药物合成反应(闻韧_第三版)第二章课后答案Chapter_2_Alkylation_Reaction

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(1)+3432(2)Br BrCH3Li(3)NO2CH2BrCO2CH3OCH323(4)KNO O+DMF H2NNH22Oo(5)INH2O+DABCO, DMF(6)MeO OMe OMe2NH, MeOH(7)MeO NHSO2NO22323(8)PhCH2CH2MgBr +N CHO THF武汉工程大学化工与制药学院(9)511O K 511(10)OOBrOMe+SnCl4o2. 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 2CO 2Me(2)R (3)CH 2(CO 2Et)2CO 2H CO 2H(4)HOH 22OH PhH 2COH 22OCH 2Ph(5)2(6)OTfCl+MePh(7)O SO2Ph OPh(8)N NCHO3(9)(10)MeO MeBrMeOMeHNHex2. 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－(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℃(10) HexNH2, Pd2(dba)3 (±)-BINAP, t-BuONa, toluene Hex= Hexyldba= dibenzylideneacetone3. 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 acidTo 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.（2）Preparation of mesitaldehyde (2,4,6-trimethyl 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 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 addition is complete, the mixture isstirred 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 andis shaken thoroughly. The organic layer is separated, and the aqueous solution 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) whichis then dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is distilled togive the crude product, b.p. 68–74° (0.9 mm.). After redistillation there is obtained 60–66 g. (81–89%)of mesitaldehyde; b.p. 113–115° (11 mm.), n20D 1.5538.3. 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）。

（参考答案）（1）答：（翻译略）反应式：反应机理：亲核取代（略）（2）答：Rieche A., et al. Org. Synth., Coll. V ol. 5: 49. 反应式：反应机理：亲电取代（傅－克反应——甲酰化）。