2022年《药物合成反应》闻韧主编第2章-烃化反应习题答案

1、药物合成反应（第三版）闻韧主编烃化反应习题及答案习题及答案其次章1. 依据以下指定原料、试剂和反应条件,写出其合成反应的主要产物OH 1 + H 3PO 4 / BF 3OEt 2O 2 Br BrCH 3Li ether NO 23 CH 2Br RNH 2CO 2CH 3Et 3N/MeOH OCH 34 O K N O + Ph OMs O DMF H 2NNH 2H2O HN EtOH, 60oC O O 5 I + DABCO, DMF NH 26 MeO OMe O Me 2NH, MeOH PhCH 23Br K CO , DMF r.t. 7 NO 2SO N H 2 2 3

2、MeO 8 PhCH 2CH 2MgBr + N CHOTHF1 药物合成反应（第三版）闻韧主编习题及答案9 OAC Br 1 C 5H 11O K 2 C 5H11OH Me HO 10 + OMe O SnCl 40oC Br 1. 依据以下指定原料、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33注释1 OCCHO 2 CH 3CH 33 NO 2Mu F., et al. J. Med. Chem., 2022, 45: 4774. NR OCH 3O4 Rossi F. M., et al. Tetrahedron, 1996, 52: 10279. O 5 Ph N

3、 O OPh NH 2O DABCO= HN HN O O 1,4-diazabicyclo2.2.2octane N H N N 2 药物合成反应（第三版）闻韧主编习题及答案6 O Me 2N 7 NO 2N SO 2MeO 8 PhCH 2CH 2CHO 9 H 3C O H 10 O O 待核对原始文献！Patil M. L., et al. Tetra. Lett., 1999, 40: 4437. MeO 2. 在以下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；CH 2CO 2Me 1 O R OCH 2OCH 2PhO 2 O HO HOCO 2H 3 C

4、H 2CO 2Et 2CO 2H HOH 2C CH 2OHPhH 2COH 2C O O4 4 O O 3 药物合成反应（第三版）闻韧主编习题及答案OH OCH 2PhNO 25 5 NO 2Me 6 6 O OTf + Me NHO Cl Ph N Ph SO 2Ph Ph Cl 7 7 OH OCH 3N 8 N CHO CHO 8 O 9 9 EtO EtOMe Me H Br N Hex 10 10 MeO MeO 2. 在以下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Hex= Hexyl 注释1 1. Na; 2. BrCH 2CO

5、2Me 2 1. 2 LDA, 2. RX 3 1,2-dibromoethane, TEBA, OH4 NaH, PhCH 2Br, THF 5 PhCH2Cl, K 2CO3, DMF 6 Cat. PdOAc 2, -BINAP, Cs 2CO3, THF, 70 7 PhCCH, i-PrMgCl, ZnBr2, THF 8 MeI, NaH, THF 9 1. LDA, THF, -78 ; 2. MeI, -78 to 25 10 HexNH 2, Pd2dba3 -BINAP, t-BuONa, toluene dba= dibenzylideneacetone 4 药物合成反应

6、（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,请在懂得基础上写出：（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 triethylb

7、enzylammonium 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 Erlen

8、meyer flask by rinsing the flask with three 75-mL portions of water. The mixture was magnetically stirred and cooled with an ice bath to 15C, and then carefully acidified by dropwise addition of 1 L of concentrated hydrochloric acid. The temperature of the flask was maintained between 15 and 25C dur

9、ing 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

10、 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 140C. （2） Preparation of mesitaldehyde 2,4,6-trime

11、thyl benzaldehyde A solution of 72 g. 0.60 mole of mesitylene in 375 ml. of dry methylene chloride is placed in a 1-l. three-necked flask equipped with a reflux condenser, a stirrer, and a dropping funnel. The solution is cooled in an ice bath, and 190 g. 110 ml., 1.0 mole of titanium tetrachloride

12、is added over a period of 3 minutes. While the solution is stirred and cooled, 57.5 g. 0.5 mole of dichloromethyl methyl ether2 is added dropwise over a 25-minute period. The reaction begins as indicated by evolution of hydrogen chloride when the first drop of chloro ether is added. After the additi

13、on is complete, the mixture is . stirred for 5 minutes in the ice bath, for 30 minutes without cooling, and for 15 minutes at 35 The reaction mixture is poured into a separatory funnel containing about 0.5 kg. of crushed ice and is shaken thoroughly. The organic layer is separated, and the aqueous s

14、olution is extracted with two 50- ml. portions of methylene chloride. The combined organic solution is washed three times with 75-ml. portions of water. A crystal of hydroquinone is added to the methylene chloride solution Note 1 which is then dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is distilled to give the crude product, b.p. 68 74 0.9 mm. After redistillation there is obtained 6066 g. 8189% of mesitaldehyde; b.p. 113 115