大学精品课件：药物合成反应习题.doc

1、 1 第一章 卤化反应 1，写出下列反应的主要产物（或试剂） CH3OC6H4 C H C H H Br2 CCl425 C6H4OH3C HH Br H Br O H3CCH3 O OCH3 CH3 Br Br O O CCl4 ref 5f O H3CCH3 Br C8H17 I2, CF3COOAg C8H17 O2CF3C I THF 00 O BrMe NBS OSiMe3 Me 2 HO H H I (C6H5)3PI2 C6H6 ref OAc O O Br Br Br Br O Et2O,HCL ICH2COOMe AgF FCH2COOMe OAc COCH3C HO H2O

2、 diox,100 COCBr Br,NaOH HO COOH HCl H2O 3 B2H6 BH 2 CHCH3 CHCH3 B H3C CH3 H I2 NaOCH3 CH3OH CH3CH2CHICH3 2,写出下列反应可能产物 (CH3)3CCH2OH HBr 100 封管 (CH3)2CCHCH3+(CH3)2CHCH3CH3+(CH3)3CCH2Br C H3C C COOCH3 CH3 NBS,(C6H5CO)2O2 CCl4ref H C BrH2C C COOCH3 CH3 H C H3C C COOCH3 CH2Br H CH3CCH2CH2CH3 O Br2 KClO3,

3、H2O 4045 CH3COCH2 CH2CH3 CH2COCH2CH2CH3 Br Br C H C C2H5 H C H C H3C CH3 Cl2,CH3COOH 25 Cl Cl C2H5 C H C H3C OCOCH3 Cl C2H5 C H C H3C Cl OCOCH3 C2H5 H HH + 3，写出下列反应的主要试剂及条件 C(CH2OH)4 PBr3/170180 C(CH2Br)4 HOOC(CH2)4COOH SOCl2/Ref ClCO(CH2)4COCl PhCH2COCH3 SOCl2/Ref or,Cl2/加热 PhCHCOCH3 Cl 4 O COOH O

4、or I2/LTA/CCl4/ref HgO/I2/加热 or AgNO3 KOH I2 加热 第二章 烃化反应 4，完成下列反应 COOCH3 OH OH CH3I NaOH COOCH3 OCH3 OH OH OCH3 OH Me2SO4 K2CO3 OCH3 OCH3 OH H3C H2 C O CH2 CH3OH,H2SO4 CH3OH,CH3ONa H3C H2 C OCH3 CH2OH H3C H2 C OH CH2OH 5 (H2C)5 C NH O Me2SO4(H2C)5 C NCH3 O NO2 ClO2N PhNH2 95 NO2 NHPhO2N HO H H3CC6H4

5、SO2O H CH3C6H4SO2Cl (EtO2C)2HC H CH2(COOC2H5)2 C2H5ONa C2H5OH NH2 CH2OH Raney-Ni,加热 NHCH2 O H3C LDA/CH3OCH2CH2OCH3 -400 OLi H3C 6 2,完成下列反应过程 O C C O NCH(COOC2H5)2 O C C O NC(COOC2H5)2 Na C2H5ONa C2H5OH ClCH2COOC2H5 150160 O C C O NC(COOC2H5)2 CH2COOC2H5 HCl H2O CH3COOH H2NCHCOOH CH2COOH CHO + CH3NH2

6、 H2/Raney-Ni CH2NHCH3 O CH2NCH3 CH2CH2OH C6H5CH2NH2 (C2H5O)2PH O C6H5CH2NHP(OC2H5)2 O H2CCHCH2Br/ 50%NaOH (n-C4Hg)4NHSO4 C6H5CH2NP(OC2H5)2 O CH2CHCH2 C6H5CH2N HCl CH2CHCH2 HCl 7 O CH3 (H3C)3C NH2 C6H6 ref带水 N CH3 (H3C)3C C2H5MgBr O ref N CH3 (H3C)3C MgBr H2C O ref CCH2Cl CH3 O CH3 (H3C)3C CH2C=CH2 C

7、H3 第三章 酰化反应 H3CO OCH3 OCH3 + CH3COCl AlCl3 H3CO OCH3 OCH3 C CH3 O CCCH2OHO2N H OH NHCOCHCl2 H + CH3(CH2)16COCl N /C6H6 CCCH2OOC(CH2)16CH3O2N H OH NHCOCHCl2 H 8 ClCH2CONH S CCOOH NOCH3 + H2N N S N N N N CH3 O H2CS DCC THF N N S N N N N CH3 O H2CS ClCH2CONH S C NOCH3 O C CH3 CH3 (CH2)5COClAlCl3 ClCH2C

8、H2Cl CH3 CH3 O OCH3 H3CO H3CO H3CO Zn(CN)2/HCl DMF/POCl3 H2O OCH3 H3CO H3CO H3CO CHO +C6H5N CHO CH3 ACONa H2O POCl3 9095 CHO 9 CH3COCH2COOC2H5 + HO 140 45小时 H3CCOCH2COO 2，完成下列合成路线 OH Et2SO4,NaOH 或C2H5X,NaOH OC2H5 DMF POCl3 OC2H5 CHO Cl2 OC2H5 COCl N S O H2N CH3 CH3 COONa N S O NH CH3 CH3 COONa OC2H5

9、 OC 以苯和丁二酸为起始原料合成四氢萘 +O O O AlCl3CH2CH2COOH O Zn-Hg HCl CH2CH2CHOOH HF CH3 H2O O Zn Hg HCl 10 第四章 缩合 COCH3+HCHO + CH3NH COCH2CH2N CH3 COCH2CH2N CH3 CH3NH COCH2CH2N(CH3)2COCH3+HCHO +HN(CH3)2 Ph3PHCHCH3 + CHO H H CH3 + H CH3 H CH3CH2CH2COCH3+CH3COOC2H5 碱 CH3CH2CH2COCH2COCH3 CHO H + BrCH2COOC2H5 Zn+C6H

10、6 H2O (C2H5)2O CCHCOOC2H5 2，完成下列反应式 O CH3 +O2NCHO OH H2O H3C O HCNO2 11 OO 2Ph3PCHCH3 H3CHCCHCH3 O + CH2O (过量) Ca(OH)2 H2O O HOH2C HOH2C CH2OH CH2OH C6H5CHO (C2H5CH2CO)2O,C3H7COOK NaOH C H C COOH C2H5 O ClCH2COOCH3 CH3ONa O COOCH3 H2O OH O COOH H CHO (EtO)2C=O+C6H5CH2CN C2H5ONa C6H5 H CC O OC2H5 CN

11、(C6H5)3PCH2CH=CH2 Cl NaNH2 液NH3 C6H6 回流 (C6H5)3PCHCH=CH2 12 O CH2CH2CHO H3C C6H6 25% O CH2CH2CH=CHCH=CH2 H3C CH3 CO2CH3 O + BrCH2CO2CH3 Zn C6H6 (C2H5)2O CH3CO2H H2O CH3 CO2CH3 C H COOCH3 3,完成下列合成反应 从甲苯 C COOEt COOEt C2H5 CH3 Br2/hv CH2Br NaCN CH2CN COOC2H5 COOC2H5 HC CN O COOC2H5 EtOH H CH COOEt COO

12、Et EtONa C2H5Br C COOEt COOEt C2H5 H+ 加热 CH COOEt COOEt 13 CH3 CH3 H2C CH3 H C CH3 CHO CH3 CH3 H2C CH3 H C CH3 CHO CrO2Cl2 CCl4 H2O H3C CHO CH3CH2CHO C2H5ONa H3C C H CCHO CH3 Pd-C H2 125 4，填写下列各部产物 甲基丙醛 HCHO/OH A(C5H10O2) HCN H3O B(C6H12O4) +H2O C(C6H10O3) NH2CH2CH2COOCH2Ph D H3O+ A H3CCCHO CH2OH CH

13、3 B H3CCCH CH2OH CH3 OH CN C H3CCCH H2C CH3 O O OH D H3CC H C CH2OH CH3 H NCH2CH2COOCH2Ph OH O E(C9H17NO5)+PhCH2OH H3CC H C CH2OH CH3 H NCH2CH2COOH OH O E 14 COCH3 O (C2H5)2NCH2CH2COCH3 CH3 CH3ONa,CH3OH,C6H6 COCH3 O CH2CH2COCH3 KOH CH3OH H2O H3O+ CH3 O OHC ZnBrCH2COOEt CH3ONa,CH3OH,C6H6 C H CHCOOEt

14、LAH CH2CH2CH2OH HBr KCN CH2CH2CH2CN H3O COOH AlCl3 SOCl2 O 第五章 氧化反应 1，完成下列反应式 CH3 NO2 CrO3/Ac2O H2SO4 CHO NO2 15 CH3 NO2CrO/H2O 高温 高压 COOH CH3 CH3 CH3COCl AlCl3 CH3 CH3 COCH3 Br2 NaOH H + CH3 CH3 COOH HOOH R MnO2 CHCl3 HOO R O OcA KMnO4, KIO4,H2O BaOH, K2CO3 35 O O OAc OH CH3 OCH3 NO2 CH3 OCH3 NO2 C

15、rO2Cl2 CS2 25 16 HOCH2OH (C5H5N)2 CrO3 CH2Cl2 HOCHO 0.5MSeO2 C2H5OH OH 回流 H3CO OH H3CO O HO DMSO-DCC H3PO4 RT HO RO C RO CH3 O C CH3 O O H2O2 NaOH 17 COOOHCl H3C H3C H H H O H (C2H5)2O 25 H COCH3 H OCOCH3 C6H5COOOH CHCl3 2,试以化学表示实现下列变化的各步反应 CHO CHO COOH C2H5 C2H5 稀NaOH Ag2O CONH2 C2H5 SOCl2 NH3 RCO3

16、H CONH2 C2H5 O HO(CH2)6CH3 H3CSO2Cl H3CSO2O(CH2)6CH3 DMSO OHC(CH2)5CH3 18 OH H2SO4 KMnO4 OH OH Pb(OAc)4 CHO CHO 稀NaOH CHO OH CrO3 H2SO4 H2O SeO2 O KOH Bu-t O Bu-t HCl,加热 O Bu-t 第六章 还原反应 1，完成下列反应 CH3CH=CHCHO 0.25MNaBH4 CH3CH=CHCH2OH NO2 NH2NH2 H2O Pd-C/C2H2OH NH2 O 0.25MNaBH4 or 0.25MLiAlH4 or M PV O

17、H O C(CH2)3 OCH3 OCH3 Br O C(CH2)3 OCH3 OCH3 Br Zn-Hg HCl 19 B2H6 THF 25 2 BH H2O2 NaOH CH3 H H OH H3CO O Cl Pb-BaSO4 H2 Q-S H3CO O H CH3 CH3 2PHCH2CH=CH2 + Pd/C 2PHCH2CH2CH3+ O H2/(Ph3O)3RhCl O O O Ph H2/Pd-C AcOH,HClO4 HOCH2CH2OCH2CH2Ph 20 N H3CO OC CH=CH2 N H3CO HOHC CH=CH2 Al(OCH(CH3)2)3 (CH3)2C

18、HOH 2,改错 COOEtHOOC LAH C2H6 COOEtHOH2C LAH CH2OHHOH2C CH3COCOOEt Zn-Hg HCl CH3CHOHCOOEt CH3 O CH3 H3CH H3CCH3 LAH CH3 H CH3 H3CH H3CCH3 HO 3，完成下列合成题 1，试由环己醇、氯乙酸、乙醇合成 H2C (H2C)7CH2 C=O 21 OH Cl(CH2)6Cl ClCH2COOH CH2(COOC2H5)2 2CH2(COOC2H5)2 +Cl(CH2)6Cl C2H5ONa (C2H5OOC)2 CH(CH2)6CH(COOC2H5)2 H2O NaOH

19、 EtOH H+ C2H5OOC(CH2)8COOC2H5 Na C6H4(CH3)2 ref H2C (H2C)7CHOH C=O H2C (H2C)7CH2 C=OZn/HCl HOAc 2，试由 O OCH3 合成 O O OCH3 0.25MNaBH4 OH OCH3 H2O H+ OH O H+ O 3，试由 COOEt H H CH2CH2COOH 制备 O O 22 COOEt H H CH2CH2COOH Na C2H5OH H CH2CH2COONa H CH2OH H+ O O 第七章 重排反应 1，完成下列反应式 OH OH 稀H2SO4 O CONH2 OHH HHO

20、OHH OHH CH2OH NaOCl/H2O CONH2 OHH HHO OHH OHH CH2OH 23 N C2H 5 CH2C6H4OCH3 CH3 C6H5Li Et2O NCH3 C2H5 CH2C6H9PH2CO + N C2H5 CH2C6H5OCH3P CH3 N -Cl PhLi/PhH N 加热 N CH3 CH2N(CH3)3 NaNH2/NH3 N CH3 CH2N(CH3)2 CH3 OH OH CH3 H+ -H2O COCH3 CH3 OCH3 CONH2 OCH3 NaOCl/NaOH OCH3 NH2 OCH3 24 NC EtOOC HNHC EtOOC

21、180 O CH3 CH3 PhNEt2 ref 2H OH OCH3 OCH3 HO CH2NH2 CH3 NaNO2/H+ O H3C 25 HO CH3C(OEt)3 142147 8 days CH2COOEt CHMe2 Me2 HO CO2Me Me HCl-HOAc-Ac2O H3O+ CHMe2 CO2Me Me NH2 二，完成下列合成过程 O CHO 2KCN O H C O C OOH O C O C OO HNO3 KOH H+ O O COOH OH 26 O CHO + OC2H5 CH3 O O 加热 O O H O CHO 加热 O OHC O CH3 CHO H2C CH3 Et OCH3 +H3COOC CH2 OH CH3 2,4-O2NC6H5OH/Tol 100 8hr O COOCH3 H CH3 Et claisen重排 COOCH3 Et O CH3 NaBH4 CH3OHCOOCH3 Et OH CH3 H2C CH3 OCH3 OCH3 Et O Et Et COOCH3 CH3 claisen重排 27 COOCH3 Et O EtCH3 NaBH4 CH3OH COOCH3 EtEtCH3