杂环的酚羟基的卤代

经典化学合成反应标准操作

杂环的酚羟基或醚的烷氧基卤代反应

目

录

1

．

2

．

前言< /p>

………………………………………………………………2

氯代

………………………………………………………………2

2.1

杂环的酚羟基的用三氯氧磷氯代反应示 例……………………………

2

2.2

杂环的酚羟基用三氯氧磷与五氯化磷混合处理氯代反应示例………

3

< br>2.3

杂环的酚醚甲氧基用三氯氧磷氯代反应示例………………………

3

．

溴代< /p>

………………………………………………………………

4

3.1

杂环的酚羟基用

POBr

3

溴代反应示例（一）………………………

4

3.2

杂环的酚羟基用

POBr

3

溴代反应示例（二）……………………… ……

4

3.3

杂环的酚羟基用四丁基 溴化胺法溴代反应示例………………………

5

3.4

杂环的甲氧基用

PBr

3

溴代反应示例………………………………

5

4

．

参考文 献

…………………………………………………………

6

经典合成反应标准操作

—

1

．

前言

< /p>

杂环的酚羟基的通常较易被卤代，其也是杂环一种常见的官能团的转换方式

之一，卤代反应常见的有氯代、溴代反应。另外，在存在吸电子基的杂环上，不

仅酚羟基容易被卤代，而且烷氧基（甲氧基，乙氧基等）也很容易被卤代。因此

其也是合 成的一种策略。

经常有文献首先将杂环卤代物用甲氧基取代后，

利用甲

氧基推电子效应完成一系列转化后，再将甲氧基卤代回来。

2.

氯代

杂环 的酚羟基的氯代一般用三氯氧磷

1,2,3

或三氯氧磷与五氯化 磷混合

4,5

处理。

使

用五氯化磷的条件更强，

用于难以发生的杂环的酚羟基的氯代反应。

的氯代也可用三氯氧磷直接处理

6

.

2.1

杂环的酚羟基的用三氯氧磷氯代反应示例

1

O

2

N

N

1

I

OH

POCl

3

O

2

N

N

2

I

Cl

2-Hydroxy-3-iodo-5-nitropyridine

1

(70.5

g,

0.27

mol)

was

added

to

quinoline

(16

mL, 0.133 mol).

The reaction flask was cooled to 5 degree and phosphoryl chloride

(25 mL, 0.27 mol) was added dropwise.

The mixture was blanketed with argon and

heated

to

120

degree

for

2

h.

Upon

complete

consumption

of

the

precursor,

as

indicated by TLC, the mixture was cooled to room temperature and 100 mL of H

2

O

was added.

The mixture was then cooled to 0 degree, and the resulting brown solid

was

filtered.

Recrystallization

from

ethanol

gave

sand-color

crystals

2

(60

g,

0.21mol, 78% yield).

Page 1 of 6

经典合成反应标准操作

—

杂环的酚羟基的卤代反应

2.2

杂环的酚羟基用三氯氧磷与五氯化磷混合处理氯代反应示例

5

PCl

5

/ POCl

3

N

1

OH

N

2

Cl

To a solution of 10.5 g of

1

in 16 mL of phosphorus oxychloride was heated to reflux

and added 20 g of phosphorus pentachloride in small portions over a period of 1.5 hr.

The oil bath temperature was then raised to 165 degree and kept there for 1 hr.

The

phosphorus oxychloride was removed under reduced pressure, 50 g of ice then added,

and the mixture made strongly basic by adding a concentrated KOH solution.

When

this was steam distilled, a colorless heavy oil was obtained, which was separated by

two extractions with

100-mL portions

of

ether.

The ether was dried

and removed,

and the residue distilled, giving a colorless oil (4.0 g, 34%).

2.3

杂环的酚醚甲氧基用三氯氧磷氯代反应示例

O

Bn

S

N

1

< br>POCl

3

N

2

Cl

Bn

S

A mixture of

1

(10 mmol) and phosphoryl chloride (20 mL) was refluxed for 0.5 hr.

Then the excess of phosphoryl chloride was evaporated

in vacuo

.

The residue was

carefully poured onto ice (30 g) and neutralized with conc. ammonia at

0-5 degree.

The

solid

was

filtered

off,

washed

with

water

and

air-dried.

The

product

was

purified by crystallized from ethanol to give 86-94% yields.

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