Transcript Aldehydes and Ketones - University of Nebraska Omaha

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
H3C
C
H3C
CH3
C
CH3
H3C
Step 2. Oxygen on alcohol does nucleophilic
attack on carbonyl carbon.
O
H3C
C
H
O
H
CH3
H2
C
H3C
CH3
H
O
H
C
CH3
O
H2
C
CH3
O
H
C
CH3
Step 3. Deprotonation of the oxonium ion yields
the hemiacetal.
H3C
H
O
H
C
CH3
O
H2
C
H3C
CH3
O
H
C
CH3
O
H2
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
O
A cyclic acetal
BrMg
+ Mg
eth er
O
A Grign ard reagent
• And the Grignard reagent reacts with the
benzaldehyde.
O
-
H + BrMg
Ph
O MgBr
O
+
O
O
Ph
A magnesium alkoxide
O
• Proton transfer completes the alcohol synthesis
and excess water undoes the cyclic acetal.
-
+
O MgBr
Ph
OH
O
O
HCl, H2 O
Ph
O
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.