北大有机课件 第十四章杂环化合物2

1、2021-10-20有机chapter 14 heterocyclic compounds（杂环化合物）（杂环化合物） heterocycle / heterocyclic compound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):heterocyclesaturated heterocycles 饱和杂环化合物饱和杂环化合物aromatic 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oooonhoonho2021-10-20有机一 .classification & nomenclature:按环的按环的大小大小

2、five-membered ringsix-membered ring按杂原子的按杂原子的数目数目一个一个杂原子杂环杂原子杂环两个两个杂原子杂环杂原子杂环多个多个杂原子杂环杂原子杂环按环的拼合按环的拼合形式形式单单杂环杂环(homo-heterocycle)稠稠杂环杂环(fused-heterocycle)2021-10-20有机nh12345o12345s12345pyrrole 吡咯吡咯thiophene 噻吩噻吩furan呋喃呋喃 classification & nomenclaturefive-membered ring heterocyclesnnh12345nnh12345no1

3、2345ns12345imidazole 咪唑咪唑pyrazole 吡唑吡唑oxazole口口恶恶 唑唑thiazole 噻唑噻唑on12345isoxazole异异口口恶恶 唑唑2021-10-20有机 six-membered ring heterocyclesclassification & nomenclaturepyridine 吡啶吡啶pyrimidine 嘧啶嘧啶123456n2h-pyran2h- 吡喃12345o6123456nn123456nn123456nnpyridazine 哒嗪哒嗪pyrazine 吡嗪吡嗪2021-10-20有机 fused-heterocycle

4、sclassification & nomenclaturequinoline 喹啉iso-quinoline* 异 喹啉purine* 嘌呤15823467n12345678nnnnnh123456789123456789nn101234567nhindole吲哚123456789n1015823467nnnn158234679nh12348567910nsh 蝶啶蝶啶pteridine口口丫啶丫啶acridine 吩嗪吩嗪phenazinecarbazole 咔唑咔唑phenothiazine 吩噻嗪吩噻嗪2021-10-20有机classification & nomenclaturea

5、ttention! “指示氢指示氢” 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2021-10-20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

6、呤ochoo2nnnnh2ncn(c2h5)2onnnnooh3cch3hnch3clniso3hoh5-硝基硝基-2-呋喃甲醛呋喃甲醛4-氨基嘧啶氨基嘧啶n,n-二乙基二乙基-3-吡啶甲酰胺吡啶甲酰胺1,3,7-三甲基嘌呤三甲基嘌呤-2,6-二酮二酮3-甲基甲基-5-氯喹啉氯喹啉7-碘碘-8-羟基喹啉羟基喹啉-5-磺酸磺酸2021-10-20有机classification & 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nnnnhnnnnh7h-嘌呤嘌呤9h-嘌呤嘌呤nnohohnnhhoo2,4-二羟基嘧啶二羟基嘧啶嘧啶嘧啶-2,4-二酮二酮

7、nnhh3cnhnh3c12345123455-甲基吡唑甲基吡唑3-甲基吡唑甲基吡唑2021-10-20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 噻吩噻吩吡咯并吡咯并3, 2-b 噻吩噻吩so12345abcdhns12345abc2021-10-20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-苯基咪唑并苯基咪唑并2, 1

8、-b噻唑噻唑nnsph12345abcnonnh123456nonnh12345abcd6h-吡唑并吡唑并4, 5-d口口恶恶 唑唑2021-10-20有机二二. six-membered heterocyclic compoundspyridine 吡啶吡啶1. structure: c5h5n芳香性芳香性较强的碱性较强的碱性n2021-10-20有机nnnororkekules structuren1.430.841.011.010.840.87aromaticity ? 电子云的分布电子云的分布e.s. 变难变难 n.s. 变易变易oxidation 难难reduction 易易basi

9、citysix-membered heterocyclic compounds2021-10-20有机2. physical properties(1) (偶极矩偶极矩) dipole moment = 7.41 10-38 c.m 3.90 10-38 c.m ic方向一致方向一致six-membered heterocyclic compounds(2) solubility: 吡啶可以与水以任意比例互溶吡啶可以与水以任意比例互溶2021-10-20有机3. chemical reactionsa. basicity of pyridinerch2nh2pka4.65.199.25-10.

10、0脂肪胺 basicitysix-membered heterocyclic compounds2021-10-20有机.+hcl.hclhcl-orsix-membered heterocyclic compoundsnso3ch2cl2nso3-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2021-10-20有机b. electrophilic substitution:n的的-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-位（位（ ）+kno3+h2so4no2300 co+h2so4

11、350 coso3h+br2300 cobr(20%)(71%)(33%)n1.430.841.011.010.840.87six-membered heterocyclic compounds2021-10-20有机six-membered heterocyclic compoundsn+ e+2-位nehnehnehneh不稳定不稳定n+ e+3-位nhenhenhenhe取代取代2-位位取代取代3-位位six-membered heterocyclic compounds-pyridine2021-10-20有机six-membered heterocyclic compoundsc.

12、nucleophilic substitutionnclnh3220 ocnnh290%nclnome95%naomemeoh/nbrbrnnh2br65%nh3160 ocno22, 4, 6-位的影响位的影响x的取代的取代six-membered heterocyclic compounds-pyridine2021-10-20有机six-membered heterocyclic compoundsnnanh2nh3nnh na+h2onnh 2a. e. chichibabin reactionnnc6h5 c6h5li+ lihh-的取代的取代six-membered heteroc

13、yclic compounds-pyridine2021-10-20有机six-membered heterocyclic compoundsn1.430.841.011.010.840.87nhznzhnhznzhnzhnzhnhznhznhz2-位位 (6-位位)3-位位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-pyridine2021-10-20有机six-membered heterocyclic compounds-pyridined. reactions of side chainnccc

14、hhhhhh side chain acidity of -hnch3ch2ch3nanh2nch2ch2ch3ch3inch2ch3ch2ch380%nch3nch2ch2oh +hchozncl22021-10-20有机six-membered heterocyclic compoundsnch2nch2nch2nch2nch2nch2nch2nch2nch2nch2nch2nch22-位甲基位甲基3-位甲基位甲基4-位甲基位甲基八隅体八隅体八隅体八隅体2021-10-20有机six-membered heterocyclic compoundse. oxidations & reduct

15、ionsnnch3hno3ncoohnh3ncnh2o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-氧化物氧化物 pyridine-n-oxide3-甲基吡啶甲基吡啶n-氧化物氧化物six-membered heterocyclic compounds-pyridinepyridine-n-oxide: substitution / position2021-10-20有机six-membered heterocyclic compounds-pyridineelectrophilicnoch3onach3ohno

16、och3nophmgbrh2onophnucleophilicnono2 fuming hno3/h2so490 oc, 4h90%pcl3ch2cl2nno280%h2/ni or fe/h+nnh2 90%no2021-10-20有机six-membered heterocyclic compounds-pyridinenohznohz-attack-attack-attacknohznohznozhnohznohz2021-10-20有机six-membered heterocyclic compounds-pyridinenh2/ni25 oc, 3 atmsnhpiperidiner

17、eduction2021-10-20有机six-membered heterocyclic compounds-pyrimidine嘧啶嘧啶pyrimidinenn123456sp2碱性碱性水溶性水溶性取代反应取代反应nnbr2100 ocnnbr66%nnohh3cohhno3hoac, 20 o cnnhooho2nh3c85%nnnh2nh2cln2+cl-nnnh2nh2nncl2021-10-20有机nncln-c4h9nh2nnnhc4h9-nnnch3nanh2130160 ocnnch3h2nsix-membered heterocyclic compounds-pyrimid

18、ine2, 4, 6-positionsnnhhoonnohoh(uracil, u)尿嘧啶尿嘧啶nnhnh2onnohnh2胞嘧啶胞嘧啶 (cytosine, c)nnhhooh3cnnohohh3c胸腺嘧啶胸腺嘧啶(thymine. t)tautomerism2021-10-20有机six-membered heterocyclic compounds-pyrimidinennnhnooh3ch3cch2chchchch2ohohohohvitamin b2nnnhsnh2oosulfadiazine sd 磺胺嘧啶nnhooohc2h5ph苯巴比妥苯巴比妥 phenobarbitalhc

19、l h2onnch3cloch3nhnnh.moxonidine 莫索尼定莫索尼定2021-10-20有机six-membered heterocyclic compounds-pyrimidinehnnhoofantimetabolic agentsfluorouracil 5-fuohnnooftegafurcytarabine阿糖胞苷nnonh2ohoohhonnonh2oho司他夫定司他夫定 stavudinenhnoh3coohon3zidovudine 齐多夫定齐多夫定sohonnonh2拉米夫定拉米夫定 lamivudineantiviral agents2021-10-20有机

20、six-membered heterocyclic compounds-quinoline and isoquinolinequinoline and isoquinoline15823467nquinoline 喹啉12345678niso-quinoline* 异 喹啉杂化杂化 sp2碱性碱性取代反应：取代反应： e.s. n.s.位置2021-10-20有机six-membered heterocyclic compounds-quinoline and isoquinolineelectrophilic substitutionnhno3/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-，8-位位2021-10-20有机six-membered heterocyclic compounds-quinoline and isoquinolinenucleophilic substitutionnnnh2nanh2nc2h5