有机化学Chap.14heterocycliccompoundsandvitamins

1、1Chapter 14 Heterocyclic Compounds and VitaminsHeteroatoms (杂原子杂原子): O, S, N 杂环是与与碳环相对的概念，指的是构成环的构成环的原子原子含有氮、氧或硫等原子。（杂环化合物）（杂环化合物） 杂环可以是芳环芳环（如吡啶），也可以是脂环（如四氢呋喃）2OOOOOOORRcyclic anhydridelactideThese compounds have collective feature, they are instable, the rings be opened easily.OOONHOepoxidelactonel

2、actam环上含杂原子的非杂环化合物3Section 1. Classification an Nomenclature. Classificationmono ring heterocycliccondensed ring heterocyclicpentabasichexabasicONNNNNNH稠杂环杂环4. Nomenclature 杂环化合物的命名方法有两种：音译法和系统命名法。其中最常用的是音译法音译法。 译音法是根据其英文读音，选用带“口”字旁的同音汉字来命名。若环上有取代基，以杂环作为化合物的母体。5 若环上有取代基，以杂环为母体，将环进行编号，杂原子为“1”。也可用（杂原子

3、的邻位碳原子）、来表示环上取代基的位置。 若环上有二个或二个以上相同的杂原子，则应使杂原子的位次和保持最小 若连有二个或二个以上不同的杂原子，则按OSNH N的顺序编号NS6ONHSfuran 呋喃 thiophene 噻吩pyrrole 吡咯NNHthiazole噻唑NNHimidazole咪唑pyrazole吡唑NOoxazole噁唑 11112345312451234512345Five-membered rings NHN4-Methylimidazole，4-甲基咪唑 134Consumer group finds cancer-causing chemical in colas M

4、arch 05, 2012， Los Angeles TimesThe US Food and Drug Administration (FDA) claims a person would need to drink more than 1,000 cans of Coke or Pepsi a day to take in the same dose of the chemical that was given to the animals in the lab test.The average 4-MI content for samples of regular and diet Co

5、ke, Pepsi and Dr. Pepper and Whole Foods 365 cola was 138 micrograms （微克）http:/www.bbc.co.uk/news/world-us-canada-17308181BBC，10 MARCH 201210NNpyrimidine，嘧啶嘧啶123456Npyridine, py, 吡啶吡啶1OO14dioxane 二噁烷，二氧六环二噁烷，二氧六环Six-membered rings O4H-pyran，吡喃，吡喃11Johnson & Johnsons Baby Shampoo and other childr

6、ens products were found to contain formaldehyde and 1,4-dioxane. (NowPublic: http:/ 喹啉喹啉isoquinoline异喹啉异喹啉12345671234567812345678123495678NHindole 吲哚吲哚NNNNHpurine 嘌呤嘌呤condensed heterocycles15NNCH3H5-methylimidazoleOCHO -furfuraldehyde 糠醛糠醛NCH3H3-methylindoleOHN8-hydroxylquinolineSkatole, 粪臭素粪臭素16Sec

7、tion 2 Six-Membered Heterocycles. Pyridine (吡啶)1. BasicityN17six electrons are delocalized (离域) in the ringA p orbital on N overlaps with adjacent p orbitals, making the ring completely conjugated18NHClHClNThe sequence of basicity:NH2N NH3Why ？ P. 189 14-119One sp2 hybrid orbitals contains lone pair

8、N三种杂化轨道的长度比较：sp sp2 sp3sp220NHH苯胺 (aniline)p- conjugation, delocalized (离域) 21NNH3(C2H5)2NHNH2pKa 4.6 5.2 9.25 11.0 pKa越大，越大，酸性越小，其共轭碱的碱性越大其共轭碱的碱性越大H+H+H+H+Then sequence of basicity:NH3(C2H5)2NHNH2N54Chemical Properties:1. HydrogenationOH2,PtOtetrahydrofuran, THF四氢呋喃55H2,PtNHNHtetrahydropyrrole or p

9、yrrolidine四氢吡咯，吡咯烷562. SubstitutionOBr2OBrBr2SSBr(1) Halogenation57(2) NitrationONO2HNO3/(CH3CO)2OOSNO2HNO3/(CH3CO)2OSNNO2HHNO3/(CH3CO)2ONHCH3COONO2HNO3/(CH3CO)2O =58SO3/pyridine=-N SO3+SO3/pyridineOSO3HONHSO3/pyridineNSO3HHNH(3) SulfonylationP. 19259SH2OSSO3HH2SO4S 此反应可用于从有机物中除去噻吩，或是用于提纯噻吩。60(4) Fr

10、iedel-Crafts acylation（傅-克酰化反应） NH(CH3CO)2ONHOOCH3COCl, BF3OO613. Acid and Base PropertiesNHKOH (solid)NKNHHHHH62Basicity:NHHNHHNHHH(C2H5)2NHHpKa 11.2 11.0 4.6 0.0 NH2NHNH(C2H5)2NHpKa越大，越大，酸性越小，其共轭碱的碱性越大其共轭碱的碱性越大 pyrrolidine（四氢吡咯，吡咯烷）的碱性相当于脂肪族仲胺63卟啉(Porphyrin)R=H, 卟吩(Porphine)Some important derivati

11、ves of five-membered heterocycles64叶绿素(chlorophylls a)血红素B (血基质B，heme B)6566维生素B12 (Vitamine B12, VB12)，钴胺素，氰钴胺(脱氧腺苷基脱氧腺苷基)67二、含两个杂原子的芳香五元杂环NSthiazole噻唑NNHimidazole咪唑NOoxazole噁唑 68(delocalized 离域)69NNHNNH70NONOorbital structure of oxazole (噁唑)71NSNSSorbital structure of thiazole (噻唑)72咪唑化合物的互变异构NNHN

12、HNNNHNHN23451234514-甲基咪唑5-甲基咪唑73NNHNH2组胺（histamine)N3N2N1N1、N2、N3碱性大小次序：N3 N2 N174NNCH2S(CH2)2NH C NHCH3NCNCH3HCimetidine, 西咪替丁西咪替丁, 甲腈咪胍甲腈咪胍, 泰胃美泰胃美 Histamine H2-receptor antagonist that inhibits stomach acid production，used in the treatment of heartburn（胃灼热）and peptic ulcers（消化性溃疡）.75CH2S(CH2)2NH

13、C NHCH3OC NO2(CH3)2NCH2Ranitidine,雷尼替丁雷尼替丁NCH2S(CH2)2NH CSNCNH2NH2NSO2NH2NH2Famotidine, 法莫替丁法莫替丁76NOCH3H3CCH3SONNHOCH3Omeprazole, 奥美拉唑, Losec, 洛赛克AstraZeneca, 阿斯利康 Proton pump inhibitor, 质子泵抑制剂77CH2CONHNSCH3CH3COOHOBenzylpenicillin Sodium (potassium)COONa(K)78NHNHNOCH3OSH3CAlbendazole, 阿苯达唑, 肠虫清 79S

14、ection 4 condensed heterocyclesPurine（嘌呤）HNNNNHNNNN 9H- purineHNNNNHNNNN 7H- purine9H-purine can tautomerize to form 7H-purine. Most natural products are the derivatives of 9H-purine. In contrast, most synthetical products are the derivatives of 7H-purine.80NNNNNH2HNNNNH2NOHHadenine, A, 腺嘌呤guanine,

15、G, 鸟嘌呤The four bases of DNA are adenine (A), thymine (T), guanine (G) and cytosine (C). The four bases of RNA are adenine (A), uracil (U) and guanine (G) and cytosine (C). 81Xanthine, 黄嘌呤Hypoxanthine, 次黄嘌呤Xanthine oxidase(黄嘌呤氧化酶)Xanthine oxidase(黄嘌呤氧化酶)Uric acid（尿酸）HNNNHNOHNNHNHNOOHNNHNHNHOOONNNHNOHHOOH High blood concentrations of uric acid can lead to gout（痛风）82NNNHNOHAllopurinol, 别嘌醇inhibitor of xanthine oxidaseHNNHNHNOOOAlloxanthine, 别黄嘌呤Alloxanthine is the active metabolite of allopurinol83NNNHNOHXanthine oxidase(黄嘌呤氧化酶)HNNHN