CN102796062A - Method for preparing flumorph - Google Patents
Method for preparing flumorph Download PDFInfo
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- CN102796062A CN102796062A CN2011101360867A CN201110136086A CN102796062A CN 102796062 A CN102796062 A CN 102796062A CN 2011101360867 A CN2011101360867 A CN 2011101360867A CN 201110136086 A CN201110136086 A CN 201110136086A CN 102796062 A CN102796062 A CN 102796062A
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Abstract
The invention belongs to the field of organic synthesis, and relates to a method for preparing flumorph. The method comprises the following steps: adding a metal amino compound, morpholinoethanone accounting for about 1/3 of the total content and organic solvent into a reaction bottle, slowly heating under the action of stirring until reflux, and ensuring that the added morpholinoethanone fully reacts with the metal amino compound; dripping benzophenone dissolved in the organic solvent and morpholinoethanone accounting for about 2/3 of the total content into the reaction bottle, keeping the reflux temperature, and continuously stirring and reacting until the benzophenone totally reacts; and separating the unreacted raw materials and the solvent from the reaction solution, thus obtaining the product, namely flumorph. By using the method, the production safety is improved, the production cost is reduced, and the production efficiency is improved; and the method is suitable for industrial production.
Description
Technical field
The invention belongs to the organic synthesis field, relate to a kind of method for preparing SYP-L190.
Background technology
SYP-L190 (English popular name: flumorph; Chemical name: 3-(4-fluorophenyl)-3-(3; The 4-Dimethoxyphenyl) acryloyl morpholine) is Shenyang Chemical Engineering Inst's independent research and the efficient agricultural bactericide of having realized industrialization, cucumber downy mildew, Chinese cabbage downy mildew, tomato late blight, capsicum epidemic disease, downy mildew of garpe etc. are had excellent activity.Because SYP-L190 has outstanding drug effect, the research of its preparation method also receives the attention of industry.Chinese patent CN1167568A once disclosed a kind of preparation method of SYP-L190, and adopting 4-fluoro-(3, the 4-dimethoxy) benzophenone (abbreviation benzophenone) and NSC 2764 is raw material, in the presence of sodium tert-butoxide, reflux in toluene 5-8 hour prepares title product.That but this method remains is many at long reaction time, impurity, wastewater flow rate is bigger, and the trimethyl carbinol that generates of the reaction defective that is not easy to remove." research of SYP-L190 condensation process " (" modern agricultural chemicals " Vol.8; N0.2 Apr.2009) has reported the method for preparing SYP-L190 with sodium amide in the literary composition, but confirmatory experiment is found; This method not only can't repeat the bibliographical information result; And because inflammable and the easy moisture absorption of sodium amide, it is very dangerous to add sodium amide down at the given reaction conditions of document, is difficult to assurance and keeps the safety in production; Also there is very big potential safety hazard in the post-treating method of bibliographical information in addition, can not satisfy industrial requirement.
Summary of the invention
The present invention is devoted to develop a kind of method for preparing SYP-L190 of operational safety, to satisfy industrial needs; Require simultaneously that product cost is lower, yield and purity is higher.Through intensive research, the present invention proposes a kind of new method for preparing SYP-L190.
Technical scheme of the present invention is following:
A kind of method for preparing SYP-L190 comprises following reactions step:
1) under the room temperature metal amino thing, the NSC 2764 that accounts for total consumption 1/3 and organic solvent are added in the reaction flask, stir down and slowly be warming up to backflow, the NSC 2764 of adding and metal amino thing are fully reacted;
The benzophenone that 2) will be dissolved in the organic solvent splashes in the reaction flask with the NSC 2764 that accounts for total consumption 2/3, keeps reflux temperature, continues stirring reaction to benzophenone and reacts completely;
3) in reaction solution, add moisture and go out or destroy the surplus stock in the reaction solution, obtain the product SYP-L190 after separating solvent again.
The add-on of metal amino thing is a 1.5-2.5 times of mole number of benzophenone, and the add-on of NSC 2764 is a 1.2-3 times of mole number of benzophenone.Reaction process is followed the tracks of with liquid chromatography (HPLC), and benzophenone reacts completely and is reaction end.
Reaction initial charge temperature gets final product in room temperature, and ambient temperature is between 15-25 ℃ usually.
The structural formula of the raw material NSC 2764 that relates among the described preparation method, benzophenone and product SYP-L190 is following:
The metal amino thing that reacts used is selected from sodium amide, potassium amide, amino calcium or amino aluminium etc.; Further preferred as alkali amino substance is sodium amide or potassium amide for example.The add-on of preferred as alkali amino substance is a 1.5-2.5 times of mole number of benzophenone.
React used organic solvent and be selected from inert solvents such as the heterocycle that contains 4-6 carbon atom, saturated rings alkane, aromatic hydrocarbon, preferred water-insoluble solvent; Further preferred solvent is selected from benzene, toluene or YLENE etc.The amount ranges of solvent is appreciated by those skilled in the art.
NSC 2764 adds the reaction that can make itself and basic metal amino substance in batches and is unlikely to too fierce, improves the stationarity of the operation in the industrial production.As everyone knows; Sodium amide at low temperatures with the NSC 2764 reaction temperature with; Sodium amide and NSC 2764 react the generation intermediate state at low temperatures: carbanion; Reduce the content of sodium amide in the reaction system simultaneously, effectively reduced the potential safety hazard that sodium amide too much causes under the hot conditions, shortened the reaction times simultaneously.Further discover, suitably increase the NSC 2764 consumption and more help carrying out smoothly of reaction process.The add-on of preferred NSC 2764 is a 2-3 times of mole number of benzophenone.
Concrete operations condition of the present invention is following:
Different according to used solvent, the 1st) the suitable temperature of reaction (reflux temperature) of NSC 2764 and basic metal amino substance is 70-150 ℃ in the step operation; Can carry out next-step operation when reaction solution reaches reflux temperature, react completely guaranteeing but recommend to continue 10 minutes-30 minutes stirring and refluxing reaction times.
Operation 2) in, the dropping time of reaction mixture material is to be advisable in 30-60 minute; The stirring reaction time is 10 minutes-30 minutes.
Reaction is reduced to reacting liquid temperature below 50 ℃ after accomplishing, and slowly adds cold water, prevents excess of ammonia base sodium and a large amount of water vigorous reactions, causes to dash material.Standing demix.Tell water (wherein containing excessive NSC 2764 and disrupted basic metal amino substance), again with obtaining the product SYP-L190 behind the organic phase underpressure distillation Separation and Recovery solvent.
The solvent of Separation and Recovery can recycled in following batch is produced.
Preparing method provided by the invention, easy and simple to handle, mild condition, suitability for industrialized production is reacted raw materials used and reagent all has commercially available.Product yield is more than 90%, and content is more than 95%.
Preparing method of the present invention has following beneficial effect:
1. in building-up process, pass through to change order of addition(of ingredients) and charge temperature; In product aftertreatment sepn process water filling and excess of ammonia base sodium reaction in reaction mass at low temperatures; Thereby improved the security of producing greatly, for the mass-producing that realizes SYP-L190 production provides favourable technical guarantee;
2. compared with prior art, adopt preparation method of the present invention can make the SYP-L190 product yield improve 10%, this is for reducing production costs in the large-scale industrial production, enhancing productivity, and energy-saving and emission-reduction all have very important realistic meaning.
Embodiment
Following examples are used for further explain the present invention, but the present invention only limits to this absolutely not.
Embodiment 1
With in 500 milliliters of reaction flasks of 40 milliliters of toluene addings (have and stir and prolong), add 5 gram NSC 2764s (0.038mol), 3.6 gram sodium amides (0.092mol); Be warming up to backflow, insulation reaction 30 minutes drips under reflux state then and is dissolved with 60 milliliters of toluene that 13 gram benzophenone (0.05mol) and 10 restrain NSC 2764s (0.077mol); Added in 1 hour, and dropwised, continue back flow reaction; HPLC follows the tracks of, and reaction in 0.5 hour finishes.Reaction solution is cooled to 50 ℃, to wherein slowly adding 100 ml waters, tells organic layer, and water layer merges organic layer with 80 milliliters of extracted in toluene.Toluene recovery set usefulness is sloughed in decompression, gets product 17.7 gram white solid products, content 96%, yield 91.6%, fusing point 112-113 ℃.
Embodiment 2
With in 500 milliliters of reaction flasks of 50 milliliters of toluene addings (have and stir and prolong), add 6 gram NSC 2764s (0.046mol), 3.9 gram sodium amides (0.1mol); Be warming up to backflow, insulation reaction 30 minutes drips under reflux state then and is dissolved with 70 milliliters of toluene that 13 gram benzophenone (0.05mol) and 12 restrain NSC 2764s (0.093mol); Added in 1 hour, and dropwised, continue back flow reaction; HPLC follows the tracks of, and reaction in 0.5 hour finishes.Post-processing operation gets 17.6 gram white solid products, content 97.8%, yield 92.6%, fusing point 112.5-113 ℃ with instance 1.
Embodiment 3
Feeding quantity and reaction conditions and post-processing operation all are same as embodiment 1, only make solvent with YLENE replacement toluene.Get 17.5 gram white solid products, content 95.5%, yield 90.2%, fusing point 112-113 ℃.
Embodiment 4
Feeding quantity and reaction conditions and post-processing operation all are same as embodiment 1, only make solvent with benzene replacement toluene.Get 17.6 gram white solid products, content 95.0%, yield 90.3%, fusing point 112-113 ℃.
Claims (6)
1. method for preparing SYP-L190; It is characterized in that comprising following reactions step: 1) under the room temperature metal amino thing, the NSC 2764 that accounts for total consumption 1/3 and organic solvent are added in the reaction flask; Stir down and slowly be warming up to backflow, the NSC 2764 of adding and metal amino thing are fully reacted; The benzophenone that 2) will be dissolved in the organic solvent splashes in the reaction flask with the NSC 2764 that accounts for total consumption 2/3, keeps reflux temperature, continues stirring reaction to benzophenone and reacts completely; 3) in reaction solution, add moisture and go out or destroy the surplus stock in the reaction solution, obtain the product SYP-L190 after separating solvent again; The add-on of metal amino thing is a 1.5-2.5 times of mole number of benzophenone, and the add-on of NSC 2764 is a 1.2-3 times of mole number of benzophenone.
2. according to the described preparation method of claim 1, it is characterized in that: described metal amino thing is selected from sodium amide, potassium amide, amino calcium or amino aluminium.
3. according to the described preparation method of claim 2, it is characterized in that: described metal amino thing is selected from sodium amide or potassium amide.
4. according to the described preparation method of claim 1, it is characterized in that: described organic solvent is selected from benzene, toluene or YLENE.
5. according to the described preparation method of claim 1, it is characterized in that: the add-on of NSC 2764 is a 2-3 times of mole number of benzophenone.
6. according to the described preparation method of claim 1, it is characterized in that: reaction is reduced to reacting liquid temperature below 50 ℃ after accomplishing, and slowly adds cold water, and standing demix is told water, again with obtaining the product SYP-L190 behind the organic phase underpressure distillation Separation and Recovery solvent.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110136086.7A CN102796062B (en) | 2011-05-25 | 2011-05-25 | Method for preparing flumorph |
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| CN201110136086.7A CN102796062B (en) | 2011-05-25 | 2011-05-25 | Method for preparing flumorph |
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| CN102796062A true CN102796062A (en) | 2012-11-28 |
| CN102796062B CN102796062B (en) | 2014-12-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103483245A (en) * | 2013-09-03 | 2014-01-01 | 中国农业大学 | Synthetic process improvement of novel agricultural bactericide pyrimorph |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1167568A (en) * | 1995-08-28 | 1997-12-17 | 化学工业部沈阳化工研究院 | Fungicide contg. fluorodiphenyl acrylamides |
| EP0860438A1 (en) * | 1997-02-21 | 1998-08-26 | Shenyang Research Institute of Chemical Industry | Fluorine-containing diphenyl acrylamide antimicrobial agents |
| US6020332A (en) * | 1997-02-20 | 2000-02-01 | Shenyang Research Institute Of Chemical Industry | Fluorine-containing diphenyl acrylamide antimicrobial agents |
-
2011
- 2011-05-25 CN CN201110136086.7A patent/CN102796062B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1167568A (en) * | 1995-08-28 | 1997-12-17 | 化学工业部沈阳化工研究院 | Fungicide contg. fluorodiphenyl acrylamides |
| US6020332A (en) * | 1997-02-20 | 2000-02-01 | Shenyang Research Institute Of Chemical Industry | Fluorine-containing diphenyl acrylamide antimicrobial agents |
| EP0860438A1 (en) * | 1997-02-21 | 1998-08-26 | Shenyang Research Institute of Chemical Industry | Fluorine-containing diphenyl acrylamide antimicrobial agents |
Non-Patent Citations (2)
| Title |
|---|
| 孙德群 等: "氟吗啉缩合新工艺的研究", 《现代农药》, vol. 8, no. 2, 30 April 2009 (2009-04-30), pages 32 - 33 * |
| 折冬梅 等: "杀菌剂氟吗啉的14C标记合成", 《核农学报》, vol. 21, no. 2, 20 April 2007 (2007-04-20), pages 206 - 207 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103483245A (en) * | 2013-09-03 | 2014-01-01 | 中国农业大学 | Synthetic process improvement of novel agricultural bactericide pyrimorph |
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Effective date of registration: 20160115 Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No. Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD. Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28 Patentee before: Sinochem Corporation Patentee before: Shenyang Research Institute of Chemical Industry |
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Application publication date: 20121128 Assignee: ZHONGHUA CROP PROTECTOR CO.,LTD. Assignor: SHENYANG SINOCHEM AGROCHEMICALS R&D Co.,Ltd. Contract record no.: X2021210000061 Denomination of invention: A method for preparing flumorpholine Granted publication date: 20141224 License type: Common License Record date: 20211214 |