CN106316937A - Preparation method of fluazinam - Google Patents
Preparation method of fluazinam Download PDFInfo
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- CN106316937A CN106316937A CN201510369729.0A CN201510369729A CN106316937A CN 106316937 A CN106316937 A CN 106316937A CN 201510369729 A CN201510369729 A CN 201510369729A CN 106316937 A CN106316937 A CN 106316937A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Abstract
The invention provides a preparation method of fluazinam. Fluazinam is prepared through a reaction of 2-amino-3-chloro-5-trifluoromethylpyridine and 2,4-dichloro-3,5-dinitrobenzotrifluoride with an inorganic alkali as an alkali and 2-methyltetrahydrofuran as a solvent. The preparation method of fluazinam, adopting 2-methyltetrahydrofuran as the solvent has the advantages of good reaction selectivity, short reaction time, substantial improvement of the productivity of every device, large productivity, suitableness for industrial production, small use amount of the solvent, mild reaction conditions, simplicity in operation, great simplification of the industrial process, and realization of obviously less hydrolysis byproduct due to the poor compatibility with water, and allows the highest mole yield to reach 98.4% and the highest purity to reach 99.8%.
Description
Technical field
The invention belongs to compou nd synthesis technical field, be specifically related to the preparation method of a kind of fluazinam.
Background technology
Fluazinam, the chemical chloro-N-of entitled 3-(3-chloro-5-trifluoromethyl-2-pyridine radicals)-α, α, α-three fluoro-2,6-dinitro-p-
Toluidines, molecular structural formula is:
Fluazinam is a kind of wide-spectrum bactericide, and the multiple gray mold causing Botrytis cinerea has specially good effect, to phytophthora root rot, rotten sclerotiniose,
Melasma, scab and other pathogen disease have good prevention effect.In addition to bactericidal activity, fluazinam also demonstrates
Acaricidal activity to red spider etc..
At present, the synthetic method of fluazinam mainly uses compound A (2-amido-3-5-trifluoro picoline) and compound B
(2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene), under alkali and solvent action, prepare fluazinam, by-product main in its reaction
Thing is compound D (2,4-bis-chloro-3, hydrolysate 3-chloro-4-trifluoromethyl-2 of 5-dinitro-p-trifluorotoluene, 6-dinitrophenol,DNP), tool
Precursor reactant equation is as follows.
In this synthetic method, the product purity on reaction yield and fluazinam that selects of solvent and alkali affects relatively greatly, wherein, right
The screening of solvent is particularly important, its object is to find the solvent that reaction is more complete, usage amount is few, with the product matter obtained
Amount and relatively low cost；Simultaneously as use alkali, system has water to generate, and adding recovered solvent can be with more or less
Moisture, and moisture causes the generation of hydrolysis impurity compound D, can tolerate certain moisture and generation less therefore it is necessary to find
The solvent of compound D is preferred.
In prior art, patent WO2009017241 avoid hydrolytic side reactions to produce by the consumption of raising alkali, Wen Zhongfen
Not with MIBK/AcOEt/ dioxane/THF/DME etc. as solvent, make alkali with the liquid caustic soda of 8 equivalents, with the yield system of 80-90%
Obtain fluazinam.Using anhydrous tertiary butanol in patent WO2009017239 is solvent, and solid sodium hydroxide (3 equivalent) is alkali,
Fluazinam is prepared with 78% yield；It is solvent when using the aqueous tert-butyl alcohol, and uses 48% liquid caustic soda, by increasing the equivalent of alkali extremely
8 equivalents, also can obtain the fluazinam of 72% yield.Above-mentioned patent have employed preferred alkali and solvent, obtains the fluorine of certain yield
Pyridine amine.But, seek more high yield pulp1 and the fluazinam of purity and to the good solvent of fluazinam by-product inhibition for work
Industry metaplasia produces to remain has highly significant meaning.
Summary of the invention
The shortcoming of prior art in view of the above, it is an object of the invention to provide the preparation method of a kind of fluazinam, is used for solving
The problem certainly lacking the preparation method of the fluazinam of high-purity and high yield pulp1 in prior art.
For achieving the above object and other relevant purposes, the present invention provides the preparation method of a kind of fluazinam, with the 2-chloro-5-of amino-3-
Trifluoromethyl pyridine and 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene is raw material, with inorganic base as alkali, with 2-methyltetrahydrofuran is
Solvent, reaction prepares fluazinam.
Concrete reaction equation is as follows:
The preparation method of described a kind of fluazinam, specifically includes following steps:
1) be separately added into 2-amido-3-5-trifluoro picoline, 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, inorganic base,
Stirring reaction after the mixing of 2-methyltetrahydrofuran；
Preferably, described 2-amido-3-5-trifluoro picoline and 2,4-bis-chloro-3, the molar ratio of 5-dinitro-p-trifluorotoluene
For 0.95-1.20:1.
It is highly preferred that described 2-amido-3-5-trifluoro picoline and 2,4-bis-chloro-3, feeding intake mole of 5-dinitro-p-trifluorotoluene
Ratio is 0.95-1.02:1.
Specifically, described inorganic base is selected from potassium carbonate, sodium carbonate, cesium carbonate, potassium fluoride, sodium hydroxide, potassium hydroxide, hydrogen
Any one or more combination in lithium oxide.
Preferably, described inorganic base is potassium hydroxide.
It is highly preferred that described potassium hydroxide selects technical grade purity to be 85wt%AboveSolid potassium hydroxide.
It is highly preferred that described 2-amido-3-5-trifluoro picoline and potassium hydroxide mole ratio be 1:1-8.
Most preferably, described 2-amido-3-5-trifluoro picoline and potassium hydroxide mole ratio be 1:2-4.
Preferably, described 2-amido-3-5-trifluoro picoline is 1:0.5-20 with the mass ratio of 2-methyltetrahydrofuran.
It is highly preferred that the mass ratio of described 2-amido-3-5-trifluoro picoline and 2-methyltetrahydrofuran is 1:1.0-5.0.
Further, described 2-amido-3-5-trifluoro picoline is 1:1.0-2.5 with the mass ratio of 2-methyltetrahydrofuran.
Most preferably, described 2-amido-3-5-trifluoro picoline with the mass ratio of 2-methyltetrahydrofuran is
197:300-400。
Preferably, the water content in described 2-methyltetrahydrofuran is 0.5-3.7wt%.Described 2-methyltetrahydrofuran is before the reaction
The water content without removing.
Preferably, after described mixing, the stirring response time is 2-20h.It is highly preferred that stirring the response time after described mixing is 2-6h.
Preferably, stir reaction temperature after described mixing and be-20-150 DEG C.
It is highly preferred that stir reaction temperature after described mixing to be 20-80 DEG C.
Most preferably, stir reaction temperature after described mixing and be 20-25 DEG C.
Preferably, described stirring is conventional mechanical agitation mode.After described mixing, stirring reaction is carried out at ambient pressure.
2), after adding water and being dissolved to clarification, stand separatory and take organic facies and carry out distillation and concentration, precipitation, add a small amount of water and beat
Slurry, filters, i.e. prepares fluazinam after drying.
Preferably, the amount of water being dissolved in water described in can make reactant liquor clarification be advisable.
Preferably, described distillation and concentration, precipitation are air-distillation concentration and precipitation steams to no liquid.
Preferably, described vapo(u)rizing temperature is less than 100 DEG C.It is highly preferred that described vapo(u)rizing temperature is 60-99 DEG C.
Preferably, the amount of water of described addition a small amount of water making beating is advisable stirring smoothly.
Preferably, it is filtered into the normal temperature and pressure using filter paper, filter cloth or filter screen to carry out described in filter.
Preferably, described being dried is carried out at less than 100 DEG C.It is highly preferred that described baking temperature is 50-99 DEG C.
As it has been described above, the preparation method of a kind of fluazinam of present invention offer, with potassium hydroxide as alkali, with 2-methyltetrahydrofuran
For solvent, at room temperature reaction prepares high-purity and the fluazinam of high yield, has the advantages that
(1), from the point of view of for pesticide original medicine, impurity is more means that purification yield declines and product content declines, and this
Time in bright using 2-methyltetrahydrofuran as solvent, compare and belong to the oxolane of ether solvent, DME etc. together,
By-product (compound D:3-chloro-4-trifluoromethyl-2, the 6-dinitrophenol,DNP) growing amount of hydrolysis is substantially few,
Molar yield is up to 98.4%, and purity is up to 99.8%.
(2) present invention uses 2-methyltetrahydrofuran to be solvent, its good reaction selectivity, can when denseer or
Carry out at a temperature of person is higher, it is also possible to shorten the response time, increase one-pot inventory, reduce solvent burden ratio,
Single complete equipment production capacity increases, and is suitable for industrialized production.
(3) present invention uses 2-methyltetrahydrofuran to be solvent, and solvent can reclaim and directly apply mechanically, therefore the unit consumption of solvent
Reduce with processing cost, and reaction condition be gentle, simple to operate, enormously simplify course of industrialization, also without
Need to use the water removal device of complexity during industrial implementation, energy consumption is less.
(4) consumption of the alkali used in the present invention reduces, and is beneficial to reduce cost and energy-conserving and environment-protective.
Detailed description of the invention
The present invention is expanded on further, it should be appreciated that these embodiments are merely to illustrate the present invention and need not below in conjunction with specific embodiment
In limiting the scope of the invention.
Below by way of specific instantiation, embodiments of the present invention being described, those skilled in the art can be by disclosed by this specification
Content understand other advantages and effect of the present invention easily.The present invention can also be added by the most different detailed description of the invention
To implement or application, the every details in this specification can also be based on different viewpoints and application, in the essence without departing from the present invention
Various modification or change is carried out under god.
The reagent such as dimethylformamide (DMF) of use, dimethyl sulfoxide (DMSO), acetonitrile, tetrahydrochysene in following example
Furan (THF), methylisobutylketone (MIBK), butanone (MEK), cyclopentyl methyl ether (CPME), methyl tertiary butyl ether(MTBE) (MTBE),
Glycol dimethyl ether (DME), ethyl acetate (AcOEt), 2-methyltetrahydrofuran, 2-amido-3-5-trifluoro picoline,
2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, potassium hydroxide, sodium hydroxide etc. are reagent commonly used in the art.Efficiently liquid phase
Chromatograph (HPLC), nuclear magnetic resonance, NMR (NMR) are instrument commonly used in the art.
Embodiment 1
By 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.02 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, 3.0
Mole 85% potassium hydroxide is placed in tetra-mouthfuls of reaction bulbs of 2L with the 2-methyltetrahydrofuran (moisture 0.5%) of 400g,
Stirring reaction 6 hours under 25 DEG C of room temperature.
Take 1 reactant liquor in probe tube, add 1 dilute hydrochloric acid and make the pH ＜ 6 of reactant liquor in acidity, then use acetonitrile as molten
Dilution agent reactant liquor is to 2ml, then takes wherein 1ml and carry out HPLC detection and use quantified by external standard method, measures and obtains in reactant liquor
Fluazinam content is 97.7%, and in reaction afterproduct, the concrete content of each component is shown in Table 1.
Wherein, the testing conditions of high performance liquid chromatography is: instrument: Agilent 1200 type high performance liquid chromatograph；Chromatographic column:
Symmetry C18Post (250mm × 4.6mm, 5 μm)；Column temperature: 40 DEG C；Detection wavelength: 240nm；Flow velocity: 1mL/min；
Sample size: 10 μ L；Post time:5min；Flowing phase: A phase: 0.1%HCOOH (H2O), B phase: 0.1%HCOOH
(ACN)；Analysis time: 30min；Gradient elution.Concrete gradient elution program: 0～5min, A phase: B phase volume ratio is
70:30-50:50；5～25min, A phase: B phase volume ratio is 50:50-5:95；25～30min, A phase: B phase volume
Ratio is 5:95-5:95.External standard method refers to pipette the fluazinam standard sample of different volumes after a series of dilution, and (commercially available, purity contains
Amount is 100%), use high performance liquid chromatograph sample introduction to analyze, it is thus achieved that standard sample content and the linear relationship of peak area, draw
Corresponding standard working curve, is calculated the regression equation of each standard working curve；Again response sample is used high-efficient liquid phase color
The chromatographic peak area obtained after spectrometer detection substitutes in the regression equation of standard working curve, the content of available response sample.
Then, it is dissolved in water to clarification, stands separatory and take organic facies to carry out air-distillation under the vapo(u)rizing temperature less than 100 DEG C dense
The precipitation that contracts steams to no liquid, adds the making beating of a small amount of water, filters, i.e. prepares fluazinam after drying at less than 100 DEG C
Product, finished weight is 454g.
Use again HPLC detection finished product purity content be 99.6%, molar yield is 97.5%, wherein HPLC testing conditions with
In said determination reactant liquor, the HPLC testing conditions of fluazinam content is identical.
Qualification result:
Mp:114 DEG C.
1H-NMR (CDCl3): δ=10.04 (m, 1H)；8.75(s,1H)；8.35(m,2H).
13C-NMR (CDCl3): δ=154.1,149.6,144.9,143.3,135.8,132.5,127.1,125.4,123.4,12 1.8,119.8,
118.2。
Embodiment 2
By 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.02 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, 3.0
Molar potassium hydroxide (85%) is placed in tetra-mouthfuls of reaction bulbs of 2L, 25 with the 2-methyltetrahydrofuran (moisture 3.7%) of 400g
Stirring reaction 6 hours under DEG C room temperature.
Take 1 reactant liquor in probe tube, add 1 dilute hydrochloric acid and make the pH ＜ 6 of reactant liquor in acidity, then use acetonitrile as molten
Dilution agent reactant liquor is to 2ml, then takes wherein 1ml and carry out HPLC detection and use quantified by external standard method, measures and obtains in reactant liquor
Fluazinam content is 97.6%, and in reaction afterproduct, the concrete content of each component is shown in Table 1.The testing conditions of HPLC is with embodiment 1.
Then, it is dissolved in water to clarification, stands separatory and take organic facies to carry out air-distillation under the vapo(u)rizing temperature less than 100 DEG C dense
The precipitation that contracts steams to no liquid, adds the making beating of a small amount of water, filters, i.e. prepares fluazinam after drying at less than 100 DEG C
Product, finished weight is 452g, then to use the HPLC of same detection condition to detect its purity content be 99.6%, molar yield
97.0%.Qualification result is with embodiment 1.
Embodiment 3
By 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.05 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, 4.0
Mole 85% potassium hydroxide is placed in tetra-mouthfuls of reaction bulbs of 2L with the 2-methyltetrahydrofuran (moisture 0.5%) of 300g,
Stirring reaction 4 hours under 20 DEG C of room temperature.
Take 1 reactant liquor in probe tube, add 1 dilute hydrochloric acid and make the pH ＜ 6 of reactant liquor in acidity, then use acetonitrile as molten
Dilution agent reactant liquor is to 2ml, then takes wherein 1ml and carry out HPLC detection and use quantified by external standard method, measures and obtains in reactant liquor
Fluazinam content is 98.4%, and in reaction afterproduct, the concrete content of each component is shown in Table 1.The testing conditions of HPLC is with embodiment 1.
Then, it is dissolved in water to clarification, stands separatory and take organic facies to carry out air-distillation under the vapo(u)rizing temperature less than 100 DEG C dense
The precipitation that contracts steams to no liquid, adds the making beating of a small amount of water, filters, i.e. prepares fluazinam after drying at less than 100 DEG C
Product, finished weight is 457g, then to use the HPLC of same detection condition to detect its purity content be 99.8%, and molar yield is
98.0%.Qualification result is with embodiment 1.
Embodiment 4
By 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.05 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, 4.0
Mole9 5% potassium hydroxide is placed in tetra-mouthfuls of reaction bulbs of 2L with the 2-methyltetrahydrofuran (moisture 0.5%) of 300g,
Stirring reaction 2 hours at 80 DEG C.
Take 1 reactant liquor in probe tube, add 1 dilute hydrochloric acid and make the pH ＜ 6 of reactant liquor in acidity, then use acetonitrile as molten
Dilution agent reactant liquor is to 2ml, then takes wherein 1ml and carry out HPLC detection and use quantified by external standard method, measures and obtains in reactant liquor
Fluazinam content is 96.8%, and in reaction afterproduct, the concrete content of each component is shown in Table 1.The testing conditions of HPLC is with embodiment 1.
Then, it is dissolved in water to clarification, stands separatory and take organic facies to carry out air-distillation under the vapo(u)rizing temperature less than 100 DEG C dense
The precipitation that contracts steams to no liquid, adds the making beating of a small amount of water, filters, i.e. prepares fluazinam after drying at less than 100 DEG C
Product, finished weight is 450g, then to use the HPLC of same detection condition to detect its purity content be 99.4%, molar yield
96.4%.Qualification result is with embodiment 1.
Embodiment 5
By 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.10 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, 8.0
The 2-methyltetrahydrofuran (moisture 0.5%) of molar sodium hydroxide (technical grade, purity content >=96.0%) and 400g is put
In tetra-mouthfuls of reaction bulbs of 2L, stirring reaction 20 hours at 30 DEG C.
Take 1 reactant liquor in probe tube, add 1 dilute hydrochloric acid and make the pH ＜ 6 of reactant liquor in acidity, then use acetonitrile as molten
Dilution agent reactant liquor is to 2ml, then takes wherein 1ml and carry out HPLC detection and use quantified by external standard method, measures and obtains in reactant liquor
Fluazinam content is 86.1%, and in reaction afterproduct, the concrete content of each component is shown in Table 1.The testing conditions of HPLC is with embodiment 1.
Then, it is dissolved in water to clarification, stands separatory and take organic facies to carry out air-distillation under the vapo(u)rizing temperature less than 100 DEG C dense
The precipitation that contracts steams to no liquid, adds the making beating of a small amount of water, filters, i.e. prepares fluazinam after drying at less than 100 DEG C
Product, finished weight is 364g, then to use the HPLC of same detection condition to detect its purity content be 96.2%, molar yield 78%.
Embodiment 6
Take 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.02 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, select
The 2-methyltetrahydrofuran (moisture 0.5%) of 2 mole of 85% potassium hydroxide and 300g is placed in tetra-mouthfuls of reaction bulbs of 2L,
Stirring reaction 18 hours at 20 DEG C.Course of reaction same as in Example 1, the HPLC of same detection condition is used to detect and adopt
With quantified by external standard method, measuring and obtaining fluazinam content in reactant liquor is 81.8%.The concrete content of each component in its reaction afterproduct
It is shown in Table 1.
Take 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.05 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, choosing
The 2-methyltetrahydrofuran (moisture 0.5%) selecting 6 mole of 85% potassium hydroxide and 400g is placed in tetra-mouthfuls of reaction bulbs of 2L,
Stirring reaction 12 hours at 40 DEG C.Use the HPLC detection of course of reaction same as in Example 1, same detection condition
And use quantified by external standard method, measuring and obtaining fluazinam content in reactant liquor is 95.2%.In its reaction afterproduct, each component is concrete
Content is shown in Table 1.
Meanwhile, take 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.02 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene,
Selecting 4 mole of 85% potassium hydroxide and oxolane (moisture 0.1%) to be placed in tetra-mouthfuls of reaction bulbs of 2L, at 25 DEG C, stirring is anti-
Answer 20 hours.Course of reaction same as in Example 1, the HPLC of same detection condition is used to detect and use quantified by external standard method,
Measuring and obtaining fluazinam content in reactant liquor is 89.2%.In its reaction afterproduct, the concrete content of each component is shown in Table 1.
Meanwhile, take 1.00 moles of 2-amido-3-5-trifluoro picolines, 1.05 mole 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene,
4 mole of 85% potassium hydroxide and DME (moisture 0.1%) is selected to be placed in tetra-mouthfuls of reaction bulbs of 2L, stirring reaction at 25 DEG C
20 hours.Course of reaction same as in Example 1, the HPLC of same detection condition is used to detect and use quantified by external standard method,
Measuring and obtaining fluazinam content in reactant liquor is 93.6%.In its reaction afterproduct, the concrete content of each component is shown in Table 1.
As shown in Table 1, when using different solvents to prepare fluazinam, although 2-methyltetrahydrofuran and oxolane, DME etc.
Belong to ether solvent together, but the effectiveness reacting this has notable difference, 2-methyltetrahydrofuran to be that solvent the reaction time is short, select
Property by-product (compound D) growing amount high, hydrolysis substantially few.From the point of view of pesticide original medicine, impurity is more means purification
Yield declines and product content declines.2-methyltetrahydrofuran be the reaction of solvent after post processing, molar yield is up to
To 98.4%.Data in 1-5 in conjunction with the embodiments, it is known that using 2-methyltetrahydrofuran is solvent, and it prepares the purity of fluazinam
Up to 99.8%.Meanwhile, when preparing fluazinam with 2-methyltetrahydrofuran for solvent, the kind of alkali and consumption are to reaction
Also there are large effect in conversion ratio and response time, and the inorganic base mated most with solvent 2-methyltetrahydrofuran in the present invention is hydrogen-oxygen
Change potassium.
Table 1
Embodiment 7
By using 2-methyltetrahydrofuran (moisture 0.5%) in embodiment 2,3 respectively, (moisture contains 2-methyltetrahydrofuran
Amount 3.7%) be that solvent carries out reacting the concrete content of each component in afterproduct, with patent WO2007060662,
Using other solvent to carry out reacting the concrete content of each component in afterproduct in WO2009054210 to compare, concrete data are shown in
Table 2.
Table 2
As shown in Table 2, prepare fluazinam and be better than, with 2-methyltetrahydrofuran, the patent solvent that has been reported for solvent, from fluazinam
The index such as content, the volume of production of compound D and other impurity summation all demonstrate its superiority.
So, the present invention effectively overcomes various shortcoming of the prior art and has high industrial utilization.
The principle of above-described embodiment only illustrative present invention and effect thereof, not for limiting the present invention.Any it is familiar with this skill
Above-described embodiment all can be modified under the spirit and the scope of the present invention or change by the personage of art.Therefore, such as
All that in art, tool usually intellectual is completed under without departing from disclosed spirit and technological thought etc.
Effect is modified or changes, and must be contained by the claim of the present invention.
Claims (10)
1. a preparation method for fluazinam, with 2-amido-3-5-trifluoro picoline and 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene
For raw material, with inorganic base as alkali, with 2-methyltetrahydrofuran as solvent, reaction prepares fluazinam.
The preparation method of fluazinam the most according to claim 1, it is characterised in that specifically include following steps:
1) 2-amido-3-5-trifluoro picoline, 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene, inorganic base, 2-first it are separately added into
Stirring reaction after the mixing of base oxolane；
2), after adding water and being dissolved to clarification, stand separatory and take organic facies and carry out distillation and concentration, precipitation, add the making beating of a small amount of water,
Filter, i.e. prepare fluazinam after drying.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 1) in, the described 2-chloro-5-of amino-3-
Trifluoromethyl pyridine is 0.95-1.20:1 with the molar ratio of 2,4-bis-chloro-3,5-dinitro-p-trifluorotoluene.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 1) in, described inorganic base is selected from carbon
Any one or more combination in acid potassium, sodium carbonate, cesium carbonate, potassium fluoride, sodium hydroxide, potassium hydroxide, Lithium hydrate.
The preparation method of fluazinam the most according to claim 4, it is characterised in that described inorganic base is potassium hydroxide；Described
2-amido-3-5-trifluoro picoline and potassium hydroxide mole ratio be 1:1-8.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 1) in, the described 2-chloro-5-of amino-3-
Trifluoromethyl pyridine is 1:0.5-20 with the mass ratio of 2-methyltetrahydrofuran.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 1) in, after described mixing, stirring is anti-
It is 2-20h, preferably 2-6h between Ying Shi.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 1) in, after described mixing, stirring is anti-
Temperature is answered to be-20-150 DEG C, preferably 20-80 DEG C.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 2) in, described distillation and concentration, de-
Molten for air-distillation concentrate and precipitation steam to no liquid；Described vapo(u)rizing temperature is less than 100 DEG C.
The preparation method of fluazinam the most according to claim 2, it is characterised in that step 2) in, described in be filtered into employing
The normal temperature and pressure that filter paper, filter cloth or filter screen are carried out filters；Described being dried is carried out at less than 100 DEG C.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108929264A (en) * | 2018-09-13 | 2018-12-04 | 岳晟 | A kind of preparation method of fluazinam |
| CN109988103A (en) * | 2017-12-29 | 2019-07-09 | 江苏扬农化工股份有限公司 | A method of synthesis fluazinam |
Citations (3)
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|---|---|---|---|---|
| WO2009017239A2 (en) * | 2007-08-02 | 2009-02-05 | Ishihara Sangyo Kaisha, Ltd. | Process for producing toluidine compound |
| WO2009054210A1 (en) * | 2007-10-24 | 2009-04-30 | Ishihara Sangyo Kaisha, Ltd. | Process for producing toluidine compound |
| CN101778824A (en) * | 2007-08-02 | 2010-07-14 | 石原产业株式会社 | Process for producing toluidine compound |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009017239A2 (en) * | 2007-08-02 | 2009-02-05 | Ishihara Sangyo Kaisha, Ltd. | Process for producing toluidine compound |
| CN101778824A (en) * | 2007-08-02 | 2010-07-14 | 石原产业株式会社 | Process for producing toluidine compound |
| WO2009054210A1 (en) * | 2007-10-24 | 2009-04-30 | Ishihara Sangyo Kaisha, Ltd. | Process for producing toluidine compound |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109988103A (en) * | 2017-12-29 | 2019-07-09 | 江苏扬农化工股份有限公司 | A method of synthesis fluazinam |
| CN108929264A (en) * | 2018-09-13 | 2018-12-04 | 岳晟 | A kind of preparation method of fluazinam |
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