CN103524379B - Synthesis method of trifloxystrobin - Google Patents
Synthesis method of trifloxystrobin Download PDFInfo
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- CN103524379B CN103524379B CN201310504600.7A CN201310504600A CN103524379B CN 103524379 B CN103524379 B CN 103524379B CN 201310504600 A CN201310504600 A CN 201310504600A CN 103524379 B CN103524379 B CN 103524379B
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- PODZUTRVBLTLJT-MYKJZIGRSA-N C/C(/OC)=C(/C(OC)=O)\c1ccccc1O/N=C(\C)/c1cc(C(F)(F)F)ccc1 Chemical compound C/C(/OC)=C(/C(OC)=O)\c1ccccc1O/N=C(\C)/c1cc(C(F)(F)F)ccc1 PODZUTRVBLTLJT-MYKJZIGRSA-N 0.000 description 1
- 0 C[C@](**)c1cc(C(F)(F)F)ccc1 Chemical compound C[C@](**)c1cc(C(F)(F)F)ccc1 0.000 description 1
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Abstract
The invention relates to a synthesis method of trifloxystrobin. A reaction process of the synthesis method includes water diversion treatment. By virtue of a water carrying process, the influence of water formed in the reaction on the reaction is effectively avoided, thereby reducing side reaction, and improving product yield and product quality. According to the synthesis method, a reaction liquid solvent is directly used for crystallization after the reaction so as to avoid change of a crystallization solvent and to avoid cross infection of the solvents, thus further enhancing product quality.
Description
Technical field
The present invention relates to a kind of synthetic method of oxime bacterium ester.
Background technology
Oxime bacterium ester (Trifloxystrobin) class wide-spectrum bactericide is the fungicides that the class successfully developed as sterilant lead compound from natural product Strobilurins is new.Characteristics such as there is efficient, wide spectrum, protection, treat, root out, permeate, interior suction, activity, resistance of rainwater washing against, lasting period are long.To 1,4-demethylation enzyme inhibitors, benzamides, the bacterial strain that dicarboxyl amine and benzimidazoles produce resistance is effective, with current existing sterilant without cross resistance, all there is good activity to nearly all Eumycetes (Ascomycetes, Basidiomycetes, Oomycete and imperfect fungi) disease such as Powdery Mildew, rust, glume blight, net blotch, white viral disease, rice blast etc.Go out and have outside special efficacy to Powdery Mildew, leaf spot, have good activity to rust, white viral disease, damping-off, apple apple scab.It is a kind of respiratory chain inhibitor, stops cell Triphosaden (ATP) enzymic synthesis, thus suppress its mitochondrial respiratory and play bacteriostatic action by the electron transmission pinned between cytochrome B and C1.To crop safety, because it is at soil, can explain fast in water, thus environmentally safe.On the synthesis document of oxime bacterium ester, report is a lot, and route is substantially identical, but alkali used is different with solvent, but so far, preparation technology still exists many problems, and raw material seldom arrives, and technique is imperfect, and yield is low, brings great difficulty to suitability for industrialized production.
Summary of the invention
Technical problem to be solved by this invention overcomes the deficiencies in the prior art, provides the synthetic method of a kind of economical and effective, technique simple oxime bacterium ester.
For solving above technical problem, the present invention adopts following technical scheme:
A synthetic method for oxime bacterium ester, described synthetic method comprises the following steps:
A, to after nitrogen replacement, agitator being housed, thermometer, in the reaction flask of water trap and condenser, add compound (I), alkaline matter and organic solvent also stir, be heated to reflux water-dividing, the described reflux water-dividing time is 5 ~ 6 hours, after dividing water to terminate, be cooled to room temperature, then the toluene solution of compound (II) is added drop-wise in above-mentioned reaction solution, after dropwising, at room temperature be incubated 2 ~ 4 hours, wherein, described compound (I) is 1:1.0 ~ 3.0 with the mol ratio of alkaline matter, described compound (I) is 1:0.9 ~ 2.0 with the mol ratio of compound (II), the mass concentration of the toluene solution of described compound (II) is 30% ~ 70%,
B, reacted for step a reacting liquid filtering is obtained mother liquor, add water in described mother liquor, the part by weight of described mother liquor and water is 1:0.5 ~ 2.0, then stir, leave standstill, layering, gained organic phase obtains oxime bacterium ester solution through washing, wherein, terminate when described washing is 5 ~ 8 to wash the pH of rear water;
C, the oxime bacterium ester solution crystallisation by cooling obtained by step b, filter and obtain white solid oxime bacterium ester.
Further, in step a, described alkaline matter is one or more the combination in sodium hydroxide, potassium hydroxide, sodium carbonate and salt of wormwood.Described alkaline matter is avoided using sodium methylate, sodium hydrogen, sodium amide, and adopts sodium hydroxide, potassium hydroxide, sodium carbonate or salt of wormwood, and cost of material is cheap, and security is good.
Further, in step a, described organic solvent is selected from benzene, toluene, hexanaphthene or dimethylbenzene.Described organic solvent is avoided using N, dinethylformamide (DMF), N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO) (DMSO), acetone, acetonitrile, and use the easily recovered solvent such as benzene, toluene, hexanaphthene or dimethylbenzene, can reduce costs, reduce environmental pollution.
Further, in step a, described in reaction process, point water is the method that azeotropic divides water.
Further, in step c, interim cooling method is taked in described cooling.Described stage cooling is specific as follows: first oxime bacterium ester solution is cooled to 18 DEG C ~ 25 DEG C, is incubated 0.5 ~ 1.5 hour, and then is cooled to 8 DEG C ~ 15 DEG C, be incubated 1.5 ~ 2.5 hours, be finally cooled to 3 DEG C ~ 7 DEG C, be incubated 3.5 ~ 4.5 hours.
In the present invention, all described raw material, all by being purchased and/or taking known means to prepare, when not illustrated, all meets the requirement of stdn chemical product.
Due to the enforcement of technique scheme, the present invention compared with prior art tool has the following advantages:
There is in synthetic method of the present invention turnout science and engineering skill, by band water process in reaction process, effectively avoid the water formed in reacting on the impact of reaction, reduce the generation of side reaction, improve product yield and quality product.
After the completion of reaction, reacting liquid filtering obtains mother liquor to synthetic method of the present invention, adds water, then stir in mother liquor, and leave standstill, layering, gained organic phases washed with water obtains oxime bacterium ester solution, oxime bacterium ester solution crystallisation by cooling, filters and obtains white solid oxime bacterium ester.In reaction solution, do not add other solvent in last process as recrystallisation solvent, but directly with the solvent of reaction solution as recrystallisation solvent, avoid the crossed contamination on solvent that replacing recrystallisation solvent causes.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described.
Embodiment 1
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), sodium hydroxide (4.2g, 0.100mol, 95%) and toluene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 6, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (35.6g, 95%), yield 82.9%.
Embodiment 2
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), potassium hydroxide (6.2g, 0.100mol, 90%) and benzene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 6.5, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (36.9g, 95%), yield 85.9%.
Embodiment 3
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), sodium hydroxide (4.2g, 0.100mol, 95%) and hexanaphthene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) hexanaphthene (20.0g) is dissolved in, the cyclohexane solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7.5, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (37.1g, 95%), yield 86.4%.
Embodiment 4
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), potassium hydroxide (6.2g, 0.100mol, 90%) and hexanaphthene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) hexanaphthene (20.0g) is dissolved in, the cyclohexane solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (38.0g, 95%), yield 88.5%.
Embodiment 5
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), salt of wormwood (14.5g, 0.100mol, 95%) and dimethylbenzene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (38.6g, 95%), yield 89.9%.
Embodiment 6
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), sodium carbonate (11.2g, 0.100mol, 95%) and dimethylbenzene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (37.6g, 95%), yield 87.5%.
Embodiment 7
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), sodium carbonate (22.3g, 0.200mol, 95%) and toluene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (58.7g, 0.195mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (35.3g, 95%), yield 82.1%.
Embodiment 8
To after nitrogen replacement, agitator being housed, water trap, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), sodium carbonate (16.7g, 0.150mol, 95%) and toluene (45.0g), start to stir, be heated to reflux water-dividing, reflux 4 hours, water is divided to terminate, stop heating, be cooled to room temperature, by compound ii (45.1g, 0.15mol, 95%) toluene (20.0g) is dissolved in, the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip 0.5 hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (36.5g, 95%), yield 84.9%.
Comparative example 1
To after nitrogen replacement, agitator being housed, in the reaction flask of condenser and thermometer, add chemical compounds I (21.0g, 0.100mol, 97%), salt of wormwood (14.5g, 0.100mol, 95%) and N, dinethylformamide (45.0g), start to stir, control temperature of reaction at 50 DEG C, be incubated 4 hours, be cooled to room temperature, by compound ii (31.6g, 0.105mol, 95%) N is dissolved in, dinethylformamide (20.0g), the toluene solution of compound ii is dropped in above-mentioned reaction solution, drip half an hour, 30 DEG C of insulations, be incubated after 3 hours, sampling analysis, after reaction terminates, processing reaction.In reaction solution, add water (50g) and hexanaphthene (50g), stir 10 minutes, leave standstill, layering, organic phase washing (washing twice, each 50ml), after washing, the pH of water is 7, organic phase decrease temperature crystalline, and 20 DEG C are incubated 1 hour, fraction solids is separated out, 10 DEG C are incubated 2 hours, and 5 DEG C are incubated 4 hours, filter, obtain white solid oxime bacterium ester (32.3g, 95%), yield 75.2%.
Above to invention has been detailed description; its object is to allow the personage being familiar with this art can understand content of the present invention and be implemented; can not limit the scope of the invention with this; and the invention is not restricted to the embodiments described; the equivalence change that all spirit according to the present invention are done or modification, all should be encompassed within protection scope of the present invention.
Claims (4)
1. a synthetic method for oxime bacterium ester, is characterized in that, described synthetic method comprises the following steps:
A, to after nitrogen replacement, agitator being housed, thermometer, in the reaction flask of water trap and condenser, add compound (I), alkaline matter and organic solvent also stir, be heated to reflux water-dividing, the described reflux water-dividing time is 5 ~ 6 hours, after dividing water to terminate, be cooled to room temperature, then the toluene solution of compound (II) is added drop-wise in above-mentioned reaction solution, after dropwising, at room temperature be incubated 2 ~ 4 hours, wherein, described compound (I) is 1:1.0 ~ 3.0 with the mol ratio of alkaline matter, described compound (I) is 1:0.9 ~ 2.0 with the mol ratio of compound (II), the mass concentration of the toluene solution of described compound (II) is 30% ~ 70%, described organic solvent is selected from benzene, toluene, hexanaphthene or dimethylbenzene, described point of water is the method that azeotropic divides water,
B, reacted for step a reacting liquid filtering is obtained mother liquor, add water in described mother liquor, the part by weight of described mother liquor and water is 1:0.5 ~ 2.0, then stir, leave standstill, layering, gained organic phase obtains oxime bacterium ester solution through washing, wherein, terminate when described washing is 5 ~ 8 to wash the pH of rear water;
C, the oxime bacterium ester solution crystallisation by cooling obtained by step b, filter and obtain white solid oxime bacterium ester.
2. synthetic method according to claim 1, is characterized in that, in step a, described alkaline matter is one or more the combination in sodium hydroxide, potassium hydroxide, sodium carbonate and salt of wormwood.
3. synthetic method according to claim 1, is characterized in that, in step c, interim cooling method is taked in described cooling.
4. synthetic method according to claim 3, it is characterized in that, in step c, described stage cooling is specific as follows: first oxime bacterium ester solution is cooled to 18 DEG C ~ 25 DEG C, be incubated 0.5 ~ 1.5 hour, and then be cooled to 8 DEG C ~ 15 DEG C, be incubated 1.5 ~ 2.5 hours, finally be cooled to 3 DEG C ~ 7 DEG C, be incubated 3.5 ~ 4.5 hours.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1321144A (en) * | 1998-09-30 | 2001-11-07 | 巴斯福股份公司 | Process for preparing trione bis (oxime ether) derivatives, and trione mono-and trione bis (oxime ether) derivatives obtained thereby |
| CN101941921A (en) * | 2010-09-03 | 2011-01-12 | 岳阳迪普化工技术有限公司 | Method for preparing trifloxystrobin |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1321144A (en) * | 1998-09-30 | 2001-11-07 | 巴斯福股份公司 | Process for preparing trione bis (oxime ether) derivatives, and trione mono-and trione bis (oxime ether) derivatives obtained thereby |
| CN101941921A (en) * | 2010-09-03 | 2011-01-12 | 岳阳迪普化工技术有限公司 | Method for preparing trifloxystrobin |
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