CN100500629C - Method for preparing 2-Methyl-1[4-(trifluoromethoxy)phenyl] propan-1-one - Google Patents
Method for preparing 2-Methyl-1[4-(trifluoromethoxy)phenyl] propan-1-one Download PDFInfo
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- CN100500629C CN100500629C CNB2006100287473A CN200610028747A CN100500629C CN 100500629 C CN100500629 C CN 100500629C CN B2006100287473 A CNB2006100287473 A CN B2006100287473A CN 200610028747 A CN200610028747 A CN 200610028747A CN 100500629 C CN100500629 C CN 100500629C
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- isobutyric acid
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Abstract
A method for producing trifluo-methyl phenyl-isotutone is carried out by taking isobutyric acid derivative as raw material, reacting with trifluo-methyl bromo-Grignard reagent at normal temperature and under catalyst condition. It costs low, has gentle reactive condition and short reactive time and no destroying chemicals, and the recovery percent reaches to 50-78%.
Description
Technical field
The present invention relates to agricultural plant growth conditioning agent field, relate in particular to a kind of method of making plant-growth regulator flurprimidol intermediate.
Prior art
To Trifluoromethoxyphen-l isobutyl ketone (hereinafter to be referred as PTMI), structural formula (I) is an intermediate of making plant-growth regulator flurprimidol (Flurprimidol).Flurprimidol is mainly used in the weeds that prevent in lawn and the flowers as a plant growth regulators, makes the growth velocity of grass drop to original about 28%.Flurprimidol also is used for the rice cropping phase, and plant height is reduced, and brings out and tillers, and promotes the growth of root.
The PTMI production method of external report has two kinds at present.The patent USP4 that first U.S. Eli Lilly company delivered in 1977,002,628, adopt Grignard reagent and isopropyl cyanide reaction to trifluoro-methoxyl bromobenzene, generate PTMI, reaction needs to reflux yield 40% 10 hours:
Another kind method is the patent USP4 that French Rhone-Poulenc company delivered in 1984,446,078, and the employing anhydrous hydrogen fluoride is a solvent, boron triflouride gas is a catalyzer, in 20 ℃, 10kg/cm
2In autoclave pressure, make under the condition Trifluoromethyl phenyl ether and isobutyryl chloride carried out Friedel-Crafts prepared in reaction PTMI:
Reaction times is 20 hours, and reaction yield is 60%, and product purity is 70%.
More than two kinds of classical ways significant deficiency is all arranged when suitability for industrialized production PTMI:
It is raw material that first method adopts isopropyl cyanide, long reaction time, and yield is lower than 40%, and raw materials cost and production cost are higher when causing suitability for industrialized production.
Second method need be used severe toxicity, severe corrosive gas HF and BF
3, the stopping property to equipment material and equipment when suitability for industrialized production has very high requirement.The recovery of these toxic gases also is an insoluble problem in the suitability for industrialized production with applying mechanically.
Summary of the invention
Technical problem to be solved by this invention is to provide the method for a kind of manufacturing to the Trifluoromethoxyphen-l isobutyl ketone, and to solve long reaction time in the prior art, yield is low, production cost height, the defective that toxicity is big.
Manufacturing provided by the present invention is to the method for Trifluoromethoxyphen-l isobutyl ketone, adopt derivatives of isobutyric acid (III), as acid anhydrides, carboxylic acid halides, acid amides is raw material, with trifluoro-methoxyl bromobenzene Grignard reagent (II) is reacted under normal temperature and catalytic condition, the method of high produced in yields PTMI, this method comprises the steps:
1. the derivatives of isobutyric acid with formula (III) is dissolved in the solvent, every mole of 200～300 milliliters of solvent of derivatives of isobutyric acid;
2. with formula (II) the trifluoro-methoxyl bromobenzene Grignard reagent is added dropwise in the above-mentioned derivatives of isobutyric acid solution, react;
3. after having reacted, be hydrolyzed, extract, dry, desolvate, rectifying obtains product;
Reaction formula is:
Wherein the solvent of step described in 1. is one or more in anhydrous diethyl ether, anhydrous THF or the dry toluene, when adopting THF to be solvent, the toluene that should add 1:1～1:2 (V/V) can reduce the loss of THF in water like this in reacted hydrolytic process.R in the derivatives of isobutyric acid of formula (III) is
---Cl or
Step is 1:0.5-2 to the add-on of trifluoro-methoxyl bromobenzene Grignard reagent and the mol ratio of derivatives of isobutyric acid in 2..
Add the trifluoro-methoxyl bromobenzene Grignard reagent reacted before, add the catalyzer of 0.01-0.15 moles/mole derivatives of isobutyric acid in the derivatives of isobutyric acid solution, what will help to react finishes, described catalyzer is anhydrous LiCl, anhydrous AlCl
3Or among the anhydrous CuCl one or more.Catalyzer joins earlier in the solution of derivatives of isobutyric acid before reaction, reaction again after stirring.
Add catalyzer amount be preferably 0.05～0.08 moles/mole derivatives of isobutyric acid.
The temperature of this reaction is-50～50 ℃, and preferred temperature of reaction is 0～25 ℃.
Preferred is 1:1 to the add-on of trifluoro-methoxyl bromobenzene Grignard reagent and the mol ratio of derivatives of isobutyric acid.The derivatives of isobutyric acid consumption makes the reaction can not be complete for a short time, and consumption can make too much that impurity increases in the product.
During reaction Grignard reagent is added dropwise in the derivatives of isobutyric acid solution of continuous stirring, and in the scope that temperature control is requiring in the cooling of reaction flask external application mixture of ice and water makes.React little heat release, even continual stirring can reach requirement.
The dropping time is 0.5～2.0 hour.The suitable dropping time is 0.6～1.2 hour.React again after adding and to finish reaction in 0.5 hour.
After finishing, reaction can be hydrolyzed according to a conventional method (Fieser, Louis F., Fieser and Fieser ' sreagents for organic synthesis, Vol.1, Page 418-419, NewYork, Wiley, 1967).Be divided into two-phase after the hydrolysis, water is incorporated organic phase into after extracting with toluene, through anhydrous Na
2SO
4Drying, solvent is sloughed in decompression.Rectifying obtains the PTMI product then.
In the above-mentioned reaction, raw material to the trifluoro-methoxyl bromobenzene Grignard reagent by to trifluoro-methoxyl bromobenzene and MAGNESIUM METAL at anhydrous diethyl ether, in tetrahydrofuran (THF) (THF) solvent according to a conventional method reaction make:
Wherein the mol ratio to trifluoro-methoxyl bromobenzene and MAGNESIUM METAL is 1:1～1:1.05, and solvent adopts anhydrous diethyl ether or anhydrous THF, and its consumption is every mole of magnesium 400～800ml solvent.
The Grignard reagent for preparing is in N
2Room temperature preservation under the gas shiled, the shelf time can be 1hr～12hr, is advisable with 1～3hr.Overlong time can make impurity increase in the reaction after product, and yield descends.
Manufacturing of the present invention is to the method for Trifluoromethoxyphen-l isobutyl ketone, and compared with prior art, its yield brings up to 50～78% from original below 40%, reaction conditions gentleness (normal-temperature reaction), reaction times short (0.5～2 hour).Therefore production cost and raw materials cost are declined to a great extent, also avoided using the chemical substance of severe toxicity, severe corrosive simultaneously.
Embodiment
Embodiment 1:
Add isopropylformic acid chlorine 106.5 grams (1.0 moles) in the 1000ml reaction flask, 200 milliliters of toluene, 80 milliliters of anhydrous tetrahydro furans.Stirring and N
2Under the gas shiled, room temperature adds anhydrous AlCl
38 grams (0.06 mole), anhydrous CuCl6 gram (0.06 mole) makes and is uniformly dispersed.
241g (1.0 moles) is added dropwise to 25 gram (1.03 moles) magnesium to trifluoro-methoxyl bromobenzene, in the feed liquid of 1 iodine and 500 milliliters of anhydrous tetrahydro furans, makes Grignard reagent after 3 hours 38～45 ℃ of reactions.Then this Grignard reagent was evenly splashed in 45 minutes in the reaction flask, temperature remains on 20 ± 2 ℃ of reactions in making with the ice-water bath cooling, adds and reacts 30 minutes again.
Pour reactant into saturated NH
4Hydrolysis in the solution that 850 milliliters of the Cl aqueous solution and 150 milliliters of concentrated hydrochloric acids form, phase-splitting.Water is incorporated in the organic phase with toluene 150 milliliters * 3 extractions.Use anhydrous Na
2SO
4Drying, filtering Na
2SO
4After boil off tetrahydrofuran (THF), toluene.Rectification under vacuum gets the product 162g of 89～91 ℃/6.5mmHg of fraction.GC analyzes content 99.18%, and reaction yield is in to trifluoro-methoxyl bromobenzene 69.1%.
Embodiment 2-5:
Reaction method is identical with embodiment 1, and the raw material and the reaction result of employing see the following form:
Claims (4)
1. a manufacturing is characterized in that to the method for Trifluoromethoxyphen-l isobutyl ketone this method comprises the steps:
1. the derivatives of isobutyric acid with formula (III) is dissolved in the solvent, every mole of 200～300 milliliters of solvent of derivatives of isobutyric acid;
2. with formula (II) the trifluoro-methoxyl bromobenzene Grignard reagent is added dropwise in the above-mentioned derivatives of isobutyric acid solution, react; Temperature of reaction is-50～50 ℃; Before adding is reacted the trifluoro-methoxyl bromobenzene Grignard reagent, add the catalyzer of 0.01-0.15 moles/mole derivatives of isobutyric acid in the derivatives of isobutyric acid solution, described catalyzer is anhydrous LiCl, anhydrous AlCl
3Or among the anhydrous CuCl one or more;
3. after having reacted, be hydrolyzed, extract, dry, desolvate, rectifying obtains product;
Reaction formula is:
Wherein the solvent of step described in 1. is one or more in anhydrous diethyl ether, anhydrous THF or the dry toluene; R in the derivatives of isobutyric acid of formula (III) is
Or
Step is 1:0.5-2 to the add-on of trifluoro-methoxyl bromobenzene Grignard reagent and the mol ratio of derivatives of isobutyric acid in 2..
2. method according to claim 1, the add-on that it is characterized in that catalyzer are 0.05～0.08 moles/mole derivatives of isobutyric acid.
3. method according to claim 1 is characterized in that temperature of reaction is 0～25 ℃.
4. method according to claim 1 is characterized in that described is 1:1 to the add-on of trifluoro-methoxyl bromobenzene Grignard reagent and the mol ratio of derivatives of isobutyric acid.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100287473A CN100500629C (en) | 2006-07-07 | 2006-07-07 | Method for preparing 2-Methyl-1[4-(trifluoromethoxy)phenyl] propan-1-one |
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| CNB2006100287473A CN100500629C (en) | 2006-07-07 | 2006-07-07 | Method for preparing 2-Methyl-1[4-(trifluoromethoxy)phenyl] propan-1-one |
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| CN100500629C true CN100500629C (en) | 2009-06-17 |
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| CN109456164A (en) * | 2018-11-03 | 2019-03-12 | 浙江大学 | The preparation method of isobutyrophenone |
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Effective date of registration: 20180111 Address after: 361000 Xinchang Road, Haicang Xinyang Industrial Zone, Xiamen, Fujian Province, No. 30 Patentee after: XIAMEN DOINGCOM CHEMICAL CO.,LTD. Address before: No. 200, Tianlin Road, Shanghai Patentee before: Shanghai Fine Chemical Co.,Ltd. |
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