厦门大学化学化工学院：《有机化学》课程教学资源（课件讲稿，英文版）Chapter 17 Aldehydes and Ketones II. Aldol Reactions（17.4-17.6）The Aldol Reaction：The Addition of Enolate Anions to Aldehydes and Ketones

ORGANIC CHEMISTRY Chapter 17 17. 4 The Aldol reaction: The addition of Enolate anions to aldehydes and stones Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.4 The Aldol Reaction: The Addition of Enolate Anions to Aldehydes and Ketones

ORGANIC CHEMISTRY Chapter 17 10% NaoH. H,o OH 2 CHCHO ChrCHCHoCHo 3-Hydroxybutanal (50%) B-hydroxyaldehyde Aldol addition(aldol reaction) ("aldol") OH Naoh 2 PhChoCHO PhCh,CH— CHCHO Etoh Ph 90 Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 Aldol addition (aldol reaction) 2 CH3CHO CH3CHCH2CHO OH 10% NaOH, H2O 5°C 3-Hydroxybutanal (50%) β−hydroxyaldehyde ("aldol") 2 PhCH2CHO PhCH2CH OH CHCHO Ph 90% EtOH NaOH

ORGANIC CHEMISTRY Chapter 17 Mechanism CH2-C一H=CH2-C-H CH=C-H+ H-OH H OH CH3 H + CH,-C-H CH,=C-H H-OH OH CH3CH一CH2-C-H—CH3CH-CH2-C-H+OH Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 Mechanism Mechanism OH CH2 C H O H CH2 C H O CH2 C H O + CH2 C H O CH3 C H O + CH3 CH O CH2 C H O CH2 C H O H OH CH3 CH OH CH2 C H O + OH H OH

ORGANIC CHEMISTRY Chapter 17 17. 4a Dehydration of the aldol Addition product g The aldols formed in aldol additions can be easily dehydrated to yield conjugated enals(enones). oH O h or oh + h2o H An aldo A conjugated enal(enone) Aldol condensation -A condensation reaction is one in which molecules are joined through the intermolecular elimination of a small molecule such as water or an alcohol Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.4A Dehydration of the Aldol Addition Product The aldols formed in aldol additions can be easily dehydrated to yield conjugated enals (enones). C OH C C O H C C C O H+ or OH ∆ + H2O An aldol A conjugated enal (enone) Aldol condensation — A condensation reaction is one in which molecules are joined through the intermolecular elimination of a small molecule such as water or an alcohol

ORGANIC CHEMISTRY Chapter 17 Mechanism OH CH3 -CHTCH-C-H CH2ch=ch-C-H OH + H-oh oh o The conditions needed for aldol dehydration are often only a bit more vigorous(slightly higher temperature for example)than the conditions needed for the aldol dimerization itself o As a result, conjugated enals(enones are often obtained directly from aldol reactions and the intermediate B-hydroxy carbonyl compounds arent usually isolated Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 Mechanism Mechanism CH3 CH OH CH C H O OH H CH3 CH CH C H O + H OH + OH The conditions needed for aldol dehydration are often only a bit more vigorous (slightly higher temperature, for example) than the conditions needed for the aldol dimerization itself. As a result, conjugated enals (enones) are often obtained directly from aldol reactions, and the intermediate β-hydroxy carbonyl compounds aren’t usually isolated

ORGANIC CHEMISTRY Chapter 17 17.4b Synthetic applications OH OH OH Nabh 2RCH’CHO RCHoCH-CHCHO RCHoCH-CHCHOH HO R R Aldehyde An aldol HA a13-diol HoO RCHOCH=CCHO H2/N R high LiAIH4 pressure An a B-unsaturated aldehyde H/Pd-C RCH,,oH RCH2 CH2-CHCHO RCH,CH=CCH,OH R R R A saturated alcohol An aldehyde An allylic alcohol Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.4B Synthetic Applications 2 RCH2CHO OH H2O RCH2CH CHCHO R OH NaBH4 RCH2CH CHCH2OH R OH Aldehyde An aldol HA A 1,3-diol H2O RCH2CH CCHO R LiAlH4 RCH2CH CCH2OH R H2/Ni high pressure RCH2CH2 CHCH2OH R H2/Pd-C RCH2CH2 CHCHO R A saturated alcohol An α,β-unsaturated aldehyde An aldehyde An allylic alcohol

ORGANIC CHEMISTRY Chapter 17 17. 4C The reversibility of Aldol Additions o The aldol addition is reversible- retro-aldol reaction OH OH CH3-C-CH2-C-CH3-CH3-C-CH2-C-CH HO CH CH (5%) H2O CH3 -C CH2-C-CH3 2 CH3-C-CH3 OH CH (95% Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.4C The Reversibility of Aldol Additions The aldol addition is reversible — retro-aldol reaction. CH3 C OH CH2 C CH3 O OH + CH3 CH3 C O CH2 C CH3 O CH3 H2O CH3 C O CH3 CH3 C CH3 O CH2 C CH3 O OH H2O (5%) 2 (95%)

ORGANIC CHEMISTRY Chapter 17 17.4D Acid-Catalyzed Aldol Condensations +OH OH H CH3C-CH2=CH3C一CH CH3-C-CH3 + tOH OH OH CH2-c--ch CH3-C=CH, CH2-c--ch +OH OH CH3C一CH H CH3-C-CH2-C-CH3 CH Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.4D Acid-Catalyzed Aldol Condensations CH3 C CH3 O CH3 C CH3 OH CH3 C CH3 OH CH3 C CH2 OH CH3 C CH3 OH CH3 C CH3 OH CH3 C CH2 OH CH3 C CH2 OH C O CH3 CH3 H+ H+ H+

ORGANIC CHEMISTRY Chapter 17 17.5 Crossed Aldol reactions Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 17.5 Crossed Aldol Reactions

ORGANIC CHEMISTRY Chapter 17 OH CH3CHO CH&&CH,CHO HO OH OH CH3CH-CHCHO+ CH? CH2CH--CHCHO CH OH OH CH3CH-CHCHO+ CH3 CH CH-CHOCHO CH3 Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 17 CH3CHO + CH3CH2CHO CH3CH CH2CHO OH CH3CH CHCHO OH CH3 CH3CH2CH CHCHO OH CH3 CH3CH2CH CH2CHO OH OH H2O + + +