CN117567364A - Process for optimally producing high-efficiency haloxyfop-R-methyl - Google Patents
Process for optimally producing high-efficiency haloxyfop-R-methyl Download PDFInfo
- Publication number
- CN117567364A CN117567364A CN202311450122.6A CN202311450122A CN117567364A CN 117567364 A CN117567364 A CN 117567364A CN 202311450122 A CN202311450122 A CN 202311450122A CN 117567364 A CN117567364 A CN 117567364A
- Authority
- CN
- China
- Prior art keywords
- kettle
- water
- haloxyfop
- methyl
- dimethylacetamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- MFSWTRQUCLNFOM-SECBINFHSA-N haloxyfop-P-methyl Chemical group C1=CC(O[C@H](C)C(=O)OC)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl MFSWTRQUCLNFOM-SECBINFHSA-N 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 28
- 230000008569 process Effects 0.000 title claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 84
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims abstract description 75
- 229940113088 dimethylacetamide Drugs 0.000 claims abstract description 75
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 69
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 69
- 238000005406 washing Methods 0.000 claims abstract description 56
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 46
- 238000000605 extraction Methods 0.000 claims abstract description 44
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000003756 stirring Methods 0.000 claims abstract description 33
- ABNQGNFVSFKJGI-UHFFFAOYSA-N 2,3-dichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C(Cl)=C1 ABNQGNFVSFKJGI-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000002904 solvent Substances 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 238000010438 heat treatment Methods 0.000 claims abstract description 28
- 229940017219 methyl propionate Drugs 0.000 claims abstract description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000001816 cooling Methods 0.000 claims abstract description 23
- 239000000463 material Substances 0.000 claims abstract description 23
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000008367 deionised water Substances 0.000 claims abstract description 22
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 22
- 239000007787 solid Substances 0.000 claims abstract description 22
- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000007599 discharging Methods 0.000 claims abstract description 11
- 238000001704 evaporation Methods 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 238000010025 steaming Methods 0.000 claims abstract description 3
- 239000012071 phase Substances 0.000 claims description 66
- 238000004519 manufacturing process Methods 0.000 claims description 15
- UUYSCNGPNOYZMC-SSDOTTSWSA-N methyl (2r)-2-(4-hydroxyphenoxy)propanoate Chemical compound COC(=O)[C@@H](C)OC1=CC=C(O)C=C1 UUYSCNGPNOYZMC-SSDOTTSWSA-N 0.000 claims description 11
- 239000002808 molecular sieve Substances 0.000 claims description 11
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 11
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 235000011181 potassium carbonates Nutrition 0.000 description 18
- 230000003287 optical effect Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- XVBWGQSXLITICX-UHFFFAOYSA-N 2,3-dichloro-5-(trichloromethyl)pyridine Chemical compound ClC1=CC(C(Cl)(Cl)Cl)=CN=C1Cl XVBWGQSXLITICX-UHFFFAOYSA-N 0.000 description 6
- GOCUAJYOYBLQRH-UHFFFAOYSA-N 2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoic acid Chemical compound C1=CC(OC(C)C(O)=O)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl GOCUAJYOYBLQRH-UHFFFAOYSA-N 0.000 description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- NMJNUBBLJFJUKE-UHFFFAOYSA-N 4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxyphenol Chemical compound C1=CC(O)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl NMJNUBBLJFJUKE-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000002363 herbicidal effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- YHSAMQAMZAWZPE-UHFFFAOYSA-N butyl 2-[4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxyphenoxy]propanoate Chemical group C1=CC(OC(C)C(=O)OCCCC)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl YHSAMQAMZAWZPE-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- AQIHDXGKQHFBNW-UHFFFAOYSA-N 2-(4-hydroxyphenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=C(O)C=C1 AQIHDXGKQHFBNW-UHFFFAOYSA-N 0.000 description 1
- SMTKGMYGLYWNDL-UHFFFAOYSA-N 2-bromo-3-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Br)C(Cl)=C1 SMTKGMYGLYWNDL-UHFFFAOYSA-N 0.000 description 1
- SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 description 1
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 1
- GDSROTVTTLUHCO-UHFFFAOYSA-N 3-chloro-2-fluoro-5-(trifluoromethyl)pyridine Chemical compound FC1=NC=C(C(F)(F)F)C=C1Cl GDSROTVTTLUHCO-UHFFFAOYSA-N 0.000 description 1
- 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
- 241001013934 Erigeron breviscapus Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- VAIZTNZGPYBOGF-CYBMUJFWSA-N fluazifop-P-butyl Chemical group C1=CC(O[C@H](C)C(=O)OCCCC)=CC=C1OC1=CC=C(C(F)(F)F)C=N1 VAIZTNZGPYBOGF-CYBMUJFWSA-N 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- ACEONLNNWKIPTM-GSVOUGTGSA-N methyl (2r)-2-bromopropanoate Chemical compound COC(=O)[C@@H](C)Br ACEONLNNWKIPTM-GSVOUGTGSA-N 0.000 description 1
- XEUQMYXHUMKCJY-BYPYZUCNSA-N methyl (2s)-2-methylsulfonyloxypropanoate Chemical compound COC(=O)[C@H](C)OS(C)(=O)=O XEUQMYXHUMKCJY-BYPYZUCNSA-N 0.000 description 1
- MFSWTRQUCLNFOM-UHFFFAOYSA-N methyl 2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoate Chemical group C1=CC(OC(C)C(=O)OC)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl MFSWTRQUCLNFOM-UHFFFAOYSA-N 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention provides a process for optimally producing high-efficiency haloxyfop-R-methyl. Step 1: adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; the reaction is kept at a temperature under the environment of introducing nitrogen and heating and stirring; step 2: cooling the synthesis kettle in the step 1 until the reaction materials are at normal temperature, vacuumizing and heating the synthesis kettle, and evaporating dimethylacetamide under negative pressure; step 3: cooling the synthesis kettle for steaming out the dimethylacetamide in the step 2 to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; step 4: stirring a water-washing extraction kettle, standing, removing a lower water phase, adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle, removing alkaline substances, and discharging the water phase to obtain an oil phase; step 5: adding deionized water for washing for multiple times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; step 6: and heating and desolventizing the desolventizing kettle to obtain the haloxyfop-R-methyl. The method improves the conversion rate of the raw materials in the process of preparing the haloxyfop-R-methyl.
Description
Technical Field
The invention relates to a chemical method, in particular to an improvement of a haloxyfop synthesis process.
Background
haloxyfop-P-butyl (Fluazifop-P-butyl), also known as FUBA. The specific synthetic process is complex, and the chemical substances and the reaction conditions involved are different from one production process to another. In general, the synthesis of haloxyfop requires the use of various organic compounds as starting materials, such as phenoxyacetic acid, trichlorofluoromethane, methanol, hydrofluoric acid, sodium hydroxide, etc., to obtain the final product through a series of chemical reactions and refining processes. The haloxyfop-R-methyl is a common herbicide, has strong systemic conduction and can be used for various broad-leaf crops such as soybean, cotton, peanut, rape and the like.
Chinese patent document CN103787961A discloses a method for synthesizing high-efficiency haloxyfop-R-methyl, which comprises the following steps of (1) reacting 2-chloro-5-chloromethylpyridine with a catalyst under chlorine for 28-32 hours at 130-145 ℃, and cooling after the reaction is completed to synthesize 2, 3-dichloro-5-trichloromethyl pyridine; (2) The crude product of the 2, 3-dichloro-5-trichloromethyl pyridine reacts with hydrogen fluoride for 8 hours at the temperature of 235-240 ℃ under the atmospheric pressure of 6-10, and water washing and reduced pressure distillation are carried out after the reaction is finished to synthesize the 2, 3-dichloro-5-trifluoromethyl pyridine; (3) 2, 3-dichloro-5-trifluoromethyl pyridine and (R) -2- (4-hydroxyphenoxy) methyl propionate react under DMSO to synthesize high-efficiency haloxyfop-butyl, wherein the mol ratio of the 2, 3-dichloro-5-trifluoromethyl pyridine to the (R) -2- (4-hydroxyphenoxy) methyl propionate is 1:1.1.
patent document US5049675a discloses a solvent-free process for preparing herbicidal 2- (4- (pyridinyl-2-oxy) phenoxy) propanoates. The process comprises coupling esters of 2-fluoropyridine and 2- (4-hydroxyphenoxy) propionic acid in the presence of anhydrous base and without the addition of solvent. Patent document US4840664a discloses herbicidal pyridine compounds and a process for preparing the same. Chinese patent document CN100467452C discloses a method for preparing haloxyfop-methyl with high optical purity, which is carried out according to the following steps: (1) 2, 3-dichloro-5-trifluoromethyl pyridine and hydroquinone are used as starting materials, in the presence of K2CO3 as alkali, the reaction is carried out in N, N-dimethylformamide solvent at 105-110 ℃, and the intermediate 3-chloro-2- (4-hydroxyphenoxy) -5-trifluoromethyl pyridine is prepared after the reaction is finished through separation and purification; (2) 3-chloro-2- (4-hydroxy phenoxy) -5-trifluoromethyl pyridine and (L) -2-methylsulfonyloxypropionic acid methyl ester are subjected to nucleophilic substitution reaction at 70-110 ℃ by taking chlorobenzene as a solvent in the presence of K2CO3 as a base, and the target product haloxyfop-butyl is obtained after the reaction is finished and is subjected to post-treatment. According to the invention, chlorobenzene is taken as a solvent for the reaction of 3-chloro-2- (4-hydroxyphenoxy) -5-trifluoromethylpyridine and (L) -2-methanesulfonyloxy methyl propionate, and the prepared haloxyfop-R-methyl has higher optical purity and ee value of more than 92%.
Chinese patent document CN106279006A discloses a green and environment-friendly preparation method of high-purity fine-cover grass energy, which takes 2-fluoro-3-chloro-5-trifluoromethyl pyridine and (R) - (+) -2- (4-hydroxy phenoxy) methyl propionate as raw materials to react under the action of alkali and solvent to generate fine-cover grass energy. The preparation method disclosed by the invention has the advantages of mild reaction conditions, few operation steps, short reaction time, high yield, no need of crystallization and rectification purification, and the extracted erigeron breviscapus has a color close to colorless, and the content of an HPLC external standard is more than 98%. The Chinese patent document CN114213320A discloses a preparation method of high-efficiency haloxyfop-R-methyl, which comprises the following steps: using hydroquinone as a raw material, and reacting with (R) -2-bromopropionic acid methyl ester in the presence of an alkaline reagent to generate an intermediate (R) -2- (4-hydroxyphenoxy) propionic acid methyl ester; and then under the action of a catalyst, the high-efficiency haloxyfop-R-methyl is directly prepared with 3-chloro-2-bromo-5-trifluoromethylpyridine.
The haloxyfop-R-methyl produced by the prior art has the advantages of mature and stable production, and the haloxyfop-R-methyl is widely applied as a common pesticide. Controlling production costs is an important development goal.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a process for optimally producing high-efficiency haloxyfop-R-methyl.
The invention adopts the following scheme to realize the purposes:
a process for optimally producing high-efficiency haloxyfop-R-methyl comprises the following steps:
step 1: adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; the reaction is kept at a temperature under the environment of introducing nitrogen and heating and stirring;
step 2: cooling the synthesis kettle in the step 1 until the reaction materials are at normal temperature, vacuumizing and heating the synthesis kettle, and evaporating dimethylacetamide under negative pressure;
step 3: cooling the synthesis kettle for steaming out the dimethylacetamide in the step 2 to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle;
step 4: stirring a water-washing extraction kettle, standing, removing a lower water phase, adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle, removing alkaline substances, and discharging the water phase to obtain an oil phase;
step 5: adding deionized water for washing for multiple times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle;
step 6: and heating and desolventizing the desolventizing kettle to obtain the haloxyfop-R-methyl.
Further, wherein in step 1, 2, 3-dichloro-5-trifluoromethylpyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxy phenoxy) propionic acid methyl ester is 1:0.01-0.02:1.05-1.08.
Further, the weight ratio of R- (+) -2- (4-hydroxyphenoxy) methyl propionate to dimethylacetamide in the synthesis kettle in the step 1 is 1:3-5.
Further, wherein the dimethylacetamide solvent in step 1 is dehydrated to a water content of less than 0.03wt% using a molecular sieve.
Further, wherein the aqueous phase of step 4 is treated with calcium hydride.
Further, wherein the addition of hydrochloric acid is stopped when the pH measured in step 4 is 6.5-7.
Further, the temperature is heated to 70-95 ℃ in the step 1 and kept for 1-3 hours.
Further, the temperature is heated to 80-85 ℃ and kept for 1.5-2 hours in the step 1.
Further, the vacuumizing and heating temperature of the synthesis kettle in the step 2 is 65-85 ℃.
Further, the desolventizing temperature of the desolventizing kettle in the step 6 is 112-115 ℃.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the method of the invention improves the optical rotation of MAQ, thus the conversion rate can reach 98% based on 2, 3-dichloro-5-trifluoromethyl pyridine. Meanwhile, the invention reduces the usage amount of R- (+) -2- (4-hydroxy phenoxy) methyl propionate.
Detailed Description
In order to make the technical problems solved by the present invention, the technical solutions adopted and the technical effects achieved more clear, the technical solutions of the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to fall within the scope of the invention.
The process for optimally producing the high-efficiency haloxyfop-R-methyl comprises the following steps: adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, wherein the dimethylacetamide solvent is dehydrated by using a molecular sieve until the water content is less than 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; heating to 70-95 deg.C under nitrogen and stirring, and maintaining for 1-3 hr. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 65-85 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 112-115 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxy phenoxy) propionic acid methyl ester is 1:0.01-0.02:1.05-1.08. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 3-5:1.
commercial dimethylacetamide has various concentrations, and it is particularly noted in the present invention that either recycled dimethylacetamide or commercially available dimethylacetamide can be used. However, in any event, dimethylacetamide put into use industrially cannot meet the water content requirement under the present inventive concept: the methods of controlling the water content of dimethylacetamide, which are common in the laboratory, cannot be used in industrial production. Thus, in the present invention, it is necessary to treat the dimethylacetamide with a 4A molecular sieve before using it, thereby removing water. Immediately after treatment, it must be taken into use to avoid further absorption of moisture in the air by dimethylacetamide.
Example 1
Adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, wherein the dimethylacetamide solvent is dehydrated by using a molecular sieve until the water content is less than 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 70℃and incubated for 3 hours. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 65 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 112 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.01:1.05. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 3:1.
example 2
Adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, wherein the dimethylacetamide solvent is dehydrated by using a molecular sieve until the water content is less than 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 95℃and incubated for 1 hour. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 85 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 115 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.02:1.08. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 5:1.
example 3
Adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, wherein the dimethylacetamide solvent is dehydrated by using a molecular sieve until the water content is less than 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 80℃and incubated for 1 hour. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 70 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 114 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.015:1.06. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 4:1.
example 4
Adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, wherein the dimethylacetamide solvent is dehydrated by using a molecular sieve until the water content is less than 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 85℃and incubated for 2 hours. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 80 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 114 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.02:1.06. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 4:1.
comparative example 1
Adding a dimethylacetamide solvent into a synthesis kettle, forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, and removing water from the dimethylacetamide solvent by using a molecular sieve until the water content is 2wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 80℃and incubated for 1 hour. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 70 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 114 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.015:1.06. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 4:1.
comparative example 2
Adding a dimethylacetamide solvent into a synthesis kettle, forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide, and removing water from the dimethylacetamide solvent by using a molecular sieve until the water content is 2wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 80℃and incubated for 1 hour. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 70 ℃, and evaporating dimethylacetamide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 114 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.015:1.06. The weight ratio of the pre-added dimethylacetamide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate in the synthesis kettle is 8:1.
comparative example 3
Adding dimethyl sulfoxide solvent into a synthesis kettle, forming a solution of 2, 3-dichloro-5-trifluoromethyl pyridine and dimethyl sulfoxide, and removing water from the dimethyl sulfoxide solvent by using a molecular sieve until the water content is 0.03wt%; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; under nitrogen and stirring, the mixture was heated to 80℃and incubated for 1 hour. Then cooling the synthesis kettle until the reaction materials are at normal temperature, vacuumizing the synthesis kettle, heating to 70 ℃, and evaporating dimethyl sulfoxide under negative pressure; cooling the synthesis kettle to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl sulfoxide is pre-added in the water-washing extraction kettle; stirring a water-washing extraction kettle, standing, removing a lower water phase, treating the water phase by using calcium hydride, then adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle until the pH value is 6.5-7, removing alkaline substances, and discharging the water phase to obtain an oil phase; adding deionized water into the oil phase for washing for many times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle; and heating the desolventizing kettle to 114 ℃ to desolventize, thereby obtaining haloxyfop-R-methyl.
In the invention, 2, 3-dichloro-5-trifluoromethyl pyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxyphenoxy) propionic acid methyl ester is 1:0.015:1.06. The weight ratio of the dimethyl sulfoxide to the R- (+) -2- (4-hydroxyphenoxy) methyl propionate added in the synthesis kettle is 4:1.
in the invention, several points of controlling the production of haloxyfop are: 1. and removing water from the solvent. The dimethyl acetamide with extremely low moisture content is used as a solvent to improve the optical rotation of the MAQ, and the optical rotation of the MAQ is not obviously different from that of the dimethyl sulfoxide when the dimethyl acetamide is used in the traditional method, mainly the optical rotation of the dimethyl acetamide is reduced due to the moisture content, and the optical rotation of the dimethyl sulfoxide cannot be improved even after the dimethyl sulfoxide is dehydrated. 2. The optical rotation is improved, so that the reaction materials are further saved, the molar consumption of R- (+) -2- (4-hydroxyphenoxy) methyl propionate is reduced, impurities are further reduced, and the subsequent impurity removal and wastewater treatment difficulties are further reduced; 3. the water contained in dimethylacetamide reacts with dimethylacetamide under the acid-base action to produce impurities. Thus, the inventors have found that the use of dimethylacetamide as a solvent for removing water from dimethylacetamide can increase the optical rotation of MAQ, thereby reducing the use of solvent and reducing the amount of reactants. The reaction yield and the purity of the product are comprehensively improved.
The haloxyfop in the above examples were taken for analysis. Detection was performed by High Performance Liquid Chromatography (HPLC).
The yield of haloxyfop calculated on 2, 3-dichloro-5-trifluoromethylpyridine is as follows:
| yield is good | |
| Example 1 | 98.1 |
| Example 2 | 98.8 |
| Example 3 | 99.0 |
| Example 4 | 98.9 |
| Comparative example 1 | 94.3 |
| Comparative example 2 | 94.5 |
| Comparative example 3 | 94.2 |
The invention improves the conversion rate and the purity through improving the reaction conditions; as can be seen from examples and comparative examples, the reduction of the water content of the solvent brings about an improvement in purity, a reduction in the number of crystallization and an improvement in yield.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that it will be apparent to those skilled in the art that modifications and variations can be made without departing from the technical principles of the present invention, and these modifications and variations should also be regarded as the scope of the invention.
Claims (10)
1. A process for optimally producing high-efficiency haloxyfop-R-methyl comprises the following steps:
step 1: adding a dimethylacetamide solvent into a synthesis kettle, and forming a solution of 2, 3-dichloro-5-trifluoromethylpyridine and dimethylacetamide; adding potassium carbonate solid and R- (+) -2- (4-hydroxyphenoxy) methyl propionate solid; the reaction is kept at a temperature under the environment of introducing nitrogen and heating and stirring;
step 2: cooling the synthesis kettle in the step 1 until the reaction materials are at normal temperature, vacuumizing and heating the synthesis kettle, and evaporating dimethylacetamide under negative pressure;
step 3: cooling the synthesis kettle for steaming out the dimethylacetamide in the step 2 to normal temperature, and adding toluene; subsequently adding water; fully stirring and transferring the materials in the synthesis kettle to a water-washing extraction kettle; dimethyl acetamide is pre-added in the water-washing extraction kettle;
step 4: stirring a water-washing extraction kettle, standing, removing a lower water phase, adding deionized water and a proper amount of hydrochloric acid into the water-washing extraction kettle, removing alkaline substances, and discharging the water phase to obtain an oil phase;
step 5: adding deionized water for washing for multiple times to obtain a clean oil phase, and transferring the oil phase to a desolventizing kettle;
step 6: and heating and desolventizing the desolventizing kettle to obtain the haloxyfop-R-methyl.
2. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein in step 1, 2, 3-dichloro-5-trifluoromethylpyridine: potassium carbonate: the molar ratio of R- (+) -2- (4-hydroxy phenoxy) propionic acid methyl ester is 1:0.01-0.02:1.05-1.08.
3. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein the weight ratio of R- (+) -2- (4-hydroxy phenoxy) methyl propionate to dimethylacetamide in the synthesis kettle in the step 1 is 1:3-5.
4. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein the dimethylacetamide solvent in the step 1 is dehydrated by using a molecular sieve until the water content is less than 0.03 weight percent.
5. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein the aqueous phase of step 4 is treated with calcium hydride.
6. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein the addition of hydrochloric acid is stopped when the pH measured in step 4 is 6.5-7.
7. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that:
wherein in the step 1, the mixture is heated to 70-95 ℃ and is kept for 1-3 hours.
8. The process for the optimized production of haloxyfop-R-methyl according to claim 7, characterized in that: wherein in the step 1, the mixture is heated to 80-85 ℃ and is kept for 1.5-2 hours.
9. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that: wherein the vacuumizing heating temperature of the synthesis kettle in the step 2 is 65-85 ℃.
10. The process for the optimized production of haloxyfop-R-methyl according to claim 1, characterized in that: wherein the desolventizing temperature of the desolventizing kettle in the step 6 is 112-115 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311450122.6A CN117567364A (en) | 2023-11-02 | 2023-11-02 | Process for optimally producing high-efficiency haloxyfop-R-methyl |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311450122.6A CN117567364A (en) | 2023-11-02 | 2023-11-02 | Process for optimally producing high-efficiency haloxyfop-R-methyl |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117567364A true CN117567364A (en) | 2024-02-20 |
Family
ID=89887211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311450122.6A Pending CN117567364A (en) | 2023-11-02 | 2023-11-02 | Process for optimally producing high-efficiency haloxyfop-R-methyl |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117567364A (en) |
-
2023
- 2023-11-02 CN CN202311450122.6A patent/CN117567364A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100362009C (en) | 2-deoxidized glucose preparation method | |
| CN117567364A (en) | Process for optimally producing high-efficiency haloxyfop-R-methyl | |
| CN114426517B (en) | Preparation method of 2-chloro-3-cyanopyridine | |
| CN112812002B (en) | Preparation method of (R) - (+) -2- (4-hydroxyphenoxy) propionic acid | |
| CN101781264A (en) | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole | |
| CN112479853B (en) | Preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride | |
| CN108715576B (en) | Preparation method of 3-ethoxy-4-carboxyl phenylacetic acid | |
| CN113149899A (en) | Method for preparing 4-trifluoromethyl nicotinic acid | |
| CN112745221A (en) | Preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid | |
| CN115073364B (en) | Preparation method of 6-nitropyridin-3-ol | |
| CN111303045A (en) | Production process of 2-ethoxy-4, 6-difluoropyrimidine | |
| CN112939893A (en) | Synthesis method of 4- (4-aminophenyl) -3-morpholinone | |
| CN112409124B (en) | Preparation method and application of epoxiconazole intermediate | |
| CN114213343B (en) | Preparation and purification methods of celecoxib intermediate | |
| CN112321535B (en) | Preparation method of immaric acid or hydrochloride thereof | |
| CN112479995B (en) | Preparation method of 2-chloro-N, N-dimethylnicotinamide | |
| CN111574385B (en) | Synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine | |
| CN109134312B (en) | Preparation method of 2-phenyl acrylonitrile | |
| CN114057540B (en) | Method for preparing 2, 5-dimethyl benzyl chloride | |
| CN115536518B (en) | Preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid | |
| CN108794389B (en) | Preparation method of 2,3,5, 6-tetrachloro-4-methylsulfonylpyridine | |
| CN114736116B (en) | Preparation method of high-purity palmitic anhydride | |
| CN112142728B (en) | Imazethapyr intermediate and synthesis method and application thereof | |
| CN106432109A (en) | Preparation method of quizalofop-P-ethyl | |
| US6452046B2 (en) | Process for producing 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |