CN113201020B - Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate - Google Patents
Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate Download PDFInfo
- Publication number
- CN113201020B CN113201020B CN202110308149.6A CN202110308149A CN113201020B CN 113201020 B CN113201020 B CN 113201020B CN 202110308149 A CN202110308149 A CN 202110308149A CN 113201020 B CN113201020 B CN 113201020B
- Authority
- CN
- China
- Prior art keywords
- triphenylphosphine
- bis
- carbonyl
- ruthenium dichloride
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- -1 bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate Chemical compound 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims description 10
- 239000000243 solution Substances 0.000 claims abstract description 71
- 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 58
- 239000003960 organic solvent Substances 0.000 claims abstract description 25
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims abstract description 22
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000010438 heat treatment Methods 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 110
- 238000006243 chemical reaction Methods 0.000 claims description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 10
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 7
- 238000007605 air drying Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 4
- MGJURKDLIJVDEO-UHFFFAOYSA-N formaldehyde;hydrate Chemical compound O.O=C MGJURKDLIJVDEO-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 2
- 239000002253 acid Substances 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 abstract description 2
- 230000035484 reaction time Effects 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- 150000001875 compounds Chemical class 0.000 description 58
- 230000015572 biosynthetic process Effects 0.000 description 44
- 238000003786 synthesis reaction Methods 0.000 description 44
- 239000003208 petroleum Substances 0.000 description 38
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 33
- 239000007788 liquid Substances 0.000 description 30
- 239000007791 liquid phase Substances 0.000 description 30
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 28
- 238000002390 rotary evaporation Methods 0.000 description 22
- 239000003054 catalyst Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 235000019445 benzyl alcohol Nutrition 0.000 description 11
- OYLTYHXSZIVBOZ-UHFFFAOYSA-N 4-benzylthiomorpholine Chemical compound C=1C=CC=CC=1CN1CCSCC1 OYLTYHXSZIVBOZ-UHFFFAOYSA-N 0.000 description 9
- 238000004262 preparative liquid chromatography Methods 0.000 description 9
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 8
- 238000005804 alkylation reaction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 229910052707 ruthenium Inorganic materials 0.000 description 7
- 230000029936 alkylation Effects 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 229910000510 noble metal Inorganic materials 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- HBLYPCZZIIUFRO-UHFFFAOYSA-N 2-ethylthiomorpholine Chemical compound CCC1CNCCS1 HBLYPCZZIIUFRO-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- LPKCVVMDZKZBOB-UHFFFAOYSA-N 4-(2-methoxyethyl)thiomorpholine Chemical compound COCCN1CCSCC1 LPKCVVMDZKZBOB-UHFFFAOYSA-N 0.000 description 2
- LCLLBJKQZSUIPI-UHFFFAOYSA-N 4-(2-phenylethyl)thiomorpholine Chemical compound C1CSCCN1CCC1=CC=CC=C1 LCLLBJKQZSUIPI-UHFFFAOYSA-N 0.000 description 2
- GNINBUWYUZONOO-UHFFFAOYSA-N 4-(3-phenylpropyl)thiomorpholine Chemical compound C=1C=CC=CC=1CCCN1CCSCC1 GNINBUWYUZONOO-UHFFFAOYSA-N 0.000 description 2
- WVQOMHQCPFZSHI-UHFFFAOYSA-N 4-(cyclohexylmethyl)thiomorpholine Chemical compound C(C1CCCCC1)N1CCSCC1 WVQOMHQCPFZSHI-UHFFFAOYSA-N 0.000 description 2
- XXDYICWCXNQCSJ-UHFFFAOYSA-N 4-(naphthalen-1-ylmethyl)thiomorpholine Chemical compound C=1C=CC2=CC=CC=C2C=1CN1CCSCC1 XXDYICWCXNQCSJ-UHFFFAOYSA-N 0.000 description 2
- XDBTZKGSODUZAM-UHFFFAOYSA-N 4-(pyridin-2-ylmethyl)thiomorpholine Chemical compound C=1C=CC=NC=1CN1CCSCC1 XDBTZKGSODUZAM-UHFFFAOYSA-N 0.000 description 2
- ICBANYDRDPPZDR-UHFFFAOYSA-N 4-(thiophen-2-ylmethyl)thiomorpholine Chemical compound C=1C=CSC=1CN1CCSCC1 ICBANYDRDPPZDR-UHFFFAOYSA-N 0.000 description 2
- PSGMZFKEMBBBOA-UHFFFAOYSA-N 4-[(2-methylphenyl)methyl]thiomorpholine Chemical compound CC1=CC=CC=C1CN1CCSCC1 PSGMZFKEMBBBOA-UHFFFAOYSA-N 0.000 description 2
- KRHUBMQFRIQXCZ-UHFFFAOYSA-N 4-[(3,5-dimethoxyphenyl)methyl]thiomorpholine Chemical compound COC1=CC(OC)=CC(CN2CCSCC2)=C1 KRHUBMQFRIQXCZ-UHFFFAOYSA-N 0.000 description 2
- PWWDEQSIYFSCSF-UHFFFAOYSA-N 4-[(3-bromophenyl)methyl]thiomorpholine Chemical compound BrC1=CC=CC(CN2CCSCC2)=C1 PWWDEQSIYFSCSF-UHFFFAOYSA-N 0.000 description 2
- NCZPEABQJMHRAM-UHFFFAOYSA-N 4-[(3-fluorophenyl)methyl]thiomorpholine Chemical compound FC1=CC=CC(CN2CCSCC2)=C1 NCZPEABQJMHRAM-UHFFFAOYSA-N 0.000 description 2
- IRWWSBXYHHHRLU-UHFFFAOYSA-N 4-[(3-iodophenyl)methyl]thiomorpholine Chemical compound IC1=CC=CC(CN2CCSCC2)=C1 IRWWSBXYHHHRLU-UHFFFAOYSA-N 0.000 description 2
- YCZICELDYBXAHR-UHFFFAOYSA-N 4-[(3-methoxyphenyl)methyl]thiomorpholine Chemical compound COC1=CC=CC(CN2CCSCC2)=C1 YCZICELDYBXAHR-UHFFFAOYSA-N 0.000 description 2
- PGGZEZVGUUKGKB-UHFFFAOYSA-N 4-[(3-methylphenyl)methyl]thiomorpholine Chemical compound CC1=CC=CC(CN2CCSCC2)=C1 PGGZEZVGUUKGKB-UHFFFAOYSA-N 0.000 description 2
- JPOACEZEVCRRPB-UHFFFAOYSA-N 4-[(4-methylphenyl)methyl]thiomorpholine Chemical compound C1=CC(C)=CC=C1CN1CCSCC1 JPOACEZEVCRRPB-UHFFFAOYSA-N 0.000 description 2
- RCCWZWJLILTAEV-UHFFFAOYSA-N 4-[[3-(trifluoromethyl)phenyl]methyl]thiomorpholine Chemical compound FC(F)(F)C1=CC=CC(CN2CCSCC2)=C1 RCCWZWJLILTAEV-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- NLNHXTDJCGWOGR-UHFFFAOYSA-N 4-benzyl-2-ethylthiomorpholine Chemical compound CCC1CN(CCS1)CC2=CC=CC=C2 NLNHXTDJCGWOGR-UHFFFAOYSA-N 0.000 description 2
- QHTYJNLRRWTKON-UHFFFAOYSA-N 4-butylthiomorpholine Chemical compound CCCCN1CCSCC1 QHTYJNLRRWTKON-UHFFFAOYSA-N 0.000 description 2
- ZECOPOAPYOOZHM-UHFFFAOYSA-N 4-propyl-2,3-dihydro-1,4-benzothiazine Chemical compound C1=CC=C2N(CCC)CCSC2=C1 ZECOPOAPYOOZHM-UHFFFAOYSA-N 0.000 description 2
- MGCDHLCYJZAAKL-UHFFFAOYSA-N 4-propylthiomorpholine Chemical compound CCCN1CCSCC1 MGCDHLCYJZAAKL-UHFFFAOYSA-N 0.000 description 2
- GSBHDOKAOPOXNC-UHFFFAOYSA-N CC(CN1CCSCC1)=C=O Chemical compound CC(CN1CCSCC1)=C=O GSBHDOKAOPOXNC-UHFFFAOYSA-N 0.000 description 2
- 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 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 description 2
- KFSURFCUSYJVKV-UHFFFAOYSA-N CCCN(CCC)C(C=C1)=CC=C1SC(F)(F)F Chemical compound CCCN(CCC)C(C=C1)=CC=C1SC(F)(F)F KFSURFCUSYJVKV-UHFFFAOYSA-N 0.000 description 2
- KYRYJZBMZCQFIN-UHFFFAOYSA-N CCCN(CCC)c1cccc(SC)c1 Chemical compound CCCN(CCC)c1cccc(SC)c1 KYRYJZBMZCQFIN-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- NJQCVMQBRUNMQQ-UHFFFAOYSA-N FC1=CC(F)=CC(CN2CCSCC2)=C1 Chemical compound FC1=CC(F)=CC(CN2CCSCC2)=C1 NJQCVMQBRUNMQQ-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- PBLNHHSDYFYZNC-UHFFFAOYSA-N (1-naphthyl)methanol Chemical compound C1=CC=C2C(CO)=CC=CC2=C1 PBLNHHSDYFYZNC-UHFFFAOYSA-N 0.000 description 1
- LOGIHEKXJKHXEC-UHFFFAOYSA-N (3,5-difluorophenyl)methanol Chemical compound OCC1=CC(F)=CC(F)=C1 LOGIHEKXJKHXEC-UHFFFAOYSA-N 0.000 description 1
- AUDBREYGQOXIFT-UHFFFAOYSA-N (3,5-dimethoxyphenyl)methanol Chemical compound COC1=CC(CO)=CC(OC)=C1 AUDBREYGQOXIFT-UHFFFAOYSA-N 0.000 description 1
- FSWNRRSWFBXQCL-UHFFFAOYSA-N (3-bromophenyl)methanol Chemical compound OCC1=CC=CC(Br)=C1 FSWNRRSWFBXQCL-UHFFFAOYSA-N 0.000 description 1
- 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
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-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
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 description 1
- KCHLDNLIJVSRPK-UHFFFAOYSA-N 3-methylsulfanylaniline Chemical compound CSC1=CC=CC(N)=C1 KCHLDNLIJVSRPK-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
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- DJXQYJXQDQXQTG-UHFFFAOYSA-N 4-hydroxythiomorpholine Chemical compound ON1CCSCC1 DJXQYJXQDQXQTG-UHFFFAOYSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 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
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- CHOFGKGPPXLMRB-UHFFFAOYSA-N 6-(2-methylsulfanylethyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine Chemical compound CSCCN1CCc2ccsc2C1 CHOFGKGPPXLMRB-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- 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
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 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
- 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 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 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
- 125000003566 oxetanyl group Chemical group 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
- 125000004344 phenylpropyl group Chemical group 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
- 150000003303 ruthenium Chemical class 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, which comprises the following steps: adding triphenylphosphine into an organic solvent A, and heating to 50-100 ℃ to dissolve the triphenylphosphine to obtain a solution A; adding ruthenium trichloride into an organic solvent B, and dissolving to obtain a solution B; then, the solution B and a formaldehyde aqueous solution with the mass fraction of 37 percent are sequentially and rapidly added into the solution A, and the mixture reacts for 0.5 to 2 hours at the temperature of between 80 and 130 ℃; and (3) carrying out post-treatment on the obtained reaction liquid A to obtain bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate. Compared with the synthesis method of Colt and the like, the method can well avoid the use of strong acid, reduce the damage to operators in the experimental process, greatly shorten the reaction time, simplify the post-treatment of the experiment and improve the experimental efficiency.
Description
(I) technical field
The invention relates to a preparation method of ruthenium catalyst containing triphenylphosphine ligand, namely bis (triphenylphosphine) carbonyl monohydrate ruthenium dichloride.
(II) background of the invention
Noble metal catalysts play an increasingly important role in catalytic reactions. Because of the electronic structure characteristics of the ruthenium metal outer layer, all elements in the periodic table have the most oxidation number, and each electronic structure has various geometric structures, so that a foundation is provided for synthesizing various ruthenium complexes. And because of the excellent catalytic performance of the ruthenium catalyst, compared with the characteristic of low price of other noble metals, the ruthenium catalyst is developed more rapidly and has wider application. Currently, the main application fields of ruthenium catalysts are (asymmetric) catalytic hydrogenation, olefin metathesis, carbon alkylation, nitrogen alkylation, etc. In the process of carbon alkylation or nitrogen alkylation reaction with alcohol as reactant, only non-polluted water is generated as a byproduct, which meets the requirement of green development, thereby attracting the interest of more and more researchers. This places even greater demands on the synthesis and research of the catalyst. Since the first report by Grigg et al in 1981, the direct nitrogen alkylation of alcohols to amines over ruthenium catalysts by a hydrogen-donating mechanism. More and more noble metal catalysts are used in this direction of research. However, noble metal catalyzed sulfur-containing compounds have been rarely reported due to the significant poisoning effect of sulfur atoms on noble metals. However, the sulfur-containing amine compound plays an important role in drugs and natural products, and therefore, it is important to find a catalyst capable of catalyzing the sulfur-containing compound.
Disclosure of the invention
The invention aims to provide a synthesis method of a ruthenium catalyst and application of the catalyst in alkylation of sulfur-containing amide nitrogen.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, which comprises the following steps:
adding triphenylphosphine into an organic solvent A, and heating to 50-100 ℃ (preferably 100 ℃) to dissolve the triphenylphosphine to obtain a solution A; adding ruthenium trichloride into an organic solvent B, and dissolving to obtain a solution B; then, the solution B and 37 percent formaldehyde aqueous solution are sequentially and rapidly added into the solution A, and the mixture reacts for 0.5 to 2 hours (most preferably 0.8 hour) at 80 to 130 ℃ (preferably 120 ℃); after the obtained reaction liquid A is subjected to post-treatment A, bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate is obtained; the mass ratio of the ruthenium trichloride to the triphenylphosphine is 1-6 (preferably 1; the organic solvent A and the organic solvent B are both organic solvents, and A and B are used for distinguishing the organic solvents added at different stages. The organic solvent a and the organic solvent B are preferably the same solvent.
Further, the organic solvent A and the organic solvent B are respectively and independently ethanol, acetonitrile, ethylene glycol monomethyl ether or toluene, preferably ethylene glycol methyl ether.
Preferably, the volume of the organic solvent A is 5 to 15mL/mmol, most preferably 6.7mL/mmol, based on the amount of triphenylphosphine.
Preferably, the volume of the organic solvent B is 5-15 mL/mmol, most preferably 10mL/mmol, based on the amount of the ruthenium trichloride.
Further, the post-treatment A comprises the following steps: and cooling, filtering and air-drying the reaction liquid A to obtain the bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate.
Preferably, the cooling temperature is from 20 ℃ to 50 ℃, most preferably 25 ℃; the air drying temperature is 40-100 ℃, and the drying time is 2-10 h, most preferably 50 ℃ and 8h.
The invention provides application of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate as a homogeneous catalyst in nitrogen alkylation reaction containing thioamine.
Further, the application is as follows: dissolving the compound 1 and the compound 2 in an organic solvent D, adding bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, reacting for 2-10 h (preferably 6 h) at 80-160 ℃ (preferably 140 ℃), and carrying out aftertreatment treatment on the obtained reaction liquid B to obtain a compound shown in a formula 3; the mass ratio of compound 1 to compound 2 is 0.5 to 10, most preferably 3; the dosage of the bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate is 0.2-5 mol% of the amine compound 2;
in formulae 1 and 3, R 1 Selected from one of the following: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-biphenylyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3, 5-dimethoxyphenyl, 3, 5-difluorophenyl, 2-pyridyl, 2-thienyl, 1-naphthyl, methyl, ethyl, propyl, butyl, pentyl, hexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, oxetanyl, 2-tetrahydrofurylmethyl, adamantylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl, phenethyl, phenylpropyl, 3-hydroxypropyl, 4-hydroxybutyl, 3-methylbutyl, 3-dimethylbutyl, methoxymethyl, methoxypropyl, methylthiomethyl, 1-ethylketo;
r in the formula 2 2 And R 3 And (3) connecting to form a ring, wherein the structural formula shown in the formula 2 is selected from one of the following formulas:
preferably, in formulae 1 and 3, R 1 Is phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 2-iodophenyl, 3-trifluoromethylphenyl, 3, 5-dimethoxyphenyl, 3, 5-difluorophenyl, 2-pyridyl, 2-thienyl, 1-naphthyl, ethyl, propyl, butyl, pentyl, cyclopentyl, cyclohexyl, benzyl, phenethyl, methoxymethyl, methoxypropyl, methylthiomethyl or 1-acetonyl;
preferably, the amine compound 2 is a compound represented by one of formulas a to i;
further preferably, the compound 3 is one of the following:
(1) 4-benzylthiomorpholine
(2) 4- (2-methylbenzyl) thiomorpholine
(3) 4- (3-methylbenzyl) thiomorpholine
(4) 4- (4-methylbenzyl) thiomorpholine
(5) 4- (3-methoxybenzyl) thiomorpholine
(6) 4- (3-fluorobenzyl) thiomorpholine
(7) 4- (3-bromobenzyl) thiomorpholine
(8) 4- (3-iodobenzyl) thiomorpholine
(9) 4- (3-trifluoromethylbenzyl) thiomorpholine
(10) 4- (3, 5-dimethoxybenzyl) thiomorpholine
(11) 4- (3, 5-difluorobenzyl) thiomorpholine
(12) 4- (pyridin-2-ylmethyl) thiomorpholine
(13) 4- (thien-2-ylmethyl) thiomorpholine
(14) 4- (naphthalen-1-ylmethyl) thiomorpholine
(15) 4-propylthiomorpholine
(16) 4-butylthiomorpholine
(17) 4- (cyclohexylmethyl) thiomorpholine
(18) 4-phenethylthiomorpholine
(19) 4- (3-phenylpropyl) thiomorpholine
(20) 4- (2-methoxyethyl) thiomorpholine
(21) 4- (2-Carbonylpropyl) thiomorpholine
(22) 4-benzyl-2-ethylthiomorpholine
(23) 4-benzyl-2, 2-dimethylthiomorpholine
(24) 4-propyl-3, 4-dihydro-2H-benzo [ b ] [1,4] thiazine
(25) 4-benzylthiomorpholine 1, 1-dioxide
(26) 6- (2- (methylthio) ethyl) -4,5,6, 7-tetrahydrothieno [2,3-c ] pyridine
(27) 3- (4-Propylpiperazin-1-yl) benzo [ d ] isothiazole
(28) N, N-dipropyl-4- ((trifluoromethyl) thio) aniline
(29) 3- (methylthio) -N, N-dipropylaniline
(30) 4- ((4-Nitrophenyl) thio) -N, N-dipropylaniline.
When the temperature of the reaction system is higher than the boiling point of the solvent, the reaction is preferably carried out in a pressure resistant pipe.
Further, the organic solvent D is tetrahydrofuran, dioxane, toluene, xylene, N-dimethylformamide, dimethyl sulfoxide or t-amyl alcohol, and most preferably toluene.
Preferably, the volume of the organic solvent D is 0.1 to 5mL/mmol, most preferably 1mL/mmol, based on the amount of the amine compound 2.
Further, the post-treatment B is: cooling the reaction liquid B to room temperature, desolventizing, purifying by using a fast preparative liquid chromatograph, eluting by using a mixed solution of ethyl acetate and petroleum ether with a volume ratio of 2-20 (preferably 5);
compared with the prior art, the invention has the beneficial effects that:
(1) Compared with the synthetic method of Colt and the like, the method can well avoid the use of strong acid, reduce the damage to operators in the experimental process, greatly shorten the reaction time, simplify the post-treatment of the experiment and improve the experimental efficiency.
(2) The synthesized catalyst successfully realizes metal-catalyzed nitrogen alkylation containing the thioamine; based on the principle of hydrogen borrowing, the green synthesis of the aminated compound is successfully realized; lays an important foundation for the metal catalysis of sulfur-containing compounds in the synthesis of medicaments.
(3) Compared with other ruthenium catalysts, the bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate has higher catalytic activity in catalyzing the reaction of alcohol compounds and amine compounds.
Description of the drawings
FIG. 1 shows a single crystal structure of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate.
(V) detailed description of the preferred embodiments
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. Numerous technical details are set forth in order to provide a thorough understanding of the present invention, including the use of certain specific terms. However, the technical solution claimed in the present application can be implemented without these technical details and without some changes and modifications to the following embodiments.
The yield in the following examples is calculated without considering the purity as:
Y＝(m yield of the product /M Product of )/N Starting materials
m Yield of the product Mass of product including impurities, M Product of Is the relative molecular mass of the target product, N Starting materials The amount of material that is the reactant for which the amount of material is smaller.
The flash preparative liquid chromatograph used in the following examples was a Biotage purification apparatus, model Biotage Isolera One.
Example 1: synthesis of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate
Adding 3.16g (12 mmol) of triphenylphosphine into 80mL of ethylene glycol monomethyl ether, and heating to 100 ℃ to dissolve the triphenylphosphine to form a triphenylphosphine solution; adding 1.04g (4 mmol) of hydrated ruthenium trichloride into 40mL of ethylene glycol monomethyl ether, and uniformly stirring to dissolve the hydrated ruthenium trichloride to form a ruthenium trichloride solution; then, the mixture and 40mL of formaldehyde water solution with the mass fraction of 37% are sequentially and rapidly added into the triphenylphosphine solution; heating the reaction to 120 ℃ and reacting for 0.8h; and finally, cooling, filtering and air-drying the reaction liquid to obtain 2.82g of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate solid, wherein the yield is 95% and the liquid phase purity is 98%. The catalyst structure was determined by single crystal X-ray diffraction analysis as shown in figure 1.
Example 2: synthesis of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate
Adding 3.16g (12 mmol) of triphenylphosphine into 60mL of ethanol, and heating to 50 ℃ to dissolve the triphenylphosphine to form a triphenylphosphine solution; adding 0.5g (2 mmol) of hydrated ruthenium trichloride into 30mL of ethanol, and uniformly stirring to dissolve the hydrated ruthenium trichloride to form a ruthenium trichloride solution; then sequentially and rapidly adding the mixture and 10mL of formaldehyde water solution with the mass fraction of 37% into the triphenylphosphine solution; heating the reaction to 80 ℃ and reacting for 2h; and finally, cooling, filtering and air-drying the reaction liquid to obtain 1.19g of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate solid, wherein the yield is 40% and the liquid phase purity is 96%.
Example 3: synthesis of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate
Adding 3.16g (12 mmol) of triphenylphosphine into 180mL of acetonitrile, and heating to 80 ℃ to dissolve the triphenylphosphine to form a triphenylphosphine solution; adding 3g (12 mmol) of hydrated ruthenium trichloride into 60mL of acetonitrile, and uniformly stirring to dissolve the hydrated ruthenium trichloride to form a ruthenium trichloride solution; then sequentially and quickly adding the mixture and 180mL of formaldehyde aqueous solution with the mass fraction of 37% into the triphenylphosphine solution; heating the reaction to 90 ℃ and reacting for 0.5h; finally, the reaction solution is cooled, filtered and air-dried, and 3.12g of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate solid is obtained, the yield is 30%, and the liquid phase purity is 96%.
Example 4: synthesis of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate
Adding 3.16g (12 mmol) of triphenylphosphine into 80mL of toluene, and heating to 100 ℃ to dissolve the triphenylphosphine to form a triphenylphosphine solution; adding 1.04g (4 mmol) of hydrated ruthenium trichloride into 40mL of toluene, and uniformly stirring to dissolve the hydrated ruthenium trichloride to form a ruthenium trichloride solution; then, the mixture and 40mL of formaldehyde water solution with the mass fraction of 37% are sequentially and rapidly added into the triphenylphosphine solution; heating the reaction to 130 ℃ and reacting for 1.2h; finally, the reaction solution is cooled, filtered and air-dried, and 2.73g of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate solid is obtained, the yield is 92%, and the liquid phase purity is 97%.
Example 5: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydratePutting the mixture into a pressure resistant tube, and reacting for 6 hours at 140 ℃. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500MHz, CDCl 3 )δ7.38–7.31(m,4H),7.30–7.25(m,1H),3.54(s,2H),2.77–2.65(m,8H). 13 C NMR(126MHz,CDCl 3 )δ138.01,129.00(2C),128.20(2C),127.05,63.64, 54.87(2C),27.97(2C).HRMS(ES+)m/z calcd for C 11 H 15 NS([M+H] + )194.0098, found 194.0999.
Example 6: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure tube together with 0.01mmol (9.4 mg) of tris (triphenylphosphine) ruthenium dichloride and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and rotary-distilled under reduced pressure to obtain 0.023g of the compound represented by formula 3, with a yield of 12% and a liquid phase purity of 99%.
Example 7: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.108g, 1mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 0.1mL of tetrahydrofuran, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 80 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluent containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.088g of the compound represented by formula 3, with a yield of 46% and a liquid phase purity of 99%.
Example 8: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (1.08g, 10mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of xylene, and added together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate to a pressure resistant tube, followed by reaction at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.164g of the compound represented by formula 3, with a yield of 85% and a liquid phase purity of 99%.
Example 9: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 5mL dioxane and added to a pressure vessel along with 0.01mmol (7.4 mg) bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 80 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.106g of the compound represented by formula 3, in 55% yield and 99% liquid-phase purity.
Example 10: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of N, N-dimethylformamide and added to a pressure vessel along with 0.002mmol (1.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 160 ℃ for 2 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.073g of the compound represented by formula 3, with a yield of 38% and a liquid phase purity of 99%.
Example 11: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of dimethyl sulfoxide, and added to a pressure-resistant tube together with 0.05mmol (37.2 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 10 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5.
Example 12: synthesis of 4-benzylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of t-amyl alcohol and added to a pressure tube together with 0.05mmol (37.2 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 10h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5.
Example 13: synthesis of 4- (2-methylbenzyl) thiomorpholine
2-methylbenzyl alcohol (0.360g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of methylBenzene was added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz, CDCl 3 )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 C 12 H 17 NS([M+H] + )208.1154,found 208.1155.
Example 14: synthesis of 4- (3-methylbenzyl) thiomorpholine
3-methylbenzyl alcohol (0.360g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether: 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.193g of the compound represented by formula 3, in a yield of 93%, and in a liquid phase purity of 99%. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 C 12 H 17 NS([M+H] + )208.1154,found 208.1158.
Example 15: synthesis of 4- (4-methylbenzyl) thiomorpholine
4-methylbenzyl alcohol (0.360g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, followed by reaction at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 for C 12 H 17 NS([M+H] + )208.1154,found 208.1155.
Example 16: synthesis of 4- (3-methoxybenzyl) thiomorpholine
3-Methoxybenzyl alcohol (0.408g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and the resulting solution was charged into a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.178g of the compound represented by formula 3, with a yield of 80% and a liquid phase purity of 99%. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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/z calcd for C 12 H 17 NOS([M+H] + )224.1104,found 224.1110.
Example 17: synthesis of 4- (3-fluorobenzyl) thiomorpholine
3-Fluorobenzyl alcohol (0.378g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and the resulting solution was charged into a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.148g of the compound represented by formula 3, with a yield of 70% and a liquid phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ161.43(d, 1 J C-F ＝246.6Hz,1C),131.41(d, 3 J C-F ＝4.54 Hz,1C),128.82(d, 3 J C-F ＝8.3Hz,1C),124.45(d, 2 J C-F ＝14.6Hz,1C),123.85 (d, 4 J C-F ＝3.5Hz,1C),115.27(d, 2 J C-F ＝22.2Hz,1C),55.96(d,J C-F ＝1.76Hz,1C), 54.62(2C),27.98(2C).HRMS(ES+)m/z calcd for C 11 H 14 FNS([M+H] + )212.0904, found 212.0909.
Example 18: synthesis of 4- (3-bromobenzyl) thiomorpholine
3-bromobenzyl alcohol (0.561g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. Cooling the obtained reaction liquid to room temperature, carrying out desolvation, carrying out rapid preparative liquid chromatography purification (the volume ratio of ethyl acetate to petroleum ether is 5The product was rotary-distilled to give 0.261g of the compound represented by formula 3 in a yield of 96% and a liquid-phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )δ7.48(s,1H),7.40–7.36(m,1H),7.23(d,J＝7.7Hz,1H),7.18(t,J＝7.7 Hz,1H),3.47(s,2H),2.73–2.63(m,8H). 13 C NMR(126MHz,CDCl 3 )δ140.62, 131.72,130.12,129.74,127.41,122.41,62.87,54.81(2C),27.91(2C).HRMS(ES+) m/z calcd for C 11 H 14 BrNS([M+H] + )274.0082,found 274.0092.
Example 19: synthesis of 4- (3-iodobenzyl) thiomorpholine
3-iodobenzyl alcohol (0.702g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.313g of the compound represented by formula 3, with a yield of 98% and a liquid phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 C 11 H 14 INS([M+H] + )319.9964,found 319.9970.
Example 20: synthesis of 4- (3-trifluoromethylbenzyl) thiomorpholine
3-Trifluoromethylbenzyl alcohol (0.558g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and the solution was charged into a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, 140 ℃ CAnd reacting for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.149g of the compound represented by formula 3, with a yield of 57% and a liquid phase purity of 99%. 1 H NMR (500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ137.79,131.73,130.15,128.68(q, 2 J C-F ＝30.2Hz,1C), 126.81,125.78(q, 3 J C-F ＝5.9Hz,1C),124.5(q, 1 J C-F ＝274.6Hz,1C),58.90,55.08 (2C),28.11(2C).HRMS(ES+)m/z calcd for C 12 H 14 F 3 NS([M+H] + )262.0872,found 262.0879.
Example 21: synthesis of 4- (3, 5-dimethoxybenzyl) thiomorpholine
3, 5-Dimethoxybenzyl alcohol (0.504g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether: 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.202g of the compound represented by formula 3, in 80% yield and 99% liquid-phase purity. 1 H NMR (500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 for C 13 H 19 NO 2 S([M+H] + )254.1209,found 254.1217.
Example 22: synthesis of 4- (3, 5-difluorobenzyl) thiomorpholine
3, 5-Difluorobenzyl alcohol (0.432g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate to a pressure resistant tube to react at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ163.03(dd, 1 J C-F ＝248.2,12.7Hz, 2C),142.72(t, 3 J C-F ＝8.7Hz,1C),111.19(dd, 2 J C-F ＝19.3,5.7Hz,2C),102.40 (t, 2 J C-F ＝25.4Hz,1C),62.70(t, 4 J C-F ＝2.0Hz,1C),54.90(2C),27.98(2C).HRMS (ES+)m/z calcd for C 11 H 13 F 2 NS([M+H] + )230.0810,found 230.0820.
Example 23: synthesis of 4- (pyridin-2-ylmethyl) thiomorpholine
2-Pyridylcarbinol (0.327g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.155g of the compound represented by formula 3, in 80% yield and 99% liquid-phase purity. 1 H NMR(500 MHz,CDCl 3 )δ8.41(m,1H),7.50(m,1H),7.25(d,J＝7.7Hz,1H),7.25(d,J＝7.7 Hz,1H),7.02(m,2H),2.61(m,4H),2.58–2.49(m,4H). 13 C NMR(126MHz, CDCl 3 )δ158.00,148.82,135.99,122.70,121.66,64.79,54.67(2C),27.50(2C). HRMS(ES+)m/z calcd for C 10 H 14 N 2 S([M+H] + )195.0950,found 195.0958.
Example 24: synthesis of 4- (thien-2-ylmethyl) thiomorpholine
2-Thiophenemethanol (0.342g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and rotary-distilled under reduced pressure to obtain 0.173g of the compound represented by formula 3, yield 87%, and liquid-phase purity 99%. 1 H NMR(500 MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ141.46, 126.48,126.08,125.12,57.89,54.61(2C),28.02(2C).HRMS(ES+)m/z calcd for C 9 H 13 NS 2 ([M+H] + )200.0562,found 200.0561.
Example 25: synthesis of 4- (naphthalen-1-ylmethyl) thiomorpholine
1-Naphthalenemethanol (0.474g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure vessel along with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the objective compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.156g of the compound of formula 3The compound is shown in the yield of 64 percent and the liquid phase purity of 99 percent. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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/z calcd for C 15 H 17 NS([M+H] + )244.1154,found 244.1158.
Example 26: synthesis of 4-propylthiomorpholine
N-propanol (0.180g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and rotary-distilled under reduced pressure to obtain 0.126g of the compound represented by formula 3, yield 87%, and liquid phase purity 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ61.35,54.99(2C),27.97(2C),19.58, 11.87.HRMS(ES+)m/z calcd for C 7 H 15 NS([M+H] + )146.0998,found 146.1000.
Example 27: synthesis of 4-butylthiomorpholine
N-butanol (0.222g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. Cooling the obtained reaction solution to room temperature, removingDissolving, purifying by a rapid preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), collecting eluent containing the target compound, and carrying out reduced pressure rotary evaporation to obtain 0.121g of the compound shown in the formula 3, wherein the yield is 76%, and the liquid phase purity is 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ59.17,55.03(2C), 28.63,27.98(2C),20.71,13.99.HRMS(ES+)m/z calcd for C 8 H 17 NS([M+H] + ) 160.1154,found 160.1158.
Example 28: synthesis of 4- (cyclohexylmethyl) thiomorpholine
Cyclohexylmethanol (0.342g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether: 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.173g of the compound represented by formula 3, with a yield of 87% and a liquid phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 ) δ66.28,55.61(2C),35.03,31.85(2C),27.99(2C),26.79,26.13(2C).HRMS(ES+) m/z calcd for C 11 H 21 NS([M+H] + )200.1467,found 200.1474.
Example 29: synthesis of 4-phenethylthiomorpholine
2-Phenylethanol (0.360g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and reacted with 0.01mmol (7.4 mmol)mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate were added together in a pressure tube and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.124g of the compound represented by formula 3, with a yield of 60% and a liquid phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 C 12 H 17 NS([M+H] + )208.1154,found 208.1156.
Example 30: synthesis of 4- (3-phenylpropyl) thiomorpholine
3-phenylpropanol (0.402g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (the volume ratio of ethyl acetate to petroleum ether was 5. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ 142.00,128.35(2C),128.29(2C),125.76,58.55,54.95(2C),33.56,28.12,27.93(2C). HRMS(ES+)m/z calcd for C 13 H 19 NS([M+H] + )222.1311,found 222.1317.
Example 31: synthesis of 4- (2-methoxyethyl) thiomorpholine
Ethylene glycol monomethyl ether (0.228g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene, and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, followed by reaction at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.090g of the compound represented by formula 3, in a yield of 56%, and in a liquid phase purity of 99%. 1 H NMR(500MHz, CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ69.93,58.88,58.56, 55.27(2C),27.71(2C).HRMS(ES+)m/z calcd for C 7 H 15 NOS([M+H] + )162.0947, found 162.0948.
Example 32: synthesis of 4- (2-carbonylpropyl) thiomorpholine
2-hydroxyacetone (0.222g, 3mmol) and thiomorpholine (0.103g, 1mmol) were dissolved in 1mL of toluene and added to a pressure tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.116g of the compound represented by formula 3, in a yield of 73%, and in a liquid phase purity of 99%. 1 H NMR(500 MHz,CDCl 3 )δ3.18(s,2H),2.76–2.67(m,8H),2.13(s,3H). 13 C NMR(126MHz, CDCl 3 )δ206.66,68.78,55.07(2C),27.73(2C),27.62.HRMS(ES+)m/z calcd for C 7 H 13 NOS([M+H] + )160.0791,found 160.0790.
Example 33: synthesis of 4-benzyl-2-ethylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and 2-ethylthiomorpholine (0.131g, 1mmol) were dissolved in 1mL of toluene and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500 MHz,CDCl 3 )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＝11.6,9.4 Hz,1H),1.64–1.41(m,2H),0.99(t,J＝7.5Hz,3H). 13 C NMR(126MHz,CDCl 3 ) 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/z calcd for C 13 H 19 NS([M+H] + )222.1311,found 222.1319.
Example 34: synthesis of 4-benzyl-2, 2-dimethylthiomorpholine
Benzyl alcohol (0.324g, 3mmol) and 2-ethylthiomorpholine (0.131g, 1mmol) were dissolved in 1mL of toluene and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (the volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500 MHz,CDCl 3 )δ7.44–7.32(m,5H),3.55(s,2H),2.84–2.65(m,4H),2.44(s,2H), 1.37(s,6H). 13 C NMR(126MHz,CDCl 3 )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 C 13 H 19 NS([M+H] + )222.1311,found 222.1319.
Example 35: synthesis of 4-propyl-3, 4-dihydro-2H-benzo [ b ] [1,4] thiazine
N-propanol (0.180g, 3 mmol) and 3, 4-dihydro-2H-benzo [ b ] were added][1,4]Thiazine (0.151g, 1mmol) was dissolved in 1mL of toluene and added to a pressure tube along with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a flash preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.112g of the compound represented by formula 3, in 58% yield and 99% liquid-phase purity. 1 H NMR(500MHz,CDCl 3 )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). 13 C NMR (126MHz,CDCl 3 )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 C 11 H 15 NS([M+H] + )194.0998, found 194.0996.
Example 36: synthesis of 4-benzylthiomorpholine 1, 1-dioxide
Benzyl alcohol (0.324g, 3mmol) and thiomorpholine oxide (0.135g, 1mmol) were dissolved in 1mL of toluene and added to a pressure vessel along with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR(500MHz, CDCl 3 )δ7.40–7.20(m,5H),3.65(s,2H),3.13–3.03(m,4H),3.00–2.93(m, 4H). 13 C NMR(126MHz,CDCl 3 )δ137.18,128.69(2C),128.46(2C),127.56,61.32, 51.35(2C),50.44(2C).HRMS(ES+)m/z calcd for C 11 H 15 NO 2 S([M+H] + )226.0896, found 226.0903.
Example 37:6- (2- (methylthio) ethyl) -4,5,6, 7-tetrahydrothieno [2,3-c ]]Synthesis of pyridine
Methylthioethanol (0.276g, 3mmol) and 4,5,6, 7-tetrahydrothieno [2, 3-c)]Pyridine (0.139g, 1 mmol) was dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.153g of the compound represented by formula 3, with a yield of 72% and a liquid phase purity of 99%. 1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 C 10 H 15 NS 2 ([M+H] + )214.0719,found 214.0725.
Example 38: synthesis of 3- (4-propylpiperazin-1-yl) benzo [ d ] isothiazole
N-propanol (0.180g, 3 mmol) and 3- (piperazin-1-yl) benzo [ d]Isothiazole (0.219g, 1mmol) was dissolved in 1mL of toluene, and added to a pressure resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, followed by reaction at 140 ℃ for 6 hours. Cooling the obtained reaction solution to room temperature, desolventizing, and rapidly preparing liquid chromatogramPurifying by an instrument (the volume ratio of ethyl acetate to petroleum ether is 5: 100), collecting an eluent containing the target compound, and carrying out reduced pressure rotary evaporation to obtain 0.201g of the compound shown in the formula 3, wherein the yield is 77%, and the liquid phase purity is 99%. 1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 calcd for C 14 H 19 N 3 S([M+H] + )262.1372,found 262.1384.
Example 39: synthesis of N, N-dipropyl-4- ((trifluoromethyl) thio) aniline
N-propanol (0.180g, 3mmol) and 4- ((trifluoromethyl) thio) aniline (0.193g, 1mmol) were dissolved in 1mL of toluene and added to a pressure tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 6h. The obtained reaction solution was cooled to room temperature, desolventized, purified by flash preparative liquid chromatography (ethyl acetate: petroleum ether volume ratio 5: 100), and the eluate containing the target compound was collected and subjected to rotary evaporation under reduced pressure to obtain 0.258g of the compound represented by formula 3, in a yield of 93%, and in a liquid phase purity of 99%. 1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )δ 149.98,138.13(2C),129.88(q, 1 J C-F ＝309.2Hz,1C),111.90(2C),106.98,52.79 (2C),20.28(2C),11.34(2C).HRMS(ES+)m/z calcd for C 13 H 18 F 3 NS([M+H] + ) 278.1185,found 278.1197.
Example 40: synthesis of 3- (methylthio) -N, N-dipropylaniline
N-propanol (0.180g, 3mmol) and 3- (methylthio) aniline (0.139g, 1mmol) were dissolved in 1mL of toluene and added to a pressure vessel along with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl-ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5. 1 H NMR (500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 C 13 H 21 NS([M+H] + )224.1467,found 224.1476.
Example 41: synthesis of 4- ((4-nitrophenyl) thio) -N, N-dipropylaniline
N-propanol (0.180g, 3mmol) and 4- ((4-nitrophenyl) thio) aniline (0.246g, 1mmol) were dissolved in 1mL of toluene and added to a pressure-resistant tube together with 0.01mmol (7.4 mg) of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate and reacted at 140 ℃ for 6 hours. The obtained reaction solution was cooled to room temperature, desolventized, purified by a fast preparative liquid chromatograph (volume ratio of ethyl acetate to petroleum ether is 5: 100), and the eluent containing the target compound was collected and subjected to reduced pressure rotary evaporation to obtain 0.182g of the compound represented by formula 3, with a yield of 55% and a liquid phase purity of 99%. 1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 )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 for C 18 H 22 N 2 O 2 S([M+H] + )331.1475,found 331.1483。
Claims (7)
1. A preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate is characterized by comprising the following steps:
adding triphenylphosphine into an organic solvent A, and heating to 50-100 ℃ to dissolve the triphenylphosphine to obtain a solution A; adding ruthenium trichloride into an organic solvent B, and dissolving to obtain a solution B; then, the solution B and 37 percent formaldehyde water solution are sequentially and rapidly added into the solution A, and the mixture reacts for 0.5 to 2 hours at the temperature of between 80 and 130 ℃; after the obtained reaction liquid A is subjected to post-treatment A, bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate is obtained; the mass ratio of the ruthenium trichloride to the triphenylphosphine is 1-6, the volume of the formaldehyde aqueous solution with the mass fraction of 37 percent is 5-15 mL/mmol based on the mass of the ruthenium trichloride,
the organic solvent A and the organic solvent B are respectively and independently ethanol, acetonitrile, ethylene glycol monomethyl ether or toluene; the volume of the organic solvent A is 5-15 mL/mmol based on the mass of triphenylphosphine; the volume of the organic solvent B is 5-15 mL/mmol based on the amount of the ruthenium trichloride.
2. A process for the preparation of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate according to claim 1, wherein: the organic solvent A and the organic solvent B are ethylene glycol monomethyl ether.
3. A process for the preparation of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate according to claim 1, wherein: the mass ratio of the ruthenium trichloride to the triphenylphosphine was 1.
4. The method of claim 1 for the preparation of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate, wherein: the reaction condition is 120 ℃ for 0.8h.
5. A process for the preparation of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate according to claim 1, wherein: the volume of the formaldehyde aqueous solution with the mass fraction of 37 percent is 10mL/mmol based on the mass of the ruthenium trichloride.
6. The process for the preparation of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate according to claim 1, characterized in that said post-treatment a is: and cooling, filtering and air-drying the reaction liquid A to obtain the bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate.
7. The method of claim 6, wherein the ruthenium dichloride bis (triphenylphosphine) carbonyl monohydrate comprises: the cooling temperature is 20-50 ℃; the air drying temperature is 40-100 ℃, and the drying time is 2-10 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110308149.6A CN113201020B (en) | 2021-03-23 | 2021-03-23 | Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110308149.6A CN113201020B (en) | 2021-03-23 | 2021-03-23 | Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113201020A CN113201020A (en) | 2021-08-03 |
| CN113201020B true CN113201020B (en) | 2022-10-04 |
Family
ID=77025604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110308149.6A Active CN113201020B (en) | 2021-03-23 | 2021-03-23 | Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113201020B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110790794A (en) * | 2019-10-25 | 2020-02-14 | 西安凯立新材料股份有限公司 | Preparation method of tri (triphenylphosphine) carbonyl hydrogen chloride ruthenium solid |
-
2021
- 2021-03-23 CN CN202110308149.6A patent/CN113201020B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113201020A (en) | 2021-08-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gianni et al. | Silver triflate/p-TSA co-catalysed synthesis of 3-substituted isocoumarins from 2-alkynylbenzoates | |
| CN110372611B (en) | Method for selectively synthesizing polysubstituted dihydro quinazolinone or quinazolinone | |
| CN115477614A (en) | Benzimidazole column [5] arene N-heterocyclic carbene ligand and preparation method and application thereof | |
| CN113201020B (en) | Preparation method of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate | |
| CN104910104A (en) | Method for synthesizing dihydrofuran derivatives under catalytic action of copper | |
| CN113087684B (en) | Application of bis (triphenylphosphine) carbonyl ruthenium dichloride monohydrate | |
| CN111233849A (en) | Novel isoquinoline-oxazoline chiral ligand and preparation and application thereof | |
| CN110627717B (en) | Branched 1, 4-diene amide derivative and synthesis method thereof | |
| CN115160211B (en) | Green synthesis method of isoindolinone compound | |
| CN101327450B (en) | Aminoacid ion liquid carried Salen metallic catalyst and preparation method | |
| CN113582865B (en) | Preparation method of alpha, alpha-disubstituted chiral amino acid ester | |
| CN114149379B (en) | Synthesis method for synthesizing multi-substituted oxazole product from simple aromatic carboxylic acid and cyano-substituted ester compound | |
| CN103748065B (en) | The manufacture method of 2-alkenyl amine compound | |
| CN105949136B (en) | A kind of synthetic method of 1,5- substitution -1,2,3- triazole compound | |
| CN114773174A (en) | Synthetic method of alpha-deuterated carbonyl compound | |
| CN110483323B (en) | Preparation method of asymmetric imide compound | |
| US8729303B2 (en) | 2,2′,6,6′-tetrasubstituted aminophosphine ligand and its synthesis method | |
| CN103664875B (en) | Isosorbide-5-Nitrae, the synthetic method of 5,6-tetrahydropyrimidinederivatives derivatives | |
| CN109096139A (en) | A kind of preparation method of alpha-carbonyl amide derivatives | |
| CN113582929B (en) | Synthetic method of 2,5-disubstituted imidazole compound | |
| CN111662202A (en) | Synthetic method of alpha-ketoamide compound | |
| CN110845288B (en) | Asymmetric synthesis method of chiral beta-amino aldehyde compound | |
| CN102060851B (en) | Method for preparing polyhydroquinolines | |
| CN109942553A (en) | A kind of synthesis of tri- substituted-tetrahydro 2H- pyran-2-one compound of chirality 3,4,6- and its method for transformation | |
| CN115466171B (en) | Preparation method of 2, 3-dihydro-1H-cyclopenteno [ a ] naphthalene derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |