CN114805156B - 一种在室温、水相条件下铜催化制备不对称芳基硒醚类化合物的方法 - Google Patents
一种在室温、水相条件下铜催化制备不对称芳基硒醚类化合物的方法 Download PDFInfo
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- CN114805156B CN114805156B CN202210472798.4A CN202210472798A CN114805156B CN 114805156 B CN114805156 B CN 114805156B CN 202210472798 A CN202210472798 A CN 202210472798A CN 114805156 B CN114805156 B CN 114805156B
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- -1 aryl seleno ether compound Chemical class 0.000 title claims abstract description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 26
- 239000010949 copper Substances 0.000 title abstract description 12
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title abstract description 6
- 229910052802 copper Inorganic materials 0.000 title abstract description 6
- 238000006555 catalytic reaction Methods 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- 150000001879 copper Chemical class 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 239000004094 surface-active agent Substances 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 239000012298 atmosphere Substances 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 239000000047 product Substances 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 30
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 12
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 239000002274 desiccant Substances 0.000 claims description 10
- 238000004821 distillation Methods 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 9
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000012044 organic layer Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- NHUBNHMFXQNNMV-UHFFFAOYSA-N 2-ethynylpyridine Chemical compound C#CC1=CC=CC=N1 NHUBNHMFXQNNMV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 4
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 4
- 239000010413 mother solution Substances 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 4
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 4
- 229960005055 sodium ascorbate Drugs 0.000 claims description 4
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 claims description 4
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000012452 mother liquor Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 3
- 125000005504 styryl group Chemical group 0.000 claims description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 2
- 229960000878 docusate sodium Drugs 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 17
- 239000004327 boric acid Substances 0.000 abstract description 5
- XIMIGUBYDJDCKI-UHFFFAOYSA-N diselenium Chemical compound [Se]=[Se] XIMIGUBYDJDCKI-UHFFFAOYSA-N 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 78
- NNXSGISAOBFVLS-UHFFFAOYSA-N 1-methoxy-4-phenylselanylbenzene Chemical compound C1=CC(OC)=CC=C1[Se]C1=CC=CC=C1 NNXSGISAOBFVLS-UHFFFAOYSA-N 0.000 description 37
- 239000002202 Polyethylene glycol Substances 0.000 description 17
- 239000007788 liquid Substances 0.000 description 17
- 229920001223 polyethylene glycol Polymers 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 239000003446 ligand Substances 0.000 description 8
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 150000001543 aryl boronic acids Chemical class 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 3
- 238000006880 cross-coupling reaction Methods 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- ZEVMYKUQDOHHTP-UHFFFAOYSA-N 1-methoxy-4-phenylseleninylbenzene Chemical compound C1=CC(OC)=CC=C1[Se](=O)C1=CC=CC=C1 ZEVMYKUQDOHHTP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- WPMWEFXCIYCJSA-UHFFFAOYSA-N Tetraethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCO WPMWEFXCIYCJSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical compound C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- KLRHPHDUDFIRKB-UHFFFAOYSA-M indium(i) bromide Chemical compound [Br-].[In+] KLRHPHDUDFIRKB-UHFFFAOYSA-M 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- ARWXFTYBPFRIBM-UHFFFAOYSA-N 1-(butyldiselanyl)butane Chemical compound CCCC[Se][Se]CCCC ARWXFTYBPFRIBM-UHFFFAOYSA-N 0.000 description 1
- LURBCACEKXUJEG-UHFFFAOYSA-N 1-methoxy-4-(4-methoxyphenyl)selanylbenzene Chemical compound C1=CC(OC)=CC=C1[Se]C1=CC=C(OC)C=C1 LURBCACEKXUJEG-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 101710134784 Agnoprotein Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 238000006964 Chan-Lam coupling reaction Methods 0.000 description 1
- 229910016509 CuF 2 Inorganic materials 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- VUYXVWGKCKTUMF-UHFFFAOYSA-N tetratriacontaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO VUYXVWGKCKTUMF-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
- C07C391/02—Compounds containing selenium having selenium atoms bound to carbon atoms of six-membered aromatic rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B47/00—Formation or introduction of functional groups not provided for in groups C07B39/00 - C07B45/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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Abstract
本发明公开了一种在室温、水相条件下铜催化制备不对称芳基硒醚类化合物的方法,所述方法为:将铜盐、PEG‑PyTa、表面活性剂和溶剂水混合,于室温下搅拌混匀,然后加入化合物(II)和化合物(III),在空气气氛、0~60℃条件下反应6~12h,之后反应液经后处理,得到产物不对称有机硒醚类化合物(I);本发明开发的催化方法安全性高、催化剂体系可多次循环套用,产物分离简便、生产成本低、三废量小,并且底物范围广,收率高,特别是各种强吸电子取代和有位阻的芳基硼酸与二芳基(烷基)二硒醚反应均能获得极佳的收率;
Description
技术领域
本发明涉及一种不对称芳基硒醚类化合物的制备方法,具体为一种以空气为氧化剂,在室温和水相条件下铜催化二有机二硒醚与芳基硼酸氧化交叉偶联法制备不对称芳基硒醚类化合物的方法。
背景技术
不对称芳基硒醚(I)是一类重要的有机化合物,广泛应用于医药、农药、材料和有机合成等领域。特别是最近研究发现,该类化合物具有抗病毒、抗菌、抗氧化、抗高血压、抗肿瘤和抗癌等生理活性。近些年来,已经发展了许多种合成不对称芳基硒醚类化合物的方法。其中,过渡金属催化的芳基硼酸(II)与有机二硒醚(III)的氧化交叉偶联法(也称为Cham-Lam氧化偶联法)是最常见的合成路线之一。该路线直接以空气为氧化剂,毋需添加其他当量辅助试剂(如碱或还原剂),具有原子经济性高的优点。此外,反应原料二有机二硒醚和芳基硼酸稳定性高,毒性小,商业大量可得。
到目前为止,已经报道了一些过渡金属催化剂体系用于催化该反应。文献1(Synlett,2005,13,2007-2010)首次报道了该合成方法,以10mol%的CuI为催化剂,二甲基亚砜(DMSO)为反应介质,在敞口接触空气和100℃的反应条件下搅拌反应7小时,制备了10个不对称芳基硒醚类化合物,收率为62-95%。该催化体系对苯环上有强吸电子取代基(如:乙酰基)的芳基硼酸,或者二烷基二硒醚(如:二正丁基二硒醚)的反应效果较差,相应偶联产物的收率均小于70%。随后,文献2--文献8相继报道了其他铜基催化体系来改进该反应,如:CuI-联吡啶(BPY),纳米CuO,纳米CuFe2O4,负载纳米Cu的活性炭,负载CuI的MCM-41-BPY,CuI-丙三醇,CuI-微波照射等(J.Org.Chem.,2007,72,1241-1245;Tetrahedron Lett.,2009,50,6635-6638;Green Chem.,2012,14,1030-1034;RSC Advances,2013,3,117-125;ChemCatChem,2015,7,405-412;New J.Chem.,2015,39,2106-2115;Molecules,2017,22,1367);除了铜基催化剂以外,文献9--文献11还报道了以InBr3(Org.Biomol.Chem.,2009,7,4858-5861),Fe粉(Adv.Synth.Catal.,2009,351,1585-1594)和AgNO3(J.Org.Chem.,2016,81,11472-11476)为催化剂来催化该反应。虽然上述过渡金属催化体系为不对称芳基硒醚的制备提供了一条简便、快捷和经济的途径,有些催化剂还可以循环使用。但是所有这些催化剂体系均需要较高的反应温度(100-130℃之间)以及有机溶剂中才能进行。为了提高空气的氧化效率,绝大多数催化剂体系还需要额外添加大量的DMSO为共同氧化剂,甚至直接以DMSO为反应溶剂。考虑到该反应需要消耗氧气,一般在敞口充分接触空气的条件下进行,这样的反应条件显然存在严重的安全隐患,大大影响了这些方法的实际应用价值。此外,DMSO毒性大,回收困难,后处理过程复杂,以及产生大量的三废。
发明内容
本发明旨在为不对称芳基硒醚类化合物的合成提供一种经济、安全性高、环境友好和底物适用性广的新方法。
本发明反应以二芳基(烷基)二硒醚(II)和芳基(杂芳基)硼酸(III)为起始原料,水为反应介质,CuBr为催化剂,自制的PEG-PyTa为配体,十二烷基硫酸钠(SDS)为乳化剂,在敞口接触空气和室温条件下,反应数小时制备得到相应的不对称芳基硒醚(I)。
由于反应以纯水为介质,催化剂PEG-PyTa/CuBr和SDS均易溶于水,而反应产物不对称芳基硒醚基本不溶于水,因此产物与水溶性的催化体系分离简便。经过萃取或过滤分离产物后,余下溶有催化剂的水相可循环回收套用多次。不仅简化了后处理过程,还大大减少了三废量,具有重要的实际应用前景。
本发明的技术方案如下:
一种不对称有机硒醚类化合物(I)的制备方法,所述的制备方法为:
将铜盐、PEG-PyTa、表面活性剂和溶剂水混合,于室温(25~30℃)下搅拌混匀(优选搅拌30min),然后加入化合物(II)和化合物(III),在空气气氛、0~60℃(优选25~30℃)条件下反应6~12h,之后反应液经后处理,得到产物不对称有机硒醚类化合物(I);
所述化合物(II)、化合物(III)、铜盐、PEG-PyTa的物质的量之比为1:2~4:0.05~0.3:0.03~0.8,优选1:3:0.2:0.1;
所述铜盐选自:CuCl、CuI、CuBr、CuF2、CuCl2、CuBr2、Cu(OAc)2、Cu(NO3)2、Cu(OTf)2或CuSO4,优选CuBr;
所述PEG-PyTa为:PEG1500-PyTa、PEG2000-PyTa或PEG5000-PyTa,优选PEG2000-PyTa;
所述表面活性剂选自:十二烷基硫酸钠(SDS)、十二烷-1-磺酸钠(SDSO3)、十二烷基苯磺酸钠(SDBS)、多库酯钠、曲拉通X-100、聚氧乙烯月桂醚(Brij-30)、吐温40或十六烷基三甲基氯化铵(CTAC),优选十二烷基硫酸钠(SDS);
所述溶剂水的体积用量以化合物(II)的物质的量计为4~6mL/mmol;
所述表面活性剂的用量为溶剂水质量的1~3wt%,优选2wt%;
所述后处理的方法为:反应结束后(GC监测至化合物II完全转化),加入甲基叔丁基醚萃取2次,合并有机层,依次用饱和氯化钠水溶液洗涤,无水硫酸钠干燥和真空浓缩,粗产物以石油醚/乙酸乙酯(体积比95:5)混合液为洗脱剂,经200目硅胶柱层析纯化,收集含目标化合物的洗脱液,蒸除溶剂后得到目标产物(I);
式(I)、式(II)、式(III)中,
R为C1-C8烷基、苄基、含O或S的杂芳基、C6-C10芳基或取代的C6-C10芳基,所述取代的C6-C10芳基的芳环上被一个或多个取代基取代,所述取代基各自独立选自C1-C3烷基或卤素;优选的R为苯基、4-甲基苯基、4-氟苯基、4-氯苯基、2,4,6-三甲基苯基、噻吩-3-基、苄基或正丁基;
Ar为含O或S的杂芳基、苯乙烯基、C6-C10芳基或取代的C6-C10芳基,所述取代的C6-C10芳基的芳环上被一个或多个取代基取代,所述取代基各自独立选自C1-C3烷基、C1-C3烷氧基、卤素、C1-C3烷酰基、三氟甲基、硝基或甲氧羰基;优选的Ar为苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2,6-二甲基苯基、4-甲氧基苯基、2-氟苯基、3-氟苯基、4-氟苯基、2-氯苯基、3-氯苯基、4-氯苯基、4-乙酰基苯基、4-三氟甲基苯基、4-甲氧羰基苯基、4-硝基苯基、呋喃-3-基、噻吩-3-基、萘-1-基或苯乙烯基。
本发明中,配体PEG-PyTa的制备方法可参考文献Catal.Comm.,2017,101,5-9。具体的PEG-PyTa的制备方法例如:
(1)将PEG-OH和甲磺酰氯溶于二氯甲烷,降温至5~10℃,加入吡啶,在该温度下反应12h,反应结束后,加入冰水淬灭,并滴加20w%氢氧化钠水溶液使pH为7,分出有机层,无水Na2SO4干燥,过滤除去干燥剂,母液真空旋转蒸馏回收二氯甲烷,残余物用甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到PEG-OMs;
所述PEG-OH与甲磺酰氯的物质的量之比为1:2~4;
所述PEG-OH即聚乙二醇,选自PEG1500、PEG2000或PEG5000,可通过常规途径商购获得;
(2)将所得PEG-OMs溶于DMF(N,N-二甲基甲酰胺),升温至65℃,在氮气保护下,分批加入叠氮化钠,加毕,在该温度下反应12h,反应结束后,混合物冷却至室温,真空旋转蒸馏回收DMF,残余物用二氯甲烷溶解,依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,真空旋转蒸馏回收二氯甲烷,残余物用甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到PEG-N3;
所述PEG-OMs与叠氮化钠的物质的量之比为1:3~5;
(3)将所得PEG-N3溶于甲醇/水=1:1(v/v),然后依次加入2-乙炔基吡啶、硫酸铜和抗坏血酸钠,反应混合物在45℃下搅拌24h,反应结束后,真空浓缩至粘稠,加入5w%氨水搅拌12h,所得水溶液用二氯甲烷萃取3次,合并有机层,依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,真空旋转蒸馏回收二氯甲烷,残余物用甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到PEG-PyTa;
所述PEG-N3与2-乙炔基吡啶、硫酸铜和抗坏血酸钠的物质的量之比为1:2~3:0.1~0.3:0.1~0.3。
与现有技术相比,本发明的有益效果主要体现在:
(1)本发明以空气为氧源,水为反应介质,自制PEG-PyTa为配体,普通商业可得的铜盐为催化剂,通过二芳基(烷基)二硒醚和芳基(杂芳基)硼酸的氧化交叉偶联法制备了一系列不对称芳基硒醚类化合物,催化剂体系还可以多次循环套用,开发的催化方法安全性高、产物分离简便、生产成本低、三废量小。
(2)底物范围广,收率高,特别是各种强吸电子取代和有位阻的芳基硼酸与二有机二硒醚(包括二烷基二硒醚)反应均能获得极佳的收率。
附图说明
图1本发明的典型反应式。
图2配体PEG-PyTa的制备路线。
具体实施方式
下面通过具体实施例进一步描述本发明,但本发明的保护范围并不仅限于此。
配体PEG2000-PyTa的制备方法如下:
称取60.0g商购可得的PEG2000-OH和13.8g甲基磺酰氯溶于250mL二氯甲烷中,冰水浴降温至5-10℃。于30min内滴加14.5g吡啶,滴毕,在该温度下继续搅拌反应12h。反应结束后,加入200mL冰水淬灭反应,并逐渐滴加20%氢氧化钠水溶液使溶液的pH为7左右。分液,有机层依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液经真空旋转蒸馏回收二氯甲烷。残余物用500mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到62.1g PEG2000-OMs。
称取43.8g PEG2000-OMs溶于250mL DMF中,升温至65℃。在氮气保护下,分批加入5.3g叠氮化钠,在该温度下继续搅拌反应12h。反应结束后,冷却到室温,真空旋转蒸馏回收DMF。残余物用100mL二氯甲烷溶解,然后依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液真空旋转蒸馏回收二氯甲烷。残余物用350mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到37.5g PEG2000-N3。
称取41.6g PEG2000-N3溶于100mL体积比为1:1的甲醇/水溶液中,室温下搅拌均匀后,依次加入5.1g 2-乙炔基吡啶、1.0g硫酸铜和0.8g抗坏血酸钠。然后,升温至45℃搅拌反应24h。反应结束后,反应液真空浓缩至粘稠,残余物用50mL5w%氨水溶解,并在室温下搅拌12h。所得水溶液用二氯甲烷萃取3次,合并有机层,用依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液真空旋转蒸馏回收二氯甲烷。残余物用350mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到40.5g PEG2000-PyTa。
实施例1(4-甲氧基苯基)苯基硒醚的制备
于开口反应管中,加入CuBr(0.058g,0.4mmol)、PEG2000-PyTa(0.469g,0.2mmol)、SDS(0.20g)和10mL水,在室温下搅拌30min。然后,加入二苯基二硒醚(0.65g,2.0mmol)和4-甲氧基苯硼酸(0.93g,6.0mmol),在敞口充分接触空气下继续搅拌反应6h。反应结束后,加入5mL甲基叔丁基醚萃取2次。合并萃取液,并依次用饱和食盐水洗涤,无水Na2SO4干燥,除去干燥剂,真空旋转蒸馏回收甲基叔丁基醚。残余物经硅胶柱层析法纯化(石油醚/乙酸乙酯=95:5),得到1.01g(4-甲氧基苯基)苯基硒醚产品,收率96%,外观为淡黄色液体。1H NMR(500MHz,CDCl3)δ7.49-7.39(m,2H),7.37(dd,J=7.7,1.3Hz,1H),7.32-7.19(m,5H),7.10(td,J=7.5,1.8Hz,1H),2.44(s,3H);13C NMR(125MHz,CDCl3)δ159.9,136.6,133.3,131.0,129.2,126.5,120.0,115.2,55.4.
实施例2(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuCl(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.99g,收率94%。
实施例3(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuI(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.97g,收率92%。
实施例4(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuF2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.81g,收率77%。
实施例5(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuCl2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.71g,收率67%。
实施例6(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuBr2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.82g,收率78%。
实施例7(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量Cu(OAc)2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.24g,收率23%。
实施例8(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量Cu(NO3)2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,无法得到4-甲氧基苯苯基硒醚产品。
实施例9(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量Cu(OTf)2(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,无法得到(4-甲氧基苯基)苯基硒醚产品。
实施例10(4-甲氧基苯基)苯基硒醚的制备
所用铜盐为0.2当量CuSO4(以二芳基二硒醚物质的量计),其他操作和反应条件同实施例1,无法得到(4-甲氧基苯基)苯基硒醚产品。
实施例11(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%SDSO3(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.99g,收率94%。
实施例12(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%SDBS(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.93g,收率88%。
实施例13(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%多库酯钠(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.96g,收率91%。
实施例14(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%曲拉通X-100(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.35g,收率33%。
实施例15(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%Brij-30(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.45g,收率43%。
实施例16(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%吐温40(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.68g,收率65%。
实施例17(4-甲氧基苯基)苯基硒醚的制备
所用表面活性剂为2wt%CTAC(以溶剂水的质量计),其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.31g,收率29%。
实施例18(4-甲氧基苯基)苯基硒醚的制备
所用配体为PEG1500-PyTa,其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.99g,收率94%。
实施例19(4-甲氧基苯基)苯基硒醚的制备
所用配体为PEG5000-PyTa,其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.93g,收率88%。
实施例20(4-甲氧基苯基)苯基硒醚的制备
反应温度为45-50℃,其他操作和反应条件同实施例1,得到(4-甲氧基苯基)苯基硒醚产品0.95g,收率90%。
实施例21(4-甲氧基苯基)苯基硒醚的制备
反应在氮气氛围下进行,其他操作和反应条件同实施例1,无法得到(4-甲氧基苯基)苯基硒醚产品。
实施例22-47
于开口反应管中,加入CuBr(0.058g,0.4mmol)、PEG2000-PyTa(0.469g,0.2mmol)、SDS(0.20g)和10mL水,在室温下搅拌30min。然后,加入二有机二硒醚(2.0mmol)和(杂)芳基硼酸(6.0mmol),在敞口充分接触空气下继续搅拌反应6-12h,反应过程用GC进行检测。反应结束后,经相同的后处理得到相应的芳基硒醚产品,并计算收率。实验结果见表1。
表1二有机二硒醚与(杂)芳基硼酸反应制备不对称芳基硒醚类化合物
实施例22~47制备产物的表征数据:
实施例22:
黄色液体;1H NMR(500MHz,CDCl3)δ7.50(d,J=6.5Hz,4H),7.30(d,J=4.8Hz,6H);13C NMR(125MHz,CDCl3)δ133.1,131.2,129.4,127.4;77Se NMR(95.5MHz,CDCl3)δ421.37.
实施例23:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.47-7.41(m,1H),7.38(dd,J=7.8,1.3Hz,1H),7.32-7.22(m,5H),7.10(td,J=7.5,1.8Hz,1H),2.44(s,3H);13C NMR(125MHz,CDCl3)δ140.0,133.8,132.8,131.8,130.9,130.3,129.5,127.9,127.2,126.8,22.4;77Se NMR(95.5MHz,CDCl3)δ380.16.
实施例24:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.51-7.43(m,2H),7.34(s,1H),7.27(dd,J=5.0,2.0Hz,4H),7.18(t,J=7.6Hz,1H),7.10(d,J=7.5Hz,1H),2.32(s,3H);13C NMR(125MHz,CDCl3)δ139.2,133.9,132.8,131.5,130.8,130.3,129.4,129.3,128.4,127.3,21.4;77Se NMR(95.5MHz,CDCl3)δ424.33.
实施例25:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.50-7.42(m,4H),7.30-7.25(m,3H),7.15(d,J=7.9Hz,2H),2.38(s,3H);13C NMR(125MHz,CDCl3)δ137.7,134.0,132.2,132.1,130.3,129.3,127.0,126.9,21.2;77Se NMR(95.5MHz,CDCl3)δ424.97.
实施例26:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.29-7.21(m,1H),7.21-7.14(m,4H),7.14-7.07(m,3H),2.49(s,5H);13C NMR(125MHz,CDCl3)δ143.8,133.1,130.3,129.2,129.1,128.6,127.9,125.5,24.4;77Se NMR(95.5MHz,CDCl3)δ305.15.
实施例27:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.59-7.52(m,1H),7.33(dd,J=5.6,1.7Hz,1H),7.30-7.22(m,1H),7.09(td,J=8.5,8.1,1.3Hz,1H),7.03(td,J=7.6,1.3Hz,1H);13CNMR(125MHz,CDCl3)δ161.1(d,J=243.7Hz),134.1,134.0(d,J=2.7Hz),129.6,129.3(d,J=7.6Hz),128.8(d,J=1.6Hz),128.1,125.0(d,J=3.5Hz),118.7(d,J=22.0Hz),115.6(d,J=23.1Hz);77Se NMR(95.5MHz,CDCl3)δ351.05.
实施例28:
黄色液体;1H NMR(500MHz,CDCl3)δ7.59-7.49(m,2H),7.33(dd,J=5.4,2.0Hz,3H),7.27-7.15(m,2H),7.09(dd,J=8.8,2.0Hz,1H),6.93(td,J=7.6,7.1,2.3Hz,1H);13CNMR(125MHz,CDCl3)δ163.0(d,J=206.2Hz),134.2,133.9(d,J=6.9Hz),130.5(d,J=8.1Hz),129.7(d,J=10.0Hz),128.2,127.6(d,J=3.0Hz),118.9(d,J=22.6Hz),114.1(d,J=21.2Hz);77Se NMR(95.5MHz,CDCl3)δ431.59.
实施例29:
黄色液体;1H NMR(500MHz,CDCl3)δ7.55-7.46(m,2H),7.46-7.40(m,2H),7.35-7.22(m,3H),7.01(t,J=8.7Hz,2H);13C NMR(125MHz,CDCl3)δ162.7(d,J=247.7Hz),135.8(d,J=7.9Hz),132.3,131.8,129.4,127.3,125.3(d,J=3.4Hz),116.7(d,J=21.6Hz);77Se NMR(95.5MHz,CDCl3)δ418.44.
实施例30:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.76-7.56(m,2H),7.47-7.35(m,4H),7.13(td,J=7.6,1.6Hz,1H),7.05(td,J=7.6,1.4Hz,1H),6.96(dd,J=7.9,1.6Hz,1H);13C NMR(125MHz,CDCl3)δ136.1,133.9,133.6,130.8,129.9,129.5,128.9,128.1,127.4,127.4;77Se NMR(95.5MHz,CDCl3)δ417.00.
实施例31:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.56-7.49(m,2H),7.40(t,J=1.8Hz,1H),7.36-7.28(m,4H),7.24-7.14(m,2H);13C NMR(125MHz,CDCl3)δ135.0,134.0,133.6,131.9,130.4,130.3,129.9,129.7,128.1,127.3;77Se NMR(95.5MHz,CDCl3)δ431.76.
实施例32:
黄色液体;1H NMR(500MHz,CDCl3)δ7.53-7.45(m,2H),7.42-7.37(m,2H),7.34-7.29(m,3H),7.29-7.24(m,2H);13C NMR(125MHz,CDCl3)δ134.2,133.6,133.3,130.8,129.7,129.6,127.8;77Se NMR(95.5MHz,CDCl3)δ415.05.
实施例33:
白色固体;mp 61℃;1H NMR(500MHz,CDCl3)δ7.80(d,J=8.5Hz,2H),7.61(dd,J=7.9,1.7Hz,2H),7.43-7.23(m,5H),2.57(s,3H);13C NMR(125MHz,CDCl3)δ197.4,140.4,135.3,135.2,130.4,129.8,129.0,128.7,128.6,26.6;77Se NMR(95.5MHz,CDCl3)δ433.11.
实施例34:
黄色固体;mp 59℃;1H NMR(500MHz,CDCl3)δ7.61-7.56(m,2H),7.46(q,J=8.6Hz,4H),7.40-7.33(m,2H);13C NMR(125MHz,CDCl3)δ137.9,134.9,131.1,129.8,128.9(q,J=32.7Hz),128.8,128.6,126.0(q,J=3.7Hz),124.2(q,J=272.0Hz);77Se NMR(95.5MHz,CDCl3)δ463.50.
实施例35:
白色固体;mp 70℃;1H NMR(500MHz,CDCl3)δ7.87(d,J=8.4Hz,2H),7.58(dd,J=7.8,1.8Hz,2H),7.43-7.25(m,5H),3.89(s,3H);13C NMR(125MHz,CDCl3)δ166.9,139.7,135.0,130.5,130.2,129.8,128.8,128.6,128.3,52.2;77Se NMR(95.5MHz,CDCl3)δ431.88.
实施例36:
黄色固体;mp 58℃;1H NMR(500MHz,CDCl3)δ8.02(d,J=8.9Hz,2H),7.66-7.61(m,2H),7.47-7.38(m,3H),7.35(d,J=9.0Hz,2H);13C NMR(125MHz,CDCl3)δ146.8,144.0,135.9,130.1,129.7,129.4,127.3,124.0;77Se NMR(95.5MHz,CDCl3)δ445.16.
实施例37:
白色固体;mp 52℃;1H NMR(500MHz,CDCl3)δ8.45-8.36(m,1H),7.92-7.87(m,2H),7.82(dd,J=7.1,1.2Hz,1H),7.59-7.53(m,2H),7.48-7.38(m,3H),7.28-7.22(m,3H);13C NMR(125MHz,CDCl3)δ134.3,134.2,133.9,131.9,131.8,129.5 129.4,129.3,128.7,127.7,127.0,126.9,126.4,126.1;77Se NMR(95.5MHz,CDCl3)δ358.45.
实施例38:
黄色液体;1H NMR(500MHz,CDCl3)δ7.62-7.56(m,3H),7.30(dd,J=4.9,2.8Hz,1H),7.28-7.22(m,2H),7.22-7.17(m,2H);13C NMR(125MHz,CDCl3)δ132.7,132.2,131.0,129.2,128.8,126.7,122.7;77Se NMR(95.5MHz,CDCl3)δ336.64.
实施例39:
棕色液体;1H NMR(500MHz,CDCl3)δ7.69-7.63(m,1H),7.60-7.54(m,2H),7.50(t,J=1.6Hz,1H),7.32-7.16(m,2H),6.64(d,J=1.7Hz,1H);13C NMR(125MHz,CDCl3)δ146.7,144.0,131.5,129.9,129.1,127.7,126.4,115.7;77Se NMR(95.5MHz,CDCl3)δ246.83.
实施例40:
淡黄色液体;1H NMR(500MHz,CDCl3)δ7.61(dd,J=7.7,1.8Hz,2H),7.41-7.34(m,7H),7.33-7.26(m,1H),7.24(d,J=15.8Hz,1H),6.94(d,J=15.7Hz,1H);13C NMR(125MHz,CDCl3)δ137.1,135.2,132.6,130.2,129.4,128.7,127.7,127.5,126.1,119.5;77Se NMR(95.5MHz,CDCl3)δ392.10.
实施例41:
淡黄色固体;mp 49℃;1H NMR(500MHz,CDCl3)δ7.40(d,J=8.0Hz,1H),7.11(d,J=7.9Hz,1H),2.35(s,1H);13C NMR(125MHz,CDCl3)δ137.2,133.1,130.2,127.8,21.2;77SeNMR(95.5MHz,CDCl3)δ285.16.
实施例42:
淡黄色固体;mp 70℃;1H NMR(500MHz,CDCl3)δ7.79(d,J=8.5Hz,2H),7.60(dd,J=8.8,5.3Hz,2H),7.38-7.25(m,2H),7.07(t,J=8.7Hz,2H),2.56(s,3H);13C NMR(125MHz,CDCl3)δ197.2,163.2(d,J=247.5Hz),140.4,137.6(d,J=8.7Hz),135.2,129.8,128.9,122.9(d,J=3.7Hz),117.0(d,J=22.5Hz),26.87;77Se NMR(95.5MHz,CDCl3)δ424.85.
实施例43:
白色固体;mp 64℃;1H NMR(500MHz,CDCl3)δ7.81(d,J=8.5Hz,2H),7.50(d,J=8.5Hz,2H),7.39(d,J=8.4Hz,2H),7.35-7.26(m,2H),2.57(s,3H);13C NMR(125MHz,CDCl3)δ198.3,139.4,136.2,135.5,134.9,130.6,129.9,129.0,126.9,27.4;77Se NMR(95.5MHz,CDCl3)δ428.43.
实施例44:
黄色固体;mp 64℃;1H NMR(500MHz,CDCl3)δ7.12(d,J=8.9Hz,2H),7.02(s,2H),6.78(d,J=8.9Hz,2H),3.77(s,3H),2.51(s,6H),2.34(s,3H);13C NMR(125MHz,CDCl3)δ158.1,143.2,138.6,130.7,128.7,127.8,123.2,114.9,55.1,24.2,20.9;77Se NMR(95.5MHz,CDCl3)δ285.02.
实施例45:
黄色液体;1H NMR(500MHz,CDCl3)δ7.38(dd,J=3.0,1.2Hz,1H),7.36-7.26(m,3H),7.13-7.08(m,3H),2.34(s,3H);13C NMR(125MHz,CDCl3)δ136.9,132.3,131.89,130.1,128.0,128.0,126.6,123.6,21.1;77Se NMR(95.5MHz,CDCl3)δ333.92.
实施例46:
淡黄色固体;mp 104℃;1H NMR(500MHz,CDCl3)δ7.82(d,J=8.5Hz,2H),7.50(d,J=8.4Hz,2H),7.35-7.18(m,5H),4.22(s,2H),2.58(s,3H);13C NMR(125MHz,CDCl3)δ197.4,138.6,137.6,135.4,131.4,128.9,128.7,128.6,127.2,31.4,26.5;77Se NMR(95.5MHz,CDCl3)δ377.05.
实施例47:
橙色液体;1H NMR(500MHz,CDCl3)δ7.43(d,J=7.7Hz,2H),7.11(d,J=7.7Hz,2H),2.91(t,J=7.5Hz,2H),2.36(s,3H),1.68-1.73(m,J=7.5Hz,2H),1.42-1.49(m,J=7.4Hz,2H),1.02-0.86(m,3H);13C NMR(125MHz,CDCl3)δ136.7,133.1,129.9,126.8,32.4,28.1,23.0,21.1,13.6;77Se NMR(95.5MHz,CDCl3)δ284.07.
实施例48:催化剂的套用制备(4-甲氧基苯基)苯基硒醚
第一次反应结束后,生成的产物用甲基叔丁基醚萃取,配体PEG2000-PyTa、SDS、铜催化剂和反应介质水留在反应试管中(部分CuBr变成CuO失活,需要补加一半量的CuBr以保持催化效率)。将CuBr(0.029g,0.2mmol),二苯基二硒醚(0.62g,2.0mmol)和4-甲氧基苯硼酸(0.93g,6.0mmol)加入到该反应试管中进行Chan-Lam反应,具体操作同实施例1。后处理得到(4-甲氧基苯基)苯基硒醚1.02g,收率97%。催化剂再继续使用5次,分离收率依次为96%,95%,94%,95%,82%。
Claims (6)
1.一种不对称有机硒醚类化合物(I)的制备方法,其特征在于,所述的制备方法为:
将铜盐、PEG-PyTa、表面活性剂和溶剂水混合,于室温下搅拌混匀,然后加入化合物(II)和化合物(III),在空气气氛、0~60℃条件下反应6~12h,之后反应液经后处理,得到产物不对称有机硒醚类化合物(I);
式(I)、式(II)、式(III)中,
R为苯基、4-甲基苯基、4-氟苯基、4-氯苯基、2,4,6-三甲基苯基、噻吩-3-基、苄基或正丁基;
Ar为苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2,6-二甲基苯基、4-甲氧基苯基、2-氟苯基、3-氟苯基、4-氟苯基、2-氯苯基、3-氯苯基、4-氯苯基、4-乙酰基苯基、4-三氟甲基苯基、4-甲氧羰基苯基、4-硝基苯基、呋喃-3-基、噻吩-3-基、萘-1-基或苯乙烯基;
所述铜盐选自:CuCl、CuI、CuBr、CuF2、CuCl2或CuBr2;
所述表面活性剂选自:十二烷基硫酸钠、十二烷-1-磺酸钠、十二烷基苯磺酸钠、多库酯钠或吐温40;
所述PEG-PyTa的制备方法如下:
称取60.0g商购可得的PEG2000-OH和13.8g甲基磺酰氯溶于250mL二氯甲烷中,冰水浴降温至5-10℃。于30min内滴加14.5g吡啶,滴毕,在该温度下继续搅拌反应12h。反应结束后,加入200mL冰水淬灭反应,并逐渐滴加20%氢氧化钠水溶液使溶液的pH为7左右。分液,有机层依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液经真空旋转蒸馏回收二氯甲烷。残余物用500mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到62.1gPEG2000-OMs;
称取43.8g PEG2000-OMs溶于250mL DMF中,升温至65℃。在氮气保护下,分批加入5.3g叠氮化钠,在该温度下继续搅拌反应12h。反应结束后,冷却到室温,真空旋转蒸馏回收DMF。残余物用100mL二氯甲烷溶解,然后依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液真空旋转蒸馏回收二氯甲烷。残余物用350mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到37.5g PEG2000-N3;
称取41.6g PEG2000-N3溶于100mL体积比为1:1的甲醇/水溶液中,室温下搅拌均匀后,依次加入5.1g 2-乙炔基吡啶、1.0g硫酸铜和0.8g抗坏血酸钠。然后,升温至45℃搅拌反应24h。反应结束后,反应液真空浓缩至粘稠,残余物用50mL 5w%氨水溶解,并在室温下搅拌12h。所得水溶液用二氯甲烷萃取3次,合并有机层,用依次用饱和食盐水洗涤,无水Na2SO4干燥,过滤除去干燥剂,母液真空旋转蒸馏回收二氯甲烷。残余物用350mL甲基叔丁基醚稀释,析出沉淀,过滤,滤饼在30℃下真空干燥3h,得到40.5g PEG2000-PyTa。
2.如权利要求1所述的不对称有机硒醚类化合物(I)的制备方法,其特征在于,反应温度条件为25~30℃。
3.如权利要求1所述的不对称有机硒醚类化合物(I)的制备方法,其特征在于,所述化合物(II)、化合物(III)、铜盐、PEG-PyTa的物质的量之比为1:2~4:0.05~0.3:0.03~0.8。
4.如权利要求1所述的不对称有机硒醚类化合物(I)的制备方法,其特征在于,所述溶剂水的体积用量以化合物(II)的物质的量计为4~6mL/mmol。
5.如权利要求1所述的不对称有机硒醚类化合物(I)的制备方法,其特征在于,所述表面活性剂的用量为溶剂水质量的1~3wt%。
6.如权利要求1所述的不对称有机硒醚类化合物(I)的制备方法,其特征在于,所述后处理的方法为:反应结束后,加入甲基叔丁基醚萃取2次,合并有机层,依次用饱和氯化钠水溶液洗涤,无水硫酸钠干燥和真空浓缩,粗产物以石油醚/乙酸乙酯体积比95:5混合液为洗脱剂,经200目硅胶柱层析纯化,收集含目标化合物的洗脱液,蒸除溶剂后得到目标产物(I)。
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