Chemistry Reference
In-Depth Information
H
3
C
O
HO
O
O
H
2
O
O
O
H
H
N
N
O
HO
H
3
C
H
H
CH
3
CH
3
H
H
Diamorphine
Morphine
O
+ 2CH
3
C
OH
Figure 8.21
The structure and hydrolysis of diamorphine.
Diamorphine injection is prepared by dissolving the contents of a
sealed container in Water for Injections BP immediately prior to use. The
instability of the ester groups precludes sterilisation of the injection by
autoclaving.
A close inspection of the structure of diamorphine will show that the
molecule also contains 'benzylic' hydrogen atoms, on the CH
2
adjacent to
the benzene ring. This site is susceptible to oxidation and, for this reason,
diamorphine should be stored in a well-closed container protected from
light.
Penicillin
Penicillin (and, for that matter cephalosporin) antibiotics are cyclic amides
and are very prone to hydrolysis. Normal amide bonds are more resistant to
hydrolysis than are esters, but in penicillins the amide is cyclised into a four-
membered b-lactam ring. The bond angles in this ring are close to 90
, in
contrast to an open-chain amide in which the bond angle is 120
(sp
2
hybridised carbon). This unnatural bond angle in the b-lactam ring means
that the ring is very easily opened by nucleophiles, particularly water.
The effect is compounded by the geometry of the fused bicyclic ring
system. The b-lactam and thiazolidine rings of penicillin do not lie in the
same plane (in fact, they lie almost perpendicular to each other), so reson-
ance effects within the cyclic amide are prevented, which leaves the
carbonyl carbon atom much more d
than expected and hence more liable
