CN106167459B - A method of synthesis alkenyl thiocyanates derivative - Google Patents
A method of synthesis alkenyl thiocyanates derivative Download PDFInfo
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- CN106167459B CN106167459B CN201610579617.2A CN201610579617A CN106167459B CN 106167459 B CN106167459 B CN 106167459B CN 201610579617 A CN201610579617 A CN 201610579617A CN 106167459 B CN106167459 B CN 106167459B
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- bromine
- silver
- ethyl acetate
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- -1 alkenyl thiocyanates Chemical class 0.000 title claims abstract description 59
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 77
- 239000002904 solvent Substances 0.000 claims abstract description 56
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 337
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 116
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 112
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 111
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 76
- 239000003208 petroleum Substances 0.000 claims description 58
- 238000004440 column chromatography Methods 0.000 claims description 56
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 56
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 56
- 229960000583 acetic acid Drugs 0.000 claims description 55
- 238000001914 filtration Methods 0.000 claims description 55
- 239000012046 mixed solvent Substances 0.000 claims description 55
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 54
- 239000012362 glacial acetic acid Substances 0.000 claims description 54
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical group [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 54
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 53
- 229910052794 bromium Inorganic materials 0.000 claims description 53
- 238000010438 heat treatment Methods 0.000 claims description 44
- 239000003480 eluent Substances 0.000 claims description 38
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 38
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 38
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 32
- 229940071536 silver acetate Drugs 0.000 claims description 32
- 150000001345 alkine derivatives Chemical class 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001246 bromo group Chemical class Br* 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- VGFXMTYQWCLOAF-UHFFFAOYSA-N [Br].C#CCCCCC Chemical class [Br].C#CCCCCC VGFXMTYQWCLOAF-UHFFFAOYSA-N 0.000 claims description 3
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 claims description 3
- QEPPHIJQCNEGDG-UHFFFAOYSA-N bromine;ethynylbenzene Chemical compound [Br].C#CC1=CC=CC=C1 QEPPHIJQCNEGDG-UHFFFAOYSA-N 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- FPPKJUCLFSOWGJ-UHFFFAOYSA-N [Br].C#CCCCCCC Chemical class [Br].C#CCCCCCC FPPKJUCLFSOWGJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- SDLBJIZEEMKQKY-UHFFFAOYSA-M silver chlorate Chemical compound [Ag+].[O-]Cl(=O)=O SDLBJIZEEMKQKY-UHFFFAOYSA-M 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- OQMDOZHMBLTXQR-UHFFFAOYSA-N [Br].C(CCCCCC)C#C Chemical class [Br].C(CCCCCC)C#C OQMDOZHMBLTXQR-UHFFFAOYSA-N 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 150000002730 mercury Chemical class 0.000 abstract description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000006365 thiocyanation reaction Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 80
- 238000007445 Chromatographic isolation Methods 0.000 description 53
- 239000007864 aqueous solution Substances 0.000 description 53
- 238000011097 chromatography purification Methods 0.000 description 53
- 238000010992 reflux Methods 0.000 description 53
- 238000003756 stirring Methods 0.000 description 53
- 238000001035 drying Methods 0.000 description 51
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 25
- 229910052709 silver Inorganic materials 0.000 description 25
- 239000004332 silver Substances 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 230000006837 decompression Effects 0.000 description 20
- 239000005864 Sulphur Substances 0.000 description 18
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 17
- 238000010828 elution Methods 0.000 description 17
- 239000007788 liquid Substances 0.000 description 17
- 239000011777 magnesium Substances 0.000 description 17
- 229910052749 magnesium Inorganic materials 0.000 description 17
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical class C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 16
- 239000000052 vinegar Substances 0.000 description 16
- 235000021419 vinegar Nutrition 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- ZBFUSCQTNRGAFV-UHFFFAOYSA-N [Br].C#C.ClC1=CC=CC=C1 Chemical class [Br].C#C.ClC1=CC=CC=C1 ZBFUSCQTNRGAFV-UHFFFAOYSA-N 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241001597008 Nomeidae Species 0.000 description 3
- JCIUDSYSSHATDL-UHFFFAOYSA-N [Br].C#C Chemical compound [Br].C#C JCIUDSYSSHATDL-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 description 2
- CHMIJPWCUHAEOF-UHFFFAOYSA-N C#C.C(CC)C1=CC=CC=C1.[Br] Chemical class C#C.C(CC)C1=CC=CC=C1.[Br] CHMIJPWCUHAEOF-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WPIXUAQTSAWDJO-UHFFFAOYSA-N [Br].C#C.FC=1C=CC=CC1 Chemical class [Br].C#C.FC=1C=CC=CC1 WPIXUAQTSAWDJO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 150000003567 thiocyanates Chemical class 0.000 description 2
- 0 *C(CCCCl)=CBr Chemical compound *C(CCCCl)=CBr 0.000 description 1
- ZNTJVJSUNSUMPP-UHFFFAOYSA-N 1-ethyl-4-ethynylbenzene Chemical class CCC1=CC=C(C#C)C=C1 ZNTJVJSUNSUMPP-UHFFFAOYSA-N 0.000 description 1
- OTDGZDMGSFBZLI-UHFFFAOYSA-N 1-ethynyl-3,5-difluorobenzene Chemical class FC1=CC(F)=CC(C#C)=C1 OTDGZDMGSFBZLI-UHFFFAOYSA-N 0.000 description 1
- ZASXCTCNZKFDTP-UHFFFAOYSA-N 1-ethynyl-3-methoxybenzene Chemical class COC1=CC=CC(C#C)=C1 ZASXCTCNZKFDTP-UHFFFAOYSA-N 0.000 description 1
- RENYIDZOAFFNHC-UHFFFAOYSA-N 1-ethynyl-3-methylbenzene Chemical class CC1=CC=CC(C#C)=C1 RENYIDZOAFFNHC-UHFFFAOYSA-N 0.000 description 1
- XTKBMZQCDBHHKY-UHFFFAOYSA-N 1-ethynyl-4-(trifluoromethyl)benzene Chemical class FC(F)(F)C1=CC=C(C#C)C=C1 XTKBMZQCDBHHKY-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical class COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- KSZVOXHGCKKOLL-UHFFFAOYSA-N 4-Ethynyltoluene Chemical class CC1=CC=C(C#C)C=C1 KSZVOXHGCKKOLL-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- NMOJAXCSURVGEY-UHFFFAOYSA-N N#CC#N.[S] Chemical compound N#CC#N.[S] NMOJAXCSURVGEY-UHFFFAOYSA-N 0.000 description 1
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical group NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- WDQPRBKCNORRAR-UHFFFAOYSA-N [Ag].CS(=O)(=O)O.[F] Chemical compound [Ag].CS(=O)(=O)O.[F] WDQPRBKCNORRAR-UHFFFAOYSA-N 0.000 description 1
- ZATMOHHDUZPZAW-UHFFFAOYSA-N [Br].C#CCCCC#C Chemical compound [Br].C#CCCCC#C ZATMOHHDUZPZAW-UHFFFAOYSA-N 0.000 description 1
- MKUWFZFFZHKSOV-UHFFFAOYSA-N [Br].C(C)C1=CC=C(C=C1)C#C Chemical class [Br].C(C)C1=CC=C(C=C1)C#C MKUWFZFFZHKSOV-UHFFFAOYSA-N 0.000 description 1
- QMHHGJVGLPZQDG-UHFFFAOYSA-N [Br].C1(=CC=CC=C1)CCCC#C Chemical class [Br].C1(=CC=CC=C1)CCCC#C QMHHGJVGLPZQDG-UHFFFAOYSA-N 0.000 description 1
- MRDBCCVIYJCLLR-UHFFFAOYSA-N [Br].COC1=CC=C(C=C1)C#C Chemical class [Br].COC1=CC=C(C=C1)C#C MRDBCCVIYJCLLR-UHFFFAOYSA-N 0.000 description 1
- XBFYCSZJQKSNES-UHFFFAOYSA-N [Br].COC=1C=C(C=CC1)C#C Chemical class [Br].COC=1C=C(C=CC1)C#C XBFYCSZJQKSNES-UHFFFAOYSA-N 0.000 description 1
- QFHQLQYFHZSOBY-UHFFFAOYSA-N [Br].FC(C1=CC=C(C=C1)C#C)(F)F Chemical class [Br].FC(C1=CC=C(C=C1)C#C)(F)F QFHQLQYFHZSOBY-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical class BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- OSSQSXOTMIGBCF-UHFFFAOYSA-N non-1-yne Chemical class CCCCCCCC#C OSSQSXOTMIGBCF-UHFFFAOYSA-N 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/04—Thiocyanates having sulfur atoms of thiocyanate groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/10—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to medication chemistry synthesis technical fields, disclose a kind of method of synthesis alkenyl thiocyanates derivative.This approach includes the following steps：In the reaction vessel, alkynes halogen, rhodanate is added as raw material, reaction is heated under conditions of silver salt is catalyst, organic solvent is solvent, gained reaction solution is cooled to room temperature then purifies to get the alkenyl thiocyanates derivative after reaction；The present invention is using alkynes halogen, rhodanate as raw material, and under the catalysis of silver salt, thiocyanation reaction, one-step synthesis alkenyl thiocyanates derivative occurs.Avoid the use of the dangerous material such as the concentrated sulfuric acid, mercury salt.Reaction raw materials are simple and easy to get, and operation is safe and simple, and reaction process is environmental-friendly, substrate applicability is wide, and functional group compatibility is strong, and separation yield is higher, selecting property of product configuration is good, can be amplified to gram-grade scale, and the halogen that product retains conveniently can be converted further.
Description
Technical field
The invention belongs to medication chemistry synthesis technical fields, more particularly to a kind of to synthesize the new of alkenyl thiocyanates derivative
Method.
Background technology
The compound of thiocyanate ester has very extensive biological medicine activity, is many bioactive molecules and natural
The important structural unit of product.And some researches show that thiocyanate ester compounds to show superior answer in terms of electrochemical reduction
Use potential.In addition to this, thiocyanate ester compound is important synthetic intermediate, can be transformed into sulfonic acid, and sulfonic acid chloride is thio
Carbamate, mercaptan, the compounds such as sulphonyl nitrile.For this purpose, researcher has carried out a large amount of research to this kind of compound, hair
Now many sulfocyanic ester compounds have strong inhibiting effect to parasite, bacterium and virus etc..Although such compound tool
There is so important application, but regrettably the synthetic method of thiocyanate ester compound is seldom, builds alkenyl thiocyanic acid
The method of ester type compound is with regard to less.
The prior synthesizing method of structure alkenyl thiocyanates derivative will generally use the dangerous material such as the concentrated sulfuric acid, mercury salt
(Giffard M,Cousseau J,Chemical Communications,1979(22):1026-1027； Giffard M,
Cousseau J,Gouin L,Tetrahedron,1985,41(4):801-810；Giffard M, Cousseau J,Gouin
L,et al.,Journal of organometallic chemistry,1985,287(3): 287-303).Such method is most
Big problem is to be easy pollution environment in production process, and has certain toxic action to experimental implementation person；In addition to this, it produces
The configuration preference of object is not strong, and functional group compatibility difference is also the problem of physical presence.Therefore, the structure alkene of development environment close friend
The synthetic method of base thiocyanates derivative is constantly subjected to the extensive concern of scientific circles and industrial quarters.
In Synthetic Organic Chemistry, alkynes halogen is a kind of organic synthesis building block having very much research significance and practical value.Closely
Nian Lai, the function dough reaction based on alkynes halogen receive significant attention.(Trofimov A,Chernyak N, Gevorgyan V.,
Journal of the American Chemical Society,2008,130(41): 13538-13539；Yun S Y,
Kim M,Lee D,et al.,Journal of the American Chemical Society,2008,131(1):24-
25；Usanov D L,Yamamoto H,Journal of the American Chemical Society,2011,133
(5):1286-1289；Murali R,Rao N N,Cha J K,Organic letters,2015,17(15):3854-3856；
Tan H,Li H,Ji W,et al.,Angewandte Chemie International Edition,2015,54(29):
8374-8377；Lehnherr D,Alzola J M, Lobkovsky E B,et al.,Chemistry–A European
Journal,2015,21(50): 18122-18127).But there is presently no be that raw material directly synthesizes alkenyl sulphur using alkynes halogen
The report of cyanic acid ester derivant.
Invention content
In order to overcome the shortcomings and deficiencies of the prior art described above, the primary purpose of the present invention is that providing a kind of synthesis alkenyl
The new method of thiocyanates derivative.
The purpose of the present invention is realized by following proposal:
A kind of new method of synthesis alkenyl thiocyanates derivative, mainly includes the following steps that:
In the reaction vessel, alkynes halogen is added, rhodanate is raw material, silver salt is catalyst, organic solvent is solvent
Under the conditions of heat reaction, after reaction by gained reaction solution be cooled to room temperature then purify to get the alkenyl thiocyanic acid
Ester derivant.
Its reaction is shown below:
Wherein, R is aryl or fatty alkyl, and X is chlorine, bromine or iodine.
The rhodanate can be potassium rhodanide or ammonium thiocyanate.
The alkynes halogen can be arylalkyne chlorine, arylalkyne bromine, arylalkyne iodine, alkyl alkynes chlorine, alkyl alkynes bromine or alkyl alkynes iodine.
Preferably, the alkynes chlorine is arylalkyne bromine or alkyl alkynes bromine.
It is furthermore preferred that the arylalkyne bromine includes phenylacetylene bromine, and 2- chlorobenzene acetylene bromines, 2- bromobenzene acetylene bromines, 2,4- bis-
Methyl phenylacetylene bromine, 3- chlorobenzene acetylene bromines, 3- fluorobenzene acetylene bromines, 3- methyl phenylacetylene bromines, 3- Methoxy-phenylacetylene bromines, 3- bromobenzenes
Acetylene bromine, 3- acetylene bromothiophenes, 3,5- difluoro phenylacetylene bromines, 4- chlorobenzene acetylene bromines, 4- Methoxy-phenylacetylene bromines, 4- ethyoxyls
Phenylacetylene bromine, 4- methyl phenylacetylene bromines, 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylene bromines, 4- trifluoromethyl phenylacetylene bromines, 4- n-propylbenzene acetylene bromines；
The alkyl alkynes halogen includes：Isosorbide-5-Nitrae-last of the ten Heavenly stems diine bromine, 1,6- heptadiyne bromine, 1- hexin bromines, 1- heptyne bromines, 1- octyne bromines, 1- nonyls
Alkynes bromine, 1- decine bromines, 1- acetylenebromide cyclohexene, 3- cyclohexyl -1- propine bromines, 3- phenyl -1- propine bromines, 3- cyclopenta -1-
Propine bromine, 4- phenyl -1- butine bromines, the chloro- 1- pentynes bromines of 5-, 5- phenyl -1- pentyne bromines, 5- methyl-1s-hexin bromine, 5- cyano
- 1- pentyne bromines, cyclopenta acetylene bromine.
The molar ratio of alkynes halogen and rhodanate used is 1:(1~4).
The silver salt can be silver chlorate, silver bromide, silver nitrate, silver oxide, silver trifluoromethanesulfonate, silver carbonate, tetrafluoro boron
At least one of sour silver, silver acetate and silver trifluoroacetate.Above-mentioned silver catalyst agent is all solid, they can be dissolved in reaction institute
In the organic solvent needed.
Preferably, the silver salt is silver acetate.
The molar ratio of silver salt used and alkynes halogen is 0.1:1.
The organic solvent is at least one of glacial acetic acid and ethyl alcohol.
The described heating reaction refer to be stirred to react 1 at 80~100 DEG C~for 24 hours.
The purifying refers to filtering reaction solution, and sodium bicarbonate solution is added and is extracted with ethyl acetate three times, collects
Organic phase is dried with magnesium sulfate, then vacuum distillation remove organic solvent, obtain crude product, then to the crude product of gained into
Row column chromatography.
Wherein, the eluent of the column chromatography is the mixed solvent of petroleum ether and ethyl acetate；Petroleum ether and acetic acid second
The volume ratio of ester is (10~200):1.
Preferably, the volume ratio of the petroleum ether and ethyl acetate is 100:1.
The present invention mechanism be:
Using alkynes halogen, rhodanate as raw material, under the catalysis of silver salt, thiocyanation reaction, one-step synthesis alkenyl sulphur cyanogen occurs
Acid ester derivant.
The present invention compared with the existing technology, has the following advantages and advantageous effect:
The present invention builds the synthetic method of alkenyl thiocyanates, avoids the use of the dangerous material such as the concentrated sulfuric acid, mercury salt.Reaction
Raw material is simple and easy to get, and operation is safe and simple, and reaction process is environmental-friendly, and substrate applicability is wide, and functional group compatibility is strong, point
Higher from yield, selecting property of product configuration is good, can be amplified to gram-grade scale, and the halogen that product retains conveniently can further turn
Change.The synthesis of such compound has extensive use in the synthesis of pesticide, medicine and natural products.
Description of the drawings
Fig. 1 is the NOE nuclear magnetic resonance maps of the product obtained by embodiment 1-16.
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of 43 products therefrom of embodiment.
Fig. 3 is the carbon-13 nmr spectra figure of 43 products therefrom of embodiment.
Fig. 4 is the hydrogen nuclear magnetic resonance spectrogram of 53 products therefrom of embodiment.
Fig. 5 is the carbon-13 nmr spectra figure of 53 products therefrom of embodiment.
Specific implementation mode
With reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Agents useful for same can routinely be bought from market in embodiment.
Embodiment 1
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 84%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3065,2924,2854,2357,2120,735,692cm-1.
1H NMR(400MHz,CDCl3):δ7.49-7.43(m,5H),6.79(s,1H).
13C NMR(100MHz,CDCl3):δ135.3,134.4,130.2,128.9,128.1,110.6, 108.3ppm.
HRMS(ESI)m/z:C9H6BrNS[M+Na]+Calculated value：261.9297；Experiment value：261.9294.
Infer that products therefrom obtains structure and is according to data above:Illustrate to successfully synthesize target product.
Embodiment 2
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the chlorine of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Change silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 56%.
Embodiment 3
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the bromine of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Change silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 53%.
Embodiment 4
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the nitre of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 73%.
Embodiment 5
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the oxygen of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Change silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 49%.
Embodiment 6
In 25 milliliters of reaction vessels equipped with reflux condensing tube, be added 0.2mmol phenylacetylenes bromines, 0.02 mmol three
Fluorine methanesulfonic acid silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop
Heating and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate is dry
Dry, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is body
Product is than being 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 62%.
Embodiment 7
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the carbon of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 50%.
Embodiment 8
In 25 milliliters of reaction vessels equipped with reflux condensing tube, be added 0.2mmol phenylacetylenes bromines, 0.02 mmol four
Silver fluoborate, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid after being stirred to react 3 hours under the conditions of 100 DEG C, stop adding
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 51%.
Embodiment 9
In 25 milliliters of reaction vessels equipped with reflux condensing tube, be added 0.2mmol phenylacetylenes bromines, 0.02 mmol three
Fluoroacetic acid silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid after being stirred to react 3 hours under the conditions of 100 DEG C, stop adding
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 63%.
Embodiment 10
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the ammonium thiocyanate of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 68%.
Embodiment 11
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.2mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 73%.
Embodiment 12
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.8mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 81%.
Embodiment 13
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 80 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 74%.
Embodiment 14
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 90 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 77%.
Embodiment 15
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 1 hour under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 56%.
Embodiment 16
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid after being stirred to react 24 hours under the conditions of 100 DEG C, stop heating
And stirring, it is cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying subtracts
Pressure revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 69%.
The NOE nuclear magnetic resonance maps of product obtained by embodiment 1-16 are as shown in Figure 1.Illustrate sulphur cyanogen in the product of gained
Acid group and bromine atom are cis-structure in the same side of double bond.
Embodiment 17
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes chlorine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 56%.
Embodiment 18
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes iodine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 21%.
Embodiment 19
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol phenylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of ethyl alcohol after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and stir
It mixes, is cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression rotation
Solvent is evaporated off, then by column chromatographic isolation and purification, obtains target product, it is 100 that column chromatography eluent used, which is volume ratio,:
1 petroleum ether:Ethyl acetate mixed solvent, yield 64%.
Embodiment 20
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol Isosorbide-5-Nitraes-last of the ten Heavenly stems diine bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 88%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3074,2935,2863,2357,2160,1738,1599,1459,819,766cm-1.
1H NMR(400MHz,CDCl3):δ 6.87 (s, 1H), 3.40 (d, J=2.0Hz, 2H), 2.21 (tt, J=7.1,
2.1Hz, 2H), 1.56-1.48 (m, 2H), 1.39-1.29 (m, 4H), 0.91 (t, J=7.0Hz, 3H)
13C NMR(100MHz,CDCl3):δ128.6,109.2,108.0,86.7,77.3,31.0,28.2, 27.5,
22.1,18.6,13.9ppm.
HRMS(ESI)m/z:C11H14BrNS[M+Na]+Calculated value：293.9923；Experiment value： 293.9928.
Infer that products therefrom obtains structure and is according to data above:Illustrate successfully to synthesize
Target product.
Embodiment 21
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 1,6- heptadiynes bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 74%.
Embodiment 22
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol 1- heptyne bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 96%.
Embodiment 23
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol cyclopenta acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 89%.
Embodiment 24
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol 1- hexins bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 95%.
Embodiment 25
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol 1- n-heptylacetylenes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 92%.
Embodiment 26
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol 1- octynes bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 95%.
Embodiment 27
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 1- acetylene bromines cyclohexene,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 79%.
Embodiment 28
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 2,4- dimethyl benzene acetylene bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 57%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3069,2988,2924,2860,2357,2160,1763,1242,1053,818,746, 698cm-1.
1H NMR(400MHz,CDCl3):δ 7.09 (dd, J=14.8,8.8Hz, 3H), 6.48 (s, 1H), 2.34 (s,
6H).
13C NMR(100MHz,CDCl3):δ140.6,136.6,134.8,132.0,131.5,129.8, 127.0,
108.3,107.9,21.3,19.4ppm.
HRMS(ESI)m/z:C11H10BrNS[M+Na]+Calculated value：289.9610；Experiment value： 289.9612.
Infer that products therefrom obtains structure and is according to data above:Illustrate to successfully synthesize target production
Object.
Embodiment 29
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 2- chlorobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 52%.
Embodiment 30
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 2- bromobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 61%.
Embodiment 31
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3,5- difluoro phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 62%.
Embodiment 32
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3- phenyl -1- propine bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 82%.
Embodiment 33
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 3- fluorobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 76%.
Embodiment 34
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3- cyclohexyl -1- propine bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 87%.
Embodiment 35
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3- cyclopenta -1- propine bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 89%.
Embodiment 36
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3- methyl phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution and be extracted with ethyl acetate three times after filtering, magnesium sulfate
Dry, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is
Volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 57%.
Embodiment 37
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 3- Methoxy-phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 75%.
Embodiment 38
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 3- chlorobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 71%.
Embodiment 39
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 3- bromobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 78%.
Embodiment 40
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 3- acetylene bromothiophene, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 75%.
Embodiment 41
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- phenyl -1- butine bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 76%.
Embodiment 42
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- methyl phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, ethyl acetate is added after filtering and with the water-soluble sodium bicarbonate aqueous solution of sodium bicarbonate
It is used in combination acetic acid ethyl fluid to extract three times, magnesium sulfate drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains
Target product, it is 100 that column chromatography eluent used, which is volume ratio,:1 petroleum ether:Ethyl acetate mixed solvent, yield are
80%.
Embodiment 43
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- Methoxy-phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 67%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3065,2937,2839,2357,2158,1560,1503,1456,1297,1249,1175, 1027,
833,789cm-1.
1H NMR(400MHz,CDCl3):δ 7.26 (d, J=8.1Hz, 2H), 7.15 (d, J=8.0Hz, 2H), 6.64 (s,
1H), 2.30 (s, 3H), as shown in Figure 2.
13C NMR(100MHz,CDCl3)：δ140.5,134.5,132.5,129.6,128.0,109.6, 108.6,
21.3ppm as shown in Figure 3.
HRMS(ESI)m/z:C10H8BrNOS[M+Na]+Calculated value：291.9402；Experiment value： 291.9400.
Infer that products therefrom obtains structure and is according to data above:Illustrate to successfully synthesize target
Product.
Embodiment 44
In 25 milliliters of reaction vessels equipped with reflux condensing tube, 0.2mmol 4- chlorobenzene acetylene bromine, 0.02mmol is added
Silver acetate, 0.4mmol potassium rhodanide and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop plus
Heat and stirring, are cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying,
Vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is volume ratio
It is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 74%.
Embodiment 45
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- trifluoromethyl phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 67%.
Embodiment 46
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylenes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 81%.
Embodiment 47
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- ethoxybenzene acetylene bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 66%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3067,2982,2930,2892,2158,1602,1505,1298,1250,1176,835, 793,
744cm-1.
1H NMR(400MHz,CDCl3):δ7.39-7.34(m,2H),6.93-6.89(m,2H),6.67(s, 1H),4.05
(q, J=7.0Hz, 2H), 1.42 (t, J=7.0Hz, 3H)
13C NMR(100MHz,CDCl3):δ160.4,134.4,129.5,127.5,114.7,108.8, 108.7,
63.6,14.7ppm.
HRMS(ESI)m/z:C11H10BrNOS[M+Na]+Calculated value：305.9559；Experiment value： 305.9560.
Infer that products therefrom obtains structure and is according to data above:Illustrate to successfully synthesize target
Product.
Embodiment 48
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 4- n-propylbenzene acetylene bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 81%.
Embodiment 49
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the vinegar of 0.2mmol 1- decine bromine, 0.02 mmol is added
Sour silver, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid, after being stirred to react 3 hours under the conditions of 100 DEG C, stop heating and
Stirring, is cooled to room temperature, and sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, magnesium sulfate drying, decompression
Revolving removes solvent, then by column chromatographic isolation and purification, obtains target product, and column chromatography eluent used is that volume ratio is
100:1 petroleum ether:Ethyl acetate mixed solvent, yield 89%.
Embodiment 50
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 5- phenyl -1- pentynes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 74%.
Embodiment 51
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 5- cyano -1- pentynes bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 93%.
Embodiment 52
In 25 milliliters of reaction vessels equipped with reflux condensing tube, addition 0.2mmol 5- methyl-1s-hexin bromine,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 93%.
Embodiment 53
In 25 milliliters of reaction vessels equipped with reflux condensing tube, the chloro- 1- pentynes bromines of addition 0.2mmol 5-,
The silver acetate of 0.02mmol, the potassium rhodanide of 0.4mmol and 2 milliliters of glacial acetic acid are stirred to react 3 hours under the conditions of 100 DEG C
Afterwards, stop heating and stirring, be cooled to room temperature, sodium bicarbonate aqueous solution is added after filtering and is extracted with ethyl acetate three times, sulphur
Sour magnesium drying, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used elution
Liquid is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 91%.
The structural characterization data of products therefrom are as follows:
IR(KBr):3070,2957,2855,2357,2159,1835,1241,1057cm-1.
1H NMR(400MHz,CDCl3)：δ 6.55 (s, 1H), 3.59 (t, J=6.1Hz, 2H), 2.79 (t, J=7.2Hz,
2H), 2.15-2.07 (m, 2H), as shown in Figure 4.
13C NMR(100MHz,CDCl3)：δ 132.2,108.6,107.7,43.1,33.9,29.9ppm, as shown in Figure 5.
ESI-HRMS m/z：C6H7BrClNS[M+Na]+Calculated value:261.9063, experiment value: 261.9060.
Infer that products therefrom obtains structure and is according to data above:Illustrate to successfully synthesize target production
Object.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (6)
1. a kind of method of synthesis alkenyl thiocyanates derivative, it is characterised in that include the following steps:
In the reaction vessel, alkynes halogen, rhodanate is added for raw material, in the condition that silver salt is catalyst, organic solvent is solvent
Gained reaction solution is cooled to room temperature then to purify and spread out to get the alkenyl thiocyanates by lower heating reaction after reaction
Biology；
Its reaction is shown below:
Wherein, R is aryl or fatty alkyl, and X is chlorine, bromine or iodine；The rhodanate is potassium rhodanide or ammonium thiocyanate；
The alkynes halogen is arylalkyne chlorine, arylalkyne bromine, arylalkyne iodine, alkyl alkynes chlorine, alkyl alkynes bromine or alkyl alkynes iodine；
The silver salt be silver chlorate, silver bromide, silver nitrate, silver trifluoromethanesulfonate, silver carbonate, silver tetrafluoroborate, silver acetate and
At least one of silver trifluoroacetate；
The organic solvent is at least one of glacial acetic acid and ethyl alcohol.
2. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：
The alkynes halogen is arylalkyne bromine or alkyl alkynes bromine.
3. the method for synthesis alkenyl thiocyanates derivative according to claim 2, it is characterised in that：
The arylalkyne bromine includes phenylacetylene bromine；
The alkyl alkynes bromine includes：1- hexin bromines, 1- heptyne bromines, 1- octyne bromines, 1- n-heptylacetylene bromines, 1- decine bromines, 5- methyl-1s-
Hexin bromine.
4. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：
The molar ratio of alkynes halogen and rhodanate used is 1:(1~4)；
The molar ratio of silver salt used and alkynes halogen is 0.1:1.
5. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：
The described heating reaction refer to be stirred to react 1 at 80~100 DEG C~for 24 hours.
6. the method for synthesis alkenyl thiocyanates derivative according to claim 1, it is characterised in that：
The purifying refers to filtering reaction solution, and sodium bicarbonate solution is added and is extracted with ethyl acetate three times, collects organic
Phase is dried with magnesium sulfate, and then vacuum distillation removes organic solvent, obtains crude product, then carries out column to the crude product of gained
Chromatography；
Wherein, the eluent of column chromatography is the mixed solvent of petroleum ether and ethyl acetate；The volume ratio of petroleum ether and ethyl acetate
For (10~200):1.
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