中国药科大学药物合成习题答案

1、 # 药物合成反应习题参考答案第一章卤化反应写出下列反应的主要产物（或试剂）H3COC6H4f&Hr # # #H-3cH3H-HCICIC- #4 #4 # #4 #2写出下列反应的可能产物 4 # #4 # #4 # #4 3.写出下列反应的主要试剂及条件A第二章烃化反应完成下列反应CH3OHCH&HCHQN备加热 #H3CLDA/CH3OCH2CH2OCH3%C0乙乙0-400oC,酮过量OLi完成下列反应过程 # # # #H2N-C(COOC2H5)2CH2COOC2HfiH2/Raney-Nich2nhch、Iln-c(cooc2h5)3CH2COOC2H& # # # #ceH5

2、CH2NHP(OG2H5)HCI # # # # 第三章酰化反应1.完成下列反应cOcH3H3cO+OCH3OCH3CH3COCIAICI3”H3COOCH3OCH3O2NHNHCOCHClC-C-ch2oh2OHHPyO2N+CH3(CH2)16COCI3216c6h6HNhcochci2CH2OCO(CH2)16CH3OhHOcH3H2NclcH2cONHcO2HcH2SOCH3COOHNNNCH3DCCTHFclcH2cONHCONHCH2SCOOHnNnNCH3cH3cH3(CH2)5COClAQI3clcH2cH2cl,0occH3cH3OcH3OcH3H3cOH3cOH3CODMF

3、/POCI3!H3COCHOH3cOH3cOCHOCH3poci.+C6H5NCHOOC OIIch3cccoc2h5+ho3H225140C45hrOIICH3CcCO3H22.完成下列合成路线OH:NaOH/C2H5Br；CHO1.H2NCOCIOC2H5卫OC2H5DM匕25-POCl3CH3CH3CO2Na一CONHOC2H5OC2H5SCH3CH3CO2Na以苯和丁二酸酐为起始原料合成四氢萘PEAOHZn-HgOHHCl(gas)Zn-HgHCI(gas)第四章缩合反应改错（只能改动一处）3 CH3CH2CH2CCH3+CH3COOC2H5CHO+xClCH2CO2C2H5Zn+C6

4、H6：(C2H5)2。Hc=chcooc2h525BrCH2CO2C2H52.完成下列反应式NO2CH3+cHO2molPh3P=CHCH；OH/H2OH3cHc+CH2O(excess)Ca(OH)2./(CsH7CO)2OC6h5Cho殊OCICH2CO2CHqO2NcHcH3H2OcH3HOH2cHOH2ccH2OHcH2OHcOOHCCCO2HO5HOCO2cHO # C2H5ONa25+C6H5CH2CN(CO2C2H5)2orC2H5OCO2C2H5HO”c6h5c-c-oc2h652CN # # # #(c6H5)3P-BrNaNH2CC二CH22Ph3P=CH-CH=CH2h2

5、H2-32CH2CH2CHOO叫厂C6H6 # #ch2ch2ch=ch-ch=ch2O.H3COCH3cO2cH3O+CH3ZnCH3CO2HBrCHzCQCH3C6H6(C2H5)2O,ref.H2OCH3CO2CH3CHCO2CH3H3CO完成下列合成过程CH3cooc2h5CC2H5COOC2H5CH3NBSCH2BrKCNCH2CNh+/h2oC2H5OHH22SO54CH2CO2C2H5 OC2H5OOC2H5CHC(CO2C2H5)2CH(CO2C2H5)2C2H52252C2H5Br/C2H5ONa2525C2H5ONa25CH3CH3H2CCCHO2H # # # #CH3C

6、H3CH3CH3CrO2Cl2CHOch3ch2choNaOHCHOH2,Pd/C-CH2CH(CH3)CHOCH3CH3CH3CH3填写下列各部分产物(1) # # #(2)CH3HCHOH3CCH2OHH3CCHO一OHH3CCHOAH3CH3CHOOCH3OH3CCH2OHH3CCH-CO2HOhNH2CH2CH2CO2CH2PhCH3-H3COHCHCONHCH2CH2CO2CH2PhCH2OHch3ohh3cChconhch2ch2co2hCH2OH+PhCH2OHCOCH3OCH3(C2H5)2Nch2ch2coch3CH3ONaCH3OHC6H6COCH。3COCH3KOHCH3

7、OH/H2O,ref.H3O+ (3)OHCLAH-OHSOCI2CNHO2C(4)MeOHCMeMeCO2EtHCOOH,HCIorDMF/POCI3MeNCO2EtH2CH2(CO2H)2PiperidineHO2C-HC=HCMe1完成下列反应式(1)OHOH(2)HHOHHCONH2OHHOHOHCH2OH(3)NCH2CH3C2H5AAZZZW*第五章diluteH2SO4NaOCI/H2OOCH3MeNHCO2Et重排反应HOHHCHOHOHOHCH2OHC6H5LiNCH3Et2O4C2H5CH2OCH3 (4)C6H5LiL-5benzene,heatCl(5)CH2N(CH3

8、)2(6)(7)(8)(9)NCH3CH2N(CH3)3CH3OHOHCH3OCH3OCH3CONH2NCEtOOCCH3OCH3OCH3(10)H+-H2ONaNH2/NH3-NCh3CH3CH3ONaOCI,NaOH180oCPhNEt2reflux2hHOCH2NH2NaNO2/H+CH3OHCH3OCH3OCH3NH2NCEtOOCOCH3CH3O #O (11)HOO #O #O #O #(12)21.HCI-HOAc-Ac2O2.H3O+CHMe2nh2O #O #O #O #2完成下列合成过程(1)O #O #O #O #CNpccOCNaOAcNaOHHQCOOHOHO #O

9、#O #O #(2)CH3OCH2OH+OC2H5CH3CHOCopeOOCH3ClaisenOOch3h2,Pd-CCHOchoOCH3O #O #O O #(3)C2HOCH3OH+H3CO2CCH32,4-O2NC6H5OHTolC2H5CH3OCO2CH3Claisen_RearrangementC2H5CH3CO2CH3 # C2H5NaBH4MeOHC2H5CH3CO2CH3OCH3C2H5CH3C2H5OOHco2ch3C2H5C2H5NaBH4MeOHCH3CO2CH3OH # # # #第六章氧化反应1.完成下列反应式TOC o 1-5 h z HYPERLINK l boo

10、kmark67CH3CHOCrO3/Ac2Oh2so4NO2NO2 HYPERLINK l bookmark121ch3cooh3-Na2Cr2O7,H2O.：叫CCH3J1.Br2,NaOH；，12.H+*CH3CH3COOHCH3cH3CH3COCIAlCl31cH3 #HOMnO2OHCHCI325ChoOAcROOAc # # # #KMnO4/KIO4/H20_BaOH/K2CO3/35COOHOCH3no2CrO2CI2OCH3cs225CCHONO2OCH3 # # # #0.5MSeO2C2H5OH,ref.25HOH3cOHOCH2OH(C5H5N)2CrO3HOCHOch2

11、ci225COHOHODMSO-DccAH3PO4RTH3cO RO(11)H3CHH3CH(12)2.CH3CO;H2O2,NaOHjHClCOOOHH3CHH3H(C2H5)2O25CHCHOH3ROC6H5COOOHCOCH3HCHCl325COCOCH3H试以化学式表示实现下列变化的各步反应1.SOCl22.NH3CONH2C2H5CHOC2H5rco3hH3CHO(CH2)6CH3SO2ClH3COH1-H9SO4r2.KMnO4OHOHAgzOSO2O(CH2)6CH3PbQAchOH1.CrO3-H2SO4-H2OBu-t2.SeO2CH3COOCOOHC2H5CONH2OC2H

12、5DMSOjCHOaqNaOH)CHO1.KOHBu-t2.HC1,OHC(CH2)5CH3CHOBu-t 1、完成下列反应H3CH3C第七章还原反应CH。0.25MNaBH4no2nh2nh2h2oPd-C/C2H5OH250.25MNaBH4OHOCHCO(CH2)2CH2CH3HCH3BrB2H6H3CCH2OHNH23OCH3ATHF,25CZn-Hg.HCCH2(CH2)2CH2OCH3OCH3BrH3CCH3fHCH32BHH3CNaOHyjh2o.CHH3OHCHOCH3CH3；Pd-BaSO4/H2OCH3CH3COClCHO2PhCH2C=CH2+Pd/C2PhCH2-CH2

13、CH3 H2/(Ph3P)3RhCIOHOH2/Pd-CPhAcOH,HCIO4H3COOCNNai(och(ch3)2)3CCH2(ch3)2chohH3COHoCHN2.改错COOHCH2OHCH2OHLAH(/COOEtCOOEtCH2OHOnZn-HgHCICH3CCOOEtCH3CH2COOEt(CH313ch33ch313COH-C-OHOH-C-H1,LAH11H3CCH尸h3c_c_hHCCH31h3c丫-ch3f31H3C_C-ch3H3C-C-CH33CH3CCHOOEtOHcH3cH3CCHH # 3.完成下列合成题试由环己醇，氯乙酸，乙醇合成OC10OH-H2O-13Z

14、nC“HOci(ch2)6CIPd/C,H2cich2coohNaCN_时5日ch2(cooc2h5)2CH2(COOC2H5)2+Cl(CH2)6ClC2H5ONa(COOC2H5)2CH(CH2)6CH(COOC2H5)2NaOH,H2O_EtOH,H+C2H5OOC(CH2)8COOC2H5Na,NH3PhCH3HOO(CH2)2O(CH2)2 # # # #OO试由OCH3合成O0.25NaBH4OCH3OHH2OH+OCH3OHH+O # # # #HOHCOOEtO试由HCH2CH2COOH制备HHCOOEtNa/NH3HCH2CH2COOHHCH2OHH+CH2CH2COOHH2

15、2HOOHPh Ph #第八章合成设计原理请用切断法对下列化合物进行逆合成分析（标明反应条件及试剂），要求最后所得原料和试剂为最简单易得之商品。1.OH+BrMgPh2.FGIH2LindlarcatalystOOBrMgCuX1,4-addition3.PhFGAPhClCH3COCH2CO2C2H5322254.OHOHOOH5.OHPh=PhPhHSS+O # 6.PhSO2CH2C3H7CONH2CO2C2H5OHCO2C2H5OO # #OC2H525OO # # # #CO2HCO2CH8.CC22HH55OOOpch2co2ch3 # # # #MichaeladditionOO

16、+Oc2H5c2H5oNa25oc2H5oo # # # # # # #cH2(cO2c2H5)2+二.设计下列化合物的合成，并写出它们的合成反应式1.(1)RetrosyntheticAnalysis: Michaeladdition*o(2)Synthesis:Ba(OH)2Soxhletextractor厂、NaNH2厂、So2.(1)RetrosyntheticAnalysis:oHPhPhoHPhoHPhoTMSPh3P=CPh2+HoTMSHOOHHOOTMS(2)Synthesis:HOOH-1molTMSClTEAOPh3P=CPh2Ph32HOTMSSwernOxidationOTMS=OTMSOsO4PhOHPhPhOTMSOHH+PhPhOHO