北大有机课件 第十四章-杂环化合物2

2020/6/13有机Chapter14HeterocyclicCompounds（杂环化合物）Heterocycle/HeterocyclicCompound构成环系的原子除C外，还有其它杂原子。O,S,N.Hetero-atom(杂原子):HeterocycleSaturatedHeterocycles饱和杂环化合物AromaticHeterocycles芳香杂环化合物体现各自功能团的性质OOOONHOONHO2020/6/13有机一.Classification&Nomenclature:按环的大小Five-memberedringSix-memberedring按杂原子的数目一个杂原子杂环两个杂原子杂环多个杂原子杂环按环的拼合形式单杂环(homo-heterocycle)稠杂环(fused-heterocycle)2020/6/13有机NH12345O12345S12345pyrrole吡咯thiophene噻吩furan呋喃Classification&NomenclatureFive-memberedringheterocyclesNNH12345NNH12345NO12345NS12345imidazole咪唑pyrazole吡唑oxazole口恶唑thiazole噻唑ON12345Isoxazole异口恶唑2020/6/13有机Six-memberedringheterocyclesClassification&Nomenclaturepyridine吡啶pyrimidine嘧啶123456N2H-pyran2H-吡喃12345O6123456NN123456NN123456NNPyridazine哒嗪Pyrazine吡嗪2020/6/13有机Fused-heterocyclesClassification&Nomenclaturequinoline喹啉iso-quinoline*异喹啉Purine*嘌呤15823467N12345678NNNNNH123456789123456789NN101234567NHIndole吲哚123456789N1015823467NNNN158234679NH12348567910NSH蝶啶pteridine口丫啶acridine吩嗪phenazinecarbazole咔唑Phenothiazine吩噻嗪2020/6/13有机Classification&NomenclatureAttention!“指示氢”or“标氢”—最多的非累积双键外的饱和氢NNHNO1H-吡咯2H-吡咯4H-吡喃3H-吲哚没有达到最多的非累积双键，“外加氢”的标注NH2，5-二氢吡咯O四氢呋喃NH六氢吡啶2020/6/13有机Classification&Nomenclature取代杂环的命名：编号原则：单杂环、稠杂环；最小编号和优先顺序法则12345678NNNNNH123456789iso-quinoline*异喹啉Purine*嘌呤OCHOO2NNNNH2NCN(C2H5)2ONNNNOOH3CCH3HNCH3ClNISO3HOH5-硝基-2-呋喃甲醛4-氨基嘧啶N,N-二乙基-3-吡啶甲酰胺1,3,7-三甲基嘌呤-2,6-二酮3-甲基-5-氯喹啉7-碘-8-羟基喹啉-5-磺酸2020/6/13有机Classification&Nomenclature互变异构的存在，编号及名称的改变NNNNHNNNNH7H-嘌呤9H-嘌呤NNOHOHNNHHOO2,4-二羟基嘧啶嘧啶-2,4-二酮NNHH3CNHNH3C12345123455-甲基吡唑3-甲基吡唑2020/6/13有机Classification&Nomenclature拼合杂环的命名：非特定稠环基本环附加环稠合边的表示呋喃并[2,3-b]噻吩吡咯并[3,2-b]噻吩SO12345abcdHNS12345abc2020/6/13有机Classification&Nomenclature拼合杂环的命名：整体稠环编号，取代基位置NNSPh12345675-苯基咪唑并[2,1-b]噻唑NNSPh12345abcNONNH123456NONNH12345abcd6H-吡唑并[4,5-d]口恶唑2020/6/13有机二.Six-memberedHeterocycliccompoundsPyridine吡啶1.Structure:C5H5N芳香性较强的碱性N2020/6/13有机NNNororKekule’sstructureN1.430.841.011.010.840.87Aromaticity?电子云的分布E.S.变难N.S.变易Oxidation难Reduction易BasicitySix-memberedHeterocycliccompounds2020/6/13有机2.Physicalproperties(1)(偶极矩)Dipolemoment=7.4110-38c.m3.9010-38c.mIC方向一致Six-memberedHeterocycliccompounds(2)Solubility:吡啶可以与水以任意比例互溶2020/6/13有机3.Chemicalreactionsa.BasicityofPyridineRCH2NH2pKa4.65.199.25-10.0脂肪胺BasicitySix-memberedHeterocycliccompounds2020/6/13有机..+HCl...HClHCl-orSix-memberedHeterocycliccompoundsNSO3CH2Cl2NSO3-Pyr.SO3磺化试剂NNCOPhCl-PhCOCl酰化试剂NNCH3CH3II-甲基化试剂2020/6/13有机b.ElectrophilicSubstitution:N的-I钝化环反应条件剧烈取代反应发生在3-位（）+KNO3+H2SO4NO2300Co+H2SO4350CoSO3H+Br2300CoBr(20%)(71%)(33%)N1.430.841.011.010.840.87Six-memberedHeterocycliccompounds2020/6/13有机Six-memberedHeterocycliccompoundsN+E+2-位NEHNEHNEHNEH不稳定N+E+3-位NHENHENHENHE取代2-位取代3-位Six-memberedHeterocycliccompounds-Pyridine2020/6/13有机Six-memberedHeterocycliccompoundsc.NucleophilicSubstitutionNClNH3220oCNNH290%NClNOMe95%NaOMeMeOH/NBrBrNNH2Br65%NH3160oCNO22,4,6-位的影响—X的取代Six-memberedHeterocycliccompounds-Pyridine2020/6/13有机Six-memberedHeterocycliccompoundsNNaNH2NH3NNHNa+H2ONNH2A.E.ChichibabinReactionNNC6H5C6H5Li+LiHH-的取代Six-memberedHeterocycliccompounds-Pyridine2020/6/13有机Six-memberedHeterocycliccompoundsN1.430.841.011.010.840.87NHZNZHNHZNZHNZHNZHNHZNHZNHZ2-位(6-位)3-位4-位八电子氮负离子八电子氮负离子Six-memberedHeterocycliccompounds-Pyridine2020/6/13有机Six-memberedHeterocycliccompounds-Pyridined.ReactionsofsidechainNCCCHHHHHHSideChainAcidityof-HNCH3CH2CH3NaNH2NCH2CH2CH3CH3INCH2CH3CH2CH380%NCH3NCH2CH2OH+HCHOZnCl22020/6/13有机Six-memberedHeterocycliccompoundsNCH2NCH2NCH2NCH2NCH2NCH2NCH2NCH2NCH2NCH2NCH2NCH22-位甲基3-位甲基4-位甲基八隅体八隅体2020/6/13有机Six-memberedHeterocycliccompoundse.Oxidations&ReductionsNNCH3HNO3NCOOHNH3NCNH2O侧链的氧化烟碱烟酸烟酰胺NCH3+H2O2(30%)CH3COOH70oC,24hNCH3ON-氧化物Pyridine-N-oxide3-甲基吡啶N-氧化物Six-memberedHeterocycliccompounds-PyridinePyridine-N-oxide:Substitution/Position2020/6/13有机Six-memberedHeterocycliccompounds-PyridineElectrophilicNOCH3ONaCH3OHNOOCH3NOPhMgBrH2ONOPhNucleophilicNONO2FumingHNO3/H2SO490oC,4h90%PCl3CH2Cl2NNO280%H2/NiorFe/H+NNH290%NO2020/6/13有机Six-memberedHeterocycliccompounds-PyridineNOHZNOHZ-attack-attack-attackNOHZNOHZNOZHNOHZNOHZ2020/6/13有机Six-memberedHeterocycliccompounds-PyridineNH2/Ni25oC,3atmsNHpiperidineReduction2020/6/13有机Six-memberedHeterocycliccompounds-Pyrimidine嘧啶PyrimidineNN123456sp2碱性水溶性取代反应NNBr2100oCNNBr66%NNOHH3COHHNO3HOAc,20oCNNHOOHO2NH3C85%NNNH2NH2ClN2+Cl-NNNH2NH2NNCl2020/6/13有机NNCln-C4H9NH2NNNHC4H9-nNNCH3NaNH2130~160oCNNCH3H2NSix-memberedHeterocycliccompounds-Pyrimidine2,4,6-positionsNNHHOONNOHOH(Uracil,U)尿嘧啶NNHNH2ONNOHNH2胞嘧啶(Cytosine,C)NNHHOOH3CNNOHOHH3C胸腺嘧啶(Thymine.T)tautomerism2020/6/13有机Six-memberedHeterocycliccompounds-PyrimidineNNNHNOOH3CH3CCH2CHCHCHCH2OHOHOHOHVitaminB2NNNHSNH2OOSulfadiazineSD磺胺嘧啶NNHOOOHC2H5Ph苯巴比妥PhenobarbitalHClH2ONNCH3ClOCH3NHNNH..Moxonidine莫索尼定2020/6/13有机Six-memberedHeterocycliccompounds-PyrimidineHNNHOOFAntimetabolicAgentsFluorouracil5-FUOHNNOOFTegafurCytarabine阿糖胞苷NNONH2OHOOHHONNONH2OHO司他夫定StavudineNHNOH3COOHON3Zidovudine齐多夫定SOHONNONH2拉米夫定Lamivudin