药物合成反应(第三版_闻韧)第二章课后答案

(4) NaH, PhCH2Br, THF (5) PhCH2Cl, K2CO3, DMF (6) Cat. Pd(OAc)2, (±)-BINAP, Cs2CO3, THF, 70℃ (7) PhC≡CH, i-PrMgCl, ZnBr2, THF (8) MeI, NaH, THF (9) 1. LDA, THF, -78℃; 2. MeI, -78 to 25℃
(4)
+
DMF
HN O
I
(5)
+
NH2
OMe O
(6) MeO
O O
DABCO, DMF
Me2NH, MeOH r.t.
H2NNH2·H2O EtOH, 60oC
(7) MeO
N SO2 H
NO2
Ph(CH2)3Br K2CO3, DMF
(8) PhCH2CH2MgBr +
N CHO THF
1
《药物合成反应》（第三版） 闻韧主编
(1)
O
(2)
O
O
R
O
HO
HO
(3) CH2(CO2Et)2
HOH2C (4)
O
CH2OH O
CO2H CO2H
PhH2COH2C
O
CH2OCH2Ph O
3
《药物合成反应》（第三版） 闻韧主编
OH
(5) NO2
OCH2Ph NO2
(6) Cl
OTf
Me
+
NH
Ph
Cl
Me N
Ph
习题及答案
(7) O SO2Ph
《药物合成反应》源自文库第三版） 闻韧主编
第二章 烃化反应习题及答案
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
OH
(1)
+
H3PO4 / BF3·OEt2
习题及答案
O Br
(2)
Br
CH3Li ether
NO2
(3)
CH2Br
RNH2
Et3N/MeOH
CO2CH3
OCH3
K
OMs
O N O Ph
(10) HexNH2, Pd2(dba)3 (±)-BINAP, t-BuONa, toluene
Hex= Hexyl dba= dibenzylideneacetone
4
《药物合成反应》（第三版） 闻韧主编
习题及答案
O
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）。 （1）Preparation of cyclopropane 1,l-dicarboxylic acid
To a 1-L solution of aqueous 50% sodium hydroxide (Note 1), mechanically stirred in a 2-L, three-necked flask, was added, at 25°C, 114.0 g (0.5 mol) of triethylbenzylammonium chloride (Note 2). To this vigorously stirred suspension was added a mixture of 80.0 g (0.5 mol) of diethyl malonate and 141.0 g (0.75 mol) of 1,2-dibromoethane all at once. The reaction mixture was vigorously stirred for 2 hr (Note 3). The contents of the flask were transferred to a 4-L Erlenmeyer flask by rinsing the flask with three 75-mL portions of water. The mixture was magnetically stirred and cooled with an ice bath to 15°C, and then carefully acidified by dropwise addition of 1 L of concentrated hydrochloric acid. The temperature of the flask was maintained between 15 and 25°C during acidification. The aqueous layer was poured into a 4-L separatory funnel and extracted three times with 900 mL of ether. The aqueous layer was saturated with sodium chloride and extracted three times with 500 mL of ether. The ether layers were combined, washed with 1 L of brine, dried (MgSO4), and decolorized with activated carbon. Removal of the solvent by rotary evaporation gave 55.2 g of a semisolid residue. The residue was triturated with 100 mL of benzene. Filtration of this mixture gave 43.1–47.9 g (66–73%) of 1 as white crystals, mp 137–140°C.
(8)
OH
N
CHO
O Ph
N CHO
OCH3
O
(9) EtO
(10) MeO
EtO Me
Br
MeO
Me H N Hex
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) 1. Na; 2. BrCH2CO2Me
(2) 1. 2 LDA, 2. RX (3) 1,2-dibromoethane, TEBA, OH－
N N
2
《药物合成反应》（第三版） 闻韧主编
(6)
O
Me2N (7)
MeO
NO2 N SO2
习题及答案
(8) PhCH2CH2CHO
(9)
H3C O
H
(10)
O O
MeO
待核对原始文献！ Patil M. L., et al. Tetra. Lett., 1999, 40: 4437.
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。 CH2CO2Me
Ph HN O
O (5)
N H
Mu F., et al. J. Med. Chem., 2002, 45: 4774.
NH2 Ph
HN O O
Rossi F. M., et al. Tetrahedron, 1996, 52: 10279.
DABCO= 1,4-diazabicyclo[2.2.2]octane
习题及答案
OAC (9) Me
H
Br 1) C5H11O K 2) C5H11OH
O
(10)
+
O SnCl4 0oC
OMe Br
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（参考答案）
题号
答案
注释
(1)
OC(CH3)3
O (2)
CH3 CH3
(3)
NO2
NR
OCH3 O (4)
O NO