CN110563659B - 非均相铜催化一锅制备1,2,3-三唑类化合物的方法 - Google Patents
非均相铜催化一锅制备1,2,3-三唑类化合物的方法 Download PDFInfo
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- -1 1,2, 3-triazole compound Chemical class 0.000 title claims abstract description 53
- 238000000034 method Methods 0.000 title claims abstract description 39
- 239000010949 copper Substances 0.000 title claims abstract description 38
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 229910052802 copper Inorganic materials 0.000 title claims abstract description 26
- 238000005580 one pot reaction Methods 0.000 title abstract description 15
- 238000006555 catalytic reaction Methods 0.000 title description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910001868 water Inorganic materials 0.000 claims abstract description 22
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000001543 aryl boronic acids Chemical class 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000004327 boric acid Substances 0.000 claims abstract description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 3
- 238000012544 monitoring process Methods 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000000047 product Substances 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 239000012065 filter cake Substances 0.000 claims description 10
- 238000000967 suction filtration Methods 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000003480 eluent Substances 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 7
- HRUBLEPQYHPKQJ-UHFFFAOYSA-N tert-butyl 2-sulfanylpentanoate Chemical compound CCCC(S)C(=O)OC(C)(C)C HRUBLEPQYHPKQJ-UHFFFAOYSA-N 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- ZLAIUYZHCQJJCE-UHFFFAOYSA-N 2-propylsulfanylacetic acid Chemical group CCCSCC(O)=O ZLAIUYZHCQJJCE-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- SBWFWBJCYMBZEY-UHFFFAOYSA-N S-Propyl thioacetate Chemical compound CCCSC(C)=O SBWFWBJCYMBZEY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000002355 alkine group Chemical group 0.000 claims 3
- 238000001704 evaporation Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000006964 Chan-Lam coupling reaction Methods 0.000 abstract description 18
- 229920001167 Poly(triaryl amine) Polymers 0.000 abstract description 13
- 150000001345 alkine derivatives Chemical group 0.000 abstract description 9
- 239000003638 chemical reducing agent Substances 0.000 abstract description 7
- 230000003197 catalytic effect Effects 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 238000012650 click reaction Methods 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 235000010338 boric acid Nutrition 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- UIXYUQXWIFEYBN-UHFFFAOYSA-N 1,4-diphenyltriazole Chemical compound C1=C(C=2C=CC=CC=2)N=NN1C1=CC=CC=C1 UIXYUQXWIFEYBN-UHFFFAOYSA-N 0.000 description 3
- DDMCEGSOTOSBAN-UHFFFAOYSA-N 1-(2-methylphenyl)-4-phenyltriazole Chemical compound CC1=CC=CC=C1N1N=NC(C=2C=CC=CC=2)=C1 DDMCEGSOTOSBAN-UHFFFAOYSA-N 0.000 description 3
- UJPIEACGBIJOKH-UHFFFAOYSA-N 1-(4-methoxyphenyl)-4-phenyltriazole Chemical compound C1=CC(OC)=CC=C1N1N=NC(C=2C=CC=CC=2)=C1 UJPIEACGBIJOKH-UHFFFAOYSA-N 0.000 description 3
- FQURJCQNNBQIOW-UHFFFAOYSA-N 1-(4-methylphenyl)-4-phenyltriazole Chemical compound C1=CC(C)=CC=C1N1N=NC(C=2C=CC=CC=2)=C1 FQURJCQNNBQIOW-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 150000004982 aromatic amines Chemical class 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- FUHLSYNEUNRFQQ-UHFFFAOYSA-N 1-(4-bromophenyl)-4-phenyltriazole Chemical compound C1=CC(Br)=CC=C1N1N=NC(C=2C=CC=CC=2)=C1 FUHLSYNEUNRFQQ-UHFFFAOYSA-N 0.000 description 2
- RYZQEWVESFLNKP-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-phenyltriazole Chemical compound FC1=CC=C(C=C1)N1N=NC(=C1)C1=CC=CC=C1 RYZQEWVESFLNKP-UHFFFAOYSA-N 0.000 description 2
- RODAHMWLOQOTBW-UHFFFAOYSA-N 2-(1-phenyltriazol-4-yl)propan-2-ol Chemical compound N1=NC(C(C)(O)C)=CN1C1=CC=CC=C1 RODAHMWLOQOTBW-UHFFFAOYSA-N 0.000 description 2
- FTBGPTZQAAMBJS-UHFFFAOYSA-N 4-(4-methylphenyl)-1-phenyltriazole Chemical compound C1=CC(C)=CC=C1C1=CN(C=2C=CC=CC=2)N=N1 FTBGPTZQAAMBJS-UHFFFAOYSA-N 0.000 description 2
- HXCDNWMCENKBLZ-UHFFFAOYSA-N 4-(4-phenyltriazol-1-yl)benzaldehyde Chemical compound C1(=CC=CC=C1)C=1N=NN(C=1)C1=CC=C(C=O)C=C1 HXCDNWMCENKBLZ-UHFFFAOYSA-N 0.000 description 2
- RHBVLBJBWHFEMC-UHFFFAOYSA-N 4-(ethoxymethyl)-1-phenyltriazole Chemical compound N1=NC(COCC)=CN1C1=CC=CC=C1 RHBVLBJBWHFEMC-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- LIYOJGGWQAHKDI-UHFFFAOYSA-N 4-cyclopropyl-1-phenyltriazole Chemical compound C1(CC1)C=1N=NN(C=1)C1=CC=CC=C1 LIYOJGGWQAHKDI-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 2
- 229960005055 sodium ascorbate Drugs 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000000177 1,2,3-triazoles Chemical class 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- B01J31/1616—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts
- B01J31/1625—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups
- B01J31/1633—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups covalent linkages via silicon containing groups
-
- 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
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/223—At least two oxygen atoms present in one at least bidentate or bridging ligand
- B01J31/2239—Bridging ligands, e.g. OAc in Cr2(OAc)4, Pt4(OAc)8 or dicarboxylate ligands
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
- B01J2231/324—Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions
- B01J2231/328—Cycloadditions involving more than 2 components or moieties, e.g. intra-/intermolecualar [2+2+2] or [2+2+1], e.g. Pauson-Khand type
-
- 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
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0213—Complexes without C-metal linkages
- B01J2531/0216—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
-
- 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
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
一种制备式(II)所示1‑芳基‑4‑取代‑1,2,3‑三唑类化合物的方法,所述方法为:将芳基硼酸(1)、NaN3、非均相铜催化剂、溶剂水混合,于25~60℃下搅拌反应4~8h,TLC监测至芳基硼酸(1)完全转化后,用N2置换反应体系中的空气,加入端炔烃(2),N2保护下于40~80℃下反应6~10h,之后反应液经后处理,得到产物(II);本发明以Cu@SBA‑15‑PTAA为催化剂,在不需要额外添加还原剂的作用下,通过一锅Chan‑Lam/Click串联法制备了系列1‑芳基‑4‑取代‑1,2,3‑三唑类化合物,开发的催化方法绿色、安全、经济、三废量小,并且目标产物收率高,底物适用范围广;
Description
(一)技术领域
本发明涉及一种1,2,3-三唑类化合物的制备方法,具体涉及一种非均相铜催化一锅Chan-Lam/Click串联法制备1,2,3-三唑类化合物的方法。
(二)背景技术
1,2,3-三唑是一类重要的有机含氮杂环,可通过端炔烃与有机叠氮化合物经过[3+2]环加成反应而制备。虽然,该反应在加热的条件下即可进行。但往往需要较高的温度(一般大于150℃),并且反应选择性差,普遍得到1,4-和1,5-二取代的混合物。2002年,Sharpless和Meldal同时发现Cu(I)可以催化该反应,不仅使得反应可以在温和的条件下进行,同时可以选择性地得到1,4-二取代产物。从此以后,Cu催化端炔烃与有机叠氮化合物的[3+2]环加成反应成为制备1,2,3-三唑类化合物最重要的方法(也简称为Click反应)。到目前为止,通过Click反应已成功制备了大量的1,4-二取代-1,2,3-三唑类化合物,这些化合物广泛地应用于医药、农药、高分子材料、催化等领域。
经Click反应制备1,2,3-三唑类化合物需要以有机叠氮化物为原料,这类化合物挥发性很强和易爆,分离纯化不仅损失很大,还存在一定的安全隐患。因此,采用不分离叠氮化合物,一锅串联法是制备1,4-二取代-1,2,3-三唑类化合物最理想和安全的制备方法。烷基叠氮化物比较容易获得,可由卤代烃(RX)和NaN3经亲核取代反应在线生成,过去10年间报道了许多铜催化一锅亲核取代/Click串联法制备1-烷基-4-取代-1,2,3-三唑类化合物(I)的方法。但是,芳基叠氮化物不能通过芳基卤代物(ArX)和NaN3的亲核取代反应获得,因此一锅亲核取代/Click法串联法不能应用于制备1-芳基-4-取代-1,2,3-三唑类化合物(II)。芳基叠氮化物的制备主要有两种途径:(1)以芳胺(Ar-NH2)为原料经重氮化、叠氮化钠取代二步法;(2)以芳基硼酸(Ar-B(OH)2)为原料,在铜催化和有氧条件下,与叠氮化钠发生形成C-N键的氧化偶联法,也称为Chan-Lam反应。方法1的重氮化反应需要在强酸性条件下才能进行,因此该方法不能应用于含有对酸敏感官能团的底物。此外,苯环上有吸电子取代基的芳胺,重氮化困难,收率较低,从而影响最终反应的收率。方法2操作简单,反应温和,原料芳基硼酸毒性小、稳定和商业易得。更重要的是Chan-Lam反应和Click反应均以铜为催化剂,容易实现一锅串联反应。因此,发展一锅Chan-Lam/Click串联法应用于1-芳基-4-取代-1,2,3-三唑类化合物的制备具有显著的优势,实际应用价值高。
文献1(Tetrahedron Letters,2007,48,3525-3529)首次报道了该一锅串联法,该方法以10%的CuSO4为催化剂,首先在空气氛围中将芳基硼酸与NaN3在甲醇中发生Chan-Lam反应,制得相应的芳基叠氮化物。由于CuSO4只能催化Chan-Lam反应,不能催化Click反应。因此,在Chan-Lam反应结束后,需要额外加入5当量的抗坏血酸钠和与甲醇等体积的水,将CuSO4在线还原成具有催化活性的Cu(I)。然后加入端炔烃,发生Click反应,最终制备得到一系列1-芳基-4-取代-1,2,3-三唑类化合物,收率为63-96%。该方法最大的缺点是CuSO4不能同时催化Chan-Lam反应和Click反应,需要额外加入大量的还原剂(抗坏血酸钠)。其他缺点还包括,CuSO4对吸电子取代芳基硼酸与NaN3偶联反应的催化活性差,用量大和无法重复使用等。
为了避免额外加入大量的还原剂,过去几年报道了一些对Chan-Lam反应和Click反应均具有催化活性的自制铜催化剂,并应用于一锅Chan-Lam/Click串联法制备1-芳基-4-取代-1,2,3-三唑类化合物。如:文献2(Organic & Biomolecular Chemistry,2012,10,4543-4548)以CuSO4负载的β环糊精(Cu2-β-CD)为催化剂,在催化剂用量为5mol%,不额外补加还原剂的情况下,经一锅Chan-Lam/Click串联法制备了一系列1-芳基-4-取代-1,2,3-三唑类化合物,收率为89-97%。反应以纯水为反应介质,绿色经济。但该方法需要使用大大过量的NaN3(3当量,过量的NaN3作为还原剂,将Cu(II)还原为Cu(I)催化Click反应),并且催化剂无法重复使用。
文献3(Tetrahedron,2012,68,8156-8162)以CuO负载的黏土(Caly-CuO)为催化剂,催化剂用量为10mol%,以1:1的水和乙腈为反应介质,采用类似的一锅Chan-Lam/Click串联法制备了一系列1-芳基-4-取代-1,2,3-三唑类化合物,收率为83-98%,该催化剂可以重复使用5次,收率从97%下降到86%。该方法的主要缺点是催化剂用量大,使用2当量的NaN3和需要以有机共溶剂为反应介质。
文献4(Tetrahedron Letters,2015,56,1968-1972)以CuSO4负载的壳聚糖催化剂(Chitosan@CuSO4)为催化剂,催化剂用量为10mol%,水为反应介质,也类似的制备了一系列1-芳基-4-取代-1,2,3-三唑衍生物,收率为71-90%。该方法使用1.2当量的NaN3,催化剂可以重复使用5次,收率从90%下降到79%。但是仍存在催化剂的活性不高和用量大,产物收率偏低的缺点。
综合以上可以发现,现有铜催化Chan-Lam/Click一锅串联制备1-芳基-4-取代-1,2,3-三唑类化合物的方法具有以下一项或多项缺点,如:催化剂的活性不高,催化剂的用量较大,催化剂无法回收和套用,需要以有机共溶剂为反应介质,一些产物的收率较低等。
R为烷基,1-烷基-4-取代-1,2,3-三唑(I)
R为芳基,1-芳基-4-取代-1,2,3-三唑(II)
(三)发明内容
本发明目的是提供一种新型、简便、高效、绿色的制备1-芳基-4-取代-1,2,3-三唑类化合物(II)的方法。反应以芳基硼酸和NaN3为起始原料,水为反应介质,自制的Cu@SBA-15-PTAA为固相催化剂(含Cu量为1.29mmol/g,制备方法见New Journal of Chemistry,2018,42,1612-1616),在敞口空气条件下,经Chan-Lam反应制备得到相应的芳基叠氮化物。然后,向反应混合物中加入端炔烃,氮气保护,不需要额外加入还原剂和有机共溶剂,在相同的铜催化剂作用下,发生Click反应,一锅法制备得到1-芳基-4-取代-1,2,3-三唑衍生物。
本发明催化剂活性高,用量小。反应以纯水为介质,Cu@SBA-15-PTAA为非均相铜催化剂,因此产物分离简单。产物分离后,余下的催化剂和水相可回收套用多次。本发明方法绿色、经济、三废量少,具有广阔的应用前景。
本发明的技术方案如下:
一种制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,所述方法为:
将芳基硼酸(1)、NaN3、非均相铜催化剂、溶剂水混合,于25~60℃下搅拌反应4~8h,TLC监测至芳基硼酸(1)完全转化后,用N2置换反应体系中的空气,加入端炔烃(2),N2保护下于40~80℃(最优为50℃)下反应6~10h,之后反应液经后处理,得到产物1-芳基-4-取代-1,2,3-三唑类化合物(II);
所述非均相铜催化剂为丙硫基乙酸功能化的SBA-15分子筛负载Cu催化剂,可记作Cu@SBA-15-PTAA;
所述芳基硼酸(1)、NaN3、端炔烃(2)、非均相铜催化剂的物质的量之比为1:1~1.5:1~1.5:0.01~0.06,优选1:1.1:1.1:0.03;
所述溶剂水的体积用量以芳基硼酸(1)的物质的量计为1~5mL/mmol,优选2mL/mmol;
所述芳基硼酸(1)与NaN3反应的温度为25~60℃,芳基上为给电子取代的芳基硼酸最优温度为25℃,芳基上为吸电子取代的芳基硼酸最优温度为50℃;
所述后处理的方法为:反应结束后,待反应体系冷却至室温(20~25℃),加入与溶剂水不相溶的有机溶剂(例如乙酸乙酯或二氯甲烷)溶解产物,离心,分出上层有机相,相同萃取操作重复1-2次,余下悬浮有催化剂的水相可继续使用5次以上,仍能保持催化活性,合并有机萃取液,无水硫酸钠干燥,过滤,滤液减压回收溶剂,得到的粗产品进行柱层析纯化,以石油醚/乙酸乙酯(体积比为20:1)的混合液为洗脱剂洗脱,收集含目标化合物的洗脱液,减压蒸除洗脱剂并干燥,得到目标产物1-芳基-4-取代-1,2,3-三唑类化合物(II);
式(1)、式(2)或式(II)中,
Ar为苯基、取代苯基或稠环芳基;所述取代苯基的苯环上被一个或多个取代基取代,所述取代基各自独立为C1~C4烷基、C1~C3烷氧基、乙烯基、卤素、三氟甲基、甲酰基、乙酰基、酯基、氰基或硝基;所述稠环芳基例如为萘基;
优选的,所述Ar为下列之一:苯基、对甲基苯基、间甲基苯基、邻甲基苯基、对甲氧基苯基、间甲氧基苯基、邻甲氧基苯基、对叔丁基苯基、对乙烯基苯基、对氟苯基、对氯苯基、对溴苯基、对三氟甲基苯基、对甲酰基苯基、对乙酰基苯基、对甲氧羰基苯基、对氰基苯基、对硝基苯基或1-萘基;
R为苯基、取代苯基、烷基或杂原子官能团取代的烷基;所述取代苯基的苯环上被一个或多个取代基取代,所述取代基各自独立为C1~C3烷氧基、C1~C4烷基、氨基、羟基、卤素、乙酰基、酯基、氰基或硝基;所述烷基为C1~C6烷基、环烷基;所述杂原子官能团取代烷基的杂原子官能团为醚基、羟基或氨基;
优选的,所述R为下列之一:苯基、对甲氧基苯基、对甲基苯基、对氨基苯基、对羟基苯基、对氟苯基、对氯苯基、对溴苯基、对乙酰基苯基、对甲氧羰基苯基、对氰基苯基、对硝基苯基、正丁基、环丙基、乙氧基甲基、苯甲氧基甲基、苯胺基甲基、α-羟基异丙基或α-羟基苄基。
本发明方法的反应式如下:
本发明中,所述非均相铜催化剂(Cu@SBA-15-PTAA)的制备方法可参考NewJournal of Chemistry,2018,42,1612-1616。具体的,所述非均相铜催化剂的制备方法为:
(1)将SBA-15分子筛与甲苯混合,室温下搅拌均匀,然后加入2-(3-(三甲氧基硅基)丙硫基)乙酸叔丁酯,回流反应24h,之后但反应体系降至室温,抽滤,滤饼依次用甲苯、乙醇洗涤,所得固体于80℃真空烘箱中干燥2h,得到丙硫基乙酸叔丁酯功能化的SBA-15分子筛(记作SBA-15-PTAE);
所述SBA-15分子筛可通过常规途径商购获得;
所述SBA-15分子筛与2-(3-(三甲氧基硅基)丙硫基)乙酸叔丁酯的质量比为1:1~1.5;
(2)将所得丙硫基乙酸叔丁酯功能化的SBA-15分子筛与甲苯混合,室温下搅拌均匀,加入85wt%磷酸,水解反应6h,之后用乙醇稀释反应液,抽滤,滤饼用乙醇洗涤至中性,80℃真空烘箱中干燥2h,得到丙硫基乙酸功能化的SBA-15分子筛(记作SBA-15-PTAA);
所述85wt%磷酸的体积用量以丙硫基乙酸叔丁酯功能化的SBA-15分子筛的质量计为3.5~4mL/g;
(3)将Cu(OAc)2·H2O用去离子水溶解,然后加入所得丙硫基乙酸功能化的SBA-15分子筛,室温下搅拌8~12h,之后反应混合物抽滤,滤饼依次用水、乙醇洗涤,得到的固体在80℃下真空干燥2h,得到所述非均相铜催化剂;
所述Cu(OAc)2·H2O与丙硫基乙酸功能化的SBA-15分子筛的质量比为0.1~0.15:1。
所述非均相铜催化剂的合成路线如下:
与现有技术相比,本发明的有益效果主要体现在:
(1)本发明以自制Cu@SBA-15-PTAA为催化剂,在不需要额外添加还原剂的作用下,通过一锅Chan-Lam/Click串联法制备了系列1-芳基-4-取代-1,2,3-三唑类化合物,开发的催化方法绿色、安全、经济、三废量小。
(2)本发明所用的铜催化剂用量少,并且是非均相铜催化剂,与产物分离简单,该铜催化剂可以多次循环使用。
(3)本发明以纯水为反应介质,产物不溶于水,通过简单的有机溶剂萃取即可分离,后处理简便,产物萃取后的水相还可以多次套用,大大减少了三废。
(4)本发明方法得到的目标产物收率高,底物适用范围广,特别是可以应用于转化许多含强吸电子基团的芳基硼酸,相应的1-芳基-4-取代-1,2,3-三唑类化合物能够获得较好的收率。
(四)具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此。
以下实施例中用到的非均相铜催化剂Cu@SBA-15-PTAA为自制,含Cu量为1.29mmol/g,
称取4.0g商业可得的SBA-15分子筛于500mL单口圆底烧瓶中,加入250mL甲苯,室温下搅拌均匀后,加入4.3g 2-(3-(三甲氧基硅基)丙硫基)乙酸叔丁酯,回流反应24小时。反应物抽滤,滤饼依次用甲苯、乙醇洗涤,所得固体于80℃真空烘箱中干燥2h,得5.2g丙硫基乙酸叔丁酯功能化的SBA-15分子筛(SBA-15-PTAE)。
将5.2g上述SBA-15-PTAE分子筛置于250mL的单口圆底烧瓶中,加入60mL甲苯,室温下搅拌均匀,加入20mL磷酸(85%),水解反应6个小时。加入250mL乙醇稀释反应液,抽滤,滤饼用乙醇洗涤至中性,80℃真空烘箱中干燥2h,得4.8g丙硫基乙酸功能化的SBA-15分子筛(SBA-15-PTAA)。
称取0.12g Cu(OAc)2·H2O于50mL单口圆底烧瓶中,加入30mL去离子水溶解,然后加入1.0g SBA-15-PTAA,室温下搅拌过夜。反应物抽滤,滤饼依次水、乙醇洗涤,得到的固体在80℃下真空干燥2h,得到1.08g负载催化剂Cu@SBA-15-PTAA。
实施例1 1,4-二苯基-1,2,3-三唑的制备
于10mL螺口耐压反应试管中,依次加入苯硼酸(0.122g,1mmol)、NaN3(0.072g,1.1mmol)和Cu@SBA-15-PTAA(0.024g,0.03mmol)和2mL水。敞口空气条件下,室温反应4h,TLC检测苯硼酸已经全部转化为叠氮苯。用氮气置换试管空腔中的空气,加入苯乙炔(0.112g,1.1mmol),旋紧螺口塞,然后将反应试管置于50℃油浴中反应6小时。待反应结束后,将反应试管冷却至室温,加入2mL乙酸乙酯,搅拌使生成的产物溶解,离心,分出上层乙酸乙酯萃取液。重复萃取2次,使产物萃取完全。剩余的催化剂和水相不需要进一步处理,即可套用。合并乙酸乙酯萃取液,无水硫酸钠干燥,过滤,真空浓缩回收乙酸乙酯,粗产品经柱层析纯化(体积比20:1石油醚/乙酸乙酯为洗脱剂),得到1,4-二苯基-1,2,3-三唑0.210g,收率95%,产品为白色固体,熔点:185.6℃。1H NMR(500MHz,CDCl3):δ=8.22(s,1H),7.94-7.93(m,2H),7.83-7.81(m,2H),7.59-7.56(m,2H),7.50-7.47(m,3H),7.41-7.38(m,1H);13CNMR(125MHz,CDCl3):δ=148.4,137.1,130.3,129.8,128.9,128.8,128.4,125.9,120.6,117.6;GC-MS(EI):m/z 221(M+),193(100).
实施例2~37
采用不同的芳基硼酸、端炔与NaN3反应制备1-芳基-4-取代-1,2,3-三唑类化合物,实验操作同实施例1,结果见表1。其中实施例2-12和19-27,第一步Chan-Lam反应的温度为室温,实施例13-18,第一步Chan-Lam反应的温度为50℃。所有实施例中第二步Click反应的温度均为50℃。
表1不同芳基硼酸和端炔为原料与NaN3反应制备二芳基酮
实施例38催化剂的套用制备1,4-二苯基-1,2,3-三唑
第一次反应结束后,生成的产物用乙酸乙酯萃取,催化剂Cu@SBA-15-PTAA和反应介质水留在反应试管中。将苯硼酸(0.122g,1mmol)和NaN3(0.072g,1.1mmol)加入到该反应试管中进行Chan-Lam反应,待苯硼酸全部转化为叠氮苯,加入苯乙炔(0.112g,1.1mmol),进行Click反应,具体操作同实施例1。后处理得到1,4-二苯基-1,2,3-三唑0.208g,收率95%。催化剂再继续使用四次,收率依次为94%,92%,90%,87%。
部分产物的表征数据:
1-(4’-甲基苯基)-4-苯基-1H-1,2,3-三唑(实施例2)
白色固体,熔点:167.3℃;1H NMR(500MHz,CDCl3):δ=8.17(s,1H),7.93-7.91(m,2H),7.68-7.67(m,2H),7.48-7.45(m,2H),7.39-7.33(m,3H),2.44(s,3H);13C NMR(125MHz,CDCl3):δ=148.3(s),138.9(s),134.8(s),130.4(s),130.2(s),128.9(s),128.3(s),125.8(s),120.4(s),117.6(s),21.1(s);GC-MS(EI):m/z 235(M+),91(100).
1-(2’-甲基苯基)-4-苯基-1H-1,2,3-三唑(实施例4)
白色固体,熔点:87.0℃;1H NMR(500MHz,CDCl3):δ=7.98(s,1H),7.95-7.93(m,2H),7.49-7.34(m,7H),2.28(s,3H);13C NMR(125MHz,CDCl3):δ=147.5(s),136.4(s),133.7(s),131.5(s),130.3(s),129.8(s),128.9(s),128.2(s),126.8(s),125.9(s),125.7(s),121.1(s),17.8(s);GC-MS(EI):m/z235(M+),207(100).
1-(4’-甲氧基苯基)-4-苯基-1H-1,2,3-三唑(实施例5)
白色固体,熔点:164.7℃;1H NMR(500MHz,CDCl3):δ=8.13(s,1H),7.93-7.91(m,2H),7.72-7.69(m,2H),7.49-7.46(m,2H),7.40-7.37(m,1H),7.07-7.05(m,2H),3.90(s,3H);13C NMR(125MHz,CDCl3):δ=156.0(s),148.3(s),130.7(s),130.5(s),128.9(s),128.3(s),125.9(s),122.3(s),117.8(s),114.9(s),55.7(s);GC-MS(EI):m/z 251(M+),223(100).
1-(4’-氟苯基)-4-苯基-1H-1,2,3-三唑(实施例10)
黄色固体,熔点:211.0℃;1H NMR(500MHz,DMSO):δ=9.30(s,1H),8.01(dd,J=8.6,4.7Hz,2H),7.95(d,J=7.6Hz,2H),7.51(t,J=8.0Hz,4H),7.40(t,J=7.3Hz,1H);13CNMR(125MHz,DMSO):δ=161.6(d,J=247.7Hz),147.4(s),133.2(s),130.2(s),129.0(s),128.3(s),125.3(s),122.4(d,J=8.6Hz),119.9(s),116.8(d,J=23.0Hz);GC-MS(EI):m/z239(M+),211(100).
1-(4’-溴苯基)-4-苯基-1H-1,2,3-三唑(实施例12)
黄色固体,熔点:230.3℃;1H NMR(500MHz,DMSO):δ=9.35(s,1H),7.95(d,J=8.2Hz,4H),7.86(d,J=8.5Hz,2H),7.51(t,J=7.5Hz,2H),7.40(t,J=7.3Hz,1H);13C NMR(125MHz,DMSO):δ=147.5(s),135.9(s),132.8(s),130.1(s),129.0(s),128.3(s),125.3(s),121.9(s),121.4(s),119.6(s);GC-MS(EI):m/z 299(M+),192(100).
1-(4’-甲酰基苯基)-4-苯基-1H-1,2,3-三唑(实施例15)
白色固体,熔点:222.5℃;1H NMR(500MHz,DMSO):δ=10.10(s,1H),9.48(s,1H),8.23(d,J=8.6Hz,2H),8.18-8.17(m,2H),7.98-7.96(m,2H),7.52(t,J=7.7Hz,2H),7.43-7.40(m,1H);13C NMR(125MHz,DMSO):δ=192.1(s),147.7(s),140.5(s),135.7(s),131.3(s),129.9(s),129.1(s),128.5(s),125.4(s),120.1(s),119.8(s);GC-MS(EI):m/z 251(M+),208(100).
1-苯基-4-(4’-甲基苯基)-1H-1,2,3-三唑(实施例21)
白色固体,熔点:173.2℃;1H NMR(500MHz,DMSO):δ=8.15(s,1H),7.81-7.78(m,4H),7.56-7.53(m,2H),7.46-7.44(m,1H),7.27(d,J=6.5Hz,2H),2.40(s,3H);13C NMR(125MHz,DMSO):δ=148.5,138.31,137.1,129.8,129.6,128.7,127.4,125.7,120.5,117.2,21.3;GC-MS(EI):m/z 235(M+),91(100).
1-苯基-4-环丙基-1H-1,2,3-三唑(实施例32)
白色固体,熔点:78.2℃;1H NMR(500MHz,CDCl3):δ=7.71-7.69(m,3H),7.52-7.48(m,2H),7.43-7.40(m,1H),2.06-2.01(m,1H),1.03-0.98(m,2H),0.97-0.92(m,2H);13C NMR(125MHz,CDCl3):δ=151.0(s),137.2(s),129.7(s),128.4(s),120.4(s),117.9(s),7.8(s),6.7(s);GC-MS(EI):m/z 185(M+),156(100).
1-苯基-4-乙氧甲基-1H-1,2,3-三唑(实施例33)
无色液体;1H NMR(500MHz,CDCl3):δ=8.00(s,1H),7.75-7.73(m,2H),7.55-7.52(m,2H),7.46-7.43(m,1H),4.73(s,2H),3.68-3.64(m,2H),1.27(t,J=7.0Hz,3H);13C NMR(125MHz,CDCl3):δ=146.3(s),137.1(s),129.8(s),128.7(s),120.6(s),66.3(s),64.1(s),15.2(s);GC-MS(EI):m/z 203(M+),77(100).
2-(1-苯基-1H-1,2,3-三唑-4-基)-2-丙醇(实施例36)
白色固体,熔点:97.9℃;1H NMR(500MHz,CDCl3):δ=7.94(s,1H),7.72-7.70(m,2H),7.52-7.48(m,2H),7.44-7.41(m,1H),3.11(s,1H),1.71(s,6H);13C NMR(125MHz,CDCl3):δ=156.4(s),137.1(s),129.7(s),128.6(s),120.5(s),117.6(s),68.6(s),30.5(s);GC-MS(EI):m/z 203(M+),160(100)。
Claims (5)
1.一种制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,其特征在于,所述方法为:
将芳基硼酸(1)、NaN3、非均相铜催化剂、溶剂水混合,于25~60℃下搅拌反应4~8h,TLC监测至芳基硼酸(1)完全转化后,用N2置换反应体系中的空气,加入端炔烃(2),N2保护下于40~80℃下反应6~10h,之后反应液经后处理,得到产物1-芳基-4-取代-1,2,3-三唑类化合物(II);
所述非均相铜催化剂为丙硫基乙酸功能化的SBA-15分子筛负载Cu催化剂;
所述芳基硼酸(1)、NaN3、端炔烃(2)、非均相铜催化剂的物质的量之比为1:1~1.5:1~1.5:0.01~0.06;
式(1)、式(2)或式(II)中,
Ar为苯基、取代苯基或稠环芳基;所述取代苯基的苯环上被一个或多个取代基取代,所述取代基各自独立为C1~C4烷基、C1~C3烷氧基、乙烯基、卤素、三氟甲基、甲酰基、乙酰基、酯基、氰基或硝基;
R为苯基、取代苯基、烷基或杂原子官能团取代的烷基;所述取代苯基的苯环上被一个或多个取代基取代,所述取代基各自独立为C1~C3烷氧基、C1~C4烷基、氨基、羟基、卤素、乙酰基、酯基、氰基或硝基;所述烷基为C1~C6烷基、环烷基;所述杂原子官能团取代烷基的杂原子官能团为醚基、羟基或氨基。
2.如权利要求1所述制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,其特征在于,所述芳基硼酸(1)、NaN3、端炔烃(2)、非均相铜催化剂的物质的量之比为1:1.1:1.1:0.03。
3.如权利要求1所述制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,其特征在于,所述溶剂水的体积用量以芳基硼酸(1)的物质的量计为1~5mL/mmol。
4.如权利要求1所述制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,其特征在于,所述后处理的方法为:反应结束后,待反应体系冷却至室温,加入与溶剂水不相溶的有机溶剂溶解产物,离心,分出上层有机相,相同萃取操作重复1-2次,合并有机萃取液,无水硫酸钠干燥,过滤,滤液减压回收溶剂,得到的粗产品进行柱层析纯化,以石油醚/乙酸乙酯体积比为20:1的混合液为洗脱剂洗脱,收集含目标化合物的洗脱液,减压蒸除洗脱剂并干燥,得到目标产物1-芳基-4-取代-1,2,3-三唑类化合物(II)。
5.如权利要求1所述制备式(II)所示1-芳基-4-取代-1,2,3-三唑类化合物的方法,其特征在于,所述非均相铜催化剂的制备方法为:
(1)将SBA-15分子筛与甲苯混合,室温下搅拌均匀,然后加入2-(3-(三甲氧基硅基)丙硫基)乙酸叔丁酯,回流反应24h,之后反应体系降至室温,抽滤,滤饼依次用甲苯、乙醇洗涤,所得固体于80℃真空烘箱中干燥2h,得到丙硫基乙酸叔丁酯功能化的SBA-15分子筛;
所述SBA-15分子筛与2-(3-(三甲氧基硅基)丙硫基)乙酸叔丁酯的质量比为1:1~1.5;
(2)将所得丙硫基乙酸叔丁酯功能化的SBA-15分子筛与甲苯混合,室温下搅拌均匀,加入85wt%磷酸,水解反应6h,之后用乙醇稀释反应液,抽滤,滤饼用乙醇洗涤至中性,80℃真空烘箱中干燥2h,得到丙硫基乙酸功能化的SBA-15分子筛;
所述85wt%磷酸的体积用量以丙硫基乙酸叔丁酯功能化的SBA-15分子筛的质量计为3.5~4mL/g;
(3)将Cu(OAc)2·H2O用去离子水溶解,然后加入所得丙硫基乙酸功能化的SBA-15分子筛,室温下搅拌8~12h,之后反应混合物抽滤,滤饼依次用水、乙醇洗涤,得到的固体在80℃下真空干燥2h,得到所述非均相铜催化剂;
所述Cu(OAc)2·H2O与丙硫基乙酸功能化的SBA-15分子筛的质量比为0.1~0.15:1。
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