Aldehydes and Ketones
Structure and properties
Nomenclature
Synthesis (some review)
Reactions (some review)
Spectroscopy – mass spec, IR, NMR
Structure and properties
Aldehydes and ketones are the simplest
carbonyl containing compounds.
O
R
R'
Structure and properties
The carbonyl carbon and oxygen are sp2 hybridized.
Structure and properties
The carbon oxygen double bond is very polarized. The
dipole moments of aldehydes and ketones are larger than
most alkyl halides and ether.
Cl
O
O
H C H
H
CH3
u = 2.7 D
H3C
CH3
u = 2.9 D
H
u = 1.9 D
The high polarization of the carbonyl is due to the electronegativity
of oxygen and the separation of charge in the resonance form.
Structure and properties
London dispersion
Dipole-Dipole
Hydrogen bonding
The large polarization of the carbonyl functional group
produces dipole-dipole interaction between the molecules of
aldehydes and ketones.
Structure and properties
Hydrogen bonding does not occur between aldehyde and
ketone molecules. Hydrogen bonding can occur with other
molecules such as water, alcohols and amines.
Solubility



Soluble in alcohols.
Lone pair of electrons on oxygen of
carbonyl can accept a hydrogen bond from
O-H or N-H.
Acetone and acetaldehyde are miscible in
water. Solubility does decrease with longer
chain length (> 4-5 carbons).
Naming Ketones (IUPAC)
Replace -e with -one. Indicate the position of the carbonyl with
a number. For diones, don’t drop the final –e. Just add –dione.
Number the chain so that carbonyl carbon has the lowest
number.
For cyclic ketones the carbonyl carbon is assigned the number 1.
-CHO > RCOR > R-OH > R-NH2 > C=C > C=C
Naming Ketones (IUPAC)
O
O
CH3
C CH CH3
CH3
3-methyl-2-butanone
3-methylbutan-2-one
Br
3-bromocyclohexanone
O
CH3
C CH CH2OH
CH3
4-hydroxy-3-methyl-2-butanone
4-hydroxy-3-methylbutan-2-one
Naming Ketones (IUPAC)
O
O
O
OCH2CH3
CH3
Cl Cl
O
Common Names for Ketones


Named as alkyl attachments to -C=O.
Use Greek letters instead of numbers.
(alpha, beta and gamma)
O
O
CH3
C CH CH3
CH3
methyl isopropyl ketone
CH3CH C CH CH3
Br
CH3
a-bromoethyl isopropyl
ketone
Common Ketones to know:
O
O
CH3
CH3
CH3
Acetone
O
methyl ethyl ketone (MEK)
O
O
CH3
Acetophenone
CH2CH3
CH2CH3
propiophenone
benzophenone
Naming Aldehydes



IUPAC: Replace -e with -al.
The aldehyde carbon is number 1.
If -CHO is attached to a ring, use the
suffix -carbaldehyde.
Examples
CH3
CH2
CH3
O
CH CH2
C H
3-methylpentanal
CHO
2-cyclopentenecarbaldehyde
cyclopent-2-en-1-carbaldehyde
Examples
OH
OHC
CHO
CHO
Cl Cl
Name as Substituent


On a molecule with a higher priority
functional group, C=O is oxo- and -CHO is
formyl.
Aldehyde priority is higher than ketone.
COOH
CH3
O
CH3
O
C
CH CH2
C
H
3-methyl-4-oxopentanal
CHO
3-formylbenzoic acid
Aldehyde Common Names


Use the common name of the acid.
Drop -ic acid and add -aldehyde.




1 C: formic acid, formaldehyde
2 C’s: acetic acid, acetaldehyde
3 C’s: propionic acid, propionaldehyde
4 C’s: butyric acid, butyraldehyde.
CH3
Br
O
CH CH2
C H
-bromobutyraldehyde
3-bromobutanal
Common Aldehyde
O
O
H
H3C
H
Formaldehyde
H
CH3CH2
acetaldehyde
CHO
O
O
H
propionaldehyde
CH3CH2CH2
butyraldehyde
CHO
CHO
CH3
Benzaldehyde
p-tolualdehyde
2-naphthaldehyde
H
Common Aldehyde
Common forms of aldehydes.
Formalin is a 40% solution of formaldehyde in water.
There are two dry forms of formaldehyde the cyclic trimer trioxane and
paraformaldehyde.
O
O
O
O
Trioxane
O
O
O
n
paraformaldehyde
Heating these materials convert them to formaldehyde.
IR Spectroscopy

Very strong C=O stretch around 1710 cm-1.

Conjugation lowers C=O frequency to 1685-1690 cm-1.

Ring strain raises frequency.
(Cycolpentanone 1745 cm-1, cycolpropanone 1810 cm-1 )

Additional C-H stretch for aldehyde: two absorptions
at 2710 cm-1 and 2810 cm-1.
NMR Spectroscopy
1H

Aldehyde protons are in the δ 9-10 range.

CH3 adjacent to a carbonyl singlet at δ 2.1.

CH2 adjacent to a carbonyl give multiple peaks at δ 2.5.
NMR Spectroscopy
13C


Carbonyl carbon singlet in the 175-210 ppm range.
Carbons alpha to the carbonyl are in the 30-40 ppm
range.
1H
NMR Spectroscopy
13C
NMR Spectroscopy
Mass Spectroscopy
Mass Spectroscopy
Mass Spectroscopy
Industrial Importance



Acetone and methyl ethyl ketone are
important solvents.
Formaldehyde used in polymers like
Bakelite.
Flavorings and additives like vanilla,
cinnamon, artificial butter.
Common aldehydes and Ketones
Synthesis Review

Oxidation



2 alcohol + Na2Cr2O7  ketone
1 alcohol + PCC  aldehyde
Ozonolysis of alkenes.
Synthesis
Review

2 alcohol + Na2Cr2O7  ketone
OH
Na2Cr2O7 , H2SO4
or H2CrO4
or KMnO4
OH
Na2Cr2O7 , H2SO4
or H2CrO4
or KMnO4
Synthesis Review

1 alcohol + PCC  aldehyde
N
OH
OH
OH
H
-
CrO3Cl
Synthesis Review

Ozonolysis of alkenes.
Synthesis Review

Predict the products of the following reactions.
1) O3
2) (CH3)2S
Synthesis Review


Friedel-Crafts acylation of aromatic rings
 Acid chloride/AlCl3 + benzene  ketone
Gatterman-Koch
 CO + HCl + AlCl3/CuCl + benzene 
benzaldehyde
Synthesis Review
O
Z
Z
1) R
Cl
Z
O
AlCl3
+
2) H2O
Z = H , halogen or donor group
Predict the products.
O
OCH3
1) H3C
2) H2O
Cl
AlCl3
O
Synthesis Review
Z
Z
CO, HCl, AlCl3 / CuCl
Z
O
H
+
Z = H , activating group
Predict the products.
OCH3
CO, HCl, AlCl3 / CuCl
OCH3
Br
O
H
Synthesis Review
 Hydration of alkyne


Use HgSO4, H2SO4, H2O : a methyl ketone is
obtained with a terminal alkyne.
Use Sia2BH followed by H2O2 in NaOH
for aldehyde.
Synthesis Review
 Hydration of alkyne
2+
Hg , H2SO4
CH3CH2CH2C CH
O
CH3CH2CH2CCH3
H2O
Predict the products.
2+
Hg , H2SO4
CH3CH2CH2C CCH3
H2O
Synthesis Review
 Hydration of alkyne to an aldehyde
O
1) Sia2BH
CH3CH2CH2C CH
CH3CH2CH2CH2C
2) H2O2 , NaOH
H
Synthesis Using 1,3-Dithiane

Remove H+ with n-butyllithium.
• Alkylate with primary alkyl halide, then hydrolyze.
R-X is a primary halide or tosylate.
Ketones from 1,3-Dithiane
After the first alkylation, the second H can be
removed using BuLi and the resulting anion
react with another primary alkyl halide. Giving
a ketone upon hydrolyze.
BuLi
S
H
S
CH2CH3
S
S
_
CH3Br
CH2CH3
O
+
S
CH3
S
H , HgCl 2
H2O
CH2CH3
CH3
C
CH2CH3
Examples of using 1,3-Dithiane
1) BuLi
S
S
2) (CH3)2CHCH2Cl
+
3) H , HgCl2 , H2O
1) BuLi
S
S
2) C6H5CH2Cl
+
3) H , HgCl2 , H2O
Ketones from Carboxylates


Organolithium compounds attack the carbonyl and form a
dianion.
Neutralization with aqueous acid produces an unstable
hydrate that loses water to form a ketone.
The reaction can be done by first treating with one eq. of LiOH
followed by a alkyl/aryl lithium reagent. Consider what is happening in
each step (mechanistically how does the reaction work?).
Ketones from Carboxylates
O
1) LiOH
OH
2) CH3Li
3) H3O
O
+
1) LiOH
OH
2) C6H5Li
3) H3O
+
Ketones from Nitriles


A Grignard or organolithium reagent attacks the nitrile
carbon.
The imine salt is then hydrolyzed to form a ketone.
C N
CH3CH2MgBr +
CN
ether
1) CH3Li
2) H3O
+
1) C6H5Li
CN
2) H3O
+
C
N MgBr
CH2CH3
O
H3O
+
C
CH2CH3
Aldehydes from Acid Chlorides
A mild reducing agent can reduce an acid chloride
to an aldehyde.
O
CH3CH2CH2C
O
Cl
LiAlH(O-t-Bu)3
CH3CH2CH2C
What would happen if you used LAH?
Acid Chlorides are prepared by treating an acid with
thionyl chloride (SOCl2).
Show the synthesis of benzaldehyde from toluene.
H
Ketones from Acid Chlorides
Treatment of an acid chloride with lithium
dialkylcuprate (R2CuLi) can also be used to
synthesize ketones.
O
(CH3CH2CH2)2CuLi +
CH3CH2C Cl
O
CH3CH2C CH2CH2CH3
Reagent preparation:
2 CH3CH2CH2Li
CuI
(CH3CH2CH2)2CuLi
Ketones from Acid Chlorides
O
(CH2=CHCH2)2CuLi
CCL
O
CCl
(C6H5CH2)2CuLi
How it the lithium reagent made?
Nucleophilic Addition
The addition of a nucleophile to the carbonyl carbon is the most
common reaction of aldehydes and ketones.
Note: The carbonyl carbon is an electrophilic center.
Nucleophilic Addition

There two general types of addition reactions.


Strong nucleophiles attack the carbonyl carbon, forming an
alkoxide ion. The resulting alkoxide is then protonated to give an
alcohol. (see previous slide)
Weak nucleophiles attack a carbonyl if it has been protonated
(acid conditions). Protonation of the carbonyl increases the
reactivity of the carbonyl carbon toward nucleophilic attack.
The final step is deprotonation of the nucleophile.
Nucleophilic Addition
Strong nucleophile addition.
O
O
+
R
-
-
Nuc
R
Nuc
R'
OH
H-Nuc
R
Nuc
R'
R'
If the carbonyl carbon becomes a stereo center in the
product, both enantiomer are produced.
Weak nucleophile addition.
+
O
R
H
R'
O
R
H
OH
H-Nuc
OH
Base
R
Nuc
R'
H
R'
R
Nuc
R'
Nucleophilic Addition

Grignard reaction
Grignard reagents add to aldehydes to give secondary alcohols and
ketones to give tertiary alcohols. (one exception: CH2O)
Mg
R X
R Mg
ether
"Grignard"
1)R'CHO
R Mg
X
2) H3O
X
+
OH
RCHR'
OH
1)C6H5CHO
R Mg
X
2) H3O+
R
Addition of Water hydration



In acid, water is the nucleophile.
In base, hydroxide is the nucleophile.
Aldehydes are more electrophilic since they have fewer e-donating alkyl groups. (more reactive)
O
H
C
+
H
H2O
O
CH3
C
CH3
+
H2O
Classify the products?
OH
C
H
H
HO
HO
CH3
K =
2000
OH
C
CH3
K = 0.002
Addition of Alcohols
The addition of alcohols to the carbonyl is similar to the
addition of water.
Mechanism




The formation of acetals and ketals is acid catalyzed.
Adding H+ to carbonyl makes it more reactive with
weak nucleophile, ROH.
The addition of a single alcohol produces a
hemiacetal. Under the acidic reaction conditions
water is loss, followed by addition of a second
molecule of ROH forming the acetal.
All steps are equilibrium processes (reversible) .
Mechanism for Hemiacetal



The acid catalyst protonates the carbonyl.
Alcohol (a weak nucleophile) then adds to the carbonyl.
Loss of H+ gives the hemiacetal.
Hemiacetal to Acetal
HO
OCH3
+
HO
H
OCH3
OCH3
+
H+
+ HOH
HOCH3
OCH3
HOCH3
+
+
CH3O
H
OCH3
CH3O
OCH3
Cyclic Acetals


Formation of cyclic acetals is used as a way of protecting the carbonyl
group from under going nucleophilic attack in subsequent reactions. The
protecting group can be remove by treatment with dilute acid.
Cyclic acetals are made by reacting the aldehyde or ketone with a diol
O
+
CH2
HO
CH2
OH
H3O
Sugars commonly exist as acetals or hemiacetals.
+
CH2 CH2
O
O
Acetals as Protecting Groups


Hydrolyze easily in acid, stable in base.
Aldehydes more reactive than ketones.
O
O
H+
+
O
H
CH2CH2
O
OH OH
H
O
Selective Reaction of Ketone


React with strong nucleophile (base).
Remove protective group.
O
O
HO
CH3
H+ / H2O
CH3MgBr
O
O
H
CH3
O
H
O
O
H
Selective Reaction of aldehydes
and Ketones
How could the following synthesis be done.
O
OH
O
CH2CH2
H
Addition of HCN


CN- adds to the carbonyl group to give cyanohydrin.
The order of reactivity is: formaldehyde > aldehydes > ketones >>
bulky ketones.
O
CH3CH2
C
HO
CH3
+
HCN
CN
C
CH3CH2
The nitrile group can be convert to an acid group by acid
hydrolysis.
OH
OH
+
H
CN
CO2H
α-hydroxy acid
CH3
Formation of Imines


The formation of an imine involves an initial nucleophilic
attack by ammonia or a primary amine on the carbonyl
carbon. Followed by subsequent loss of a water molecule.
The C=O becomes a C=N-R group where R= H, alkyl or aryl
H+
H3C
H3C
H2N
H
H CH3
R
R N C OH
C O
C O
Ph
Ph
CH3
R N C OH
H
Ph
CH3
H2O
H
CH3
H+
R N C O
H
Ph
R N C OH
Ph
H
H
“imine” also called a
Schiff base when R is an alkyl group
H
+ H3O+
Ph
CH3
CH3
R N C
R N C
H
H
Ph
CH3
R N C
Ph
H2O
Ph
Important N-containing derivatives
Formation of N derivatives
O
NH2NHCONH2
+
H
NH2OH
O



H+
Loss of water is acid catalyzed, but acid deactivates the nucleophiles.
NH3 + H+  NH4+ (not nucleophilic).
Optimum pH is around 4.5.
Wittig Reaction


This reaction involves the nucleophilic addition of a phosphorus
ylides to the carbonyl carbon.
The product of a Wittig reaction is an alkene.
Phosphorus Ylides


The ylide is prepared by first reacting triphenylphosphine with an unhindered
alkyl halide (methyl or primary halide) to form a phosphonium salt.
Treatment with butyllithium then abstracts a hydrogen from the carbon
attached to phosphorus to produce the ylide.
Ph3P
+
Ph3P
+ CH3CH2Br
CH2CH3
_
+
Ph3P
BuLi
CH2CH3 Br
+
Ph3P
_
CHCH3
ylide
Mechanism for Wittig


The negative C on ylide attacks the positive C of carbonyl to form a
betaine.
Oxygen combines with phosphine to form the phosphine oxide.
+
+
Ph3P
_
Ph3P
H3C
C O
CHCH3
Ph
+
Ph3P
_
O
H C C CH3
CH3 Ph
Ph3P
O
H C C CH3
CH3 Ph
O
H C C CH3
CH3 Ph
Ph3P
H
H3C
O
C C
CH3
Ph
Wittig Reaction

Purpose are synthetic route for the preparation of the following
compounds.
CH2
Oxidation of Aldehydes
Aldehydes are easily oxidized to carboxylic acids.
+
)
3 2
Tollens Test
Tollens reagent is prepared by adding ammonia to a AgNO3 solution
until the precipitate dissolves.
Addition of Tollens reagent to a solution containing an aldehyde results
in the formation of a silver mirror.


O
R C H + 2
_
+
3 OH
+
Ag(NH3)2
_
+
3 OH
O
H2O
2 Ag + R C O
O
H2O
2 Ag + R C O
_
+
4 NH3 + 2 H2O
_
+
4
Reduction Reagents



Sodium borohydride, NaBH4, reduces C=O, but
not C=C.
Lithium aluminum hydride, LiAlH4, much
stronger, difficult to handle.
Hydrogen gas with catalyst also reduces the C=C
bond.
Catalytic Hydrogenation



Catalytic hydrogenation is widely used in industry.
Raney nickel, finely divided Ni powder saturated
with hydrogen gas.
Pt and Rh also used as catalysts.
O
OH
Raney Ni
H
Deoxygenation


Reduction of C=O to CH2
Two methods:


Clemmensen reduction if molecule is stable in
hot acid.
Wolff-Kishner reduction if molecule is stable in
very strong base.
Clemmensen Reduction
O
C
CH2CH3
Zn(Hg)
CH2CH2CH3
HCl, H2O
O
CH2
C
Zn(Hg)
H
HCl, H2O
CH2
CH3
Wolff-Kisher Reduction


Form hydrazone, then heat with strong base like
KOH or potassium t-butoxide.
Use a high-boiling solvent: ethylene glycol,
diethylene glycol, or DMSO.
CH2
C H
O
H2N NH2
CH2
C H
NNH2
KOH
heat
CH2
CH3