CN112939850B - 一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法 - Google Patents
一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法 Download PDFInfo
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 150000001543 aryl boronic acids Chemical class 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title claims abstract 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000011259 mixed solution Substances 0.000 claims abstract description 13
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 11
- 150000003222 pyridines Chemical class 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 7
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 3
- -1 aryl boric acid Chemical compound 0.000 claims description 9
- 238000010523 cascade reaction Methods 0.000 claims description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 6
- 238000006482 condensation reaction Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000000376 reactant Substances 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 13
- 150000001299 aldehydes Chemical class 0.000 description 11
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 5
- FRZHWQQBYDFNTH-UHFFFAOYSA-N 2,4,6-triphenylpyridine Chemical compound C1=CC=CC=C1C1=CC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=C1 FRZHWQQBYDFNTH-UHFFFAOYSA-N 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 150000008365 aromatic ketones Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- DYVCOAWQHUXDNI-UHFFFAOYSA-N 4-(2-methylphenyl)-2,6-diphenylpyridine Chemical compound CC1=CC=CC=C1C1=CC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=C1 DYVCOAWQHUXDNI-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FNLDRAROVORXHU-UHFFFAOYSA-N 2,6-bis(4-methylphenyl)-4-phenylpyridine Chemical compound C1=CC(C)=CC=C1C1=CC(C=2C=CC=CC=2)=CC(C=2C=CC(C)=CC=2)=N1 FNLDRAROVORXHU-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000013132 MOF-5 Substances 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/08—Preparation by ring-closure
- C07D213/09—Preparation by ring-closure involving the use of ammonia, amines, amine salts, or nitriles
- C07D213/12—Preparation by ring-closure involving the use of ammonia, amines, amine salts, or nitriles from unsaturated compounds
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
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- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
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Abstract
本发明公开了一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，包括如下步骤，将将钯催化剂、醛、芳基硼酸、配体和氧化剂溶解于乙腈中，在回流条件下，搅拌24‑72小时，得到混合液；过滤混合液，浓缩滤液，经柱层析，得到多取代吡啶。本发明方法反应物均无需过量，原料利用率较高，反应在中性条件下进行，反应物分子和产物分子中的官能团不受影响，尤其适合制备利用传统缩合反应相对较难制备的多取代吡啶，反应条件温和，操作简单，原子经济型高，适于在工业生产中应用。
Description
技术领域
本发明涉及一种合成吡啶环结构的方法，具体涉及一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，属于吡啶类化合物制备技术领域。
背景技术
吡啶环作为一种基本的结构单元，存在于多种天然产物，药物前体，功能材料中，被广泛应用于农药、医药、染料、化学试剂、和精细化工产品中。传统的合成吡啶环的方法一般是将羰基化合物与胺类物质缩合，包括芳香醛、芳香酮、醋酸铵的缩合，苄胺与芳香酮的缩合等。但由于反应过程中存在反应条件苛刻、产率低等缺点，因此不符合可持续发展的需求。近年来，化学家们越来越倾向于温和条件下过渡金属催化的方法来合成吡啶环，以便增加合成产率及底物普适性。例如过渡金属催化的[2+2+2]或[4+2]腈与烯烃的环加成反应，过渡金属催化的肟醚与芳香醛、二甲基甲酰胺、二甲基胺等的加成反应等。由于腈类可以与多种有机物发生碳钯化反应制备芳香酮，所以近两年有人报道了通过腈类的碳钯化反应合成吡啶环的方法。但是，这些反应必须用二腈类、δ-酮基腈类、拉电子基团取代的腈类做底物，直接利用脂肪腈的碳钯化反应制备吡啶环的反应还未见报道。
发明内容
本发明提供了一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，可以在温和条件下高效地制备各种吡啶衍生物。
本发明方法主要采用脂肪腈类的碳钯化反应及串联缩合反应制备多种吡啶衍生物，反应中脂肪腈作为C4N1供体、醛作为C1供体共同构建吡啶环，打破脂肪腈不能通过碳钯化反应直接制备吡啶环的技术壁垒。
由于脂肪腈的碳钯化反应可以产生亚胺中间体及酮，因此，脂肪腈既作为酮源，也作为氮源，通过与醛的缩合反应可以制备吡啶环结构。
本发明方法所涉及的化学反应方程式如下：
利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，包括如下步骤：
(1)将钯催化剂、醛、芳基硼酸、配体和氧化剂溶解于乙腈中得到混合液A；作为优选，所述醛、钯催化剂、配体、芳基硼酸、氧化剂的摩尔比为1：0.02～0.5：0.04-0.5：2-4：1-3。
所述的醛为RCHO，其中R为
/>
(n＝1,2,3,4,5,6)；
所述的钯催化剂为醋酸钯、三氟乙酸钯、氯化钯、四三苯基膦钯或负载纳米钯催化剂(Pd/Al2O3，Pd/C,Pd/MOF-5)；
所述的配体为
所述的芳基硼酸为ArB(OH)2,其中Ar为
(n＝1,2,3,4,5),/>
所述的氧化剂为AgCO3,AgTFA,Cu(OAc)2,
(2)将混合液A在回流条件下，搅拌24-72小时，得到混合液B；
依据所用原料种类的不同，所述的回流条件可对应不同的温度；步骤(2)中的反应，其反应时间并没有严格的限制，通过定时取样，用薄层色谱法(TLC)等现有手段进行跟踪分析，当其中一种原料或多种原料都反应完毕，视为反应的终点即可。
(3)过滤混合液B，浓缩滤液，经柱层析，得到多种取代吡啶。
与现有技术相比，本发明具有如下有益效果：
本发明方法通过醛、芳基硼酸、乙腈的串联反应制备吡啶环结构，反应物均无需大大过量。与原有技术相比，无需活化的腈类作为反应底物，直接利用工业商品乙腈进行碳钯化反应，减少了预活化的反应步骤，实现一锅法合成吡啶衍生物。反应中乙腈即作为C4N1供体又作为溶剂，原料利用率较高，具有极高的原子经济性。反应在中性条件下进行，反应物分子和产物分子中的官能团不受影响，尤其适合制备利用传统缩合反应相对较难制备的多取代吡啶。反应条件温和，反应温度低于100℃，操作简单，产率较高，适用于在工业生产中应用。
具体实施方式
实施例1
本实施例通过苯甲醛、苯硼酸与乙腈的串联反应制备2,4,6-三苯基吡啶。
将0.5mmol苯甲醛、0.05mmol醋酸钯、0.1mmol联吡啶、1.0mmol苯硼酸与1mmolAgTFA溶解于2mL乙腈中，将得到的反应混合液回流36小时；过滤所得到的混合液，浓缩滤液，经柱层析，即可得到2,4,6-三苯基吡啶，产率约为51％。
核磁监测数据如下：1H NMR(600MHz,CDCl3)δ8.24–8.17(m,4H),7.88(s,2H),7.76–7.70(m,2H),7.54–7.48(m,6H),7.48–7.42(m,3H)；13C NMR(151MHz,CDCl3)δ157.5,150.3,139.6,139.1,129.2,129.1,129.0,128.8,127.2,127.2,117.2.
实施例2
本实施例通过苯甲醛、苯硼酸与乙腈的串联反应制备2,4,6-三苯基吡啶。
将0.5mmol苯甲醛、50mg 3wt％Pd/Al2O3、0.1mmol的1,10-菲罗啉、1.5mmol苯硼酸与1mmol
溶解于2mL乙腈中，将得到的反应混合液回流48小时；过滤所得到的混合液，浓缩滤液，经柱层析，即可得到2,4,6-三苯基吡啶，产率约为64％。
核磁监测数据如下：1H NMR(600MHz,CDCl3)δ8.24–8.17(m,4H),7.88(s,2H),7.76–7.70(m,2H),7.54–7.48(m,6H),7.48–7.42(m,3H)；13C NMR(151MHz,CDCl3)δ157.5,150.3,139.6,139.1,129.2,129.1,129.0,128.8,127.2,127.2,117.2.
实施例3
本实施例通过邻甲基苯甲醛、苯硼酸与乙腈的串联反应制备2,6-二苯基-4-邻甲基苯基吡啶。
将0.5mmol邻甲基苯甲醛、0.05mmol醋酸钯、0.1mmol的联吡啶、1.5mmol苯硼酸与1mmol
溶解于2mL乙腈中，将得到的反应混合液回流48小时；过滤所得到的混合液，浓缩滤液，经柱层析，即可得到2,6-二苯基-4-邻甲基苯基吡啶，产率约为79％。
核磁监测数据如下：1H NMR(600MHz,CDCl3)δ8.18(d,J＝7.7Hz,4H),7.67(s,2H),7.51(t,J＝7.5Hz,4H),7.44(t,J＝7.3Hz,2H),7.38-7.29(m,4H),2.37(s,3H)；13C NMR(151MHz,CDCl3)δ156.8,151.6,139.8,139.3,135.2,130.7,129.3,129.1,128.7,128.4,127.2,126.2,119.5,20.4.
实施例4～12
实施例4～12中均利用实施例3的反应条件以及物料配比，仅改变醛以及芳基硼酸的种类，各实施例中所用的芳基酯和所得到的产物及产物收率参见表1。
表1
实施例4～12中目标产物的核磁监测数据如下：
实施例4：2,6-二苯基-4-对甲基苯基吡啶
1H NMR(600MHz,CDCl3)δ8.20(d,J＝7.4Hz,4H),7.88(s,2H),7.66(d,J＝8.0Hz,2H),7.51(t,J＝7.6Hz,4H),7.44(t,J＝7.3Hz,2H),7.33(d,J＝7.9Hz,2H),2.44(s,3H)；13CNMR(151MHz,CDCl3)δ157.5,150.1,139.6,139.1,136.1,129.9,129.0,128.7,127.2,127.0,117.0,21.3.
实施例5：2,6-二苯基-4-对甲氧基苯基吡啶
1H NMR(600MHz,CDCl3)δ8.20(d,J＝7.3Hz,4H),7.86(s,2H),7.71(d,J＝8.7Hz,2H),7.51(t,J＝7.6Hz,4H),7.44(t,J＝7.3Hz,2H),7.05(d,J＝8.7Hz,2H),3.88(s,3H)；13CNMR(151MHz,CDCl3)δ160.5,157.5,149.7,139.6,131.3,129.0,128.7,128.4,127.2,116.7,114.6,55.5.
实施例6：2,6-二苯基-4-邻氯苯基吡啶
1H NMR(600MHz,CDCl3)δ8.19(d,J＝7.4Hz,4H),7.78(s,2H),7.56-7.54(m,1H),7.51(t,J＝7.6Hz,4H),7.46-7.42(m,3H),7.41-7.37(m,2H)；13C NMR(151MHz,CDCl3)δ156.9,148.7,139.3,138.5,132.3,130.9,130.3,129.7,129.1,128.7,127.2,127.2,119.5.
实施例7：2,6-二苯基-4-对硝基苯基吡啶
1H NMR(600MHz,CDCl3)δ8.39(d,J＝8.7Hz,2H),8.21(d,J＝7.4Hz,4H),7.90(d,J＝8.7Hz,2H),7.88(s,2H),7.53(t,J＝7.5Hz,4H),7.48(t,J＝7.2Hz,2H)；13C NMR(151MHz,CDCl3)δ158.0,148.2,147.9,145.5,139.0,129.5,128.9,128.2,127.2,124.4,117.0.
实施例8：2,6-二苯基-4-(2-甲基-4-氟苯基)吡啶
1H NMR(600MHz,CDCl3)δ8.20–8.15(m,4H),7.62(s,2H),7.52–7.48(m,4H),7.46–7.42(m,2H),7.28(dd,J＝8.4,5.9Hz,1H),7.04(dd,J＝9.7,2.5Hz,1H),7.03–6.99(m,1H),2.35(s,3H)；13C NMR(151MHz,CDCl3)δ162.6(d,J＝247.2Hz,1C),156.9,150.5,139.3,137.8(d,J＝8.0Hz,1C),135.8(d,J＝3.1Hz,1C),130.9(d,J＝8.4Hz,1C),129.2,128.8,127.1,119.5,117.3(d,J＝21.2Hz,1C),113.1(d,J＝21.2Hz,1C),20.6(d,J＝1.3Hz,1C).
实施例9：2,6-二苯基-4-(2-噻吩)吡啶
1H NMR(600MHz,CDCl3)δ8.21–8.15(m,4H),7.86(s,2H),7.62–7.60(m,1H),7.52(t,J＝7.6Hz,4H),7.47–7.43(m,3H),7.17(dd,J＝4.9,3.7Hz,1H)；13C NMR(151MHz,CDCl3)δ157.7,143.1,141.9,139.3,129.2,128.7,128.4,127.2,127.0,125.3,115.4.
实施例10：2,6-二-(4-甲基苯基)-4-苯基吡啶
1H NMR(600MHz,CDCl3)δ8.10(d,J＝8.1Hz,4H),7.83(s,2H),7.74(d,J＝7.3Hz,2H),7.52(dd,J＝9.6,5.4Hz,2H),7.46(t,J＝7.3Hz,1H),7.31(d,J＝7.9Hz,4H),2.43(s,6H)；13C NMR(151MHz,CDCl3)δ157.4,150.1,139.3,139.0,136.8,129.4,129.1,128.9,127.2,127.1,116.6,21.4.
实施例11：2,6-二-(4-三甲基硅基苯基)-4-苯基吡啶
1H NMR(600MHz,CDCl3)δ8.17(d,J＝8.0Hz,4H),7.89(s,2H),7.75(d,J＝7.2Hz,2H),7.67(d,J＝7.9Hz,4H),7.54(t,J＝7.5Hz,2H),7.48(t,J＝7.3Hz,1H),0.32(s,18H)；13C NMR(151MHz,CDCl3)δ158.7,151.4,142.7,140.8,140.1,134.8,130.3,130.2,128.3,127.6,118.5.
实施例12：2,6-二-(4-三氟甲氧基苯基)-4-苯基吡啶
1H NMR(600MHz,CDCl3)δ8.20(d,J＝8.1Hz,4H),7.86(s,2H),7.72(d,J＝7.5Hz,2H),7.54(t,J＝7.4Hz,2H),7.51-7.47(m,1H),7.35(d,J＝8.2Hz,4H)；13C NMR(151MHz,CDCl3)δ156.3,150.8,150.1,138.6,137.9,129.3,129.3,128.6,127.2,121.1,120.5(q,J＝257.5Hz,1C),117.4.
Claims (4)
1.一种利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，其特征在于：包括如下步骤：
S1将钯催化剂、醛、芳基硼酸、配体和氧化剂溶解于乙腈中得到混合液A；
所述的醛为RCHO，其中R为
所述的钯催化剂为醋酸钯或Pd/Al2O3；
所述的配体为
所述的芳基硼酸为ArB(OH)2,其中Ar为
(n＝1,2,3,4,5),
所述的氧化剂为AgTFA,
S2将混合液A在回流条件下，搅拌24-72小时，得到混合液B；
S3过滤混合液B，浓缩滤液，经柱层析，得到多种取代吡啶。
2.根据权利要求1所述的利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，其特征在于：所述的醛与钯催化剂的摩尔比为1：0.02～0.5。
3.根据权利要求1所述的利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，其特征在于：所述的醛与芳基硼酸的摩尔比为1：2～4。
4.根据权利要求1所述的利用醛、芳基硼酸、乙腈的串联反应合成吡啶环结构的方法，其特征在于：所述的醛与氧化剂的摩尔比为1：1～3。
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