CN1332171A - Improved prep. of 3-trifluoro methyl-5-hydroxy-pyrazole phosphate derivatives in the presence of hydrosolvent - Google Patents
Improved prep. of 3-trifluoro methyl-5-hydroxy-pyrazole phosphate derivatives in the presence of hydrosolvent Download PDFInfo
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- CN1332171A CN1332171A CN00122691A CN00122691A CN1332171A CN 1332171 A CN1332171 A CN 1332171A CN 00122691 A CN00122691 A CN 00122691A CN 00122691 A CN00122691 A CN 00122691A CN 1332171 A CN1332171 A CN 1332171A
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- CN
- China
- Prior art keywords
- hydroxy
- trifluoro methyl
- acid ester
- pyrazoxon
- solvent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
Abstract
The present invention provided is a preparation method in making 3-trifluoromethyl-5-hydroxylpyrazole phosphoric acid ester derivatives using water as a solvent in place of organic solvent. Using halophosphate in the esterification reaction between derivatives of 5-hydroxylpyrazole and halophosphate as materials with catalysts such as dimethylaminopyridine and strong inorganic bases like hydroxides of alkali metal. The reaction process shortens the reaction time and offers high yield because the pure product is obtained by a simple extraction method, having excellent applied value in the industry.
Description
The present invention relates in the presence of water solvent the improvement preparation method of 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant.In more detail, the present invention uses 5-hydroxy-pyrazole derivative and halogen-phosphate derivative as raw material, implements by esterification.This method selects for use Dimethylamino pyridine class material to make catalyzer, select for use alkali metal hydroxide to make inorganic strong alkali, the eliminating of maximum possible the use of organic solvent, replace with water solvent, not only shorten the reaction times to greatest extent, and had the effect that the preparation yield is improved.Especially by using inorganic strong alkali and water solvent, make that the separation of 3-trifluoro methyl-5-hydroxy pyrazoles and halogen-phosphate class unreacting substance is easy, being the recyclable high purity purpose product that obtains with extraction one class simple process for refining only, is the improvement preparation method of 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant shown in the industrial following Chemical formula 1 with fine practical value.
In the formula: R
1Expression hydrogen atom or halogen atom;
R
2Expression C
1～C
6The straight or branched low alkyl group;
R
3Expression C
1～C
6Straight or branched lower alkoxy, C
1～C
6Straight or branched is low
Level alkylthio, phenoxy group or sulfo-phenoxy group;
R
4Expression hydrogen atom, C
1～C
6Straight or branched low alkyl group, phenyl or substituted benzene
Base, when being substituted-phenyl, substituting group is halogen atom, trifluoromethyl
Perhaps C
1～C
6The straight or branched lower alkoxy;
X represents oxygen or sulphur atom.
Pyrethrin (ピ レ ト ロ イ De) compounds is the price height not only, and takes care of, decomposes easily in air when using and lost efficacy.Although these shortcomings are arranged, they remain the outstanding sterilant that always is widely used.But after using repeatedly for many years, insect has produced resistance to agricultural chemicals, and this compounds can not be brought into play the effective insecticidal effect, and must use in a large number could be effectively.
So, had with the pyrazoles phosphate derivative to replace the scheme (No. 16993rd, Korean Patent) of pyrethrin compounds as sterilant.But these pyrazole compounds do not satisfy physiologically active, the insecticidal effect that particularly resists property of medicine vegetables worm butterfly, rice grub, aphid group etc. extremely a little less than.
On the one hand, the material that the inventor will develop is to have good physiologically active than above-mentioned pyrazoles phosphate derivative, the sterilant of more extensive insecticidal effect.This sterilant is the novel 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of representing with Chemical formula 1 (No. the 36480th, Korean Patent, No. the 1st, 837,380, Japanese Patent, No. the 4th, 822,779, United States Patent (USP)).
By research repeatedly to efficient, the mass production method of the represented novel cpd of Chemical formula 1, replace the purpose of possible method of the organic solvent of, high price harmful to environment with water solvent for exploitation, the present invention has developed a kind of preparation method of improvement.In detail, preparation method of the present invention is: in the esterification of 5-hydroxy-pyrazole derivative and halogen phosphoric acid derivatives, select for use Dimethylamino pyridine and alkali metal hydroxide inorganic strong alkali material as catalyzer, adopt the reaction conditions of esterification, even used organic solvent can be got rid of with water solvent to greatest extent to replace, reaction can be carried out smoothly, and on process for purification, needn't use column chromatography to separate, just can reclaim with simple extraction and obtain highly purified purpose product.
So the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant that the objective of the invention is to represent for Chemical formula 1 provides the improvement preparation method of industrialized production practicality.
The present invention is the preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant represented of Chemical formula 1, and the 5-hydroxy-pyrazole derivative that this method is represented by Chemical formula 2 and the halogen-phosphate derivative of chemical formula 3 expressions set out, and carry out through esterification.
The invention is characterized in and use Dimethylamino pyridine, alkali metal hydroxide inorganic strong alkali material to make catalyzer, use water as solvent and carry out esterification.
In the formula, R
1, R
2, R
3, R
4, X definition identical with aforementioned definitions, Hal represents halogen atom.
Below just the present invention elaborate.
The present invention relates to the preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant represented as disclosed Chemical formula 1 in No. the 4th, 822,779, No. the 36480th, the Korean Patent, No. the 1st, 837,380, Japanese Patent, United States Patent (USP).Preparation method of the present invention, greatly got rid of the high price organic solvent that uses as reaction solvent, industrial utility value is risen, reduced discharging to environmentally hazardous substance, and the use by alkali metal hydroxide inorganic strong alkali and water solvent, also having and can effectively remove unreacted reactant, omitted the effect such as the process for refining of column chromatography one class complexity, is a kind of preparation method of improvement.
According to the present invention, the preparation method of the compound that Chemical formula 1 is represented is described in detail as follows:
Shown in the following reaction formula, the raw materials used material of the present invention is the 5-hydroxy-pyrazole derivative that Chemical formula 2 is represented, though they exist with tautomer in reaction solvent, and it exists ratio different because of reaction solvent, but the inventor studies show that, actual esterification and tautomer are irrelevant, can obtain the identical purpose product of identical yield.So although the 5-hydroxy-pyrazole derivative is actually the mixture of its tautomer, the present invention still simply represents with Chemical formula 2.
On the one hand, according to the present invention, catalyst system therefor is a Dimethylamino pyridine, specifically 2-Dimethylamino pyridine or 4-Dimethylamino pyridine.
On the other hand, according to the present invention, used alkali is alkali metal hydroxide during esterification, all can as sodium hydroxide, potassium hydroxide etc.When enforcement is of the present invention, if use organic basess such as inorganic weak bases such as alkaline carbonate, supercarbonate or aminated compounds, then can not carry out smoothly owing to esterification, when reaction finishes, by product 3-trifluoro methyl-5-hydroxy pyrazoles and halogen-phosphate are difficult to remove, final purpose degree of purity of production and yield are low, need treating process just can isolate the purpose product.
On the contrary, if carry out esterification, after reaction ends, obtain highly purified purpose product even only just can reclaim with methylene dichloride, chloroform kind solvent according to reaction conditions of the present invention.Its reason is: 3-trifluoro methyl-5-hydroxy pyrazoles that exists as unreacted reactant and halogen-phosphate by with the reaction of alkali, can transfer to water layer automatically with the form of hydroxy salt.So method produced according to the present invention is even without the refining step of column chromatography one class complexity, also can reclaim and obtain highly purified purpose product.
Maximum feature of the present invention is that also water is as reaction solvent.Used water and a small amount of organic solvent mix use in case of necessity, and organic solvent can be from C
3-C
8Material such as rudimentary hydro carbons (as: pentane, hexane, heptane, octane), ether, tetrahydrofuran (THF), methylene dichloride, chloroform, acetonitrile in select.At this moment, organic solvent will be lower than 50% to the volume fraction of water, if usage quantity exceeds 50% (volume), purpose and effect that the present invention will limit the organic solvent usage quantity will can not get sufficient embodiment.
Under the above-mentioned reaction conditions, esterification can be finished in 3 hours under the reflux temperature of water, and the preparation yield is more than 85%.The compound of representing with Chemical formula 2 by the moment of completely consumed as reaction end, in reaction at the end, can easily confirm by methods such as TLC, GC.After esterification is all over, then available well-known method as: with organic solvent extraction above-mentioned reaction soln, extraction liquid washes with water more for several times and desolvates to remove, and carries out operations such as necessary vapor enrichment, recrystallization, column chromatography for separation afterwards again.In addition, the purpose product of the present invention represented of above-mentioned Chemical formula 1 can be used methods such as NMR, IR, MS to identify to confirm.
Now describe the present invention in detail, but the invention is not restricted to these examples with following embodiment.
Embodiment 1 in the presence of 4-Dimethylamino pyridine catalyzer and water solvent, 0, the preparation of 0-diethyl-O-(1-phenyl-3-trifluoromethyl-5-pyrazoles) thiophosphatephosphorothioate:
With 1-phenyl-3-trifluoro methyl-5-hydroxy pyrazoles (5.00g, 0.022mol) and NaOH (1.76g, 0.044mol) be dissolved in water (100mL), add diethyl chlorothio phosphoric acid ester (4.13g, 0.022mol) and the 4-Dimethylamino pyridine (following brief note is 4-DMAP, 0.1g, 1.0mmol), afterwards, stirring and refluxing is 3 hours.After reaction ends,, use MgSO after cleaning with methylene dichloride (50ml * 2) extractive reaction mixture, extraction liquid washed several times with water
4Drying is removed and is desolvated, and obtains faint yellow oily title compound (7.36g, yield 88%, purity＞95%).
1HNMR(CDCl
3)：δ7.5(m，5H)，6.4(s，1H)，4.2(q，4H)，1.3(t，6H)Mass(m/e)：380
Adopt the method identical, under the listed condition of table 1, carry out repeatedly esterification, result such as table 1 with embodiment 1.
Table 1
| Reaction conditions | Yield (%) | Reaction times (hour) | |||
| Catalyzer | Alkali | Solvent | Temperature | ||
| Catalyst-free | NaOH | Water | Reflux temperature | 81 | ?6 |
| Room temperature | ＜15 | ?48 | |||
| 4-DMAP | ?NaOH | Water | Reflux temperature | 88 | ?3 |
| Room temperature | 92 | ?48 | |||
| 4-DMAP | ?NaOH | Water | Reflux temperature | 87 | ?3 |
| Room temperature | 84 | ?48 | |||
Still adopt method similarly to Example 1, under the listed condition of table 2, carry out esterification:
Table 2
| Reaction conditions | Yield (%) | Reaction times (hour) | |||
| Catalyzer | Alkali | Solvent | Temperature | ||
| 4-DMAP | ?NaOH | Water | Reflux temperature | 88 | ?3 |
| 4-DMAP | ?NaOH | Water/methylene dichloride | Reflux temperature | 86 | ?5 |
| 4-DMAP | ?NaOH | Water/acetonitrile 1/1, v/v | Reflux temperature | 84 | ?7 |
| 4-DMAP | ?NaOH | Methylene dichloride | Reflux temperature | ＜5 | ?8 |
Table 2 is the result show: under same reaction conditions (4-DMAP catalyzer, NaOH class inorganic strong alkali reflux), if only use methylene dichloride as reaction solvent, then because the NaOH major part can not be dissolved, the result makes the preparation yield low.
On the contrary, according to the present invention, use water solvent separately, since unreacted 5-hydroxypyrazoles and halogen-phosphate by with the reaction of NaOH, become the form of hydroxy salt at water layer, can remove automatically, utilize the chromatography chromatographic separation, can obtain purity 95% the above object product.In addition, water mixes as the reaction solvent use with a small amount of organic solvent in case of necessity, also can obtain satisfied result.
But, the purpose of this invention is to provide the improvement preparation method who is fit to industrialized production,, mix use with water and organic solvent and compare, more wish to make water separately as solvent as reaction solvent from purpose of the present invention.
Embodiment 2 4-Dimethylamino pyridine catalyzer and water solvent exist down, and 0, the preparation of 0-diethyl-O-(1-methyl-3-trifluoromethyl-5-pyrazoles) thiophosphatephosphorothioate:
1-methyl-3-trifluoro methyl-5-hydroxy pyrazoles (1.66g, 0.01mol) and NaOH (0.8g is 0.02mol) in water-soluble (50ml), add diethyl chlorothio phosphoric acid salt (1.89g, 0.01mol) and the 4-Dimethylamino pyridine (0.1g, 0.8mmol), afterwards, stirred 48 hours under the room temperature.After reaction finished, with ethylene dichloride extractive reaction mixing solutions (30mL * 2), extraction liquid washed with water for several times again, uses MgSO
4Dry removing desolvated, and obtains faint yellow oily title compound (2.80g, yield 88%, purity＞95%).
1HNMR(CDCl
3)：δ6.3(s，1H)，3.9(q，4H)，3.6(s，3H)，1.2(t，6H)Mass(m/e)：318
As indicated above, effect of the present invention is: use separately aqueous solvent can obtain 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant, and yield is enough high. Effect of the present invention also is: need to use the solvent of tonnage number of stages when producing in a large number, owing to replaced organic solvent with aqueous solvent, both reduce production cost, significantly reduce again the discharging of environmentally harmful organic substance.
Claims (6)
1. the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant preparation method that represents of Chemical formula 1, the halogen-phosphate derivative of 5-hydroxy-pyrazole derivative that this method is represented by Chemical formula 2 and chemical formula 3 expressions carries out the ester reaction to be realized, it is characterized in that above-mentioned esterification uses Dimethylamino pyridine to make catalyzer, use the alkali metal hydroxide inorganic strong alkali, use water as solvent
In the formula: R
1Expression hydrogen atom or halogen atom;
R
2Expression C
1～C
6The straight or branched low alkyl group;
R
3Expression C
1～C
6Straight or branched lower alkoxy, C
1～C
6Straight or branched lower alkylthio, phenoxy group or sulfo-phenoxy group;
R
4Expression hydrogen atom, C
1～C
6Straight or branched low alkyl group, phenyl or substituted-phenyl, when being substituted-phenyl, substituting group is halogen atom, trifluoromethyl or C
1～C
6The straight or branched lower alkoxy;
X represents oxygen, sulphur atom;
Hal represents halogen atom.
2. the improvement preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of claim 1 record is characterized in that Dimethylamino pyridine is 2-Dimethylamino pyridine or 4-Dimethylamino pyridine.
3. the improvement preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of claim 1 record is characterized in that basic metal gold oxide compound is sodium hydroxide or potassium hydroxide.
4. the improvement preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of claim 1 record is characterized in that esterification carries out in the temperature range of backflow at normal temperature.
5. the improvement preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of claim 1 record when it is characterized in that esterification is carried out, can mix to use being selected from C
3～C
8The organic solvent of lower hydrocarbon, ether, tetrahydrofuran (THF), methylene dichloride, chloroform and acetonitrile, usage quantity are below 50% (volume) of water solvent.
6. the improvement preparation method of the 3-trifluoro methyl-5-hydroxy pyrazoxon acid ester derivant of claim 1 record, it is characterized in that the compound that Chemical formula 1 is represented is 0,0-diethyl-O-(1-phenyl-3-trifluoromethyl-5-pyrazoles) thiophosphatephosphorothioate or 0,0-diethyl-O-(1-methyl-3-trifluoromethyl-5-pyrazoles) thiophosphatephosphorothioate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR35729/2000 | 2000-06-27 | ||
| KR1020000035729A KR100351631B1 (en) | 2000-06-27 | 2000-06-27 | A improved process for preparing 3-trifluoromethyl-5- hydroxypyrazole phosphonic acid ester derivatives in water solvent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1332171A true CN1332171A (en) | 2002-01-23 |
| CN1142169C CN1142169C (en) | 2004-03-17 |
Family
ID=19674247
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB001226916A Expired - Fee Related CN1142169C (en) | 2000-06-27 | 2000-08-16 | Improved prep. of 3-trifluoro methyl-5-hydroxy-pyrazole phosphate derivatives in the presence of hydrosolvent |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR100351631B1 (en) |
| CN (1) | CN1142169C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104322549A (en) * | 2013-11-21 | 2015-02-04 | 海南正业中农高科股份有限公司 | Pesticide composition containing flupyrazofos and spinosad |
| CN113839089A (en) * | 2020-06-24 | 2021-12-24 | 张家港市国泰华荣化工新材料有限公司 | Lithium ion battery electrolyte and lithium ion battery containing same |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101113161B1 (en) * | 2010-02-10 | 2012-02-14 | 주식회사 유티솔 | A System For Controlling Diming of Lamps Using IP Based Combo Sensor |
| CN104336057B (en) * | 2013-11-21 | 2016-09-07 | 海南正业中农高科股份有限公司 | Composition pesticide containing Flupyrazofos-containpesticide Yu chrysanthemum lactone component |
| KR20160072608A (en) | 2014-12-15 | 2016-06-23 | 주식회사 케이디파워 | Led illumination apparatus |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2049692A1 (en) * | 1970-10-09 | 1972-04-13 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Pyrazolo (thiono) phosphorus (phosphonic) acid esters, process for their preparation and their use as insecticides and acaricides |
| JPS6055075B2 (en) * | 1979-03-30 | 1985-12-03 | 武田薬品工業株式会社 | Pyrazole phosphate esters, their production method and insecticides and acaricides |
| JPS6116371A (en) * | 1984-07-03 | 1986-01-24 | Toshiba Corp | Digital fluorography device |
| JPH0723386B2 (en) * | 1987-08-28 | 1995-03-15 | 三井東圧化学株式会社 | Pyrazolacetic acid derivative, method for producing the same, and insecticide / miticide containing the compound |
-
2000
- 2000-06-27 KR KR1020000035729A patent/KR100351631B1/en not_active IP Right Cessation
- 2000-08-16 CN CNB001226916A patent/CN1142169C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104322549A (en) * | 2013-11-21 | 2015-02-04 | 海南正业中农高科股份有限公司 | Pesticide composition containing flupyrazofos and spinosad |
| CN104322549B (en) * | 2013-11-21 | 2015-12-30 | 海南正业中农高科股份有限公司 | Composition pesticide containing pyrrole fluorine sulphur phosphorus and pleocidin |
| CN113839089A (en) * | 2020-06-24 | 2021-12-24 | 张家港市国泰华荣化工新材料有限公司 | Lithium ion battery electrolyte and lithium ion battery containing same |
| CN113839089B (en) * | 2020-06-24 | 2022-11-29 | 张家港市国泰华荣化工新材料有限公司 | Lithium ion battery electrolyte and lithium ion battery containing same |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20020005213A (en) | 2002-01-17 |
| CN1142169C (en) | 2004-03-17 |
| KR100351631B1 (en) | 2002-09-11 |
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