第十四章-杂环化合物2.ppt

1、Chapter 14 Heterocyclic Compounds（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):,Heterocycle,Saturated Heterocycles 饱和杂环化合物,Aromatic Heterocycles 芳香杂环化合物,体现各自功能团的性质,一 .Classification & Nomenclature:,按环的大小,Five-membered ring,Six-membered ring,按杂原子的数目,一个杂原子杂

2、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),pyrrole 吡咯,thiophene 噻吩,furan 呋喃,Classification & Nomenclature,Five-membered ring heterocycles,imidazole 咪唑,pyrazole 吡唑,oxazole 口恶 唑,thiazole 噻唑,Isoxazole 异口恶 唑, Six-membered ring heterocycles,Classification & Nomenclature,pyridi

3、ne 吡啶,pyrimidine 嘧啶,2H-pyran 2H- 吡喃,Pyridazine 哒嗪,Pyrazine 吡嗪, Fused-heterocycles,Classification & Nomenclature,quinoline 喹啉,iso-quinoline* 异 喹啉,Purine* 嘌呤,Indole 吲哚,蝶啶 pteridine,口丫啶 acridine,吩嗪 phenazine,carbazole 咔唑,Phenothiazine 吩噻嗪,Classification & Nomenclature,Attention!, “指示氢” or “标氢”,最多的非累积双键

4、外的饱和氢, 没有达到最多的非累积双键，“外加氢” 的标注,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,iso-quinoline* 异 喹啉,Purine* 嘌呤,5-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,Classification & Nomenclature, 互变异构的存在，编号及名称的改变,7H-嘌呤,9H-嘌呤,2,4-二羟基嘧啶,嘧啶-2,4-二酮,5-甲基吡唑,3-甲基吡唑

5、,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,Classification & Nomenclature, 拼合杂环的命名：,整体稠环编号，取代基位置,5-苯基咪唑并2, 1-b噻唑,6H-吡唑并4, 5-d口恶 唑,二. Six-membered Heterocyclic compounds,Pyridine 吡啶,1. Structure:,C5H5N,芳香性,较强的碱性,Kekules structure,Aromaticity ?,电子云的分布,E.S. 变

6、难,N.S. 变易,Oxidation 难,Reduction 易,Basicity,Six-membered Heterocyclic compounds,2. Physical properties,(1) (偶极矩) Dipole moment, = 7.4110-38 c.m 3.90 10-38 c.m,I,C,方向一致,Six-membered Heterocyclic compounds,(2) Solubility:,吡啶可以与水以任意比例互溶,3. Chemical reactions,a. Basicity of Pyridine,Basicity,Six-membered

7、 Heterocyclic compounds,Six-membered Heterocyclic compounds,Pyr.SO3,磺化试剂,酰化试剂,甲基化试剂,b. Electrophilic Substitution:,N的-I,钝化环,反应条件剧烈,取代反应 发生在3-位（）,Six-membered Heterocyclic compounds,Six-membered Heterocyclic compounds,不稳定,取代2-位,取代3-位,Six-membered Heterocyclic compounds-Pyridine,Six-membered Heterocyc

8、lic compounds,c. Nucleophilic Substitution,2, 4, 6-位的影响,X的取代,Six-membered Heterocyclic compounds-Pyridine,Six-membered Heterocyclic compounds,E. Chichibabin Reaction,H-的取代,Six-membered Heterocyclic compounds-Pyridine,Six-membered Heterocyclic compounds,2-位 (6-位),3-位,4-位,八电子氮负离子,八电子氮负离子,Six-membered

9、Heterocyclic compounds-Pyridine,Six-membered Heterocyclic compounds-Pyridine,d. Reactions of side chain,Side Chain,Acidity of -H,Six-membered Heterocyclic compounds,2-位甲基,3-位甲基,4-位甲基,八隅体,八隅体,Six-membered Heterocyclic compounds,e. Oxidations & Reductions,侧链的氧化,烟碱,烟酸,烟酰胺,N-氧化物 Pyridine-N-oxide,3-甲基吡啶N

10、-氧化物,Six-membered Heterocyclic compounds-Pyridine,Pyridine-N-oxide:,Substitution / Position,Six-membered Heterocyclic compounds-Pyridine,Electrophilic,Nucleophilic,Six-membered Heterocyclic compounds-Pyridine,-attack,-attack,-attack,Six-membered Heterocyclic compounds-Pyridine,piperidine,Reduction,S

11、ix-membered Heterocyclic compounds-Pyrimidine,嘧啶Pyrimidine,sp2,碱性,水溶性,取代反应,Six-membered Heterocyclic compounds-Pyrimidine,2, 4, 6-positions,(Uracil, U)尿嘧啶,胞嘧啶 (Cytosine, C),胸腺嘧啶(Thymine. T),tautomerism,Six-membered Heterocyclic compounds-Pyrimidine,Vitamin B2,Sulfadiazine SD 磺胺嘧啶,苯巴比妥 Phenobarbital,

12、Moxonidine 莫索尼定,Six-membered Heterocyclic compounds-Pyrimidine,Antimetabolic Agents,Fluorouracil 5-FU,Tegafur,Cytarabine阿糖胞苷,司他夫定 Stavudine,Zidovudine 齐多夫定,拉米夫定 Lamivudine,Antiviral Agents,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Quinoline and Isoquinoline,quinoline 喹啉,iso-quin

13、oline* 异 喹啉,杂化 sp2,碱性,取代反应：,E.S. N.S.,位置,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Electrophilic Substitution,异环取代,5-，8-位,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Nucleophilic Substitution,发生在吡啶环上，2(1)、4位上,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,The Reactions of Side Chain,2(1), 4位侧链,-H,Six-membered Heterocyclic compounds-Quinoline and Isoquinol