CN113087684B - 二(三苯基膦)羰基一水合二氯化钌的应用 - Google Patents
二(三苯基膦)羰基一水合二氯化钌的应用 Download PDFInfo
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- CN113087684B CN113087684B CN202110308135.4A CN202110308135A CN113087684B CN 113087684 B CN113087684 B CN 113087684B CN 202110308135 A CN202110308135 A CN 202110308135A CN 113087684 B CN113087684 B CN 113087684B
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- China
- Prior art keywords
- thiomorpholine
- triphenylphosphine
- compound
- bis
- ruthenium dichloride
- Prior art date
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- -1 bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate Chemical compound 0.000 title claims abstract description 96
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 40
- 239000003960 organic solvent Substances 0.000 claims abstract description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 117
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 114
- 150000001875 compounds Chemical class 0.000 claims description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 76
- 238000001816 cooling Methods 0.000 claims description 44
- 239000007788 liquid Substances 0.000 claims description 39
- 239000003208 petroleum Substances 0.000 claims description 38
- 238000002390 rotary evaporation Methods 0.000 claims description 37
- 239000003480 eluent Substances 0.000 claims description 36
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- OYLTYHXSZIVBOZ-UHFFFAOYSA-N 4-benzylthiomorpholine Chemical compound C=1C=CC=CC=1CN1CCSCC1 OYLTYHXSZIVBOZ-UHFFFAOYSA-N 0.000 claims description 10
- 229940125782 compound 2 Drugs 0.000 claims description 9
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 4
- 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 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- PWWDEQSIYFSCSF-UHFFFAOYSA-N 4-[(3-bromophenyl)methyl]thiomorpholine Chemical compound BrC1=CC=CC(CN2CCSCC2)=C1 PWWDEQSIYFSCSF-UHFFFAOYSA-N 0.000 claims description 4
- IRWWSBXYHHHRLU-UHFFFAOYSA-N 4-[(3-iodophenyl)methyl]thiomorpholine Chemical compound IC1=CC=CC(CN2CCSCC2)=C1 IRWWSBXYHHHRLU-UHFFFAOYSA-N 0.000 claims description 4
- PGGZEZVGUUKGKB-UHFFFAOYSA-N 4-[(3-methylphenyl)methyl]thiomorpholine Chemical compound CC1=CC=CC(CN2CCSCC2)=C1 PGGZEZVGUUKGKB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 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
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- LPKCVVMDZKZBOB-UHFFFAOYSA-N 4-(2-methoxyethyl)thiomorpholine Chemical compound COCCN1CCSCC1 LPKCVVMDZKZBOB-UHFFFAOYSA-N 0.000 claims description 3
- LCLLBJKQZSUIPI-UHFFFAOYSA-N 4-(2-phenylethyl)thiomorpholine Chemical compound C1CSCCN1CCC1=CC=CC=C1 LCLLBJKQZSUIPI-UHFFFAOYSA-N 0.000 claims description 3
- GNINBUWYUZONOO-UHFFFAOYSA-N 4-(3-phenylpropyl)thiomorpholine Chemical compound C=1C=CC=CC=1CCCN1CCSCC1 GNINBUWYUZONOO-UHFFFAOYSA-N 0.000 claims description 3
- WVQOMHQCPFZSHI-UHFFFAOYSA-N 4-(cyclohexylmethyl)thiomorpholine Chemical compound C(C1CCCCC1)N1CCSCC1 WVQOMHQCPFZSHI-UHFFFAOYSA-N 0.000 claims description 3
- XXDYICWCXNQCSJ-UHFFFAOYSA-N 4-(naphthalen-1-ylmethyl)thiomorpholine Chemical compound C=1C=CC2=CC=CC=C2C=1CN1CCSCC1 XXDYICWCXNQCSJ-UHFFFAOYSA-N 0.000 claims description 3
- XDBTZKGSODUZAM-UHFFFAOYSA-N 4-(pyridin-2-ylmethyl)thiomorpholine Chemical compound C=1C=CC=NC=1CN1CCSCC1 XDBTZKGSODUZAM-UHFFFAOYSA-N 0.000 claims description 3
- PSGMZFKEMBBBOA-UHFFFAOYSA-N 4-[(2-methylphenyl)methyl]thiomorpholine Chemical compound CC1=CC=CC=C1CN1CCSCC1 PSGMZFKEMBBBOA-UHFFFAOYSA-N 0.000 claims description 3
- NCZPEABQJMHRAM-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]thiomorpholine Chemical compound FC1=CC=CC(CN2CCSCC2)=C1 NCZPEABQJMHRAM-UHFFFAOYSA-N 0.000 claims description 3
- YCZICELDYBXAHR-UHFFFAOYSA-N 4-[(3-methoxyphenyl)methyl]thiomorpholine Chemical compound COC1=CC=CC(CN2CCSCC2)=C1 YCZICELDYBXAHR-UHFFFAOYSA-N 0.000 claims description 3
- JPOACEZEVCRRPB-UHFFFAOYSA-N 4-[(4-methylphenyl)methyl]thiomorpholine Chemical compound C1=CC(C)=CC=C1CN1CCSCC1 JPOACEZEVCRRPB-UHFFFAOYSA-N 0.000 claims description 3
- RCCWZWJLILTAEV-UHFFFAOYSA-N 4-[[3-(trifluoromethyl)phenyl]methyl]thiomorpholine Chemical compound FC(F)(F)C1=CC=CC(CN2CCSCC2)=C1 RCCWZWJLILTAEV-UHFFFAOYSA-N 0.000 claims description 3
- KFAMTQFKYUXQKV-UHFFFAOYSA-N 4-benzyl-1,4-thiazinane 1,1-dioxide Chemical compound C1CS(=O)(=O)CCN1CC1=CC=CC=C1 KFAMTQFKYUXQKV-UHFFFAOYSA-N 0.000 claims description 3
- NLNHXTDJCGWOGR-UHFFFAOYSA-N 4-benzyl-2-ethylthiomorpholine Chemical compound CCC1CN(CCS1)CC2=CC=CC=C2 NLNHXTDJCGWOGR-UHFFFAOYSA-N 0.000 claims description 3
- QHTYJNLRRWTKON-UHFFFAOYSA-N 4-butylthiomorpholine Chemical compound CCCCN1CCSCC1 QHTYJNLRRWTKON-UHFFFAOYSA-N 0.000 claims description 3
- ZECOPOAPYOOZHM-UHFFFAOYSA-N 4-propyl-2,3-dihydro-1,4-benzothiazine Chemical compound C1=CC=C2N(CCC)CCSC2=C1 ZECOPOAPYOOZHM-UHFFFAOYSA-N 0.000 claims description 3
- MGCDHLCYJZAAKL-UHFFFAOYSA-N 4-propylthiomorpholine Chemical compound CCCN1CCSCC1 MGCDHLCYJZAAKL-UHFFFAOYSA-N 0.000 claims description 3
- MMQGADOBCJMQAT-UHFFFAOYSA-N CC1(C)SCCN(CC2=CC=CC=C2)C1 Chemical compound CC1(C)SCCN(CC2=CC=CC=C2)C1 MMQGADOBCJMQAT-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- ZGZUKKMFYTUYHA-HNNXBMFYSA-N (2s)-2-amino-3-(4-phenylmethoxyphenyl)propane-1-thiol Chemical compound C1=CC(C[C@@H](CS)N)=CC=C1OCC1=CC=CC=C1 ZGZUKKMFYTUYHA-HNNXBMFYSA-N 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 2
- ICBANYDRDPPZDR-UHFFFAOYSA-N 4-(thiophen-2-ylmethyl)thiomorpholine Chemical compound C=1C=CSC=1CN1CCSCC1 ICBANYDRDPPZDR-UHFFFAOYSA-N 0.000 claims description 2
- KRHUBMQFRIQXCZ-UHFFFAOYSA-N 4-[(3,5-dimethoxyphenyl)methyl]thiomorpholine Chemical compound COC1=CC(OC)=CC(CN2CCSCC2)=C1 KRHUBMQFRIQXCZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- GSBHDOKAOPOXNC-UHFFFAOYSA-N CC(CN1CCSCC1)=C=O Chemical compound CC(CN1CCSCC1)=C=O GSBHDOKAOPOXNC-UHFFFAOYSA-N 0.000 claims description 2
- YSJSGZISGVDKKI-UHFFFAOYSA-N CCCN(CCC)C(C=C1)=CC=C1SC(C=C1)=CC=C1[N+]([O-])=O Chemical compound CCCN(CCC)C(C=C1)=CC=C1SC(C=C1)=CC=C1[N+]([O-])=O YSJSGZISGVDKKI-UHFFFAOYSA-N 0.000 claims description 2
- KYRYJZBMZCQFIN-UHFFFAOYSA-N CCCN(CCC)c1cccc(SC)c1 Chemical compound CCCN(CCC)c1cccc(SC)c1 KYRYJZBMZCQFIN-UHFFFAOYSA-N 0.000 claims description 2
- NJQCVMQBRUNMQQ-UHFFFAOYSA-N FC1=CC(F)=CC(CN2CCSCC2)=C1 Chemical compound FC1=CC(F)=CC(CN2CCSCC2)=C1 NJQCVMQBRUNMQQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000002815 homogeneous catalyst Substances 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- CHOFGKGPPXLMRB-UHFFFAOYSA-N 6-(2-methylsulfanylethyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine Chemical compound CSCCN1CCc2ccsc2C1 CHOFGKGPPXLMRB-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 abstract description 17
- 238000010438 heat treatment Methods 0.000 abstract description 10
- MGJURKDLIJVDEO-UHFFFAOYSA-N formaldehyde;hydrate Chemical compound O.O=C MGJURKDLIJVDEO-UHFFFAOYSA-N 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 abstract 1
- 230000035484 reaction time Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 120
- 230000015572 biosynthetic process Effects 0.000 description 43
- 238000003786 synthesis reaction Methods 0.000 description 43
- 239000007791 liquid phase Substances 0.000 description 41
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 31
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- 239000003054 catalyst Substances 0.000 description 13
- 235000019445 benzyl alcohol Nutrition 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 8
- 229910052707 ruthenium Inorganic materials 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
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- 230000029936 alkylation Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 229910000510 noble metal Inorganic materials 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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- 238000001914 filtration Methods 0.000 description 4
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- WBBPRCNXBQTYLF-UHFFFAOYSA-N 2-methylthioethanol Chemical compound CSCCO WBBPRCNXBQTYLF-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- IIGNZLVHOZEOPV-UHFFFAOYSA-N 3-Methoxybenzyl alcohol Chemical compound COC1=CC=CC(CO)=C1 IIGNZLVHOZEOPV-UHFFFAOYSA-N 0.000 description 1
- JJCKHVUTVOPLBV-UHFFFAOYSA-N 3-Methylbenzyl alcohol Chemical compound CC1=CC=CC(CO)=C1 JJCKHVUTVOPLBV-UHFFFAOYSA-N 0.000 description 1
- QDHRSLFSDGCJFX-UHFFFAOYSA-N 3-fluorobenzyl alcohol Chemical compound OCC1=CC=CC(F)=C1 QDHRSLFSDGCJFX-UHFFFAOYSA-N 0.000 description 1
- QGCCNWSXJHGUNL-UHFFFAOYSA-N 3-iodo-benzyl alcohol Chemical compound OCC1=CC=CC(I)=C1 QGCCNWSXJHGUNL-UHFFFAOYSA-N 0.000 description 1
- JGSIAOZAXBWRFO-UHFFFAOYSA-N 3-methylsulfanyl-1-phenyl-4,5-dihydrobenzo[g]indazole Chemical compound C1CC2=CC=CC=C2C2=C1C(SC)=NN2C1=CC=CC=C1 JGSIAOZAXBWRFO-UHFFFAOYSA-N 0.000 description 1
- KCHLDNLIJVSRPK-UHFFFAOYSA-N 3-methylsulfanylaniline Chemical compound CSC1=CC=CC(N)=C1 KCHLDNLIJVSRPK-UHFFFAOYSA-N 0.000 description 1
- JYHGFCBHXIDYOU-UHFFFAOYSA-N 4,4,6-trimethyl-1,3-oxazinane-2-thione Chemical compound CC1CC(C)(C)NC(=S)O1 JYHGFCBHXIDYOU-UHFFFAOYSA-N 0.000 description 1
- ZBPKGHOGUVVDLF-UHFFFAOYSA-N 4-(4-nitrophenyl)sulfanylaniline Chemical compound C1=CC(N)=CC=C1SC1=CC=C([N+]([O-])=O)C=C1 ZBPKGHOGUVVDLF-UHFFFAOYSA-N 0.000 description 1
- OHHHTUXVBNGOGI-UHFFFAOYSA-N 4-(trifluoromethylsulfanyl)aniline Chemical compound NC1=CC=C(SC(F)(F)F)C=C1 OHHHTUXVBNGOGI-UHFFFAOYSA-N 0.000 description 1
- DJXQYJXQDQXQTG-UHFFFAOYSA-N 4-hydroxythiomorpholine Chemical compound ON1CCSCC1 DJXQYJXQDQXQTG-UHFFFAOYSA-N 0.000 description 1
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 1
- KRDOFMHJLWKXIU-UHFFFAOYSA-N ID11614 Chemical compound C1CNCCN1C1=NSC2=CC=CC=C12 KRDOFMHJLWKXIU-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-methylmorpholine Substances CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
- BXEHKCUWIODEDE-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]methanol Chemical compound OCC1=CC=CC(C(F)(F)F)=C1 BXEHKCUWIODEDE-UHFFFAOYSA-N 0.000 description 1
- 238000005865 alkene metathesis reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- HNXIGCWJKNNFCH-UHFFFAOYSA-L carbon monoxide dichlororuthenium triphenylphosphane Chemical compound [O+]#[C-].Cl[Ru]Cl.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 HNXIGCWJKNNFCH-UHFFFAOYSA-L 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- WIWBLJMBLGWSIN-UHFFFAOYSA-L dichlorotris(triphenylphosphine)ruthenium(ii) Chemical compound [Cl-].[Cl-].[Ru+2].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 WIWBLJMBLGWSIN-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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Abstract
本发明提供了一种二(三苯基膦)羰基一水合二氯化钌,所述方法为:将三苯基膦加入有机溶剂A中,升温至50~100℃使其溶解,得到溶液A;将三氯化钌加入有机溶剂B中,溶解,得到溶液B;然后将溶液B与质量分数为37%的甲醛水溶液依次快速加入到所述溶液A中,80~130℃反应0.5h~2h;所得反应液A经后处理A,得二(三苯基膦)羰基一水合二氯化钌。与Colt等人合成方法相比,本发明能很好的避免强酸的使用,减少实验过程中对操作人员的伤害,同时反应时间大幅度缩短,以及实验后处理简洁,提高了实验效率。
Description
(一)技术领域
本发明涉及一种含三苯基膦配体的钌催化剂,二(三苯基膦)羰基一水合二氯化钌的应用。
(二)背景技术
贵金属催化剂在催化反应中扮演着越来越重要的角色。其中由于钌金属外层电子结构特点,在周期表中所有元素中具有最多氧化价,每个电子结构又具有多种几何结构,这为合成多种钌配合物提供了基础。又由于钌催化剂优异的催化性能,相对于其他贵金属价格便宜的特点,使其发展更加迅速、应用更广。目前,钌催化剂主要应用的领域有(不对称)催化加氢、烯烃复分解、碳烷基化、氮烷基化等。而在醇作为反应物的碳烷基化或氮烷基化反应过程中,只有无污染的水做为副产物产生,符合绿色发展的要求,所以吸引了越来越多研究者的兴趣。这对于催化剂的合成和研究提出的更高的要求。自从1981年Grigg等人第一次报道了通过借氢机理,醇在钌催化剂下直接氮烷基化合成胺以后。越来越多的贵金属催化剂被用于此研究方向。然而由于硫原子对贵金属明显的毒化作用,几乎很少有报道贵金属催化含硫化合物。但是含硫胺化合物在药物和天然产物中占有重要地位,因此寻找一种能催化含硫化合物的催化剂显得尤为重要。
(三)发明内容
本发明所要解决的问题是在提供一种钌催化剂的合成方法,及其该催化剂在含硫胺化物氮烷基化的应用。
为了实现上述目的,本发明采用如下技术方案:
本发明二(三苯基膦)羰基一水合二氯化钌是用一种新方法制备的,所述方法为:
将三苯基膦加入有机溶剂A中,升温至50~100℃(优选为100℃)使其溶解,得到溶液A;将三氯化钌加入有机溶剂B中,溶解,得到溶液B;然后将溶液B与质量分数为37%的甲醛水溶液依次快速加入到所述溶液A中,80~130℃(优选为120℃)反应0.5h~2h(最优选为0.8h);所得反应液A经后处理A,得二(三苯基膦)羰基一水合二氯化钌;所述三氯化钌与三苯基膦的物质的量之比为1:1~6(优选1:3),所述质量分数为37%的甲醛水溶液的体积以三氯化钌的物质的量计为5~15mL/mmol(优选10mL/mmol);所述有机溶剂A与有机溶剂B都是有机溶剂,这里用A、B只是为了区分不同阶段加入的有机溶剂。优选有机溶剂A与有机溶剂B为相同溶剂。
进一步,所述的有机溶剂A和有机溶剂B分别独立为乙醇、乙腈、乙二醇甲醚或甲苯,优选为乙二醇甲醚。
优选地,所述的有机溶剂A的体积以三苯基膦的物质的量计为5~15mL/mmol,最优选为6.7mL/mmol。
优选地,所述的有机溶剂B的体积以三氯化钌的物质的量计为5~15mL/mmol,最优选为10mL/mmol。
进一步,所述后处理A为:将所述反应液A冷却,抽滤,空气干燥,即得所述二(三苯基膦)羰基一水合二氯化钌。
优选地,所述冷却的温度为20℃~50℃,最优选为25℃;所述空气干燥温度为40℃~100℃,干燥时间2h~10h,最优选为50℃,8h。
本发明的主要目的是提出了一种二(三苯基膦)羰基一水合二氯化钌作为均相催化剂在含硫胺化物的氮烷基化反应中的应用。
进一步,所述的应用为:将化合物1和化合物2溶于有机溶剂D中,加入二(三苯基膦)羰基一水合二氯化钌,80℃~160℃(优选为140℃)反应2h~10h(优选为6h),所得反应液B经后处理B,得到式3所示化合物;化合物1与化合物2的物质的量之比为0.5~10:1,最优选为3:1;所述二(三苯基膦)羰基一水合二氯化钌的用量为0.2~5mol/100mol化合物2;
式1和3中,R1选自下列之一:苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2-甲氧基苯基、3-甲氧基苯基、4-甲氧基苯基、4-联二苯基、2-氟苯基、3-氟苯基、4-氟苯基、2-溴苯基、3-溴苯基、4-溴苯基、2-碘苯基、3-碘苯基、4-碘苯基、2-三氟甲基苯基、3-三氟甲基苯基、4-三氟甲基苯基、3,5-二甲氧基苯基、3,5-二氟苯基、2-吡啶基、2-噻吩基、1-萘基、甲基、乙基、丙基、丁基、戊基、己基、环丙甲基、环丁甲基、环戊甲基、环己甲基、氧杂环丁基、2-四氢呋喃甲基、金刚烷甲基、环丙基、环丁基、环戊基、环己基、苯甲基、苯乙基、苯丙基、3-羟基丙基、4-羟基丁基、3-甲基丁基、3,3-二甲基丁基、甲氧基甲基、甲氧基丙基、甲硫基甲基、1-乙酮基;
式2中R2与R3连接成环,式2所示结构式选自下列之一:
作为优选,式1和3中,R1为苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2-甲氧基苯基、3-甲氧基苯基、2-氟苯基、3-氟苯基、2-溴苯基、3-溴苯基、2-碘苯基、3-碘苯基、3-三氟甲基苯基、3,5-二甲氧基苯基、3,5-二氟苯基、2-吡啶基、2-噻吩基、1-萘基、乙基、丙基、丁基、戊基、环戊基、环己基、苯甲基、苯乙基、甲氧基甲基、甲氧基丙基、甲硫基甲基或1-乙酮基。
进一步优选,所述化合物3为下列之一:
(1)4-苄基硫代吗啉
(2)4-(2-甲基苄基)硫代吗啉
(3)4-(3-甲基苄基)硫代吗啉
(4)4-(4-甲基苄基)硫代吗啉
(5)4-(3-甲氧基苄基)硫代吗啉
(6)4-(3-氟苄基)硫代吗啉
(7)4-(3-溴苄基)硫代吗啉
(8)4-(3-碘苄基)硫代吗啉
(9)4-(3-三氟甲基苄基)硫代吗啉
(10)4-(3,5-二甲氧基苄基)硫代吗啉
(11)4-(3,5-二氟苄基)硫代吗啉
(12)4-(吡啶-2-基甲基)硫代吗啉
(13)4-(噻吩-2-基甲基)硫代吗啉
(14)4-(萘-1-基甲基)硫代吗啉
(15)4-丙基硫代吗啉
(16)4-丁基硫代吗啉
(17)4-(环己基甲基)硫代吗啉
(18)4-苯乙基硫代吗啉
(19)4-(3-苯丙基)硫代吗啉
(20)4-(2-甲氧基乙基)硫代吗啉
(21)4-(2-羰基丙基)硫代吗啉
(22)4-苄基-2-乙基硫代吗啉
(23)4-苄基-2,2-二甲基硫代吗啉
(24)4-丙基-3,4-二氢-2H-苯并[b][1,4]噻嗪
(25)4-苄硫基吗啉1,1-二氧化物
(26)6-(2-(甲硫基)乙基)-4,5,6,7-四氢噻吩并[2,3-c]吡啶
(27)3-(4-丙基哌嗪-1-基)苯并[d]异噻唑
(28)N,N-二丙基-4-((三氟甲基)硫代)苯胺
(29)3-(甲硫基)-N,N-二丙基苯胺
(30)4-((4-硝基苯基)硫基)-N,N-二丙基苯胺。
反应体系温度大于溶剂沸点时,优选所述反应在耐压管中进行。
进一步,所述有机溶剂D为四氢呋喃、二氧六环、甲苯、二甲苯、N,N-二甲基甲酰胺、二甲基亚砜或叔戊醇,最优选为甲苯。
优选地,所述有机溶剂D的体积以所述胺类化合物2的物质的量计为0.1~5mL/mmol,最优选为1mL/mmol。
进一步,所述后处理B为:将所述反应液B冷却至室温,脱溶,利用快速制备液相色谱仪纯化,以体积比为2~20:100(优选为5:100)的乙酸乙酯与石油醚的混合溶液为洗脱液进行洗脱,收集含目标化合物的洗脱液,减压旋蒸得到式3所示化合物。
与现有技术相比,本发明的有益效果在于:
相比于其他钌催化剂而言,二(三苯基膦)羰基一水合二氯化钌在催化醇类化合物和胺类化合物的反应中催化活性更高。
(四)附图说明
图1.二(三苯基膦)羰基一水合二氯化钌单晶结构。
(五)具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例,对本发明进一步详细说明。在一些专业术语的使用上,为了使普通读者更好地理解,本发明提出了很多技术细节。但是,即使没有这些技术细节和对以下各实施方式的一些改变和修改,也可以实现本申请所要求保护的技术方案。
下述实施例中收率的计算公式(不考虑纯度)为:
Y=(m产量/M产物)/N原料
m产量为包括杂质的产物的质量,M产物为目标产物的相对分子质量,N原料为物质的量较小的反应物的物质的量。
以下实施例中所用快速制备液相色谱仪为Biotage公司的纯化仪,型号是BiotageIsolera One。
实施例1:二(三苯基膦)羰基一水合二氯化钌的合成
将3.16g(12mmol)三苯基膦加入到80mL乙二醇甲醚中,升温至100℃使其溶解形成三苯基膦溶液;将1.04g(4mmol)水合三氯化钌加入到40mL乙二醇甲醚中,搅拌均匀使其溶解形成三氯化钌溶液;然后与40mL质量分数为37%的甲醛水溶液依次快速加入到三苯基膦溶液中;将反应升温至120℃,反应0.8h;最后将上述反应液冷却,抽滤,空气干燥,即获得2.82g二(三苯基膦)羰基一水合二氯化钌固体,收率为95%,液相纯度98%。通过单晶X-射线衍射分析,确定催化剂结构如图1所示。
实施例2:二(三苯基膦)羰基一水合二氯化钌的合成
将3.16g(12mmol)三苯基膦加入到60mL乙醇中,升温至50℃使其溶解形成三苯基膦溶液;将0.5g(2mmol)水合三氯化钌加入到30mL乙醇中,搅拌均匀使其溶解形成三氯化钌溶液;然后与10mL质量分数为37%的甲醛水溶液依次快速加入到三苯基膦溶液中;将反应升温至80℃,反应2h;最后将上述反应液冷却,抽滤,空气干燥,即获得1.19g二(三苯基膦)羰基一水合二氯化钌固体,收率为40%,液相纯度96%。
实施例3:二(三苯基膦)羰基一水合二氯化钌的合成
将3.16g(12mmol)三苯基膦加入到180mL乙腈中,升温至80℃使其溶解形成三苯基膦溶液;将3g(12mmol)水合三氯化钌加入到60mL乙腈中,搅拌均匀使其溶解形成三氯化钌溶液;然后与180mL质量分数为37%的甲醛水溶液依次快速加入到三苯基膦溶液中;将反应升温至90℃,反应0.5h;最后将上述反应液冷却,抽滤,空气干燥,即获得3.12g二(三苯基膦)羰基一水合二氯化钌固体,收率为30%,液相纯度96%。
实施例4:二(三苯基膦)羰基一水合二氯化钌的合成
将3.16g(12mmol)三苯基膦加入到80mL甲苯中,升温至100℃使其溶解形成三苯基膦溶液;、将1.04g(4mmol)水合三氯化钌加入到40mL甲苯中,搅拌均匀使其溶解形成三氯化钌溶液;然后与40mL质量分数为37%的甲醛水溶液依次快速加入到三苯基膦溶液中;将反应升温至130℃,反应1.2h;最后将上述反应液冷却,抽滤,空气干燥,即获得2.73g二(三苯基膦)羰基一水合二氯化钌固体,收率为92%,液相纯度97%。
实施例5:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.183g式3所示化合物,收率95%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.38–7.31(m,4H),7.30–7.25(m,1H),3.54(s,2H),2.77–2.65(m,8H).13C NMR(126MHz,CDCl3)δ138.01,129.00(2C),128.20(2C),127.05,63.64,54.87(2C),27.97(2C).HRMS(ES+)m/z calcd for C11H15NS([M+H]+)194.0098,found194.0999.
实施例6:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(9.4mg)的三(三苯基膦)二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.023g式3所示化合物,收率12%,液相纯度99%。
实施例7:4-苄基硫代吗啉的合成
将苄醇(0.108g,1mmol)和硫代吗啉(0.103g,1mmol)溶于0.1mL四氢呋喃中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,80℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.088g式3所示化合物,收率46%,液相纯度99%。
实施例8:4-苄基硫代吗啉的合成
将苄醇(1.08g,10mmol)和硫代吗啉(0.103g,1mmol)溶于1mL二甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.164g式3所示化合物,收率85%,液相纯度99%。
实施例9:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于5mL二氧六环中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,80℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.106g式3所示化合物,收率55%,液相纯度99%。
实施例10:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL N,N-二甲基甲酰胺中,并与0.002mmol(1.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,160℃反应2h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.073g式3所示化合物,收率38%,液相纯度99%。
实施例11:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL二甲基亚砜中,并与0.05mmol(37.2mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应10h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.121g式3所示化合物,收率63%,液相纯度99%。
实施例12:4-苄基硫代吗啉的合成
将苄醇(0.324g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL叔戊醇中,并与0.05mmol(37.2mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应10h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.150g式3所示化合物,收率78%,液相纯度99%。
实施例13:4-(2-甲基苄基)硫代吗啉的合成
将2-甲基苄醇(0.360g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.168g式3所示化合物,收率81%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.30–7.24(m,1H),7.22–7.13(m,3H),3.48(s,2H),2.73(dd,J=6.3,2.8Hz,4H),2.67(dd,J=5.4,4.0Hz,4H),2.37(s,3H).13C NMR(126MHz,CDCl3)δ137.58,136.19,130.31,129.83,127.10,125.46,61.56,54.99(2C),28.15(2C),19.22.HRMS(ES+)m/z calcd for C12H17NS([M+H]+)208.1154,found 208.1155.
实施例14:4-(3-甲基苄基)硫代吗啉的合成
将3-甲基苄醇(0.360g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.193g式3所示化合物,收率93%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.22(t,J=7.5Hz,1H),7.15–7.07(m,3H),3.50(s,2H),2.76–2.66(m,8H),2.37(s,3H).13C NMR(126MHz,CDCl3)δ137.88,137.83,129.79,128.10,127.84,126.16,63.69,54.92(2C),27.97(2C),21.37.HRMS(ES+)m/z calcd for C12H17NS([M+H]+)208.1154,found 208.1158.
实施例15:4-(4-甲基苄基)硫代吗啉的合成
将4-甲基苄醇(0.360g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.194g式3所示化合物,收率94%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.21(d,J=7.9Hz,2H),7.14(d,J=7.9Hz,2H),3.50(s,2H),2.75–2.65(m,8H),2.38–2.32(m,3H).13C NMR(126MHz,CDCl3)δ136.69,134.88,129.04(2C),128.92(2C),63.41,54.86(2C),28.01(2C),21.07.HRMS(ES+)m/z calcd forC12H17NS([M+H]+)208.1154,found 208.1155.
实施例16:4-(3-甲氧基苄基)硫代吗啉的合成
将3-甲氧基苄醇(0.408g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.178g式3所示化合物,收率80%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.26–7.21(m,1H),6.93–6.88(M,2H),6.84–6.78(m,1H),3.82(s,3H),3.51(s,2H),2.76–2.66(m,8H).13C NMR(126MHz,CDCl3)δ159.68,139.81,129.17,121.30,114.48,112.46,63.57,55.18,54.92(2C),28.01(2C).HRMS(ES+)m/zcalcd for C12H17NOS([M+H]+)224.1104,found 224.1110.
实施例17:4-(3-氟苄基)硫代吗啉的合成
将3-氟苄醇(0.378g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.148g式3所示化合物,收率70%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.37(td,J=7.5,1.7Hz,1H),7.28–7.21(m,1H),7.12(td,J=7.5,1.0Hz,1H),7.06–7.01(m,1H),3.61(s,2H),2.79–2.73(m,4H),2.73–2.67(m,4H).13CNMR(126MHz,CDCl3)δ161.43(d,1JC-F=246.6Hz,1C),131.41(d,3JC-F=4.54Hz,1C),128.82(d,3JC-F=8.3Hz,1C),124.45(d,2JC-F=14.6Hz,1C),123.85(d,4JC-F=3.5Hz,1C),115.27(d,2JC-F=22.2Hz,1C),55.96(d,JC-F=1.76Hz,1C),54.62(2C),27.98(2C).HRMS(ES+)m/zcalcd for C11H14FNS([M+H]+)212.0904,found 212.0909.
实施例18:4-(3-溴苄基)硫代吗啉的合成
将3-溴苄醇(0.561g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.261g式3所示化合物,收率96%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.48(s,1H),7.40–7.36(m,1H),7.23(d,J=7.7Hz,1H),7.18(t,J=7.7Hz,1H),3.47(s,2H),2.73–2.63(m,8H).13C NMR(126MHz,CDCl3)δ140.62,131.72,130.12,129.74,127.41,122.41,62.87,54.81(2C),27.91(2C).HRMS(ES+)m/zcalcd for C11H14BrNS([M+H]+)274.0082,found 274.0092.
实施例19:4-(3-碘苄基)硫代吗啉的合成
将3-碘苄醇(0.702g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.313g式3所示化合物,收率98%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.69(s,1H),7.60(d,J=7.9Hz,1H),7.28(d,J=6.4Hz,1H),7.06(t,J=7.7Hz,1H),3.46(s,2H),2.75–2.65(m,8H).13C NMR(126MHz,CDCl3)δ140.64,137.81,136.21,130.02,128.20,94.41,62.86,54.88(2C),27.95(2C).HRMS(ES+)m/z calcd for C11H14INS([M+H]+)319.9964,found 319.9970.
实施例20:4-(3-三氟甲基苄基)硫代吗啉的合成
将3-三氟甲基苄醇(0.558g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.149g式3所示化合物,收率57%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.79(d,J=7.7Hz,1H),7.64(d,J=7.8Hz,1H),7.53(t,J=7.5Hz,1H),7.34(t,J=7.6Hz,1H),3.68(s,2H),2.73(td,J=9.4,3.4Hz,8H).13C NMR(126MHz,CDCl3)δ137.79,131.73,130.15,128.68(q,2JC-F=30.2Hz,1C),126.81,125.78(q,3JC-F=5.9Hz,1C),124.5(q,1JC-F=274.6Hz,1C),58.90,55.08(2C),28.11(2C).HRMS(ES+)m/z calcd for C12H14F3NS([M+H]+)262.0872,found 262.0879.
实施例21:4-(3,5-二甲氧基苄基)硫代吗啉的合成
将3,5-二甲氧基苄醇(0.504g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.202g式3所示化合物,收率80%,液相纯度99%。1H NMR(500MHz,CDCl3)δ6.50(d,J=2.3Hz,2H),6.37(t,J=2.3Hz,1H),3.80(s,6H),3.47(s,2H),2.70(q,J=6.7Hz,8H).13C NMR(126MHz,CDCl3)δ160.75(2C),140.66,106.78(2C),98.99,63.69,55.30(2C),54.92(2C),28.00(2C).HRMS(ES+)m/z calcd forC13H19NO2S([M+H]+)254.1209,found 254.1217.
实施例22:4-(3,5-二氟苄基)硫代吗啉的合成
将3,5-二氟苄醇(0.432g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.133g式3所示化合物,收率58%,液相纯度99%。1H NMR(500MHz,CDCl3)δ6.92–6.85(m,2H),6.69(tt,J=8.9,2.4Hz,1H),3.49(s,2H),2.76–2.65(m,8H).13C NMR(126MHz,CDCl3)δ163.03(dd,1JC-F=248.2,12.7Hz,2C),142.72(t,3JC-F=8.7Hz,1C),111.19(dd,2JC-F=19.3,5.7Hz,2C),102.40(t,2JC-F=25.4Hz,1C),62.70(t,4JC-F=2.0Hz,1C),54.90(2C),27.98(2C).HRMS(ES+)m/z calcd forC11H13F2NS([M+H]+)230.0810,found 230.0820.
实施例23:4-(吡啶-2-基甲基)硫代吗啉的合成
将2-吡啶甲醇(0.327g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.155g式3所示化合物,收率80%,液相纯度99%。1H NMR(500MHz,CDCl3)δ8.41(m,1H),7.50(m,1H),7.25(d,J=7.7Hz,1H),7.25(d,J=7.7Hz,1H),7.02(m,2H),2.61(m,4H),2.58–2.49(m,4H).13C NMR(126MHz,CDCl3)δ158.00,148.82,135.99,122.70,121.66,64.79,54.67(2C),27.50(2C).HRMS(ES+)m/zcalcd for C10H14N2S([M+H]+)195.0950,found 195.0958.
实施例24:4-(噻吩-2-基甲基)硫代吗啉的合成
将2-噻吩甲醇(0.342g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.173g式3所示化合物,收率87%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.27-7.23(m,1H),6.98–6.94(m,1H),6.93–6.89(m,1H),3.75(s,2H),2.81-2.73(m,4H),2.73–2.65(m,4H).13C NMR(126MHz,CDCl3)δ141.46,126.48,126.08,125.12,57.89,54.61(2C),28.02(2C).HRMS(ES+)m/z calcd for C9H13NS2([M+H]+)200.0562,found 200.0561.
实施例25:4-(萘-1-基甲基)硫代吗啉的合成
将1-萘甲醇(0.474g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.156g式3所示化合物,收率64%,液相纯度99%。1H NMR(500MHz,CDCl3)δ8.31(d,J=8.3Hz,1H),7.91–7.86(m,1H),7.81(dd,J=7.0,2.1Hz,1H),7.57–7.50(m,2H),7.47–7.40(m,2H),3.94(s,2H),2.85–2.78(m,4H),2.71–2.64(m,4H).13C NMR(126MHz,CDCl3)δ133.87,133.79,132.52,128.39,128.01,127.44,125.71,125.62,125.05,124.73,61.84,55.10(2C),28.09(2C).HRMS(ES+)m/zcalcd for C15H17NS([M+H]+)244.1154,found 244.1158.
实施例26:4-丙基硫代吗啉的合成
将正丙醇(0.180g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.126g式3所示化合物,收率87%,液相纯度99%。1H NMR(500MHz,CDCl3)δ2.76–2.62(m,8H),2.35–2.27(m,2H),1.54–1.43(m,2H),0.88(t,J=7.4Hz,3H).13C NMR(126MHz,CDCl3)δ61.35,54.99(2C),27.97(2C),19.58,11.87.HRMS(ES+)m/z calcd for C7H15NS([M+H]+)146.0998,found 146.1000.
实施例27:4-丁基硫代吗啉的合成
将正丁醇(0.222g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.121g式3所示化合物,收率76%,液相纯度99%。1H NMR(500MHz,CDCl3)δ2.76–2.63(m,8H),2.39–2.30(m,2H),1.51–1.40(m,2H),1.35–1.22(m,2H),0.91(t,J=7.3Hz,3H).13C NMR(126MHz,CDCl3)δ59.17,55.03(2C),28.63,27.98(2C),20.71,13.99.HRMS(ES+)m/z calcd for C8H17NS([M+H]+)160.1154,found 160.1158.
实施例28:4-(环己基甲基)硫代吗啉的合成
将环己基甲醇(0.342g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.173g式3所示化合物,收率87%,液相纯度99%。1H NMR(500MHz,CDCl3)δ2.70–2.59(m,8H),2.12(d,J=7.1Hz,2H),1.78–1.61(m,5H),1.52–1.41(m,1H),1.27–1.09(m,3H),0.91–0.77(m,2H).13C NMR(126MHz,CDCl3)δ66.28,55.61(2C),35.03,31.85(2C),27.99(2C),26.79,26.13(2C).HRMS(ES+)m/z calcdfor C11H21NS([M+H]+)200.1467,found 200.1474.
实施例29:4-苯乙基硫代吗啉的合成
将2-苯乙醇(0.360g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.124g式3所示化合物,收率60%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.33–7.27(m,2H),7.25–7.18(m,3H),2.87–2.76(m,6H),2.76–2.70(m,4H),2.69–2.62(m,2H).13C NMR(126MHz,CDCl3)δ140.21,128.69(2C),128.40(2C),126.07,61.19,54.92(2C),33.10,27.97(2C).HRMS(ES+)m/z calcd for C12H17NS([M+H]+)208.1154,found 208.1156.
实施例30:4-(3-苯丙基)硫代吗啉的合成
将3-苯丙醇(0.402g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.133g式3所示化合物,收率60%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.32–7.26(m,2H),7.24–7.16(m,3H),2.76–2.67(m,8H),2.67–2.61(m,2H),2.46–2.38(m,2H),1.87–1.78(m,2H).13C NMR(126MHz,CDCl3)δ142.00,128.35(2C),128.29(2C),125.76,58.55,54.95(2C),33.56,28.12,27.93(2C).HRMS(ES+)m/z calcd for C13H19NS([M+H]+)222.1311,found 222.1317.
实施例31:4-(2-甲氧基乙基)硫代吗啉的合成
将乙二醇甲醚(0.228g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.090g式3所示化合物,收率56%,液相纯度99%。1H NMR(500MHz,CDCl3)δ3.50(t,J=5.6Hz,2H),3.34(s,3H),2.80–2.74(m,4H),2.72–2.67(m,4H),2.61(t,J=5.6Hz,2H).13C NMR(126MHz,CDCl3)δ69.93,58.88,58.56,55.27(2C),27.71(2C).HRMS(ES+)m/z calcd for C7H15NOS([M+H]+)162.0947,found162.0948.
实施例32:4-(2-羰基丙基)硫代吗啉的合成
将2-羟基丙酮(0.222g,3mmol)和硫代吗啉(0.103g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.116g式3所示化合物,收率73%,液相纯度99%。1H NMR(500MHz,CDCl3)δ3.18(s,2H),2.76–2.67(m,8H),2.13(s,3H).13C NMR(126MHz,CDCl3)δ206.66,68.78,55.07(2C),27.73(2C),27.62.HRMS(ES+)m/z calcd forC7H13NOS([M+H]+)160.0791,found 160.0790.
实施例33:4-苄基-2-乙基硫代吗啉的合成
将苄醇(0.324g,3mmol)和2-乙基硫代吗啉(0.131g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.137g式3所示化合物,收率62%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.44–7.20(m,5H),3.55(q,J=13.3Hz,2H),3.08–2.94(m,2H),2.89–2.80(m,2H),2.64–2.53(m,1H),2.42–2.33(m,1H),2.18(dd,J=11.6,9.4Hz,1H),1.64–1.41(m,2H),0.99(t,J=7.5Hz,3H).13C NMR(126MHz,CDCl3)δ138.19,128.89(2C),128.18(2C),126.99,63.44,60.98,54.61,42.75,27.68,26.54,11.53.HRMS(ES+)m/zcalcd for C13H19NS([M+H]+)222.1311,found 222.1319.
实施例34:4-苄基-2,2-二甲基硫代吗啉的合成
将苄醇(0.324g,3mmol)和2-乙基硫代吗啉(0.131g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.150g式3所示化合物,收率68%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.44–7.32(m,5H),3.55(s,2H),2.84–2.65(m,4H),2.44(s,2H),1.37(s,6H).13C NMR(126MHz,CDCl3)δ138.75,128.61(2C),128.16(2C),126.91,67.42,63.35,54.83,39.91,27.89(2C),26.20.HRMS(ES+)m/z calcd for C13H19NS([M+H]+)222.1311,found 222.1319.
实施例35:4-丙基-3,4-二氢-2H-苯并[b][1,4]噻嗪的合成
将正丙醇(0.180g,3mmol)和3,4-二氢-2H-苯并[b][1,4]噻嗪(0.151g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.112g式3所示化合物,收率58%,液相纯度99%。1HNMR(500MHz,CDCl3)δ7.09(d,J=7.6Hz,1H),7.07–7.00(m,1H),6.72(d,J=8.3Hz,1H),6.65(t,J=7.4Hz,1H),3.70–3.61(m,2H),3.33–3.25(m,2H),3.11–3.03(m,2H),1.71(dd,J=15.0,7.5Hz,2H),1.02(td,J=7.3,1.0Hz,3H).13C NMR(126MHz,CDCl3)δ143.21,127.71,125.73,117.26,116.70,112.48,54.25,49.85,25.55,19.47,11.38.HRMS(ES+)m/z calcd for C11H15NS([M+H]+)194.0998,found 194.0996.
实施例36:4-苄硫基吗啉1,1-二氧化物的合成
将苄醇(0.324g,3mmol)和硫代吗啉氧化物(0.135g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.221g式3所示化合物,收率98%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.40–7.20(m,5H),3.65(s,2H),3.13–3.03(m,4H),3.00–2.93(m,4H).13C NMR(126MHz,CDCl3)δ137.18,128.69(2C),128.46(2C),127.56,61.32,51.35(2C),50.44(2C).HRMS(ES+)m/z calcd for C11H15NO2S([M+H]+)226.0896,found226.0903.
将甲硫基乙醇(0.276g,3mmol)和4,5,6,7-四氢噻吩并[2,3-c]吡啶(0.139g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h全。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.153g式3所示化合物,收率72%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.08(d,J=5.1Hz,1H),6.73(d,J=5.1Hz,1H),3.62(t,J=1.5Hz,2H),2.91(t,J=5.4Hz,2H),2.87–2.78(m,4H),2.75–2.70(m,2H),2.16(s,3H).13C NMR(126MHz,CDCl3)δ133.47,133.25,125.12,122.66,57.11,52.90,50.77,31.80,25.30,15.83.HRMS(ES+)m/z calcd for C10H15NS2([M+H]+)214.0719,found 214.0725.
实施例38:3-(4-丙基哌嗪-1-基)苯并[d]异噻唑的合成
将正丙醇(0.180g,3mmol)和3-(哌嗪-1-基)苯并[d]异噻唑(0.219g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.201g式3所示化合物,收率77%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.83(dd,J=59.3,8.2Hz,2H),7.37(dt,J=15.2,7.3Hz,2H),3.60–3.49(m,4H),2.70–2.61(m,4H),2.42–2.33(m,2H),1.61–1.48(m,2H),0.93(t,J=7.4Hz,3H).13C NMR(126MHz,CDCl3)δ163.83,152.64,127.94,127.35,123.81,123.71,120.41,60.63,52.94(2C),49.96(2C),19.89,11.87.HRMS(ES+)m/z calcdfor C14H19N3S([M+H]+)262.1372,found 262.1384.
实施例39:N,N-二丙基-4-((三氟甲基)硫代)苯胺的合成
将正丙醇(0.180g,3mmol)和4-((三氟甲基)硫代)苯胺(0.193g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.258g式3所示化合物,收率93%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.48–7.42(m,2H),6.66–6.59(m,2H),3.34–3.22(m,4H),1.72–1.60(m,4H),0.97(t,J=7.4Hz,6H).13C NMR(126MHz,CDCl3)δ149.98,138.13(2C),129.88(q,1JC-F=309.2Hz,1C),111.90(2C),106.98,52.79(2C),20.28(2C),11.34(2C).HRMS(ES+)m/z calcd for C13H18F3NS([M+H]+)278.1185,found 278.1197.
实施例40:3-(甲硫基)-N,N-二丙基苯胺的合成
将正丙醇(0.180g,3mmol)和3-(甲硫基)苯胺(0.139g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.199g式3所示化合物,收率89%,液相纯度99%。1H NMR(500MHz,CDCl3)δ7.16(t,J=8.0Hz,1H),6.59(d,J=7.0Hz,2H),6.49(dd,J=9.0,2.0Hz,1H),3.34–3.22(m,4H),2.52(s,3H),1.66(dd,J=15.1,7.5Hz,4H),0.98(t,J=7.4Hz,6H).13C NMR(126MHz,CDCl3)δ148.45,138.88,129.44,113.49,110.10,109.08,52.80(2C),20.38(2C),16.01,11.39(2C).HRMS(ES+)m/z calcd for C13H21NS([M+H]+)224.1467,found 224.1476.
实施例41:4-((4-硝基苯基)硫基)-N,N-二丙基苯胺的合成
将正丙醇(0.180g,3mmol)和4-((4-硝基苯基)硫代)苯胺(0.246g,1mmol)溶于1mL甲苯中,并与0.01mmol(7.4mg)的二(三苯基膦)羰基一水合二氯化钌一同加入耐压管中,140℃反应6h。所得反应液冷却至室温,脱溶,快速制备液相色谱仪纯化(乙酸乙酯:石油醚的体积比为5:100),收集含目标化合物的洗脱液,减压旋蒸得到0.182g式3所示化合物,收率55%,液相纯度99%。1H NMR(500MHz,CDCl3)δ8.06–8.00(m,2H),7.39–7.31(m,2H),7.15–7.08(m,2H),6.72–6.66(m,2H),3.34–3.27(m,4H),1.73–1.61(m,4H),0.98(t,J=7.4Hz,6H).13C NMR(126MHz,CDCl3)δ151.86,149.39,144.66,137.09(2C),125.03(2C),123.79(2C),112.61(2C),111.96,52.79(2C),20.35(2C),11.40(2C).HRMS(ES+)m/z calcd forC18H22N2O2S([M+H]+)331.1475,found 331.1483。
Claims (9)
1.一种二(三苯基膦)羰基一水合二氯化钌作为均相催化剂在含硫胺化物的氮烷基化反应中的应用,所述的应用为:将化合物1和化合物2溶于有机溶剂D中,加入二(三苯基膦)羰基一水合二氯化钌,80℃~160℃反应2h~10h,所得反应液B经后处理B,得到式3所示化合物;化合物1与化合物2的物质的量之比为0.5~10:1;所述二(三苯基膦)羰基一水合二氯化钌的用量为0.2~5mol/100mol化合物2;
式1和3中,R1选自下列之一:苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2-甲氧基苯基、3-甲氧基苯基、4-甲氧基苯基、4-联二苯基、2-氟苯基、3-氟苯基、4-氟苯基、2-溴苯基、3-溴苯基、4-溴苯基、2-碘苯基、3-碘苯基、4-碘苯基、2-三氟甲基苯基、3-三氟甲基苯基、4-三氟甲基苯基、3,5-二甲氧基苯基、3,5-二氟苯基、2-吡啶基、2-噻吩基、1-萘基、甲基、乙基、丙基、丁基、戊基、己基、环丙甲基、环丁甲基、环戊甲基、环己甲基、氧杂环丁基、2-四氢呋喃甲基、金刚烷甲基、环丙基、环丁基、环戊基、环己基、苯甲基、苯乙基、苯丙基、3-羟基丙基、4-羟基丁基、3-甲基丁基、3,3-二甲基丁基、甲氧基甲基、甲氧基丙基、甲硫基甲基、1-乙酮基;
式2所示结构式选自下列之一:
2.如权利要求1所述的应用,其特征在于:式1和3中,R1为苯基、2-甲基苯基、3-甲基苯基、4-甲基苯基、2-甲氧基苯基、3-甲氧基苯基、2-氟苯基、3-氟苯基、2-溴苯基、3-溴苯基、2-碘苯基、3-碘苯基、3-三氟甲基苯基、3,5-二甲氧基苯基、3,5-二氟苯基、2-吡啶基、2-噻吩基、1-萘基、乙基、丙基、丁基、戊基、环戊基、环己基、苯甲基、苯乙基、甲氧基甲基、甲氧基丙基、甲硫基甲基或1-乙酮基。
3.如权利要求1所述的应用,其特征在于所述化合物3为下列之一:
4-苄基硫代吗啉、4-(2-甲基苄基)硫代吗啉、4-(3-甲基苄基)硫代吗啉、4-(4-甲基苄基)硫代吗啉、4-(3-甲氧基苄基)硫代吗啉、4-(3-氟苄基)硫代吗啉、4-(3-溴苄基)硫代吗啉、4-(3-碘苄基)硫代吗啉、4-(3-三氟甲基苄基)硫代吗啉、4-(3,5-二甲氧基苄基)硫代吗啉、4-(3,5-二氟苄基)硫代吗啉、4-(吡啶-2-基甲基)硫代吗啉、4-(噻吩-2-基甲基)硫代吗啉、4-(萘-1-基甲基)硫代吗啉、4-丙基硫代吗啉、4-丁基硫代吗啉、4-(环己基甲基)硫代吗啉、4-苯乙基硫代吗啉、4-(3-苯丙基)硫代吗啉、4-(2-甲氧基乙基)硫代吗啉、4-(2-羰基丙基)硫代吗啉、4-苄基-2-乙基硫代吗啉、4-苄基-2,2-二甲基硫代吗啉、4-丙基-3,4-二氢-2H-苯并[b][1,4]噻嗪、4-苄硫基吗啉1,1-二氧化物、6-(2-(甲硫基)乙基)-4,5,6,7-四氢噻吩并[2,3-c]吡啶、3-(4-丙基哌嗪-1-基)苯并[d]异噻唑、N,N-二丙基-4-((三氟甲基)硫代)苯胺、3-(甲硫基)-N,N-二丙基苯胺、4-((4-硝基苯基)硫基)-N,N-二丙基苯胺。
4.如权利要求1所述的应用,其特征在于:所述有机溶剂D为四氢呋喃、二氧六环、甲苯、二甲苯、N,N-二甲基甲酰胺、二甲基亚砜或叔戊醇。
5.如权利要求4所述的应用,其特征在于:所述有机溶剂D为甲苯。
6.如权利要求4所述的应用,其特征在于:所述有机溶剂D的体积以所述化合物2的物质的量计为0.1~5mL/mmol。
7.如权利要求1所述的应用,其特征在于:反应条件为140℃反应6h。
8.如权利要求1所述的应用,其特征在于:所述化合物1与化合物2的物质的量之比为3:1。
9.如权利要求1所述的应用,其特征在于所述后处理B为:将所述反应液B冷却至室温,脱溶,利用快速制备液相色谱仪纯化,以体积比为2~20:100的乙酸乙酯与石油醚的混合溶液为洗脱液进行洗脱,收集含目标化合物的洗脱液,减压旋蒸得到式3所示化合物。
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