CN117964531A - 一种苯唑草酮中间体的制备方法 - Google Patents
一种苯唑草酮中间体的制备方法 Download PDFInfo
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- CN117964531A CN117964531A CN202211307097.1A CN202211307097A CN117964531A CN 117964531 A CN117964531 A CN 117964531A CN 202211307097 A CN202211307097 A CN 202211307097A CN 117964531 A CN117964531 A CN 117964531A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 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 title abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 65
- 238000000034 method Methods 0.000 claims abstract description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical group 0.000 claims abstract description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
- 239000000460 chlorine Substances 0.000 claims abstract description 5
- 125000004185 ester group Chemical group 0.000 claims abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
- 239000011737 fluorine Substances 0.000 claims abstract description 5
- 239000011630 iodine Substances 0.000 claims abstract description 5
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 79
- -1 N-diethylformamide Chemical compound 0.000 claims description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 10
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 5
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 5
- 239000001632 sodium acetate Substances 0.000 claims description 5
- 235000017281 sodium acetate Nutrition 0.000 claims description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
- 229940043376 ammonium acetate Drugs 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 2
- 239000003570 air Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 2
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 claims description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims 2
- 239000000843 powder Substances 0.000 claims 2
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- FJLHLDBEZKTSOK-UHFFFAOYSA-N n-ethyl-n-methylformamide Chemical compound CCN(C)C=O FJLHLDBEZKTSOK-UHFFFAOYSA-N 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 239000004291 sulphur dioxide Substances 0.000 claims 1
- 235000010269 sulphur dioxide Nutrition 0.000 claims 1
- 239000001117 sulphuric acid Substances 0.000 claims 1
- 235000011149 sulphuric acid Nutrition 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 27
- 238000003786 synthesis reaction Methods 0.000 abstract description 27
- 239000000543 intermediate Substances 0.000 abstract description 7
- 150000001408 amides Chemical group 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 239000005492 Carfentrazone-ethyl Substances 0.000 abstract 1
- 239000012074 organic phase Substances 0.000 description 8
- 239000002994 raw material Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000009987 spinning Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 125000000547 substituted alkyl group Chemical group 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
- 235000005822 corn Nutrition 0.000 description 3
- 230000032798 delamination Effects 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 238000002390 rotary evaporation Methods 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
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 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
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 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
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 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
- 239000003054 catalyst Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([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
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 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
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/56—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
本发明公开了一种通式为V所示的4‑甲硫基‑3‑醛基‑2‑甲基苯甲酸酯类苯唑草酮中间体的合成方法,其反应合成路线如下:其中,R为酯基,羧酸,酰胺或氰基,R1和R2分别独立的选自烷基,优选C1‑C4烷基,X为卤素,优选氟、氯、溴和碘。本发明提供的制备方法各步反应选择性好,收率较高,有效解决了其它一些苯唑草酮中间体的合成技术难题,整条工艺路线较易实现工业化。
Description
技术领域
本发明涉及农药合成领域,特别是涉及一种用于制备苯唑草酮化合物中间体4-甲硫基-3-醛基-2-甲基苯甲酸酯类化合物的制备方法。
背景技术
苯唑草酮是巴斯夫首创研制的苯甲酯吡唑酮类除草剂,属于对羟基苯基丙酮酸酯双氧化酶(HPPD)类抑制剂,其英文通用名称为topramezone,中文名称为苯唑草酮或苯吡唑草酮,商品名为CampusR或“苞卫”。能有效防除玉米地一年生禾本科杂草和阔叶杂草,对玉米安全,但其使用范围也已逐渐扩大至水稻及甘蔗等作物,且与其他农药可安全进行复配使用。2018年全球苯唑草酮市场规模约为1.09亿美元,原药应用总量约为269.35吨,其中用于玉米的市场占比高达65.55%左右,其他作物约占34.45%。苯唑草酮因其优异的药效,具有广阔的市场前景,但是其难度极高的合成工艺使其售价高昂并因此限制了它的广泛推广和使用。
目前报道的苯唑草酮的制备工艺主要是以下两条:
路线1:
路线2:
其中路线1中化合物(8)的制备(参见专利:US20026469176)需要经过超低温反应构建异噁唑环,同时该路线还用到剧毒的一氧化碳和昂贵的金属钯催化剂,导致成本居高不下。路线2中化合物(7)报道有以下的制备方法:
1)参见专利:US6100421
本路线中溴代反应步骤选择性低,导致反应后分离和纯化困难;
2)参见专利:CN201410083163
本路线中起始原料的来源困难,也是参照US20026469176中的方法制备,同时在转变为羧基的过程中用到正丁基锂在-100~-60℃的超低温条件下反应,工业化生产困难;
3)参见专利:CN201910517379
本路线中的起始原料同样来源困难,在羟胺和腈基的反应过程中由于羟胺有双反应官能团,不可避免的产生大量杂质。
上述工艺路线长,反应条件较为苛刻,反应收率不高,存在大量三废,并且处理难度大。
综上,现有方法在制备苯唑草酮中间体化合物时,存在三废量大、成本高、生产环境恶劣等缺点。
申请人在CN202210390195.X中披露了化合物:
该化合物作为中间体化合物用于制备苯唑草酮可以克服现有技术中合成苯唑草酮工艺中存在的缺陷,新的合成苯唑草酮的工艺条件反应条件温和,绿色环保,使得合成苯唑草酮具有较高的收率,对降低苯唑草酮合成成本,将有利于苯唑草酮的推广和使用。
发明内容
本发明提供一种苯唑草酮中间体4-甲硫基-3-醛基-2-甲基苯甲酸酯类化合物的制备方法。
具体的,本发提供一种式V:
化合物的合成方法,其中,R为酯基,羧酸,酰胺或氰基。
本发明采用如下技术方案,一种式V化合物的制备方法,包括如下反应步骤:
步骤(1)、式I化合物与维尔斯迈尔试剂反应,制得式II所示化合物;
步骤(2)、将步骤(1)制备得到的式II所示化合物水解得到式III化合物;
步骤(3)、将步骤(2)制备得到的式III化合物在碱存在条件下与甲硫醇钠进行取代反应得到式IV;
步骤(4)、将步骤(3)制备得到的式IV化合物氧化制得式V化合物,其中,式I、式II、式III、式IV和式V的结构如下:
其中R为酯基,羧酸,酰胺或氰基,R1和R2分别独立的选自任选取代的烷基,优选任选取代的C1-C4烷基,X为卤素,优选氟、氯、溴和碘。
本发明的有益效果:
1、本发明制备式V化合物的反应条件温和,工艺绿色环保,使用式V化合物合成苯唑草酮可以降低苯唑草酮原药的合成成本。
2、本发明式V化合物合成过程中的原料易得,反应收率高,易于工业化。
具体实施方式
在下文中,详细地描述本发明的实施例。然而,这些实施例是示范性的,本发明不限于此,且本发明是由权利要求的范围定义。
如本文中所使用,当未另外提供具体定义时,下列用在说明书和权利要求书中的术语具有如下含义。
本发明中的“酯基”是指-COOR0;其中R0指任选取代的烷基,任选取代芳基或杂芳基;
本发明中的“酰胺基”是指-CONRaRb;其中Ra,Rb为相同或不同的氢,任选取代的烷基,任选取代的芳基或杂芳基;
本发明中的烷基或烷烃是指直链或支链烷基,优选C1-C10烷基,具体地例如,甲基、乙基、丙基、异丙基、正丁基、异丁基、叔丁基、戊基、己基、庚基、辛基、壬基及癸基等,更有选C1-C4烷基,例如甲基、乙基、丙基、2-丙基、正丁基、异丁基或叔丁基等。
本发明中的芳基优选为苯基或萘基。
杂芳基:指含1个或多个N、O、S杂原子的五元环或六元环。例如吡咯基、呋喃基、噻吩基、咪唑基、吡唑基、恶唑基、噻唑基、异恶唑基、异噻唑基、吡啶基、嘧啶基、哒嗪基、哒嗪酮基、吲哚基、苯并呋喃基、苯并恶唑基、苯并噻吩基、苯并噻唑基、苯并异恶唑基、苯并异噻唑基、苯并咪唑基、苯并吡唑基、喹喔啉基等。
“氰基”指-CN。
“羧酸”指-COOH。
当基团被取代时,取代基为烷基、卤素、-OH、NO2、-CN、氨基。
卤素指氟、氯、溴和碘。
本发明一方面提供一种式V化合物的制备方法,包括如下反应步骤:
步骤(1)、式I化合物与维尔斯迈尔试剂反应,制得式II所示化合物;
步骤(2)、将步骤(1)制备得到的式II所示化合物水解得到式III化合物;
步骤(3)、将步骤(2)制备得到的式III化合物在碱性条件下与甲硫醇钠进行取代反应得到式IV;
步骤(4)、将步骤(3)制备得到的式IV化合物氧化制得式V化合物,其中,式I、式II、式III、式IV和式V的结构如下:
其中,R为酯基,羧酸,酰胺或氰基,R1和R2分别独立的选自任选取代的烷基,优选任选取代的C1-C4烷基,X为卤素,优选氟、氯、溴和碘。
其中,步骤(1)的反应式如下:
上述步骤(1)反应中所述的维尔斯迈尔试剂为DMF、N,N-二乙基甲酰胺、N-甲基-N-乙基甲酰胺中的一种与三氯氧磷、三溴氧磷、氯化亚砜、草酰氯中的一种反应所制得。反应温度为0-100℃,优选为10-60℃。
其中,上述反应步骤(2)反应式如下:
步骤(2)中式II所示化合物经过水解得到式III化合物,水解优选在酸存在下水解,所述的酸为无机酸,优选硫酸、盐酸、磷酸,最优选为盐酸。水解反应是在溶剂中进行,所述的溶剂为有机溶剂、水中一种或多种,所述的有机溶剂为卤代烷烃,优选二氯甲烷、二氯乙烷中一种。
上述反应中,步骤(3)的反应式如下:
式III化合物在碱存在条件下与甲硫醇钠进行取代反应得到式IV。
上述反应中所述的碱为有机碱或无机碱;所述的无机碱为氢氧化钠、氢氧化钾、碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾一种或多种;所述的有机碱优选甲醇钠、乙醇钠、醋酸钠、醋酸铵一种或多种;更优选为碳酸氢钠、醋酸钠、醋酸铵中一种或多种。上述反应在非质子极性溶剂中进行,所述的非极性溶剂优选六甲基磷酰三胺、二甲亚砜、四氢呋喃、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、二氧六环中任意一种或几种组合,最优选为六甲基磷酰三胺、二甲亚砜、乙腈中任意一种或几种组合。其中式III化合物、碱和甲硫醇钠的用量摩尔比为1:0.1-2:1-4,优选1:0.1-0.5:1-3。
上述反应中,步骤(4)的反应式如下:
式IV化合物通过氧化剂氧化制得式V化合物。反应中使用的氧化剂为空气、过氧化氢、次氯酸钠、硫粉、二氧化硫、氯化亚砜、磺酰氯、浓硫酸、二氯化硫和三氧化硫中一种,优选为过氧化氢、氯化亚砜、硫粉中一种;其中,式IV化合物与氧化剂用量的摩尔比为1:0.1-5,优选为1:1-2;上述反应的反应温为10-50℃。
以下将通过实施例对本发明进行详细描述。以下实施例中反应物和产物的量通过液相色谱(Agilent HPLC 1260)测得。以下实施例中,反应的转化率和选择性通过以下公式计算:
转化率=(原料投入摩尔量-产物中残留的原料摩尔量)/原料投入摩尔量×100%选择性=目标产物的实际摩尔量/目标产物的理论摩尔量×100%
实施例1化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
1.1化合物4-溴-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,投入7.3g DMF(0.1mol),降温至10℃以下,然后缓慢滴加58g三溴氧磷(0.2mol),滴完后继续搅拌反应1小时,然后升温至20℃缓慢滴加18.2g(0.1mol)哈格曼乙酯,滴加完后保温反应2小时,中控反应完全后,旋蒸除去过量的三溴氧磷和生成的其它溶剂,得到粗产品,收率80%。
1.2化合物4-溴-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入30g化合物4-溴-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯(0.1mol)和100gDCM(二氯甲烷),加入10g36.5%的盐酸和50g水室温搅拌2小时,反应结束后静置分层,旋干有机相得到目标化合物4-溴-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯,收率96%。
1.3化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入27.2g化合物4-溴-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯(0.1mol)和100g六甲基磷酰三胺,再加入8.4g的碳酸氢钠(0.1mol),室温下缓慢滴加70g 20%的甲硫醇钠溶液(0.2mol),滴加完保温反应0.5小时,中控反应完全,反应液中加入100g DCM,100g水,萃取分层,旋干有机相,得到目标化合物,收率90%。
1.4化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入24g化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯(0.1mol),200g DCM,室温下缓慢滴加12g氯化亚砜(0.1mol),滴加结束后升温至40℃反应3小时,取样中控反应完全,得到目标化合物(1H NMR(400MHz,CDCl3)δ=10.65(s,1H),7.91(d,J=8.6,1H),7.22(d,J=8.6,1H),4.38(q,J=7.1,2H),2.84(s,3H),2.48(s,3H),1.40(t,J=7.1,3H),收率92%。
实施例2化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
2.1化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,投入7.3g DMF(0.1mol),降温至10℃以下,然后缓慢滴加26g草酰氯(0.2mol),滴完后继续搅拌反应0.5小时,然后升温至60℃缓慢滴加18.2g(0.1mol)哈格曼乙酯,滴加完后保温反应2小时,中控反应完全后,得到粗产品,收率79%。
2.2化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入26g(0.1mol)化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯和100gDCM,加入10g 36.5%盐酸和50g水室温搅拌2小时,反应结束后静置分层,旋干有机相得到目标化合物,收率96%。
2.3化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入23g(0.1mol)化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯和100g DMSO,再加入8.2g的醋酸钠(0.1mol),室温下缓慢滴加70g 20%的甲硫醇钠溶液(0.2mol),滴加完保温反应0.5小时,中控反应完全,反应液中加入100g DCM,100g水,萃取分层,旋干有机相,得到目标化合物,收率82%。
2.4化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入24g(0.1mol)化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯,200g DCE(二氯乙烷),室温下缓慢滴加12g(0.1mol)氯化亚砜,滴加结束后升温至40℃反应3小时,取样中控反应完全,得到目标化合物,收率92%。
实施例3化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
3.1化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,投入7.3g DMF(0.1mol),降温至10℃以下,然后缓慢滴加60g(0.4mol)三氯氧磷,滴完后继续搅拌反应0.5小时,然后升温至60℃缓慢滴加18.2g(0.1mol)哈格曼乙酯,滴加完后保温反应2小时,中控反应完全后,旋蒸除去多余的三氯氧磷,得到粗产品,收率83%。
3.2化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入26g(0.1mol)化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯和100gDCM,加入10g 36.5%盐酸和50g水室温搅拌2小时,反应结束后静置分层,旋干有机相得到目标化合物,收率96%。
3.3化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入23g(0.1mol)化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯和100g乙腈,再加入4.2g(0.05mol)的碳酸氢钠,室温下缓慢滴加70g(0.2mol)20%的甲硫醇钠溶液,滴加完保温反应0.5小时,中控反应完全,反应液中加入100gDCM,100g水,萃取分层,旋干有机相,得到目标化合物,收率90%。
3.4化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入24g(0.1mol)化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯,200g DCE,40℃下缓慢滴加23g(0.2mol)30%的过氧化氢,滴加结束后保温反应2小时,取样中控反应完全,得到目标化合物,收率90%。
实施例4化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
4.1化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,投入7.3g DMF(0.1mol),降温至10℃以下,然后缓慢滴加60g(0.4mol)三氯氧磷,滴完后继续搅拌反应0.5小时,然后升温至60℃缓慢滴加18.2g(0.1mol)哈格曼乙酯,滴加完后保温反应2小时,中控反应完全后,旋蒸除去多余的三氯氧磷,得到粗产品,收率83%。
4.2化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入26g(0.1mol)化合物4-氯-3-((二甲氨基)亚甲基)-2-甲基环六-1,4-二烯-1-甲酸乙酯和100gDCM,加入10g 36.5%盐酸和50g水室温搅拌2小时,反应结束后静置分层,旋干有机相得到目标化合物,收率96%。
4.3化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入23g(0.1mol)化合物4-氯-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯和100g乙腈,再加入5.3g(0.05mol)的碳酸钠,室温下缓慢滴加70g(0.2mol)20%的甲硫醇钠溶液,滴加完保温反应0.5小时,中控反应完全,反应液中加入100gDCM,100g水,萃取分层,旋干有机相,得到目标化合物,收率84%。
4.4化合物3-甲酰基-2-甲基-4-(甲硫基)苯甲酸乙酯的合成
在装有机械搅拌、温度计、冷凝管的四口瓶中,加入24g(0.1mol)化合物4-甲硫基-3-甲酰基-2-甲基环六-1,3-二烯-1-甲酸乙酯,200g DCE,40℃下缓慢滴加23g(0.2mol)30%的过氧化氢,滴加结束后保温反应2小时,取样中控反应完全,得到目标化合物,收率90%。
根据本发明所述的制备4-甲硫基-3-醛基-2-甲基苯甲酸酯类化合物的方法可以获得较高的反应转化率和选择性。成本大大降低。
以上详细描述了本发明的优选实施方式,但是,本发明并不限于上述实施方式中的具体细节,在本发明的技术构思范围内,可以对本发明的技术方案进行多种简单变型,这些简单变型均属于本发明的保护范围。
Claims (7)
1.一种式V化合物的制备方法,其特征在于,包括如下反应步骤:
步骤(1)、式Ⅰ化合物与维尔斯迈尔试剂反应,制得式II所示化合物;
步骤(2)、将步骤(1)制备得到的式II所示化合物水解得到式III化合物;
步骤(3)、将步骤(2)制备得到的式III化合物在碱存在条件下与甲硫醇钠进行取代反应得到式IV;
步骤(4)、将步骤(3)制备得到的式IV化合物通过氧化剂氧化得到式V化合物,
其中,式I、式II、式III、式IV和式V的结构如下:
其中,R为酯基,羧酸,酰胺基或氰基,R1和R2分别独立的选自烷基,优选C1-C4烷基,X为卤素,优选氟、氯、溴和碘。
2.根据权利要求1所述的式V化合物的制备方法,其特征在于,步骤(1)中所述的维尔斯迈尔试剂是由DMF、N,N-二乙基甲酰胺、N-甲基-N-乙基甲酰胺中的一种与三氯氧磷、三溴氧磷、氯化亚砜及草酰氯中的一种制备得到;式Ⅰ化合物与维尔斯迈尔试剂反应温度为0-100℃,优选为10-60℃。
3.根据权利要求1或2所述的式V化合物的制备方法,其特征在于,步骤(2)中水解优选在酸存在下水解,所述的酸为无机酸,优选硫酸、盐酸、磷酸,最优选为盐酸,水解反应是在溶剂中进行,所述的溶剂为有机溶剂、水中一种或多种,所述的有机溶剂为卤代烷烃,优选二氯甲烷、二氯乙烷中一种。
4.根据权利要求1-3任一项所述的式V化合物的制备方法,其特征在于,步骤(3)所述的碱为有机碱或无机碱;所述的无机碱为氢氧化钠、氢氧化钾、碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾一种或多种;所述的有机碱为甲醇钠、乙醇钠、醋酸钠、醋酸铵一种或多种;优选为碳酸氢钠、醋酸钠、醋酸铵中一种或多种。
5.根据权利要求1-4任一项所述的式V化合物的制备方法,其特征在于,步骤(3)的反应在非质子极性溶剂中进行,所述非极性溶剂为六甲基磷酰三胺、二甲亚砜、四氢呋喃、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、二氧六环中任意一种或几种组合,优选为六甲基磷酰三胺、二甲亚砜、乙腈中任意一种或几种组合。
6.根据权利要求1-5任一项所述的式V化合物的制备方法,其特征在于,步骤(3)中所述的式III化合物、碱和甲硫醇钠的用量摩尔比为1:0.1-2:1-4,优选1:0.1-0.5:1-3。
7.根据权利要求1-6任一项所述的式V化合物的制备方法,其特征在于,步骤(4)中所述的氧化剂为空气、过氧化氢、次氯酸钠、硫粉、二氧化硫、氯化亚砜、磺酰氯、浓硫酸、二氯化硫和三氧化硫中一种,优选为过氧化氢、氯化亚砜、硫粉中一种;所述式IV化合物与氧化剂用量的摩尔比为1:0.1-5,优选为1:1-2,反应温为10-50℃。
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