CN110305156A - A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond - Google Patents
A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond Download PDFInfo
- Publication number
- CN110305156A CN110305156A CN201910666222.XA CN201910666222A CN110305156A CN 110305156 A CN110305156 A CN 110305156A CN 201910666222 A CN201910666222 A CN 201910666222A CN 110305156 A CN110305156 A CN 110305156A
- Authority
- CN
- China
- Prior art keywords
- oxygen bond
- containing nitrogen
- formula
- alkynes
- preparation
- 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.)
- Granted
Links
- 150000001345 alkine derivatives Chemical class 0.000 title claims abstract description 80
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- -1 polysubstituted alcohol compound Chemical class 0.000 claims abstract description 70
- 239000000758 substrate Substances 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 18
- 239000010703 silicon Substances 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
- 239000002585 base Substances 0.000 claims description 86
- 238000006243 chemical reaction Methods 0.000 claims description 64
- 150000001875 compounds Chemical class 0.000 claims description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 33
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 26
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 claims description 19
- 229910052741 iridium Inorganic materials 0.000 claims description 16
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 16
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical compound [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 13
- 239000003863 metallic catalyst Substances 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 239000000460 chlorine Chemical group 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical group [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 11
- 229940071536 silver acetate Drugs 0.000 claims description 11
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 10
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052707 ruthenium Inorganic materials 0.000 claims description 3
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- YTZKOQUCBOVLHL-UHFFFAOYSA-N p-methylisopropylbenzene Natural products CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- PZSJYEAHAINDJI-UHFFFAOYSA-N rhodium(3+) Chemical compound [Rh+3] PZSJYEAHAINDJI-UHFFFAOYSA-N 0.000 claims description 2
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical class [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 abstract description 20
- DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical compound N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 abstract description 18
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 230000009467 reduction Effects 0.000 abstract description 9
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 abstract 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 80
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 60
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000005905 alkynylation reaction Methods 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 16
- 239000000243 solution Substances 0.000 description 14
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 12
- HSYLTRBDKXZSGS-UHFFFAOYSA-N silver;bis(trifluoromethylsulfonyl)azanide Chemical compound [Ag+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F HSYLTRBDKXZSGS-UHFFFAOYSA-N 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 238000002390 rotary evaporation Methods 0.000 description 9
- IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 8
- PNEFIWYZWIQKEK-UHFFFAOYSA-N carbonic acid;lithium Chemical compound [Li].OC(O)=O PNEFIWYZWIQKEK-UHFFFAOYSA-N 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 150000003141 primary amines Chemical class 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 150000001336 alkenes Chemical group 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000005311 nuclear magnetism Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- CJQKFKQIFQGELD-UHFFFAOYSA-N propan-2-ylsilicon Chemical compound CC(C)[Si] CJQKFKQIFQGELD-UHFFFAOYSA-N 0.000 description 3
- 239000002689 soil Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 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
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000004175 fluorobenzyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000004344 phenylpropyl group Chemical group 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- SCVLUSJOUNMHOH-UHFFFAOYSA-N tert-butyl(methyl)silicon Chemical compound C[Si]C(C)(C)C SCVLUSJOUNMHOH-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
- LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 description 1
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 1
- FJOACTZFMHZHSC-UHFFFAOYSA-N 2,3,5,6-tetrafluoro-4-(trifluoromethyl)aniline Chemical compound NC1=C(F)C(F)=C(C(F)(F)F)C(F)=C1F FJOACTZFMHZHSC-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 1
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 229910021640 Iridium dichloride Inorganic materials 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012675 alcoholic extract Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000012650 click reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to technical field of organic synthesis more particularly to a kind of alkynes derivatives and its preparation method and application containing nitrogen-oxygen bond.The present invention provides a kind of alkynes derivative containing nitrogen-oxygen bond, shown in the structural formula such as formula (I) of the alkynes derivative containing nitrogen-oxygen bond, wherein R1And R2The independent aromatic heterocyclic selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, the substituted aryl of C5~C30 or C5~C30, R3To replace silicon substrate.In the present invention, alkynes derivative of the present invention containing nitrogen-oxygen bond contains the nitrogen-oxygen key easily converted, and the primary amine of high added value and the polysubstituted alcohol compound containing alkynyl can be obtained by reduction, is had a good application prospect in organic synthesis field；Also, alkynes derivative of the present invention containing nitrogen-oxygen bond, which contains, can be convenient the silicon substrate left away with what alkynes was connected directly, can further obtain end alkine compounds.
Description
Technical field
The invention belongs to technical field of organic synthesis more particularly to a kind of alkynes derivatives and its preparation side containing nitrogen-oxygen bond
Method and application.
Background technique
Alkynes has unique physical property such as rigidity, optical property and chemical property abundant such as can be with simple and direct efficient
Carry out electrophilic addition, nucleophilic addition, Diels-Alder reaction building molecule complexity, alkynes can also click on reaction
(Click reaction) completes the chemical synthesis of varied molecule fast and reliablely.Although alkynes is used as in material, medicine
The ubiquitous functional group in equal fields.But existing alkynes synthetic method depends on transition metal-catalyzed end alkynes
The coupling reaction of hydrocarbon constructs Csp2- Csp key, i.e., most of acetylene hydrocarbon compounds for still concentrating on alkene, aromatic hydrocarbons substitution；
The prior art constructs alkyl-substituted end alkynes, is so far still a significant challenge of organic synthesis field:
1) if directly constructing both ends using the strategy that alkyl halide is reacted with alkynyl reagent is the interior of alkyl
Alkynes is easier to quick β-H elimination reaction occurs to obtain then usually by the generated in-situ alkyl metal catalyst species of alkyl halide
Olefin by-products, to be difficult to obtain targeted transformation；
If 2) directly construct alkyl-substituted end using the strategy that alkyl C-H bond is reacted with alkynyl reagent
Terminal Acetylenes, the strategy have good step economy and Atom economy.However, it is contemplated that alkyl Csp3The activity of-H key is very
It is low, and alkyl substrate usually contains the alkyl Csp of multiple and different types3- H key, this is but also explore can be directly to alkyl
Csp3The alkynylation reaction of the direct regioselectivity of-H key still has great challenge.
The prior art is by simple alkyl Csp3- H key passes through Csp3Selective functional group's strategy of-H key constructs alkynes
Example is very limited, and focuses primarily upon use and be difficult to the functional group converted or/and expensive group synthesizes, such as
The amide of 4- trifluoromethyl -2,3,5,6- tetrafluoroaniline, the amide derivatives of 8- aminoquinoline promote Csp as guiding base3-
The selective alkynylation reaction of H key.Although it is oriented to base and is difficult to convert or be difficult to be limited with good catalytic efficiency
Its extensive use.
In summary, efficiently synthesize alkyl alkynes, especially the acetylene hydrocarbon compound containing easily conversion functional group, still need into
The exploitation of one step, the type of alkynes derivative is limited at present, also needs to be widened.
Summary of the invention
In view of this, the present invention provides a kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond, is used for
A kind of new alkynes derivative containing nitrogen-oxygen bond is provided, the type of the alkynes derivative containing nitrogen-oxygen bond is widened.
The specific technical solution of the present invention is as follows:
A kind of alkynes derivative containing nitrogen-oxygen bond, shown in the structural formula such as formula (I) of the alkynes derivative containing nitrogen-oxygen bond:
Wherein, R1And R2The independent substituted aryl for being selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, C5~C30
Or the aromatic heterocyclic of C5~C30, R3To replace silicon substrate.
Alkynes derivative of the present invention containing nitrogen-oxygen bond contains the nitrogen-oxygen key easily converted, can be obtained by reduction high additional
The primary amine of value and polysubstituted alcohol compound containing alkynyl, have a good application prospect in organic synthesis field.Also, this
Alkynes derivative of the invention containing nitrogen-oxygen bond, which contains, can be convenient the silicon substrate left away with what alkynes triple carbon-carbon bonds were connected directly, can be into one
Step obtains end alkine compounds.
In the present invention, the alkynes derivative containing nitrogen-oxygen bond can such as be passed through by being simply converted into the alcohol compound containing alkynyl
LAH (lithium aluminium hydride) reduction and TBAF (tetrabutyl ammonium fluoride) desiliconization, alcohol target product of the acquisition containing alkynyl that can be quantified.
Preferably, R1And R2It is independent to be selected from hydrogen, alkyl, naphthenic base, phenyl, substituted-phenyl, naphthalene, furyl, thiophene
Base, indyl or pyrrole radicals, R3Selected from triisopropylsilyl, dimethyl tertiary butyl silicon substrate or oxygen silicon ether containing cyclohexyl.
Further, R1And R2It is independent to be selected from hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, benzyl, benzene second
Base, phenylpropyl, phenyl, naphthalene, furyl, thienyl, indyl or pyrrole radicals, R3Selected from triisopropylsilyl (- TIPS), two
Methyl tertbutyl silicon substrate (- TMS) or oxygen silicon ether containing cyclohexyl.
Further, R1And R2It is independent to be selected from hydrogen, methyl, ethyl, benzyl, the fluoro- benzyl of 4-, 2- chlorobenzyl, 2- bromobenzyl
Base or phenethyl, R3For triisopropylsilyl (- TIPS).
Preferably, the alkynes derivative containing nitrogen-oxygen bond shown in formula (I) is selected from
The preparation method of the present invention also provides a kind of alkynes derivative containing nitrogen-oxygen bond, comprising the following steps:
Compound shown in compound shown in formula (II) and formula (III) is reacted under catalyst, is obtained shown in formula (I)
The alkynes derivative containing nitrogen-oxygen bond；
Wherein,
R1And R2It is independent selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, the substituted aryl of C5~C30 or C5~
The aromatic heterocyclic of C30, R3To replace silicon substrate, X is hydrogen, bromine, chlorine, iodine or heterocyclic group containing iodine, and heterocyclic group containing iodine is preferably
The catalyst is metallic catalyst, the metal of the metallic catalyst be selected from one of palladium, ruthenium, rhodium and iridium or
It is a variety of.
Existing alkynes synthetic method depends on the coupling reaction of transition metal-catalyzed terminal alkyne to construct
Csp2- Csp key, so that the acetylene hydrocarbon compound that product concentrates on alkene, aromatic hydrocarbons replaces.Based on substrate simple and easy to get, pass through height
The synthetic strategy rapid build of effect still has great challenge in the alkynes derivative containing nitrogen-oxygen bond with important synthesis value.
Reason is: 1) often facing generated in-situ Csp from the Sonogashira of alkyl halide reaction3Metallic bond easily occurs quickly
β-H eliminate, obtain olefin(e) compound；If 2) directly with alkyl Csp3- H key, which sets out, constructs alkynes, although it is with fabulous
Step economy, but it is this kind of reaction have it is extremely challenging, on the one hand, relatively flexible alkyl Csp3- H key bond energy is high,
So that extremely difficult to the activation of this inert chemi-cal key；It may also be noted that for one specifically containing the alkane of nitrogen-oxygen bond
For based compound, the Csp usually various containing quantity, type is complicated3- H key, this to activate a specific Csp3-H
The great challenge of key；More importantly the alkyl compound containing nitrogen-oxygen bond is due to easily occurring oxygen under oxidisability or alkaline condition
Change and (become ketone, aldehyde or carboxylic acid etc.), eliminate side reactions such as (isomers as alkene), so that transition metal-catalyzed alkylol
Direct Csp3The selective function dough reaction of-H key is still one significant challenge of organic synthesis field so far.
In order to realize inertia alkyl Csp3The reactivity and selectivity of-H key function dough reaction, currently, guiding strategy
It is widely applied in the selective function dough reaction of inertia c h bond.However, (such as U.S. Scripps is ground common guiding base
Study carefully professor's Yu Jinquan amide compound for using polyfluoro aniline to replace as guiding base, the Chatani of Osaka, Japan university
Professor use amide derived from 8- aminoquinoline as be oriented to base) promotion direct alkyl Csp3- H key alkynylation reaction, however
This kind of guiding base is often not easy conversion or expensive, this is but also entire reaction process practical application relatively difficult to achieve.
More challenge, for the direct Csp of the alkyl compound containing nitrogen-oxygen bond3For the alkynyl of-H key, by
It Glaser easily occurs under transition metal-catalyzed reacts to be total in alkynyl reagent such as end alkynes or the alkynes of function dough
Yoke diine side reaction, and substantially reduce the generation of targeted transformation.
The present invention is reacted under the effect of the catalyst using compound shown in compound and formula (III) shown in formula (II),
The alkynes derivative shown in formula (I) containing nitrogen-oxygen bond is obtained, it can be efficiently highly selective to compound shown in formula (II)
Csp3- H key carries out alkynylation reaction.Also, compound shown in compound shown in formula (II) and formula (III) be widely present in medicine,
The fields such as material, raw material is common to be easy to get, and the obtained alkynes derivative containing nitrogen-oxygen bond contains the nitrogen-oxygen key easily converted, Ke Yitong
It crosses reduction and obtains the primary amine of high added value and the polysubstituted alcohol compound containing alkynyl, have in organic synthesis field good
Application prospect.
Preparation method of the present invention is based on metal catalytic, directly carries out Csp to the alkyl compound containing nitrogen-oxygen bond3- H key alkynyl
Change reaction, has the following characteristics that 1) preparation method of the present invention is directly with inertia Csp3- H key, which sets out, constructs alkynes, has good
Atom economy, step economy meet the synthesis theory of Green Chemistry；2) substituent group of the silicon substrate as alkynes, can be with
Convenient removing, and then obtain end alkynes；3) contain the nitrogen-oxygen key easily converted, energy in alkynes derivative of the product containing nitrogen-oxygen bond
Enough further realize efficiently synthesizing for primary amine and the polysubstituted alcohol compound containing alkynyl；4) chemistry of preparation method of the present invention
Conversion has fabulous position specific, i.e. the reaction organic metal cyclic intermediate nitrogenous by in-situ preparation, and then one
Grade Csp3The alkynylation reaction that regioselectivity is carried out on-H key, obtains the alkynes derivative containing nitrogen-oxygen bond.
Preparation method of the present invention based on the alkyl compound containing nitrogen-oxygen bond nitrogen-oxygen key have be easily introduced, easily conversion etc. it is excellent
Point avoids and easily occurs to eliminate in the reaction of catalysis oxidation C-H bond function dough and aoxidize side reaction, to be carbonylated
The problems such as closing object or olefin by-products, not only solves the side reactions such as oxidation, the elimination of the alkyl compound containing nitrogen-oxygen bond, also mentions
A kind of tactful Csp to the acetylene hydrocarbon compound containing nitrogen-oxygen bond being simple and efficient is supplied3- H key carries out Efficient Conversion.Present invention preparation
Nitrogen-oxygen key in the alkynes derivative containing nitrogen-oxygen bond that method obtains can be converted into the alcohols containing alkynyl by reduction reaction
Object and primary amine are closed, realizes that the alkyl compound containing nitrogen-oxygen bond is converted into the alcohol containing alkynyl, nitrogen-oxygen bond is as seamless homing device.This
Invention preparation method can pass through the adjusting of nitrogen-oxygen key structure, realize five yuan metal ring intermediates of the conversion through nitrogen atom,
Reach the Csp of regioselectivity3The alkynylation reaction of-H key；Also, the conversion is only to level-one Csp3The reaction of-H key.
For preparation method of the present invention to the applied widely of substrate, the alkynes containing nitrogen-oxygen bond of obtained regioselectivity is derivative
Object is easy to subsequent transformation, directly can carry out later period modification to the active alcohol derivatives of potential source biomolecule.
In the present invention, the metallic catalyst is more preferably the metallic catalyst that metal is divalent ruthenium or trivalent rhodium.
It is preferably, described to react compound shown in compound shown in formula (II) and formula (III) specifically:
Compound shown in compound shown in formula (II) and formula (III) is dissolved in atent solvent, in oxidant and metal catalytic
Under the action of agent, reacted under alkaline condition.
Preferably, the metallic catalyst is selected from palladium acetate (Pd (OAc)2), palladium chloride (PdCl2), ruthenium trichloride
(RuCl3), dichloro (p -Methylisopropylbenzene base) ruthenium (II) dimer ([Ru (p-cymene) Cl2]2), dichloro (pentamethyl ring penta
Dialkylene) close rhodium (III) dimer ([Cp*RhCl2]2) ,-two (hexafluoro-antimonic acid) rhodium ([Cp* of three acetonitrile of pentamethylcyclopentadiene base
Rh(MeCN)3][SbF6]2) and dichloro (pentamethylcyclopentadiene base) conjunction iridium (III) dimer ([Cp*IrCl2]2One of)
Or a variety of, more preferably-two (hexafluoro-antimonic acid) rhodium of three acetonitrile of pentamethylcyclopentadiene base and/or dichloro (pentamethylcyclopentadiene
Base) close iridium (III) dimer.
When metallic catalyst is that dichloro (pentamethylcyclopentadiene base) closes iridium (III) dimer, reaction is preferably added to double
Trifluoromethanesulfonimide silver salt (AgNTf2), double trifluoromethanesulfonimide silver salt seize agent as a kind of chloride ion, with two
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer and is used together, and can seize dichloro (pentamethylcyclopentadiene base) conjunction
Chloride ion on iridium (III) dimer, so that the trivalent iridium catalyst species of in-situ preparation more electron deficient, it is electrophilic to enhance its
Property.
In the present invention, R1And R2It is independent to be selected from hydrogen, alkyl, naphthenic base, phenyl, substituted-phenyl, naphthalene, furyl, thiophene
Base, indyl or pyrrole radicals, R3Selected from triisopropylsilyl, dimethyl tertiary butyl silicon substrate or oxygen silicon ether containing cyclohexyl.
Further, R1And R2It is independent to be selected from hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, benzyl, benzene second
Base, phenylpropyl, phenyl, naphthalene, furyl, thienyl, indyl or pyrrole radicals, R3Selected from triisopropylsilyl (- TIPS), two
Methyl tertbutyl silicon substrate (- TMS) or oxygen silicon ether containing cyclohexyl.
Further, R1And R2It is independent to be selected from hydrogen, methyl, ethyl, benzyl, the fluoro- benzyl of 4-, 2- chlorobenzyl, 2- bromobenzyl
Base or phenethyl, R3For triisopropylsilyl (- TIPS).
In the present invention, the alkynes derivative containing nitrogen-oxygen bond shown in formula (I) is selected from
Compound shown in formula (II) by commercially available alcohol pass through with n-Hydroxyphthalimide carry out Mitsnobu reacted with
And hydrazine hydrate hydrazinolysis obtains corresponding primary amine, then is condensed to yield with cyclohexanone.
Compound shown in formula (II) is preferably
Compound shown in formula (III) is selected from
Preferably, the oxidant be selected from silver acetate, silver carbonate, three fluosulfonic acid silver, silver nitrate, copper acetate, cuprous halide,
One of copper halide, three iron halides and ferric nitrate are a variety of, more preferably copper acetate；
The alkali of the alkaline condition is adjusted in sodium acetate, cesium acetate, potassium acetate, sodium carbonate, lithium carbonate and potassium phosphate
One or more, more preferably sodium acetate.
Preferably, the temperature of the reaction be 60 DEG C~150 DEG C, more preferably 80 DEG C~120 DEG C, further preferably
100℃；
The time of the reaction is 8h~48h, more preferably 8h~36h.
In the present invention, atent solvent be selected from toluene, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, N, N '-dimethyl formamide, N,
N '-dimethyl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide, acetonitrile, 1,2- dichloroethanes, ethyl alcohol or acetone, more preferably
1,2- dichloroethanes.
Preferably, the molar ratio of compound shown in compound shown in formula (II) and formula (III) is 1:1~1:4；
The dosage of the metallic catalyst is 1mol%~5mol% of compound amount shown in formula (II), more preferably
2mol%.
In the present invention, the dosage of alkali is (5~50) mol% of compound amount shown in formula (II), more preferably
15mol%；
The dosage of oxidant is (10~300) mol%, more preferably 30mol% of compound amount shown in formula (II).
Compound shown in formula (II) is 0.1mol/L~3.0mol/L, preferably 0.2mol/L in the concentration of atent solvent；
Compound shown in formula (III) is 0.5mol/L~3.0mol/L, preferably 1.0mol/L in the concentration of atent solvent.
In the present invention, the preparation method of the alkynes derivative containing nitrogen-oxygen bond preferably includes following steps: under air atmosphere,
Compound (0.1mmol) shown in formula (II) is sequentially added in the reactor, dichloro (pentamethylcyclopentadiene base) closes iridium (III) two
Aggressiveness (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), lithium carbonate (14.8mg) and silver acetate (33.4mg), with note
The 1,2- dichloroethane solution (1.0mL) of compound (0.3mmol) shown in emitter injection formula (III) is placed in 100 into reactor
12h is reacted at DEG C, through thin-layer chromatographic analysis determine reaction terminate, by reaction solution after suction filtered through kieselguhr with 400 mesh silica gel through revolving
Inspissation contraction at dry powder, then use column chromatography for separation reaction product, 400 mesh silica gel 5g, solvent be volume ratio be 200:1 extremely
The petroleum ether and ethyl acetate of 20:1 obtains the alkynes derivative containing nitrogen-oxygen bond.
For oxynitrides derived from alkylol easily occur reset, oxidation, elimination reaction obtain ketone, carbonyls,
The by-products such as alkene, so that the direct oxidation Csp that alcoholic extract hydroxyl group promotes3The reaction of-H key function dough is rarely reported, system of the present invention
Preparation Method not only provides efficient, the high-selectivity synthesis method of the alkynes derivative containing nitrogen-oxygen bond, also provides derived from alcohols
The oxidation Csp of nitrogen oxides induction3- H key function dough provides new approaches.In addition, alkynes derivative of the present invention containing nitrogen-oxygen bond
Containing the nitrogen-oxygen key easily converted, the primary amine of high added value and the polysubstituted alcohol compound containing alkynyl can be obtained by reduction,
The fine chemicals of two kinds of high added values can be quickly obtained by a chemical conversion, therefore, the present invention will also select for position
The alkyl Csp of selecting property3The function dough reaction field of-H key provides certain theoretical direction.
Often contain that quantity is various and type Csp abundant for the common alkyl compound containing nitrogen-oxygen bond3- H key (one
Grade, second level, three-level Csp3- H key etc., or even also contain aryl Csp2- H key), catalyst system of the invention can effectively identify not
Congener c h bond, and react through metallic catalyst and five yuan of organic metal cyclic intermediates of substrate nitrogen-atoms in-situ preparation,
Position specific in level-one Csp3Alkynylation reaction occurs on-H key, obtains the alkynes derivative containing nitrogen-oxygen bond accordingly, energy
Enough realize the Csp of position specific3- H key alkynyl is worth with important synthesis.
The present invention also provides described in above-mentioned technical proposal containing nitrogen-oxygen bond alkynes derivative and/or above-mentioned technical proposal institute
State application of the alkynes derivative in medicine preparation containing nitrogen-oxygen bond made from preparation method.
Alkynes derivative of the present invention containing nitrogen-oxygen bond contains the nitrogen-oxygen key easily converted, can be obtained by reduction high additional
The primary amine of value and polysubstituted alcohol compound containing alkynyl, have a good application prospect in organic synthesis field.Also, R3
When to replace silicon substrate, alkynes analog derivative of the present invention containing nitrogen-oxygen bond contains can be convenient with what alkynes triple carbon-carbon bonds were connected directly
The silicon substrate left away can further obtain end alkine compounds.
In the present invention, the alkynes derivative containing nitrogen-oxygen bond can such as be passed through by being simply converted into the alcohol compound containing alkynyl
LAH (lithium aluminium hydride) reduction and TBAF (tetrabutyl ammonium fluoride) desiliconization, alcohol target product of the acquisition containing alkynyl that can be quantified.
In conclusion the present invention provides a kind of alkynes derivative containing nitrogen-oxygen bond, the alkynes containing nitrogen-oxygen bond is derivative
Shown in the structural formula of object such as formula (I), wherein R1And R2It is independent selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, C5~
The substituted aryl of C30 or the aromatic heterocyclic of C5~C30, R3To replace silicon substrate.In the present invention, alkynes of the present invention containing nitrogen-oxygen bond spreads out
Biology can obtain the primary amine of high added value and the polysubstituted alcohols containing alkynyl containing the nitrogen-oxygen key easily converted by reduction
Object is closed, is had a good application prospect in organic synthesis field.Also, alkynes derivative of the present invention containing nitrogen-oxygen bond contain with
What alkynes was connected directly can be convenient the silicon substrate left away, and can further obtain end alkine compounds.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 is cyclohexanone O- (5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether that the embodiment of the present invention 1 provides
The nuclear magnetic resonance of (1a)1H spectrogram；
Fig. 2 is cyclohexanone O- (5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether that the embodiment of the present invention 1 provides
The nuclear magnetic resonance of (1a)13C spectrogram；
Fig. 3 is cyclohexanone O- (2- methyl -5- (the triisopropylsilyl) -4- pentynyl -2- that the embodiment of the present invention 2 provides
Base) oxime ether (1b) nuclear magnetic resonance1H spectrogram；
Fig. 4 is cyclohexanone O- (2- methyl -5- (the triisopropylsilyl) -4- pentynyl -2- that the embodiment of the present invention 2 provides
Base) oxime ether (1b) nuclear magnetic resonance13C spectrogram；
Fig. 5 is cyclohexanone O- (6- (triisopropylsilyl) -5- hexin base -3- base) oxime ether that the embodiment of the present invention 3 provides
The nuclear magnetic resonance of (1c)1H spectrogram；
Fig. 6 is cyclohexanone O- (6- (triisopropylsilyl) -5- hexin base -3- base) oxime ether that the embodiment of the present invention 3 provides
The nuclear magnetic resonance of (1c)13C spectrogram；
Fig. 7 is cyclohexanone O- (1- phenyl -5- (the triisopropylsilyl) -4- pentynyl -2- that the embodiment of the present invention 4 provides
Base) oxime ether (1d) nuclear magnetic resonance1H spectrogram；
Fig. 8 is cyclohexanone O- (1- phenyl -5- (the triisopropylsilyl) -4- pentynyl -2- that the embodiment of the present invention 4 provides
Base) oxime ether (1d) nuclear magnetic resonance13C spectrogram；
Fig. 9 is cyclohexanone O- (1- (4- fluorophenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 5 provides
Alkynes -2- base) oxime ether (1e) nuclear magnetic resonance1H spectrogram；
Figure 10 is cyclohexanone O- (1- (4- fluorophenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 5 provides
Alkynes -2- base) oxime ether (1e) nuclear magnetic resonance13C spectrogram；
Figure 11 is cyclohexanone O- (1- (2- chlorphenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 6 provides
Alkynes -2- base) oxime ether (1f) nuclear magnetic resonance1H spectrogram；
Figure 12 is cyclohexanone O- (1- (2- chlorphenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 6 provides
Alkynes -2- base) oxime ether (1f) nuclear magnetic resonance13C spectrogram；
Figure 13 is cyclohexanone O- (1- (2- bromophenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 7 provides
Alkynes -2- base) oxime ether (1g) nuclear magnetic resonance1H spectrogram；
Figure 14 is cyclohexanone O- (1- (2- bromophenyl) -5- (triisopropylsilyl) -4- penta that the embodiment of the present invention 7 provides
Alkynes -2- base) oxime ether (1g) nuclear magnetic resonance13C spectrogram；
Figure 15 is cyclohexanone O- (1- phenyl -6- (the triisopropylsilyl) -5- hexin -3- that the embodiment of the present invention 8 provides
Base) oxime ether (1h) nuclear magnetic resonance1H spectrogram；
Figure 16 is cyclohexanone O- (1- phenyl -6- (the triisopropylsilyl) -5- hexin -3- that the embodiment of the present invention 8 provides
Base) oxime ether (1h) nuclear magnetic resonance13C spectrogram；
Figure 17 is the nuclear magnetic resonance for the 4- pentyne -2- alcohol (4a) that the embodiment of the present invention 9 provides1H spectrogram；
Figure 18 is the nuclear magnetic resonance for the 4- pentyne -2- alcohol (4a) that the embodiment of the present invention 9 provides13C spectrogram.
Specific embodiment
The present invention provides a kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond is a kind of new for providing
The alkynes derivative containing nitrogen-oxygen bond, widen the type of the alkynes derivative containing nitrogen-oxygen bond.
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
For a further understanding of the present invention, the present invention will be described in detail combined with specific embodiments below.
Embodiment 1
The present embodiment carries out the preparation of cyclohexanone O- (5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1a),
Reaction equation is as follows:
Under air atmosphere, compound 2a (15.5mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), the acetone with syringe injection 3a containing acetylene hydrocarbon compound (54.0mg, 0.3mmol) are molten
Liquid (1.0mL), which is placed at 120 DEG C into reactor, to react for 24 hours, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through silicon
After filtering with 400 mesh silica gel dry powder is made through concentrated by rotary evaporation in diatomaceous earth, then using column chromatography for separation reaction product, 400 mesh silica gel 5g,
Solvent is the petroleum ether and ethyl acetate that volume ratio is 200:1 to 20:1, obtains cyclohexanone O- (5- (triisopropylsilyl)-
4- pentynyl -2- base) oxime ether (1a), 25.1mg, purity 95%, yield 75%.
Magnetic resonance detection is carried out to cyclohexanone O- (5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1a), is asked
Refering to fig. 1 to Fig. 2, as a result are as follows:1H NMR (400MHz, CDCl3): δ 4.27-4.23 (m, 1H), 2.64 (dd, J=4.0Hz,
16.8Hz, 1H), 2.46-2.40 (m, 3H), 2.18 (t, J=6.0Hz, 2H), 1.66-1.65 (m, 2H), 1.59-1.58 (m,
4H), 1.34 (d, J=6.4Hz, 3H), 1.07-1.05 (m, 21H)；13C NMR(100MHz,CDCl3):δ160.3,105.4,
81.8,76.4,32.3,27.1,26.8,25.9,25.8,25.4,18.6,18.5,11.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the position the β Csp of oxygen atom under the assistance of nitrogen-oxygen key3-
The alkynylation reaction of H key, the present embodiment reaction have fabulous regioselectivity.
Embodiment 2
The present embodiment carries out cyclohexanone O- (2- methyl -5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1b)
Preparation, reaction equation are as follows:
Under air atmosphere, compound 2b (16.9mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), the acetone with syringe injection 3a containing acetylene hydrocarbon compound (54.0mg, 0.3mmol) are molten
Liquid (1.0mL), which is placed at 120 DEG C into reactor, to react for 24 hours, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through silicon
After filtering with 400 mesh silica gel dry powder is made through concentrated by rotary evaporation in diatomaceous earth, then using column chromatography for separation reaction product, 400 mesh silica gel 5g,
Solvent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone-O- (2- methyl -5- (three isopropyls
Base silicon substrate) -4- pentynyl -2- base) oxime ether (1b), 27.2mg, purity 95%, yield 78%.
It is total that nuclear-magnetism is carried out to cyclohexanone-O- (2- methyl -5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1b)
Vibration detection, please refers to Fig. 3 to Fig. 4, as a result are as follows:1H NMR(400MHz,CDCl3): δ=2.57 (s, 2H), 2.49-2.40 (m,
2H), 2.18 (t, J=6.0Hz, 2H), 1.70-1.60 (m, 2H), 1.58-1.56 (m, 4H), 1.37 (s, 6H), 1.08-1.07
(m,21H)；13C NMR(100MHz,CDCl3): δ=158.2,105.4,80.4,77.5,31.4,30.7,26.1,25.0,
24.8,24.2,17.6,10.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the position the β Csp of oxygen atom under the assistance of nitrogen-oxygen key3-
The alkynylation reaction of H key, the present embodiment reaction have fabulous regioselectivity.
Embodiment 3
The present embodiment carries out the preparation of cyclohexanone O- (6- (triisopropylsilyl) -5- hexin base -3- base) oxime ether (1c),
Reaction equation is as follows:
Under air atmosphere, compound 2c (16.9mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), with the acetone soln of syringe injection 3b containing acetylene hydrocarbon compound (78mg, 0.3mmol)
(1.0mL), which is placed at 120 DEG C into reactor, to react for 24 hours, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through diatom
Dry powder is made through concentrated by rotary evaporation with 400 mesh silica gel after soil suction filtration, then uses column chromatography for separation reaction product, 400 mesh silica gel 5g, exhibition
Opening agent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone O- (6- (triisopropylsilyl) -5-
Hexin base -3- base) oxime ether (1c), 24.8mg, purity 95%, yield 71%.
Magnetic resonance detection is carried out to cyclohexanone O- (6- (triisopropylsilyl) -5- hexin base -3- base) oxime ether (1c), is asked
Refering to Fig. 5 to Fig. 6, as a result are as follows:1H NMR(400MHz,CDCl3): δ=4.08-4.02 (m, 1H), 2.61 (dd, J=4.4Hz,
16.8Hz,1H),2.51-2.43(m,3H),2.18(m,2H),1.73-1.64(m,2H),1.59-1.58(m,6H),1.11-
1.04 (m, 21H), 0.95 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3): δ=160.4,105.5,81.7,
81.3,32.3,27.1,25.9,25.8,25.43,25.41,24.6,18.6,18.5,17.7,11.3,9.7。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the position the β Csp of oxygen atom under the assistance of nitrogen-oxygen key3-
The alkynylation reaction of H key, even if existing simultaneously γ level-one Csp in the compound containing nitrogen-oxygen bond3- H key.
Embodiment 4
The present embodiment carries out cyclohexanone O- (1- phenyl -5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1d)
Preparation, reaction equation are as follows:
Under air atmosphere, compound 2d (23.1mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), with the acetone soln of syringe injection 3b containing acetylene hydrocarbon compound (78mg, 0.3mmol)
(1.0mL), which is placed at 120 DEG C into reactor, reacts 18h, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through diatom
Dry powder is made through concentrated by rotary evaporation with 400 mesh silica gel after soil suction filtration, then uses column chromatography for separation reaction product, 400 mesh silica gel 5g, exhibition
Opening agent is the petroleum ether and ethyl acetate that volume ratio is 200:1 to 20:1, obtains cyclohexanone O- (1- phenyl -5- (triisopropyl silicon
Base) -4- pentynyl -2- base) oxime ether (1d), 32.9mg, purity 95%, yield 80%.
Nuclear magnetic resonance is carried out to cyclohexanone O- (1- phenyl -5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1d)
Detection, please refers to Fig. 7 to Fig. 8, as a result are as follows:1H NMR(400MHz,CDCl3):δ7.27-7.26(m,4H),7.23-7.18(m,
1H), 4.37-4.31 (m, 1H), 3.11 (dd, J=5.6Hz, 8.8Hz, 1H), 3.02 (dd, J=6.8Hz, 14.0Hz, 1H),
2.58-2.49(m,2H),2.47-2.43(m,2H),2.19-2.16(m,2H),1.65-1.56(m,6H),1.25(s,2H),
1.10-1.09(m,19H)；13C NMR(100MHz,CDCl3): δ=160.6,138.4,129.7,128.1,126.1,105.3,
82.5,80.8,38.4,32.2,29.7,27.1,25.8,24.2,18.7,18.6,18.5,18.4,17.7,12.3,11.4,
11.2。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the regional choice of oxygen atom under the assistance of nitrogen-oxygen key
The β Csp in property ground3The alkynylation reaction of-H key, there is no occur in common more active benzyl position or aryl c h bond position for reaction
Conversion.
Embodiment 5
The present embodiment carries out cyclohexanone O- (1- (4- fluorophenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether
The preparation of (1e), reaction equation are as follows:
Under air atmosphere, compound 2e (24.9mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), the acetone with syringe injection 3a containing acetylene hydrocarbon compound (54.0mg, 0.3mmol) are molten
Liquid (1.0mL), which is placed at 120 DEG C into reactor, reacts 20h, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through silicon
After filtering with 400 mesh silica gel dry powder is made through concentrated by rotary evaporation in diatomaceous earth, then using column chromatography for separation reaction product, 400 mesh silica gel 5g,
Solvent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone O- (1- (4- fluorophenyl) -5- (three
Isopropyl silicon substrate) -4- pentyne -2- base) oxime ether (1e), 31.3mg, purity 95%, yield 73%.
Nuclear-magnetism is carried out to cyclohexanone O- (1- (4- fluorophenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether (1e)
Resonance detection, please refers to Fig. 9 to Figure 10, as a result are as follows:1H NMR(400MHz,CDCl3):δ7.33-7.31(m,2H),7.16-
7.13 (m, 2H), 4.45-4.41 (m, 2H), 3.26 (dd, J=4.8Hz, 14.0Hz, 1H), 3.11 (dd, J=8.0Hz,
14.0Hz, 1H), 2.62 (d, J=5.2Hz, 2H), 2.49-2.35 (m, 2H), 2.13 (d, J=6.0Hz, 2H), 1.63-1.54
(m,6H),1.09-1.08(m,21H)；13C NMR(100MHz,CDCl3): δ=159.6,135.5,133.5,130.9,
128.3,126.6,125.3,104.0,81.5,78.1,35.5,31.1,26.0,24.8,24.7,24.5,24.0,17.6,
17.54,17.48,16.7,11.3,10.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the regional choice of oxygen atom under the assistance of nitrogen-oxygen key
The β Csp in property ground3The alkynylation reaction of-H key, the compatible fluorine functional group common in material, field of medicaments of reaction.
Embodiment 6
The present embodiment carries out cyclohexanone O- (1- (2- chlorphenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether
The preparation of (1f), reaction equation are as follows:
Under air atmosphere, compound 2f (26.5mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), the acetone with syringe injection 3c containing acetylene hydrocarbon compound (85.6mg, 0.2mmol) are molten
Liquid (1.0mL), which is placed at 120 DEG C into reactor, reacts 16h, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through silicon
After filtering with 400 mesh silica gel dry powder is made through concentrated by rotary evaporation in diatomaceous earth, then using column chromatography for separation reaction product, 400 mesh silica gel 5g,
Solvent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone O- (1- (2- chlorphenyl) -5- (three
Isopropyl silicon substrate) -4- pentyne -2- base) oxime ether (1f), 33.8mg, purity 95%, yield 76%.
Nuclear-magnetism is carried out to cyclohexanone O- (1- (2- chlorphenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether (1f)
Resonance detection, please refers to Figure 11 to Figure 12, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.21 (dd, J=5.6Hz, 8.4Hz,
1H), 6.95 (t, J=8.8Hz, 2H), 4.33-4.27 (m, 1H), 3.09 (dd, J=5.6Hz, 9.6Hz, 1H), 2.98 (dd, J
=6.8Hz, 14.0Hz, 1H), 2.56 (dd, J=4.0Hz, 16.8Hz, 1H), 2.45 (dd, J=7.2Hz, 16.8Hz, 3H),
2.19-2.16(m,2H),1.60-1.57(m,6H),1.10-1.07(m,21H)；13C NMR(100MHz,CDCl3): δ=
160.8,134.0,133.9,131.1,115.0,114.8,105.1,82.6,80.7,37.5,32.2,29.7,27.1,
25.83,25.78,25.6,24.2,18.7,18.5,17.8,17.7,12.3,11.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the regional choice of oxygen atom under the assistance of nitrogen-oxygen key
The β Csp in property ground3The alkynylation reaction of-H key, and do not react in the position of benzyl position or aryl chloride, it shows good
Regioselectivity and chemo-selective.
Embodiment 7
The present embodiment carries out cyclohexanone O- (1- (2- bromophenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether
The preparation of (1g), reaction equation are as follows:
Under air atmosphere, compound 2g (30.9mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), the acetone with syringe injection 3a containing acetylene hydrocarbon compound (54.0mg, 0.3mmol) are molten
Liquid (1.0mL), which is placed at 120 DEG C into reactor, to react for 24 hours, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through silicon
After filtering with 400 mesh silica gel dry powder is made through concentrated by rotary evaporation in diatomaceous earth, then using column chromatography for separation reaction product, 400 mesh silica gel 5g,
Solvent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone O- (1- (2- bromophenyl) -5- (three
Isopropyl silicon substrate) -4- pentyne -2- base) oxime ether (1g), 31.8mg, purity 95%, yield 65%.
Nuclear-magnetism is carried out to cyclohexanone O- (1- (2- bromophenyl) -5- (triisopropylsilyl) -4- pentyne -2- base) oxime ether (1g)
Resonance detection, please refers to Figure 13 to Figure 14, as a result are as follows:1H NMR(400MHz,CDCl3): δ=7.52 (d, J=8.4Hz, 1H),
7.33 (d, J=7.6Hz, 1H), 7.20 (t, J=7.2Hz, 1H), 7.07-7.03 (m, 1H), 4.47-4.47 (m, 1H), 3.29-
3.09(m,2H),2.65-2.63(m,1H),2.44-2.39(m,2H),2.19-2.13(m,3H),163-1.54(m,6H),
1.26-1.25(m,3H),1.13-1.02(m,21H)；13C NMR(100MHz,CDCl3): δ=159.6,158.8,137.6,
137.3,131.6,130.9,130.8,126.6,126.0,124.0,104.0,81.5,78.1,40.7,38.0,31.2,
31.1,26.05,26.02,24.9,24.8,24.7,24.5,24.4,17.7,10.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the regional choice of oxygen atom under the assistance of nitrogen-oxygen key
The β Csp in property ground3The alkynylation reaction of-H key, reaction have fabulous regioselectivity.More importantly reaction can be simultaneous
Hold the Arylbromide Compounds for being widely used in coupling reaction.
Embodiment 8
The system of the present embodiment progress cyclohexanone O- (1- phenyl -6- (triisopropylsilyl) -5- hexin -3- base) oxime ether (1h)
Standby, reaction equation is as follows:
Under air atmosphere, compound 2h (24.5mg, 0.1mmol) containing nitrogen-oxygen bond, two are sequentially added in the reactor
Chlorine (pentamethylcyclopentadiene base) closes iridium (III) dimer (3.2mg), double trifluoromethanesulfonimide silver salt (5.8mg), carbonic acid
Lithium (14.8mg) and silver acetate (33.4mg), with the acetone soln of syringe injection 3a containing acetylene hydrocarbon compound (78mg, 0.3mmol)
(1.0mL), which is placed at 120 DEG C into reactor, to react for 24 hours, determines that reaction terminates through thin-layer chromatographic analysis, by reaction solution through diatom
Dry powder is made through concentrated by rotary evaporation with 400 mesh silica gel after soil suction filtration, then uses column chromatography for separation reaction product, 400 mesh silica gel 5g, exhibition
Opening agent is the petroleum ether and ethyl acetate that volume ratio is 100:1 to 20:1, obtains cyclohexanone O- (1- phenyl -6- (triisopropyl silicon
Base) -5- hexin -3- base) oxime ether (1h), 33.1mg, purity 95%, yield 78%.
Nuclear magnetic resonance inspection is carried out to cyclohexanone O- (1- phenyl -6- (triisopropylsilyl) -5- hexin -3- base) oxime ether (1h)
It surveys, please refers to Figure 15 to Figure 16, as a result are as follows:1H NMR(400MHz,CDCl3): δ=7.19-7.17 (m, 2H), 7.13-7.07
(m,3H),4.13-4.01(m,1H),2.71-2.39(m,3H),2.47-2.39(m,3H),2.13-2.10(m,2H),1.59-
1.52(m,6H),1.18-1.17(m,2H),1.04-0.94(m,21H)；13C NMR(100MHz,CDCl3): δ=160.6,
142.3,128.45,128.42,128.3,125.7,105.3,80.0,79.4,37.5,34.3,32.35,32.28,31.8,
31.7,25.9,25.45,25.40,18.6,11.3。
This example demonstrates that the compound containing nitrogen-oxygen bond can realize the position the β Csp of oxygen atom under the assistance of nitrogen-oxygen key3-
The alkynylation reaction of H key, reaction have fabulous regioselectivity, react not in common more active benzyl position or aryl C-
The reaction of H key, and β second level Csp are existed simultaneously in substrate2When-H key, reaction is only single to be occurred in level-one Csp3On-H key.
Embodiment 9
The present embodiment carries out the preparation of 4- pentyne -2- alcohol (4a), and reaction equation is as follows:
Under nitrogen atmosphere, in O- containing cyclohexanone (5- (triisopropylsilyl) -4- pentynyl -2- base) oxime ether (1a)
Lithium aluminium hydride (LAH, 19mg, 0.5mmol) is added in the reactor of the diethyl ether solution (4.0mL) of (67.0mg, 0.2mmol), and
It reacts 48 hours at room temperature.Reaction solution is added tetrabutyl ammonium fluoride (104.4mg, 0.4mmol) after suction filtered through kieselguhr, with
After continue to react at room temperature 1 hour.Dry powder is made through concentrated by rotary evaporation with 400 mesh silica gel after suction filtered through kieselguhr in reaction solution,
Column chromatography for separation reaction product is used again, and 400 mesh silica gel 5g, solvent is the petroleum ether and second that volume ratio is 100:1 to 20:1
Acetoacetic ester obtains the alcohol derivatives 4- pentyne -2- alcohol (4a) containing alkynyl, 14.4mg, purity 95%, yield 86%.
Magnetic resonance detection is carried out to 4- pentyne -2- alcohol (4a), please refers to Figure 17 to Figure 18, as a result are as follows:1H NMR
(400MHz,CDCl3): δ=3.92-3.91 (m, 1H), 2.68-2.48 (m, 1H), 2.36-2.25 (m, 2H), 2.03-2.02
(m,1H),1.23-1.21(m,3H)；13C NMR(100MHz,CDCl3): δ=80.9,66.1,28.7,22.1.
This example demonstrates that can alkynes derivative by the present invention containing nitrogen-oxygen bond obtain through reduction, desilication reaction containing end
The alcohol derivatives of alkynes, to realize formal alcohol-induced Csp3The alkynylation reaction of-H key.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of alkynes derivative containing nitrogen-oxygen bond, which is characterized in that the structural formula of the alkynes derivative containing nitrogen-oxygen bond is such as
Shown in formula (I):
Wherein, R1And R2The independent substituted aryl or C5 for being selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, C5~C30
The aromatic heterocyclic of~C30, R3To replace silicon substrate.
2. the alkynes derivative according to claim 1 containing nitrogen-oxygen bond, which is characterized in that R1And R2It is independent to be selected from hydrogen, alkane
Base, naphthenic base, phenyl, substituted-phenyl, naphthalene, furyl, thienyl, indyl or pyrrole radicals, R3Selected from triisopropylsilyl,
Dimethyl tertiary butyl silicon substrate or oxygen silicon ether containing cyclohexyl.
3. the alkynes derivative according to claim 1 containing nitrogen-oxygen bond, which is characterized in that containing nitrogen-oxygen bond shown in formula (I)
Alkynes derivative is selected from:
4. a kind of preparation method of the alkynes derivative containing nitrogen-oxygen bond, which comprises the following steps:
Compound shown in compound shown in formula (II) and formula (III) is reacted under catalyst, obtains containing shown in formula (I)
The alkynes derivative of nitrogen-oxygen bond；
Wherein,
R1And R2The independent substituted aryl or C5~C30 for being selected from hydrogen, the alkyl of C1~C20, the aryl of C5~C30, C5~C30
Aromatic heterocyclic, R3To replace silicon substrate, X is hydrogen, bromine, chlorine, iodine or heterocyclic group containing iodine；
The catalyst is metallic catalyst, and the metal of the metallic catalyst is selected from one of palladium, ruthenium, rhodium and iridium or more
Kind.
5. the preparation method according to claim 4, which is characterized in that the metallic catalyst be selected from palladium acetate, palladium chloride,
Ruthenium trichloride, dichloro (p -Methylisopropylbenzene base) ruthenium (II) dimer, dichloro (pentamethylcyclopentadiene base) close rhodium (III) two
Aggressiveness ,-two (hexafluoro-antimonic acid) rhodium of three acetonitrile of pentamethylcyclopentadiene base and dichloro (pentamethylcyclopentadiene base) close iridium (III) two
One of aggressiveness is a variety of.
6. the preparation method according to claim 4, which is characterized in that described by compound shown in formula (II) and formula (III) institute
Show that compound is reacted under catalyst specifically:
Compound shown in compound shown in formula (II) and formula (III) is dissolved in atent solvent, in oxidant and metallic catalyst
Under effect, reacted under alkaline condition.
7. preparation method according to claim 6, which is characterized in that the oxidant is selected from silver acetate, silver carbonate, trifluoro
One of sulfonic acid silver, silver nitrate, copper acetate, cuprous halide, copper halide, three iron halides and ferric nitrate are a variety of；
Adjust one of the alkali of the alkaline condition in sodium acetate, cesium acetate, potassium acetate, sodium carbonate, lithium carbonate and potassium phosphate
Kind is a variety of.
8. preparation method according to claim 6, which is characterized in that the temperature of the reaction is 60 DEG C~150 DEG C；
The time of the reaction is 8h~48h.
9. preparation method according to claim 6, which is characterized in that chemical combination shown in compound shown in formula (II) and formula (III)
The molar ratio of object is 1:1~1:4；
The dosage of the metallic catalyst is 1mol%~5mol% of compound amount shown in formula (II).
10. alkynes derivative and/or claim 4 to 9 any one described in claims 1 to 3 any one containing nitrogen-oxygen bond
Application of the alkynes derivative in medicine preparation containing nitrogen-oxygen bond made from the preparation method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910666222.XA CN110305156B (en) | 2019-07-23 | 2019-07-23 | Alkyne derivative containing nitrogen-oxygen bond and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910666222.XA CN110305156B (en) | 2019-07-23 | 2019-07-23 | Alkyne derivative containing nitrogen-oxygen bond and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110305156A true CN110305156A (en) | 2019-10-08 |
| CN110305156B CN110305156B (en) | 2022-04-19 |
Family
ID=68081096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910666222.XA Active CN110305156B (en) | 2019-07-23 | 2019-07-23 | Alkyne derivative containing nitrogen-oxygen bond and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110305156B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113292593A (en) * | 2021-06-24 | 2021-08-24 | 广东工业大学 | Alcohol derivative-oriented aromatic ring remote hydrocarbon activation method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108640944A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of conjugated enynes amides compound and its preparation method and application |
| CN108640945A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of amides compound and the preparation method and application thereof |
| CN109942616A (en) * | 2019-04-18 | 2019-06-28 | 广东工业大学 | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl |
-
2019
- 2019-07-23 CN CN201910666222.XA patent/CN110305156B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108640944A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of conjugated enynes amides compound and its preparation method and application |
| CN108640945A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of amides compound and the preparation method and application thereof |
| CN109942616A (en) * | 2019-04-18 | 2019-06-28 | 广东工业大学 | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl |
Non-Patent Citations (3)
| Title |
|---|
| SOBENINA, L. N.ET AL: "Reaction of vinylacetylene with ketoximes under Trofimov-reaction conditions", 《ZHURNAL ORGANICHESKOI KHIMII》 * |
| THEODORA W.GREENE等原著: "8.炔键的保护", 《有机合成中的保护基》 * |
| 吴世晖等: "仿生环化合成睾丸激素", 《有机合成 下册》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113292593A (en) * | 2021-06-24 | 2021-08-24 | 广东工业大学 | Alcohol derivative-oriented aromatic ring remote hydrocarbon activation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110305156B (en) | 2022-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kowalski et al. | Alkynolate anions via a new rearrangement: the carbon analog of the Hofmann reaction | |
| CN110156660A (en) | A kind of isoindoline analog derivative and preparation method thereof | |
| WO2014077321A1 (en) | Aluminum catalyst | |
| CN109942616A (en) | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl | |
| CN102127024A (en) | Method for synthesizing 4-aryl-1H-1,2,3-triazole by using 1,1-dibromo-1-olefin | |
| CN110305156A (en) | A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond | |
| CN108358868B (en) | Preparation method of 2-substituted benzothiazole compound | |
| CN102146020B (en) | Method for synthesizing 1,3-diphenyl-1-propanol compound | |
| CN107641080B (en) | A kind of dihydronaphthalene ketones derivant and preparation method thereof containing spirane structure | |
| CN110256480A (en) | A kind of nitogen-contained heterocycle derivant and its preparation method and application containing alkynyl | |
| CN109867691A (en) | A kind of aryl amine derivant and its preparation method and application | |
| CN108640944A (en) | A kind of conjugated enynes amides compound and its preparation method and application | |
| Klix et al. | A practical, large-scale procedure for the preparation of N-protected α-amino ketones from α-amino acids | |
| CN110305155A (en) | A kind of imine derivative and its preparation method and application containing alkynyl | |
| CN109942615A (en) | A kind of aryl amine derivant and its preparation method and application containing alkynyl | |
| WO2020220651A1 (en) | Method for synthesizing chiral 2-hydroxy-1,4-dicarbonyl compound and pantolactone | |
| CN110317172A (en) | A kind of azepine Fluorenone analog derivative and its preparation method and application | |
| CN110054611A (en) | A kind of biaryl ring derivatives and preparation method thereof that cyano replaces | |
| CN106146238B (en) | Fullerene alkynyl derivatives and preparation method thereof | |
| CN110818582A (en) | GABA analogue and salt thereof, and synthesis method, application and medicament thereof | |
| Subirats et al. | Amino thiols versus amino alcohols in the asymmetric alkynylzinc addition to aldehydes | |
| CN105820096B (en) | A kind of method for preparing substitution ethyl aryl sulfone | |
| Heureux et al. | Short, asymmetric synthesis of epi-morphine ACNO analogues | |
| CN111320646B (en) | 1, 4-eneyne compound and preparation method and application thereof | |
| CN110194713A (en) | A kind of ɑ, beta unsaturated ketone compound and its preparation method and application |
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 |