WHY THIS CHAPTER? As with nucleophilic additions and nucleophilic acyl substitutions, many laboratory schemes, pharmaceutical syntheses, and biochemical pathways make frequent use of carbonyl $\alpha$-substitution reactions. Their great value comes from the fact that they constitute one of the few general methods for forming carbon-carbon bonds, thereby making it possible to build larger molecules from smaller precursors. In this chapter, we'll see how and why these reactions occur.

We said in the Preview of Carbonyl Chemistry that much of the chemistry of carbonyl compounds can be explained by just four fundamental reaction types: nucleophilic additions, nucleophilic acyl substitutions, $\alpha$ substitutions, and carbonyl condensations. Having studied the first two of these reactions in the past three chapters, let's now look in more detail at the third major carbonyl-group process-the $\boldsymbol{a}$-substitution reaction.


CHAPTER CONTENTS - 22.1 Keto-Enol Tautomerism

Alpha-substitution reactions occur at the position next to the carbonyl group-the $\alpha$ position-and involve the substitution of an $\alpha$ hydrogen atom by an electrophile, E, through either an enol or enolate ion intermediate. Let's begin by learning more about these two species.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0784.jpg?height=540&width=839&top_left_y=191&top_left_x=643)


A carbonyl compound with a hydrogen atom on its $\alpha$ carbon is in equilibrium with its corresponding enol isomer (Section 9.4). This spontaneous interconversion between two isomers, usually with the change in position of a hydrogen, is called tautomerism, from the Greek tauto, meaning "the same," and meros, meaning "part." The individual keto and enol isomers are called tautomers.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0784.jpg?height=397&width=1361&top_left_y=1032&top_left_x=374)


Note the difference between tautomers and resonance forms. Tautomers are constitutional isomers-different compounds with different structures-while resonance forms are different representations of a single compound. Tautomers have their atoms arranged differently, while resonance forms differ only in the position of their $\pi$ and nonbonding electrons.


Most monocarbonyl compounds exist almost entirely in their keto form at equilibrium, and it's usually difficult to isolate the pure enol. Cyclohexanone, for example, contains only about $0.0001 \%$ of its enol tautomer at room temperature. The percentage of enol tautomer is even lower for carboxylic acids, esters, and amides. The enol can only predominate when stabilized by conjugation or intramolecular hydrogen bonding. Thus, 2,4-pentanedione is about $76 \%$ enol tautomer. Although enols are scarce at equilibrium, they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0784.jpg?height=294&width=1091&top_left_y=1902&top_left_x=520)


Cyclohexanone


Acetone -

Keto-enol tautomerism of carbonyl compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that loses $\mathrm{H}^{+}$from its $\alpha$ carbon to yield a neutral enol (FIGURE 22.2a). This proton loss from the cation intermediate is similar to what occurs during an E1 reaction when a carbocation loses $\mathrm{H}^{+}$to form an alkene (Section 11.10).

Base-catalyzed enol formation occurs because the presence of a carbonyl group makes the hydrogens on the $\alpha$ carbon weakly acidic. Thus, a carbonyl compound can act as an acid and donate one of its $\alpha$ hydrogens
to a sufficiently strong base. The resultant resonance-stabilized anion, an enolate ion, is then protonated to yield a neutral compound. If protonation of the enolate ion takes place on the $\alpha$ carbon, the keto tautomer is regenerated and no net change occurs. If, however, protonation takes place on the oxygen atom, an enol tautomer is formed (FIGURE 22.2b).


FIGURE 22.2 MECHANISM -

Mechanism of enol formation under both acid-catalyzed and base-catalyzed conditions. (a) Acid catalysis involves (1) initial protonation of the carbonyl oxygen followed by (2) removal of $\mathrm{H}^{+}$from the $\alpha$ position. (b) Base catalysis involves (1) initial deprotonation of the $\alpha$ position to give an enolate ion, followed by (2) reprotonation on oxygen.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0785.jpg?height=1055&width=1629&top_left_y=665&top_left_x=248)


FIGURE 22.2 MECHANISM -

Note that only the hydrogens on the $\alpha$ position of carbonyl compounds are acidic. Hydrogens at $\beta, \gamma, \delta$, and so on, aren't acidic and can't be removed by base because the resulting anions can't be resonance-stabilized by the carbonyl group.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0785.jpg?height=329&width=1199&top_left_y=1906&top_left_x=463)


FIGURE 22.2 MECHANISM -

PROBLEM Draw structures for the enol tautomers of the following compounds:
22-1 (a) Cyclopentanone (b) Methyl thioacetate (c) Ethyl acetate (d) Propanal (e) Acetic acid (f) Phenylacetone


FIGURE 22.2 MECHANISM -

PROBLEM How many acidic hydrogens does each of the molecules listed in Problem 22-1 have? Identify them. 22-2


FIGURE 22.2 MECHANISM -

PROBLEM Draw structures for all monoenol forms of the following molecule. Which would you expect to be 22-3 most stable? Explain.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0786.jpg?height=299&width=372&top_left_y=306&top_left_x=421)


FIGURE 22.2 MECHANISM - 22.2 Reactivity of Enols: $\boldsymbol{\alpha}$-Substitution Reactions

What kind of chemistry do enols have? Because their double bonds are electron-rich, enols behave as nucleophiles and react with electrophiles in much the same way that alkenes do. But because of resonanceelectron donation of a lone pair of electrons on the neighboring oxygen, enols are more electron-rich and correspondingly more reactive than alkenes. Notice in the following electrostatic potential map of ethenol $\left(\mathrm{H}_{2} \mathrm{C}=\mathrm{CHOH}\right)$ how there is a substantial electron density (yellow-red) on the $\alpha$ carbon.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0786.jpg?height=359&width=1082&top_left_y=970&top_left_x=500)


When an alkene reacts with an electrophile, $\mathrm{E}^{+}$, initial addition gives an intermediate cation and subsequent reaction with a nucleophile, such as a halide ion, yields an addition product (Section 7.7). When an enol reacts with an electrophile, however, only the initial addition step is the same (FIGURE 22.3). Instead of reacting with a nucleophile to give an addition product, the intermediate cation loses the -OH proton to give an $\alpha$-substituted carbonyl compound.


FIGURE 22.3 MECHANISM -

General mechanism of a carbonyl $\boldsymbol{\alpha}$-substitution reaction. In step 3, the initially formed cation loses $\mathrm{H}^{+}$to regenerate a carbonyl compound.


FIGURE 22.3 MECHANISM -


FIGURE 22.3 MECHANISM -

2 An electron pair from the enol oxygen attacks an electrophile ( $\mathrm{E}^{+}$), forming a new bond and leaving a cation intermediate that is stabilized by resonance between two forms.


FIGURE 22.3 MECHANISM - 22.3 Alpha Halogenation of Aldehydes and Ketones

A particularly common $\alpha$-substitution reaction in the laboratory is the halogenation of aldehydes and ketones at their $\alpha$ positions by reaction with $\mathrm{Cl}_{2}, \mathrm{Br}_{2}$, or $\mathrm{I}_{2}$ in acidic solution. Bromine in acetic acid solvent is often used.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0787.jpg?height=262&width=827&top_left_y=1666&top_left_x=649)


From the Hawaiian alga Asparagopsis taxiformis
This form of halogenation is a typical $\alpha$-substitution reaction that proceeds by acid-catalyzed formation of an enol intermediate, as shown in FIGURE 22.4.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0788.jpg?height=1655&width=1205&top_left_y=197&top_left_x=460)


Evidence for the mechanism shown in FIGURE 22.4 includes the observation that acid-catalyzed halogenations show second-order kinetics and follow the rate law


$$
\text { Reaction rate }=k[\text { Ketone }]\left[\mathrm{H}^{+}\right]
$$


In other words, the rate of halogenation depends only on the concentrations of ketone and acid and is independent of halogen concentration. Since halogen is not involved in the rate-limiting step, chlorination, bromination, and iodination of a given substrate all occur at the same rate.


Furthermore, if an aldehyde or ketone is treated with $\mathrm{D}_{3} \mathrm{O}^{+}$, the acidic $\alpha$ hydrogens are replaced by deuterium. For a given ketone, the rate of deuterium exchange is identical to the rate of halogenation, implying that a common intermediate-presumably the enol-is involved in both processes.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0789.jpg?height=407&width=1050&top_left_y=176&top_left_x=532)
$\alpha$-Bromo ketones are useful in the laboratory because they can be dehydrobrominated by base treatment to yield $\alpha, \beta$-unsaturated ketones. For example, 2-methylcyclohexanone gives 2-bromo-2-methylcyclohexanone on halogenation, and the $\alpha$-bromo ketone gives 2-methyl-2-cyclohexenone when heated in pyridine. The reaction takes place by an E2 elimination pathway (Section 11.8) and is a good method for introducing a $\mathrm{C}=\mathrm{C}$ bond into a molecule. Note that bromination of 2-methylcyclohexanone occurs primarily on the more highly substituted $\alpha$ position because the more highly substituted enol is favored over the less highly substituted one (Section 7.6).
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0789.jpg?height=299&width=1006&top_left_y=894&top_left_x=554)


PROBLEM Write the complete mechanism for the deuteration of acetone on treatment with $\mathrm{D}_{3} \mathrm{O}^{+}$.
22-4
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0789.jpg?height=109&width=454&top_left_y=1252&top_left_x=418)


PROBLEM Show how you might prepare 1-penten-3-one from 3-pentanone.
22-5


FIGURE 22.3 MECHANISM - 22.4 Alpha Bromination of Carboxylic Acids

The $\alpha$ bromination of carbonyl compounds by $\mathrm{Br}_{2}$ in acetic acid is limited to aldehydes and ketones because acids, esters, and amides don't enolize to a sufficient extent. Carboxylic acids, however, can be $\alpha$ brominated by a mixture of $\mathrm{Br}_{2}$ and $\mathrm{PBr}_{3}$ in the Hell-Volhard-Zelinskii (HVZ) reaction.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0789.jpg?height=223&width=1001&top_left_y=1710&top_left_x=562)

The Hell-Volhard-Zelinskii reaction is a bit more complex than it looks and actually involves $\alpha$ substitution of an acid bromide enol rather than a carboxylic acid enol. The process begins by reaction of the carboxylic acid with $\mathrm{PBr}_{3}$ to form an acid bromide plus HBr (Section 21.4). The HBr then catalyzes enolization of the acid bromide, and the resultant enol reacts with $\mathrm{Br}_{2}$ in an $\alpha$-substitution reaction to give an $\alpha$-bromo acid bromide. Addition of water hydrolyzes the acid bromide in a nucleophilic acyl substitution reaction and yields the $\alpha$-bromo carboxylic acid product.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0790.jpg?height=571&width=1362&top_left_y=178&top_left_x=379)


PROBLEM If methanol rather than water is added at the end of a Hell-Volhard-Zelinskii reaction, an ester 22-6 rather than an acid is produced. Show how you would carry out the following transformation, and propose a mechanism for the ester-forming step.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0790.jpg?height=150&width=686&top_left_y=890&top_left_x=416)


FIGURE 22.3 MECHANISM - 22.5 Acidity of Alpha Hydrogen Atoms: Enolate Ion Formation

As noted in Section 22.1, a hydrogen on the $\alpha$ position of a carbonyl compound is weakly acidic and can be removed by a strong base to yield an enolate ion. In comparing acetone ( $\mathrm{p} K_{\mathrm{a}}=19.3$ ) with ethane ( $\mathrm{p} K_{\mathrm{a}} \approx 60$ ), for instance, the presence of a neighboring carbonyl group increases the acidity of the ketone over the alkane by a factor of $10^{40}$.
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Ethane
( $\mathrm{p} K_{\mathrm{a}} \approx 60$ )


Proton abstraction from a carbonyl compound occurs when the $\alpha \mathrm{C}-\mathrm{H}$ bond is oriented roughly parallel to the $p$ orbitals of the carbonyl group. The $\alpha$ carbon atom of the enolate ion is $s p^{2}$-hybridized and has a $p$ orbital that overlaps the neighboring carbonyl $p$ orbitals. Thus, the negative charge is shared by the electronegative oxygen atom, and the enolate ion is stabilized by resonance (FIGURE 22.5).
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0790.jpg?height=405&width=1668&top_left_y=1830&top_left_x=258)

FIGURE 22.5 Mechanism of enolate-ion formation by abstraction of an $\alpha$ proton from a carbonyl compound. The enolate ion is stabilized by resonance, and the negative charge (red) is shared by the oxygen and the $\alpha$ carbon atom, as indicated in the electrostatic potential map.


Because carbonyl compounds are only weakly acidic, a strong base is needed for the formation of an enolateion. If an alkoxide ion, such as sodium ethoxide, is used as base, deprotonation of acetone only takes place to the extent of about $0.1 \%$ because acetone is a weaker acid than ethanol ( $\mathrm{p} K_{\mathrm{a}}=16$ ). If, however, a more powerful base is used, then a carbonyl compound is completely converted into its enolate ion.


In practice, the strong base lithium diisopropylamide [ $\mathrm{LiN}\left(i-\mathrm{C}_{3} \mathrm{H}_{7}\right)_{2}$; abbreviated LDA] is commonly used for making enolate ions. As the lithium salt of the weak acid diisopropylamine, $\mathrm{p} K_{\mathrm{a}}=36$, LDA can readily deprotonate most carbonyl compounds. It is easily prepared by reaction of butyllithium with diisopropylamine and is soluble in organic solvents because of its two alkyl groups.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0791.jpg?height=608&width=1039&top_left_y=368&top_left_x=543)


Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. TABLE 22.1 lists the approximate $\mathrm{p} K_{\mathrm{a}}$ values of different types of carbonyl compounds and shows how these values compare to other acidic substances we've seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions.


| Functional group | Example | $\mathrm{p} K_{\mathrm{a}}$ |
| :---: | :---: | :---: |
| Carboxylic acid | <smiles>CC=O</smiles> | 5 |
| 1,3-Diketone | <smiles>CC(=O)C=O</smiles> | 9 |
| 3-Keto ester | <smiles>CC(=O)C=O</smiles> | 11 |
| 1,3-Diester | <smiles>CC(=O)CC(C)=O</smiles> | 13 |
| Alcohol | $\mathrm{CH}_{3} \mathrm{OH}$ | 16 |
| Acid chloride | <smiles>CC(Cl)Cl</smiles> | 16 |
| Aldehyde | <smiles>C=O</smiles> | 17 |
| Ketone | <smiles>CC(C)=O</smiles> | 19 |

| Functional group | Example | $\mathrm{p} K_{\mathrm{a}}$ |
| :---: | :---: | :---: |
| Thioester | <smiles>C[AsH2]=O</smiles> | 21 |
| Ester | <smiles>CC(C)=O</smiles> | 25 |
| Nitrile | $\mathrm{CH}_{3} \mathrm{C}=\mathrm{N}$ | 25 |
| $N, N$-Dialkylamide | <smiles>CCCCCC(C)=O</smiles> | 30 |
| Dialkylamine | $\mathrm{HN}\left(\mathrm{i}-\mathrm{C}_{3} \mathrm{H}_{7}\right)_{2}$ | 36 |


When a hydrogen atom is flanked by two carbonyl groups, its acidity is enhanced further. TABLE 22.1 thus shows that 1,3 -diketones ( $\beta$-diketones), 3 -oxo esters ( $\beta$-keto esters), and 1,3 -diesters (malonic esters) are more acidic than water. The enolate ions derived from these $\beta$-dicarbonyl compounds are stabilized by sharing the negative charge of the two neighboring carbonyl oxygens. The enolate ion of 2,4 -pentanedione, for instance, has three resonance forms. Similar resonance forms can be drawn for other doubly stabilized enolate ions.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0792.jpg?height=549&width=1131&top_left_y=1230&top_left_x=497)


WORKED EXAMPLE 22.1 -


Identifying the Acidic Hydrogens in a Compound -


Strategy -

Hydrogens on carbon next to a carbonyl group are acidic. In general, a $\beta$-dicarbonyl compound is most acidic, a ketone or aldehyde is next most acidic, and a carboxylic acid derivative is least acidic. Remember that alcohols, phenols, and carboxylic acids are also acidic because of their -OH hydrogens.


Solution -


Solution -

PROBLEM Identify the most acidic hydrogens in each of the following molecules:
22-7 (a)
$\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CHO}$
(b) $\left(\mathrm{CH}_{3}\right)_{3} \mathrm{C}-\mathrm{COCH}_{3}$
(c) $\mathrm{CH}_{3} \mathrm{CO}_{2} \mathrm{H}$
(d) Benzamide
(e) $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CN}$
(f) $\mathrm{CH}_{3} \mathrm{CON}\left(\mathrm{CH}_{3}\right)_{2}$


Solution -

PROBLEM Draw a resonance structure of the acetonitrile anion, ${ }^{-}: \mathrm{CH}_{2} \mathrm{C} \equiv \mathrm{N}$, and account for the acidity of 22-8 nitriles.


Solution - 22.6 Reactivity of Enolate Ions

Enolate ions are more useful than enols for two reasons. First, pure enols can't normally be isolated but are instead generated only as short-lived intermediates in low concentration. By contrast, stable solutions of pure enolate ions are easily prepared from most carbonyl compounds by reaction with a strong base. Second, enolate ions are more reactive than enols and undergo many reactions that enols don't. Whereas enols are neutral, enolate ions are negatively charged, making them much better nucleophiles.


Because they are resonance hybrids of two nonequivalent forms, enolate ions can be looked at either as vinylic alkoxides ( $\mathrm{C}=\mathrm{C}-\mathrm{O}^{-}$) or as $\alpha$-keto carbanions ( ${ }^{-} \mathrm{C}-\mathrm{C}=\mathrm{O}$ ). Thus, enolate ions can react with electrophiles either on oxygen or on carbon. Reaction on oxygen yields an enol derivative, while reaction on carbon yields an $\alpha$-substituted carbonyl compound (FIGURE 22.6). Both kinds of reactivity are known, but reaction on carbon is more common.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0793.jpg?height=448&width=468&top_left_y=1459&top_left_x=506)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0793.jpg?height=361&width=568&top_left_y=1435&top_left_x=1055)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0793.jpg?height=112&width=451&top_left_y=1814&top_left_x=1059)
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An enol derivative
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An $\alpha$-substituted
carbonyl compound


FIGURE 22.6 The electrostatic potential map of acetone enolate ion shows how the negative charge is delocalized over both the oxygen and the $\boldsymbol{\alpha}$ carbon. As a result, two modes of reaction of an enolate ion with an electrophile $\mathrm{E}^{+}$are possible. Reaction on carbon to yield an $\alpha$-substituted carbonyl product is more common.


As an example of enolate ion reactivity, aldehydes and ketones undergo base-promoted $\alpha$ halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it's not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, halogen reacts with it immediately, removing it from the reaction and driving the equilibrium toward further enolate ion
formation.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0794.jpg?height=207&width=993&top_left_y=252&top_left_x=563)

Base-promoted halogenation of aldehydes and ketones is seldom used in practice because it's difficult to stop the reaction at the monosubstituted product. An $\alpha$-halogenated ketone is generally more acidic than the starting, unsubstituted ketone because of the electron-withdrawing inductive effect of the halogen atom. Thus, the monohalogenated products are themselves rapidly turned into enolate ions and further halogenated.


If excess base and halogen are used, a methyl ketone is triply halogenated and then cleaved by base in the haloform reaction. The products are a carboxylic acid plus a so-called haloform (chloroform, $\mathrm{CHCl}_{3}$; bromoform, $\mathrm{CHBr}_{3}$; or iodoform, $\mathrm{CHI}_{3}$ ). Note that the second step of the reaction is a nucleophilic acyl substitution of ${ }^{-} \mathrm{CX}_{3}$ by ${ }^{-} \mathrm{OH}$. That is, a halogen-stabilized carbanion acts as a leaving group.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0794.jpg?height=421&width=1265&top_left_y=841&top_left_x=430)


PROBLEM Why do you suppose ketone halogenations in acidic media are referred to as being acid-catalyzed, 22-9 whereas halogenations in basic media are base-promoted? In other words, why is a full equivalent of base required for halogenation?


Solution - 22.7 Alkylation of Enolate lons

Perhaps the most useful reaction of enolate ions is their alkylation by treatment with an alkyl halide, thereby forming a new $\mathrm{C}-\mathrm{C}$ bond and joining two smaller pieces into one larger molecule. Alkylation occurs when the nucleophilic enolate ion reacts with the electrophilic alkyl halide in an $\mathrm{S}_{\mathrm{N}} 2$ reaction and displaces the leaving group by backside attack.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0794.jpg?height=248&width=1097&top_left_y=1681&top_left_x=514)


Alkylation reactions are subject to the same constraints that affect all $S_{N} 2$ reactions (Section 11.3). Thus, the leaving group X in the alkylating agent $\mathrm{R}-\mathrm{X}$ can be chloride, bromide, or iodide. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don't react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because a backside approach is sterically prevented.


$$
\mathrm{R}-\mathrm{X}\left\{\begin{array}{l}
-\mathrm{X}: \text { Tosylate }>-\mathrm{I}>-\mathrm{Br}>-\mathrm{Cl} \\
\mathrm{R}-: \text { Allylic } \approx \text { Benzylic }>\mathrm{H}_{3} \mathrm{C}->\mathrm{RCH}_{2}-
\end{array}\right.
$$


The Malonic Ester Synthesis -

One of the oldest and best known carbonyl alkylation reactions is the malonic ester synthesis, a method for preparing a carboxylic acid from an alkyl halide while lengthening the carbon chain by two atoms.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0795.jpg?height=120&width=521&top_left_y=189&top_left_x=799)


The Malonic Ester Synthesis -

Diethyl propanedioate, commonly called diethyl malonate, or malonic ester, is relatively acidic ( $\mathrm{p} K_{\mathrm{a}}=13$ ) because its $\alpha$ hydrogens are flanked by two carbonyl groups. Thus, malonic ester is easily converted into its enolate ion by reaction with sodium ethoxide in ethanol. The enolate ion, in turn, is a good nucleophile that reacts rapidly with an alkyl halide to give an $\alpha$-substituted malonic ester. Note in the following examples that the abbreviation "Et" is used for an ethyl group, $-\mathrm{CH}_{2} \mathrm{CH}_{3}$.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0795.jpg?height=308&width=1166&top_left_y=540&top_left_x=482)


The Malonic Ester Synthesis -

The product of a malonic ester alkylation has one acidic $\alpha$ hydrogen remaining, so the alkylation process can be repeated to yield a dialkylated malonic ester.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0795.jpg?height=307&width=1145&top_left_y=950&top_left_x=490)


The Malonic Ester Synthesis -

On heating with aqueous hydrochloric acid, the alkylated (or dialkylated) malonic ester undergoes hydrolysis of its two ester groups followed by decarboxylation (loss of $\mathrm{CO}_{2}$ ) to yield a substituted monocarboxylic acid.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0795.jpg?height=123&width=866&top_left_y=1359&top_left_x=646)


The Malonic Ester Synthesis -

$$
\begin{array}{lc}
\text { An alkylated } & \text { A carboxylic } \\
\text { malonic ester } & \text { acid }
\end{array}
$$


The Malonic Ester Synthesis -

Decarboxylation is not a general reaction of carboxylic acids. Rather, it is unique to compounds that have a second carbonyl group two atoms away from the $-\mathrm{CO}_{2} \mathrm{H}$. That is, only substituted malonic acids and $\beta$-keto acids undergo loss of $\mathrm{CO}_{2}$ on heating. The decarboxylation reaction occurs by a cyclic mechanism and involves initial formation of an enol, thereby accounting for the need to have a second carbonyl group appropriately positioned.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0795.jpg?height=587&width=1002&top_left_y=1772&top_left_x=556)


The Malonic Ester Synthesis -

As noted previously, the overall effect of malonic ester synthesis is to convert an alkyl halide into a carboxylic acid while lengthening the carbon chain by two atoms ( $\mathrm{RX} \rightarrow \mathrm{RCH}_{2} \mathrm{CO}_{2} \mathrm{H}$ ).
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0796.jpg?height=629&width=1353&top_left_y=187&top_left_x=386)


The Malonic Ester Synthesis -

A malonic ester synthesis can also be used to prepare cycloalkanecarboxylic acids. For example, when 1,4 -dibromobutane is treated with diethyl malonate in the presence of two equivalents of sodium ethoxide base, the second alkylation step occurs intramolecularly to yield a cyclic product. Hydrolysis and decarboxylation then give cyclopentanecarboxylic acid. Three-, four-, five-, and six-membered rings can be prepared in this way, but yields decrease for larger ring sizes.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0796.jpg?height=278&width=1276&top_left_y=1048&top_left_x=454)


The Malonic Ester Synthesis -

1,4-Dibromobutane
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0796.jpg?height=258&width=1050&top_left_y=1362&top_left_x=662)


WORKED EXAMPLE 22.2 -


Using Malonic Ester Synthesis to Prepare a Carboxylic Acid -

How would you prepare heptanoic acid using a malonic ester synthesis?


Strategy -

A malonic ester synthesis converts an alkyl halide into a carboxylic acid having two more carbons. Thus, a seven-carbon acid chain must be derived from the five-carbon alkyl halide 1-bromopentane.


Strategy -

Solution


Strategy -

$$
\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Br}+\mathrm{CH}_{2}\left(\mathrm{CO}_{2} \mathrm{Et}\right)_{2} \xrightarrow[\text { 2. } \mathrm{H}_{3} \mathrm{O}^{+} \text {, heat }]{\text { 1. }{ }^{+}{ }^{-} \text {OEt }} \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{COH}
$$


Strategy -

PROBLEM How could you use a malonic ester synthesis to prepare the following compounds? Show all steps.


22-10 (a) -


22-10 (a) -

PROBLEM Monoalkylated and dialkylated acetic acids can be prepared by malonic ester synthesis, but 22-11 trialkylated acetic acids $\left(\mathrm{R}_{3} \mathrm{C}-\mathrm{CO}_{2} \mathrm{H}\right)$ can't be prepared. Explain.


22-10 (a) -

PROBLEM How could you use a malonic ester synthesis to prepare the following compound?
22-12
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0797.jpg?height=354&width=543&top_left_y=365&top_left_x=409)


The Acetoacetic Ester Synthesis -

Just as the malonic ester synthesis converts an alkyl halide into a carboxylic acid, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone having three more carbons.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0797.jpg?height=167&width=573&top_left_y=914&top_left_x=776)

Ethyl 3-oxobutanoate, commonly called ethyl acetoacetate, or acetoacetic ester, is much like malonic ester in that its $\alpha$ hydrogens are flanked by two carbonyl groups. It is therefore readily converted into its enolate ion, which can be alkylated by reaction with an alkyl halide. A second alkylation can also be carried out if desired, since acetoacetic ester has two acidic $\alpha$ hydrogens.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0797.jpg?height=654&width=1210&top_left_y=1272&top_left_x=463)


The Acetoacetic Ester Synthesis -

On heating with aqueous HCl , the alkylated (or dialkylated) acetoacetic ester is hydrolyzed to a $\beta$-keto acid, which then undergoes decarboxylation to yield a ketone product. The decarboxylation occurs in the same way as in the malonic ester synthesis and involves a ketone enol as the initial product.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0797.jpg?height=280&width=917&top_left_y=2066&top_left_x=607)


The Acetoacetic Ester Synthesis -

The three-step sequence of (1) enolate ion formation, (2) alkylation, and (3) hydrolysis/decarboxylation is applicable to all $\beta$-keto esters with acidic $\alpha$ hydrogens, not just to acetoacetic ester itself. For example, cyclic $\beta$-keto esters, such as ethyl 2-oxocyclohexanecarboxylate, can be alkylated and decarboxylated to give 2 -substituted cyclohexanones.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0798.jpg?height=410&width=1557&top_left_y=185&top_left_x=300)


WORKED EXAMPLE 22.3 -


Using Acetoacetic Ester Synthesis to Prepare a Ketone -

How would you prepare 2-pentanone by an acetoacetic ester synthesis?


Strategy -

An acetoacetic ester synthesis yields a methyl ketone by adding three carbons to an alkyl halide.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0798.jpg?height=251&width=668&top_left_y=945&top_left_x=726)

Thus, the acetoacetic ester synthesis of 2-pentanone must involve reaction of bromoethane.
Solution
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0798.jpg?height=169&width=928&top_left_y=1325&top_left_x=596)


Strategy -


Strategy -

PROBLEM Which of the following compounds can't be prepared by an acetoacetic ester synthesis? Explain.
22-14
(a) Phenylacetone
(b) Acetophenone
(c) 3,3-Dimethyl-2-butanone


Strategy -

PROBLEM How would you prepare the following compound using an acetoacetic ester synthesis?
22-15
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0798.jpg?height=307&width=472&top_left_y=2015&top_left_x=420)


Strategy -

Direct Alkylation of Ketones, Esters, and Nitriles
Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to carry out because they involve relatively acidic dicarbonyl compounds. As a result, sodium ethoxide in ethanol can be used to prepare the
necessary enolate ions. Alternatively, however, it's also possible in many cases to directly alkylate the $\alpha$ position of monocarbonyl compounds. A strong, sterically hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used.


Strategy -

Ketones, esters, and nitriles can all be alkylated using LDA or related dialkylamide bases in tetrahydrofuran (THF). Aldehydes, however, rarely give high yields of pure products because their enolate ions undergo carbonyl condensation reactions instead of alkylation. (We'll study this condensation reaction in the next chapter.) Some specific examples of alkylation reactions are shown.


Strategy -

> Ethyl 2-methylpropanoate


Strategy -

Ethyl 2,2-dimethylpropanoate (87\%)
Ketone
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0799.jpg?height=560&width=1216&top_left_y=1254&top_left_x=479)


Strategy -

2,2-Dimethylcyclohexanone (6\%)


Nitrile -


Nitrile -

Phenylacetonitrile
2-Phenylpropanenitrile (71\%)


Nitrile -

2-Phenylpropanenitrile (71\%)


Nitrile -

Note in the ketone example that alkylation of 2-methylcyclohexanone leads to a mixture of products because both possible enolate ions are formed. In general, the major product in such cases occurs by alkylation at the less hindered, more accessible position. Thus, alkylation of 2-methylcyclohexanone occurs primarily at C6 (secondary) rather than C 2 (tertiary).


WORKED EXAMPLE 22.4 -


Using an Alkylation Reaction to Prepare a Substituted Ester -


Ethyl 1-methylcyclohexanecarboxylate


Strategy -

An alkylation reaction is used to introduce a methyl or primary alkyl group onto the $\alpha$ position of a ketone, ester, or nitrile by $\mathrm{S}_{\mathrm{N}} 2$ reaction of an enolate ion with an alkyl halide. Thus, we need to look at the target molecule and identify any methyl or primary alkyl groups attached to an $\alpha$ carbon. In the present instance, the target has an $\alpha$ methyl group, which might be introduced by alkylation of an ester enolate ion with iodomethane.


Solution -


Solution -

Ethyl cyclohexanecarboxylate

Ethyl 1-methylcyclo-
hexanecarboxylate


Biological Alkylations -

Alkylations are rare but not unknown in biological chemistry. One example occurs during biosynthesis of the antibiotic indolmycin from indolylpyruvate when a base abstracts an acidic hydrogen from an $\alpha$ position and the resultant enolate ion carries out an $\mathrm{S}_{\mathrm{N}} 2$ alkylation reaction on the methyl group of $S$-adenosylmethionine (SAM; Section 11.6). Although it's convenient to speak of "enolate ion" intermediates in biological pathways, it's unlikely that they exist for long in an aqueous cellular environment. Rather, proton removal and alkylation
probably occur at essentially the same time (FIGURE 22.7).
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0801.jpg?height=411&width=321&top_left_y=258&top_left_x=376)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0801.jpg?height=392&width=668&top_left_y=273&top_left_x=718)
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Biological Alkylations -

Indolylpyruvate
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0801.jpg?height=502&width=456&top_left_y=687&top_left_x=1287)


Biological Alkylations -

Indolmycin (an antibiotic)
FIGURE 22.7 The biosynthesis of indolmycin from indolylpyruvate occurs through a pathway that includes an alkylation reaction of a short-lived enolate ion intermediate.


(8) CHEMISTRY MATTERS -


Barbiturates -

The use of herbal remedies to treat illness and disease goes back thousands of years, but the medical use of chemicals prepared in the laboratory has a much shorter history. Barbiturates, a large class of drugs with a wide variety of uses, constitute one of the earliest successes of medicinal chemistry. The synthesis and medical use of barbiturates goes back to 1904 when Bayer, a German chemical company, first marketed a compound called barbital, trade named Veronal, as a treatment for insomnia. Since that time, more than 2500 different barbiturate analogs have been synthesized by drug companies, more than 50 have been used medicinally, and about a dozen are still in use as anesthetics, anticonvulsants, sedatives, and anxiolytics.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-0802.jpg?height=609&width=901&top_left_y=758&top_left_x=612)


Barbiturates -

FIGURE 22.8 Different barbiturates come in a multitude of colors, giving rise to similarly colorful street names when the drugs are abused. (credit: "Medications" by freestocks.org/Flickr, Public Domain)


Barbiturates -

The synthesis of barbiturates is relatively simple and relies on reactions that are now familiar: enolate alkylations and nucleophilic acyl substitutions. Starting with diethyl malonate, alkylation of the corresponding enolate ion with simple alkyl halides provides a wealth of different disubstituted malonic esters. Reaction with urea, $\left(\mathrm{H}_{2} \mathrm{~N}\right)_{2} \mathrm{C}=\mathrm{O}$, then gives the product barbiturates by a twofold nucleophilic acyl substitution reaction of the ester groups with the $-\mathrm{NH}_{2}$ groups of urea (FIGURE 22.9). Amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal) are typical examples.
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Diethyl malonate -


Diethyl malonate -

Secobarbital