CN113511991A - 一种卤代烷烃硫醚化和硫代羰基化的合成方法 - Google Patents
一种卤代烷烃硫醚化和硫代羰基化的合成方法 Download PDFInfo
- Publication number
- CN113511991A CN113511991A CN202110773028.9A CN202110773028A CN113511991A CN 113511991 A CN113511991 A CN 113511991A CN 202110773028 A CN202110773028 A CN 202110773028A CN 113511991 A CN113511991 A CN 113511991A
- Authority
- CN
- China
- Prior art keywords
- reaction
- thioetherification
- thiocarbonylation
- alkyl
- tert
- Prior art date
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- Granted
Links
- 238000005936 thiocarbonylation reaction Methods 0.000 title claims abstract description 32
- 150000001335 aliphatic alkanes Chemical class 0.000 title claims abstract description 21
- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- 238000005732 thioetherification reaction Methods 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 13
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 9
- ZBHWGKWEVFYBBE-UHFFFAOYSA-N C(C=1C(O)=CC=CC1)(=O)N.C(C=1C(O)=CC=CC1)(=O)N.C(C)[Co] Chemical compound C(C=1C(O)=CC=CC1)(=O)N.C(C=1C(O)=CC=CC1)(=O)N.C(C)[Co] ZBHWGKWEVFYBBE-UHFFFAOYSA-N 0.000 claims abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- -1 methoxy, ethoxy, tert-butoxy Chemical group 0.000 claims description 28
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 24
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 22
- 239000008096 xylene Substances 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 10
- OTZCUZNBNWORAD-UHFFFAOYSA-N CC[Co] Chemical compound CC[Co] OTZCUZNBNWORAD-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 150000001350 alkyl halides Chemical class 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 4
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- MVHJGIFBMMWKED-UHFFFAOYSA-L copper triphenylphosphane dibromide Chemical compound [Cu+2].[Br-].[Br-].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MVHJGIFBMMWKED-UHFFFAOYSA-L 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 4
- FWBOFUGDKHMVPI-UHFFFAOYSA-K dicopper;2-oxidopropane-1,2,3-tricarboxylate Chemical compound [Cu+2].[Cu+2].[O-]C(=O)CC([O-])(C([O-])=O)CC([O-])=O FWBOFUGDKHMVPI-UHFFFAOYSA-K 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- LFKXWKGYHQXRQA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;iron Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LFKXWKGYHQXRQA-FDGPNNRMSA-N 0.000 claims description 2
- 229940011182 cobalt acetate Drugs 0.000 claims description 2
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 claims description 2
- FJDJVBXSSLDNJB-LNTINUHCSA-N cobalt;(z)-4-hydroxypent-3-en-2-one Chemical compound [Co].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O FJDJVBXSSLDNJB-LNTINUHCSA-N 0.000 claims description 2
- LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 abstract description 6
- 150000007970 thio esters Chemical class 0.000 abstract description 5
- 231100000086 high toxicity Toxicity 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract 2
- 238000005987 sulfurization reaction Methods 0.000 abstract 2
- 125000000524 functional group Chemical group 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- DMMJVMYCBULSIS-UHFFFAOYSA-N Methyl 3-(methylthio)propanoate Chemical compound COC(=O)CCSC DMMJVMYCBULSIS-UHFFFAOYSA-N 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 14
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000007789 gas Substances 0.000 description 14
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 14
- 239000007788 liquid Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- 238000010183 spectrum analysis Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 239000011734 sodium Substances 0.000 description 12
- 239000012043 crude product Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 8
- QBPYSJJNOYHIPX-UHFFFAOYSA-N 2-hydroxy-n-(2-hydroxybenzoyl)benzamide Chemical compound OC1=CC=CC=C1C(=O)NC(=O)C1=CC=CC=C1O QBPYSJJNOYHIPX-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000000758 substrate Substances 0.000 description 6
- SBMNMKRUXIRDFB-UHFFFAOYSA-N o-tert-butyl butanethioate Chemical class CCCC(=S)OC(C)(C)C SBMNMKRUXIRDFB-UHFFFAOYSA-N 0.000 description 5
- 239000004809 Teflon Substances 0.000 description 4
- 229920006362 Teflon® Polymers 0.000 description 4
- 125000005012 alkyl thioether group Chemical group 0.000 description 4
- 239000000956 alloy Substances 0.000 description 4
- 229910045601 alloy Inorganic materials 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 238000003760 magnetic stirring Methods 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 150000001351 alkyl iodides Chemical class 0.000 description 3
- 229910017052 cobalt Inorganic materials 0.000 description 3
- 239000010941 cobalt Substances 0.000 description 3
- JLTGEVBJTKIKDC-UHFFFAOYSA-N 1-ethoxy-4-(3-iodobutyl)benzene Chemical compound CCOC1=CC=C(CCC(C)I)C=C1 JLTGEVBJTKIKDC-UHFFFAOYSA-N 0.000 description 2
- CAOMCZAIALVUPA-UHFFFAOYSA-N 3-(methylthio)propionic acid Chemical compound CSCCC(O)=O CAOMCZAIALVUPA-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- XYNZKHQSHVOGHB-UHFFFAOYSA-N copper(3+) Chemical compound [Cu+3] XYNZKHQSHVOGHB-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- HEMCKDNYXPMXAR-UHFFFAOYSA-N 1-(2,2-difluoroethoxy)-4-(3-iodobutyl)benzene Chemical compound CC(CCC(C=C1)=CC=C1OCC(F)F)I HEMCKDNYXPMXAR-UHFFFAOYSA-N 0.000 description 1
- IYCTYQWDSXVKHT-UHFFFAOYSA-N 1-(3-iodobutyl)-4-(trifluoromethoxy)benzene Chemical compound CC(CCC(C=C1)=CC=C1OC(F)(F)F)I IYCTYQWDSXVKHT-UHFFFAOYSA-N 0.000 description 1
- JXDLVVCLHOLTLN-UHFFFAOYSA-N 1-(3-iodobutyl)-4-methylbenzene Chemical compound C(CCC1=CC=C(C)C=C1)(I)C JXDLVVCLHOLTLN-UHFFFAOYSA-N 0.000 description 1
- HWANVQYTMOMUDD-UHFFFAOYSA-N 1-butyl-2-methylsulfanyl-4-(trifluoromethoxy)benzene Chemical compound CCCCC(C=CC(OC(F)(F)F)=C1)=C1SC HWANVQYTMOMUDD-UHFFFAOYSA-N 0.000 description 1
- ZCDFLVRVGQABDN-UHFFFAOYSA-N 1-butyl-4-ethoxy-2-methylsulfanylbenzene Chemical compound CCCCC(C=CC(OCC)=C1)=C1SC ZCDFLVRVGQABDN-UHFFFAOYSA-N 0.000 description 1
- LVRSEMQKXIYPQL-UHFFFAOYSA-N 1-chloro-3-(3-iodobutyl)benzene Chemical compound CC(CCC1=CC=CC(Cl)=C1)I LVRSEMQKXIYPQL-UHFFFAOYSA-N 0.000 description 1
- WSFGTMVZTGMHBA-UHFFFAOYSA-N 1-chloro-3-(3-methylsulfanylbutyl)benzene Chemical compound CC(CCC1=CC(Cl)=CC=C1)SC WSFGTMVZTGMHBA-UHFFFAOYSA-N 0.000 description 1
- JNSUJAVOIZXEKV-UHFFFAOYSA-N 1-fluoro-4-(3-iodobutyl)benzene Chemical compound CC(CCC(C=C1)=CC=C1F)I JNSUJAVOIZXEKV-UHFFFAOYSA-N 0.000 description 1
- LEGJZMMDTVFVSP-UHFFFAOYSA-N 1-fluoro-4-(3-methylsulfanylbutyl)benzene Chemical compound CC(CCC(C=C1)=CC=C1F)SC LEGJZMMDTVFVSP-UHFFFAOYSA-N 0.000 description 1
- FJOWFBHQISJLHD-UHFFFAOYSA-N 1-methyl-4-(3-methylsulfanylbutyl)benzene Chemical compound CSC(C)CCC1=CC=C(C)C=C1 FJOWFBHQISJLHD-UHFFFAOYSA-N 0.000 description 1
- AOPDRZXCEAKHHW-UHFFFAOYSA-N 1-pentoxypentane Chemical compound CCCCCOCCCCC AOPDRZXCEAKHHW-UHFFFAOYSA-N 0.000 description 1
- DUNOUGNOLVTPBP-UHFFFAOYSA-N 1-tert-butyl-4-iodocyclohexane Chemical compound CC(C)(C)C1CCC(I)CC1 DUNOUGNOLVTPBP-UHFFFAOYSA-N 0.000 description 1
- GYRPZDAHJXUOAD-UHFFFAOYSA-N 2-(3-iodobutyl)naphthalene Chemical compound CC(CCC1=CC2=CC=CC=C2C=C1)I GYRPZDAHJXUOAD-UHFFFAOYSA-N 0.000 description 1
- GBESGWRDCMWOIU-UHFFFAOYSA-N 2-(3-methylsulfanylbutyl)naphthalene Chemical compound CC(CCC1=CC2=CC=CC=C2C=C1)SC GBESGWRDCMWOIU-UHFFFAOYSA-N 0.000 description 1
- AUNKHUQNKUEUJA-UHFFFAOYSA-N 2-iodododecane Chemical compound CCCCCCCCCCC(C)I AUNKHUQNKUEUJA-UHFFFAOYSA-N 0.000 description 1
- ANKQAKXTIZPRIX-UHFFFAOYSA-N 2-methylsulfanyldodecane Chemical compound CCCCCCCCCCC(C)SC ANKQAKXTIZPRIX-UHFFFAOYSA-N 0.000 description 1
- NDEHZONFJLYJEH-UHFFFAOYSA-N 3-iodobutylbenzene Chemical compound CC(I)CCC1=CC=CC=C1 NDEHZONFJLYJEH-UHFFFAOYSA-N 0.000 description 1
- NUAWVYATOQIPJH-UHFFFAOYSA-N 3-methylsulfanylbutylbenzene Chemical compound CSC(C)CCC1=CC=CC=C1 NUAWVYATOQIPJH-UHFFFAOYSA-N 0.000 description 1
- DRGHCRKOWMAZAO-UHFFFAOYSA-N 4-(Methylthio)-2-butanone Chemical class CSCCC(C)=O DRGHCRKOWMAZAO-UHFFFAOYSA-N 0.000 description 1
- FAMVDGNPZHSKDQ-UHFFFAOYSA-N 4-iodopentoxybenzene Chemical compound CC(CCCOC1=CC=CC=C1)I FAMVDGNPZHSKDQ-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OGIJAYVDOAHFNA-UHFFFAOYSA-N CC(CCC(C=C1)=CC=C1SC)I Chemical compound CC(CCC(C=C1)=CC=C1SC)I OGIJAYVDOAHFNA-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- DLKQCLIBMWAKOH-UHFFFAOYSA-N [Co+4] Chemical compound [Co+4] DLKQCLIBMWAKOH-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
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Abstract
本发明涉及有机合成技术领域,具体涉及一种卤代烷烃硫醚化和硫代羰基化的合成方法;利用3‑甲硫基丙酸甲酯衍生物作为硫化试剂,实现卤代烷烃的硫醚化和硫羰基化;利用IPrCuCl做催化剂,实现硫醚化;在一氧化碳存在下,利用IPrCuCl和双水杨酰胺乙基钴共催化获得硫酯。该硫化试剂容易合成,反应条件比较温和,实用性强。本发明避免使用强烈气味、高毒性、环境污染的硫醇,具有良好的官能团耐受性和优异的收率与纯度,且不需要苛刻的反应条件,适合工业化生产。
Description
技术领域
本发明涉及有机合成技术领域,具体涉及一种卤代烷烃硫醚化和硫代羰基化的合成方法。
背景技术
烷基硫醚是一类含有硫原子、通式为R-S-R1的化合物,烷基硫酯是一类含有一个硫原子和一分子酰基(烷烃与一碳氧双键分子所形成的共价键)的酯类化合物,它们都是多种药物的结构单元。许多硫醚和硫酯化合物具有显著的生物活性,在抗肿瘤、抗癌、抗病毒、杀菌、消炎和抗寄生虫等方面具有重要的医用价值。如林可霉素的第三代产品克林霉素中含有硫醚结构,是有效的革兰氏半合成抗生素药物(Chen Y,Wang J.K.Journal ofChemical&Engineering Data 2007:52:1908.)。氟替卡松丙酸酯是一种含硫酯的化合物,被用作治疗哮喘(Zhou J,Jin C,Su W.Organic Process Research&Development.2014:18:928.)。
烷基硫醚传统合成方法主要通过卤代烷烃与金属硫醇盐或硫醇的取代。然而,这些方法具有一些共同的缺点,包括收率低,底物制备繁琐,底物适用范围窄,硫醇的难闻气味和高毒性。烷基硫酯因其多样性的生物学特性而备受关注。然而,在现有的硫代羰基化的例子中,起始底物主要集中在Csp2-X键上。
鉴于上述缺陷,本发明创作者经过长时间的研究和实践终于获得了本发明。
发明内容
本发明的目的在于解决烷基硫醚传统合成方法收率低,底物制备繁琐,底物适用范围窄,硫醇的难闻气味和高毒性,卤代烷烃硫代羰基化的起始底物主要集中在Csp2-X键上的问题,提供了一种卤代烷烃硫醚化和硫代羰基化的合成方法。
为了实现上述目的,本发明公开了一种卤代烷烃硫醚化的合成方法,由式I化合物与式II化合物在催化剂作用下制得,硫醚化反应路线如下:
其中,R为氢、C1-6烷基、苯甲基、苯乙基、苯丙基、卤素、卤素取代烷基中的任意一种;
R1为氢、C1-6烷基、苯甲基、苯乙基、苯丙基、卤素、卤素取代烷基中的任意一种;
R2为氢、C1-6烷基、甲氧基、乙氧基、叔丁氧基、苯基中的任意一种;
R3为氢或C1-6烷基;
R4为C1-6烷基、苯甲基、苯乙基、苯丙基、卤素取代烷基中的任意一种;
X为碘原子、溴原子、氯原子中的任意一种。
所述硫醚化反应中催化剂为醋酸钯、氯化钯、钯碳、碳酸银、四氟硼酸四(乙腈)铜、三氟甲烷磺酸铜、溴三(三苯基膦)铜、氯化铜、乙酸铜、IPrCuCl、柠檬酸铜中的任意一种或几种组合;
所述硫醚化反应中碱为碳酸钾,碳酸钠,碳酸铯,磷酸钾,磷酸氢二钾,叔丁醇锂,叔丁醇钠,叔丁醇钾,甲醇钠,甲醇钾,三乙胺,DBU中的任意一种或几种组合;
所述硫醚化反应中溶剂为二甲基亚砜、DMF、DMA、苯、甲苯、二甲苯、甲醇、苯甲醚、1,2-二氯乙烷,四氢呋喃、乙腈、乙酸乙酯、叔丁醇、乙醇、异丙醇、水中的任意一种或几种组合。
优选的,所述硫醚化反应中催化剂为IPrCuCl,所述硫醚化反应中碱为叔丁醇钠,所述硫醚化反应中溶剂为二甲苯。
所述硫醚化反应中催化剂的用量为0.002~0.02mol,所述硫醚化反应温度为25~180℃。
优选的,所述硫醚化反应中催化剂的用量为0.01mmol,所述硫醚化反应温度为140℃。
本发明还公开了一种卤代烷烃硫代羰基化的合成方法,由式I化合物与式II化合物在一氧化碳,催化剂和碱的作用下在制备烷基硫酯,羰基化反应路线如下:
其中,R为氢、C1-6烷基、苯甲基、苯乙基、苯丙基、卤素、卤素取代烷基中的任意一种;
R1为氢、C1-6烷基、苯甲基、苯乙基、苯丙基、卤素、卤素取代烷基中的任意一种;
R2为氢、C1-6烷基、甲氧基、乙氧基、叔丁氧基、苯基中的任意一种;
R3为氢或C1-6烷基;
R4为C1-6烷基、苯甲基、苯乙基、苯丙基、卤素取代烷基中的任意一种;
X为碘原子、溴原子、氯原子中的任意一种。
所述硫代羰基化反应中催化剂为醋酸钯、氯化钯、钯碳、碳酸银、四氟硼酸四(乙腈)铜、三氟甲烷磺酸铜、溴三(三苯基膦)铜、氯化铜、乙酸铜、IPrCuCl、柠檬酸铜、双乙酰基水杨酸钴、双水杨酰胺乙基钴、乙酸钴、乙酰丙酮钴、乙酰丙酮铁、乙酰丙酮亚铁、三氟甲磺酸铁中的任意一种或几种组合;
所述硫代羰基化反应中碱为碳酸钾,碳酸钠,碳酸铯,磷酸钾,磷酸氢二钾,叔丁醇锂,叔丁醇钠,叔丁醇钾,甲醇钠,甲醇钾,三乙胺,DBU中的任意一种或几种组合;
所述硫代羰基化反应中溶剂为二甲基亚砜、DMF、DMA、苯、甲苯、二甲苯、甲醇、苯甲醚、1,2-二氯乙烷,四氢呋喃、乙腈、乙酸乙酯、叔丁醇、乙醇、异丙醇、水中的任意一种或几种组合。
所述硫代羰基化反应中催化剂为IPrCuCl和双水杨酰胺乙基钴,所述硫代羰基化反应中碱为叔丁醇钾,所述硫代羰基化反应中溶剂为二甲苯,所述IPrCuCl和双水杨酰胺乙基钴的用量均为0.01mmol。
所述硫代羰基化反应温度为25~180℃,CO的压强为1~40bar。
所述硫代羰基化反应温度为80℃,CO的压强为30bar。
上述反应的初步机理如图1所示。首先,对于Cu催化的烷基碘代物的甲硫基化的反应机理,IPrCuCl A不可逆地从烷基碘中提取一个碘原子,产生一个以碳为中心的自由基和IPrCuI B。之后是自由基加成到铜络合物B,形成铜(III)中间体C。中间体C与D反应,形成所需的硫化物4,同时再生活性Cu(I)物种用于下一个催化循环,其中D是由A和起始硫酯2反应形成。
对于Cu/Co催化的烷基碘代物的硫代羰基化反应,铜(III)中间体C将与钴(II)配合物E发生金属转移反应,形成钴(IV)配合物F。接下来,在C-Co键中插入CO形成酰基钴中间体H,之后与甲基硫醇配位形成关键中间体I。中间体I进行还原消除以产生所需的硫酯产物3并再生活性钴物种E。
与现有技术比较本发明的有益效果在于:本发明提供卤代烷烃的硫醚化和硫代羰基化的一般合成方法,该方法通过铜催化的卤代烷烃和3-甲硫基丙酸甲酯衍生物进行转硫化,在一氧化碳存在下,通过铜和钴共催化卤代烷烃和3-甲硫基丙酸叔丁酯衍生物合成烷基硫酯;卤代烷烃的硫醚化是以IPrCuCl为催化剂,叔丁醇钠做碱在140℃条件下,由卤代烷烃和4-甲硫基-2-丁酮的衍生物合成烷基硫醚。卤代烷烃的硫代羰基化在一氧化碳存在下,选用IPrCuCl和双水杨酰胺乙基钴为催化剂,叔丁醇钾做碱,在80℃获得烷基硫酯;实现了多官能化烷基硫醚和烷基硫酯的合成,本发明具有方法简便又经济,实用性强,避免使用强烈气味、高毒性、环境污染的硫醇,
附图说明
图1为本发明反应初步机理图。
具体实施方式
本文所用的术语“C1-6烷基”是指具有1-6个碳原子的饱和的直链或支链烃基,例如甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基、异己基等。
本文所用的术语“DMF”是指N,N-二甲基甲酰胺,“DMA”是指N,N-二甲基乙酰胺,“IPrCuCl”是指氯[1,3-双(2,6-二异丙苯基)咪唑-2-亚基]铜(I),“DBU”是指1,8-二氮杂二环[5.4.0]十一碳-7-烯。
实施例1
制备2-甲硫基-4-对甲基苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入1-(3-碘丁基)-4-甲基苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(31mg,80%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.10(d,J=4.9Hz,4H),2.75–2.69(m,2H),2.66(p,J=6.8Hz,1H),2.33(d,J=4.8Hz,3H),2.07(d,J=4.9Hz,3H),1.87(m,1H),1.77(m,1H),1.31(d,J=6.7Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ138.81,135.19,128.99,128.22,40.52,38.09,32.73,20.91,20.77,12.79。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=194(M+,21),146(38),131(100),105(60),75(20)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd forC12H18SNa[M+Na]+:217.1021,Found:217.1017。
实施例2
制备4-甲硫基苯戊醚,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入(4-碘戊氧基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(35mg,83%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.27(m,2H),7.01–6.80(m,3H),3.97(m,2H),2.73(h,J=6.8Hz,1H),2.08(s,3H),1.96–1.84(m,2H),1.78–1.62(m,2H),1.31(d,J=6.7Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ158.98,129.37,120.55,114.49,67.56,40.93,32.75,26.80,20.82,12.93。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=210(M+,5),117(100),94(12),69(65),61(41)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C12H18OSNa[M+Na]+:233.0971,Found:233.0964。
实施例3
制备2-甲硫基-4-乙氧基苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入1-乙氧基-4-(3-碘丁基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(33mg,74%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.15–7.05(m,2H),6.85–6.76(m,2H),4.01(q,J=7.0Hz,2H),2.77–2.55(m,3H),2.06(s,3H),1.85(m,1H),1.74(m,1H),1.39(t,J=7.0Hz,3H),1.30(d,J=6.8Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ157.13,133.85,129.21,114.43,63.40,40.47,38.22,32.29,20.80,14.86,12.81。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=224(M+,44),176(71),161(40),133(78),107(100),89(38),77(34),61(12)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C13H20OSNa[M+Na]+:247.1127,Found:247.1121。
实施例4
制备2-甲硫基-4-三氟甲氧基苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入1-(3-碘丁基)-4-(三氟甲氧基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(34.8mg,66%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.23–7.17(m,2H),7.12(d,J=8.1Hz,2H),2.75(t,J=7.9Hz,2H),2.64(h,J=6.8Hz,1H),2.06(s,3H),1.85(m,1H),1.77(m,1H),1.31(d,J=6.7Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ147.41,140.65,129.56,120.87,120.49(d,J=128.3Hz),40.43,37.85,32.49,20.82,12.74。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=264(M+,40),216(80),201(100),175(70),135(12),131(45),109(30),75(60),61(14)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C12H15OF3SNa[M+Na]+:287.0688,Found:287.0687。
实施例5
制备2-甲硫基-4-对氟苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入1-氟-4-(3-碘丁基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(34mg,86%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.14(m,2H),6.95(t,J=8.7Hz,2H),2.71(t,J=7.9Hz,2H),2.63(h,J=6.8Hz,1H),2.06(s,3H),1.84(m,1H),1.78–1.69(m,1H),1.30(d,J=6.8Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ161.24(d,J=244.6Hz),137.48(d,J=3.0Hz),129.66(d,J=7.5Hz),115.04(d,J=19.6Hz),40.42,38.08,32.36,20.82,12.79。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=198(M+,30),150(58),135(100),109(92),75(27)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C11H16FS[M+H]+:199.0951,Found:199.0946。
实施例6
制备2-甲硫基-4-(3-氯苯基)丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入1-氯-3-(3-碘丁基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(36mg,84%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.19(d,J=7.9Hz,2H),7.17–7.13(m,1H),7.07(d,J=7.4Hz,1H),2.72(t,J=8.0Hz,2H),2.64(h,J=6.8Hz,1H),2.06(s,3H),1.90–1.80(m,1H),1.77(m,1H),1.34–1.27(m,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ143.98,134.11,129.55,128.50,126.57,126.00,40.44,37.68,32.87,20.83,12.77。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=214(M+,25),166(32),151(15),131(100),89(32),75(46)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C11H15ClSNa[M+Na]+:237.0475,Found:237.0468。
实施例7
制备2-甲硫基-4-对甲硫基苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入(4-(3-碘丁基)苯基)(甲基)硫烷(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(28mg,62%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.23–7.16(m,2H),7.15–7.07(m,2H),2.70(m,2H),2.64(h,J=6.8Hz,1H),2.46(s,3H),2.06(s,3H),1.85(m,1H),1.79–1.68(m,1H),1.30(d,J=6.8Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ139.08,135.32,128.92,127.24,40.45,37.92,32.64,20.81,16.35,12.80。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=226(M+,87),178(96),137(88),131(100),89(38),75(28),61(12)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C12H18S2Na[M+Na]+:249.0742,Found:249.0738。
实施例8
制备2-(3-甲硫基丁基)萘,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入2-(3-碘丁基)萘(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(41mg,90%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.88–7.75(m,3H),7.65(s,1H),7.45(m,2H),7.36(m,1H),2.93(m,2H),2.71(h,J=6.8Hz,1H),2.09(s,3H),2.03–1.91(m,1H),1.89(m,1H),1.36(d,J=6.9Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ139.42,133.62,131.99,127.89,127.56,127.36,127.24,126.39,125.88,125.11,40.55,37.84,33.34,20.86,12.85。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=230(M+,70),182(60),167(100),142(90),115(60),89(30),75(40),61(11)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C15H18SNa[M+Na]+:253.1021,Found:253.1016。
实施例9
制备2-甲硫基-4-苯基丁烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv.)和烘干的搅拌子。在充N2下加入(3-碘丁基)苯(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(29mg,81%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.28(t,J=7.5Hz,2H),7.19(m,3H),2.75(t,J=7.6Hz,2H),2.67(h,J=6.8Hz,1H),2.07(s,3H),1.93–1.83(m,1H),1.82–1.74(m,1H),1.32(d,J=6.8Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ141.93,128.37,128.32,125.77,40.55,37.99,33.21,20.80,12.81。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=180(M+,30),132(50),117(100),91(75),75(25)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C11H17S[M+H]+:181.1046,Found:181.1044。
实施例10
制备2-甲硫基十二烷,反应路线如下:
在25mL的试管中加入IPrCuCl(4.87mg,0.01mmol)、NaOtBu(76.8mg,4equiv)和烘干的搅拌子。在充N2下加入2-碘十二烷(0.2mmol,1equiv.),3-(甲硫基)丙酸甲酯(0.6mmol,3equiv.)及二甲苯(2mL)。将所得溶液加热至140℃并在此温度下搅拌反应24小时。然后,冷却到室温。在减压条件下除去溶剂,粗产物通过硅胶柱色谱纯化洗脱液石油醚,分离得无色液体(35.4mg,82%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ2.63(h,J=6.7Hz,1H),2.05(s,3H),1.54(q,J=6.7Hz,1H),1.43(m,1H),1.37(t,J=7.0Hz,2H),1.26(q,J=5.9Hz,17H),0.87(t,J=7.0Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ41.24,36.45,31.85,29.56,29.51,29.26,27.03,22.61,20.68,14.01,13.02。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=216(M+,17),210(7),168(4),111(10),97(18),75(100),57(40)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C13H29S[M+H]+:217.1985,Found:217.1980。
实施例11
制备S-甲基-1,4-二氧杂螺[4.5]癸烷-8-硫代甲酸酯,合成路线如下:
向4mL螺旋盖小瓶中装入IPrCuCl(4.87mg,0.01mmol)、双水杨酰胺乙基钴(3.25mg,0.01mmol)、8-碘-1,4-二氧杂螺[4.5]癸烷(0.2mmol,1equiv.)、3-甲硫基丙酸叔丁酯(0.6mmol,3equiv.)、二甲苯(2mL)、KOtBu(67.2mg,3equiv.)和干燥搅拌子。小瓶由聚四氟乙烯隔膜和酚醛树脂盖封闭,并通过针头与大气相连。然后将小瓶固定在合金板上并放入Parr4560系列高压反应釜(300mL)中。在室温下,用30bar的一氧化碳冲洗高压反应釜。高压反应釜放在加热板上,加热板上装有磁力搅拌和铝块。反应在80℃下加热20小时。之后,将高压反应釜冷却至室温,释放压力。减压除去溶剂后,用硅胶柱层析(洗脱液:PE/EA=500-30:1)分离得无色液体(24.2mg,56%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ3.93(s,4H),2.51(m,1H),2.26(s,3H),2.00–1.87(m,2H),1.87–1.72(m,4H),1.54(m,2H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ202.48,107.84,64.29,50.75,33.80,26.90,11.26。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=216(M+,3),169(3),141(15),99(100),86(35),55(25)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C10H16O3SNa[M+Na]+:239.0712,Found:239.0712。
实施例12
制备4-叔丁基环己基甲酸甲硫酯,合成路线如下:
向4mL螺旋盖小瓶中装入IPrCuCl(4.87mg,0.01mmol)、双水杨酰胺乙基钴(3.25mg,0.01mmol)、1-(叔丁基)-4-碘代环己烷(0.2mmol,1equiv.)、3-甲硫基丙酸叔丁酯(0.6mmol,3equiv.)、二甲苯(2mL)、KOtBu(67.2mg,3equiv.)和干燥搅拌子。小瓶由聚四氟乙烯隔膜和酚醛树脂盖封闭,并通过针头与大气相连。然后将小瓶固定在合金板上并放入Parr 4560系列高压反应釜(300mL)中。在室温下,用30bar的一氧化碳冲洗高压反应釜。高压反应釜放在加热板上,加热板上装有磁力搅拌和铝块。反应在80℃下加热20小时。之后,将高压反应釜冷却至室温,释放压力。减压除去溶剂后,用硅胶柱层析(洗脱液:PE/EA=500-30:1)分离得无色液体(19mg,57%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ2.41(m,1H),2.25(s,3H),2.04–1.94(m,2H),1.88–1.80(m,2H),1.43(m,2H),1.05–0.96(m,3H),0.83(s,9H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ203.60,52.81,47.23,32.36,30.02,27.42,26.54,11.17。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=167(M+,30),139(15),123(8),83(50),57(100)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C12H22OSNa[M+Na]+:237.1284,Found:237.1278。
实施例13
制备2-甲基-4-(2,2-二氟乙氧基)苯基丁酸甲硫酯,合成路线如下:
向4mL螺旋盖小瓶中装入IPrCuCl(4.87mg,0.01mmol)、双水杨酰胺乙基钴(3.25mg,0.01mmol)、1-(2,2-二氟乙氧基)-4-(3-碘丁基)苯(0.2mmol,1equiv.)、3-甲硫基丙酸叔丁酯(0.6mmol,3equiv.)、二甲苯(2mL)、KOtBu(67.2mg,3equiv.)和干燥搅拌子。小瓶由聚四氟乙烯隔膜和酚醛树脂盖封闭,并通过针头与大气相连。然后将小瓶固定在合金板上并放入Parr4560系列高压反应釜(300mL)中。在室温下,用30bar的一氧化碳冲洗高压反应釜。高压反应釜放在加热板上,加热板上装有磁力搅拌和铝块。反应在80℃下加热20小时。之后,将高压反应釜冷却至室温,释放压力。减压除去溶剂后,用硅胶柱层析(洗脱液:PE/EA=500-30:1)分离得无色液体(26.5mg,46%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.11(t,J=7.7Hz,2H),6.92–6.66(m,2H),6.06(m,1H),4.15(m,2H),2.66(h,J=7.0Hz,1H),2.56(q,J=7.6Hz,2H),2.36–2.18(m,3H),2.03(m,1H),1.67(m,1H),1.20(t,J=6.9Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ203.84,156.05,135.05,129.46,115.33,114.63,113.73,112.13,67.49,47.81,35.82,32.38,17.82,11.31。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=288(M+,10),241(126),184(24),171(100),104(45),77(12)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C14H18O2F2SNa[M+Na]+:311.0889,Found:311.0880。
实施例14
制备2-甲基-4-对乙氧基苯基丁酸甲硫酯,合成路线如下:
向4mL螺旋盖小瓶中装入IPrCuCl(4.87mg,0.01mmol)、双水杨酰胺乙基钴(3.25mg,0.01mmol)、1-乙氧基-4-(3-碘丁基)苯(0.2mmol,1equiv.)、3-甲硫基丙酸叔丁酯(0.6mmol,3equiv.)、二甲苯(2mL)、KOtBu(67.2mg,3equiv.)和干燥搅拌子。小瓶由聚四氟乙烯隔膜和酚醛树脂盖封闭,并通过针头与大气相连。然后将小瓶固定在合金板上并放入Parr 4560系列高压反应釜(300mL)中。在室温下,用30bar的一氧化碳冲洗高压反应釜。高压反应釜放在加热板上,加热板上装有磁力搅拌和铝块。反应在80℃下加热20小时。之后,将高压反应釜冷却至室温,释放压力。减压除去溶剂后,用硅胶柱层析(洗脱液:PE/EA=500-30:1)分离得无色液体(28.2mg,56%)。
核磁共振氢谱分析结果如下:
1H NMR(600MHz,Chloroform-d)δ7.07(d,J=8.6Hz,2H),6.80(d,J=8.6Hz,2H),4.00(q,J=6.9Hz,2H),2.67(q,J=7.0Hz,1H),2.57–2.52(m,2H),2.29(d,3H),2.02(m,1H),1.71–1.63(m,1H),1.39(t,J=7.0Hz,3H),1.19(d,J=7.0Hz,3H)。
核磁共振碳谱分析结果如下:
13C NMR(151MHz,Chloroform-d)δ203.99,157.19,133.44,129.23,114.39,63.38,47.83,35.93,32.39,17.81,14.86,11.34。
气相色谱-质谱联用仪分析结果如下:
GC-MS(EI,70ev):m/z(%)=252(M+,30),205(30),148(96),120(22),107(100),77(20)。
电喷雾质谱分析结果如下:
HRMS(ESI)calcd for C14H20O2SNa[M+Na]+:275.1076,Found:275.1070。
以上所述仅为本发明的较佳实施例,对本发明而言仅仅是说明性的,而非限制性的。本专业技术人员理解,在本发明权利要求所限定的精神和范围内可对其进行许多改变,修改,甚至等效,但都将落入本发明的保护范围内。
Claims (10)
2.如权利要求1所述的一种卤代烷烃硫醚化的合成方法,其特征在于,所述硫醚化反应中催化剂为醋酸钯、氯化钯、钯碳、碳酸银、四氟硼酸四(乙腈)铜、三氟甲烷磺酸铜、溴三(三苯基膦)铜、氯化铜、乙酸铜、IPrCuCl、柠檬酸铜中的任意一种或几种组合;
所述硫醚化反应中碱为碳酸钾,碳酸钠,碳酸铯,磷酸钾,磷酸氢二钾,叔丁醇锂,叔丁醇钠,叔丁醇钾,甲醇钠,甲醇钾,三乙胺,DBU中的任意一种或几种组合;
所述硫醚化反应中溶剂为二甲基亚砜、DMF、DMA、苯、甲苯、二甲苯、甲醇、苯甲醚、1,2-二氯乙烷,四氢呋喃、乙腈、乙酸乙酯、叔丁醇、乙醇、异丙醇、水中的任意一种或几种组合。
3.如权利要求1所述的一种卤代烷烃硫醚化的合成方法,其特征在于,所述硫醚化反应中催化剂为IPrCuCl,所述硫醚化反应中碱为叔丁醇钠,所述硫醚化反应中溶剂为二甲苯。
4.如权利要求1所述的一种卤代烷烃硫醚化的合成方法,其特征在于,所述硫醚化反应中催化剂的用量为0.002~0.02mmol,所述硫醚化反应温度为25~180℃。
5.如权利要求1所述的一种卤代烷烃硫醚化的合成方法,其特征在于,所述硫醚化反应中催化剂的用量为0.01mmol,所述硫醚化反应温度为140℃。
7.如权利要求1所述的一种卤代烷烃硫代羰基化的合成方法,其特征在于,所述硫代羰基化反应中催化剂为醋酸钯、氯化钯、钯碳、碳酸银、四氟硼酸四(乙腈)铜、三氟甲烷磺酸铜、溴三(三苯基膦)铜、氯化铜、乙酸铜、IPrCuCl、柠檬酸铜、双乙酰基水杨酸钴、双水杨酰胺乙基钴、乙酸钴、乙酰丙酮钴、乙酰丙酮铁、乙酰丙酮亚铁、三氟甲磺酸铁中的任意一种或几种组合;
所述硫代羰基化反应中碱为碳酸钾,碳酸钠,碳酸铯,磷酸钾,磷酸氢二钾,叔丁醇锂,叔丁醇钠,叔丁醇钾,甲醇钠,甲醇钾,三乙胺,DBU中的任意一种或几种组合;
所述硫代羰基化反应中溶剂为二甲基亚砜、DMF、DMA、苯、甲苯、二甲苯、甲醇、苯甲醚、1,2-二氯乙烷,四氢呋喃、乙腈、乙酸乙酯、叔丁醇、乙醇、异丙醇、水中的任意一种或几种组合。
8.如权利要求1所述的一种卤代烷烃硫代羰基化的合成方法,其特征在于,所述硫代羰基化反应中催化剂为IPrCuCl和双水杨酰胺乙基钴,所述硫代羰基化反应中碱为叔丁醇钾,所述硫代羰基化反应中溶剂为二甲苯,所述IPrCuCl和双水杨酰胺乙基钴的用量均为0.01mmol。
9.如权利要求1所述的一种卤代烷烃硫代羰基化的合成方法,其特征在于,所述硫代羰基化反应温度为25~180℃,CO的压强为1~40bar。
10.如权利要求1所述的一种卤代烷烃硫代羰基化的合成方法,其特征在于,所述硫代羰基化反应温度为80℃,CO的压强为30bar。
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