1. Reactions with electrophiles at C
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

2. Reactions with electrophiles at C
-Nitration
Not complete selectivity
Not HNO3 (explotions)

3. Reactions with electrophiles at C -Halogenation
ca 108 times more reactive than PhH
Chlorination
Bromination
Iodination

4. Reactions with electrophiles at C -Acylation
(FC alkylation not good react)
(strong Lewis acid, AlCl3, polym.)
-Condensation with carbonyl comps
c.f.

5. 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

6. 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

7. Reactions with electrophiles at Sulfur
React. with carbenes

8. Reactions with electrophiles at Sulfur
React. with carbenes

9. Reactions with electrophiles at Sulfur
Reactions with nucleophiles
NB! Electron rich Aryl

10. Reactions with nucleophiles

11. C-metallation and further reactions

12. Pd cat. couplings Reat with radicals Cycloadditions Easier with furan
Seldom synthetically usefull
Cycloadditions
Easier with furan

13. Oxythiophenes Aminothiophenes c.f. c.f. Aminopyrroles
-Amino (not iminoform) - unstable

14. Synthesis of Thiophenes
Carbonyl condensations
Strategy a

15. Strategy a, cont.
Strategy b
Strategy c

16. Strategy d
Hinsberg synth.

17. Miscellaneous carbonyl reactions

18. Cycloadditions