CN104151233A - Preparation method of agricultural bactericide - Google Patents
Preparation method of agricultural bactericide Download PDFInfo
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- CN104151233A CN104151233A CN201410420257.2A CN201410420257A CN104151233A CN 104151233 A CN104151233 A CN 104151233A CN 201410420257 A CN201410420257 A CN 201410420257A CN 104151233 A CN104151233 A CN 104151233A
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- 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
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Abstract
The invention discloses a preparation method of an agricultural bactericide. The method includes following steps: carrying out a reaction between 3-isochromanone, which is used for a starting raw material, and an acetol of a formamide compound, performing hydrolysis to obtain 4-([alpha]-hydroxyl)-methylene-2-H-benzopyrane-3-(4H)-one, performing methylation to obtain 4-(methoxylmethylene)-3-isobenzopyrone, preparing (E)-2-(2-halomethyl)-3-methoxylmethyl acrylate from the 4-(methoxylmethylene)-3-isobenzopyrone in methanol, a third inert solvent and a halogenation reagent, and performing a reaction between the (E)-2-(2-halomethyl)-3-methoxylmethyl acrylate and 2-hydroxyl-6-trifluoromethylpyridine or 6-trifluoromethyl-2-pyridine alkoxide to obtain picoxystrobin. The method is short in reaction processes, is mild in conditions, is simple and convenient in post treatment, is less in waste gas, waste water and waste solid, is high in yield and is suitable for industrial production. Appearance of the agricultural bactericide is good and an external standard content of the agricultural bactericide is more than 98%.
Description
Technical field
The present invention relates to a kind of preparation method of disinfectant use in agriculture, belong to organic synthesis field.
Background technology
ZEN 90160 belongs to mitochondrial respiratory inhibitor, and its mechanism of action is by cytochrome b and C
1between transfer transport suppress mitochondrial breathing.The bacterial strain that 14-demethylation enzyme inhibitors, benzamides, dicarboxylic dihydrazides amine and benzimidazoles is produced to resistance is effective.Once ZEN 90160 is absorbed by blade, will in xylem, move, with current, in haulage system, flow; It also flows and in xylem, flows again after absorption enters blade from gas phase in the gas phase of blade surface.Without rain condition, descend with ZEN 90160 (250g a.i./hm
2) the spraying crop of processing and spraying is equally processed after 2h to be exposed to rainfall amount be 10mm, the crop that reaches 1h compares, result shows that the two is consistent to the prevention effect of Folium Hordei Vulgaris rot.Systemic activity and evaporation just because of ZEN 90160 are active, thereby after dispenser, effective constituent can effectively be reallocated and fully be transmitted, so ZEN 90160 has better therapeutic activity than commercial Azoxystrobin and oxime bacterium ester.
Be mainly used in preventing and treating foliage disease as leaf blight, leaf rust, glume blight, brown spot, Powdery Mildew etc., compare with existing strobilurin series bactericidal agent, wheat leaf blight, net blotch and moire disease are had to stronger result for the treatment of.
The preparation method of the synthetic ZEN 90160 intermediate of bibliographical information and product mainly contains at present:
(1) patent CN1105105 discloses the preparation method of a kind of 2-(6-5-flumethiazine-2-oxygen ylmethyl) phenylacetic acid methyl esters, first 3-isochromanome is become to double sodium salt by sodium-hydroxide treatment, after azeotropic water removing, uses
n-methyl-2-pyrrolidone is made solvent and is reacted with 2-chloro-6-trifluoromethylpyridine, then reacts and obtains intermediate with methyl-sulfate.
The method total recovery is low, needs column chromatography just can obtain pure intermediate, is unfavorable for the suitability for industrialized production of ZEN 90160.
(2) patent CN1168718 discloses a kind of preparation method of ZEN 90160, first 2-hydroxyl-6-5-flumethiazine is converted into pyridine alkoxide, under the condition existing at catalyzer, react with 2-chloromethylbenzene methyl acetate and obtain 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenylacetic acid methyl esters, react with methyl-formiate again and obtain 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenyl-acrolactic acid methyl esters, finally by methylating, obtain ZEN 90160.
The method has been used the lower methyl-formiate of boiling point, and large usage quantity, and industrial safety coefficient is low, be unfavorable for industrialization operation, also the present invention allow expensive 2-hydroxyl-6-5-flumethiazine intermediate first participate in reaction, consume large, cost is high, and the market competitiveness is low.
(3) patent CN103626691 describes the synthetic of ZEN 90160 in detail, take 3-isochromanome as starting raw material, through halogenation, obtain (2-halogenated methyl phenyl) methyl acetate, obtain 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenylacetic acid methyl esters with 6-trifluoromethyl-2 hydroxy pyrimidine reactant salt again, again with aldolization after hydrolysis obtain 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenyl-acrolactic acid methyl esters, finally by methylating, obtain ZEN 90160.
Above preparation method improves enol composite part in patent CN1168718, uses boiling point higher
n,N-dimethylformamide dimethyl acetal is made solvent, form enamine and through hydrolysis, obtain enol again, although raw material is easy to get, reactions steps is more, complex operation, catalyst levels is large and be difficult for reclaiming, be not suitable for scale operation, also the present invention allow expensive 2-hydroxyl-6-5-flumethiazine intermediate first participate in reaction, raw material consumption is large, cost is high, and the market competitiveness is low.
Find after deliberation, in above preparation method, be all that 2-hydroxyl-6-5-flumethiazine or its alkoxide are reacted to preparation 2-(6-5-flumethiazine-2-oxygen ylmethyl) phenylacetic acid methyl esters with 2-chloromethylbenzene methyl acetate and analogue thereof, the invention provides one and prepare ZEN 90160 with above route diverse ways, and the method reactions steps is short, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high, are applicable to suitability for industrialized production, product appearance is good, and external standard content is greater than 98%; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine intermediate finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
summary of the invention
The preparation method who the object of the present invention is to provide a kind of disinfectant use in agriculture, it is short that the present invention has reaction scheme, safety simple to operate, mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and cost significantly reduces, and has greatly improved the feature of the market competitiveness.
For achieving the above object, technical scheme of the present invention is:
A preparation method for disinfectant use in agriculture, comprises the steps:
1) get raw materials of compound 3-isochromanome (I), chemical formula is as follows, with the acetal of Carbox amide in the first inert solvent, under 10～120 ℃ of conditions, react 1-12h, then with acid or metal-salt or its hydrate, in the first inert solvent, be hydrolyzed and obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), chemical formula is as follows;
2) 4-step 1) being made (Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) is in the second inert solvent, add alkali and methylating reagent, under-10～60 ℃ of conditions, reaction 1～12h, reaction finishes by washing, extraction, distillation obtains the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), and chemical formula is as follows;
3) by step 2) the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) that makes is dissolved in methyl alcohol, the 3rd inert solvent and halide reagent, in-10～120 ℃, reaction 2～12h, reaction finishes to obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) by distillation; Or by step 2) the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) that makes is dissolved in the 3rd inert solvent and halide reagent, in-10～120 ℃, reaction 1～12h, after reaction finishes, distill halide reagent, drip and react with methyl alcohol to finishing again, through distillation, obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV), chemical formula is as follows;
4) get raw materials of compound 2-hydroxyl-6-5-flumethiazine (V), chemical formula is as follows, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) making with step 3) under alkaline condition in the 4th inert solvent 20～120 ℃, reaction 3～12h, obtains ZEN 90160; Or by raw materials of compound 2-hydroxyl-6-5-flumethiazine (V) at the 5th inert solvent and alkali, under 50～120 ℃ of conditions, react 5～10h, after distillation, obtain 6-trifluoromethyl-2-pyridine alkoxide (VI), chemical formula is as follows, in the 6th inert solvent, (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) and step 3) make, in 20～120 ℃, reaction 3～12h, obtains ZEN 90160; After reaction finishes, in reaction solution, add appropriate water, then obtain ZEN 90160 solution through extraction, fractionation by distillation solvent obtains the thick product of ZEN 90160; The thick product purification of ZEN 90160 is obtained to disinfectant use in agriculture ZEN 90160 sterling.
Described step 1) in, temperature of reaction is preferably 80～120 ℃, and the reaction times is preferably 3～4h; Described step 2) in, temperature of reaction is preferably 0～40 ℃, and the reaction times is preferably 3～4h; In described step 3), temperature of reaction is preferably-10～80 ℃, and the reaction times is preferably 3～5h; (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make under alkaline condition in the 4th inert solvent, temperature of reaction is preferably 20～50 ℃, and the reaction times is preferably 7～9h; In described step 4), 2-hydroxyl-6-5-flumethiazine (V), at the 5th inert solvent and alkali, preferably reacts 4～8h under 90～120 ℃ of conditions; In described step 4) in the 6th inert solvent, (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) and step 3) make, be preferable over 20～50 ℃, reaction 7～9h.
In described step 1) the first inert solvent adopt normal hexane, sherwood oil, methyl tertiary butyl ether, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), glycol dimethyl ether, ethylene glycol diethyl ether, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; The acetal of described Carbox amide is a kind of in dimethylformamide dimethyl acetal, dimethyl formamide diethyl acetal, dimethyl formamide dibutyl acetal, dimethyl formamide dibenzyl acetal and diethylformamide diethyl acetal; Described acid is a kind of in hydrochloric acid, sulfuric acid, tosic acid monohydrate and acetic acid; Described metal-salt or its hydrate are a kind of in titanium tetrachloride, titanium tetrabromide, Iron(III) chloride hexahydrate, Nickel dichloride hexahydrate, six hydration aluminum chlorides.
Described step 2) in the second inert solvent adopt toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described step 2) in, alkali adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, and the mol ratio of alkali and 3-isochromanome (I) is 0.2～2.0:1; Described methylating reagent adopts a kind of in methyl iodide, methyl-sulfate, methylcarbonate, and the mol ratio of methylating reagent and 3-isochromanome (I) is 1.0～3.0:1;
In described step 3), the 3rd inert solvent adopts normal hexane, sherwood oil, methylene dichloride, 1, a kind of in 2-ethylene dichloride, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus; Described halide reagent adopts a kind of in thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus, and the mol ratio of halide reagent and 4-(methoxy methyl thiazolinyl)-different benzopyrone of 3-is 1.0～4.0:1; In described (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV), halogen adopts chlorine or bromine;
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make alkali during with the 4th inert solvent reaction under alkaline condition adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C
1-C
5straight chain or the alkoxide of side chain in a kind of; Described the 4th inert solvent adopt toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described the 5th inert solvent adopts a kind of in toluene, chlorobenzene, dimethylbenzene, trimethylbenzene, hexanaphthene;
In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C
1-C
5straight chain or the alkoxide of side chain in a kind of; In described 6-trifluoromethyl-2-pyridine alkoxide (VI), M is atoms metal; Described the 6th inert solvent adopt toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide.
Described step 2) in the second inert solvent preferably adopt toluene, dimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, acetonitrile,
n,Na kind of in-dimethyl formamide and dimethyl sulfoxide (DMSO); Described step 2) in, alkali preferably adopts a kind of in sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 3-isochromanome (I) is 0.2～1.5:1; Described methylating reagent preferably adopts methyl iodide or methyl-sulfate;
In described step 3), the 3rd inert solvent preferably adopts sherwood oil, methylene dichloride, 1, a kind of in 2-ethylene dichloride, toluene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus;
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) alkali when the 4th inert solvent reaction under alkaline condition that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make preferably adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 0.2～2.0:1; Described the 4th inert solvent preferably adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,Na kind of in-dimethyl formamide, dimethyl sulfoxide (DMSO); Described the 5th inert solvent preferably adopts a kind of in toluene, chlorobenzene, dimethylbenzene, trimethylbenzene, hexanaphthene;
In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction preferably adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1～3.0:1, atoms metal preferably adopts a kind of in lithium, sodium or potassium in described 6-trifluoromethyl-2-pyridine alkoxide (VI); Described the 6th inert solvent preferably adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,Na kind of in-dimethyl formamide, dimethyl sulfoxide (DMSO).
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make alkali when the 4th inert solvent reaction under alkaline condition further preferably adopts a kind of in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 0.2～1.5:1; In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction further preferably adopts a kind of in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1～2:1.
Chemical equation of the present invention is as follows:
The invention has the beneficial effects as follows: the present invention makes key intermediate (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) for starting raw material through polystep reaction by 3-isochromanome (I), then utilize (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) further to react preparation ZEN 90160 with 2-hydroxyl-6-5-flumethiazine (V) or its alkoxide (VI).It is short that the present invention has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment
Following examples result is used for further illustrating the present invention, but does not mean that restriction the present invention.Intermediate source is as follows: intermediate 3-isochromanome and 2-hydroxyl-6-5-flumethiazine are purchased from lark prestige Science and Technology Ltd..
Embodiment 1
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, as shown in table 1, comprise the steps: 1) 3-isochromanome (I) 40 g (0. 27 mo1), add 150 mL dimethylformamide dimethyl acetals (DMFDMA), heat up 40 ℃ to back flow reaction 4 h, analysis shows that reaction stops, decompression steams solvent, add 200mL toluene and 21.4g (0. 09mo1) Nickel dichloride hexahydrate, stirring at room 3h, filter solid 30mL toluene wash.Filtrate is concentrated obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly can react for next step.
2) step 1) in obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) and be dissolved in 150mL dimethyl sulfoxide (DMSO), under stirring, add wherein salt of wormwood 41.4 g (0.3mo1), methyl-sulfate 50.4g (0.4mo1), control 40 ℃ of temperature, react after 3 hours, after reaction finishes, add wherein 150 mL water, water is extracted with ethyl acetate (3*50 mL), merge organic phase, with anhydrous magnesium sulfate drying, filter and collect filtrate, decompression steams solvent, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 50.0 g, content 93.8%, yield 91.5%.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 50.0g be dissolved in 100mL methyl alcohol, in 1h, in 10 ℃, add 50mL thionyl chloride, 10 ℃ of reaction 3h, after analysis shows to have reacted, by mixture concentrating under reduced pressure, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, through recrystallization, obtain 59.1g, content 92.1%, yield 91.6 %.
4) in reaction flask, add successively 2-hydroxyl-6-5-flumethiazine 20.0 g (0.12 mol) and 100 mL
n,N-dimethyl formamide, add wherein again 6.0 g (0.15 mol) sodium hydroxide and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 30.1 g (0.13 mol), 40 ℃ of reaction 8h, after reaction finishes, in reaction solution, add 100 mL water, add wherein 150 mL ethyl acetate, separated organic phase, water is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, recrystallization obtains 36.3g ZEN 90160, the concentrated continuation of mother liquor crystallization obtains 6.3 g ZEN 90160, amount to 42.6g, content 98.5% (external standard method detection), yield 93.2%.It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 2
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 1, and its difference is: described step 2), the mol ratio of alkali and 3-isochromanome (I) is 1:1; The mol ratio of methylating reagent and 3-isochromanome (I) is 1.5:1; The mol ratio of halide reagent and the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is 1.5:1; In described step 4), the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1.1:1; Other differences are as shown in table 1.Crude product obtains 74.2g ZEN 90160 through crystallization, and mother liquor is concentrated to be continued crystallization and obtain 9g ZEN 90160, amounts to 83.2g, content 98.4% (external standard method detection), it is benchmark that yield 82%(be take starting raw material 3-isochromanome (I) 40g).It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 3
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 1, and its difference is: described step 2), the mol ratio of alkali and 3-isochromanome (I) is 1:1; The mol ratio of methylating reagent and 3-isochromanome (I) is 1.5:1; The mol ratio of halide reagent and the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is 1.5:1; In described step 4), the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1.2:1; Other differences are as shown in table 1.Crude product obtains 76g ZEN 90160 through crystallization, and mother liquor is concentrated to be continued crystallization and obtain 9.6g ZEN 90160, amounts to 85.6g, content 98.2% (external standard method detection), it is benchmark that yield 84.8%(be take starting raw material 3-isochromanome (I) 40g).It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 4
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 1, described step 2) in the mol ratio of alkali and 3-isochromanome (I) be 1:1; The mol ratio of methylating reagent and 3-isochromanome (I) is 2.0:1; The mol ratio of halide reagent and the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is 2.0:1; In described step 4), the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1.1:1; Other differences are as shown in table 1.Crude product obtains 76.6g ZEN 90160 through crystallization, and mother liquor is concentrated to be continued crystallization and obtain 7g ZEN 90160, amounts to 83.6g, content 98.6% (external standard method detection), it is benchmark that yield 83.2%(be take starting raw material 3-isochromanome (I) 40g).It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 5
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, as shown in table 2, comprise the steps: 1) 3-isochromanome (I) 40 g (0. 27 mo1), add 150 mL dimethylformamide dimethyl acetals (DMFDMA), heat up 110 ℃ to back flow reaction 3h, analysis shows that reaction stops, decompression steams solvent, adds 200mL toluene and 19 g (0. 10mo1) titanium tetrachloride, stirring at room 3 hours, filter solid 30mL toluene wash.Filtrate is concentrated obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly can react for next step.
2) step 1) in obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) and be dissolved in 150mL
n,N-dimethyl formamide, under stirring, add wherein sodium carbonate 30.5g (0. 29mo1), methyl-sulfate 37. 8 g (0. 3mo1), control 20 ℃ of temperature, after reaction 4h, after having reacted, add wherein 150 mL water, water is extracted with ethyl acetate (3*50 mL), merges organic phase, with anhydrous magnesium sulfate drying, filter and collect filtrate, decompression steams solvent, obtains the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 48.8 g, content 95.3%, yield 90.6%.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 48.8 g be dissolved in the mixed solution of 60mL methyl alcohol and 50mL toluene, be cooled to 0 ℃ of left and right, control temperature and add 34.5 g (0. 29mo1) thionyl chloride, add rear nature to room temperature reaction 4h, after analysis shows to have reacted, by mixture concentrating under reduced pressure, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, through recrystallization, obtain 57.7g, content 94.7%, yield 92.8%.
4) to being equipped with in the reaction flask of division box, add successively 2-hydroxyl-6-5-flumethiazine (V) 20.0 g (0.12 mol) and toluene 100 mL, add sodium hydroxide 4.9 g (0.12 mol), heat up 110 ℃ to back flow reaction 8h, separate the water of generation simultaneously.Reaction finishes rear Distillation recovery toluene, in reaction flask, add 80 mL dimethyl sulfoxide (DMSO) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 30.1 g (0.13 mol), 40 ℃ of reaction 3 h, after reaction finishes, reaction solution is poured in 100 mL water, add wherein 150 mL ethyl acetate, separated organic phase, water is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, recrystallization obtains 36.7g ZEN 90160, the concentrated continuation of mother liquor crystallization obtains 5.5 g ZEN 90160, amount to 42.2g, content 98.7% (external standard method detection), yield 92.6%.It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 6
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, as shown in table 2, comprise the steps: 1) 3-isochromanome (I) 40 g (0. 27 mo1), add 150 mL dimethylformamide dimethyl acetals (DMFDMA), heat up 80 ℃ to back flow reaction 5h, analysis shows that reaction stops, and decompression steams solvent, adds 200mL
n,N-dimethyl formamide and 50 mL hydrochloric acid, 45 ℃ are stirred 3h, after reaction finishes, in reaction solution, add 100 mL water, add wherein 150 mL ethyl acetate, separated organic phase, water is extracted with ethyl acetate (3*50 mL), merges organic phase, and decompression steams solvent, obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly can react for next step.
2) step 1) in obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) and be dissolved in 150mL
n,N-dimethyl formamide, under stirring, add wherein salt of wormwood 37.3 g (0. 27mo1), methyl-sulfate 37. 8 g (0. 3mo1), control 0 ℃ of temperature, react after 7 hours, after reaction finishes, add wherein 150 mL water, water is extracted with ethyl acetate (3*50 mL), merges organic phase, with anhydrous magnesium sulfate drying, decompression steams solvent, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 50.0 g, content 93.0%, yield 90.7%.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) 50.0 g be dissolved in 200mL methylene dichloride, in 1h, in-5 ℃, add 44 g (0. 30 mo1) thionyl chloride, room temperature reaction 5h, analysis shows that reaction stops, by mixture underpressure distillation, distilled and in backward reaction flask, dripped 150mL methyl alcohol, room temperature reaction 3 h, after reaction finishes, methyl alcohol is removed in decompression, obtains compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, through recrystallization, obtains 67.1g, content 95.7%, yield 92.0%.
4) to being equipped with in the reaction flask of division box, add successively 2-hydroxyl-6-5-flumethiazine 20.0 g (0.12 mol) and dimethylbenzene 100 mL, add potassium hydroxide 6.8 g (0.12 mol), heat up 110 ℃ to reacting 6h.Reaction finishes rear Distillation recovery dimethylbenzene, in reaction flask, adds 80 mL
n,N-dimethyl formamide and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 37.1 g (0.13 mol), 30 ℃ of reaction 8h, after reaction finishes, reaction solution is poured in 100 mL water, add wherein 150 mL ethyl acetate, separated organic phase, water is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, and recrystallization obtains 35.4g ZEN 90160, the concentrated continuation of mother liquor crystallization obtains 5.7 g ZEN 90160, amount to 41.1g, content 98.9% (external standard method detection), yield 92.2%.It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 7
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 5, described step 2) in the mol ratio of alkali and 3-isochromanome (I) be 1.5:1; The mol ratio of methylating reagent and 3-isochromanome (I) is 3.0:1; The mol ratio of halide reagent and the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is 4.0:1; In described step 4), the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 2.0:1; Other differences are as shown in table 2.Crude product obtains 78.6g ZEN 90160 through crystallization, and mother liquor is concentrated to be continued crystallization and obtain 7.2g ZEN 90160, amounts to 85.8g, content 98.4% (external standard method detection), it is benchmark that yield 85.1%(be take starting raw material 3-isochromanome (I) 40g).It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Embodiment 8
The preparation method of a kind of disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 6, described step 2) in the mol ratio of alkali and 3-isochromanome (I) be 1.1:1; The mol ratio of methylating reagent and 3-isochromanome (I) is 2:1; The mol ratio of halide reagent and the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is 3:1; In described step 4), the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1:1; Other differences are as shown in table 2.Crude product obtains 74.5g ZEN 90160 through crystallization, and mother liquor is concentrated to be continued crystallization and obtain 8.7g ZEN 90160, amounts to 83.2g, content 98.8% (external standard method detection), it is benchmark that yield 82.9%(be take starting raw material 3-isochromanome (I) 40g).It is short that the present embodiment has reaction scheme, safety simple to operate, and mild condition, aftertreatment is simple and easy to do, and the three wastes are few, and yield is high and purity is high and the production method of applicable extensive upper ZEN 90160 of producing; Moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume significantly and reduce, cost significantly reduces, and has greatly improved the market competitiveness.
Table 1
Table 2
| Embodiment | The first inert solvent | Carbox amide | Acid | Metal-salt or its hydrate | The second inert solvent | Step 2) alkali in | Methylating reagent |
| 5 | Toluene | Dimethylformamide dimethyl acetal | ? | Tetrahydro-titanium | N,N-dimethyl formamide | Sodium carbonate | Methyl-sulfate |
| 6 | N,N-dimethyl formamide | Dimethylformamide dimethyl acetal | Hydrochloric acid | ? | N,N-dimethyl formamide | Salt of wormwood | Methyl-sulfate |
| 7 | Methyl tertiary butyl ether | Diethylformamide diethyl acetal | Tosic acid monohydrate | ? | Methyl tertiary butyl ether | Potassium hydroxide | Methyl iodide |
| 8 | Trimethylbenzene | Dimethyl formamide dibutyl acetal | ? | Ferric chloride hexahydrate | Acetonitrile | Sodium hydroxide | Methyl-sulfate |
| Embodiment | The 3rd inert solvent | Halide reagent | The alkali of using during with the 4th inert solvent reaction | The 4th inert solvent | The 5th inert solvent | The alkali of using during with the 5th inert solvent reaction | The 6th inert solvent |
| 5 | Toluene | Thionyl chloride | ? | ? | Toluene | Sodium hydroxide | Dimethyl sulfoxide (DMSO) |
| 6 | Methylene dichloride | Thionyl chloride | ? | ? | Dimethylbenzene | Potassium hydroxide | N,N-dimethyl formamide |
| 7 | Tribromo oxygen phosphorus | Thionyl bromide | ? | ? | Chlorobenzene | Sodium methylate | Acetonitrile |
| 8 | Thionyl bromide | Thionyl bromide | ? | ? | Hexanaphthene | Potassium hydroxide | Tetrahydrofuran (THF) |
Claims (5)
1. a preparation method for disinfectant use in agriculture, is characterized in that, comprises the steps:
1) get raw materials of compound 3-isochromanome (I), chemical formula is as follows, with the acetal of Carbox amide in the first inert solvent, under 10～120 ℃ of conditions, react 1-12h, then with acid or metal-salt or its hydrate, in the first inert solvent, be hydrolyzed and obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), chemical formula is as follows;
2) 4-step 1) being made (Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) is in the second inert solvent, add alkali and methylating reagent, under-10～60 ℃ of conditions, reaction 1～12h, reaction finishes by washing, extraction, distillation obtains the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), and chemical formula is as follows;
3) by step 2) the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) that makes is dissolved in methyl alcohol, the 3rd inert solvent and halide reagent in-10～120 ℃, reaction 2～12h, reaction finishes to obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) by distillation; Or by step 2) the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) that makes is dissolved in the 3rd inert solvent and halide reagent, in-10～120 ℃, reaction 1～12h, after reaction finishes, distill halide reagent, drip and react with methyl alcohol to finishing again, through distillation, obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV), chemical formula is as follows;
4) get raw materials of compound 2-hydroxyl-6-5-flumethiazine (V), chemical formula is as follows, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) making with step 3) under alkaline condition in the 4th inert solvent 20～120 ℃, reaction 3～12h, obtains ZEN 90160; Or by raw materials of compound 2-hydroxyl-6-5-flumethiazine (V) at the 5th inert solvent and alkali, under 50～120 ℃ of conditions, react 5～10h, after distillation, obtain 6-trifluoromethyl-2-pyridine alkoxide (VI), chemical formula is as follows, in the 6th inert solvent, (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) and step 3) make, in 20～120 ℃, reaction 3～12h, obtains ZEN 90160; After reaction finishes, in reaction solution, add appropriate water, then obtain ZEN 90160 solution through extraction, fractionation by distillation solvent obtains the thick product of ZEN 90160; The thick product purification of ZEN 90160 is obtained to disinfectant use in agriculture ZEN 90160 sterling.
。
2. the preparation method of a kind of disinfectant use in agriculture as claimed in claim 1, is characterized in that, described step 1) in temperature of reaction be 80～120 ℃, the reaction times is 3～4h; Described step 2) in, temperature of reaction is 0～40 ℃, and the reaction times is preferably 3～4h; In described step 3), temperature of reaction is-10～80 ℃, and the reaction times is 3～5h; (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make under alkaline condition in the 4th inert solvent, temperature of reaction is 20～50 ℃, and the reaction times is 7～9h; In described step 4), 2-hydroxyl-6-5-flumethiazine (V), at the 5th inert solvent and alkali, reacts 4～8h under 90～120 ℃ of conditions; In described step 4), in the 6th inert solvent, 6-trifluoromethyl-2-pyridine alkoxide (VI) and (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that step 3) makes, in 20～50 ℃, react 7～9h.
3. the preparation method of a kind of disinfectant use in agriculture according to claim 1, it is characterized in that, in described step 1) the first inert solvent adopt normal hexane, sherwood oil, methyl tertiary butyl ether, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), glycol dimethyl ether, ethylene glycol diethyl ether, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; The acetal of described Carbox amide is a kind of in dimethylformamide dimethyl acetal, dimethyl formamide diethyl acetal, dimethyl formamide dibutyl acetal, dimethyl formamide dibenzyl acetal and diethylformamide diethyl acetal; Described acid is a kind of in hydrochloric acid, sulfuric acid, tosic acid monohydrate and acetic acid; Described metal-salt or its hydrate are a kind of in titanium tetrachloride, titanium tetrabromide, Iron(III) chloride hexahydrate, Nickel dichloride hexahydrate, six hydration aluminum chlorides; Described step 2) in the second inert solvent adopt toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described step 2) in, alkali adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, and the mol ratio of alkali and 3-isochromanome (I) is 0.2～2.0:1; Described methylating reagent adopts a kind of in methyl iodide, methyl-sulfate, methylcarbonate, and the mol ratio of methylating reagent and 3-isochromanome (I) is 1.0～3.0:1;
In described step 3), the 3rd inert solvent adopts normal hexane, sherwood oil, methylene dichloride, 1, a kind of in 2-ethylene dichloride, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus; Described halide reagent adopts a kind of in thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus, and the mol ratio of halide reagent and 4-(methoxy methyl thiazolinyl)-different benzopyrone of 3-is 1.0～4.0:1; In described (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV), halogen adopts chlorine or bromine;
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make alkali during with the 4th inert solvent reaction under alkaline condition adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C
1-C
5straight chain or the alkoxide of side chain in a kind of; Described the 4th inert solvent adopt toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described the 5th inert solvent adopts a kind of in toluene, chlorobenzene, dimethylbenzene, trimethylbenzene, hexanaphthene;
In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C
1-C
5straight chain or the alkoxide of side chain in a kind of; In described 6-trifluoromethyl-2-pyridine alkoxide (VI), M is atoms metal; Described the 6th inert solvent adopt toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
na kind of in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide.
4. the preparation method of a kind of disinfectant use in agriculture according to claim 3, is characterized in that:
Described step 2) in the second inert solvent adopt toluene, dimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, acetonitrile,
n,Na kind of in-dimethyl formamide and dimethyl sulfoxide (DMSO); Described step 2) in, alkali adopts a kind of in sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 3-isochromanome (I) is 0.2～1.5:1; Described methylating reagent adopts methyl iodide or methyl-sulfate;
In described step 3), the 3rd inert solvent adopts sherwood oil, methylene dichloride, 1, a kind of in 2-ethylene dichloride, toluene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus;
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make alkali when the 4th inert solvent reaction under alkaline condition adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 0.2～2.0:1; Described the 4th inert solvent adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,Na kind of in-dimethyl formamide, dimethyl sulfoxide (DMSO); Described the 5th inert solvent adopts a kind of in toluene, chlorobenzene, dimethylbenzene, trimethylbenzene, hexanaphthene;
In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction adopts a kind of in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium methylate, sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1～3.0:1, atoms metal adopts a kind of in lithium, sodium or potassium in described 6-trifluoromethyl-2-pyridine alkoxide (VI); Described the 6th inert solvent adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,Na kind of in-dimethyl formamide, dimethyl sulfoxide (DMSO).
5. the preparation method of a kind of disinfectant use in agriculture according to claim 4, is characterized in that,
(E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) make alkali when the 4th inert solvent reaction under alkaline condition adopts a kind of in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 0.2～1.5:1;
In described step 4), the alkali of 2-hydroxyl-6-5-flumethiazine (V) when the 5th inert solvent and alkali reaction adopts a kind of in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood, and the mol ratio of alkali and 2-hydroxyl-6-5-flumethiazine (V) is 1～2:1.
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| CN107382722A (en) * | 2017-08-08 | 2017-11-24 | 江苏克胜集团股份有限公司 | A kind of synthetic method of disinfectant use in agriculture ZEN 90160 intermediate |
| CN108558818A (en) * | 2018-04-28 | 2018-09-21 | 帕潘纳(北京)科技有限公司 | A kind of preparation method of methoxy methylene based compound |
| CN108821974A (en) * | 2018-08-17 | 2018-11-16 | 中国科学院兰州化学物理研究所 | A kind of preparation method of alkoxy acrylic ester |
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| GB2546498A (en) * | 2016-01-19 | 2017-07-26 | Rotam Agrochem Int Co Ltd | Novel crystalline form of picoxystrobin, method of preparing and use of the same |
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| CN107382722A (en) * | 2017-08-08 | 2017-11-24 | 江苏克胜集团股份有限公司 | A kind of synthetic method of disinfectant use in agriculture ZEN 90160 intermediate |
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| CN108558818B (en) * | 2018-04-28 | 2020-08-28 | 帕潘纳(北京)科技有限公司 | Preparation method of methoxymethyl alkenyl compound |
| CN110467567A (en) * | 2018-05-09 | 2019-11-19 | 南通泰禾化工股份有限公司 | A kind of preparation method of ZEN 90160 |
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| CN108821974B (en) * | 2018-08-17 | 2020-10-27 | 中国科学院兰州化学物理研究所 | Preparation method of alkoxy acrylate |
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Application publication date: 20141119 |