CN107739343B - Environment-friendly process for producing quizalofop-p-ethyl - Google Patents
Environment-friendly process for producing quizalofop-p-ethyl Download PDFInfo
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- CN107739343B CN107739343B CN201710802152.7A CN201710802152A CN107739343B CN 107739343 B CN107739343 B CN 107739343B CN 201710802152 A CN201710802152 A CN 201710802152A CN 107739343 B CN107739343 B CN 107739343B
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- 239000005614 Quizalofop-P-ethyl Substances 0.000 title claims abstract description 59
- OSUHJPCHFDQAIT-GFCCVEGCSA-N quizalofop-P-ethyl Chemical group C1=CC(O[C@H](C)C(=O)OCC)=CC=C1OC1=CN=C(C=C(Cl)C=C2)C2=N1 OSUHJPCHFDQAIT-GFCCVEGCSA-N 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 66
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims abstract description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- WFOKVKYNVKVWFK-UHFFFAOYSA-N 2,6-dichloroquinoxaline Chemical compound N1=C(Cl)C=NC2=CC(Cl)=CC=C21 WFOKVKYNVKVWFK-UHFFFAOYSA-N 0.000 claims abstract description 30
- UVYFSLAJRJHGJB-UHFFFAOYSA-N 4-(6-chloroquinoxalin-2-yl)oxyphenol Chemical compound C1=CC(O)=CC=C1OC1=CN=C(C=C(Cl)C=C2)C2=N1 UVYFSLAJRJHGJB-UHFFFAOYSA-N 0.000 claims abstract description 30
- 235000014121 butter Nutrition 0.000 claims abstract description 28
- SJAZZQLTKBYDHN-UHFFFAOYSA-N 6-chloro-1h-quinoxalin-2-one Chemical compound C1=C(Cl)C=CC2=NC(O)=CN=C21 SJAZZQLTKBYDHN-UHFFFAOYSA-N 0.000 claims abstract description 15
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 claims abstract description 13
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 230000020477 pH reduction Effects 0.000 claims abstract description 8
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 69
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 238000005406 washing Methods 0.000 claims description 17
- 238000000967 suction filtration Methods 0.000 claims description 16
- 239000012065 filter cake Substances 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- -1 2, 6-dichloroquinoxaline toluene Chemical compound 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 14
- 238000005070 sampling Methods 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 10
- 239000012454 non-polar solvent Substances 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 8
- 238000004321 preservation Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 229940126062 Compound A Drugs 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- SSQNAPWMQSPZRM-UHFFFAOYSA-N benzene-1,4-diol;sodium Chemical compound [Na].OC1=CC=C(O)C=C1 SSQNAPWMQSPZRM-UHFFFAOYSA-N 0.000 claims description 4
- 238000004042 decolorization Methods 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 235000017788 Cydonia oblonga Nutrition 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000011084 recovery Methods 0.000 abstract description 8
- 239000012535 impurity Substances 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 239000002910 solid waste Substances 0.000 abstract description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract description 2
- 230000007062 hydrolysis Effects 0.000 abstract description 2
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 2
- 230000007935 neutral effect Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 238000006266 etherification reaction Methods 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an environment-friendly process for producing quizalofop-p-ethyl, which is characterized in that hydroquinone is firstly reacted with sodium hydroxide to prepare sodium salt of hydroquinone, then the sodium salt is reacted with 2, 6-dichloro quinoxaline to obtain 4- (6-chloro-2-quinoxalyloxy) phenol, then the phenol is reacted with ethyl p-toluenesulfonate to obtain the quizalofop-p-ethyl, and then the generated quizalofop-p-ethyl butter is subjected to alkaline hydrolysis, acidification and recovery of 6-chloro-2-hydroxy quinoxaline. The synthesis process has the advantages that the reaction and the post-treatment are carried out in an organic solvent, the alkalinity of a reaction system is reduced, the defect that impurities are easily generated due to the fact that the water phase reaction alkalinity is too strong is overcome, the hydrolysis of the raw material 2, 6-dichloro quinoxaline is reduced, the content of 4- (6-chloro-2-quinoxalyloxy) phenol is over 98 percent, the yield is over 92 percent, the 6-chloro-2-hydroxy quinoxaline in the quizalofop-p-ethyl butter is recovered, the solid waste discharge capacity is reduced, the environment is protected, and the intermediate cost of the quizalofop-p-ethyl is reduced.
Description
Technical Field
The invention relates to the technical field of pesticide synthesis, in particular to an environment-friendly process for producing quizalofop-p-ethyl.
Background
Quizalofop-p-ethyl is a post-emergence selective herbicide developed by Nippon Nissan chemical industry, shows strong killing effect on annual and perennial gramineous weeds, is safe to broadleaf crops, can be widely used for preventing and killing gramineous weeds of crops such as cotton, rape, peanut, soybean and various broadleaf vegetables, and has wide technical synthesis and preparation processing prospects.
At present, two synthetic routes for quizalofop-p-ethyl exist, one is to take 2, 6-dichloro quinoxaline as a raw material to perform a reaction shown in equation 1, and directly or further perform an esterification reaction to obtain quizalofop-p-ethyl, and the other is to prepare 4- (6-chloro-2-quinoxalyloxy) phenol to react with ethyl p-toluenesulfonate to obtain quizalofop-p-ethyl, as shown in equation 2.
Equation 1
Equation 2
Compared with the two existing methods, the former method is easy to generate ester bond fracture in the Willamson condensation process, and the yield of the process of preparing quizalofop-p-ethyl from acid by the subsequent esterification reaction is low. The latter is reacted to directly obtain the product, the steps are simple, the process is easy to control, and the method has greater advantages than the former and is convenient for realizing industrialization. The influence of the intermediate 4- (6-chloro-2-quinoxalyloxy) phenol in the equation 2 on the quality of the synthesized quizalofop-p-ethyl is very important.
At present, the prior art mainly introduces the aqueous phase etherification reaction of 2, 6-dichloro quinoxaline and potassium hydroxide, the reaction system has strong alkalinity, active chlorine in the 2, 6-dichloro quinoxaline is easy to hydrolyze, the etherification reaction yield is influenced, and secondly, due to the large alkali concentration, two molecules of 2, 6-dichloro quinoxaline and one molecule of hydroquinone have more impurities and the content of etherification products is low;
the etherification reaction of 2, 6-dichloro quinoxaline and sodium hydroxide in a mixed solvent of toluene and DMF, DMF is used in the reaction, the solubility of the product is stronger, the dosage ratio of the 2, 6-dichloro quinoxaline to alkali is about 1:5, diether impurities are more, in addition, ice water is needed for post-treatment, the steps are complex, the ice water is mixed with the solvent and is not easy to treat, and the solvent recovery is influenced.
In the existing technology, the solid quizalofop-p-ethyl butter is produced after the solvent is recovered from the mother liquor generated during crystallization in the preparation process of quizalofop-p-ethyl, and the butter contains more quizalofop-p-ethyl and also contains impurities generated in the synthesis process, so that the solid quizalofop-p-ethyl butter is directly discharged, and the environment is seriously polluted. How to further treat the quizalofop-P-ethyl butter and reduce the environmental pollution is also an urgent problem in the field.
Disclosure of Invention
Aiming at the technical background, the invention aims to provide an environment-friendly process for producing quizalofop-p-ethyl, which comprises the steps of firstly reacting hydroquinone with sodium hydroxide to prepare sodium salt of hydroquinone, then reacting with 2, 6-dichloro quinoxaline to obtain 4- (6-chloro-2-quinoxalyloxy) phenol, and then reacting with ethyl p-toluenesulfonate to obtain the quizalofop-p-ethyl. The synthesis process optimizes the original process, has the advantages of carrying out reaction and post-treatment in an organic solvent, avoiding the defect that impurities are easily generated due to excessively strong alkalinity of aqueous phase reaction, recovering 6-chloro-2-hydroxyquinoxaline in the quizalofop-p-ethyl butter under a certain condition by alkaline hydrolysis of the quizalofop-p-ethyl butter, reducing solid waste amount, relieving environmental protection pressure, synthesizing quizalofop-p-ethyl original medicine by chlorination and etherification of the recovered 6-chloro-2-hydroxyquinoxaline, and reducing the intermediate cost of the quizalofop-p-ethyl.
Specifically, the specific technical scheme of the preparation method of the environment-friendly quizalofop-p-ethyl is as follows:
(1) preparation of 4- (6-chloro-2-quinoxalinyloxy) phenol: adding hydroquinone and sodium hydroxide under the protection of nitrogen, adding toluene to dissolve, heating to 65-95 ℃ to react to generate hydroquinone sodium salt, heating to 99-105 ℃, dropwise adding the hydroquinone sodium salt into 2, 6-dichloroquinoxaline toluene solution, carrying out heat preservation reaction, carrying out sampling detection, cooling the mixed solution to room temperature when the content of the 2, 6-dichloroquinoxaline is lower than 0.5%, carrying out suction filtration, washing out salts generated by reaction on a filter cake by using hot water, and obtaining 4- (6-chloro-2-quinoxalyloxy) phenol;
(2) preparing quizalofop-p-ethyl: mixing 4- (6-chloro-2-quinoxalinyloxy) phenol and potassium carbonate, adding an ether nonpolar solvent, heating to 93-95 ℃ for refluxing and carrying out water carrying, dropwise adding ethyl p-toluenesulfonate into the mixture after no water exists, continuing reflux reaction after the dropwise addition is finished, sampling and tracking a reaction mixture system until the residual content of the 4- (6-chloro-2-quinoxalinyloxy) phenol of the raw material is less than 0.1%, cooling to about 70 ℃ for washing, decompressing after the washing is finished, removing the solvent, and adding absolute ethyl alcohol for crystallization to obtain quizalofop-p-ethyl;
(3) treating the fine quinoline butter: and recovering the solvent from the mother liquor generated in the crystallization process to generate solid quizalofop-p-ethyl butter, and performing alkaline hydrolysis and acidification on the quizalofop-p-ethyl butter to recover 6-chloro-2-hydroxyquinoxaline.
The molar ratio of the reaction materials 2, 6-dichloro quinoxaline, hydroquinone and sodium hydroxide in the step (1) is 2, 6-dichloro quinoxaline: hydroquinone: sodium hydroxide is 1: 1.05-1.3: 1.05-1.15.
The amount of the toluene used for dissolving the hydroquinone and the sodium hydroxide in the step (1) is 5.0 to 8.0 times of the weight of the hydroquinone.
The amount of toluene in the toluene solution of 2, 6-dichloroquinoxaline in the above step (1) is 10 to 13 times of the weight of 2, 6-dichloroquinoxaline.
The molar ratio of the materials in the synthesis reaction in the step (2) is 4- (6-chloro-2-quinoxalyloxy) phenol: potassium carbonate: ethyl p-toluenesulfonate =1: 1.5-3.0: 1.05-1.15.
The mass ratio of the usage amount of the synthetic reaction solvent in the step (1) is 4- (6-chloro-2-quinoxalinyloxy) phenol: non-polar solvent =1: 20-25.
The specific treatment steps of the quinquail butter obtained in the step (3) are that the quinquail butter is dissolved in water or an organic solvent with the weight of 20-35 times of the self weight of the quinquail butter, inorganic strong base or organic strong base or alkali metal is added, the temperature is raised to 90-95 ℃, reflux reaction is carried out until all oily matters are dissolved, the temperature is lowered to 75-85 ℃, filtration is carried out, and suction filtration is carried out at 1-5 ℃ to obtain a sodium salt compound filter cake with the general formula C, wherein the chemical structural formula of the sodium salt compound C is as follows:
dissolving a sodium salt compound filter cake with a general formula C in water, adding activated carbon at 75-95 ℃ for decolorization, carrying out hot filtration, dropwise adding acid at room temperature for acidification, reacting under an acidic condition to generate a compound A, carrying out suction filtration, washing with water, and drying to obtain 6-chloro-2-hydroxyquinoxaline, wherein the chemical structural formula of the compound A is as follows:
the inorganic strong base is sodium hydroxide or potassium hydroxide, the organic strong base is sodium ethoxide or sodium methoxide, the metal base is metal sodium, the organic solvent is ethanol, and the dosage of the base is 4-6 times of the dosage of quizalofop-p-ethyl in butter.
The acid is hydrochloric acid or sulfuric acid, the pH value in the acidification process is controlled to be 4-6, and the drying temperature is 100 ℃.
In summary, compared with the existing method, the method provided by the application has the advantages that the etherification method provided by the application is used for preparing 4- (6-chloro-2-quinoxalinyloxy) phenol by reacting in an organic solvent toluene, the mode of aqueous phase Willamson etherification in which most of phenol participates in the prior art is changed, the alkalinity of a reaction system is greatly reduced, the generation of impurities is reduced, the hydrolysis of 2, 6-dichloroquinoxaline serving as a raw material is greatly reduced, the utilization rate of the raw material is improved, and the yield of 4- (6-chloro-2-quinoxalinyloxy) phenol is improved. The method is more convenient to operate, the solvent toluene is filtered off only by cooling to room temperature, the solid etherate is washed by hot water, and the toluene recovery rate is high.
The process of obtaining quizalofop-p-ethyl by using potassium carbonate as a catalyst to catalyze the reaction of 4- (6-chloro-2-quinoxalyloxy) phenol and ethyl p-toluenesulfonate, which optimizes the reaction conditions and shortens the reaction time on the premise of not influencing the purity of the quizalofop-p-ethyl.
The quizalofop-p-ethyl crystallization-generated quizalofop-p-ethyl butter is subjected to alkaline hydrolysis and acidification, and the 6-chloro-2-hydroxyquinoxaline in the quizalofop-p-ethyl butter is obtained by recycling, so that the solid waste discharge is reduced, the environment is protected, and the intermediate of the quizalofop-p-ethyl technical product can be further synthesized by chlorination and etherification through the recycled 6-chloro-2-hydroxyquinoxaline, so that the intermediate cost of the quizalofop-p-ethyl is reduced.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described with the following embodiments, but the present invention is by no means limited to these examples.
Example 1:
under the protection of nitrogen, 11.6g (0.105 mol) of hydroquinone and 4.3g (0.105 mol) of sodium hydroxide are weighed, 60g of toluene is added, the temperature is raised to 85 ℃, the reaction is carried out for 0.5h, and the temperature is reduced and the mixture is transferred to a constant pressure dropping funnel for standby. Under the protection of nitrogen, 20.2g (0.1 mol) of 2, 6-dichloro quinoxaline and 220g of toluene are added, the temperature is raised to 100 ℃, the sodium salt of the prepared hydroquinone is dripped, dripping is finished for 1h, heat preservation is carried out for 6h after dripping is finished, sampling and tracking are carried out, the temperature is lowered to room temperature after the 2, 6-dichloro quinoxaline content is lower than 0.5 percent and qualified, after suction filtration and pumping-drying of a filter cake, hot water is used for washing to be neutral, 25.3g of 4- (6-chloro-2-quinoxalyloxy) phenol with the content of 96.2 percent is obtained, and the yield is 89..
Under the protection of nitrogen, 0.1mol of synthesized 4- (6-chloro-2-quinoxalyloxy) phenol, 21.6g (0.156 mol) of potassium carbonate are added, 710g of non-polar solvent is added, after the temperature is raised to be anhydrous, ethyl p-toluenesulfonate (0.105mol,28.9g) is added dropwise for about 1h, then reflux reaction is carried out for 5h, sampling and tracking are carried out, after the mixture is qualified, the mixture is washed by water until the mixture is clear and transparent, the solvent is evaporated under reduced pressure, 280g of anhydrous ethanol is added for crystallization, and 33.6g of quizalofop-p-ethyl is obtained, the content is 96.0%, and the yield is.
30.8g of quizalofop-p-ethyl butter (the content is 65 percent and 0.05 mol) is added into a 1000ml four-mouth bottle, 8.8g of NaOH (the content is 98 percent and 0.2 mol) and 650g of water are added, the temperature is raised to reflux, the temperature is kept for 6 hours, oily matters are gradually dissolved, the temperature is reduced to about 80 ℃ after the oily matters are completely dissolved, the hot filtration is carried out, the solution is cooled to about 2 ℃ and is filtered, and the sodium salt compound filter cake is obtained.
Adding 10g of sodium salt compound and 150g of hot water into a 500ml four-mouth bottle, adding 1g of activated carbon, decoloring for about 30min at about 80 ℃, carrying out hot filtration, cooling to room temperature, dropwise adding hydrochloric acid, acidifying to PH =5, carrying out suction filtration, and washing with hot water until the filtrate is transparent and the pH value is neutral. Drying at 100 ℃ to obtain 5.59g of the product 6-chloro-2-hydroxyquinoxaline dry weight, with the recovery rate of 58.6 percent and the effective content of 94.6 percent.
Example 2:
weighing 14.3g (0.13 mol) of hydroquinone and 4.7g (0.115 mol) of sodium hydroxide under the protection of nitrogen, adding 72g of toluene, heating to 85 ℃, reacting for 0.5h, cooling, and transferring to a constant-pressure dropping funnel for later use. Under the protection of nitrogen, 20.2g (0.1 mol) of 2, 6-dichloro quinoxaline and 220g of toluene are added, the temperature is raised to 100 ℃, the sodium salt of the prepared hydroquinone is dripped, dripping is finished for 1h, heat preservation is carried out for 6h after dripping is finished, sampling and tracking are carried out, the temperature is lowered to room temperature after the 2, 6-dichloro quinoxaline content is lower than 0.5 percent and qualified, after suction filtration and pumping-drying of a filter cake, hot water is used for washing to be neutral, 25.7g of 4- (6-chloro-2-quinoxalyloxy) phenol with the content of 98.5 percent is obtained, and the yield is 92..
Under the protection of nitrogen, 0.1mol of synthesized 4- (6-chloro-2-quinoxalyloxy) phenol and 21.6g of potassium carbonate are added, 730g of non-polar solvent is added, after the mixture is heated to be anhydrous, ethyl p-toluenesulfonate (0.115mol and 31.7g) is added dropwise for about 1h, then reflux reaction is carried out for 5h, sampling and tracking are carried out, after the mixture is qualified, the mixture is washed by water until the mixture is clear and transparent, the solvent is evaporated under reduced pressure, 230g of anhydrous ethanol is added for crystallization, and 34.3g of quizalofop-p-ethyl is obtained, the content is 98.3%, and the yield is 90..
30.8g of quizalofop-p-ethyl butter (the content is 65 percent and 0.05 mol) is added into a 1000ml four-mouth bottle, 13.2g of NaOH (the content is 98 percent and 0.33 mol) and 650g of water are added, the temperature is raised to reflux, the temperature is kept for 4 hours, oily matters are gradually dissolved, the temperature is reduced to about 80 ℃ after the oily matters are completely dissolved, the hot filtration is carried out, the solution is cooled to about 2 ℃ and is filtered, and the sodium salt compound filter cake is obtained.
Adding 12.3g of sodium salt compound and 150g of hot water into a 500ml four-mouth bottle, adding 1g of activated carbon, decoloring for about 30min at about 80 ℃, carrying out hot filtration, cooling to room temperature, dropwise adding hydrochloric acid, acidifying to pH =5, carrying out suction filtration, and washing with hot water until the filtrate is transparent and the pH value is neutral. Drying at 100 ℃ to obtain 5.58g of the product 6-chloro-2-hydroxyquinoxaline dry weight, with the recovery rate of 60.2 percent and the effective content of 94.8 percent.
Example 3:
12.7g (0.115 mol) of hydroquinone and 4.3g (0.105 mol) of sodium hydroxide are weighed under the protection of nitrogen, 75g of toluene is added, the temperature is raised to 85 ℃, the reaction is carried out for 0.5h, and the temperature is reduced and the mixture is transferred to a constant pressure dropping funnel for standby. Under the protection of nitrogen, 20.2g (0.1 mol) of 2, 6-dichloro quinoxaline and 250g of toluene are added, the temperature is raised to 100 ℃, the sodium salt of the prepared hydroquinone is dripped, dripping is finished for 1h, heat preservation is carried out for 6h after dripping is finished, sampling and tracking are carried out, the temperature is lowered to room temperature after the 2, 6-dichloro quinoxaline content is lower than 0.5 percent and qualified, after suction filtration and pumping-drying of a filter cake, hot water is used for washing to be neutral, 25.8g of 4- (6-chloro-2-quinoxalyloxy) phenol with the content of 98.8 percent is obtained, and the yield is 93..
Under the protection of nitrogen, 0.1mol of the synthesized 4- (6-chloro-2-quinoxalyloxy) phenol and 21.6g of potassium carbonate are added, 700g of a nonpolar solvent is added, after the temperature is raised until no water exists, ethyl p-toluenesulfonate (0.115mol,31.7g) is added dropwise for about 1h, then reflux reaction is carried out for 5h, sampling and tracking are carried out, after the mixture is qualified, the mixture is washed by water until the mixture is clear and transparent, the solvent is evaporated under reduced pressure, 200g of absolute ethyl alcohol is added for crystallization, and 34.7g of quizalofop-p-ethyl is obtained, the content is 98.1%, and the yield.
30.8g of quizalofop-p-ethyl butter (the content is 65 percent and 0.05 mol) is added into a 1000ml four-mouth bottle, 6.2g of NaOH (the content is 98 percent and 0.15 mol) and 650g of water are added, the temperature is raised to reflux, the temperature is kept for 7 hours, oily matters are gradually dissolved, the temperature is reduced to about 80 ℃ after the oily matters are completely dissolved, the hot filtration is carried out, the solution is cooled to about 3 ℃ and is filtered, and the sodium salt compound filter cake is obtained.
Adding 8.9g of sodium salt compound and 150g of hot water into a 500ml four-mouth bottle, adding 1g of activated carbon, decoloring for about 30min at about 80 ℃, carrying out hot filtration, cooling to room temperature, dropwise adding hydrochloric acid, acidifying to pH =5, carrying out suction filtration, and washing with hot water until the filtrate is transparent and the pH value is neutral. Drying at 100 ℃ to obtain 5.16g of the product 6-chloro-2-hydroxyquinoxaline dry weight, with the recovery rate of 53.8 percent and the effective content of 94.0 percent.
Example 4:
12.7g (0.115 mol) of hydroquinone and 4.5g (0.11 mol) of sodium hydroxide are weighed under the protection of nitrogen, 75g of toluene is added, the temperature is raised to 85 ℃, the reaction is carried out for 0.5h, and the temperature is reduced and the mixture is transferred to a constant pressure dropping funnel for standby. Under the protection of nitrogen, 20.2g (0.1 mol) of 2, 6-dichloro quinoxaline and 220g of toluene are added, the temperature is raised to 100 ℃, the sodium salt of the prepared hydroquinone is dripped, dripping is finished for 1h, heat preservation is carried out for 6h after dripping is finished, sampling and tracking are carried out, the temperature is lowered to room temperature after the 2, 6-dichloro quinoxaline content is lower than 0.5 percent and qualified, after suction filtration and pumping-drying of a filter cake, hot water is used for washing to be neutral, 25.8g of 4- (6-chloro-2-quinoxalyloxy) phenol with the content of 98.4 percent is obtained, and the yield is 93..
Under the protection of nitrogen, 0.1mol of 4- (6-chloro-2-quinoxalyloxy) phenol obtained by the previous reaction and 21.6g of potassium carbonate are added, 700g of a non-polar solvent is added, after the temperature is raised to be anhydrous, ethyl p-toluenesulfonate (0.115mol and 31.7g) is added dropwise for about 1h, then reflux reaction is carried out for 5h, sampling and tracking are carried out, after the mixture is qualified, the mixture is washed by water until the mixture is clear and transparent, the solvent is evaporated under reduced pressure, 200g of absolute ethyl alcohol is added for crystallization, and 34.7g of quizalofop-p-ethyl is obtained, the content is 98.6%, and.
600g of quizalofop-p-ethyl mother liquor (the content is 3.7 percent, 0.06mol, ethanol is used as a solvent) is added into a 1000ml four-mouth bottle, 54.4g of sodium ethoxide solution (the content is 30 percent, 0.24 mol) is added, the temperature is raised to reflux, the temperature is kept for 4 hours, 1g of activated carbon is added for decolorization, the temperature is reduced to about 60 ℃, heat filtration is carried out, the pressure is reduced to 0.095MPa for desolventization, the temperature is 45 ℃, the residual solution is steamed until the residual solution is 60g, the temperature is reduced to about-8 ℃, and suction filtration is carried.
Adding 10.8g of sodium salt compound and 150g of hot water into a 500ml four-mouth bottle, adding 1g of activated carbon, decoloring for about 30min at about 80 ℃, carrying out hot filtration, cooling to room temperature, dropwise adding hydrochloric acid, acidifying to pH =5, carrying out suction filtration, and washing with hot water until the filtrate is transparent and the pH value is neutral. Drying at 100 ℃, and obtaining 6.53g of the product 6-chloro-2-hydroxyquinoxaline with the recovery rate of 57.2% and the effective content of 94.9%.
Example 5:
26.4g (0.24 mol) of hydroquinone and 9.4g (0.23 mol) of sodium hydroxide are weighed under the protection of nitrogen, 150g of toluene is added, the temperature is raised to 85 ℃, the reaction is carried out for 0.5h, and the temperature is reduced and the mixture is transferred to a constant-pressure dropping funnel for standby. Under the protection of nitrogen, 40.4g (0.2 mol) of 2, 6-dichloro quinoxaline and 440g of recovered toluene phase are added, the temperature is raised to 101 ℃, the prepared sodium salt of hydroquinone is dripped, the dripping is finished for 1h, the temperature is kept for 6h after the dripping is finished, the temperature is lowered to the room temperature after the sampling tracking of the 2, 6-dichloro quinoxaline content is lower than 0.5 percent, the filter cake is pumped and drained, the toluene phase is recovered, the filter cake is washed by hot water to be neutral, and 25.6g of 4- (6-chloro-2-quinoxalyloxy) phenol with the content of 98.1 percent and the yield of 92.0 percent are obtained.
Under the protection of nitrogen, 0.1mol of 4- (6-chloro-2-quinoxalyloxy) phenol synthesized in the previous step and 21.6g of potassium carbonate are added, 700g of a nonpolar solvent is added, after the temperature is raised to be anhydrous, ethyl p-toluenesulfonate (0.115mol and 31.7g) is added dropwise for about 1h, then reflux reaction is carried out for 10h, sampling and tracking are carried out, after the mixture is qualified, the mixture is washed by water until the mixture is clear and transparent, the solvent is evaporated under reduced pressure, 230g of anhydrous ethanol is added for crystallization, and 35.0g of quizalofop-p-ethyl is obtained, the content is 97.9%, and the yield.
600g of quizalofop-p-ethyl mother liquor (the content is 3.7 percent, 0.06mol, ethanol is used as a solvent) is added into a 1000ml four-mouth bottle, 90.7g of sodium ethoxide solution (the content is 30 percent, 0.40 mol) is added, the temperature is raised to reflux, the temperature is kept for 2.5 hours, 1g of activated carbon is added for decolorization, the temperature is reduced to about 60 ℃, the hot filtration is carried out, the pressure is reduced to 0.1MPa, the desolventization is carried out, the temperature is 42 ℃, the residual solution is steamed until 60g of the solution is reduced to about-8 ℃, and the filtration is.
Adding 11.9g of sodium salt compound and 150g of hot water into a 500ml four-mouth bottle, adding 1g of activated carbon, decoloring for about 30min at about 80 ℃, carrying out hot filtration, dropping hydrochloric acid after cooling to room temperature, acidifying to PH =5, carrying out suction filtration, washing with hot water until the filtrate is transparent, the PH value is neutral, and drying at 100 ℃ to obtain 6.84g of the product 6-chloro-2-hydroxyquinoxaline, wherein the recovery rate is 59.8% and the effective content is 94.7%.
Claims (8)
1. An environment-friendly process for producing quizalofop-p-ethyl, which is characterized in that:
(1) preparation of 4- (6-chloro-2-quinoxalinyloxy) phenol: adding hydroquinone and sodium hydroxide under the protection of nitrogen, adding toluene to dissolve, heating to 65-95 ℃ to react to generate hydroquinone sodium salt, heating to 99-105 ℃, dropwise adding the hydroquinone sodium salt into 2, 6-dichloroquinoxaline toluene solution, carrying out heat preservation reaction, sampling and detecting, cooling the mixed solution to room temperature when the content of the 2, 6-dichloroquinoxaline is less than 0.5%, carrying out suction filtration, washing off salt generated by reaction on a filter cake by using hot water, and obtaining 4- (6-chloro-2-quinoxalyloxy) phenol;
(2) preparing quizalofop-p-ethyl: mixing 4- (6-chloro-2-quinoxalinyloxy) phenol and potassium carbonate, adding an ether nonpolar solvent, heating to 93-95 ℃ for backflow and carrying water, dropwise adding ethyl p-toluenesulfonate into the mixture after no water exists, continuing backflow reaction after the dropwise addition is finished, sampling and tracking a reaction mixture system until the residual content of the 4- (6-chloro-2-quinoxalinyloxy) phenol of the raw material is less than 0.1%, cooling to about 70 ℃ for water washing, decompressing after the water washing is finished, removing the solvent, and adding absolute ethyl alcohol for crystallization to obtain quizalofop-p-ethyl;
(3) treating the fine quinoline butter: recovering solvent from the mother liquid produced in the crystallization process to produce solid quinoline butter, carrying out alkaline hydrolysis and acidification on the quinoline butter, and recovering 6-chloro-2-hydroxyquinoxaline;
the specific treatment of the fine quinoline butter in the step (3) is as follows: dissolving the fine quinoline butter in 20-35 times of water or organic solvent, adding inorganic strong base or organic strong base or alkali metal,
dissolving the fine quince butter in water, adding inorganic strong base, wherein the inorganic strong base is sodium hydroxide,
dissolving quindox butter in organic solvent, adding inorganic strong base or organic strong base or alkali metal, wherein the inorganic strong base is sodium hydroxide, the organic strong base is sodium ethoxide or sodium methoxide, the alkali metal is sodium metal, the organic solvent is ethanol,
heating to 90-95 ℃, carrying out reflux reaction until all oily substances are dissolved, cooling to 75-85 ℃, filtering, and carrying out suction filtration at 1-5 ℃ to obtain a sodium salt compound filter cake with the general formula C, wherein the chemical structural formula of the sodium salt compound C is as follows:
dissolving a sodium salt compound filter cake with a general formula C in water, adding activated carbon at 75-95 ℃ for decolorization, carrying out hot filtration, dropwise adding acid at room temperature for acidification, reacting under an acidic condition to generate a compound A, carrying out suction filtration, washing with water, and drying to obtain 6-chloro-2-hydroxyquinoxaline, wherein the compound A is prepared by the following steps:
2. the environment-friendly process for producing quizalofop-p-ethyl according to claim 1, which is characterized in that: in the step (1), the molar ratio of the reaction materials 2, 6-dichloro quinoxaline, hydroquinone and sodium hydroxide is 2, 6-dichloro quinoxaline: hydroquinone: sodium hydroxide is 1: 1.05-1.3: 1.05-1.15.
3. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1 or 2, wherein: the toluene used for dissolving the hydroquinone and the sodium hydroxide in the step (1) is 5.0 to 8.0 times of the weight of the hydroquinone.
4. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1 or 2, wherein: the amount of toluene in the toluene solution of 2, 6-dichloroquinoxaline in the step (1) is 10-13 times of the weight of 2, 6-dichloroquinoxaline.
5. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1, which is characterized in that: the molar ratio of materials in the synthesis reaction in the step (2) is 4- (6-chloro-2-quinoxalinyloxy) phenol: potassium carbonate: ethyl p-toluenesulfonate 1: 1.5-3.0: 1.05-1.15.
6. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1, which is characterized in that: the mass ratio of the usage amount of the synthetic reaction solvent in the step (2) is 4- (6-chloro-2-quinoxalinyloxy) phenol: non-polar solvent ═ 1: 20-25.
7. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1, which is characterized in that: the dosage of the alkali in the step (3) is 4-6 times of that of quizalofop-p-ethyl in butter.
8. The environment-friendly process for producing quizalofop-p-ethyl according to claim 1, which is characterized in that: the acid in the step (3) is hydrochloric acid or sulfuric acid, the pH value in the acidification process is controlled to be 4-6, and the drying temperature is 100 ℃.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333194A (en) * | 2007-06-29 | 2008-12-31 | 山东京博控股发展有限公司 | Method for preparing quizalofop-p-ethyl |
| CN101875642A (en) * | 2010-06-13 | 2010-11-03 | 山东京博控股发展有限公司 | Synthetic method of 4-(6-chloroquinoxalin-2-yloxy) phenol |
| CN102250023A (en) * | 2011-08-08 | 2011-11-23 | 山东京博控股股份有限公司 | High yield synthetic method for quizalofop-p-ethyl |
| CN101941947B (en) * | 2010-08-27 | 2012-06-27 | 山东京博控股股份有限公司 | Synthesis method of 2-chloro-6-chloroquinoxaline |
| CN102584724A (en) * | 2012-02-06 | 2012-07-18 | 京博农化科技股份有限公司 | Preparation method for quizalofop-p-ethyl |
-
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- 2017-09-07 CN CN201710802152.7A patent/CN107739343B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333194A (en) * | 2007-06-29 | 2008-12-31 | 山东京博控股发展有限公司 | Method for preparing quizalofop-p-ethyl |
| CN101875642A (en) * | 2010-06-13 | 2010-11-03 | 山东京博控股发展有限公司 | Synthetic method of 4-(6-chloroquinoxalin-2-yloxy) phenol |
| CN101941947B (en) * | 2010-08-27 | 2012-06-27 | 山东京博控股股份有限公司 | Synthesis method of 2-chloro-6-chloroquinoxaline |
| CN102250023A (en) * | 2011-08-08 | 2011-11-23 | 山东京博控股股份有限公司 | High yield synthetic method for quizalofop-p-ethyl |
| CN102584724A (en) * | 2012-02-06 | 2012-07-18 | 京博农化科技股份有限公司 | Preparation method for quizalofop-p-ethyl |
Non-Patent Citations (1)
| Title |
|---|
| Quinoxaline chemistry. Part XVII. Methyl [4-(substituted 2-quinoxalinyloxy) phenyl] acetates and ethyl N-{[4-(substituted 2-quinoxalinyloxy) phenyl] acetyl} glutamates analogs of methotrexate: synthesis and evaluation of in vitro anticancer activity;Sandra Piras et al.,;《FARMACO》;20041231;第59卷;第187页Scheme 1，第189页右栏第倒数第1段和第191页左栏第12-13行 * |
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