Aldehydes and Ketones

Structure of Aldehydes and Ketones

• Both aldehydes and ketones have a carbonyl
group, a carbon atom doubly bonded to an
oxygen atom, C=O.
• Aldehydes have a carbonyl group bonded to
an H atom.
• Ketones have a carbonyl group bonded to two
carbon atoms.
• In this and several following chapters, we study
the physical and chemical properties of classes
of compounds containing the carbonyl group,
C=O.
• aldehydes and ketones (Chapter 12)
• carboxylic acids (Chapter 13)
• acid halides, acid anhydrides, esters, and amides
(Chapter 14)
 Nomenclature of Aldehydes and Ketones
• IUPAC nomenclature
• The parent chain is the longest chain that contains the
carbonyl group.
• For an aldehyde, change the suffix from –e to –al; for
a ketone change the suffix from –e to –one
• For an unsaturated aldehyde or ketone, show the
carbon-carbon double bond by changing the infix from
–an– to –en–; the location of the suffix determines the
numbering pattern.
• For a cyclic molecule in which –CHO is bonded to the
ring, add the suffix –carbaldehyde.
• Some aromatic aldehydes and ketones have reserved
names. (We need to know benzaldehyde,
acetophenone, benzophenone.)
Some examples
 Precedence of Functional Groups
• When a molecule has several functional groups,
which functional group uses a suffix and which
functional group uses a prefix follows a preset
order of precedence (priority).
• Precedence in decreasing order (highest on top)
(lower precedence prefix in parenthesis)
• carboxylic acid
• aldehyde (oxo-)
• ketone (oxo-)
• alcohol (hydroxy-)
• thiol (mercapto-) [book has thiol and amine backwards]
• amine (amino-)
• alkene/alkyne (alkenyl/alkynyl)
• Use prefixes to name functional group with lower
precedence.
• Common names
• For aldehydes, the common name is derived from the
common name of the corresponding carboxylic acid.
• Know formaldehyde and acetaldehyde.
• For ketones, name the alkyl or aryl groups bonded to
the carbonyl carbon and add the word ketone.
• Order branches according to molecular weight.
• Know acetone.
 Physical Properties of Aldehydes and Ketones
• Oxygen is more electronegative than carbon (3.5
versus 2.5); and therefore, a C=O group is polar.

• Aldehydes and ketones are polar compounds and interact

in the pure state by dipole-dipole interactions.
• They have higher boiling points and are more soluble in
water than nonpolar compounds of comparable molecular
weight.
• In liquid aldehydes and ketones, there are
moderate intermolecular attractions between
the carbon pole (+) of one molecule and the
oxygen pole (-) of another molecule.

• Hydrogen bonding is not possible between (purely)

aldehyde or ketone molecules.
• Aldehydes and ketones have lower boiling points than
alcohols and carboxylic acids, compounds in which
hydrogen bonding between molecules is possible.
• Formaldehyde, acetaldehyde, and acetone are
infinitely soluble in water.
• Aldehydes and ketones become less soluble in
water as the hydrocarbon portion of the molecule
increases in size.
 Reactions of Aldehydes and Ketones
• Nucleophilic addition to  bond, AN
• Grignard reactions (adding carbanion to carbonyl group)
• Imine formation
• Acetal and hemi-acetal formation
• Keto-enol tautomerism
• Racemization at an -carbon
• Oxidation
• Chromic acid oxidation of aldehydes
• Nitric acid oxidation of ketones
• Tollens test
• Reduction
• Catalytic reduction
• Metal hydride reduction
• Reductive amination
 AN Reactions with Aldehydes and Ketones
• When a nucleophile adds to a carbonyl group (the
electrophile), the resulting tetrahedral carbonyl
addition intermediate (TCAI) has several different
possible mechanistic routes.
• These mechanistic routes are usually determined
by how many electronegative atoms are attached
to the tetrahedral carbon.
 AN Reactions Organized by Nucleophile
1. Very strong nucleophiles in very basic medium:
addition of hydrides (reduction) and carbanions.
• AN occurs first, then proton transfer (PT) occurs as a
separate step.
• Grignard reactions, metal hydride reductions

2. Moderate nucleophiles/bases: addition of nitrogen

and cyanide nucleophiles.
• ANand PT occur very close in time.
• Imine formation

3. Weak nucleophiles/bases: addition of water and

alcohols.
• PT occurs first, then AN
• Hemiacetal and acetal formation
 Grignard Reagents
• Addition of carbon nucleophiles (carbanions) is
one of the most important types of nucleophilic
additions to a C=O group.
• A new carbon-carbon bond is formed in the process.
• Carbanions can be formed using Grignard
reagents.
 Victor Grignard was awarded the Nobel Prize for
chemistry in 1912 for their discovery and application to
organic synthesis.
 Grignard reagents have the general formula RMgX,
where R is an alkyl or aryl group and X is a halogen.
• Grignard reagents are prepared by adding an
alkyl or aryl halide to a suspension of Mg metal
in diethyl ether.
• Given the difference in electronegativity between
carbon and magnesium (2.5 – 1.3), the C-Mg
bond is polar covalent, with C– and Mg+.
• In its reactions, a Grignard reagent behaves as a
carbanion.
• Carbanion: An anion in which carbon has an
unshared pair of electrons and bears a negative
charge.
• A carbanion is an excellent nucleophile and adds
readily to the carbonyl group of aldehydes and ketones.
• Reaction with protic acids
• Grignard reagents are very strong bases and react
with Brønsted-Lowry acids to form alkanes.

• Any compound containing an O-H, N-H, or S-H group

reacts with a Grignard reagent by proton transfer.

• Initially, this proton transfer is undesirable.

• One can’t use water, alcohols or amines as solvents.
• Reaction of a Grignard reagent with a carbonyl
group yields an alcohol.
• Reaction with formaldehyde gives a 1° alcohol.

• Reaction with any aldehyde other than formaldehyde

gives a 2° alcohol.
 • Reaction with a ketone gives a 3° alcohol.

• Reactions with Grignard reagents are done in

diethyl ether or THF.
• Once the addition to carbonyl group is done, the
reaction is completed by adding water to do a final
proton transfer (and remove the magnesium
halide ion).
 Imines
• Imine: A compound containing a C=N bond;
also called a Schiff base.
• Formed by the reaction of an aldehyde or ketone with
ammonia or a 1° amine and catalyzed with acid.

• Schiff bases are important as intermediates in the

synthesis and metabolism of amino acids.
 Addition of Alcohols
• Hemiacetal: A molecule containing an –OH group
and an -OR group bonded to the same carbon.

• Hemiacetals are minor components of an equilibrium

mixture except where a 5- or 6-membered ring can
form.
• Acetal: A molecule containing two –OR groups
bonded to the same carbon.

• Cyclic hemiacetals are very important in

understanding the structure of sugars like glucose
and fructose.
 Mechanism of Acid-Catalyzed
Hemiacetal Formation
Step 1. Add a proton: Proton transfer from HA to
the carbonyl oxygen.
H Cl H
O O O H

H3C C CH3 H3C C CH3 H3C C CH3

Step 2. Oxygen on alcohol does nucleophilic

attack on carbonyl carbon.
O H
O H
H3C C CH3
H3C C CH3
H2 H2
H O C CH3 H O C CH3
Step 3. Deprotonation of the oxonium ion yields
the hemiacetal.
O H O H

H3C C CH3 H3C C CH3

H2 H2
H O C CH3 O C CH3

• Hemiacetal and acetal formation can be

catalyzed with base (OH-) as well.
• Note that this reaction with the weak
nucleophile, ethanol, (PT) occurred first,
then AN.
Mechanism for Acid-catalyzed Conversion of
Hemiacetal to Acetal
Step 1. Add a proton: Proton transfer from HA to
the hemiacetal oxygen.

Step 2. Break a bond to give a stabilized ion.

(Leaving group is water.)
Step 3. Reaction of an electrophile with a
nucleophile to form a new covalent bond.

Step 4. Deprotonation: Proton transfer to A–

gives the acetal and regenerates the
acid catalyst.
• The formation of acetals is an equilibrium
reaction and is reversible.
• To form an acetal, experimental conditions are
used that remove water as it is formed (such as
high heat), thus driving the equilibrium reaction
toward acetal formation.
• By manipulating the equilibrium (using a large
excess of water), an acetal can be converted
back to the original aldehyde or ketone.
 Acetals as a Carbonyl-Protecting Group
• One way to synthesize the hydroxyaldehyde on
the right is by a Grignard reaction.

• But the aldehyde of the bromoaldehyde must be protected; often by

converting it to a cyclic acetal. (or else the Grignard reagent will react with the
other end of the molecule)
• Now magnesium and ether are added to make the
Grignard reagent.
O O
Br + Mg BrMg
O ether O
A cyclic acetal A Grignard reagent

• And the Grignard reagent reacts with the

benzaldehyde.
O - +
O O Mg Br O
Ph H + BrMg Ph O
O
A magnesium alkoxide

• Proton transfer completes the alcohol synthesis and

excess water undoes the cyclic acetal.
- + OH O
O MgBr O
HCl, H2 O
Ph O Ph H + HO OH
 Keto-Enol Tautomerism
• Enol: A molecule containing an -OH group
bonded to a carbon of a carbon-carbon double
bond

• The keto form

predominates at
equilibrium for most
simple aldehydes and
ketones.
• Interconversion of keto and enol forms is
catalyzed by both acid and base.
• Mechanism for acid catalysis
Step 1. Add a proton to the carbonyl oxygen.

Step 2 Take a proton away from the -carbon to A-.

 Racemization at an -Carbon
• When an enantiomerically pure aldehyde or
ketone with at least one -hydrogen is treated
with a trace of acid or base, it gradually becomes
a racemic mixture; it loses all optical activity.
• Racemization occurs because of the formation of
the achiral enol that is intermediate between the
two enantiomers.
 Oxidation
• Aldehydes are one of the most easily oxidized of
all functional groups.
• Ketones are not normally oxidized by H2CrO4.
• Instead, chromic acid is used to oxidize 2°
alcohols to ketones.
• They are oxidized by HNO3 at higher temperatures.
• Oxidation is via the enol and a multi-step mechanism.

• Adipic acid is one of the starting materials for the synthesis

of nylon 66.
 Silver Mirror Test for Aldehydes
• Tollens’ reagent: Prepared by adding NaOH to
AgNO3 (aq) to precipitate Ag2O, then adding
ammonia to form the silver-ammonia complex ion.
• Tollens’ reagent is specific for the oxidation of
aldehydes. If silver deposits on the walls of the
container as a silver mirror when Tollens’ reagent
is mixed with an unknown substance, the
substance must be an aldehyde.
 Reduction
• Aldehydes are reduced to 1° alcohols.
• Ketones are reduced to 2° alcohols.

• Reductions are done in two ways.

• Catalytic Hydrogenation
• Reaction with Metal Hydrides
 Catalytic Reduction
• Catalytic reductions are generally carried out at
from 25°C to 100°C and 1 atm to 5 atm of H2.

• A carbon-carbon
double bond may
also be reduced
under these
conditions.
 Metal Hydride Reductions
• Reductions that are more specific than catalytic
reduction involve metal hydrides.
• The most common metal hydrides that are used
for the reduction of aldehydes and ketones are
NaBH4 and LiAlH4.
• Both reagents are sources of hydride ion, H:–, a very
strong nucleophile.
• Reductions with NaBH4 are most commonly
carried out in aqueous methanol, in pure
methanol, or in ethanol.
• One mole of NaBH4 reduces four moles of
aldehyde or ketone.
• The key step in metal hydride reductions is
transfer of a hydride ion (a nucleophile) to the
C=O group (an electrophile) to form the new
covalent bond of a tetrahedral carbonyl
addition compound.
• Metal hydride reducing agents do not
normally reduce carbon-carbon double bonds,
and selective reduction of either C=O or C=C
is often possible.

• If reduction of the carbon-carbon double

bonds is desired instead, the carbonyl group
can be “protected” by forming a cyclic acetal.
 Reductive Amination
• Reductive amination: The formation of an
imine followed by its reduction to an amine.

• Reductive amination is a valuable method for the

conversion of ammonia to a 1° amine, and conversion
of a 1° amine to a 2° amine.