药物合成反应 (第三版 闻韧) 课后答案Chapter 1 Halogenation Reaction

第一章 卤化反应习题及答案

1. 根据以下指定原料、试剂和反应条件，写出其合成反应的主要产物。 (1)(CH 3)2NCH 2CH 2OH

SOCl 2

(2)

CuCl 24

(3)

P, Br 2o

(4)CH 2CHCOOCH 3

干燥 HBr 2 (5)CH 3CH 2CH 2CH 2CH 2COOH

SOCl 2

4o

(6)

S CH 3

2266

(7)

H 3C CH 3

NBS, H 2SO 43o

(8)

NHCOCH 3

CH 3

Br 2,CH 3COOH o

(9)

OH

C CH 3

CH 2t -BuOCl, CHCl 3

o

(10)

NBS, (C 6H 5

)3P

(11)

KI, H 3PO 4

(12)

C 6H 5

H 3

Br 2,Cl 4o (13)CH 3

CH CH CH 3

232

(14)(CH 3)3CCH 2OH

HBr

(15)

O

O

P

2

(16)

NBS, Et 3N ·3HF 22o

(17)

O

H

Br 2

4o

(18)

O

23o

2. 在下列指定原料和产物的反应式中分别填入必需的化学试剂（或反应物）和反应条件。 (1)CH 3CH 2CH 2CH 2CH CHCH 3

CH 3CH 2CH 2CHCH

CHCH 3

Br

(2)

COOH

Br

(3)

(4)

OH

Br

(5)

2CH 2Br

Br

(6)

(7)(CH 3)3CCH 2OH

(CH 3)3CCH 2Br

(8)O

O

BocHN

O O

BocHN

Br

(9)

O

O

Br O

O Br

Br

2. 在下列指定原料和产物的反应式中分别填入必需的化学试剂（或反应物）和反应条件。（参考答案）

题号答案注释

(1) NBS/(PhCO)2O, CCl4, △

(2) Br2/HgO/tetrachloroethane

NaNO2, HCl, H2O; 2. HPF6; 3. △ (168℃)

(3) 1.

(4) Ph3P, Br2, CH3CN, △ (200-340℃)

(5) NBS/(PhCO)2O, CCl4

refluxing (10min. )

acetone,

(6) NaI,

(7) Bu3P, Br2, DMF

(8) NBS/hv, CCl4

(9) NBS/(PhCO)2O, CCl4, reflux

3. 阅读（翻译）以下有关反应操作的原文，请在理解基础上写出：（1）此反应的完整反应式（原料、

试剂和主要反应条件）；（2）此反应的反应机理（历程）。

The apparatus consists of a 1-l. three-necked flask equipped with a condenser, a dropping funnel, and

a stirrer terminating in a stiff, crescent-shaped Teflon polytetrafluoroethylene paddle. The stirrer motor must have good torque (Note 1). The assembled apparatus, which is protected from moisture by means of drying tubes in the condenser and funnel, is preferably predried. About 216–224 g. (1.62–1.68 moles) of powdered anhydrous aluminum chloride is added to the apparatus with as little exposure to the moisture of the air as possible (Note 2). While the free-flowing catalyst is stirred (Note 3), 81 g. (0.67 mole) of acetophenone is added from the dropping funnel in a slow stream over a period of 20–30 minutes. Considerable heat is evolved, and, if the drops of ketone are not dispersed, darkening or charring occurs. When about one-third of the acetophenone has been added, the mixture becomes a viscous ball-like mass that is difficult to stir. Turning of the stirrer by hand or more rapid addition of ketone is necessary at this point. The addition of ketone, however, should not be so rapid as to produce a temperature above 180°. Near the end of the addition, the mass becomes molten and can be stirred easily without being either heated

or cooled. The molten mass, in which the acetophenone is complexed with aluminum chloride, ranges in color from tan to brown.

Bromine (128 g., 0.80 mole) is added dropwise to the well-stirred mixture over a period of 40 minutes (Note 4). After all the bromine has been added, the molten mixture is stirred at 80–85° on a steam bath for

1 hour, or until it solidifies if that happens first (Note 5). The complex is added in portions to a well-stirred mixture of 1.3 l. of cracked ice and 100 ml. of concentrated hydrochloric acid in a 2-l. beaker (Note 6). Part

of the cold aqueous layer is added to the reaction flask to decompose whatever part of the reaction mixture remains there, and the resulting mixture is added to the beaker. The dark oil that settles out is extracted from the mixture with four 150-ml. portions of ether. The extracts are combined, washed consecutively with 100 ml. of water and 100 ml. of 5% aqueous sodium bicarbonate solution, dried with anhydrous sodium sulfate, and transferred to a short-necked distillation flask. The ether is removed by distillation at atmospheric pressure, and crude 3-bromoacetophenone is stripped from a few grams of heavy dark residue

by distillation at reduced pressure. The colorless distillate is carefully fractionated in a column 20 cm. long and 1.5 cm. in diameter that is filled with Carborundum or Heli-Pak filling. The combined middle fractions

of constant refractive index are taken as 3-bromoacetophenone; weight, 94–100 g. (70–75%); b.p. 75–76°/0.5 mm.; n D25 1.5738–1.5742; m.p. 7–8° (Note 7) and (Note 8).