CHAPTER 18 ENOLS AND ENOLATES n the preceding chapter you learned that nucleophilic addition to the carbonyl group is one of the fundamental reaction types of organic chemistry. In addition to its own reactivity, a carbonyl group can affect the chemical properties of aldehydes and ketones other ways. Aldehydes and ketones are in equilibrium with their enol isomers RoCHCR′、RC=CR′ In this chapter you'll see a number of processes in which the enol, rather than the alde hyde or a ketone, is the reactive species. There is also an important group of reactions in which the carbonyl group acts as a powerful electron-withdrawing substituent, increasing the acidity of protons on the adjacent carbons R2CCR This proton is far more acidic than a hydrogen in an alkane Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
701 CHAPTER 18 ENOLS AND ENOLATES I n the preceding chapter you learned that nucleophilic addition to the carbonyl group is one of the fundamental reaction types of organic chemistry. In addition to its own reactivity, a carbonyl group can affect the chemical properties of aldehydes and ketones in other ways. Aldehydes and ketones are in equilibrium with their enol isomers. In this chapter you’ll see a number of processes in which the enol, rather than the aldehyde or a ketone, is the reactive species. There is also an important group of reactions in which the carbonyl group acts as a powerful electron-withdrawing substituent, increasing the acidity of protons on the adjacent carbons. This proton is far more acidic than a hydrogen in an alkane. R2CCR H O Aldehyde or ketone R2CHCR O Enol R2C CR OH Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTEr EIGHTEEN Enols and enolates As an electron-withdrawing group on a carbon-carbon double bond, a carbonyl group renders the double bond susceptible to nucleophilic attack: R,C=CHCR Normally, carbon-carbon double bonds are attacked by electrophiles; a carbon-carbon double bond that is conjugated to a carbonyl group is attacked by nucleophiles. The presence of a carbonyl group in a molecule makes possible a number of chem- ical reactions that are of great synthetic and mechanistic importance. This chapter is com- plementary to the preceding one; the two chapters taken together demonstrate the extra- ordinary range of chemical reactions available to aldehydes and ketones. 18.1 THE Q-CARBON ATOM AND ITS HYDROGENS It is convenient to use the Greek letters a, B, Y, and so forth, to locate the carbons in a molecule in relation to the carbonyl group. The carbon atom adjacent to the carbonyl is the a-carbon atom, the next one down the chain is the B carbon, and so on. Butanal, for example, has an a carbon, a p carbon, and a y carbon Carbonyl group CH3CH,CH,CH no greek letter assigned to Hydrogens take the same Greek letter as the carbon atom to which they are attached. A hydrogen connected to the a-carbon atom is an a hydrogen. Butanal has two a protons, two B protons, and three y protons. No Greek letter is assigned to the hydro- gen attached directly to the carbonyl group of an aldehyde PROBLEM 18.1 How many a hydrogens are there in each of the following? (a)3, 3-Dimethyl-2-butanon (c) Benzyl methyl ketone (b)2, 2-Dimethylpropanal SAMPLE SOLUTION (a) This ketone has two different a carbons, but only one of them has hydrogen substituents. There are three equivalent a hydrogens. the other nine hydrogens are attached to B-carbon atoms CH3-C--C--CH3 3, 3-Dimethyl-2-butanone her than nucleophilic addition to the carbonyl group, the most important reac- tions of aldehydes and ketones involve substitution of an a hydrogen. A particularly well studied example is halogenation of aldehydes and ketones Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
As an electron-withdrawing group on a carbon–carbon double bond, a carbonyl group renders the double bond susceptible to nucleophilic attack: The presence of a carbonyl group in a molecule makes possible a number of chemical reactions that are of great synthetic and mechanistic importance. This chapter is complementary to the preceding one; the two chapters taken together demonstrate the extraordinary range of chemical reactions available to aldehydes and ketones. 18.1 THE -CARBON ATOM AND ITS HYDROGENS It is convenient to use the Greek letters , , , and so forth, to locate the carbons in a molecule in relation to the carbonyl group. The carbon atom adjacent to the carbonyl is the -carbon atom, the next one down the chain is the carbon, and so on. Butanal, for example, has an carbon, a carbon, and a carbon. Hydrogens take the same Greek letter as the carbon atom to which they are attached. A hydrogen connected to the -carbon atom is an hydrogen. Butanal has two protons, two protons, and three protons. No Greek letter is assigned to the hydrogen attached directly to the carbonyl group of an aldehyde. PROBLEM 18.1 How many hydrogens are there in each of the following? (a) 3,3-Dimethyl-2-butanone (c) Benzyl methyl ketone (b) 2,2-Dimethylpropanal (d) Cyclohexanone SAMPLE SOLUTION (a) This ketone has two different carbons, but only one of them has hydrogen substituents. There are three equivalent hydrogens. The other nine hydrogens are attached to -carbon atoms. Other than nucleophilic addition to the carbonyl group, the most important reactions of aldehydes and ketones involve substitution of an hydrogen. A particularly well studied example is halogenation of aldehydes and ketones. 3,3-Dimethyl-2-butanone CH3±C±C±CH3 CH3 CH3 O X W W Carbonyl group is reference point; no Greek letter assigned to it. O CH3CH2CH2CH Normally, carbon–carbon double bonds are attacked by electrophiles; a carbon–carbon double bond that is conjugated to a carbonyl group is attacked by nucleophiles. O R2C CHCR 702 CHAPTER EIGHTEEN Enols and Enolates Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
18.3 Mechanism of a Halogenation of Aldehydes and Ketones 18.2 C HALOGENATION OF ALDEHYDES AND KETONES Aldehydes and ketones react with halogens by substitution of one of the a hydrogens R,CCR+ X2 →R,CCR HX Aldehyde Halo a-Halo aldehyde Hydrogen The reaction is regiospecific for substitution of an a hydrogen. None of the hydrogens farther removed from the carbonyl group are affected Cl HCl Cyclohexanone Chlorine 2-Chlorocyclohexanone Hydrogen (61-66%) chloride Nor is the hydrogen directly attached to the carbonyl group in aldehydes affected Only the a hydrogen is replace CH CHCI3 HBr Cyclohexanecarbaldehyde Bromine 1-Bromocyclohexanecarbaldehyde(80%) Hydrogen PROBLEM 18.2 Chlorination of 2-butanone yields two isomeric products, each having the molecular formula CaH,Clo. Identify these two compounds a Halogenation of aldehydes and ketones can be carried out in a variety of sol- vents(water and chloroform are shown in the examples, but acetic acid and diethyl ether are also often used). The reaction is catalyzed by acids. Since one of the reaction prod- ucts, the hydrogen halide, is an acid and therefore a catalyst for the reaction, the proces is said to be autocatalytic. Free radicals are not involved, and the reactions occur at room temperature in the absence of initiators. Mechanistically, acid-catalyzed haloge nation of aldehydes and ketones is much different from free-radical halogenation of alkanes. Although both processes lead to the replacement of a hydrogen by a halogen, they do so by completely different pathways 18.3 MECHANISM OF C HALOGENATION OF ALDEHYDES AND KETONES In one of the earliest mechanistic investigations in organic chemistry, Arthur Lapworth discovered in 1904 that the rates of chlorination and bromination of acetone were the same. Later he found that iodination of acetone proceeded at the same rate as chlorination Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
18.2 HALOGENATION OF ALDEHYDES AND KETONES Aldehydes and ketones react with halogens by substitution of one of the hydrogens: The reaction is regiospecific for substitution of an hydrogen. None of the hydrogens farther removed from the carbonyl group are affected. Nor is the hydrogen directly attached to the carbonyl group in aldehydes affected. Only the hydrogen is replaced. PROBLEM 18.2 Chlorination of 2-butanone yields two isomeric products, each having the molecular formula C4H7ClO. Identify these two compounds. Halogenation of aldehydes and ketones can be carried out in a variety of solvents (water and chloroform are shown in the examples, but acetic acid and diethyl ether are also often used). The reaction is catalyzed by acids. Since one of the reaction products, the hydrogen halide, is an acid and therefore a catalyst for the reaction, the process is said to be autocatalytic. Free radicals are not involved, and the reactions occur at room temperature in the absence of initiators. Mechanistically, acid-catalyzed halogenation of aldehydes and ketones is much different from free-radical halogenation of alkanes. Although both processes lead to the replacement of a hydrogen by a halogen, they do so by completely different pathways. 18.3 MECHANISM OF HALOGENATION OF ALDEHYDES AND KETONES In one of the earliest mechanistic investigations in organic chemistry, Arthur Lapworth discovered in 1904 that the rates of chlorination and bromination of acetone were the same. Later he found that iodination of acetone proceeded at the same rate as chlorination O Cyclohexanone Cl2 Chlorine H2O O Cl 2-Chlorocyclohexanone (61–66%) Hydrogen chloride HCl Aldehyde or ketone R2CCR H O R2CCR X O -Halo aldehyde or ketone Halogen X2 Hydrogen halide HX H 18.3 Mechanism of Halogenation of Aldehydes and Ketones 703 HBr Hydrogen bromide CH O H Cyclohexanecarbaldehyde Br2 Bromine CH O Br 1-Bromocyclohexanecarbaldehyde (80%) CHCl3 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTEr EIGHTEEN Enols and enolates and bromination. Moreover, the rates of all three halogenation reactions, although first order in acetone, are independent of the halogen concentration. Thus, the halogen does not participate in the reaction until after the rate-determining step. These kinetic obser vations, coupled with the fact that substitution occurs exclusively at the a-carbon atom, ed Lapworth to propose that the rate-determining step is the conversion of acetone to a more reactive form. its enol isomer: this chapter is an electrostatic CHACHa= Acetone Propen-2-o1(enol Once formed, this enol reacts rapidly with the halogen to form an a-halo ketone OH CH3C= 2 CH3 CCH2X HX Propen-2-0 Halogen a-Halo derivative Hydrogen form of ac of acetone halide PROBLEM 18.3 Write the structures of the enol forms of 2-butanone that react with chlorine to give 1-chloro-2-butanone and 3-chloro-2-butanone far ahead of Both parts of the Lapworth mechanism, enol formation and enol halogenation, are new to us. Lets examine them in reverse order. We can understand enol halogenation ow organic reactions occur. by analogy to halogen addition to alkenes. An enol is a very reactive kind of alkene. Its For an account of Lapworth's carbon-carbon double bond bears an electron-releasing hydroxyl group, which activates nistry, see the it toward attack by electrophiles ovember 1972 issue of the OH on,pp.750-752. CHSC-CH, +Br-Br: ICH3-C-CH,Br:+Br Bromine Stabilized carbocation (enol form The hydroxyl group stabilizes the carbocation by delocalization of one of the ared electron pairs of oxygen: CH, Br CH3-C-CH, Br able resonance More stable 6 electrons on form: all aton tively charged c Participation by the oxygen lone pairs is responsible for the rapid attack on the carbon-carbon double bond of an enol by bromine. We can represent this participation explicitly: Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
and bromination. Moreover, the rates of all three halogenation reactions, although firstorder in acetone, are independent of the halogen concentration. Thus, the halogen does not participate in the reaction until after the rate-determining step. These kinetic observations, coupled with the fact that substitution occurs exclusively at the -carbon atom, led Lapworth to propose that the rate-determining step is the conversion of acetone to a more reactive form, its enol isomer: Once formed, this enol reacts rapidly with the halogen to form an -halo ketone: PROBLEM 18.3 Write the structures of the enol forms of 2-butanone that react with chlorine to give 1-chloro-2-butanone and 3-chloro-2-butanone. Both parts of the Lapworth mechanism, enol formation and enol halogenation, are new to us. Let’s examine them in reverse order. We can understand enol halogenation by analogy to halogen addition to alkenes. An enol is a very reactive kind of alkene. Its carbon–carbon double bond bears an electron-releasing hydroxyl group, which activates it toward attack by electrophiles. The hydroxyl group stabilizes the carbocation by delocalization of one of the unshared electron pairs of oxygen: Participation by the oxygen lone pairs is responsible for the rapid attack on the carbon–carbon double bond of an enol by bromine. We can represent this participation explicitly: Less stable resonance form; 6 electrons on positively charged carbon. CH3 CH2Br C O More stable resonance form; all atoms (except hydrogen) have octets of electrons. CH3 C CH2Br H O H Br Bromide ion CH3 CH2Br C OH Stabilized carbocation very fast Br Br Bromine CH3C CH2 OH Propen-2-ol (enol form of acetone) -Halo derivative of acetone CH3CCH2X O Halogen X2 Hydrogen halide HX Propen-2-ol (enol form of acetone) CH3C CH2 OH fast Acetone CH3CCH3 O Propen-2-ol (enol form of acetone) CH3C CH2 OH slow 704 CHAPTER EIGHTEEN Enols and Enolates The graphic that opened this chapter is an electrostatic potential map of the enol of acetone. Lapworth was far ahead of his time in understanding how organic reactions occur. For an account of Lapworth’s contributions to mechanistic organic chemistry, see the November 1972 issue of the Journal of Chemical Education, pp. 750–752. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
18.4 Enolization and Enol Content OH CH3C=CH2 CH3C—CH,Br:+ Br-br Writing the bromine addition step in this way emphasizes the increased nucleophilicity of the enol double bond and identifies the source of that increased nucleophilicity as the lic PROBLEM 18 4 Represent the reaction of chlorine with each of the enol forms of 2-butanone (see Problem 18.3)according to the curved arrow formalism just described The cationic intermediate is simply the protonated form(conjugate acid) of the a-halo ketone. Deprotonation of the cationic intermediate gives the product -H: Br CH3, Br Hy Having now seen how an enol, once formed, reacts with a halogen, let us consider the process of enolization itself 18.4 ENOLIZATION AND ENOL CONTENT Enols are related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto-enol tautomerism. (Tautomerism refers to an interconversion between two struc- The keto and enol forms are tures that differ by the placement of an atom or a group. constitutional isomers. Using each other RCH, CR RCHECR Keto form Enol form The mechanism of enolization involves two separate proton-transfer steps rather than a one-step process in which a proton jumps from carbon to oxygen. It is relatively slow in neutral media. The rate of enolization is catalyzed by acids as shown by the mechanism in Figure 18.1. In aqueous acid, a hydronium ion transfers a proton to the carbonyl oxygen in step l, and a water molecule acts as a Bronsted base to remove a proton from the a-carbon atom in step 2. The second step is slower than the first. The first step involves proton transfer between oxygens, and the second is a proton transfer from carbon to oxygen. You have had earlier experience with enols in their role as intermediates in the hydration of alkynes (Section 9. 12). The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound The amount of enol present at equilibrium, the enol content, is quite small for sim- ple aldehydes and ketones. The equilibrium constants for enolization, as shown by the following examples, are much less than 1 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Writing the bromine addition step in this way emphasizes the increased nucleophilicity of the enol double bond and identifies the source of that increased nucleophilicity as the enolic oxygen. PROBLEM 18.4 Represent the reaction of chlorine with each of the enol forms of 2-butanone (see Problem 18.3) according to the curved arrow formalism just described. The cationic intermediate is simply the protonated form (conjugate acid) of the -halo ketone. Deprotonation of the cationic intermediate gives the products. Having now seen how an enol, once formed, reacts with a halogen, let us consider the process of enolization itself. 18.4 ENOLIZATION AND ENOL CONTENT Enols are related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto–enol tautomerism. (Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group.) The mechanism of enolization involves two separate proton-transfer steps rather than a one-step process in which a proton jumps from carbon to oxygen. It is relatively slow in neutral media. The rate of enolization is catalyzed by acids as shown by the mechanism in Figure 18.1. In aqueous acid, a hydronium ion transfers a proton to the carbonyl oxygen in step 1, and a water molecule acts as a Brønsted base to remove a proton from the -carbon atom in step 2. The second step is slower than the first. The first step involves proton transfer between oxygens, and the second is a proton transfer from carbon to oxygen. You have had earlier experience with enols in their role as intermediates in the hydration of alkynes (Section 9.12). The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound. The amount of enol present at equilibrium, the enol content, is quite small for simple aldehydes and ketones. The equilibrium constants for enolization, as shown by the following examples, are much less than 1. Keto form RCH2CR O Enol form RCH CR OH tautomerism Cationic intermediate Br O CH3CCH2Br H CH3CCH2Br O Bromoacetone H Br Hydrogen bromide Br CH3 C CH2Br Br Br CH3C CH2 OH OH 18.4 Enolization and Enol Content 705 The keto and enol forms are constitutional isomers. Using older terminology they are referred to as tautomers of each other. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
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
