CN1367769A - Process for catalyzing oxidation of organic compounds - Google Patents
Process for catalyzing oxidation of organic compounds Download PDFInfo
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- CN1367769A CN1367769A CN00811067A CN00811067A CN1367769A CN 1367769 A CN1367769 A CN 1367769A CN 00811067 A CN00811067 A CN 00811067A CN 00811067 A CN00811067 A CN 00811067A CN 1367769 A CN1367769 A CN 1367769A
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- 230000003647 oxidation Effects 0.000 title claims abstract description 21
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 21
- 150000002894 organic compounds Chemical class 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims description 47
- 239000002904 solvent Substances 0.000 claims description 71
- 238000006243 chemical reaction Methods 0.000 claims description 32
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 11
- 239000012429 reaction media Substances 0.000 claims description 11
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 9
- 239000003444 phase transfer catalyst Substances 0.000 claims description 7
- 230000005540 biological transmission Effects 0.000 claims description 5
- 239000000376 reactant Substances 0.000 claims description 5
- 125000003118 aryl group Polymers 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003849 aromatic solvent Substances 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 150000005621 tetraalkylammonium salts Chemical group 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001931 aliphatic group Polymers 0.000 claims description 2
- XJWSAJYUBXQQDR-UHFFFAOYSA-M dodecyltrimethylammonium bromide Chemical group [Br-].CCCCCCCCCCCC[N+](C)(C)C XJWSAJYUBXQQDR-UHFFFAOYSA-M 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 230000007704 transition Effects 0.000 claims 3
- 230000003197 catalytic effect Effects 0.000 abstract description 9
- 239000000010 aprotic solvent Substances 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 description 21
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 15
- -1 N-oxide compound Chemical class 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 230000001590 oxidative effect Effects 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 6
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 description 6
- 229960002640 nordazepam Drugs 0.000 description 6
- 229910004013 NO 2 Inorganic materials 0.000 description 5
- 229960003529 diazepam Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 description 5
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 239000011877 solvent mixture Substances 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- 239000011572 manganese Substances 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- AKPLHCDWDRPJGD-UHFFFAOYSA-N nordazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 AKPLHCDWDRPJGD-UHFFFAOYSA-N 0.000 description 4
- AQNQGBUEVCAVML-UHFFFAOYSA-N oxazepane Chemical compound C1CCNOCC1 AQNQGBUEVCAVML-UHFFFAOYSA-N 0.000 description 4
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
- JSTXCWJWQKRPIU-UHFFFAOYSA-N 6-chloro-1-methyl-4-phenylquinazolin-2-one Chemical compound N=1C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 JSTXCWJWQKRPIU-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000036267 drug metabolism Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960003188 temazepam Drugs 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- DBKIXSRJBMRMMF-UHFFFAOYSA-N 6-chloro-4-phenyl-1h-quinazolin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N=C1C1=CC=CC=C1 DBKIXSRJBMRMMF-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- JZRYQZJSTWVBBD-UHFFFAOYSA-N pentaporphyrin i Chemical compound N1C(C=C2NC(=CC3=NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 JZRYQZJSTWVBBD-UHFFFAOYSA-N 0.000 description 2
- 150000004032 porphyrins Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- XEMRAKSQROQPBR-UHFFFAOYSA-N (trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=CC=C1 XEMRAKSQROQPBR-UHFFFAOYSA-N 0.000 description 1
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 1
- WACNXHCZHTVBJM-UHFFFAOYSA-N 1,2,3,4,5-pentafluorobenzene Chemical compound FC1=CC(F)=C(F)C(F)=C1F WACNXHCZHTVBJM-UHFFFAOYSA-N 0.000 description 1
- AJKNNUJQFALRIK-UHFFFAOYSA-N 1,2,3-trifluorobenzene Chemical compound FC1=CC=CC(F)=C1F AJKNNUJQFALRIK-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- NGXVDUIXYSLOHT-UHFFFAOYSA-N C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C=CC(N1)=C2.[Cl] Chemical compound C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C=CC(N1)=C2.[Cl] NGXVDUIXYSLOHT-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum 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
- 238000011084 recovery Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B33/00—Oxidation in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen 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)
- Catalysts (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
Oxidation of organic compounds is catalyzed by addition of a catalytic amount of a metalloporphyrin in a non-reactive aprotic solvent.
Description
Invention field
The research of drug metabolism is the drug research of costliness and the important component part of performance history.In human and other Mammalss, many medicines carry out metabolism by the enzymatic oxidizing reaction that contains protoheme and cytopigment.FscP is the main enzyme that relates in the oxidation of drug metabolism, contains heme moiety in its active centre.
The synthetic metalloporphyrin can advantageously be used for imitating the catalytic oxidation that occurs in living things system, in order to generate and identify the oxidation products of the medicine candidate thing of the quantity of permission in the research in vivo.
PCT application WO96/08455 discloses a kind of method of coming the oxygenerating product with the various compositions of synthetic metalloporphyrin, secondary oxidizer and solvent.Solvent is generally CH
3CN/CH
3C
l2 compositions.One of main trouble of these class methods is, they usually obtain the incomplete productive rate of the single product sought and low transformation efficiency.Therefore, they seldom reliably mode be used for whole discovery procedure.In fact, their application is limited to experiment validity usually.
Summary of the invention
According to the present invention, the inventor is surprised to find that, can improve the productive rate of the oxidizing reaction that relates to metalloporphyrin in significant mode by using the inert aprotonic solvent, and they are synthetic applicable to interesting organic compound metabolite.
Therefore, an object of the present invention is a kind of method for oxidation of organic compound.Described method comprise selected organic compound in the presence of the inert aprotonic solvent with the metalloporphyrin and the oxidant reaction of catalytic quantity, therefrom reclaim the product of wanting that obtains then.
Method of the present invention is specially adapted to drug research and exploitation, because it can be used to carry out the pre-evaluation of such metabolic process, when given compound was tested in vivo, described metabolic process may take place.These pre-evaluations can be carried out fast, and needn't carry out experiment in the expensive time-consuming body.In addition, method of the present invention obtains the more single product of high yield than the method for using prior art.In other words, method of the present invention has been opened up in the mode of system more the selected compounds that carries out this method has been made and analyzed the single possibility that may metabolite of high number more.
Detailed Description Of The Invention
So, the present invention relates to the method that a kind of the efficient oxidation prepares the organic compound metabolite.The present invention includes interesting organic compound in non-reacted non-proton transmission solution with the metalloporphyrin and the oxidant reaction of catalytic quantity.The present invention also comprises recovery and identifies the reaction product of wanting.
As above-mentioned, several drugs carries out metabolism by oxidizing reaction.So method of the present invention advantageously is applicable to the interesting organic compound that contains the one or more functional groups that react under oxidizing condition.Some are described hereinafter in these functional groups, but as those skilled in the art be readily appreciated that, do not plan to provide functional group inventory exhaustively.In fact, method of the present invention can be used for any can be in some way by the organic compound of the oxydasis that relates in the oxidation of drug metabolism.
Preferably, contain heteroatoms for example the compound of nitrogen or sulphur can specifically be oxidized to higher oxidation state by method of the present invention oxidation effectively, more specifically be oxidized to their highest oxidation state.For example, primary amine can be easy to change into corresponding azanol, nitroso-group or nitro-derivative; And tertiary amine changes into corresponding N-oxide compound.
Equally, according to the present invention, c h bond also can be easy to hydroxylation and become the C-OH key by the oxygenizement of catalysis of metalloporphyrin.Example comprises active c h bond, for example is in c h bond or the carbon atom and the adjacent c h bond of heteroatoms (for example N, S, O etc.) of benzylic positions.These c h bonds particularly have reactivity to these reaction conditionss.Use this method, primary alconol can change into corresponding aldehyde; And aldehyde can change into corresponding acid, and further decarboxylation of described acid.
Use method of the present invention, secondary alcohol can change into corresponding ketone.
According to the present invention, carbon-to-carbon double bond can pass through the oxygenizement epoxidation of catalysis of metalloporphyrin, and corresponding phenol of the oxidable one-tenth of aromatic base or quinone.
The significant parameter that relates in the methods of the invention is raw material (being generally interesting organic compound), reactant (generally including metalloporphyrin), oxygenant and inert aprotonic solvent and comprises temperature of reaction and the reaction conditions in reaction times.To further go through each in these parameters below.
Metalloporphyrin
The synthetic metalloporphyrin is open in International Patent Application WO 96/08455.As used herein, term " metalloporphyrin " refers to the porphyrin compound of molecular formula (I):
In the formula, R
1, R
2And R
3Represent hydrogen or electron-withdrawing group independently, for example Cl, F, Br, SO
3Na etc.; R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Represent hydrogen or electron-withdrawing group independently, for example Cl, F, Br, NO
2, CN, SO
3Na etc.; R
12Be Cl, acetate moiety etc.; M chosen from Fe, manganese, chromium, ruthenium, cobalt, copper and mickel.
Preferred metalloporphyrin comprises four (pentafluorophenyl group) porphyrin Manganous chloride tetrahydrate (III), is abbreviated as Mn (TPFPP) Cl here, and it is such compound in the above-mentioned molecular formula (I), and wherein M is a manganese, R
1, R
2And R
3Be fluorine, R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
12Be chlorine.
Preferred metalloporphyrin comprises that also four (pentafluorophenyl group) porphyrin iron(ic) chloride is abbreviated as Fe (TPFPP) Cl, and it is such compound in the above-mentioned molecular formula (I), and wherein M is an iron, R
1, R
2And R
3Be fluorine, R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
12Be chlorine.
Four (2, the 6-dichlorophenyl) porphyrin Manganous chloride tetrahydrate is abbreviated as Mn (TDCPP) Cl, and it is such compound in the above-mentioned molecular formula (I), and wherein M is a manganese, R
1Be muriate, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
17Be chlorine;
Four (2, the 6-dichlorophenyl) porphyrin iron(ic) chloride is abbreviated as Fe (TDCPP) Cl, and it is such compound in the above-mentioned molecular formula (I), and wherein M is an iron, R
1Be muriate, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
12Be chlorine;
Four (2, the 6-dichlorophenyl)-eight chlorine porphyrin iron(ic) chloride are abbreviated as Fe (TDCPCl
8P) Cl, it is such compound in the above-mentioned molecular formula (I), wherein M is an iron, R
1Be muriate, R
2And R
3Be hydrogen, R
4, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be muriate, and R
12Be chlorine;
The Mn ((Cl of above-mentioned molecular formula (I)
2Ph)
4(NO
2) P) the Cl compound, wherein M is a manganese, R
1Be muriate, R
4Be NO
2, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
12Be chlorine;
The Mn ((Cl of above-mentioned molecular formula (I)
2Ph)
4(NO
2) P) the Cl compound, wherein M is a manganese, R
1Be muriate, R
5And R
6Be NO
2, R
2, R
3, R
7, R
8, R
9, R
10And R
11Be hydrogen, and R
12Be chlorine;
The quantity of catalysis of metalloporphyrin agent is generally 0.5-10% (mole), is preferably about 1% (mole).
Oxygenant
Various oxygenants all can be used for the present invention.Should be pointed out that in the method for the present invention that it seems that the person's character of oxygenant be not limiting factor.Therefore, those skilled in the art can select suitable oxygenant at various compound of the oxidizing reaction that is used for catalysis of metalloporphyrin.A series of possible oxygenants comprise but the anhydrous Equivalent that is not limited to iodosobenzene, aqueous hydrogen peroxide solution (concentration is about 30 to 45%), hydrogen peroxide for example SPC-D, perhydrit title complex etc., Potassium peroxysulfate, clorox, tert-butyl hydroperoxide, cumene hydroperoxide, metachloroperbenzoic acid and monoperphthalic acid magnesium.Preferred oxygenant comprises iodosobenzene, any hydrogen peroxide cource and Potassium peroxysulfate.
For example in the presence of the basic imidazoles of imidazoles, ammonium acetate, N-, amine n-oxide, tetrabutyl ammonium acetate, tert .-butylpyridine, pyridine, 4-picoline and the 2, use the oxidation of hydrogen peroxide more effective at cocatalyst.Referring to " state of the art of bionic oxidation catalyzer development " Rocha Gonsalves, A.M; Pereira, M.M. Journal of Molecular Catalysis magazine; Chemistry, 1996,113,209.
Solvent
The oxidation of catalysis of metalloporphyrin of the present invention is carried out in inert solvent, and in fact the latter can be contained one or more solvents.When used herein, term " inert aprotonic solvent " is used for naming any such solvent or solvent mixture, and when estimating with general mode, it is not with any tangible mode and raw material or and reaction.More particularly, described solvent not with oxidant reaction.In addition, described solvent also should resist and takes the hydrogen effect by force.
Under the situation of solvent mixture, this mixture contains so-called " main solvent " and " auxilliary solvent " usually.But several solvents that should be pointed out that similarity can be used to make main solvent.Similarly consider to be applicable to the final mixture of auxilliary solvent.
In solvent mixture, the quantity of main solvent is greater than auxilliary solvent.
In fact, what give that whole solvent mixture provides whole character is main solvent, and it plays a crucial role in the method for the invention.So main solvent should be inert and non-proton transmission.
In order to reach degree as much as possible, main solvent should have the ability of dissolving raw material (i.e. You Xingqu organic compound) and metalloporphyrin.
The example of main solvent includes but not limited to polyhalogenated aliphatic solvents, for example 1,1, and 2-three chloro-1,2,2-trichloroethane etc. or polyhalogenated aromatic solvent for example 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, penta fluoro benzene etc.Preferred polyhalogenated solvent comprises polyfluorizated aromatic substance, for example phenylfluoroform etc.Phenylfluoroform is most preferred solvent, and it will dissolve the ability of various organic compound and the low reactivity of oxidizing condition is combined.
Though those skilled in the art can determine the optimal number of the main solvent that will use by the experiment of routine under each individual cases, the suitable concentration of raw material in selected solvent can be in 0.1-0.5 volumetric molar concentration range, preferred 0.1 volumetric molar concentration.
The auxilliary quantity of solvent in mixture is less, the character that its adding provides some to add for whole solvent mixture; In some aspects, it is useful, but it does not influence reaction itself in tangible mode.
In first embodiment of the inventive method, if any is insoluble to main solvent in interesting organic compound or the oxygenant, so auxilliary solvent can be used to improve their solvabilities in reaction medium.
For example, if raw material is insoluble to phenylfluoroform or any available main solvent, for the solvability of improving in reaction medium can be used auxilliary solvent.Preferred solvent comprises the auxilliary solvent of height polar and low nucleophilicity.Preferably, should select the character of auxilliary solvent like this, so that generate the title complex maximization with metalloporphyrin.2,2,2 tfifluoroethyl alcohol, particularly 1,1,1,3,3,3-hexafluoro propan-2-ol (being also referred to as hexafluoroisopropanol or HFIP) is the typical example of the auxilliary solvent that can be used for the inventive method.More particularly, in a kind of above-mentioned organic solvent, hexafluoroisopropanol may be to be applicable to the oxidizing reaction of using iodosobenzene to carry out, because this auxilliary solvent helps this specific oxygenant to be dissolved in reaction medium.
With respect to main solvent, be used to make the quantity of the auxilliary solvent of raw material or oxygenant and final catalyst dissolution should remain on low relatively level.Though those skilled in the art can be identified for the optimal number of the auxilliary solvent of each individual cases by the experiment of routine, with respect to main solvent, the solubility that is fit to can be in 1-30%, preferred 1-20%, more preferably 1-10% range.
In second embodiment of the inventive method, also can use auxilliary solvent in order to make reactant be easy in reaction medium, shift.For example, under being formed with the situation of reaction mixture of two phase liquid, raw material or one or several reactant use auxilliary solvent.
For example, be that the aqueous solution and reaction are under the situation of two phase reaction at oxygenant, can make the miscible auxilliary solvent of water, so that oxygenant is easy to shift in organic phase.A spot of auxilliary solvent for example hexafluoroisopropanol is preferred.This auxilliary solvent can be miscible with water, and it can promote the dissolving of raw material.
The quantity that is used for the auxilliary solvent that second embodiment represents with catalytic amount is generally 0.25-1 equivalent, preferred 0.3-0.5 equivalent, 0.4 equivalent more preferably from about with respect to raw material.
As the replacement scheme of second embodiment of the present invention, can use phase-transfer catalyst promote any reactant transfer to react mutually in.For example, when using aqueous oxidizing agent solution, can use phase-transfer catalyst to come the promotes oxidn agent to transfer in the organic phase.
The example of phase-transfer catalyst comprises tetraalkylammonium salt (for example Trimethyllaurylammonium bromide etc.).The quantity that is used for the phase-transfer catalyst of representing with catalytic quantity of second embodiment is generally 0.05-0.5 equivalent, 0.10 equivalent more preferably from about with respect to raw material.
The temperature and time of reaction
Be reflected under-20 to 100 ℃ approximately, preferred about-10 to 40 ℃ and carry out.
But those skilled in the art it should be noted that and can use sonication to improve speed of reaction.Reaction is preferably carried out in the supersound process that is cooled to 0 ℃ is bathed.
Usually, the reaction times changes between several minutes to 2 hour.Available TLC (thin-layer chromatography) or HPLC (high-pressure liquid chromatography) analytical technology monitoring reaction process; When oxidizing reaction reaches stationary point, when surpassing this point and not observing obvious conversion, stopped reaction.
Embodiment
Following examples are used for illustrating the enforcement of the inventive method, to the present invention without limits.
The degree of purity of production that makes, structure (identity) and physics-chem characteristic are measured as follows:
---purity is anti-phase by the analysis on Merck Lachrom instrument
The observation Rf (Rf value) that HPLC and used eluent obtain identifies;
---the product structure that obtains with the works of supposing confirms with proton NMR spectrum and mass spectrum.
1HNMR spectrum on the Bruker instrument under 400MHz record, compound dissolution in containing deuteriochloroform, mark in doing with tetramethylsilane.The chemistry change, proton number and and the D that have write down the characteristic of signal, represented with ppm
2The exchange capacity of O.
Mass spectrum is gone up record at Micromass Platform LC spectrograph (simple four utmost points of band positively ionized electrospray).Infrared spectra is record on the Nicolet spectrograph.
Term " flash chromatography on the silicon oxide chromatographic column " refers to (1978) such as Still, organic chemistry magazine, the method for 43:2923.The purity of eluting fraction was identified before they are collected and vaporize.
" vaporization " of term solvent, " elimination " or " concentrating " may be about the dewatering agent that is fit to Na for example
2SO
4Or MgSO
4Discussion refer to later on relaxing distillation under the heating below 30 ℃ at the pressure of 25-50mmHg (3.3-6.7 kPa) with in water-bath.
Embodiment 1
In trifluoro-benzene with the catalytic iodosobenzene of four (pentafluorophenyl group) porphyrin Manganous chloride tetrahydrate (III) (PhIO) oxidation diazepam (1)
In this reaction, generate nordiazepam (2), temazepam (3), oxazepan (4), 6-chloro-4-phenyl-1-methyl-2-(1H)-quinazolinone (5) and 6-chloro-4-phenyl-2-(1H)-quinazolinone (6).
With 10 microlitre 25Mm 5,10,15,20-four (pentafluorophenyl group)-21H, the phenylfluoroform solution of 23H-porphyrin Manganous chloride tetrahydrate (III) (0.25 micromole, 1% (mole)) is added to 240 microlitres and contains in the phenylfluoroform solution of 25 micromole's diazepams (1), and per 1 hour branch 3 times is with (3 * 5.5 milligrams of iodosobenzenes, 3 * 25 micromoles, 3 equivalents) be added in the stirred solution of generation.Add the back with analyzing HPLC monitoring reaction 1 hour at every turn; The thick solution of 5 microlitres and 100 microlitre 5mM are expelled in 150 * 4.8 millimeters chromatographic columns of Nuclesil5C18 with the sample that the methanol solution of the phenyl methyl ketone (interior mark) of 395 microliter methanol dilution makes, with 50/50 methanol wash-out 45 minutes under 1 ml/min.By nordiazepam (2), temazepam (3), oxazepan (4) of identifying generation than the school with authoritative sample (Sigma company).Their retention time was respectively 21.9,16.7 and 13.3 minutes.Respectively the 25.1 6-chloro-1-methyl-4-phenyl-1H-quinazoline-2-ketone (5) that go out with 20.5 minutes wash-outs and 6-chloro-4-phenyl-1H-quinazoline-2-ketone (6) in lock out operation by separate and with (1968) such as Felix, the heterocyclic chemistry magazine, 5,731 and Sulkowski etc., (1962), the organic chemistry magazine, 27,4424
1HNMR and MS data are relatively identified.
The product productive rate that reaction obtains is listed following table in:
| PhIO (equivalent) | The product that obtains: productive rate (%) 123456 |
| ????1 ????2 ????3 | ????31???19????12???3????4?????0 ????5????17????6????7????11????4 ????1????9?????2????5????10????3 |
At 1 of prior art condition: 1CH
2Cl
2/ CH
3The reaction result that carries out under the CN solvent is listed following table in:
| PhIO (equivalent) | The product that obtains: productive rate (%) 123 |
| ????1 ????2 ????3 | ????86????l????1 ????83????1????2 ????79????1????2 |
Two groups of results comparison shows that, solvent for example phenylfluoroform replaces the application of traditional methylene dichloride/acetonitrile to obtain better diazepam transformation efficiency and generates the more product of more number with significantly better productive rate.
Embodiment 2
With four (pentafluorophenyl group) porphyrin Manganous chloride tetrahydrate (III) catalytic 30% aqueous hydrogen peroxide solution oxidation diazepam (1) in phenylfluoroform
This imidazoles (Battioni etc., (1988), American Chemical Society's magazine, 110,8462) and ammonium acetate (Thelled etc., (1994), American Chemical Society's magazine, 1035) that is reflected at catalytic quantity exists more effective down.
In this reaction process, generate nordiazepam (2), temazepam (3), oxazepan (4), 6-chloro-4-phenyl-1-methyl-2-(1H)-quinazolinone (5), diazepam N-oxide compound (7) and nordiazepam N-oxide compound (8).
With 10 microlitre 25Mm5,10,15,20-four (pentafluorophenyl group)-21H, 23H porphyrin Manganous chloride tetrahydrate (III) (0.25 micromole, 1% (mole)) and 1,1,1,3,3,3-hexafluoro-2-propyl alcohol (1.1 microlitres, 10.4 micromole, 0.4 equivalent) solution in phenylfluoroform is added to 240 microlitres and contains in the solution of phenylfluoroform of 25 micromole's diazepams (1).In 2 hours with 30% hydrogen peroxide (2.6 microlitres, 25 micromoles, 1 equivalent), imidazoles (the 6.5 microlitre 1M aqueous solution, 6.5 micromole, 0.25 equivalent) and the drips of solution of ammonium acetate (the 25 microlitre 1M aqueous solution, 25 micromoles, 1 equivalent) be added in the stirred solution of generation.Add after 30 minutes, pass through to analyze the HPIC monitoring reaction in embodiment 1 identical mode.Added 1 equivalent, 30% aqueous hydrogen peroxide solution (2.6 microlitres, 25 micromoles, 1 equivalent) in per then 10 minutes, until use till the 15 equivalent oxygenants.After adding 2,5,10 and 15 equivalent hydrogen peroxide, monitoring reaction.By the sample that makes with the metachloroperbenzoic acid reaction with diazepam and nordiazepam relatively (referring to Ebel etc., (1979) Arzeim-Forsch 29,1317), identify diazepam N-oxide compound (7) (retention time 8.4 minutes) and nordiazepam N-oxide compound (6.7 minutes).
The productive rate of reaction product is listed following table in:
| ??H 2O 2(equivalent) | The product that obtains: productive rate (%) | |||||||
| ????1 | ??2 | ??3 | ??4 | ??5 | ??6 | ???7 | ???8 | |
| ????1 ????2 ????5 ????10 ????15 | ????71????????4???????????7??????????0???????????1??????????5???????????5???????????0 ????58????????8???????????10?????????1???????????1??????????9???????????9???????????1 ????41????????10??????????13?????????1???????????3??????????10??????????10??????????1 ????26????????10??????????12?????????2???????????5??????????8???????????8???????????2 ????19????????10??????????14?????????2???????????8??????????6???????????6???????????2 | |||||||
1: 1CH
2Cl
2/ CH
3CN replaces trichlorotoluene zotrichloride and hexafluoroisopropanol to list following table in as the result who assists the similar reaction of carrying out in the solvent:
| ?H 2O 2(equivalent) | The product that obtains: productive rate (%) 1237 |
| ??1 ??2 ??5 ??10 ??15 | ????84????1????1????2 ????77????2????1????3 ????74????5????3????6 ????74????6????7????7 ????74????5????9????7 |
When oxidation is carried out with hydrogen peroxide in two-phase system, replace in product, obtaining higher diazepam transformation efficiency and productive rate with phenylfluoroform in the presence of methylene dichloride/acetonitrile solvent system at hexafluoroisopropanol.
Confirm the validity of method of the present invention from the PRELIMINARY RESULTS of ongoing other experiments at present to the compound oxidation of relative different structure parameter.
Claims (18)
1. the method for a selected oxidation of organic compounds, described method comprise want oxidation selected organic compound in the inert aprotonic solvent with the reaction medium reaction that contains metalloporphyrin and oxygenant, reclaim and identify the reaction product of wanting then.
2. according to the process of claim 1 wherein that the inert aprotonic solvent is polyhalogenated aliphatic solvents or aromatic solvent.
3. according to the method for claim 2, wherein the inert aprotonic solvent is polyhalogenated aromatic solvent.
4. according to the method for claim 3, wherein solvent is a phenylfluoroform.
5. according to the process of claim 1 wherein that described reaction medium contains the non-proton transmission main solvent of inert and improves selected organic compound deliquescent auxilliary solvent in reaction medium.
6. according to the method for claim 5, wherein said auxilliary solvent is the solvent of polar and low nucleophilicity.
7. according to the method for claim 6, wherein said auxilliary solvent is 2,2,2 tfifluoroethyl alcohol or 1,1,1,3,3,3-hexafluoro propan-2-ol.
8. according to the method for claim 5, wherein the concentration of auxilliary solvent is 1-30%.
9. according to the process of claim 1 wherein that described reaction medium is a two phase liquid.
10. according to the method for claim 9, wherein said reaction medium contains the non-proton transmission main solvent of inert and has selected organic compound from a phase transition to another auxilliary solvent of ability mutually.
11. according to the method for claim 10, wherein auxilliary solvent is a hexafluoroisopropanol.
12. according to the method for claim 9, wherein said reaction medium comprises and contains second organic phase that first of oxygenant contains water and contain selected organic compound and metalloporphyrin in the inert aprotonic solvent.
13. according to the method for claim 12, wherein said second contains the non-proton transmission main solvent of inert mutually and has oxygenant from a phase transition to another auxilliary solvent of ability mutually.
14. according to the method for claim 13, wherein said auxilliary solvent is that water is miscible.
15. according to the method for claim 13, wherein said auxilliary solvent is 1,1,1,3,3,3-hexafluoro propan-2-ol.
16. according to the method for claim 9, comprising phase-transfer catalyst is sent into reaction medium, described phase-transfer catalyst has the ability of reactant from a phase transition to another phase.
17. according to the method for claim 16, wherein phase-transfer catalyst is a tetraalkylammonium salt.
18. according to the method for claim 17, wherein tetraalkylammonium salt is a Trimethyllaurylammonium bromide.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14807999P | 1999-08-10 | 1999-08-10 | |
| US60/148,079 | 1999-08-10 | ||
| US15010199P | 1999-08-20 | 1999-08-20 | |
| US60/150,101 | 1999-08-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1367769A true CN1367769A (en) | 2002-09-04 |
Family
ID=26845496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00811067A Pending CN1367769A (en) | 1999-08-10 | 2000-08-09 | Process for catalyzing oxidation of organic compounds |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP1208069A1 (en) |
| JP (1) | JP2003506419A (en) |
| KR (1) | KR20020024323A (en) |
| CN (1) | CN1367769A (en) |
| AU (1) | AU776140B2 (en) |
| BR (1) | BR0013018A (en) |
| CA (1) | CA2380851A1 (en) |
| CZ (1) | CZ2002452A3 (en) |
| HK (1) | HK1047428A1 (en) |
| HU (1) | HUP0202521A2 (en) |
| IL (1) | IL147452A0 (en) |
| MX (1) | MXPA02001388A (en) |
| PL (1) | PL356156A1 (en) |
| RU (1) | RU2002103336A (en) |
| TR (1) | TR200200330T2 (en) |
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| CN102503860A (en) * | 2011-11-14 | 2012-06-20 | 武汉大学 | Synthetic method of 1, 3-two substituted ureas and carbamate |
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| FR2807032B1 (en) | 2000-03-29 | 2003-04-18 | Warner Lambert Co | MODIFICATION OF CHEMOSLECTIVITY DURING THE OXIDATION OF NITROGEN ORGANIC COMPOUNDS |
| PT107020B (en) * | 2013-06-21 | 2015-07-09 | Univ Aveiro | PROCESS FOR THE PRODUCTION OF INDIGO AND ITS DERIVATIVES |
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| IT1217608B (en) * | 1988-05-17 | 1990-03-30 | Istituto Guido Donegami Spa | PROCESS FOR THE PREPARATION OF EPOXY |
| DD291748A5 (en) * | 1990-02-01 | 1991-07-11 | Bitterfeld Chemie | PROCESS FOR PREPARING ALLYL HYDROXYLATED TERPENOIDES OF HYDROCARBONS |
| US5760216A (en) * | 1994-09-15 | 1998-06-02 | Abbott Laboratories | Use of synthetic metalloporphyrins for preparation and prediction of drug metabolites |
-
2000
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- 2000-08-09 HU HU0202521A patent/HUP0202521A2/en unknown
- 2000-08-09 KR KR1020027001738A patent/KR20020024323A/en not_active Application Discontinuation
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- 2000-08-09 WO PCT/EP2000/007726 patent/WO2001010797A1/en not_active Application Discontinuation
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- 2000-08-09 BR BR0013018-4A patent/BR0013018A/en not_active IP Right Cessation
- 2000-08-09 EP EP00960420A patent/EP1208069A1/en not_active Withdrawn
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102503860A (en) * | 2011-11-14 | 2012-06-20 | 武汉大学 | Synthetic method of 1, 3-two substituted ureas and carbamate |
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| EP1208069A1 (en) | 2002-05-29 |
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| RU2002103336A (en) | 2003-09-20 |
| KR20020024323A (en) | 2002-03-29 |
| CZ2002452A3 (en) | 2002-05-15 |
| WO2001010797A1 (en) | 2001-02-15 |
| JP2003506419A (en) | 2003-02-18 |
| AU776140B2 (en) | 2004-08-26 |
| BR0013018A (en) | 2002-04-16 |
| IL147452A0 (en) | 2002-08-14 |
| YU4902A (en) | 2004-09-03 |
| PL356156A1 (en) | 2004-06-14 |
| MXPA02001388A (en) | 2004-07-16 |
| HK1047428A1 (en) | 2003-02-21 |
| AU7273800A (en) | 2001-03-05 |
| CA2380851A1 (en) | 2001-02-15 |
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