CN106892942B - A kind of preparation method of beta-amido ethylphosphonic acid derivative - Google Patents
A kind of preparation method of beta-amido ethylphosphonic acid derivative Download PDFInfo
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- CN106892942B CN106892942B CN201710079473.9A CN201710079473A CN106892942B CN 106892942 B CN106892942 B CN 106892942B CN 201710079473 A CN201710079473 A CN 201710079473A CN 106892942 B CN106892942 B CN 106892942B
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- mmol
- beta
- gram
- reaction
- amido
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 168
- 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
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims abstract description 48
- -1 phosphine compound Chemical class 0.000 claims abstract description 47
- 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 12
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 135
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 238000004809 thin layer chromatography Methods 0.000 claims description 56
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 46
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 44
- 238000004440 column chromatography Methods 0.000 claims description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound 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
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical group [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 7
- 239000000908 ammonium hydroxide Substances 0.000 claims description 7
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 claims description 6
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-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
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-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
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 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
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-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
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-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
- 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
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 claims description 3
- QROGIFZRVHSFLM-QHHAFSJGSA-N [(e)-prop-1-enyl]benzene Chemical compound C\C=C\C1=CC=CC=C1 QROGIFZRVHSFLM-QHHAFSJGSA-N 0.000 claims description 3
- XYLMUPLGERFSHI-UHFFFAOYSA-N alpha-Methylstyrene Chemical compound CC(=C)C1=CC=CC=C1 XYLMUPLGERFSHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 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
- 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
- 239000000126 substance Substances 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 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
- AEIOZWYBDBVCGW-UHFFFAOYSA-N 2-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC=C1N AEIOZWYBDBVCGW-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
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 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
- 150000002825 nitriles Chemical class 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
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
- 238000004519 manufacturing process Methods 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000007858 starting material Substances 0.000 abstract description 5
- 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
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
- 239000000047 product Substances 0.000 description 82
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 53
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 238000004458 analytical method Methods 0.000 description 51
- 239000000203 mixture Substances 0.000 description 51
- 238000003786 synthesis reaction Methods 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 41
- 238000000926 separation method Methods 0.000 description 39
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical class CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- QQVDJLLNRSOCEL-UHFFFAOYSA-N (2-aminoethyl)phosphonic acid Chemical compound [NH3+]CCP(O)([O-])=O QQVDJLLNRSOCEL-UHFFFAOYSA-N 0.000 description 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 4
- 150000003008 phosphonic acid esters Chemical class 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000012043 crude product 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
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 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 2
- 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 2
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000006722 reduction reaction Methods 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
- NHNUFAASKXPOQA-UHFFFAOYSA-N (3-acetamido-2-hydroxyphenyl)arsonic acid Chemical compound C(C)(=O)NC=1C(=C(C=CC1)[As](O)(=O)O)O NHNUFAASKXPOQA-UHFFFAOYSA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- KQJQPCJDKBKSLV-UHFFFAOYSA-N 1-bromo-3-ethenylbenzene Chemical compound BrC1=CC=CC(C=C)=C1 KQJQPCJDKBKSLV-UHFFFAOYSA-N 0.000 description 1
- 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
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-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
- YUKIZXVYHFBFQT-UHFFFAOYSA-N C1(=CC=CC=C1)C(CP(O)(O)=O)NC(=O)C1=CC=C(C=C1)[N+](=O)[O-] Chemical compound C1(=CC=CC=C1)C(CP(O)(O)=O)NC(=O)C1=CC=C(C=C1)[N+](=O)[O-] YUKIZXVYHFBFQT-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000425573 Talanes Species 0.000 description 1
- POAYMPYIPZOYQW-UHFFFAOYSA-N [2-amino-2-(4-cyanophenyl)ethyl]phosphonic acid Chemical compound NC(CP(O)(O)=O)C1=CC=C(C=C1)C#N POAYMPYIPZOYQW-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 230000000202 analgesic effect Effects 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
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 230000000694 effects Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- XSQNOFMFKVYSNL-UHFFFAOYSA-N ethene;toluene Chemical group C=C.CC1=CC=CC=C1 XSQNOFMFKVYSNL-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- OTYNBGDFCPCPOU-UHFFFAOYSA-N phosphane sulfane Chemical compound S.P[H] OTYNBGDFCPCPOU-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- DHNUAKOQUGJUGA-UHFFFAOYSA-N silicon;sulfane Chemical compound [Si].S DHNUAKOQUGJUGA-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 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
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 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
- 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
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- 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)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
-
- 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
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5333—Arylalkane phosphine oxides or thioxides
-
- 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation methods of beta-amido ethylphosphonic acid derivative, ethene derivatives, ammonia derivative, organic phosphine compound, silver nitrate, the copper bromide of catalytic amount and solvent are added in reactor, reaction is carried out at 30~50 DEG C, beta-amido ethyl phosphine acyl derivative is made, hydrochloric acid is added further to react, obtains more beta-amido ethylphosphonic acid derivatives.The present invention is starting material using ethene derivatives, and raw material is easy to get, there are many type；Product types that benefit is obtained by the present invention multiplicity, not only can be directly using can be used for other further reactions again.Meanwhile reaction condition is mild, operation and last handling process are simple, concise production process, yield is higher, is suitable for large-scale production.
Description
The application is that application No. is the divisional application of 201510360967.5 Chinese invention patent application, the Shens of original application
It please day are as follows: on June 26th, 2015, application No. is: 201510360967.5, denomination of invention are as follows: a kind of beta-amido ethyl phosphono spreads out
The preparation method of biology.
Technical field
The present invention relates to a kind of nitrogenous organic phosphine compounds, and in particular to a kind of preparation of beta-amido ethylphosphonic acid derivative
Method belongs to organic synthesis field.
Background technique
The structure of beta-amido ethyl phosphine acyl derivative is similar to beta-amino acids, has extensive physiological activity, such as antibacterial, thorn
Swash nerve, influence cell growth and metabolism, analgesic, adjust blood pressure, coordinate plant growth the effects of, therefore can be used as medicine,
Pesticide, antagonist, anthocyanidin synthetic inhibitor, fructose diphosphate enzyme inhibitor etc. use (referring to Maier, 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 the prior art, beta-amido ethyl phosphine acyl derivative synthetic method mainly include the following types:
1, from nitrile, in the presence of organolithium reagent, sodium borohydride reduction agent, β-is obtained through addition, reduction and hydrolysis
Amido ethyl phosphine acyl derivative；This method needs the synthesis of equivalent, sodium borohydride reduction agent, severe reaction conditions, instead
Answer step more.
2, from β-carbonylic phosphonic acid ester through obtaining beta-amido ethyl phosphine acyl derivative with hydrazine reaction, reduction and hydrolysis；It should
Method is needed using β-carbonylic phosphonic acid ester as starting material, and raw material is difficult to obtain, and reaction step is more, and yield is lower.
3, beta-amido ethyl phosphine acyl derivative is obtained from β-carbonylic phosphonic acid ester through ammonification, reduction and hydrolysis；This method
It needing using β-carbonylic phosphonic acid ester as starting material, raw material is difficult to obtain, and need to use expensive sodium cyanoborohydride as reducing agent,
Yield is lower.
4, bromo heteroaryl hydrocarbon reacts under alkaline condition with beta-aminoethyl phosphonate ester, then hydrolyzes to obtain through acid condition
Beta-amido ethyl phosphine acyl derivative；This method need using beta-aminoethyl phosphonate ester as starting material, raw material is difficult to obtain, yield compared with
It is low.
Although there are reaction conditions in conclusion the prior art can prepare some beta-amido ethyl phosphine acyl derivatives
The defect harsh, reaction raw materials are rare, reaction cost is high and product structure is few；Therefore exploitation reaction condition is mild, is applicable in model
Enclose extensively, reaction step is few, yield is high, it is at low cost, meet Green Chemistry requirement beta-amido ethyl phosphine acyl derivative preparation side
Method is extremely important.
Summary of the invention
Goal of the invention of the invention is to provide a kind of preparation method of beta-amido ethyl phosphine acyl derivative.
To achieve the above object of the invention, the technical solution adopted by the present invention is that: a kind of beta-amido ethyl phosphine acyl derivative
Preparation method includes the following steps, by ethene derivatives, ammonia derivative, organic phosphine compound, silver nitrate, copper bromide and solvent
It is added in reactor, is reacted in 30~50 DEG C, beta-amido ethyl phosphine acyl derivative is made；
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: silver nitrate: copper bromide 1: (1~4): (1
~2): (1~3): (0.1~0.3)；
The general structure of the ethene derivatives are as follows:；
Wherein R11、R4、R5Selection take one of following scheme:
(1)R11、R4It is all hydrogen, R5For carboxyl；
(2) R4For one of methyl, bromine, phenyl, R5For hydrogen, R11For phenyl；
(3) R5For one of methyl, bromine, phenyl, R11For phenyl, R4For hydrogen；
(4) R4、R5It is all hydrogen, R11For；
The structural formulaMiddle R1、R2、R3Selection take one of following scheme:
(1) R1For one of hydrogen, methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R2、R3All
For hydrogen；
(2) R2For one of methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R1、R3All it is
Hydrogen；
(3) R3For one of methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R1、R2All it is
Hydrogen；
The general structure of the ammonia derivative are as follows:, wherein R6For hydrogen, methyl, ethyl, propyl, hexyl, 6-
Fast quinoline -9- the base of acetylaminohydroxyphenylarsonic acid, 2- cyano-phenyl or；
The structural formulaIn, R7、R8And R9Selection take one of following scheme:
(1) R7When for one of hydrogen, methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R8And R9All it is
Hydrogen；
(2) R8When for one of methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R9It is all hydrogen；
(3) R9When for one of methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R8It is all hydrogen；
The organic phosphine compound is as shown in having structure general formula:
R10For one of methoxyl group, ethyoxyl, isopropoxy, tert-butoxy, phenyl；
The solvent is selected from: one of methanol, ethyl alcohol, acetonitrile, acetic acid, propionic acid, methylene chloride or toluene.
The general formula of the chemical structure for the beta-amido ethyl phosphine acyl derivative that the present invention obtains are as follows:
。
In above-mentioned technical proposal, the ethene derivatives are selected from acrylic acid, styrene, 2-methyl styrene, 3- methylbenzene
Ethylene, 4- methyl styrene, 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- chlorostyrene, 3- chlorostyrene, 4-
Chlorostyrene, a- methyl styrene, Beta-methyl styrene, 1,2- diphenylethlene, 4- cyano styrene, in 4- nitrostyrolene
One kind.The ammonia derivative is selected from ammonium hydroxide, the fast quinoline of 6- acetylaminohydroxyphenylarsonic acid 9- amino, propylamine, aniline, 2-aminotoluene, 3- methyl
Aniline, 4- methylaniline, 2- aminoanisole, 3- aminoanisole, 4- aminoanisole, 2- ethyl aniline, 2- tert-butyl benzene
Amine, 2- fluoroaniline, 3- fluoroaniline, 4- fluoroaniline, 2- chloroaniline, 3- chloroaniline, 4- chloroaniline, 2- bromaniline, 3- bromaniline, 4-
One of bromaniline, 4- nitroaniline, 2- cyano-aniline.The organic phosphine compound is selected from dimethyl phosphite, diethyl
One of base phosphite ester, diisopropyl phosphite, diphenyl phosphine oxide.
In above-mentioned technical proposal, in molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: silver nitrate: bromination
Copper is 1: (1~4): (1~2): (1~3): (0.1~0.3)；Preferably 1: 3: 1.5: 2: 0.2.Accelerator dosage is few, not only simple
The purification process for having changed product reduces the generation of waste, and should have industry with positive realistic meaning.
In preferred technical solution, the solvent is acetonitrile.
In preferred technical solution, reaction temperature is 40 DEG C.Method reaction condition of the invention is mild, simple, without multiple
Miscellaneous operation, obtains that product yield is very high, and ensure that the safety of reaction process.
In above-mentioned technical proposal, in air, using thin-layer chromatography tracking reaction until being fully completed.
In preferred technical solution, purification processes are carried out to product after reaction；After reaction, reaction solution is through column layer
Analysis separation, obtains target product beta-amido ethyl phosphine acyl derivative.
Above-mentioned product beta-amido ethyl phosphine acyl derivative can further react to obtain beta-amido ethylphosphonic acid derivative, specifically
After reaction for 30~50 DEG C, hydrochloric acid is added, is then refluxed for reacting, obtains beta-amido ethylphosphonic acid derivative；β-the amine
The chemical structural formula of base ethylphosphonic acid derivative are as follows:
。
In above-mentioned technical proposal, the mass concentration of the hydrochloric acid is 20%；In molar ratio, beta-amido ethyl phosphine acyl derivative:
Hydrochloric acid is 1: 2.
In above-mentioned technical proposal, when back flow reaction, using thin-layer chromatography tracking reaction until being fully completed.
In above-mentioned technical proposal, after back flow reaction, sodium hydroxide solution is added in reaction solution, it is then that reaction solution is dense
It is reduced to dry, is recrystallized to give target product beta-amido ethylphosphonic acid derivative with methanol/propylene oxide.
The reaction process of technical solution of the present invention may be expressed as:
Due to the application of the above technical scheme, compared with the prior art, the invention has the following advantages:
It 1. the present invention is not necessarily to organic ligand only with a small amount of promotor, i.e., is that starting material is efficient using ethene derivatives
Product is prepared, without using noble metal reagent and other additives, raw material availability is high, product yield high；Simplify product
Purification process reduces the generation of waste, effectively reduces cost, and should have industry with positive realistic meaning.
2. preparation method disclosed by the invention is applied widely, raw material is easy to get, there are many type；It is applicable not only to alkyl Asia
Phosphate applies also for diphenyl phosphate oxygen, and overcomes interfering with each other for reactive group for the first time, and carboxyl is successfully introduced product
Structure, obtained product types multiplicity, not only can directly using can be used for again other it is further react, expansion significantly
The product structure of beta-amido ethyl phosphine acyl derivative, be conducive to develop beta-amido ethyl phosphine acyl derivative organic synthesis, pesticide,
The application of medicine, inhibitor etc.；The prior art is overcome to be only capable of being directed to the defect of less substrate.
3. preparation method reaction condition disclosed by the invention is mild, operation and last handling process are simple, it is only necessary to 40 DEG C
Reaction, the yield of highest available 92%, especially for due to steric hindrance and conjugation influence and the raw material that cannot react very well,
The product yield for still reaching 65% or more efficiently solves cumbersome prior art operation, process hazard, severe reaction conditions, production
Object yield is low, the few defect of product structure；It is suitable for industrialized production.
Specific embodiment
The present invention will be further described below with reference to examples:
The synthesis of one: 2- amino -2- phenylethyl phosphonic acids of embodiment
Methanol (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), ammonium hydroxide (0.12 g, 4.0
Mmol), dimethyl phosphite (0.22 g, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
Object 2- amino -2- phenylethyl phosphonate ester (yield 81%)；1H NMR (400 MHz, CDCl3): 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)。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- amino -2- phenylethyl phosphonic acids (yield 75%).Its analysis data are as follows:1H NMR (300 MHz,
D2O): 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- chlorphenyl) ethylphosphonic acid
Ethyl alcohol (6 mL) is added in the reactor, 4- chlorostyrene (0.139 gram, 1 mmol), ammonium hydroxide (0.12 g, 4.0
Mmol), dimethyl phosphite (0.22 g, 1 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 30 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
Object 2- amino -2- (4- chlorphenyl) ethyl phosphonate (yield 84%).Its analysis data are as follows:1H NMR (400 MHz,
CDCl3): 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)。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- amino -2- (4- chlorphenyl) ethylphosphonic acid (yield 77%).Its analysis data are as follows:1H NMR (300
MHz, D2O): δ7.60-7.20 (m, 4H), 4.13-4.34 (m, 1H), 1.62-1.83 (m, 2H) 。
The synthesis of three: 2- aminoethyl phosphonic acid of embodiment
Acetonitrile (6 mL) is added in the reactor, acrylic acid (0.072 gram, 1 mmol), ammonium hydroxide (0.24 g, 8.0
Mmol), phosphonous acid diethylester (0.276 gram, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 50 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
Object 2- aminoethylphosphonate (yield 78%).Its analysis data are as follows:1H NMR (300 MHz, D2O): 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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- aminoethyl phosphonic acid (yield 71%).Its analysis data are as follows:1H NMR (300 MHz, D2O): δ
4.09-4.33 (m, 2H), 1.61-1.83 (m, 2H) 。
Example IV: fast -9 base of quinoline -9- amino of 2-(6- amino) ethylphosphonic acid synthesis
Acetonitrile (6 mL) is added in the reactor, acrylic acid (0.072 gram, 1 mmol), the fast quinoline of 6- acetylaminohydroxyphenylarsonic acid 9- amino
(0.192 g, 1.0 mmol), phosphonous acid diethylester (0.276 gram, 2 mmol), silver nitrate (0.340 gram, 2 mmol),
Copper bromide (0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate；
15 mL, 20% hydrochloric acid is added in reaction flask, mixture is heated to reflux, and TLC tracking reaction is until terminate；It is added
Reaction solution, is then concentrated to dryness by suitable sodium hydroxide solution, and it is fast to be recrystallized to give 2-(6- amino with methanol/propylene oxide
- 9 base of quinoline -9- amino) ethylphosphonic acid (yield 72%).Its analysis data are as follows:1H NMR (300 MHz, D2O): 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- chlorphenyl) ethylphosphonic acid
Acetonitrile (6 mL) is added in the reactor, 4- chlorostyrene (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), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
The third amino of object 2- -2- (4- chlorphenyl) ethyl phosphonate (yield 82%).Its analysis data are as follows:1H NMR (400 MHz,
CDCl3): 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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give the third amino of 2- -2- (4- chlorphenyl) ethylphosphonic acid (yield 71%).Its analysis data are as follows:1H NMR (300
MHz, D2O): 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 six: 2- anilino- -2- phenylethyl phosphonic acids of embodiment
Acetonitrile (6 mL) is added in the reactor, styrene (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), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
Object 2- anilino- -2- phenylethyl phosphonate ester (yield 86%).Its analysis data are as follows:1H NMR (400 MHz, CDCl3):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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- anilino- -2- phenylethyl phosphonic acids (yield 76%).Its analysis data are as follows:1H NMR (300 MHz,
D2O): 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) 。
Seven: 2- amino -2-(4- cyano-phenyl of embodiment) ethylphosphonic acid synthesis
Acetonitrile (6 mL) is added in the reactor, 4- cyano styrene (0.129g, 1 mmol), ammonium hydroxide (0.12g, 4.0
Mmol), dimethyl phosphite (0.22 g, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, a half-reaction is taken out
Liquid, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtain target production
Object 2- amino -2-(4- cyano-phenyl) ethyl phosphonate (yield 78%).Its analysis data are as follows:1H NMR (400 MHz,
CDCl3): 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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- amino -2-(4- cyano-phenyl) ethylphosphonic acid (yield 68%).Its analysis data are as follows:1H NMR (300
MHz, CDCl3): 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) 。
Eight: 2- amino -2-(4- nitrobenzophenone of embodiment) ethylphosphonic acid synthesis
Acetonitrile (6 mL) is added in the reactor, 4- nitrostyrolene (0.15 g, 1 mmol), ammonium hydroxide (0.12 g,
4.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045
Gram, 0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, it is anti-to take out half
Liquid is answered, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtains target
Product 2- amino -2-(4- nitrobenzophenone) ethyl phosphonate (yield 81%).Its analysis data are as follows:1H NMR (400
MHz, CDCl3): 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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- amino -2-(4- nitrobenzophenone) ethylphosphonic acid (yield 72%).Its analysis data are as follows:1H NMR (300
MHz, CDCl3): δ 8.20 (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 nine: 2- phenyl -2- of embodiment (4- nitrobenzene amido) ethylphosphonic acid
Methanol (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 4- nitroaniline (0.276 g,
2.0 mmol), dimethyl phosphite (0.22 g, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045
Gram, 0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, it is anti-to take out half
Liquid is answered, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated obtains target
Product 2- phenyl -2- (4- nitrobenzene amido) ethyl phosphonate (yield 77%).Its analysis data are as follows:1H NMR (400
MHz, CDCl3): 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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- phenyl -2- (4- nitrobenzene amido) ethylphosphonic acid (yield 66%).Its analysis data are as follows:1H NMR
(300 MHz, D2O): δ 8.10 (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) 。
Ten: 2- phenyl -2-(2- cyano-aniline base of embodiment) ethylphosphonic acid synthesis
Methanol (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 2- cyano-aniline (0.236 g,
2.0 mmol), phosphonous acid diethylester (0.276 gram, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C, and TLC tracking reaction is until terminate.After reaction, it takes out
Half reaction solution, the crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1) obtained after concentrated, obtains
To target product 2- phenyl -2-(2- cyano-aniline base) ethyl phosphonate (yield 80%).Its analysis data are as follows:1H NMR
(400 MHz, CDCl3): δ 7.00-7.60 (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) 。
7.5 mL, 20% hydrochloric acid is added in the other half remaining reaction solution in reaction flask, mixture is heated to reflux, TLC
Tracking reaction is until terminate；Suitable sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methanol/propylene oxide
It is recrystallized to give 2- phenyl -2-(2- cyano-aniline base) ethylphosphonic acid (yield 71%).Its analysis data are as follows:1H NMR
(300 MHz, D2O): 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
Formic acid (6 mL) is added in the reactor, styrene (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), copper bromide (0.045 gram, 0.2
), mmol mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；The crude product warp obtained after reaction
Column chromatography for separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 65%).The analysis number of product
According to as follows:1H NMR (400 MHz, CDCl3): 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
Acetic acid (6 mL) is added in the reactor, styrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
76%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): 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
Methylene chloride (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 4- bromaniline (0.51 gram, 3
Mmol is good), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 30 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
86%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.76–7.68 (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) diphenyl phosphine oxide synthesis
Toluene (6 mL) is added in the reactor, 3- methyl styrene (0.118 gram, 1 mmol), aniline (0.373 gram, 4
Mmol is kept), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
88%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.80–7.69 (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) diphenyl phosphine oxide synthesis
Toluene (6 mL) is added in the reactor, 4- methyl styrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
91%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.78–7.68 (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) diphenyl phosphine oxide synthesis
Methylene chloride (6 mL) is added in the reactor, styrene (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), copper bromide (0.045
Gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；It obtains after reaction
Crude by column chromatography separates (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 72%).Product
Analysis data it is as follows:1H NMR (400 MHz, CDCl3): δ 7.78–7.67 (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) diphenyl phosphine oxide synthesis
Methanol (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
81%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.77–7.69 (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) diphenyl phosphine oxide synthesis
Methanol (6 mL) is added 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), copper bromide (0.045
Gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；It obtains after reaction
Crude by column chromatography separates (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 82%).Product
Analysis data it is as follows:1H NMR (400 MHz, CDCl3):δ 7.77–7.66 (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- methoxybenzene amido) ethyl) diphenyl phosphine oxide synthesis
Methanol (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 2- aminoanisole (0.346 gram,
3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
89%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79–7.68 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
66%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79–7.63 (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- chlorphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, 3- chlorostyrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
85%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.72 (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
Acetonitrile (6 mL) is added in the reactor, styrene (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), copper bromide (0.045 gram, 0.2
), mmol mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；The crude product warp obtained after reaction
Column chromatography for separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 92%).The analysis number of product
According to as follows:1H NMR (400 MHz, CDCl3): δ 7.43 (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) diphenyl phosphine oxide synthesis
Propionic acid (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 3- methylaniline (0.321 gram, 3
Mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.510 gram, 3 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
87%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79–7.69 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 2- tert-butyl aniline (0.45 gram, 3
Mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
72%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.76–7.65 (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- ethylo benzene amido) ethyl) diphenyl phosphine oxide synthesis
Ethyl alcohol (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 2- ethyl aniline (0.363 gram, 3
Mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
79%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3) δ 7.80–7.72 (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) diphenyl phosphine oxide synthesis
Ethyl alcohol (6 mL) is added in the reactor, styrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
84%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.81–7.71 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 4- methylaniline (0.321 gram, 3
Mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.028 gram, 0.1 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
67%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79–7.69 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, Beta-methyl styrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
85%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.94–7.87 (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- methoxyphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.068 gram, 0.3 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
84%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.77 (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- methoxyphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
86%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.83–7.75 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
85%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.73 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, α-methylstyrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
71%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.89 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
68%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.86–7.65 (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) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
87%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3) δ 7.78–7.67 (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- chlorphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, 4- chlorostyrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
82%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.75–7.66 (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- chlorphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, 2- chlorostyrene (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
66%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.84–7.77(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- methoxybenzene amido) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), 3- aminoanisole (0.369 gram,
3 mmol), diphenyl phosphine oxide (0.303 gram, 1.5 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
91%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79–7.69 (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- methoxyphenyl) -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added 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), copper bromide
(0.045 gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；After reaction
Obtained crude by column chromatography separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield
88%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.77–7.67 (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) phosphonic acids diisopropyl ester synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), aniline (0.278,3 mmol),
Diisopropyl phosphite (0.332 gram, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram,
0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；The thick production obtained after reaction
Object obtains target product (yield 85%) through column chromatography for separation (petroleum ether/acetone/methylene chloride=20/1/1).Point of product
It is as follows to analyse data:1H NMR (400 MHz, CDCl3): 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) 。
Example IV ten: (1,2- diphenyl -2- anilino-) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, 1,2- talan (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), copper bromide (0.045
Gram, 0.2 mmol), mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；It obtains after reaction
Crude by column chromatography separates (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 73%).Product
Analysis data it is as follows:1H NMR (400 MHz, CDCl3): δ 7.93–7.83 (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) 。
Example IV 11: (2- phenyl -2- anilino-) ethyl) dimethyl phosphonate synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (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), copper bromide (0.045 gram, 0.2
), mmol mixture is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；The crude product warp obtained after reaction
Column chromatography for separation (petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 85%).The analysis number of product
According to as follows:1H NMR (400 MHz, CDCl3): δ 7.43 (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) 。
Example IV 12: (2- phenyl -2- amino) ethyl) diphenyl phosphine oxide synthesis
Acetonitrile (6 mL) is added in the reactor, styrene (0.104 gram, 1 mmol), diphenyl phosphine oxide (0.3 gram,
1.5 mmol), silver nitrate (0.340 gram, 2 mmol) and copper bromide (0.045 gram, 0.2 mmol) are passed through ammonia, mixing
Object is stirred to react at 40 DEG C；TLC tracking reaction is until be fully completed；The crude by column chromatography separation obtained after reaction
(petroleum ether/acetone/methylene chloride=20/1/1), obtains target product (yield 73%).The analysis data of product are as follows:1H
NMR (400 MHz, CDCl3): δ 7.77-7.60 (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 (9)
1. a kind of preparation method of beta-amido ethylphosphonic acid derivative, which is characterized in that include the following steps, by ethylene derivative
Object, ammonia derivative, organic phosphine compound, silver nitrate, copper bromide and solvent are added in reactor, react in 30~50 DEG C, reaction
After, obtain beta-amido ethyl phosphine acyl derivative；Then hydrochloric acid is added, is then refluxed for reacting, obtains beta-amido ethylphosphonic acid
Derivative；
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: silver nitrate: copper bromide 1: (1~4): (1~2):
(1~3): (0.1~0.3)；
The general structure of the ethene derivatives are as follows:；
Wherein R11、R4、R5Selection take one of following scheme:
(1)R11、R4It is all hydrogen, R5For carboxyl；
(2) R4For one of methyl, bromine, phenyl, R5For hydrogen, R11For phenyl；
(3) R5For one of methyl, bromine, phenyl, R11For phenyl, R4For hydrogen；
(4) R4、R5It is all hydrogen, R11For；
The structural formulaMiddle R1、R2、R3Selection take one of following scheme:
(1) R1For one of hydrogen, methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R2、R3All it is
Hydrogen；
(2) R2For one of methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R1、R3It is all hydrogen；
(3) R3For one of methyl, methoxyl group, ethyl, tert-butyl, fluorine, chlorine, bromine, cyano and nitro, R1、R2It is all hydrogen；
The general structure of the ammonia derivative are as follows:, wherein R6For hydrogen, methyl, ethyl, propyl, hexyl, 6- acetyl ammonia
Fast quinoline -9- the base of base -, 2- cyano-phenyl or；
The structural formulaIn, R7、R8And R9Selection take one of following scheme:
(1) R7When for one of hydrogen, methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R8And R9It is all hydrogen；
(2) R8When for one of methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R9It is all hydrogen；
(3) R9When for one of methyl, ethyl, tert-butyl, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R8It is all hydrogen；
The organic phosphine compound is as shown in having structure general formula:
R10For one of methoxyl group, ethyoxyl, isopropoxy, tert-butoxy；
The solvent is selected from: one of methanol, ethyl alcohol, acetonitrile, acetic acid, propionic acid, methylene chloride or toluene；
The chemical structural formula of the beta-amido ethylphosphonic acid derivative are as follows:
。
2. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: the ethylene derivative
Object is selected from acrylic acid, styrene, 2-methyl styrene, 3- methyl styrene, 4- methyl styrene, 2- methoxy styrene, 3-
Methoxy styrene, 4- methoxy styrene, 2- fluorobenzene ethene, 3- fluorobenzene ethene, 4- fluorobenzene ethene, 2- bromstyrol, 3- bromine
Styrene, 4- bromstyrol, 2- chlorostyrene, 3- chlorostyrene, 4- chlorostyrene, α-methylstyrene, Beta-methyl styrene,
One of 1,2- diphenylethlene, 4- cyano styrene, 4- nitrostyrolene；The ammonia derivative is selected from ammonium hydroxide, propylamine, benzene
Amine, 2-aminotoluene, 3- methylaniline, 4- methylaniline, 2- aminoanisole, 3- aminoanisole, 4- aminoanisole, 2-
Ethyl aniline, 2- tert-butyl aniline, 2- fluoroaniline, 3- fluoroaniline, 4- fluoroaniline, 2- chloroaniline, 3- chloroaniline, 4- chloroaniline,
One of 2- bromaniline, 3- bromaniline, 4- bromaniline, 4- nitroaniline；The organic phosphine compound is selected from dimethyl phosphorous
One of acid esters, diethyl phosphite, diisopropyl phosphite.
3. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: prepare beta-amido second
Using thin-layer chromatography tracking reaction until being fully completed when base phosphono derivative.
4. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: in molar ratio, second
Ene derivative: ammonia derivative: organic phosphine compound: silver nitrate: copper bromide 1: 3: 1.5: 2: 0.2.
5. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: the solvent is second
Nitrile；The reaction temperature for preparing beta-amido ethyl phosphine acyl derivative is 40 DEG C.
6. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: prepare beta-amido second
Base phosphono derivative carries out purification processes to product after reaction；Specially after reaction, reaction solution is through column chromatography point
From obtaining beta-amido ethyl phosphine acyl derivative.
7. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: the matter of the hydrochloric acid
Measuring concentration is 20%；In molar ratio, beta-amido ethyl phosphine acyl derivative: hydrochloric acid 1: 2.
8. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: when back flow reaction,
Using thin-layer chromatography tracking reaction until being fully completed.
9. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that: back flow reaction terminates
Afterwards, sodium hydroxide solution is added in reaction solution, is then concentrated to dryness reaction solution, is recrystallized to give mesh with methanol/propylene oxide
Mark product beta-amido ethylphosphonic acid derivative.
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| CN110272450B (en) * | 2017-09-08 | 2021-08-17 | 江苏强盛功能化学股份有限公司 | Beta-thiocarbonyl diphosphonic acid derivative and preparation method thereof |
| CN107973819B (en) * | 2017-11-23 | 2019-12-17 | 烟台大学 | beta-phosphorylated nitrate compound and preparation method thereof |
| CN108329347B (en) * | 2018-01-15 | 2020-05-01 | 苏州大学 | Method for preparing β -chloroalkenylphosphono derivatives |
| CN108727428B (en) * | 2018-07-09 | 2020-05-08 | 苏州大学 | β -aminophosphonic acid derivatives and process for their preparation |
| WO2020010586A1 (en) | 2018-07-12 | 2020-01-16 | 苏州大学张家港工业技术研究院 | β-AMINO PHOSPHONIC ACID DERIVATIVE AND PREPARATION METHOD THEREFOR |
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| US4151229A (en) * | 1973-11-14 | 1979-04-24 | Ciba-Geigy Corporation | Process for the manufacture of aminoalkyl-phosponic acid esters |
| CN104341449A (en) * | 2014-09-30 | 2015-02-11 | 苏州大学 | Method for preparing beta-carbonyl phosphonate derivatives |
| CN104370960A (en) * | 2014-09-30 | 2015-02-25 | 苏州大学 | Preparation method of beta-hydroxyphosphonate derivatives |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4151229A (en) * | 1973-11-14 | 1979-04-24 | Ciba-Geigy Corporation | Process for the manufacture of aminoalkyl-phosponic acid esters |
| CN104341449A (en) * | 2014-09-30 | 2015-02-11 | 苏州大学 | Method for preparing beta-carbonyl phosphonate derivatives |
| CN104370960A (en) * | 2014-09-30 | 2015-02-25 | 苏州大学 | Preparation method of beta-hydroxyphosphonate derivatives |
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| β-胺基乙基膦酸的合成研究;郑可利;《三明师专学报》;19991231;第1卷;第30-31页 * |
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| CN106892942A (en) | 2017-06-27 |
| CN105017312B (en) | 2017-05-10 |
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