CN116751172A - Synthesis method of diiodinated 1,2, 3-triazole compound - Google Patents
Synthesis method of diiodinated 1,2, 3-triazole compound Download PDFInfo
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- -1 diiodinated 1,2, 3-triazole compound Chemical class 0.000 title claims abstract description 58
- 238000001308 synthesis method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 63
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 30
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 25
- 239000002904 solvent Substances 0.000 claims abstract description 25
- 239000007789 gas Substances 0.000 claims abstract description 24
- 150000001879 copper Chemical class 0.000 claims abstract description 13
- 239000000654 additive Substances 0.000 claims abstract description 12
- 230000000996 additive effect Effects 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 150000001540 azides Chemical class 0.000 claims abstract description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 7
- 150000001447 alkali salts Chemical class 0.000 claims abstract description 7
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 53
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 38
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 23
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 238000006352 cycloaddition reaction Methods 0.000 abstract description 10
- BIEAMRHKHMPDPL-UHFFFAOYSA-N 4,5-diiodo-2h-triazole Chemical class IC=1N=NNC=1I BIEAMRHKHMPDPL-UHFFFAOYSA-N 0.000 abstract description 8
- 150000000177 1,2,3-triazoles Chemical class 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 abstract description 2
- 208000012839 conversion disease Diseases 0.000 abstract description 2
- 239000012535 impurity Substances 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 238000002360 preparation method Methods 0.000 description 21
- 239000012295 chemical reaction liquid Substances 0.000 description 20
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 19
- 238000000926 separation method Methods 0.000 description 18
- RWPISZUNOCYFHY-UHFFFAOYSA-N 4-iodo-2h-triazole Chemical compound IC1=CNN=N1 RWPISZUNOCYFHY-UHFFFAOYSA-N 0.000 description 17
- 238000001035 drying Methods 0.000 description 17
- 238000000605 extraction Methods 0.000 description 17
- 238000005406 washing Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 12
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 12
- 239000010949 copper Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000002194 synthesizing effect Effects 0.000 description 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 5
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 3
- 229910020366 ClO 4 Inorganic materials 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 230000026045 iodination Effects 0.000 description 3
- 238000006192 iodination reaction Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- QOVQEONXPGQIHT-UHFFFAOYSA-N 1-azido-2-bromobenzene Chemical compound BrC1=CC=CC=C1N=[N+]=[N-] QOVQEONXPGQIHT-UHFFFAOYSA-N 0.000 description 1
- MHTPYRQIAMETSQ-UHFFFAOYSA-N 1-azido-2-chlorobenzene Chemical compound ClC1=CC=CC=C1N=[N+]=[N-] MHTPYRQIAMETSQ-UHFFFAOYSA-N 0.000 description 1
- XBXJQBGKICADKR-UHFFFAOYSA-N 1-azido-2-methoxybenzene Chemical compound COC1=CC=CC=C1N=[N+]=[N-] XBXJQBGKICADKR-UHFFFAOYSA-N 0.000 description 1
- ZKGVLNVASIPVAU-UHFFFAOYSA-N 1-azido-2-methylbenzene Chemical compound CC1=CC=CC=C1N=[N+]=[N-] ZKGVLNVASIPVAU-UHFFFAOYSA-N 0.000 description 1
- GIDLBMJGNCUXLD-UHFFFAOYSA-N 1-azido-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=[N+]=[N-])=C1 GIDLBMJGNCUXLD-UHFFFAOYSA-N 0.000 description 1
- KLKGUBBTVRHUGD-UHFFFAOYSA-N 1-azido-3-bromobenzene Chemical compound BrC1=CC=CC(N=[N+]=[N-])=C1 KLKGUBBTVRHUGD-UHFFFAOYSA-N 0.000 description 1
- NTTKOAYXVOKLEH-UHFFFAOYSA-N 1-azido-3-chlorobenzene Chemical compound ClC1=CC=CC(N=[N+]=[N-])=C1 NTTKOAYXVOKLEH-UHFFFAOYSA-N 0.000 description 1
- WRMGCIOUNQGMSR-UHFFFAOYSA-N 1-azido-3-methylbenzene Chemical compound CC1=CC=CC(N=[N+]=[N-])=C1 WRMGCIOUNQGMSR-UHFFFAOYSA-N 0.000 description 1
- QNHZUKXPSZACNB-UHFFFAOYSA-N 1-azido-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=[N+]=[N-])C=C1 QNHZUKXPSZACNB-UHFFFAOYSA-N 0.000 description 1
- WHSJSMSBFMDFHK-UHFFFAOYSA-N 1-azido-4-bromobenzene Chemical compound BrC1=CC=C(N=[N+]=[N-])C=C1 WHSJSMSBFMDFHK-UHFFFAOYSA-N 0.000 description 1
- HZVGOEUGZJFTNN-UHFFFAOYSA-N 1-azido-4-chlorobenzene Chemical compound ClC1=CC=C(N=[N+]=[N-])C=C1 HZVGOEUGZJFTNN-UHFFFAOYSA-N 0.000 description 1
- FKNVPEYWUNMHOR-UHFFFAOYSA-N 1-azido-4-ethylbenzene Chemical compound CCC1=CC=C(N=[N+]=[N-])C=C1 FKNVPEYWUNMHOR-UHFFFAOYSA-N 0.000 description 1
- YVXDRCDGBCOJHX-UHFFFAOYSA-N 1-azido-4-methylbenzene Chemical compound CC1=CC=C(N=[N+]=[N-])C=C1 YVXDRCDGBCOJHX-UHFFFAOYSA-N 0.000 description 1
- JKHFKRIGVRZLEA-UHFFFAOYSA-N 1-azidononane Chemical compound CCCCCCCCCN=[N+]=[N-] JKHFKRIGVRZLEA-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- YURUKVUJGYBZDU-UHFFFAOYSA-N 4-azidobenzonitrile Chemical compound [N-]=[N+]=NC1=CC=C(C#N)C=C1 YURUKVUJGYBZDU-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 239000005997 Calcium carbide Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000002355 alkine group Chemical group 0.000 description 1
- UDLLFLQFQMACJB-UHFFFAOYSA-N azidomethylbenzene Chemical compound [N-]=[N+]=NCC1=CC=CC=C1 UDLLFLQFQMACJB-UHFFFAOYSA-N 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZXBVATFSHBMXOL-UHFFFAOYSA-N copper;2h-triazole Chemical compound [Cu].C=1C=NNN=1 ZXBVATFSHBMXOL-UHFFFAOYSA-N 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- PPKDSHDYUBDVKL-UHFFFAOYSA-N diazonio-(4-methoxyphenyl)azanide Chemical compound COC1=CC=C([N-][N+]#N)C=C1 PPKDSHDYUBDVKL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000004079 stearyl 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])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])[H] 0.000 description 1
- CLZWAWBPWVRRGI-UHFFFAOYSA-N tert-butyl 2-[2-[2-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-5-bromophenoxy]ethoxy]-4-methyl-n-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]anilino]acetate Chemical compound CC1=CC=C(N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)C(OCCOC=2C(=CC=C(Br)C=2)N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)=C1 CLZWAWBPWVRRGI-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention belongs to the fields of medicine synthesis and organic chemical industry, and relates to a synthesis method of diiodo 1,2, 3-triazole compounds, which comprises the steps of adding an azide compound, an additive and a solvent into a reaction container, replacing air in the reaction container with nitrogen, introducing acetylene gas into the reaction system, stirring and reacting at 0-50 ℃, and separating reaction products after the reaction is finished to obtain diiodo 1,2, 3-triazole compounds. According to the invention, based on cycloaddition reaction of acetylene and azide, copper salt, alkali and iodized salt are used as additives, and the expected product is obtained through cycloaddition reaction of organic molecules containing azide functional groups, so that a synthesis system of diiodo 1,2, 3-triazole compounds is established, the synthesis efficiency of 1,2, 3-triazole compounds is improved, the reaction system is mild, the reaction conversion rate is high, the impurities are few, the purification is easy, and the operability is strong.
Description
Technical Field
The invention belongs to the fields of medicine synthesis and organic chemical industry, relates to a method for synthesizing a compound, and in particular relates to a method for synthesizing a diiodo 1,2, 3-triazole compound.
Background
The 1,2, 3-triazole is an important pentacyclic aromatic heterocycle and has wide application in the fields of medicines, pesticides, materials and the like. As an important intermediate of 1,2,3 triazole, iodo-1, 2, 3-triazole is a special triazole structural compound, and can be used for constructing polysubstituted 1,2, 3-triazole and derivatives thereof, for example, wu and Chen et al convert 5-iodo-1, 4-disubstituted-1, 2, 3-triazole into 1,4, 5-trisubstituted-1, 2, 3-triazole through Suzuki coupling reaction, heck coupling reaction and Sonogashira coupling reaction. In 2020, related literature reports a strategy for synthesizing benzoxazole compounds by taking iodotriazole as a stable diazo precursor.
At present, there are various methods for preparing iodo-1, 2, 3-triazole, which reactions include: synthesizing iodo-1, 2, 3-triazole by cycloaddition reaction of iodo-alkyne and azide under copper catalysis; preparation of 1,2, 3-triazole by iodination of triazole-metal intermediate of cyclization reaction of terminal alkyne with azide with iodination reagent, etc. the triazole-metal intermediate includes triazolyl magnesium halide, triazole-copper intermediate, and the iodination reagent or component includes ICl, I 2 CuI and NBS, cu (ClO) 4 ) 2 NaI. And 4-iodo-1, 2, 3-triazole or 5-iodo-1, 2, 3-triazole can be synthesized by these reactions. Among them, the cycloaddition tandem reaction of azide and alkyne is the most common strategy for the synthesis of iodotriazole. The 5-iodotriazole can be prepared by synthesizing the iodotriazole through cycloaddition reaction by taking azido-alkyne as a raw material. In 2005, related literature reports the synthesis research of in-situ preparation of 5-iodotriazole by using electrophiles such as iodine chloride and the like, and chemical amounts of CuI and ICl are used as iodinated reagents in the reaction. 2008 reported a Cu produced by the oxidation-reduction reaction of CuI and NBS + And I + A method for synthesizing iodo-triazole by catalysis. Redox formation I + Can be Cu + The carbanion intermediate generated by the cycloaddition reaction of the catalyzed azido alkyne is captured, so that the efficient synthesis of the iodotriazole is realized. Thereafter, multiple studies continue to develop differentSynthesis of iodotriazole by the reaction system, e.g. Cu (ClO) 4 ) 2 /NaI，CuCl 2 NaI, etc. The cycloaddition of iodoalkynes to azides is also a common method for preparing iodotriazoles. Although the above studies have enabled the synthesis of 4-iodo-1, 2, 3-triazole or 5-iodo-1, 2, 3-triazole, these synthesis reactions have only enabled the synthesis of monoiodo-1, 2, 3-triazole compounds. After searching, no related report on the synthesis method of diiodo 1,2, 3-triazole exists.
Disclosure of Invention
The invention aims to provide a synthesis method of diiodo 1,2, 3-triazole compounds, which is based on cycloaddition reaction of acetylene and azide compounds, and a synthesis system of diiodo 1,2, 3-triazole compounds is established by taking copper salt, alkali and iodized salt as additives.
The invention adopts the technical scheme that:
a synthetic method of diiodo 1,2, 3-triazole compounds comprises the following steps:
in a solvent, the azide compound of the formula I reacts with acetylene in the presence of an additive to generate a compound of the formula II, wherein the compound of the formula II is a diiodo 1,2, 3-triazole compound with two iodine atoms, and R is optionally aryl and alkyl; the additive is a mixture of copper salt, alkali and iodized salt.
Further, the synthetic method of the diiodo 1,2, 3-triazole compound comprises the following specific steps: adding an azide compound, an additive and a solvent into a reaction container, replacing air in the reaction container with nitrogen, then introducing acetylene gas, and stirring at 0-50 ℃ for reaction; after the reaction is finished, separating a reaction product to obtain a diiodo 1,2, 3-triazole compound; the additive is a mixture of copper salt, alkali and iodized salt. The reaction may be carried out under pressure or under normal pressure. The acetylene can be industrial acetylene gas or can be prepared by in-situ reaction of calcium carbide and water.
Further, the solvent is one of dimethyl sulfoxide, acetonitrile, N-dimethylformamide, tetrahydrofuran, hexamethylphosphoric tetramine, dioxane, methyl tertiary butyl ether, 2-methylfuran, or a mixture of any two or more, wherein N, N-dimethylformamide is preferable.
Further, the molar ratio of the copper salt to the azide is 1:1-1:4.
Further, the copper salt is a divalent copper salt (e.g. CuBr 2 、CuCl 2 、Cu(NO 3 ) 2 ,Cu(ClO 4 ) 2 Etc.) or hydrates of cupric salts (e.g. CuCl) 2 ·2H 2 O，Cu(NO 3 ) 2 ·3H 2 O,Cu(ClO 4 ) 2 ·6H 2 O, etc.), among which CuCl is preferred 2 ·2H 2 O。
Further, the base is one of triethylamine, pyridine, N-diisopropylethylamine, N-lutidine, 1, 10-phenanthroline and its substituent, 2' -bipyridine or sodium carbonate, wherein pyridine is preferred.
According to the invention, based on cycloaddition reaction of acetylene and azide, copper salt, alkali and iodized salt are used as additives, and the expected product is obtained through cycloaddition reaction of organic molecules containing azide functional groups, so that a synthesis system of diiodo 1,2, 3-triazole compounds is established, the synthesis efficiency of 1,2, 3-triazole compounds is improved, the reaction system is mild, the reaction conversion rate is high, the impurities are few, the purification is easy, and the operability is strong.
Detailed Description
The following describes the embodiments of the present invention in further detail with reference to examples. The following examples are illustrative of the invention and are not intended to limit the scope of the invention. The experimental methods in the following examples are conventional methods unless otherwise specified. Materials, reagents, and the like used in the examples described below are commercially available with analytically pure reagents as preferred reagents unless otherwise specified.
Example one, preparation of 1-phenyl-4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
scheme one: to a dry 10mL flask was added sequentially azidobenzene (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1-phenyl-4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
Scheme II: to a dry 10mL flask was added sequentially azidobenzene (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), DMAP (2.0 mmol,2.0 equiv.), dimethyl sulfoxide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 10℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to the operation, so that the corresponding product 1-phenyl-4, 5-diiodo-1, 2, 3-triazole can be prepared, and the yield is 45%.
Yellow solid；mp:152.9-155.7℃；71％yield； 1 H NMR(400MHz,CDCl 3 )δ7.59–7.55(m,3H),7.50(dd,J＝6.8,3.0Hz,2H). 13 C NMR(100MHz,CDCl 3 )δ137.22,130.63,129.57,129.47,126.12,125.94,102.57,91.51.
Example two, preparation of 1- (p-tolyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
scheme one: to a dry 10mL flask was added sequentially p-tolylazide (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (4.0 mmol,4.0 equiv.), naI (8.0 mmol,4.0 equiv.), N, N-lutidine (2.0 mmol,2.0 equiv.), N-methylpyrrolidineKetone (4.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-tolyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 70%.
Scheme II: the copper salt required in the reaction is replaced by CuBr 2 (1.0 mmol,1.0 equiv.) the base used was replaced with 2,6-Lutidine (1.0 mmol,1.0 equiv.) after the reaction was completed, the reaction mixture was subjected to the above procedure to give the corresponding objective product in 48% yield.
White soild；mp:144.9-147.5℃；37％yield；1H NMR(400MHz,Chloroform-d)δ7.40–7.32(m,4H),2.46(s,3H).13C NMR(100MHz,Chloroform-d)δ140.98,134.77,130.10,125.70,102.32,91.69,21.47.
Example preparation of tris, 1- (p-ethylphenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
p-ethylphenylazide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cu (ClO 4 ) 2 ·6H 2 O (2.0 mmol,2.0 equiv.), KI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 30℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-ethylbenzene) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 69%.
Pale yellow solid；mp:179.5-181.4℃；67％yield； 1 H NMR(400MHz,CDCl 3 )δ7.44–7.31(m,4H),2.74(q,J＝7.6Hz,2H),1.28(t,J＝7.6Hz,3H). 13 C NMR(100MHz,CDCl 3 ) Delta 147.04,134.79,128.86,125.68,102.32,91.81,28.67,15.40 preparation of example four, 1- (p-methoxyphenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
4-Methoxyphenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cu (NO 3 ) 2 ·3H 2 O (2.0 mmol,2.0 equiv.), tetrabutylammonium iodide (4.0 mmol,4.0 equiv.), N, N-diethylisopropylamine (2.0 mmol,2.0 equiv.), N-methylpyrrolidone (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-methoxyphenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 62%.
White solid；mp:142.1-145.2℃；60％yield； 1 H NMR(400MHz,CDCl 3 )δ7.40(d,J＝8.9Hz,1H),7.04(d,J＝8.9Hz,1H),3.89(s,2H). 13 C NMR(100MHz,CDCl 3 )δ161.09,130.13,127.34,114.60,102.07,92.19,55.81.
Example five preparation of 1- (p-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask was added sequentially 4-bromophenyl azide (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (8.0 mmol,4.0 equiv.), 1, 10-phenanthroline (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 61%.
Pale yellow soild；mp:177.3-180.8℃；60％yield； 1 H NMR(400MHz,CDCl 3 )δ8.04(s,0.06H),7.71(d,J＝8.7Hz,2H),7.46–7.37(m,2H). 13 C NMR(100MHz,CDCl 3 )δ136.10,132.87,127.40,124.91,102.88,91.37.
Example six, preparation of 1- (p-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask was added sequentially 4-chlorophenyl azide (1.0 mmol,1.0 equiv.) and CuBr 2 (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (4.0 mmol,2.0 equiv.), N, N-dimethyl-acyl-ethylamine (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 40℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
Pale yellow solid；mp:177.3-180.5℃；56％yield； 1 H NMR(400MHz,CDCl 3 )δ7.57–7.52(m,1H),7.47(d,J＝8.8Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ136.78,135.55,129.85,127.17,102.82,91.56.
EXAMPLE seven preparation of 1- (p-trifluoromethylphenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask was added sequentially 4-trifluoromethylphenyl azide (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is extracted, washed, dried and desolventizedThe reagent is separated by column chromatography to obtain the corresponding product 1- (p-trifluoromethyl phenyl) -4, 5-diiodo-1, 2, 3-triazole with the yield of 61 percent.
Pale yellow solid；mp:169.4-173.4℃；55％yield； 1 H NMR(400MHz,CDCl 3 )δ7.85(d,J＝8.4Hz,1H),7.71(d,J＝8.4Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ139.72,132.57(q,J＝33.2Hz),126.86(q,J＝3.8Hz),126.28,123.44(q,J＝272.8Hz),103.33,91.23.
Example eight, preparation of 1- (p-cyanophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask was added sequentially 4-azidobenzonitrile (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 35℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (p-cyanophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 68%.
Pale yellow soild；mp:180.3-185.9℃；68％yield； 1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝8.6Hz,1H),7.74(d,J＝8.7Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ140.22,134.21,133.61,126.50,120.78,117.50,114.63.
EXAMPLE nine preparation of 1- (m-tolyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
m-methylphenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 45℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (m-tolyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 68%.
White solid；mp:112.7-123.6℃；51％yield； 1 H NMR(400MHz,CDCl 3 )δ7.44(t,J＝7.7Hz,1H),7.36(d,J＝7.7Hz,1H),7.32–7.25(m,2H),2.45(s,3H). 13 CNMR(100MHz,Chloroform-d)δ139.91,137.08,131.36,129.26,126.42,122.94,102.43,91.57,21.44.
EXAMPLE ten preparation of 1- (m-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
m-bromophenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (m-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
White solid；mp:164.0-169.6℃；53％yield； 1 H NMR(400MHz,CDCl 3 )δ8.07(s,0.03H),7.91(s,0.03H),7.74–7.67(m,2H),7.53–7.41(m,2H). 13 C NMR(100MHz,CDCl 3 ) Delta 138.04,133.78,130.81,129.06,124.58,122.94,102.93,91.39 preparation of example eleven, 1- (m-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
m-chlorophenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 20℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (m-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
Yellow solid；mp:156.4-159.1℃；58％yield； 1 H NMR(400MHz,CDCl 3 )δ8.07(s,0.03H),7.86(s,0.09H),7.58–7.53(m,2H),7.51(d,J＝8.6Hz,1H),7.44(dt,J＝7.6,1.8Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ137.97,135.33,130.87,130.60,126.25,124.13,102.93,91.36.
EXAMPLE twelve, preparation of 1- (m-trifluoromethylphenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
m-trifluoromethylphenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 35℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (m-trifluoromethylphenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 58%.
White solid；mp:143.6-148.1℃；61％yield； 1 H NMR(400MHz,CDCl 3 )δ7.84(d,J＝2.4Hz,2H),7.79–7.69(m,2H). 13 C NMR(100MHz,CDCl 3 )δ137.45,132.27(q,J＝33.6Hz),130.40,129.13,127.36(q,J＝3.5Hz),123.21(q,J＝273.0Hz),123.05(q,J＝3.9Hz),103.17,91.47.
Example preparation of tridecyl, 1- (o-tolyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
o-methylphenyl azide (1.0 mmol,1.0 equiv.) and Cu (OAc) were added sequentially to a dry 10mL flask 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 40℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (o-tolyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
White solid；mp:154.1-159.5℃；51％yield； 1 H NMR(400MHz,CDCl 3 )δ7.86(s,0.03H),7.47(td,J＝7.5,1.3Hz,1H),7.42–7.32(m,2H),7.19(dd,J＝7.9,1.3Hz,1H),2.03(s,3H). 13 C NMR(100MHz,CDCl 3 )δ136.37,135.56,131.37,131.20,127.58,127.01,101.23,93.34,17.52.
Example preparation of fourteen, 1- (O-methoxyphenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
o-methoxyphenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finishedThen, the reaction liquid is extracted, washed, dried and the solvent is removed, and the corresponding product 1- (o-methoxyphenyl) -4, 5-diiodo-1, 2, 3-triazole is obtained through column chromatography separation, and the yield is 50%.
White solid；mp:158.3-160.6℃；46％yield； 1 H NMR(400MHz,CDCl 3 )δ7.54(ddd,J＝8.2,7.6,1.7Hz,1H),7.29(dd,J＝7.7,1.7Hz,1H),7.14–7.05(m,2H),3.81(s,3H). 13 C NMR(100MHz,CDCl 3 )δ154.14,132.60,128.59,125.90,120.87,112.34,101.07,94.15,55.86.
Example pentadec, preparation of 1- (o-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
o-bromophenyl azide (1.0 mmol,1.0 equiv.) was added sequentially to a dry 10mL flask, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 40℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (o-bromophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 56%.
White solid；mp:158.6-160.9℃；56％yield； 1 H NMR(400MHz,CDCl 3 )δ7.80(dd,J＝7.9,1.5Hz,1H),7.57–7.45(m,2H),7.37(dd,J＝7.6,1.8Hz,1H). 13 CNMR(100MHz,CDCl 3 )δ136.59,133.96,132.69,129.56,128.64,121.97,93.59,89.04.
Example preparation of sixteen, 1- (o-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
at a dry state of 10To a mL flask was added sequentially chlorophenyl azide (1.0 mmol,1.0 equiv.), cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (o-chlorophenyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 64%.
White solid；mp:179.1-183.2℃；57％yield； 1 H NMR(400MHz,CDCl 3 )δ8.07(s,0.01H),7.89(s,0.09H),7.63(dd,J＝8.0,1.5Hz,1H),7.56(td,J＝7.7,1.7Hz,1H),7.49(td,J＝7.7,1.6Hz,1H),7.39(dd,J＝7.8,1.7Hz,1H). 13 C NMR(100MHz,CDCl 3 ) Delta 134.93,132.54,132.24,130.81,129.46,127.98,101.38,93.66 preparation of example seventeen, 1-benzyl-4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
to a dry 10mL flask was added sequentially benzyl azide (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was further introduced, and the reaction was stirred at room temperature for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1-benzyl-4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 56%.
White solid；mp:96.9-98.2℃；56％yield； 1 H NMR(400MHz,CDCl 3 )δ7.39–7.29(m,2H),7.30–7.21(m,1H),5.64(s,1H). 13 C NMR(100MHz,CDCl 3 )δ133.71,129.00,128.77,127.92,101.80,90.68,55.59.
Example preparation of octadecyl, 1-n-octyl-4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask, nonylazide (1.0 mmol,1.0 equiv.) was added sequentially, cuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 20℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1-n-octyl-4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 53%.
White solid；mp:46.0-46.7℃；53％yield； 1 H NMR(400MHz,CDCl 3 )δ4.40(t,J＝7.4Hz,2H),1.85(q,J＝7.5Hz,2H),1.35-1.10(m,10H),0.83(t,J＝6.9Hz,2H).
Example nineteen, preparation of 1- (. Alpha. -naphthyl) -4, 5-diiodo-1, 2, 3-triazole
The structural formula is as follows:
in a dry 10mL flask was added sequentially α -naphthylazidobenzene (1.0 mmol,1.0 equiv.) CuCl 2 ·2H 2 O (2.0 mmol,2.0 equiv.), naI (4.0 mmol,4.0 equiv.), pyridine (2.0 mmol,2.0 equiv.), N, N-dimethylformamide (2.0 mL). After the air in the flask was replaced with nitrogen, acetylene gas was introduced, and the reaction was stirred at 45℃for 24 hours. After the reaction is finished, the reaction liquid is subjected to extraction, washing, drying and solvent removal, and column chromatography separation is carried out to obtain the corresponding product 1- (alpha-naphthyl) -4, 5-diiodo-1, 2, 3-triazole, wherein the yield is 50%.
Yellow solid；mp:171.3-175.4℃；44％yield； 1 H NMR(400MHz,CDCl 3 )δ8.08(d,J＝8.3Hz,1H),7.98(d,J＝7.7Hz,1H),7.66–7.55(m,2H),7.57–7.44(m,2H),7.15(dd,J＝8.4,1.0Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ134.14,133.58,131.66,129.28,128.49,128.30,127.42,125.87,124.98,122.25,101.49,94.41.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that it will be apparent to those skilled in the art that several modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the scope of the invention.
Claims (6)
1. The synthesis method of the diiodinated 1,2, 3-triazole compound is characterized by comprising the following steps:
in a solvent, the azide compound of the formula I reacts with acetylene in the presence of an additive to generate a compound of the formula II, wherein the compound of the formula II is a diiodo 1,2, 3-triazole compound with two iodine atoms, and R is optionally aryl and alkyl; the additive is a mixture of copper salt, alkali and iodized salt.
2. The synthesis method according to claim 1, wherein: the specific process of the synthesis method is as follows: adding an azide compound, an additive and a solvent into a reaction container, replacing air in the reaction container with nitrogen, then introducing acetylene gas, and stirring at 0-50 ℃ for reaction; after the reaction is finished, separating a reaction product to obtain a diiodo 1,2, 3-triazole compound; the additive is a mixture of copper salt, alkali and iodized salt.
3. The synthesis method according to claim 1, wherein: the solvent is one of dimethyl sulfoxide, acetonitrile, N-dimethylformamide, tetrahydrofuran, hexamethylphosphoric tetramine, dioxane, methyl tertiary butyl ether and 2-methyl furan, or a mixture of any two or more.
4. The synthesis method according to claim 1, wherein: the mol ratio of the copper salt to the azide is 1:1-1:4.
5. The synthesis method according to claim 1, wherein: the copper salt is a cupric salt or a hydrate of cupric salt.
6. The synthesis method according to claim 1, wherein: the alkali is one of triethylamine, pyridine, N-diisopropyl ethylamine, N-dimethyl pyridine, 1, 10-phenanthroline and its substituent, 2' -bipyridine or sodium carbonate.
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