Transcript Organic Synthesis of aromatic compounds

Starter
1) Suggest a two-step synthesis for 3aminopropanoic acid from 3bromopropanol.
2) Suggest a two step synthesis for butanol
acid from ethyl butanoate.
Organic Synthesis of aromatic
compounds
L.O.:
Devise multi-stage synthetic routes for preparing
aromatic organic compounds.
Structures of benzene and 3-chloronitrobenzene
Converting benzene into nitrobenzene
Chlorination of an aromatic ring
Task:
Propose a retro-synthesis of paracetamol
Chirality in pharmaceutical synthesis
• Explain that the synthesis of pharmaceuticals often
requires the production of a single optical isomer.
• Explain that synthetic molecules often contain a
mixture of optical isomers, whereas natural molecules
often have only one optical isomer.
• Explain that the synthesis of a pharmaceutical that is
a single optical isomer increases costs, reduces side
effects and improves pharmacological activity.
• Describe strategies for the synthesis of a
pharmaceutical with a single optical isomer.
N
HO
N
O
+
O
Very potent M3 antagonist.
Clinical candidate for COPD
Task:
1) Dr Bravo synthesised the above compound
as a mixture of enantiomers. In pairs discuss
the disadvantages of using the mixture of
enantiomers as a clinical candidate for
COPD.
2) In pairs discuss possible solutions to
overcome the problems aforementioned.
1) Disadvantages:
o One of the enantiomers may have a harmful
effect
o Larger dose needed.
2)
o Purifying the mixture using chiral HPLC
o Synthesise a single chiral isomer
Modern chiral synthesis
How to prepare a single chiral isomer:
o Using enzymes.
o Chiral pool synthesis (starting from chiral
molecules)
o Use transition element complexes.
Stereoisomers of thalidomide
Pharmacological activity depends on whether or
not a drug can interact with a receptor site in a
biological system.
Structure of ibuprofen, used in many medicines
to relieve pain