Chemistry Reference
In-Depth Information
whereupon addition of base (e.g. sodium hydroxide solution) will
regenerate trimethoprim free base. This can then be back
extracted into an organic solvent, removed and dried (with
MgSO
4
), and trimethoprim can be isolated by evaporation of
organic solvent. If this extraction is carried out exhaustively, no
trimethoprim will remain in the original organic phase, which
may be evaporated to yield sulfamethoxazole.
Alternatively, the sulfamethoxazole may be converted to its
sodium salt by addition of sodium hydroxide solution. The
sulfamethoxazole sodium will be more soluble in the aqueous
phase and can be removed as above, acidified with mineral acid
(e.g. dilute hydrochloric acid solution) and extracted into fresh
organic solvent. The organic phase is dried and evaporated as
before. This will leave trimethoprim in the original organic layer.
The answers are shown in Figure 11.3.
A3.2
Nicotine is the addictive alkaloid found in leaves of the tobacco
plant (
Nicotiana tabacum
or
N. rustica
). It is a colourless or pale
yellow oil that darkens on exposure to air (due to oxidation). Pure
nicotine is a deadly poison with an LD
50
in mice of 0.3 mg kg
-1
if
given intravenously. From the structure shown in Figure 3.26,
nicotine is clearly a base with two basic centres. The pyridine
nitrogen has a p
K
a
of 6.16, while the
N
-methylpyrrolidine has a
p
K
a
of 10.96. This means that only one of the nitrogen atoms is
sufficiently basic to ionise at a pH of 7.4, so the structure of nico-
tine that predominates at the pH of plasma is the mono-cation
shown in Figure 11.4. Since the mono-cation predominates at the
pH of blood and intracellular fluid, it would be reasonable to
assume that this is the form that is active at the receptor. Further
evidence for the active form of nicotine is given by considering the
natural agonist.
A3.3
