748 CHAPTER 18 Carbonyl Compounds II
represents any species in the
solution that is capable of donating a
proton, and represents any species in
the solution that is capable of removing
a proton.
≠B
HB
In the first step of the mechanism for imine formation, the amine attacks the car-
bonyl carbon. Gain of a proton by the alkoxide ion and loss of a proton by the ammo-
nium ion forms a neutral tetrahedral intermediate. The neutral tetrahedral intermediate,
called a carbinolamine, is in equilibrium with two protonated forms. Protonation can
take place on either the nitrogen or the oxygen atom. Elimination of water from the
oxygen-protonated intermediate forms a protonated imine that loses a proton to yield
the imine.
The equilibrium favors the nitrogen-protonated tetrahedral intermediate because nitro-
gen is more basic than oxygen. The equilibrium can be forced toward the imine by
removing water as it is formed or by precipitation of the imine product.
Overall, the addition of a nitrogen nucleophile to an aldehyde or a ketone is a
nucleophilic addition–elimination reaction: nucleophilic addition of an amine to form
an unstable tetrahedral intermediate, followed by elimination of water. The tetrahedral
intermediates are unstable because the newly formed carbon is bonded to an oxy-
gen and to a nitrogen—another electronegative atom. Water is eliminated, and loss of
a proton from the resulting protonated imine forms a stable imine.
In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nu-
cleophile forms a stable tetrahedral compound because the newly formed carbon is
notbonded to a second electronegative atom. Thus, aldehydes and ketones undergo
nucleophilic addition reactionswith carbon and hydrogen nucleophiles, whereas they
undergo nucleophilic addition–elimination reactionswith nitrogen nucleophiles.
The pH at which imine formation is carried out must be carefully controlled. There
must be sufficient acid present to protonate the tetrahedral intermediate so that
rather than the much more basic HO-is the leaving group. However, if too much acid
H 2 O
sp^3
sp^3
an imine
O +
C O
CH 3 CH 2 NH 2 + H 2 O
an imine
+ H 2 NCH 2 C
CH 3 CH 2
CH 3 CH 2
NCH 2 + H 2 O
benzaldehyde
an aldehyde
3-pentanone
a ketone
C NCH 2 CH 3
H
C
H
CH 3 CH 2
CH 3 CH 2
ethylamine
a primary amine
benzylamine
a primary amine
catalytic
H+
catalytic
H+
A compound with an carbon bonded
to an oxygen and to another
electronegative atom is unstable.
sp^3
an imine a protonated imine
neutral tetrahedral
intermediate
a carbinolamine
mechanism for imine formation
O + RNH 2
+ H 2 O
O
NH 2 R
HB+ HB+
+ NHR
NHR
OH OH
NH 2 R
HB+
H
OH
+
+
+
NR
−
H B
NR
H B
N–protonated
carbinolamine
O–protonated
carbinolamine
elimination
of water