CN114276312A - Synthetic method of high-purity metamifop - Google Patents
Synthetic method of high-purity metamifop Download PDFInfo
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- CN114276312A CN114276312A CN202111648324.2A CN202111648324A CN114276312A CN 114276312 A CN114276312 A CN 114276312A CN 202111648324 A CN202111648324 A CN 202111648324A CN 114276312 A CN114276312 A CN 114276312A
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- metamifop
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- dichlorobenzoxazole
- hydroxyphenoxy
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- ADDQHLREJDZPMT-AWEZNQCLSA-N (S)-metamifop Chemical compound O=C([C@@H](OC=1C=CC(OC=2OC3=CC(Cl)=CC=C3N=2)=CC=1)C)N(C)C1=CC=CC=C1F ADDQHLREJDZPMT-AWEZNQCLSA-N 0.000 title claims abstract description 34
- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000005917 acylation reaction Methods 0.000 claims abstract description 15
- LVVQTPZQNHQLOM-UHFFFAOYSA-N 2,6-dichloro-1,3-benzoxazole Chemical compound C1=C(Cl)C=C2OC(Cl)=NC2=C1 LVVQTPZQNHQLOM-UHFFFAOYSA-N 0.000 claims abstract description 13
- LDVAIJZDACHGML-UHFFFAOYSA-N 2-fluoro-n-methylaniline Chemical compound CNC1=CC=CC=C1F LDVAIJZDACHGML-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- AQIHDXGKQHFBNW-ZCFIWIBFSA-N (2r)-2-(4-hydroxyphenoxy)propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC=C(O)C=C1 AQIHDXGKQHFBNW-ZCFIWIBFSA-N 0.000 claims abstract description 6
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 6
- 238000001308 synthesis method Methods 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 238000006482 condensation reaction Methods 0.000 claims description 16
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 238000006266 etherification reaction Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000012670 alkaline solution Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 6
- 239000003444 phase transfer catalyst Substances 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- FBUBSODDMFONTH-LLVKDONJSA-N (2r)-n-(2-fluorophenyl)-2-(4-hydroxyphenoxy)-n-methylpropanamide Chemical compound O([C@H](C)C(=O)N(C)C=1C(=CC=CC=1)F)C1=CC=C(O)C=C1 FBUBSODDMFONTH-LLVKDONJSA-N 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000001577 simple distillation Methods 0.000 claims description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 17
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- SXERGJJQSKIUIC-UHFFFAOYSA-N 2-Phenoxypropionic acid Chemical compound OC(=O)C(C)OC1=CC=CC=C1 SXERGJJQSKIUIC-UHFFFAOYSA-N 0.000 abstract description 7
- JJOOKXUUVWIARB-UHFFFAOYSA-N 6-chloro-1,3-benzoxazole Chemical compound ClC1=CC=C2N=COC2=C1 JJOOKXUUVWIARB-UHFFFAOYSA-N 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 4
- 230000010933 acylation Effects 0.000 abstract description 3
- 239000000575 pesticide Substances 0.000 abstract description 3
- 239000012467 final product Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000007788 liquid Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 5
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 4
- -1 4-chloro-1, 3-benzoxazol-2-yloxy Chemical group 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 244000025670 Eleusine indica Species 0.000 description 2
- 235000014716 Eleusine indica Nutrition 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- RONDWVAGJJILEH-UHFFFAOYSA-N 2-bromo-n-(2-fluorophenyl)-n-methylpropanamide Chemical compound CC(Br)C(=O)N(C)C1=CC=CC=C1F RONDWVAGJJILEH-UHFFFAOYSA-N 0.000 description 1
- ADDQHLREJDZPMT-UHFFFAOYSA-N 2-{4-[(6-chloro-1,3-benzoxazol-2-yl)oxy]phenoxy}-N-(2-fluorophenyl)-N-methylpropanamide Chemical compound C=1C=C(OC=2OC3=CC(Cl)=CC=C3N=2)C=CC=1OC(C)C(=O)N(C)C1=CC=CC=C1F ADDQHLREJDZPMT-UHFFFAOYSA-N 0.000 description 1
- 235000001602 Digitaria X umfolozi Nutrition 0.000 description 1
- 235000017898 Digitaria ciliaris Nutrition 0.000 description 1
- 235000005476 Digitaria cruciata Nutrition 0.000 description 1
- 235000006830 Digitaria didactyla Nutrition 0.000 description 1
- 235000005804 Digitaria eriantha ssp. eriantha Nutrition 0.000 description 1
- 235000010823 Digitaria sanguinalis Nutrition 0.000 description 1
- 244000058871 Echinochloa crus-galli Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241001553700 Euphorbia lathyris Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 244000144886 lesser spear grass Species 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- FBUBSODDMFONTH-UHFFFAOYSA-N n-(2-fluorophenyl)-2-(4-hydroxyphenoxy)-n-methylpropanamide Chemical compound C=1C=CC=C(F)C=1N(C)C(=O)C(C)OC1=CC=C(O)C=C1 FBUBSODDMFONTH-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention belongs to the field of synthesis of organic chemical intermediates, and particularly relates to a synthetic method of a pesticide intermediate metamifop. A synthesis method of high-purity metamifop takes (R) -2- (4-hydroxyphenoxy) propionic acid and 2, 6-dichlorobenzoxazole as raw materials, firstly etherifies and synthesizes the raw materials into (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid, then prepares corresponding acyl chloride through acylation, and then reacts with N-methyl-2-fluoroaniline to generate metamifop; compared with the prior art, the method has the advantages of practicability, high reaction efficiency, high purity of the reaction final product, lower synthesis cost, safe reaction operation, simple post-treatment and less three wastes.
Description
Technical Field
The invention belongs to the field of synthesis of organic chemical intermediates, and particularly relates to a synthetic method of a pesticide intermediate metamifop.
Background
Metamifop (Metamifop) is an aryloxyphenoxypropionate herbicide developed by Korea institute of chemical technology, has CAS number of 256412-89-2, molecular formula of C23H18ClFN2O4, molecular weight of 440.8 and trade name of "good Hanqiu". The chemical name is (R) -2- { (4-chloro-1, 3-benzoxazol-2-yloxy) phenoxy } -2' -fluoro-N-methylacryloyl aniline, and the English chemical name is (2R) -2- {4- [ (6-chloro-1,3-benzoxazol-2-yl) oxy ] phenoxy } -N- (2-fluoropheny) -N-methylpropanamide. Unlike most of these herbicides, metamifop is safe to rice, can effectively control main weeds in paddy fields, such as barnyard grass, crab grass, moleplant seed and goosegrass, and can be used for weeding in direct seeding and transplanted paddy fields. The metamifop has low toxicity, is safe to the environment and has wide miscibility, is expected to be used for weeding other crops and lawns, and is a herbicide with great development prospect.
The first method is to take N- (2-fluorophenyl) -N-methyl-2-bromopropionamide and hydroquinone as raw materials to perform substitution reaction in the presence of potassium carbonate to prepare N- (2-fluorophenyl) -N-methyl-2- (4-hydroxyphenoxy) propionamide, and then react with 2, 6-dichlorobenzoxazole to synthesize metamifop. But the reaction condition is more complex and the byproducts are more; and the product is purified by adopting a column chromatography, so that the reaction efficiency is low, the cost is higher, and the method is not suitable for industrial production.
The second method is to synthesize the metamifop by taking 2- [4- (6-chloro-2-benzoxazolyloxy) -phenoxy ] propane-N- (2-fluorophenyl) amide and methyl iodide as raw materials, sodium hydride as a catalyst and anhydrous tetrahydrofuran as a solvent. In the route, the toxicity of methyl iodide is too high, the danger of sodium hydride is very high, and the use of sodium hydride as an acid-binding agent can cause difficult post-treatment, generate more 'three wastes', and is also not suitable for industrial production.
The third method is to generate the metamifop by the one-step reaction of the raw materials of (R) -2- (4- (6-chlorobenzoxazolyl) oxy) phenoxypropionic acid and N-methyl o-fluoroaniline, and the method has the advantages of low yield, use of triphenylphosphine and triethylamine, generation of a large amount of waste water and waste gas and environmental friendliness.
The (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid is an important pesticide intermediate and has wide sources. Therefore, the invention is technically improved on the basis of the third method, and provides a high-efficiency, high-yield and high-purity metamifop synthesis method aiming at the technical defects at present.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the synthesis method of high-purity metamifop, which has the advantages of high reaction efficiency, high purity of reaction final products and lower synthesis cost, and has the advantages of safe reaction operation, simple post-treatment, less three wastes and reusable reaction solvent.
In order to realize the aim, the invention adopts the following technical scheme that a method for synthesizing high-purity metamifop, taking (R) -2- (4-hydroxyphenoxy) propionic acid and 2, 6-dichlorobenzoxazole as raw materials, reacting at normal temperature for 0.5H-2.5H under the condition of alkaline solution and phase transfer catalyst to etherify and synthesize (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid, (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid and bis (trichloromethyl) carbonate to prepare corresponding acyl chloride through 0.5H-1.5H acylation reaction at normal temperature, then carrying out condensation reaction with N-methyl-2-fluoroaniline at the temperature of 0-30 ℃ for 0.5H-2.5H to generate metamifop;
the reaction process is as follows:
(1) and (3) etherification reaction:
(2) acylation reaction:
(3) condensation reaction:
preferably, the molar ratio of the 2, 6-dichlorobenzoxazole to the (R) -2- (4-hydroxyphenoxy) propionic acid-N- (2-fluorophenyl) -methyl amide to the alkaline solution is 0.8-1.2: 1.0: 0.5-5; the optimal molar ratio is 0.98: 1: 3.
preferably, the phase transfer catalyst is at least one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride.
Preferably, the solvent used in the etherification reaction is water and DMF; the solvent used in the acylation reaction and the condensation reaction is at least one of toluene, acetonitrile, dichloroethane, dichloromethane, DMF, DMSO, sulfolane, and most preferably toluene.
Preferably, the solvent used in the acylation reaction and the condensation reaction can be recycled and reused by simple distillation, the post-treatment is simple, and the synthesis cost is reduced.
Preferably, the temperature of the condensation reaction is selected to be 13-15 ℃, and the reaction time is 0.5-1H.
Compared with the prior art, the invention has at least the following beneficial effects:
(1) because only one phase transfer catalyst is used in the whole synthesis process, the synthesis cost is reduced;
(2) the reaction temperature in the whole synthesis process is normal temperature, so the required reaction equipment is simpler and the operation is safer;
(3) because the solvent used in the acylation reaction and the condensation reaction, such as toluene, can be simply distilled (can be recovered, the post-treatment is simple, the three wastes are less, the synthesis cost is reduced, and the solvent can be repeatedly used;
(4) the purity of the product reaches more than 99 percent, and the content is more than 98 percent.
Drawings
FIG. 1 is a liquid phase spectrum of a batch of metamifop finished products of the present invention;
FIG. 2 is a liquid phase spectrum of a two-batch metamifop finished product of the present invention;
FIG. 3 is a liquid phase spectrum of a three-batch metamifop finished product.
Detailed Description
The invention will be further explained with reference to specific embodiments, without limiting the invention.
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments will be clearly and completely described below with reference to the accompanying drawings of the present invention, and the described embodiments are only a part of the embodiments of the present invention and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental procedures described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all reagent products which can be purchased in the market.
Referring to figures 1, 2 and 3,
example 1
A synthetic method of high-purity metamifop comprises the following specific steps:
firstly, adding 7g of sodium hydroxide and 25g of water into a four-mouth bottle A at normal pressure, starting stirring and dissolving, adding 0.56g of tetrabutylammonium bromide, 2.5g of potassium carbonate, 16g of (R) -2- (4-hydroxyphenoxy) propionic acid and 1g of anhydrous sodium sulfite at room temperature, stirring for 15min, and then adding 10g of water and 10g of DMF10 g; meanwhile, preparing a single-neck bottle A, adding 17g of 2, 6-dichlorobenzoxazole and DMF19g into the single-neck bottle A, and stirring and dissolving for later use; controlling the temperature to be 35-38 ℃, dropwise adding the 2, 6-dichlorobenzoxazole dissolving solution in the single-mouth bottle A into the four-mouth bottle A, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the reaction is finished; adding 19g of concentrated hydrochloric acid and 19g of water into the other single-mouth bottle B, slowly dropwise adding the alkaline clear liquid in the four-mouth bottle A into the single-mouth bottle B until all the alkaline clear liquid is added, carrying out suction filtration, adding water to wash the solution to be neutral, and drying the solution at 65 ℃ for 48 hours to obtain 27g of an intermediate A (namely, (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid) to complete etherification reaction;
taking another four-mouth bottle B, adding the intermediate A27g, 100g of toluene and DMF1g, stirring, dropwise adding a bis (trichloromethyl) carbonate solution at room temperature, wherein the bis (trichloromethyl) carbonate solution is formed by adding 14g of bis (trichloromethyl) carbonate into 50ml of toluene, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the end; standing for layering, removing tar at the lower layer, and obtaining an upper intermediate B (namely acyl chloride) toluene solution for later use to complete acylation reaction;
sequentially adding 25g of toluene, 5g of N-methyl-2-fluoroaniline and 11.58g of sodium bicarbonate into a four-mouth bottle C, stirring and cooling to 10 ℃, dropwise adding the obtained toluene solution of the upper-layer intermediate B, controlling the dropwise adding temperature to be 13-15 ℃, and carrying out HPLC tracking reaction until the reaction is finished; after decompression desolventizing, adding 100g of water, and performing suction filtration to obtain a product to complete condensation reaction;
finally, drying for 24h at 45 ℃ to obtain about 13.5g of a product with the purity of 99.5 percent and the content of 98.3 percent; the toluene solvent used in the acylation and condensation reactions was distilled to obtain about 130g of recovered toluene.
Sodium hydroxide is used in the etherification reaction process in this embodiment 1 to provide an alkaline solution condition; potassium carbonate was used to ensure stability of the reaction to ensure that the reaction could be completed in a forward hundred percent; the anhydrous sodium sulfite is used to achieve better separation of the reaction solvent, water and intermediate products, i.e. better demixing.
Example 2
A synthetic method of high-purity metamifop comprises the following specific steps:
firstly, adding 7g of sodium hydroxide and 25g of water into a four-mouth bottle A at normal pressure, starting stirring and dissolving, adding 1.0g of tetrabutylammonium bromide, 2.5g of potassium carbonate, 16g of (R) -2- (4-hydroxyphenoxy) propionic acid and 1g of anhydrous sodium sulfite at room temperature, stirring for 15min, and then adding 10g of water and 10g of DMF10 g; meanwhile, preparing a single-mouth bottle A, adding 17g of 2, 6-dichlorobenzoxazole and DMF19g, and stirring and dissolving for later use; controlling the temperature to be 35-38 ℃, dropwise adding the 2, 6-dichlorobenzoxazole dissolving solution in the single-mouth bottle A into the four-mouth bottle A, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the reaction is finished; adding 19g of concentrated hydrochloric acid and 19g of water into the other single-mouth bottle B, slowly dropwise adding alkaline clear liquid in the four-mouth bottle A until all the alkaline clear liquid is added, carrying out suction filtration, adding water to wash the solution to be neutral, and drying the solution at 65 ℃ for 48 hours to obtain 27.2g of an intermediate A (namely, (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid) to complete etherification reaction;
adding the intermediate A27.2g, toluene 100g and DMF1g into another four-mouth bottle B, stirring, dropwise adding a bis (trichloromethyl) carbonate solution at room temperature, wherein the bis (trichloromethyl) carbonate solution is a solution prepared by adding 14g of bis (trichloromethyl) carbonate into 50ml of toluene, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the end; standing for layering, removing tar at the lower layer, and preparing an intermediate B (namely acyl chloride) toluene solution at the upper layer for later use to complete the acylation reaction;
sequentially adding 25g of toluene, 5g of N-methyl-2-fluoroaniline and 11.58g of sodium bicarbonate into a four-mouth bottle C, stirring and cooling to 10 ℃, dropwise adding the obtained toluene solution of the upper-layer intermediate B, controlling the dropwise adding temperature to be 13-15 ℃, and carrying out HPLC tracking reaction until the reaction is finished; after decompression desolventizing, adding 100g of water, and performing suction filtration to obtain a product to complete condensation reaction;
finally, drying for 24h at 45 ℃ to obtain about 13.5g of a product with the purity of 99.3 percent and the content of 98.0 percent; the toluene solvent used in the acylation and condensation reactions was distilled to obtain about 130g of recovered toluene.
Sodium hydroxide is used in the etherification reaction process in this embodiment 2 to provide an alkaline solution condition; potassium carbonate was used to ensure stability of the reaction to ensure that the reaction could be completed in a forward hundred percent; the anhydrous sodium sulfite is used to achieve better separation of the reaction solvent, water and intermediate products, i.e. better demixing.
Example 3
A synthetic method of high-purity metamifop comprises the following specific steps:
firstly, adding 7g of sodium hydroxide and 25g of water into a four-mouth bottle A at normal pressure, starting stirring and dissolving, adding 0.5g of benzyltriethylammonium chloride, 2.5g of potassium carbonate, 16g of (R) -2- (4-hydroxyphenoxy) propionic acid and 1g of anhydrous sodium sulfite at room temperature, stirring for 15min, and then adding 10g of water and 10g of DMF10 g; meanwhile, preparing a single-mouth bottle A, adding 17g of 2, 6-dichlorobenzoxazole and DMF19g, and stirring and dissolving for later use; controlling the temperature to be 35-38 ℃, dropwise adding the 2, 6-dichlorobenzoxazole dissolving solution in the single-mouth bottle A into the four-mouth bottle A, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the reaction is finished; and adding 19g of concentrated hydrochloric acid and 19g of water into the other single-mouth bottle B, slowly and dropwise adding alkaline clear liquid in the four-mouth bottle A until all the alkaline clear liquid is added, carrying out suction filtration, adding water, washing to be neutral, drying at 65 ℃ for 48h to obtain 25g of intermediate A (namely (R) -2- (4- (6-chlorobenzoxazole) oxy) phenoxypropionic acid), and finishing the etherification reaction.
Taking another four-mouth bottle B, adding the intermediate A25g, 100g of toluene and DMF1g, stirring, dropwise adding a bis (trichloromethyl) carbonate solution at room temperature, wherein the bis (trichloromethyl) carbonate solution is formed by adding 14g of bis (trichloromethyl) carbonate into 50ml of toluene, and after the dropwise adding is finished, carrying out HPLC (high performance liquid chromatography) tracking reaction until the completion; standing for layering, removing tar at the lower layer, and preparing an intermediate B (namely acyl chloride) toluene solution at the upper layer for later use to complete the acylation reaction; sequentially adding 25g of toluene, 5g of N-methyl-2-fluoroaniline and 11.58g of sodium bicarbonate into a four-mouth bottle C, stirring and cooling to 10 ℃, dropwise adding the obtained toluene solution of the upper-layer intermediate B, controlling the dropwise adding temperature to be 13-15 ℃, and carrying out HPLC tracking reaction until the reaction is finished; after decompression desolventizing, adding 100g of water, and performing suction filtration to obtain a product to complete condensation reaction;
finally, drying for 24h at 45 ℃ to obtain about 14g of product with the purity of 99.6 percent and the content of 98.0 percent.
The analysis method of the product obtained by the synthesis method comprises the following steps:
the quantitative analysis of the experiment adopts an external standard method, and the standard substance is obtained by recrystallizing the product for 5 times.
The analytical instrument is an Agilent 1260II high performance liquid chromatograph, and the mobile phase is as follows: acetonitrile: water: 700: 300, selecting 240nm as the detection wavelength of the substance, and obtaining the liquid phase spectrogram of the metamifop finished product shown in the attached figure 1.
The WRS-1B type digital melting point instrument is used for measuring the melting point of the product, the average value is taken after 5 times of parallel measurement, the melting point of the metamifop is 76.3-78.3 ℃, and the literature reference value of the product is 77.0-78.5 ℃.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (7)
1. A synthetic method of high-purity metamifop is characterized by comprising the following steps: taking (R) -2- (4-hydroxyphenoxy) propionic acid and 2, 6-dichlorobenzoxazole as raw materials, reacting at normal temperature for 0.5H-2.5H under the conditions of alkaline solution and phase transfer catalyst to etherify and synthesize (R) -2- (4- (6-chlorobenzoxazolyl) oxy) phenoxypropionic acid, (R) -2- (4- (6-chlorobenzoxazolyl) oxy) phenoxypropionic acid and bis (trichloromethyl) carbonate, performing acylation reaction for 0.5H-1.5H under the normal temperature condition to prepare corresponding acyl chloride, and then performing condensation reaction for 0.5H-2.5H with N-methyl-2-fluoroaniline at the temperature of 0-30 ℃ to generate metamifop;
the reaction process is as follows:
(1) and (3) etherification reaction:
(2) acylation reaction:
(3) condensation reaction:
2. the synthesis method of high-purity metamifop as claimed in claim 1, characterized in that the molar ratio of the 2, 6-dichlorobenzoxazole, the (R) -2- (4-hydroxyphenoxy) propionic acid-N- (2-fluorophenyl) -methylamide and the alkaline solution is 0.8-1.2: 1.0: 0.5-5.
3. The synthesis method of high-purity metamifop according to claim 2, characterized in that the molar ratio of the 2, 6-dichlorobenzoxazole, the (R) -2- (4-hydroxyphenoxy) propionic acid-N- (2-fluorophenyl) -methylamide and the alkaline solution is 0.98: 1: 3.
4. the method for synthesizing metamifop according to claim 1, wherein the phase transfer catalyst is at least one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride.
5. The method for synthesizing high-purity metamifop according to claim 1, characterized in that the solvent used in the etherification reaction is water and DMF; the solvent used in the acylation reaction and the condensation reaction is at least one of toluene, acetonitrile, dichloroethane, dichloromethane, DMF, DMSO, sulfolane, and most preferably toluene.
6. The method for synthesizing metamifop with high purity as claimed in claim 1, wherein the solvent used in the acylation reaction and the condensation reaction can be recovered for reuse by simple distillation.
7. The method for synthesizing high-purity metamifop according to claim 1, wherein the condensation reaction temperature is selected from 13 ℃ to 15 ℃ and the reaction time is selected from 0.5H to 1H.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20100048510A (en) * | 2008-10-31 | 2010-05-11 | 주식회사 동부하이텍 | Enhanced preparation method of optical (r)-phenoxypropionic acid-n-methyl-n-2-fluorophenylamide compound |
| CN108378043A (en) * | 2018-03-27 | 2018-08-10 | 安徽圣丰生化有限公司 | A kind of herbicidal composition of Han metamifops and dichloro quinolinic acid |
| CN109362744A (en) * | 2018-10-15 | 2019-02-22 | 安徽圣丰生化有限公司 | A kind of herbicidal composition containing metamifop and dichloro quinolinic acid |
| CN111732554A (en) * | 2020-08-20 | 2020-10-02 | 湖南速博生物技术有限公司 | Synthesis method of metamifop intermediate |
| CN113620898A (en) * | 2021-08-13 | 2021-11-09 | 江苏富鼎化学有限公司 | Synthesis method of metamifop |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100048510A (en) * | 2008-10-31 | 2010-05-11 | 주식회사 동부하이텍 | Enhanced preparation method of optical (r)-phenoxypropionic acid-n-methyl-n-2-fluorophenylamide compound |
| CN108378043A (en) * | 2018-03-27 | 2018-08-10 | 安徽圣丰生化有限公司 | A kind of herbicidal composition of Han metamifops and dichloro quinolinic acid |
| CN109362744A (en) * | 2018-10-15 | 2019-02-22 | 安徽圣丰生化有限公司 | A kind of herbicidal composition containing metamifop and dichloro quinolinic acid |
| CN111732554A (en) * | 2020-08-20 | 2020-10-02 | 湖南速博生物技术有限公司 | Synthesis method of metamifop intermediate |
| CN113620898A (en) * | 2021-08-13 | 2021-11-09 | 江苏富鼎化学有限公司 | Synthesis method of metamifop |
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