CN118420608A - Preparation method of pyrazophos - Google Patents
Preparation method of pyrazophos Download PDFInfo
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- CN118420608A CN118420608A CN202410395802.0A CN202410395802A CN118420608A CN 118420608 A CN118420608 A CN 118420608A CN 202410395802 A CN202410395802 A CN 202410395802A CN 118420608 A CN118420608 A CN 118420608A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 43
- JOOMJVFZQRQWKR-UHFFFAOYSA-N pyrazophos Chemical compound N1=C(C)C(C(=O)OCC)=CN2N=C(OP(=S)(OCC)OCC)C=C21 JOOMJVFZQRQWKR-UHFFFAOYSA-N 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- 230000035484 reaction time Effects 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 239000003960 organic solvent Substances 0.000 claims description 19
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical group [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 11
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 6
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 claims description 5
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 3
- 229920002866 paraformaldehyde Polymers 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 239000003446 ligand Substances 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 235000010265 sodium sulphite Nutrition 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 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 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- VTNQPKFIQCLBDU-UHFFFAOYSA-N Acetochlor Chemical compound CCOCN(C(=O)CCl)C1=C(C)C=CC=C1CC VTNQPKFIQCLBDU-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000004009 herbicide Substances 0.000 description 5
- WVQBLGZPHOPPFO-UHFFFAOYSA-N 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl)acetamide Chemical compound CCC1=CC=CC(C)=C1N(C(C)COC)C(=O)CCl WVQBLGZPHOPPFO-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CASLETQIYIQFTQ-UHFFFAOYSA-N 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfonyl]-5,5-dimethyl-4h-1,2-oxazole Chemical compound CN1N=C(C(F)(F)F)C(CS(=O)(=O)C=2CC(C)(C)ON=2)=C1OC(F)F CASLETQIYIQFTQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- -1 cyclic secondary amine Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 244000304962 green bristle grass Species 0.000 description 2
- 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 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- WVQBLGZPHOPPFO-LBPRGKRZSA-N (S)-metolachlor Chemical compound CCC1=CC=CC(C)=C1N([C@@H](C)COC)C(=O)CCl WVQBLGZPHOPPFO-LBPRGKRZSA-N 0.000 description 1
- YMCWJQIZJIKFHO-UHFFFAOYSA-N 3-chloro-5,5-dimethyl-4h-1,2-oxazole Chemical compound CC1(C)CC(Cl)=NO1 YMCWJQIZJIKFHO-UHFFFAOYSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 240000001592 Amaranthus caudatus Species 0.000 description 1
- 235000009328 Amaranthus caudatus Nutrition 0.000 description 1
- 244000036975 Ambrosia artemisiifolia Species 0.000 description 1
- 235000003129 Ambrosia artemisiifolia var elatior Nutrition 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000743774 Brachypodium Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 235000003222 Helianthus annuus Nutrition 0.000 description 1
- 235000005052 Milium effusum Nutrition 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- 239000005617 S-Metolachlor Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 244000062793 Sorghum vulgare Species 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000012735 amaranth Nutrition 0.000 description 1
- 239000004178 amaranth Substances 0.000 description 1
- 235000003484 annual ragweed Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000006263 bur ragweed Nutrition 0.000 description 1
- 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 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000003488 common ragweed Nutrition 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 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
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000442 meristematic effect Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 235000009736 ragweed Nutrition 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002352 surface water Substances 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 238000003911 water pollution Methods 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides a novel preparation method of haloxyfop-methyl. The preparation method provided by the invention has the advantages of high reaction yield, high product purity, mild reaction conditions, short reaction time and short reaction route. In addition, the preparation method provided by the invention has the advantages of easily available raw materials, low cost, good safety, no need of using a chloridizing reagent, less three wastes, excellent and friendly environment and suitability for green large-scale production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of topiramate.
Background
Pyroxasulfuron (CAS No. 447399-55-5), an isoxazole herbicide, developed by Japanese chemical Co., ltd., has the chemical structure shown below:
pyroxasulfuron sulfone (Pyroxasulfone)
The haloxyfop-methyl is a broad-spectrum herbicide, the action mechanism of the haloxyfop-methyl is similar to that of acetochlor and related herbicides, the haloxyfop-methyl is absorbed by weed young roots and young buds after application, early growth of seedlings is inhibited, meristematic tissues and coleoptile are destroyed, and the haloxyfop-methyl is a potential inhibitor in biosynthesis of VLCFA (very long side chain fatty acid) in plants, but the haloxyfop-butyl is widely applied to crops and has biological activity far greater than that of acetochlor and metolachlor. In addition, the dosage per unit area is 8-10 times lower than that of acetochlor and other chloroacetamide herbicides, and the water solubility is lower (3.l mg/L at 20 ℃), which shows that the water is very little in possibility of surface water and underground water pollution through rainfall and leaching, and the ecological damage can be reduced.
The weed killing spectrum of the paraquat is similar to that of the chloracetamide herbicides such as acetochlor and metolachlor, but the weed killing spectrum of the paraquat is superior to that of the metolachlor on the control effect of almost all weeds such as Shangma, ragweed, broadleaf brachypodium, millet and green bristlegrass, and the stable control effect can be achieved for 85 days after spraying; under drought conditions, the effect of the anti-flaming agent on green bristlegrass, sunflower attack and amaranth is better than that of the S-metolachlor; the effective period of low-dose control of various weeds is longer. The haloxyfop-R-methyl has the outstanding characteristics of low dosage per unit area, good weeding effect and long weeding duration, and is likely to partially replace varieties such as acetochlor, metolachlor and the like in the future.
In the preparation method of the fenpyrad disclosed in the prior art, the reaction route is long, the operation process is complex, and the chlorination steps are needed; or the preparation method needs to use expensive cyclic secondary amine reagent, which not only increases the production cost, but also causes the cyclic secondary amine to react with hydrochloric acid in the system to generate cyclic ammonium chloride salt, thereby being unfavorable for the reaction. In addition, the existing method has the problems of low yield of the fenpyrad, low raw material conversion rate, large amount of byproducts, difficult post-treatment, easy environmental pollution and the like.
Disclosure of Invention
In order to solve the technical problems, the invention provides a preparation method of haloxyfop-R-methyl, which comprises the following steps:
Reacting the compound shown in the formula (4) with a compound shown in the formula (5) to obtain the fenpyrad shown in the formula (1);
wherein R is selected from leaving groups such as halogen, e.g. fluorine, chlorine, bromine, iodine.
According to an embodiment of the invention, the molar ratio of the compound of formula (4) to the compound of formula (5) is 1 (1-2), preferably 1 (1.1-1.5), for example 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.
According to an embodiment of the present invention, the above reaction is carried out under catalytic conditions; preferably, the catalyst is selected from copper catalysts, such as copper iodide; preferably, the copper catalyst is used in combination with a ligand, such as 2-picolinic acid.
According to an embodiment of the present invention, the above reaction is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), sulfolane, acetonitrile.
According to an embodiment of the present invention, in the above reaction, the reaction temperature is-10℃to 150℃and preferably 30℃to 70℃such as 30℃35℃40℃45℃50℃55℃60℃65℃or 70 ℃.
According to an embodiment of the present invention, in the above reaction, the reaction time is 0.5h to 10h, for example 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h.
According to an embodiment of the present invention, after the reaction is completed, the organic solvent is removed, and extraction separation is performed by using water and ethyl acetate; preferably, after extraction, the acetic acid phase is desolventized, toluene is added, and recrystallization purification is performed.
According to an embodiment of the present invention, the preparation method of the above compound of formula (4) is as follows:
synthesizing a compound of formula (4) from a compound of formula (3) in the presence of a reducing agent;
According to an embodiment of the present invention, in the above process for preparing the compound of formula (4), the molar ratio of the compound of formula (3) to the reducing agent is 1 (1 to 5), preferably 1 (1.1 to 2.0), for example 1:1.5. Wherein each of the aforementioned "1.1 to 2.0" is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.0.
According to an embodiment of the present invention, in the above-mentioned method for producing the compound of formula (4), the reducing agent is selected from sodium sulfite or sodium bisulfite, for example sodium bisulfite.
According to an embodiment of the present invention, the preparation method of the compound of formula (4) above is performed in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), sulfolane and acetonitrile; such as N, N-Dimethylformamide (DMF).
According to an embodiment of the present invention, in the above-mentioned process for preparing the compound of formula (4), the reaction temperature is-10℃to 150℃and preferably 30℃to 70℃such as 30℃35℃40℃45℃50℃55℃60℃65℃or 70 ℃.
According to an embodiment of the present invention, in the above-mentioned preparation method of the compound of formula (4), the reaction time is 0.2h to 5h, for example, 0.5h, 1h, 2h, 3h, 4h, 5h.
According to an embodiment of the present invention, after the completion of the reaction, the preparation method of the compound of formula (4) above directly proceeds to the subsequent reaction without post-treatment.
According to an embodiment of the present invention, the preparation method of the compound of formula (3) above is as follows:
Reacting a compound of formula (2) with formaldehyde or paraformaldehyde, and sodium bisulphite in the presence of a base to synthesize a compound of formula (3);
According to an embodiment of the present invention, in the preparation method of the compound of formula (3), the molar ratio of the compound of formula (2), formaldehyde (or paraformaldehyde) to sodium bisulphite is 1 (1-5): 1-5, preferably 1 (1.1-2.0): 1.1-2.0, for example 1:1.5:1.5. Wherein each of the aforementioned "1.1 to 2.0" is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.0.
According to an embodiment of the present invention, in the method for producing the compound of formula (3) above, the base is selected from one, two or more of an organic base and an inorganic base, for example, one, two or more of sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert-butoxide, sodium tert-butoxide, triethylamine and the like, for example, sodium hydroxide.
According to an embodiment of the present invention, in the above process for the preparation of the compound of formula (3), the molar ratio of the compound of formula (2) to the base (e.g. sodium hydroxide) is 1 (1 to 5), preferably 1 (1.1 to 2.0), for example 1:1.5. Wherein each of the aforementioned "1.1 to 2.0" is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2.0.
According to an embodiment of the present invention, the preparation method of the compound of formula (3) above is performed in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloroethane, dichloromethane, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMAC), sulfolane and acetonitrile; such as tetrahydrofuran THF.
According to an embodiment of the present invention, in the above-mentioned method for producing the compound of formula (3), the reaction temperature is-10℃to 150℃and preferably 30℃to 70℃such as 30℃35℃40℃45℃50℃55℃60℃65℃or 70 ℃.
According to an embodiment of the present invention, in the above-mentioned method for preparing the compound of formula (3), the reaction time is 0.5h to 8h, for example, 1h, 2h, 3h, 4h, 5h, 6h.
According to an embodiment of the present invention, the preparation method of the compound of formula (3) above specifically includes: sequentially adding the compound 2, alkali, sodium bisulphite and an organic solvent, and then dropwise adding formaldehyde to obtain the compound of the formula (3).
According to the embodiment of the invention, in the preparation method of the compound of the formula (3), after the reaction is finished, dichloroethane is added to reflux and split water, and then dichloroethane is removed, so that the compound of the formula (3) in a white solid form is obtained.
According to an embodiment of the present invention, the process for preparing the compound of formula (2) is as follows:
Reacting a compound of formula (6) with 1-chloro-2-fluoromethane to obtain a compound of formula (2);
According to an embodiment of the present invention, the process for the preparation of the compound of formula (2) is carried out in the presence of water and an organic solvent. For example, the organic solvent is selected from one, two or more of methanol, ethanol, acetonitrile, and the like. For example, the volume ratio of water to organic solvent is (1-9): (9-1), for example (2-8): (8-2), (3-7): (7-3), (4-6): (6-4) or 1:1.
According to an embodiment of the present invention, in the process for the preparation of the compound of formula (2), the molar ratio of the compound of formula (6) to 1-chloro-2-fluoromethane is (0.5-5): 0.5-5, preferably (1.0-3.0): 1.0-3.0, e.g. 1:2, 1:1, etc. Wherein each of the above-mentioned "1.0 to 3.0" is at least 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0.
According to an embodiment of the present invention, in the process for preparing the compound of formula (2), the reaction temperature is 10℃to 20 ℃.
According to an embodiment of the present invention, in the preparation method of the compound of formula (2), the reaction time is 0.5h to 5h, for example 1h, 2h, 3h, 4h, 5h.
According to an embodiment of the present invention, after the reaction of the preparation method of the compound of formula (2) is completed, extraction is performed with ethyl acetate, and desolventization is performed to obtain compound 2.
According to an embodiment of the present invention, the process for preparing the compound of formula (6) is as follows:
reacting methyl hydrazine and ethyl trifluoroacetoacetate to obtain a compound of a formula (6);
According to an embodiment of the present invention, the molar ratio of methyl hydrazine to ethyl trifluoroacetoacetate in the process for the preparation of the compound of formula (6) is (0.5-5): (0.5-5), preferably (1.0-3.0): (1.0-3.0), e.g., 2:1, 1:1, 1:2, etc. Wherein each of the above-mentioned "1.0 to 3.0" is at least 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0.
According to an embodiment of the present invention, the preparation of the compound of formula (6) is carried out in the presence of an organic solvent. For example, the organic solvent is selected from one, two or more of methanol, ethanol and acetonitrile.
According to an embodiment of the present invention, in the method for producing the compound of formula (6), the reaction temperature is a reflux reaction temperature.
According to an embodiment of the present invention, in the preparation method of the compound of formula (6), the reaction time is 0.5h to 10h, for example 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h.
According to an embodiment of the present invention, in the process for preparing the compound of formula (6), after the reaction is completed, the intermediate product is obtained by cooling, crystallizing and drying.
Advantageous effects
The invention provides a novel preparation method of haloxyfop-methyl. The preparation method provided by the invention has the advantages of high reaction yield, high product purity, mild reaction conditions, short reaction time and short reaction route. In addition, the preparation method provided by the invention has the advantages of easily available raw materials, low cost, good safety, no need of using a chloridizing reagent, less three wastes, excellent and friendly environment and suitability for green large-scale production.
Detailed Description
The technical scheme of the invention will be further described in detail below with reference to specific embodiments. It is to be understood that the following examples are illustrative only and are not to be construed as limiting the scope of the invention. All techniques implemented based on the above description of the invention are intended to be included within the scope of the invention.
In the following examples, all materials were commercially available from Beijing coupling technologies Co., ltd unless otherwise specified.
In the following examples, the contents (purity) of the reactants and products were measured by high performance liquid chromatography (AGILENT HPLC 1260).
Example 1: synthesis of Compound 2
Adding 1moL of methyl hydrazine and 500mL of absolute ethyl alcohol into a 500mL four-necked flask, stirring and heating to about 50 ℃, dropwise adding 1moL of ethyl trifluoroacetoacetate, heating and refluxing for 5h, cooling and crystallizing, decompressing and filtering, drying to obtain a yellow solid, continuously adding 30mL of water and 100mL of acetonitrile at 10-20 ℃, starting to introduce 2.0moL of freon (1-chloro-2-fluoromethane), carrying out heat preservation reaction for 3h, extracting with ethyl acetate after the reaction is finished, and desolventizing to obtain the compound 2, wherein the yield is 85% and the purity is 95%.
The reaction route is as follows:
EXAMPLE 2 Synthesis of Compound 3
In a 500mL four-port bottle, compound 2 (1 mol), sodium hydroxide 1.5mol (30%), sodium bisulphite 1.5mol, THF 100g and 40-50 ℃ are added, formaldehyde aqueous solution 1.5mol is started to be added dropwise, the reaction is continued for 1h after 2h dropwise addition, the area of the compound 2 detected by liquid phase HPLC is smaller than 0.5%, dichloroethane is added after refluxing and water separation is carried out after the reaction is completed, white solid is obtained, the yield is 95.0% (calculated by the compound 2), and the content is 94.5%.
The reaction route is as follows:
Example 3: synthesis of Compound 1
Adding compound 3 (1 mol) into a 500mL four-port bottle, reacting for 1h at 40-50 ℃ with 1.5mol of sodium bisulphite and 500g of DMF, detecting that the area of the compound 3 is smaller than 0.5% by liquid phase HPLC, obtaining DMF mother liquor of the compound 4 after the reaction is finished, adding 5g of cuprous iodide and 5g of 2-picolinic acid as catalysts, adding 1mol of compound 5 (3-chloro-5, 5-dimethyl-4, 5-dihydro-isoxazole; R is chlorine), adding 40-50 ℃ for reacting for 5h, adding 500g of water and 500g of ethyl acetate after the liquid phase detection is finished, distilling under reduced pressure to recover the solvent, extracting and layering, removing the organic phase by dissolving, continuously adding 300g of toluene, recrystallizing to obtain the target compound 1 sulfone metaxazole with the content of 99% and the yield of 98% (calculated by the compound 3).
The reaction route is as follows:
The preferred embodiments of the present application are described above in detail. The scope of the application is not limited thereto. Within the scope of the technical idea of the application, a person skilled in the art can make numerous variants of the technical solution of the application, including combinations of the individual technical features in any other suitable way, these simple variants and combinations being likewise covered by the scope of protection of the claims of the application.
Claims (10)
1. A method for preparing metazopyr, wherein the method comprises the following steps:
Reacting the compound shown in the formula (4) with a compound shown in the formula (5) to obtain the fenpyrad shown in the formula (1);
Wherein R is selected from leaving groups.
2. The process according to claim 1, wherein the molar ratio of the compound of formula (4) to the compound of formula (5) is 1 (1-2);
Preferably, the above reaction is carried out under catalytic conditions; preferably, the catalyst is selected from copper catalysts, such as copper iodide; preferably, the copper catalyst is used in combination with a ligand, such as 2-picolinic acid;
preferably, the above reaction is carried out in the presence of an organic solvent;
Preferably, in the above reaction, the reaction temperature is-10 ℃ to 150 ℃; preferably, in the above reaction, the reaction time is 0.5h to 10h.
3. The process according to claim 1 or 2, wherein the process for preparing the compound of formula (4) is as follows:
synthesizing a compound of formula (4) from a compound of formula (3) in the presence of a reducing agent;
4. the process according to claim 3, wherein in the process for producing the compound of formula (4), the molar ratio of the compound of formula (3) to the reducing agent is 1 (1) to (5);
Preferably, in the above process for the preparation of the compound of formula (4), the reducing agent is selected from sodium bisulphite or sodium sulphite, preferably sodium bisulphite;
preferably, the preparation of the compound of formula (4) above is carried out in the presence of an organic solvent;
Preferably, in the preparation method of the compound of the formula (4), the reaction temperature is-10 ℃ to 150 ℃;
Preferably, in the preparation method of the compound of the formula (4), the reaction time is 0.2h-5h;
preferably, after the reaction of the preparation method of the compound of the formula (4) is finished, the subsequent reaction is directly carried out without post-treatment.
5. The process according to claim 3 or 4, wherein the process for preparing the compound of formula (3) is as follows:
Reacting a compound of formula (2) with formaldehyde or paraformaldehyde, and sodium bisulphite in the presence of a base to synthesize a compound of formula (3);
6. The process according to claim 5, wherein in the process for producing the compound of formula (3), the molar ratio of the compound of formula (2), formaldehyde to sodium bisulfite is 1 (1 to 5): 1 to 5;
preferably, in the above method for producing a compound of formula (3), the base is selected from one, two or more of an organic base and an inorganic base;
Preferably, in the above process for producing a compound of formula (3), the molar ratio of the compound of formula (2) to the base (e.g., sodium hydroxide) is 1 (1 to 5);
preferably, the above process for the preparation of the compound of formula (3) is carried out in the presence of an organic solvent;
Preferably, in the preparation method of the compound of the formula (3), the reaction temperature is-10 ℃ to 150 ℃;
preferably, in the above preparation method of the compound of formula (3), the reaction time is 0.5h to 8h.
7. The process according to claim 5 or 6, wherein the process for preparing the compound of formula (2) is as follows:
Reacting a compound of formula (6) with 1-chloro-2-fluoromethane to obtain a compound of formula (2);
8. The process according to claim 7, wherein the process for preparing the compound of formula (2) is carried out in the presence of water and an organic solvent;
Preferably, in the preparation method of the compound of the formula (2), the molar ratio of the compound of the formula (6) to the 1-chloro-2-fluoromethane is (0.5-5): 0.5-5;
preferably, in the preparation method of the compound of the formula (2), the reaction temperature is 10-20 ℃;
Preferably, in the process for the preparation of the compound of formula (2), the reaction time is from 0.5h to 5h.
9. The process according to claim 7 or 8, wherein the process for preparing the compound of formula (6) is as follows:
reacting methyl hydrazine and ethyl trifluoroacetoacetate to obtain a compound of a formula (6);
10. The process according to claim 9, wherein the molar ratio of methyl hydrazine to ethyl trifluoroacetoacetate in the process for producing the compound of the formula (6) is from 0.5 to 5:0.5 to 5;
Preferably, the process for the preparation of the compound of formula (6) is carried out in the presence of an organic solvent; for example, the organic solvent is selected from one, two or more of methanol, ethanol and acetonitrile;
Preferably, in the preparation method of the compound of formula (6), the reaction temperature is a reflux reaction temperature;
preferably, in the process for the preparation of the compound of formula (6), the reaction time is from 0.5h to 10h.
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