realize easily: the present invention only adopts thermostat water bath, the decompress filter device, and simple devices such as prolong, the equipment used cost is low, and is simple to operate.
3. environmental pollution is little: agents useful for same trichloromethane of the present invention can be recycled repeatedly, and all the other reagent are promptly environment friendly and pollution-free after handling a little.
4. acrylketone gained target product 2[(3-phenyl)]-the purity height of 3-methyl-quinoxaline, impurity is few.
Description of drawings
Fig. 1 is the 2[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline
1H-NMR figure
Fig. 2 is the 2-[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline
13C-NMR figure
Fig. 3 is the 2-[(3-phenyl) acrylketone]-IR (KBr) of 3-methyl-quinoxaline figure
Fig. 4 is the 2-[(3-phenyl) acrylketone]-ESI-MS of 3-methyl-quinoxaline figure
Embodiment
Embodiment 1
1) in the 500ml four-hole bottle, adds benzo furazan 0.1mol, Virahol 100mL, methyl ethyl diketone 11g; Tri N-Propyl Amine 0.1mol, back flow reaction 4h, 1atm distills precipitation, gained solid ethyl alcohol recrystallization; get yellow crystals 1,4-dioxy, 3-methyl-2-ethanoyl quinoxaline (C
11H
10N
2O
3) 15g.
2) in the 500ml four-hole bottle, add 1, the 4-dioxy, 3-methyl-2-ethanoyl quinoxaline 11g, 60% ethanol 250mL stirs 1.0h, adds Na in batches
2S
2O
40.50mol, back flow reaction 4h postcooling.After the cooling, add 25 ℃ of distilled water, divide three extractions, merge organic phase with trichloromethane 600mL.Organic phase is dry down at 25 ℃ with anhydrous magnesium sulfate.Filter precipitation.Resistates carries out recrystallization with ethanol, gets faint yellow needle-like crystal 5g, i.e. 3-methyl-2-ethanoyl quinoxaline (C
11H
10N
2O), melting range 72-74 ℃.
3) in the 500ml four-hole bottle, add 3-methyl-2-ethanoyl quinoxaline 4.7g, phenyl aldehyde 2.7g, 2N sodium hydroxide 10mL, stirring reaction 2h.Filter, get faint yellow solid 5g, i.e. 2-[(3-phenyl) acrylketone]-3-methyl-quinoxaline (C
18H
14N
2O), melting range is 147～148 ℃.
Embodiment 2
1) according to the method back flow reaction 8h of embodiment 1 step 1), recrystallizing methanol.All the other are with embodiment 1 step 1).Obtain 1,4-dioxy, 3-methyl-2-ethanoyl quinoxaline 13g.
2) according to embodiment 1 step 2) method do reaction solvent with dehydrated alcohol 250mL, add 1,4-dioxy, 3-methyl-2-ethanoyl quinoxaline 2g, heating reflux reaction 8h.All the other are with embodiment 1 step 2).Obtain 3-methyl-2-ethanoyl quinoxaline 4.5g, 72.3～74.2 ℃ of melting ranges.。
3) the method stirring reaction 7h according to embodiment 1 step 3) obtains the 2-[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline.All the other are with embodiment 1 step 3).Obtain the 2-[(3-phenyl) acrylketone]-3-methyl-quinoxaline 4.7g, 147.2～148.3 ℃ of melting ranges.
1) according to the method back flow reaction 2h of embodiment 1 step 1).All the other are with embodiment 1 step 1).Obtain 1,4-dioxy, 3-methyl-2-ethanoyl quinoxaline 13g.
2) according to embodiment 1 step 2) method do reaction solvent with dehydrated alcohol 300mL, heating reflux reaction 8h.All the other are with embodiment 1 step 2).Obtain 3-methyl-2-ethanoyl quinoxaline 4.5g, 71.80～73.8 ℃ of melting ranges.。
3) the method stirring reaction 1h according to embodiment 1 step 3) obtains the 2-[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline.All the other are with embodiment 1 step 3).Obtain the 2-[(3-phenyl) acrylketone]-3-methyl-quinoxaline 4.7g, 146.5～147.8 ℃ of melting ranges.
Embodiment 4
1) according to embodiment 1 step 1) method back flow reaction 10h.All the other are with embodiment 1 step 1).Obtain 1,4-dioxy, 3-methyl-2-ethanoyl quinoxaline 13g.
2) according to embodiment 1 step 2) method does reaction solvent with dehydrated alcohol 100mL, heating reflux reaction 8h.All the other are with embodiment 1 step 2).Obtain 3-methyl-2-ethanoyl quinoxaline 4.5g, 72.6～74.3 ℃ of melting ranges.。
3) obtain the 2-[(3-phenyl according to embodiment 1 step 3) method stirring reaction 9h) acrylketone]-the 3-methyl-quinoxaline.
All the other are with embodiment 1 step 3).Obtain the 2-[(3-phenyl) acrylketone]-3-methyl-quinoxaline 4.7g, 147～148.2 ℃ of melting ranges.
The product of the present invention preparation is as follows through ultraviolet, infrared, nucleus magnetic resonance, mass spectrum and ultimate analysis detected result:
1The H-NMR collection of illustrative plates: 2.98ppm among the figure (unimodal) is-CH
3 1The H displacement; 7.00-8.20ppm be
Group
1The H displacement, wherein 7.80,7.85 and 7.99,8.04ppm may be for-CH=CH-'s
1The H displacement.(annotate: internal standard substance matter tetramethylsilane
1The H chemical shift is 0.00ppm, the solvent deuterochloroform
1The H chemical shift is 7.20ppm).See Fig. 1.
13The C-NMR collection of illustrative plates: 24.39ppm is-CH among the figure
3 13The C displacement, 123.49-153.84ppm is
Group
13The C displacement, 191.35ppm is
13The C displacement.(annotate: solvent C DCl
3 13The C displacement is 77.7ppm).See Fig. 2.
IR (KBr) spectrum: 3053cm
-1Be υ
=CH-The hydrocarbon stretching vibration of phenyl ring and alkene; 2992,2919 cm
-1Be υ
-CH3The hydrocarbon stretching vibration of methyl; 1673 cm
-1Be υ
-C=OCarbonylic stretching vibration; 1575 cm
-1Be υ
C=CConjugation alkene and the stretching vibration of phenyl ring carbon carbon; 1327,1444 cm
-1Be υ
-CH3Hydrocarbon flexural vibration; 980 cm
-1Be υ
C=CH-The hydrocarbon flexural vibration of alkene; 775 cm
-1Be hydrocarbon outer formation vibration of phenyl ring.See Fig. 3.
ESI-MS: m/z 274 is a molecular ion peak among the figure; M/z 245 may reset for compound and slough CO or CH
2=CH
2After fragment ion peak; M/z 142 is
Fragment ion peak, m./z 103 is
Fragment ion peak is base peak; M/z 77 is
Fragment ion peak.(annotate: adopt the electron impact ionization source, 70ev).See Fig. 4.
Ultimate analysis: measured value C:78.29%, H:5.48%, O:10.53%; Theoretical value C:78.81%, H:5.14%, O:10.21%.
By
1H-NMR,
13C-NMR, IR, UV, MS and ultimate analysis, the structure of proving conclusively this compound is consistent with the structure that provides.
Claims (1)
1.2-[(3-acrylketone phenyl)]-chemical synthesis process of 3-methyl-quinoxaline, its step is as follows:
1) in reactor, adds molecular volume successively than being benzo furazan, Virahol, methyl ethyl diketone and the Tri N-Propyl Amine of 1mol: 1000ml: 1mol: 1mol, distillation removes solvent behind back flow reaction 4～8h, the gained solid is with methyl alcohol or ethyl alcohol recrystallization, the gained yellow crystals is 1,4-dioxy-3-methyl-2-ethanoyl quinoxaline;
2) with step 1) products therefrom 1,4-dioxy-3-methyl-2-ethanoyl quinoxaline and 60～95% ethanolic soln 100-300ml join in the reactor, add Na after the stirring and dissolving
2S
2O
4Wherein 1, mole/the volume of 4-dioxy-3-methyl-2-ethanoyl quinoxaline and ethanolic soln is 0.05mol: 250ml, back flow reaction and cooling back add distilled water, with trichloromethane or ethyl acetate extraction, merge organic phase, with anhydrous magnesium sulfate drying, filtration, precipitation, gained resistates dehydrated alcohol recrystallization, getting faint yellow needle-like crystal is 3-methyl-2-ethanoyl quinoxaline;
3) with step 2) products therefrom 3-methyl-2-ethanoyl quinoxaline, phenyl aldehyde, 2N sodium hydroxide be that 4.7g: 2.7g: 10ml joins in the reactor successively by mass volume ratio; stirring reaction 2～7h after-filtration, getting light yellow crystal is the 2-[(3-phenyl) acrylketone]-the 3-methyl-quinoxaline.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100513708A CN101007786B (en) | 2007-01-24 | 2007-01-24 | 2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100513708A CN101007786B (en) | 2007-01-24 | 2007-01-24 | 2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101007786A CN101007786A (en) | 2007-08-01 |
| CN101007786B true CN101007786B (en) | 2010-07-28 |
Family
ID=38696487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100513708A Expired - Fee Related CN101007786B (en) | 2007-01-24 | 2007-01-24 | 2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101007786B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103420926B (en) * | 2013-06-07 | 2016-05-11 | 华中农业大学 | The chemical synthesis process of four kinds of metabolites of quinocetone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2007
- 2007-01-24 CN CN2007100513708A patent/CN101007786B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Non-Patent Citations (7)
| Title |
|---|
| John P. Dirlam et al..Thermochemical and Theoretical Study of Some Quinoxaline1,4-Dioxides and of Pyrazine 1,4-Dioxide..Journal of Organic Chemistry42 8.1977,42(8),1360-4. |
| John P. Dirlam et al..Thermochemical and Theoretical Study of Some Quinoxaline1,4-Dioxides and of Pyrazine 1,4-Dioxide..Journal of Organic Chemistry42 8.1977,42(8),1360-4. * |
| Matoba, Katsuhide等.Acid-catalyzed cyclization of chalcones derived fromvarious nitrogenous heteroaromatic compounds.Chemical & Pharmaceutical Bulletin29 9.1981,29(9),2442-50. |
| Matoba, Katsuhide等.Acid-catalyzed cyclization of chalcones derived fromvarious nitrogenous heteroaromatic compounds.Chemical & * |
| Pharmaceutical Bulletin29 9.1981,29(9),2442-50. * |
| 张丽芳等.薄层色谱法监测脱二氧喹烯酮的合成.化学世界47 5.2006,47(5),269-270. |
| 张丽芳等.薄层色谱法监测脱二氧喹烯酮的合成.化学世界47 5.2006,47(5),269-270. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101007786A (en) | 2007-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100999522B (en) | Preparation process of palmatine | |
| CN107778279B (en) | Preparation method of atorvastatin calcium intermediate | |
| CN101012195A (en) | Method of preparing 4-hydroxy-6-decyloxy-7-ethoxy-3-quinoline carboxylic acid ethyl ester | |
| CN105541773B (en) | A kind of preparation method of 3,4- dihydros -4- aryl-coumarin class compounds | |
| CN101735029B (en) | Synthesis method of hellebore aldehyde | |
| CN103880623A (en) | 4,2',4'-triethoxy-5' substituted chalcone derivatives and preparation method and application thereof | |
| CN101007786B (en) | 2[(3-phenyl) acrylketony]-3-methylquinoxaline chemical synthesis method | |
| CN101007785B (en) | 2[(3-phenyl) acrylketone]-3-methylquinoxaline chemical synthesis method | |
| CN103755659A (en) | 6-cinnamon acyl-2H-benzo [b] [1, 4] oxazine-3 (4H)-ketone compound and application thereof | |
| CN100436441C (en) | Method for preparing 3-formacyl chromone derivative | |
| CN105272918B (en) | Halogenation -1- alkyl -3- vinyl -2,4,5- triarylimidazoles and preparation method and purposes | |
| CN106134378B (en) | A kind of preparation method of trihydroxy-isoflavone | |
| CN102766108A (en) | Method for preparing benzoxazole C2 position ammoniated derivatives | |
| CN110172058B (en) | 7-azaspiro [5.6] dodecane-10-one compound and preparation method and application thereof | |
| CN103664854B (en) | A kind of synthetic method of flavanone derivatives | |
| CN112679326A (en) | Preparation method of 3, 4-dimethoxy benzaldehyde | |
| CN100439354C (en) | Synthesis method of (4R,5R) -4, 5-bis (aminomethyl) -1, 3-dioxolane compound | |
| CN109627228A (en) | A kind of synthetic method of 3- oxetanone | |
| CN103145613B (en) | Method for synthesizing (E)-3-[2-cyclopropyl-4-(4-fluorophenyl) quinolinyl-2-propenal | |
| CN112574242B (en) | Preparation method of benzo-heterocycle-3-boric acid | |
| CN102320944A (en) | Preparation process of vertraldethyde | |
| CN100427474C (en) | Method of preparing 3-methylquinoxaline-2-carboxylic acid | |
| CN101456845B (en) | 4,5-diaryl-2-sulfhydryl miazines compounds and synthetic method thereof and pharmaceutical use | |
| CN102070427B (en) | Synthesis methods of flocumafen and flocumafen intermediate | |
| CN106749169B (en) | Chiral preparation method of Ertiprotafib |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100728 Termination date: 20200124 |