CN1303061C - Liquid phase synthesis process of oxime strain ester by poly-ethandiol - Google Patents
Liquid phase synthesis process of oxime strain ester by poly-ethandiol Download PDFInfo
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- CN1303061C CN1303061C CNB2004100167504A CN200410016750A CN1303061C CN 1303061 C CN1303061 C CN 1303061C CN B2004100167504 A CNB2004100167504 A CN B2004100167504A CN 200410016750 A CN200410016750 A CN 200410016750A CN 1303061 C CN1303061 C CN 1303061C
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Abstract
The present invention discloses a liquid phase synthesis process of trifloxystrobin by polyethyleneglycol, wherein (a) by means of hydroxyl on polyethyleneglycol to make a condensation reaction with 2-methylacetophenone acid, the 2-methylacetophenone acid is loaded onto the polyethyleneglycol to obtain 2-(2'-methylphenyl)-2-polyglycol carboxy acetate; (b) the 2-(2'-methylphenyl)-2-polyglycol carboxy acetate obtained in step (a) reacts with a methoxyamine hydrochloride to obtain 2-(2'-methylphenyl)-2-polyglycol carboxy acetate-O-methyl ketone oxime; (c) the compound obtained in step (b) is bromized to obtain 2-(2'-bromomethylphenyl)-2-polyglycol carboxy acetate-O-methyl ketone oxime; (d) under an alkaline condition, the compound obtained in step (c) is condensed together with meta-trifluoromethyl acetophenone oxime to obtain 2-[1'-{[(3'-trifluoromethylphenyl)-ethyl-imine]O}-O-tolyl]-2-polyglycol carboxy acetate-O-methyl ketone oxime; (e) the ester exchange reaction of the compound obtained in step (d) and methanol is carried out to obtain trifloxystrobin. On the basis of not changing the property of the trifloxystrobin as a product, the present invention simplifies the steps of separation and purification in a reaction process and reduces costs.
Description
Technical field
The present invention relates to a kind of preparation method of organic compound agricultural chemicals, relate in particular to a kind of with the synthetic oxime bacterium ester of polyoxyethylene glycol load liquid phase ((E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime) synthetic method.
Background technology
Oxime bacterium ester class wide-spectrum bactericide is the new fluorine-containing sterilant of successfully developing as the sterilant lead compound from natural product Strobilurins of a class.Be characterized in: efficient, wide spectrum, protection, treat, root out, infiltration, systemic activity, resistance of rainwater washing against, characteristic such as the lasting period is long.To 1, the bacterial strain of 4-demethylation enzyme inhibitors, benzamides, dicarboxylic dihydrazides amine and benzimidazoles generation resistance is effective, does not have cross resistance with at present existing sterilant.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 there is good activity.Except that Powdery Mildew, leaf spot are had the special efficacy, rust, oidium, damping-off, apple apple scab there is good activity.To crop safety, capable of being fast degraded in soil, water because of it, so environmentally safe.
Carry out on the polyoxyethylene glycol that liquid phase is synthetic to be used for synthetic polypeptide nucleotide and oligose and small molecules combinatorial libraries in a large number, but also be not used in the synthetic of oxime bacterium ester.
Summary of the invention
The object of the present invention is to provide the method for the synthetic oxime bacterium ester of a kind of polyoxyethylene glycol load liquid phase.
The present invention is achieved through the following technical solutions:
1,2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester
Hydroxyl on the polyoxyethylene glycol and the condensation reaction of o-methyl-benzene acetonic acid get 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester, this synthetic reaction medium is methyl alcohol, methylene dichloride, trichloromethane, acetonitrile or N, dinethylformamide, temperature is 0-40 ℃, preferred temperature is 20 ℃, condensing agent is DCC (dicyclohexylcarbodiimide), HOBt (1-hydroxy benzo triazole) or with acid and acyl chloride reaction, again with the polyoxyethylene glycol condensation.
2,2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester reacts with methoxy amine hydrochlorate under alkaline condition, this synthetic used reaction medium is methyl alcohol, methylene dichloride, trichloromethane, acetonitrile or N, dinethylformamide, alkaline reagents is triethylamine, pyridine, sodium hydroxide, potassium hydroxide etc., temperature is 10-80 ℃, preferred temperature is 60 ℃, and the pH value is 8-13, and preferred pH value is 10.
3,2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime obtains 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime through bromination, this synthetic used reaction medium is methyl alcohol, methylene dichloride, trichloromethane, acetonitrile or N, dinethylformamide, bromide reagent is bromine, NBS (N-bromo-succinimide), temperature of reaction is 10-70 ℃, and preferred temperature is 50 ℃.
4,2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime synthetic
2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime under alkaline condition with the condensation of m-trifluoromethyl acetophenone oxime, 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime.Reaction is sodium hydride, hydrolith, sodium hydroxide, potassium hydroxide, sodium amide etc. with alkali.Temperature of reaction is 20-70 ℃, and preferred temperature is 60 ℃.Reaction medium is methyl alcohol, methylene dichloride, trichloromethane, acetonitrile or N, dinethylformamide.The mol ratio of alkali and trifluoromethyl acetophenone oxime is 0.8-2.5: 1, and preferred molar ratio is 1.2: 1.
5, oxime bacterium ester is synthetic
2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime carries out transesterification reaction with methyl alcohol and gets oxime bacterium ester under highly acidic resin and sulphuric acid catalysis, the amount of catalyzer is 0.1-1%, methyl alcohol and 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-mol ratio of 2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is 1-20: 1, and temperature of reaction is 20-65 ℃.
The present invention, has simplified and has separated the step of purifying in the reaction process on the basis that does not change product property with the synthetic oxime bacterium ester of polyoxyethylene glycol load liquid phase, provides broad thinking for polyoxyethylene glycol is used for organic synthesis.
Embodiment
1,2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester
In the 100ml round-bottomed flask that stirring and reflux condensing tube are housed, add 2g (0.01mol) 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid and 5ml thionyl chloride, stirring at room 5 hours, rotation boils off excessive thionyl chloride, add a small amount of exsiccant normal heptane, rotation boils off normal heptane, in flask, add 20ml methylene dichloride and 10g polyoxyethylene glycol, room temperature reaction 8 hours, steaming vibrating dichloromethane adds ether, is settled out 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester, dissolve with methylene dichloride, steaming vibrating dichloromethane adds ether, gets purer 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester of 9.8g.
2,2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
In the 100ml three-necked bottle, add 9.8g 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester, 0.8g (0.01mol) methoxy amine hydrochlorate and 20ml95% ethanol, adding 1ml triethylamine adjusting pH is 10, temperature is 60 ℃, after the stirring and refluxing 10 hours, boil off solvent, add ether, be settled out 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime, add methylene dichloride and make resolution of precipitate, add ether, separate out precipitation, get 9.5g2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime.
3,2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
9.5g 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-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.Temperature of reaction is 50 ℃, reacts 8 hours, steams solvent, adds ether, separates out precipitation, and precipitation is dissolved in methylene dichloride, adds ether, gets 9.3g 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime.
4,2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime synthetic
1g (0.04mol) NaH is joined in the 50ml tetrahydrofuran (THF), at room temperature, add 2g (0.01mol) m-trifluoromethyl acetophenone oxime, after the heated and stirred 1 hour, add 9g 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime and 20ml tetrahydrofuran (THF), continue heated and stirred reaction 5 hours, temperature of reaction is controlled at about 60 ℃, steam solvent, add ether, separate out precipitation, precipitation is dissolved in methylene dichloride, add ether, obtain 8.9g 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime solid.
5, oxime bacterium ester is synthetic
With 9g 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime and 20ml methyl alcohol places three-necked bottle, reflux 8 hours, boil off solvent, go out product with acetic acid ethyl dissolution, steam solvent, get 0.6g oxime bacterium ester, fusing point: 70 ℃ with the sherwood oil recrystallization
1H?NMR(CDCl
3)：δ＝2.21(s，3H)，3.82(s，3H)，3.93(s，3H)，5.13(s，2H)，7.1-7.8(m，7H).
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 (6)
1, a kind of polyoxyethylene glycol liquid phase synthesis type (I) oxime bacterium ester ((E, E)-2-[1 '-(3 '-trifluoromethyl)-ethyl-imines-oxygen-tolyl]-2-carbonylic acetic acid methyl esters-O-ketoxime) method, this method comprises the steps:
Oxime bacterium ester (I)
(a) 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester
By hydroxyl on the polyoxyethylene glycol and the condensation reaction of o-methyl-benzene acetonic acid, the o-methyl-benzene acetonic acid is loaded on the polyoxyethylene glycol, get 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester;
(b) 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester reacts with methoxy amine hydrochlorate under alkaline condition, gets the synthetic of 2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime;
(c) 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime is synthetic
2-(2 '-aminomethyl phenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime obtains 2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime through bromination;
(d) 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime synthetic
2-(2 '-2-bromomethylphenyl)-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime under alkaline condition with the condensation of m-trifluoromethyl acetophenone oxime, 2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime;
(e) oxime bacterium ester is synthetic
2-[1 '-{ [(3 '-trifluoromethyl)-ethyl-imines] oxygen }-O-tolyl]-2-carbonylic acetic acid macrogol ester-O-methyl ketoxime and methyl alcohol carries out transesterify and gets oxime bacterium ester.
The method of 2, synthesizing oxime bacterium ester according to the described polyoxyethylene glycol liquid phase of claim 1, it is characterized in that: the reaction medium in described (a) and (b), (c) step is organic solvent methyl alcohol, methylene dichloride, trichloromethane, acetonitrile or N, a kind of in the dinethylformamide.
3, according to the method for the synthetic oxime bacterium ester of the described polyoxyethylene glycol liquid phase of claim 1, it is characterized in that:
Used condensing agent is dicyclohexylcarbodiimide or 1-hydroxy benzo triazole or with acid and acyl chloride reaction, again with the polyoxyethylene glycol condensation in described (a) step.
4. according to the method for the synthetic oxime bacterium ester of the described polyoxyethylene glycol liquid phase of claim 1, it is characterized in that: the alkali of reaction (b) usefulness is a kind of in triethylamine, pyridine, sodium hydroxide or the potassium hydroxide.
5. according to the method for the synthetic oxime bacterium ester of the described polyoxyethylene glycol liquid phase of claim 1, it is characterized in that: used bromide reagent is a kind of in bromine or the N-bromo-succinimide in the described step (c).
6. according to the method for the synthetic oxime bacterium ester of the described polyoxyethylene glycol liquid phase of claim 1, it is characterized in that:
Reaction (d) used alkali is a kind of in sodium hydride, hydrolith, sodium amide, sodium hydroxide or the potassium hydroxide.
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| CNB2004100167504A CN1303061C (en) | 2004-03-05 | 2004-03-05 | Liquid phase synthesis process of oxime strain ester by poly-ethandiol |
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| CNB2004100167504A CN1303061C (en) | 2004-03-05 | 2004-03-05 | Liquid phase synthesis process of oxime strain ester by poly-ethandiol |
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| CN1303061C true CN1303061C (en) | 2007-03-07 |
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| CN102952036A (en) * | 2012-11-18 | 2013-03-06 | 大连九信生物化工科技有限公司 | Preparation method of trifloxystrobin |
| CN111333535B (en) * | 2020-04-20 | 2022-03-01 | 江苏食品药品职业技术学院 | Preparation method of trifloxystrobin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0460575A1 (en) * | 1990-06-05 | 1991-12-11 | Ciba-Geigy Ag | Aromatic compounds |
| US5238956A (en) * | 1990-08-22 | 1993-08-24 | Imperial Chemical Industries Plc | Fungicidal aromatic dioxime |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0460575A1 (en) * | 1990-06-05 | 1991-12-11 | Ciba-Geigy Ag | Aromatic compounds |
| US5238956A (en) * | 1990-08-22 | 1993-08-24 | Imperial Chemical Industries Plc | Fungicidal aromatic dioxime |
| US5346902A (en) * | 1990-08-22 | 1994-09-13 | Imperial Chemical Industries Plc | Fungicidal diazinyl dioxime |
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Granted publication date: 20070307 Termination date: 20100305 |