厦门大学化学化工学院：《有机化学》课程教学资源（课件讲稿，双语版）第十一章 羧酸衍生物（11.6-11.7）

116酯缩合反应 Ester Condensation reactions

Organic Chemistry Organic Chemistry Xiamen Xiamen University University 11.6 酯缩合反应 Ester Condensation Reactions

The claisen condensation reaction Esters, like aldehydes and ketones,are weakly acidic. When an ester with an alpha hydrogen is treated with one equivalent of a base such as sodium ethoxide, a reversible condensation reaction occurs to yield a p-keto ester product. This reaction between two ester components is known as the Claisen condensation reaction

Organic Chemistry Organic Chemistry Xiamen Xiamen University University The Claisen Condensation Reaction „ Esters, like aldehydes and ketones, are weakly acidic. When an ester with an alpha hydrogen is treated with one equivalent of a base such as sodium ethoxide, a reversible condensation reaction occurs to yield a β−keto ester product. This reaction between two ester components is known as the Claisen condensation reaction

a For example, ethyl acetate yield ethyl 3 acetoacetate on treatment with base EtoNa H,O oO C:2 CH3COEt EtoH H + CH2C-CHcOEt EtOH ⑤.乙酸乙酯 乙酰乙酸乙酯 Ethyl acetate Ethyl acetoacetate g Claisen酯缩合:含α氢的酯在碱的作用下 两分子酯发生缩合反应,生成β-羰基酸酯同 时消去一分子醇

Organic Chemistry Organic Chemistry Xiamen Xiamen University University For example, ethyl acetate yield ethyl acetoacetate on treatment with base. CH 3COEt O 2 EtOH EtONa H 2 O H + CH 3 C O CHCOEt O + E t O H 乙酸乙酯 乙酰乙酸乙酯 E thyl acetate Ethyl acetoacetate Claisen 酯缩合 含α−氢的酯在碱的作用下 两分子酯发生缩合反应 生成 β−羰基酸酯同 时消去一分子醇

Mechanism CH3 CO2Et+ EtO-CH2CO2Et EtOH 3. pKa 24-5 CH3-C-OEt +)CH2CO2Et-CHx-C-OEt CH,CO Et 一—CH3-C-CH2CO2Et+EtO O EtO 9CH3-C-CH, CO,= -CH3-C-CHCO2Et+ EtOH pKa 11 CH3C-Ch, Co,Et

Organic Chemistry Organic Chemistry Xiamen Xiamen University University Mechanism CH 3CO 2Et + EtO −










− CH 2CO 2Et + EtOH CH 3 C OE t O − + CH 2CO 2Et


































































CH 3 C O E t O − CH 2CO 2Et








































































CH 3 C CH 2CO 2Et O + EtO − CH 3 C CH 2CO 2Et O






















EtO − CH 3 C − CHCO 2Et O + EtOH











H + CH 3 C C H 2CO 2Et O










pKa 24.5 pKa 11

g只含一个-H的酯缩合时用更强的碱促使 平衡移动 E2(CH3)2CHCO2 C2H5 +(C6H3)CN3 ELO o cH ( CH3)2CH-C-CCO2C2H5 +( C6H5)3CH pKa 36 (C6H5)3C o cH C(CH3)2C-C-CCO2C2H5 CH

Organic Chemistry Organic Chemistry Xiamen Xiamen University University 只含一个α− H的酯缩合时用更强的碱促使 平衡移动 2 (CH 3 ) 2CHCO 2 C 2 H 5 + (C 6 H 5 ) 3 C − Na +

























Et 2 O + (C 6 H 5 ) (C H 3 ) 2CH C CCO 2 C 2 H 5 3 C H O CH 3 CH 3 (C H 3 ) 2 C C CCO 2 C 2 H 5 O CH 3 CH 3














(C 6 H 5 ) 3 C pKa 36

酯缩合反应常用的碱 Ph3CNa/苯,醚 NaH/苯,醚 ③NaNH2/苯,甲苯,醚,液氨 a t-BuoK/t-BuOH 司 EtoNa/EtOH ■RL/醚

Organic Chemistry Organic Chemistry Xiamen Xiamen University University 酯缩合反应常用的碱 „ Ph 3CNa / 苯 醚 „ NaH / 苯 醚 „ NaNH 2 / 苯 甲苯 醚 液氨 „ t-BuOK /t-BuOH „ EtONa /EtOH „ RLi / 醚

Dieckmann condensation Intramolecular claisen condensation can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones Called the Dieckmann condensation the reaction works best on 1, 6-diesters and 1,7 e diesters, and the products of such reactions are five-and six- membered 画ccc阝- keto esters

Organic Chemistry Organic Chemistry Xiamen Xiamen University University Dieckmann Condensation „ Intramolecular Claisen condensation can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones. Called the Dieckmann condensation, the reaction works best on 1,6-diesters and 1,7- diesters, and the products of such reactions are five￾and six-membered cyclic β-keto esters

CO2et EtON/ CO2Et,.+ CO,Et COE苯,80℃ 86% CO,Et CO,Et CO,Et 2 t EtoNa H,O EtoH H 54%

Organic Chemistry Organic Chemistry Xiamen Xiamen University University H +























O CO 2Et O − CO 2Et CO 2Et CO 2Et









EtONa









苯 80 86 O O CO 2Et CO 2Et EtOH EtONa H 2 O H + O O O CO 2Et 54%

不对称二酯的缩合 CH CH CH3 co,et CO,Et EtoNa H,o O O Co,Et Etoh H COEt g反应总是形成热力学稳定的产物为主 ⑨D

Organic Chemistry Organic Chemistry Xiamen Xiamen University University 不对称二酯的缩合 CO 2Et CO 2Et CH 3 EtOH EtONa H 2 O H + CH 3 O CO 2Et CH 3 O CO 2Et 反应总是形成热力学稳定的产物为主

3 Mixed Claisen Condensations q- the mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones. Mixed claisen condensations are generally successful only when one of the two ester components has no alpha hydrogens and thus cant form an enolate ion

Organic Chemistry Organic Chemistry Xiamen Xiamen University University Mixed Claisen Condensations „ The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones.Mixed Claisen condensations are generally successful only when one of the two ester components has no alpha hydrogens and thus can’t form an enolate ion