of B-Dicarbonyl compoundg s Chap 20. Synthesis and reactio 20.1 Introduction Compounds having two carbonyl groups separated by an intervening carbon are called B-dicarbony l compunds, and these compounds are highly versatile reagents for organic synthesis pKa=10-14 acidic R CH2 ROC-CH2 OR H The B-dicarbonyl system Aβ- keto ester A malonic ester β二酮 β-酮酯 丙二酸酯
Chap 20. Synthesis and Reactions of β- Dicarbonyl compounds 20.1 Introduction Compounds having two carbonyl groups separated by an intervening carbon are called β-dicarbonyl compunds, and these compounds are highly versatile reagents for organic synthesis. O C O H H The -dicarbonyl system R O CH2 O OR' A − keto ester ROC O CH2 O OR' A malonic ester -二 酮 -酮 酯 丙 二 酸 酯 pKa = 10-14 acidic
20.2 The claisen condensation The synthesis of B-keto esters When ethyl acetate reacts with sodium ethoxide, it undergoes a condensation reaction After acidification, the product is a B-keto esters, Condensations of this type occur with many other esters and are known generally as claisen condensation(克莱森缩合) NaoCrH5 CH3coc2H5 HCH, COC2Hs HOC)s -CH3, COC2Hs CH3CH2OH Ethyl acetate Ethyl acetoacetate (removed by distillation)
20.2 The claisen condensation: The synthesis of β-keto esters When ethyl acetate reacts with sodium ethoxide, it undergoes a condensation reaction. After acidification, the product is a β-keto esters , Condensations of this type occur with many other esters and are known generally as claisen condensation (克莱森缩合） CH3COC2H5 O + HCH2COC2H5 O Ethyl acetate NaOC2H5 HOC2H5 CH3CCH2COC2H5 + CH3CH2OH O Ethyl acetoacetate (removed by distillation)
Ethyl pentanoate CH2CH2 CH3 NaocrHs CH3CH2CH, CH2 CCHCOC2Hs CH3 CH,OH CH2 CH removed by distillation) (77%) General reaction: Naoh RCH2COCH, CH3+ HCHCOCH,CH RCH, CCHCOC2Hs CH3CH2OH HOCH R (removed by distillation
NaOC2H5 HOC2H5 CH3CH2CH2CH2CCHCOC2H5 + CH3CH2OH O (removed by distillation) CH3CH2CH2CH2COCH2CH3 O + HCHCOCH2CH3 O CH2CH2CH3 CH2CH2CH3 Ethyl pentanoate (77%) NaOC2H5 HOC2H5 RCH2CCHCOC2H5 + CH3CH2OH O (removed by distillation) RCH2COCH2CH3 O + HCHCOCH2CH3 O R R General Reaction;
Reaction mechanism NaoC2H5 CH3COC2H5 HCH2COC2Hs -CH3CCH2COC2Hs+ CH3CH2OH HOCH5 Ethyl acetate Ethyl acetoacetate (removed by distillation) Step 1 CH3COC2H5 Naocasr NacH, Co0C2Hs CH3CH2OH Ethyl acetate Step 2 CHaCOC,Hs NaCH,COOCHs-CH3C--CH2COOC2Hg OCH2 CH3 CHaCCH,COCHs+ CH3 CH20 Ethyl acetoacetate
Reaction mechanism; CH3COC2H5 O Ethyl acetate NaOC2H5 Step 1 NaCH2COOC2H5 + CH3CH2OH CH3COC2H5 O + HCH2COC2H5 O Ethyl acetate NaOC2H5 HOC2H5 CH3CCH2COC2H5 + CH3CH2OH O Ethyl acetoacetate (removed by distillation) CH3COC2H5 O CH3CCH2COC2H5 + CH3CH2O - O Ethyl acetoacetate Step 2 + NaCH2COOC2H5 CH3C O- CH2COOC2H5 OCH2CH3
1)NaoCH,CH CH3CH,OCCH_ CH, CH, CH2COCHCH3 2 cooCH2CH Diethyl hexanedioate 己二酸二乙酯 分子内的c1 alsen酯缩合 )NaoCH,Ch CH3 CH2OCCH2 CH2CH2 CH2 CH2COCH2 CH3 COOCH2 CH3 Diethyl heptanedioate 庚二酸二乙酯 分子内的c1 aisen酯缩合 t cHrCH,OH
CH3CH2OCCH2CH2CH2CH2COCH2CH3 O O 1) NaOCH2CH5 2) H + O COOCH2CH3 Diethyl hexanedioate 己 二 酸 二 乙 酯 分 子 内 的 Claisen酯 缩 合 CH3CH2OCCH2CH2CH2CH2CH2COCH2CH3 O O 1) NaOCH2CH5 2) H + COOCH2CH3 Diethyl heptanedioate 庚 二 酸 二 乙 酯 分 子 内 的 Claisen酯 缩 合 O + CH3CH2OH
20.2A Crossed claisen condensations(交叉克菜森缩合) Crossed Claisen condensations are possible when one ester component has no a ydrogens and is, therefore unable to undergo self-condensation ), CH3 OCH, CH,+ CH3 COoCH Ethyl benzoate no a -hydrogen OCH2 CH3 Ethyl benzoylacetate (60%)
20.2A Crossed Claisen condensations (交叉克莱森缩合） Crossed Claisen condensations are possible when one ester component has no α- hydrogens and is, therefore, unable to undergo self-condensation. O OCH2CH3 + CH3COOC2H5 1) NaOCH2CH3 2) H + O H2 C O OCH2CH3 Ethyl benzoate Ethyl benzoylacetate (60%) no -hydrogen
OCH2CH3 )NaoCH,2CH CH2COC2H5 CrHsoCoCHs no a-hydrogen OCH2 CH3 Ethyl phenylacetate Diethyl carbonate 苯乙酸乙酯 甲酸二乙酯 Diethyl phenylmalonate (65%) 苯基丙二酸乙酯 1)NaoCH, CH3 CH2COC2 H5 H3 CH2CO C-OCH2 CH3 no a-hydrogen Ethyl phenylacetate Diethyl oxalate 苯乙酸乙酯 草酸二乙酯 c—cocH2CH OCH2CH
1) NaOCH2CH3 2) H + no -hydrogen CH2COC2H5 O + C2H5OCOC2H5 O Ethyl phenylacetate Diethyl carbonate 苯 乙 酸 乙 酯 甲 酸 二 乙 酯 O O OCH2CH3 OCH2CH3 Diethyl phenylmalonate (65%) 苯 基 丙 二 酸 乙 酯 1) NaOCH2CH3 2) H + no -hydrogen CH2COC2H5 O + Ethyl phenylacetate Diethyl oxalate 苯 乙 酸 乙 酯 草 酸 二 乙 酯 C O O COCH2CH3 OCH2CH3 O C O H3CH2CO OCH2CH3 O
20.2B Acylation of other carbanions(其它负碳离子酰基化) a NaOH,CH 3 Nat 1)H3CH2Co OCH2CH3 2) OCH2 CH3 (67%)
20.2B Acylation of other carbanions(其它负碳离子酰基化） O NaOCH2CH3 O - Na + O O O OCH2CH3 (67%) O O 1) H3CH2CO OCH2CH3 2) H+
20. 3 The acetoacetic ester synthesis: Synthesis of substituted acetones R—X CH CH2tR or CH3 cH—R R—X CH CCH,COOCH,CH
20.3 The Acetoacetic ester synthesis: Synthesis of substituted acetones CH3 O CH2 R or CH3 O CH R R CH3CCH2COOCH2CH3 O R X R X
CH3CCH2TCH2CH2CH2CH3 )NaoCH,Ch CH3 CH,CH,CI B CH3,CH3 CH3 CCHCOOCH2 CH3 SN2 Acetoacetic ester 乙酰乙酸乙酯 Nucleophile reagent Naoh 2)H3O CH3CCH—cH2 CH2CH2CH3 CH3CCH—cH2cH2CH2CH3 水解 COOCH2 CH3 CooNa heat CH3CCH—cH2cH2cHcH3 CH3CCH2+CH2CH2CH2CH3 CO COCH 脱羧
CH3 CCH2 O CH2 CH2 CH2 CH3 CH3CCH2COOCH2CH3 O 1) NaOCH2CH3 CH3CCHCOOCH2CH3 O - Na + Acetoacetic ester 乙 酰 乙 酸 乙 酯 Nucleophile reagent CH3CH2CH2CH2 Br SN2 CH3CCH O COOCH2CH3 CH2CH2CH2CH3 1) NaOH 2) H3O + CH3CCH O COONa CH2CH2CH2CH3 CH3CCH O COOH CH2CH2CH2CH3 heat - CO2 CH3CCH2 O CH2CH2CH2CH3 脱 羧 水 解