Lecture 1
THE CHEMISTRY OF THE CARBONYL GROUP
Textbook references:
McMurry - Chapter 18 (preview pp. 743-752 only), 19, 20, 21, 22, 23.
Streitweiser et al. - Chapters 14, 15, 18, 19, 20, 27.
Warren - Chemistry of the Carbonyl Group (Wiley).
The carbonyl group:
:
- O
:
+ C
Reactivity depends on substituents:
R
O
O
O
O
C
C
C
C
H
R
Aldehyde
R
Ketone
R
OH
R
Carboxylic
acid
Cl
Acyl halide
The electronic structure of the carbonyl group:
p
p

sp2

C
O
sp2
C
O
ALDEHYDES AND KETONES
- O
- O
+ C
R
H
+ C
R
R
Aldehyde
Ketone
Polarity: O is more electronegative than C.
Carbonyl compounds are electron deficient - ELECTROPHILIC - at the
carbonyl carbon atom.
Synthesis: Oxidation of alcohols:
RCH2OH
PCC
- H2
1 alcohol
RCH=O
aldehyde
+
PCC = Pyridinium chlorochromate =
RR1CHOH
2 alcohol
PCC*
- H2
NH
RR1C=O
ketone
* Or Na2Cr2 O7, Sodium dichromate
[CrO3Cl]Š
REACTIONS OF ALDEHYDES AND KETONES
Electron rich: electrophiles
- especially H + - can attack
+ C
here.
:
- O
:
Electron deficient:
nucleophiles can
attack here.
NUCLEOPHILIC ATTACK AT THE CARBONYL CARBON:
(1) REACTION WITH OXYGEN NUCLEOPHILES - ADDITION OF
WATER - FORMATION OF HYDRATES:
O
HO
+ H2 O
C
OH
C
gem*- or 1,1-diol: i.e.
hydrated carbonyl
compound.
*From the Latin geminal = twins.
Used to indicate two substituents
on the same carbon atom.
In aqueous solution the equilibrium position depends on the nature of
aldehyde or ketone:
Formaldehyde
HCHO ..... almost 100% hydrate
Other aldehydes RCHO ..... ca. 50% of each form
Ketones
R2CO ..... almost entirely ketone.
Mechanism of hydration: Nucleophilic attack of the water molecule
on the carbonyl carbon.
_
O
:
- O
:
+ C
R
H
+
OH2
HO
C
C
R
H
R
:
Tetrahedral
intermediate
:OH2
OH
H
gem - diol
(hydrate)
The hydrate cannot be isolated - so how do we know that it is formed?
Isotopic labelling experiment:
O
O18
H2O18
C
C
R
R
H
+ H2 O18
- H2O
18
H
- H 2O
O18 H
HO
+ H2O
C
R
H
In pure water (pH = 7) formation of the hydrate is slow but is much
accelerated by presence of catalytic amounts of H+ or OH–.
Acid catalysis:
H
+O
:
H 3O
:
C
R
:
O
H
+
O:
C
H
R
H
R
C
+
+ H 2O
H
Increased
electrophilicity
:
:OH2
+
OH2
HO
C
HO
R
HO
OH
H
H
C
H
:
+
O
R
:OH2
+ H 3O +
C
H
R
H
Base catalysis:
B:H+ + OH
B: + H2 O
-
O
O
HO
C
R
O
- H
H
HO
:
: OH:
[Powerful
nucleophile]
R
+ OH-
C
C
H
OH
H
R
H
(2) REACTION WITH OXYGEN NUCLEOPHILES - ALCOHOLS FORMATION OF ACETALS:
O
+ ROH
C
R
H+
H
HO
OR
C + ROH
RO
H+
C
R
H
Hemiacetal
(or ketone)
OR
R
H
Acetal
Mechanism:
H
:
+O
H3O+
C
C
H
R
H
R
:
+
O
HO
C
+
C
H
R
H
O
R
+
O
HO
R
R
H
C
H
H
HO
:OH2
OR
+ H3O+
C
R
H
Hemiacetal
R
H
:
R
O
:
:
O
H
OR H O+
3
+
H2O
:
HO
:
R
O
R - H2O
+O
O
C
C
+
C
C
R
R
H
H
R
R
H
R
H
N.B. Intramolecular nucleophilic displacement
reaction. H2O is an excellent leaving group
R
+O
+
O
RO
C
H
R
- H+
RO
H
C
R
R
OR
C
R
H
H
:
:
O
R
H
Overall:
:
:
O
C
R
+ 2 ROH
H
H3O+
RO
OR
C
R
+ H2O
H
To force equilibrium to the right remove product water as it is formed e.g. by distilling off or other technique (Deane-Stark trap).
:
:
O
C
R
+ 2 ROH
RO
H3O+
OR
C
H
R
+ H2O
H
Acetals are unstable under acidic conditions - hydrolysed to aldehydes
or ketones - reversing along the same mechanistic pathway as for their
formation. (Practice writing the mechanism of acid hydrolysis starting
from the acetal).
Acetals are stable under basic conditions - used as protecting group
for aldehydes and ketones under basic conditions.
Hemiacetals are not useful for carbonyl protection - unstable under acid
and basic conditions:
O
H
RO
C
R
O
-
O
C
C
H
R
RO + H2O
:
OH
:
RO
H
R
ROH + OH
+ RO
H
-
-
Some specific examples:
O
EtO
OEt
EtOH
H3O+
O
+
Ph
CH3
HO
OH
Ethane-1,2-diol
aka ethylene glycol
H3O+
- H2O
O
O
Ph
CH3
H3O+
Cyclic acetals are more easily formed and more stable than their acyclic
analogues - widely used as protecting groups.
Exercise: Try writing the mechanism for the reaction of acetaldehyde,
CH3CH=O, with ethane 1,2-diol and a trace of acid catalyst to form the
corresponding cyclic acetal.
(3) REACTION WITH NITROGEN NUCLEOPHILES - 1° AMINES FORMATION OF IMINES:
CH3
:
:
O
N
C
CH3
+ H2NCH3
+ H2O
C
CH3
CH3
CH3
Imine aka Schiff base
Mechanism:
H3O
+
R
HO
H
R
+
H 2O
C
C
C
+
NH2R
H
R
:
O
+
OH
NHR
C
H
:NH2 R
Proton
transfer
R
H
- H2O
H
R
N
- H+
C
R
H
R
N+
C
R
H
Question: Imine formation is acid catalysed as illustrated above but
will not proceed if more than a catalytic trace of acid is present. Can
you guess why?
(4) REACTION WITH CARBON NUCLEOPHILES - CARBANIONS
(4a) Organoalkali and Organomagnesium (Grignard) reagents
R
+
Li
R
C
R
+
MgI
organolithium
C Na+ sodium acetylide (alkynide)
organomagnesium - Grignard reagent
All act as sources of R i.e. of carbanions, very strongly
nucleophilic carbon
O
O
_
C
CH3
C
C
R
H
-
C
H
CH3
C
C
R
H2O
Note the irreversible formation
of a carbon-carbon bond when the
carbanion attacks the carbonyl
carbon - compare the reversible
attack of O and N nucleophiles.
OH
C
H
CH3
C
C
R
Similarly:
O
O
CH3Li or
C
CH3
CH3MgI
CH3
-
C
CH3
CH3
H 2O
This chemistry will be
studied in greater depth
in Module CM2005
CH3
OH
C
CH3
CH3
CH3
(4b) Cyanide anion - formation of cyanohydrins
OH
O
+ HCN
C
CH3
CH3
O
O
-
C
CH3
C
CH3
CH3
CH3
C
N
CN
-
C
CH3
CH3
CN
HCN
OH
C
CH3
CH3
CN