Carey - Organic Chemistry - chapt18

Carey - Organic Chemistry - chapt18

(Parte 1 de 4)


In 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 enolisomers.

In this chapter you’l 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.

Aldehyde or ketone

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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.

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. Ahydrogen 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 18.1How 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. Aparticularly well studied example is halogenation of aldehydes and ketones.



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.

702CHAPTER EIGHTEENEnols and Enolates

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18.2 HALOGENATION OF ALDEHYDES AND KETONES Aldehydes and ketones react with halogens by substitutionof one of the hydrogens:

The reaction is regiospecificfor 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 18.2Chlorination 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 notinvolved, 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.

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


Cl2 Chlorine

O Cl

Hydrogen chloride


Aldehyde or ketone

-Halo aldehydeor ketone Halogen

Hydrogen halide


Hydrogen bromide


Br2 Bromine

Br1-Bromocyclohexanecarbaldehyde (80%) CHCl3

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE 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 18.3Write 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.

More stable resonance form; all atoms (except hydrogen) have octets of electrons.


Bromide ion

Stabilized carbocation very fastBr BrBromine CH3CC H2

Propen-2-ol (enol form of acetone)

-Halo derivative of acetone

Hydrogen halide

Propen-2-ol (enol form of acetone)

OH fast

Acetone CH3CCH3

Propen-2-ol (enol form of acetone)

OH slow

704CHAPTER EIGHTEENEnols 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, p. 750–752.

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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 18.4Represent 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.


Enols are related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto–enol tautomerism.(Tautomerismrefers 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.

OH tautomerism

Cationic intermediate



H Br Hydrogen bromide

Br Br CH3CC H2

The keto and enol forms are constitutional isomers. Using older terminology they are referred to as tautomersof each other.

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In these and numerous other simple cases, the keto form is more stable than the enol by some 45–60 kJ/mol (1–14 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)

2-Buten-2-ol (enol form)


1-Buten-2-ol (enol form)


Acetaldehyde (keto form)


Vinyl alcohol (enol form)

Acetone (keto form)

Propen-2-ol (enol form)

706CHAPTER EIGHTEENEnols 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


HydroniumionConjugate acid ofcarbonyl 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

Conjugate acid ofcarbonyl compound Water slow BNA

FIGURE 18.1 Mechanism of acid-catalyzed enolization of an aldehyde or ketone in aqueous solution.

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PROBLEM 18.5Write 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 nota resonance form of a carbonyl compound; the two are constitutional isomers of each other.


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.

A1,3 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

2,4-Pentanedione (20%) (keto form)

4-Hydroxy-3-penten-2-one (80%) (enol form)


OH O K 4

K is too large to measure. O

2,4-Cyclohexadienone (keto form, not aromatic)

Phenol (enol form, aromatic)

2,4-Dimethyl-3-pentanone (keto form)

2,4-Dimethyl-2-penten-3-ol (enol form)

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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 18.6Write 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.


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





708CHAPTER EIGHTEENEnols and Enolates



O---H separation in intramolecular hydrogen bond is 166 pm

124 pm103 pm 133 pm

FIGURE 18.2 (a) A molecular model and (b) bond distances in the enol form of 2,4-pentanedione.

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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.

Electron delocalization in conjugate base of ketone

18.6Base-Catalyzed Enolization: Enolate Anions709 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


HydroxideionConjugate base ofcarbonyl 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

Conjugate base ofcarbonyl compound Water fast BNA

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?

(Parte 1 de 4)