CN116947921A - 一种制备联烯基磷酸酯化合物的方法 - Google Patents
一种制备联烯基磷酸酯化合物的方法 Download PDFInfo
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- phosphite
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- -1 alkenyl phosphate compound Chemical class 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 31
- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 25
- 239000010452 phosphate Substances 0.000 title claims abstract description 25
- 239000000758 substrate Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 150000008301 phosphite esters Chemical class 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 10
- JRTIUDXYIUKIIE-KZUMESAESA-N (1z,5z)-cycloocta-1,5-diene;nickel Chemical compound [Ni].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 JRTIUDXYIUKIIE-KZUMESAESA-N 0.000 claims description 7
- 239000003446 ligand Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- GDELZQKEFMWYKA-UHFFFAOYSA-N but-3-en-1-ynylbenzene Chemical group C=CC#CC1=CC=CC=C1 GDELZQKEFMWYKA-UHFFFAOYSA-N 0.000 claims description 6
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 6
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 claims description 2
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 229910052786 argon Inorganic materials 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000011261 inert gas Substances 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 229910052723 transition metal Inorganic materials 0.000 abstract 1
- 150000003624 transition metals Chemical class 0.000 abstract 1
- 238000004440 column chromatography Methods 0.000 description 10
- 238000004896 high resolution mass spectrometry Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 230000005311 nuclear magnetism Effects 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 7
- 239000007858 starting material Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 2
- WHQUHTXULUACFD-KRWDZBQOSA-N (3s)-4-[[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]methoxy-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1COP(O)(=O)C[C@@H](O)CC(O)=O WHQUHTXULUACFD-KRWDZBQOSA-N 0.000 description 2
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 2
- PSWDQTMAUUQILQ-UHFFFAOYSA-N 2-[(6-methoxy-4-methylquinazolin-2-yl)amino]-5,6-dimethyl-1h-pyrimidin-4-one Chemical compound N1=C(C)C2=CC(OC)=CC=C2N=C1NC1=NC(=O)C(C)=C(C)N1 PSWDQTMAUUQILQ-UHFFFAOYSA-N 0.000 description 2
- 229940126650 Compound 3f Drugs 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 2
- 229940125796 compound 3d Drugs 0.000 description 2
- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
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- 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
- C07F9/38—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
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
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- Molecular Biology (AREA)
Abstract
本发明涉及一种制备联烯基磷酸酯化合物的方法。具体地是在过渡金属催化下,以烯炔与亚磷酸酯为原料一步构建联烯基磷酸酯化合物化合物。本发明使用的方法,试剂廉价易得,操作简单、底物适用范围广。
Description
技术领域
本发明涉及一种制备联烯基磷酸酯化合物的方法。
背景技术
有机膦化合物是非常重要的一类有机化合物,其在有机功能材料、农药、医药和有机小分子催化等领域都有广泛的应用前景(参考文献[1]Kalek,M.;Johansson,T.;Jezowska,M.;Stawinski,J.Org.Lett.2010,12,4702–4704.)。而联烯化合物拥有独特的累积二烯官能团结构,可以用于不同大小碳环,杂环化合物的合成(参考文献[2]M.Kalek,J.Stawinski,Adv.Synth.Catal.2011,353,1741–1755.)。因此合成含有联烯基骨架结构的磷酸酯具有十分重要的研究意义。现有的有机膦化合物合成方法存在能耗高、污染大、选择性差、对设备腐蚀性强等问题。本成果使用更稳定的磷酸酯作为底物与烯炔反应,开发出一种独特的联烯基磷酸酯化合物制备方法。该方法具有反应条件温和,选择性好,原子经济性好等优势。
发明内容
本发明的目的在于提供联烯基磷酸酯化合物的方法。
具体操作步骤如下:
氮气保护条件下,在反应器中加入催化剂、配体和溶剂,然后加入乙烯基苯基乙炔(1)和亚磷酸酯(2),于20℃–100℃,优选40℃下反应5–24小时(优选18-22小时);反应结束后,分离得到联烯基磷酸酯化合物(3)。
催化剂为双(三苯基膦)氯化镍、双(1,5-环辛二烯)镍、四三苯基膦钯和碘化亚铜的一种或两种,优选双(1,5-环辛二烯)镍;配体为三苯基膦、三环己基膦、联吡啶、1,1'-联萘-2,2'-双二苯膦、双(2-二苯基膦苯基)醚和4,5-双二苯基膦-9,9-二甲基氧杂蒽中的一种或两种,优选4,5-双二苯基膦-9,9-二甲基氧杂蒽。溶剂为1,2-二氯乙烷、二氯甲烷、氯仿、四氢呋喃、1,4-二氧六环、N,N-二甲基甲酰胺中的一种或两种以上,优选四氢呋喃;溶剂的用量为每毫摩尔原料2用溶剂5-50毫升,优选5-15毫升。
本发明使用的方法,试剂廉价易得,操作简单、底物适用范围广。
具体实施方式
为了更好地理解本发明,通过以下实例进行说明。
实施例1:
氮气条件下,于反应体系中加入双(1,5-环辛二烯)镍(5mol%,相对于原料2a)、4,5-双二苯基膦-9,9-二甲基氧杂蒽(5mol%,相对于原料2a)和四氢呋喃(1mL),再加入乙烯基苯基乙炔(1a,0.30mmol)和亚磷酸二甲酯(2a,0.20mmol),40℃下反应20小时,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3a),收率为84%。
化合物3a的结构经核磁及高分辨质谱确认,数据如下:
化合物3a,无色透明液体。1H NMR(400MHz,CDCl3)δ7.53(d,J=8.1Hz,2H),7.36–7.29(m,2H),7.28–7.20(m,1H),5.73(dq,J=14.7,7.4Hz,1H),3.77(d,J=11.2Hz,6H),1.86(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3)δ211.7(d,J=4.3Hz),132.2(d,J=8.7Hz),128.7,127.7,127.6(d,J=6.0Hz),95.8(d,J=190.8Hz),89.7(d,J=15.2Hz),53.27(d,J=6.2Hz),53.19(d,J=6.2Hz),13.2(d,J=6.9Hz).31P NMR(162MHz,CDCl3)δ18.79.HRMScalculated for C12H15O3PNa[M+Na]+261.0651,found 261.0664.
实施例2:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1b和2a的加入量分别是0.30mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3b),收率为82%。
化合物3b的结构经核磁及高分辨质谱确认,数据如下:
化合物3b,无色透明液体。1H NMR(400MHz,CDCl3)δ7.42(d,J=7.9Hz,2H),7.14(d,J=8.0Hz,2H),5.71(dq,J=12.6,7.3Hz,1H),3.77(d,J=11.3Hz,6H),2.33(s,3H),1.85(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ211.4(d,J=4.4Hz),137.5,129.4,129.0(d,J=8.6Hz),127.5(d,J=6.0Hz),95.5(d,J=189.7Hz),89.5(d,J=15.1Hz),53.2(d,J=6.1Hz),53.1(d,J=6.1Hz),21.13,13.18(d,J=6.9Hz);31P NMR(162MHz,CDCl3):δ19.09.HRMS calculated for C13H18O3P[M+H]+253.0988,found 253.0994.
实施例3:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1c和2a的加入量分别是0.30mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3c),收率为90%。
化合物3c的结构经核磁及高分辨质谱确认,数据如下:化合物3c,无色透明液体。1H NMR(400MHz,CDCl3)δ7.42(d,J=8.1Hz,2H),6.83(d,J=8.7Hz,2H),5.67(dq,J=12.5,7.3Hz,1H),3.76(s,3H),3.73(d,J=11.3Hz,6H),1.82(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ211.0(d,J=4.4Hz),159.2,128.8(d,J=6.1Hz),124.1(d,J=8.8Hz),114.1,95.2(d,J=189.5Hz),89.6(d,J=15.2Hz),55.3,53.2(d,J=6.0Hz),53.1(d,J=6.2Hz),13.3(d,J=6.9Hz).31P NMR(162MHz,CDCl3):δ19.18.HRMS calculated for C13H18O4P[M+H]+269.0937,found 269.0944.
实施例4:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1d和2a的加入量分别是0.40mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3d),收率为83%。
化合物3d的结构经核磁及高分辨质谱确认,数据如下:
化合物3d,无色透明液体。1H NMR(400MHz,CDCl3)δ7.44(d,J=8.0Hz,2H),7.16(d,J=8.0Hz,2H),5.71(dq,J=12.4,7.3Hz,1H),3.77(d,J=11.3Hz,6H),2.62(q,J=7.6Hz,2H),1.85(t,J=7.3Hz,3H),1.21(t,J=7.6Hz,3H).13C NMR(100MHz,CDCl3)δ211.4(d,J=4.4Hz),143.9,129.3(d,J=8.6Hz),128.2,127.5(d,J=5.9Hz),95.6(d,J=189.5Hz),89.5(d,J=15.1Hz),53.2(d,J=6.1Hz),53.1(d,J=6.1Hz),28.5,15.5,13.2(d,J=6.9Hz).31P NMR(162MHz,CDCl3):δ19.09.HRMS calculated for C14H20O3P[M+H]+267.1145,found 267.1147.
实施例5:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1e和2a的加入量分别是0.30mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3e),收率为96%。
化合物3e的结构经核磁及高分辨质谱确认,数据如下:
化合物3e,无色透明液体。1H NMR(400MHz,CDCl3)δ7.65–7.55(m,6H),7.43(t,J=7.7Hz,2H),7.37–7.32(m,1H),5.78(dq,J=12.5,7.3Hz,1H),3.81(d,J=11.3Hz,6H),1.89(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ211.7(d,J=4.2Hz),140.6,140.5,131.1(d,J=8.7Hz),128.8,128.0(d,J=5.9Hz),127.4,127.3,127.0,95.5(d,J=189.8Hz),89.8(d,J=15.0Hz),53.2,13.2(d,J=6.8Hz).31P NMR(162MHz,CDCl3):δ18.80.HRMS calculatedfor C18H20O3P[M+H]+315.1145,found 315.1160.
实施例6:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1f和2a的加入量分别是0.30mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3f),收率为76%。
化合物3f的结构经核磁及高分辨质谱确认,数据如下:
化合物3f,无色透明液体。1H NMR(400MHz,CDCl3)δ7.49–7.36(m,4H),5.73(dq,J=12.3,7.3Hz,1H),3.76(d,J=11.3Hz,6H),1.86(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3)δ211.5(d,J=4.1Hz),131.8,131.3(d,J=9.0Hz),129.3(d,J=6.0Hz),121.8,95.2(d,J=192.2Hz),90.2(d,J=15.1Hz),53.4(d,J=6.1Hz),53.3(d,J=6.3Hz),13.1(d,J=6.8Hz).31PNMR(162MHz,CDCl3)δ18.12.HRMS calculated for C12H15O3PBr[M+H]+316.9937,found 316.9942.
实施例7:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1g和2a的加入量分别是0.35mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3g),收率为44%。
化合物3g的结构经核磁及高分辨质谱确认,数据如下:
化合物3g,无色透明液体。1H NMR(400MHz,CDCl3)δ7.66(d,J=8.2Hz,2H),7.57(d,J=8.3Hz,2H),5.80(dq,J=12.2,7.4Hz,1H),3.79(d,J=11.3Hz,6H),1.89(t,J=7.4Hz,3H).13C NMR(101MHz,CDCl3)δ212.3(d,J=2.0Hz),136.2(d,J=9.3Hz),129.7(d,J=32.1Hz),128.0(d,J=5.9Hz),126.6(q,236.9Hz),125.7(q,J=3.8Hz),95.4(d,J=193.0Hz),90.4(d,J=14.7Hz),53.4(d,J=6.2Hz),53.3(d,J=6.3Hz),13.1(d,J=6.8Hz).31PNMR(162MHz,CDCl3):δ17.75.19F NMR(376MHz,CDCl3):δ-62.65.HRMScalculated for C13H15F3O3P[M+H]+307.0705,found 307.0708.
实施例8:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1h和2a的加入量分别是0.30mmol和0.20mmol,反应结束后,柱层析分离得到联烯基磷酸酯化合物(3h),收率为60%。
化合物3h的结构经核磁及高分辨质谱确认,数据如下:
化合物3h,无色透明液体。1H NMR(400MHz,CDCl3)δ7.32(d,J=8.2Hz,2H),6.63(d,J=8.5Hz,2H),5.67(dq,J=12.5,7.3Hz,1H),3.75(d,J=11.3Hz,6H),1.83(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ210.7(d,J=4.6Hz),146.2,128.8(d,J=6.2Hz),121.6(d,J=8.8Hz),115.3,95.5(d,J=189.4Hz),89.5(d,J=15.4Hz),53.3(d,J=6.2Hz),53.2(d,J=6.2Hz),13.5(d,J=7.0Hz).31P NMR(162MHz,CDCl3):δ19.59.HRMS calculated forC12H17NO3P[M+H]+254.0941,found 254.0942.
实施例9:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1a和2b的加入量分别是0.40mmol和0.20mmol,催化剂双(1,5-环辛二烯)镍(10mol%,相对于原料2a)、配体4,5-双二苯基膦-9,9-二甲基氧杂蒽(20mol%,相对于原料2a)。反应结束后,柱层析分离得到联烯基磷酸酯化合物(3i),收率为75%。但2b需要用含有碱性的碳酸锂(与2b的摩尔比是1:1)除去2b中含有的微量酸。具体除酸方法:在THF作为溶剂的条件下,溶剂的用量为每毫摩尔原料2b用溶剂10毫升,加入碳酸锂和底物2b,搅拌过夜(12小时),过滤,除去碳酸锂,旋转蒸发除去溶剂即可。
化合物3i的结构经核磁及高分辨质谱确认,数据如下:
化合物3i,无色透明液体。1H NMR(400MHz,CDCl3)δ7.55(d,J=7.7Hz,2H),7.32(t,J=7.6Hz,2H),7.25(t,J=7.9Hz,1H),5.70(dq,J=12.3,7.3Hz,1H),4.27–4.00(m,4H),1.85(t,J=7.1Hz,3H),1.30(t,J=7.1Hz,6H).13C NMR(100MHz,CDCl3)δ211.5(d,J=4.3Hz),132.5(d,J=8.8Hz),128.7,127.8(d,J=5.9Hz),127.6,97.0(d,J=190.1Hz),89.5(d,J=15.1Hz),62.8(d,J=5.9Hz),62.7(d,J=5.9Hz),16.4(d,J=6.7Hz),13.2(d,J=6.7Hz).31P NMR(162MHz,CDCl3)δ16.02.HRMS calculated for C14H20O3P[M+H]+267.1145,found 267.1146.
实施例10:
其操作过程和条件与实施例1相同,不同之处见上述反应式,其中1a和2b的加入量分别是0.35mmol和0.20mmol,催化剂双(1,5-环辛二烯)镍(20mol%,相对于原料2a)、4,5-双二苯基膦-9,9-二甲基氧杂蒽(20mol%,相对于原料2a)反应结束后,柱层析分离得到联烯基磷酸酯化合物(3j),收率为75%。但2c需要用碳酸锂处理(方法(过程和条件)与实施例9相同)
化合物3j的结构经核磁及高分辨质谱确认,数据如下:
化合物3j,无色透明液体。1H NMR(400MHz,CDCl3)δ7.56(d,J=7.4Hz,2H),7.32(t,J=7.6Hz,2H),7.23(t,J=7.3Hz,1H),5.68(dq,J=12.2,7.3Hz,1H),4.73(dhept,J=7.6,6.1Hz,2H),1.85(t,J=7.1Hz,3H),1.34(t,J=5.5Hz,6H),1.24(t,J=6.6Hz,6H).13C NMR(175MHz,CDCl3)δ211.5(d,J=4.5Hz),133.0(d,J=8.4Hz),128.5,127.9(d,J=5.7Hz),127.4,98.3(d,J=191.1Hz),89.3(d,J=15.2Hz),71.4(d,J=6.2Hz),24.3(t,J=3.8Hz),24.2(t,J=3.9Hz),23.8(t,J=5.7Hz),23.7(t,J=5.6Hz),13.2(d,J=6.9Hz).31PNMR(162MHz,CDCl3)δ13.83.HRMS calculated for C16H24O3P[M+H]+295.1458,found295.1468.
对比例1:
操作过程同实施例9,与实施例9不同之处在于:2b没有经过碱预处理,则体系中没有3i生成。
对比例2:
操作过程同实施例10,与实施例10不同之处在于:2c没有经过碱预处理,则体系中没有3j生成。
对比例3:
操作过程同实施例1,与实施例1不同之处在于:体系中不加入催化剂,则体系中没有3a生成。
对比例4:
操作过程同实施例1,与实施例1不同之处在于:体系中不加入配体,则体系中没有3a生成。
Claims (7)
1.一种制备联烯基磷酸酯化合物的方法,其特征在于:
乙烯基苯基乙炔(1)和亚磷酸酯(2)反应生成联烯基磷酸酯化合物(3,联烯基磷酸酯化合物3的结构式中“·”表示碳原子),反应式如下:
其中R选自氢、甲基、甲氧基、乙基、苯基、溴、三氟甲基和氨基中的一种或两种以上,其于乙烯基苯基乙炔(1)中的个数为1个、2个、3个、4个或5个,优选1个或2个;
R’选自甲基、乙基、异丙基中的一种或两种以上,亚磷酸酯(2)和联烯基磷酸酯化合物(3)中的二个取代基R’可以相同或不同,优选相同。
2.按照权利要求1所述的制备联烯基磷酸酯化合物的方法,其特征在于:
过程如下:在氮气或惰性气体(如氩气)中的一种或二种以上保护条件下,将催化剂、配体、溶剂、乙烯基苯基乙炔(1)和亚磷酸酯(2)混合,于20℃–100℃(优选25℃-50℃)下反应5–22小时(优选18-22小时);反应结束后,分离得联烯基磷酸酯(3)。
3.按照权利要求1或2所述的方法,其特征在于:
催化剂为双(三苯基膦)氯化镍、双(1,5-环辛二烯)镍、四三苯基膦钯和碘化亚铜中的一种或两种以上,优选双(1,5-环辛二烯)镍;
配体为三苯基膦、三环己基膦、联吡啶、1,1'-联萘-2,2'-双二苯膦、双(2-二苯基膦苯基)醚和4,5-双二苯基膦-9,9-二甲基氧杂蒽中的一种或两种以上,优选4,5-双二苯基膦-9,9-二甲基氧杂蒽;
催化剂和配体的摩尔比例为1:1–1:5,优选为1:1-1:2。
4.按照权利要求1或2所述的方法,其特征在于:
溶剂为1,2-二氯乙烷、二氯甲烷、氯仿、四氢呋喃、1,4-二氧六环、N,N-二甲基甲酰胺中的一种或两种以上,优选四氢呋喃;溶剂的用量为每毫摩尔亚磷酸酯(2)用溶剂5-30毫升,优选5-15毫升。
5.按照权利要求1或2所述的方法,其特征在于:
亚磷酸酯(2)与催化剂的摩尔比例为5:1-100:1,优选20:1-30:1。
6.按照权利要求1或2所述的方法,其特征在于:
乙烯基苯基乙炔(1)和亚磷酸酯(2)的摩尔比例为1:1-10:1,优选1.5-2.5:1。
7.按照权利要求1或2所述的方法,其特征在于:
除亚磷酸二甲酯底物外的亚磷酸酯(2)在使用前需要经过除酸过程,具体除酸方法:在THF作为溶剂的条件下,溶剂的用量为每毫摩尔亚磷酸酯(2)用溶剂5-50毫升(优选5:10-15毫升),加入碳酸锂和亚磷酸酯(2),碳酸锂和亚磷酸酯(2)的摩尔比为1:1-10:1,优选1:1-3:1,搅拌12-15小时(优选12-13小时),过滤,除去碳酸锂,旋转蒸发除去溶剂即可。
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