CN118146160A - Preparation method and application of metazopyr and intermediate thereof - Google Patents
Preparation method and application of metazopyr and intermediate thereof Download PDFInfo
- Publication number
- CN118146160A CN118146160A CN202410345000.9A CN202410345000A CN118146160A CN 118146160 A CN118146160 A CN 118146160A CN 202410345000 A CN202410345000 A CN 202410345000A CN 118146160 A CN118146160 A CN 118146160A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- methyl
- metazachlor
- preparation
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- 238000006243 chemical reaction Methods 0.000 claims abstract description 83
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 41
- 239000000543 intermediate Substances 0.000 claims description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000007069 methylation reaction Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 13
- RZSJYVBYLBNFGQ-UHFFFAOYSA-N difluoromethane hydrochloride Chemical compound FCF.Cl RZSJYVBYLBNFGQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000005580 Metazachlor Substances 0.000 claims description 10
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 claims description 10
- STEPQTYSZVCJPV-UHFFFAOYSA-N metazachlor Chemical compound CC1=CC=CC(C)=C1N(C(=O)CCl)CN1N=CC=C1 STEPQTYSZVCJPV-UHFFFAOYSA-N 0.000 claims description 10
- 238000010791 quenching Methods 0.000 claims description 10
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 8
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 7
- 239000012022 methylating agents Substances 0.000 claims description 5
- 230000011987 methylation Effects 0.000 claims description 5
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 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 claims 2
- 239000002994 raw material Substances 0.000 abstract description 7
- 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 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- -1 5-difluoromethoxy-4-substituted-1-methyl-3-trifluoromethyl pyrazole Chemical class 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- GZGJIACHBCQSPC-UHFFFAOYSA-N methyl 3-chloropropanoate Chemical compound COC(=O)CCCl GZGJIACHBCQSPC-UHFFFAOYSA-N 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- XZDWVMFSTKIDHG-UHFFFAOYSA-N 4-(chloromethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazole Chemical compound CN1N=C(C(F)(F)F)C(CCl)=C1OC(F)F XZDWVMFSTKIDHG-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 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 5
- 230000000171 quenching effect Effects 0.000 description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- GRVQNUKLGXWBNL-UHFFFAOYSA-N 2,2,2-trifluoro-N-methylacetohydrazide Chemical compound CN(N)C(C(F)(F)F)=O GRVQNUKLGXWBNL-UHFFFAOYSA-N 0.000 description 3
- WQRHIGNAKDJJKN-UHFFFAOYSA-N 2-methyl-5-(trifluoromethyl)-1h-pyrazol-3-one Chemical compound CN1NC(C(F)(F)F)=CC1=O WQRHIGNAKDJJKN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229960004394 topiramate Drugs 0.000 description 3
- AGXPLJDEOKTGGR-UHFFFAOYSA-N 5-(difluoromethoxy)-1,4-dimethyl-3-(trifluoromethyl)pyrazole Chemical compound CC1=C(OC(F)F)N(C)N=C1C(F)(F)F AGXPLJDEOKTGGR-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VAWFDIIAHPIUDB-UHFFFAOYSA-N [5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methanol Chemical compound CN1N=C(C(F)(F)F)C(CO)=C1OC(F)F VAWFDIIAHPIUDB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000012320 chlorinating reagent Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 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 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 1
- OFUCCBIWEUKISP-UHFFFAOYSA-N 2,2,2-trifluoroacetohydrazide Chemical compound NNC(=O)C(F)(F)F OFUCCBIWEUKISP-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- ARJPLYZBOHQOCK-UHFFFAOYSA-N 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4h-1,2-oxazole Chemical compound CN1N=C(C(F)(F)F)C(CSC=2CC(C)(C)ON=2)=C1OC(F)F ARJPLYZBOHQOCK-UHFFFAOYSA-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
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000005779 Fenpyrazamine Substances 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- GWPLIEAQIAPXBY-UHFFFAOYSA-N [5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methanethiol Chemical compound CN1N=C(C(F)(F)F)C(CS)=C1OC(F)F GWPLIEAQIAPXBY-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 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
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- UKDLORMZNPQILV-UHFFFAOYSA-N ethyl 3-hydroxypropanoate Chemical compound CCOC(=O)CCO UKDLORMZNPQILV-UHFFFAOYSA-N 0.000 description 1
- UTOHZQYBSYOOGC-UHFFFAOYSA-N fenpyrazamine Chemical compound O=C1N(C(C)C)N(C(=O)SCC=C)C(N)=C1C1=CC=CC=C1C UTOHZQYBSYOOGC-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012946 outsourcing Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229950009390 symclosene Drugs 0.000 description 1
- LZNOWAWVWWPHES-UHFFFAOYSA-N tert-butyl 3-sulfanylpropanoate Chemical compound CC(C)(C)OC(=O)CCS LZNOWAWVWWPHES-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method and application of haloxyfop-methyl and an intermediate thereof. The preparation method of the metazopyr and the intermediate thereof comprises the following steps: the compound I and the compound II are subjected to a first reaction in an alkali-containing solvent to obtain a compound III; the compound I comprises at least one of the following structures: R 1 is selected from any one of H and methyl; the structural formulas of the compound II and the compound III are respectively as follows: R 2 is selected from at least one of methyl, ethyl and tert-butyl; r 3 is selected from H, -CH 2Cl、-CH2OH、-CH2 SH, And
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method and application of haloxyfop-methyl and an intermediate thereof.
Background
Pyroxathiolane (chemical name 3- [5- (difluoromethoxy) -1-methyl-3- (trifluoromethyl) pyrazol-4-ylmethyl sulfonyl ] -4, 5-dihydro-5, 5-dimethyl-1, 2-isoxazole) has the following structure:
the fenpyrazamine is a pre-emergence soil treatment agent, and has very large future potential in the market due to the characteristics of low resistance, high activity, good safety and the like.
The literature reports that there are a plurality of synthetic process routes of the haloxyfop-methyl and the intermediate compound A thereof, which are respectively as follows:
Wherein, the compounds A-D are all core intermediates of the fenpyrad, and the compounds B-D are core intermediates of the compound A. Therefore, 5-difluoromethoxy-4-substituted-1-methyl-3-trifluoromethyl pyrazole has important influence on the preparation cost and the technological advancement of the haloxyfop-butyl.
The current synthetic routes of the compounds B to D are multiple, and the synthetic routes are respectively as follows:
(1) Taking 5-hydroxy-1-methyl-3-trifluoromethyl-1H pyrazole as a raw material, reacting with formaldehyde, and reacting with chlorodifluoromethane after the reaction to obtain 5-difluoromethoxy-4-hydroxymethyl-1-methyl-3-trifluoromethyl pyrazole; then reacts with a chloro reagent to obtain 5-difluoromethoxy-4-chloromethyl-1-methyl-3-trifluoromethyl pyrazole, and the specific synthetic route is as follows. The method is widely used for industrial production, and has the defect that 5-hydroxy-1-methyl-3-trifluoromethyl-1H pyrazole is high in price; the reaction operation is complicated.
(2) Taking 5-difluoromethoxy-4-methyl-1-methyl-3-trifluoromethyl-pyrazole as a raw material, and reacting with a halogenated reagent and an initiator to obtain the 5-difluoromethoxy-4-chloromethyl-1-methyl-3-trifluoromethyl-pyrazole, wherein the specific synthetic route is as follows. The disadvantage is that 5-difluoromethoxy-4-methyl-1-methyl-3-trifluoromethyl-pyrazole is expensive; the halogenated reagent is bromine, NBS, dibromohydantoin, NCS, dichloro hydantoin or trichloroisocyanuric acid, wherein the bromine has strong oxidizing property and extremely strong corrosiveness, and the halogen-containing wastewater needs special treatment; during the use, an initiator AIBN or BPO is added.
(3) The 5-difluoromethoxy-4-chloromethyl-3-trifluoromethyl-1H pyrazole is taken as a raw material and reacts with an N-methylating agent to obtain the 5-difluoromethoxy-4-chloromethyl-1-methyl-3-trifluoromethyl pyrazole, and the specific synthetic route is as follows. The defect is that 5-difluoromethoxy-4-chloromethyl-3-trifluoromethyl-1H pyrazole needs to be prepared from hydrazine hydrate, the process is complex, and the price is high.
(4) The 5-difluoromethoxy-4-chloromethyl-3-trifluoromethyl-1H pyrazole is taken as a raw material, and is synthesized through 3 steps, and the specific synthetic route is as follows.
The method has high synthesis cost and needs expensive raw materials or dangerous materials. Therefore, the development of the synthesis technology of the 5-difluoromethoxy-4-substituted-1-methyl-3-trifluoromethyl pyrazole intermediate of the paraquat sulfone which is safe, environment-friendly and low in cost has important industrial value.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide a preparation method of metazachlor and an intermediate thereof, which has low cost and high preparation efficiency.
The invention also aims to provide application of the preparation method of the haloxyfop-R-methyl and the intermediate thereof in preparation of the haloxyfop-R-methyl.
In order to achieve the above purpose, the invention provides a preparation method of metazachlor and its intermediates, comprising the following steps:
carrying out a first reaction on the compound I and the compound II in an alkali-containing solvent to obtain a compound III;
The compound I comprises at least one of the following structures:
R 1 is selected from any one of H and methyl;
the structural formulas of the compound II and the compound III are respectively as follows:
R 2 is selected from at least one of methyl, ethyl and tert-butyl; r 3 is selected from H, -CH 2Cl、-CH2OH、-CH2 SH, At least one of them.
In a specific embodiment of the present invention, the preparation method further comprises: after the first reaction, adding difluoro chloromethane to carry out alkylation reaction to obtain a compound IV;
the structural formula of the compound IV is as follows:
In a specific embodiment of the present invention, the base comprises at least one of sodium hydroxide, sodium methoxide, sodium ethoxide, and potassium tert-butoxide. Further, the solvent includes at least one of methanol, ethanol, and acetonitrile.
In a specific embodiment of the present invention, the molar ratio of the compound I to the compound II is (1 to 1.5) to 1.
In a specific embodiment of the present invention, the molar ratio of the base to the compound I is (3 to 5) to 1; the dosage of the solvent is 1 to 3 times of the mass sum of the compound I and the compound II.
In a specific embodiment of the present invention, the temperature of the first reaction is 40 to 80 ℃, and the time of the first reaction is 2 to 8 hours.
In a specific embodiment of the present invention, the molar ratio of the difluoromethane chloride to the compound i used in the first reaction is (1.5 to 2.5) to 1.
In a specific embodiment of the invention, the alkylation reaction temperature is-75-90 ℃, and the alkylation reaction time is 1-10 h. Further, the alkylation reaction temperature is 10-30 ℃, and the alkylation reaction time is 1-3 h.
In a specific embodiment of the present invention, the temperature of the system of the first reaction is reduced to below 30 ℃ prior to the addition of difluoromethane.
In a specific embodiment of the present invention, after the alkylation reaction, the method further comprises: and adding water to quench the reaction, adding dichloromethane to extract, collecting an organic phase, and distilling under reduced pressure until no liquid is distilled off to obtain the compound IV.
In a specific embodiment of the present invention, when R 1 is H, further comprising, after the first reaction: carrying out N-methylation reaction on the material subjected to the first reaction and a methylation reagent to obtain a compound V; then adding difluoro chloromethane into the N-methylation reaction system to carry out alkylation reaction to obtain a compound VI;
The structural formulas of the compound V and the compound VI are respectively as follows:
In a specific embodiment of the present invention, in the N-methylation reaction, the methylation reagent is at least one of dimethyl sulfate and methyl iodide.
In a specific embodiment of the present invention, the molar ratio of the methylating agent to the compound I used in the first reaction is (1 to 1.5) to 1.
In a specific embodiment of the present invention, when R 1 is H, the molar ratio of difluoromethane chloride employed in the alkylation reaction to compound I employed in the first reaction is (1.5-2.5) to 1.
In a specific embodiment of the present invention, when R 1 is H, the alkylation reaction temperature is-75 to 90 ℃, and the alkylation reaction time is 1 to 10 hours. Further, the alkylation reaction temperature is 10-30 ℃, and the alkylation reaction time is 1-3 h.
In a specific embodiment of the present invention, when R 1 is H, after the alkylation reaction, it further comprises: adding water to quench the reaction, adding dichloromethane to extract, collecting an organic phase, and distilling under reduced pressure until no liquid is distilled off to obtain the compound VI.
The invention also provides application of the preparation method of the paraquat sulfone and the intermediate thereof in preparation of paraquat sulfone.
Compared with the prior art, the invention has the beneficial effects that:
The invention can prepare 5-difluoromethoxy-4-substituted-1-methyl-3-trifluoromethyl pyrazole through the mixed reaction of the compound I, the compound II or the compound I, the compound II and difluoro-chloromethane, has simple and convenient operation and high efficiency, and avoids using expensive materials such as trifluoro-acetoacetic acid ethyl ester or materials such as thionyl chloride and phosphorus oxychloride. In addition, the intermediate quality of the paraquat sulfone prepared by the method is stable, and the paraquat sulfone can be directly used for the subsequent production of paraquat sulfone.
Detailed Description
The technical solution of the present invention will be clearly and completely described in conjunction with the specific embodiments, but it will be understood by those skilled in the art that the examples described below are some, but not all, examples of the present invention, and are intended to be illustrative only and should not be construed as limiting the scope of the present invention. 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 be within the scope of the invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The preparation method of the metazopyr and the intermediate thereof comprises the following steps:
carrying out a first reaction on the compound I and the compound II in an alkali-containing solvent to obtain a compound III;
The compound I comprises at least one of the following structures:
R 1 is selected from any one of H and methyl;
the structural formulas of the compound II and the compound III are respectively as follows:
R 2 is selected from at least one of methyl, ethyl and tert-butyl; r 3 is selected from H, -CH 2Cl、-CH2OH、-CH2 SH, At least one of them.
Wherein,Refers to the site where the R 3 group is attached to the corresponding compound structure.
The invention can prepare the compound III through the reaction of the compound I and the compound II, and has simple operation and high efficiency.
Wherein, the compound I can comprise at least one of the compound I 1 and the compound I 2, and the structural formulas are as follows:
Compound I 1 is selected from Compound I 2 is selected from
Wherein, the compound I 2 can be prepared from the compound I 1, and the specific steps include: the compound I 1 is reacted with a chlorinating reagent to give the compound I 2. Wherein the chlorinating agent may comprise at least one of NCS, thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, solid phosgene, and benzenesulfonyl chloride.
To be used forFor example, may include the following steps:
adding a proper amount of organic solvent into a reaction bottle, 284G of phosphorus oxychloride 1.2 equivalents were added with stirring. After 5 hours at room temperature, the solvent is distilled off, and the mixture is distilled under high vacuum to obtain yellowish oily substance/>300G, HPLC purity 99.3%. The structural test characterization proves that the target structural product is obtained.
When R 1 is methyl, i.e. Compound I isWhen the intermediate is used, the intermediate and the compound II are subjected to a first reaction under a certain condition to obtain a compound III, and difluoromethane chloride can be directly added into a system after the first reaction to continuously carry out alkylation reaction, so that the intermediate/>, the intermediate of the fenpyr-diethyl is obtainedThe synthetic route can be referred to as follows:
in various embodiments, the specific structure that compound II may take may be as follows:
The compound II adopted in the preparation of the pyrifos and the intermediate thereof of the invention is available for outsourcing, and part of the compound II can also be prepared according to the following synthetic route so as to The following description is given for the sake of example:
The specific preparation method can comprise the following steps:
(1) 205g (1.5 mol) of potassium carbonate, 600g of acetonitrile and 130 (1.08 mol) of 3-mercaptopropionic acid methyl ester are added into a reaction vessel, the mixture is stirred uniformly, the temperature is controlled at 25-30 ℃, 142g (1.08 mol) of 3-chloro-5, 5-dimethyl-4, 5-dihydroisoxazole is added into the system dropwise, after the dropwise addition is completed for about 1 hour, the temperature is raised to 50 ℃, and the reaction is continued for 5 hours. The salt was removed by filtration, water was added, extraction was performed twice with ethyl acetate, the ethyl acetate layers were combined, washed with water, brine, and then the organic solvent was removed in vacuo to give 216g of a pale yellow oil with a yield of 99.5% and HPLC purity of 99.6%.
(2) Adding 600g of acetonitrile and 3g (0.01 mol) of sodium tungstate into the reacted material in the step (1), controlling the reaction temperature to be 40-50 ℃, and beginning to dropwise add 127g (1.5 mol and 40%) of hydrogen peroxide into the system for about 1 hour. The reaction was continued for 5h, and the central control showed complete reaction. Cooling to room temperature, quenching the reaction with water, extracting with ethyl acetate twice, combining ethyl acetate layers, washing with water, washing with brine, and then removing the organic solvent in vacuo to give 263g of the product in 98% yield with 99.2% HPLC purity.
The other similar structures of the present invention can be suitably adjusted with reference to the above-described method.
The specific structural formula of the prepared fenpyrad and the intermediate thereof can be shown as follows:
When the structure is obtained as The subsequent reaction may be carried out according to the following route, but is not limited thereto:
When R 1 is H, i.e. Compound I is When the compound II reacts with the compound II under a certain condition, N-methylation reaction is carried out; then difluoro chloromethane can be added into the system after the N-methylation reaction to continue the alkylation reaction, thus obtaining the intermediate/>, of the sulfone metaxazoleThe synthetic route can be referred to as follows:
In a specific embodiment of the present invention, when R 1 is H, further comprising, after the first reaction: carrying out N-methylation reaction on the material subjected to the first reaction and a methylation reagent to obtain a compound V; then adding difluoro chloromethane into the N-methylation reaction system to carry out alkylation reaction to obtain a compound VI;
The structural formulas of the compound V and the compound VI are respectively as follows:
in a specific embodiment of the present invention, the base comprises at least one of sodium hydroxide, sodium methoxide, sodium ethoxide, and potassium tert-butoxide. Further, the solvent includes at least one of methanol, ethanol, and acetonitrile.
In a specific embodiment of the present invention, the molar ratio of compound I to compound II is (1 to 1.5) to 1.
In various embodiments, the molar ratio of compound I to compound II may be in the range of 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, or any two thereof. By further regulating the proportion of the raw materials within the range, the compound II is completely reacted.
In a specific embodiment of the present invention, the molar ratio of base to compound I is (3 to 5) to 1; the dosage of the solvent is 1 to 3 times of the mass sum of the compound I and the compound II.
As in the various embodiments, the molar ratio of base to compound i may be 3:1, 3.5:1, 4:1, 4.5:1, 5:1, or a range of any two thereof; the solvent may be used in an amount of 1 times, 1.5 times, 2 times, 2.5 times, 3 times or any two of the total mass of the compound I and the compound II, but is not limited thereto, and the reaction materials may be uniformly mixed to react.
In a specific embodiment of the invention, the temperature of the first reaction is 40 to 80 ℃ and the time of the first reaction is 2 to 8 hours.
As in the various embodiments, the temperature of the first reaction may be 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃ or a range of any two of them, and the time of the first reaction may be 2h, 4h, 6h, 8h or a range of any two of them. The time of the first reaction can be adjusted according to the actual reaction progress to ensure that the reaction is sufficient.
In practical operation, it is preferable to add the compound II in the form of dropwise addition to the mixed system of the compound I and the alkali-containing solvent, and the reaction stability is ensured by controlling the speed of the dropwise addition, for example, the time of the dropwise addition may be 30 to 100 minutes, but is not limited thereto.
In a specific embodiment of the present invention, the molar ratio of difluoromethane chloride to compound I employed in the first reaction is from (1.5 to 2.5) to 1.
As in the various embodiments, the molar ratio of difluoromethane chloride to compound i may be 1.5:1, 1.8:1, 2:1, 2.2:1, 2.5:1 or any two of these.
In a specific embodiment of the invention, the alkylation reaction temperature is from-75 to 90℃and the alkylation reaction time is from 1 to 10 hours. Further, the alkylation reaction temperature is 10-30 ℃, and the alkylation reaction time is 1-3 h.
As in the various embodiments, the temperature of the alkylation reaction may be-75 ℃, -50 ℃, -20 ℃,0 ℃,10 ℃, 20 ℃, 30 ℃,50 ℃, 80 ℃, 90 ℃ or a range consisting of any two thereof, and the time of the alkylation reaction may be 1h, 2h, 5h, 8h, 10h or a range consisting of any two thereof.
In a specific embodiment of the invention, the temperature of the system of the first reaction is reduced to below 30 ℃ before the addition of difluoromethane.
The reaction of the invention can be carried out in one reaction system, after the first reaction, the first reaction system is directly cooled to 30 ℃, 25 ℃, 20 ℃ and the like without post-treatment, and the difluoromethane can be introduced for continuous reaction, thereby simplifying the reaction procedure.
In a specific embodiment of the present invention, after the alkylation reaction, further comprising: adding water to quench the reaction, adding dichloromethane to extract, collecting an organic phase, and distilling under reduced pressure until no liquid is distilled off to obtain a compound IV.
In actual operation, the water added in the quenching reaction can be used in a conventional amount, for example, the amount can be about 1 time of the volume of the reaction system; the amount of dichloromethane may be about 1 time the volume of the system to be extracted according to conventional extraction, but is not limited thereto.
In a specific embodiment of the present invention, in the N-methylation reaction, the methylating agent is at least one of dimethyl sulfate and methyl iodide.
In a specific embodiment of the present invention, the molar ratio of methylating agent to compound I employed in the first reaction is (1 to 1.5) to 1.
In practice, the N-methylation reaction may be carried out according to the procedure of a conventional N-methylation reaction, without limitation.
In a specific embodiment of the present invention, when R 1 is H, the molar ratio of difluoromethane chloride employed in the alkylation reaction to compound I employed in the first reaction is from (1.5 to 2.5) to 1.
As in the various embodiments, when R 1 is H, the molar ratio of difluoromethane chloride employed in the alkylation reaction to compound i employed in the first reaction may be in the range of 1.5:1, 1.8:1, 2:1, 2.2:1, 2.5:1, or any two thereof.
In a specific embodiment of the invention, when R 1 is H, the alkylation reaction temperature is-75-90 ℃ and the alkylation reaction time is 1-10H. Further, the alkylation reaction temperature is 10-30 ℃, and the alkylation reaction time is 1-3 h.
When R 1 is H, the temperature of the alkylation reaction may be referred to as the temperature and time for the alkylation reaction when R 1 is methyl.
In a specific embodiment of the present invention, when R 1 is H, after the alkylation reaction, further comprising: adding water to quench the reaction, adding dichloromethane to extract, collecting an organic phase, and distilling under reduced pressure until no liquid is distilled off to obtain a compound VI.
When R 1 is H, after the alkylation reaction, the work-up procedure may be referred to as the specific procedure when R 1 is methyl.
The invention also provides application of the preparation method of any one of the paraquat sulfone and the intermediate thereof in preparation of paraquat sulfone.
In actual operation, the intermediate of the haloxyfop-R-methyl with a corresponding structure is prepared according to any one of the preparation methods of the haloxyfop-R-methyl and the intermediate thereof, and then the subsequent preparation of the haloxyfop-R-methyl is carried out according to a conventional synthetic route.
Example 1
The embodiment provides a preparation method of a topiramate intermediate, which comprises the following synthetic routes:
The method comprises the following specific steps:
(1) 500g of methanol, 216g (4 mol) of sodium methoxide and 153g (1.08 mol) of trifluoroacetyl methyl hydrazine are added into a reaction vessel, uniformly stirred, the temperature is controlled between 25 ℃ and 30 ℃, 132g (1.08 mol) of methyl 3-chloropropionate is added into the system dropwise, after the dropwise addition is completed for about 1 hour, the temperature is raised to 65 ℃, and the reaction is continued for 5 hours.
(2) Cooling the material reacted in the step (1) to 25 ℃, introducing 185g (2.16 mol) of difluoromethane chloride under stirring, reacting for 1h at 25 ℃, adding 500mL of water for quenching reaction after the reaction is finished, then adding 1000mL of dichloromethane for extraction, removing water phase, collecting organic phase, distilling to recover solvent, distilling under reduced pressure until no liquid is distilled, and collecting 275g of 5-difluoromethoxy-4-chloromethyl-1-methyl-3-trifluoromethyl pyrazole, wherein the yield is 96%, and the HPLC purity is 99.3%.
Example 2
This example refers to the preparation method of example 1, differing only in: the methyl 3-chloropropionate is replaced by an equivalent amount of methyl 3- (5, 5-dimethyl-4, 5-dihydroisoxazol-3-sulfanyl) propionate.
The synthetic route is as follows:
The final product 3- [ [5- (difluoromethoxy) -1-methyl-3- (trifluoromethyl) pyrazol-4-yl ] methylsulfanyl ] -5, 5-dimethyl-4H-1, 2-oxazole was produced in 92% yield with an HPLC purity of 99.4%.
Example 3
This example refers to the preparation method of example 1, differing only in: the methyl 3-chloropropionate is replaced by ethyl 3-hydroxypropionate in an equal amount.
The synthetic route is as follows:
the final product 5-difluoromethoxy-4-hydroxymethyl-1-methyl-3-trifluoromethylpyrazole was obtained in 97% yield and 99.6% purity by HPLC.
Example 4
This example refers to the preparation method of example 1, differing only in: the methyl 3-chloropropionate is replaced by the tert-butyl 3-mercaptopropionate in an equal amount.
The synthetic route is as follows:
The final product 5-difluoromethoxy-4-mercaptomethyl-1-methyl-3-trifluoromethylpyrazole was obtained in 93% yield and 98.6% purity by HPLC.
Example 5
This example refers to the preparation method of example 1, differing only in: the methyl 3-chloropropionate is replaced by a compound II 1 with the same mass, and the structural formula of the compound II 1 is as follows:
the synthetic route is as follows:
the final product yield was 98% and HPLC purity 99.6%.
Example 6
This example refers to the preparation method of example 1, differing only in: the amount of methyl 3-chloropropionate used in step (1) was varied to be 88g (0.72 mol).
The product yield of this example was 95% and HPLC purity 97.6%.
Example 7
This example refers to the preparation method of example 1, differing only in: the amount of difluoromethane chloride in step (2) was varied to 139g (1.62 mol).
The product yield of this example was 94% and HPLC purity 99.6%.
Example 8
This example refers to the preparation method of example 1, differing only in: the amount of difluoromethane used in step (2) was varied to be 232g (2.7 mol).
The product yield of this example was 93% and the HPLC purity was 99.0%.
Example 9
This example refers to the preparation method of example 1, differing only in: in step (1), the trifluoroacetyl methyl hydrazine is replaced by an equal amount of compound I 2. Compound I 2 has the structural formula
The product yield of this example was 96% and HPLC purity 99.1%.
Example 10
This example refers to the preparation method of example 1, differing only in: in the step (1), the sodium methoxide is replaced by an equal amount of potassium tert-butoxide.
The product yield of this example was 92% and HPLC purity 98.1%.
Example 11
The embodiment provides a preparation method of a topiramate intermediate, and the synthetic route is as follows:
The method comprises the following specific steps:
(1) 500g of methanol, 216g (4 mol) of sodium methoxide and 138g (1.08 mol) of trifluoroacetyl hydrazine are added into a reaction vessel, uniformly stirred, the temperature is controlled between 25 ℃ and 30 ℃, 132g (1.08 mol) of methyl 3-chloropropionate is dropwise added into the system, after the dropwise addition is completed for about 1 hour, then the temperature is raised to 65 ℃, and the reaction is continued for 5 hours.
(2) The reaction mass obtained in step (1) was cooled to 25℃and 204g (1.62 mmol) of dimethyl sulfate was added dropwise. After about 1 hour of completion of the dropwise addition. The central control showed complete reaction.
(3) 185G (2.16 mol) of difluoromethane chloride is introduced into the material after the reaction in the step (2) under stirring, the reaction is carried out for 1h at 25 ℃, 500mL of water is added for quenching reaction after the reaction is finished, 1000mL of dichloromethane is added for extraction, the water phase is removed, the organic phase is collected, the solvent is recovered by distillation, reduced pressure distillation is carried out until no liquid is distilled, 262g of 5-difluoromethoxy-4-chloromethyl-1-methyl-3-trifluoromethyl pyrazole is obtained, the yield is 92%, and the HPLC purity is 99.0%.
Example 12
The embodiment provides a preparation method of a topiramate intermediate, and the synthetic route is as follows:
(1) 500g of methanol, 216g (4 mol) of sodium methoxide and 153g (1.08 mol) of trifluoroacetyl methyl hydrazine are added into a reaction vessel, the mixture is stirred uniformly, the temperature is controlled between 25 ℃ and 30 ℃, 95g (1.08 mol) of ethyl acetate is added dropwise into the system, after the dropwise addition is completed for about 1 hour, the temperature is raised to 65 ℃, and the reaction is continued for 5 hours.
(2) And (3) cooling the material reacted in the step (1) to 25 ℃, adding 500mL of water for quenching reaction, then adding 1000mL of dichloromethane for extraction, removing the water phase, collecting the organic phase, distilling and recovering the solvent, distilling under reduced pressure until no liquid is distilled off, and collecting 170g of 5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazole, wherein the yield is 95%, and the HPLC purity is 99.8%.
According to the invention, the 5-difluoromethoxy-4-substituted-1-methyl-3-trifluoromethyl pyrazole is prepared by carrying out a mixed reaction on the compound I and the compound II and difluoro-chloromethane, so that the operation is simple and convenient, the efficiency is high, expensive materials such as trifluoro-acetoacetic acid ethyl ester and the like or materials such as thionyl chloride and phosphorus oxychloride and the like are avoided, and a new route is provided for the industrial production of the sulfone-pyraclonil.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (10)
1. The preparation method of the metazopyr and the intermediate thereof is characterized by comprising the following steps:
carrying out a first reaction on the compound I and the compound II in an alkali-containing solvent to obtain a compound III;
The compound I comprises at least one of the following structures:
R 1 is selected from any one of H and methyl;
the structural formulas of the compound II and the compound III are respectively as follows:
R 2 is selected from at least one of methyl, ethyl and tert-butyl; r 3 is selected from H, -CH 2Cl、-CH2OH、-CH2 SH, At least one of them.
2. The method for preparing metazachlor and its intermediates according to claim 1, further comprising: after the first reaction, adding difluoro chloromethane to carry out alkylation reaction to obtain a compound IV;
the structural formula of the compound IV is as follows:
Preferably, in the first reaction, the base includes at least one of sodium hydroxide, sodium methoxide, sodium ethoxide, and potassium tert-butoxide;
Preferably, in the first reaction, the solvent includes at least one of methanol, ethanol and acetonitrile.
3. The method for preparing metazachlor and its intermediates according to claim 1, wherein the molar ratio of the compound i to the compound ii is (1-1.5):1;
And/or the molar ratio of the base to the compound I is (3 to 5) to 1;
and/or the solvent is used in an amount of 1 to 3 times the sum of the masses of the compound I and the compound II.
4. The method for preparing metazachlor and its intermediates according to claim 1, wherein the temperature of the first reaction is 40-80 ℃;
and/or the time of the first reaction is 2-8 h.
5. The method for preparing metazachlor and its intermediates according to claim 2, wherein the molar ratio of difluoromethane to the compound i used in the first reaction is (1.5-2.5):1;
Preferably, the temperature of the alkylation reaction is between 75 ℃ below zero and 90 ℃, and the time of the alkylation reaction is between 1 and 10 hours;
preferably, the alkylation reaction temperature is 10-30 ℃, and the alkylation reaction time is 1-3 h.
6. The process for the preparation of metazachlor and intermediates thereof according to claim 2, wherein the temperature of the system of the first reaction is reduced to below 30 ℃ before the addition of difluoromethane chloride;
preferably, after the alkylation reaction, the method further comprises: and adding water to quench the reaction, adding dichloromethane to extract, collecting an organic phase, and distilling under reduced pressure until no liquid is distilled off to obtain the compound IV.
7. The method for preparing metazachlor and its intermediates according to claim 1, wherein when R 1 is H, further comprising, after the first reaction: carrying out N-methylation reaction on the material subjected to the first reaction and a methylation reagent to obtain a compound V; then adding difluoro chloromethane into the N-methylation reaction system to carry out alkylation reaction to obtain a compound VI;
The structural formulas of the compound V and the compound VI are respectively as follows:
8. the method for preparing metazachlor and its intermediates according to claim 7, wherein in the N-methylation reaction, the methylation reagent is at least one of dimethyl sulfate and methyl iodide;
Preferably, the molar ratio of the methylating agent to the compound I used in the first reaction is (1 to 1.5) to 1.
9. The process for preparing metazachlor and its intermediates as claimed in claim 7, wherein when R 1 is H, the molar ratio of difluoromethane chloride used in the alkylation reaction to compound i used in the first reaction is (1.5-2.5) to 1.
10. Use of the preparation method of paraquat chloride and its intermediates according to any one of claims 1-9 for preparing paraquat chloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410345000.9A CN118146160A (en) | 2024-03-25 | 2024-03-25 | Preparation method and application of metazopyr and intermediate thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410345000.9A CN118146160A (en) | 2024-03-25 | 2024-03-25 | Preparation method and application of metazopyr and intermediate thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118146160A true CN118146160A (en) | 2024-06-07 |
Family
ID=91285042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410345000.9A Pending CN118146160A (en) | 2024-03-25 | 2024-03-25 | Preparation method and application of metazopyr and intermediate thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118146160A (en) |
-
2024
- 2024-03-25 CN CN202410345000.9A patent/CN118146160A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI508956B (en) | Preparation method of methylene disulfonate compound | |
| JP3930736B2 (en) | Method for producing pyridinemethanol compound | |
| US7273937B2 (en) | Process for the preparation of Tazarotene | |
| KR101135088B1 (en) | Process for preparing 1,3-propenesultone | |
| TW202108566A (en) | Method for producing methylene disulfonate compound | |
| CN118146160A (en) | Preparation method and application of metazopyr and intermediate thereof | |
| CN111548257B (en) | Preparation method of (4-isopropoxy-2-methyl) phenyl isopropyl ketone | |
| CN102245591B (en) | Process for manufacturing 5-formyl-pyridine-2,3-dicarboxylic acid esters | |
| JP6260385B2 (en) | Method for producing 2-hydroxymethyl-2,3-dihydro-thieno [3,4-b] [1,4] dioxin-5,7-dicarboxylic acid dialkyl ester | |
| CN108017522B (en) | Preparation process of 2, 6-dibromobenzene methane sulfonyl chloride | |
| CN111170933B (en) | Preparation method of 2-chloro-5-nitropyridine | |
| WO1979000023A1 (en) | A novel process for preparation of a therapeutically active pyridine compound | |
| CN111410654A (en) | Synthesis of 3-bromo-5- (2-ethylimidazo [1,2-a ] pyridine-3-carbonyl) -2-hydroxybenzonitrile | |
| CN102190569B (en) | Method for preparing Prasugrel intermediate alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide | |
| CN114450270A (en) | Preparation method and intermediate of xaflufen | |
| NO20025652L (en) | Process for the preparation of trifluoroethoxy-substituted benzoic acids | |
| CN118146159A (en) | Preparation method and application of haloxyfop-methyl intermediate | |
| JP4582286B2 (en) | Sulfooxyalkynylthiophene compound and process for producing the same | |
| EP3915984B1 (en) | Synthesis of 3-bromo-5-(2-ethylimidazo[1,2-alpha]pyridine-3-carbonyl)-2-hydroxybenzonitrile | |
| CN109456257B (en) | Preparation method of high-yield 2-chloro-5-nitropyridine | |
| KR101348304B1 (en) | Method of preparing of (2Z)-3-[(6-methylpyridin-3-yl)methyl-1,3-thiazolidin-2-ylidene]cyanamice | |
| CN108473431B (en) | Method for producing benzyl 2-aminonicotinate derivative | |
| EP3609877B1 (en) | Process for the synthesis of firocoxib | |
| WO2023082149A1 (en) | Process and intermediates for preparation of isofetamid | |
| US20220064184A1 (en) | Method for preparing 2-arylmalonic acid derivative and intermediate, and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |