CN108484535B - 一种制备茚草酮的方法 - Google Patents
一种制备茚草酮的方法 Download PDFInfo
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- CN108484535B CN108484535B CN201810206971.XA CN201810206971A CN108484535B CN 108484535 B CN108484535 B CN 108484535B CN 201810206971 A CN201810206971 A CN 201810206971A CN 108484535 B CN108484535 B CN 108484535B
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- Prior art keywords
- ethyl
- hours
- room temperature
- indene
- chlorophenyl
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- 238000000034 method Methods 0.000 title claims abstract description 22
- 235000019239 indanthrene blue RS Nutrition 0.000 title claims abstract description 11
- UHOKSCJSTAHBSO-UHFFFAOYSA-N indanthrone blue Chemical compound C1=CC=C2C(=O)C3=CC=C4NC5=C6C(=O)C7=CC=CC=C7C(=O)C6=CC=C5NC4=C3C(=O)C2=C1 UHOKSCJSTAHBSO-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 37
- CBEKYPINWJEJBP-UHFFFAOYSA-N 2-ethylindene-1,3-dione Chemical compound C1=CC=C2C(=O)C(CC)C(=O)C2=C1 CBEKYPINWJEJBP-UHFFFAOYSA-N 0.000 claims abstract description 13
- -1 (2- (3-chlorphenyl) oxirane-2-yl) methyl Chemical group 0.000 claims abstract description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 64
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 44
- 239000007787 solid Substances 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 31
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 30
- 238000001035 drying Methods 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 238000010992 reflux Methods 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
- 238000001816 cooling Methods 0.000 claims description 21
- 239000012074 organic phase Substances 0.000 claims description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 16
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 16
- AQQHYYZCFBBVIW-UHFFFAOYSA-N 2-(3-chlorophenyl)prop-2-en-1-ol Chemical compound OCC(=C)C1=CC=CC(Cl)=C1 AQQHYYZCFBBVIW-UHFFFAOYSA-N 0.000 claims description 14
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 13
- UZYYNLUVALVDOZ-UHFFFAOYSA-N 1-chloro-3-(3-chloroprop-1-en-2-yl)benzene Chemical compound ClCC(=C)C1=CC=CC(Cl)=C1 UZYYNLUVALVDOZ-UHFFFAOYSA-N 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 239000008346 aqueous phase Substances 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- PMAAYIYCDXGUAP-UHFFFAOYSA-N Indanofan Chemical compound O=C1C2=CC=CC=C2C(=O)C1(CC)CC1(C=2C=C(Cl)C=CC=2)CO1 PMAAYIYCDXGUAP-UHFFFAOYSA-N 0.000 claims description 9
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 claims description 8
- JRGGUPZKKTVKOV-UHFFFAOYSA-N 1-bromo-3-chlorobenzene Chemical compound ClC1=CC=CC(Br)=C1 JRGGUPZKKTVKOV-UHFFFAOYSA-N 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 7
- 229960000583 acetic acid Drugs 0.000 claims description 7
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 7
- 239000012362 glacial acetic acid Substances 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007818 Grignard reagent Substances 0.000 claims description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 6
- 150000004795 grignard reagents Chemical class 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 5
- 229910052749 magnesium Inorganic materials 0.000 claims description 5
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims 15
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims 3
- 239000002245 particle Substances 0.000 claims 3
- 229920006395 saturated elastomer Polymers 0.000 claims 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 3
- 238000009987 spinning Methods 0.000 claims 1
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000000575 pesticide Substances 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract 3
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 244000058871 Echinochloa crus-galli Species 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000005907 Indoxacarb Substances 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006735 epoxidation reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- VBCVPMMZEGZULK-NRFANRHFSA-N indoxacarb Chemical compound C([C@@]1(OC2)C(=O)OC)C3=CC(Cl)=CC=C3C1=NN2C(=O)N(C(=O)OC)C1=CC=C(OC(F)(F)F)C=C1 VBCVPMMZEGZULK-NRFANRHFSA-N 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HRADVHZVMOMEPU-UHFFFAOYSA-N 3-iodopyrrolidine-2,5-dione Chemical compound IC1CC(=O)NC1=O HRADVHZVMOMEPU-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 244000152970 Digitaria sanguinalis Species 0.000 description 1
- 235000010823 Digitaria sanguinalis Nutrition 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 244000152045 Themeda triandra Species 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- NYCVSSWORUBFET-UHFFFAOYSA-M sodium;bromite Chemical compound [Na+].[O-]Br=O NYCVSSWORUBFET-UHFFFAOYSA-M 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/32—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions without formation of -OH groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
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Abstract
本发明属于农药技术领域,公开了一种茚草酮(2‑((2‑(3‑氯苯基)环氧乙烷‑2‑基)甲基)‑2‑乙基‑1H‑茚‑1,3(2H)‑二酮)的方法。茚草酮的两个中间体1‑卤‑3‑(3‑氯丙‑1‑烯‑2‑基)苯和2‑乙基‑1H‑茚‑1,3(2H)‑二酮。本发明公开了这两个中间的制备方法及用这两个中间体合成茚草酮的方法。该工艺路线新颖,步骤短,收率高,生产成本低,具有较大的实施价值和社会经济效益。
Description
技术领域
本发明属于农药技术领域,涉及一种化学合成方法,特别涉及一种制备茚草酮的方法。
背景技术
茚草酮(2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H) -二酮)对水稻田中包括主要杂草稗草在内的一年生杂草,在低剂量情况下即表现出很高的除草活性,且有效期长,对移栽水稻十分安全。茚草酮不仅在低剂量时有效,而且在水中具有良好的扩散性,作为水稻田用除草剂,可加工成各种各样的剂型。另外,茚草酮对草坪安全性高,其对早熟禾和马唐等一年生杂草从具有很高的抑制活性,因此也可以作为草坪除草剂使用。茚草酮以0.075-0.15kg (a.i.)/hm2的剂量对从发芽前至3叶期的稗草具有明显的效果,杀草叶龄期较长。对稗草以0.15kg(a.i.)/hm2的剂量一次施药,具有42d以上的持效期。
茚草酮的结构式为
目前,茚草酮的制备方法已有报到,日本三菱公司公开的合成方法中(EP398258A1)给出了两种中间体2-乙基茚满-1,3-二酮与1-氯-(1-氯甲基乙烯)苯及终产物的合成路线(见如下反应式)。该方法存在路线长,纯化困难等缺点。
发明内容
有鉴于此,为解决现有茚草酮制备技术步骤长,危险性高,条件要求苛刻等缺点,本发明提供了一条新的制备方法,该方法工艺简便,原料廉价易得,收率高,安全性高。适于工业化生产。
本发明制备2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3 (2H)-二酮的方法的路线如下:
具体地,本发明包括如下步骤:
(1)以3-卤氯苯为原料,在引发剂存在下与镁屑反应,制得式1的(3-氯苯基)卤化镁;
其中,X代表氯,溴或碘;
(2)将制得的(3-氯苯基)卤化镁在催化剂存在下与丙炔醇反应,制得式2 的2-(3-氯苯基)丙-2-烯-1-醇;
(3)将制得的2-(3-氯苯基)丙-2-烯-1-醇与卤代试剂反应,制得式3的1- 卤-3-(3-氯丙-1-烯-2-基)苯;
其中,X代表氯,溴或碘;
(4)以邻苯二甲酸二乙酯为原料,在碱存在下与丁酸乙酯发生克莱森酯缩合反应,再经脱羧制得式4的2-乙基-1H-茚-1,3(2H)-二酮;
(5)将制得的式3的1-卤-3-(3-氯丙-1-烯-2-基)苯与制得的式4的2-乙基 -1H-茚-1,3(2H)-二酮在碱性条件下反应制得式5的2-(2-(3-氯苯基)烯丙基) -2-乙基-1H-茚-1,3(2H)-二酮;
(6)将制得的2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的烯基氧化成环氧丙基制得目标产物式6的2-((2-(3-氯苯基)环氧乙烷-2-基) 甲基)-2-乙基-1H-茚-1,3(2H)-二酮。
其中,
步骤(1)所述的引发剂选自碘、1,2-二溴乙烷、溴乙烷、二异丁基氢化铝、碘甲烷、红铝中的一种;反应的溶剂为四氢呋喃、乙醚、甲基叔丁基醚、异丙醚;反应温度是20℃-溶剂的回流温度,优选为溶剂的回流温度;
步骤(2)所述的催化剂选自碘化亚铜、溴化亚铜、氯化亚铜中的一种;反应的溶剂为四氢呋喃、乙醚、甲基叔丁基醚、异丙醚中的一种或几种的混合物;反应温度是0℃-溶剂的回流温度,优选为溶剂的回流温度;
步骤(3)所述的卤代试剂选自二氯亚砜、三氯氧磷、五氯化磷、草酰氯、氯气、溴素、溴化氢、溴代丁二酰亚胺、四溴化碳、碘、碘代丁二酰亚胺;所述反应的溶剂为三氯氧磷、二氯亚砜、氯仿、四氯化碳、二氯甲烷、二硫化碳中的一种或几种的混合物;反应温度是-30℃-溶剂的回流温度,优选为溶剂的回流温度;
步骤(4)所述的碱选自氢化钠、乙醇钠、甲醇钠、叔丁醇钾、叔丁醇钠、氢氧化钠、氢氧化钾、叔丁基锂;所述克莱森酯缩合反应所用溶剂为丁酸乙酯、四氢呋喃、甲苯、丁醚、甲基叔丁基醚、二氧六环中的一种或几种的混合物;所述缩合反应的温度是0℃-溶剂的回流温度,优选为溶剂的回流温度;
步骤(5)所述的碱选自氢化钠、甲醇钠、乙醇钠、正丁醇钠、氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、碳酸铯、1,8-二氮杂二环十一碳-7-烯;反应的溶剂为水、乙醇、甲醇、叔丁醇、四氢呋喃、甲苯、苯、丁醚、乙醚中所述的一种或几种的混合物;反应温度是0℃-溶剂的回流温度,优选为溶剂的回流温度;
步骤(6)所述反应的氧化剂选自间氯过氧苯甲酸、双氧水、过氧乙酸、过氧丙酸、过氧单磺酸钾、过氧化叔丁醇、氧气、亚溴酸钠、亚氯酸钠、次氯酸钠。所述环氧化反应的溶剂选自二氯甲烷、氯仿、四氯化碳、苯、N,N-二甲基甲酰胺、甲醇、乙醇、丙酮、1,2-二氯乙烷、乙腈、冰醋酸中的一种或几种的混合物。所述环氧化的反应温度是0℃-溶剂的回流温度,优选为0℃。
本发明工艺路线新颖,工艺条件合理,反应步骤短,操作简单,反应收率高,生产成本低,具有较大的实施价值和社会经济效益。
下面再以实施例的方式对本发明做进一步说明,给出本发明的实施细节,但是并不是旨在限定本发明的保护范围。
具体实施方式
实施例1:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g(29.6mmol)镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴间溴氯苯。以风枪微热体系变浑浊,保持体系微沸状态滴入15 mL四氢呋喃和5.61g(29.3mmol)间溴氯苯的混合物,滴毕后,加热回流3小时。降至室温,待下步使用。向格式试剂的四氢呋喃溶液中加入0.34g(1.8mmol) 碘化亚铜,室温搅拌1小时。缓慢滴入丙炔醇0.66g(11.7mmol),滴毕后,加热回流24小时。冷却后,滴入饱和氯化铵溶液调节PH=5。以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.84g淡黄色油状液体。收率92.3%。
1H NMR(500MHz,CDCl3)δ:1.61(1H,s),4.50(2H,s),5.38(1H, d,J=0.4),5.47(1H,d,J=0.4),7.33-7.39(3H,m),7.42(1H,s)
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g(10.8mmol)2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷0.55g(3.6mmol),加热回流3小时。冷却后将体系倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次。合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后得1.92g黄色油状物。收率93.5%。
1H NMR(500MHz,CDCl3)δ:4.51(2H,s),5.29(1H,d,J=0.4),5.50 (1H,d,J=0.4),7.30-7.37(3H,m),7.44(1H,s)
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g(20mmol)邻苯二甲酸二乙酯溶于20mL正丁醚,向体系中加入 NaH 0.6g(25mmol),加入2.56g(22mmol)丁酸乙酯,加热回流6小时。冷却至室温,加入40mL水,用二氯甲烷萃取。水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取3次,合并乙酸乙酯,用无水硫酸钠干燥。旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得3.04g淡黄色晶体,收率86.8%。
1H NMR(500MHz,CDCl3)δ:0.98(3H,t,J=7.5Hz),2.04(2H,dq,J=5.7, 7.5Hz),2.97(1H,t,J=5.7Hz),7.80-7.84(2H,m),8.01-8.05(2H,m)
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g(12mmol),1-氯-3-(3-氯丙-1-烯-2- 基)苯1.92g(10.1mmol)溶于40mL DMF,加入3.62g碳酸钾及0.1g碘化钾,加热回流5小时。冷却至室温,倒入100mL水中,析出淡黄色固体,过滤,滤饼用庚烷重结晶,得白固体3.11g,收率94.7%。
1H NMR(500MHz,CDCl3)δ:0.63(3H,t,J=7.5Hz),1.97(2H,q,J=7.5Hz), 2.99(2H,s),4.93(1H,s),4.95(1H,s),6.54(1H,s),6.77-6.80(1H,m),6.95-7.08 (2H,m),7.60-7.73(4H,m)
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3 (2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL 氯仿中,在0℃下,缓慢滴入1.81g(10.5mmol)间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体。固体用甲醇水(20/3)11mL重结晶得到2.94g白色固体,收率85.4%。
1H NMR(500MHz,CDCl3)δ:0.65(3H,t,J=7.5Hz),1.80(2H,q,J =7.5Hz),2.48(1H,d,J=5.4Hz),2.59(1H,d,J=14.4Hz),2.75(1H,d,J =14.4Hz),2.83(1H,d,J=5.4Hz),6.82(1H,s),6.97-7.01(1H,m),7.09-7.11 (2H,m),7.71-7.84(4H,m)
实施例2:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g(29.6mmol)镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴1,3-二氯苯。以风枪微热体系变浑浊,保持体系微沸状态滴入15 mL四氢呋喃和4.31g(29.3mmol)1,3-二氯苯的混合物,滴毕后,加热回流3 小时。降至室温,待下步使用。向格式试剂的四氢呋喃溶液中加入0.34g(1.8 mmol)碘化亚铜,室温搅拌1小时。缓慢滴入丙炔醇0.66g(11.7mmol),滴毕后,加热回流12小时。冷却后,滴入饱和氯化铵溶液调节PH=5。以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.80g淡黄色油状液体。收率90.3%。
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g(10.8mmol)2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷0.55g(3.6mmol),室温反应6小时。反应完成倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次。合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后得1.88g黄色油状物。收率91.5%。
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g(20mmol)邻苯二甲酸二乙酯,加入NaH 0.6g(25mmol),加入 2.56g(22mmol)丁酸乙酯,120℃反应6小时,过程中体系固化,无法搅拌。冷却至室温,加入40mL水,用二氯甲烷萃取。水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取3次,合并乙酸乙酯,用无水硫酸钠干燥。旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得3.3g淡黄色晶体,收率94.2%。
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g(12mmol),1-氯-3-(3-氯丙-1-烯-2- 基)苯1.92g(10.1mmol)溶于40mL乙腈,加入3.62g碳酸钾,加热回流3 小时。冷却至室温,倒入100mL水中,以20mL乙酸乙酯萃取两次,有机相用无水硫酸镁干燥,旋干得淡绿色固体,以庚烷重结晶,得白固体3.15g,收率 95.9%。
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3
(2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL 氯仿中,在0℃下,缓慢滴入1.81g(10.5mmol)间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体。固体用甲醇水(20/3)11mL重结晶得到2.94g白色固体,收率85.4%。
实施例3:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g(29.6mmol)镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴间溴氯苯。以风枪微热体系变浑浊,保持体系微沸状态滴入15 mL四氢呋喃和5.61g(29.3mmol)间溴氯苯的混合物,滴毕后,加热回流3小时。降至室温,待下步使用。向格式试剂的四氢呋喃溶液中加入0.34g(1.8mmol) 碘化亚铜,室温搅拌1小时。缓慢滴入丙炔醇1.32g(23.4mmol),滴毕后,加热回流24小时。冷却后,滴入饱和氯化铵溶液调节PH=5。以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.82g淡黄色油状液体。收率91.3%。
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g(10.8mmol)2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷1g(6.55mmol),加热回流3小时。反应完成倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次。合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干后得1.77g黄色油状物。收率86.2%。
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g(20mmol)邻苯二甲酸二乙酯,加入20mL正丁醚,加入NaH 1.6 g(50mmol),加入2.56g(22mmol)丁酸乙酯,加热回流4小时。冷却至室温,加入40mL水,用二氯甲烷萃取。水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取 3次,合并乙酸乙酯,用无水硫酸钠干燥。旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得2.99g淡黄色晶体,收率85.4%。
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g(12mmol),1-氯-3-(3-氯丙-1-烯-2- 基)苯1.92g(10.1mmol)溶于20mL丙酮,加入3.62g碳酸钾,加热回流3 小时。冷却至室温,减压蒸除丙酮,加入30mL乙酸乙酯搅拌10分钟,抽出固体。以20mL水洗涤乙酸乙酯层,有机相用无水硫酸镁干燥,旋干得淡黄色固体,以庚烷重结晶,得白固体3.09g,收率94.1%。
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3 (2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL 氯仿中,在0℃下,缓慢滴入1.81g(10.5mmol)间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体。固体用甲醇水(20/3)11mL重结晶得到2.94g白色固体,收率85.4%。
本发明给出三个实施例,其中实施例1总收率为69.8%,实施例2总收率为67.6%,实施例3总收率为63.2%;而原研专利中通过一系列转化最终得到茚草酮的收率为45.6%;因此,本发明具有提高茚草酮生产收率节约原料,降低三废产生,优化生产操作等优点。
Claims (3)
1.一种制备2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的方法,其特征在于,包括如下步骤:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g,29.6mmol镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴间溴氯苯,以风枪微热体系变浑浊,保持体系微沸状态滴入15mL四氢呋喃和5.61g,29.3mmol间溴氯苯的混合物,滴毕后,加热回流3小时,降至室温,待下步使用,向格式试剂的四氢呋喃溶液中加入0.34g,1.8mmol碘化亚铜,室温搅拌1小时;缓慢滴入丙炔醇0.66g,11.7mmol,滴毕后,加热回流24小时,冷却后,滴入饱和氯化铵溶液调节PH=5;以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.84g淡黄色油状液体;
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g,10.8mmol 2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷0.55g,3.6mmol,加热回流3小时,冷却后将体系倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次,合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后得1.92g黄色油状物;
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g,20mmol邻苯二甲酸二乙酯溶于20mL正丁醚,向体系中加入NaH 0.6g,25mmol,加入2.56g,22mmol丁酸乙酯,加热回流6小时,冷却至室温,加入40mL水,用二氯甲烷萃取,水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取3次,合并乙酸乙酯,用无水硫酸钠干燥,旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得3.04g淡黄色晶体;
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g,12mmol,1-氯-3-(3-氯丙-1-烯-2-基)苯1.92g,10.1mmol溶于40mL DMF,加入3.62g碳酸钾及0.1g碘化钾,加热回流5小时,冷却至室温,倒入100mL水中,析出淡黄色固体,过滤,滤饼用庚烷重结晶,得白固体3.11g;
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL氯仿中,在0℃下,缓慢滴入1.81g,10.5mmol间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体,固体用甲醇水20/3 11mL重结晶得到2.94g白色固体。
2.一种制备2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的方法,其特征在于,包括如下步骤:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g,29.6mmol镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴1,3-二氯苯,以风枪微热体系变浑浊,保持体系微沸状态滴入15mL四氢呋喃和4.31g,29.3mmol 1,3-二氯苯的混合物,滴毕后,加热回流3小时,降至室温,待下步使用,向格式试剂的四氢呋喃溶液中加入0.34g,1.8mmol碘化亚铜,室温搅拌1小时,缓慢滴入丙炔醇0.66g,11.7mmol,滴毕后,加热回流12小时,冷却后,滴入饱和氯化铵溶液调节PH=5,以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.80g淡黄色油状液体;
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g,10.8mmol 2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷0.55g,3.6mmol,室温反应6小时,反应完成倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次,合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后得1.88g黄色油状物;
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g,20mmol邻苯二甲酸二乙酯,加入NaH 0.6g,25mmol,加入2.56g,22mmol丁酸乙酯,120℃反应6小时,过程中体系固化,无法搅拌,冷却至室温,加入40mL水,用二氯甲烷萃取,水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取3次,合并乙酸乙酯,用无水硫酸钠干燥,旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得3.3g淡黄色晶体;
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g,12mmol,1-氯-3-(3-氯丙-1-烯-2-基)苯1.92g,10.1mmol溶于40mL乙腈,加入3.62g碳酸钾,加热回流3小时,冷却至室温,倒入100mL水中,以20mL乙酸乙酯萃取两次,有机相用无水硫酸镁干燥,旋干得淡绿色固体,以庚烷重结晶,得白固体3.15g,收率95.9%;
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL氯仿中,在0℃下,缓慢滴入1.81g,10.5mmol间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体,固体用甲醇水20/311mL重结晶得到2.94g白色固体。
3.一种制备2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的方法,其特征在于,包括如下步骤:
(1)2-(3-氯苯基)丙-2-烯-1-醇的制备
将0.72g,29.6mmol镁屑浸没与15mL无水四氢呋喃中,加入一粒碘,室温下滴入两滴间溴氯苯,以风枪微热体系变浑浊,保持体系微沸状态滴入15mL四氢呋喃和5.61g,29.3mmol间溴氯苯的混合物,滴毕后,加热回流3小时,降至室温,待下步使用,向格式试剂的四氢呋喃溶液中加入0.34g,1.8mmol碘化亚铜,室温搅拌1小时,缓慢滴入丙炔醇1.32g,23.4mmol,滴毕后,加热回流24小时,冷却后,滴入饱和氯化铵溶液调节PH=5,以30mL乙酸乙酯萃取3次,合并有机相,以饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后向体系加入10mL甲醇有固体析出,抽出固体,减压蒸馏得到1.82g淡黄色油状液体;
(2)1-氯-3-(3-氯丙-1-烯-2-基)苯的制备
将1.84g,10.8mmol 2-(3-氯苯基)丙-2-烯-1-醇溶于10mL氯仿中,室温滴入三氯氧磷1g,6.55mmol,加热回流3小时,反应完成倒入碎冰中,搅拌至碎冰溶解,以碳酸钠调节PH=7-8,分出氯仿相,水相以5mL氯仿洗涤两次,合并氯仿,用饱和碳酸氢钠溶液洗涤,饱和氯化钠溶液洗涤,无水硫酸钠干燥,旋干后得1.77g黄色油状物;
(3)2-乙基-1H-茚-1,3(2H)-二酮的制备
将4.44g,20mmol邻苯二甲酸二乙酯,加入20mL正丁醚,加入NaH 1.6g,50mmol,加入2.56g,22mmol丁酸乙酯,加热回流4小时,冷却至室温,加入40mL水,用二氯甲烷萃取,水相用冰醋酸调节PH=7-8,用乙酸乙酯萃取3次,合并乙酸乙酯,用无水硫酸钠干燥,旋干后得到红色油状物,加入正庚烷搅拌两小时,有大量晶体析出,抽滤得2.99g淡黄色晶体;
(4)2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-乙基-1H-茚-1,3(2H)-二酮2.09g(12mmol),1-氯-3-(3-氯丙-1-烯-2-基)苯1.92g(10.1mmol)溶于20mL丙酮,加入3.62g碳酸钾,加热回流3小时,冷却至室温,减压蒸除丙酮,加入30mL乙酸乙酯搅拌10分钟,抽出固体,以20mL水洗涤乙酸乙酯层,有机相用无水硫酸镁干燥,旋干得淡黄色固体,以庚烷重结晶,得白固体3.09g;
(5)茚草酮2-((2-(3-氯苯基)环氧乙烷-2-基)甲基)-2-乙基-1H-茚-1,3(2H)-二酮的制备
2-(2-(3-氯苯基)烯丙基)-2-乙基-1H-茚-1,3(2H)-二酮3.11g溶于30mL氯仿中,在0℃下,缓慢滴入1.81g,10.5mmol间氯过氧苯甲酸,保持0℃反应5小时,反应完成后,用30mL饱和亚硫酸氢钠水溶液洗涤两次,有机相干燥旋干得黄色固体,固体用甲醇水20/311mL重结晶得到2.94g白色固体。
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