中國藥科大學(xué)藥物合成習(xí)題答案

1、 # 藥物合成反應(yīng)習(xí)題參考答案第一章鹵化反應(yīng)寫出下列反應(yīng)的主要產(chǎn)物（或試劑）H3COC6H4f&Hr # # #H-3cH3H-HCICIC- #4 #4 # #4 #2寫出下列反應(yīng)的可能產(chǎn)物 4 # #4 # #4 # #4 3.寫出下列反應(yīng)的主要試劑及條件A第二章烴化反應(yīng)完成下列反應(yīng)CH3OHCH&HCHQN備加熱 #H3CLDA/CH3OCH2CH2OCH3%C0乙乙0-400oC,酮過量OLi完成下列反應(yīng)過程 # # # #H2N-C(COOC2H5)2CH2COOC2HfiH2/Raney-Nich2nhch、Iln-c(cooc2h5)3CH2COOC2H& # # # #ceH5

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

3、/POCI3!H3COCHOH3cOH3cOCHOCH3poci.+C6H5NCHOOC OIIch3cccoc2h5+ho3H225140C45hrOIICH3CcCO3H22.完成下列合成路線OH:NaOH/C2H5Br；CHO1.H2NCOCIOC2H5衛(wèi)OC2H5DM匕25-POCl3CH3CH3CO2Na一CONHOC2H5OC2H5SCH3CH3CO2Na以苯和丁二酸酐為起始原料合成四氫萘PEAOHZn-HgOHHCl(gas)Zn-HgHCI(gas)第四章縮合反應(yīng)改錯（只能改動一處）3 CH3CH2CH2CCH3+CH3COOC2H5CHO+xClCH2CO2C2H5Zn+C6

4、H6：(C2H5)2。Hc=chcooc2h525BrCH2CO2C2H52.完成下列反應(yīng)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叫廠C6H6 # #ch2ch2ch=ch-ch=ch2O.H3COCH3cO2cH3O+CH3ZnCH3CO2HBrCHzCQCH3C6H6(C2H5)2O,ref.H2OCH3CO2CH3CHCO2CH3H3CO完成下列合成過程CH3cooc2h5CC2H5COOC2H5CH3NBSCH2BrKCNCH2CNh+/h2oC2H5OHH22SO54CH2CO2C2H5 OC2H5OOC2H5CHC(CO2C2H5)2CH(CO2C2H5)2C2H52252C2H5Br/C2H5ONa2525C2H5ONa25CH3CH3H2CCCHO2H # # # #CH3C

6、H3CH3CH3CrO2Cl2CHOch3ch2choNaOHCHOH2,Pd/C-CH2CH(CH3)CHOCH3CH3CH3CH3填寫下列各部分產(chǎn)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完成下列反應(yīng)式(1)OHOH(2)HHOHHCONH2OHHOHOHCH2OH(3)NCH2CH3C2H5AAZZZW*第五章diluteH2SO4NaOCI/H2OOCH3MeNHCO2Et重排反應(yīng)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完成下列合成過程(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 # # # #第六章氧化反應(yīng)1.完成下列反應(yīng)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試以化學(xué)式表示實現(xiàn)下列變化的各步反應(yīng)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、完成下列反應(yīng)H3CH3C第七章還原反應(yīng)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.改錯COOHCH2OHCH2OHLAH(/COOEtCOOEtCH2OHOnZn-HgHCICH3CCOOEtCH3CH2COOEt(CH313ch33ch313COH-C-OHOH-C-H1,LAH11H3CCH尸h3c_c_hHCCH31h3c丫-ch3f31H3C_C-ch3H3C-C-CH33CH3CCHOOEtOHcH3cH3CCHH # 3.完成下列合成題試由環(huán)己醇，氯乙酸，乙醇合成OC10OH-H2O-13Z

14、nC“HOci(ch2)6CIPd/C,H2cich2coohNaCN_時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試由OCH3合成O0.25NaBH4OCH3OHH2OH+OCH3OHH+O # # # #HOHCOOEtO試由HCH2CH2COOH制備HHCOOEtNa/NH3HCH2CH2COOHHCH2OHH+CH2CH2COOHH2

15、2HOOHPh Ph #第八章合成設(shè)計原理請用切斷法對下列化合物進(jìn)行逆合成分析（標(biāo)明反應(yīng)條件及試劑），要求最后所得原料和試劑為最簡單易得之商品。1.OH+BrMgPh2.FGIH2LindlarcatalystOOBrMgCuX1,4-addition3.PhFGAPhClCH3COCH2CO2C2H5322254.OHOHOOH5.OHPh=PhPhHSS+O # 6.PhSO2CH2C3H7CONH2CO2C2H5OHCO2C2H5OO # #OC2H525OO # # # #CO2HCO2CH8.CC22HH55OOOpch2co2ch3 # # # #MichaeladditionOO

16、+Oc2H5c2H5oNa25oc2H5oo # # # # # # #cH2(cO2c2H5)2+二.設(shè)計下列化合物的合成，并寫出它們的合成反應(yīng)式1.(1)RetrosyntheticAnalysis: Michaeladdition*o(2)Synthesis:Ba(OH)2Soxhletextractor廠、NaNH2廠、So2.(1)RetrosyntheticAnalysis:oHPhPhoHPhoHPhoTMSPh3P=CPh2+HoTMSHOOHHOOTMS(2)Synthesis:HOOH-1molTMSClTEAOPh3P=CPh2Ph32HOTMSSwernOxidationOTMS=OTMSOsO4PhOHPhPhOTMSOHH+PhPhOHO