Basic Organic Chemistry
Course code: CHEM 12162
(Pre-requisites : CHEM 11122)
Chapter – 06
Chemistry of Aldehydes & Ketones
Dr. Dinesh R. Pandithavidana
Office: B1 222/3
Phone: (+94)777-745-720 (Mobile)
Email: dinesh@kln.ac.lk
Carbonyl Compounds
Carbonyl Structure
• Carbon is sp2 hybridized.
• C=O bond is shorter, stronger, and
more polar than C=C bond in alkenes.
IUPAC Names for Ketones
• Replace -e with -one. Indicate the
position of the carbonyl with a number.
• Number the chain so that carbonyl
carbon has the lowest number.
• For cyclic ketones the carbonyl carbon
is assigned the number 1.
Examples
O
O
CH3
C CH CH3
CH3
Br
3-methyl-2-butanone
3-bromocyclohexanone
O
CH3
C CH CH2OH
CH3
4-hydroxy-3-methyl-2-butanone
Naming Aldehydes
• Replace -e with -al.
• The aldehyde carbon is number 1.
• If -CHO is attached to a ring, use the suffix carbaldehyde.
CH3
CH2
CH3
O
CH CH2
C H
CHO
3-methylpentanal
2-cyclopentenecarbaldehyde
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
Historical Common Names
O
O
CH3
C
C CH3
acetophenone
acetone
O
C
benzophenone
CH3
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.
Solubility
Good solvent for 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.
Formaldehyde
• Gas at room temperature.
• Formalin is a 40% aqueous solution.
H
H
O
H
C
O
O
C
C H
O
H
H
trioxane, m.p. 62°C
heat
H C H
H2O
formaldehyde,
b.p. -21°C
HO
OH
H C
H
formalin
Synthesis Review
• Oxidation
2° alcohol + Na2Cr2O7 → ketone
1° alcohol + PCC → aldehyde
• Ozonolysis of alkenes.
R'
H
C C
R
R''
1) O3
2) (CH3)2S
R'
H
C O
+ O C
R
• Hydration of terminal alkynes
Use HgSO4, H2SO4, H2O for methyl ketone
Use Sia2BH followed by H2O2 in NaOH for aldehyde.
R''
Synthesis Using 1,3-Dithiane
• Remove H+ with n-butyllithium.
BuLi
S
S
H
H
S
S
_
H
• Alkylate with primary alkyl halide,
then hydrolyze.
O
+
H , HgCl2
CH3CH2Br
S
_
H
S
S
H
S
H2O
CH2CH3
C
H
CH2CH3
Ketones from 1,3-Dithiane
• After the first alkylation, remove the second
H+, react with another primary alkyl halide,
then hydrolyze.
S
H
S
CH2CH3
H , HgCl2
CH3Br
BuLi
S
_
S
CH2CH3
O
+
S
CH3
S
CH2CH3
H2O
C
CH3
CH2CH3
Ketones from Carboxylates
• Organolithium compounds attack the carbonyl and
form a diion.
• Neutralization with aqueous acid produces an
unstable hydrate that loses water to form a ketone.
O
C
_
O Li +
_ +
O Li
_
+
C O Li
CH3
CH3Li
H3O
+
OH
O
C OH _
H2O
CH3
C
CH3
Ketones from Nitriles
• A Grignard or organolithium reagent attacks the nitrile
carbon.
• The imine salt is then hydrolyzed to form a ketone.
N MgBr
C N
CH3CH2MgBr +
ether
C
CH2CH3
O
H3O
+
C
CH2CH3
Aldehydes from Acid Chlorides
Use a mild reducing agent to prevent reduction
to primary alcohol.
O
CH3CH2CH2C
O
Cl
LiAlH(O-t-Bu)3
CH3CH2CH2C
H
Ketones from Acid Chlorides
Use lithium dialkylcuprate (R2CuLi), formed by
the reaction of 2 moles of R-Li with cuprous
iodide.
2 CH3 CH2CH2Li
CuI
(CH3CH2 CH2)2CuLi
O
(CH3CH2CH2)2CuLi +
CH3CH2C Cl
O
CH3CH2C CH2CH2CH3
Reactions of Nucleophilic Addition
• A strong nucleophile attacks the carbonyl carbon,
forming an alkoxide ion that is then protonated.
• A weak nucleophile will attack a carbonyl if it has
been protonated, thus increasing its reactivity.
• Aldehydes are more reactive than ketones.
Wittig Reaction
• Nucleophilic addition of phosphorus ylides.
• Product is alkene. C=O becomes C=C.
How to Prepare Phosphorus Ylides
• Prepared from triphenylphosphine and an
unhindered alkyl halide.
• Butyllithium then abstracts a hydrogen from the
carbon attached to phosphorus.
Ph3P
+
Ph3P
+ CH3CH2Br
+
Ph3P
CH2CH3
BuLi
+
Ph3P
_
CH2CH3 Br
ylide
_
CHCH3
Mechanism for Wittig Reaction
• 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
C CH3
CH3 Ph
H C
Ph3P
H
H3C
C
O
C
CH3
Ph
Addition of Water
• In acid, water is the nucleophile.
• In base, hydroxide is the nucleophile.
• Aldehydes are more electrophilic since they have
fewer e--donating alkyl groups.
O
H
C
HO
H
+ H 2O
O
CH3
C
CH3
C
H
HO
+ H2O
OH
CH3
H
K = 2000
OH
C
CH3
K = 0.002
Addition of HCN
• HCN is highly toxic.
• Use NaCN or KCN in base to add cyanide,
then protonate to add H.
• Reactivity formaldehyde > aldehydes >
ketones >> bulky ketones.
O
CH3CH2
C
HO
CH3
+ HCN
CH3CH2
CN
C
CH3
Formation of Imines
• Nucleophilic addition of ammonia or primary
amine, followed by elimination of water molecule.
• C=O becomes C=N-R
CH3
H3C
RNH2
C O
Ph
R
CH3
N C OH
H
Ph
R
_
C
H2N
O
+ Ph
R
CH3
N C
Ph
R
CH3
N C OH
H
Ph
Addition of Alcohol
Mechanism
• Must be acid-catalyzed.
• Adding H+ to carbonyl makes it more reactive with
weak nucleophile, ROH.
• Hemiacetal forms first, then acid-catalyzed loss of
water, then addition of second molecule of ROH
forms acetal.
• All steps are reversible.
Mechanism for Hemiacetal
O
+ OH
+
H+
H
OH
+
OH
HO
HOCH3
HO
OCH3
+
HOCH3
OCH3
+
+ H2OCH3
Hemiacetal to Acetal
HO
OCH3
+
HO
H
OCH3
OCH3
+
H+
+ HOH
HOCH3
OCH3
HOCH3
+
+
CH3O
H
OCH3
CH3O
OCH3
Cyclic Acetals
• Addition of a diol produces a cyclic acetal.
• Sugars commonly exist as acetals or
hemiacetals.
CH2 CH2
O
O
O
+
CH2
HO
CH2
OH
Acetals as Protecting Groups
• Hydrolyze easily in acid, stable in base.
• Aldehydes more reactive than ketones.
O
O
CH2
CH2
OH
HO
C
O
H
+
H
C
O
O
Selective Reaction of Ketone
• React with strong nucleophile (base)
• Remove protective group.
+
_
MgBr O
CH3
O
HO
CH 3 MgBr
C
O
O
H3O
C
O
O
CH3
+
C
O
H
Oxidation of Aldehydes
Easily oxidized to carboxylic acids.
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
• 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, H 2O
CH2
CH3
Wolff-Kishner 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