1、與含氮化合物相關(guān)的合成反應(yīng) 11 烯胺enamines作中間體1.1.1 制備和反應(yīng)機(jī)理CCOH+NHCHCNOH脫水分子篩 CCNCCOH+NHCHCNOH脫水分子篩 CCN常用的胺：NHNHNOH1.1.2 反應(yīng)的特點(diǎn)1、烯胺優(yōu)先生成少取代產(chǎn)物，而烯醇（酮）則生成多取代產(chǎn)物；2、烯胺烴化時(shí)可終止在一元烴化階段。1.1.3 烴化反應(yīng)OCH3+NHNCH312EH3OOCH3E對(duì)于烯胺，簡單的烴化試劑， 主要發(fā)生N-烴化作用。1、分子內(nèi)轉(zhuǎn)移CH3CH=CHCH2BrCH3CCH3CHN(CH3)2CH3CH=CHCH2CH3CCH3CHN(CH3)2CH3CCH3CHN(CH3)2CH3CH-

2、CHCH2H3O+CH3CCH3CHOCH3CH-CHCH2(67%)2、分子間轉(zhuǎn)移CH3CCH3CHN(CH3)2PhCH2CH3CCH3CHN(CH3)2CH3CCH3CHN(CH3)2CH2PhH3O+CH3CCH3CHOCH2PhPhCH2IN-烴化CH3CCH3CHN(CH3)2CH3CCH3CHN(CH3)2+烴化時(shí)易發(fā)生N-烴化，為了阻止N-烴化可以采用下列方法：1）增大N原子上取代基的體阻2）增大N原子上親核能力3）形成烯胺的-鹽(Li鹽)CHCHORR1+HNBu-nBu-i12 R2XH3O+CCHORR2R1RCR1CH NBu-nBu-iCHCHORR1+RCHR1CH

3、NBu-tNH2Bu-tEtMgBrRCR1CHNBu-tMgBr12 R2XH3O+CCHORR2R1RCHBrCORHNRCBrCNRn-BuLiRCLiCNRRXRCCNRR1.1.4 Michael加成反應(yīng)和環(huán)合反應(yīng)1、酮烯胺YH3O+NOY(CH2)nN+COOEtCOOEt(1)異丙苯(2) H3O+(CH2)nOCOOEtCOOEt2、醛烯胺RRCHNYRRCHNYRRNY這是一個(gè)離子加成反應(yīng)，是一個(gè)分步進(jìn)行的反應(yīng)。如R=H，則發(fā)生質(zhì)子轉(zhuǎn)移。CCHNRHYNYRH3O+CHOYROOEtONaOOOHNNO12H3O+O1.1.5環(huán)合反應(yīng)NOCH3BrNOCH3H2OOOO合成s

4、ynthon 合成子的等當(dāng)體O BrOCH3CHNO12H2OOO9 : 1N+CHONHONHOH2ONHHOO+ONH-H2OONCH3IONCH3OHCOOH1.1.6 ?；磻?yīng)(Acylation) 2分子的烯胺和1分子的酰氯反應(yīng)，其中的1分子烯胺起堿的作用。常用Et3N取代過量的原料。NN-AcylationC-AcylationNNCORRCOClCORNNNN+COR1.1.7 -位金屬化PhNMePhLiPhNMePhLiE+PhNMePhEH3O+EPhOE+可以是RX, RCOX等合成子反極性PhO1.1.8 還原反應(yīng)NHHNHH3O+H季銨化后再消除HOHHOHHH- H

5、2ONBNHB2H6EtCOOHHOHOHH2O-ONHN1B2H62EtCOOHRORONHRNRNCORRCOCl12B2H6EtCOOHRCORROCORH3O+ArCO3H用不大于C4原料合成以 為原料合成寫出下列反應(yīng)機(jī)理CHOPhNPhMeOPhHON+ClOH3O+OO1.2 4,4,6-trimethyl-5,6-dihydrooxazineNONOROHOH+CNR濃 H2SO41967年Meyers發(fā)現(xiàn)：NORNaBH4NORHH3O+RCHOCHO+CH3CHOO?NOCH3OHOH+CNCH3濃 H2SO4n-BuLiNOCH2LiONO12NaBH4H3O+ONOCH2

6、NOCH3base6.2.1合成醛NOCH2A12NaBH4H3O+n-BuLiNOCHAE+NOCHAEOHAEA= H, Ph, COOEtE= RX, , R OO, .NOCH2LiNOBrBrBr12NaBH4H3O+12MgRCORNOOHRRHOOHRR12NaBH4H3O+OHRRRXNONORRRMgXNORunstableNO:Nu?RXNOCH3CH3INOCH3CH3NaHNOCH2CH3NOCH2RCH3O合成子： 極性正常NCa) 3-位烴化(RMgX) b) 2-位烴化(RX)c) 腈氫化成醛合成酮NOR1RunstableBuLiNOR1RONCCR1RR2Mg

7、XONC XMgR2 H3O+CR1RR2ORR1R3XCR1R3CR2ORNORXCH3INOBuLiNONORRMgXNORRH3O+ORRO極性正常NORR1MNORR1NOCRR1R2MNOMCR2RR1R3XR2RR3R1NOH3O+R2ORR3R1OR1.3 4,4-dimethyloxazolineONRONR催化劑：硫酸等OHNH2+RCOOH制備：最初該化合物只作為羧酸的保護(hù)基，例如：NH2OH+HOOCBrONBr13 H3O+2 Mg ?HOOCRMgONCH3n-BuLiONCH2RXONCH2RH3O+RCH2COOH1 n-BuLi2RXH3O+CHCOOHRR4.

8、3.1 合成羧酸從凈結(jié)果來看CH2COOH極性正常ONCH2RPhHO手性合成ONPhHORHRi-Pr2NLiX-RONPhHORHLiX-R1.3.2 合成羰基化合物ONRRBuLiONRRONCCRRRMgXONCCRRMgXRH3O+RORR合成子ONONCH3IRMgXONHRH3O+RCHO合成子1.3.3 合成鄰位取代芳烴酸(及其聯(lián)苯衍生物)COOHXCOOHRH3O+NH2OHXONRMgXRONCOOHCOOHE12i-Pr2NLiNH2OHLiONE+H3O+EON合成子COOHBuchwald-Hartwig反應(yīng)反應(yīng) XR+H2NR1PdCl2(dppf), t-BuONadioxane, 100 CR = alkyl,CN,COR. R1 = aryl,alkylNHR1RArXArOAr1+HOAr1Pd(OAc)2, ligandK3PO4, Tol, 100 CX = Br, ClEscitalopram 用于抑郁癥的治療ONCNFONCNF-+-ONCNFMgXOXMgShapiro reactionE+E = electrophileR