药物合成反应习题

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 CCl42 5 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 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 丙 丙 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 H2O 40 45 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 170 180 C CH2Br 4 HOOC CH2 4COOH SOCl2 Ref ClCO CH2 4COCl PhCH2COCH3 SOCl2 Ref or Cl2 丙 丙 PhCHCOCH3 Cl 4 O COOH O or I2 LTA CCl4 ref HgO I2 丙 丙 or AgNO3 KOH I2 丙 丙 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 H3CC6H4SO2O H CH3C6H4SO2Cl EtO2C 2HC H CH2 COOC2H5 2 C2H5ONa C2H5OH NH2 CH2OH Raney Ni 丙 丙 NHCH2 O H3C LDA CH3OCH2CH2OCH3 40 0 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 150 160 O C C O NC COOC2H5 2 CH2COOC2H5 HCl H2O CH3COOH H2NCHCOOH CH2COOH CHO CH3NH2 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丙 丙 N CH3 H3C 3C C2H5MgBr O ref N CH3 H3C 3C MgBr H2C O ref CCH2Cl CH3 O CH3 H3C 3C CH2C CH2 CH3 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 ClCH2CH2Cl 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 90 95 CHO 9 CH3COCH2COOC2H5 HO 140 4 5丙 丙 H3CCOCH2COO 2 完成下列合成路线 OH Et2SO4 NaOH 丙 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 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 丙 CH3CH2CH2COCH2COCH3 CHO H BrCH2COOC2H5 Zn C6H6 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 丙 丙 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 C6H5 3PCH2CH CH2 Cl NaNH2 丙 NH3 C6H6 丙 丙 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 COOEt EtONa C2H5Br C COOEt COOEt C2H5 H 丙 丙 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 丙 丙 丙 丙 HCHO OH A C5H10O2 HCN H3O B C6H12O4 H2O C C6H10O3 NH2CH2CH2COOCH2Ph D H3O A H3CCCHO CH2OH CH3 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 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 丙 丙 丙 丙 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 CrO2Cl2 CS2 25 16 HOCH2OH C5H5N 2 CrO3 CH2Cl2 HOCHO 0 5MSeO2 C2H5OH OH 丙 丙 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 丙 NaOH Ag2O CONH2 C2H5 SOCl2 NH3 RCO3H 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 丙 NaOH CHO OH CrO3 H2SO4 H2O SeO2 O KOH Bu t O Bu t HCl 丙 丙 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 OH 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 2CHOH 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 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 合成 O OCH3 O O OCH3 0 25MNaBH4 OH OCH3 H2O H OH O H O 3 试由 制备 COOEt H H CH2CH2COOH 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 丙 H2SO4 O CONH2 OHH HHO 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 丙 丙 N C H3 CH2N CH3 3 NaNH2