CN111559971A - 一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法 - Google Patents
一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法 Download PDFInfo
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- CN111559971A CN111559971A CN202010497915.3A CN202010497915A CN111559971A CN 111559971 A CN111559971 A CN 111559971A CN 202010497915 A CN202010497915 A CN 202010497915A CN 111559971 A CN111559971 A CN 111559971A
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- olefin
- thioether
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 title claims abstract description 46
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 229910052740 iodine Inorganic materials 0.000 title claims abstract description 42
- 239000011630 iodine Substances 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 33
- 150000001336 alkenes Chemical class 0.000 title claims abstract description 30
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 150000003568 thioethers Chemical class 0.000 title claims description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 93
- 150000003462 sulfoxides Chemical class 0.000 claims abstract description 18
- 238000005580 one pot reaction Methods 0.000 claims abstract description 6
- -1 methyl Chemical group 0.000 claims description 29
- 239000000126 substance Substances 0.000 claims description 14
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 11
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 235000009518 sodium iodide Nutrition 0.000 claims description 4
- 230000000707 stereoselective effect Effects 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims description 2
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])* 0.000 claims description 2
- 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 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 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 claims 1
- 239000000654 additive Substances 0.000 abstract description 9
- 238000006467 substitution reaction Methods 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 7
- 238000010438 heat treatment Methods 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- 230000000996 additive effect Effects 0.000 abstract description 5
- 229910052799 carbon Inorganic materials 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000000047 product Substances 0.000 description 25
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 18
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 239000000758 substrate Substances 0.000 description 17
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 13
- 150000001345 alkine derivatives Chemical class 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000002194 synthesizing effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 150000003440 styrenes Chemical class 0.000 description 5
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 4
- 150000008125 alkenyl sulfides Chemical class 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 238000003541 multi-stage reaction Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 2
- HFDVRLIODXPAHB-UHFFFAOYSA-N 1-tetradecene Chemical compound CCCCCCCCCCCCC=C HFDVRLIODXPAHB-UHFFFAOYSA-N 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- VEWLDLAARDMXSB-UHFFFAOYSA-N ethenyl sulfate;hydron Chemical compound OS(=O)(=O)OC=C VEWLDLAARDMXSB-UHFFFAOYSA-N 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003463 sulfur Chemical class 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- QQBUHYQVKJQAOB-UHFFFAOYSA-N 2-ethenylfuran Chemical compound C=CC1=CC=CO1 QQBUHYQVKJQAOB-UHFFFAOYSA-N 0.000 description 1
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical compound C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- ORNUPNRNNSVZTC-UHFFFAOYSA-N 2-vinylthiophene Chemical compound C=CC1=CC=CS1 ORNUPNRNNSVZTC-UHFFFAOYSA-N 0.000 description 1
- KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical compound C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 229910002567 K2S2O8 Inorganic materials 0.000 description 1
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- YTMPFFHLIDGVHP-VQHVLOKHSA-N [(Z)-2-iodo-2-methylsulfanylethenyl]benzene Chemical compound CS\C(I)=C\c1ccccc1 YTMPFFHLIDGVHP-VQHVLOKHSA-N 0.000 description 1
- OZPOYKXYJOHGCW-VOTSOKGWSA-N [(e)-2-iodoethenyl]benzene Chemical compound I\C=C\C1=CC=CC=C1 OZPOYKXYJOHGCW-VOTSOKGWSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical group C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000010505 homolytic fission reaction Methods 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical class [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095068 tetradecene Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
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Abstract
本发明公开了一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法,该方法以烯烃、碘和亚砜为原料,在加热条件下,碘和亚砜在烯烃的同一碳原子上同时发生取代反应,不需要添加其它催化剂或添加剂,通过一锅反应,选择性地得到一种α‑碘代烯基硫醚产物;该方法反应条件温和、操作简单,无需外加催化剂或添加剂、选择性好、收率高,有利于工业化生产。
Description
技术领域
本发明涉及一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法,具体涉及一种由亚砜、碘在烯烃碳原子上的双取代反应合成α-碘代烯基硫醚衍生物的方法,属于有机合成领域。
背景技术
卤代烯基硫化物是一种具有重要合成价值的化合物,其分子中含有多个反应位点,常作为合成中间体来构建生物医药分子和光化学材料分子。卤代烯基硫醚,由于分子中同时含有卤素和硫烷基团,是有机合成化学和有机材料学等领域的热门研究材料,吸引了广大科学家的研究兴趣(Wang B W,Jiang K,Li J X,et al. 1,1-Diphenylvinylsulfideas a Functional AIEgen Derived from the Aggregation-Caused-Quenching Molecule1,1-Diphenylethene through Simple Thioetherification.Angewandte ChemieInternational Edition,2020,59(6): 2338-2343;Gu X-X,Xie M-H,Zhao X-Y,et al.AnEfficient Synthesis of Polysubstituted 1,3-Enynes from(E)-β-IodovinylSulfones and Terminal Alkynes. Chinese Journal of Chemistry,2008,26(9):1625-1629;Li X,Shi X,Fang M,et al. Iron halide-mediated regio-and stereoselectivehalosulfonylation of terminal alkynes with sulfonylhydrazides:synthesis of(E)-beta-chloro and bromo vinylsulfones.The Journal of Organic Chemistry,2013,78(18):9499-9504;Iwasaki M,Fujii T, Nakajima K,et al.Iron-induced regio-and stereoselective addition of sulfenyl chlorides to alkynes by a radicalpathway.Angewandte Chemie International Edition, 2014,53(50):13880-13884;Iwasaki M,Fujii T,Yamamoto A,et al. Palladium-catalyzed regio-andstereoselective chlorothiolation of terminal alkynes with sulfenylchlorides.Chemistry An Asian Journal,2014,9(1):58-62)。这类卤代烯基硫化物分子中含有卤素基团,特别是含有碘基团,在化学反应中是一种良好的离去基团。双键碳上的碘原子,相对于其它卤原子更容易被别的基团所取代,得到各种衍生产物。另外,分子中的硫烷基也是一类重要的基团,不仅对于生物体分子有着重要的意义,同时也容易在化学反应中被其他基团所取代或者发生自身氧化还原转化(Ettari R,Nizi E,Di Francesco M E,et al.Development of peptidomimetics with a vinyl sulfone warhead asirreversible falcipain-2inhibitors. Journal of Medicinal Chemistry,2008,51(4):988-996;Palmer J T,Rasnick D,Klaus J L,et al.Vinyl sulfones as mechanism-based cysteine protease inhibitors.Journal of Medicinal Chemistry,1995,38(17):3193-3196;Meadows D C,Sanchez T,Neamati N,et al.Ring substituent effectson biological activity of vinyl sulfones as inhibitors of HIV-1.BioorganicMedicinal Chemistry,2007,15(2):1127-1137)。因此,碘代烯基硫化物及其合成方法成为有机合成领域非常重要的研究内容,许多有机合成和材料应用科学家进行了大量的研究工作。
在过去的数十年中,合成这类碘代烯基硫化物的方法是通过炔烃的碘代-硫烷基化的加成双官能团化反应。目前已经有多个课题组报道了炔烃与烷基磺酰肼在I2、KI或CuI提供碘源的条件下,合成β-碘代烯基砜类化合物,(Wan J-P,Hu D,Bai F,etal.Stereoselective Z-halosulfonylation of terminal alkynes usingsulfonohydrazides and CuX(X=Cl,Br,I).RSC Advances,2016,6(77): 73132-73135;Yang L,Hu D,Wei L,et al.KI as iodine source for the synthesis of E-iodovinylsulfones via metal-free iodosulfonylation of terminal alkynes. Phosphorus,Sulfur,and Silicon and the Related Elements,2017,192(12): 1301-1304;Hou Y,ZhuL,Hu H,et al.Iodine promoted iodosulfonylation of alkynes with sulfonylhydrazides in an aqueous medium:highly stereoselective synthesis of (E)-β-iodo vinylsulfones.New Journal of Chemistry,2018,42(11):8752-8755;Ma Y, WangK,Zhang D,et al.Solvent Controlled Transformation between Sulfonyl Hydrazidesand Alkynes:Divergent Synthesis of Benzo[b]thiophene-1,1-dioxides and (E)-b-iodo Vinylsulfones.Advanced Synthesis&Catalysis,2018,361(3):597-602.)。反应如下式1所示。
反应式1炔烃与烷基磺酰肼反应合成β-碘代烯基砜
另外,Jiang课题组以及Sun、Liu等人也报道了基于炔烃与烷基磺酸钠的反应(GaoY,Wu W,Huang Y,et al.NBS-promoted halosulfonylation of terminal alkynes:highly regio-and stereoselective synthesis of(E)-β-halo vinylsulfones.Organic Chemical Frontiers,2014,1(4):361-364);Sun Y,Abdukader A,Lu D,et al.Synthesis of(E)-β-iodo vinylsulfones via iodine-promoted iodosulfonylation ofalkynes with sodium sulfinates in an aqueous medium at room temperature.GreenChemistry,2017,19(5):1255-1258)在来合成这类β-碘代烯基砜,反应如反应式2 所示。
反应式2炔烃与烷基磺酸钠反应合成β-碘代烯基砜
Pan和Liu等人利用二甲亚砜(DMSO)这种热门的合成子提供硫源,与H2O形成混合溶剂与炔烃、单质碘I2反应也能得到β-碘代烯基砜(Zhou P,Pan Y,Tan H, et al.I2-DMSO-H2O:A Metal-Free Combination System for the Oxidative Addition of Alkynes toAccess(E)-alpha-Iodo-beta-methylsulfonylalkenes.The Journal of OrganicChemistry,2019,84(23):15662-15668)。
反应式3炔烃与DMSO、H2O反应合成β-碘代烯基砜此外,文献还报道了一种用酮类化合物与烷基磺酰肼、I2反应,经过去氧化制备β-碘代烯基硫醚的方法(Bao Y,Yang X,Zhou Q,et al.Iodine-Promoted Deoxygenative Iodization/Olefination/Sulfenylation of Ketones with Sulfonyl Hydrazides:Access to beta-IodoalkenylSulfides.Organic Letters,2018,20(7): 1966-1969)。产物中碘原子和硫原子分别位于双键的两个碳原子上。
反应式4酮与磺酰肼反应合成β-碘代烯基硫醚
α-碘代烯基硫化合物比碘和硫原子分别位于两个碳原子上的β-碘代烯基硫化合物更容易发生取代反应,因而是具有更好反应性能和生物性能的一类碘代烯基硫化物。2001年,Jin等人报道了一种以炔基硫醚为底物与碘代三甲基硅烷 TMS-I通过加成反应制备α-碘代烯基硫醚的方法(Bao Y,Yang X,Zhou Q,et al. Iodine-PromotedDeoxygenative Iodization/Olefination/Sulfenylation of Ketones with SulfonylHydrazides:Access to beta-Iodoalkenyl Sulfides.Organic Letters,2018,20(7):1966-1969)。在该方法中,底物炔基硫醚需要通过炔烃与硫代烷烃反应提前制备,随后再与TMS-I 反应,通过两步反应得到最终产物a-碘代烯基硫醚,反应如下反应式5所示。
反应式5炔烃、硫烷烃、碘代三甲基硅烷多步反应合成α-碘代烯基硫醚 2006年,Cai等人报道了一种多步合成α-碘代烯基硫醚的方法。该方法先通过端基炔烃与格氏试剂反应得到炔基溴化镁中间体,随后与一分子氯代硫烷烃偶联,得到炔基硫醚中间体(ZhaoQ,Liu S,Li Y,et al.Design,synthesis,and biological activities of novel 2-cyanoacrylates containing oxazole,oxadiazole,or quinoline moieties.Journal ofAgricultural and Food Chemistry,2009,57(7):2849-2855)。最后,再将得到的炔基硫醚与 TMS-I反应,得到目标产物α-碘代烯基硫醚,如反应式6所示。
反应式6炔烃、氯代硫烷烃、碘代三甲基硅烷多步反应合成α-碘代烯基硫醚
2008年,Guerrero等人利用二异丁基铝试剂与预先制备的炔基硫醚反应,得到了一种金属烯基硫醚中间体(Yang W S,Shimada K,Delva D,et al.Identification ofSimple Compounds with Microtubule-Binding Activity That Inhibit Cancer CellGrowth with High Potency.ACS Medicinal Chemical Letters,2012,3(1):35-38)。随后,中间体可以在单质碘的条件下脱掉金属基团,得到α-碘代烯基硫醚类产物,反应如反应式7所示。
反应式7炔基硫醚、二异丁基铝、碘多步反应合成α-碘代烯基硫醚
另外在2006年,Cai等人报道了利用锡烷取代的烯基硫醚化合物为底物与单质碘发生碘代脱锡基化反应来合成α-碘代烯基硫醚类化合物的方法(Turchi I J, Dewar M JS.Chemistry of oxazoles.Chemical Reviews,1975,75(4):389-437),如反应式8 所示。同样在该方法中,原料锡烷取代的烯基硫醚需要提前制备。
反应式8锡烷取代烯基硫醚与碘反应合成α-碘代烯基硫醚
根据上述合成方法概述可知,虽然通过已有的方法能合成一系列目标化合物α-碘代烯基硫醚,但是这些反应仍然存在一些问题,尤其是反应需要用到难于合成的特殊合成试剂作为原料,如取代炔基硫醚化合物或金属烯基化合物,这些特殊试剂都需要提前制备。因此,从反应步骤上看,α-碘代烯基硫醚的合成都需要经过两步及以上反应才能得到产物,无法做到一步或一锅法合成。
发明内容
针对现有α-碘代烯基硫化合物合成方法需要两步甚至多步反应,需要金属有机化合物参与,对反应条件要求很高等的缺陷,本发明的目的是在于提供一种不使用金属有机物,只由端基烯烃与亚砜、碘等易得原料一步合成(Z)-α-碘代烯基硫醚的方法。
反应式9烯烃与亚砜、I2反应合成(Z)-α-碘代烯基硫醚
该方法是端基烯烃C=C双键同时与碘和亚砜发生端基碳原子上的双取代反应,反应不添加其它催化剂或添加剂,仅在加热条件下通过一锅反应,选择性地得到一种(Z)-α-碘代烯基硫醚产物;该方法反应条件温和、操作简单,无需外加催化剂或添加剂、选择性好、收率高,有利于工业化生产。
所述(Z)-α-碘代烯基硫醚衍生物具有式1结构:
所述端基烯烃结构具有式2结构:
所述亚砜具有式3结构:
其中,
R1为甲基、乙基、丙基、丁基、戊基、己基、十二烷基等烷基或者它们的取代烷基,或者为苯基及它们的取代衍生物。
R2为甲基、乙基、丙基、丁基、苄基。
所述碘为单质碘或者碘化钠、碘化钾等碘盐。
本发明的端基烯烃中,R1为芳基时,包含简单芳环基或者取代芳基。所述取代芳基,包含的取代基个数为1~2个,取代基选自卤素取代基、烷基、羟基、氨基、羧基中至少一种。卤素取代基如氟、氯、溴、碘等。烷基为C1~C10的烷基;更优选为C1~C5的短链烷基、如甲基、乙基、丙基等,也可以为含支链的烷基,如异丙基、异丁基等。
本发明的端基烯烃中,R1为烷基时,包含简单烷基和取代烷基。R1选自取代烷基时,所述取代基包含卤素、羟基、氨基、氰基、酯基、硝基、羟基中至少一种。
优选的方案,所述碘和端基烯烃之比为0.5~3:1。较优选为0.8~1.2:1。
优选的方案,所述亚砜和端基烯烃之比为3~10:1。较优选为5~6:1。
亚砜主要起到两方面的作用,一方面起到良性溶剂的作用,另一方面作为反应底物,亚砜提供一个烷硫基作为产物中的含硫基团。
优选的方案,所述反应的条件为:在大气气氛下,于80~150℃温度下,反应2~12h。较优选的条件为:在大气气氛下,于110~130℃温度下,反应3~5h。
本发明以苯乙烯与二甲亚砜及单质碘反应合成(Z)-α-碘代苯乙烯基甲基硫醚(a)来对反应机理进行说明。经过查阅和参考相关文献,设计了一系列的机理研究实验。首先,在标准条件下,用苯乙烯为底物做了一系列自由基抑制实验,结果式1所示:
式1反应抑制实验
分别采用两种自由基抑制剂TEMPO和BHT,通过添加梯度当量的抑制剂对反应进行测试。在抑制剂用量为0.5当量时,α-碘代烯基甲基硫醚产率较之前有所下降;加到1.0当量时,α-碘代烯基甲基硫醚产率明显下降。当我们加入2.0 当量的抑制剂时,两组实验的结果都显示产物α-碘代烯基甲基硫醚已经变得很少了,见式1(1)。通过两组自由基抑制实验推测:该烯烃的双取代反应可能经历了自由基的历程。如果在标准条件下加入2.0equiv BHT,并且通过GC-MS对反应进行监测,产物α-碘代烯基甲基硫醚基本检测不到,并且可以检测到自由基捕捉产物BHT-SCH3,见式1(2)。另外,在标准反应条件下在不同反应时间下监测反应,结果显示反应中可以检测到中间产物β-碘代苯乙烯,见式1(3)。
根据上面控制实验的结果以及文献报道,我们对该反应的反应机理提出了一种合理路径,如式2所示。首先,二甲亚砜(亚砜)在加热条件下缓慢发生断裂,生成一分子甲硫醇和一个分子甲醛。同时,I2在加热的条件下均裂产生单碘自由基(I·)。单碘自由基与甲硫醇相互作用,发生自由基传递产生甲基硫自由基 (CH3S·)和碘化氢HI。另一方面,端基烯烃与单质碘反应通过β-碘化取代反应得到β-碘代烯烃中间体。随即,甲基硫自由基(CH3S·)进攻β-碘代烯烃中间体得到自由基加成中间体。最后,中间体在碘的作用下得到双键保留的最终产物。同时在反应中,HI在氧化条件如DMSO的左右下可以被氧化回碘单质,完成碘的循环作用。
式2反应机理
相对现有技术,本发明的技术方案带来的有益技术效果:
1)本发明提出的由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法所采用的原料为端基烯烃、亚砜和碘,都是一些常见的普通化学原料,成本低廉,原料来源广泛,有利于工业化生产。
2)本发明提出的一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法无需使用催化剂,在大气气氛中一锅反应形成产物,工艺简单,便于工业应用。
3)本发明提出的一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法采用一锅法反应,且反应条件温和,操作简单,满足工业生产要求。
4)本发明提出的一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法对底物原料的适应范围较广,可以构建多种取代基团的α-碘代烯基硫醚。
具体实施方式
以下实施例旨在进一步说明本发明内容,而不是限制本发明权利要求的保护范围。
除另有说明外,所有反应均在Schlenk试管中进行。
所有反应原料溶剂从商业来源获得,并且不经进一步纯化而使用。
产品分离采用硅胶色谱柱,硅胶(粒度300目-400目)。
1H NMR(400MHz)、13C NMR(100MHz)和19F NMR(376MHz)检测采用Bruker ADVANCEIII光谱仪,以CDCl3为溶剂,以TMS为内标,化学位移以百万分率(ppm)计,以四甲基硅烷的0.0ppm为参考位移。使用以下缩写(或其组合)来解释多重性:s=单峰,d=双峰,t=三重峰,q=四重峰,m=多重峰, br=宽峰。偶合常数J的单位为赫兹(Hz)。化学位移以ppm表示,参考氘代氯仿在77.0ppm三重态的中心线或参考氘代DMSO在39.52ppm七重态的中心线。
GC-MS采用GC-MS QP2010设备检测,HRMS采用电子电离(EI)方法测量,质量分析仪类型为TOF,EI采用Esquire 3000plus仪器检测。
1.条件优化实验:
由苯乙烯与二甲亚砜及碘合成(Z)-(1-碘-2-苯乙烯)(甲基)硫醚(a)为例,对反应所使用的碘试剂种类及用量,反应添加剂、反应时间及温度等方面进行筛选,以寻求最佳的反应条件。
反应式9苯乙烯与DMSO、I2反应合成(Z)-(1-碘-2-苯乙烯)(甲基)硫醚
1.1碘试剂的种类和用量的筛选
首先,对反应所使用的碘试剂种类及用量进行筛选和优化。对I2、KI以及NaI 进行了筛选,结果如下表1所示。加入1.0当量(0.5mmol)I2的反应最终能以81%的收率得到a,但是换成KI或NaI的效果远不如I2。所以,最终选择最简单的单质碘I2作为碘试剂。随后,考察了I2的用量问题。当按照反应化学计量的0.5当量(0.25 mmol)加入I2时,a的收率只有57%,当加到0.8当量(0.4mmol)时,a的产率有所提升。当使用1.2当量(0.6mmol,150mg)I2,能得到最高的86%的产率。但是继续加大使用量时,会出现其它多碘取代的副产物,对a的产率影响很明显。最终选择使用1.2当量(0.6mmol,150mg)I2。
表1.碘试剂的种类和用量的筛选
1.2反应添加剂的筛选
在上述最佳条件下能以86%的收率得到a,接着尝试继续加入某种添加剂来促进提高反应产率。选择了多种常见的小分子化合物加入到原反应体系,结果通过 GC-MS监测,如表2所示。首先,尝试加入碱性物质,Na2CO3,NaOH和DBU,但是发现碱性条件对目标反应影响很大,大大降低了反应的收率。接着尝试加入酸性物质H3PO4和HCl(0.1M),发现酸对该反应也有负面影响。随后,加入一些氧化剂,希望能促进反应。加入H2O2、TBHP和K2S2O8对反应影响很大,PhI(OAc)2也没有明显的作用。根据一系列实验结果分析,最终选择不加任何添加剂。
表2.反应添加剂的筛选
1.3反应温度和时间的筛选
反应温度以及时间是影响反应产率的重要因素,进一步研究了梯度温度以及不同时间对该反应的影响,结果如下表3所示。我们已知该反应在120℃下反应4 h能以最好86%的收率得到a。继续升高温度对反应有轻微影响,降低温度对反应影响很大。当温度低于80℃时,反应产率变得很差。我们继续研究120℃下反应时间因素,反应2-3h时,产率不断升高,但是超过6h以后或者过夜12h以后,反应产率不会有提升。因此,我们最后选择在120℃油浴加热下,反应4h。
表3.反应温度和时间的筛选
1.4标准反应过程
经上述优化以后得到的标准反应过程如下:在25ml Schlenk管中加入4ml DMSO,称取0.5mmol的端基烯烃,0.6mmol(约150mg)单质碘I2。混合均匀以后,用密封塞将反应管密封以后放入120℃油浴锅磁力搅拌中加热搅拌。反应4 h之后停止加热,待反应管冷却后加入5ml左右乙酸乙酯,将混合物转移至分液漏斗。加入10ml饱和食盐水和适量硫代硫酸钠Na2S2O3。摇晃分液漏斗,萃取反应液,取上层有机层,放掉下层水层,重复两次。将有机层转移到烧杯加入无水Na2SO4干燥,最后真空旋干溶剂。旋干后的样品通过硅胶柱层析进行分离,以石油醚/乙酸乙酯为淋洗剂,最后得到产物,经真空干燥,进行NMR、MS、MS 等表征。
2、反应底物拓展
2.1简单取代苯乙烯衍生物的底物拓展
在标准反应条件下,本发明对取代苯乙烯衍生物的适用性进行考察,结果如下表4所示。苯乙烯对应的产物a最终能以83%的收率被分离得到。我们将溶剂反应物二甲亚砜换成氘代二甲亚砜(DMSO-d6),最后能成功得到对应的氘代产物 d3-a,产率为70%。苯乙烯对位有-Me或-tBu取代时,对应产物b和c产率也能达到 82%以上。对位含有-F取代时,产物收率也有81%。我们继续考察苯乙烯苯环上还有不同位置-Cl取代的反应情况,结果表明三种不同位置的含Cl取代的底物对应的产率分别为86%,78%和74%。当我们用2-乙烯基萘代替苯乙烯时,对应的产物h也能以71%的产率被分离出来。
表4取代苯乙烯衍生物的底物的适用性研究
反应条件:取代苯乙烯(0.5mmol),I2(1.2equiv,0.6mmol),DMSO(3ml),在耐压管中加热120℃持续4h。产率为分离产率。
2.2脂肪族和芳香杂环烯烃的底物拓展
通过简单的取代苯乙烯衍生物的底物适用性研究发现,该方法对与芳香端基烯烃的效果很好,对于不同取代基都有良好的适用性。随后,继续对其它端基烯烃进行考察。首先,我们对脂肪族的烯烃进行反应研究。1-辛烯在该反应条件下能以41%的收率得到对应的产物i,另外一种直链烯烃十四碳烯也能在该条件下转化为对应的产物j,3-Br丙烯在相同的条件下也可检测到目标产物k。脂肪环烯烃,环己基乙烯也能以中等的48%的产率得到对应的碘代烯基硫醚产物l。接着对杂环烯烃也进行了研究。2-乙烯基呋喃和2-乙烯基噻吩可以被转化得到对应的底物m和n。含吡啶环的底物,2-乙烯基吡啶和4-乙烯基吡啶也可以得到最终的产物o和p,但是对应产物的收率偏低。
表5脂肪族和杂环烯烃类底物的适用性研究
反应条件:烯烃(0.5mmol),I2(1.2equiv,0.6mmol),DMSO(3ml),在耐压管中加热120℃持续4h,产率为分离产率。
2.3亚砜底物的适用性研究
该发明亚砜除了含甲基的二甲亚砜以外,对于含乙基、丙基、丁基、戊基、苄基的亚砜都适用,但二甲亚砜得到的产物收率最高(见表6)。
表6亚砜底物的适用性研究
部分α-碘代烯基硫醚的结构表征
a(Z)-(1-iodo-2-phenylvinyl)(methyl)sulfane:
黄色油状物,产率83%,114.5mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.41(d,J=7.7Hz,2H),7.27(d,J=7.5Hz,1H),7.25-7.12(m,2H),6.82(s,1H),2.48(s, 3H).13C{1H}NMR(101MHz,CDCl3)δ141.61,137.50,128.31,127.92,127.85,97.01,16.64. GC-MS(m/z)=276
d3-a(Z)-(1-iodo-2-phenylvinyl)(methyl-d3)sulfane:
黄色油状物,产率70%,97.6mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.45–7.43(m,3H),7.25–7.22(m,2H),6.85(s,1H).13C{1H}NMR(101MHz,CDCl3)δ141.66,137.48,128.32,127.87,125.67,96.99.GC-MS(m/z)=279.
b(Z)-(1-iodo-2-(p-tolyl)vinyl)(methyl)sulfane:
亮黄色油状物,产率82%,119mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.33(d,J=7.6Hz,2H),7.09(d,J=7.8Hz,2H),6.78(s,1H),2.49(s,3H),2.34(s,3H). 13C{1H}NMR(101MHz,CDCl3)δ138.99,137.91,136.51,128.97,127.73,97.31,21.02,16.62. GC-MS(m/z)=290
c(Z)-(2-(4-(tert-butyl)phenyl)-1-iodovinyl)(methyl)sulfane:
深黄色油状物,产率85%,141mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.37(d,J=7.9Hz,2H),7.31(d,J=7.8Hz,2H),6.80(s,1H),2.49(s,3H),1.32(s,12H). 13C{1H}NMR(101MHz,CDCl3)δ151.09,138.86,136.63,127.52,125.24,97.24,34.51,31.22, 16.61.GC-MS(m/z)=332.
d(Z)-(2-(4-fluorophenyl)-1-iodovinyl)(methyl)sulfane:
淡黄白色油状物,产率81%,119mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1HNMR(400 MHz,CDCl3)δ7.44-7.30(m,2H),6.98(t,J=8.5Hz,2H),6.77(s,1H),2.50(s,3H).13C{1H}NMR (101MHz,CDCl3)δ162.35(d,J=248.4Hz),138.01(d,J=3.2Hz),137.62,129.44(d,J=8.1Hz), 115.13(d,J=21.8Hz),95.19,16.60.GC-MS(m/z)=294.
e(Z)-(2-(4-chlorophenyl)-1-iodovinyl)(methyl)sulfane:
淡黄色油状物,产率86%,133mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.36(d,J=7.9Hz,2H),7.25(d,J=7.7Hz,2H),6.85(s,1H),2.50(s,3H).13C{1H}NMR (101MHz,CDCl3)δ140.13,138.33,133.75,129.01,128.40,95.07,16.65.GC-MS(m/z)=310. f(Z)-(2-(3-chlorophenyl)-1-iodovinyl)(methyl)sulfane:
淡黄色油状物,产率78%,121mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H).13C{1H}NMR(101MHz, CDCl3)δ143.23,139.18,134.17,129.49,127.82,127.73,126.20,94.40,16.67.GC-MS(m/z)= 310.
g(Z)-(2-(2-chlorophenyl)-1-iodovinyl)(methyl)sulfane:
黄色油状物,产率74%,115mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H).13C{1H}NMR(101MHz, CDCl3)δ143.23,139.18,134.17,129.49,127.82,127.73,126.20,94.40,16.67.GC-MS(m/z)= 310.
h(Z)-(2-(4-bromophenyl)-1-iodovinyl)(methyl)sulfane:
亮黄色油状物,产率75%,133mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.41(d,J=8.0Hz,2H),7.30(d,J=8.1Hz,2H),6.87(s,1H),2.50(s,3H).13C{1H}NMR (101MHz,CDCl3)δ140.56,138.42,131.35,129.30,121.89,95.08,16.66.GC-MS(m/z)=356.
i(Z)-(2-(3-bromophenyl)-1-iodovinyl)(methyl)sulfane:
黄色油状物,产率70%,125mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.57(s,1H),7.36(d,J=7.9Hz,2H),7.16(t,J=7.8Hz,1H),6.91(s,1H),2.51(s,3H). 13C{1H}NMR(101MHz,CDCl3)δ143.49,139.25,130.74(s),130.51(s),129.74(s),126.73(s), 122.30(s),94.21(s),16.67.GC-MS(m/z)=356.
j(Z)-(2-(2-ethylphenyl)-1-iodovinyl)(methyl)sulfane:
黄色油状物,产率57%,86mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.30–7.16(m,3H),7.08(d,J=7.3Hz,1H),6.83(s,1H),2.65(dd,J=14.7,7.2Hz,2H), 2.50(s,3H),1.25(t,J=8.0Hz,3H).13C{1H}NMR(101MHz,CDCl3)δ137.19,128.83,128.28, 127.57,127.42,126.15,125.33,97.36,28.74,16.63,15.53.GC-MS(m/z)=304.
k(Z)-(1-iodo-2-(naphthalen-2-yl)vinyl)(methyl)sulfane:
棕黄色油状物,产率85%,53mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.87(s,1H),7.85-7.77(m,2H),7.74(d,J=8.6Hz,1H),7.58(d,J=8.9Hz,1H),7.48(t,J =5.4Hz,2H),7.00(s,1H),2.55(s,3H).13C{1H}NMR(101MHz,CDCl3)δ138.77,137.96,133.10, 132.85,128.14,127.88,127.50,127.23,126.59,126.34,125.39,97.26,16.71.GC-MS(m/z)=326.
l(Z)-(1-iodooct-1-en-1-yl)(methyl)sulfane:
淡黄色油状物,产率41%,53mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ6.32(s,1H),2.36(s,3H),1.63(m,2H),1.24(m,7.2Hz,8H),0.95(t,J=7.4Hz,3H).13C{1H} NMR(101MHz,CDCl3)δ133.09,100.79,31.55,29.62,27.89,22.55,19.19,18.42,14.06.GC-MS (m/z)=284.
m(Z)-(1-iodotetradec-1-en-1-yl)(methyl)sulfane:
橘黄色油状物,产率47%,86mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ6.32(s,1H),2.37(s,3H),2.04(s,2H),1.26(m,20H),0.96(t,J=7.4Hz,3H).13C{1H}NMR (101MHz,CDCl3)δ133.08,103.47,33.91,30.57,29.65,29.62,29.53,29.29,28.22,22.68,18.07, 16.28,14.10,13.70.GC-MS(m/z)=368.
o(Z)-(2-cyclohexyl-1-iodovinyl)(methyl)sulfane:
黄色油状物,产率48%,53mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ6.38(s,1H),2.37(s,3H),1.99–1.93(m,1H),1.87–1.71(m,5H),1.33–1.28(m,5H), 1.21–1.04(m,1H).13C{1H}NMR(101MHz,CDCl3)δ131.46,111.60,50.92,33.76,25.93,16.32. GC-MS(m/z)=282.
q(Z)-2-(2-iodo-2-(methylthio)vinyl)thiophene
橙色油状物,产率49%,55mg,洗脱剂比例:石油醚/乙酸乙酯=100/1。1H NMR(400MHz, CDCl3)δ7.10(s,1H),6.67–6.50(m,2H),6.37(s,1H),2.37(s,3H).13C{1H}NMR(101MHz,CDCl3) δ148.31,137.31,126.81,124.71,117.55,89.70,14.92.GC-MS(m/z)=282.
s(Z)-2-(2-iodo-2-(methylthio)vinyl)pyridine::
黄色油状物,产率35%,48mg,洗脱剂比例:石油醚/乙酸乙酯=5/1。1H NMR(400MHz,CDCl3) δ8.48(s,1H),7.95(s,1H),7.66-7.56(m,2H),7.09(s,1H),2.56(s,3H).13C{1H}NMR(101MHz, CDCl3)δ155.32,148.76,142.85,137.04,122.58,121.85,95.45,16.78.GC-MS(m/z)=277。
Claims (3)
2.根据权利要求1所述的一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法,其特征在于:所述碘可以是单质碘或者碘化钠或者碘化钾,优选的碘化物是单质碘。
3.根据权利要求1所述的一种由烯烃与碘及二甲基亚砜构建碘代烯基硫醚的方法,其特征在于:所述反应条件为:在大气气氛下,于80~150℃温度下,反应2~12h。较优选的条件为:在大气气氛下,于110~130℃温度下,反应3~5h。
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