CHAPTEr EIGHTEEN Enols and enolates FIGURE acid-ca enolization of Overall reaction aqueous solution RCH= CR ldehyde or ketone Step 1: A proton is transferred from the acid catalyst to the carbonyl oxygen H H RCH,CR RCH, CR Aldehyde Hydronium Conjugate acid of Step 2: A water molecule acts as a Bronsted base to remove a proton from the a carbon atom of the protonated aldehyde or ketone H RCH-CR RCH=CR′+H— H Conjugate acid of Water Hydronium CH2= CHOH K≈3×10-7 Acetaldehyde (keto form) CH3CCH3、CH2=CCH3K≈6×10 (keto form) In these and numerous other simple cases, the keto form is more stable than the enol by some 45-60 kJ/mol(11-14 kcal/mol). The chief reason for this difference is that a car- bon-oxygen double bond is stronger than a carbon-carbon double bond With unsymmetrical ketones, enolization may occur in either of two directions: CH,=,CH CH3, CH3 CH3C=CHCH3 I-Buten-2-ol 2-Butanone (keto form) (enol form) The ketone is by far the most abundant species present at equilibrium. Both enols are also present, but in very I concentrations Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
In these and numerous other simple cases, the keto form is more stable than the enol by some 45–60 kJ/mol (11–14 kcal/mol). The chief reason for this difference is that a carbon–oxygen double bond is stronger than a carbon–carbon double bond. With unsymmetrical ketones, enolization may occur in either of two directions: The ketone is by far the most abundant species present at equilibrium. Both enols are also present, but in very small concentrations. 2-Butanone (keto form) CH3CCH2CH3 O 2-Buten-2-ol (enol form) CH3C CHCH3 OH 1-Buten-2-ol (enol form) CH2 CCH2CH3 OH Acetaldehyde (keto form) CH3CH O Vinyl alcohol (enol form) CH2 CHOH K 3 107 Acetone (keto form) CH3CCH3 O Propen-2-ol (enol form) CH2 CCH3 OH K 6 109 706 CHAPTER EIGHTEEN Enols and Enolates Overall reaction: Step 1: A proton is transferred from the acid catalyst to the carbonyl oxygen. RCH2CR Aldehyde or ketone Aldehyde or ketone Enol fast O X RCH2CR H±O RCH2CR O H3O RCHœCR OH W Enol RCHœCR H±O O±H W Hydronium ion Conjugate acid of carbonyl compound Water Step 2: A water molecule acts as a Brønsted base to remove a proton from the carbon atom of the protonated aldehyde or ketone. Hydronium ion O±H X O X H H ± ± H H ± ± H H ± RCH±CR O ± Conjugate acid of carbonyl compound Water O±H X H H ± ± BNA BNA slow BNA W H FIGURE 18.1 Mechanism of acid-catalyzed enolization of an aldehyde or ketone in aqueous solution. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
18.5 Stabilized enols PROBLEM 18.5 Write structural formulas corresponding to (a) The enol form of 2, 4-dimethyl-3-pentanone b)The enol form of acetophe (c) The two enol forms of 2-methylcyclohexanone SAMPLE SOLUTION(a) Remember that enolization involves the a- carbon atom The ketone 2, 4-dimethyl-3-pentanone gives a single enol, since the two a carbons are equivalent. (CH3)2 CHCCH(CH3)2 (CH3)2C-CCH(CH3)2 2, 4-Dimethyl-3-pentanone 2, 4-Dimethyl-2-penten-3-ol (keto form) (enol form) It is important to recognize that an enol is a real substance, capable of indepen dent existence. An enol is not a resonance form of a carbonyl compound; the two are constitutional isomers of each other 18.5 STABILIZED ENOLS Certain structural features can make the keto-enol equilibrium more favorable by stabi lizing the enol form. Enolization of 2, 4-cyclohexadienone is one such example K is too large to measure. (keto form, not one Phenol (enol form, aromatic The enol is phenol, and the stabilization gained by forming an aromatic ring is more than enough to overcome the normal preference for the keto form. A 1, 3 arrangement of two carbonyl groups(compounds called B-diketones) leads to a situation in which the keto and enol forms are of comparable stability CH3CCHCCH3 F CH3C=CHCCH3 K= 4 2, 4-Pentanedione(20%o 4-Hydroxy-3-penten-2-one(80%c The two most important structural features that stabilize the enol of a B-dicarbonyl com pound are(1)conjugation of its double bond with the remaining carbonyl group and (2) the presence of a strong intramolecular hydrogen bond between the enolic hydroxyl group and the carbonyl oxygen(Figure 18.2) involved in enolization. The alternative enoy p flanked by the two carbonyls that is In B-diketones it is the methylene grou CH=CCH,CCH 4-Hydroxy-4-penten-2- Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 18.5 Write structural formulas corresponding to (a) The enol form of 2,4-dimethyl-3-pentanone (b) The enol form of acetophenone (c) The two enol forms of 2-methylcyclohexanone SAMPLE SOLUTION (a) Remember that enolization involves the -carbon atom. The ketone 2,4-dimethyl-3-pentanone gives a single enol, since the two carbons are equivalent. It is important to recognize that an enol is a real substance, capable of independent existence. An enol is not a resonance form of a carbonyl compound; the two are constitutional isomers of each other. 18.5 STABILIZED ENOLS Certain structural features can make the keto–enol equilibrium more favorable by stabilizing the enol form. Enolization of 2,4-cyclohexadienone is one such example: The enol is phenol, and the stabilization gained by forming an aromatic ring is more than enough to overcome the normal preference for the keto form. A 1,3 arrangement of two carbonyl groups (compounds called -diketones) leads to a situation in which the keto and enol forms are of comparable stability. The two most important structural features that stabilize the enol of a -dicarbonyl compound are (1) conjugation of its double bond with the remaining carbonyl group and (2) the presence of a strong intramolecular hydrogen bond between the enolic hydroxyl group and the carbonyl oxygen (Figure 18.2). In -diketones it is the methylene group flanked by the two carbonyls that is involved in enolization. The alternative enol 4-Hydroxy-4-penten-2-one CH2 CCH2CCH3 OH O 2,4-Pentanedione (20%) (keto form) CH3CCH2CCH3 O O 4-Hydroxy-3-penten-2-one (80%) (enol form) CH3C CHCCH3 OH O K 4 K is too large to measure. O 2,4-Cyclohexadienone (keto form, not aromatic) OH Phenol (enol form, aromatic) 2,4-Dimethyl-3-pentanone (keto form) (CH3)2CHCCH(CH3)2 O 2,4-Dimethyl-2-penten-3-ol (enol form) (CH3)2C CCH(CH3)2 OH 18.5 Stabilized Enols 707 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTEr EIGHTEEN Enols and enolates FIGURE 18.2(a) molecular model and (b) bond istances in the enol form of 103pm intramolecular hydrogen H bond is 166 pm 133pm 124pm CH 134pm 141 pr does not have its carbon-carbon double bond conjugated with the carbonyl group, is not as stable, and is present in negligible amounts at equilibrium PROBLEM 18.6 Write structural formulas corresponding to (a) the two most stable enol forms of CHa CCH2CH (b)The two most stable enol forms of 1-phenyl-1, 3-butanedione SAMPLE SOLUTION (a)Enolization of this 1, 3-dicarbonyl compound can involve either of the two carbonyl groups: CH3CCH2CH CHaC、∠CH CH3C Both enols have their carbon-carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond. they are of comparable stability. 18.6 BASE-CATALYZED ENOLIZATION: ENOLATE ANIONS The proton-transfer equilibrium that interconverts a carbonyl compound and its enol can be catalyzed by bases as well as by acids. Figure 18.3 illustrates the roles of hydroxide ion and water in a base-catalyzed enolization. As in acid-catalyzed enolization, protons are transferred sequentially rather than in a single step. First(step 1), the base abstracts Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
does not have its carbon–carbon double bond conjugated with the carbonyl group, is not as stable, and is present in negligible amounts at equilibrium. PROBLEM 18.6 Write structural formulas corresponding to (a) The two most stable enol forms of (b) The two most stable enol forms of 1-phenyl-1,3-butanedione SAMPLE SOLUTION (a) Enolization of this 1,3-dicarbonyl compound can involve either of the two carbonyl groups: Both enols have their carbon–carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond. They are of comparable stability. 18.6 BASE-CATALYZED ENOLIZATION: ENOLATE ANIONS The proton-transfer equilibrium that interconverts a carbonyl compound and its enol can be catalyzed by bases as well as by acids. Figure 18.3 illustrates the roles of hydroxide ion and water in a base-catalyzed enolization. As in acid-catalyzed enolization, protons are transferred sequentially rather than in a single step. First (step 1), the base abstracts CH O H O CH3C C H CH O H O CH3C C H CH3CCH2CH O O CH3CCH2CH O X O X 708 CHAPTER EIGHTEEN Enols and Enolates (a) C C CH3 O H C O CH3 H O---H separation in intramolecular hydrogen bond is 166 pm 124 pm 103 pm 133 pm 134 pm 141 pm (b) FIGURE 18.2 (a) A molecular model and (b) bond distances in the enol form of 2,4-pentanedione. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
18.6 Base-Catalyzed Enolization: Enolate Anions FIGURE 18. 3 Mechanism of Overall reaction the base-catalyzed enoliza- OH ketone in aqueous solution RCH2CR′ RCHECR Aldehyde or ketone Step 1: A proton is abstracted by hydroxide ion from the a carbon atom of the H H RCH-CR RCH一 Aldehyde Conjugate base of Water or ketone arbonyl compound Step 2: A water molecule acts as a Bronsted acid to transfer a proton to the oxygen of the enolate ion O—H RCH=CR′+:O RCH=CR’ Hydroxide carbonyl compound a proton from the a-carbon atom to yield an anion. This anion is a resonance-stabilized ecies. Its negative charge is shared by the a-carbon atom and the carbonyl oxygen. RCH-CR′←>RCH=CR Electron delocalization Protonation of this anion can occur either at the a carbon or at oxygen. Protonation of the a carbon simply returns the anion to the starting aldehyde or ketone Protonation of oxygen, as shown in step 2 of Figure 18.3, produces the enol The key intermediate in this process, the conjugate base of the carbonyl compound, Examine the enolate of is referred to as an enolate ion, since it is the conjugate base of an enol. The term"eno- tone on Learning By Model- late"is more descriptive of the electron distribution in this intermediate in that oxygen ing. How is the negative bears a greater share of the negative charge than does the a-carbon atom. harge distributed between oxygen and the a carbon The slow step in base-catalyzed enolization is formation of the enolate ion. The second step, proton transfer from water to the enolate oxygen, is very fast, as are almost all proton transfers from one oxygen atom to another. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
a proton from the -carbon atom to yield an anion. This anion is a resonance-stabilized species. Its negative charge is shared by the -carbon atom and the carbonyl oxygen. Protonation of this anion can occur either at the carbon or at oxygen. Protonation of the carbon simply returns the anion to the starting aldehyde or ketone. Protonation of oxygen, as shown in step 2 of Figure 18.3, produces the enol. The key intermediate in this process, the conjugate base of the carbonyl compound, is referred to as an enolate ion, since it is the conjugate base of an enol. The term “enolate” is more descriptive of the electron distribution in this intermediate in that oxygen bears a greater share of the negative charge than does the -carbon atom. The slow step in base-catalyzed enolization is formation of the enolate ion. The second step, proton transfer from water to the enolate oxygen, is very fast, as are almost all proton transfers from one oxygen atom to another. RCH CR O RCH CR O Electron delocalization in conjugate base of ketone 18.6 Base-Catalyzed Enolization: Enolate Anions 709 Overall reaction: Step 1: A proton is abstracted by hydroxide ion from the carbon atom of the carbonyl compound. RCH2CR Aldehyde or ketone Aldehyde or ketone Enol slow O X RCH±CR O RCH±CR O HO RCHœCR OH W Enol RCHœCR O O±H W Hydroxide ion Conjugate base of carbonyl compound Water Step 2: A water molecule acts as a Brønsted acid to transfer a proton to the oxygen of the enolate ion. Hydroxide ion O X O X H ± H H ± ± H RCHœCR O ± Conjugate base of carbonyl compound Water O W H H ± ± BNA BNA fast BNA W H FIGURE 18.3 Mechanism of the base-catalyzed enolization of an aldehyde or ketone in aqueous solution. Examine the enolate of acetone on Learning By Modeling. How is the negative charge distributed between oxygen and the carbon? Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
710 CHAPTEr EIGHTEEN Enols and enolates Our experience to this point has been that C-H bonds are not very acidic. Com- pared with most hydrocarbons, however, aldehydes and ketones have relatively acidic protons on their a-carbon atoms. Equilibrium constants for enolate formation from sim- ple aldehydes and ketones are in the 10 to 10- range(pKa= 16-20) (CH3)CHCH H++(CH3)2C=CHKa=3×10-16 2-Methylpropanal CsHsCCH3、H+C6HC=CH2Ka=1.6×10 Acetophenone (pKa=158) Delocalization of the negative charge onto the electronegative oxygen is responsi ble for the enhanced acidity of aldehydes and ketones. With Kas in the 10 to 10 range, aldehydes and ketones are about as acidic as water and alcohols. Thus, hydrox ide ion and alkoxide ions are sufficiently strong bases to produce solutions containing ignificant concentrations of enolate ions at equilibrium Diketones, such as 2, 4-pentanedione, are even more acidic contains molecular models of CH3 CCH, CCH3eH'+CH3C=CHCCH3 K=10 the enolates of acetone and 24. with respect to the distribution In the presence of bases such as hydroxide, methoxide, and ethoxide, these B-diketones are converted completely to their enolate ions. Notice that it is the methylene group ranked by the two carbonyl groups that is deprotonated. Both carbonyl groups partici pate in stabilizing the enolate by delocalizing its negative charge HC CH HC HIC CH H H PROBLEM 18.7 Write the structure of the enolate ion derived from each of the following B-dicarbonyl compounds. Give the three most stable resonance forms of each enolate (a)2-Methyl-1, 3-cyclopentanedione (b)1-Phenyl-13-butanedione SAMPLE SOLUTION (a) First identify the proton that is removed by the base. It is on the carbon between the two carbonyl groups. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Our experience to this point has been that C±H bonds are not very acidic. Compared with most hydrocarbons, however, aldehydes and ketones have relatively acidic protons on their -carbon atoms. Equilibrium constants for enolate formation from simple aldehydes and ketones are in the 1016 to 1020 range (pKa 16–20). Delocalization of the negative charge onto the electronegative oxygen is responsible for the enhanced acidity of aldehydes and ketones. With Ka’s in the 1016 to 1020 range, aldehydes and ketones are about as acidic as water and alcohols. Thus, hydroxide ion and alkoxide ions are sufficiently strong bases to produce solutions containing significant concentrations of enolate ions at equilibrium. -Diketones, such as 2,4-pentanedione, are even more acidic: In the presence of bases such as hydroxide, methoxide, and ethoxide, these -diketones are converted completely to their enolate ions. Notice that it is the methylene group flanked by the two carbonyl groups that is deprotonated. Both carbonyl groups participate in stabilizing the enolate by delocalizing its negative charge. PROBLEM 18.7 Write the structure of the enolate ion derived from each of the following -dicarbonyl compounds. Give the three most stable resonance forms of each enolate. (a) 2-Methyl-1,3-cyclopentanedione (b) 1-Phenyl-1,3-butanedione (c) SAMPLE SOLUTION (a) First identify the proton that is removed by the base. It is on the carbon between the two carbonyl groups. CH O O H3C C C H C CH3 O O H3C C C H C CH3 O O H3C C O C H C CH3 O CHCCH3 O CH3C O H Ka 109 (pKa 9) CH3CCH2CCH3 O O (CH3)2C CH O H Ka 3 1016 (pKa 15.5) (CH3)2CHCH O 2-Methylpropanal C6H5C CH2 O H Ka 1.6 1016 (pKa 15.8) C6H5CCH3 O Acetophenone 710 CHAPTER EIGHTEEN Enols and Enolates Learning By Modeling contains molecular models of the enolates of acetone and 2,4- pentanedione. Compare the two with respect to the distribution of negative charge. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website