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
O
O
O
O
N
H
O
O
N
H
O
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)
N
H
1
2
34
5
O 1
2
34
5
S 1
2
34
5
pyrrole
吡咯
thiophene
噻吩
furan
呋喃
Classification & Nomenclature
Five-membered ring heterocycles
N
N
H
1
2
34
5
N
N
H
1
2
34
5
N
O 1
2
34
5
N
S 1
2
34
5
imidazole
咪唑
pyrazole
吡唑
oxazole
口 恶 唑
thiazole
噻唑
O
N
1
2
34
5
Isoxazole
异 口 恶 唑
Six-membered ring heterocycles
Classification & Nomenclature
pyridine
吡啶
pyrimidine
嘧啶
1
2
3
4
5
6
N?
2H-pyran
2H-吡喃
1
2
3
4
5
O6
1
2
3
4
5
6
N
N
1
2
3
4
5
6
N
N
1
2
3
4
5
6
N
N
Pyridazine
哒嗪 Pyrazine吡嗪
Fused-heterocycles
Classification & Nomenclature
quinoline
喹啉
iso-quinoline*
异 喹啉 Purine*嘌呤
1
5
8
2
3
4
6
7
N 1 2
3
45
6
7
8
N
N
N
N
N
H
1
2
3
4
5
6 7
8
9
1
2
3
4
56
7
8
9 N
N
1 0
1
2
34
5
6
7
N
H
Indole
吲哚
1
2
3
45
6
7
8 9
N
1 0
1
5
8
2
3
4
6
7
N
N N
N
1
5
8
2
3
4
6
7
9N
H 1
2
3
4
8
56
7
9 1 0N
S
H
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” —最多的非累积双键外的饱和氢
N
N
H N O
1 H - 吡 咯 2 H - 吡 咯 4 H - 吡 喃 3 H - 吲 哚
没有达到最多的 非累积双键，“外加氢” 的标注
N
H
2,5 - 二 氢 吡 咯
O
四 氢 呋 喃
N
H
六 氢 吡 啶
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
1
2
3
45
6
7
8
N
N
N
N
N
H
1
2
3
4
5
6 7
8
9
iso-quinoline*
异 喹啉
Purine*
嘌呤
O C H OO 2 N
N
N
NH2
N
C N ( C 2 H 5 ) 2
O
N
N
N
N
O
O
H 3 C
C H 3 H
N
C H 3
C l NI
S O 3 H
O H
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
N
N
N
N
H
N
N
N
N
H
7H-嘌呤 9H-嘌呤
N
N
O H
O H
N
N
H
H
O
O
2,4-二羟基嘧啶 嘧啶 -2,4-二酮
N
N
H
H 3 C
N H
NH 3 C
1
2
3
4 5
1
2
34
5
5-甲基吡唑 3-甲基吡唑
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
S O
1
2
3 4
5
a
b
c
d
H N
S
1
2
3
4
5
a
b
c
Classification & Nomenclature
拼合杂环的命名,整体稠环编号，取代基位置
N
N S
P h
1
2
3
45
6
7
5-苯基咪唑并 [2,1-b]噻唑
N
N S
P h
1
2
3
4
5
a
b
c
N
O N
N
H1
2
3 4
5
6
N
O N
N
H
1
2
34
5
a
b
c
d
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
N
N N N
o r o r
Kekule’s structure
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
Aromaticity?
电子云的分布
E.S,变难
N.S,变易
Oxidation 难
Reduction 易
Basicity
Six-membered Heterocyclic compounds
2,Physical properties
(1)? (偶极矩 ) Dipole moment
= 7.41?10-38 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
R C H 2 N H 2
p K a 4,6 5,1 9 9,2 5 - 1 0,0
脂 肪 胺 > > > > Basicity
Six-membered Heterocyclic compounds
.,+ H C l
.,,H C l?H
C l - o r
Six-membered Heterocyclic compounds
N
S O 3
C H 2 C l 2 N
S O 3 -
Pyr.SO3 磺化试剂
N N
C O P h
C l -
P h C O C l 酰化试剂
N
N
C H 3
C H 3 I
I -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（?）
+ K N O 3 + H 2 S O 4
N O
2
3 0 0 C
o
+ H 2 S O 4
3 5 0 C
o
S O
3
H
+ B r 2
3 0 0 C
o
B r
( 2 0 % )
( 7 1 % )
( 3 3 % )
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
Six-membered Heterocyclic compounds
Six-membered Heterocyclic compounds
N
+ E + 2 - 位
N E
H
N E
H
N E
H
N E
H
不稳定
N
+ E + 3 - 位
N
H
E
N
H
E
N
H
E
N
H
E
取代 2-位取代 3-位
-Pyridine
Six-membered Heterocyclic compounds
c,Nucleophilic Substitution
N C l
N H 3
2 2 0 o C N N H
2
9 0 %
N C l N O M e
9 5 %
N a O M e
M e O H /
N
B r
B r
N
N H 2
B r
6 5 %
N H 3
1 6 0 o C
N O 2 2,4,6-位的影响
— X的取代
-Pyridine
Six-membered Heterocyclic compounds
N
N a N H 2 N H 3
N N H N a
+
H 2 O
N N H 2
A,E,Chichibabin
Reaction
N N C 6 H 5
C 6 H 5 L i
+ L i H
H-的取代
-Pyridine
Six-membered Heterocyclic compounds
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
N
H
Z N Z
H
N
H
Z
N
Z
H
N
Z
H
N
Z
H
N
H Z
N
H Z
N
H Z
2-位 (6-位 )
3-位
4-位八电子氮负离子八电子氮负离子
-Pyridine
Six-membered Heterocyclic compounds-Pyridine
d,Reactions of side chain
N
C
C
C
HH
H
H
H
H
Side Chain Acidity of?-H
N
C H 3
C H 2 C H 3 N a N H 2
N
C H 2
C H 2 C H 3 C H 3 I
N
C H 2 C H 3
C H 2 C H 3
8 0 %
N C H 3 N C H 2 C H 2 O H
+ H C H O
Z n C l 2
Six-membered Heterocyclic compounds
N
C H 2
N
C H 2
N
C H 2
N
C H 2
N C H
2
N C H
2
N C H
2 N C H 2
N
C H 2
N
C H 2
N
C H 2
N
C H 2
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
N
N
C H 3
H N O 3
N
C O O H N H 3
N
C N H 2
O
侧链的氧化烟碱 烟酸 烟酰胺
N
C H 3
+ H 2 O 2 ( 3 0 % )
C H 3 C O O H
7 0 o C,2 4 h N
C H 3
O
N-氧化物
Pyridine-N-oxide
3-甲基吡啶 N-氧化物
-Pyridine
Pyridine-N-oxide,Substitution / Position
Six-membered Heterocyclic compounds-Pyridine
Electrophilic
N
O
C H 3 O N a
C H 3 O H
N
O
O C H 3
N
O
P h M g B r
H 2 O N
O
P hNucleophilic
N
O
N O 2
F u m i n g H N O 3 / H 2 S O 4
9 0
o
C,4 h
9 0 %
P C l 3
C H 2 C l 2
N
N O 2
8 0 %
H 2 / N i o r
F e / H +
N
N H 2
> 9 0 %
N
O
Six-membered Heterocyclic compounds-Pyridine
N
O
H
Z
N
O
H
Z
-attack
-attack
-attack
N
O
H Z
N
O
H Z
N
O
ZH
N
O
H
Z N
O
H
Z
Six-membered Heterocyclic compounds-Pyridine
N
H 2 / N i
2 5 o C,3 a t m s N
Hpiperidine
Reduction
Six-membered Heterocyclic compounds-Pyrimidine
嘧啶 Pyrimidine
N
N
1
2
3
4
5
6
sp2
碱性水溶性取代反应
N
N
B r 2
1 0 0 o C
N
NB r 6 6 %N
N
O H
H 3 C O H
H N O 3
H O A c,2 0 o C N
N H
O
O
H
O 2 N
H 3 C 8 5 %
N
N
N H 2
N H 2
C l N 2 + C l -
N
N
N H 2
N H 2
NNC l
N
N
C l
n - C 4 H 9 N H 2
N
N
N H C 4 H 9 - nN
N
C H 3
N a N H 2
1 3 0 ~ 1 6 0 o C
N
N
C H 3
H 2 N
Six-membered Heterocyclic compounds-Pyrimidine
2,4,6-positions
N
N H
H
O
O
N
N
O H
O H
(Uracil,U)尿嘧啶
N
N
H
N H 2
O
N
N O H
N H 2
胞嘧啶 (Cytosine,C)
N
N H
H
O
O
H 3 C
N
N O H
O H
H 3 C
胸腺嘧啶 (Thymine,T)
tautomerism
Six-membered Heterocyclic compounds-Pyrimidine
N
N
N H
N O
O
H 3 C
H 3 C
C H 2 C H C H C H C H 2 O H
O H O H O H
Vitamin B2
N
N N H S N H
2
O
O
Sulfadiazine SD 磺胺嘧啶
N
N H
O
O O
H
C 2 H 5
P h
苯巴比妥 Phenobarbital
H C l H 2 O
N
N
C H 3
C l
O C H 3
N H
N
N
H
.,
Moxonidine 莫索尼定
Six-membered Heterocyclic compounds-Pyrimidine
H N
N
H
O
O
F
Antimetabolic Agents
Fluorouracil 5-FU
O
H N
N
O
O
F
Tegafur Cytarabine阿糖胞苷
N
N
O
N H 2
O
H O
O H
H O
N
N O
N H 2
O
H O
司他夫定 Stavudine
N H
N O
H 3 C
O
O
H O
N 3
Zidovudine 齐多夫定
S
O
H O
N
N O
N H 2
拉米夫定 Lamivudine
Antiviral Agents
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Quinoline and Isoquinoline
1
5
8
2
3
4
6
7
N
quinoline
喹啉
1
2
3
45
6
7
8
N
iso-quinoline*
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
N
H N O 3 / H 2 S O 4
0 o C,3 0 m i n,N
N O 2
+ N
N O 2
5
8
5 2 % 4 8 %
N
H N O 3 / H 2 S O 4
0 o C,3 0 m i n,N
N O 2
+ N
N O 2
5
8
9 0 % 1 0 %
N
B r 2 / H 2 S O 4
A g S O 4
N
B r
+
5
8
B r
N
N N
S O 3 H
5
H 2 S O 4
2 2 o C
异环取代 5-,8-位
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Nucleophilic Substitution
N N N H 2
N a N H 2
N
C 2 H 5 M g X
N
C 2 H 5
1 5 0 o C
N C l
N a O C H 3
C H 3 O H / h e a t N O M e
发生在吡啶环上,2(1),4位上
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
The Reactions of Side Chain
N C H 3 +
C O O E t
C O O E t
N a O E t / H O E t
r t,1 2 h N C H 2 C C O O E t
O
9 0 %
+N
C H 3
C H 3 C H O
Z n C l 2
1 0 0 o C
N
C H
C H 3
C H
2(1),4位侧链?-H
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Oxidation & Reduction
N
C r O 3 o r K M n O 4
N
C O O H
C O O H
氧化苯环
N
S n / H C l
o r N a / R O H
N
H
H 2 / N i
N
H
还原吡啶环
Six-membered Heterocyclic compounds-Pyran
Pyran 吡喃
O O O
O
O O O
2H-吡喃
(?-吡喃 ) 4H-吡喃(?-吡喃 )
-吡喃酮?-吡喃酮 吡喃盐正离子口 恶英嗡盐离子杂化 不饱和环醚 —— 非芳香性
O
芳香性 稳定性 /高反应活性
Six-membered Heterocyclic compounds-Pyran
O
O
O
O H
+ H C l C l -
O
O
+ C H 3 I
O
O C H 3
I -
-吡喃酮
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
O
O
O
O
N
H
O
O
N
H
O
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)
N
H
1
2
34
5
O 1
2
34
5
S 1
2
34
5
pyrrole
吡咯
thiophene
噻吩
furan
呋喃
Classification & Nomenclature
Five-membered ring heterocycles
N
N
H
1
2
34
5
N
N
H
1
2
34
5
N
O 1
2
34
5
N
S 1
2
34
5
imidazole
咪唑
pyrazole
吡唑
oxazole
口 恶 唑
thiazole
噻唑
O
N
1
2
34
5
Isoxazole
异 口 恶 唑
Six-membered ring heterocycles
Classification & Nomenclature
pyridine
吡啶
pyrimidine
嘧啶
1
2
3
4
5
6
N?
2H-pyran
2H-吡喃
1
2
3
4
5
O6
1
2
3
4
5
6
N
N
1
2
3
4
5
6
N
N
1
2
3
4
5
6
N
N
Pyridazine
哒嗪 Pyrazine吡嗪
Fused-heterocycles
Classification & Nomenclature
quinoline
喹啉
iso-quinoline*
异 喹啉 Purine*嘌呤
1
5
8
2
3
4
6
7
N 1 2
3
45
6
7
8
N
N
N
N
N
H
1
2
3
4
5
6 7
8
9
1
2
3
4
56
7
8
9 N
N
1 0
1
2
34
5
6
7
N
H
Indole
吲哚
1
2
3
45
6
7
8 9
N
1 0
1
5
8
2
3
4
6
7
N
N N
N
1
5
8
2
3
4
6
7
9N
H 1
2
3
4
8
56
7
9 1 0N
S
H
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” —最多的非累积双键外的饱和氢
N
N
H N O
1 H - 吡 咯 2 H - 吡 咯 4 H - 吡 喃 3 H - 吲 哚
没有达到最多的 非累积双键，“外加氢” 的标注
N
H
2,5 - 二 氢 吡 咯
O
四 氢 呋 喃
N
H
六 氢 吡 啶
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
1
2
3
45
6
7
8
N
N
N
N
N
H
1
2
3
4
5
6 7
8
9
iso-quinoline*
异 喹啉
Purine*
嘌呤
O C H OO 2 N
N
N
NH2
N
C N ( C 2 H 5 ) 2
O
N
N
N
N
O
O
H 3 C
C H 3 H
N
C H 3
C l NI
S O 3 H
O H
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
N
N
N
N
H
N
N
N
N
H
7H-嘌呤 9H-嘌呤
N
N
O H
O H
N
N
H
H
O
O
2,4-二羟基嘧啶 嘧啶 -2,4-二酮
N
N
H
H 3 C
N H
NH 3 C
1
2
3
4 5
1
2
34
5
5-甲基吡唑 3-甲基吡唑
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
S O
1
2
3 4
5
a
b
c
d
H N
S
1
2
3
4
5
a
b
c
Classification & Nomenclature
拼合杂环的命名,整体稠环编号，取代基位置
N
N S
P h
1
2
3
45
6
7
5-苯基咪唑并 [2,1-b]噻唑
N
N S
P h
1
2
3
4
5
a
b
c
N
O N
N
H1
2
3 4
5
6
N
O N
N
H
1
2
34
5
a
b
c
d
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
N
N N N
o r o r
Kekule’s structure
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
Aromaticity?
电子云的分布
E.S,变难
N.S,变易
Oxidation 难
Reduction 易
Basicity
Six-membered Heterocyclic compounds
2,Physical properties
(1)? (偶极矩 ) Dipole moment
= 7.41?10-38 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
R C H 2 N H 2
p K a 4,6 5,1 9 9,2 5 - 1 0,0
脂 肪 胺 > > > > Basicity
Six-membered Heterocyclic compounds
.,+ H C l
.,,H C l?H
C l - o r
Six-membered Heterocyclic compounds
N
S O 3
C H 2 C l 2 N
S O 3 -
Pyr.SO3 磺化试剂
N N
C O P h
C l -
P h C O C l 酰化试剂
N
N
C H 3
C H 3 I
I -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（?）
+ K N O 3 + H 2 S O 4
N O
2
3 0 0 C
o
+ H 2 S O 4
3 5 0 C
o
S O
3
H
+ B r 2
3 0 0 C
o
B r
( 2 0 % )
( 7 1 % )
( 3 3 % )
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
Six-membered Heterocyclic compounds
Six-membered Heterocyclic compounds
N
+ E + 2 - 位
N E
H
N E
H
N E
H
N E
H
不稳定
N
+ E + 3 - 位
N
H
E
N
H
E
N
H
E
N
H
E
取代 2-位取代 3-位
-Pyridine
Six-membered Heterocyclic compounds
c,Nucleophilic Substitution
N C l
N H 3
2 2 0 o C N N H
2
9 0 %
N C l N O M e
9 5 %
N a O M e
M e O H /
N
B r
B r
N
N H 2
B r
6 5 %
N H 3
1 6 0 o C
N O 2 2,4,6-位的影响
— X的取代
-Pyridine
Six-membered Heterocyclic compounds
N
N a N H 2 N H 3
N N H N a
+
H 2 O
N N H 2
A,E,Chichibabin
Reaction
N N C 6 H 5
C 6 H 5 L i
+ L i H
H-的取代
-Pyridine
Six-membered Heterocyclic compounds
N
1,4 3
0,8 4
1,0 11,0 1
0,8 4
0,8 7
N
H
Z N Z
H
N
H
Z
N
Z
H
N
Z
H
N
Z
H
N
H Z
N
H Z
N
H Z
2-位 (6-位 )
3-位
4-位八电子氮负离子八电子氮负离子
-Pyridine
Six-membered Heterocyclic compounds-Pyridine
d,Reactions of side chain
N
C
C
C
HH
H
H
H
H
Side Chain Acidity of?-H
N
C H 3
C H 2 C H 3 N a N H 2
N
C H 2
C H 2 C H 3 C H 3 I
N
C H 2 C H 3
C H 2 C H 3
8 0 %
N C H 3 N C H 2 C H 2 O H
+ H C H O
Z n C l 2
Six-membered Heterocyclic compounds
N
C H 2
N
C H 2
N
C H 2
N
C H 2
N C H
2
N C H
2
N C H
2 N C H 2
N
C H 2
N
C H 2
N
C H 2
N
C H 2
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
N
N
C H 3
H N O 3
N
C O O H N H 3
N
C N H 2
O
侧链的氧化烟碱 烟酸 烟酰胺
N
C H 3
+ H 2 O 2 ( 3 0 % )
C H 3 C O O H
7 0 o C,2 4 h N
C H 3
O
N-氧化物
Pyridine-N-oxide
3-甲基吡啶 N-氧化物
-Pyridine
Pyridine-N-oxide,Substitution / Position
Six-membered Heterocyclic compounds-Pyridine
Electrophilic
N
O
C H 3 O N a
C H 3 O H
N
O
O C H 3
N
O
P h M g B r
H 2 O N
O
P hNucleophilic
N
O
N O 2
F u m i n g H N O 3 / H 2 S O 4
9 0
o
C,4 h
9 0 %
P C l 3
C H 2 C l 2
N
N O 2
8 0 %
H 2 / N i o r
F e / H +
N
N H 2
> 9 0 %
N
O
Six-membered Heterocyclic compounds-Pyridine
N
O
H
Z
N
O
H
Z
-attack
-attack
-attack
N
O
H Z
N
O
H Z
N
O
ZH
N
O
H
Z N
O
H
Z
Six-membered Heterocyclic compounds-Pyridine
N
H 2 / N i
2 5 o C,3 a t m s N
Hpiperidine
Reduction
Six-membered Heterocyclic compounds-Pyrimidine
嘧啶 Pyrimidine
N
N
1
2
3
4
5
6
sp2
碱性水溶性取代反应
N
N
B r 2
1 0 0 o C
N
NB r 6 6 %N
N
O H
H 3 C O H
H N O 3
H O A c,2 0 o C N
N H
O
O
H
O 2 N
H 3 C 8 5 %
N
N
N H 2
N H 2
C l N 2 + C l -
N
N
N H 2
N H 2
NNC l
N
N
C l
n - C 4 H 9 N H 2
N
N
N H C 4 H 9 - nN
N
C H 3
N a N H 2
1 3 0 ~ 1 6 0 o C
N
N
C H 3
H 2 N
Six-membered Heterocyclic compounds-Pyrimidine
2,4,6-positions
N
N H
H
O
O
N
N
O H
O H
(Uracil,U)尿嘧啶
N
N
H
N H 2
O
N
N O H
N H 2
胞嘧啶 (Cytosine,C)
N
N H
H
O
O
H 3 C
N
N O H
O H
H 3 C
胸腺嘧啶 (Thymine,T)
tautomerism
Six-membered Heterocyclic compounds-Pyrimidine
N
N
N H
N O
O
H 3 C
H 3 C
C H 2 C H C H C H C H 2 O H
O H O H O H
Vitamin B2
N
N N H S N H
2
O
O
Sulfadiazine SD 磺胺嘧啶
N
N H
O
O O
H
C 2 H 5
P h
苯巴比妥 Phenobarbital
H C l H 2 O
N
N
C H 3
C l
O C H 3
N H
N
N
H
.,
Moxonidine 莫索尼定
Six-membered Heterocyclic compounds-Pyrimidine
H N
N
H
O
O
F
Antimetabolic Agents
Fluorouracil 5-FU
O
H N
N
O
O
F
Tegafur Cytarabine阿糖胞苷
N
N
O
N H 2
O
H O
O H
H O
N
N O
N H 2
O
H O
司他夫定 Stavudine
N H
N O
H 3 C
O
O
H O
N 3
Zidovudine 齐多夫定
S
O
H O
N
N O
N H 2
拉米夫定 Lamivudine
Antiviral Agents
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Quinoline and Isoquinoline
1
5
8
2
3
4
6
7
N
quinoline
喹啉
1
2
3
45
6
7
8
N
iso-quinoline*
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
N
H N O 3 / H 2 S O 4
0 o C,3 0 m i n,N
N O 2
+ N
N O 2
5
8
5 2 % 4 8 %
N
H N O 3 / H 2 S O 4
0 o C,3 0 m i n,N
N O 2
+ N
N O 2
5
8
9 0 % 1 0 %
N
B r 2 / H 2 S O 4
A g S O 4
N
B r
+
5
8
B r
N
N N
S O 3 H
5
H 2 S O 4
2 2 o C
异环取代 5-,8-位
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Nucleophilic Substitution
N N N H 2
N a N H 2
N
C 2 H 5 M g X
N
C 2 H 5
1 5 0 o C
N C l
N a O C H 3
C H 3 O H / h e a t N O M e
发生在吡啶环上,2(1),4位上
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
The Reactions of Side Chain
N C H 3 +
C O O E t
C O O E t
N a O E t / H O E t
r t,1 2 h N C H 2 C C O O E t
O
9 0 %
+N
C H 3
C H 3 C H O
Z n C l 2
1 0 0 o C
N
C H
C H 3
C H
2(1),4位侧链?-H
Six-membered Heterocyclic compounds-Quinoline and Isoquinoline
Oxidation & Reduction
N
C r O 3 o r K M n O 4
N
C O O H
C O O H
氧化苯环
N
S n / H C l
o r N a / R O H
N
H
H 2 / N i
N
H
还原吡啶环
Six-membered Heterocyclic compounds-Pyran
Pyran 吡喃
O O O
O
O O O
2H-吡喃
(?-吡喃 ) 4H-吡喃(?-吡喃 )
-吡喃酮?-吡喃酮 吡喃盐正离子口 恶英嗡盐离子杂化 不饱和环醚 —— 非芳香性
O
芳香性 稳定性 /高反应活性
Six-membered Heterocyclic compounds-Pyran
O
O
O
O H
+ H C l C l -
O
O
+ C H 3 I
O
O C H 3
I -
-吡喃酮
