1、Chapter 14 Heterocyclic Compounds（雜環(huán)化合物）,Heterocycle / Heterocyclic Compound 構(gòu)成環(huán)系的原子除C外，還有其它雜原子。,O, S, N.,Hetero-atom (雜原子):,Heterocycle,Saturated Heterocycles 飽和雜環(huán)化合物,Aromatic Heterocycles 芳香雜環(huán)化合物,體現(xiàn)各自功能團(tuán)的性質(zhì),一 .Classification & Nomenclature:,按環(huán)的大小,Five-membered ring,Six-membered ring,按雜原子的數(shù)目,一個(gè)雜原子雜

2、環(huán),兩個(gè)雜原子雜環(huán),多個(gè)雜原子雜環(huán),按環(huán)的拼合形式,單雜環(huán)(homo-heterocycle),稠雜環(huán)(fused-heterocycle),pyrrole 吡咯,thiophene 噻吩,furan 呋喃,Classification & Nomenclature,Five-membered ring heterocycles,imidazole 咪唑,pyrazole 吡唑,oxazole 口惡 唑,thiazole 噻唑,Isoxazole 異口惡 唑, Six-membered ring heterocycles,Classification & Nomenclature,pyridi

3、ne 吡啶,pyrimidine 嘧啶,2H-pyran 2H- 吡喃,Pyridazine 噠嗪,Pyrazine 吡嗪, Fused-heterocycles,Classification & Nomenclature,quinoline 喹啉,iso-quinoline* 異 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!, “指示氫” or “標(biāo)氫”,最多的非累積雙鍵

4、外的飽和氫, 沒(méi)有達(dá)到最多的非累積雙鍵，“外加氫” 的標(biāo)注,Classification & Nomenclature, 取代雜環(huán)的命名：,編號(hào)原則：?jiǎn)坞s環(huán)、稠雜環(huán)；最小編號(hào)和優(yōu)先順序法則,iso-quinoline* 異 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-羥基喹啉-5-磺酸,Classification & Nomenclature, 互變異構(gòu)的存在，編號(hào)及名稱的改變,7H-嘌呤,9H-嘌呤,2,4-二羥基嘧啶,嘧啶-2,4-二酮,5-甲基吡唑,3-甲基吡唑

5、,Classification & Nomenclature, 拼合雜環(huán)的命名：,非特定稠環(huán),基本環(huán),附加環(huán),稠合邊的表示,呋喃并2, 3-b 噻吩,吡咯并3, 2-b 噻吩,Classification & Nomenclature, 拼合雜環(huán)的命名：,整體稠環(huán)編號(hào)，取代基位置,5-苯基咪唑并2, 1-b噻唑,6H-吡唑并4, 5-d口惡 唑,二. Six-membered Heterocyclic compounds,Pyridine 吡啶,1. Structure:,C5H5N,芳香性,較強(qiáng)的堿性,Kekules structure,Aromaticity ?,電子云的分布,E.S. 變

6、難,N.S. 變易,Oxidation 難,Reduction 易,Basicity,Six-membered Heterocyclic compounds,2. Physical properties,(1) (偶極矩) 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:,吡啶可以與水以任意比例互溶,3. Chemical reactions,a. Basicity of Pyridine,Basicity,Six-membered

7、 Heterocyclic compounds,Six-membered Heterocyclic compounds,Pyr.SO3,磺化試劑,?；噭?甲基化試劑,b. Electrophilic Substitution:,N的-I,鈍化環(huán),反應(yīng)條件劇烈,取代反應(yīng) 發(fā)生在3-位（）,Six-membered Heterocyclic compounds,Six-membered Heterocyclic compounds,不穩(wěn)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-位的影響,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,八電子氮負(fù)離子,八電子氮負(fù)離子,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,八隅體,八隅體,Six-membered Heterocyclic compounds,e. Oxidations & Reductions,側(cè)鏈的氧化,煙堿,煙酸,煙酰胺,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,堿性,水溶性,取代反應(yīng),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 齊多夫定,拉米夫定 Lamivudine,Antiviral Agents,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Quinoline and Isoquinoline,quinoline 喹啉,iso-quin

13、oline* 異 喹啉,雜化 sp2,堿性,取代反應(yīng)：,E.S. N.S.,位置,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Electrophilic Substitution,異環(huán)取代,5-，8-位,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,Nucleophilic Substitution,發(fā)生在吡啶環(huán)上，2(1)、4位上,Six-membered Heterocyclic compounds-Quinoline and Isoquinoline,The Reactions of Side Chain,2(1), 4位側(cè)鏈,-H,Six-membered Heterocyclic compounds-Quinoline and Isoquinol