CN117986198A - Preparation method of herbicide intermediate - Google Patents
Preparation method of herbicide intermediate Download PDFInfo
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- CN117986198A CN117986198A CN202211331141.2A CN202211331141A CN117986198A CN 117986198 A CN117986198 A CN 117986198A CN 202211331141 A CN202211331141 A CN 202211331141A CN 117986198 A CN117986198 A CN 117986198A
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- methyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 230000002363 herbicidal effect Effects 0.000 title description 4
- 239000004009 herbicide Substances 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 7
- 239000000460 chlorine Substances 0.000 claims abstract description 7
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 7
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 5
- 150000001875 compounds Chemical class 0.000 claims description 128
- 238000006243 chemical reaction Methods 0.000 claims description 77
- -1 alkene compound Chemical class 0.000 claims description 49
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 24
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- 239000003513 alkali Substances 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 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
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 239000007800 oxidant agent Substances 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 230000001590 oxidative effect Effects 0.000 claims description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 9
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 9
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 230000007062 hydrolysis Effects 0.000 claims description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims description 9
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 claims description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 239000011736 potassium bicarbonate Substances 0.000 claims description 6
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 6
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 6
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 6
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 5
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 claims description 5
- 239000001632 sodium acetate Substances 0.000 claims description 5
- 235000017281 sodium acetate Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 238000007069 methylation reaction Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 3
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 2
- 239000005695 Ammonium acetate Substances 0.000 claims description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 235000019257 ammonium acetate Nutrition 0.000 claims description 2
- 229940043376 ammonium acetate Drugs 0.000 claims description 2
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
- XHXXWWGGXFUMAJ-UHFFFAOYSA-N methanethiol;sodium Chemical compound [Na].SC XHXXWWGGXFUMAJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000011987 methylation Effects 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- XJVIPPHGDPEDJL-UHFFFAOYSA-N thiourea;hydrochloride Chemical compound Cl.NC(N)=S XJVIPPHGDPEDJL-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 150000007530 organic bases Chemical class 0.000 claims 2
- 230000035484 reaction time Effects 0.000 claims 1
- JHIDHJCCPYAESR-UHFFFAOYSA-N 3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoic acid Chemical compound CC1=C(C(O)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 JHIDHJCCPYAESR-UHFFFAOYSA-N 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000000203 mixture Substances 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 13
- IYMLUHWAJFXAQP-UHFFFAOYSA-N topramezone Chemical compound CC1=C(C(=O)C2=C(N(C)N=C2)O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 IYMLUHWAJFXAQP-UHFFFAOYSA-N 0.000 description 13
- 238000010992 reflux Methods 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 238000000605 extraction Methods 0.000 description 7
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 5
- 239000005977 Ethylene Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 230000032798 delamination Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 4
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 102000016680 Dioxygenases Human genes 0.000 description 1
- 108010028143 Dioxygenases Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 238000006146 oximation reaction Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a preparation method of 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid shown in a formula VII, which comprises the following synthetic route: Wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl, R 2 is H, -COOCH 3、-COOC2H5 or-COOC (CH 3)3. The preparation method of the invention overcomes the defects of large three wastes, high cost, severe production environment and the like in the preparation process of the prior art, and the process route is green and environment-friendly, and is more suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of pesticide intermediate compound preparation, and in particular relates to a preparation method of a topramezone intermediate 4-substituted-3-aldehyde-2-methylbenzoate compound.
Background
Topramezone is a benzyl ester pyrazolone herbicide originally developed by basf, and belongs to p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors [1-3]. The English name is topramezone, the Chinese name is topramezone or topramezone, and the commodity name is CampusR or "bud guard". Can effectively prevent and remove annual grassy weeds and broadleaf weeds in corn, is safe to corn, but the application range of the herbicide is gradually widened to crops such as rice, sugarcane and the like, and can be safely compounded with other pesticides. The global topramezone market size in 2018 was about 1.09 billion dollars, the total amount of active ingredients applied was about 269.35t, with the corn field market being 65.55% and other crops being about 34.45%. The topramezone has excellent drug effect and wide market prospect, but the extremely difficult synthesis process makes the topramezone have high selling price and therefore limits the wide application of the topramezone.
The preparation process of the topramezone reported at present mainly comprises the following two steps:
Route 1:
Route 2:
Wherein the preparation of compound (8) in scheme 1 (see patent: US 20026469176) requires the construction of the isoxazole ring via ultra low temperature reactions, and the scheme also uses highly toxic carbon monoxide and expensive metallic palladium catalysts, resulting in high costs. Compound (7) in scheme 2 is reported as the following preparation method:
1) See patent nos.: US6100421
The bromination reaction step in the route has low selectivity, so that separation and purification after the reaction are difficult;
2) See patent nos.: CN201410083163
The source of the initial raw materials in the route is difficult, the preparation is also referred to the method in US20026469176, and simultaneously, the reaction of n-butyllithium at the ultralow temperature of minus 100 ℃ to minus 60 ℃ is used in the process of converting into carboxyl, so that the industrial production is difficult;
3) See patent nos.: CN201910517379
The starting materials in this route are likewise of difficult origin and, during the reaction of hydroxylamine with nitrile groups, inevitably lead to large amounts of impurities due to the double reactive functions of hydroxylamine.
In conclusion, the existing method has the defects of large three wastes, high cost, bad production environment and the like when the topramezone intermediate compound is prepared.
3- (4, 5-Dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid is a conventional important intermediate compound for preparing topramezone, and research on a proper preparation method thereof reduces the synthesis cost of topramezone and is a hot spot problem which is continuously researched by a person skilled in the art.
Disclosure of Invention
Aims at the problems of harsh process conditions, non-environment-friendly production process, low yield and the like existing in the process for preparing 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid in the prior art. The invention provides a preparation method of 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid, which has the advantages of mild process conditions, environment-friendly production process and high yield.
The invention provides a method for preparing 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid, which adopts the following technical scheme: hydrolyzing the compound of formula (VI) to obtain a compound of formula (VII),Wherein R 1 is C 1-C4 alkyl.
Further, when X 2 in the formula (V) is-SCH 3 or-SCH 2 COOH, oxidizing the compound of the formula (V) by an oxidizing agent to obtain a compound of the formula (VI);
When X 2 in the formula (V) is-SO 2CH3, the formula (V) and the formula (VI) are the same,
Wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl, R 2 is H, -COOCH 3、-COOC2H5 or-COOC (CH 3)3).
Further, the preparation of the compound of formula (V) comprises the steps of:
step (1), a compound shown in a general formula (I) is reacted with a sulfur-containing compound under alkaline conditions to prepare a compound shown in a formula (II);
step (2), performing oximation reaction on a compound shown in the formula (II) and hydroxylamine hydrochloride or hydroxylamine sulfate under alkaline conditions to obtain a compound shown in the formula (III);
Step (3), a compound shown in a formula (III) and an alkene compound are subjected to 1, 3-dipole addition in the presence of an oxidant and alkali to obtain a compound shown in a formula (IV); the alkene compound is Wherein R 2 is H, -COOCH 3、-COOC2H5 or-COOC (CH 3)3).
Step (4) of preparing a compound of formula (V) from a compound of formula (IV);
wherein, the structures of the formula (I), the formula (II), the formula (III), the formula (IV) and the formula (V) are as follows: Wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl, R 2 is H, -COOCH 3、-COOC2H5 or-COOC (CH 3)3).
The invention has the beneficial effects that
The method has the advantages of mild production process conditions, environment-friendly production process and high yield, is more suitable for industrial production, and can greatly reduce the production cost.
Detailed Description
Hereinafter, embodiments of the present invention are described in detail. However, these embodiments are exemplary, the invention is not limited thereto, and the invention is defined by the scope of the claims.
As used herein, when no specific definition is otherwise provided, the following terms used in the specification and claims have the following meanings.
Alkyl or alkane in the present invention means a straight or branched chain alkyl group, preferably a C 1-C4 alkyl group, such as methyl, ethyl, propyl, 2-propyl, n-butyl, isobutyl or tert-butyl, etc.
HMPA represents hexamethylphosphoric triamide;
NMP represents N-methylpyrrolidone;
DMSO means dimethylsulfoxide;
NBS represents N-bromosuccinimide;
NCS represents N-chlorosuccinimide;
TEMPO represents 2, 6-tetramethylpiperidine oxide.
In a general aspect, the present invention provides a method for preparing 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid, comprising the steps of:
Hydrolyzing the compound of formula (VI) to produce a compound of formula (VII), wherein, Wherein R 1 is C 1-C4 alkyl.
In the reaction, i) the compound shown in the formula (VI) is obtained by converting the formula (V), and when X 2 in the formula (V) is-SCH 3、-SCH2 COOH, the compound shown in the formula (V) is oxidized by an oxidant to obtain the compound shown in the formula (VI); ii) when X 2 in formula (V) is-SO 2CH3, the compounds of formula (VI) and formula (V) are identical;
wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl.
In the above reaction, the preparation of the compound of formula (V) comprises the steps of:
Step (1), a compound shown in a general formula (I) is reacted with a sulfur-containing compound in the presence of a base to prepare a compound shown in a formula (II); wherein the sulfur-containing compound is one of a sulfhydrylation reagent, methyl mercaptan or salt thereof or sodium methylsulfinate;
Step (2), oximating a compound shown in the formula (II) with hydroxylamine hydrochloride or hydroxylamine sulfate in the presence of alkali to prepare a compound shown in the formula (III);
Step (3), a compound shown in a formula (III) and an alkene compound are subjected to 1, 3-dipole addition in the presence of an oxidant and alkali to obtain a compound shown in a formula (IV); the alkene compound is
Step (4) of preparing a compound of formula (V) from a compound of formula (IV);
wherein, the structures of the formula (I), the formula (II), the formula (III), the formula (IV) and the formula (V) are as follows: Wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl, R 2 is H, -COOCH 3,-COOC2H5 or-COOC (CH 3)3).
The preparation reaction of the compound of the formula (V), wherein the alkali in the step (1) is one or more of sodium bicarbonate, potassium bicarbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate, ammonium acetate and sodium acetate, and the sulfur-containing compound is one of sodium methyl mercaptan, sodium methylsulfinate and thioglycollic acid; the reaction of the step (1) is carried out in a solvent, wherein the solvent is one or more solvents of DMSO, HMPA, THF, CH CN, 1, 4-dioxane, NMP and acetone, and the reaction temperature is 20-80 ℃; formula (I): alkali: the required molar ratio of sulfide is 1:0.1-3:1-10.
In the preparation reaction of the compound of the formula (V), when the sulfur-containing compound in the step (1) is a sulfhydrylation reagent, and the sulfhydrylation reagent is one of sodium sulfide, sodium hydrosulfide, hydrogen sulfide and thiourea hydrochloride, the compound of the formula (I) reacts with the sulfhydrylation reagent under alkaline conditions and then undergoes methylation reaction to prepare the compound of the formula (II), wherein the methylation reagent is one or more of methyl iodide, dimethyl sulfate and dimethyl carbonate, the reaction is carried out in an organic solvent, and the solvent is one or more solvents of DMSO, HMPA, THF, CH CN, 1, 4-dioxane, NMP and acetone; the reaction temperature is 20-80 ℃.
The preparation reaction of the compound of the formula (V) and the reaction of the step (2) are carried out in a solvent, wherein the solvent is one or more solvents selected from DCM, DCE, water, acetonitrile, tetrahydrofuran, DMSO, HMPA, THF, 1, 4-dioxane and NMP; the alkali is one or more of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium hydroxide and potassium hydroxide; the molar ratio of the alkali to hydroxylamine sulfate or hydroxylamine hydrochloride is 1-2:1.
The preparation reaction of the compound shown in the formula (V) comprises the step (3), wherein the alkali is organic alkali or inorganic alkali, the inorganic alkali is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate, and the organic alkali is one or more of triethylamine, pyridine and sodium acetate; the reaction temperature is-10-30 ℃; the reaction is carried out in a solvent which is one or more of Dichloromethane (DCM), (dichloroethane) DCE and chloroform; the oxidizing agent is preferably one or more of sodium hypochlorite, NBS and NCS.
The above-mentioned preparation reaction of the compound of formula (V), in the step (4), when R 2 is H, the formula (IV) is the same as the formula (V), when R 2 is-COOCH 3、-COOC2H5 or-COOC (CH 3)3), the hydrolysis of the formula (IV) is carried out in a solvent which is one or more of methanol, ethanol, t-butanol, toluene and DCE, the hydrolysis may be carried out in the presence of an acid or a base which is preferably sulfuric acid, acetic acid and phosphoric acid, and the base which is preferably sodium hydroxide and potassium hydroxide, and the hydrolysis temperature is 30-100 ℃ it has been found that when X 2 is-SCH 3、-SCH2 COOH, the hydrolysis is preferably carried out under acidic conditions without affecting the subsequent oxidation reaction, and when X 2 is-SO 2CH3, the hydrolysis is preferably carried out under alkaline conditions.
The above reaction of oxidizing a compound of formula (V) to produce a compound of formula (VI) when X 2 in formula (V) is-SCH 3 or-SCH 2 COOH by an oxidizing agent, hypochlorite and a peroxy compound, preferably sodium hypochlorite and hydrogen peroxide; preferably adding a catalyst in the oxidation process, wherein the catalyst is one or a combination of more of TEMPO, sulfuric acid, acetic acid, sodium tungstate and the like; the catalyst is 1-50% of the formula (V) weight, and the oxidant is 1-5 times of the formula (V) weight; the reaction temperature is 60-90 ℃.
In the above reaction, the reaction conditions for hydrolyzing the compound of formula (VI) to obtain the compound of formula (VII) are that the hydrolysis is carried out in an organic solvent, preferably toluene and xylene, in the presence of a base, and the base is an inorganic base, preferably sodium hydroxide and potassium hydroxide, at a reaction temperature of 100-120 ℃ for 1-5 hours.
The present invention will be described in detail by examples. The amounts of reactants and products in the following examples were measured by liquid chromatography (AGILENTHPLC 1260). In the following examples, the conversion and selectivity of the reaction were calculated by the following formulas:
Conversion = (molar amount of raw material charged-molar amount of raw material remaining in product)/molar amount of raw material charged x 100% selectivity = actual molar amount of target product/theoretical molar amount of target product x 100%
Example 1
Synthesis of the Compound ethyl 3-formyl-2-methyl-4- (methylthio) benzoate
22.6G of 3-formyl-2-methyl-4-chlorobenzoic acid ethyl ester and 8.4g of sodium bicarbonate are weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 100gHMPA g of sodium bicarbonate is added, 105g of 20% sodium methyl mercaptide is slowly added dropwise after the temperature is raised to 50 ℃, the dropwise addition is kept for half an hour, after the medium control reaction is completed, 300gDCM is added for extraction and delamination, and the quantitative yield is 93%.
Synthesis of Compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
23.8G of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate, which is a compound obtained by dissolving 23.8g of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate in 200g of acetonitrile, adding 7.9g of sodium carbonate and 9g of hydroxylamine hydrochloride, stirring at room temperature for 5 hours, concentrating the solvent after the reaction, adding 100g of water, extracting and layering 100gDCM, concentrating the organic phase, and obtaining the compound with the yield of 98%.
Synthesis of Compound 3- (4, 5-dihydro-isoxazol-3-yl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
25.3G of the compound ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylthio) benzoate, 4.2g of sodium bicarbonate and 200gDCM g of 8% sodium hypochlorite solution are slowly added into an autoclave, the temperature is kept for half an hour after the dropwise addition, 4MPa ethylene gas is introduced into the autoclave until the pressure of the autoclave is not reduced, the pH value of the reaction solution is adjusted to 4-5 after the reaction is finished, the reaction solution is kept stand for layering, the organic phase is dried by spinning, and the yield is 94%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27.9G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylthio) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene, 1g of concentrated sulfuric acid, 3g of acetic acid and 0.3g of sodium tungstate are added, the temperature is raised to 75 ℃, 45.5g of 30% hydrogen peroxide is slowly added dropwise, after the dropwise addition is completed, the temperature is raised to reflux for 3 hours, and after the reaction is completed, cooling, standing and layering are carried out, and the quantitative yield is 90%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the temperature is raised to reflux for 2 hours, the mixture is stood for layering after the reaction is finished, the pH of the water phase is regulated to 2-3, white solid is precipitated, and the yield is 97%.
Example 2
Synthesis of the Compound ethyl 3-formyl-2-methyl-4- (methylthio) benzoate
27G of ethyl 3-formyl-2-methyl-4-bromobenzoate and 8.4g of sodium bicarbonate are weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 100gDMSO g of 20% sodium methyl mercaptide is slowly added dropwise at room temperature, the dropwise addition is kept warm for half an hour, after the central control reaction is completed, 300gDCM is added for extraction and delamination, and the quantitative yield is 89%.
Synthesis of Compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
23.8G of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate, dissolved in 200gDCM g of sodium bicarbonate and 9g of hydroxylamine hydrochloride are weighed in a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, stirred at room temperature for 5 hours, after the reaction, the solvent is concentrated, 200g of water is added, the mixture is extracted and separated, and the organic phase is concentrated to obtain the compound with a yield of 97%.
Synthesis of Compound 3- (3- (ethoxycarbonyl) -2-methyl-6- (methylthio) phenyl) -4, 5-dihydroisoxazole-5-carboxylic acid methyl ester
25.3G of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate, 200g of DCM,4.2g of sodium bicarbonate and 280g of 8% sodium hypochlorite solution are slowly added dropwise at 0 ℃ in a four-mouth bottle with mechanical stirring, a thermometer and a condenser, the dropwise addition of 12.9g of methyl acrylate is continued for half an hour after the dropwise addition, the thermal insulation reaction is completed for 3 hours, the pH value is regulated to 4-5 after the reaction is completed, the mixture is stood for layering, the organic phase is concentrated, and the yield is 88%.
Synthesis of Compound 3- (4, 5-dihydro-isoxazol-3-yl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
33.7G of methyl 3- (3- (ethoxycarbonyl) -2-methyl-6- (methylthio) phenyl) -4, 5-dihydroisoxazole-5-carboxylate, 30g of acetic acid and 0.3g of sulfuric acid were weighed into a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, the mixture was heated to reflux, DCM was added to extract the layers after completion of the reaction, and the organic phase was concentrated to give a yield of 90%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27.9G of 3- (3- (ethoxycarbonyl) -2-methyl-6- (methylthio) phenyl) -4, 5-dihydro-isoxazole-5-carboxylic acid methyl ester of the compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene, 1g of concentrated sulfuric acid, 3g of acetic acid and 0.3g of sodium tungstate are added, the temperature is raised to 75 ℃, 45.5g of 30% hydrogen peroxide is slowly added dropwise, the temperature is raised to reflux for 3 hours after the dropwise addition, and the mixture is cooled, placed aside and layered after the reaction is finished, and the quantitative yield is 90%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of 3- (3- (ethoxycarbonyl) -2-methyl-6- (methylthio) phenyl) -4, 5-dihydro-isoxazole-5-carboxylic acid methyl ester as a compound is weighed in a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the mixture is heated to reflux for 2 hours, and then the mixture is stood for layering, the pH of the aqueous phase is adjusted to 2-3, and white solid is precipitated, and the yield is 97%.
Example 3
Synthesis of the Compound ethyl 3-formyl-2-methyl-4- (methylsulfonyl) benzoate
27G of compound (I) is weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 100g of acetonitrile is added, 13g of sodium methylsulfinate is added at room temperature, the reaction is carried out for 3 hours after the temperature is increased to 40 ℃, and after the central control reaction is completed, 300gDCM is added for extraction and delamination, and the quantitative yield is 83%.
Synthesis of Compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27G of ethyl 3-formyl-2-methyl-4- (methylsulfonyl) benzoate, which is a compound, is weighed in a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, dissolved in 200gDCM g of sodium bicarbonate, 9g of hydroxylamine hydrochloride, stirred at room temperature for 5 hours, after the reaction, the solvent is concentrated, 200g of water is added, the mixture is extracted and separated, and the organic phase is concentrated to obtain the compound with the yield of 94%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
28.5G of compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylsulfonyl) ethyl benzoate, 4.2g of sodium bicarbonate and 280g of 8% sodium hypochlorite solution are slowly added dropwise at the temperature of 200gDCM ℃ below zero in an autoclave, the temperature is kept for half an hour after the dropwise addition, 4MPa ethylene gas is introduced into the autoclave, the air pressure of the autoclave is continuously supplemented until the pressure of the autoclave is not reduced, after the reaction is finished, the pH value of the reaction solution is adjusted to 4-5, the reaction solution is kept stand for layering, and the organic phase is dried by a screw, so that the yield is 95%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the temperature is raised to reflux for 2 hours, the mixture is stood for layering after the reaction is finished, the pH of the water phase is regulated to 2-3, white solid is precipitated, and the yield is 97%.
Example 4
Synthesis of the Compound ethyl 3-formyl-2-methyl-4- (methylthio) benzoate
22.6G of compound (I) and 8.4g of sodium bicarbonate are weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 100gDMSO g of sodium methyl mercaptide is added, 105g of 20% sodium methyl mercaptide is slowly added dropwise after heating to 30 ℃, the dropwise addition is kept for half an hour, after the completion of the central control reaction, 300gDCM is added for extraction and layering, and the quantitative yield is 91%.
Synthesis of Compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
23.8G of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate, which is a compound obtained by dissolving in 200gDCM g of sodium hydroxide and 9g of hydroxylamine hydrochloride, is weighed in a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, stirred at room temperature for 5 hours, and after the reaction, the solvent is concentrated, 200g of water is added, the mixture is extracted and separated, and the organic phase is concentrated to obtain the compound, wherein the yield is 93%.
Synthesis of Compound 3- (4, 5-dihydro-isoxazol-3-yl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
25.3G of the compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylthio) benzoic acid ethyl ester, 15.2g of triethylamine, 200g of DCM and 19g of NBS are added into an autoclave, the mixture is kept at 30 ℃ for half an hour, then the temperature is reduced to 0 ℃, 4MPa ethylene gas is introduced into the autoclave, the air is continuously supplemented until the pressure of the autoclave is not reduced, after the reaction is finished, the pH of the reaction solution is regulated to 4-5, the mixture is kept stand for layering, and the organic phase is dried by a screw, so that the yield is 91%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27.9G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylthio) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene, 1g of concentrated sulfuric acid, 3g of acetic acid and 0.3g of sodium tungstate are added, the temperature is raised to 75 ℃, 45.5g of 30% hydrogen peroxide is slowly added dropwise, after the dropwise addition is completed, the temperature is raised to reflux for 3 hours, and after the reaction is completed, cooling, standing and layering are carried out, and the quantitative yield is 90%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylthio) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the temperature is raised to reflux for 2 hours, the mixture is stood for layering after the reaction is finished, the pH of the water phase is regulated to 2-3, white solid is precipitated, and the yield is 97%.
Example 5
Synthesis of the Compound ethyl 3-formyl-2-methyl-4- (methylthio) benzoate
27G of compound (I), 8.4g of sodium bicarbonate and 100g of acetonitrile are weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 11.2g of sodium sulfide are added, the temperature is raised to 40 ℃ for reaction for 5 hours, then the temperature is reduced to 30 ℃, 12.6g of dimethyl sulfate is slowly added dropwise, after the medium control reaction is completed, 300gDCM g of water is added for extraction and delamination, and the quantitative yield of 100g of water is 85%.
Synthesis of Compound (E) -3- ((hydroxyimino) methyl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
23.8G of ethyl 3-formyl-2-methyl-4- (methylthio) benzoate, which is a compound obtained by dissolving in 200gDCM g of sodium bicarbonate and 9g of hydroxylamine hydrochloride in a four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, is stirred at room temperature for 5 hours, after the completion of the reaction, the solvent is concentrated, 200g of water is added, the mixture is separated by extraction, and the organic phase is concentrated to obtain the compound with a yield of 95%.
Synthesis of Compound 3- (4, 5-dihydro-isoxazol-3-yl) -2-methyl-4- (methylthio) benzoic acid ethyl ester
28.5G of the compound 3-formyl-2-methyl-4- (methylthio) ethyl benzoate, 4.2g of sodium acetate, 200gDCM g of a sodium hypochlorite solution with the concentration of 8% are slowly added dropwise into an autoclave, the dropwise addition is carried out for half an hour after heat preservation, 4MPa ethylene gas is introduced into the autoclave, the air pressure of the autoclave is continuously supplemented until the pressure of the autoclave is not reduced, after the reaction is finished, the pH of the reaction solution is regulated to 4-5, the reaction solution is kept stand for layering, the organic phase is dried by a screw, and the yield is 91%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27.9G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylthio) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene, 1g of concentrated sulfuric acid, 3g of acetic acid and 0.3g of sodium tungstate are added, the temperature is raised to 75 ℃, 45.5g of 30% hydrogen peroxide is slowly added dropwise, after the dropwise addition is completed, the temperature is raised to reflux for 3 hours, and after the reaction is completed, cooling, standing and layering are carried out, and the quantitative yield is 90%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the temperature is raised to reflux for 2 hours, the mixture is stood for layering after the reaction is finished, the pH of the water phase is regulated to 2-3, white solid is precipitated, and the yield is 97%.
Example 6
Synthesis of Compound 2- ((4- (ethoxycarbonyl) -2-formyl-3-methylphenyl) thio) acetic acid
22.6G of compound (I), 50g of DMSO,21g of triethylamine and 9.2g of 2-mercaptoacetic acid are weighed in a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, the temperature is raised to 60 ℃ for reaction, 100g of water is added after the reaction is completed, 300gDCM is used for regulating the pH value to 3-4, and the extraction and layering are carried out, so that the yield is 82%.
Synthesis of Compound (E) -2- ((4- (ethoxycarbonyl) -2- ((hydroxyimino) methyl) -3-methylphenyl) thio) acetic acid
28.2G of 2- ((4- (ethoxycarbonyl) -2-formyl-3-methylphenyl) thio) acetic acid, which is a compound, is weighed in a four-port bottle provided with a mechanical stirring device, a thermometer and a condenser, dissolved in 200gDCM g of sodium bicarbonate, 9g of hydroxylamine hydrochloride, stirred at room temperature for 5 hours, after the reaction is finished, the solvent is concentrated, 200g of water is added, the pH is adjusted to 3-4, the mixture is extracted and layered, and the organic phase is concentrated to obtain the compound with the yield of 91%.
Synthesis of Compound 2- ((2- (4, 5-dihydroisoxazol-3-yl) -4- (ethoxycarbonyl) -3-methylphenyl) thio) acetic acid
32.9G of compound (E) -2- ((4- (ethoxycarbonyl) -2- ((hydroxyimino) methyl) -3-methylphenyl) thio) acetic acid, 8.4g of sodium bicarbonate, 200gDCM and 280g of 8% sodium hypochlorite solution are slowly added dropwise at the temperature of minus 5 ℃ into an autoclave, the dropwise addition is kept for half an hour, 4MPa ethylene gas is then introduced into the autoclave, the air is continuously supplemented until the pressure of the autoclave is not reduced, after the reaction is finished, the pH value of the reaction solution is regulated to 4-5, the reaction solution is kept stand for layering, the organic phase is dried by a screw, and the yield is 89%.
Synthesis of Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid ethyl ester
27.9G of compound 2- ((2- (4, 5-dihydro-isoxazol-3-yl) -4- (ethoxycarbonyl) -3-methylphenyl) thio) acetic acid, 200g of toluene, 1g of concentrated sulfuric acid, 3g of acetic acid and 0.3g of sodium tungstate are weighed into a four-mouth bottle provided with a mechanical stirrer, a thermometer and a condenser, 45.5g of 30% hydrogen peroxide is slowly added dropwise, the temperature is raised to reflux for 3 hours after the dropwise addition, and the mixture is cooled, kept stand and layered after the reaction is finished, so that the quantitative yield is 88%.
Synthesis of the Compound 3- (4, 5-Dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoic acid
31.1G of ethyl 3- (4, 5-dihydroisoxazol-3-yl) -2-methyl-4- (methylsulfonyl) benzoate as a compound is weighed in a four-port bottle provided with a mechanical stirrer, a thermometer and a condenser, 200g of toluene and 80g of 10% sodium hydroxide solution are added, the temperature is raised to reflux for 2 hours, the mixture is stood for layering after the reaction is finished, the pH of the water phase is regulated to 2-3, white solid is precipitated, and the yield is 97%.
The method for preparing 3- (4, 5-dihydro-3-isoxazolyl) -2-methyl-4- (methylsulfonyl) benzoic acid can obtain higher reaction conversion rate and selectivity. The cost is greatly reduced.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
Claims (10)
1. A process for the preparation of formula (VII), comprising the steps of: hydrolyzing the compound of formula (VI) to obtain a compound of formula (VII),Wherein R 1 is C 1-C4 alkyl.
2. The process according to claim 1, wherein the compound of formula (VI) is prepared by the process of formula (V),
I) When X 2 in the formula (V) is-SCH 3 or-SCH 2 COOH, oxidizing the compound shown in the formula (V) by an oxidizing agent to obtain a compound shown in the formula (VI);
ii) when X 2 in formula (V) is-SO 2CH3, formula (V) and formula (VI) are the same;
wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl.
3. The preparation method according to claim 1 or 2, wherein the preparation of the compound of formula (V) comprises the steps of:
step (1), a compound of formula (I) is reacted with a sulfur-containing compound in the presence of a base to prepare a compound of formula (II), wherein the sulfur-containing compound is one of a sulfhydrylation reagent, methyl mercaptan or a salt thereof and sodium methylsulfinate;
Step (2), oximating a compound of formula (II) with hydroxylamine hydrochloride or hydroxylamine sulfate in the presence of a base to obtain a compound of formula (III);
step (3), the compound of the formula (III) and an alkene compound are subjected to 1, 3-dipole addition in the presence of an oxidant and alkali to obtain a compound of the formula (IV); the alkene compound is
Step (4) of preparing a compound of formula (V) from a compound of formula (IV);
wherein, the structures of the formula (I), the formula (II), the formula (III), the formula (IV) and the formula (V) are as follows: Wherein X 1 is chlorine or bromine, X 2 is-SCH 3、-SCH2 COOH or-SO 2CH3,R1 is C 1-C4 alkyl, R 2 is H, -COOCH 3、-COOC2H5 or-COOC (CH 3)3).
4. The method according to claim 3, wherein the base in the step (1) is one or more of sodium bicarbonate, potassium bicarbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate, ammonium acetate, and sodium acetate, and the sulfur-containing compound is one of sodium methyl mercaptan, sodium methylsulfinate, and thioglycollic acid; the reaction of the step (1) is carried out in a solvent, wherein the solvent is one or more solvents of DMSO, HMPA, THF, CH CN, 1, 4-dioxane, NMP and acetone, and the reaction temperature is 20-80 ℃; formula (I): alkali: the required molar ratio of sulfide is 1:0.1-3:1-10.
5. The process of claim 3 or 4, wherein the reaction of step (2) is carried out in a solvent selected from one or more of Dichloromethane (DCM), dichloroethane (DCE), water, acetonitrile, tetrahydrofuran, DMSO, HMPA, THF, 1, 4-dioxane and NMP; the alkali is one or more of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium hydroxide and potassium hydroxide; the molar ratio of the alkali to hydroxylamine sulfate or hydroxylamine hydrochloride is 1-2:1.
6. The method according to any one of claims 3 to 5, wherein the base in step (3) is an organic base or an inorganic base, the inorganic base is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate, and the organic base is one or more of triethylamine, pyridine, and sodium acetate; the reaction temperature is-10-30 ℃; the reaction is carried out in a solvent which is one or more of Dichloromethane (DCM), dichloroethane (DCE) and chloroform; the oxidant is one or more of sodium hypochlorite, NBS and NCS.
7. The process according to any one of claims 3 to 6, wherein in the step (4), when R 2 in the formula (IV) is-COOCH 3、-COOC2H5 or-COOC (CH 3)3), the hydrolysis of (IV) to produce the compound of formula (V) is carried out in a solvent selected from one or more of methanol, ethanol, t-butanol, toluene and dichloroethane, the hydrolysis is carried out in the presence of an acid selected from one of sulfuric acid, acetic acid and phosphoric acid, and the alkali selected from one of sodium hydroxide and potassium hydroxide, and the hydrolysis temperature is 30 to 100 ℃.
8. The preparation method according to claim 2, wherein, when X 2 in the formula (V) is-SCH 3 and-SCH 2 COOH, the compound represented by the formula (V) is oxidized by an oxidizing agent, preferably sodium hypochlorite and hydrogen peroxide, to obtain the compound of the formula (VI); preferably, a catalyst is added in the oxidation process, wherein the catalyst is one or more of 2, 6-tetramethylpiperidine oxide (TEMPO), sulfuric acid, acetic acid, sodium tungstate and the like; the catalyst is 1-50% of the formula (V) weight, and the oxidant is 1-5 times of the formula (V) weight; the reaction temperature is 60-90 ℃.
9. The preparation method according to any one of claims 3 to 7, wherein when the sulfur-containing compound in the step (1) is a sulfhydrylating agent, the sulfhydrylating agent is one of sodium sulfide, sodium hydrosulfide, hydrogen sulfide and thiourea hydrochloride, the compound shown in the formula (I) is reacted with the sulfhydrylating agent under alkaline conditions, and then the methylation reaction is performed to obtain the formula (II), wherein the methylation agent is one or more of methyl iodide, dimethyl sulfate and dimethyl carbonate, the reaction is performed in an organic solvent, and the solvent is one or more solvents of DMSO, HMPA, THF, CH CN, 1, 4-dioxane, NMP and acetone; the reaction temperature is 20-80 ℃.
10. The process according to any one of claims 1 to 9, wherein the compound of formula (VI) is hydrolysed in an organic solvent, preferably toluene and xylene, in the presence of a base, preferably an inorganic base, preferably sodium hydroxide and potassium hydroxide, at a reaction temperature of 100 to 120 ℃ for a reaction time of 1 to 5 hours to give the compound of formula (VII).
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| CN202211331141.2A CN117986198A (en) | 2022-10-28 | 2022-10-28 | Preparation method of herbicide intermediate |
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