CN106892942A - A kind of preparation method of β amidos ethylphosphonic acid derivative - Google Patents
A kind of preparation method of β amidos ethylphosphonic acid derivative Download PDFInfo
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- CN106892942A CN106892942A CN201710079473.9A CN201710079473A CN106892942A CN 106892942 A CN106892942 A CN 106892942A CN 201710079473 A CN201710079473 A CN 201710079473A CN 106892942 A CN106892942 A CN 106892942A
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- mmol
- gram
- beta
- reaction
- amido
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- -1 amidos ethylphosphonic acid derivative Chemical class 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 218
- 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
- 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
- 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
- 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 58
- 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 50
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- 238000004440 column chromatography Methods 0.000 claims description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- 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
- 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
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 239000001294 propane Substances 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- URCAYJXJXYLGTI-UHFFFAOYSA-N ethene fluorobenzene Chemical class 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
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 7
- 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
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical class ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 claims description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical class CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 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 class BrC1=CC=CC=C1C=C SSZOCHFYWWVSAI-UHFFFAOYSA-N 0.000 claims description 3
- WGGLDBIZIQMEGH-UHFFFAOYSA-N 1-bromo-4-ethenylbenzene Chemical class BrC1=CC=C(C=C)C=C1 WGGLDBIZIQMEGH-UHFFFAOYSA-N 0.000 claims description 3
- BOVQCIDBZXNFEJ-UHFFFAOYSA-N 1-chloro-3-ethenylbenzene Chemical class 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 class COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 claims description 3
- ISRGONDNXBCDBM-UHFFFAOYSA-N 2-chlorostyrene Chemical class ClC1=CC=CC=C1C=C ISRGONDNXBCDBM-UHFFFAOYSA-N 0.000 claims description 3
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical class NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 claims description 3
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical class CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 claims description 3
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical class NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 claims description 3
- SNTUCKQYWGHZPK-UHFFFAOYSA-N 4-ethenylbenzonitrile Chemical class C=CC1=CC=C(C#N)C=C1 SNTUCKQYWGHZPK-UHFFFAOYSA-N 0.000 claims description 3
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical class NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims description 3
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical class 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical class COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 claims description 3
- SFBTTWXNCQVIEC-UHFFFAOYSA-N o-Vinylanisole Chemical class COC1=CC=CC=C1C=C SFBTTWXNCQVIEC-UHFFFAOYSA-N 0.000 claims description 3
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical class 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 class 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
- 239000000126 substance Substances 0.000 claims description 3
- JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical class CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 claims description 2
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical class NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 claims description 2
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical class NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 claims description 2
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical class NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 2
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical class NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 claims description 2
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical class NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 claims description 2
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical class NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 2
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-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
- 150000002825 nitriles Chemical class 0.000 claims description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical class 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
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000007858 starting material Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 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
- 239000000047 product Substances 0.000 description 89
- 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
- 239000000203 mixture Substances 0.000 description 52
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 238000003786 synthesis reaction Methods 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 43
- 238000003756 stirring Methods 0.000 description 42
- 239000003208 petroleum Substances 0.000 description 40
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical class CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 238000000926 separation method Methods 0.000 description 14
- 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 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 6
- 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- QQVDJLLNRSOCEL-UHFFFAOYSA-N (2-aminoethyl)phosphonic acid Chemical class [NH3+]CCP(O)([O-])=O QQVDJLLNRSOCEL-UHFFFAOYSA-N 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
- ZENKESXKWBIZCV-UHFFFAOYSA-N 2,2,4,4-tetrafluoro-1,3-benzodioxin-6-amine Chemical group O1C(F)(F)OC(F)(F)C2=CC(N)=CC=C21 ZENKESXKWBIZCV-UHFFFAOYSA-N 0.000 description 2
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical class 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
- 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 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 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
- WKGDNXBDNLZSKC-UHFFFAOYSA-N oxido(phenyl)phosphanium Chemical compound O=[PH2]c1ccccc1 WKGDNXBDNLZSKC-UHFFFAOYSA-N 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
- 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 1
- 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 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 1
- KQJQPCJDKBKSLV-UHFFFAOYSA-N 1-bromo-3-ethenylbenzene Chemical class BrC1=CC=CC(C=C)=C1 KQJQPCJDKBKSLV-UHFFFAOYSA-N 0.000 description 1
- SBYMUDUGTIKLCR-UHFFFAOYSA-N 2-chloroethenylbenzene Chemical compound ClC=CC1=CC=CC=C1 SBYMUDUGTIKLCR-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
- 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
- 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
- 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
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 230000033228 biological regulation Effects 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
- 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
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000012010 growth Effects 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
- 230000004060 metabolic process Effects 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
- 239000003921 oil Substances 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 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
- 239000010452 phosphate Substances 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
- 230000008635 plant growth Effects 0.000 description 1
- PRAHMDIEZMWIRW-UHFFFAOYSA-N propyl dihydrogen phosphite Chemical compound CCCOP(O)O PRAHMDIEZMWIRW-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 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
- 241000894007 species Species 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
- 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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Abstract
The invention discloses a kind of preparation method of β amidos ethylphosphonic acid derivative, by in ethene derivatives, ammonia derivative, organic phosphine compound, silver nitrate, the copper bromide of catalytic amount and solvent addition reactor, reaction is carried out at 30~50 DEG C, β amido ethyl phosphine acyl derivatives are obtained, add hydrochloric acid further to react, obtain more β amidos ethylphosphonic acid derivatives.The present invention is starting material using ethene derivatives, and raw material is easy to get, species is a lot；The product types that profit is obtained by the present invention are various, not only can directly using but also can be used for other further reactions.Meanwhile, reaction condition is gentle, operation and last handling process are simple, and concise production process, yield is higher, is suitable for large-scale production.
Description
The application is the divisional application of the Chinese invention patent application of Application No. 201510360967.5, the Shen of original application
Please day be：On June 26th, 2015, Application No.：201510360967.5, it is entitled：A kind of beta-amido ethyl phosphono spreads out
Biological preparation method.
Technical field
The present invention relates to a kind of nitrogenous organic phosphine compound, and in particular to a kind of preparation of beta-amido ethylphosphonic acid derivative
Method, belongs to organic synthesis field.
Background technology
The structure of beta-amido ethyl phosphine acyl derivative similar to beta-amino acids, with extensive physiologically active, such as antibacterial, thorn
Swash nerve, the growth of influence cell and metabolism, analgesic, regulation blood pressure, the effect such as coordinate plant growth, thus can as medicine,
Agricultural chemicals, antagonist, anthocyanidin synthetic inhibitor, fructose diphosphate enzyme inhibitor etc. are used（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, the synthetic method of beta-amido ethyl phosphine acyl derivative mainly has following several：
1st, from nitrile, in the presence of organolithium reagent, sodium borohydride reduction agent, beta-amido is obtained through addition, reduction and hydrolysis
Ethyl phosphine acyl derivative；The method needs the synthesis of equivalent, sodium borohydride reduction agent, severe reaction conditions, reaction step
It is rapid many.
2nd, beta-amido ethyl phosphine acyl derivative is obtained through with hydrazine reaction, reduction and hydrolysis from β-carbonylic phosphonic acid ester；Should
Method is needed with β-carbonylic phosphonic acid ester as starting material, and raw material is difficult to obtain, and reactions steps are more, and yield is relatively low.
3rd, beta-amido ethyl phosphine acyl derivative is obtained through ammonification, reduction and hydrolysis from β-carbonylic phosphonic acid ester；The method
Need with β-carbonylic phosphonic acid ester as starting material, raw material is difficult to obtain, it is necessary to using expensive sodium cyanoborohydride as reducing agent,
Yield is relatively low.
4th, bromo heteroaryl hydrocarbon and beta-aminoethyl phosphonate ester react in the basic conditions, then are obtained through acid condition hydrolysis
Beta-amido ethyl phosphine acyl derivative；The method need with beta-aminoethyl phosphonate ester as starting material, raw material is difficult to obtain, yield compared with
It is low.
In sum, although prior art can prepare some beta-amido ethyl phosphine acyl derivatives, there is reaction condition
The harsh, defect that reaction raw materials are rare, reaction cost is high and product structure is few；Therefore exploitation reaction condition is gentle, be applicable model
Enclose extensively, reactions steps are few, yield is high, low cost, meet Green Chemistry requirement beta-amido ethyl phosphine acyl derivative preparation side
Method is extremely important.
The content 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：A kind of beta-amido ethyl phosphine acyl derivative
Preparation method, comprises the following steps, by ethene derivatives, ammonia derivative, organic phosphine compound, silver nitrate, copper bromide and solvent
Add in reactor, in 30~50 DEG C of reactions, beta-amido ethyl phosphine acyl derivative is obtained；
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: silver nitrate: copper bromide is 1: (1~4): (1~2):
(1~3):（0.1~0.3）；
The general structure of the ethene derivatives is：；
Wherein R11、R4、R5Selection take one of following scheme：
(1)R11、R4All it is hydrogen, R5It is carboxyl；
(2) R4It is the one kind in methyl, bromine, phenyl, R5It is hydrogen, R11It is phenyl；
(3) R5It is the one kind in methyl, bromine, phenyl, R11It is phenyl, R4It is hydrogen；
(4) R4、R5All it is hydrogen, R11For；
The structural formulaMiddle R1、R2、R3Selection take one of following scheme：
(1) R1It is the one kind in hydrogen, methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R2、R3All it is
Hydrogen；
(2) R2It is the one kind in methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R1、R3All it is hydrogen；
(3) R3It is the one kind in methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R1、R2All it is hydrogen；
The general structure of the ammonia derivative is：, wherein R6It is hydrogen, methyl, ethyl, propyl group, hexyl, 6- acetyl
Amino-fast quinoline -9- bases, 2- cyano-phenyls or；
The structural formulaIn, R7、R8And R9Selection take one of following scheme：
(1) R7During a kind of in for hydrogen, methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R8And R9All it is hydrogen；
(2) R8During a kind of in for methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R9All it is hydrogen；
(3) R9During a kind of in for methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R8All it is hydrogen；
The organic phosphine compound is as shown in having structure formula：
R10It is the one kind in methoxyl group, ethyoxyl, isopropoxy, tert-butoxy, phenyl；
The solvent is selected from：One kind in methyl alcohol, ethanol, acetonitrile, acetic acid, propionic acid, dichloromethane or toluene.
The chemical structure of general formula of the beta-amido ethyl phosphine acyl derivative that the present invention is obtained is：
。
In above-mentioned technical proposal, the ethene derivatives are selected from acrylic acid, styrene, 2-methyl styrene, 3- methylbenzenes
Ethene, 4- methyl styrenes, 2- methoxy styrenes, 3- methoxy styrenes, 4- methoxy styrenes, 2- fluorobenzene ethenes, 3-
Fluorobenzene ethene, 4- fluorobenzene ethenes, 2- bromstyrols, 3- bromstyrols, 4- bromstyrols, 2- chlorostyrenes, 3- chlorostyrenes, 4-
In chlorostyrene, a- methyl styrenes, Beta-methyl styrene, 1,2- diphenylethlenes, 4- cyano styrenes, 4- nitrostyrolenes
One kind.The ammonia derivative is selected from ammoniacal liquor, the fast quinoline of 6- acetylaminohydroxyphenylarsonic acid 9- amino, propylamine, aniline, 2-aminotoluene, 3- methyl
Aniline, 4- methylanilines, 2- aminoanisoles, 3- aminoanisoles, 4- aminoanisoles, 2- MEAs, 2- tert-butyl benzenes
Amine, 2- fluoroanilines, 3- fluoroanilines, 4- fluoroanilines, 2- chloroanilines, 3- chloroanilines, 4- chloroanilines, 2- bromanilines, 3- bromanilines, 4-
One kind in bromaniline, 4- nitroanilines, 2- cyano-anilines.The organic phosphine compound is selected from dimethyl phosphite, diethyl
One kind in 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 letter
The purification process of product is changed, has reduced the generation of discarded object, and should have with positive realistic meaning for industry.
In preferred technical scheme, the solvent is acetonitrile.
In preferred technical scheme, reaction temperature is 40 DEG C.Method of the present invention reaction condition is gentle, simple, without multiple
Miscellaneous operation, obtains that product yield is very high, and ensure that the safety of course of reaction.
In above-mentioned technical proposal, in air, using thin-layer chromatography tracking reaction until being fully completed.
In preferred technical scheme, reaction carries out purification processes after terminating to product；After reaction terminates, reaction solution is through post layer
Analysis is separated, and obtains target product beta-amido ethyl phosphine acyl derivative.
Above-mentioned product beta-amido ethyl phosphine acyl derivative can further react and obtain beta-amido ethylphosphonic acid derivative, specifically
After terminating for 30~50 DEG C of reactions, hydrochloric acid is added, be then refluxed for reaction, obtain beta-amido ethylphosphonic acid derivative；β-the amine
The chemical structural formula of base ethylphosphonic acid derivative is：
。
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, during back flow reaction, using thin-layer chromatography tracking reaction until being fully completed.
In above-mentioned technical proposal, after back flow reaction terminates, sodium hydroxide solution is added in reaction solution, it is then that reaction solution is dense
It is reduced to dry, target product beta-amido ethylphosphonic acid derivative is recrystallized to give with methyl alcohol/expoxy propane.
The course of reaction of technical solution of the present invention is represented by：
Due to the utilization of above-mentioned technical proposal, the present invention has following advantages compared with prior art：
1. the present invention is only with a small amount of accelerator, without organic ligand, you can using ethene derivatives for starting material is efficiently prepared
Product, without using noble metal reagent and other additives, raw material availability is high, product yield high；Simplify the purification of product
Process, reduces the generation of discarded object, and effective reduces cost should have with positive realistic meaning for industry.
2. preparation method disclosed by the invention is applied widely, and raw material is easy to get, species is a lot；It is applicable not only to alkyl sub-
Phosphate, applies also for diphenyl phosphate oxygen, and overcomes interfering with each other for reactive group first, and carboxyl successfully is introduced into product
Structure, the product types for obtaining are various, not only can directly using but also can be used for other further reactions, significantly expand
The product structure of beta-amido ethyl phosphine acyl derivative, be conducive to development beta-amido ethyl phosphine acyl derivative organic synthesis, agricultural chemicals,
The application of the aspects such as medicine, inhibitor；Overcome the defect that prior art is only capable of being directed to less substrate.
3. preparation method reaction condition disclosed by the invention is gentle, operation and last handling process are simple, it is only necessary to 40 DEG C
Reaction, the yield of highest available 92%, especially for the raw material that can not be reacted very well due to steric hindrance and conjugation influence,
More than 65% product yield is still reached, cumbersome prior art operation, process hazard, severe reaction conditions, product is efficiently solved
Thing yield is low, the few defect of product structure；It is suitable for industrialized production.
Specific embodiment
With reference to embodiment, the invention will be further described：
Embodiment one：The synthesis of 2- amino -2- phenylethyl phosphonic acids
Methyl alcohol is added in the reactor（6 mL）, styrene (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), copper bromide (0.045 gram, 0.2
Mmol), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, half reaction solution, warp are taken out
The crude by column chromatography obtained after concentration is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product 2-
Amino -2- phenylethyl phosphonate esters（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)。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- amino -2- phenylethyls phosphonic acids (yield 75%).Its analyze data is 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) 。
Embodiment two：The synthesis of 2- amino -2- (4- chlorphenyls) ethylphosphonic acid
Ethanol is added in the reactor（6 mL）, 4- chlorostyrenes (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), copper bromide (0.045 gram,
0.2 mmol), in 30 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
Thing 2- amino -2- (4- chlorphenyls) ethyl phosphonate（Yield 84%）.Its analyze data is 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)。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- amino -2- (4- chlorphenyls) ethylphosphonic acid (yield 77%).Its analyze data is 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) 。
Embodiment three：The synthesis of 2- aminoethyl phosphonic acids
Acetonitrile is added in the reactor（6 mL）, acrylic acid (0.072 gram, 1 mmol), ammoniacal liquor (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), in 50 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, half reaction solution, warp are taken out
The crude by column chromatography obtained after concentration is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product 2-
Aminoethylphosphonate（Yield 78%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- aminoethyl phosphonic acids (yield 71%).Its analyze data is as follows：1H NMR (300 MHz, D2O): δ
4.09-4.33 (m, 2H), 1.61-1.83 (m, 2H) 。
Example IV：2-（The fast base of quinoline -9- amino -9 of 6- amino）The synthesis of ethylphosphonic acid
Acetonitrile is added in the reactor（6 mL）, acrylic acid (0.072 gram, 1 mmol), the 6- acetylaminohydroxyphenylarsonic acid fast quinolines of 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), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture；
The hydrochloric acid of 15 mL 20%, mixture is added to be heated to reflux in reaction bulb, TLC tracking reaction is until terminate；Add appropriate
Sodium hydroxide solution, then reaction solution is concentrated to dryness, be recrystallized to give 2- with methyl alcohol/expoxy propane（Fast quinoline-the 9- of 6- amino
The base of amino -9）Ethylphosphonic acid (yield 72%).Its analyze data is as follows：1H NMR (300 MHz, D2O): δ8.23 (s,
1H), 3.50-3.15 (m, 2H), 2.01-1.83 (m, 2H) 。
Embodiment five：The synthesis of the third amino of 2- -2- (4- chlorphenyls) ethylphosphonic acid
Acetonitrile is added in the reactor（6 mL）, 4- chlorostyrenes (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), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
The third amino of thing 2- -2- (4- chlorphenyls) ethyl phosphonate（Yield 82%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give the third amino of 2- -2- (4- chlorphenyls) ethylphosphonic acid (yield 71%).Its analyze data is 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) 。
Embodiment six：The synthesis of 2- anilino- -2- phenylethyl phosphonic acids
Acetonitrile is added in the reactor（6 mL）, 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), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, half reaction solution, warp are taken out
The crude by column chromatography obtained after concentration is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product 2-
Anilino- -2- phenylethyl phosphonate esters（Yield 86%）.Its analyze data is as follows：1H NMR (400 MHz, CDCl3): δ
8.10 (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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- anilino-s -2- phenylethyls phosphonic acids (yield 76%).Its analyze data is 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) 。
Embodiment seven：2- amino -2-（4- cyano-phenyls）The synthesis of ethylphosphonic acid
Acetonitrile is added in the reactor（6 mL）, 4- cyano styrenes (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), copper bromide (0.045 gram,
0.2 mmol), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
Thing 2- amino -2-（4- cyano-phenyls）Ethyl phosphonate（Yield 78%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- amino -2-（4- cyano-phenyls）Ethylphosphonic acid (yield 68%).Its analyze data is 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) 。
Embodiment eight：2- amino -2-（4- nitrobenzophenones）The synthesis of ethylphosphonic acid
Acetonitrile is added in the reactor（6 mL）, 4- nitrostyrolenes (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), copper bromide (0.045 gram,
0.2 mmol), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
Thing 2- amino -2-（4- nitrobenzophenones）Ethyl phosphonate（Yield 81%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- amino -2-（4- nitrobenzophenones）Ethylphosphonic acid (yield 72%).Its analyze data is 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) 。
Embodiment nine：The synthesis of 2- phenyl -2- (4- nitrobenzene amido) ethylphosphonic acid
Methyl alcohol is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 4- nitroanilines (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), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
Thing 2- phenyl -2- (4- nitrobenzene amido) ethyl phosphonate（Yield 77%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- phenyl -2- (4- nitrobenzene amido) ethylphosphonic acid (yield 66%).Its analyze data is 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) 。
Embodiment ten：2- phenyl -2-（2- cyano-aniline bases）The synthesis of ethylphosphonic acid
Methyl alcohol is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 2- cyano-anilines (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), in 40 DEG C of stirring reactions, TLC tracking reaction is until terminate for mixture.After reaction terminates, a half-reaction is taken out
Liquid, it is concentrated after the crude by column chromatography that obtains separate（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product
Thing 2- phenyl -2-（2- cyano-aniline bases）Ethyl phosphonate（Yield 80%）.Its analyze data is 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) 。
The hydrochloric acid of 7.5 mL 20%, mixture is added to be heated to reflux in remaining second half reaction solution in reaction bulb, TLC
Tracking reaction is until terminate；Appropriate sodium hydroxide solution is added, is then concentrated to dryness reaction solution, with methyl alcohol/expoxy propane
It is recrystallized to give 2- phenyl -2-（2- cyano-aniline bases）Ethylphosphonic acid (yield 71%).Its analyze data is 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：（（2- phenyl -2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Formic acid is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), aniline (0.093 gram, 1 mmol), two
Phenyl 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain 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：（（2- phenyl -2-（4- fluoroanilinos）Ethyl）The synthesis of diphenyl phosphine oxide
Acetic acid is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 4- fluoroanilines (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 76%）.The analysis number of product
According to 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：（（2- phenyl -2-（4- bromobenzene amidos）Ethyl）The synthesis of diphenyl phosphine oxide
Dichloromethane is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 4- bromanilines (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 in 30 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
86%）.The analyze data of product is 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- tolyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Toluene is added in the reactor（6 mL）, 3- methyl styrenes (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), copper bromide
(0.045 gram, 0.2 mmol), mixture is in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
88%）.The analyze data of product is 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- tolyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Toluene is added in the reactor（6 mL）, 4- methyl styrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
91%）.The analyze data of product is 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- chloroanilinos）Ethyl）The synthesis of diphenyl phosphine oxide
Dichloromethane is added in the reactor（6 mL）, styrene (0.118 gram, 1 mmol), 4- chloroanilines (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；What reaction was obtained after terminating
Crude by column chromatography is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 72%）.Product
Analyze 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- fluorophenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Methyl alcohol is added in the reactor（6 mL）, 3- fluorobenzene ethenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 81%）.The analysis number of product
According to 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- fluorophenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Methyl alcohol is added in the reactor（6 mL）, 4- fluorobenzene ethenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 82%）.The analysis number of product
According to 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 amidos）Ethyl）The synthesis of diphenyl phosphine oxide
Methyl alcohol is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 2- aminoanisoles (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
89%）.The analyze data of product is 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- bromophenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 4- bromstyrols (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 66%）.The analysis number of product
According to 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- chlorphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 3- chlorostyrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 85%）.The analysis number of product
According to 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：（（2- phenyl -2- anilino-s）Ethyl）The synthesis of diethyl phosphonate
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), aniline (0.278 gram, 3 mmol), two
Ethide phosphite ester (0.276 gram, 2 mmol), silver nitrate (0.510 gram, 3 mmol), copper bromide (0.045 gram, 0.2
), mmol mixture is in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain 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- toluidines）Ethyl）The synthesis of diphenyl phosphine oxide
Propionic acid is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 3- methylanilines (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
87%）.The analyze data of product is 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 anilinos）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), the 2- tert-butyl groups 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
72%）.The analyze data of product is 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 amidos）Ethyl）The synthesis of diphenyl phosphine oxide
Ethanol is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 2- MEAs (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
79%）.The analyze data of product is 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-aminotoluene base）Ethyl）The synthesis of diphenyl phosphine oxide
Ethanol is added in the reactor（6 mL）, 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
84%）.The analyze data of product is 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- toluidines）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 4- methylanilines (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
67%）.The analyze data of product is 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-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
85%）.The analyze data of product is 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- methoxyphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 3- methoxy styrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
84%）.The analyze data of product is 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- methoxyphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 2- methoxy styrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
86%）.The analyze data of product is 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 phenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
85%）.The analyze data of product is 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-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, AMS (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
71%）.The analyze data of product is 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- bromophenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 2- bromstyrols (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 68%）.The analysis number of product
According to 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 amidos）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 3- bromanilines (0.51,3 mmol), two
Phenyl 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 87%）.The analysis number of product
According to 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- chlorphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 4- chlorostyrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 82%）.The analysis number of product
According to 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- chlorphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 2- chlorostyrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 66%）.The analysis number of product
According to 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 amidos）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), 3- aminoanisoles (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
91%）.The analyze data of product is 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- methoxyphenyls）- 2- anilino-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 4- methoxy styrenes (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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；After reaction terminates
The crude by column chromatography for obtaining is separated（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield
88%）.The analyze data of product is 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-s）Ethyl）The synthesis of phosphonic acids diisopropyl ester
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), aniline (0.278,3 mmol), two is different
Propylphosphite (0.332 gram, 2 mmol), silver nitrate (0.340 gram, 2 mmol), copper bromide (0.045 gram, 0.2
), mmol mixture is in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 85%）.The analysis number of product
According to as follows：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-s）Ethyl）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 73%）.The analysis number of product
According to 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-s）Ethyl）The synthesis of dimethyl phosphonate
Acetonitrile is added in the reactor（6 mL）, styrene (0.104 gram, 1 mmol), aniline (0.278,3 mmol), hexichol
Base 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 in 40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude product warp that reaction is obtained after terminating
Column chromatography for separation（Petroleum ether/acetone/dichloromethane=20/1/1）, obtain 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）The synthesis of diphenyl phosphine oxide
Acetonitrile is added in the reactor（6 mL）, 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, and mixture exists
40 DEG C of stirring reactions；TLC tracking reactions are until be fully completed；The crude by column chromatography that reaction is obtained after terminating is separated（Oil
Ether/acetone/dichloromethane=20/1/1）, obtain target product（Yield 73%）.The analyze data of product is 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, it is characterised in that comprise the following steps, by ethylene derivative
Thing, ammonia derivative, organic phosphine compound, silver nitrate, copper bromide and solvent are added in reactor, in 30~50 DEG C of reactions, reaction
After end, beta-amido ethyl phosphine acyl derivative is obtained；Hydrochloric acid is subsequently adding, reaction is then refluxed for, beta-amido ethylphosphonic acid is obtained
Derivative；
In molar ratio, ethene derivatives: ammonia derivative: organic phosphine compound: silver nitrate: copper bromide is 1: (1~4): (1~2):
(1~3):（0.1~0.3）；
The general structure of the ethene derivatives is：；
Wherein R11、R4、R5Selection take one of following scheme：
(1)R11、R4All it is hydrogen, R5It is carboxyl；
(2) R4It is the one kind in methyl, bromine, phenyl, R5It is hydrogen, R11It is phenyl；
(3) R5It is the one kind in methyl, bromine, phenyl, R11It is phenyl, R4It is hydrogen；
(4) R4、R5All it is hydrogen, R11For；
The structural formulaMiddle R1、R2、R3Selection take one of following scheme：
(1) R1It is the one kind in hydrogen, methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R2、R3All it is
Hydrogen；
(2) R2It is the one kind in methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R1、R3All it is hydrogen；
(3) R3It is the one kind in methyl, methoxyl group, ethyl, the tert-butyl group, fluorine, chlorine, bromine, cyano group and nitro, R1、R2All it is hydrogen；
The general structure of the ammonia derivative is：, wherein R6It is hydrogen, methyl, ethyl, propyl group, hexyl, 6- acetyl ammonia
Base-fast quinoline -9- bases, 2- cyano-phenyls or；
The structural formulaIn, R7、R8And R9Selection take one of following scheme：
(1) R7During a kind of in for hydrogen, methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R8And R9All it is hydrogen；
(2) R8During a kind of in for methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R9All it is hydrogen；
(3) R9During a kind of in for methyl, ethyl, the tert-butyl group, methoxyl group, fluorine, chlorine, bromine, nitro, R7And R8All it is hydrogen；
The organic phosphine compound is as shown in having structure formula：
R10It is the one kind in methoxyl group, ethyoxyl, isopropoxy, tert-butoxy, phenyl；
The solvent is selected from：One kind in methyl alcohol, ethanol, acetonitrile, acetic acid, propionic acid, dichloromethane or toluene；
The chemical structural formula of the beta-amido ethylphosphonic acid derivative is：
。
2. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that：The ethylene derivative
Thing is selected from acrylic acid, styrene, 2-methyl styrene, 3- methyl styrenes, 4- methyl styrenes, 2- methoxy styrenes, 3-
Methoxy styrene, 4- methoxy styrenes, 2- fluorobenzene ethenes, 3- fluorobenzene ethenes, 4- fluorobenzene ethenes, 2- bromstyrols, 3- bromines
Styrene, 4- bromstyrols, 2- chlorostyrenes, 3- chlorostyrenes, 4- chlorostyrenes, AMS, Beta-methyl styrene,
One kind in 1,2- diphenylethlenes, 4- cyano styrenes, 4- nitrostyrolenes；The ammonia derivative is selected from ammoniacal liquor, propylamine, benzene
Amine, 2-aminotoluene, 3- methylanilines, 4- methylanilines, 2- aminoanisoles, 3- aminoanisoles, 4- aminoanisoles, 2-
MEA, 2- tert-butyl groups aniline, 2- fluoroanilines, 3- fluoroanilines, 4- fluoroanilines, 2- chloroanilines, 3- chloroanilines, 4- chloroanilines,
One kind in 2- bromanilines, 3- bromanilines, 4- bromanilines, 4- nitroanilines；The organic phosphine compound is selected from dimethyl phosphorous
One kind in acid esters, diethyl phosphite, diisopropyl phosphite, diphenyl phosphine oxide.
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 during 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 is 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
The reaction of base phosphono derivative carries out purification processes after terminating to product；After specially reaction terminates, 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
Amount concentration is 20%；In molar ratio, beta-amido ethyl phosphine acyl derivative: hydrochloric acid is 1: 2.
8. the preparation method of beta-amido ethylphosphonic acid derivative according to claim 1, it is characterised in that：During 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, then reaction solution is concentrated to dryness, mesh is recrystallized to give with methyl alcohol/expoxy propane
Mark product beta-amido ethylphosphonic acid derivative.
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| CN108727428A (en) * | 2018-07-09 | 2018-11-02 | 苏州大学 | Beta-amino phosphonate derivative and preparation method thereof |
| 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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| CN107573378B (en) * | 2017-09-08 | 2019-12-31 | 江苏强盛功能化学股份有限公司 | Beta-hydroxyiminophosphono derivatives and preparation method thereof |
| 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 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727428A (en) * | 2018-07-09 | 2018-11-02 | 苏州大学 | Beta-amino phosphonate derivative and preparation method thereof |
| 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 |
| US11401288B2 (en) | 2018-07-12 | 2022-08-02 | Soochow University | Beta-amino phosphonic acid derivative and preparation method therefor |
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| CN106892942B (en) | 2019-01-04 |
| CN105017312A (en) | 2015-11-04 |
| CN105017312B (en) | 2017-05-10 |
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