藥物合成反應(yīng)(聞韌_第三版)第二章課后答案Chapter_2_Alkylation_Reaction

1、藥物合成反應(yīng) （第三版）聞韌主編習(xí)題及答案第二章 烴化反應(yīng)習(xí)題及答案1. 根據(jù)以下指定原料、試劑和反應(yīng)條件，寫出其合成反應(yīng)的主要產(chǎn)物(1)oho+h3po4 / bf3oet2(2)brbrch3liether(3)no2ch2brco2ch3och3rnh2et3n/meoh(4)knoohnoophoms+dmfh2nnh2h2oetoh, 60oc(5)inh2o+dabco, dmf(6)meoomeome2nh, meohr.t.(7)meonhso2no2ph(ch2)3brk2co3, dmf(8) phch2ch2mgbr +nchothf1武漢工程大學(xué)化工與制藥學(xué)院藥物合成反

2、應(yīng) （第三版）聞韌主編習(xí)題及答案(9)broachme1) c5h11o k2) c5h11oh(10)oobrome+sncl40oc1. 根據(jù)以下指定原料、試劑和反應(yīng)條件，寫出其合成反應(yīng)的主要產(chǎn)物（參考答案）題號答案注釋(1) ooc(ch3)3(2) ch3ch3(3) no2och3nromu f., et al. j. med. chem., 2002, 45: 4774. (4) hnoophnoohnoophnh2rossi f. m., et al. tetrahedron, 1996, 52: 10279. (5) nhdabco= 1,4-diazabicyclo2.2.2

3、octane nn2藥物合成反應(yīng) （第三版）聞韌主編習(xí)題及答案(6) me2no(7) meonso2no2(8) phch2ch2cho (9) ohh3c(10) oomeo待核對原始文獻！patil m. l., et al. tetra. lett., 1999, 40: 4437. 2. 在下列指定原料和產(chǎn)物的反應(yīng)式中分別填入必需的化學(xué)試劑（或反應(yīng)物）和反應(yīng)條件。(1)ch2co2me(2)oohooohor(3) ch2(co2et)2co2hco2h(4)oohoh2cch2ohoophh2coh2cch2och2ph3藥物合成反應(yīng) （第三版）聞韌主編習(xí)題及答案(5)ohno2o

4、ch2phno2(6)otfcl+nhphmenclmeph(7)oso2phoph(8)nchoohnchooch3(9)etoetoo(10)meomebrmeomehnhex2. 在下列指定原料和產(chǎn)物的反應(yīng)式中分別填入必需的化學(xué)試劑（或反應(yīng)物）和反應(yīng)條件。（參考答案）題號答案注釋(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

5、, thf, 70(7) phcch, 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= hexyl dba= dibenzylideneacetone 4藥物合成反應(yīng) （第三版）聞韌主編習(xí)題及答案o3. 閱讀（翻譯）以下有關(guān)反應(yīng)操作的原文，請在理解基礎(chǔ)上寫出：（1）此反應(yīng)的完整反應(yīng)式（原料、試劑和主要反應(yīng)條件） ； （2）此反應(yīng)的反應(yīng)機理（歷程）。（1）preparation

6、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 25c, 114.0 g (0.5 mol) of triethylbenzylammonium chloride (note 2). to this vigorously stirred suspension was added a mixture of 80.0 g (

7、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 magnetica

8、lly 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 during acidification. the aqueous layer was poured into a 4-l separatory funnel and extracted thr

9、ee 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

10、 of a semisolid residue. the residue was triturated with 100 ml of benzene. filtration of this mixture gave 43.147.9 g (6673%) of 1 as white crystals, mp 137140c. （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

11、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. (

12、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 is stirred for 5 minutes in the ice bath, for 30 minutes

13、 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 solution is extracted with two 50- ml. portions of methylene chloride. the combined or

14、ganic 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. 6874 (0.9 mm.). after redistillation there is obtained 6066 g. (8189%) of mesitaldehyde; b.p. 113115 (11 mm.)