CN1317269C - 制备2－卤代吡啶甲酰胺的方法 - Google Patents
制备2－卤代吡啶甲酰胺的方法 Download PDFInfo
- Publication number
- CN1317269C CN1317269C CNB028212592A CN02821259A CN1317269C CN 1317269 C CN1317269 C CN 1317269C CN B028212592 A CNB028212592 A CN B028212592A CN 02821259 A CN02821259 A CN 02821259A CN 1317269 C CN1317269 C CN 1317269C
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- CN
- China
- Prior art keywords
- water
- haloperidid
- organic solvent
- formyl chloride
- ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 31
- 125000003118 aryl group Chemical group 0.000 claims abstract description 29
- 239000003960 organic solvent Substances 0.000 claims abstract description 27
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 239000011877 solvent mixture Substances 0.000 claims abstract description 7
- -1 acyclic ethers Chemical class 0.000 claims description 20
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 claims description 20
- 239000003513 alkali Substances 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000004432 carbon atom Chemical class C* 0.000 claims description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 11
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 11
- 239000012074 organic phase Substances 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims description 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- WWRCMNKATXZARA-UHFFFAOYSA-N 1-Isopropyl-2-methylbenzene Chemical compound CC(C)C1=CC=CC=C1C WWRCMNKATXZARA-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- HHBZZTKMMLDNDN-UHFFFAOYSA-N 2-butan-2-yloxybutane Chemical compound CCC(C)OC(C)CC HHBZZTKMMLDNDN-UHFFFAOYSA-N 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000007933 aliphatic carboxylic acids Chemical group 0.000 claims 2
- LISHNUHIAFFERV-UHFFFAOYSA-N 2-chloropyridine formyl chloride Chemical compound C(=O)Cl.ClC1=NC=CC=C1 LISHNUHIAFFERV-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 125000001475 halogen functional group Chemical group 0.000 description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical compound NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 229940031815 mycocide Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 3
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 2
- JPBWZIPCMDZOPM-UHFFFAOYSA-N 2-(4-chlorophenyl)aniline Chemical compound NC1=CC=CC=C1C1=CC=C(Cl)C=C1 JPBWZIPCMDZOPM-UHFFFAOYSA-N 0.000 description 2
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- FJBUQBPKURBOJF-UHFFFAOYSA-N formyl chloride;pyridine Chemical compound ClC=O.C1=CC=NC=C1 FJBUQBPKURBOJF-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- OIRYNNTWJJMYNB-UHFFFAOYSA-N 2-(4-fluorophenyl)aniline Chemical compound NC1=CC=CC=C1C1=CC=C(F)C=C1 OIRYNNTWJJMYNB-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- KCDNYRPDKSGQCM-UHFFFAOYSA-N 4-[4-(3-chlorophenyl)-4-(pyrrolidine-1-carbonyl)piperidin-1-yl]-1-(4-fluorophenyl)butan-1-one Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC(C=2C=C(Cl)C=CC=2)(C(=O)N2CCCC2)CC1 KCDNYRPDKSGQCM-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000004781 supercooling Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
Abstract
本发明涉及一种通过使2-卤代吡啶甲酰氯II与在氨基的邻位上具有非氢取代基的芳族伯单胺I反应而制备该芳族单胺I的2-卤代吡啶甲酰胺的方法。本发明方法的特征在于它包括在包含水和至少一种水不混溶性有机溶剂的溶剂混合物中在基于2-卤代吡啶甲酰氯II为0至低于10mol%的除I或II以外的碱存在下进行反应。
Description
本发明涉及一种制备在氨基的邻位上具有非氢取代基的芳族伯单胺的2-卤代吡啶甲酰胺，尤其是2-卤代烟酰胺的方法。
由EP-A 545 099已知在氨基的邻位上具有非氢取代基的芳族伯单胺I的2-卤代吡啶甲酰胺是杀真菌剂。它们通过使2-卤代吡啶甲酰氯与邻位取代的芳族单胺在碱，优选叔胺存在下在有机溶剂中反应而制备。碱用于结合反应中形成的卤化氢并因此至少以化学计算量使用。该方法的缺点在于少量的碱残留在最初得到的反应产物中并且必须通过复杂的提纯措施除去，以生产出符合规格的杀真菌剂。除此以外，碱的使用在制备这些杀真菌剂中构成额外的成本因素。
因此，人们对不需要使用碱而制备这些杀真菌剂的方法非常感兴趣。然而，必须考虑的是，邻位取代的芳族单胺(下文称为单胺I)因存在邻位取代基而是空间位阻的，并因而相对不那么具有反应性。另外，芳族单胺I具有足够的碱性而被反应过程中形成的卤化氢质子化，以致在没有碱的存在下通常仅发生部分转化。因此，迄今为止人们认为必须在2-卤代吡啶甲酰氯II与邻位取代的芳族单胺I的反应中使用化学计算量的辅助碱。
本发明的目的是提供一种通过使芳族伯单胺I与2-卤代吡啶甲酰氯II反应而制备2-卤代吡啶甲酰胺的方法，该方法以高产率得到所需的2-卤代吡啶甲酰胺，而不要求等摩尔使用碱。该方法尤其可用于2-卤代吡啶甲酰氯与特别是不具有反应性的2-氨基联苯型芳族单胺的反应。另外，该方法还可大规模操作。
我们发现该目的令人吃惊地由这样一种方法实现，该方法涉及使2-卤代吡啶甲酰氯II与芳族单胺I在包含水和至少一种水不混溶性有机溶剂的溶剂混合物中在基本没有或完全没有辅助碱存在下反应。由该方法实现的高产率尤其令人吃惊，因为吡啶甲酰氯非常易于水解。因此，吡啶甲酰氯通常仅在无水条件下转化。
因此，本发明提供了一种通过使2-卤代吡啶甲酰氯II与在氨基的邻位上具有非氢取代基的芳族伯单胺I反应而制备该芳族单胺I的2-卤代吡啶甲酰胺的方法，该方法包括在包含水和至少一种水不混溶性有机溶剂的溶剂混合物中在基于卤代吡啶甲酰氯II为0至低于10mol％的除I或II以外的碱存在下进行反应。
对本发明而言，水不混溶性有机溶剂包括所有有机溶剂和溶剂混合物，它们在盐酸反应条件下在与水混合时形成多相体系，该体系包含至少一种有机相和至少一种水相。通常而言，有用的溶剂是溶解少于10体积％的水或稀盐酸的那些。除了上述溶剂外还包含水混溶性非质子溶剂的溶剂混合物也是有用的，因为这些混合物在反应条件下也与水形成两相体系。
水不混溶性有机溶剂的实例包括芳族、脂族和环脂族烃类；芳族、脂族和环脂族卤代烃类；优选具有4-10个碳原子的无环醚类；具有3-10个碳原子的酯类，优选脂族或环脂族醇与优选脂族羧酸形成的那些酯，例如乙酸、丙酸或丁酸与C3-C8链烷醇形成的酯，例如乙酸、丙酸、丁酸的甲基酯、乙基酯、正丙基酯、正丁基酯或异丁基酯等；还有优选具有4-10个碳原子的酮类，如甲基·乙基酮；优选具有4-10个碳原子的脂族腈类，如丁腈；以及上述有机溶剂的混合物。有用的水混溶性溶剂的实例包括丙酮；环状醚类，如四氢呋喃、二氧六环；以及乙腈或丙腈。
水混溶性溶剂的含量通常基于有机溶剂的总量不超过50重量％，优选不超过20重量％。在优选的实施方案中，所用溶剂基本不含水混溶性溶剂(含量小于5重量％)。
优选充分溶解至少反应物I和II的有机溶剂。特别优选允许反应物浓度达到至少20重量％，尤其至少30重量％的溶剂。优选的有机溶剂的实例包括芳族，优选烷基取代的烃类，如甲苯、乙苯、邻二甲苯、间二甲苯、对二甲苯、枯烯和对甲基枯烯；卤代烃类，尤其是氯代烃类，如二氯甲烷、三氯甲烷、1，2-二氯乙烷、氯苯和二氯苯；醚类，例如C2-C4二烷基醚，如乙醚、二异丙基醚、二正丁基醚、二仲丁基醚和甲基·叔丁基醚；环状醚类，如四氢呋喃和1，3-二氧六环；以及具有3-10个碳原子的上述酯类。上述溶剂的混合物当然也合适。特别优选的溶剂和溶剂混合物含有主要量，优选大于80体积％，尤其是大于90体积％的至少一种芳族烃。特别优选的芳族烃类包括C1-C4单烷基-和C1-C4二烷基苯，尤其是二甲苯类。
根据本发明，水与有机溶剂的比例的选择应使得在反应条件下形成包含溶剂和反应产物的第一相以及第二水相。水量的选择优选应使得每mol2-卤代吡啶甲酰氯II使用的水量至少为100g，优选至少200g，尤其至少300g。通常每mol 2-卤代吡啶甲酰氯II使用不超过1kg的水。
水混溶性有机溶剂量的计算通常应使水与溶剂的体积比为10∶1至1∶10。尤其由于成本方面的原因，有利的是保持溶剂的用量尽可能少。因此优选以使反应物I和II的总量基于100重量份有机水不混溶性溶剂为至少25重量份，优选至少30重量份，尤其至少50重量份所必需的量加入溶剂。溶剂量的选择优选应使得反应物和吡啶甲酰胺在反应条件下或多或少完全溶于有机溶剂中，从而可以形成基本均匀的有机相。通常相应地每100重量份反应物(I和II的总量)使用至少100重量份溶剂，优选至少130重量份溶剂。
为了使2-卤代吡啶甲酰氯II与芳族单胺I反应，在所需量的水存在下将反应物I和II以在有机溶剂中的溶液彻底混合。这导致自发的放热反应，形成2-卤代吡啶甲酰胺。该反应通常在室温以上，但优选在40℃以上，尤其是在50℃以上的温度下进行。优选在水存在下将反应物I和II在有机溶剂中的溶液在准绝热条件下于40℃以上，尤其是于50℃以上，例如60-65℃下混合在一起，从而加热反应器内容物。在这种情况下，“准绝热条件”是指酰胺形成所释放的大部分热焓不通过冷却装置直接除去，而是引起反应器内容物温热的那些反应条件。在该反应过程中，剧烈混合通常例如通过彻底搅拌和/或通过泵送来循环反应器内容物而进行。具体而言，首先将所需量的水和芳族单胺I在所需有机溶剂中的溶液加入反应容器中，将反应器内容物加热到所需温度，然后在混合下将2-卤代吡啶甲酰氯在有机溶剂中的溶液引入反应器中。该引入的持续时间可以为几分钟至几小时。优选的准绝热方法涉及将2-卤代吡啶甲酰氯II的溶液优选尽可能快地加入，优选在1-30分钟内加入，尤其在1-15分钟内加入。2-卤代吡啶甲酰氯II在有机溶剂中的浓度通常为20-200重量份/100重量份有机溶剂。
在加料结束后，通常使各组分进一步反应一段时间，优选不超过1小时，然后开始后处理。该进一步反应优选在混合反应器内容物下进行。后处理通过常规的含水萃取方法进行。为此，通常首先将水相从可能仍旧是热的反应混合物中除去。然后通过加入无机碱的水溶液来中和有机相，任选在用额外的有机溶剂稀释之后。有用的碱的实例包括碱金属氢氧化物，如氢氧化钠或氢氧化钾，碱金属碳酸盐和碳酸氢盐，尤其是碳酸钠。中和可以一步或多步进行。中和优选包括将pH设定为6-10，尤其是7-9。中和程序优选同样在40℃以上，尤其是60℃以上，特别是85℃以上，例如在60-100℃或85-100℃的温度下进行。优选将热的碱水溶液加入热的有机相中。中和可以一步或多步进行并且在每一步骤之后将水相从有机相中除去。
进一步量的除草剂的回收通常通过用有机溶剂反萃取第一水相或合并的水相并任选以上述方式中和合并的有机溶液而实现。优选将如此回收的反萃取液送回反应中，例如送回随后的批料中。当然，该除草剂还可从反萃取液中分离。
以此方式制备的2-卤代吡啶甲酰胺从有机相中的分离以常规方式进行，例如通过浓缩和/或冷却有机溶液并结晶。结晶例如可以在种子晶体存在下进行。
为了制备2-卤代吡啶甲酰胺，反应物I和II以接近化学计算量使用，即2-卤代烟酰氯II和芳族胺I的摩尔比为0.9∶1至1∶1.1。然而，优选以至少等摩尔量或基于I至多过量10mol％，优选至多过量5mol％使用2-卤代烟酰氯II。
本发明方法能够使所有在氨基的邻位上具有非氢取代基的芳族单伯胺II转化。原则上，有用的取代基是在给定反应条件下呈惰性，即不进入与2-卤代吡啶甲酰氯II的酰氯官能团的竞争性反应的那些。该类取代基的实例包括卤素、硝基、氰基、烷基、卤代烷基、环烷基、烷氧基、烷氧基烷基、烷硫基、烷基磺酰基、芳基、杂芳基、芳基烷基和杂芳基烷基。最后提到的四种基团的芳基和杂芳基本身具有1、2或3个作为取代基提到的基团，例如卤素、硝基、氰基、烷基、卤代烷基、烷氧基、烷氧基烷基、烷硫基、烷基磺酰基、芳基和/或环烷基。除了氨基邻位上的取代基外，芳族单胺还可以带有其它上述类型的取代基，例如1或2个其它上述类型的取代基。两个键合于相邻芳族碳原子上的取代基也可以结合在一起形成碳环或杂环的5或6元环，该环自身可以例如被卤素或烷基取代。
芳族单胺优选衍生于苯胺。然而，多环芳族胺如萘基胺或苯并杂环胺也可用作单胺I。除邻位上的取代基外，芳族单胺，尤其是苯胺化合物当然还可以带有其它上述类型的取代基，例如1或2个上述类型的取代基。在本发明的优选实施方案中，使用仅在邻位取代的苯胺。
对本发明而言，烷基为优选具有1-6个碳原子，尤其是1-4个碳原子的线性或支化的饱和烃基，例如甲基、乙基、正丙基、异丙基、正丁基、2-丁基、异丁基和叔丁基。该定义同样可以用于烷氧基、烷硫基、烷氧基烷基和烷基磺酰基中的烷基部分。
对本发明而言，卤代烷基为优选具有1-4个碳原子的部分或全部卤代的，尤其是氟代的、氯代的、溴代的或碘代的线性或支化的饱和烃基，例如氯甲基、二氯甲基、三氯甲基、氟甲基、二氟甲基、一氯二氟甲基、二氯一氟甲基、三氟甲基、溴甲基、2，2，2-三氯乙基、2，2，2-三氟乙基、2-氯乙基、五氟乙基、五氯乙基、3-氯丙基、3-溴丙基等。
烷氧基烷基为被C1-C4烷氧基取代的线性或支化的烷基，例如甲氧基甲基、乙氧基甲基、正-或异-丙氧基甲基、正丁氧基甲基、1-甲氧基乙基、1-乙氧基乙基、2-甲氧基乙基、2-乙氧基乙基等。
环烷基为通常具有3-10个碳原子的单环或双环烃基，例如环丙基、环戊基、环己基、降冰片基、十氢化萘基或金刚烷基。
芳基优选为苯基或萘基，其各自可以被1、2或3个上述取代基取代。
杂芳基为可以是单环或双环且具有1-3个选自O、N和S的杂原子的杂芳族基团，但没有一个杂原子可在水相中质子化。杂芳基的实例尤其是噻吩基、呋喃基、苯并噻吩基、吲哚基等。芳基和杂芳基可以被一个或多个，例如1、2或3个上述取代基取代。
在本发明特别优选的实施方案中，使用在氨基的邻位上具有苯基取代基的芳族伯单胺I，该苯基取代基本身可以被例如1、2或3个上述取代基取代。本发明尤其涉及一种其中所用芳族单胺I为苯胺化合物的方法，其中所述苯胺化合物在氨基的邻位上具有任选被取代的苯基环，即2-氨基联苯型芳族单胺I。苯基环可以如上所述被取代且优选具有1、2或3个上述取代基。特别优选的取代基选自卤素、甲基、二氟甲基、三氟甲基、甲氧基、甲硫基或甲基磺酰基。在本发明的特殊实施方案中，所用芳族单胺I为2-(卤代苯基)苯胺，例如2-(4-氯苯基)苯胺或2-(4-氟苯基)苯胺。
用于本发明方法中的2-卤代吡啶甲酰氯优选为2-卤代烟酰氯，尤其是2-氯烟酰氯(＝2-氯-3-吡啶甲酰氯)。
本发明方法以高产率得到在氨基的邻位上具有非氢取代基的空间受阻的芳族伯单胺I的2-卤代吡啶甲酰胺，而不需要使用碱。来自常规后处理的产率通常为理论产率的80％以上。水相的反萃取通常能够使产率增加到90％以上。令人吃惊的是，在反应条件下仅形成非常少量的2-羟基烟酰胺，后者通常来自2-卤代烟酰胺的酸解。
本发明由下列实施例说明：
通过2-氯-3-烟酰氯II与2-(4-氯苯基)苯胺I的反应制备2-氯-[2-(4-氯苯基)苯基氨基羰基]吡啶
向反应容器中加入800g水和396g(1.944mol)2-氨基-4’-氯联苯在311g二甲苯中的溶液，并在搅拌下加热到内部温度为65℃。然后加入已经加热到65℃的349g(1.984mol)2-氯-3-烟酰氯在233g二甲苯中的溶液。这导致反应容器中的温度升至约95℃。加料完成后，在搅拌下将该温度再维持10分钟，然后关闭搅拌器并分离各相。排出并收集水相。将约360g热水加入有机相中，然后搅拌并加入第一部分的20重量％碳酸钠水溶液。然后分离水相并将360g热水和另外的20重量％碳酸钠溶液加入有机相中。分离水相之后，将热的有机相转移到预热的储槽中。然后在搅拌下冷却到室温并结晶出标题化合物。分离母液并干燥晶体之后，得到567g杀真菌剂。这对应于基于所用2-氨基联苯为85％的产率。
用二甲苯反萃取水相得到另外53g标题化合物。总产量为620g(理论产率的93％)。
Claims (11)
1.一种通过使2-卤代吡啶甲酰氯II与在氨基的邻位上具有非氢取代基的芳族伯单胺I反应而制备该芳族伯单胺I的2-卤代吡啶甲酰胺的方法，包括在包含水和至少一种水不混溶性有机溶剂的溶剂混合物中在基于2-卤代吡啶甲酰氯II为0至低于10mol％的除I或II以外的碱存在下进行反应，其中化合物I和II的总量基于100重量份有机溶剂为25-100重量份，该溶剂混合物在盐酸反应条件下包含至少一种有机相和至少一种水相，且所述水不混溶性有机溶剂选自：芳族烃类、卤代烃类、具有4-10个碳原子的无环醚类、脂族或环脂族醇与脂族羧酸形成的具有3-10个碳原子的酯类以及它们的混合物。
2.如权利要求1所要求的方法，其中水量为至少100g/mol 2-卤代吡啶甲酰氯II。
3.如权利要求1或2所要求的方法，其中所述水不混溶性有机溶剂选自：烷基取代的芳族烃，氯代烃类，脂族或环脂族醇与脂族羧酸形成的具有3-10个碳原子的酯，C2-C4二烷基醚，以及它们的混合物。
4.如权利要求1或2所要求的方法，其中所述水不混溶性有机溶剂选自：甲苯、乙苯、邻二甲苯、间二甲苯、对二甲苯、枯烯、对甲基枯烯；二氯甲烷、三氯甲烷、1，2-二氯乙烷、氯苯、二氯苯；乙醚、二异丙基醚、二正丁基醚、二仲丁基醚、甲基·叔丁基醚；乙酸、丙酸或丁酸与C3-C8链烷醇形成的酯；以及它们的混合物。
5.如权利要求1或2所要求的方法，其中所述水不混溶性有机溶剂选自乙酸、丙酸、丁酸的甲基酯、乙基酯、正丙基酯、正丁基酯和异丁基酯。
6.如权利要求1或2所要求的方法，其中所述反应在高于40℃的温度下进行。
7.如权利要求1或2所要求的方法，其中所述反应在不存在除I或II以外的碱下进行。
8.如权利要求1或2所要求的方法，其中2-卤代吡啶甲酰氯II和芳族伯单胺I以1∶1.1至1∶1的摩尔比反应。
9.如权利要求1或2所要求的方法，其中在芳族伯单胺I中氨基邻位上的取代基为本身任选被取代的苯基。
10.如权利要求9所要求的方法，其中芳族伯单胺I选自2-(卤代苯基)苯胺。
11.如权利要求1或2所要求的方法，其中化合物II为2-氯吡啶甲酰氯。
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| EP01126113 | 2001-11-02 | ||
| EP01126113.8 | 2001-11-02 |
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| AU (1) | AU2002346823B2 (zh) |
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| SI (1) | SI1444205T1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102325747B (zh) | 2009-02-19 | 2015-01-07 | 巴斯夫欧洲公司 | 制备2-氨基联苯类化合物的方法 |
| CN102348675B (zh) | 2009-03-09 | 2014-10-01 | 巴斯夫欧洲公司 | 制备取代2-硝基联苯的方法 |
| EP2683682A1 (de) | 2011-03-07 | 2014-01-15 | Basf Se | Verfahren zur synthese von aminobiphenylen |
| CN106103404B (zh) * | 2014-01-17 | 2017-11-24 | 迈克斯(如东)化工有限公司 | 联苯化合物的制备及应用 |
| CN103980192B (zh) * | 2014-01-20 | 2016-02-17 | 泰州百力化学股份有限公司 | 一种选择性合成不同晶型啶酰菌胺的方法 |
| CN104725303B (zh) * | 2015-02-02 | 2017-09-08 | 西安近代化学研究所 | 一种2‑氯‑n‑(4′‑氯联苯‑2‑基)烟酰胺的合成方法 |
| GB2536979B (en) * | 2015-06-04 | 2019-03-13 | Rotam Agrochem Int Co Ltd | Process for preparing boscalid |
| GB2539022B (en) * | 2015-06-04 | 2018-02-07 | Rotam Agrochem Int Co Ltd | Process for preparing boscalid |
| GB2550138B (en) | 2016-05-09 | 2019-06-12 | Rotam Agrochem Int Co Ltd | Process for preparing boscalid |
| GB2552699B (en) * | 2016-08-04 | 2021-03-10 | Rotam Agrochem Int Co Ltd | Process for preparing boscalid |
| GB2552697B (en) * | 2016-08-04 | 2021-03-10 | Rotam Agrochem Int Co Ltd | Process for the preparation of boscalid |
| GB2552696B (en) * | 2016-08-04 | 2020-03-04 | Rotam Agrochem Int Co Ltd | Process for preparing boscalid |
| WO2018060836A1 (en) * | 2016-09-28 | 2018-04-05 | Upl Limited | Process for preparation of boscalid anhydrate form i and boscalid anhydrate form ii |
| CN114634444A (zh) * | 2022-03-22 | 2022-06-17 | 泰州百力化学股份有限公司 | 一种酰胺类化合物的制备方法 |
| CN115960609B (zh) * | 2022-12-30 | 2023-10-24 | 浙江奥首材料科技有限公司 | 一种高选择性蚀刻晶圆表面氧化层的蚀刻液、其制备方法及用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2186773A (en) * | 1939-08-11 | 1940-01-09 | Lilly Co Eli | 2(p-nicotinylaminobenzenesulfon-amide) pyridine and its salts, and process of preparing them |
| EP0545099A2 (de) * | 1991-11-22 | 1993-06-09 | BASF Aktiengesellschaft | Säureanilid-Derivate und ihre Verwendung zur Bekämpfung von Botrytis |
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| CA2358091A1 (en) * | 1998-12-23 | 2000-07-06 | Eli Lilly And Company | Antithrombotic amides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2186773A (en) * | 1939-08-11 | 1940-01-09 | Lilly Co Eli | 2(p-nicotinylaminobenzenesulfon-amide) pyridine and its salts, and process of preparing them |
| EP0545099A2 (de) * | 1991-11-22 | 1993-06-09 | BASF Aktiengesellschaft | Säureanilid-Derivate und ihre Verwendung zur Bekämpfung von Botrytis |
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| Publication number | Publication date |
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| AR037513A1 (es) | 2004-11-17 |
| EA200400593A1 (ru) | 2004-10-28 |
| BR0213561B1 (pt) | 2013-04-16 |
| KR20050042031A (ko) | 2005-05-04 |
| JP4430392B2 (ja) | 2010-03-10 |
| WO2003037868A1 (de) | 2003-05-08 |
| PL370556A1 (en) | 2005-05-30 |
| CN1575281A (zh) | 2005-02-02 |
| US7241896B2 (en) | 2007-07-10 |
| ATE316959T1 (de) | 2006-02-15 |
| AU2002346823B2 (en) | 2009-03-12 |
| DE50205766D1 (de) | 2006-04-13 |
| IL161359A0 (en) | 2004-09-27 |
| HUP0401595A3 (en) | 2005-11-28 |
| MXPA04003733A (es) | 2004-07-23 |
| ES2256565T3 (es) | 2006-07-16 |
| EP1444205A1 (de) | 2004-08-11 |
| JP2005526699A (ja) | 2005-09-08 |
| CA2463625A1 (en) | 2003-05-08 |
| SI1444205T1 (sl) | 2006-06-30 |
| CA2463625C (en) | 2010-12-21 |
| DK1444205T3 (da) | 2006-05-29 |
| KR100947402B1 (ko) | 2010-03-15 |
| EP1444205B1 (de) | 2006-02-01 |
| HUP0401595A2 (hu) | 2004-11-29 |
| BR0213561A (pt) | 2004-10-26 |
| IL161359A (en) | 2012-12-31 |
| ZA200404284B (en) | 2005-06-01 |
| EA007106B1 (ru) | 2006-06-30 |
| US20040266837A1 (en) | 2004-12-30 |
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