CN100340537C - 4-(4- chlorophenoxy)-2'- chlorphenyl-alpha- Bromomethyl ketone preparation method - Google Patents
4-(4- chlorophenoxy)-2'- chlorphenyl-alpha- Bromomethyl ketone preparation method Download PDFInfo
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- CN100340537C CN100340537C CNB2006100377431A CN200610037743A CN100340537C CN 100340537 C CN100340537 C CN 100340537C CN B2006100377431 A CNB2006100377431 A CN B2006100377431A CN 200610037743 A CN200610037743 A CN 200610037743A CN 100340537 C CN100340537 C CN 100340537C
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Abstract
The present invention relates to a preparation method of germicide for farmers, particularly to a preparation method for the intermediate 4-(4-chlorophenoxy)-2'-chlorphenyl-alpha-morphine methyl ketone of cis, trans-3-Cl-4-[4-methyl-2-(1H-1, 2, 4-triazole-1-methyl)-1, 3-diopentane-2-group] phenyl-4-chlorine ether (phenyl ether methyl azole). The method improves preparation process, enhance yield, and plays an important role to industrialization large-scale production.
Description
Technical field
The present invention relates to a kind of disinfectant use in agriculture suitable, anti--3-chloro-4-[4-methyl-2-(1H-1,2,4-triazol-1-yl methyl)-1,3-dioxin-pentane-2-yl] preparation method of phenyl-4-chloro base ether (difenoconazole) intermediate 4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone.
Background technology
Difenoconazole belongs to azoles fungicide; has interior absorption; it is pure demethylation inhibitor; fungicidal spectrum is wide; foliar treatment or seed treatment can improve output and the guaranteed quality of crop; to Ascomycetes, Basidiomycetes has persistent protection and therapeutic activity with the imperfect fungi that comprises chain spore genus, the mould genus of tail spore, Colletotrichum, ball seat Pseudomonas, Phoma, Ramularia, Septoria, Venturia, Erysiphaceae, embroidery Zoopagales and some biography pathogenic bacteria.Uncinula necator, leaf spot of peanut, net blotch, target, wheat glume blight, leaf blight, rust, beet cercospora leaf spot etc. there is special efficacy.4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone is the intermediate of difenoconazole, and German Patent 3940130 has its relevant preparation method with 3836161 grades, but is difficult to reach Utopian quality and yield.As German Patent 3940130, make solvent with Glacial acetic acid, reaction solution adds water and uses dichloromethane extraction, and solvent load is bigger, and yield only is about 70%.And for example German Patent 3836161 usefulness methylene dichloride are made solvent, and reaction solution adds water, repeatedly use dichloromethane extraction again, and solvent load is very big, and yield is about about 90%, and invention can be increased to yield about 97%.Therefore, improve existing preparation technology, reduce the solvent usage quantity, improve productive rate and have very significant meaning for industrialized production.
Summary of the invention
The purpose of this invention is to provide a kind of yield height, be convenient to the disinfectant use in agriculture intermediates preparation of industrialized production.
Be specifically related to prepare the method for ω-halo acetophenone compound with Formula Il structural formula feature:
This method comprises:
The methyl phenyl ketone that will have following formula I structural formula feature is dissolved in the organic solvent, adds catalyzer, and controlled temperature adds bromizating agent solution, as bromine (Br at 0～128 ℃
2) or N-bromosuccinimide (NBS), continue stirring reaction, be washed to neutrality again, precipitation obtains halogenide.
Among its Chinese style (I), (II), A is sulphur or oxygen, and B is F, Cl, Br, R
1, R
2, R
3, R
4Be independently hydrogen, halogen, haloalkyl, alkyl, alkoxyl group, halogenated alkoxy or halogenated alkylthio separately.
Among this preparation method, described organic solvent is the one or any two or more mixture in toluene, dimethylbenzene, normal hexane, ether, Glacial acetic acid, the methylene dichloride.Described catalyzer is the one or any two or more mixture of dimethyl formamide, pyridine, tetramethyleneimine, morpholine, quaternary ammonium salt.Described bromizating agent is bromine (Br
2) or N-bromosuccinimide (NBS), the feed ratio of bromizating agent and Compound I is 1: 1～3: 1, its dropping time was controlled at 3～6 hours.
Among this preparation method, preferred temperature is controlled at 15～65 ℃.
Be operating as more specifically: 4-(4-chlorophenoxy)-2 '-chloro-acetophenone is dissolved in the organic solvent, add catalyzer, be chilled to below 65 ℃, add bromizating agent solution in the dropping mode, and continue stirring reaction, wash layering then, use alkali liquid washing again, be washed to neutrality, the decompression precipitation obtains bromide.
When bromizating agent is bromine (Br
2) time, this preparation method's reaction equation is as follows:
Wherein A is sulphur or oxygen, R
1, R
2, R
3, R
4Be independently hydrogen, halogen, haloalkyl, alkyl, alkoxyl group, halogenated alkoxy or halogenated alkylthio separately.
Preparation method of the present invention can improve the bromination yield, and wherein the bromizating agent dropping time is 3-6 hour, drips off the back sampling and follows the tracks of, up to reacting completely.
Preparation method of the present invention must the strict amount of controlling bromizating agent.If bromizating agent is few, can make that Compound I can not complete reaction, if bromizating agent is excessive too many, can cause the generation of side reaction, produce dibromo compound, reduce the quality and the yield of product, more satisfactory proportioning is: the suitable feed ratio scope of bromizating agent and Compound I is 1: 1～3: 1 (mol ratio).The suitable feed ratio scope of bromizating agent and Compound I is selected to see the following form.
| Compound I and bromizating agent feed ratio | Raw material % | Compound I I% | Dibromo compound % | Other by-products % |
| 1∶1 | 3.6 | 92.8 | 0.9 | 2.7 |
| 1∶1.1 | 0.6 | 96.9 | 1.3 | 1.2 |
| 1∶1.3 | 0.58 | 92.3 | 4.2 | 2.92 |
| 1∶1.5 | 0.71 | 90.5 | 6.4 | 2.39 |
| 1∶2 | 0.46 | 87.6 | 9.8 | 2.14 |
| 1∶2.5 | 0.55 | 83.9 | 11.5 | 4.05 |
| 1∶3 | 0.78 | 79.6 | 14.7 | 4.92 |
In addition, among the preparation method of the present invention, tighter requirement is also arranged for temperature.Improving temperature of reaction can fast reaction speed, but the too high meeting of temperature has a negative impact, thereby causes side reaction to reduce yield.So suitable temperature of reaction is controlled at 0-128 ℃, preferred range is at 15-65 ℃.
Embodiment
Describe in detail below in conjunction with embodiment.
The preparation method of embodiment 1:4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone
With 4-(4-chlorophenoxy)-2 '-chloro-acetophenone 40g, be dissolved in the 100ml dimethylbenzene, add a small amount of morpholine, temperature adds 23.2g Br below 65 ℃ in the control
2In 3.5 hours, drip off, use the gas-chromatography trace analysis, transform fully to 4-(4-chlorophenoxy)-2 '-chloro-acetophenone, reaction mixture is added water stratification, use alkali liquid washing, be washed to neutrality again, the decompression precipitation obtains light yellow solid 45.9g (gas spectrum normalizing content 97%), water insoluble, mp:69.5-71.5 ℃.
1H-NMR(CDCl
3/tetramethylsilane)：δ＝4.71ppm。
The preparation method of example 2:4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone
With 4-(4-chlorophenoxy)-2 '-chloro-acetophenone 40g, be dissolved in the 100ml dimethylbenzene, add a small amount of morpholine, temperature adds 25.8gNBS in the dropping mode below 65 ℃ in the control, drips off in 3.5 hours, use the gas-chromatography trace analysis, transform fully to 4-(4-chlorophenoxy)-2 '-chloro-acetophenone, reaction mixture is added water stratification, use alkali liquid washing, be washed to neutrality again, the decompression precipitation obtains light yellow solid 45.9g (gas spectrum normalizing content 96%), water insoluble, mp:69.5-71.5 ℃.
1H-NMR(CDCl
3/tetramethylsilane)：δ＝4.71ppm。
The preparation method of embodiment 3:4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone
With 4-(4-chlorophenoxy)-2 '-chloro-acetophenone 40g, be dissolved in the 100ml toluene, add a small amount of tetramethyleneimine, temperature is about 15 ℃ in the control, adds 23.0g Br in the dropping mode
2, in 6 hours, drip off, use the gas-chromatography trace analysis, transform fully to 4-(4-chlorophenoxy)-2 '-chloro-acetophenone, be washed to neutrality again, precipitation obtains light yellow solid 44.0g (gas spectrum normalizing content 95.2%), and is water insoluble, mp:69.5-71.5 ℃.
1H-NMR(CDCl
3/tetramethylsilane)：δ＝4.71ppm。
The preparation method of embodiment 4:4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone
With 4-(4-chlorophenoxy)-2 '-chloro-acetophenone 20g, be dissolved in the 50ml Glacial acetic acid, add a small amount of dimethyl formamide, temperature adds 13.0g NBS below 100 ℃ in the control, drips off in 3 hours, use the gas-chromatography trace analysis, transform fully to 4-(4-chlorophenoxy)-2 '-chloro-acetophenone, wash layering then, use alkali liquid washing again, be washed to neutrality again, the decompression precipitation obtains light yellow solid 23.0g (gas spectrum normalizing content 95.6%), water insoluble, mp:69.5-71.5 ℃.
1H-NMR(CDCl
3/tetramethylsilane)：δ＝4.71ppm。
The preparation method of embodiment 5:4-(4-chlorophenoxy)-2 '-chloro-phenyl--α-brooethyl ketone
With 4-(4-chlorophenoxy)-2 '-chloro-acetophenone 40g, be dissolved in the 100ml methylene dichloride, add a small amount of quaternary ammonium salt, temperature adds 26.0g NBS below 80 ℃ in the control, drips off in 3.5 hours, use the gas-chromatography trace analysis, transform fully to 4-(4-chlorophenoxy)-2 '-chloro-acetophenone, wash layering then, use alkali liquid washing again, be washed to neutrality again, the decompression precipitation obtains light yellow solid 45.6g (gas spectrum normalizing content 96.6%), water insoluble, mp:69.5-71.5 ℃.
1H-NMR(CDCl
3/tetramethylsilane)：δ＝4.71ppm。
Claims (6)
1. method for preparing ω-halo acetophenone compound with Formula Il structural formula feature:
This method comprises:
The methyl phenyl ketone that will have following formula I structural formula feature is dissolved in the organic solvent, adds catalyzer, and controlled temperature adds bromizating agent solution at 0～128 ℃, continues stirring reaction, is washed to neutrality again, and precipitation obtains halogenide,
Among its Chinese style (I), (II), A is sulphur or oxygen, and B is F, Cl, Br, R
1, R
2, R
3, R
4Be independently hydrogen, halogen, haloalkyl, alkyl, alkoxyl group, halogenated alkoxy or halogenated alkylthio separately; Described catalyzer be in dimethyl formamide, pyridine, tetramethyleneimine, morpholine, the quaternary ammonium salt one of or any two or more mixture.
2. preparation method according to claim 1 is characterized in that described organic solvent is one of the following or any two or more mixture:
Toluene, dimethylbenzene, normal hexane, ether, Glacial acetic acid, methylene dichloride.
3. preparation method according to claim 1 is characterized in that described bromizating agent is bromine or N-bromosuccinimide.
4. preparation method according to claim 1, the molar ratio that it is characterized in that described bromizating agent and Compound I is 1: 1～3: 1.
5. preparation method according to claim 1 is characterized in that the described bromizating agent dropping time is 3～6 hours.
6. preparation method according to claim 1 is characterized in that described temperature is controlled at 15～65 ℃.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100377431A CN100340537C (en) | 2006-01-12 | 2006-01-12 | 4-(4- chlorophenoxy)-2'- chlorphenyl-alpha- Bromomethyl ketone preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100377431A CN100340537C (en) | 2006-01-12 | 2006-01-12 | 4-(4- chlorophenoxy)-2'- chlorphenyl-alpha- Bromomethyl ketone preparation method |
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|---|---|
| CN1807386A CN1807386A (en) | 2006-07-26 |
| CN100340537C true CN100340537C (en) | 2007-10-03 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3836161A1 (en) * | 1988-10-24 | 1990-04-26 | Bayer Ag | Pesticides based on substituted aminothiazoles |
| DE3940130A1 (en) * | 1989-12-05 | 1991-06-06 | Hoechst Ag | METHOD FOR PRODUCING 3,4'-DICHLOR-DIPHENYL ETHER |
-
2006
- 2006-01-12 CN CNB2006100377431A patent/CN100340537C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3836161A1 (en) * | 1988-10-24 | 1990-04-26 | Bayer Ag | Pesticides based on substituted aminothiazoles |
| DE3940130A1 (en) * | 1989-12-05 | 1991-06-06 | Hoechst Ag | METHOD FOR PRODUCING 3,4'-DICHLOR-DIPHENYL ETHER |
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|---|---|
| CN1807386A (en) | 2006-07-26 |
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Jiangsu Fengshan Group Co., Ltd. Assignor: Jiangsu Pesticide Research Institute Co., Ltd. Contract fulfillment period: 2007.12.25 to 2025.8.24 contract change Contract record no.: 2008320000161 Denomination of invention: Process for the preparation of 4- (4- phenoxy) -2 '- chloro - alpha - bromo methyl ketone Granted publication date: 20071003 License type: Exclusive license Record date: 2008.9.22 |
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