CN104788392A - Synthetic method for high-purity and high-yield quinocetone - Google Patents
Synthetic method for high-purity and high-yield quinocetone Download PDFInfo
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- CN104788392A CN104788392A CN201510170057.0A CN201510170057A CN104788392A CN 104788392 A CN104788392 A CN 104788392A CN 201510170057 A CN201510170057 A CN 201510170057A CN 104788392 A CN104788392 A CN 104788392A
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- quinocetone
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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
- C07D241/50—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
Abstract
The invention discloses a synthetic method for high-purity and high-yield quinocetone. The synthetic method comprises the following steps: sequentially adding methylbenzene, mequindox, benzaldehyde and pyridine into a reaction container provided with a stirrer, a water separator and a condensation pipe, stirring and heating till the temperature is 95-112 DEG C, performing the reflux reaction for 3-5 hours, then, cooling to reduce the temperature to be 30 DEG C or below, performing suction filtration, and drying, so as to obtain the quinocetone with the purity of 98% or above and the yield of 90% or above, wherein the feeding molar ratio of the mequindox to benzaldehyde to methylbenzene to pyridine is 1:(1.05-1.1):(5-10):0.1. According to the invention, the water separator is adopted to continuously remove water as a by-product in the reaction to enable the reaction to be smoothly carried out forwards, so that the higher yield can be obtained within a shorter period of time; besides, during the preparation of the quinocetone, the product is not required to be refined, and the raw materials not reacted completely and the pyridine as a catalyst are still dissolved in the methylbenzene after the reaction is completed, and can be removed through being directly subjected to suction filtration and drying, so that the technological process is greatly simplified, the waste liquid pollution is reduced, and the production cost is reduced.
Description
Technical field
The present invention relates to a kind of synthetic method of veterinary drug, particularly relate to a kind of synthetic method of high-purity high-yield Quinocetone.
Background technology
Quinocetone, chemical name: 3-methyl-2-cinnamicacyl-quinoxaline-1,4-dioxide is a kind of veterinary drug developed by Lanzhou Livestock and Animal Drug Inst., Chinese Academy of Agricultural Science, can be used as fodder additives.Quinocetone is by the synthesis of anti-bacteria DNA; suppress pathogenic agent microbial growth breeding in digestive tube; protection intestinal beneficial flora and intestines wall are not encroached on by microorganism or parasite, thus reach the object reducing disease and occur, promote growth of animal, improve efficiency of feed utilization.Quinocetone toxicity is extremely low simultaneously, and excretion is fast, does not accumulate, noresidue, without three-induced effect, and use safety.Both be applicable to pig, be also applicable to fowl and aquatic products, be also applicable to the prophyiaxis and promoting growth of cub, poult.
Current Quinocetone mainly reacts obtained by Claisen-Schmit, shown in (1) by mequindox and phenyl aldehyde under the effect of catalyzer:
Chinese patent ZL 200410073376.1 adopts alcohols or dimethyl formamide to make solvent, mequindox and phenyl aldehyde are raw material, under the effect of basic catalyst, react after 5 hours through filtering at 20 ~ 80 DEG C, 95% washing with alcohol, dry obtained target product Quinocetone.The large usage quantity of the method Raw phenyl aldehyde and catalyzer, and reaction needs to use a large amount of washing with alcohol after terminating, and adds operation steps and production cost, and there is waste water handling problem, increased the weight of environmental protection pressure.
Chinese patent ZL 201110327882.9 adopts methyl alcohol to be solvent, and thanomin makes catalyzer, and mequindox and phenyl aldehyde are raw material, reacts through cooling after 8 ~ 48 hours, suction filtration, a large amount of methanol wash at 38 ~ 45 DEG C, obtained target product Quinocetone after dry.It is longer to there is the reaction times in this reaction, and organic solvent methanol usage is large, and product needs the problems such as refining.
Summary of the invention
In order to solve Problems existing in existing Quinocetone technology of preparing, the invention provides a kind of low cost, synthesis method of quinocetone rapidly and efficiently, products therefrom has higher purity and yield, without the need to the separating-purifying of complexity in simultaneous reactions process, simplify technical process, be more suitable for suitability for industrialized production.
The present invention is achieved through the following technical solutions:
(1) in reaction vessel, add toluene, mequindox, phenyl aldehyde and pyridine successively, be heated with stirring to 95 ~ 112 DEG C, back flow reaction 3 ~ 5 hours, described reactor is provided with water trap, and water trap is provided with prolong;
(2) reaction terminates rear cooling, suction filtration, namely obtains Quinocetone after oven dry.
Cooling temperature described in step (2) is less than 30 DEG C.
Benzene feedstock formaldehyde, mequindox and catalyst pyridine all have good solubility in toluene, step (1) selects toluene to make solvent, by stirring, material is uniformly dispersed in system, and toluene can reach good azeotropic effect with reacting the water generated in addition.
Mequindox and toluene generation condensation reaction in the present invention, the by product of generation is water.The method that constant boiling mixture distills is utilized in experimentation, being distilled by toluene-water azeotrope enters in water trap, wherein upper organic phase toluene continues to flow and gets back in reaction vessel, water is then by managing separated removal under water trap, reaction is carried out to positive dirction smoothly, ensures the high yield obtaining more than 90% within a short period of time.When the water yield in water trap no longer increases, react completely.
The water generated in reaction process is constantly removed by water trap, and the water content therefore in system is lower, and initial reaction stage can reach backflow at 95 DEG C, and along with water content constantly reduces, temperature of reaction can continue to raise, and finally reaches toluene boiling point.
Due to product Quinocetone slightly soluble in toluene, after reaction terminates, system is cooled to 30 DEG C, product can be separated out, and unreacted completely phenyl aldehyde and catalyst pyridine be still dissolved in toluene, by suction filtration, dry and can obtain the Quinocetone of purity more than 98%.Highly purified product can be obtained without the need to the separating-purifying of complexity and purification step in preparation process, decrease technical process and solvent usage quantity, reduce industrial cost, alleviate environmental protection pressure.
Mequindox described in step (1), phenyl aldehyde, toluene, the molar ratio of catalyzer is 1:1.05 ~ 1.1:5 ~ 10:0.1.The present invention, owing to have selected suitable solvent, by means of the effect of water trap simultaneously, needs a small amount of catalyzer can reach good reaction effect.
As further preferred version:
In step (1), raw material mequindox, phenyl aldehyde, toluene, catalyzer molar ratio is 1:1.1:8:0.1; Heating temperature is 110 DEG C, 4 hours reaction times.
Beneficial effect of the present invention is:
1, the present invention adopts water trap constantly to remove water byproduct in reaction process, ensure that reaction is carried out to positive dirction smoothly, can at the higher yield of short period acquisition.
2, the present invention selects toluene to make solvent, product Quinocetone slightly soluble in toluene, and phenyl aldehyde, pyridine and mequindox solvability in toluene is better, therefore after reaction terminates cooling, product Quinocetone is separated out, and unreacted raw material and catalyst pyridine are still dissolved in toluene completely, by means of only suction filtration, dry the retained material and catalyzer that can remove in Quinocetone, the product purity of more than 98% can be reached by simple operation method.Enormously simplify technical process, reduce production cost, decrease discharging of waste liquid amount, there is the advantage of energy-conserving and environment-protective.
Specific embodiment
Below in conjunction with specific experiment embodiment, the present invention is described in further detail, but the present invention does not limit by embodiment.
Embodiment 1
(1) stirring rake is being housed, prolong, in the there-necked flask of water trap, add toluene 368g (4mol) successively, mequindox 109g (0.5mol), phenyl aldehyde 58.3g (0.55mol), pyridine 3.95g (0.05mol), open and stir, after heating, material dissolves rapidly, continue to be warming up to 110 DEG C of backflows, in reflux course, the water that reaction produces and solvent toluene are distilled out together by azeotropic and enter in water trap, wherein upper toluene continues to flow and gets back in there-necked flask, lower aqueous layer is then removed by being in control under water trap to be separated, temperature rising reflux, in reflux course, the water that reaction produces is separated by water trap, react 4 hours,
(2) by step (1) gained reaction solution cooling down to 30 DEG C, have faint yellow solid to separate out, through suction filtration, 110 DEG C of oven dry obtain Quinocetone 142.5g, and purity is 99.1%, and yield is 93.1%.
Embodiment 2 ~ 3
Adopt and prepare Quinocetone, the toluene of different amounts and phenyl aldehyde with embodiment 1 same operation step and same amount mequindox, pyridine, different temperature of reaction and reaction times, obtained experimental data is as shown in table 1: table 1:
Comparative example 1
(1) stirring rake is being housed, in the there-necked flask of prolong, add toluene 368g (4mol), mequindox 109g (0.5mol), phenyl aldehyde 58.3g (0.55mol), pyridine 3.95g (0.05mol) successively, open and stir, after heating, material dissolves rapidly, continues to be warming up to 85 DEG C of backflows, because the water generated in reaction process can not be effectively separated, reaction reaches 90 DEG C and namely reaches reflux temperature, reacts 4 hours;
(2) by step (1) gained reaction solution cooling down to 30 DEG C, have faint yellow solid to separate out, through suction filtration, 110 DEG C of oven dry obtain Quinocetone 144.9g, and purity is 78.5%, and yield is 74.3%.
Comparative example 2
(1) stirring rake is being housed, prolong, in the there-necked flask of water trap, add phenyl aldehyde 58.3g (0.55mol), mequindox 109g (0.5mol), pyridine 3.95g (0.05mol) successively, be heated with stirring to 112 DEG C, material is thickness comparatively, continues stirring reaction 5 hours;
(2) by step (1) gained reactant cooling down to 30 DEG C, product is not had to separate out, and material still very thickness, cannot suction filtration, react unsuccessfully.
Comparative example 3
(1) stirring rake is being housed, prolong, in the there-necked flask of water trap, add methyl alcohol 128g (4mol), mequindox 109g (0.5mol), phenyl aldehyde 58.3g (0.55mol), pyridine 3.95g (0.05mol) successively, open and stir, after heating, material dissolution is slower, continue to be warming up to 60 DEG C of backflows, in water trap, liquid is without layering, the moisture of generation cannot be left away and remove, and reacts 5 hours;
(2) by step (1) gained reaction solution cooling down to 30 DEG C, have faint yellow solid to separate out, through suction filtration, 100 DEG C of oven dry obtain Quinocetone 89.1g, and purity is 80.4%, and yield is 46.8%.
By comparative example 1 ~ 3 and comparative example 1 ~ 3, can reach a conclusion: in the present invention, the use of water trap is the key accelerating speed of reaction, water trap can remove the water byproduct that reaction generates effectively fast, reaction is carried out to positive dirction smoothly, and water is conducive to after removing raising temperature of reaction thus further accelerating speed of reaction simultaneously.The selection also outbalance of solvent, its solvability to raw material need be considered during selective solvent, good azeotropic effect can be reached with water byproduct simultaneously, solvent toluene selected by the present invention, can comparatively good dissolving raw material and catalyzer, and to product Quinocetone slightly soluble, therefore reaction terminate after by means of only simple cooling, drying operation can by product separation, obtain highly purified Quinocetone, enormously simplify production technique, be more of value to suitability for industrialized production.
Claims (5)
1. a synthetic method for high-purity high-yield Quinocetone, is characterized in that, described synthetic method comprises the following steps:
(1) in reaction vessel, add toluene, mequindox, phenyl aldehyde and pyridine successively, be heated with stirring to 95 ~ 112 DEG C, back flow reaction 3 ~ 5 hours, described reactor is provided with water trap, and water trap is provided with prolong;
(2) reaction terminates rear cooling, suction filtration, namely obtains Quinocetone after oven dry.
2. the synthetic method of high-purity high-yield Quinocetone as claimed in claim 1, it is characterized in that, the molar ratio of the mequindox described in step (1), phenyl aldehyde, toluene, pyridine is 1:1.05 ~ 1.1:5 ~ 10:0.1.
3. the synthetic method of high-purity high-yield Quinocetone as claimed in claim 2, it is characterized in that, the mequindox described in step (1), phenyl aldehyde, toluene, pyridine molar ratio are 1:1.1:8:0.1.
4. the synthetic method of high-purity high-yield Quinocetone as claimed in claim 1, it is characterized in that, the Heating temperature described in step (1) is 110 DEG C, 4 hours reaction times.
5. the synthetic method of high-purity high-yield Quinocetone as claimed in claim 1, it is characterized in that, the cooling temperature described in step (2) is less than 30 DEG C.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN117164444A (en) * | 2023-09-01 | 2023-12-05 | 浙江宏达化学制品有限公司 | Synthesis method of salicylaldehyde |
Citations (4)
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| 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 |
| CN102311397A (en) * | 2011-10-25 | 2012-01-11 | 湖南科技大学 | High-efficient quinocetone synthetic method |
| CN102408384A (en) * | 2011-10-25 | 2012-04-11 | 湖南科技大学 | Improved synthesis method of quinocetone |
-
2015
- 2015-04-13 CN CN201510170057.0A patent/CN104788392A/en active Pending
Patent Citations (4)
| 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 |
| 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 |
| CN102311397A (en) * | 2011-10-25 | 2012-01-11 | 湖南科技大学 | High-efficient quinocetone synthetic method |
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| 梁亮.: "《化学化工专业实验》", 31 March 2009, 北京：化学工业出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN117164444A (en) * | 2023-09-01 | 2023-12-05 | 浙江宏达化学制品有限公司 | Synthesis method of salicylaldehyde |
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Application publication date: 20150722 |