CN102766043B - Preparation method for 3- (2-chloro-4- (trifluoromethyl) phenoxy) -benzoic acid - Google Patents
Preparation method for 3- (2-chloro-4- (trifluoromethyl) phenoxy) -benzoic acid Download PDFInfo
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- CN102766043B CN102766043B CN201210264087.4A CN201210264087A CN102766043B CN 102766043 B CN102766043 B CN 102766043B CN 201210264087 A CN201210264087 A CN 201210264087A CN 102766043 B CN102766043 B CN 102766043B
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- trifluoromethyl
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- salicylic acid
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Abstract
The invention belongs to the technical field of chemical synthesis, and relates to the phase transfer catalytic preparation technology. A crown-ether phase transfer catalyst is used to promote the chemical reaction, and chemical equilibrium is promoted by timely removing water generated in a system by toluene in the expected direction. A preparation method for 3- (2-chloro-4- (trifluoromethyl) phenoxy) -benzoic acid includes performing salt-forming reaction in a crown-ether catalyst and a dimethylsulfoxide/toluene mixed solvent, then performing etherification with 3, 4-dichlorobenzotrifluoride at 130-175 DEG C, and finally performing acidification to the etherate to obtain the 3- (2-chloro-4- (trifluoromethyl) phenoxy) -benzoic acid. The preparation method for the 3- (2-chloro-4- (trifluoromethyl) phenoxy) -benzoic acid has the advantages that yield is over 96%, chemical reaction rate is increased evidently, reaction period is short, the product is easy to separate, environmental pollution is low, and industrial application prospect is broad.
Description
One, technical field
The invention belongs to chemosynthesis technical field, relate to phase transfer catalytic preparation technology, particularly phase-transfer catalysis salify technology.
Two, background technology
Acifluorfen, fluoroglycofenethyl, fomesafen are widely used diphenyl ether soybean field herbicides, can prevent and treat most of broadleaf weeds and part gramineous weeds.The chloro-4-(trifluoromethyl of 3-(2-) phenoxy group)-phenylformic acid as intermediate, be used widely in synthesis fields such as weedicide acifluorfen, fluoroglycofenethyl, fomesafens.
Lu Yang is at " synthetic technology of beans field herbicidal fomesafen " (" Anhui agronomy circular ", 2006,12(12), 122) the chloro-4-(trifluoromethyl of the 3-(2-introduced in a literary composition) phenoxy group)-phenylformic acid as intermediate, adopt 3,4-bis-chlorobenzotrifluoride 110 DEG C of out-phase salifies in dimethyl sulfoxide solvent, cooling adds m-Salicylic acid again, temperature reaction, product obtains target product, yield 93.6% through the process such as water-soluble, acidifying, crystallizing and washing.
Jiang Chengyan is at " the former medicine synthesis of high-content fomesafen " (" agricultural chemicals ", 2006,45(2), 99) the chloro-4-(trifluoromethyl of the 3-(2-introduced in a literary composition) phenoxy group)-phenylformic acid is as intermediate, adopt identical starting material system, employ catalyzer, but unexposed be which kind of catalyzer, target product yield is greater than 90%.
Above-mentioned synthetic method is inhomogeneous reaction, the problem of ubiquity length reaction time, yield lower (90% ~ 94%).
Three, summary of the invention
The object of the present invention is to provide a kind of synthesis 3-(2-chloro-4-(trifluoromethyl) phenoxy group)-benzoic method, effective Reaction time shorten, improves yield.
The object of the present invention is achieved like this, crown ether-like phase transfer catalysts is adopted to promote the carrying out of chemical reaction, employing toluene removes the water generated in system in time and promotes that chemical equilibrium is carried out to anticipated orientation, thus ensure high salify rate, improve the transformation efficiency of m-Salicylic acid, improve target product 3-(2-chloro-4-(trifluoromethyl) phenoxy group)-benzoic yield.
The 3-(2-that the present invention relates to chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method comprises salify, condensation, acidification process, it is characterized in that: react and carry out under phase-transfer catalyst crown ether compound exists, use toluene as water entrainer, concrete operation step comprises simultaneously:
(1) salify: add the m-Salicylic acid of metering, potassium hydroxide, methyl-sulphoxide, toluene and crown ether-like catalyzer in reaction vessel, be warming up to backflow under stirring, band water, to anhydrous precipitation, obtains phenol potassium yl benzoic acid sylvite (compd A);
The consumption of crown compound is 1.5% ~ 8.0% of m-Salicylic acid weight, is selected from a kind of or their mixture in 18-hat-6,15-hat-5; The weight ratio of toluene and m-Salicylic acid is between 2 ~ 3.5:1;
(2) condensation: 3,4-bis-chlorobenzotrifluorides adding metering, are warming up to 130 ~ 175 DEG C, insulation reaction 4.5 ~ 6.5h, obtains the chloro-4-(trifluoromethyl of 3-(2-) phenoxy group)-potassium benzoate (compd B);
(3) acidifying and aftertreatment: after the compd B that is dissolved in water, with hcl acidifying, filtration, drying obtain the chloro-4-(trifluoromethyl of target product 3-(2-) phenoxy group)-phenylformic acid.
The 3-(2-that the present invention relates to chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method comprises salify, condensation, acidification process, potassium hydroxide and m-Salicylic acid and mol ratio between 2.0 ~ 2.3:1.
The 3-(2-that the present invention relates to chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method comprises salify, condensation, acidification process, 3,4-bis-chlorobenzotrifluoride and m-Salicylic acid and mol ratio between 1.0 ~ 1.3:1.
The 3-(2-that the present invention relates to chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method comprises salify, condensation, acidification process, and the weight ratio of methyl-sulphoxide and m-Salicylic acid is between 2.0 ~ 4.0:1.
The 3-(2-that the present invention relates to chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method, reaction time is short, and yield is high, and can reach more than 96%, comparatively traditional synthesis significantly improves; Solvent methyl-sulphoxide consumption reduces more than 50% simultaneously, significant to decreasing pollution protection of the environment.
Four, embodiment
Be further described, to contribute to understanding of the present invention, but not as the restriction to technical scheme inventing the technical scheme related to below in conjunction with embodiment.
Embodiment one
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 58g(0.936mol) potassium hydroxide, 3.6g15-hat-5,240g methyl-sulphoxide, 120g toluene, stir temperature rising reflux, slowly 110.9g(0.511mol is added to anhydrous taking out of) 3,4-bis-chlorobenzotrifluoride, be warming up to 130 ~ 140 DEG C after adding, insulation reaction 6h, it is 0.88% that hydroxy-benzoic acid remains.After being dissolved in water with hcl acidifying to pH=1, filter, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 136.3g(0.410mol), content 95.1%, yield 96.3%.
Embodiment two
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 54g(0.871mol) potassium hydroxide, 2.4g18-hat-6,180g methyl-sulphoxide, 200g toluene, stir temperature rising reflux, slowly 101.7g(0.468mol is added to anhydrous taking out of) 3,4-bis-chlorobenzotrifluoride, be warming up to 135 ~ 150 DEG C after adding, insulation reaction 6.5h, hydroxy-benzoic acid is residual reaches 0.95%.After being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 137.5g(0.416mol), content 95.5%, yield 97.5%.
Embodiment three
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 60.6g(0.98mol) potassium hydroxide, 200g methyl-sulphoxide, 180g toluene stirs, adds 3.0g18-hat-6 in batches, add rear temperature rising reflux, take out of to anhydrous in 1 hour.Slowly add 106.3g(0.489mol) 3,4-bis-chlorobenzotrifluorides, be warming up to 135 ~ 155 DEG C after adding, insulation reaction 6h, hydroxy-benzoic acid is residual reaches 0.93%.After being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 138.5g(0.417mol), content 95.1%, yield 97.9%.
Embodiment four
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 53g(0.855mol) potassium hydroxide, 160g methyl-sulphoxide, 210g toluene, 1.8g15-hat-5, add rear temperature rising reflux, take out of to anhydrous.Slowly add 120.4g(0.554mol) 3,4-bis-chlorobenzotrifluorides, be warming up to 140 ~ 150 DEG C after adding, insulation reaction 5.5h, hydroxy-benzoic acid is residual reaches 0.97%.After being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 137.2g(0.411mol), content 94.7%, yield 96.5%.
Embodiment five
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 57.2g(0.923mol) potassium hydroxide, 190g methyl-sulphoxide, 180g toluene stir, add the mixture of 4.2g18-hat-6 and 15-hat-5 in 30min, add rear temperature rising reflux, take out of to anhydrous.Slowly 97.2g(0.448mol is added in 10min) 3,4-bis-chlorobenzotrifluorides, be warming up to 150 ~ 165 DEG C after adding, insulation reaction 5h, hydroxy-benzoic acid is residual reaches 0.90%.After being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 137.6g(0.414mol), content 95.0%, yield 97.1%.
Embodiment six
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 60g(0.970mol) potassium hydroxide, 230g methyl-sulphoxide, 150g toluene, 4.2g15-hat-5, add rear temperature rising reflux, take out of to anhydrous.Slowly 95.3g(0.439mol is added in 30min) 3,4-bis-chlorobenzotrifluorides, be warming up to 130 ~ 145 DEG C after adding, insulation reaction 4.5h, hydroxy-benzoic acid is residual reaches 0.98%.After being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 137.6g(0.412mol), content 94.6%, yield 96.8%.
Embodiment seven
In 500mL flask, add 60g(0.426mol) m-Salicylic acid, 54g(0.871mol) mixture of potassium hydroxide, 210g methyl-sulphoxide, 180g toluene, 4.2g18-hat-6 and 15-hat-5, add rear temperature rising reflux, take out of to anhydrous.Slowly 93.9g(0.432mol is added in 30min) 3,4-bis-chlorobenzotrifluorides, be warming up to 150 ~ 165 DEG C after adding, insulation reaction 4.5h hydroxy-benzoic acid is residual reaches 0.96%.React complete, after being dissolved in water with hcl acidifying to pH=1, finally by filtration, dry the chloro-4-(trifluoromethyl of product 3-(2-) phenoxy group)-phenylformic acid 136.7g(0.411mol), content 95.0%, yield 96.4%.
Claims (4)
1. a 3-(2-chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method comprises salify, condensation, acidification process, it is characterized in that: salt-forming reaction is carried out under phase-transfer catalyst crown ether compound exists, use toluene as water entrainer, concrete operation step comprises simultaneously:
(1) salify: add the m-Salicylic acid of metering, potassium hydroxide, methyl-sulphoxide, toluene and crown ether-like catalyzer in reaction vessel, be warming up to backflow under stirring, band water, to anhydrous precipitation, obtains phenol potassium yl benzoic acid sylvite (compd A);
The consumption of crown compound is 1.5% ~ 8.0% of m-Salicylic acid weight, is selected from a kind of or their mixture in 18-hat-6,15-hat-5; The weight ratio of toluene and m-Salicylic acid is between 2 ~ 3.5:1;
(2) condensation: 3,4-bis-chlorobenzotrifluorides adding metering, are warming up to 130 ~ 175 DEG C, insulation reaction 4.5 ~ 6.5h, obtains the chloro-4-(trifluoromethyl of 3-(2-) phenoxy group)-potassium benzoate (compd B);
(3) acidifying and aftertreatment: after the compd B that is dissolved in water, with hcl acidifying, filtration, drying obtain the chloro-4-(trifluoromethyl of target product 3-(2-) phenoxy group)-phenylformic acid.
2. 3-(2-according to claim 1 chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method's potassium hydroxide and m-Salicylic acid and mol ratio between 2.0 ~ 2.3:1.
3. 3-(2-according to claim 1 chloro-4-(trifluoromethyl) phenoxy group)-benzoic preparation method 3,4-bis-chlorobenzotrifluoride and m-Salicylic acid and mol ratio between 1.0 ~ 1.3:1.
4. arbitrary 3-(2-chloro-4-(trifluoromethyl according to claims 1 to 3) phenoxy group)-benzoic preparation method, the weight ratio of methyl-sulphoxide and m-Salicylic acid is between 2.0 ~ 4.0:1.
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| CN107032979A (en) * | 2017-06-12 | 2017-08-11 | 青岛瀚生生物科技股份有限公司 | The preparation method of 3 (trifluoromethyl of 2 chlorine 4) phenoxy benzoic acids |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4031131A (en) * | 1975-09-29 | 1977-06-21 | Rohm And Haas Company | Process for preparing phenoxybenzoic acids |
| CN101274889A (en) * | 2008-05-14 | 2008-10-01 | 青岛瀚生生物科技股份有限公司 | Preparation for 3-(2-Chloro-alpha,alpha,alpha-trifluoro-p-tolyoxy) benzoic acid |
| CN101362698A (en) * | 2007-12-14 | 2009-02-11 | 青岛瀚生生物科技股份有限公司 | Loctofen preparation method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4031131A (en) * | 1975-09-29 | 1977-06-21 | Rohm And Haas Company | Process for preparing phenoxybenzoic acids |
| CN101362698A (en) * | 2007-12-14 | 2009-02-11 | 青岛瀚生生物科技股份有限公司 | Loctofen preparation method |
| CN101274889A (en) * | 2008-05-14 | 2008-10-01 | 青岛瀚生生物科技股份有限公司 | Preparation for 3-(2-Chloro-alpha,alpha,alpha-trifluoro-p-tolyoxy) benzoic acid |
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Address after: 256500 Boxing County Economic Development Zone, Binzhou, Shandong Patentee after: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Address before: 256500 Binzhou Shandong Boxing Economic Development Zone Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. |
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Address after: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee after: Shandong Jingbo Agrochemical Technology Co.,Ltd. Address before: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. |