ch18 lecture 1 march 7

ch18 lecture 1 march 7 - Chapter 18 Enols and Enolates 18.1...

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Unformatted text preview: Chapter 18 Enols and Enolates 18.1 Terminology O CH3CH CH CH The reference atom is the carbonyl carbon. Other carbons are designated , , , etc. on the basis of their position with respect to the carbonyl carbon. Hydrogens take the same Greek letter as the carbon to which they are attached. 2 2 Acidity of -Hydrogen O R2C H enolate ion pKa = 16-20 R2C O CR' R2C O CR' + H+ CR' Acidity of -Hydrogen O (CH3)2CHCH O CCH3 pKa = 15.5 pKa = 18.3 -Diketones are much more acidic O H3C C H C O C H CH3 pKa = 9 O H3C C C H O C CH3 + H+ -Diketones are much more acidic O H3C C O C H O C CH3 enolate of -diketone is stabilized; negative charge is shared by both oxygens O H3C C C H C CH3 -Diketones are much more acidic O H3C C O C H O C O CH3 H3C C O C H C CH3 O H3C C C H C CH3 18.2 aldol condensation O RCH2CH + OH pKa = 16-20 O RCHCH + HOH pKa = 16 A basic solution contains comparable amounts of the aldehyde and its enolate. Aldehydes undergo nucleophilic addition. Enolate ions are nucleophiles. What about nucleophilic addition of enolate to aldehyde? O RCHCH O RCHCH RCH2CH O O RCHCH RCH2CH OH RCH2CH O O 2RCH2CH NaOH RCH2CH OH O CHCH R Aldol Addition O RCH2CH OH CHCH R product is called an "aldol" because it is both an aldehyde and an alcohol Aldol Addition of Acetaldehyde O 2CH3CH NaOH, H2O 5C CH3CH OH Acetaldol (50%) O CH2CH Aldol Addition of Butanal O 2CH3CH2CH2CH KOH, H2O 6C O CH3CH2CH2CH OH (75%) CHCH CH2CH3 Aldol Condensation O 2RCH2CH NaOH RCH2CH OH O CHCH R Aldol Condensation O 2RCH2CH NaOH RCH2CH OH NaOH heat RCH2CH O CHCH R heat O CCH R Aldol Condensation of Butanal O 2CH3CH2CH2CH NaOH, H2O 80-100C O CH3CH2CH2CH (86%) CCH CH2CH3 Dehydration of Aldol Addition Product H C C O C C O C OH C dehydration of -hydroxy aldehyde can be catalyzed by either acids or bases Dehydration of Aldol Addition Product H C C O NaOH C C O C OH C OH in base, the enolate is formed Dehydration of Aldol Addition Product H C C O NaOH C C O C OH C OH the enolate loses hydroxide to form the , -unsaturated aldehyde Aldol reactions of ketones O 2CH3CCH3 2% 98% OH O CH3CCH2CCH3 CH3 the equilibrium constant for aldol addition reactions of ketones is usually unfavorable Intramolecular Aldol Condensation O O Na2CO3, H2O heat O via: OH (96%) O Intramolecular Aldol Condensation O O Na2CO3, H2O heat (96%) even ketones give good yields of aldol condensation products when the reaction is intramolecular O Mixed aldol condensations O O NaOH CH3CH + CH3CH2CH There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. What is the product? O O O CH3CH O CH2CH CH3CH + CH3CH2CH CH2CH O CH3CHCH OH What is the product? O O O CH3CH2CH O CH2CH CH3CH + CH3CH2CH CHCH CH3 O CH3CHCH OH What is the product? O O O CH3CH O CH2CH CH3CH + CH3CH2CH CHCH CH3 O CH3CHCH OH What is the product? O O O CH3CH2CH O CH2CH CH3CH + CH3CH2CH CH2CH O CH3CHCH OH In order to effectively carry out a mixed aldol condensation: need to minimize reaction possibilities usually by choosing one component that cannot form an enolate Formaldehyde O HCH formaldehyde cannot form an enolate formaldehyde is extremely reactive toward nucleophilic addition Formaldehyde O O K2CO3 waterether O (CH3)2CHCHCH CH OH (52%)2 HCH + (CH3)2CHCH2CH Aromatic Aldehydes O CH3O CH aromatic aldehydes cannot form an enolate Aromatic Aldehydes O CH3O CH + NaOH, H2O O CH3CCH3 30C O CH3O CH CHCCH3 (83%) Alkylation of enolates using SN2 rxns Enolate ions are nucleophiles and react with alkyl halides. However, alkylation of simple enolates does not work well. Enolates derived from -diketones can be alkylated efficiently. Example O O + CH3I K2CO3 O O CH3CCH2CCH3 CH3CCHCCH3 CH3 (75-77%) 18.5 Mechanism of Halogenation Two stages: first stage is conversion of aldehyde or ketone to the corresponding enol; is ratedetermining second stage is reaction of enol with halogen; is faster than the first stage now examine first stage Mechanism of Enolization (In general) H H O H O H O R2C H CR' R2C O H CR' Mechanism of Enolization (Base-catalyzed) O O H R2C H CR' Mechanism of Enolization (Base-catalyzed) O H H O R2C O H CR' H Mechanism of Enolization (Base-catalyzed) O H H O R2C CR' Mechanism of Enolization (Base-catalyzed) R2C O H O H CR' Mechanism of Enolization (Acid-catalyzed) H H O R2C H CR' O + H Mechanism of Enolization (Acid-catalyzed) + O R2C H CR' H H O H Mechanism of Enolization (Acid-catalyzed) + O H O H H R2C H CR' Mechanism of Enolization (Acid-catalyzed) H + O H R2C H O H CR' Enol Content O R2CHCR' keto percent enol is usually very small keto form usually 45-60 kJ/mol more stable than enol OH R2C CR' enol Enol Content Acetaldehyde O CH3CH H2C OH CH K = 3 x 10-7 Acetone O CH3CCH3 H2C OH CCH3 K = 6 x 10-9 18.6 2,4-Cyclohexadienone O H H H H H H H H OH H H H keto form is less stable than enol form keto form is not aromatic enol form is aromatic 1,3-Diketones (also called -diketones) Example: 2,4-pentanedione O O OH CH3C O CHCCH3 CH3CCH2CCH3 (20%) (80%) keto form is less stable than enol form Enol form of 2,4-pentanedione Enol form of 2,4-pentanedione intramolecular hydrogen bond 103 pm H O 133 pm C H3C 134 pm C H C=C and C=O are conjugated C 141 pm CH3 166 pm O 124 pm 18.7 O R2CCR' + H General Reaction O X 2 H+ R2CCR' + X HX X is Cl2, Br2, or I2. 2 Substitution is specific for replacement of hydrogen. Catalyzed by acids. One of the products is an acid (HX); the reaction is autocatalytic. Not a free-radical reaction. Example O + Cl 2 O H2O Cl + HCl (61-66%) Example O CH H + Br 2 O CHCl3 CH Br + HBr (80%) Notice that it is the proton on the carbon that is replaced, not the one on the carbonyl carbon. 18.8 Mechanism of Halogenation Experimental Facts specific for replacement of H at the carbon equal rates for chlorination, bromination, and iodination first order in ketone; zero order in halogen Interpretation no involvement of halogen until after the rate-determining step Mechanism of Halogenation Two stages: first stage is conversion of aldehyde or ketone to the corresponding enol; is ratedetermining second stage is reaction of enol with halogen; is faster than the first stage Mechanism of Halogenation O RCH2CR' slow RCH OH CR' X fast 2 O RCHCR' X enol Enol is key intermediate Mechanism of Halogenation Two stages: first stage is conversion of aldehyde or ketone to the corresponding enol; is ratedetermining second stage is reaction of enol with halogen; is faster than the first stage examine second stage first Reaction of enol with Br2 OH OH R2C Br CR' R2C Br CR' + Br + Br carbocation is stabilized by electron release from oxygen + OH R2C Br CR' Loss of proton from oxygen completes the process H O R2C Br Br +O R2C Br Br H CR' CR' ...
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