THIOPHENES

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THIOPHENES
Reactions with electrophiles at C Preferably at
C-2 / C-5 (cf pyrroles)

• -Protonation
• Much more stable under acidic conditions than
  pyrroles and furans
• Protonation at C-2 /C-5

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Reactions with electrophiles at C

• -Nitration
• Not complete selectivity
• Not HNO3 (explotions)

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Reactions with electrophiles at C
-Halogenation ca 108 times more reactive than PhH
Chlorination
Bromination
Iodination
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Reactions with electrophiles at C
-Acylation (FC alkylation not good react)
(strong Lewis acid, AlCl3, polym.)
-Condensation with carbonyl comps
c.f.
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Reactions with electrophiles at C
-Condensation with carbonyl comps, cont.
-Condensation with imines / iminium ions
Mannich react.
in case of pyrrol, Mannich reag. generated in
situ
Thiophene (and furan) Preformed reagent
generally required
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Reactions with electrophiles at Sulfur

• Possible for thiophene S in 3rd row
• Not possible for furan / pyrrole O and N in 2nd
  row
• Probably sp3 S. tetrahedral
• Works best for electron rich thiophenes

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Reactions with electrophiles at Sulfur
React. with carbenes
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Reactions with electrophiles at Sulfur
React. with carbenes
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Reactions with electrophiles at Sulfur
Reactions with nucleophiles NB! Electron rich Aryl
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Reactions with nucleophiles
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C-metallation and further reactions
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Pd cat. couplings
Reat with radicals Seldom synthetically usefull
Cycloadditions
Easier with furan
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Oxythiophenes
c.f.
Aminothiophenes
c.f. Aminopyrroles
-Amino (not iminoform) - unstable
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Synthesis of Thiophenes
Carbonyl condensations
Strategy a
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Strategy a, cont.
Strategy b
Strategy c
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Strategy d
Hinsberg synth.
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Miscellaneous carbonyl reactions
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Cycloadditions