CN1100754C - 三氟乙酰乙酰苯胺的制备方法 - Google Patents
三氟乙酰乙酰苯胺的制备方法 Download PDFInfo
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- CN1100754C CN1100754C CN97180717A CN97180717A CN1100754C CN 1100754 C CN1100754 C CN 1100754C CN 97180717 A CN97180717 A CN 97180717A CN 97180717 A CN97180717 A CN 97180717A CN 1100754 C CN1100754 C CN 1100754C
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- QJYDWPJWCSDYAG-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxo-n-phenylbutanamide Chemical class FC(F)(F)C(=O)CC(=O)NC1=CC=CC=C1 QJYDWPJWCSDYAG-UHFFFAOYSA-N 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 20
- ZPQNVNQWYSTELD-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxobutanoyl chloride Chemical compound FC(F)(F)C(=O)CC(Cl)=O ZPQNVNQWYSTELD-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000011230 binding agent Substances 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- 150000001721 carbon Chemical group 0.000 claims description 36
- -1 methylidene, ethyl Chemical group 0.000 claims description 35
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 239000011737 fluorine Substances 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 239000003999 initiator Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- VWTRUQRYDJEGBN-UHFFFAOYSA-N N-acetyl-2,2,2-trifluoro-N-phenylacetamide Chemical compound FC(F)(F)C(=O)N(C(=O)C)C1=CC=CC=C1 VWTRUQRYDJEGBN-UHFFFAOYSA-N 0.000 claims 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 abstract description 3
- 150000001448 anilines Chemical class 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- LIQBKSIZAXKCPA-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxobutanoic acid Chemical compound OC(=O)CC(=O)C(F)(F)F LIQBKSIZAXKCPA-UHFFFAOYSA-N 0.000 description 9
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 9
- 150000003931 anilides Chemical class 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000004982 aromatic amines Chemical class 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical class CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- KWKBEEYUAVEMPV-UHFFFAOYSA-N 2-fluoro-3-oxobutanamide Chemical class CC(=O)C(F)C(N)=O KWKBEEYUAVEMPV-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- NURQLCJSMXZBPC-UHFFFAOYSA-N 3,4-dimethylpyridine Chemical compound CC1=CC=NC=C1C NURQLCJSMXZBPC-UHFFFAOYSA-N 0.000 description 2
- HWWYDZCSSYKIAD-UHFFFAOYSA-N 3,5-dimethylpyridine Chemical compound CC1=CN=CC(C)=C1 HWWYDZCSSYKIAD-UHFFFAOYSA-N 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000002650 habitual effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- MWOODERJGVWYJE-UHFFFAOYSA-N 1-methyl-1-phenylhydrazine Chemical compound CN(N)C1=CC=CC=C1 MWOODERJGVWYJE-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical class CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- NTSLROIKFLNUIJ-UHFFFAOYSA-N 5-Ethyl-2-methylpyridine Chemical compound CCC1=CC=C(C)N=C1 NTSLROIKFLNUIJ-UHFFFAOYSA-N 0.000 description 1
- KNCHDRLWPAKSII-UHFFFAOYSA-N 5-ethyl-2-methylpyridine Natural products CCC1=CC=NC(C)=C1 KNCHDRLWPAKSII-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000001334 alicyclic compounds Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical class CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
- 229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000003502 gasoline Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002897 organic nitrogen compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical class CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
一种生产通式(I)的三氟乙酰乙酰苯胺的新方法，式中R1的定义如说明书所述。该方法包括任选地在酸结合剂存在下和任意地在稀释剂存在下，三氟乙酰乙酰氯与通式(III)的苯胺反应。通式(I)化合物适合作生产除草有效的尿嘧啶衍生物的中间体。
Description
本发明涉及三氟乙酰乙酰苯胺新的制备方法，三氟乙酰乙酰苯胺可以用作制备有除草活性的尿嘧啶衍生物的中间体。
已知N-芳基-三氟乙酰乙酰胺可以通过将三氟乙酰乙酸酯与芳基胺反应制备(参见DE-A4218159，EP-A0598436和J.Het.Chem.2(1965)，124)。然而，此方法有缺点，即它应用不广泛和所需产物只得到相对低的产率，主要是因为副反应的干扰。这样，在相当大的程度上，芳基胺与三氟甲基相邻的羰基反应。所得的烯胺容易与另外的芳基胺分子反应，得到双加合物。此反应可以用以下反应式说明：R＝烷基(例如甲基或乙基)此外，已知N-芳基-三氟乙酰乙酰胺可以通过从上述结构的双加合物中消去一分子芳基胺来制备(参见DE-A4218159)。此方法的缺点是其比上述的方法需要多一步。并且，产率也不能满足实现工业规模生产的需要。
已发现，如果合适的话在酸结合剂存在下和如果适合的话在稀释剂的存在下，反应温度为-20℃-+40℃，通式(I)的三氟乙酰乙酰苯胺
其中R1代表卤素或基团
其中
R2代表卤素或任意取代的烷基和
R3代表任意取代的烷基，任意取代的环烷基或代表任意取代的芳基，可以通过通式(II)的三氟乙酰乙酰氯与通式(III)的苯胺反应得到， 
其中R1定义如上。
非常惊奇的是，按本发明的方法平稳地进行反应可以以高产率获得通式(I)的三氟乙酰乙酰苯胺。这是没想到的，具体地说，因为作为起始物的三氟乙酰乙酰氯即使在低温度下，也只在短时间内稳定(参见Chem.Abstr.
1964，2788f和GB-A 931689)。也很惊奇的是，通式(III)的其中R1代表基团-NH-SO2-R3的苯胺，不显示三氟乙酰乙酰氯与磺酰氨基的任何值得一提的反应。
本发明的方法有许多优点。因为，所需的起始物容易以简单的方法并可大量得到。此外，反应的实施和所需物质的分离都没任何问题。特别有利的是，三氟乙酰乙酰苯胺可以高产率和高纯度获得。此外，此方法可广泛使用。
用三氟乙酰乙酰氯和4-氰基-2-氟-5-甲基磺酰基氨基-苯胺作为起始物，本发明的反应过程可以用以下反应式说明：
按本发明方法进行反应所需的通式(II)的三氟乙酰乙酰氯起始物是已知的(参见GB-A 931689)。
通式(III)提供了 按本发明方法进行反应进一步所需的起始物苯胺的一般定义。优选使用的通式(III)的化合物，其中
R1代表氟、氯、溴或基团其中
R2代表氢或代表1-6个碳原子的烷基，该烷基可以任意被氰基、卤素、1-4个碳原子的烷氧基、1-4个碳原子的烷硫基、烷基部分有1-4个碳原子的烷基羰基或烷基部分有1-4个碳原子的烷基氨基羰基取代，和
R3代表任意被氰基、卤素、1-4个碳原子的烷氧基、1-4个碳原子的烷硫基、1-4个碳原子的烷基羰基、1-4个碳原子的烷氧基羰基、1-4个碳原子的烷基氨基羰基或苯基取代的1-6个碳原子的烷基，
或代表任意被相同或不同的选自卤素、氰基和1-4个碳原子的烷基单至三取代的3-6个碳原子的环烷基，或代表
任意被相同或不同的取代基单至三取代的苯基，取代基选自卤素、氰基、1-4个碳原子的烷基、1或2个碳原子和1-5卤原子的卤代烷基、1-4个碳原子的烷氧基和1或2个碳原子和1-5卤原子的卤代烷氧基。
特别优选使用的通式(III)的苯胺，其中
R1代表氟、氯或基团其中
R2代表氢或代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，以上各基团均可以任意被氰基、氟、氯、甲氧基、乙氧基、甲硫基、乙硫基、乙酰基、丙酰基、甲氧基羰基、乙氧基羰基、甲基氨基羰基或乙基氨基羰基取代，和
R3代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，以上各基团均可以任意被氰基、氟、氯、甲氧基、乙氧基、甲硫基、乙硫基、乙酰基、丙酰基、甲氧基羰基、乙氧基羰基、甲基氨基羰基或乙基氨基羰基或苯基取代，或
代表任意被相同或不同的取代基单至三取代的环戊基、环己基或环丙基，其中取代基选自氟、氯、氰基、甲基和乙基，或代表
任意被相同或不同的取代基单至三取代的苯基，其中取代基选自氟、氯、氰基、甲基、乙基、三氟甲基、甲氧基、乙氧基、三氟甲氧基和二氟甲氧基。
通式(III)的苯胺是已知的或可以通过已知的方法制备(参见EP-A0648772)。
进行本发明方法适合的酸受体是所有惯用的无机或有机碱。优选使用碱金属碳酸盐和碳酸氢盐或碱土金属碳酸盐和碳酸氢盐，例如碳酸钠、碳酸钾或碳酸钙、碳酸氢钠、碳酸氢钾或碳酸氢钙，和碱性有机氮化合物，特别优选三甲胺、三乙胺、三丙胺、三丁胺、乙基-二异丙基胺、N，N-二甲基-环己胺、乙基-二环己胺、N，N-二甲基-苯胺、N，N-二甲基-苄胺、吡啶、2-甲基-吡啶、3-甲基-吡啶、4-甲基-吡啶、2，4-二甲基吡啶、2，6-二甲基-吡啶、3，4-二甲基-吡啶和3，5-二甲基-吡啶、5-乙基-2-甲基-吡啶、4-二甲基氨基-吡啶、N-甲基-哌啶、1，4-二氮双环[2，2，2]-辛烷(DABCO)、1，5-二氮双环[4，3，0]-壬-5-烯(DBN)或1，8-二氮双环[5，4，0]-十一碳-7-烯(DBU)。
进行本发明方法适合的稀释剂是所有惯用的惰性、有机溶剂。优选使用脂族化合物、脂环化合物或芳族化合物、任意卤代的烃，例如汽油、苯、甲苯、二甲苯、氯苯、二氯苯、石油醚、正己烷、环己烷、二氯甲烷、氯仿、四氯化碳；此外还包括醚类，例如乙醚、二异丙基醚、二噁烷、四氢呋喃、乙二醇二甲醚或乙二醇二乙醚；叔丁基甲醚或叔戊基-甲醚，此外还包括腈类，例如乙腈、丙腈或丁腈，和酯类，例如乙酸甲酯或乙酸乙酯。
当进行本发明方法时，反应温度可以在一定范围内改变。一般来说，反应温度为-20℃-+40℃，优选-10℃-+30℃。
本发明的方法一般在常压下进行。但是，也可在加压下进行反应。
本发明的方法优选在保护性气体例如氮气或氩气的存在下进行。
当进行本发明的方法时，相对于每摩尔通式(III)的苯胺一般使用1-3摩尔的通式(II)的三氟乙酰乙酰氯，优选使用1-1.9mol，和一般使用1-3摩尔酸结合剂，优选使用1-1.9摩尔。在一优选具体方案中，将通式(III)的苯胺和酸结合剂先加到稀释剂中，然后向稀释剂中滴加入通式(II)的三氟乙酰乙酰氯。通过惯用的方法进行后处理。一般来说，将所得的晶体产物过滤出、洗涤和干燥。可以通过惯用的方法除去可能存在的任何杂质(参见制备实施例)。
按本发明可制备的通式(I)的三氟乙酰乙酰苯胺存在通式如下的“酮”形式或通式如下的“水合物”形式或通式如下的“烯醇”形式，其是通式(I)的互变异构形式，
为了简便，在每种情况下仅用“酮”的形式。
按本发明可制备的通式(I)的三氟乙酰乙酰苯胺是合成有除草特性的尿嘧啶衍生物的有用中间体。
因此，在酸结合剂例如吡啶或4-二甲基氨基吡啶的存在下，和在稀释剂例如甲苯或四氢呋喃的存在下，反应温度为-20℃-+150℃下，通式如下的尿嘧啶衍生物
其中R1的定义如上和R4代表氢、羟基、氨基，代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基或叔丁氧基，以上各基团均可以任意被羟基、氰基、氟、氯、甲氧基、乙氧基取代，或代表氰基、氟、氯或溴任意取代的丙烯基、丁烯基、丙炔基或丁炔基，可以通过通式(I)的三氟乙酰乙酰苯胺与碳酰氯反应来制备，
其中R1的定义如上，和如果适合的话，在酸结合剂存在下和如果适合的话，在稀释剂例如乙醇的存在下，反应温度为-50℃-+80℃，将得到的通式(V)的苯基噁嗪-二酮与通式(VI)的氨基化合物反应来制备，
其中R1的定义如上，
H2N-R4 (VI)其中R4的定义如上。
通式(IV)的尿嘧啶衍生物和它们作为除草剂的用途是已知的(参见EP-A0408382，EP-A0648749和WO95-32952)。
通过以下实施例说明本发明的方法。制备实施例 实施例1 
在氩气气氛和20-22℃下，在15分钟内，将40.4g的35％浓度的三氟乙酰乙酰氯(81mmol)的二氯甲烷溶液边搅拌边滴加入10.3g(45mmol)的4-氰基-2-氟-5-甲基磺酰氨基-苯胺和4.28g(54mmol)的吡啶的110ml二氯甲烷悬浮液中。滴加后，用10ml二氯甲烷漂洗滴液漏斗，并将其滴加到此反应混合物中。用薄层色谱监测反应进程。反应15分钟后，将此混合物冷却至0℃，过滤出得到的沉淀，用二氯甲烷漂洗和干燥。将得到的15g粉状物质与水混合。用乙酸乙酯萃取得到的混合物三次。合并有机相，硫酸钠干燥后，减压浓缩。减压干燥剩余的产物。得到12.2g的N-(4-氰基-2-氟-5-甲磺酰基氨基-苯基)-4，4，4-三氟-3-氧代-丁酰胺(理论产率73.8％)，为固体形式，熔点186-191℃。实施例2 
在氩气气氛和搅拌下，在25分钟内，将713g的三氟乙酰乙酰氯(1.43mmol，35％浓度溶液)的二氯甲烷溶液滴加入冷却至10℃的169.5g(1.1mol)的2，5-二氟-4-氰基-苯胺、104.5g(1.32mol)的吡啶和640ml二氯甲烷混合物中。滴加后，用20ml二氯甲烷漂洗滴液漏斗，并将其滴加到此反应混合物中。用薄层色谱监测反应进程。在22℃下搅拌此反应混合物1小时，然后冷却至0℃并在此温度下搅拌15分钟。过滤沉淀物，用二氯甲烷洗涤和干燥。将得到的209.3g粗产物与水混合。用乙酸乙酯重复萃取得到的混合物。用浓盐酸调节水相至强酸性和用乙酸乙酯再萃取一次。合并有机相，用水洗涤，然后硫酸钠干燥。将过滤后的残余溶液减压浓缩。减压干燥剩余的产物。得到150.4g的N-(4-氰基-2，5-二氟-苯基)-4，4，4-三氟-3-氧代-丁酰胺(理论产率47.1％)，为白色固体，熔点176-181℃。
按上述方式重复后处理母液，进一步将通式(I-2)化合物的水合物分式产物分离。总产率为理论值的54％。实施例3 
按实施例1的方法，从4-氰基-2-氟-5-乙基磺酰基氨基-苯胺得到N-(4-氰基-2-氟-5-乙基磺酰基氨基-苯基)-4，4，4-三氟-3-氧代丁酰胺，熔点185-187℃。应用实施例A通式(V-1)化合物的制备
在40℃下，将120g 20％浓度的碳酰氯的甲苯溶液边搅拌边滴加入60g(0.20mol)的N-(4-氰基-2，5-二氟-苯基)-3-氧代-4，4，4-三氟-1-丁酰胺、40ml吡啶、4g的4-二甲基氨基-吡啶和1.5升的甲苯的混合物中。然后将此混合物在40℃再搅拌4小时。接着用氮气冲洗过量的碳酰氯。用水洗涤剩余的混合物三次，硫酸钠干燥和过滤。在真空水泵下从滤液中小心地蒸馏除去溶剂。
得到63.7g(理论值的77.5％)的3-(4-氰基-2，5-二氟-苯基)-3，4-二氢-6-三氟甲基-2H-1，3-噁嗪-2，4-二酮，为粘性物质，缓慢结晶。
通式(IV-1)化合物的制备
在室温下(约20℃)，将7ml的25％浓度的氨水溶液(0.10mol的NH3)搅拌下滴加到15.9g(0.05mol)的3-(4-氰基-2，5-二氟-苯基)-3，4-二氢-6-三氟甲基-2H-1，3-噁嗪-2，4-二酮和100ml的乙醇的混合物中。反应混合物于室温下搅拌20小时。然后在真空水泵下浓缩此混合物和将残余物溶于乙酸乙酯。用水洗涤所得的溶液，硫酸钠干燥和过滤。减压浓缩滤液，用少量异丙醇消化此残余物和通过抽滤分离得到的晶体产物。
得到11.8g(理论值的74％)的1-(4-氰基-2，5-二氟-苯基)-3，6-二氢-2，6-二氧代-4-三氟甲基-1(2H)-嘧啶，熔点234℃。
Claims (9)
1.通式(I)的三氟乙酰乙酰-苯胺的制备方法其中
R1代表氟、氯、溴或基团其中
R2代表氢或代表1-6个碳原子的烷基，该烷基可以任意被氰基、卤素、1-4个碳原子的烷氧基、1-4个碳原子的烷硫基、烷基部分有1-4个碳原子的烷基羰基或烷基部分有1-4个碳原子的烷基氨基羰基取代，和
R3代表任意被氰基、卤素、1-4个碳原子的烷氧基、1-4个碳原子的烷硫基、1-4个碳原子的烷基羰基、1-4个碳原子的烷氧基羰基、1-4个碳原子的烷基氨基羰基或苯基取代的1-6个碳原子的烷基，
或代表任意被相同或不同的取代基单至三取代的3-6个碳原子的环烷基，取代基选自卤素、氰基和1-4个碳原子的烷基，或代表
任意被相同或不同的取代基单至三取代的苯基，取代基选自卤素、氰基和1-4个碳原子的烷基、1-4个碳原子的烷氧基和1或2个碳原子和1-5卤原子的卤代烷氧基，该方法的特征在于，如果合适的话在酸结合剂存在下和如果适合的话在稀释剂的存在下，反应温度为-20℃-+40℃，通式(II)的三氟乙酰乙酰氯与通式(III)的苯胺反应，其中
R1定义如上。
2.权利要求1的方法，其特征在于使用通式(III)的苯胺为起始物，其中
R1代表氟、氯或基团
其中
R2代表氢或代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，以上各基团均可以任意被氰基、氟、氯、甲氧基、乙氧基、甲硫基、乙硫基、乙酰基、丙酰基、甲氧基羰基、乙氧基羰基、甲基氨基羰基或乙基氨基羰基取代和
R3代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，以上各基团均可以任意被氰基、氟、氯、甲氧基、乙氧基、甲硫基、乙硫基、乙酰基、丙酰基、甲氧基羰基、乙氧基羰基、甲基氨基羰基或乙基氨基羰基或苯基取代或
代表任意被相同或不同的取代基单至三取代的环戊基、环己基或环丙基，其中取代基选自氟、氯、氰基、甲基和乙基，或代表
任意被相同或不同的取代基单至三取代的苯基，其中取代基选自氟、氯、氰基、甲基、乙基、甲氧基、乙氧基、三氟甲氧基和二氟甲氧基。
3.权利要求1的方法，其特征在于使用通式(III)的苯胺为起始物，其中
R1代表氟、氯、溴或基团
其中
R2代表氢或代表1-6个碳原子的烷基，和
R3代表1-6个碳原子的烷基或代表3-6个碳原子的环烷基或代表苯基。
4.权利要求1的方法，其特征在于使用通式(III)的苯胺为起始物，其中
R1代表氟、氯或基团
其中
R2代表氢或代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，和
R3代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基或代表环戊基、环己基或环丙基，或代表苯基。
5.权利要求1的方法，其特征在于使用通式(III)的苯胺为起始物，其中
R1代表氟、氯、溴或基团其中
R2代表氢，和
R3代表1-6个碳原子的烷基。
6.权利要求1的方法，其特征在于使用通式(III)的苯胺为起始物，其中
R1代表氟、氯或基团其中
R2代表氢，和
R3代表甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基。
7.权利要求1的方法，其特征在于使用如下式的苯胺为起始物
8.权利要求1的方法，其特征在于使用如下式的苯胺为起始物
9.权利要求1的方法，其特征在于使用如下式的苯胺为起始物
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| CN97180717A Expired - Fee Related CN1100754C (zh) | 1996-12-19 | 1997-12-08 | 三氟乙酰乙酰苯胺的制备方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6136975A (zh) |
| EP (1) | EP0948482B1 (zh) |
| JP (1) | JP2001506249A (zh) |
| CN (1) | CN1100754C (zh) |
| AU (1) | AU5560798A (zh) |
| BR (1) | BR9714233A (zh) |
| DE (2) | DE19652955A1 (zh) |
| DK (1) | DK0948482T3 (zh) |
| HK (1) | HK1029329A1 (zh) |
| IL (1) | IL130090A (zh) |
| WO (1) | WO1998027057A2 (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB931689A (en) * | 1960-12-17 | 1963-07-17 | Hoechst Ag | Process for the manufacture of fluorinated acetoacetic acid chlorides and the solutions thereof |
| EP0648772A1 (de) * | 1993-10-18 | 1995-04-19 | Bayer Ag | 4-Cyanophenyliminoheterocyclen |
| WO1995032952A1 (en) * | 1994-05-27 | 1995-12-07 | Ciba-Geigy Ag | Process for the preparation of 3-aryluracils |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2797217A (en) * | 1957-06-25 | Dihydro oxazine diones | ||
| AU627906B2 (en) * | 1989-07-14 | 1992-09-03 | Nissan Chemical Industries Ltd. | Uracil derivatives and herbicides containing the same as active ingredient |
| DE4218159C2 (de) * | 1992-06-02 | 1997-07-31 | Luitpold Pharma Gmbh | 4,4,4-Trifluoracetessigsäureamide, Verfahren zu ihrer Herstellung und Arzneimittel |
| US5681794A (en) * | 1993-08-18 | 1997-10-28 | Bayer Aktiengesellschaft | N-cyanoaryl-nitrogen heterocycles |
| ES2110667T3 (es) * | 1993-08-18 | 1998-02-16 | Bayer Ag | N-cianoaril-heterociclos nitrogenados. |
| DE19543676A1 (de) * | 1995-05-03 | 1996-11-07 | Bayer Ag | Verfahren zur Herstellung von substituierten Aryluracilen |
-
1996
- 1996-12-19 DE DE19652955A patent/DE19652955A1/de not_active Withdrawn
-
1997
- 1997-12-08 EP EP97952043A patent/EP0948482B1/de not_active Expired - Lifetime
- 1997-12-08 CN CN97180717A patent/CN1100754C/zh not_active Expired - Fee Related
- 1997-12-08 WO PCT/EP1997/006842 patent/WO1998027057A2/de active IP Right Grant
- 1997-12-08 US US09/319,644 patent/US6136975A/en not_active Expired - Fee Related
- 1997-12-08 JP JP52726198A patent/JP2001506249A/ja not_active Ceased
- 1997-12-08 IL IL13009097A patent/IL130090A/xx not_active IP Right Cessation
- 1997-12-08 AU AU55607/98A patent/AU5560798A/en not_active Abandoned
- 1997-12-08 DK DK97952043T patent/DK0948482T3/da active
- 1997-12-08 BR BR9714233-6A patent/BR9714233A/pt not_active IP Right Cessation
- 1997-12-08 DE DE59706910T patent/DE59706910D1/de not_active Expired - Fee Related
-
2000
- 2000-07-05 HK HK00104129A patent/HK1029329A1/xx not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB931689A (en) * | 1960-12-17 | 1963-07-17 | Hoechst Ag | Process for the manufacture of fluorinated acetoacetic acid chlorides and the solutions thereof |
| EP0648772A1 (de) * | 1993-10-18 | 1995-04-19 | Bayer Ag | 4-Cyanophenyliminoheterocyclen |
| WO1995032952A1 (en) * | 1994-05-27 | 1995-12-07 | Ciba-Geigy Ag | Process for the preparation of 3-aryluracils |
Also Published As
| Publication number | Publication date |
|---|---|
| IL130090A (en) | 2003-06-24 |
| IL130090A0 (en) | 2000-02-29 |
| AU5560798A (en) | 1998-07-15 |
| HK1029329A1 (en) | 2001-03-30 |
| JP2001506249A (ja) | 2001-05-15 |
| EP0948482B1 (de) | 2002-04-03 |
| BR9714233A (pt) | 2000-04-18 |
| US6136975A (en) | 2000-10-24 |
| DE59706910D1 (de) | 2002-05-08 |
| CN1240423A (zh) | 2000-01-05 |
| DK0948482T3 (da) | 2002-07-22 |
| DE19652955A1 (de) | 1998-06-25 |
| WO1998027057A3 (de) | 1998-07-23 |
| WO1998027057A2 (de) | 1998-06-25 |
| EP0948482A2 (de) | 1999-10-13 |
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