§13-3六元杂环化合物PPT课件

1、13-3 六元杂环化合物六元杂环化合物( (Six-membered heterocyclic compounds)一、吡啶一、吡啶 (pyridine)1、Structure of pyridineNN.sp2sp2sp2pNnucleophic substitutionpyridinepyridine ringnitrogen atomelectrophilic substitutionoxidationreductionreaction with electrophic reagents2、Chemical properties of pyridine （1）Reactions with

2、 electrophilic reagents a、Reactions on nitrogen atomNHNNHNH2Basicity： N.N+ H+NHApplication:NH3CINNNNCH3Ph COClpetrol ether, -20oCCOPhI-Cl-SO3CH2Cl2, r.t.SO3-Br2CCl4BrBr-Examples:b b、Electrophilic substitutions on pyridine ringNHOSN The activity of pyridine on electrophilic substitutions is much lowe

3、r than benzene, but similar with nitrobenzene.The activity of electrophilic substitutions :The electrophilic substitutions of pyridine mainly occur on 3-,5-positions.Explain:NE+2-,6-positionNHE+NHE+NHE+ 4-position 3-,5-positionNHENHENHENHENHENHE+NHE+NHENHENHENHE+Examples:NCl2, AlCl3NNO2NCl100oC300oC

4、NBrH2SO4浓HgSO4,220oCNSO3HH2SO4,浓浓HNO3300oC, 1dBr2, Cat.N20oCNH2Br2, HOAcNNH2BrComparison ：NH2Br2/H2ONH2BrBrBrExamples:N300oCNBrBr2, Cat（2） Reactions with nucleophilic reagentsi） The activity of pyridine on nucleophilic substitutions is higher than benzene. ii） The nucleophilic substitutions of pyrid

5、ine mainly occur on 2-,6- and 4-positions.Explain:N2-,6-positionNHNuNHNuNHNu4-position3-,5-positionNHNUNHNuNHNUNHNuNH NuNH NuNu-NHNuNHNuNHNUNHNuNHNUa、Leaving-group-replaced nucleophilic substitutionsReview:NH3ClNO2NH2NO2NO2NO2 ClClNO2CH3ONaCH3OHOCH3ClNO2ClBrNO2CH3ONaCH3OHOCH3BrNO2ClClNO2CH3ONaCH3OHO

6、CH3ClNO2ClBrNO2CH3ONaCH3OHOCH3BrNO2NH3ClNO2NH2NO2NO2NO2NNH2BrNOCH3NClCH3ONaCH3OH,NBrBrNH3, H2O160oCb、Hydrogen-replaced nucleophilic substitutionsNaNH2NNH- Na+NNH2NH2OPh N(CH3)2齐齐巴宾反应（齐齐巴宾反应（Chichibabin reaction）NPhNPhLiNLiPh110oC8h（3）Oxidationoxidationoxidation of side chainoxidation of pyridine rin

7、goxidation of nitrogen atomNH3CNCH3NCOOHHNO3Pyridine ring is more stable than benzene ring in acidic oxidant.NNCH3HNO3NCOOHNCOOHKMnO4H+NNH2O2HOAcNO吡啶吡啶-N-氧化物氧化物 (pyridine-N-oxide)Change the position of electrophilic substitution in pyridine to 4-position.Application：Example:NNO2NNH2O2HOAcNOPCl3NO-+N

8、NO2NO2HNO3H2SO4（4）Reduction reactions Pyridine ring is more active than benzene ring with reducing agents.NNHHH = Na/EtOH, H2/Pt六氢吡啶，哌啶六氢吡啶，哌啶(piperidine)3、Synthesis of pyridine ring systemn韩奇（韩奇（Hantzsch A）合成法）合成法CROORORC OROORCHONH3NHRROOCRCOORR+1,4-二氢吡啶二氢吡啶(1,4-dihydropyridine)尼群地平尼群地平(nitrendipi

9、ne)NHEtOOCCOOEtH3CCH3NO2Review: the synthesis of pyrrole derivativesRROO+ RNH2H+NRRRNHRRROOCCOORRRRROOCCOORROORRROOCORCOOROROOCRO+NH3+ RCHO12345Possible reaction mechanism：CROORORC OROORCHONH3NRROOCRCOORR+CROOROR+RC OROH2N+Michael additionCROORORRC OROH2N-H2ONHRROOCRCOORRO1)H2O2) -CO2NRRRImprovement

10、 of Hantzsch method：CH3ROArCHOCH3ORNH4OAc+MWIH2ONArRRS. Tu et al., Tetrahedron, 2007, 63, 381-388.CH3ArOArCHONH4OAc+OOMWIDMFNArArOS. Tu et al., Tetrahedron, 2007, 48, 1369-1374.茚茚-1,3-二酮二酮(indene-1,3-dione)茚并吡啶茚并吡啶(indenopridine)end1. Synthesizing medicine for heart disease: 心痛定心痛定NEtOOCCOOEtH3CCH3NO2NEtOOCCOOEtH3CCH3NO2H3COCH3ONH4OAcEtOOCCOOEtCHONO2+Analysis:endExercise:2. SynthesizingNCH3PhPhAnalysis:NCH3PhPhCH3PhOCH3PhOCH3CHONH4OAc+NCH3PhPhCH2PhOH2CPhOCH3CHONH4OAc+COOR