CN104230794A - Method for synthesizing high-efficiency green agriculture bactericide - Google Patents
Method for synthesizing high-efficiency green agriculture bactericide Download PDFInfo
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- 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 method for synthesizing high-efficiency green agriculture bactericide. The method comprises the following steps: preparing 4-(alpha-hydroxyl) methylene-2-H-benzopyran-3-(4H)-ketone by taking 3-isodihydrocoumarin as an initial raw material, performing methylation to obtain 4-(methoxy-methylene)-3-isobenzopyrone, reacting 4-(methoxy-methylene)-3-isobenzopyrone with a halogenations reagent and methanol to obtain (E)-2-(2-halogen methyl phenyl)-3-methoxy-methyl acrylate, and reacting (E)-2-(2-halogen methyl phenyl)-3-methoxy-methyl acrylate with 2-hydroxyl-6-trifluoromethyl picoline or 6-trifluoromethyl-2-pyridine alcoholate, thereby obtaining picoxystrobin. The method is short in reaction step, gentle in condition, simple, convenient and feasible in aftertreatment, less in waste water, waste gas and waste residue, low in cost, high in yield, applicable to industrialization production and good in product appearance, and the external standard content is greater than 98%.
Description
Technical field
The present invention relates to a kind of synthetic method of efficient green 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.Bacterial strain 14-demethylation enzyme inhibitors, benzamides, dicarboxylic dihydrazides amine and benzimidazoles being produced to resistance is effective.ZEN 90160, once be absorbed by blade, will move, flow with current in haulage system in xylem; It also flows and flows in xylem again after absorption enters blade from gas phase in the gas phase of blade surface.Descend with ZEN 90160 (250g a.i./hm without rain condition
2) spraying process crop and 2h after process of spraying equally is exposed to rainfall amount is 10mm, reaches the crop of 1h and compare, result shows that the two is consistent to the prevention effect of Folium Hordei Vulgaris rot.Just because of systemic activity and the evaporate active of ZEN 90160, thus after dispenser, effective constituent can effectively be reallocated and fully transmit, and therefore 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., compared with existing strobilurin series bactericidal agent, have stronger result for the treatment of to wheat leaf blight, net blotch and moire disease.
The preparation method of current bibliographical information synthesis ZEN 90160 intermediate and product mainly contains:
(1) patent CN1105105 discloses the preparation method of a kind of 2-(6-5-flumethiazine-2-oxygen ylmethyl) phenylacetate, first 3-isochromanome sodium-hydroxide treatment is become double sodium salt, uses after azeotropic water removing
n-methyl-2-pyrrolidone makees solvent and 2-chloro-6-trifluoromethylpyridine reacts, and is then obtained by reacting 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, be obtained by reacting 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenylacetate with 2-chloromethylbenzene methyl acetate under catalyzer existent condition, being obtained by reacting 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenyl-acrolactic acid methyl esters again with methyl-formiate, obtaining ZEN 90160 finally by methylating.
The method has used the lower methyl-formiate of boiling point, and large usage quantity, industrial safety coefficient is low, be unfavorable for industrial operation, moreover the present invention allows 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.
(3) patent CN103626691 describes the synthesis of ZEN 90160 in detail, with 3-isochromanome for starting raw material, (2-halomethylphenyl) methyl acetate is obtained through halogenation, 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenylacetate is obtained again with 6-trifluoromethyl-2 hydroxy pyrimidine reactant salt, being hydrolyzed and obtaining 2-[2 '-(6 '-5-flumethiazine-2-oxygen base) methyl] phenyl-acrolactic acid methyl esters again with after aldolization, obtaining ZEN 90160 finally by methylating.
Above preparation method improves enol composite part in patent CN1168718, uses boiling point higher
n,N-dimethylformamide dimethyl acetal makes solvent, form enamine and obtain enol through hydrolysis again, although raw material is easy to get, reactions steps is more, complex operation, catalyst levels greatly and not easily reclaim, be not suitable for scale operation, moreover the present invention allows 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, all 2-hydroxyl-6-5-flumethiazine or its alkoxide and 2-chloromethylbenzene methyl acetate and analogue thereof are reacted prepare 2-(6-5-flumethiazine-2-oxygen ylmethyl) phenylacetate in above preparation method, 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, yield is high, be applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consume and significantly reduce, cost significantly reduces, substantially increase the market competitiveness.
summary of the invention
The object of the present invention is to provide a kind of synthetic method of efficient green disinfectant use in agriculture, it is short that the present invention has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, and the three wastes are few, yield is high and purity is high, be 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 finally participate in reaction, consume and significantly reduce, cost significantly reduces, and substantially increases the market competitiveness.
For achieving the above object, technical scheme of the present invention is:
A synthetic method for efficient green disinfectant use in agriculture, comprises the steps:
1) raw materials of compound 3-isochromanome (I) is got, chemical formula is as follows, be dissolved in the first inert solvent, under-10 ~ 100 DEG C of conditions, add alkoxide anion source, then add alkyl formate or formic acid aryl ester, under-10 ~ 60 DEG C of conditions, reaction 1 ~ 12h, through acidifying after reaction terminates, extraction, distillation obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), and chemical formula is as follows;
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) step 1) obtained is in the second inert solvent, add alkali and methylating reagent, under-10 ~ 60 DEG C of conditions, reaction 1 ~ 12h, through washing after reaction terminates, extraction, distillation obtains the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), and chemical formula is as follows;
3) by step 2) the obtained 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is dissolved in methyl alcohol, the 3rd inert solvent and halide reagent, in-10 ~ 120 DEG C, reaction 2 ~ 12h, obtains (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) through distillation after reaction terminates; Or by step 2) the obtained 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is dissolved in the 3rd inert solvent and halide reagent, in-10 ~ 120 DEG C, reaction 1 ~ 12h, after reaction terminates, distill halide reagent, dripping reacts to terminating with methyl alcohol again, and obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) through distillation, chemical formula is as follows;
4) raw materials of compound 2-hydroxyl-6-5-flumethiazine (V) is got, chemical formula is as follows, with obtained (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) of step 3) in the 4th inert solvent 20 ~ 120 DEG C in the basic conditions, 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, 5 ~ 10h is reacted under 50 ~ 120 DEG C of conditions, 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained after distillation, chemical formula is as follows, in the 6th inert solvent, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained with step 3), in 20 ~ 120 DEG C, reaction 3 ~ 12h, obtains ZEN 90160; After reaction terminates, in reaction solution, add appropriate water, then obtain ZEN 90160 solution through extraction, fractionation by distillation solvent obtains the thick product of ZEN 90160; Thick for ZEN 90160 product purification is obtained efficient green disinfectant use in agriculture ZEN 90160 sterling.
Described step 1) in 3-isochromanome (I) be dissolved in the first inert solvent after preferably at 0 ~ 60 DEG C, add alkoxide anion source; Add alkyl formate or formic acid aryl ester again, preferably at 0 ~ 60 DEG C of reaction 3 ~ 4h; Described step 2) in temperature of reaction be preferably 0 ~ 40 DEG C, the reaction times is preferably 3 ~ 4h; In described step 3), temperature of reaction is preferably-10 ~ 80 DEG C, and the reaction times is preferably 3 ~ 5h; (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) obtain is in the basic conditions in the 4th inert solvent, temperature of reaction is preferably 20 ~ 50 DEG C, and the reaction times is preferably 7 ~ 9h; In described step 4), 2-hydroxyl-6-5-flumethiazine (V) is at the 5th inert solvent and alkali, preferably under 90 ~ 120 DEG C of conditions, reacts 4 ~ 8h; In described step 4) in the 6th inert solvent, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained with step 3), be preferable over 20 ~ 50 DEG C, reaction 7 ~ 9h.
In described step 1) 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,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described alkoxide anion source adopts the C of sodium, potassium, calcium, magnesium
2-C
5straight chain or side chain alkoxide in one; Alkyl in described alkyl formate is C
1-C
10straight chain, side chain, have or there is no the one in substituent naphthenic hydrocarbon, and the mol ratio of alkyl formate and 3-isochromanome (I) is 1.0 ~ 5.0:1, in described formic acid aryl ester, aryl is have or do not have the one in substituent phenyl ring, hetero-aromatic ring, and the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 1.0 ~ 5.0:1;
Described step 2) in 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,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described step 2) in alkali adopt sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium bicarbonate, saleratus, sodium methylate, one in sodium ethylate, and the mol ratio of alkali and 3-isochromanome (I) is 0.2 ~ 2.0:1; Described methylating reagent adopts the one 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 the one in normal hexane, sherwood oil, methylene dichloride, 1,2-ethylene dichloride, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus; Described halide reagent adopts the one in thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus, and the mol ratio of halide reagent and the different benzopyrone of 4-(methoxy methyl thiazolinyl)-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 the phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C with alkali during the 4th inert solvent reaction in the basic conditions
1-C
5straight chain or side chain alkoxide in one; Described 4th inert solvent employing toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described 5th inert solvent adopts the one of 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 side chain alkoxide in one; In described 6-trifluoromethyl-2-pyridine alkoxide (VI), M is atoms metal; Described 6th inert solvent employing toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide.
In described step 1) the first inert solvent preferably adopt methyl tertiary butyl ether, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), glycol dimethyl ether, ethylene glycol diethyl ether, acetonitrile,
n,None in-dimethyl formamide and dimethyl sulfoxide (DMSO).Described alkoxide anion source preferably adopts the one in sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, propyl carbinol sodium, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkoxide anion source and 3-isochromanome (I) is 1.0 ~ 3.0:1; Described alkyl formate preferably adopts the one in methyl-formiate, ethyl formate, n-propyl formate, isopropyl formate, n-buty formate or t-butyl formate; Described formic acid aryl ester preferably adopts phenyl formate or benzyl formate, and the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 1.0 ~ 3.0:1;
Described step 2) in the second inert solvent preferably adopt toluene, dimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, acetonitrile,
n,None in-dimethyl formamide and dimethyl sulfoxide (DMSO); Described step 2) in alkali preferably adopt one 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 the one in sherwood oil, methylene dichloride, 1,2-ethylene dichloride, toluene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus;
The alkali of (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) in the basic conditions when the 4th inert solvent reaction that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) preferably adopts the one 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 4th inert solvent preferably adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,None in-dimethyl formamide, dimethyl sulfoxide (DMSO); Described 5th inert solvent preferably adopts the one 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 the one 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, in described 6-trifluoromethyl-2-pyridine alkoxide (VI), atoms metal preferably adopts the one in lithium, sodium or potassium; Described 6th inert solvent preferably adopt toluene, tetrahydrofuran (THF), acetonitrile,
n,None in-dimethyl formamide, dimethyl sulfoxide (DMSO).
In described step 1), alkoxide anion source preferably adopts the one in sodium ethylate, sodium tert-butoxide or potassium tert.-butoxide further, and the mol ratio of alkoxide anion source and 3-isochromanome (I) is 1.1 ~ 2.0:1; Described alkyl formate preferably adopts the one in methyl-formiate, ethyl formate, n-buty formate or t-butyl formate further, and the mol ratio of alkyl formate and 3-isochromanome (I) is 1.0 ~ 3.0:1; The alkali of (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) in the basic conditions when the 4th inert solvent reaction that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) preferably adopts the one in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood further, 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 preferably adopts the one in sodium hydroxide, potassium hydroxide, sodium bicarbonate, saleratus, sodium carbonate or salt of wormwood further, 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 for starting raw material obtains key intermediate (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) through polystep reaction by 3-isochromanome (I), is then utilized (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) to react further with 2-hydroxyl-6-5-flumethiazine (V) or its alkoxide (VI) and prepares ZEN 90160.It is short that the present invention has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases 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 synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, as shown in table 1, comprise the steps: 1) 0 DEG C time, by 100 g (0.67 mol, 99%) 3-isochromanome (I) is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL toluene wherein, sodium ethylate 50 g (0.73mol) is added wherein under stirring, ethyl formate 54.8 g (0.74 mol), react 3 hours post analysis to show to react completely, add 150 mL ice cold waters wherein, and be adjusted to neutrality with 100 mL concentrated hydrochloric acids, be separated organic phase, aqueous phase toluene extraction (3*50 mL), merge organic phase, with anhydrous magnesium sulfate drying and concentrating under reduced pressure obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly may be used for next step reaction.
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4H)-one (II) step 1) obtained is added in four mouthfuls of reaction flasks of 2000 mL, adds 400 mL wherein
n,N-dimethyl formamide, sodium carbonate 85.0 g (0.80 mol) is added wherein under stirring, methyl-sulfate 110.0 g (0.87 mol), control temperature is at 0 DEG C, react after 3 hours, after reaction terminates, add 150 mL water wherein, aqueous phase is extracted with ethyl acetate (3*80 mL), merge organic phase, with anhydrous magnesium sulfate drying, decompression steams solvent, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), directly may be used for next step reaction.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) be dissolved in the mixed solution of 150 mL methyl alcohol and 200 mL toluene, be cooled to about 0 DEG C, add 131.0 g (1.1 mol) thionyl chloride, at 0 DEG C of reaction 2h after adding, after analysis shows to react completely, by mixture concentrating under reduced pressure, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, 155.0 g are obtained through recrystallization, content 93.9%, yield 90.3%.(with 3-isochromanome for benchmark obtains the total recovery of (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate for 90.3%)
4) by step 3) in product (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 155.0 g be dissolved in 340 mL
n,N-dimethyl formamide, add 28.8g (0.72 mol) sodium hydroxide and 97.8 g (0.6mol) 2-hydroxyl-6-5-flumethiazine (V) more wherein, 30 DEG C of reaction 3h, after analysis shows to react completely, add in 150 mL water in reaction solution, add 150 mL ethyl acetate wherein, be separated organic phase, aqueous phase is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, recrystallization obtains 200.2 g ZEN 90160, mother liquor concentrations continues crystallization and obtains 7.2 g ZEN 90160, amount to 207.4 g, content 98.2% (external standard method detection), yield 92.5%.It is short that the present embodiment has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 2
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, as shown in table 1, comprise the steps: 1) 30 DEG C time, by 100 g (0.67 mol, 99%) 3-isochromanome (I) is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL tetrahydrofuran (THF)s wherein, n-propyl alcohol sodium 70 g (0.85mol) is added wherein under stirring, add methyl-formiate 46.2 g (0.77 mol) wherein, react 4 hours, after reaction terminates, add 150 mL water wherein, and be adjusted to neutrality with 100 mL concentrated hydrochloric acids, aqueous phase is extracted with ethyl acetate (3*100 mL), merge organic phase, underpressure distillation, obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly may be used for next step reaction.
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4H)-one (II) step 1) obtained is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL dimethyl sulfoxide (DMSO) wherein, salt of wormwood 117.3 g (0.85mol) is added wherein under stirring, drip methyl iodide 99.5 g (0.7 mol) wherein again, control temperature 30 DEG C, react after 4 hours, after reaction terminates, add 150 mL water wherein, aqueous phase is extracted with ethyl acetate (3*80 mL), merge organic phase, decompression steams solvent, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), directly may be used for next step reaction.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) be cooled to about 20 DEG C, add 113.1g (0.95 mol) thionyl chloride, room temperature is to back flow reaction 2h, after analysis shows that reaction terminates, underpressure distillation, distill in backward reaction flask and dripped 200 mL methyl alcohol, 20 DEG C of reaction 3 h, after reaction terminates, decompression removing methyl alcohol, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, 154.2 g are obtained through recrystallization, content 95.1%, yield 91.2%.(with 3-isochromanome for benchmark obtains the total recovery of (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate for 91.2%)
4) in reaction flask, add the mixed solution of 2-hydroxyl-6-5-flumethiazine (V) 20.0 g (0.12 mol) and 100 mL dimethyl sulfoxide (DMSO) successively, add 7.8 g (0.14 mol) potassium hydroxide and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 30.1 g (0.13 mol) more wherein, 20 DEG C of reaction 8h, after reaction terminates, 100 mL water are added in reaction solution, add 150 mL ethyl acetate wherein, be separated organic phase, aqueous phase is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, recrystallization obtains 36.3g ZEN 90160, mother liquor concentrations continues crystallization and 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 reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 3
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 1, and its difference is: the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 1.5:1; The mol ratio of alkoxide anion source and 3-isochromanome (I) is 1.5:1; 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 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 recrystallization obtains 73.9 g ZEN 90160, mother liquor concentrations continues crystallization and obtains 10.3 g ZEN 90160, amount to 84.2 g, content 98.6% (external standard method detection), yield 83.7%(with starting raw material 3-isochromanome (I) 40g for benchmark).It is short that the present embodiment has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 4
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 2, and the mol ratio of alkyl formate and 3-isochromanome (I) is 3.0:1; The mol ratio of alkoxide anion source and 3-isochromanome (I) is 2:1; 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 1.8:1; Other differences are as shown in table 1.Crude product recrystallization obtains 72.3 g ZEN 90160, mother liquor concentrations continues crystallization and obtains 12.7 g ZEN 90160, amount to 85.0 g, content 98.2% (external standard method detection), yield 84.1%(with starting raw material 3-isochromanome (I) 40g for benchmark).It is short that the present embodiment has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 5
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, as shown in table 2, comprise the steps: 1) 45 DEG C time, by 100 g (0.67 mol, 99%) 3-isochromanome (I) is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL dimethylbenzene wherein, potassium tert.-butoxide 82.5 g (0.74mol) is added wherein under stirring, add t-butyl formate 82.6 g (0.81 mol) wherein, react 3.5 hours, after reaction terminates, add 150 mL cold water wherein, and be adjusted to neutrality with 100 mL concentrated hydrochloric acids, be separated organic phase, aqueous phase is with xylene extraction (3*50 mL), merge organic phase, underpressure distillation, obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly may be used for next step reaction.
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4H)-one (II) step 1) obtained is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL acetonitriles wherein, add sodium carbonate 90.1 g (0.85mol) wherein, methyl-sulfate 110.0 g (0.87 mol), control temperature 10 DEG C, react after 3.2 hours, after reaction terminates, add 150 mL water wherein, aqueous phase is extracted with ethyl acetate (3*80 mL), merge organic phase, with anhydrous magnesium sulfate drying and concentrating under reduced pressure, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), directly may be used for next step reaction.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) be dissolved in the mixed solution of 150mL methyl alcohol and 200mL methylene dichloride, 113.1g (0.95 mol) thionyl chloride is added in-10 DEG C in 1h, room temperature reaction 5h, analysis shows to react completely, by mixture concentrating under reduced pressure, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, 159.1g is obtained through recrystallization, content 93.7%, yield 92.5%.(with 3-isochromanome for benchmark obtains the total recovery of (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate for 92.5%)
4) in the reaction flask that division box is housed, 2-hydroxyl-6-5-flumethiazine (V) 20.0 g (0.12 mol) and toluene 100 mL is added successively, add sodium hydroxide 4.9 g (0.12 mol), be warming up to 120 DEG C of back flow reaction 8h, separate the water of generation simultaneously.Reaction terminates rear Distillation recovery toluene, 80 mL dimethyl sulfoxide (DMSO) and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 30.1 g (0.13 mol) is added in reaction flask, 30 DEG C of reaction 8 h, after reaction terminates, reaction solution is poured in 100 mL water, add 150 mL ethyl acetate wherein, be separated organic phase, aqueous phase is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, recrystallization obtains 36.7g ZEN 90160, mother liquor concentrations continues crystallization and 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 reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 6
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, as shown in table 2, comprise the steps: 1) 60 DEG C time, by 100 g (0.67 mol, 99%) 3-isochromanome (I) is added in four mouthfuls of reaction flasks of 2000 mL, add 400 mL chlorobenzenes wherein, sodium tert-butoxide 76.8g (0.8mol) is added wherein under stirring, add n-buty formate 86.7g (0.85mol) wherein, react 3.8 hours, after reaction terminates, add 150 mL water wherein, and be adjusted to neutrality with 100 mL concentrated hydrochloric acids, aqueous phase is extracted with ethyl acetate (3*100 mL), merge organic phase, underpressure distillation, obtain 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), directly may be used for next step reaction.
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4H)-one (II) step 1) obtained and salt of wormwood 77.7 g (0.74 mol) join in methyl tertiary butyl ether (400 mL), suspension agitation 1 hour, then with at 40 DEG C methyl iodide 121 g (0.85 mol) is dripped in 3.8 hours, the mixture of gained is stirred 9 hours at ambient temperature, after reaction terminates, add 150 mL water wherein, aqueous phase is extracted with ethyl acetate (3*80 mL), merge organic phase, decompression steams solvent, obtain the compound 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), directly may be used for next step reaction.
3) by step 2) in the product 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) be dissolved in 200mL dimethylbenzene, 167.5 g (0.81 mol) thionyl chloride is added in 10-20 DEG C in 1h, 75 DEG C of reaction 2h, analysis shows that reaction stops, distillation, distill in backward reaction flask and added 200mL methyl alcohol, room temperature reaction 3 h, after reaction terminates, decompression removing methyl alcohol, obtain compound (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) crude product, 151.0 g are obtained through recrystallization, content 96.8%, yield 90.7%.(with 3-isochromanome for benchmark obtains the total recovery of (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate for 90.7%)
4) in the reaction flask that division box is housed, 2-hydroxyl-6-5-flumethiazine (V) 20.0 g (0.12 mol) and dimethylbenzene 100mL is added successively, add potassium hydroxide 6.8 g (0.12 mol), be warming up to 110 DEG C of back flow reaction 5h, separate the water of generation simultaneously.Reaction terminates rear Distillation recovery dimethylbenzene, adds 80 mL in reaction flask
n,N-dimethyl formamide and (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (IV) 37.1 g (0.13 mol), 45 DEG C of reaction 5h, after reaction terminates, reaction solution is poured in 100 mL water, add 150 mL ethyl acetate wherein, be separated organic phase, aqueous phase is extracted with ethyl acetate (3*50 mL), merge organic phase, decompression steams solvent, and recrystallization obtains 35.4g ZEN 90160, mother liquor concentrations continues crystallization and 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 reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 7
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 5, and the mol ratio of alkyl formate and 3-isochromanome (I) is 5.0:1; The mol ratio of alkoxide anion source and 3-isochromanome (I) is 3.0:1; 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 recrystallization obtains 69.9 g ZEN 90160, mother liquor concentrations continues crystallization and obtains 14.1g ZEN 90160, amount to 84.0 g, content 98.9% (external standard method detection), yield 83.8%(with starting raw material 3-isochromanome (I) 40g for benchmark).It is short that the present embodiment has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 8
The synthetic method of a kind of efficient green disinfectant use in agriculture of the present embodiment, step is roughly as embodiment 6, and the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 2.5:1; The mol ratio of alkoxide anion source and 3-isochromanome (I) is 2.0:1; Described step 2) in the mol ratio of alkali and 3-isochromanome (I) be 0.8:1; 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 3.0:1; 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 recrystallization obtains 71.6 g ZEN 90160, mother liquor concentrations continues crystallization and obtains 11.3g ZEN 90160, amount to 82.9 g, content 98.7% (external standard method detection), yield 82.5%(with starting raw material 3-isochromanome (I) 40g for benchmark).It is short that the present embodiment has reactions steps, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, is applicable to suitability for industrialized production, product appearance is good, external standard content is greater than 98%, moreover the present invention allows expensive 2-hydroxyl-6-5-flumethiazine finally participate in reaction, consumes and significantly reduces, cost significantly reduces, and substantially increases the market competitiveness.
Embodiment 9
(patent CN1178894 and embodiment 2 simultaneous test)
Step following 1) at 0 DEG C, to 3-isochromanome (6.35g under nitrogen protection, 42.9 mmol) anhydrous tetrahydro furan (70 mL) solution add sodium methylate (4.63 g, 85.8 mmo1), temperature slightly raises, mixture is chilled to 4 DEG C again, methyl-formiate (5.1 g are added at this temperature in 10 minutes, 85.86 mmol), add rear continuation to stir 10 minutes at 0 DEG C, naturally room temperature (21 DEG C) is warming up to, now start thickening and release carbon monoxide, add tetrahydrofuran (THF) (50 mL) again and continue to stir, after 3.5 h, at 0 DEG C, other sodium methylate and methyl-formiate are added reactor, naturally room temperature reaction is warming up to.22 h post analysis show that reaction stops.Reaction mass is poured into (200 mL) in cold water, be acidified to Congo red with concentrated hydrochloric acid (18 mL), be separated organic phase, aqueous phase is with dichloromethane extraction (3*180 mL), merge organic phase, wash with water (2*100 mL), with anhydrous sodium sulfate drying and vacuum concentration obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (6.985 g, 80%).
2) under stirring, the product (3 .03 g, 17.22mmol) of step 1 is dissolved in anhydrous
n,N-dimethyl formamide (50 mL), adds salt of wormwood (3.568,25.79mmol), is cooled to 2 DEG C, in 10 minutes, add methyl-sulfate (1.63g, 17.14mmol), keeps temperature to be no more than 4 DEG C simultaneously.Add rear continuation to stir 30 minutes at 4 DEG C, then rise to room temperature.In reaction mass impouring water (50 mL) after 2 hours.Be separated organic phase, aqueous phase is extracted with ethyl acetate (3*50 mL), merge organic phase, wash with water (2 * 50 mL), dry and vacuum concentration obtains compound 4-(α-methoxyl group) methylene radical-2-H-chromene-3-(4 H)-one (3 g, 85%).
3) a lower thionyl chloride (8.11 g of room temperature, 68.5 mmo1) be added drop-wise to 4-(α-methoxyl group) methylene radical-2-H-chromene-3-(4 H)-one (0.5 g, 2.63 mmo1) in, solution return 4 h, then makes its at room temperature hold over night.Excessive thionyl chloride is removed in distillation, then at room temperature adds methyl alcohol (5 mL).Add rear reaction mass to reflux 1.5 h.Decompression steams methyl alcohol after this, then obtains (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate (0.458 g, 72%).(with 3-isochromanome for benchmark obtains the total recovery of (E)-2-(2-chloromethyl phenyl)-3-methoxy-methyl acrylate for 49%)
The present invention with 3-isochromanome (I) for gained total recovery during starting raw material synthesis (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) is at 90-95%, control experiment yield only has 49%, yield of the present invention is far away higher than control experiment, there is reaction scheme short, safety simple to operate, mild condition, aftertreatment is simple and easy to do, the three wastes are few, and yield is high and purity is high, cost is low and applicable scale operation.
Table 1
Table 2
| Embodiment | First inert solvent | Alkoxide anion source | Alkyl formate | Formic acid aryl ester | Second inert solvent | Step 2) in alkali | Methylating reagent |
| 5 | Dimethylbenzene | Potassium tert.-butoxide | T-butyl formate | Acetonitrile | Sodium carbonate | Methyl-sulfate | |
| 6 | Chlorobenzene | Sodium tert-butoxide | N-buty formate | Methyl tertiary butyl ether | Salt of wormwood | Methyl iodide | |
| 7 | Methyl tertiary butyl ether | Propyl carbinol sodium | N-propyl formate | Tetrahydrofuran (THF) | Sodium carbonate | Methyl-sulfate | |
| 8 | N,N-dimethyl formamide | Sodium ethylate | Benzyl formate | Chlorobenzene | Salt of wormwood | Methyl-sulfate | |
| Embodiment | 3rd inert solvent | Halide reagent | With alkali during the 4th inert solvent reaction | 4th inert solvent | 5th inert solvent | With alkali during the 5th inert solvent reaction | 6th inert solvent |
| 5 | Methylene dichloride | Thionyl chloride | Toluene | Sodium hydroxide | Dimethyl sulfoxide (DMSO) | ||
| 6 | Dimethylbenzene | Thionyl chloride | Dimethylbenzene | Potassium hydroxide | N,N-dimethyl formamide | ||
| 7 | Thionyl bromide | Thionyl bromide | Chlorobenzene | Sodium ethylate | Acetonitrile | ||
| 8 | Phosphorus oxychloride | Thionyl chloride | Hexanaphthene | Potassium hydroxide | Tetrahydrofuran (THF) |
Claims (5)
1. a synthetic method for efficient green disinfectant use in agriculture, is characterized in that, comprises the steps:
1) raw materials of compound 3-isochromanome (I) is got, chemical formula is as follows, be dissolved in the first inert solvent, under-10 ~ 100 DEG C of conditions, add alkoxide anion source, then add alkyl formate or formic acid aryl ester, under-10 ~ 60 DEG C of conditions, reaction 1 ~ 12h, through acidifying after reaction terminates, extraction, distillation obtains 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II), and chemical formula is as follows;
2) 4-(Alpha-hydroxy) methylene radical-2-H-chromene-3-(4 H)-one (II) step 1) obtained is in the second inert solvent, add alkali and methylating reagent, under-10 ~ 60 DEG C of conditions, reaction 1 ~ 12h, through washing after reaction terminates, extraction, distillation obtains the 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III), and chemical formula is as follows;
3) by step 2) the obtained 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is dissolved in methyl alcohol, the 3rd inert solvent and halide reagent, in-10 ~ 120 DEG C, reaction 2 ~ 12h, obtains (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) through distillation after reaction terminates; Or by step 2) the obtained 4-different benzopyrone of (methoxy methyl thiazolinyl)-3-(III) is dissolved in the 3rd inert solvent and halide reagent, in-10 ~ 120 DEG C, reaction 1 ~ 12h, after reaction terminates, distill halide reagent, dripping reacts to terminating with methyl alcohol again, and obtain (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) through distillation, chemical formula is as follows;
4) raw materials of compound 2-hydroxyl-6-5-flumethiazine (V) is got, chemical formula is as follows, with obtained (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) of step 3) in the 4th inert solvent 20 ~ 120 DEG C in the basic conditions, 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, 5 ~ 10h is reacted under 50 ~ 120 DEG C of conditions, 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained after distillation, chemical formula is as follows, in the 6th inert solvent, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained with step 3), in 20 ~ 120 DEG C, reaction 3 ~ 12h, obtains ZEN 90160; After reaction terminates, in reaction solution, add appropriate water, then obtain ZEN 90160 solution through extraction, fractionation by distillation solvent obtains the thick product of ZEN 90160; Thick for ZEN 90160 product purification is obtained efficient green disinfectant use in agriculture ZEN 90160 sterling.
。
2. the synthetic method of a kind of efficient green disinfectant use in agriculture as claimed in claim 1, is characterized in that, described step 1) in 3-isochromanome (I) be dissolved in the first inert solvent after at 0 ~ 60 DEG C, add alkoxide anion source; Add alkyl formate or formic acid aryl ester again, at 0 ~ 60 DEG C of reaction 3 ~ 4h; Described step 2) in temperature of reaction be 0 ~ 40 DEG C, the reaction times is preferably 3 ~ 4h; In described step 3), temperature of reaction is-10 ~ 80 DEG C, and the reaction times is 3 ~ 5h; (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) and step 3) obtain is in the basic conditions in the 4th inert solvent, temperature of reaction is 20 ~ 50 DEG C, and the reaction times is 7 ~ 9h; In described step 4), 2-hydroxyl-6-5-flumethiazine (V) is at the 5th inert solvent and alkali, under 90 ~ 120 DEG C of conditions, react 4 ~ 8h; In described step 4) in the 6th inert solvent, (E)-2-(2-monochloromethyl the phenyl)-3-methoxy-methyl acrylate (IV) that 6-trifluoromethyl-2-pyridine alkoxide (VI) is obtained with step 3), in 20 ~ 50 DEG C, reaction 7 ~ 9h.
3. the synthetic method of a kind of efficient green disinfectant use in agriculture according to claim 1, it is characterized in that, in described step 1) 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,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described alkoxide anion source adopts the C of sodium, potassium, calcium, magnesium
2-C
5straight chain or side chain alkoxide in one; Alkyl in described alkyl formate is C
1-C
10straight chain, side chain, have or there is no the one in substituent naphthenic hydrocarbon, and the mol ratio of alkyl formate and 3-isochromanome (I) is 1.0 ~ 5.0:1, in described formic acid aryl ester, aryl is have or do not have the one in substituent phenyl ring, hetero-aromatic ring, and the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 1.0 ~ 5.0:1;
Described step 2) in 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,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described step 2) in alkali adopt sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, cesium carbonate, sodium bicarbonate, saleratus, sodium methylate, one in sodium ethylate, and the mol ratio of alkali and 3-isochromanome (I) is 0.2 ~ 2.0:1; Described methylating reagent adopts the one 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 the one in normal hexane, sherwood oil, methylene dichloride, 1,2-ethylene dichloride, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus; Described halide reagent adopts the one in thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus, and the mol ratio of halide reagent and the different benzopyrone of 4-(methoxy methyl thiazolinyl)-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 the phenyl)-3-methoxy-methyl acrylate (IV) that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) adopts sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, C with alkali during the 4th inert solvent reaction in the basic conditions
1-C
5straight chain or side chain alkoxide in one; Described 4th inert solvent employing toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide; Described 5th inert solvent adopts the one 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 side chain alkoxide in one; In described 6-trifluoromethyl-2-pyridine alkoxide (VI), M is atoms metal; Described 6th inert solvent employing toluene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, acetonitrile,
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), dimethyl sulfone,
none in-methyl-2-pyrrolidone, tetramethylene sulfone and hexamethylphosphoramide.
4. the synthetic method of a kind of efficient green disinfectant use in agriculture according to claim 3, it is characterized in that, in described step 1) first inert solvent adopt methyl tertiary butyl ether, toluene, dimethylbenzene, trimethylbenzene, chlorobenzene, tetrahydrofuran (THF), glycol dimethyl ether, ethylene glycol diethyl ether, acetonitrile,
n,None in-dimethyl formamide and dimethyl sulfoxide (DMSO); Described alkoxide anion source adopts the one in sodium ethylate, n-propyl alcohol sodium, sodium isopropylate, propyl carbinol sodium, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkoxide anion source and 3-isochromanome (I) is 1.0 ~ 3.0:1; Described alkyl formate adopts the one in methyl-formiate, ethyl formate, n-propyl formate, isopropyl formate, n-buty formate or t-butyl formate; Described formic acid aryl ester adopts phenyl formate or benzyl formate, and the mol ratio of formic acid aryl ester and 3-isochromanome (I) is 1.0 ~ 3.0:1;
Described step 2) in second inert solvent adopt toluene, dimethylbenzene, chlorobenzene, tetrahydrofuran (THF), methyl tertiary butyl ether, acetonitrile,
n,None in-dimethyl formamide and dimethyl sulfoxide (DMSO); Described step 2) in alkali adopt one 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 the one in sherwood oil, methylene dichloride, 1,2-ethylene dichloride, toluene, thionyl chloride, thionyl bromide, phosphorus oxychloride or tribromo oxygen phosphorus;
The alkali of (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) in the basic conditions when the 4th inert solvent reaction that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) adopts the one 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 4th inert solvent employing toluene, tetrahydrofuran (THF), acetonitrile,
n,None in-dimethyl formamide, dimethyl sulfoxide (DMSO); Described 5th inert solvent adopts the one 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 the one 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, in described 6-trifluoromethyl-2-pyridine alkoxide (VI), atoms metal adopts the one in lithium, sodium or potassium; Described 6th inert solvent employing toluene, tetrahydrofuran (THF), acetonitrile,
n,None in-dimethyl formamide, dimethyl sulfoxide (DMSO).
5. the synthetic method of a kind of efficient green disinfectant use in agriculture according to claim 4, it is characterized in that, in described step 1), alkoxide anion source adopts the one in sodium ethylate, sodium tert-butoxide or potassium tert.-butoxide, and the mol ratio of alkoxide anion source and 3-isochromanome (I) is 1.1 ~ 2.0:1; Described alkyl formate adopts the one in methyl-formiate, ethyl formate, n-buty formate or t-butyl formate, and the mol ratio of alkyl formate and 3-isochromanome (I) is 1.0 ~ 3.0:1;
The alkali of (E)-2-(2-monochloromethyl phenyl)-3-methoxy-methyl acrylate (IV) in the basic conditions when the 4th inert solvent reaction that in described step 4), 2-hydroxyl-6-5-flumethiazine (V) is obtained with step 3) adopts the one 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 the one 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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