21_01_06 - Chapter 21 Chapter Ester Enolates 21.1 21.1...

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Unformatted text preview: Chapter 21 Chapter Ester Enolates 21.1 21.1 Ester α-Hydrogens and Their pKa’s Introduction Introduction O OR H H O OR H O OR Hydrogens α to an ester carbonyl group are less to acidic, pKa ≅ 24, than α of aldehydes and 24, of ketones, pKa ≅ 16-20. 16 The decreased acidity is due the decreased electron withdrawing ability of an ester carbonyl. Electron delocalization decreases the positive character of the ester carbonyl group. Introduction Introduction O R C H C O C H OR' The preparation and reactions of β-dicarbonyl compounds, especially β-keto esters, is the main focus of this chapter. A proton on the carbon flanked by the two carbonyl groups is relatively acidic, easily and quantitatively removed by alkoxide ions. Introduction Introduction O R C C O C H OR' pKa ~ 11 11 H – CH3CH2O CH O R C –C H •• O C OR' Introduction Introduction •• •• O• • R C –C H •• •O • –• •• • • O• OR' R C C H •O • •• C C OR' The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups. Introduction Introduction •• •• •• •• – •O • •• O• • R C –C H •• •O • O• • OR' R C C H C C OR' The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups. 21.2 21.2 The Claisen Condensation The Claisen Condensation The O 2RCH2COR' COR' 1. NaOR' 2. H3O+ O O RCH2CCHCOR' + R'OH CCHCOR' R β-Keto esters are made by the reaction shown, which is called the Claisen condensation. Ethyl esters are typically used, with sodium ethoxide as the base. Example Example O 2CH3COCH2CH3 COCH CH 1. NaOCH2CH3 CH 2. H3O+ O O CH3CCH2COCH2CH3 CCH COCH CH (75%) Product from ethyl acetate is called ethyl ethyl acetoacetate or acetoacetic ester. or acetoacetic Another example Another O 2CH3CH2COCH2CH3 CH COCH CH Reaction involves bond formation between the αcarbon atom of one ethyl propanoate molecule and the carbonyl carbon of the other. 1. NaOCH2CH3 CH 2. H3O+ O O CH3CH2CCHCOCH2CH3 CH CH CH3 (81%) 21.3 21.3 Intramolecular Claisen Condensation: The Dieckmann Reaction Example O O CH3CH2OCCH2CH2CH2CH2COCH2CH3 CH CH OCCH CH CH CH COCH CH 1. NaOCH2CH3 CH 2. H3O+ O O COCH2CH3 COCH CH (74-81%) via O• • •• O CH3CH2OCCH2CH2CH2CH2COCH2CH3 CH CH OCCH CH CH COCH CH NaOCH2CH3 CH O• • •• O• • •• – CH3CH2OCCH2CH2CH2CHCOCH2CH3 CH OCCH CH CH CH •• via via CH3CH2O CH •• •• •• • O •– • • •• O• • C C H2C H2C CHCOCH2CH3 CH CH2 O• • •• O• • •• – CH3CH2OCCH2CH2CH2CHCOCH2CH3 CH OCCH CH CH CH •• via via CH3CH2O CH •• •• •• • O •– • • •• O• • C C H2C H2C CHCOCH2CH3 CH CH2 via via CH3CH2O CH •• •• •• • O •– • • •• O• • C C H2C H2C CHCOCH2CH3 CH CH2 •• •O • •• – CH3CH2O • CH CH • •• C + H2C H2C O• • CHCOCH2CH3 CH CH2 •• 21.4 21.4 Mixed Claisen Condensations Mixed Claisen Condensations Mixed As with mixed aldol condensations, mixed Claisen condensations are best carried out when the reaction mixture contains one compound that can form an enolate and another that cannot. Mixed Claisen Condensations Mixed These types of esters cannot form an enolate. O HCOR O ROCOR O ROC O COR COR O COR Example Example O O COCH3 + CH3CH2COCH3 COCH 1. NaOCH3 2. H3O+ O O (60%) CCHCOCH3 CH3 21.5 21.5 Acylation of Ketones with Esters Acylation of Ketones with Esters Acylation Esters that cannot form an enolate can be used to acylate ketone enolates. Example Example O O CH3CH2OCOCH2CH3 CH CH 1. NaH 2. H3O+ O O COCH2CH3 CH (60%) + Example Example O COCH2CH3 + CH O CH3C 1. NaOCH2CH3 1. CH 2. H3O+ O O CCH2C (62-71%) Example Example O O CH3CH2CCH2CH2COCH2CH3 CH CCH CH COCH CH 1. NaOCH3 2. H3O+ O CH3 O (70-71%) 21.6 21.6 Ketone Synthesis via β-Keto Esters Ketone Synthesis Ketone O O O RCH2CCH2R + CO2 CCH RCH2CCHCOH CCHCOH R β-Keto acids decarboxylate readily to give ketones (Section 19.17). Ketone Synthesis Ketone O O H2O O O RCH2CCHCOR' CCHCOR' RCH2CCHCOH + R'OH CCHCOH R R β-Keto acids decarboxylate readily to give ketones (Section 19.17). β-Keto acids are available by hydrolysis of βketo esters. Ketone Synthesis Ketone O 2RCH2COR' COR' 1. NaOR' 2. H3O+ O O RCH2CCHCOR' + R'OH CCHCOR' R β-Keto acids decarboxylate readily to give ketones (Section 19.17). β-Keto acids are available by hydrolysis of βketo esters. β-Keto esters can be prepared by the Claisen condensation. Example Example O 2 CH3CH2CH2CH2COCH2CH3 CH CH CH COCH CH 1. NaOCH2CH3 CH 2. H3O+ O O CH3CH2CH2CH2CCHCOCH2CH3 CH CH CH CCHCOCH CH CH2CH2CH3 CH CH (80%) Example Example O O CH3CH2CH2CH2CCHCOH CH CH CH CCHCOH CH2CH2CH3 CH CH 1. KOH, H2O, 70-80°C O, 2. H3O+ O O CH3CH2CH2CH2CCHCOCH2CH3 CH CH CH CCHCOCH CH CH2CH2CH3 CH CH Example Example O O CH3CH2CH2CH2CCHCOH CH CH CH CCHCOH CH2CH2CH3 CH CH 70-80°C O CH3CH2CH2CH2CCH2CH2CH2CH3 CH CH CH CCH CH CH CH (81%) Last Slide ...
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This note was uploaded on 04/23/2010 for the course CHEM CHEM2220 taught by Professor Andreana during the Fall '10 term at Wayne State University.

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