第十四章β–二羰基化合物β–二羰基化合物:β–二酮(α,β-diketone)β–酮酸酯(β-ketoester)丙二酸二酯(malonicester)RCOOR'COCH2ROCOORCOCH2RCOR'COCH2均有活泼亚甲基14.1酮–烯醇互变异构(ketoandenoltautomerism)R2CCR'HOR2CCR'OHtautomerization(互变异构)由分子内的原子或基团连接的位置不同而产生的异构——互变异构14.1.1酸和碱对酮–烯醇平衡的影响酸催化的酮–烯醇互变异构:CCHOHRR'+H:B快CCHOHRR'H慢B:CCOHRR'H+H:B碱催化的酮–烯醇互变异构:HO:+CCHOHRR'慢CCOHRR'CCOHRR'+H2OCCOHRR'+OHHCCOHRR'H快+OH14.1.2化合物的结构对酮–烯醇平衡的影响CH3CHOCH2CHOH酮式烯醇式乙醛(~100)(很少)CO比CC更稳定键能差:45~60kJ•mol-1丙酮(99%)(1.5×10-4%)OOH环己酮CH3CCH3OCH2CCH3OH(98.8%)(1.2%)乙酰乙酸乙酯(β–丁酮酸乙酯):(ethylacetoacetate)1:0.09CH3CCH2COEtOOCH3CCHCOEtOOH:互变异构CH3CCH2COEtOOH++CH3CCHCOEtOO烯醇负离子(enolateion)β–二羰基化合物的酸性:H3CCOCCOOC2H5HH3CCOCCOOC2H5HH3CCCCOOC2H5HO共振杂化体中的极限结构14.2乙酰乙酸乙酯的合成及其应用14.2.1乙酰乙酸乙酯的合成2CH3COC2H5O1.NaOC2H5CH3CCH2COC2H5OO2.H3O++C2H5OH乙酸乙酯乙酰乙酸乙酯(三乙)(75%)(三氧代丁酸乙酯)Claisen酯缩合反应Claisen酯缩合反应机理:第一步碱进攻α–H,产生烯醇负离子:CH2COEtONaOC2H5CH2COEtOC2H5OHCHCOEtOH2第二步烯醇负离子对另一酯分子的亲核加成:CH2COEtOCH3COEtO+CH3COEtOCH2COEtOCOEtOOCH2COEt四面体中间体第三步离去基团的消除,恢复羰基结构:CH3COCH2COEtO+OC2H5CH3COEtOCH2COEtO第四步β–酮酸酯脱质子:CH3COCHCOEtO+OC2H5CH3COCHCOEtOH+C2H5OH第五步碳负离子的质子化(酸化):CH3CCHCOEtOO+OHHHCH3CCHCOEtOOH+H2O反应特点:•底物:含有两个α–氢的酯•β–酮酸酯的去质子与酸化•C―C键的生成•生成含两个官能团的产物分子RCH2COOCH2CH3+HCHCROCH2CH3O①NaOC2H5②H3O+RCH2COCHCROCH2CH3O+CH3CH2OH含一个α–氢原子的酯缩合反应CH3CCH3HCOCH2CH3OPh3CNa2CH3CHCCH3OCCH3CH3COCH2CH3O+CH3CH2OH交错Claisen酯缩合反应RCH2COOR'HCOROROCOROROCCOROOCORO甲酸酯碳酸酯草酸酯苯甲酸酯无α-氢有α-氢HCOOC2H5CH3COOC2H5OC2H5-HCOCH2COOC2H5+CH3COCH2COOC2H5+C2H5OHCOOC2H5COOC2H5CH3COOC2H5OC2H5-COOC2H5COCH2COOC2H5CH3COCH2COOC2H5+C2H5OH无α-氢有α-氢CH2COC2H5O+C2H5OCOC2H5O(1)NaOC2H5(2)H3O+CHCOC2H5OCOC2H5O(65%)C2H5OCCOC2H5OO+CH3COC2H5OC2H5ONaC2H5OCCOOCH2COC2H5O+CH3CCH2COC2H5OO+C2H5OH分子内酯缩合——DieckmanncondensationCH2CH2COOC2H5CH2CH2COOC2H5(1)NaOC2H5,C6H6,80℃(2)H3O+,80%OHCOOC2H5二元酯五元或六元环状β–酮酸酯己二酸乙酯2–氧代环戊甲酸乙酯COOCH2CH3CHCOCH2CH3COOCH2CH3CHCOCH2CH3OO乙酰乙酸乙酯的工业制法:CCH2OCO+C2H5OHH2SO4CH3CCH2COC2H5CH2OO二乙烯酮14.2.2乙酰乙酸乙酯的性质酮式分解:在稀碱或稀酸的作用下β–酮酸加热脱羧生成酮CH3COCH2COEtO5%NaOH/△CH3COCH2CONaOH+CH3COCH2COOHCH3COCH3+CO2β–羰基酸受热分解的机理:RCCCOOOHHHRCCCOOOHHHRCCH2OH+COO酸式分解:与浓碱共热,C―C键断裂得2分子羧酸盐CH3CCH2COC2H5OO40%NaOH△2CH3CONaO+C2H5OH反应机理:HO+CH3CCH2COC2H5OOCH3CCH2COC2H5OOOHCH3COOH+CH2COC2H5OCH3COO+CH3COC2H5OCH3COC2H5OOHCH3COO+C2H5OH烷基化反应:碳负离子与RX作用CH3CCH2COC2H5OOC2H5ONaCH3CCHCOC2H5OORXCH3CCHCOC2H5OORRX:伯、仲卤代烷14.2.3乙酰乙酸乙酯在合成上的应用合成甲基酮或α–烷基取代羧酸烷基化酮式分解或酸式分解CH3CCH2COC2H5OO①C2H5ONa②CH3CH2CH2BrCH3CCHCOC2H5OOCH2CH2CH3①C2H5ONa②CH3ICH3CCCOOC2H5OCH2CH2CH3CH3CH3CCCOOC2H5OCH2CH2CH3CH3①稀OH,②H+,③△酮式分解①40%OH,②H+酸式分解CH3CCHCH2CH2CH3OCH3CH3CH2CH2CHCOOHCH3CH3COCH2COOC2H5①C2H5ONa②Br(CH2)4BrCH3COCHCOOC2H5CH2(CH2)3BrC2H5ONaCH3COCOOC2H5①稀OH,②H+③△COCH3β–二酮的合成:CH3COCH2COOC2H5①NaH②C6H5COClCH3COCHCOOC2H5COC6H5①稀OH,②H+③△CH3COCH2COC6H514.3丙二酸酯的合成及其应用14.3.1丙二酸二乙酯的合成及其应用CH2COONaClNaCNCH2COONaCNC2H5OHH2SO4CH2COOC2H5COOC2H5丙二酸二乙酯的合成:H5C2OCOCH2COC2H5OpKa=13+C2H5OC2H5OHH5C2OCOCHCOC2H5OH5C2OCOCHCOC2H5OCH3CH2ICH3CH2CHCOOC2H5COOC2H5①NaOH,H2O②H+,△CH3CH2CH2CO2HCH3CH2CCH2CH2CH3COOC2H5COOC2H5CH3CH2CH2CHCO2HCH2CH3二次烷基化合成一元羧酸①NaOC2H5②CH3CH2CH2Br①NaOH,H2O②H+二元羧酸的合成CH2BrCH2Br+2Na+[CH(COOC2H5)2]CH2CH(CO2C2H5)2CH2CH(CO2C2H5)2CH2CH2CO2HCH2CH2CO2H①NaOH/H2O②H3O+环烷酸的合成3~6元环H5C2OCOH2CH5C2OCO①C2H5ONa+②BrCH2CH2CH2BrH5C2OCOCHCH2CH2CH2BrH5C2OCOC2H5ONa+①水解②脱羧CH2CH2CH2CHHOCOH5C2OCOCCH2OCH2CH2BrCH2CH2CH2BrH5C2OCOH5C2OCOCOH5C2OC14.4Knoevenagel缩合醛、酮与含活泼α–氢的化合物在弱碱(胺、吡啶、哌啶)作用下发生缩合反应CHO+CH2(COOH)2N,97℃-H2OCHC(COOH)2-CO2CHCHCOOH(80~95%)H14.5Michael加成含活泼氢的化合物与α,β–不饱和化合物进行共轭加成(1,4-加成)O+CH2(COOC2H5)2C2H5ONaC2H5OHOCH(COOC2H5)22–环己烯酮3–氧代环己基丙二酸二乙酯(90%)CH2CHCN+CH3CCH2CCH3OO(C2H5)3N,叔丁醇室温丙烯腈2,4–戊二酮CH2CH2CNCH3CCHCCH3OO4–乙酰基–5–氧代己腈(77%)①,苯,回流②H+,NHH2OOCH3OOOCH3+CH2CHCCH3OKOHCH3OH,回流OOCH3O2–甲基–1,3–环己二酮2–甲基–2–(3'–氧代丁基)–1,3–环己二酮(85%)(65%)Robinson环化反应14.6其它含活泼亚甲基的化合物ZCH2Z'CHO,COR,COOH,CONR2,CN,NO2(CH3)2CHI+CO2C2H5CH2CN①C2H5ONa/C2H5OH②H3O+(CH3)2CHCO2C2H5CHCN①C2H5ONa/C2H5OH②(CH3)2CHI(CH3)2CHCO2C2H5CCNCH(CH3)2(95%)烷基化反应:Michael加成反应:CH2CCH3COOC2H5+CH2COOC2H5CN①C2H5ONa②H3O+CH2CHCH3COOC2H5CNCHH5C2OOC2–甲基–丙烯酸乙酯氰基乙酸乙酯2–甲基–4–氰基戊二酸二乙酯