CN111559971A - Method for constructing iodoalkenyl thioether from olefin, iodine and dimethyl sulfoxide - Google Patents
Method for constructing iodoalkenyl thioether from olefin, iodine and dimethyl sulfoxide 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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- Prior art keywords
- reaction
- iodine
- olefin
- thioether
- yield
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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
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Abstract
The invention discloses a method for constructing iodo-alkenyl thioether from olefin, iodine and dimethyl sulfoxide, which takes the olefin, the iodine and the sulfoxide as raw materials, under the heating condition, the iodine and the sulfoxide simultaneously carry out substitution reaction on the same carbon atom of the olefin, other catalysts or additives are not needed to be added, and an alpha-iodo-alkenyl thioether product is selectively obtained through one-pot reaction; the method has the advantages of mild reaction conditions, simple operation, no need of additional catalyst or additive, good selectivity, high yield and contribution to industrial production.
Description
Technical Field
The invention relates to a method for constructing iodoalkenyl thioether from olefin, iodine and dimethyl sulfoxide, in particular to a method for synthesizing an alpha-iodoalkenyl thioether derivative through a disubstituted reaction of sulfoxide and iodine on an olefin carbon atom, and belongs to the field of organic synthesis.
Background
The halogenated alkenyl sulfide is a compound with important synthetic value, and the molecule of the halogenated alkenyl sulfide contains a plurality of reaction sites, and is often used as a synthetic intermediate to construct biomedical molecules and photochemical material molecules. Halogenated alkenyl sulfides are popular research materials in the fields of organic synthetic Chemistry and organic materials science due to the fact that molecules contain both halogen and sulfanyl groups, and attract the research interests of the scientists (Wang B W, Jiang K, Li J X, et al, 1-halogenated sulfur fibers a Functional AIEigen Derived from the aging-catalyzed molar semiconductor 1, 1-halogenated sulfur through silicon, Ionic chemical Edition 2020,59(6): 2338. 2343; Gu X-X, Xie M-H, ZHalo X-Y, et al, ethylene Synthesis of polymeric compounds 1, 3-En. beta. -alkyl sulfides, Li-alkyl sulfide, J.E.E.S. Pat. No. 5. J.E.S. Pat. No. 5. J.S.S. J. Journal of Organic Chemistry,2013,78(18): 9499-9504; iwasaki M, Fujii T, Nakajima K, et al, Iron-induced regions-and stereoselective addition of sulfenyl chlorides to alkyls by a radial path, Angewandte Chemie International Edition, 2014,53(50): 13880-13884; iwasaki M, Fujii T, Yamamoto A, et al, Palladium-catalyzed region-and specific selectivity of chemical alkyl chlorides, chemistry An Asian Journal,2014,9(1): 58-62). The halogeno-alkenyl sulfide molecule contains halogen group, especially iodine group, and is a good leaving group in chemical reaction. The iodine atom on the double bond carbon is easier to be replaced by other groups compared with other halogen atoms, and various derivative products are obtained. Furthermore, sulfanyl groups in molecules are also an important group, which not only have important significance for biomolecules, but also are easily replaced by other groups in chemical reactions or undergo self-redox transformation (Ettari R, Nizi E, Di France sco M E, et al. development of peptides with a vinyl sulfate sensitive amino-2 inhibitors. Journal of medical Chemistry,2008,51(4): 988. sup. kinetic 996; palm J T, Rasnick D, Klaus J L, V. vinyl sulfates as mechanical-based Chemistry. Journal of medical Chemistry,1995,38(17):3193, 96; Journal of biological Chemistry,1995, 38. sup. 3196; HIV Chemistry, C, Journal of chemical Chemistry,2007, chemical Chemistry, N.2. idea of chemical reactions, III, et al., III, N.7). Therefore, iodoalkenylsulfide and its synthesis method become very important research contents in the field of organic synthesis, and many scientists for organic synthesis and material application have conducted a great deal of research work.
In the past decades, the method of synthesizing such iodoalkenylsulfides has been by addition bifunctional reactions of iodo-thioalkylation of alkynes. There are several groups of problems reported in I2β -iodoalkenylsulfone compounds are synthesized under the condition that KI or CuI provides an iodine source, (Wan J-P, Hu D, Bai F, ethyl. stereoselective Z-halosulfurylation of tertiary alkyl ketones using sulfonic acid amides and CuX (X ═ Cl, Br, I), RSC Advances,2016,6(77): 73132, 73135; Yang L, Hu D, Wei L, et al]thiophene-1,1-dioxides and (E)-b-iodo Vinylsulfones.Advanced Synthesis&Catalysis,2018,361(3), 597-602). The reaction is shown in the following formula 1.
Reaction formula 1 reaction of alkyne and alkyl sulfonyl hydrazide to synthesize beta-iodoalkenyl sulfone
In addition, Jiang group and Sun, Liu et al also reported reactions based on alkynes with sodium alkylsulfonates (GaoY, Wu W, Huang Y, et al. NBS-catalyzed halosulfonation of tertiary alkyls: highly fresh region-and stereoselective synthesis of (E) - β -halo vinylic sulfonates organic Chemical front, 2014,1(4): 361-364); sun Y, Abdukader A, Lu D, et al.Synthesis of (E) - β -iodovinylsulfones via iodine-catalyzed iodosulfonations of alkyl with sodium sulfides. Greenchemistry,2017,19(5):1255-1258) in the synthesis of such β -iodoalkenylsulfones, as shown in equation 2.
Reaction formula 2 reaction of alkyne and sodium alkylsulfonate to synthesize beta-iodoalkenyl sulfone
Pan and Liu et al use a hot synthon, dimethyl sulfoxide (DMSO), to provide a sulfur source with H2O forms a mixed solvent with alkyne and elementary iodine I2The reaction also yielded β -iodoalkenylsulfone (Zhou P, Pan Y, Tan H, et al.I.)2-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)。
Reaction formula 3 alkyne and DMSO, H2Synthesis of β -iodoalkenylsulfone by O reaction furthermore, a method of using ketones with alkyl sulfonyl hydrazides, I2Reaction, preparation of β -iodoalkenylsulfide by deoxidation (Bao Y, Yang X, Zhou Q, et al, iodine-catalyzed deoxidation/ionization/sulfenamation of Ketone with sulfo Hydrazides: Access to beta-Iodoalkylsulfides. organic Letters,2018,20(7): 1966-1969.) the product has an iodine atom and a sulfur atom located on two carbon atoms of the double bond.
Reaction formula 4 ketone and sulfonyl hydrazide reaction to synthesize beta-iodoalkenyl thioether
Alpha-iodoalkenylsulfur compounds are more susceptible to substitution than beta-iodoalkenylsulfur compounds in which iodine and sulfur atoms are located on two carbon atoms, respectively, and are therefore iodoalkenylsulfur compounds with better reactivity and biological properties. In 2001, Jin et al reported a method for preparing α -iodoalkenylsulfide by addition reaction of alkynylthio ether as a substrate with iodotrimethylsilane TMS-I (Bao Y, Yang X, Zhou Q, et al, Iodine-protein deoxygenization/ionization of olefins with sulfonic hydryls: Access to Iodoalkyl sulfides. organic Letters,2018,20(7): 1966-1969). In the method, a substrate alkynyl thioether needs to be prepared in advance by the reaction of alkyne and thioalkane, and then reacts with TMS-I, and a final product, namely the a-iodoalkenylthioether is obtained by a two-step reaction, which is shown in the following reaction formula 5.
Reaction formula 5 synthesis of alpha-iodoalkenylsulfide by multi-step reaction of alkyne, thioalkane and iodotrimethylsilane 2006, Cai et al reported a method for multi-step synthesis of alpha-iodoalkenylsulfide. The method comprises the steps of firstly reacting terminal alkyne with Grignard reagent to obtain alkynyl magnesium bromide intermediate, and then coupling with one molecule of chlorosulfane to obtain alkynyl thioether intermediate (ZhaoQ, Liu S, Li Y, et al design, synthesis, and biological activities of novel 2-cyanoacyl ligands oxidizing, or quinoline moities. journal of agricultural and Food Chemistry,2009,57(7): 2849-2855). And finally, reacting the obtained alkynyl thioether with TMS-I to obtain a target product, namely the alpha-iodoalkenyl thioether, as shown in a reaction formula 6.
Reaction formula 6 alkyne, chloro-sulfur alkane and iodo-trimethyl silane multistep reaction to synthesize alpha-iodo-alkenyl thioether
In 2008, Guerrero et al reacted diisobutylaluminum reagent with previously prepared alkynyl sulfide to obtain a metal alkenyl sulfide intermediate (Yang W S, Shimada K, Delva D, et al. identification of simple Compounds with Microtile-Binding Activity at least in High efficiency Cancer cell with High potential. ACS medical Chemical Letters,2012,3(1): 35-38). Subsequently, the intermediate can remove the metal group under the condition of elementary iodine to obtain the α -iodoalkenylsulfide product, and the reaction is shown as reaction formula 7.
Reaction formula 7 alkynyl thioether, diisobutylaluminum and iodine multistep reaction to synthesize alpha-iodoalkenylthioether
In 2006, Cai et al reported a method for synthesizing α -iodoalkenylsulfide compounds by iododetinning reaction of elemental iodine with stannane-substituted alkenylsulfide compounds as substrates (Turchi I J, Dewar M JS. chemistry of oxo. chemical Reviews,1975,75(4):389-437), as shown in equation 8. Also in this process, the starting stannane-substituted alkenyl sulfide needs to be prepared in advance.
Reaction formula 8 stannane substituted alkenyl thioether and iodine react to synthesize alpha-iodoalkenyl thioether
As can be seen from the above summary of synthetic methods, although a series of α -iodoalkenylthioethers as the target compounds can be synthesized by the existing methods, these reactions still have problems, particularly, the reactions require a special synthetic reagent which is difficult to synthesize, such as a substituted alkynyl thioether compound or a metal alkenyl compound, as a raw material, and these special reagents need to be prepared in advance. Therefore, from the reaction steps, the synthesis of the alpha-iodoalkenylsulfide can obtain the product only by two or more steps, and cannot be synthesized by a one-step or one-pot method.
Disclosure of Invention
Aiming at the defects that the existing alpha-iodoalkenylsulfur compound synthesis method needs two-step or even multi-step reaction, needs metal organic compounds to participate, has high requirements on reaction conditions and the like, the invention aims to provide a method for synthesizing (Z) -alpha-iodoalkenylsulfide in one step only by using easily available raw materials such as terminal olefin, sulfoxide, iodine and the like without using metal organic matters.
Reaction of formula 9 olefin with sulfoxide, I2Reaction for synthesizing (Z) - α -iodoalkenyl thioether
The method is that terminal group olefin C ═ C double bond simultaneously reacts with iodine and sulfoxide to generate double substitution reaction on terminal group carbon atom, no other catalyst or additive is added in the reaction, and a (Z) -alpha-iodoalkenyl thioether product is selectively obtained by one-pot reaction only under heating condition; the method has the advantages of mild reaction conditions, simple operation, no need of additional catalyst or additive, good selectivity, high yield and contribution to industrial production.
The (Z) -alpha-iodoalkenylthioether derivative has a structure shown in a formula 1:
the terminal olefin structure has the structure of formula 2:
the sulfoxide has the structure of formula 3:
wherein the content of the first and second substances,
R1alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, and dodecyl, substituted alkyl groups thereof, or phenyl groups and substituted derivatives thereof.
R2Methyl, ethyl, propyl, butyl and benzyl.
The iodine is elementary iodine or iodine salt such as sodium iodide, potassium iodide and the like.
In the terminal olefin of the invention, R1When aryl, it includes a simple aromatic ring group or a substituted aromatic group. The number of the substituent groups contained in the substituted aryl group is 1-2, and the substituent groups are selected from at least one of halogen substituent groups, alkyl groups, hydroxyl groups, amino groups and carboxyl groups. Halogen substituents such as fluorine, chlorine, bromine, iodine, and the like. Alkyl is C1～C10Alkyl groups of (a); more preferably C1～C5The lower alkyl group of (2) such as methyl, ethyl, propyl, etc., may also be a branched alkyl group such as isopropyl, isobutyl, etc.
In the terminal olefin of the invention, R1When alkyl, simple alkyl and substituted alkyl groups are included. R1When the substituent is selected from substituted alkyl, the substituent comprises at least one of halogen, hydroxyl, amino, cyano, ester group, nitro and hydroxyl.
In a preferred embodiment, the ratio of iodine to terminal olefin is 0.5 to 3: 1. More preferably 0.8 to 1.2: 1.
Preferably, the ratio of the sulfoxide to the terminal olefin is 3-10: 1. More preferably 5 to 6: 1.
The sulfoxide serves mainly as a benign solvent on the one hand and as a reaction substrate on the other hand, the sulfoxide provides an alkylthio group as the sulfur-containing group in the product.
In a preferred embodiment, the reaction conditions are as follows: reacting for 2-12 h at 80-150 ℃ in the atmosphere. More preferred conditions are: reacting for 3-5 h at 110-130 ℃ in the atmosphere.
The reaction mechanism is explained by synthesizing (Z) -alpha-iodostyryl methyl sulfide (a) through the reaction of styrene, dimethyl sulfoxide and elemental iodine. Through consulting and referring to relevant documents, a series of mechanism research experiments are designed. First, a series of radical inhibition experiments were performed using styrene as a substrate under standard conditions, and the results are shown in formula 1:
reaction inhibition experiment of formula 1
The reaction was tested by adding a gradient of equivalents of inhibitor using two free radical inhibitors TEMPO and BHT, respectively, α -iodoalkenylmethyl sulfide yield decreased from before at 0.5 equivalents of inhibitor and α -iodoalkenylmethyl sulfide yield decreased significantly at 1.0 equivalents when we added 2.0 equivalents of inhibitor, the results of both sets of experiments showed that the product α -iodoalkenylmethyl sulfide had become very poor, see formula 1 (1). from two sets of free radical inhibition experiments, it was speculated that the double substitution reaction of the olefin may have undergone a history of free radicals, if 2.0equiv BHT was added under standard conditions and the reaction was monitored by GC-MS, the product α -iodoalkenylmethyl sulfide was essentially undetectable and the free radical product BHT-SCH could be detected3See formula 1(2) additionally, the reaction was monitored under standard reaction conditions at various reaction times, and the results showed that intermediate β -iodostyrene could be detected in the reaction, see formula 1 (3).
Based on the results of the above control experiments and literature reports, we propose a reasonable path for the reaction mechanism of the reaction, as shown in formula 2. First, dimethylsulfoxide (sulfoxide) is slowly broken under heating to generate one molecule of methyl mercaptan and one molecule of formaldehyde. At the same time, I2Homolytic cleavage under heating produces monoiodo radicals (I.cndot.). The monoiodo radical interacts with methyl mercaptan and undergoes radical transfer to produce methyl sulfur radical (CH)3S.) and hydrogen iodide HI. in another aspect, a terminal olefin is reacted with elemental iodine to provide a β -iodoolefin intermediate via β -iodination substitution, whereupon a methyl sulfide radical (CH)3S.) attacks β -iodoolefin intermediate to obtain a free radical addition intermediate, and finally, the intermediate is subjected to the action of iodine to obtain a final product with double bonds preserved.
Reaction mechanism of formula 2
Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:
1) the raw materials adopted by the method for constructing the iodoalkenyl thioether from the olefin, the iodine and the dimethyl sulfoxide are terminal group olefin, sulfoxide and iodine, are common chemical raw materials, have low cost and wide raw material sources, and are beneficial to industrial production.
2) The method for constructing the iodoalkenyl thioether from the olefin, the iodine and the dimethyl sulfoxide provided by the invention does not need to use a catalyst, and the iodoalkenyl thioether can react in one pot in the atmosphere to form a product, so that the process is simple and convenient for industrial application.
3) The method for constructing iodoalkenyl thioether from olefin, iodine and dimethyl sulfoxide provided by the invention adopts a one-pot reaction, has mild reaction conditions and simple operation, and meets the requirements of industrial production.
4) The method for constructing the iodoalkenyl thioether from the olefin, the iodine and the dimethyl sulfoxide has wide application range to substrate raw materials, and can construct alpha-iodoalkenyl thioether with various substituent groups.
Detailed Description
The following examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.
All reactions were performed in Schlenk tubes unless otherwise noted.
All reaction starting solvents were obtained from commercial sources and used without further purification.
The product is separated by silica gel chromatographic column and silica gel (granularity is 300-400 meshes).
1H NMR (400MHz), 13C NMR (100MHz) and 19F NMR (376MHz) measurements were performed using a Bruker ADVANCEEIII spectrometer with CDCl3As solvent, TMS as internal standard, chemical shifts in parts per million (ppm) and reference shifts of 0.0ppm tetramethylsilane. The following abbreviations (or combinations thereof) are used to explain the multiplicity:s is singlet, d is doublet, t is triplet, q is quartet, m is multiplet, br is broad. Coupling constant J is in Hertz (Hz). Chemical shifts are expressed in ppm, with the center line for the triplet state referenced to deuterated chloroform at 77.0ppm or the center line for the heptad state referenced to deuterated DMSO at 39.52 ppm.
The GC-MS adopts a GC-MS QP2010 device for detection, the HRMS adopts an Electron Ionization (EI) method for measurement, the type of the mass analyzer is TOF, and the EI is detected by an Esquire 3000plus instrument.
1. Condition optimization experiment:
for example, the synthesis of (Z) - (1-iodo-2-styrene) (methyl) sulfide (a) from styrene, dimethyl sulfoxide and iodine is carried out by selecting the type and amount of the iodine reagent used in the reaction, the reaction additive, the reaction time and temperature, and the like, and searching for the optimum reaction conditions.
Reaction formula 9 styrene with DMSO, I2Reaction for synthesizing (Z) - (1-iodo-2-styrene) (methyl) thioether
1.1 selection of the type and amount of iodine reagent
Firstly, the type and the amount of the iodine reagent used in the reaction are screened and optimized. To I2KI and NaI were screened and the results are shown in Table 1 below. 1.0 equivalent (0.5mmol) of I was added2The reaction of (2) finally gave a in 81% yield, but the effect of replacing KI or NaI was far less than that of I2. Therefore, the simplest elemental iodine I is finally selected2As an iodine reagent. Subsequently, I is examined2The amount of the catalyst used. When 0.5 equivalent (0.25 mmol) of I is added in accordance with the reaction stoichiometry2The yield of a was only 57%, and when added to 0.8 eq (0.4mmol), the yield of a increased. When using 1.2 equivalents (0.6mmol, 150mg) of I2The highest yield of 86% was obtained. However, when the amount of the catalyst used is increased, other polyiodinated by-products appear, and the influence on the yield of a is obvious. The final selection used 1.2 equivalents (0.6mmol, 150mg) of I2。
TABLE 1 screening of the type and amount of iodine reagent
1.2 screening of reaction additives
Under the above optimum conditions a was obtained in 86% yield, and then an attempt was made to continue to add certain additives to promote an increase in reaction yield. A variety of common small molecule compounds were selected and added to the original reaction system, and the results were monitored by GC-MS, as shown in Table 2. First, an alkaline substance, Na, was tried to be added2CO3NaOH and DBU, but it was found that alkaline conditions greatly affected the target reaction, greatly reducing the yield of the reaction. Then, the addition of acidic substance H was attempted3PO4And HCl (0.1M), the acid was also found to have a negative effect on the reaction. Subsequently, some oxidizing agent is added, desirably to promote the reaction. Addition of H2O2TBHP and K2S2O8Very influential on the reaction, PhI (OAc)2Nor was there any significant effect. According to the analysis of a series of experimental results, no additive is finally added.
TABLE 2 screening of reaction additives
1.3 screening of reaction temperature and time
The reaction temperature and time are important factors affecting the reaction yield, and the effect of the gradient temperature and different times on the reaction was further studied, and the results are shown in table 3 below. We know that this reaction gives a in the best 86% yield after 4h at 120 ℃. Further temperature increases have a slight effect on the reaction, and temperature decreases have a significant effect on the reaction. When the temperature is lower than 80 ℃, the reaction yield becomes poor. We continued to investigate the reaction time factor at 120 ℃ and the yield increased continuously from 2 to 3h but did not increase after 6h or 12h overnight. Therefore, we finally chose to react for 4h with heating in an oil bath at 120 ℃.
TABLE 3 screening of reaction temperature and time
1.4 Standard reaction procedure
The standard reaction procedure obtained after the above optimization is as follows: 4ml DMSO was added to a 25ml Schlenk tube, and 0.5mmol terminal olefin, 0.6mmol (about 150mg) elemental iodine I were weighed2. After being mixed evenly, the reaction tube is sealed by a sealing plug and then put into a 120 ℃ oil bath pot for magnetic stirring, heating and stirring. After 4 hours of reaction, heating was stopped, and after the reaction tube was cooled, about 5ml of ethyl acetate was added, and the mixture was transferred to a separatory funnel. Adding 10ml of saturated saline water and a proper amount of sodium thiosulfate Na2S2O3. Shaking the separating funnel, extracting the reaction solution, taking the upper organic layer, draining the lower aqueous layer, and repeating twice. The organic layer was transferred to a beaker and anhydrous Na was added2SO4Drying, and finally spin-drying the solvent in vacuum. And (3) separating the dried sample by silica gel column chromatography, taking petroleum ether/ethyl acetate as an eluent to finally obtain a product, and carrying out characterization such as NMR, MS and the like by vacuum drying.
2. Reaction substrate development
2.1 substrate expansion of simple substituted styrene derivatives
The applicability of the substituted styrene derivatives under standard reaction conditions was examined and the results are shown in table 4 below. The product a corresponding to styrene can finally be isolated in 83% yield. The solvent reactant dimethyl sulfoxide is replaced by deuterated dimethyl sulfoxide (DMSO-d6), and finally the corresponding deuterated product d can be successfully obtained3A, yield 70%. When the para-position of the styrene is substituted by-Me or-tBu, the yield of the corresponding products b and c can also reach more than 82 percent. The yield of the product was also 81% when the para position contained a-F substitution. We continued to examine the reaction conditions in which the benzene ring of styrene still has a substitution at different positions-Cl,the results show that the substrate containing Cl substitution at three different positions corresponds to yields of 86%, 78% and 74%, respectively. When we replaced styrene with 2-vinylnaphthalene, the corresponding product h could also be isolated in 71% yield.
TABLE 4 study of the suitability of substrates of substituted styrene derivatives
Reaction conditions are as follows: substituted styrene (0.5mmol), I2(1.2equiv,0.6mmol), DMSO (3ml), was heated in a pressure tube at 120 ℃ for 4 h. The yield is an isolated yield.
2.2 substrate extension of aliphatic and heteroaromatic olefins
The simple substrate applicability research of the substituted styrene derivative shows that the method has good effect on aromatic terminal group olefin and good applicability on different substituent groups. Subsequently, the investigation was continued for other terminal olefins. First, we carried out reaction studies on aliphatic olefins. 1-octene gives the corresponding product i in 41% yield under the reaction conditions, and another linear olefin tetradecene is converted under the conditions to the corresponding product j, 3-Br propene, under the same conditions the target product k is also detectable. The corresponding iodoalkenylsulfide product l is also obtained in a moderate yield of 48% in the aliphatic cycloalkene, cyclohexylethylene. The heterocyclic olefins were subsequently investigated. 2-vinylfuran and 2-vinylthiophene can be converted to give the corresponding substrates m and n. Substrates containing pyridine rings, 2-vinylpyridine and 4-vinylpyridine, also give the final products o and p, but the yields of the corresponding products are low.
TABLE 5 suitability study of aliphatic and heterocyclic olefinic substrates
Reaction conditions are as follows: olefin (0.5mmol), I2(1.2equiv,0.6mmol), DMSO (3ml), was heated in a pressure tube at 120 ℃ for 4h, the yield being the isolated yield.
2.3 study of the suitability of sulfoxide substrates
The sulfoxide of the invention is applicable to sulfoxide containing ethyl, propyl, butyl, pentyl and benzyl except dimethyl sulfoxide containing methyl, but the yield of the product obtained by the dimethyl sulfoxide is highest (see table 6).
TABLE 6 study of the suitability of sulfoxide substrates
Structural characterization of a moiety of alpha-iodoalkenylsulfide
a(Z)-(1-iodo-2-phenylvinyl)(methyl)sulfane:
Yellow oil, yield 83%, 114.5mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.41(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)141.61,137.50,128.31,127.92,127.85,97.01,16.64. GC-MS(m/z)＝276
d3-a(Z)-(1-iodo-2-phenylvinyl)(methyl-d3)sulfane:
Yellow oil, yield 70%, 97.6mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.45–7.43(m,3H),7.25–7.22(m,2H),6.85(s,1H).13C{1H}NMR(101MHz,CDCl3)141.66,137.48,128.32,127.87,125.67,96.99.GC-MS(m/z)＝279.
b(Z)-(1-iodo-2-(p-tolyl)vinyl)(methyl)sulfane:
Bright yellow oil, yield 82%, 119mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.33(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)138.99,137.91,136.51,128.97,127.73,97.31,21.02,16.62. GC-MS(m/z)＝290
c(Z)-(2-(4-(tert-butyl)phenyl)-1-iodovinyl)(methyl)sulfane:
Dark yellow oil, yield 85%, 141mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.37(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)151.09,138.86,136.63,127.52,125.24,97.24,34.51,31.22, 16.61.GC-MS(m/z)＝332.
d(Z)-(2-(4-fluorophenyl)-1-iodovinyl)(methyl)sulfane:
Pale yellow oil, yield 81%, 119mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1HNMR(400 MHz,CDCl3)7.44-7.30(m,2H),6.98(t,J＝8.5Hz,2H),6.77(s,1H),2.50(s,3H).13C{1H}NMR (101MHz,CDCl3)162.35(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:
Pale yellow oil, yield 86%, 133mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.36(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)140.13,138.33,133.75,129.01,128.40,95.07,16.65.GC-MS(m/z)＝310. f(Z)-(2-(3-chlorophenyl)-1-iodovinyl)(methyl)sulfane:
Pale yellow oil, yield 78%, 121mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H).13C{1H}NMR(101MHz, CDCl3)143.23,139.18,134.17,129.49,127.82,127.73,126.20,94.40,16.67.GC-MS(m/z)＝ 310.
g(Z)-(2-(2-chlorophenyl)-1-iodovinyl)(methyl)sulfane:
Yellow oil, yield 74%, 115mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.42(s,1H),7.31(m,1H),7.21(m,2H),6.92(s,1H),2.52(s,3H).13C{1H}NMR(101MHz, CDCl3)143.23,139.18,134.17,129.49,127.82,127.73,126.20,94.40,16.67.GC-MS(m/z)＝ 310.
h(Z)-(2-(4-bromophenyl)-1-iodovinyl)(methyl)sulfane:
Bright yellow oil, yield 75%, 133mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.41(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)140.56,138.42,131.35,129.30,121.89,95.08,16.66.GC-MS(m/z)＝356.
i(Z)-(2-(3-bromophenyl)-1-iodovinyl)(methyl)sulfane:
Yellow oil, yield 70%, 125mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.57(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)143.49,139.25,130.74(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:
Yellow oil, yield 57%, 86mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.30–7.16(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)137.19,128.83,128.28, 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:
Brown yellow oil, yield 85%, 53mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.87(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)138.77,137.96,133.10, 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:
Pale yellow oil, yield 41%, 53mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)6.32(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)133.09,100.79,31.55,29.62,27.89,22.55,19.19,18.42,14.06.GC-MS (m/z)＝284.
m(Z)-(1-iodotetradec-1-en-1-yl)(methyl)sulfane:
Orange oil, yield 47%, 86mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)6.32(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)133.08,103.47,33.91,30.57,29.65,29.62,29.53,29.29,28.22,22.68,18.07, 16.28,14.10,13.70.GC-MS(m/z)＝368.
o(Z)-(2-cyclohexyl-1-iodovinyl)(methyl)sulfane:
Yellow oil, yield 48%, 53mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)6.38(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)131.46,111.60,50.92,33.76,25.93,16.32. GC-MS(m/z)＝282.
q(Z)-2-(2-iodo-2-(methylthio)vinyl)thiophene
Orange oil, yield 49%, 55mg, eluent ratio: petroleum ether/ethyl acetate 100/1.1H NMR(400MHz, CDCl3)7.10(s,1H),6.67–6.50(m,2H),6.37(s,1H),2.37(s,3H).13C{1H}NMR(101MHz,CDCl3) 148.31,137.31,126.81,124.71,117.55,89.70,14.92.GC-MS(m/z)＝282.
s(Z)-2-(2-iodo-2-(methylthio)vinyl)pyridine::
Yellow oil, yield 35%, 48mg, eluent ratio: petroleum ether/ethyl acetate 5/1.1H NMR(400MHz,CDCl3) 8.48(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)155.32,148.76,142.85,137.04,122.58,121.85,95.45,16.78.GC-MS(m/z)＝277。
Claims (3)
1. A method for constructing iodoalkenyl thioether from olefin, iodine and dimethyl sulfoxide is characterized in that: olefin and iodine are stirred and heated to react in a sulfoxide solution system in an atmosphere by one pot to obtain a stereospecific (Z) -alpha-iodoalkenyl thioether derivative;
the (Z) alpha-iodoalkenylthioether derivative has a structure of formula 1:
the olefin structure has the structure of formula 2:
the sulfoxide has the structure of formula 3:
wherein the content of the first and second substances,
R1alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclohexyl and dodecyl, or bromine-substituted alkyl groups thereof; or phenyl and substituted benzene, wherein the substituent is as follows: methyl, ethyl, isopropyl, halogen; the position of the substituent can be ortho, para and meta of the benzene ring;
R2methyl, ethyl, propyl, butyl, pentyl and benzyl.
2. The method of claim 1, wherein the method comprises the steps of: the iodine may be elemental iodine or sodium or potassium iodide, with the preferred iodide being elemental iodine.
3. The method of claim 1, wherein the method comprises the steps of: the reaction conditions are as follows: reacting for 2-12 h at 80-150 ℃ in the atmosphere. More preferred conditions are: reacting for 3-5 h at 110-130 ℃ in the atmosphere.
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| CN113045463A (en) * | 2021-03-26 | 2021-06-29 | 湖南科技学院 | Synthesis method of (E) -3-arylthio-2-iodoethyl acrylate compound |
| CN113072472A (en) * | 2021-04-07 | 2021-07-06 | 湖南科技学院 | Synthesis method of 2-methylmercapto-maleic diester compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104710332A (en) * | 2015-02-17 | 2015-06-17 | 温州大学 | Method for preparing alkenyl sulfide |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (4)
| Title |
|---|
| MASANORI WATANABE 等: "Reaction of magnesium alkylidene carbenoids with lithium acetylides and lithium thiolates: a novel synthesis of conjugated enynes and vinyl sulfides", TETRAHEDRON, vol. 61, pages 4409 - 4418 * |
| PENG ZHOU 等: "I2-DMSO-H2O: A Metal-Free Combination System for the Oxidative Addition of Alkynes to Access (E) -alpha - Iodo - beta - methylsulfonylalkenes", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 84, no. 23, pages 15662 - 15668 * |
| 曹重仲: "碘促进的烯烃C=C上的取代和氧化环加成反应", 湖南大学博士学位论文, pages 1 - 276 * |
| 武侠: "基于I2/DMSO 体系实现选择性氧化Ｃ-Ｈ 键构筑多羰基化合物及杂环结构体", 华中师范大学博士学位论文, pages 1 - 443 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113045463A (en) * | 2021-03-26 | 2021-06-29 | 湖南科技学院 | Synthesis method of (E) -3-arylthio-2-iodoethyl acrylate compound |
| CN113045463B (en) * | 2021-03-26 | 2023-02-03 | 湖南科技学院 | Synthesis method of (E) -3-arylthio-2-iodoethyl acrylate compound |
| CN113072472A (en) * | 2021-04-07 | 2021-07-06 | 湖南科技学院 | Synthesis method of 2-methylmercapto-maleic diester compound |
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