1、2022-12-19有机Chapter 14 Heterocyclic CompoundsChapter 14 Heterocyclic Compounds（杂环化合（杂环化合物）物）Heterocycle Heterocycle/Heterocyclic CompoundHeterocyclic Compound构成环系的原子除C外，还有其它杂原子。O,S,N.Hetero-atomHetero-atom(杂原子):HeterocycleHeterocycleSaturated HeterocyclesSaturated Heterocycles 饱和杂环化合物饱和杂环化合物Aromatic
2、 HeterocyclesAromatic Heterocycles 芳香杂环化合物芳香杂环化合物体现各自功能团的性质OOOONHOONHO2022-12-19有机一.Classification&Nomenclature:按环的大小按环的大小Five-membered ringSix-membered ring按杂原子的数目按杂原子的数目一个杂原子杂环一个杂原子杂环两个杂原子杂环两个杂原子杂环多个杂原子杂环多个杂原子杂环按环的拼合形式按环的拼合形式单杂环单杂环(homo-heterocycle)(homo-heterocycle)稠杂环稠杂环(fused-heterocycle)(fused
3、-heterocycle)2022-12-19有机NH12345O12345S12345pyrrolpyrrole e 吡咯吡咯thiophenethiophene 噻吩噻吩furanfuran呋喃呋喃 Classification&NomenclatureFive-membered ring heterocyclesFive-membered ring heterocyclesNNH12345NNH12345NO12345NS12345imidazoleimidazole 咪唑咪唑pyrazolepyrazole 吡唑吡唑oxazoleoxazole口口恶恶 唑唑thiazolethiazo
4、le 噻唑噻唑ON12345IsoxazoleIsoxazole异异口口恶恶 唑唑2022-12-19有机 Six-membered ring heterocyclesSix-membered ring heterocyclesClassification&Nomenclaturepyridinepyridine 吡啶吡啶pyrimidinepyrimidine 嘧啶嘧啶123456N2H-pyran2H-吡喃12345O6123456NN123456NN123456NNPyridazinePyridazine 哒嗪哒嗪PyrazinePyrazine 吡嗪吡嗪2022-12-19有机 Fus
5、ed-heterocyclesFused-heterocyclesClassification&Nomenclaturequinoline 喹啉iso-quinoline*异 喹啉Purine*嘌呤15823467N12345678NNNNNH123456789123456789NN101234567NHIndole吲哚123456789N1015823467NNNN158234679NH12348567910NSH 蝶啶蝶啶pteridinepteridine口口丫啶丫啶acridineacridine 吩嗪吩嗪phenazinephenazinecarbazolecarbazole 咔唑咔
6、唑PhenothiazinePhenothiazine 吩噻嗪吩噻嗪2022-12-19有机Classification&NomenclatureAttention!Attention!“指示氢指示氢”or or“标氢标氢”最多的非累积双键外的饱和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 没有达到最多的没有达到最多的非累积双键，非累积双键，“外加氢外加氢”的标注的标注NH2，5-二氢吡咯O四氢呋喃NH六氢吡啶2022-12-19有机Classification&Nomenclature 取代杂环的命名：取代杂环的命名：编号原则：单杂环、稠杂环；最小编号和优
7、先顺序法则编号原则：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)2ONNNNOOH3CCH3HNCH3ClNISO3HOH5-5-硝基硝基-2-2-呋喃甲醛呋喃甲醛4-4-氨基嘧啶氨基嘧啶N,N-N,N-二乙基二乙基-3-3-吡啶甲酰胺吡啶甲酰胺1,3,7-1,3,7-三甲基嘌呤三甲基嘌呤-2,6-2,6-二酮二酮3-3-甲基甲基-5-5-氯喹啉氯喹啉7-7-碘碘-8-8-羟基喹啉羟基喹啉-5-5-磺酸磺酸2022-12-19有机Classification&
8、Nomenclature 互变异构的存在，编号及名称的改变互变异构的存在，编号及名称的改变NNNNHNNNNH7 7H H-嘌呤嘌呤9 9H H-嘌呤嘌呤NNOHOHNNHHOO2,4-2,4-二羟基嘧啶二羟基嘧啶嘧啶嘧啶-2,4-2,4-二酮二酮NNHH3CNHNH3C12345123455-5-甲基吡唑甲基吡唑3-3-甲基吡唑甲基吡唑2022-12-19有机Classification&Nomenclature 拼合杂环的命名：拼合杂环的命名：非特定稠环非特定稠环基本环基本环附加环附加环稠合边的表示稠合边的表示呋喃并呋喃并2,3-b 2,3-b 噻吩噻吩吡咯并吡咯并3,2-b 3,2-b
9、噻吩噻吩SO12345abcdHNS12345abc2022-12-19有机Classification&Nomenclature 拼合杂环的命名：拼合杂环的命名：整体稠环编号，取代基位置整体稠环编号，取代基位置NNSPh12345675-5-苯基咪唑并苯基咪唑并2,1-b2,1-b噻唑噻唑NNSPh12345abcNONNH123456NONNH12345abcd6 6H H-吡唑并吡唑并4,5-d4,5-d口口恶恶 唑唑2022-12-19有机二二.Six-membered Heterocyclic compounds.Six-membered Heterocyclic compounds
10、Pyridine Pyridine 吡吡啶啶1.Structure:1.Structure:C C5 5H H5 5N N芳香性芳香性较强的碱性较强的碱性N2022-12-19有机NNNororKekules structureN1.430.841.011.010.840.87Aromaticity?电子云的分布电子云的分布E.S.E.S.变难变难 N.S.N.S.变易变易Oxidation Oxidation 难难Reduction Reduction 易易BasicityBasicitySix-membered Heterocyclic compoundsSix-membered Hete
11、rocyclic compounds2022-12-19有机2.Physical properties2.Physical properties(1)(1)(偶极矩偶极矩)Dipole moment)Dipole moment =7.41=7.41 1010-38-38 c.m 3.90 c.m 3.90 1010-38-38 c.m c.m IC方向一致方向一致Six-membered Heterocyclic compoundsSix-membered Heterocyclic compounds(2)Solubility:(2)Solubility:吡啶可以与水以任意比例互溶吡啶可以与水
12、以任意比例互溶2022-12-19有机3.Chemical reactions3.Chemical reactionsa.Basicity of PyridineRCH2NH2pKa4.65.199.25-10.0脂肪胺 BasicityBasicitySix-membered Heterocyclic compoundsSix-membered Heterocyclic compounds2022-12-19有机.+HCl.HClHCl-orSix-membered Heterocyclic compoundsSix-membered Heterocyclic compoundsNSO3CH
13、2Cl2NSO3-Pyr.SO3磺化试剂磺化试剂NNCOPhCl-PhCOCl酰化试剂酰化试剂NNCH3CH3II-甲基化试剂甲基化试剂2022-12-19有机b.Electrophilic Substitution:N N的的-I-I钝化环钝化环反应条件剧烈反应条件剧烈取代反应取代反应 发生在发生在3-3-位（位（）+KNO3+H2SO4NO2300 Co+H2SO4350 CoSO3H+Br2300 CoBr(20%)(71%)(33%)N1.430.841.011.010.840.87Six-membered Heterocyclic compoundsSix-membered Hete
14、rocyclic compounds2022-12-19有机Six-membered Heterocyclic compoundsSix-membered Heterocyclic compoundsN+E+2-位NEHNEHNEHNEH不稳定不稳定N+E+3-位NHENHENHENHE取代取代2-2-位位取代取代3-3-位位Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridine2022-12-19有机Six-membered Heterocyclic compoundsS
15、ix-membered Heterocyclic compoundsc.Nucleophilic Substitutionc.Nucleophilic SubstitutionNClNH3220 oCNNH290%NClNOMe95%NaOMeMeOH/NBrBrNNH2Br65%NH3160 oCNO22,4,6-2,4,6-位的影响位的影响XX的取代的取代Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridine2022-12-19有机Six-membered Hetero
16、cyclic compoundsSix-membered Heterocyclic compoundsNNaNH2NH3NNH Na+H2ONNH 2A.A.E.ChichibabinE.Chichibabin Reaction ReactionNNC6H5 C6H5Li+LiHH H-的取代的取代Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridine2022-12-19有机Six-membered Heterocyclic compoundsSix-membered He
17、terocyclic compoundsN1.430.841.011.010.840.87NHZNZHNHZNZHNZHNZHNHZNHZNHZ2-2-位位 (6-(6-位位)3-3-位位4-4-位位八电子氮负离子八电子氮负离子八电子氮负离子八电子氮负离子Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridine2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-
18、PyridinePyridined.Reactions of side chaind.Reactions of side chainNCCCHHHHHH Side Chain Side Chain Acidity of Acidity of -H-HNCH3CH2CH3NaNH2NCH2CH2CH3CH3INCH2CH3CH2CH380%NCH3NCH2CH2OH+HCHOZnCl22022-12-19有机Six-membered Heterocyclic compoundsSix-membered Heterocyclic compoundsNCH2NCH2NCH2NCH2NCH2NCH2N
19、CH2NCH2NCH2NCH2NCH2NCH22-2-位甲基位甲基3-3-位甲基位甲基4-4-位甲基位甲基八隅体八隅体八隅体八隅体2022-12-19有机Six-membered Heterocyclic compoundsSix-membered Heterocyclic compoundse.Oxidations&Reductionse.Oxidations&ReductionsNNCH3HNO3NCOOHNH3NCNH2O侧链的氧化侧链的氧化烟碱烟碱烟酸烟酸烟酰胺烟酰胺NCH3+H2O2(30%)CH3COOH70 oC,24hNCH3O N-N-氧化物氧化物 Pyridine-N-ox
20、idePyridine-N-oxide3-3-甲基吡啶甲基吡啶N-N-氧化物氧化物Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridinePyridine-N-oxidePyridine-N-oxide:Substitution/Position2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridineElectrophilicElec
21、trophilicNOCH3ONaCH3OHNOOCH3NOPhMgBrH2ONOPhNucleophilicNucleophilicNONO2 Fuming HNO3/H2SO490 oC,4h90%PCl3CH2Cl2NNO280%H2/Ni or Fe/H+NNH2 90%NO2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridineNOHZNOHZ-attack-attack-attackNOHZNOHZNOZHNOHZNOHZ2022-12-1
22、9有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyridinePyridineNH2/Ni25 oC,3 atmsNHpiperidineReductionReduction2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyrimidinePyrimidine嘧啶嘧啶PyrimidinePyrimidineNN123456spsp2 2碱性碱性水溶性水溶性取代反应取代反应
23、NNBr2100 oCNNBr66%NNOHH3COHHNO3HOAc,20 o CNNHOOHO2NH3C85%NNNH2NH2ClN2+Cl-NNNH2NH2NNCl2022-12-19有机NNCln-C4H9NH2NNNHC4H9-nNNCH3NaNH2130160 oCNNCH3H2NSix-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyrimidinePyrimidine2,4,6-positionsNNHHOONNOHOH(Uracil,U)(Uracil,U)尿嘧啶尿嘧啶NNHNH2ON
24、NOHNH2胞嘧啶胞嘧啶 (Cytosine,C)(Cytosine,C)NNHHOOH3CNNOHOHH3C胸腺嘧啶胸腺嘧啶(Thymine.T)(Thymine.T)tautomerismtautomerism2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyrimidinePyrimidineNNNHNOOH3CH3CCH2CHCHCHCH2OHOHOHOHVitamin B2NNNHSNH2OOSulfadiazine SD 磺胺嘧啶NNHOOOHC2H5Ph苯巴比
25、妥苯巴比妥 PhenobarbitalPhenobarbitalHCl H2ONNCH3ClOCH3NHNNH.Moxonidine Moxonidine 莫索尼定莫索尼定2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyrimidinePyrimidineHNNHOOFAntimetabolic AgentsAntimetabolic AgentsFluorouracil 5-FUOHNNOOFTegafurCytarabine阿糖胞苷NNONH2OHOOHHONNONH
26、2OHO司他夫定司他夫定 StavudineStavudineNHNOH3COOHON3Zidovudine Zidovudine 齐多夫定齐多夫定SOHONNONH2拉米夫定拉米夫定 LamivudineLamivudineAntiviral AgentsAntiviral Agents2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-Quinoline and IsoquinolineQuinoline and IsoquinolineQuinoline and Isoqu
27、inolineQuinoline and Isoquinoline15823467Nquinoline 喹啉12345678Niso-quinoline*异 喹啉杂化杂化 spsp2 2碱性碱性取代反应：取代反应：E.S.N.S.位置2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-Quinoline and IsoquinolineQuinoline and IsoquinolineElectrophilic SubstitutionElectrophilic Substit
28、utionNHNO3/H2SO40 oC,30 min.NNO2+NNO25852%48%NHNO3/H2SO40 oC,30 min.NNO2+NNO25890%10%NBr2/H2SO4AgSO4NBr+58BrNNNSO3H5H2SO422 oC异环取代异环取代5-5-，8-8-位位2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-Quinoline and IsoquinolineQuinoline and IsoquinolineNucleophilic Substi
29、tutionNucleophilic SubstitutionNNNH2NaNH2NC2H5MgXNC2H5150 oCNClNaOCH3CH3OH/heatNOMe发生在吡啶环上，发生在吡啶环上，2(1)2(1)、4 4位上位上2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-Quinoline and IsoquinolineQuinoline and IsoquinolineThe Reactions of Side ChainThe Reactions of Side
30、ChainNCH3+COOEtCOOEtNaOEt/HOEtrt,12hNCH2CCOOEtO90%+NCH3CH3CHOZnCl2100 oCNCHCH3CH2(1),4位侧链-H2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-Quinoline and IsoquinolineQuinoline and IsoquinolineOxidation&ReductionOxidation&ReductionNCrO3 or KMnO4NCOOHCOOH氧化苯环氧化苯环NSn/
31、HClor Na/ROHNHH2/NiNH还原吡啶环还原吡啶环2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyranPyranPyran Pyran 吡喃吡喃OOOOOOO2 2H H-吡喃吡喃(-吡喃吡喃)4 4H H-吡喃吡喃(-吡喃吡喃)-吡喃酮吡喃酮-吡喃酮吡喃酮吡喃盐正离子吡喃盐正离子口口恶英嗡盐离子恶英嗡盐离子杂化杂化不饱和环醚不饱和环醚非芳香性非芳香性O芳香性芳香性 稳定性稳定性/高反应活性高反应活性2022-12-19有机Six-membered Heterocyclic compounds-Six-membered Heterocyclic compounds-PyranPyranOOOOH+HClCl-OO+CH3IOOCH3I-吡喃酮吡喃酮可编辑感感谢谢下下载载
