Chemistry Reference
In-Depth Information
alternatively:
O
O
O
B
O
H
S
N
2
CH
2
CH
2
CH
2
Br
Br
Br
resonance stabilization
new 7-membered
ring
Now LDA is a very strong base, and it is also a large base. We deduce that it can only remove a proton
from the less-hindered position, i.e. the COCH
3
, and this leads to seven-membered ring formation.
To say
tert
-butoxide is a smaller base and removes a proton from the alternative site is not sufficient.
If it can remove a proton from the hindered position, then it can also remove one from the less-hindered
position, so we ought to get a mixture of the two possible products. Here, we need to remember that although
LDA forms the enolate anion in an irreversible manner, enolate anion formation using
tert
-butoxide is an
equilibrium and, therefore, reversible. Therefore, we see formation of the more favourable product, i.e. that
with the five-membered ring.
O
O
O
O
CH
3
KO
t
B
u
KO
t
Bu
CH
2
CH
3
CH
3
Br
Br
Br
more favoured product
(c) The obvious change here is that three molecules of formaldehyde react with one molecule of acetaldehyde.
Formaldehyde is in excess; the reaction is initiated by mild base, sodium carbonate. Combination of these
compounds under basic conditions suggests enolate anion chemistry. Only acetaldehyde can form an enolate
anion; the less-substituted formaldehyde is a better electrophile than acetaldehyde, and it is also present in
excess. In the product, we can visualize the original acetaldehyde fragment carrying three CH
2
OH substituents.
The product is readily rationalized in terms of three similar aldol reactions, utilizing all three of the acidic
hydrogens in acetaldehyde.
CH
2
OH
Na
2
CO
3
H
2
O
CH
2
OH
HCHO
excess
CH
3
CHO
+
HOH
2
C
CHO
original acetaldehyde
HO
O
O
O
O
H
H
H
H
H
H
H
base removes a proton from
α
to carbonyl, generating an
enolate anion
resonance stabilization
enolate anion as
nucleophile adds to
carbonyl
O
these hydrogens are also acidic;
enolate anion formation and aldol
reaction can be repeated twice more
OH
H
H
O
O
H
O
H
H
HO
H
H
anion abstracts
proton from solvent
H
H
H
H
OH
H
H
H
H
OH
O
HOH
aldol product
