CN116751174A - Synthesis method of aryl substituted 1,3, 4-oxadiazole derivative - Google Patents
Synthesis method of aryl substituted 1,3, 4-oxadiazole derivative Download PDFInfo
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- CN116751174A CN116751174A CN202310666398.1A CN202310666398A CN116751174A CN 116751174 A CN116751174 A CN 116751174A CN 202310666398 A CN202310666398 A CN 202310666398A CN 116751174 A CN116751174 A CN 116751174A
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- CN
- China
- Prior art keywords
- substituted
- aryl
- oxadiazole
- oxadiazole derivative
- mol
- Prior art date
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- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 title claims abstract description 46
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 38
- 238000001308 synthesis method Methods 0.000 title abstract description 25
- -1 diazonium tetrafluoroborate Chemical class 0.000 claims abstract description 107
- 239000012954 diazonium Substances 0.000 claims abstract description 105
- 238000006243 chemical reaction Methods 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 29
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 238000005859 coupling reaction Methods 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims description 83
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 41
- 125000001033 ether group Chemical group 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 25
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims description 22
- 239000012414 tert-butyl nitrite Substances 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 230000002194 synthesizing effect Effects 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- 150000002367 halogens Chemical group 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical class ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000006193 diazotization reaction Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000012716 precipitator Substances 0.000 claims description 3
- 125000003158 alcohol group Chemical group 0.000 claims 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 10
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 10
- 239000003446 ligand Substances 0.000 abstract description 5
- 229910052763 palladium Inorganic materials 0.000 abstract description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 5
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 4
- 229910000510 noble metal Inorganic materials 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 78
- 238000005481 NMR spectroscopy Methods 0.000 description 78
- 229910052739 hydrogen Inorganic materials 0.000 description 78
- 239000001257 hydrogen Substances 0.000 description 78
- 238000001228 spectrum Methods 0.000 description 78
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- 239000012074 organic phase Substances 0.000 description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 30
- 239000000047 product Substances 0.000 description 27
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- ZEOMRHKTIYBETG-UHFFFAOYSA-N 2-phenyl-1,3,4-oxadiazole Chemical compound O1C=NN=C1C1=CC=CC=C1 ZEOMRHKTIYBETG-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 150000001989 diazonium salts Chemical class 0.000 description 23
- 238000000926 separation method Methods 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 239000003480 eluent Substances 0.000 description 19
- 239000007788 liquid Substances 0.000 description 19
- 239000012065 filter cake Substances 0.000 description 18
- 239000012046 mixed solvent Substances 0.000 description 18
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
- 239000011572 manganese Substances 0.000 description 17
- 238000003810 ethyl acetate extraction Methods 0.000 description 16
- 238000003809 water extraction Methods 0.000 description 16
- 125000004429 atom Chemical group 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 238000005286 illumination Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- DCJKUXYSYJBBRD-UHFFFAOYSA-N 2,5-diphenyl-1,3,4-oxadiazole Chemical compound C1=CC=CC=C1C1=NN=C(C=2C=CC=CC=2)O1 DCJKUXYSYJBBRD-UHFFFAOYSA-N 0.000 description 3
- IRMWPVKUGNEIGA-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-1,3,4-oxadiazole Chemical compound ClC1=CC(Cl)=CC=C1C1=NN=CO1 IRMWPVKUGNEIGA-UHFFFAOYSA-N 0.000 description 3
- CCNNEJPCNXRSQA-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-5-phenyl-1,3,4-oxadiazole Chemical compound ClC1=CC(Cl)=CC=C1C1=NN=C(C=2C=CC=CC=2)O1 CCNNEJPCNXRSQA-UHFFFAOYSA-N 0.000 description 3
- GYESXRJGLIKNAM-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1,3,4-oxadiazole Chemical compound C1=CC(OC)=CC=C1C1=NN=CO1 GYESXRJGLIKNAM-UHFFFAOYSA-N 0.000 description 3
- PGLXSBJEJSUXOB-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole Chemical compound C1=CC(OC)=CC=C1C1=NN=C(C=2C=CC=CC=2)O1 PGLXSBJEJSUXOB-UHFFFAOYSA-N 0.000 description 3
- VIXOOTOYIUQAMC-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NN=CO1 VIXOOTOYIUQAMC-UHFFFAOYSA-N 0.000 description 3
- SQDUJUPAOYJRKY-UHFFFAOYSA-N 2-phenyl-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NN=C(C=2C=CC=CC=2)O1 SQDUJUPAOYJRKY-UHFFFAOYSA-N 0.000 description 3
- HSRRBGFRHJMPJX-UHFFFAOYSA-N 2-tert-butyl-5-(4-methoxyphenyl)-1,3,4-oxadiazole Chemical compound C1=CC(OC)=CC=C1C1=NN=C(C(C)(C)C)O1 HSRRBGFRHJMPJX-UHFFFAOYSA-N 0.000 description 3
- DWSUGUDZPQYIFP-UHFFFAOYSA-N 2-tert-butyl-5-phenyl-1,3,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NN=C1C1=CC=CC=C1 DWSUGUDZPQYIFP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- KQCMTOWTPBNWDB-UHFFFAOYSA-N 2,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C=C1Cl KQCMTOWTPBNWDB-UHFFFAOYSA-N 0.000 description 2
- QOJQHOGSXXSMKX-UHFFFAOYSA-N 2,4-dichlorobenzohydrazide Chemical compound NNC(=O)C1=CC=C(Cl)C=C1Cl QOJQHOGSXXSMKX-UHFFFAOYSA-N 0.000 description 2
- ATCRIUVQKHMXSH-UHFFFAOYSA-N 2,4-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Cl ATCRIUVQKHMXSH-UHFFFAOYSA-N 0.000 description 2
- SETCKKFZFOFBSI-UHFFFAOYSA-N 2-tert-butyl-1,3,4-oxadiazole Chemical compound CC(C)(C)C1=NN=CO1 SETCKKFZFOFBSI-UHFFFAOYSA-N 0.000 description 2
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000004802 cyanophenyl group Chemical group 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 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 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 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
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- FYKZHAJQLBLBJO-UHFFFAOYSA-N 1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]propan-2-ol Chemical compound COC1=CC=CC=C1N1CCN(CC(O)COC=2C=C(C=CC=2)C=2OC(C)=NN=2)CC1 FYKZHAJQLBLBJO-UHFFFAOYSA-N 0.000 description 1
- OARJXUPBZNUYBG-UHFFFAOYSA-N 2,2-dimethylpropanehydrazide Chemical compound CC(C)(C)C(=O)NN OARJXUPBZNUYBG-UHFFFAOYSA-N 0.000 description 1
- NGEBYTLALFOQKI-UHFFFAOYSA-N 2-[4-[4-[[5-(3,4-difluoroanilino)-1,3,4-oxadiazole-2-carbonyl]amino]phenyl]cyclohexyl]acetic acid Chemical compound C1CC(CC(=O)O)CCC1C(C=C1)=CC=C1NC(=O)C(O1)=NN=C1NC1=CC=C(F)C(F)=C1 NGEBYTLALFOQKI-UHFFFAOYSA-N 0.000 description 1
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 1
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 1
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 1
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 1
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 1
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
- SNFCXVRWFNAHQX-UHFFFAOYSA-N 9,9'-spirobi[fluorene] Chemical compound C12=CC=CC=C2C2=CC=CC=C2C21C1=CC=CC=C1C1=CC=CC=C21 SNFCXVRWFNAHQX-UHFFFAOYSA-N 0.000 description 1
- FMMWHPNWAFZXNH-UHFFFAOYSA-N Benz[a]pyrene Chemical compound C1=C2C3=CC=CC=C3C=C(C=C3)C2=C2C3=CC=CC2=C1 FMMWHPNWAFZXNH-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940127193 DGAT1 inhibitor Drugs 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YOWVEYCZVUOQAB-SOFGYWHQSA-N Furamizole Chemical compound O1C(N)=NN=C1C(\C=1OC=CC=1)=C\C1=CC=C([N+]([O-])=O)O1 YOWVEYCZVUOQAB-SOFGYWHQSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Natural products C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- CWRYPZZKDGJXCA-UHFFFAOYSA-N acenaphthene Chemical compound C1=CC(CC2)=C3C2=CC=CC3=C1 CWRYPZZKDGJXCA-UHFFFAOYSA-N 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001717 carbocyclic compounds Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005401 electroluminescence Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- UOHSQQPZJHQLIC-UHFFFAOYSA-N furan;1h-imidazole Chemical compound C=1C=COC=1.C1=CNC=N1 UOHSQQPZJHQLIC-UHFFFAOYSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005067 haloformyl group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 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
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 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
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 229950007126 nesapidil Drugs 0.000 description 1
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- CSHWQDPOILHKBI-UHFFFAOYSA-N peryrene Natural products C1=CC(C2=CC=CC=3C2=C2C=CC=3)=C3C2=CC=CC3=C1 CSHWQDPOILHKBI-UHFFFAOYSA-N 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- IFLREYGFSNHWGE-UHFFFAOYSA-N tetracene Chemical compound C1=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C21 IFLREYGFSNHWGE-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/107—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/70—Complexes comprising metals of Group VII (VIIB) as the central metal
- B01J2531/72—Manganese
-
- 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
- B01J31/20—Carbonyls
-
- 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
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention relates to a synthesis method of an aryl substituted 1,3, 4-oxadiazole derivative, which comprises the following steps: under the conditions of Mn-containing catalyst and blue light, carrying out coupling reaction on the 1,3, 4-oxadiazole derivative and aryl-substituted diazonium tetrafluoroborate; the Mn-containing catalyst is selected from Mn 2 (CO) 10 、CpMn(CO) 3 And Mn (CO) 5 One or more of Br. The method has mild reaction conditions, high atom utilization rate and high product yield, and the Mn-containing catalyst adopted is cheap and easy to obtain, thereby avoiding the noble metal palladium and phosphine ligand catalyst with high cost and greatly reducing the synthesisCost is achieved; in addition, the operation is safe, the environment is protected, the process is simple and easy to implement, and the method is suitable for large-scale production.
Description
Technical Field
The invention relates to the technical field of synthesis of organic compounds, in particular to a synthesis method of aryl substituted 1,3, 4-oxadiazole derivatives.
Background
1,3, 4-oxadiazole is a five-membered heterocyclic molecule widely used, and has better pharmacokinetic properties due to the enhanced hydrolyzability and metabolic stability of the oxadiazole ring, and 1,3, 4-oxadiazole is used for synthesizing various drug molecules, such as Ralterravir (Ralterravir) which inhibits HIV, anti-retrovirus Ai Shengte (Isentess), anti-hypertensive drug Nesaldil (Nesapidil), antibiotic furan imidazole (Furamizole), and DGAT-1 inhibitor AZD 3988 for treating obesity and diabetes. In addition, aryl substituted 1,3, 4-oxadiazole derivatives can also be used for electroluminescence, preparation of OLED materials, and the like.
The current general method for constructing the 1,3, 4-oxadiazole heterocycle mainly adopts hydrazide, carboxylic acid, aldehyde ketone, semicarbazide, thiourea or carbon disulfide and other carbonyl-containing compounds to dehydrate and close the ring to obtain the substituted 1,3, 4-oxadiazole heterocycle containing corresponding functional groups. For example, a 2, 5-unsymmetrical disubstituted 1,3, 4-oxadiazole derivative synthesized by energizing a graphite-platinum electrode with a substituted hydrazide and a substituted α -carbonyl carboxylic acid has been reported; or 2, 4-dichlorobenzoyl hydrazine is synthesized by taking 2, 4-dichlorobenzoic acid as an initiator, and then the 2, 4-dichlorobenzoyl hydrazine reacts with carbon disulfide to synthesize the aryl substituted 1,3, 4-oxadiazole thioether compound. In addition, synthesis of aryl substituted 1,3, 4-oxadiazoles by benzaldehyde and preformed diazonium trivalent iodine reagents under illumination has also been reported. There are few reports of schemes for synthesizing aryl-substituted 1,3, 4-oxadiazole derivatives directly through in situ substitution of 1,3, 4-oxadiazole heterocycles.
The scheme for synthesizing aryl 1,3, 4-oxadiazole derivatives directly through 1,3, 4-oxadiazole heterocycle in situ substitution is known at present as follows: by TMP using 1,3, 4-oxadiazole heterocycles 2 The Zn.2LiCl reagent is prepared into Zn complex of oxadiazole heterocycle, and then the Zn complex is coupled with aryl iodide to synthesize aryl substituted 1,3, 4-oxadiazole derivative, wherein palladium and phosphine ligand are used as catalysts for the coupling reaction, and the palladium is noble metal and the phosphine ligand is expensive, so that the production cost of the reaction is high. In addition, TMP 2 Zn.2LiCl reagent is highly inflammable, the reaction is dangerous, and the large-scale production is difficult to realize.
Disclosure of Invention
Based on the above, the invention provides a synthesis method of aryl substituted 1,3, 4-oxadiazole derivatives, which has the advantages of easily available raw materials, mild reaction conditions, high atom utilization rate, high product yield and low cost, and is suitable for industrial production.
The technical proposal is as follows:
a method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative, comprising the steps of:
under the conditions of Mn-containing catalyst and blue light, carrying out coupling reaction on the 1,3, 4-oxadiazole derivative and aryl-substituted diazonium tetrafluoroborate;
the Mn-containing catalyst is selected from Mn 2 (CO) 10 、CpMn(CO) 3 And Mn (CO) 5 One or more of Br.
In one embodiment, the 1,3, 4-oxadiazole derivative has the structure shown in formula (I):
each R is 1 Each independently selected from alkyl, or aryl substituted or unsubstituted with R;
r is selected from any integer from 0 to 2;
each R is independently selected from halogen, cyano, amino, hydroxy, alkyl, alkoxy, or haloalkyl.
In one embodiment, each R 1 Independently selected from C1-C10 alkyl, or aryl with R substituted or unsubstituted ring atom number of 6-30.
In one embodiment, each R is independently selected from the group consisting of halogen, cyano, amino, hydroxy, C1-C20 straight chain alkyl, C3-C20 branched alkyl, C3-C20 cycloalkyl, C1-C20 straight chain alkoxy, C3-C20 branched alkoxy, C3-C20 cycloalkoxy, halo C1-C20 straight chain alkyl, halo C3-C20 branched alkyl, and halo C3-C20 cycloalkyl.
In one embodiment, the aryl substituted diazonium tetrafluoroborate salt has the structure shown in formula (II) below:
each R is 2 Each independently selected from alkyl, alkoxy, fluoroalkyl, or halogen;
m is selected from any integer from 0 to 5.
In one embodiment, the R 2 Ortho-or para-substituted with respect to the diazo group.
In one embodiment, each R 2 Independently selected from C1-C10 alkyl, C1-C10 alkoxy, C1-C10 fluoroalkyl or halogen.
In one embodiment, the molar ratio of the 1,3, 4-oxadiazole derivative to the aryl-substituted diazonium tetrafluoroborate is 1: (1-2.5).
In one embodiment, the molar ratio of the Mn-containing catalyst to 1,3, 4-oxadiazole derivative is (1-10): 100.
in one embodiment, the coupling reaction is carried out at a temperature of 5-40 ℃ for a time of 0.5-10 hours.
In one embodiment, the solvent used in the coupling reaction is one or a mixture of two of dimethyl sulfoxide and N, N-dimethylformamide.
In one embodiment, the method of preparing the aryl-substituted diazonium tetrafluoroborate salt comprises the steps of:
mixing a primary ammonia substituted aryl derivative with tetrafluoroboric acid aqueous solution in a solvent for reaction to generate tetrafluoroborate;
diazotizing the tetrafluoroborate and nitrous acid compounds, and adding a precipitator to separate out aryl substituted tetrafluoroborate diazonium salt.
In one embodiment, the solvent is an alcoholic solvent.
In one embodiment, the nitrous compound is t-butyl nitrite.
In one embodiment, the precipitant is methyl tertiary ether.
In one embodiment, the diazotization reaction is performed at a temperature of 0 ℃ +/-5 ℃ for 0.5-2 hours.
The invention has at least the following beneficial effects:
according to the invention, the manganese-containing compound is used as a catalyst, and under the action of blue light, the coupling reaction of the 1,3, 4-oxadiazole derivative and the aryl-substituted diazonium tetrafluoroborate can be effectively catalyzed, so that the aryl-substituted 1,3, 4-oxadiazole derivative is prepared, and the reaction condition is mild, the atom utilization rate is high, and the product yield is high. In addition, the method has the following advantages:
(1) The Mn-containing catalyst adopted in the reaction is cheap and easy to obtain, so that the noble metal palladium and phosphine ligand catalyst with high cost is avoided, and the aryl tetrafluoroboric acid diazonium salt is easy to prepare and stable, so that the synthesis cost is greatly reduced;
(2) The aryl-substituted 1,3, 4-oxadiazole derivative is synthesized directly through 1,3, 4-oxadiazole heterocycle in-situ substitution, so that the steps are few, and the production efficiency is high;
(3) The reaction condition is mild, the operation is safe, the environment is protected, the process is simple and easy to implement, and the method is suitable for large-scale production.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Terminology
Unless otherwise indicated or contradicted, terms or phrases used herein have the following meanings:
the term "and/or", "and/or" as used herein includes a selection of any one of two or more of the listed items and also includes any and all combinations of the listed items, including any two or more of the listed items, or all combinations of the listed items. It should be noted that, when at least three items are connected by at least two conjunctions selected from the group consisting of "and/or", "and/or", it is to be understood that, in the present invention, the technical solutions certainly include technical solutions that all use "logical and" connection, and also certainly include technical solutions that all use "logical or" connection. For example, "a and/or B" includes three parallel schemes A, B and a+b. For another example, the technical schemes of "a, and/or B, and/or C, and/or D" include any one of A, B, C, D (i.e., the technical scheme of "logical or" connection), and also include any and all combinations of A, B, C, D, i.e., any two or three of A, B, C, D, and also include four combinations of A, B, C, D (i.e., the technical scheme of "logical and" connection).
In the present invention, "plural" means at least two, for example, two, three, etc., and "multi-layer" means at least two, for example, two, three, etc., unless specifically defined otherwise. In the description of the present invention, the meaning of "several" means at least one, such as one, two, etc., unless specifically defined otherwise.
All steps of the present invention may be performed sequentially or randomly unless otherwise specified. For example, the method comprises steps (a) and (b), meaning that the method may comprise steps (a) and (b) performed sequentially, or may comprise steps (b) and (a) performed sequentially. For example, the method may further comprise step (c), meaning that step (c) may be added to the method in any order, e.g., the method may comprise steps (a), (b) and (c), steps (a), (c) and (b), steps (c), (a) and (b), etc.
In the present invention, "preferable", "preferred", "better", etc. are merely embodiments or examples for better effects, and it should be understood that the scope of the present invention is not limited thereto.
In the present invention, "further", "still further", "particularly" and the like are used for descriptive purposes to indicate differences in content but should not be construed as limiting the scope of the invention.
In the present invention, the technical features described in an open manner include a closed technical scheme composed of the listed features, and also include an open technical scheme including the listed features.
In the present invention, a numerical range (i.e., a numerical range) is referred to, and optional numerical distributions are considered to be continuous within the numerical range and include two numerical endpoints (i.e., a minimum value and a maximum value) of the numerical range and each numerical value between the two numerical endpoints unless otherwise specified. When a numerical range merely points to integers within the numerical range, both end integers of the numerical range are included, as well as each integer between the two ends, unless expressly stated otherwise. Further, when a plurality of range description features or characteristics are provided, these ranges may be combined. In other words, unless otherwise indicated, the ranges disclosed herein are to be understood to include any and all subranges subsumed therein.
In the present invention, the number of atoms described by a numerical range includes both the end points of the integer of the numerical range and also includes each integer of the two end points. For example, "C1-C10 alkyl" means an alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
In the present invention, the "number of ring atoms" means the number of atoms among atoms constituting the ring itself of a structural compound (for example, a monocyclic compound, a condensed ring compound, a crosslinked compound, a carbocyclic compound, a heterocyclic compound) in which atoms are bonded to form a ring. When the ring is substituted with a substituent, the atoms contained in the substituent are not included in the ring-forming atoms. The same applies to the "number of ring atoms" described below, unless otherwise specified. For example, the number of ring atoms of the benzene ring is 6, and the number of ring atoms of the naphthalene ring is 10.
In the present invention,represents the attachment site of the undefined substituent R.
In the present invention, "halogen" or "halo" refers to F, cl, br or I.
In the present invention, the term "alkyl" refers to a monovalent residue of a saturated hydrocarbon containing a primary (positive) carbon atom, or a secondary carbon atom, or a tertiary carbon atom, or a quaternary carbon atom, or a combination thereof, losing one hydrogen atom. The phrase containing the term, for example, "C1-C10 alkyl" refers to an alkyl group containing 1 to 10 carbon atoms, which may be, independently of each other, C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, or C10 alkyl. Suitable examples include, but are not limited to: methyl (Me, -CH) 3 ) Ethyl (Et, -CH) 2 CH 3 ) 1-propyl (n-Pr, n-propyl, -CH 2 CH 2 CH 3 ) 2-propyl (i-Pr, i-propyl, -CH (CH) 3 ) 2 ) 1-butyl (n-Bu, n-butyl, -CH) 2 CH 2 CH 2 CH 3 ) 2-methyl-1-propyl (i-Bu, i-butyl, -CH) 2 CH(CH 3 ) 2 ) 2-butyl (s-Bu, s-butyl, -CH (CH) 3 )CH 2 CH 3 ) 2-methyl-2-propyl (t-Bu, t-butyl, -C (CH) 3 ) 3 ) 1-pentyl (n-pentyl, -CH) 2 CH 2 CH 2 CH 2 CH 3 ) 2-pentyl (-CH (CH) 3 )CH 2 CH 2 CH 3 ) 3-pentyl (-CH (CH) 2 CH 3 ) 2 ) 2-methyl-2-butyl (-C (CH) 3 ) 2 CH 2 CH 3 ) 3-methyl-2-butyl (-CH (CH) 3 )CH(CH 3 ) 2 ) 3-methyl-1-butyl (-CH) 2 CH 2 CH(CH 3 ) 2 ) 2-methyl-1-butyl (-CH) 2 CH(CH 3 )CH 2 CH 3 ) 1-hexyl (-CH) 2 CH 2 CH 2 CH 2 CH 2 CH 3 ) 2-hexyl (-CH (CH) 3 )CH 2 CH 2 CH 2 CH 3 ) 3-hexyl (-CH (CH) 2 CH 3 )(CH 2 CH 2 CH 3 ) 2-methyl-2-pentyl (-C (CH) 3 ) 2 CH 2 CH 2 CH 3 ) 3-methyl-2-pentyl (-CH (CH) 3 )CH(CH 3 )CH 2 CH 3 ) 4-methyl-2-pentyl (-CH (CH) 3 )CH 2 CH(CH 3 ) 2 ) 3-methyl-3-pentyl (-C (CH) 3 )(CH 2 CH 3 ) 2 ) 2-methyl-3-pentyl (-CH (CH) 2 CH 3 )CH(CH 3 ) 2 ) 2, 3-dimethyl-2-butyl (-C (CH) 3 ) 2 CH(CH 3 ) 2 ) 3, 3-dimethyl-2-butyl (-CH (CH) 3 )C(CH 3 ) 3 And octyl (- (CH) 2 ) 7 CH 3 )。
In the present invention, "haloalkyl" refers to an alkyl group substituted with one or more halogen (chlorine, fluorine, bromine or iodine) atoms. Polyhaloalkyl groups have the same or mixed types of halogen atoms. "perhaloalkyl" means that each hydrogen atom in the alkyl group is replaced with a halogen atom. A haloalkyl group "fully halogenated" with respect to a particular carbon atom means that all of the hydrogen atoms attached to that carbon atom are replaced with halogen atoms. Representative mono-, di-and tri-haloalkyl groups include: chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodomethyl, iodoethyl, chloropropyl, bromopropyl, iodopropyl, 1-dichloromethyl, 1-dibromomethyl, 1-dichloropropyl, 1, 2-dibromopropyl, 2, 3-dibromopropyl, 1-chloro-2-bromoethyl, 2-chloro-3-bromopropyl, trifluoromethyl, trichloromethyl, and the like. It is understood that "fluoroalkyl" refers to an alkyl group substituted with one or more fluorine atoms.
In the present invention, "cycloalkyl" refers to a non-aromatic hydrocarbon containing a ring carbon atom, and may be a monocyclic alkyl group, a spirocycloalkyl group, or a bridged cycloalkyl group. The phrase containing the term, for example, "C3-C10 cycloalkyl" refers to cycloalkyl groups containing 3 to 10 carbon atoms, which at each occurrence may be, independently of one another, C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl or C10 cycloalkyl. Suitable examples include, but are not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. In addition, "cycloalkyl" may also contain one or more double bonds, and representative examples of cycloalkyl groups containing a double bond include cyclopentenyl, cyclohexenyl, cyclohexadienyl, and cyclobutenyl.
In the present invention, "substituted" means that a hydrogen atom in a substituted group is substituted by a substituent.
In the present invention, "substituted or unsubstituted" means that the defined group may or may not be substituted. When a defined group is substituted, it is understood that the defined group may be substituted with one or more substituents R selected from, but not limited to: deuterium, cyano, isocyano, nitro or halogen, alkyl containing 1 to 9C atoms, cycloalkyl containing 3 to 9C atoms, -NR' R ", silane, carbonyl, alkoxycarbonyl, aryloxycarbonyl, carbamoyl, haloformyl, formyl, isocyanate, thiocyanate, isothiocyanate, hydroxy, trifluoromethyl, which may be further substituted with substituents acceptable in the art; it is understood that R 'and R "in-NR' R" are each independently selected from, but not limited to: H. deuterium atoms, cyano groups, isocyano groups, nitro groups or halogen groups, alkyl groups containing 1 to 9C atoms, cycloalkyl groups containing 3 to 9C atoms.
In the present invention, "aromatic group" or "aryl" refers to a hydrocarbon group containing at least one aromatic ring, including monocyclic groups and polycyclic ring systems. These polycyclic rings may have two or more rings in which two carbon atoms are shared by two adjacent rings, i.e., fused rings. Polycyclic, these cyclic species, at least one of which is aromatic or heteroaromatic. For the purposes of the present invention, aromatic groups or aryl groups include not only aromatic systems, but also systems in which a plurality of aromatic groups may also be interrupted by short non-aromatic units (e.g. C atoms). Thus, systems such as 9,9' -spirobifluorene, 9-diaryl fluorene, etc., are likewise considered aromatic groups for the purposes of this invention.
Specifically, examples of the aromatic group are: benzene, naphthalene, anthracene, phenanthrene, perylene, naphthacene, pyrene, benzopyrene, triphenylene, acenaphthene, fluorene, and derivatives of these aryl groups.
The temperature parameter in the present invention is not particularly limited, and may be a constant temperature treatment or may vary within a predetermined temperature range. It should be appreciated that the constant temperature process described allows the temperature to fluctuate within the accuracy of the instrument control. Allows for fluctuations within a range such as + -5 ℃, + -4 ℃, + -3 ℃, + -2 ℃, + -1 ℃.
The traditional method for constructing the 1,3, 4-oxadiazole heterocycle requires that a hydrazide or diazo trivalent iodine reagent containing a target oxadiazole heterocycle substituent is prepared in advance, and then the substituted 1,3, 4-oxadiazole heterocycle containing corresponding functional groups is synthesized through ring closure, but the reaction directly participated by the 1,3, 4-oxadiazole heterocycle is hardly reported, and the technology cannot solve the re-arylation reaction of the derivative containing the 1,3, 4-oxadiazole heterocycle.
Aryl substitution reactions utilizing direct participation of 1,3, 4-oxadiazole heterocycles have been reported, but require the use of noble metal palladium and a more noble phosphine ligand as catalysts, and TMP 2 Zn.2LiCl reagent is highly inflammable, the reaction is dangerous, and the large-scale production is difficult to realize.
The invention provides a synthesis method of aryl substituted 1,3, 4-oxadiazole derivatives, which has the advantages of easily available raw materials, mild reaction conditions, high atom utilization rate, high product yield and low cost, and is suitable for industrial production.
The technical proposal is as follows:
a method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative, comprising the steps of:
under the conditions of Mn-containing catalyst and blue light, carrying out coupling reaction on the 1,3, 4-oxadiazole derivative and aryl-substituted diazonium tetrafluoroborate;
The Mn-containing catalyst is selected from Mn 2 (CO) 10 、CpMn(CO) 3 And Mn (CO) 5 One or more of Br.
The Mn-containing catalyst is cheap and easy to obtain, can effectively catalyze the coupling reaction of the 1,3, 4-oxadiazole derivative and aryl-substituted tetrafluoroboric acid diazonium salt under the action of blue light, and can prepare the aryl-substituted 1,3, 4-oxadiazole derivative, and the reaction condition is mild, the atomic utilization rate is high, and the product yield is high.
In one embodiment, the Mn-containing catalyst is CpMn (CO) 3 。
In one embodiment, the wavelength of blue light is 450nm to 500nm.
In one embodiment, the 1,3, 4-oxadiazole derivative has the structure shown in formula (I):
each R is 1 Each independently selected from alkyl, or aryl substituted or unsubstituted with R;
r is selected from any integer from 0 to 2;
each R is independently selected from halogen, cyano, amino, hydroxy, alkyl, alkoxy, or haloalkyl.
Further, each R is independently selected from the group consisting of halogen, cyano, amino, hydroxy, C1-C20 straight chain alkyl, C3-C20 branched chain alkyl, C3-C20 cycloalkyl, C1-C20 straight chain alkoxy, C3-C20 branched chain alkoxy, C3-C20 cycloalkoxy, halogenated C1-C20 straight chain alkyl, halogenated C3-C20 branched chain alkyl, halogenated C3-C20 cycloalkyl. Further, each R is independently selected from F, cl, br, I, cyano, amino, C1-C10 straight chain alkyl, C3-C10 branched alkyl, C3-C10 cycloalkyl, C1-C10 straight chain alkoxy, C3-C10 branched alkoxy, C3-C10 cycloalkoxy, fluoro C1-C10 straight chain alkyl, fluoro C3-C10 branched alkyl, fluoro C3-C20 cycloalkyl.
Further, each R 1 Independently selected from C1-C10 alkyl, or aryl with R substituted or unsubstituted ring atom number of 6-30. Further, the aryl group having 6 to 30 ring atoms is selected from phenyl, naphthyl, phenanthryl, anthryl, benzophenanthryl, biphenyl, terphenyl. Further, each R 1 Independently selected from methyl, ethyl, isopropyl, tert-butyl, phenyl, trifluoromethylphenyl, methoxyphenyl, halophenyl, alkylphenyl, or cyanophenyl. Further, each R 1 Each independently selected from methyl, ethyl, isopropyl, tert-butyl, phenyl, trifluoromethylphenyl, methoxyphenyl, fluorophenyl, alkylphenyl, or cyanophenyl.
It is understood that r is selected from any integer from 0 to 2, including but not limited to 0, 1 and 2.
In one embodiment, the 1,3, 4-oxadiazole derivative is selected from the group consisting of
In one embodiment, the aryl substituted diazonium tetrafluoroborate salt has the structure shown in formula (II) below:
each R is 2 Each independently selected from alkyl, alkoxy, fluoroalkyl, or halogen;
m is selected from any integer from 0 to 5.
Further, each R 2 Independently selected from C1-C10 alkyl, C1-C10 alkoxy, C1-C10 fluoroalkyl or halogen. Further, each R 2 Each independently selected from methyl, methoxy, trifluoromethyl or halogen.
It will be appreciated that m is selected from any integer from 0 to 5, including but not limited to 0, 1, 2, 3,4 and 5, preferably 0, 1 or 2.
In one embodiment, the R 2 Ortho-or para-substituted with respect to the diazo group.
In one embodiment, the aryl substituted diazonium tetrafluoroborate salt is selected from the group consisting of a diazonium phenyl tetrafluoroborate salt, a diazonium 4-trifluoromethylphenyl tetrafluoroborate salt, a diazonium 4-methoxyphenyl tetrafluoroborate salt, and a diazonium 2, 4-dichlorophenyl tetrafluoroborate salt.
In one embodiment, the aryl-substituted 1,3, 4-oxadiazole derivative has the structure shown in formula (III):
p is 1, r-p is 0 or 1;
p is 2 and r-p is 0.
The synthetic route for aryl-substituted 1,3, 4-oxadiazole derivatives having the structure shown in the following formula (III) is as follows:
in one embodiment, the method of preparing the aryl-substituted diazonium tetrafluoroborate salt comprises the steps of:
mixing a primary ammonia substituted aryl derivative with tetrafluoroboric acid aqueous solution in a solvent for reaction to generate tetrafluoroborate;
diazotizing the tetrafluoroborate and nitrous acid compounds, and adding a precipitator to separate out aryl substituted tetrafluoroborate diazonium salt.
In one embodiment, the solvent is an alcoholic solvent. Optionally, the solvent is methanol and/or ethanol.
In one embodiment, the nitrous compound is t-butyl nitrite.
In one embodiment, the precipitant is methyl tertiary ether.
In one embodiment, the temperature of the diazotisation reaction is 0 ℃ ± 5 ℃, including but not limited to-5 ℃, -2 ℃, 0 ℃, 1 ℃, 2 ℃,3 ℃,4 ℃ and 5 ℃.
In one embodiment, the diazotization reaction time is 0.5h to 2h, including but not limited to 0.5h, 1h, 1.5h, 2h.
In one embodiment, the molar ratio of the 1,3, 4-oxadiazole derivative to the aryl-substituted diazonium tetrafluoroborate is 1: (1-2.5), including but not limited to 1:1. 1:1.2, 1:1.5, 1:1.8, 1:2.0, 1:2.2 and 1:2.5.
in one embodiment, the molar ratio of the Mn-containing catalyst to 1,3, 4-oxadiazole derivative is (1-10): 100, including but not limited to 1: 100. 2:100, 3:100, 5:100, 6:100, and 10:100.
In one embodiment, the coupling reaction is at a temperature of 5℃to 40℃including, but not limited to, 5 ℃, 10 ℃, 15 ℃, 20 ℃, 22 ℃, 23 ℃, 25 ℃, 26 ℃, 28 ℃, 30 ℃, 32 ℃, 34 ℃, 36 ℃, 38 ℃, and 40 ℃.
In one embodiment, the coupling reaction is performed for a period of time ranging from 0.5h to 10h, including but not limited to 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 6h, 7h, 8h, 9h, and 10h.
In one embodiment, the solvent used in the coupling reaction is one or a mixture of two of dimethyl sulfoxide and N, N-dimethylformamide.
In one embodiment, the method for preparing the aryl-substituted diazonium tetrafluoroborate salt further comprises the steps of:
and (3) purifying the aryl substituted diazonium tetrafluoroborate.
In one embodiment, the purification treatment of the aryl-substituted diazonium tetrafluoroborate salt comprises:
ethyl acetate and water are added into the reaction liquid to extract and separate liquid, the organic phase is saturated, washed for 3 times by saline water, dried and filtered, and a mixed solvent (v: v is 1 (1-20)) of normal hexane and ethyl acetate is adopted as an eluent to pass through a column for separation, so that a clean product is obtained.
The present invention is described in further detail below in connection with specific examples.
The room temperature described in the examples and comparative examples below refers to 25 ℃.+ -. 5 ℃.
(2) In the following examples and comparative examples, the catalyst:
C1:Mn 2 (CO) 10 ；C2:CpMn(CO) 3 ；C3:Mn(CO) 5 Br。
(3) Synthesis of 1,3, 4-oxadiazole derivatives:
(1) S1, 3, 4-oxadiazoleIs synthesized by the following steps:
after Ar was replaced three times with a multi-necked flask, 108g of polyphosphoric acid was added, the mixture was heated to 100℃and phosphorus pentoxide (12 g,42 mmol) was added thereto, followed by stirring for 15 minutes, and then N.N' -dimethylhydrazide (12 g,136 mmol) was added thereto and stirring was continued for 4 hours. The reaction mixture was poured into 100g of ice to quench, neutralized with solid sodium hydrogencarbonate, extracted 3 times with methylene chloride, and the organic phase was dried over anhydrous sodium sulfate and dried by spin to give 2.86g of the product in 30% yield.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3 ,400MHz):δ＝8.51(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, it is known that the target compound 1,3, 4-oxadiazole is synthesizedDenoted by S1.
(2) S2: 2-tert-butyl-1, 3, 4-oxadiazoleIs synthesized by the following steps:
a multi-port bottle is connected with a distillation device, pivaloyl hydrazine (8.80 g,76.0 mmol), trimethyl orthoformate (12.5 mL,114 mmol) and p-toluenesulfonic acid hydrate (217 mg,1.14 mmol) are added into a reaction bottle, the temperature is controlled to 80-120 ℃ for 2h, methanol is distilled off in the reaction process, and after the reaction, 6.58g of pale yellow liquid is obtained by reduced pressure distillation, and the yield is 69%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3 ,400MHz)δ1.45(9H),8.32(1H).
from the above-mentioned nuclear magnetic resonance hydrogen spectrum data, it is known that the target compound 2-tert-butyl-1, 3, 4-oxadiazole is synthesized Denoted by S2.
Example 1:
this example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, tetrafluoroboric acid mass fraction 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2): 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C1 (0.39 g, 2% mol of S1) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times with saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to pass through a column for separation, so that 3.6g of clean product is obtained, and the yield is 49%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, 400MHz)δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Example 2: synthesis of 2-phenyl-1, 3, 4-oxadiazole
This example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by (a)
Aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, tetrafluoroboric acid mass fraction 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether was added, the mixture was filtered, the methyl tertiary ether was washed, and the cake was collected to give the product phenyl tetrafluoroboric acid diazonium salt (16.3 g, yield 85%).
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.21 g, 2% mol of S1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h under the condition of 24W blue light illumination at 25 ℃, ethyl acetate and water extraction liquid are added after the reaction is finished, an organic phase saturated saline solution is washed for 3 times, and then the organic phase saturated saline solution is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to obtain 6.2g of clean product through column separation, and the yield is 85%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, )δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Example 3:
this example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) Synthesis of 2-phenyl-1, 3, 4-oxadiazole
Phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C3 (0.27 g, 2% mol of S1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h under the condition of 24W blue light illumination at 25 ℃, ethyl acetate and water extraction liquid are added after the reaction is finished, an organic phase saturated saline solution is washed for 3 times, and then the organic phase saturated saline solution is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to obtain 4.6g of clean product through column separation, and the yield is 63%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, )δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Example 4:
this example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps: />
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by (a)
Phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.11 g, 1% mol of S1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h under the condition of 24W blue light illumination at 25 ℃, ethyl acetate and water extraction liquid are added after the reaction is finished, an organic phase saturated saline solution is washed for 3 times, and then the organic phase saturated saline solution is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to obtain a clean product by column separation, 3.8g is obtained, and the yield is 52%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, )δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Example 5:
this example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.53 g, 5% mol of S1) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is used as an eluent to pass through a column for separation, so that 6.4g of clean product is obtained, and the yield is 88%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, )δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Example 6:
this example provides a 2-tert-butyl-5-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-tert-butyl-5-phenyl-1, 3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S2 (6.0 g,0.05mol)，CpMn(CO) 3 (0.21 g, 2% mol of S2) and 20 mM DS were added to the flask and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is used as an eluent to pass through a column for separation, so that 8.8g of clean product is obtained, and the yield is 87%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl3):δ8.06-8.03(2H),δ7.52-7.48(3H),δ1.49(9H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-tert-butyl-5-phenyl-1, 3, 4-oxadiazole, represented by P2, was synthesized.
Example 7:
this example provides a 2- (4-trifluoromethylphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) 4-trifluoromethyl phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps: />
4-trifluoromethylaniline (16.1 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0℃and tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise thereto, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 24.7g of 4-trifluoromethyl phenyl tetrafluoroboric acid diazonium salt with the yield of 95 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.90(2H),δ8.41(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 4-trifluoromethylphenyl tetrafluoroborate diazonium salt was synthesized.
(2) Synthesis of 2- (4-trifluoromethylphenyl) -1,3, 4-oxadiazole:
under Ar atmosphere, 4-trifluoromethylphenyl tetrafluoroborate diazonium salt (13 g,0.05 mol) and 1,3, 4-oxadiazole S1 (3.5 g,0.05 mol) were combined with CpMn (CO) 3 (0.21 g, 2% mol of S1) and 20 mM DS were added to the flask and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times with saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is adopted as an eluent to pass through a column for separation, so that 7.0g of clean product is obtained, and the yield is 79%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3 )δ8.55(1H),δ8.10(2H),δ7.68(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2- (4-trifluoromethylphenyl) -1,3, 4-oxadiazole, represented by P3, was synthesized.
Example 8:
this example provides a 2- (4-methoxyphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) 4-methoxyphenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
para-aminoanisole (12.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10min, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1h. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 15.5g of 4-methoxy phenyl tetrafluoroboric acid diazonium salt with the yield of 70 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.60(2H),δ7.48(2H),δ4.04(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 4-methoxyphenyl tetrafluoroboric acid diazonium salt was synthesized.
(2) 2- (4-methoxyphenyl) -1,3, 4-oxadiazoleIs synthesized by (a)
Under Ar atmosphere, 4-methoxyphenyl tetrafluoroborate diazonium salt (11.1 g,0.05 mol) and 1,3, 4-oxadiazole S1 (3.5 g,0.05 mol) were added with CpMn (CO) 3 (0.21 g, 2% mol of S1) and 20ml of LDMSO are added into a reaction bottle to react for 1h under the condition of 24W blue light illumination, ethyl acetate and water are added after the reaction is finished, the separated liquid is extracted, the organic phase is washed for 3 times by saturated saline, then the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is adopted as an eluent to obtain 9.8g of clean product through column separation, and the yield is 92%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl3)δ8.41(1H),δ8.02(2H),δ7.02(2H),δ3.88(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2- (4-methoxyphenyl) -1,3, 4-oxadiazole, represented by P4, was synthesized.
Example 9:
this example provides a 2- (2, 4-dichlorophenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) 2, 4-dichlorophenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
2, 4-dichloroaniline (16.2 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10min, cooled to 0℃and tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise thereto, and after returning to room temperature, stirred for 1h. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 23.0g of 2, 4-dichlorophenyl tetrafluoroboric acid diazonium salt with the yield of 88%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.64(1H),δ8.05(1H),δ7.66(1H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2, 4-dichlorophenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2- (2, 4 dichlorophenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
2, 4-dichlorophenyl tetrafluoroborate diazonium salt (13.04 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.21 g, 2% mol of S1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h under the condition of 24W blue light, ethyl acetate and water extraction liquid are added after the reaction is finished, and after the organic phase saturated saline is washed for 3 times, the organic phase saturated saline is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to obtain 9.6g of clean product through column separation, and the yield is 89%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl3)δ8.57(1H),δ7.96(1H),δ7.58(1H),δ7.41(1H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2- (2, 4 dichlorophenyl) -1,3, 4-oxadiazole, represented by P5, was synthesized.
Example 10:
this example provides a 2-tert-butyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps: />
(1) 4-methoxyphenyl tetrafluoroboric acid diazonium saltIs synthesized by (a)
Para-aminoanisole (12.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10min, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1h. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 15.5g of 4-methoxy phenyl tetrafluoroboric acid diazonium salt with the yield of 70 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6,300MHz)δ8.60(2H),δ7.48(2H),δ4.04(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 4-methoxyphenyl tetrafluoroboric acid diazonium salt was synthesized.
(2) 2-tert-butyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
4-Methoxyphenyl tetrafluoroborate diazonium salt (11.1 g,0.05 mol) and S2 (6.0 g,0.05 mol), C2 (0.21 g, 2% mol of S2) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times with saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is adopted as an eluent to pass through a column for separation, so that 9.5g of clean product is obtained, and the yield is 82%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ7.92(2H),δ7.12(2H),δ3.84(3H),δ1.41(9H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-tert-butyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazole, represented by P6, was synthesized.
Example 11:
this example provides a 2-tert-butyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) 4-trifluoromethyl phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
4-trifluoromethylaniline (16.1 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0℃and tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise thereto, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 24.7g of 4-trifluoromethyl phenyl tetrafluoroboric acid diazonium salt with the yield of 95 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6，300MHz,)δ8.90(2H),δ8.41(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 4-trifluoromethylphenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-tert-butyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
4-trifluoromethylphenyl tetrafluoroborate diazonium salt (13 g,0.05 mol) and S2 (6.0 g,0.05 mol), C2 (0.21 g, 2% mol of S2) and 20 mM LDMSO are added into a reaction bottle under Ar atmosphere, under the condition of 24W blue light illumination, ethyl acetate and water extraction liquid separation are added after the reaction is finished and the organic phase saturated saline water is washed for 3 times, and then the mixture is dried and filtered, and a mixed solvent (v: v is 1:10) of normal hexane and ethyl acetate is used as an eluent to obtain 12.7g of clean product through column separation, and the yield is 93%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.19(1H),δ7.93(1H),δ1.43(4H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-tert-butyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazole was synthesized and represented by P7.
Example 12:
this example provides a 2-tert-butyl-5- (2, 4-dichlorophenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) 2, 4-dichlorophenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
2, 4-dichloroaniline (16.2 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10min, cooled to 0℃and tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise thereto, and after returning to room temperature, stirred for 1h. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 23.0g of 2, 4-dichlorophenyl tetrafluoroboric acid diazonium salt with the yield of 88%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6,300mHz)δ8.64(1H),δ8.05(1H),δ7.66(1H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2, 4-dichlorophenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-tert-butyl-5- (2, 4-dichlorophenyl) 1,3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (13 g,0.05 mol) and S2 (6.0 g,0.05 mol), C2 (0.21 g, 2% mol of S2) and 20 mM DS were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is used as an eluent to pass through a column for separation, so that 12.3g of clean product is obtained, and the yield is 91%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.04(1H),δ7.93(1H),δ7.62(1H)δ1.42(9H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-tert-butyl-5- (2, 4-dichlorophenyl) 1,3, 4-oxadiazole was synthesized and represented by P8.
Example 13:
this example provides a 2, 5-diphenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6,300mHz)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2, 5-diphenyl-1, 3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and P1 (10 g,0.05 mol), C2 (0.21 g, 2% mol of P1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h under the condition of 24W blue light illumination, ethyl acetate and water extraction liquid separation are added after the reaction is finished, an organic phase saturated saline solution is washed for 3 times, and then the organic phase saturated saline solution is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is adopted as an eluent to obtain 8.4g of clean product through column separation, and the yield is 76%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.15-8.08(4H),δ7.66-7.60(6H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2, 5-diphenyl-1, 3, 4-oxadiazole, represented by P9, was synthesized.
Example 14:
this example provides a 2-phenyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and P4 (10 g,0.05 mol), C2 (0.21 g, 2% mol of P4) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water were added to separate the solution, and the organic phase was washed 3 times with saturated brine, dried and filtered, and the mixture of n-hexane and ethyl acetate (v: 1:10) was used as an eluent to obtain 9.96g of a clean product in 79% yield by column separation.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.15-8.11(2H),δ8.11-8.05(2H),δ7.54(3H),δ7.09-7.00(2H),δ3.90(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-5- (4-methoxyphenyl) -1,3, 4-oxadiazole, represented by P10, was synthesized.
Example 15:
this example provides a 2-phenyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and P3 (8.8 g,0.05 mol), C2 (0.21 g, 2% mol of P3) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is adopted as an eluent to pass through a column for separation, so that 10.0g of clean product is obtained, and the yield is 69%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl3)δ8.41(1H),δ8.37(1H),δ8.20-8.16(2H),δ7.84(1H),δ7.71(1H),δ7.62-7.55(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazole was synthesized and represented by P11.
Example 16:
this example provides a 2-phenyl-5- (2, 4-dichlorophenyl) -1,3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-5- (2, 4-dichlorophenyl) -1,3, 4-oxadiazoleIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and P5 (10.8 g,0.05 mol), C2 (0.21 g, 2% mol of P5) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W blue light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:10) is used as an eluent to pass through a column for separation, so that 11.9g of clean product is obtained, and the yield is 82%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl3)δ8.24(1H)δ8.15-8.11(2H)δ7.91(1H)δ7.76(1H)δ7.64(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-5- (2, 4-dichlorophenyl) -1,3, 4-oxadiazole, represented by P12, was synthesized.
Comparative example 1:
this comparative example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2) 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.21 g, 2% mol of S1) and 20ml of LDMSO are added into a reaction bottle under Ar atmosphere, and reacted for 1h at 25 ℃ under the condition of white light illumination, ethyl acetate and water extraction liquid are added after the reaction is finished, an organic phase saturated saline solution is washed for 3 times, and then the organic phase saturated saline solution is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is adopted as an eluent to obtain 2.6g of clean product through column separation, and the yield is 36%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, 400MHz)δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Comparative example 2:
this comparative example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps:
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt, and the yield is 85%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2): 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.21 g, 2% mol of S1) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, and reacted at 25℃for 1 hour under 24W of red light. After the reaction, ethyl acetate and water extraction liquid are added, and after the organic phase is washed for 3 times by saturated saline, the organic phase is dried and filtered, and a mixed solvent of normal hexane and ethyl acetate (v: v is 1:5) is used as an eluent to pass through a column for separation, so that 0.4g of clean product is obtained, and the yield is 5%.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(CDCl 3, )δ8.48(1H),δ8.11–8.05(2H),δ7.57–7.49(3H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound 2-phenyl-1, 3, 4-oxadiazole, represented by P1, was synthesized.
Comparative example 3:
this comparative example provides a 2-phenyl-1, 3, 4-oxadiazoleThe synthesis method of (2) comprises the following steps: />
(1) Phenyl tetrafluoroboric acid diazonium saltIs synthesized by the following steps:
aniline (9.3 g,0.1 mol) and an aqueous tetrafluoroboric acid solution (35.2 g, mass fraction of tetrafluoroboric acid 50%,0.2 mol) were added to 100 ethanol, stirred for 10 minutes, cooled to 0 ℃, tert-butyl nitrite (23 g, purity 90%,0.2 mol) was slowly added dropwise, and after returning to room temperature, stirred for 1 hour. 500mL of methyl tertiary ether is added, the mixture is filtered, the methyl tertiary ether is washed, and a filter cake is collected to obtain 16.3g of phenyl tetrafluoroboric acid diazonium salt with the yield of 85 percent.
The nmr hydrogen spectrum data were tested as follows:
1 H NMR(DMSO-d6)δ8.66(2H),δ8.26(1H),δ7.98(2H).
from the above nuclear magnetic resonance hydrogen spectrum data, the target compound phenyl tetrafluoroborate diazonium salt was synthesized.
(2): 2-phenyl-1, 3, 4-oxadiazolesIs synthesized by the following steps:
phenyl tetrafluoroborate diazonium salt (9.6 g,0.05 mol) and S1 (3.5 g,0.05 mol), C2 (0.21 g, 2% mol of S1) and 20 mM LDMSO were added to a reaction flask under Ar atmosphere, reacted at 25℃for 1 hour under dark conditions, and no product was centrally controlled after the reaction was completed.
The yields and yields of the examples and comparative examples are shown in table 1:
TABLE 1
As can be seen from Table 1, examples 1 to 16 derive 1,3, 4-oxadiazole under Mn-containing catalyst and blue light conditions as compared with comparative examples 1 to 3The aryl-substituted 1,3, 4-oxadiazole derivative is prepared by coupling reaction of the aryl-substituted diazonium tetrafluoroborate, and has the advantages of mild reaction conditions, high atom utilization rate, high product yield and CpMn (CO) 3 Has better catalytic effect.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples merely represent a few embodiments of the present invention, which facilitate a specific and detailed understanding of the technical solutions of the present invention, but are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. It should be understood that, based on the technical solutions provided by the present invention, those skilled in the art may obtain technical solutions through logic analysis, reasoning or limited experiments, which are all within the scope of protection of the appended claims. The scope of the patent of the invention should therefore be determined with reference to the appended claims, which are to be construed as in accordance with the doctrines of claim interpretation.
Claims (10)
1. A method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative, comprising the steps of:
under the conditions of Mn-containing catalyst and blue light, carrying out coupling reaction on the 1,3, 4-oxadiazole derivative and aryl-substituted diazonium tetrafluoroborate;
the Mn-containing catalyst is selected from Mn 2 (CO) 10 、CpMn(CO) 3 And Mn (CO) 5 One or more of Br.
2. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 1, wherein the 1,3, 4-oxadiazole derivative has a structure represented by the following formula (I):
each R is 1 Each independently selected from alkyl, or aryl substituted or unsubstituted with R;
r is selected from any integer from 0 to 2;
each R is independently selected from halogen, cyano, amino, hydroxy, alkyl, alkoxy, or haloalkyl.
3. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 2, wherein each R is 1 Independently selected from C1-C10 alkyl, or aryl with R substituted or unsubstituted ring atom number of 6-30.
4. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 2, wherein each R is independently selected from the group consisting of halogen, cyano, amino, hydroxy, C1-C20 linear alkyl, C3-C20 branched alkyl, C3-C20 cycloalkyl, C1-C20 linear alkoxy, C3-C20 branched alkoxy, C3-C20 cycloalkoxy, halogenated C1-C20 linear alkyl, halogenated C3-C20 branched alkyl, and halogenated C3-C20 cycloalkyl.
5. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 1, characterized in that the aryl-substituted diazonium tetrafluoroborate has a structure represented by the following formula (II):
Each R is 2 Each independently selected from alkyl, alkoxy, fluoroalkyl, or halogen;
m is selected from any integer from 0 to 5.
6. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 5, wherein R is 2 Ortho-or para-substituted with a diazo group; and/or
Each R is 2 Independently selected from C1-C10 alkyl, C1-C10 alkoxy, C1-C10 fluoroalkyl or halogen.
7. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to any one of claims 1 to 6, wherein the molar ratio of the 1,3, 4-oxadiazole derivative to the aryl-substituted diazonium tetrafluoroborate is 1: (1-2.5); and/or
The mole ratio of the Mn-containing catalyst to the 1,3, 4-oxadiazole derivative is (1-10): 100; and/or
The temperature of the coupling reaction is 5-40 ℃ and the time is 0.5-10 h.
8. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to any one of claims 1 to 6, wherein the solvent used in the coupling reaction is one or a mixture of two of dimethyl sulfoxide and N, N-dimethylformamide.
9. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to any one of claims 1 to 6, characterized in that the method for preparing an aryl-substituted diazonium tetrafluoroborate comprises the steps of:
Mixing a primary ammonia substituted aryl derivative with tetrafluoroboric acid aqueous solution in a solvent for reaction to generate tetrafluoroborate;
diazotizing the tetrafluoroborate and nitrous acid compounds, and adding a precipitator to separate out aryl substituted tetrafluoroborate diazonium salt.
10. The method for synthesizing an aryl-substituted 1,3, 4-oxadiazole derivative according to claim 9, wherein the solvent is an alcohol solvent; and/or
The nitrous acid compound is tert-butyl nitrite; and/or
The precipitant is methyl tertiary ether; and/or
The temperature of the diazotization reaction is 0+/-5 ℃ and the time is 0.5-2 h.
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