CN100334070C - Tech. for synthesizing high productivity oxime kresoxim - Google Patents
Tech. for synthesizing high productivity oxime kresoxim Download PDFInfo
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Abstract
The present invention discloses a technology for synthesizing high productivity of oxime fungus ester, which relates to the preparation of oxime fungus ester. The technology is carried out according to the following sequences: 1.2'-methylacetophenone is used as a raw material, and potassium permanganate is oxidized to obtain 2-(2'-methyl phenyl)-2-carbonyl acetic acid; 2. the 2-(2'-methyl phenyl)-2-carbonyl acetic acid reacts with methyl alcohol to obtain 2-(2'-methyl phenyl)-2-carbonyl acetic methyl ester; 3. the 2-(2'-methyl phenyl)-2-carbonyl acetic methyl ester reacts with methoxyl group amine to obtain (E)-2-(2'-methyl phenyl)-2-carbonyl acetic acid methyl ester-0-methyl ketone oxime; 4. the (E)-2-(2'-methyl phenyl)-2-carbonyl acetic acid methyl ester-0-methyl ketone oxime is bromized to obtain (E)-2-(2'-bromine methyl phenyl)-2-carbonyl acetic acid methyl ester-0-methyl ketone oxime; 5. inter-trifluoromethyl acetophenone oxime is prepared; 6. products in step 4 and step 5 react to obtain oxime fungus ester. The present invention converts the two isomers (E, Z) of methoxy group oxime into an E-isomer. The total yield of the present invention is 39%, which is six times of the prior art. The present invention has the advantages of low cost, little waste water discharge and mild, simple and convenient operation condition, and the present invention is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of oxime bacterium ester ((E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime) synthesis technique.The synthesis technique that belongs to the agricultural chemicals organic compound.
Background technology
Oxime bacterium ester ((E with following structure, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime) be the fluorine-containing sterilant of wide spectrum, can obtain as the exploitation of sterilant lead compound with natural product Strobilurins.Because it has efficiently; wide spectrum; protection; treatment; root out; infiltration; systemic activity; resistance of rainwater washing against; characteristics such as the lasting period is long; and to 1; 4-demethylation enzyme inhibitors; benzamides; the bacterial strain of dicarboxylic dihydrazides amine and benzimidazoles generation resistance is effective; there is not cross resistance with at present existing sterilant; to nearly all Eumycetes (Ascomycetes; Basidiomycetes; Oomycete and imperfect fungi) disease such as Powdery Mildew; rust; Ying's rot; net blotch; oidium; rice blast etc. all have good activity; especially to Powdery Mildew; leaf spot has special efficacy; to rust; oidium; damping-off; the apple apple scab has good activity; and to crop safety; at soil; capable of being fast degraded in the water; environmentally safe, thereby caused extensive concern.But so far, there are many problems in preparation technology, and perhaps raw material seldom arrives, and perhaps technology is imperfect, and perhaps productive rate is low etc., can not satisfy the requirement of actual use.
Oxime bacterium ester
In order to prepare the alpha-ketoacid ester, Domagala with methyl phenyl ketone as raw material, through oxidation, resterification obtains, but need to carry out esterification, cause toxicity big, see (' A mild with methyl-chloroformate, rapid, and convenientesterification of α-ketoacids. ' Domagala J M.Tetrahedron Lett., 1980,21:4997), Nimitz has synthesized the alpha-ketoacid ester with Grignard reagent and imidazolone acid esters, the imidazolone acid esters that this reaction is used is more difficult to get, and sees (' A new synthesis of α-keto esters and acids. ' Nimitz J S, Mosher H S.J.Org.Chem., 1981,46 (1): 211).Peter provides oxime bacterium ester final step condensation reaction, but a complete synthesis technique is not provided, and sees (AromatischeVerbingdungen.Peter I H.EP460575,1991).
Chinese invention patent application " a kind of preparation method of oxime bacterium ester " (publication number CN1560027A, 2004) has proposed a kind of method for preparing oxime bacterium ester, key step be oxidation, esterification, bromination, with the reaction of methoxyl group amine, condensation, overall yield has only 6%.Reason be since bromide stability bad, so compound afterwards each the step reaction treatment the time become easily, influence productive rate.Particularly (E Z) be converted into only a kind of E-isomer, so productive rate is not high to this application two kinds of isomer of the methoxyl group oxime that generates.
Summary of the invention
The object of the invention be to provide a kind of high yield oxime bacterium ester ((E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime) complete synthesis technique, overall yield can reach 39%.
In order to achieve the above object, the present invention is on Chinese invention patent application CN1560027A basis, synthesis technique is revised, bromination is placed on methoxyl group amine reaction back, make two kinds of isomer (E of the methoxyl group oxime of generation, Z) can both be converted into required a kind of E-isomer that only contains, therefore productive rate significantly is improved, and overcome the disadvantageous effect of the stable bad generation of bromide, be crystal owing to reacting the methoxyl group oxime compound that obtains simultaneously with methoxyl group amine, the product separation that carries out is later on purified and can be purified by recrystallization, has simplified sepn process.Key step of the present invention is: oxidation, esterification, synthetic with the reaction of methoxyl group amine, bromination, condensation and product.
The present invention is that in the following sequence six steps are carried out:
The first step, oxidation make 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid.
Be 1 in molar ratio by o-methyl-benzene ethyl ketone and potassium permanganate earlier: 0.8-2.5, preferred mol ratio is to measure at 1: 1.1.PH with the o-methyl-benzene ethyl ketone is controlled at 8-13 then, preferably the pH value is 9, in temperature is-10-40 ℃ preferred 0-30 ℃, best temperature is to react under 10 ℃ and the agitation condition, at last with ordinary method separate product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid.
In second step, esterification gets 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters.
At first with 732 storng-acid cation exchange resins and the vitriol oil as catalyzer, the amount of catalyzer is the 0.1-10% weight percent of the first step product.Then by methyl alcohol: the mol ratio of the first step product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid is 50-200: 1 measures, and temperature of reaction is 20-65 ℃, and backflow 4-5 hour, aligning the pH value again was 6-8 neutrality.Separate at last product.
In the 3rd step, obtain (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-0-methyl ketoxime with the reaction of methoxyl group amine.
Earlier by second product 2-(2-the aminomethyl phenyl)-2-carbonylic acetic acid methyl esters that goes on foot: methoxy amine hydrochlorate: reaction medium=1: 1-2: the 50-200 mol ratio is measured, and mixes and stirs.Reaction medium is ethanol or methyl alcohol.Adding alkaline conditioner pyridine, triethylamine, diethylamine, sodium hydroxide, potassium hydroxide etc. are 8-13 with the pH value levelling of above-mentioned reaction system, and preferred pH value is 10.Temperature of reaction is 10-80 ℃, and preferred temperature is 60 ℃.Stirring and refluxing 4h, carry out the reaction that (Z) is converted into (E) at last in isolating product: carry out in acidic methanol solution, acid is hydrochloric acid, sulfuric acid etc., and the concentration of acid is 1N, and (Z) mol ratio with solvent is 1: 10-40.Temperature of reaction is 30-80 ℃, and preferred temperature is 60 ℃, and the 4 hours waters that reflux neutralize, and separates to such an extent that only contain a kind of product (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-0-methyl ketoxime of E-isomer at last.
In the 4th step, bromination gets (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime.
Bromination reaction adopts the direct bromination of bromine and carries out bromination with N-bromo-succinimide (NBS).Reaction solvent is tetracol phenixin, methylene dichloride and trichloromethane etc.Temperature of reaction is 10-70 ℃, and preferred temperature is 50 ℃.Go on foot the product that makes by the 3rd earlier: bromine: solvent=1: 5: the 10-50 mol ratio is measured, then product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime is dissolved in 2/3 solvent, getting bromine in addition is dissolved in 1/3 solvent, and be added drop-wise in the reaction system, with the irradiation of 250W mercury lamp, color is reddish-brown after the dripping bromine, after reddish-brown disappears, continue dripping bromine, react after 5 hours reddish-brown and do not disappear and show to react and finish last separating obtained product.
The 5th step, m-trifluoromethyl acetophenone oxime synthetic.
The solvent of reaction usefulness is ethanol, first alcohol and water etc.The pH value of solution is 5-9.With the m-trifluoromethyl methyl phenyl ketone: oxammonium hydrochloride: the mol ratio of solvent is 0.5-1.2: 1: 50-200 adds reaction flask, transfer the pH (pH=7-9) about 8 of solution then, stirring and refluxing was poured in the frozen water after 3 hours, with the concentrated hydrochloric acid adjust pH is 2, carries out separating obtained product at last.
The 6th step, with the 4th and the 5th step product synthetic oxime bacterium ester.
Earlier and (E) by the trifluoromethyl acetophenone oxime-and the mol ratio of 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime is 0.8-1.5: 1 measures, and preferred molar ratio is 1: 1.The mol ratio of measuring alkali and trifluoromethyl acetophenone oxime then is 1-5: 1, and preferred molar ratio is 3: 1; The alkali of reaction usefulness is sodium hydride, or hydrolith, or sodium hydroxide, or potassium hydroxide, or sodium methylate, or sodium amide; Measure alkali and reaction medium=1: 10 mol ratio again and alkali is joined in the reaction medium, reaction medium is N, dinethylformamide, or tetrahydrofuran (THF).Then at room temperature, add the trifluoromethyl acetophenone oxime, behind the heated and stirred 1h, add (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime, continue the solid of heated and stirred reaction, temperature of reaction is 10-70 ℃, and preferred temperature is 25 ℃.With TLC (ethyl acetate: sherwood oil=1: 9) follow the tracks of reaction mechanism, raw material point disappears on thin-layer chromatography, stopped reaction, pour in the frozen water, separate out solid, filter, difference water and ether drip washing solid, collect solid sherwood oil recrystallization, obtain oxime bacterium ester of the present invention: (E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime solid.
The most outstanding advantage of the present invention is:
1. because the present invention is placed on methoxyl group amine reaction back to bromination, successfully realized (Z) transformation to (E), make two kinds of isomer (E of the methoxyl group oxime of generation, Z) can both be converted into and only contain a kind of E-isomer, therefore productive rate significantly is improved, overall yield reaches 39% (overall yield of preceding patent about 6%), has reduced cost.
2. compare with traditional synthesis process, the present invention has reduced discharge of wastewater a large amount of in the oxidizing reaction, has avoided the employing methyl-chloroformate to carry out esterification.
3. the most of operational condition gentleness of the present invention is easy and simple to handle, is fit to suitability for industrialized production.
Embodiment
How further specify the present invention below by embodiment realizes:
Embodiment 1
The first step, 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid synthetic
In the 500mL round-bottomed flask, add 2g (0.015mol) o-methyl-benzene ethyl ketone, 1g sodium hydroxide, 200mL water,, 3.5g (0.02mol) potassium permanganate is added in the flask in batches at ice-water bath with under stirring.A collection of to the end potassium permanganate adds, and the color in the reaction system continues to keep 1h constant, and reaction finishes, and drips sodium sulfite solution the red-purple of mixed solution is taken off, and suction filtration is removed the Manganse Dioxide solid, and the aqueous solution is removed unreacted raw material with extracted with diethyl ether.Water is acidified to pH=1 with concentrated hydrochloric acid, and the adularescent solid occurs, and with 3 * 50mL extracted with diethyl ether, white solid is dissolved in ether.Collect the organic phase anhydrous magnesium sulfate drying, boil off ether, obtain 2.2g xanchromatic 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid liquid, productive rate 90%.
IR(KBr，cm
-1)：1749，1686.
1HNMR(CDCl
3)：δ＝2.61(s，3H，ArCH
3)，7.26-7.69(m，4H，ArH)，9.1(s，1H，COOH).
Second step, (2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters synthetic
Under agitation, the 0.05mL vitriol oil is slowly added in the 100mL round-bottomed flask that fills 2g (0.012mol) 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid, methyl alcohol 40mL, TLC (ethyl acetate: sherwood oil=1: 8) follow the tracks of reaction, finish behind the about 5h of reflux, reaction solution is poured in the 100mL beaker, with saturated sodium hydrogen carbonate solution adjust pH is neutral, with 3 * 50mL extracted with diethyl ether, anhydrous magnesium sulfate drying, boil off 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters liquid that obtains the 1.96g yellow oily behind the ether, productive rate 90%.
IR(KBr，cm
-1)：1749，1686，1609，1455，1315，1287，1203，1001，735.
1H?NMR(CDCl
3)：δ＝2.58(s，3H，ArCH
3)，3.94(s，3H，COOCH
3)，7.27-7.68(m，4H，ArH).
The 3rd step, (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime synthetic
In the 100mL three-necked bottle, add 1.6g (0.009mol) 2-(2-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters, 1.6g (0.02mol) methoxy amine hydrochlorate and 20mL 95% ethanol, adding 2mL triethylamine adjusting pH is alkalescence, TLC (ethyl acetate: sherwood oil=1: 9) follow the tracks of reaction, pour in the frozen water after the stirring and refluxing 4h, with extracted with diethyl ether (3 * 50mL), organic phase with the 50mL washing once, the anhydrous sodium sulfate drying organic phase, boil off the debris behind the ether, in debris, add 20mL methyl alcohol and 0.2mL concentrated hydrochloric acid reflux 4h, pour in the 100mL water, neutralization, with extracted with diethyl ether (3 * 50mL), the anhydrous sodium sulfate drying organic phase, boil off debris behind the ether through purification by silica gel column chromatography (ethyl acetate: sherwood oil=1: 20), obtain 1.6g (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime crystal, productive rate 86%.
1H?NMR(CDCl
3)：δ＝2.20(s，3H，ArCH
3)，3.84(s，3H，NOCH
3)，4.05(s，3H，COOCH
3)，7.10-7.30(m，4H，ArH).
The 4th step, (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-0-methyl ketoxime synthetic
1g (0.006mol) 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime is dissolved in the 20mL tetracol phenixin and places the 100mL three-necked bottle, getting 1.5mL (0.03mol) bromine is dissolved in the 10mL tetracol phenixin and places constant pressure funnel to be added dropwise to three-necked bottle, shine with the 250W mercury lamp, color takes on a red color after the dripping bromine, reaction was less than 10 minutes, color promptly shoals, and continues dripping bromine, and color fade is very fast.(ethyl acetate: sherwood oil=1: 8) follow the tracks of reaction process, TLC shows that the basic disappearance of raw material point finishes reaction behind the 5h with TLC in the reaction process.To its solution earlier once, saturated sodium bicarbonate (NaHCO with the 50mL washing
3) solution gives a baby a bath on the third day after its birth time.The organic phase anhydrous magnesium sulfate drying steams solvent, obtains the tawny product.Through purification by silica gel column chromatography (ethyl acetate: sherwood oil=1: 10), obtain 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters liquid of 1.1g yellow oily, productive rate 80%.
1H?NMR(CDCl
3)：δ＝3.86(s，3H，NOCH
3)，4.05(s，3H，COOCH
3)，4.33(s，2H，ArCH
2Br)，7.13-7.49(m，4H，ArH).
The 5th step, m-trifluoromethyl acetophenone oxime synthetic
Add 1g (0.005mol) m-trifluoromethyl methyl phenyl ketone, 0.5g (0.007mol) oxammonium hydrochloride, 20mL dehydrated alcohol in the 100mL three-necked bottle, add sodium hydrate solid, the pH that transfers solution is about 8, behind the stirring and refluxing 3h, pouring in the frozen water, is 2 with the concentrated hydrochloric acid adjust pH, has this moment a large amount of white solid things to occur in the solution, filter,, drain to neutral with distillation washing white solid, the gained solid is carried out recrystallization with sherwood oil, obtain white needle-like crystals 0.98g, productive rate 97%.
1HNMR(CDCl
3)：δ＝2.35(s，3H，-CH
3)，7.48-7.90(m，4H，ArH).
The 6th step, oxime bacterium ester synthetic
0.5g (0.009mol) sodium methylate is joined in the 50mL tetrahydrofuran (THF), at room temperature, add 0.7g (0.0034mol) m-trifluoromethyl acetophenone oxime, behind the heated and stirred 1h, add 1.1g (0.004mol) (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime and 20mL N, dinethylformamide, continue the heated and stirred reaction, (ethyl acetate: sherwood oil=1: 9) follow the tracks of reaction mechanism, raw material point disappears on thin-layer chromatography, stopped reaction with TLC, pour in the frozen water, separate out solid, filter, respectively water and ether drip washing solid, collect solid sherwood oil recrystallization, obtain 1.1g (E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime solid, productive rate 70%.Fusing point: 72-73 ℃.
IR：(KBr，cm
-1)2946，2880，1738，1124，1073，1010.
1H?NMR(CDCl
3)：δ＝2.21(s，3H，-N＝C-CH
3)，3.80(s，3H，-COO-CH
3)，4.02(s，3H，＝N-O-CH
3)，5.15(s，2H，Ar-CH
2-O-N＝)，7.18-7.87(m，7H，Ar-H)
Embodiment 2
Other steps repeat embodiment 1 by same steps as, just wherein the synthetic of 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters in the 3rd step undertaken by following step: 1g (0.006mol) (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime is dissolved in the 20mL tetracol phenixin and places the 100mL three-necked bottle, add 1.5g (0.012mol) NBS (N-bromo-succinimide) and 0.2g BPO (benzoyl peroxide), with the irradiation of 250W mercury lamp.(ethyl acetate: sherwood oil=1: 8) follow the tracks of reaction process, TLC shows that the basic disappearance of raw material point finishes reaction with TLC in the reaction process.To its solution earlier once, saturated sodium bicarbonate (NaHCO with the 50mL washing
1) solution gives a baby a bath on the third day after its birth time.The organic phase anhydrous magnesium sulfate drying steams solvent, obtains the tawny product.Through purification by silica gel column chromatography (ethyl acetate: sherwood oil=1: 10), obtain 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters liquid of 1.15g yellow oily, productive rate 83%.
1H?NMR(CDCl
3)：δ＝3.86(s，3H，NOCH
3)，4.05(s，3H，COOCH
3)，4.33(s，2H，ArCH
2Br)，7.13-7.49(m，4H，ArH).
The above is preferred embodiment of the present invention only, is not to be used for limiting scope of the present invention, and is all according to equalization variation and modification that the present invention did, is all claim of the present invention and contains.
Claims (1)
1, a kind of synthesis technique of high productivity oxime kresoxim is that in the following sequence six steps are carried out:
The first step, oxidation obtain 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid:
Mol ratio by o-methyl-benzene ethyl ketone and potassium permanganate is 1 earlier: 0.8-2.5 is measured; PH with the o-methyl-benzene ethyl ketone is controlled at 8-13 then, and under alkaline condition, temperature is-10-40 ℃, agitation condition down with the potassium permanganate oxidation reaction, separate acquisition product: 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid at last;
In second step, esterification gets 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters:
At first with 732 storng-acid cation exchange resins and the vitriol oil as catalyzer, the amount of catalyzer is the 0.1-10% weight percent of the first step product, then by methyl alcohol: the mol ratio of the first step product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid is 1-20: 1 measures, temperature of reaction is 20-65 ℃, backflow 4-5 hour, align the pH value again and carry out esterification, separate making 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl at last for neutral 6-8;
The 3rd the step, with methoxyl group amine react (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime:
Earlier by second product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters that goes on foot: methoxy amine hydrochlorate: reaction medium=1: 1-2: 25 mol ratios are measured, mix and stir, reaction medium is ethanol or methyl alcohol, by adding the alkaline conditioner pyridine, or triethylamine, or diethylamine, or sodium hydroxide, or potassium hydroxide is 8-13 with the levelling of the pH value of above-mentioned reaction system, temperature of reaction is 10-80 ℃, and stirring and refluxing 4h carries out the reaction that (Z) is converted into (E): carry out at last in acidic methanol solution in isolating product, acid is hydrochloric acid or sulfuric acid, the concentration of acid is 1N, and (Z) mol ratio with solvent is 1: 10-40, and temperature of reaction is 30-80 ℃, the 4 hours waters that reflux neutralize, and separate product (E)-2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime that is only contained a kind of E-isomer at last;
In the 4th step, bromination gets (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime:
This bromination reaction adopts the direct bromination of bromine, or carry out bromination with N-bromo-succinimide, reaction solvent is a tetracol phenixin, or methylene dichloride, or trichloromethane, temperature of reaction is 10-70 ℃, the first product that makes by the 3rd step: bromine: solvent=mol ratio was measured in 1: 5: 20, then product 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime was dissolved in 2/3 solvent, got bromine in addition and was dissolved in 1/3 solvent and is added drop-wise in the reaction system, shine with the 250W mercury lamp, color is red-brown after the dripping bromine, after red-brown disappears, continues dripping bromine, react after 5 hours red-brown and do not disappear and show that reaction finishes, separate at last product;
The 5th step, preparation m-trifluoromethyl acetophenone oxime:
The solvent of reaction usefulness is ethanol or methyl alcohol or water, and the pH value is 5-9; Earlier by the m-trifluoromethyl methyl phenyl ketone: oxammonium hydrochloride: the mol ratio of solvent is 0.5-1.2: 1: 50-200 is measured, and adds reaction flask, transfers pH at 7-9 then, after the stirring and refluxing 3 hours, pouring in the frozen water, is 2 with the concentrated hydrochloric acid adjust pH, separate at last, obtain the m-trifluoromethyl acetophenone oxime;
In the 6th step, synthesize oxime bacterium ester with the 4th and the 5th step product:
Earlier and (E) by the m-trifluoromethyl acetophenone oxime-and the mol ratio of 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime is 0.8-1.5: 1 measures; The mol ratio of measuring alkali and trifluoromethyl acetophenone oxime then is 1-5: 1; The alkali of reaction usefulness is sodium hydride, or hydrolith, or sodium hydroxide, or potassium hydroxide, or sodium methylate, or sodium amide; Measure alkali and reaction medium=1: 10 mol ratio again, and alkali is joined in the reaction medium, reaction medium is N, dinethylformamide, or tetrahydrofuran (THF); Then at room temperature, add the trifluoromethyl acetophenone oxime, after the heated and stirred 1 hour, add (E)-2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid methyl esters-O-methyl ketoxime, continue the solid of heated and stirred reaction, control reaction temperature is 10-70 ℃, follow the tracks of reaction mechanism with TLC, raw material point disappears on thin-layer chromatography, and stopped reaction is poured in the frozen water, separate out solid, filter water and ether, or tetrahydrofuran (THF) or ethyl acetate drip washing solid respectively, collect solid, use the sherwood oil recrystallization, obtain overall yield of the present invention and reach 39% oxime bacterium ester: solid (E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime.
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| CN103922924A (en) * | 2014-04-29 | 2014-07-16 | 南京工业大学 | Preparation method of 2-(2'-methyl phenyl)-2-carbonyl acetic acid |
| CN110845358B (en) * | 2018-08-20 | 2022-10-21 | 南通泰禾化工股份有限公司 | Preparation method of (E) -2- (2-methylphenyl) -2-methoxyimino methyl acetate |
| CN112480024A (en) * | 2020-12-11 | 2021-03-12 | 山东金城医药化工有限公司 | Method for producing trans isomer of aminothiazoly loximate |
| CN113683527B (en) * | 2021-10-26 | 2022-03-01 | 江苏七洲绿色科技研究院有限公司 | Preparation method of trifloxystrobin |
| CN115490612A (en) * | 2022-10-24 | 2022-12-20 | 河北威远生物化工有限公司 | Synthesis method of trifloxystrobin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5346902A (en) * | 1990-08-22 | 1994-09-13 | Imperial Chemical Industries Plc | Fungicidal diazinyl dioxime |
| CN1560027A (en) * | 2004-03-05 | 2005-01-05 | 同济大学 | Preparation process of oxime strain ester |
-
2005
- 2005-11-18 CN CNB200510110511XA patent/CN100334070C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5346902A (en) * | 1990-08-22 | 1994-09-13 | Imperial Chemical Industries Plc | Fungicidal diazinyl dioxime |
| CN1560027A (en) * | 2004-03-05 | 2005-01-05 | 同济大学 | Preparation process of oxime strain ester |
Non-Patent Citations (1)
| Title |
|---|
| 肟、肟醚（酯）类化合物的构性转化及其机理 刘天麟 谢建华，化学通报，第9期 1997 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102992991A (en) * | 2012-11-29 | 2013-03-27 | 江苏长青农化股份有限公司 | Synthesis process for trifloxystrobin intermediate 2-methyl-alpha-carbonyl phenylacetic acid |
| CN102992991B (en) * | 2012-11-29 | 2016-02-10 | 江苏长青农化股份有限公司 | The synthesis technique of oxime bacterium fat intermediate 2-methyl-alpha-carbonyl toluylic acid |
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| CN1793115A (en) | 2006-06-28 |
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