CN105017312A - Preparation method of beta-aminoethylphosphonyl derivatives - Google Patents
Preparation method of beta-aminoethylphosphonyl derivatives Download PDFInfo
- Publication number
- CN105017312A CN105017312A CN201510360967.5A CN201510360967A CN105017312A CN 105017312 A CN105017312 A CN 105017312A CN 201510360967 A CN201510360967 A CN 201510360967A CN 105017312 A CN105017312 A CN 105017312A
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- China
- Prior art keywords
- mmol
- gram
- beta
- reaction
- methyl
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 217
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims abstract description 98
- 229910001961 silver nitrate Inorganic materials 0.000 claims abstract description 49
- -1 phosphine compound Chemical class 0.000 claims abstract description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 34
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 13
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 13
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 7
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 96
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 90
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 claims description 59
- 238000004809 thin layer chromatography Methods 0.000 claims description 56
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 48
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 46
- 238000004440 column chromatography Methods 0.000 claims description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Chemical group 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 238000001953 recrystallisation Methods 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 claims description 9
- URCAYJXJXYLGTI-UHFFFAOYSA-N ethene fluorobenzene Chemical compound C=C.FC1=CC=CC=C1 URCAYJXJXYLGTI-UHFFFAOYSA-N 0.000 claims description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 7
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 claims description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 6
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- SSZOCHFYWWVSAI-UHFFFAOYSA-N 1-bromo-2-ethenylbenzene Chemical compound BrC1=CC=CC=C1C=C SSZOCHFYWWVSAI-UHFFFAOYSA-N 0.000 claims description 3
- WGGLDBIZIQMEGH-UHFFFAOYSA-N 1-bromo-4-ethenylbenzene Chemical compound BrC1=CC=C(C=C)C=C1 WGGLDBIZIQMEGH-UHFFFAOYSA-N 0.000 claims description 3
- BOVQCIDBZXNFEJ-UHFFFAOYSA-N 1-chloro-3-ethenylbenzene Chemical compound ClC1=CC=CC(C=C)=C1 BOVQCIDBZXNFEJ-UHFFFAOYSA-N 0.000 claims description 3
- NVZWEEGUWXZOKI-UHFFFAOYSA-N 1-ethenyl-2-methylbenzene Chemical compound CC1=CC=CC=C1C=C NVZWEEGUWXZOKI-UHFFFAOYSA-N 0.000 claims description 3
- PECUPOXPPBBFLU-UHFFFAOYSA-N 1-ethenyl-3-methoxybenzene Chemical compound COC1=CC=CC(C=C)=C1 PECUPOXPPBBFLU-UHFFFAOYSA-N 0.000 claims description 3
- JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical compound CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 claims description 3
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 claims description 3
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 claims description 3
- ISRGONDNXBCDBM-UHFFFAOYSA-N 2-chlorostyrene Chemical compound ClC1=CC=CC=C1C=C ISRGONDNXBCDBM-UHFFFAOYSA-N 0.000 claims description 3
- AEIOZWYBDBVCGW-UHFFFAOYSA-N 2-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC=C1N AEIOZWYBDBVCGW-UHFFFAOYSA-N 0.000 claims description 3
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 claims description 3
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 claims description 3
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 claims description 3
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 claims description 3
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 claims description 3
- SNTUCKQYWGHZPK-UHFFFAOYSA-N 4-ethenylbenzonitrile Chemical compound C=CC1=CC=C(C#N)C=C1 SNTUCKQYWGHZPK-UHFFFAOYSA-N 0.000 claims description 3
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims description 3
- IZVRAXUGTRXXMC-UHFFFAOYSA-N C(C)(=O)NC1=CC=CC(=C1[As](O)(O)=O)O Chemical compound C(C)(=O)NC1=CC=CC(=C1[As](O)(O)=O)O IZVRAXUGTRXXMC-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 claims description 3
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 claims description 3
- SFBTTWXNCQVIEC-UHFFFAOYSA-N o-Vinylanisole Chemical compound COC1=CC=CC=C1C=C SFBTTWXNCQVIEC-UHFFFAOYSA-N 0.000 claims description 3
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 claims description 3
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims description 3
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- KQJQPCJDKBKSLV-UHFFFAOYSA-N 1-bromo-3-ethenylbenzene Chemical compound BrC1=CC=CC(C=C)=C1 KQJQPCJDKBKSLV-UHFFFAOYSA-N 0.000 claims description 2
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 claims description 2
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 claims description 2
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 2
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 claims description 2
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000003999 initiator Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 abstract 1
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 123
- 239000000203 mixture Substances 0.000 description 53
- 238000003786 synthesis reaction Methods 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 43
- 238000003756 stirring Methods 0.000 description 42
- 239000003921 oil Substances 0.000 description 41
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 16
- 238000010992 reflux Methods 0.000 description 10
- QQVDJLLNRSOCEL-UHFFFAOYSA-N (2-aminoethyl)phosphonic acid Chemical compound [NH3+]CCP(O)([O-])=O QQVDJLLNRSOCEL-UHFFFAOYSA-N 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 150000003008 phosphonic acid esters Chemical class 0.000 description 4
- RIUVXCFTSFBTEA-UHFFFAOYSA-N (2-amino-2-phenylethyl)phosphonic acid Chemical class OP(=O)(O)CC(N)C1=CC=CC=C1 RIUVXCFTSFBTEA-UHFFFAOYSA-N 0.000 description 3
- OHAAYVPYAYXJJY-UHFFFAOYSA-N (2-anilino-2-phenylethyl)phosphonic acid Chemical class N(C1=CC=CC=C1)C(CP(O)(O)=O)C1=CC=CC=C1 OHAAYVPYAYXJJY-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- JJPBKCZJVYSKGV-UHFFFAOYSA-N diethoxyphosphane Chemical compound CCOPOCC JJPBKCZJVYSKGV-UHFFFAOYSA-N 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- GGIINFMSIDXOPX-UHFFFAOYSA-N [2-amino-2-(4-chlorophenyl)ethyl]phosphonic acid Chemical compound OP(=O)(O)CC(N)C1=CC=C(Cl)C=C1 GGIINFMSIDXOPX-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- DHNUAKOQUGJUGA-UHFFFAOYSA-N silicon;sulfane Chemical compound [Si].S DHNUAKOQUGJUGA-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WUFZZXNLTWQGJY-UHFFFAOYSA-N C1(=CC=CC=C1)C(CP(C1=CC=CC=C1)(C1=CC=CC=C1)=O)NC(=O)C1=CC=C(C=C1)Br Chemical compound C1(=CC=CC=C1)C(CP(C1=CC=CC=C1)(C1=CC=CC=C1)=O)NC(=O)C1=CC=C(C=C1)Br WUFZZXNLTWQGJY-UHFFFAOYSA-N 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- HSCOXPSFUDNRGS-UHFFFAOYSA-N N-(2-diphenylphosphoryl-1-phenylethyl)-4-fluoroaniline Chemical compound C1(=CC=CC=C1)C(CP(C1=CC=CC=C1)(C1=CC=CC=C1)=O)NC1=CC=C(C=C1)F HSCOXPSFUDNRGS-UHFFFAOYSA-N 0.000 description 1
- IFOOABKNGLKLLE-UHFFFAOYSA-N OP(OC1=CC=CC=C1)(OC1=CC=CC=C1)=O.OP(OC1=CC=CC=C1)(OC1=CC=CC=C1)=O.O Chemical compound OP(OC1=CC=CC=C1)(OC1=CC=CC=C1)=O.OP(OC1=CC=CC=C1)(OC1=CC=CC=C1)=O.O IFOOABKNGLKLLE-UHFFFAOYSA-N 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- XYLMUPLGERFSHI-UHFFFAOYSA-N alpha-Methylstyrene Chemical compound CC(=C)C1=CC=CC=C1 XYLMUPLGERFSHI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229930014669 anthocyanidin Natural products 0.000 description 1
- 150000001452 anthocyanidin derivatives Chemical class 0.000 description 1
- 235000008758 anthocyanidins Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- OTYNBGDFCPCPOU-UHFFFAOYSA-N phosphane sulfane Chemical compound S.P[H] OTYNBGDFCPCPOU-UHFFFAOYSA-N 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3882—Arylalkanephosphonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
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- C07F9/40—Esters thereof
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Abstract
The invention discloses a preparation method of beta-aminoethylphosphonyl derivatives. The method comprises the following steps: adding an ethylene derivative, an ammonia derivative, an organic phosphine compound, silver nitrate, a catalytic amount of copper bromide, and a solvent into a reactor, reacting at 30-50DEG C to prepare a beta-aminoethylphosphonyl derivative, adding hydrochloric acid, and further reacting to obtain more beta-aminoethylphosphonyl derivatives. The ethylene derivative is used as an initiator, so raw materials are easy to obtain and have many kinds; and the products obtained by using the method are various, can be directly used, and can also be used in other further reactions. The method has the advantages of mild reaction conditions, simple reaction operation and post-treatment process, concise production technology, high yield, and suitableness for large scale production.
Description
Technical field
The present invention relates to a kind of nitrogenous organic phosphine compound, be specifically related to a kind of preparation method of beta-amido ethyl phosphono derivative, belong to organic synthesis field.
Background technology
The similar of beta-amido ethyl phosphono derivative is in beta-amino acids, there is physiologically active widely, as the effect such as metabolism and growth, pain relieving, adjustment blood pressure, coordinate plant growth that is antibacterial, the cell that excites nerve, affects, therefore can use (see Maier as medicine, agricultural chemicals, antagonist, anthocyanidin synthetic inhibitor, fructose diphosphate enzyme inhibitors etc., L. Phosphorus Sulfur 1983,14,295; Abbenante, Giovanni; Australian J. Chem., 1997,50,523-527; L. Maier, P. J. Diel, Phosphorus, Sulfur Silicon., 1995,107,245-255; L. Maier, P. J. Diel, Phosphorus, Sulfur Silicon., 1996,109-110,341-344; Erion, M. D.; Dang, Q.; Reddy, M. R.; Kasibhatla, S. R.; Huang, J. W.; Lipscomb, W. N.; Poelje, P. D. J. Am. Chem.Soc. 2007,129,15480-15490; Dang, Q.; Brown, B. S.; Liu, Y.; Rydzewski, R. M.; Robinson, E. D.; Poelje, P. D.; Reddy, M. R.; Erion, M. D. J. Med. Chem. 2009,52,2880 – 2898.).
In prior art, the synthetic method of beta-amido ethyl phosphono derivative mainly contains following several:
1, from nitrile, under organolithium reagent, sodium borohydride reduction agent exist, beta-amido ethyl phosphono derivative is obtained through addition, reduction and hydrolysis; The method needs synthesis, the sodium borohydride reduction agent of equivalent, and severe reaction conditions, reactions steps is many.
2, from β-carbonylic phosphonic acid ester through obtaining beta-amido ethyl phosphono derivative with hydrazine reaction, reduction and hydrolysis; The method needs with β-carbonylic phosphonic acid ester for initiator, and raw material is difficult to obtain, and reactions steps is many, and productive rate is lower.
3, beta-amido ethyl phosphono derivative is obtained from β-carbonylic phosphonic acid ester through ammonification, reduction and hydrolysis; The method needs with β-carbonylic phosphonic acid ester for initiator, and raw material is difficult to obtain, and needs to use expensive sodium cyanoborohydride as reductive agent, and productive rate is lower.
4, mix aromatic hydrocarbons and beta-aminoethyl phosphonic acid ester of bromo reacts in the basic conditions, then obtains beta-amido ethyl phosphono derivative through acidic conditions hydrolysis; The method needs with beta-aminoethyl phosphonic acid ester for initiator, and raw material is difficult to obtain, and productive rate is lower.
In sum, although prior art can prepare some beta-amido ethyl phosphono derivatives, there is severe reaction conditions, reaction raw materials is rare, reaction cost is high and product structure is few defect; Therefore exploitation reaction conditions is gentle, applied widely, reactions steps is few, productive rate is high, cost is low, it is extremely important to meet the beta-amido ethyl phosphono derivative preparation method of Green Chemistry requirement.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of preparation method of beta-amido ethyl phosphono derivative.
To achieve the above object of the invention, the technical solution used in the present invention is: a kind of preparation method of beta-amido ethyl phosphono derivative, comprise the following steps, ethene derivatives, ammonia derivative, organic phosphine compound, Silver Nitrate, cupric bromide and solvent are added in reactor, in 30 ~ 50 DEG C of reactions, obtained beta-amido ethyl phosphono derivative;
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: Silver Nitrate: cupric bromide is 1: (1 ~ 4): (1 ~ 2): (1 ~ 3): (0.1 ~ 0.3);
The general structure of described ethene derivatives is:
;
Wherein R
11, R
4, R
5selection take one of following scheme:
(1) R
11, R
4be all hydrogen, R
5for carboxyl;
(2) R
4for the one in methyl, bromine, phenyl, R
5for hydrogen, R
11for phenyl;
(3) R
5for the one in methyl, bromine, phenyl, R
11for phenyl, R
4for hydrogen;
(4) R
4, R
5be all hydrogen, R
11for
;
Described structural formula
middle R
1, R
2, R
3selection take one of following scheme:
(1) R
1for the one in hydrogen, methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
2, R
3be all hydrogen;
(2) R
2for the one in methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
1, R
3be all hydrogen;
(3) R
3for the one in methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
1, R
2be all hydrogen;
The general structure of described ammonia derivative is:
, wherein R
6for hydrogen, methyl, ethyl, propyl group, hexyl or
;
Described structural formula
in, R
7, R
8and R
9selection take one of following scheme:
(1) R
7during for a kind of in hydrogen, methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
8and R
9be all hydrogen;
(2) R
8during for a kind of in methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
7and R
9be all hydrogen;
(3) R
9during for a kind of in methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
7and R
8be all hydrogen;
Described organic phosphine compound is as shown in having structure general formula:
R
10for the one in methoxyl group, oxyethyl group, isopropoxy, tert.-butoxy, phenyl;
Described solvent is selected from: the one in methyl alcohol, ethanol, acetonitrile, acetic acid, propionic acid, methylene dichloride or toluene.
The chemical structure of general formula of the beta-amido ethyl phosphono derivative that the present invention obtains is:
。
In technique scheme, described ethene derivatives is selected from the one in vinylformic acid, vinylbenzene, 2-methyl styrene, 3-vinyl toluene, 4-vinyl toluene, 2-methoxy styrene, 3-methoxy styrene, 4-methoxy styrene, 2-fluorobenzene ethene, 3-fluorobenzene ethene, 4-fluorobenzene ethene, 2-bromstyrol, 3-bromstyrol, 4-bromstyrol, 2-chloro-styrene, 3-chloro-styrene, 4-chloro-styrene, a-vinyl toluene, Beta-methyl vinylbenzene, 1,2-diphenylethlene, 4-cyano-styrene, 4-nitrostyrolene.Described ammonia derivative is selected from the one in ammoniacal liquor, the amino fast quinoline of 6-acetylaminohydroxyphenylarsonic acid 9-, propylamine, aniline, 2-aminotoluene, 3-monomethylaniline, 4-monomethylaniline, 2-anisidine, 3-anisidine, 4-anisidine, 2-ethylaniline, 2-tertiary butyl aniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-bromaniline, 3-bromaniline, 4-bromaniline, 4-N-methyl-p-nitroaniline, 2-cyano-aniline.Described organic phosphine compound is selected from the one in dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, diphenyl phosphine oxide.
In technique scheme, in molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: Silver Nitrate: cupric bromide is 1: (1 ~ 4): (1 ~ 2): (1 ~ 3): (0.1 ~ 0.3); Be preferably 1: 3: 1.5: 2: 0.2.Accelerator level is few, not only simplify the purification process of product, reduces the generation of waste, and should have for industry and have positive realistic meaning.
In preferred technical scheme, described solvent is acetonitrile.
In preferred technical scheme, temperature of reaction is 40 DEG C.Method reaction conditions of the present invention is gentle, simple, without the need to the operation of complexity, obtains product yield very high, and ensure that the safety of reaction process.
In technique scheme, in air, thin-layer chromatography is utilized to follow the tracks of reaction until terminate completely.
In preferred technical scheme, reaction terminates to carry out purification processes to product afterwards; After reaction terminates, reaction solution, through column chromatography for separation, obtains target product beta-amido ethyl phosphono derivative.
Above-mentioned product can be obtained by reacting the beta-amido ethyl phosphono derivative of more structures further, is specially after 30 ~ 50 DEG C of reactions terminate, adds hydrochloric acid, then back flow reaction, obtain beta-amido ethyl phosphono derivative; The chemical structural formula of described beta-amido ethyl phosphono derivative is:
。
In technique scheme, the mass concentration of described hydrochloric acid is 20%; In molar ratio, beta-amido ethyl phosphono derivative: hydrochloric acid is 1: 2.
In technique scheme, during back flow reaction, thin-layer chromatography is utilized to follow the tracks of reaction until terminate completely.
In technique scheme, after back flow reaction terminates, in reaction solution, add sodium hydroxide solution, then reaction solution is concentrated into dry, obtain target product beta-amido ethyl phosphono derivative with methyl alcohol/propylene oxide recrystallization.
The reaction process of technical solution of the present invention can be expressed as:
Due to the utilization of technique scheme, the present invention compared with prior art has following advantages:
1. the present invention only adopts a small amount of promotor, and without the need to organic ligand, ethene derivatives can be utilized efficiently to prepare product for initiator, without the need to using precious metal reagent and other additives, raw material availability is high, and product yield is high; Simplify the purification process of product, reduce the generation of waste, effectively reduce costs, should have for industry and there is positive realistic meaning.
2. preparation method disclosed by the invention is applied widely, and raw material is easy to get, kind is a lot; Be not only applicable to alkyl phosphite, also be applicable to diphenyl phosphate oxygen, and overcome interfering with each other of reactive group first, carboxyl is introduced product structure by success, the product types obtained is various, not only directly can use, and but also may be used for other and further react, and greatly expand the product structure of beta-amido ethyl phosphono derivative, be conducive to the application of development beta-amido ethyl phosphono derivative in organic synthesis, agricultural chemicals, medicine, inhibitor etc.; Overcoming prior art only can for the defect of less substrate.
3. preparation method's reaction conditions gentleness disclosed by the invention, operation and last handling process are simple, only need 40 DEG C of reactions, the highest obtain 92% yield, especially for the raw material that can not react very well due to steric hindrance and conjugative effect impact, still reach the product yield of more than 65%, efficiently solve prior art complex operation, process hazard, severe reaction conditions, product yield are low, the defect that product structure is few; Be suitable for suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
The synthesis of embodiment one: 2-amino-2-phenylethyl phosphonic acids
Add methyl alcohol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), ammoniacal liquor (0.12 g, 4.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-amino-2-phenylethyl phosphonic acid ester (productive rate 81%);
1h NMR (400 MHz, CDCl
3):
δ8.50 (s, 2H), 7.18-7.42 (m, 5H
),4.11-4.31 (m, 1H
), 3.63 (d,
j=10.8 Hz, 6H), 1.60-1.80 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-amino-2-phenylethyl phosphonic acids (productive rate 75%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ7.20-7.40 (m, 5H
),4.11-4.31 (m, 1H
), 1.60-1.80 (m, 2H
).
The synthesis of embodiment two: 2-amino-2-(4-chloro-phenyl-) ethylphosphonic acid
Add ethanol (6 mL) in the reactor, 4-chloro-styrene (0.139 gram, 1 mmol), ammoniacal liquor (0.12 g, 4.0 mmol), dimethyl phosphite (0.22 g, 1 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 30 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-amino-2-(4-chloro-phenyl-) ethyl phosphonate (productive rate 84%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.50 (s, 2H), 7.57 – 7.43 (m, 4H), 4.11-4.31 (m, 1H
), 3.64 (d,
j=10.8 Hz, 6H), 1.61-1.80 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-amino-2-(4-chloro-phenyl-) ethylphosphonic acid (productive rate 77%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ7.60-7.20 (m, 4H
),4.13-4.34 (m, 1H
), 1.62-1.83 (m, 2H).
The synthesis of embodiment three: 2-aminoethyl phosphonic acid
Add acetonitrile (6 mL) in the reactor, vinylformic acid (0.072 gram, 1 mmol), ammoniacal liquor (0.24 g, 8.0 mmol), phosphonous acid diethyl ester (0.276 gram, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 50 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-aminoethylphosphonate (productive rate 78%).Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ4.30-4.50 (m, 1H
), 4.10 3.95 (m, 4H), 1.72-1.93 (m, 2H), 1.27 (t,
j=7.1 Hz, 6H).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-aminoethyl phosphonic acid (productive rate 71%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ4.09-4.33 (m, 2H
), 1.61-1.83 (m, 2H).
Amino-9 bases of the amino fast quinoline-9-of embodiment four: 2-(6-) synthesis of ethylphosphonic acid
Add acetonitrile (6 mL) in the reactor, vinylformic acid (0.072 gram, 1 mmol), amino fast quinoline (0.192 g of 6-acetylaminohydroxyphenylarsonic acid 9-, 1.0 mmol), phosphonous acid diethyl ester (0.276 gram, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
In reaction flask, add 15 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution be concentrated into dry, obtain amino-9 bases of the amino fast quinoline-9-of 2-(6-with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 72%).Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ8.23 (s, 1H), 3.50-3.15 (m, 2H
), 2.01-1.83 (m, 2H
).
The synthesis of embodiment five: 2-third amino-2-(4-chloro-phenyl-) ethylphosphonic acid
Add acetonitrile (6 mL) in the reactor, 4-chloro-styrene (0.139 gram, 1 mmol), propylamine (0.118 g, 2.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-third amino-2-(4-chloro-phenyl-) ethyl phosphonate (productive rate 82%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.53 (s, 2H), 7.57 – 7.43 (m, 4H), 4.11-4.31 (m, 2H
), 3.64 (d,
j=10.8 Hz, 6H), 2.60-2.40 (m, 2H
), 1.61-1.80 (m, 2H
),1.55-1.40 (m, 2H
), 0.95-0.84 (m, 3H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-third amino-2-(4-chloro-phenyl-) ethylphosphonic acid (productive rate 71%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ7.58-7.22 (m, 4H
),4.13-4.34 (m, 1H
), 2.63-2.42 (m, 2H), 1.62-1.83 (m, 2H), 1.52-1.38 (m, 2H), 0.95-0.78 (m, 3H).
The synthesis of embodiment six: 2-anilino-2-phenylethyl phosphonic acids
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), aniline (0.186 g, 2.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-anilino-2-phenylethyl phosphonic acid ester (productive rate 86%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.10 (s, 1H), 7.18-7.42 (m, 5H
),6.60-7.10 (m, 5H
),4.11-4.31 (m, 1H
), 3.63 (d,
j=10.8 Hz, 6H), 1.60-1.84 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-anilino-2-phenylethyl phosphonic acids (productive rate 76%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ7.41-7.30 (m, 5H), 7.15-7.00 (m, 2H), 6.90-6.60 (m, 3H), 4.09-4.25 (m, 1H
), 1.63-1.78 (m, 2H
).
Embodiment seven: 2-amino-2-(4-cyano-phenyl) synthesis of ethylphosphonic acid
Add acetonitrile (6 mL) in the reactor, 4-cyano-styrene (0.129g, 1 mmol), ammoniacal liquor (0.12g, 4.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-amino-2-(4-cyano-phenyl) ethyl phosphonate (productive rate 78%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.90 (s, 2H), 7.80 – 7.40 (m, 4H), 4.11-4.31 (m, 1H
), 3.64 (d,
j=10.8 Hz, 6H), 1.61-1.80 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution be concentrated into dry, obtain 2-amino-2-(4-cyano-phenyl with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 68%).Its analytical data is as follows:
1h NMR (300 MHz, CDCl
3):
δ7.79 (d,
j=7.2 Hz, 2 H), 7.44 (d,
j=6.9 Hz, 2 H), 4.60-4.49 (m, 1 H), 2.20-2.01 (m, 2 H).
Embodiment eight: 2-amino-2-(4-nitrophenyl) synthesis of ethylphosphonic acid
Add acetonitrile (6 mL) in the reactor, 4-nitrostyrolene (0.15 g, 1 mmol), ammoniacal liquor (0.12 g, 4.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-amino-2-(4-nitrophenyl) ethyl phosphonate (productive rate 81%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.90 (s, 2H), 8.20 (d,
j=7.8 Hz, 2H), 7.66 (d,
j=7.8 Hz, 2H), 4.11-4.31 (m, 1H
), 3.64 (d,
j=10.8 Hz, 6H), 1.61-1.80 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution be concentrated into dry, obtain 2-amino-2-(4-nitrophenyl with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 72%).Its analytical data is as follows:
1h NMR (300 MHz, CDCl
3):
δ8.20 (d,
j=7.2 Hz, 2 H), 7.61 (d,
j=6.9 Hz, 2 H), 4.59-4.51 (m, 1 H), 2.19-2.05 (m, 2 H).
The synthesis of embodiment nine: 2-phenyl-2-(4-oil of mirbane amido) ethylphosphonic acid
Add methyl alcohol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 4-N-methyl-p-nitroaniline (0.276 g, 2.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-phenyl-2-(4-oil of mirbane amido) ethyl phosphonate (productive rate 77%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ8.01 (d,
j=7.8 Hz, 2H), 7.18-7.42 (m, 5H
),6.92 (d,
j=7.8 Hz, 2H), 6.80 (s, 1H), 4.11-4.31 (m, 1H
), 3.64 (d,
j=10.8 Hz, 6H), 1.61-1.80 (m, 2H
).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution is concentrated into dry, obtain 2-phenyl-2-(4-oil of mirbane amido) ethylphosphonic acid (productive rate 66%) with methyl alcohol/propylene oxide recrystallization.Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ8.10 (d,
j=7.2 Hz, 2 H), 7.46-7.10 (m, 5H), 6.80 (d,
j=6.9 Hz, 2 H), 4.13-4.34 (m, 1H
), 2.63-2.42 (m, 2H).
Embodiment ten: 2-phenyl-2-(2-cyano-aniline base) synthesis of ethylphosphonic acid
Add methyl alcohol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 2-cyano-aniline (0.236 g, 2.0 mmol), phosphonous acid diethyl ester (0.276 gram, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate.After reaction terminates, take out half reaction solution, the crude by column chromatography obtained after concentrated is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product 2-phenyl-2-(2-cyano-aniline base) ethyl phosphonate (productive rate 80%).Its analytical data is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.00-7.60 (m, 10H
),4.11-4.31 (m, 1H
), 4.09 3.95 (m, 4H), 1.61-1.80 (m, 2H
), 1.27 (t,
j=7.1 Hz, 6H).
In reaction flask, add 7.5 mL 20% hydrochloric acid in second half reaction solution remaining, mixture reflux, TLC follows the tracks of reaction until terminate; Add appropriate sodium hydroxide solution, then reaction solution be concentrated into dry, obtain 2-phenyl-2-(2-cyano-aniline base with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 71%).Its analytical data is as follows:
1h NMR (300 MHz, D
2o):
δ7.60-7.20 (m, 7H), 7.10-6.80 (m, 2H), 4.09-4.23 (m, 1H
), 1.62-1.85 (m, 2H
).
Embodiment 11: the synthesis of ((2-phenyl-2-anilino) ethyl) diphenyl phosphine oxide
Add formic acid (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), aniline (0.093 gram, 1 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 65%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.68 (m, 4H), 7.56 – 7.42 (m, 6H), 7.37 (d,
j=7.2 Hz, 2H), 7.31 – 7.25 (m, 2H), 7.24 – 718 (m, 1H), 7.04 (dd,
j=8.3,7.5 Hz, 2H), 6.65 (t,
j=7.3 Hz, 1H), 6.44 (d,
j=7.7 Hz, 2H), 5.79 (s, 1H), 4.60 (td,
j=9.8,3.7 Hz, 1H), 2.89 – 2.65 (m, 2H).
Embodiment 12: the synthesis of ((2-phenyl-2-(4-fluoroanilino) ethyl) diphenyl phosphine oxide
Add acetic acid (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 4-fluoroaniline (0.22 gram, 2 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 76%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.78 – 7.68 (m, 4H), 7.57 – 7.43 (m, 6H), 7.35 (d,
j=7.2 Hz, 2H), 7.28 (t,
j=7.4 Hz, 2H), 7.25 – 7.18 (m, 1H), 6.81 – 6.67 (m, 2H), 6.47 – 6.32 (m, 2H), 5.57 (s, 1H), 4.49 (td,
j=9.9,3.4 Hz, 1H), 2.87 – 2.64 (m, 2H).
Embodiment 13: the synthesis of ((2-phenyl-2-(4-bromobenzene amido) ethyl) diphenyl phosphine oxide
Add methylene dichloride (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 4-bromaniline (0.51 gram, 3 mmol are good), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 30 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 86%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.76 – 7.68 (m, 4H), 7.58 – 7.44 (m, 6H), 7.33 – 7.26 (m, 4H), 7.24 – 7.20 (m, 1H), 7.11 (d,
j=8.2 Hz, 2H), 6.32 (d,
j=8.2 Hz, 2H), 5.87 (s, 1H), 4.50 (t,
j=8 Hz, 1H), 2.85 – 2.69 (m, 2H).
Embodiment 14: ((2-(3-tolyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add toluene (6 mL) in the reactor, 3-vinyl toluene (0.118 gram, 1 mmol), aniline (0.373 gram, 4 mmol keep), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 88%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.80 – 7.69 (m, 4H), 7.56 – 7.43 (m, 6H), 7.18 (d,
j=3.2 Hz, 3H), 7.11 – 6.99 (m, 3H), 6.65 (t,
j=7.3 Hz, 1H), 6.48 (d,
j=7.8 Hz, 2H), 5.73 (s, 1H), 4.59 (td,
j=9.8,3.8 Hz, 1H), 2.89 – 2.66 (m, 2H), 2.28 (s, 3H).
Embodiment 15: ((2-(4-tolyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add toluene (6 mL) in the reactor, 4-vinyl toluene (0.118 gram, 1 mmol), aniline (0.28 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 91%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.78 – 7.68 (m, 4H), 7.57 – 7.40 (m, 6H), 7.25 (d,
j=8.0 Hz, 2H), 7.12 – 7.00 (m, 4H), 6.65 (t,
j=7.3 Hz, 1H), 6.46 (d,
j=7.7 Hz, 2H), 5.88 (s, 1H), 4.58 (td,
j=9.8,3.8 Hz, 1H), 2.87 – 2.64 (m, 2H), 2.30 (s, 3H).
Embodiment 16: (2-phenyl-2-(4-chloroanilino) ethyl) synthesis of diphenyl phosphine oxide
Add methylene dichloride (6 mL) in the reactor, vinylbenzene (0.118 gram, 1 mmol), 4-chloroaniline (0.36 gram, 3 mmol), diphenyl phosphine oxide (0.202 gram, 1 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 72%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.78 – 7.67 (m, 4H), 7.57 – 7.43 (m, 6H), 7.35 – 7.26 (m, 4H), 7.21 (t,
j=7.1 Hz, 1H), 6.97 (d,
j=8.7 Hz, 2H), 6.36 (d,
j=8.7 Hz, 2H), 6.18 (s, 1H), 4.50 (td,
j=9.8,3.5 Hz, 1H), 2.88 – 2.66 (m, 2H).
Embodiment 17: ((2-(3-fluorophenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add methyl alcohol (6 mL) in the reactor, 3-fluorobenzene ethene (0.122 gram, 1 mmol), aniline (0.36 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 81%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.77 – 7.69 (m, 4H), 7.55 – 7.43 (m, 6H), 7.26 – 7.20 (m, 1H), 7.14 (d,
j=7.7 Hz, 1H), 7.11 – 7.01 (m, 3H), 6.87 (td,
j=8.2,2.1 Hz, 1H), 6.67 (t,
j=7.3 Hz, 1H), 6.43 (d,
j=7.8 Hz, 2H), 5.85 (s, 1H), 4.59 (td,
j=10.0,3.8 Hz, 1H), 2.85 – 2.67 (m, 2H).
Embodiment 18: ((2-(4-fluorophenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add methyl alcohol (6 mL) in the reactor, 4-fluorobenzene ethene (0.122 gram, 1 mmol), aniline (0.36 gram, 3 mmol), diphenyl phosphine oxide (0.404 gram, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 82%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.77 – 7.66 (m, 4H), 7.55 – 7.50 (m, 2H), 7.49 – 7.42 (m, 4H), 7.36 – 7.29 (m, 2H), 7.05 (dd,
j=8.5,7.4 Hz, 2H), 6.92 (t,
j=8.7 Hz, 2H), 6.67 (t,
j=7.3 Hz, 1H), 6.44 (d,
j=7.7 Hz, 2H), 5.99 (s, 1H), 4.62 (td,
j=10.0,3.9 Hz, 1H), 2.87 – 2.66 (m, 2H).
Embodiment 19: (2-phenyl-2-(2-anisole amido) ethyl) synthesis of diphenyl phosphine oxide
Add methyl alcohol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 2-anisidine (0.346 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 89%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.68 (m, 4H), 7.54 – 7.39 (m, 6H), 7.35 (d,
j=7.2 Hz, 2H), 7.24 (t,
j=7.4 Hz, 2H), 7.17 (t,
j=7.2 Hz, 1H), 6.77 – 6.69 (m, 1H), 6.65 – 6.57 (m, 2H), 6.23 (s, 1H), 5.55 (s, 1H), 4.77 (td,
j=9.4,4.2 Hz, 1H), 3.83 (s, 3H), 2.98 – 2.71 (m, 2H).
Embodiment 20: ((2-(4-bromophenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 4-bromstyrol (0.181 gram, 1 mmol), aniline (0.278 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.170 gram, 1 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 66%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.63 (m, 4H), 7.59 – 7.41 (m, 6H), 7.35 (d,
j=7.5 Hz, 2H), 7.23 (d,
j=7.6 Hz, 2H), 7.06 (s, 2H), 6.67 (s, 1H), 6.43 (d,
j=6.2 Hz, 2H), 5.91 (s, 1H), 4.60 (s, 1H), 2.92 – 2.61 (m, 2H).
Embodiment 21: ((2-(3-chloro-phenyl-)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 3-chloro-styrene (0.181 gram, 1 mmol), aniline (0.278 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 85%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.72 (d,
j=9.3 Hz, 4H), 7.58 – 7.40 (m, 6H), 7.33 (s, 1H), 7.27 (d,
j=8.0 Hz, 1H), 7.17 (d,
j=8.1 Hz, 2H), 7.05 (d,
j=6.9 Hz, 2H), 6.69 (t,
j=6.4 Hz, 1H), 6.44 (d,
j=7.2 Hz, 2H), 6.00 (s, 1H), 4.58 (t,
j=7.9 Hz, 1H), 2.90 – 2.60 (m, 2H).
Embodiment 22: the synthesis of ((2-phenyl-2-anilino) ethyl) diethyl phosphonate
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), aniline (0.278 gram, 3 mmol), diethyl phosphite (0.276 gram, 2 mmol), Silver Nitrate (0.510 gram, 3 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 92%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.43 (d,
j=7.4 Hz, 2H), 7.35 (t,
j=7.5 Hz, 2H), 7.25 (d,
j=7.2 Hz, 1H), 7.10 (t,
j=7.9 Hz, 2H), 6.69 (t,
j=7.3 Hz, 1H), 6.56 (d,
j=7.8 Hz, 2H), 5.26 (s, 1H), 4.73 (ddd,
j=13.3,8.2,5.5 Hz, 1H), 4.12 – 3.99 (m, 4H), 2.41 – 2.23 (m, 2H), 1.30 – 1.24 (m, 6H).
Embodiment 23: (2-phenyl-2-(3-toluidine) ethyl) synthesis of diphenyl phosphine oxide
Add propionic acid (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 3-monomethylaniline (0.321 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.510 gram, 3 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 87%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.69 (m, 4H), 7.56 – 7.43 (m, 6H), 7.36 (d,
j=7.2 Hz, 2H), 7.29 – 7.25 (m, 2H), 7.20 (t,
j=7.2 Hz, 1H), 6.91 (t,
j=7.8 Hz, 1H), 6.48 (d,
j=7.4 Hz, 1H), 6.36 (s, 1H), 6.18 (d,
j=7.9 Hz, 1H), 5.85 (s, 1H), 4.61 (td,
j=9.8,3.7 Hz, 1H), 2.87 – 2.67 (m, 2H), 2.20 (s, 3H).
Embodiment 24: (2-phenyl-2-(2-tertiary-butyl anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 2-tertiary butyl aniline (0.45 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 72%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.76 – 7.65 (m, 4H), 7.62 – 7.37 (m, 7H), 7.32 – 7.28 (m, 2H), 7.19 (t,
j=7.3 Hz, 2H), 7.12 (t,
j=7.2 Hz, 1H), 6.88 – 6.82 (m, 1H), 6.70 – 6.58 (m, 1H), 6.28 (d,
j=8.0 Hz, 1H), 5.83 (s, 1H), 4.88 – 4.78 (m, 1H), 3.02 – 2.78 (m, 2H), 1.62 (s, 9H).
Embodiment 25: (2-phenyl-2-(2-ethylbenzene amido) ethyl) synthesis of diphenyl phosphine oxide
Add ethanol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 2-ethylaniline (0.363 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 79%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3)
δ7.80 – 7.72 (m, 4H), 7.57 – 7.43 (m, 6H), 7.40 – 7.34 (m, 2H), 7.31 – 7.26 (m, 2H), 7.24 – 7.18 (m, 1H), 7.11 (d,
j=6.9 Hz, 1H), 6.84 (td,
j=7.9,1.5 Hz, 1H), 6.66 (td,
j=7.4,0.8 Hz, 1H), 6.14 (d,
j=7.7 Hz, 1H), 5.88 (s, 1H), 4.68 (td,
j=10.0,3.5 Hz, 1H), 2.96 – 2.78 (m, 2H), 2.77 – 2.62 (m, 2H), 1.41 (t,
j=7.5 Hz, 3H).
Embodiment 26: (2-phenyl-2-(2-toluidine) ethyl) synthesis of diphenyl phosphine oxide
Add ethanol (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 2-aminotoluene (0.321 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 84%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.81 – 7.71 (m, 4H), 7.55 – 7.43 (m, 6H), 7.38 (d,
j=7.3 Hz, 2H), 7.29 (t,
j=7.4 Hz, 2H), 7.22 (t,
j=7.2 Hz, 1H), 7.08 (d,
j=7.1 Hz, 1H), 6.84 (t,
j=7.4 Hz, 1H), 6.61 (t,
j=7.3 Hz, 1H), 6.14 (d,
j=8.0 Hz, 1H), 5.81 (s, 1H), 4.68 (td,
j=9.9,3.3 Hz, 1H), 2.95 – 2.74 (m, 2H), 2.36 (s, 3H).
Embodiment 27: (2-phenyl-2-(4-toluidine) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 4-monomethylaniline (0.321 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.028 gram, 0.1 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 67%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.69 (m, 4H), 7.55 – 7.43 (m, 6H), 7.36 (d,
j=7.3 Hz, 2H), 7.30 – 7.25 (m, 2H), 7.20 (t,
j=7.2 Hz, 1H), 6.85 (d,
j=8.1 Hz, 2H), 6.36 (d,
j=8.3 Hz, 2H), 5.67 (s, 1H), 4.58 (td,
j=9.8,3.5 Hz, 1H), 2.85 – 2.66 (m, 2H), 2.18 (s, 3H).
Embodiment 28: (1-methyl-2-phenyl-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, Beta-methyl vinylbenzene (0.119 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 85%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.94 – 7.87 (m, 2H), 7.84 – 7.75 (m, 2H), 7.62 – 7.48 (m, 4H), 7.43 – 7.38 (m, 2H), 7.37 – 7.31 (m, 4H), 7.31 – 7.25 (m, 1H), 7.05 (t
j=7.9 Hz, 2H), 6.68 (t,
j=7.3 Hz, 1H), 6.43 (d,
j=7.9 Hz, 2H), 5.79 (s, 1H), 4.44 (dd,
j=6.9,2.7 Hz, 1H), 2.78 – 2.66 (m, 1H), 1.20 (dd,
j=15.5,7.4 Hz, 3H).
Embodiment 29: ((2-(3-p-methoxy-phenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 3-methoxy styrene (0.134 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.068 gram, 0.3 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 84%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.77 (s, 5H), 7.62 – 7.42 (m, 6H), 7.23 (s, 1H), 7.02 (d,
j=42.9 Hz, 4H), 6.73 (d,
j=33.5 Hz, 2H), 6.50 (s, 2H), 5.59 (s, 1H), 4.59 (s, 1H), 3.79 (s, 3H), 2.95 – 2.65 (m, 2H).
Embodiment 30: ((2-(2-p-methoxy-phenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 2-methoxy styrene (0.134 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 86%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.83 – 7.75 (m, 2H), 7.71 – 7.62 (m, 2H), 7.53 – 7.38 (m, 7H), 7.18 – 7.12 (m, 1H), 7.06 (t,
j=7.8 Hz, 2H), 6.86 – 6.76 (m, 2H), 6.64 (t,
j=7.2 Hz, 1H), 6.47 (d,
j=7.9 Hz, 2H), 5.91 (s, 1H), 4.99 (td,
j=10.8,3.6 Hz, 1H), 3.86 (s, 3H), 3.00 – 2.71 (m, 2H).
Embodiment 31: ((2-(2-aminomethyl phenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 2-methyl styrene (0.118 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 85%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.73 (s, 4H), 7.48 (d,
j=24.0 Hz, 7H), 7.06 (d,
j=32.3 Hz, 5H), 6.63 (s, 1H), 6.36 (s, 2H), 5.83 (s, 1H), 4.69 (s, 1H), 2.68 (d,
j=27.0 Hz, 2H), 2.22 (s, 3H).
Embodiment 32: (2-methyl-2-phenyl-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, alpha-methyl styrene (0.118 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 71%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.89 (dd,
j=10.7,7.5 Hz, 2H), 7.76 – 7.51 (m, 7H), 7.50 – 7.45 (m, 1H), 7.44 – 7.37 (m, 2H), 7.36 – 7.31 (m, 2H), 7.26 (t,
j=7.2 Hz, 1H), 7.01 (t,
j=7.8 Hz, 2H), 6.65 (t,
j=7.0 Hz, 1H), 6.44 (s, 1H), 6.38 (d,
j=7.7 Hz, 2H), 3.02 (t,
j=12.8 Hz, 1H), 2.79 (dd,
j=15.1,8.0 Hz, 1H), 1.76 (s, 3H).
Embodiment 33: ((2-(2-bromophenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 2-bromstyrol (0.181 gram, 1 mmol), aniline (0.276 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 68%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.86 – 7.65 (m, 4H), 7.63 (dd,
j=7.8,1.4 Hz, 1H), 7.54 – 7.42 (m, 7H), 7.17 (t,
j=7.5 Hz, 1H), 7.05 (t,
j=7.9 Hz, 3H), 6.65 (t,
j=7.3 Hz, 1H), 6.39 (d,
j=7.9 Hz, 2H), 6.25 (s, 1H), 4.84 (td,
j=10.5,3.2 Hz, 1H), 2.93 – 2.63 (m, 2H).
Embodiment 34: (2-phenyl-2-(3-bromobenzene amido) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 3-bromaniline (0.51,3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 87%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3)
δ7.78 – 7.67 (m, 4H), 7.57 – 7.44 (m, 6H), 7.34 – 7.26 (m, 4H), 7.24 – 7.19 (m, 1H), 6.87 (t,
j=7.9 Hz, 1H), 6.75 (d,
j=7.7 Hz, 1H), 6.58 (s, 1H), 6.35 (d,
j=8.0 Hz, 1H), 6.04 (s, 1H), 4.54 (td,
j=9.5,6.2 Hz, 1H), 2.85 – 2.67 (m, 2H).
Embodiment 35: ((2-(4-chloro-phenyl-)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 4-chloro-styrene (0.138 gram, 1 mmol), aniline (0.278,3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 82%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.75 – 7.66 (m, 4H), 7.54 (t,
j=7.2 Hz, 2H), 7.45 (t,
j=7.0 Hz, 4H), 7.31 – 7.27 (m, 2H), 7.19 (d,
j=8.4 Hz, 2H), 7.05 (t,
j=7.8 Hz, 2H), 6.68 (t,
j=7.3 Hz, 1H), 6.45 (d,
j=7.9 Hz, 2H), 6.07 (s, 1H), 4.61 (td,
j=10.1,3.8 Hz, 1H), 2.88 – 2.64 (m, 2H).
Embodiment 36: ((2-(2-chloro-phenyl-)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 2-chloro-styrene (0.138 gram, 1 mmol), aniline (0.278,3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 66%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.84 – 7.77 (m, 2H), 7.74 – 7.67 (m, 2H), 7.66 – 7.60 (m, 1H), 7.55 – 7.41 (m, 6H), 7.31 (d,
j=4.9 Hz, 1H), 7.16 – 7.10 (m, 2H), 7.05 (t,
j=7.7 Hz, 2H), 6.66 (t,
j=7.2 Hz, 1H), 6.42 (d,
j=7.8 Hz, 2H), 6.05 (s, 1H), 4.93 (t,
j=9.0 Hz, 1H), 2.95 – 2.67 (m, 2H).
Embodiment 37: (2-phenyl-2-(3-anisole amido) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), 3-anisidine (0.369 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 91%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.79 – 7.69 (m, 4H), 7.56 – 7.44 (m, 6H), 7.36 (d,
j=7.3 Hz, 2H), 7.26 (d,
j=7.6 Hz, 2H), 7.20 (t,
j=7.2 Hz, 1H), 6.95 (t,
j=8.1 Hz, 1H), 6.24 (dd,
j=8.1,1.7 Hz, 1H), 6.09 (d,
j=7.7 Hz, 1H), 6.02 (s, 1H), 5.90 (s, 1H), 4.59 (td,
j=9.9,3.4 Hz, 1H), 3.65 (s, 3H), 2.90 – 2.67 (m, 2H).
Embodiment 38: ((2-(4-p-methoxy-phenyl)-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, 4-methoxy styrene (0.134 gram, 1 mmol), aniline (0.278 gram, 3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 88%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.77 – 7.67 (m, 4H), 7.56 – 7.38 (m, 6H), 7.27 (d,
j=8.7 Hz, 2H), 7.05 (t,
j=7.9 Hz, 2H), 6.78 (d,
j=8.7 Hz, 2H), 6.66 (t,
j=7.3 Hz, 1H), 6.47 (d,
j=7.9 Hz, 2H), 5.99 (s, 1H), 4.58 (td,
j=9.8,3.8 Hz, 1H), 3.78 (s, 3H), 2.90 – 2.66 (m, 2H).
Embodiment 39: (2-phenyl-2-anilino) ethyl) synthesis of phosphonic acids diisopropyl ester
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), aniline (0.278,3 mmol), diisopropyl phosphite (0.332 gram, 2 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 85%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.43 (d,
j=7.4 Hz, 2H), 7.35 (t,
j=7.5 Hz, 2H), 7.25 (d,
j=7.2 Hz, 1H), 7.09 (t,
j=7.9 Hz, 2H), 6.68 (t,
j=7.3 Hz, 1H), 6.54 (d,
j=7.9 Hz, 2H), 5.30 (s, 1H), 4.78 – 4.62 (m, 3H), 2.35 – 2.11 (m, 2H), 1.39 – 1.21 (m, 12H).
Embodiment 40: (1,2-phenylbenzene-2-anilino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, stilbene (0.18 gram, 1 mmol), aniline (0.278,3 mmol), diphenyl phosphine oxide (0.3 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 73%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.93 – 7.83 (m, 2H), 7.72 – 7.41 (m, 6H), 7.38 – 4.34 (m, 1H), 7.29 (d,
j=7.1 Hz, 3H), 7.19 – 6.99 (m, 10H), 6.67 (t,
j=7.3 Hz, 1H), 6.48 (d,
j=7.9 Hz, 2H), 6.00 (s, 1H), 4.88 – 4.77 (m, 1H), 3.83 (d,
j=4.4 Hz, 1H).
Embodiment 41: (2-phenyl-2-anilino) ethyl) synthesis of dimethyl phosphonate
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), aniline (0.278,3 mmol), diphenyl phosphine oxide (0.3 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol), cupric bromide (0.045 gram, 0.2 mmol), mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 85%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.43 (d,
j=7.4 Hz, 2H), 7.35 (t,
j=7.5 Hz, 2H), 7.25 (d,
j=7.2 Hz, 1H), 7.10 (t,
j=7.9 Hz, 2H), 6.69 (t,
j=7.3 Hz, 1H), 6.56 (d,
j=7.8 Hz, 2H), 5.26 (s, 1H), 4.73 (ddd,
j=13.3,8.2,5.5 Hz, 1H), 2.41 – 2.23 (m, 2H), 1.30 – 1.24 (s, 6H).
Embodiment 42: (2-phenyl-2-amino) ethyl) synthesis of diphenyl phosphine oxide
Add acetonitrile (6 mL) in the reactor, vinylbenzene (0.104 gram, 1 mmol), diphenyl phosphine oxide (0.3 gram, 1.5 mmol), Silver Nitrate (0.340 gram, 2 mmol) and cupric bromide (0.045 gram, 0.2 mmol), pass into ammonia, mixture is at 40 DEG C of stirring reactions; TLC follows the tracks of reaction until terminate completely; The crude by column chromatography obtained after reaction terminates is separated (sherwood oil/acetone/methylene dichloride=20/1/1), obtains target product (productive rate 73%).The analytical data of product is as follows:
1h NMR (400 MHz, CDCl
3):
δ7.77-7.60 (m, 2H), 7.55-7.40 (m, 8H), 7.35-7.20 (m, 5H), 5.11 (s, 2H), 4.05-3.90 (m, 1H), 2.04 – 1.80 (m, 2H).
Claims (10)
1. the preparation method of a beta-amido ethyl phosphono derivative, it is characterized in that, comprise the following steps, ethene derivatives, ammonia derivative, organic phosphine compound, Silver Nitrate, cupric bromide and solvent are added in reactor, in 30 ~ 50 DEG C of reactions, obtained beta-amido ethyl phosphono derivative;
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: Silver Nitrate: cupric bromide is 1: (1 ~ 4): (1 ~ 2): (1 ~ 3): (0.1 ~ 0.3);
The general structure of described ethene derivatives is:
;
Wherein R
11, R
4, R
5selection take one of following scheme:
(1) R
11, R
4be all hydrogen, R
5for carboxyl;
(2) R
4for the one in methyl, bromine, phenyl, R
5for hydrogen, R
11for phenyl;
(3) R
5for the one in methyl, bromine, phenyl, R
11for phenyl, R
4for hydrogen;
(4) R
4, R
5be all hydrogen, R
11for
;
Described structural formula
middle R
1, R
2, R
3selection take one of following scheme:
(1) R
1for the one in hydrogen, methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
2, R
3be all hydrogen;
(2) R
2for the one in methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
1, R
3be all hydrogen;
(3) R
3for the one in methyl, methoxyl group, ethyl, the tertiary butyl, fluorine, chlorine, bromine, cyano group and nitro, R
1, R
2be all hydrogen;
The general structure of described ammonia derivative is:
, wherein R
6for hydrogen, methyl, ethyl, propyl group, hexyl or
;
Described structural formula
in, R
7, R
8and R
9selection take one of following scheme:
(1) R
7during for a kind of in hydrogen, methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
8and R
9be all hydrogen;
(2) R
8during for a kind of in methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
7and R
9be all hydrogen;
(3) R
9during for a kind of in methyl, ethyl, the tertiary butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R
7and R
8be all hydrogen;
Described organic phosphine compound is as shown in having structure general formula:
R
10for the one in methoxyl group, oxyethyl group, isopropoxy, tert.-butoxy, phenyl;
Described solvent is selected from: the one in methyl alcohol, ethanol, acetonitrile, acetic acid, propionic acid, methylene dichloride or toluene;
The chemical structure of general formula of described beta-amido ethyl phosphono derivative is:
。
2. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, it is characterized in that: described ethene derivatives is selected from vinylformic acid, vinylbenzene, 2-methyl styrene, 3-vinyl toluene, 4-vinyl toluene, 2-methoxy styrene, 3-methoxy styrene, 4-methoxy styrene, 2-fluorobenzene ethene, 3-fluorobenzene ethene, 4-fluorobenzene ethene, 2-bromstyrol, 3-bromstyrol, 4-bromstyrol, 2-chloro-styrene, 3-chloro-styrene, 4-chloro-styrene, a-vinyl toluene, Beta-methyl vinylbenzene, 1, 2-diphenylethlene, 4-cyano-styrene, one in 4-nitrostyrolene, described ammonia derivative is selected from the one in ammoniacal liquor, the amino fast quinoline of 6-acetylaminohydroxyphenylarsonic acid 9-, propylamine, aniline, 2-aminotoluene, 3-monomethylaniline, 4-monomethylaniline, 2-anisidine, 3-anisidine, 4-anisidine, 2-ethylaniline, 2-tertiary butyl aniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-bromaniline, 3-bromaniline, 4-bromaniline, 4-N-methyl-p-nitroaniline, 2-cyano-aniline, described organic phosphine compound is selected from the one in dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, diphenyl phosphine oxide.
3. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, is characterized in that: utilize thin-layer chromatography to follow the tracks of reaction until terminate completely.
4. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, is characterized in that: in molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: Silver Nitrate: cupric bromide is 1: 3: 1.5: 2: 0.2.
5. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, is characterized in that: described solvent is acetonitrile; Temperature of reaction is 40 DEG C.
6. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, is characterized in that: reaction terminates to carry out purification processes to product afterwards; Be specially after reaction terminates, reaction solution, through column chromatography for separation, obtains target product beta-amido ethyl phosphono derivative.
7. the preparation method of beta-amido ethyl phosphono derivative according to claim 1, is characterized in that: after reaction terminates, add hydrochloric acid, then back flow reaction, obtain beta-amido ethyl phosphono derivative; The chemical structural formula of described beta-amido ethyl phosphono derivative is:
。
8. the preparation method of beta-amido ethyl phosphono derivative according to claim 7, is characterized in that: the mass concentration of described hydrochloric acid is 20%; In molar ratio, beta-amido ethyl phosphono derivative: hydrochloric acid is 1: 2.
9. the preparation method of beta-amido ethyl phosphono derivative according to claim 7, is characterized in that: during back flow reaction, utilizes thin-layer chromatography to follow the tracks of reaction until terminate completely.
10. the preparation method of beta-amido ethyl phosphono derivative according to claim 7, it is characterized in that: after back flow reaction terminates, sodium hydroxide solution is added in reaction solution, then reaction solution is concentrated into dry, obtains target product beta-amido ethyl phosphono derivative with methyl alcohol/propylene oxide recrystallization.
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| CN108727428B (en) * | 2018-07-09 | 2020-05-08 | 苏州大学 | β -aminophosphonic acid derivatives and process for their preparation |
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| CN106892942A (en) | 2017-06-27 |
| CN105017312B (en) | 2017-05-10 |
| CN106892942B (en) | 2019-01-04 |
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