CHAPTER 19: CARBONYL COMPOUNDS III
A hydrogen bonded to a carbon adjacent to a carbonyl carbon is sufficiently acidic to be
removed by a strong base.
The carbon adjacent to a carbonyl carbon is called an α-carbon. A hydrogen bonded to an α-
carbon is therefore called an α-hydrogen.
19.1 The Acidity of an α-Hydrogen
A compound that contains a relatively acidic hydrogen bonded to an sp carbon is called a
The α-hydrogen of a ketone or an aldehyde is more acidic than the α-hydrogen of an
An α-hydrogen is more acidic because the base formed when a proton is removed from an α-
carbon is relatively stable.
The electrons left behind when a proton is removed from the α-carbon of an ester are not as
readily delocalized onto the carbonyl oxygen as they would be in an aldehyde or a ketone.
This is because the oxygen of the OR group of the ester also has a lone pair that can be
delocalized onto the carbonyl oxygen. Thus, the 2 pairs of electrons compete for
delocalization onto the same oxygen.
If the α-carbon is between 2 carbonyl groups, the acidity of an α-hydrogen is even greater.
Β-keto ester – an ester with a second carbonyl group at the β-position.
Β-diketone – a ketone with a second carbonyl group at the β-position. The acidity of α-hydrogens bonded to carbons flanked by 2 carbonyl groups increases
because the electrons left behind when the protons is removed can be delocalized onto 2
19.2 Keto–Enol Tautomers
Tautomers are isomers that are in rapid equilibrium.
Keto-enol tautomers differ in the location of a double bon and a hydrogen.
For most ketones, the enol tautomer is much less stable than the keto tautomer.
19.3 Keto–Enol Interconversion
The interconversion of the keto and enol tautomers is called keto-enol interconversion,
keto-enol tautomerization, or enolization. The interconversion can be catalyzed by either a
base or an acid. 19.4 How Enolate Ions and Enols React
The resonance contributors of the enolate ion show that it has 2 electron-rich sites: the α-
carbon and the oxygen. The resonance contributor with negatively charged oxygen makes
the greater contribution to the hybrid.
The enolate ion is an example of an ambident nucleophile. An ambident nucleophile is a
nucleophile with 2 nucleophilic sites (“two teeth”).
Which nucleophilic site (C or O) reacts with an electrophile depends on the electrophile and
on the reaction conditions. Protonation occurs preferentially on oxygen (the kinetic product),
because of the greater concentration of negative charge on the more electronegative oxygen
When the electrophile is something other than a proton, carbon is more likely to be the
nucleophile because carbon is a better nucleophile than oxygen.
The mechanism for the formation of an enolate ion and its subsequent reaction with an
electrophile is shown below. The overall reaction is an α-substitution reaction; one electrophile (E ) is substituted for
another (H ) at the α-carbon.
The resonance contributors of the enol show that it too has 2 electron-rich sites: the α-carbon
and the oxygen.
The mechanism for the formation of an enol and its subsequent reaction with an electrophile
is shown below.
In summary, a carbonyl compound with an α-hydrogen can undergo a substitution reaction
at the α-carbon. The substitution reaction can be catalyzed by a base (forming an enolate
ion) or by an acid (forming an enol).
19.5 Halogenation of the α-Carbon of Aldehydes and Ketones
When Br ,2Cl 2 or I2is added to a solution of an aldehyde or a ketone, a halogen replaces one
or more of the α-hydrogens of the carbonyl compound.
In the acid-catalyzed reaction, the halogen replaces one of the α-hydrogens: Base-Promoted Halogenation
When excess Br , 2l , 2r I i2 added to a basic solution of an aldehyde or a ketone, the
halogen replaces all the α-hydrogens. These 2 steps are repeated until all the α-hydrogens are replaced by the halogen.
The Haloform Reaction
In the presence of excess base and excess halogen, a methyl ketone is converted into a
The conversion of a methyl ketone to a carboxylate ion is called a Haloform reaction
because one of the products is Haloform – either CHCl (3hloroform), CHBr (bro3oform),
or CHI 3iodoform).
19.6 Halogenation of the α-Carbon of Carboxylic Acids: The Hell-Volhard-Zelinski
Hell-Volhard-Zelinski reaction (HVZ reaction) – heating a carboxylic acid with Br + P
in order to convert it into an α-bromocarboxylic acid. 19.7 α-Halogenated Carbonyl Compounds are Useful in Synthesis
Removing a proton from an α-carbon makes the α-carbon a nucleophile.
When the α-position is halogenated, the α-carbon becomes electrophilic – it reacts with
Substituting a bromine for a hydrogen bonded to an α-carbon makes the α-carbon an
19.8 Using LDA to Form an Enolate Ion
When LDA (lithium diisopropylamide) is used to removed the α-hydrogen, essentially all
the carbonyl compound is converted to the enolate ion because LDA is a much stronger base
than the base being formed. Therefore, LDA is the base of choice for those reactions that
require the carbonyl compound to be completely converted to an enolate ion before it reacts
with an electrophile. 19.9 Alkylating the α-Carbon of Carbonyl Compounds
Putting an alkyl group on the α-carbon of a carbonyl compound is an important reaction
because it gives us another way to form a carbon-carbon bond. Alkylation is carried out by
first removing a proton from the α-carbon with a strong base such as LDA and then adding
the appropriate alkyl halide. Because the alkylation is aN S 2 reaction, it works best with
methyl halides and primary alkyl halides.
Enolate ions can be alkylated on the α-carbon.
19.10 Alkylation and Acylation of the α-Carbon Using an Enamine Intermediate
Enamines react with electrophiles in the same way that enolate ions do. Because the alkylation step is an SN2 reaction, only primary alkyl halides or methyl halides
should be used. One advantage to using an enamine intermediate to alkylate an aldehyde or a
ketone is that only the monoalkylated product is formed.
In addition to using enamine intermediates to alkylate aldehydes and ketones, they can also
be used to acylate these compounds.