CN1602301A - 4-甲基-7-氨基喹诺酮的制备工艺 - Google Patents
4-甲基-7-氨基喹诺酮的制备工艺 Download PDFInfo
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- CN1602301A CN1602301A CNA028246616A CN02824661A CN1602301A CN 1602301 A CN1602301 A CN 1602301A CN A028246616 A CNA028246616 A CN A028246616A CN 02824661 A CN02824661 A CN 02824661A CN 1602301 A CN1602301 A CN 1602301A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title abstract description 5
- 230000008569 process Effects 0.000 title abstract description 4
- MJXYFLJHTUSJGU-UHFFFAOYSA-N 7-amino-4-methyl-1h-quinolin-2-one Chemical class NC1=CC=C2C(C)=CC(=O)NC2=C1 MJXYFLJHTUSJGU-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 239000002253 acid Substances 0.000 claims abstract description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
- 125000003118 aryl group Chemical group 0.000 claims abstract description 24
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 125000003368 amide group Chemical group 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 11
- 125000002577 pseudohalo group Chemical group 0.000 claims abstract description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 9
- 150000003863 ammonium salts Chemical class 0.000 claims abstract description 9
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 84
- -1 nitro, sulfo group Chemical group 0.000 claims description 66
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 238000005516 engineering process Methods 0.000 claims description 27
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 27
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 21
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 14
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 230000008878 coupling Effects 0.000 claims description 10
- 238000010168 coupling process Methods 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- 239000002994 raw material Substances 0.000 claims description 10
- 238000009835 boiling Methods 0.000 claims description 9
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 8
- 239000005864 Sulphur Substances 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 230000005540 biological transmission Effects 0.000 claims description 8
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 7
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 7
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 7
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 claims description 5
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 5
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 5
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 claims description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims description 3
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- ZNCXUFVDFVBRDO-UHFFFAOYSA-N pyridine;sulfuric acid Chemical compound [H+].[O-]S([O-])(=O)=O.C1=CC=[NH+]C=C1 ZNCXUFVDFVBRDO-UHFFFAOYSA-N 0.000 claims description 3
- QUJLPICXDXFRSN-UHFFFAOYSA-N scandium;trifluoromethanesulfonic acid Chemical compound [Sc].OS(=O)(=O)C(F)(F)F QUJLPICXDXFRSN-UHFFFAOYSA-N 0.000 claims description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- NVJUHMXYKCUMQA-UHFFFAOYSA-N 1-ethoxypropane Chemical compound CCCOCC NVJUHMXYKCUMQA-UHFFFAOYSA-N 0.000 claims description 2
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-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
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-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
- 229940055858 aluminum chloride anhydrous Drugs 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 150000003950 cyclic amides Chemical class 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 claims description 2
- MRVDPBDPQPBGMS-UHFFFAOYSA-N trifluoromethanesulfonic acid;yttrium Chemical compound [Y].OS(=O)(=O)C(F)(F)F MRVDPBDPQPBGMS-UHFFFAOYSA-N 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 1
- 238000005580 one pot reaction Methods 0.000 claims 1
- DLRJIFUOBPOJNS-UHFFFAOYSA-N phenetole Chemical compound CCOC1=CC=CC=C1 DLRJIFUOBPOJNS-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 11
- 239000003054 catalyst Substances 0.000 abstract 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 125000004001 thioalkyl group Chemical group 0.000 abstract 1
- 239000000047 product Substances 0.000 description 33
- 239000000725 suspension Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- LXTWQCCQOZDVPB-UHFFFAOYSA-N 7-amino-6-chloro-4-methyl-1h-quinolin-2-one Chemical compound NC1=C(Cl)C=C2C(C)=CC(=O)NC2=C1 LXTWQCCQOZDVPB-UHFFFAOYSA-N 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000007524 organic acids Chemical class 0.000 description 12
- 238000001291 vacuum drying Methods 0.000 description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 239000000049 pigment Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 7
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000001993 dienes Chemical class 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- QYAZQIHXOQOZHT-UHFFFAOYSA-L O.S(=O)(=O)([O-])OS(=O)(=O)[O-].[Na+].[Na+] Chemical compound O.S(=O)(=O)([O-])OS(=O)(=O)[O-].[Na+].[Na+] QYAZQIHXOQOZHT-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N beta-methylpyridine Natural products CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 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 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 150000004780 naphthols Chemical class 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 150000003009 phosphonic acids Chemical class 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000007966 viscous suspension Substances 0.000 description 2
- 150000005045 1,10-phenanthrolines Chemical class 0.000 description 1
- IQOCHTVYLJERAT-UHFFFAOYSA-N 1-butoxybutane pyridine Chemical compound C(CCC)OCCCC.N1=CC=CC=C1 IQOCHTVYLJERAT-UHFFFAOYSA-N 0.000 description 1
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical class CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 1
- YHGKEORTCHVBQH-UHFFFAOYSA-N 2,4,6-tri(propan-2-yl)benzenesulfonic acid Chemical compound CC(C)C1=CC(C(C)C)=C(S(O)(=O)=O)C(C(C)C)=C1 YHGKEORTCHVBQH-UHFFFAOYSA-N 0.000 description 1
- UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical class CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 1
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical class CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- MWVTWFVJZLCBMC-UHFFFAOYSA-N 4,4'-bipyridine Chemical class C1=NC=CC(C=2C=CN=CC=2)=C1 MWVTWFVJZLCBMC-UHFFFAOYSA-N 0.000 description 1
- ZWUBBMDHSZDNTA-UHFFFAOYSA-N 4-Chloro-meta-phenylenediamine Chemical compound NC1=CC=C(Cl)C(N)=C1 ZWUBBMDHSZDNTA-UHFFFAOYSA-N 0.000 description 1
- BMFRPDMORIMGSG-UHFFFAOYSA-N 4-amino-2-oxo-1h-quinoline-3-sulfonic acid Chemical compound C1=CC=C2C(N)=C(S(O)(=O)=O)C(=O)NC2=C1 BMFRPDMORIMGSG-UHFFFAOYSA-N 0.000 description 1
- XFXYPUUMJJIELC-UHFFFAOYSA-N 5-amino-4-methyl-1h-quinolin-2-one Chemical compound C1=CC(N)=C2C(C)=CC(O)=NC2=C1 XFXYPUUMJJIELC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
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- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
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- YDKGFHFIDFISJC-UHFFFAOYSA-N C1CCCC2CCCCC12.[I] Chemical compound C1CCCC2CCCCC12.[I] YDKGFHFIDFISJC-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- WFKPHYKFAOXUTI-UHFFFAOYSA-N NP-101A Chemical compound CC(=O)NC1=CC=CC=C1C(N)=O WFKPHYKFAOXUTI-UHFFFAOYSA-N 0.000 description 1
- 229920000557 Nafion® Polymers 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- GTZOZDOTOWNSJH-UHFFFAOYSA-N [O].CCCCCCC Chemical compound [O].CCCCCCC GTZOZDOTOWNSJH-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- GCPWJFKTWGFEHH-UHFFFAOYSA-N acetoacetamide Chemical compound CC(=O)CC(N)=O GCPWJFKTWGFEHH-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
- 238000006149 azo coupling reaction Methods 0.000 description 1
- BEHLMOQXOSLGHN-UHFFFAOYSA-N benzenamine sulfate Chemical compound OS(=O)(=O)NC1=CC=CC=C1 BEHLMOQXOSLGHN-UHFFFAOYSA-N 0.000 description 1
- OFWBDYUSWOSTGT-UHFFFAOYSA-N benzenesulfonic acid;toluene Chemical compound CC1=CC=CC=C1.OS(=O)(=O)C1=CC=CC=C1 OFWBDYUSWOSTGT-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical group CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 description 1
- 229940043232 butyl acetate Drugs 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
- 239000007795 chemical reaction product Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 238000005837 enolization reaction Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-O hydron;quinoline Chemical group [NH+]1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-O 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- LYXSEGMJYXGXSO-UHFFFAOYSA-N iodine;toluene Chemical compound [I].CC1=CC=CC=C1 LYXSEGMJYXGXSO-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- CDXVUROVRIFQMV-UHFFFAOYSA-N oxo(diphenoxy)phosphanium Chemical compound C=1C=CC=CC=1O[P+](=O)OC1=CC=CC=C1 CDXVUROVRIFQMV-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920002717 polyvinylpyridine Polymers 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- GGZRVXCSRWTOME-UHFFFAOYSA-N pyridine;toluene Chemical compound C1=CC=NC=C1.CC1=CC=CC=C1 GGZRVXCSRWTOME-UHFFFAOYSA-N 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- GQKZRWSUJHVIPE-UHFFFAOYSA-N sec-amyl acetate Natural products CCCC(C)OC(C)=O GQKZRWSUJHVIPE-UHFFFAOYSA-N 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
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- VXIRGWZFJQYTAC-UHFFFAOYSA-M trifluoromethanesulfonate;yttrium(3+) Chemical compound [Y+3].[O-]S(=O)(=O)C(F)(F)F VXIRGWZFJQYTAC-UHFFFAOYSA-M 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Quinoline Compounds (AREA)
Abstract
本发明涉及通式(I)化合物的制备工艺,该工艺包含在一种非质子传递有机溶剂中,在催化活性量的一种强酸(催化剂)或一种能释放出强酸的试剂或一种强酸的铵盐的存在下,该催化剂也可以是起始原 料/产物的一部分,使通式(II)化合物转化成通式(I)化合物,式中,R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2或C1-8烷基、C1-8烷氧基或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子或C1-8烷基或芳基或芳烷基,R10是基团-C(O)CH2C(O)CH3,R11是氢原子或酰基,或者R10和R11是基团-C(O)CH2C(O)CH3。按照本发明的工艺执行简单,高产率地导致高化学纯度和高异构体纯度的产品。
Description
技术领域
本发明涉及式(I)的4-甲基-7-氨基喹诺酮的制备工艺。按照本发明的工艺执行简单,并高产率地导致高化学纯度和高异构体纯度的产品。
背景技术
4-甲基-6-氯-7-氨基喹诺酮的制备工艺是已知的:
US-A-3 119 808描述了例如4-甲基-6-氯-7-氨基喹诺酮的合成。首先,使1mol 4-氯间苯二胺在甲苯中与2mol双烯酮反应。然后,通过在盐酸水溶液中加热,使N,N-二乙酰乙酰基产物的结晶沉淀转化成4-甲基-6-氯-7-氨基喹诺酮。
按照DE-A-95 86 47,4-甲基-6-氯-7-氨基喹诺酮是通过先使4-氯-间苯二胺在水中与双烯酮反应、然后在硫酸的存在下加热使所得到的油状乙酰乙酰基化合物转化成4-甲基-6-氯-7-氨基喹诺酮而得到的。
进而,DE-A-24 44 519描述下式的1,2-二氢-2-氧代-4-甲基喹啉衍生物的制备工艺:
式中R是氢原子或基团-C(O)CH2C(O)CH3,其中,1mol间苯二胺分别与1mol或2mol双烯酮,在添加约5%冰乙酸的有机溶剂例如甲醇、乙酸丁酯、四氯化碳或甲苯中或在冰乙酸中,在100℃以下的温度反应。
以上所述工艺并非均匀地进行,就是说,生成了大量次级产物,从而不得不通过反应产物的重结晶将其分离出去。例如,在DE-A-9586 47中所述程序的情况下,除所希望的产物4-甲基-6-氯-7-氨基喹诺酮外,还以约14%的数量生成了所不希望的异构体4-甲基-5-氨基-6-氯喹诺酮:
发明内容
因此,本发明的目标是提供7-氨基喹啉酮、尤其4-甲基-6-氯-7-氨基喹诺酮的一种制备工艺,该工艺执行简单并以高产率导致高化学纯度和高异构体纯度的产品。
这一目标是用通式(I)化合物的制备工艺实现的:
该工艺包含使通式(II)化合物
在一种非质子传递有机溶剂中,在催化活性量的一种强酸或一种能释放出强酸的试剂或一种强酸的铵盐的存在下,该催化剂也可以是起始原料/产物的一部分,转化成式I的化合物,
式中,R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2、C1-8烷基、C1-8烷氧基或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子或者C1-8烷基或者芳基或芳烷基,R10是基团-C(O)CH2C(O)CH3,R11是氢原子或酰基,或者R10和R11是基团-C(O)CH2C(O)CH3。
因取代方式而异,式II化合物转化成式I化合物的反应条件也会改变。式II化合物向式I化合物的转化一般是在20~200℃、尤其90~130℃的温度进行的。按照本发明,非质子传递溶剂要理解成是其pKa值大于17的溶剂。非质子传递有机溶剂一般选自开链或环状酰胺,例如N,N-二甲基甲酰胺(DMF)、N,N-二甲基乙酰胺(DMA)、N-甲基吡咯烷酮(NMP),二甲基亚砜(DMSO),胺类例如伯、仲、叔烷胺类,如二正丁胺,环状芳基胺、尤其吡啶和烷基吡啶,例如2-、3-或4-甲基吡啶,和烷芳基胺类、环烷基胺类例如哌嗪、哌啶、吗啉及其N-烷基化衍生物,开链或环状酯类,例如乙酸正丁酯、γ-丁内酯或碳酸1,2-亚丙酯、丁腈,二苯醚,醚类、尤其2~8个碳原子的醚类,例如二乙醚、甲基乙基醚、二正丙醚、二异丙醚、甲基正丁基醚、甲基叔丁基醚、乙基正丙基醚、二正丁醚、四氢呋喃、1,4-二噁烷、1,2-二甲氧基乙烷、二-β-甲氧基乙基醚;脂肪族烃类,例如己烷、庚烷、低沸点或高沸点石油醚;环脂族烃类,例如环己烷、甲基环己烷、十氢萘;芳香族烃类,例如苯、甲苯、邻-、间-和对-二甲苯、乙苯、1,2,3,4-四氢萘、以及也商业上可得的芳香族溶剂和溶剂混合物,例如壳牌化学公司以商品名Shellsol销售和德国Exxon化学公司以商品名Solvesso例如Solvesso100、Solvesso150、Solvesso200(芳香族C10-C13烃溶剂)、SHELLSOL A100(芳香族C9-C10烃溶剂)或SHELLSOL A150(芳香族C10-C11烃溶剂)销售的那些,芳香族烃与醚类的混合物,例如Dow化学公司以商品名DowthermA销售的联苯与二苯醚的低共熔溶剂;卤代脂肪族或芳香族烃,例如二氯甲烷、氯仿、四氯化碳、氯苯和二氯苯;以及这样的溶剂的混合物,最好的是脂肪族醚类例如二丁醚,芳香族烃例如甲苯、Solvesso150或1,2,3,4-四氢萘,脂肪族烃例如汽油(沸点范围110-140℃)或十氢萘,芳香族烃与醚类的混合物例如DowthermA,和开链与环状酯类例如碳酸1,2-亚丙酯或乙酸正丁酯,甲苯,和二正丁醚。
式II化合物向式I化合物的转化可以在强无水无机酸例如氯化氢、溴化氢、磷酸、亚磷酸(膦酸)、硫酸、氨基磺酸、NaHSO4、过氯酸、硼酸、四氟硼酸及其酸式盐例如碳酸氢盐和硫酸氢盐,无机固体酸例如沸石、硅酸盐和泥质土,以及路易斯酸例如AlCl3、FeCl3、ZnCl2,副族III元素和镧系元素的三氟甲磺酸盐例如三氟甲磺酸钪(III)、三氟甲磺酸钇(III)和三氟甲磺酸镱(III),强有机酸例如卤代羧酸如一、二和三卤乙酸例如一氯、三氟和三氯乙酸,磺酸即有基团-SO3H作为官能团的硫酸的有机(芳香族、脂肪族、环脂族)衍生物,例如甲磺酸、叔丁基磺酸、叔辛基磺酸、叔十二烷基磺酸、环己基氨基磺酸、苯磺酸、对甲苯磺酸或氨基苯磺酸、十二烷基苯磺酸、基磺酸、2,4,6-三异丙基苯磺酸,或有机膦酸即有P-C键的膦酸的有机衍生物,例如苯基膦酸或对甲苯膦酸的存在下进行。强有机酸及其铵盐也可以是聚合物结合酸,例如全氟化树脂磺酸,如聚(全氟烯磺酸)例如Nafion,和盐类,例如甲苯磺酸聚乙烯基吡啶鎓。特别好的是对甲苯磺酸和对甲苯磺酸吡啶鎓(PPTS)以及十二烷基苯磺酸,或者强有机酸或无机酸的铵盐尤其吡啶鎓盐。
强有机酸的铵盐,除了与NH4 +的盐外,要理解成也是从伯、仲、叔铵阳离子衍生的盐,四价氮也可以是5员环或6员环的一员,这些环还可以含有另外的杂原子例如S、N和O。这样的铵阳离子的实例是式(IX)化合物:
或
式中R10、R10′和R10″彼此独立地是氢原子或者直链或枝化C1-8烷基,R11、R12和R13是氢原子、直链或枝化C1-8烷基、无取代或有1~3个C1-4烷基取代的C5-7环烷基例如环己基或3,3,5-三甲基环己基,或者芳基或芳烷基,较好的是吡啶鎓盐,也较好的是2,6-卢剔啶鎓盐、2,4,6-可力丁鎓盐、2,6-二叔丁基吡啶鎓盐、2,6-二叔丁基-4-甲基吡啶鎓盐、2,4,6-三叔丁基吡啶鎓盐和2,6-二苯基吡啶鎓盐。多个吡啶环彼此相联也是可以的。这样的化合物的实例是4,4′-联吡啶鎓盐,较好的2,2′-联吡啶鎓盐和2,2′:6′,2 ″-四吡啶鎓盐。R10、R10′和R10″合在一起也可以形成芳香族的、杂芳香族的、脂肪族的和杂脂肪族的环系。这样的环系的实例是喹啉鎓盐和四氢喹啉鎓盐。1,10-菲咯啉鎓盐和2,2′-联喹啉鎓盐是较好的。强有机酸的铵盐也可以是起始原料或产物的一部分。
进而,式II化合物向式I化合物的转化可以在一种能在所使用的反应条件下释放出强无机酸或有机酸的试剂的存在下,例如在水如溶剂中存在的残留水的存在下进行。能释放出强无机酸或有机酸的试剂的实例是SO3/吡啶络合物,无机酸的酰卤或者对称酐或不对称酐,例如P2O5、SO3、POCl3、SOCl2、PCl3或PCl5,或者有机酸如磺酸的酰卤或者对称酐或不对称酐,例如甲磺酰氯、甲苯磺酰氯或甲苯磺酐,或者羧酸的酰卤或者对称酐或不对称酐,例如2,4,6-三甲基苯甲酰氯或苯甲酰氯。较好的是以上提到的强有机酸的酰卤和酐。
催化剂同样可以是起始原料/产物的一部分。这样的催化剂的实例是式I或II的化合物,其中,取代基R5、R6和R8中至少一个是磺酸基(磺基)或磺酸基的盐(见实施例3)。
按照本发明,强有机酸或无机酸要理解成是一种其pKa值小于2.5的酸,碘值亦然。
下列催化剂是特别好的:
对甲苯磺酸吡啶鎓(PPTS)、十二烷基苯磺酸吡啶鎓、四氟硼酸吡啶鎓、硫酸氢吡啶鎓、吡啶/SO3络合物、
对甲苯磺酸、苯磺酸、十二烷基苯磺酸、对甲苯磺酰氯、对甲苯磺酸酐、苯甲酰氯、2,4,6-三甲基苯甲酰氯、硫酸、酰胺基硫酸(氨基磺酸)、硫酸氢钠、无水氯化锌、无水氯化铁(III)、无水氯化铝、三氟甲磺酸钪(III)、三氟甲磺酸钇(III)、三氟甲磺酸镱(III)、碘。
这些酸是以催化活性量使用的。当该催化剂不是起始原料或产物的一部分时,该酸的催化活性量,以式II化合物为基准,一般是0.1~20wt%、较好是5~15wt%。当该催化剂(例如,呈磺酸基、磺酸基的铵盐的形式,或呈一种能释放出磺酸基的基团的形式)是起始原料或产物的一部分时,催化剂量对应于所使用的起始原料量。
高异构体纯度和高化学纯度的产物是尤其当使用无水溶剂和试剂时得到的,若反应期间生成的水诸如通过反应水的蒸馏脱除而立即从反应平衡中撤出,则进一步提高异构体纯度和化学纯度。
按照本发明的工艺特别适用于式I化合物的制备,式中R8是氢原子或者式中R6是卤原子或拟卤素尤其氯原子或磺基且R5和R8是氢原子。
按照本发明,C1-8烷基要理解为是直链或枝化烷基,例如甲基、乙基、正丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基、正戊基、2-戊基、3-戊基、2,2-二甲基丙基、己基、庚基、2,4,4-三甲基戊基、2-乙基己基或辛基,较好的是C1-4烷基。按照本发明,C1-8烷氧基要理解为是直链或枝化O-C1-8烷基、较好O-C1-4烷基,例如甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、仲丁氧基、异丁氧基、叔丁氧基、正戊氧基、2-戊氧基、3-戊氧基、2,2-二甲基丙氧基、正己氧基、正庚氧基、正辛氧基、1,1,3,3-四甲基丁氧基或2-乙基己氧基。按照本发明,酰基要理解为是C2-18酰基、较好C2-8酰基,例如乙酰基、丙酰基、丁酰基或苯甲酰基。按照本发明,芳基要理解为是C6-24芳基、较好C6-12芳基,该芳基可以是无取代的或者有C1-4烷基或C1-4烷氧基取代的,例如苯基、4-甲基苯基、4-甲氧基苯基或萘基。按照本发明,芳烷基要理解为是C7-24芳烷基、较好C7-12芳烷基,该芳烷基可以是无取代的或者有1~3个C1-4烷基取代的,例如苄基、2-苄基-2-丙基、β-苯基乙基、α,α-二甲基苄基或ω-苯基丁基。按照本发明,芳氧基要理解为是C6-24芳氧基、较好C6-12芳氧基,例如苯氧基或4-甲基苯氧基。按照本发明,酰胺基要理解为是一个酰化氮原子,例如乙酰胺基、苯甲酰胺或4一氯苯甲酰胺基。按照本发明,硫烷基要理解为是一个有烷基取代的硫原子,烷基是在上述意义上理解的,例如甲硫基、乙硫基或叔丁硫基。按照本发明,硫芳基要理解为是一个有芳基取代的硫原子,芳基是在上述意义上理解的,例如苯硫基、4-甲基苯硫基或萘硫基。按照本发明,烷磺酰基要理解为是一种经由SO2单元键合的烷基,烷基是在上述意义上理解的,例如甲磺酰基、乙磺酰基或叔丁磺酰基。按照本发明,芳磺酰基要理解为是一种经由SO2单元键合的芳基,芳基是在上述意义上理解的,例如苯磺酰基、4-甲基苯磺酰基或萘磺酰基。按照本发明,烷基亚磺酰基要理解为是一种经由SO单元键合的烷基,烷基是在上述意义上理解的,例如甲基亚磺酰基、乙基亚磺酰基或叔丁基亚磺酰基。按照本发明,芳基亚磺酰基要理解为是一种经由SO单元键合的芳基,芳基是在上述意义上理解的,例如苯基亚磺酰基、4-甲基苯基亚磺酰基或萘基亚磺酰基。按照本发明,膦酰基要理解为是一种P(O)(OH)2基或其酯,例如膦酸二甲酯、膦酸二乙酯、膦酸二苯酯或膦酸二苄酯。“卤原子”这一术语包括氟、氯、溴或碘原子。“拟卤素”这一术语包括氰酸根、硫氰酸根(硫氰根)、叠氮根和氰根。
按照本发明的工艺导致高产率、高化学纯度和高异构体纯度的式I化合物,在4-甲基-7-氨基喹诺酮的情况下“异构体纯度”是例如理解为4-甲基-7-氨基喹诺酮与4-甲基-5-氨基喹诺酮之比的。例如,在4-甲基-6-氯-7-氨基喹诺酮的情况下,按照本发明的工艺导致产率可高达96%、异构体纯度95%以上的粗产品。在惯常精制例如乙醇重结晶之后,产率是90%,异构体纯度大于或等于98%。
因此,本发明也涉及通式(I)化合物
尤其4-甲基-6-氯-7-氨基喹诺酮或4-甲基-6-磺基-7-氨基喹诺酮,式中R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2、C1-8烷基、C1-8烷氧基、或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子、C1-8烷基或者芳基或芳烷基,其特征在于异构体纯度大于95%、尤其大于或等于98%。
用来作为闭环反应起始原料的式II化合物原则上可以通过类似于DE-C-749975中所述工艺的、1,3-二氨基苯或其衍生物与双烯酮在水溶液中的反应得到,但以下所述程序是较好的。
式中R10是基团-C(O)CH2C(O)CH3且R11是氢原子的式II化合物是通过1mol式(III)化合物
与1~1.5mol、尤其1.1~1.3mol式(IV)双烯酮
或与1~1.5mol、尤其1.1~1.3mol式(V)酯
或与1~1.5mol、尤其1.1~1.3mol 2,2,6-三甲基-4H-1,3-二噁烯-4-酮
在水性溶剂或有机溶剂、较好有机溶剂、最好非质子传递有机溶剂中的反应得到的,式中R5、R6和R8同以上定义,R12是C1-6烷基、芳基例如苯基、或芳烷基例如苄基。
式中R10是基团-C(O)CH2C(O)CH3且R11是酰基的式II化合物是相应地通过式(VII)化合物的反应得到的
式中R5、R6和R8同以上定义,且R11是酰基。
式中R10和R11是基团-C(O)CH2C(O)CH3的式II化合物是通式1mol
式(III)化合物
与2~3mol、尤其2.1~2.5mol式(IV)双烯酮
或与2~3mol、尤其2.1~2.5mol式(V)酯
或与2~3mol、尤其2.1~2.5mol 2,2,6-三甲基-4H-1,3-二噁烯-4-酮
在一种水性溶剂或有机溶剂、较好有机溶剂、最好非质子传递有机溶剂中的反应得到的,式中R5、R6、R8和R12同以上定义。
关于非质子传递溶剂,适用以上定义和优先级。如果式III化合物与双烯酮反应,则反应一般在0~60℃、较好20~40℃、尤其在常温进行。在与乙酰乙酸酯或2,2,6-三甲基-4H-1,3-二噁烯-4-酮反应的情况下,温度一般是80~170℃、尤其100~140℃。
式II产物可以进行分离、任选地进行精制、然后转化成式I化合物。然而,较好的是,将该强有机酸或该强有机酸的铵盐添加到非质子传递有机溶剂中的式II“中间体”中,使该式II“中间体”就地转化成式I化合物。就是说,按照本发明,较好的是,将式III化合物向式II化合物的转化以及所得到式II化合物向式I化合物的转化作为“单罐式反应”进行。
按照本发明的工艺中使用的或在其中作为中间体发生的式II化合物是新型的,而且使所希望的式I化合物能以高产率、高异构体纯度和高化学纯度合成。因此,本发明也涉及式(II)化合物
式中,R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2、C1-8烷基、C1-8烷氧基或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子或者C1-8烷基或者芳基或芳烷基,R10是基团-C(O)CH2C(O)CH3,R11是氢原子或酰基,或者R10和R11是基团-C(O)CH2C(O)CH3。
较好的是,R10是基团-C(O)CH2C(O)CH3且R11是氢原子。也较好的是式中取代基R5、R6和R8中至少一个不是氢原子的化合物,式中当R5和R8是氢原子时R6是氟原子、溴原子、碘原子、拟卤素、基团COOR1或CONHR2、C1-8烷基尤其C2-8烷基、C1-8烷氧基、尤其C2-8烷氧基、或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基的化合物,式中R8不是氢原子的化合物,式中R5不是氢原子和甲基的化合物。
以下所列的式II化合物是最好的:
化合物 | R5 | R6 | R8 | R10 | R11 |
B1 | H | Cl | H | C(O)CH2C(O)CH3 | H |
B2 | H | CH3 | H | C(O)CH2C(O)CH3 | H |
B3 | H | H | CH3 | C(O)CH2C(O)CH3 | H |
B4 | H | OCH3 | H | C(O)CH2C(O)CH3 | H |
B5 | H | CO2CH3 | H | C(O)CH2C(O)CH3 | H |
B6 | COOH | H | H | C(O)CH2C(O)CH3 | H |
B7 | CF3 | H | H | C(O)CH2C(O)CH3 | H |
B8 | SO3H | H | CH3 | C(O)CH2C(O)CH3 | H |
式I化合物是偶氮颜料制备用、作为重氮成分重要的起始原料(见例如DE-A-2905937和PCT/EP01/12178),式I化合物与适当偶合成分反应生成式(VI)化合物
式中R5、R6和R8同以上定义且A是一种偶合成分的残基。
式I化合物向式VI化合物的转化包含重氮化和偶合。
式I化合物的重氮化是,例如,用亚硝酸盐诸如碱金属亚硝酸盐如亚硝酸钠,在一种含无机酸的介质中例如在一种含盐酸的介质中,一般在-5~40℃、较好-5~10℃的温度进行的。
偶氮偶联反应由重氮化合物与亲核伙伴(偶联成分)的亲电取代反应组成。对偶联成分的偶联是以本身已知的方式。在酸性或中性至弱碱性pH值例如1~10的pH值、在例如-5~40℃、较好0~30℃的温度进行的。
按照本发明的工艺,有利地是通过将新鲜制备的重氮化合物溶液或悬浮液慢慢添加到弱酸性至中性的偶联成分溶液或悬浮液中、添加碱金属氢氧化物溶液例如氢氧化钠溶液使pH维持在例如pH4.5~8的中性范围、然后搅拌所得到的颜料悬浮液直至反应完成并将产物过滤分离进行的。
偶氮颜料的偶联成分一般是芳香核上有亲核中心的芳香族系、尤其萘酚或有反应性亚甲基的可烯醇化化合物(见例如Azoic CouplingComponents in Colour Index,3rd Edition,Vol.4.The Societyof Dyers和Colorists,1971,pp 4355-4364,37500-37625),偶联成分较好选自下列一组:
a)
型亚甲基活性化合物,尤其乙酰乙酸芳基化物;
b)2-羟基萘及其3-羧基衍生物,例如2′-羟基-3′-萘甲酰苯胺(萘酚AS衍生物);
c)吡唑啉酮衍生物、尤其下式的吡唑啉酮衍生物
式中R20是C1-4烷基、尤其甲基,或基团COOR1,R1同以上定义、尤其甲酯基或乙酯基,R21是氢原子、卤原子或磺基或C1-4烷基、尤其甲基(见W.Herbst,K.Hunger,Industrielle Organische Pigmente,第2全修订版,1995,pp198-203)。当使用异构体纯度大于95%的4-甲基-6-氯-7-氨基喹诺酮(PCT/EP01/12178)制备
时,所得到颜料的色相没有红移,相对大量污染物存在时情况也是如此,但该颜料显示出改善的颜色(色度)和改善的耐老化度。
具体实施方式
以下实施例说明本发明,但不限制其范围。除非另有指出,否则异构体纯度是借助于考虑了相关应答因子的HPLC确定的。
实施例1
4-甲基-6-氯-7-氨基喹诺酮(PPTS)
28.6g 4-氯-1,3-苯二胺在22℃悬浮于400ml甲苯中。在30分钟历程中在25±2℃向该灰色悬浮液中添加17.6g双烯酮的100ml甲苯溶液,该悬浮液迅速变成溶液,然后单双烯酮化产物以米黄色固体形式沉淀出来。然后搅拌在22℃进行6小时。然后添加5g对甲苯磺酸吡啶鎓(PPTS),混合物在回流下沸腾16小时。使该黄色悬浮液冷却到30℃,同时搅拌,然后在30℃添加30ml 1N NaOH。然后进一步添加100ml水。粗产物在22℃过滤、用水洗涤至中性、在60℃真空干燥过夜。得到38.5g(产率:92%,4-甲基-6-氯-7-氨基喹诺酮与4-甲基-5-氨基-6-氯喹诺酮的异构体比>95∶5)熔点350℃的米黄色固体。用乙醇重结晶导致异构体纯度98~99%、熔点358℃、产率90%的产物。
实施例2
4-甲基-6-氯-7-氨基喹诺酮(TsOH)
90.5g用水加湿的4-氯-1,3-苯二胺(干重:54.4g)导入一个2.5升磺化烧瓶内的850ml甲苯中,该烧瓶有一个KPG(校准的准确玻璃)搅拌器、内温度计、有回流冷凝器的水分离器和计泡计,棕色悬浮液边激烈搅拌边在回流下沸腾,同时恒沸地除去约36ml残留水。将混合物冷却至室温,在25±2℃的内温下在30分钟历程中将38.3g双烯酮的100ml甲苯溶液添加到该灰色悬浮液中,该悬浮液迅速变成溶液,然后该加合物以米黄色固体形式沉淀出来。搅拌在22℃进行6小时。然后添加7.6g对甲苯磺酸一水合物,然后混合物在回流下沸腾16小时。分离出约6ml水。暗黄色悬浮液搅拌冷却,然后在30℃添加48ml 1N NaOH。然后添加200ml水、进行2小时搅拌。灰色粗产物在22℃过滤、用水洗涤至中性、在60℃真空干燥过夜。得到73.8g(产率:93%,4-甲基-6-氯-7-氨基喹诺酮与4-甲基-5-氨基-6-氯喹诺酮的异构体比=97∶3)米黄色固体。用乙醇重结晶导致异构体纯度≥98%、熔点358℃、产率90%的产物。
下表显示污染物对所制备颜料的品质的影响,具体参照以下所示按照PCT/EP01/12178(实施例1)合成的偶氮颜料:
主色(一种AM标准涂料中5%着色颜料) | 耐过喷度 | 1000小时后耐老化度 | 污染1) | |
色度 | 色调 | 30min/130℃ | ΔE | % |
83.9 | 94.5 | 4.8 | 2.9 | 不可检测 |
82.4 | 95.2 | 4.6 | 3.0 | 1-2 |
81.8 | 95.8 | 4.6 | 4.1 | 5 |
79.4 | 93.9 | 4.7 | 7.0 | 18 |
76.7 | 93.3 | 4.6 | 8.3 | 22 |
1)按照HPLC分析在起始原料(4-甲基-6-氯-7-氨基喹诺酮)中的异构体污染物(4-甲基-5-氨基-6-氯喹诺酮)。
从表中可以看出,增加污染物数量导致颜料色相显著红移。除红移外,更高的污染物水平导致颜料有更差的颜色(色度)和更差的耐老化度。
实施例3
4-甲基-6-磺基-7-氨基喹诺酮的吡啶鎓盐的制备
27.23g 2-氨基-4-乙酰乙酰胺基苯磺酸在150ml吡啶中搅拌,棕黄色悬浮液在回流下沸腾。17小时后使绿色悬浮液在搅拌下冷却到70℃,混合物在射水真空下浓缩至干。绿色固体在25℃收集于60ml甲醇中、过滤、先用甲醇洗涤、然后用水洗涤、在60℃真空干燥过夜。得到26.4g(产率:79%,4-甲基-6-磺基-7-氨基喹诺酮吡啶鎓盐与4-甲基-5-氨基-6-磺基喹诺酮吡啶鎓盐的异构体比>96.1∶3.9)熔点235℃的米黄色固体。
异构体纯的氨基喹诺酮磺酸可以从该吡啶鎓盐通过在沸腾乙酸中溶解、冷却到25℃、随后过滤而得到。真空干燥后,得到95%熔点362℃的白色固体(DE-A-958647:340-350℃,分解)。
实施例4
28.6g 4-氯-1,3-苯二胺在22℃悬浮于400ml甲苯中。在30分钟的历程中在25±2℃,将17.6g双烯酮的100ml甲苯溶液添加到该灰色悬浮液中,该悬浮液迅速变成溶液,然后单双烯酮化产物以米黄色固体形式沉淀出来。反应混合物在22℃搅拌6小时、然后冷却到10℃、过滤、用甲苯洗涤。滤饼在60℃真空干燥过夜。得到44.6g(产率:98%)熔点106℃的米黄色固体。
实施例5~46
将906.6mg(4mmol)N-(3-氨基-4-氯苯基)乙酰乙酰胺和0.4mmol催化剂导入8ml溶剂中。该溶液或悬浮液在100℃搅拌加热16小时。所得到的悬浮液冷却到70℃;添加3ml绝对乙醇,悬浮液在回流下加热2小时。将悬浮液冷却到室温、过滤、用2ml绝对乙醇洗涤、再次用1ml绝对乙醇洗涤、然后用20ml水洗涤,所得到的残留物在60℃真空干燥过夜。干燥产物用HPLC(高性能液相色谱法)分析并与真实样品比较。
用不同溶剂和催化剂得到的产率和产物分布列于表1中。
产物A: 产物B: 产物C:
表1
实施例 | 溶剂 | 催化剂 | 产率〔%〕 | 产物A〔%〕 | 产物B〔%〕 | 产物C〔%〕 |
5 | 二丁醚 | 四氟硼酸吡啶鎓 | 94.6 | 97.5 | 2.3 | 0.2 |
6 | 二丁醚 | 对甲苯磺酸吡啶鎓 | 94.1 | 96.6 | 3.0 | 0.3 |
7 | 二丁醚 | 对甲苯磺酸 | 93.5 | 95.1 | 4.5 | 0.4 |
8 | 甲苯 | 四氟硼酸吡啶鎓 | 93.4 | 98.1 | 1.7 | 0.2 |
9 | 汽油(沸点范围110-140℃) | 对甲苯磺酸吡啶鎓 | 93.4 | 96.9 | 3.0 | 0.1 |
10 | 二丁醚 | 碘 | 93.2 | 97.3 | 2.5 | 0.1 |
11 | 二丁醚 | 硫酸氢钠水合物 | 93.2 | 94.3 | 5.3 | 0.3 |
12 | 二丁醚 | 十二烷基苯磺酸/吡啶(1∶1) | 92.8 | 95.3 | 4.2 | 0.4 |
13 | 二丁醚 | 十二烷基苯磺酸吡啶鎓 | 92.7 | 95.1 | 4.3 | 0.5 |
14 | 十氢萘 | 对甲苯磺酸吡啶鎓 | 92.7 | 96.8 | 3.0 | 0.2 |
15 | 二丁醚 | 吡啶/SO3加合物 | 92.0 | 94.5 | 5.2 | 0.3 |
16 | 二丁醚 | 氯化锌(无水) | 91.4 | 98.1 | 1.4 | 0.4 |
17 | DowthermA | 对甲苯磺酸吡啶鎓 | 91.3 | 96.1 | 3.6 | 0.3 |
18 | 二丁醚 | 氯化铁(III)(无水) | 91.1 | 97.0 | 2.5 | 0.5 |
19 | 甲苯 | 吡啶/SO3加合物 | 91.1 | 95.8 | 4.1 | 0.1 |
20 | 甲苯 | 氯化铁(III)(无水) | 90.7 | 98.0 | 1.7 | 0.3 |
21 | 1,2,3,4-四氢萘 | 对甲苯磺酸吡啶鎓 | 90.6 | 97.2 | 2.7 | 0.1 |
22 | 甲苯 | 硫酸氢钠水合物 | 90.5 | 95.7 | 4.0 | 0.2 |
23 | 甲苯 | 对甲苯磺酸吡啶鎓 | 90.5 | 96.7 | 3.1 | 0.2 |
24 | 十氢萘 | 碘 | 89.8 | 96.8 | 3.0 | 0.2 |
实施例 | 溶剂 | 催化剂 | 产率〔%〕 | 产物A〔%〕 | 产物B〔%〕 | 产物C〔%〕 |
25 | 甲苯 | 苯磺酸 | 89.6 | 96.3 | 3.6 | 0.1 |
26 | 二丁醚 | 十二烷基苯磺酸 | 89.2 | 96.0 | 3.6 | 0.3 |
27 | 十氢萘 | 十二烷基苯磺酸 | 88.8 | 95.1 | 4.4 | 0.5 |
28 | 碳酸1,2-亚丙酯 | 对甲苯磺酸吡啶鎓 | 88.6 | 96.5 | 3.4 | 0.1 |
29 | 二丁醚 | 0.5对甲苯磺酸酐 | 88.6 | 96.4 | 3.3 | 0.3 |
30 | 甲苯 | 碘 | 88.5 | 97.4 | 2.5 | 0.1 |
31 | 甲苯 | 对甲苯磺酸 | 88.5 | 98.1 | 1.7 | 0.1 |
32 | 十氢萘 | 对甲苯磺酸 | 88.2 | 96.0 | 3.7 | 0.2 |
33 | 碳酸1,2-亚丙酯 | 碘 | 87.8 | 97.8 | 2.1 | 0.1 |
34 | 二丁醚 | 对甲苯磺酰氯 | 87.8 | 96.4 | 3.5 | 0.1 |
35 | 甲苯 | 0.5对甲苯磺酸酐 | 87.7 | 96.6 | 3.3 | 0.1 |
36 | 二丁醚 | 三氟甲磺酸钇(III) | 87.3 | 99.0 | 0.7 | 0.3 |
37 | 十氢萘 | 0.5对甲苯磺酸酐 | 87.1 | 96.2 | 3.6 | 0.2 |
38 | 1,2,3,4-四氢萘 | 碘 | 87.0 | 97.3 | 2.4 | 0.2 |
39 | 二丁醚 | 三氟甲磺酸镱(III) | 86.5 | 98.9 | 0.9 | 0.2 |
40 | 甲苯 | 三氟甲磺酸镱(III) | 86.4 | 99.2 | 0.7 | 0.1 |
41 | 1,2,3,4-四氢萘 | 0.5对甲苯磺酸酐 | 86.3 | 96.3 | 3.4 | 0.2 |
42 | 甲苯 | 三氟甲磺酸钇(III) | 86.3 | 99.4 | 0.5 | 0.1 |
43 | γ-丁内酯 | 碘 | 80.2 | 98.8 | 1.1 | 0.1 |
44 | N,N-二甲基乙酰胺 | 对甲苯磺酸吡啶鎓 | 68.1 | 99.2 | 0.6 | 0.1 |
45 | N-甲基吡咯烷酮 | 对甲苯磺酸吡啶鎓 | 65.7 | 99.0 | 0.9 | 0.1 |
46 | 甲苯 | 硫酸氢吡啶鎓 | 89.7 | 93.0 | 6.9 | 0.1 |
比较例6 | 甲苯 | (参考) | 16.4 | 0.1 | 0.1 | 99.8 |
比较例1(DE-A-2444519)
将28.6g 4-氯-1,3-苯二胺在22℃悬浮于400ml甲苯中。在30分钟历程中在25±2℃向该灰色悬浮液中添加17.7g双烯酮的100ml甲苯溶液,该悬浮液迅速变成溶液,然后单双烯酮化产物以固体形式沉淀出来。然后搅拌在22℃进行6小时。然后添加1.2g AcOH(100%),混合物在回流下沸腾16小时。将暗棕色粘性悬浮液搅拌冷却到30℃,然后在30℃添加30ml 1N NaOH。然后进一步添加100ml水和200ml25%NaCl水溶液;使混合物冷却到10℃,进一步搅拌2小时。将上清液水相和浅棕色有机相滗析出来,剩余的粘性黑棕色残留物与200ml异丙醇一起搅拌。将暗色结晶物料滤出,滤液中溶解的成分通过添加150g冰沉淀;再次进行过滤,合并的沉淀物用50ml水洗涤、暗棕色粗产物在60℃真空干燥过夜。得到12.5g(产率:30%)棕色固体(熔点230℃),按照HPLC,该固体以约10%数量含有所希望的4-甲基-6-氯-7-氨基喹诺酮。
比较例2(DE-A-24 44 519)
将21.6g 1,3-苯二胺在22℃悬浮于400ml甲苯中。在30分钟历程中在25±2℃,向该灰色悬浮液中添加17.7g双烯酮的100ml甲苯溶液,该悬浮液变成粘性物料。然后搅拌在22℃进行6小时。然后添加1.2g AcOH(100%),混合物在回流下沸腾16小时。将黄色粘性悬浮液搅拌冷却到30℃,然后在30℃添加30ml 1N NaOH。然后进一步添加100ml水和200ml 25%NaCl水溶液,将混合物冷却到10℃,然后进一步搅拌2小时。将黄色悬浮液过滤、然后用1500ml水洗涤,深黄色粗产物在60℃真空干燥过夜。得到31.3g(产率:90%)熔点249℃的深黄色固体,以90%的数量含有所希望的4-甲基-7-氨基喹诺酮。用甲醇重结晶后,得到熔点280℃的白色结晶。
比较例3(DE-A-958647)
将17.2g 95%4-氯-1,3-二氨基苯熔解于250g温水中。在搅拌下,在1小时历程中在90~95℃,滴加9.3g双烯酮,乙酰乙酰基化合物部分地以油状形式析出。在添加27g 2N硫酸之后,混合物在95℃加热2小时。油状乙酰乙酰基化合物迅速变成微细结晶暗棕色沉淀。热的反应混合物用30ml 2N NaOH中和,进一步搅拌30分钟。将热的反应混合物过滤,用100ml冷水分批洗涤至中性。深棕色产物在60℃真空干燥。得到18g(产率78%,4-甲基-6-氯-7-氨基喹诺酮∶4-甲基-5-氨基-6-氯喹诺酮∶尚未鉴定产物=约86∶13∶1)熔点345℃的暗棕色固体。
比较例4(DE-A-1278039)
8.4g双烯酮与15g甲苯一起搅拌,以能使反应热引起温度上升到60~70℃的速率添加7.2g 4-氯-1,3-二氨基苯。在60~70℃搅拌1小时后,将混合物冷却到15℃。将50g水和10g HCl(37%)导入该黑色油状物中,然后将混合物蒸馏直至达到95~100℃的沸腾温度。将该温度维持2小时。约1小时后,在黑色溶液变成悬浮液。然后使该灰绿色悬浮液冷却到15℃、搅拌30分钟、过滤。将灰绿色滤饼导入50g水中;添加5g乙酸钠,使混合物沸腾1小时。然后,将混合物冷却到室温、将悬浮液过滤。灰色产物用200g冷水洗涤至中性、在60℃真空干燥。得到6g(产率58%,4-甲基-6-氯-7-氨基喹诺酮与4-甲基-5-氨基-6-氯喹诺酮的异构体比=约53∶47)熔点290℃的灰色固体。
比较例5(DE-A-958647)
将18.8g(0.1mol)4-磺基-1,3-苯二胺悬浮于150ml水中,将悬浮液加热到35℃。在60分钟的历程中,在35~40℃,向该灰色悬浮液中添加9.3g(0.11mol)双烯酮。在30分钟历程中将混合物加热到92℃;然后向该黄绿色悬浮液中添加4g 5N HCl,混合物进一步在回流下沸腾2小时。然后进一步添加33g 5N HCl。将悬浮液冷却到22℃、过滤、用合计150ml冷水分批洗涤。灰色产物在60℃真空干燥过夜。得到9g(产率35%,4-甲基-6-磺基-7-氨基喹诺酮∶4-甲基-5-氨基-6-磺基喹诺酮∶尚未鉴定产物之比=71∶21∶8)熔点288℃的米黄色固体。
Claims (12)
1.通式(I)化合物的制备工艺
该工艺包含使通式(II)化合物
在一种非质子传递有机溶剂中,在催化活性量的一种强酸(催化剂)或一种能释放出强酸的试剂或一种强酸的铵盐的存在下转化成式I化合物,该催化剂也可以是起始原料/产物的一部分,
式中,R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2、C1-8烷基、C1-8烷氧基或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子或者C1-8烷基或者芳基或芳烷基,R10是基团-C(O)CH2C(O)CH3,R11是氢原子或酰基,或者R10和R11是基团-C(O)CH2C(O)CH3。
4.按照权利要求1~3中任何一项的工艺,其中,式II化合物向式I化合物的转化是在20~200℃的温度进行的。
5.按照权利要求1~4中任何一项的工艺,式中R6是磺基、卤原子或拟卤素、尤其氯原子。
6.按照权利要求1~5中任何一项的工艺,式中R5和R8是氢原子。
7.按照权利要求1~6中任何一项的工艺,其中,非质子传递有机溶剂选自脂肪族醚类,尤其有2~8个碳原子的那些,例如二乙醚、甲基乙基醚、二正丙醚、二异丙醚、甲基正丁基醚、甲基叔丁基醚、乙基正丙基醚、二正丁醚、四氢呋喃、1,4-二噁烷、1,2-二甲氧基乙烷、二-β-甲氧基乙基醚;有7~10个碳原子的芳香族-脂肪族醚类,例如茴香醚、苯乙醚;有12~16个碳原子的芳香族醚类,例如二苯醚或二甲苯醚;脂肪族烃类,例如己烷、庚烷、低沸点或高沸点石油醚;环脂族烃类,例如环己烷、甲基环己烷、十氢萘;芳香族烃类,例如苯、甲苯、邻二甲苯、间二甲苯、对二甲苯、乙基苯、1,2,3,4-四氢萘、联苯;卤代脂肪族或芳香族烃,例如二氯甲烷、氯仿、四氯化碳、氯苯、二氯苯;开链或环状的酯类,例如乙酸正丁酯、碳酸1,2-亚丙酯、γ-丁内酯;开链或环状的酰胺类,例如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮,和这样的溶剂的混合物。
8.按照权利要求1~7中任何一项的工艺,其中,该催化剂选自对甲苯磺酸吡啶鎓(PPTS)、十二烷基苯磺酸吡啶鎓、四氟硼酸吡啶鎓、硫酸氢吡啶鎓、吡啶/SO3络合物、对甲苯磺酸、苯磺酸、十二烷基苯磺酸、对甲苯磺酰氯、对甲苯磺酸酐、苯甲酰氯、2,4,6-三甲基苯甲酰氯、硫酸、酰胺基硫酸(氨基磺酸)、硫酸氢钠、无水氯化锌、无水氯化铁(III)、无水氯化铝、三氟甲磺酸钪(III)、三氟甲磺酸钇(III)、三氟甲磺酸镱(III)和碘。
9.按照权利要求1~8中任何一项的工艺,其中,式III化合物向式II化合物的转化和所得到式II化合物向式I化合物的转化是作为一种一罐式反应(one-pot reaction)进行的。
12.通式(I)化合物
式中R5、R6和R8彼此独立地是氢原子、硝基、磺基、卤原子、拟卤素、基团COOR1或CONHR2或C1-8烷基、C1-8烷氧基或芳氧基、酰胺基、硫烷基或硫芳基、烷基-或芳基-磺酰基、烷基-或芳基-亚磺酰基、三氟甲基或膦酰基,R1和R2是氢原子、C1-8烷基或者芳基或芳烷基,其异构体纯度大于95%、尤其大于或等于98%。
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CN114907260A (zh) * | 2022-05-27 | 2022-08-16 | 河南省科学院高新技术研究中心 | 一种利用离子液体制备4-溴甲基喹啉酮的方法 |
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DE10107813A1 (de) * | 2001-02-20 | 2002-09-05 | Bosch Gmbh Robert | Drucksensormodul |
US7459469B2 (en) | 2004-11-10 | 2008-12-02 | Targacept, Inc. | Hydroxybenzoate salts of metanicotine compounds |
CN103232389A (zh) * | 2013-05-08 | 2013-08-07 | 浙江新三和医药化工股份有限公司 | 2-氯甲基-4-甲氧基-3,5-二甲基吡啶盐酸盐的制备方法 |
US11345873B2 (en) * | 2019-08-14 | 2022-05-31 | Valvoline Licensing And Intellectual Property Llc | Lubricant composition containing ashless TBN molecules |
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US2152786A (en) * | 1936-07-09 | 1939-04-04 | Carbide & Carbon Chem Corp | Preparation of acetoacetyl aromatic acid amides |
US2311054A (en) * | 1939-06-30 | 1943-02-16 | Eastman Kodak Co | Preparation of amino compounds |
US2688543A (en) * | 1950-12-20 | 1954-09-07 | Gen Aniline & Film Corp | Poly-acetoacetyl derivatives of polyamines as azo components in diazotype photoprinting material |
DE958647C (de) * | 1952-12-28 | 1957-02-21 | Hoechst Ag | Verfahren zur Herstellung von 7-Amino-2-oxy-4-methyl-chinolinen |
US2936306A (en) | 1957-05-17 | 1960-05-10 | Ciba Ltd | Azo-dyestuffs |
US3119808A (en) * | 1960-11-14 | 1964-01-28 | Ici Ltd | 7-(monoacetoacet monoarylide)-azo-4-methyl-2-hydroxy-quinoline coloring matters |
DE1278039B (de) * | 1960-11-18 | 1968-09-19 | Ici Ltd | Verfahren zur Herstellung von Azofarbstoffen |
US3304328A (en) * | 1963-10-25 | 1967-02-14 | Fmc Corp | Preparation of acetoacetarylamides |
FR1451064A (fr) * | 1965-10-22 | 1966-06-24 | Fmc Corp | Procédé d'obtention d'acéto-acétarylamides en milieu aqueux |
US3933886A (en) | 1971-10-04 | 1976-01-20 | Henkel & Cie Gmbh | Diamino-nitro-benzene compounds |
US3907494A (en) * | 1971-10-04 | 1975-09-23 | Therachemie Chem Therapeut | Hair dyes based on diamino-nitro-benzene compounds |
DE2149467A1 (de) * | 1971-10-04 | 1973-04-12 | Therachemie Chem Therapeut | Haarfaerbemittel |
US4064131A (en) | 1973-09-20 | 1977-12-20 | Lonza, Ltd. | Process for the production of 1,2-dihydro-2-oxo-4-methyl-7-acetoacetic acid amido-quinoline |
JPS5058080A (zh) * | 1973-09-20 | 1975-05-20 | ||
FR2286813A1 (fr) * | 1974-10-03 | 1976-04-30 | Roussel Uclaf | Nouveaux crotonanilides substitues, procede de preparation et compositions pesticides les contenant |
DE2519036A1 (de) * | 1975-04-29 | 1976-11-11 | Hoechst Ag | Verfahren zur herstellung von acetoacetylarylamiden |
DE3604050A1 (de) * | 1986-02-08 | 1987-08-13 | Boehringer Mannheim Gmbh | Thioether, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
JPS62215660A (ja) * | 1986-03-17 | 1987-09-22 | Nippon Kayaku Co Ltd | アゾ化合物及びそれを用いる基材の染色法 |
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JP2005518373A (ja) | 2005-06-23 |
AU2002358085A1 (en) | 2003-06-23 |
US20050222397A1 (en) | 2005-10-06 |
KR20040065577A (ko) | 2004-07-22 |
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US7144993B2 (en) | 2006-12-05 |
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