1. Synthesis of Pyridines
From 1,5-dicarbonyl and ammonia (c.f. chapt. 3)
From 1,3-dicarbonyl and enamine (c.f. chapt. 3)
From 2 equivs. 1,3-dicarbonyl , aldehyde and ammonia - Hantzsch Synthesis
Various syntheses from other heterocycles

2. PYRIDINES
Reaction with electrophiles - react. on N:
Protonation
Nitration
Sulfonation
Amination
Halogenation
Alkylation
Acylation

3. } Reaction with electrophiles - react. on C:
Electrophilic Aromatic Substitution
Electron defficient / Poor nucleophiles
Difficult
Electrophiles may react at N }
Not:
FC alkylation
FC acylation
Nitration
Sulfonation
Halogenation
React. in 3-pos.

4. Nitration
Bakke:
[1,5]-sigmatropic rearrang.

5. Sulfonation
Possible intermediates
Halogenation

6. } Attack in the 2-pos (not 4-pos)
Reaction with Nucleophiles
X=H, Substitution with “hydride” transfer
Nu: NaNH2 - amination - Chichibabin reaction
Nu: BuLi, PhLi etc - alkylation / arylation
Nu: NaOH - “hydroxylation” - NB! High temp
} Attack in the 2-pos (not 4-pos)
X=LG, Displacement of good leaving group
X: Halogen (F>>Cl,>Br,>I), -OSO2R, -NO2, -OR
Via Pyridyne

7. Metallation and Reactions with Electrophiles

8. Direct Reactions with Electrophiles: Additions, Substitutions
Some examples (c.f. react. with ArLi)

9. Pd-Catalyzed Coupling reactions
a) On metallated pyridines
b) On halopyridines
Reactivity
X=I>X=Br/OTf>X=Cl

10. Radical Reactions
a) Reactions with C-radicals: Minisci React.
b) Generation of / Reaction on pyridylradicals

11. Reductions
Photochemistry

12. Oxy-, Thio- and Aminopyridines
Structure - Tautomerism

13. Reactions on Pyridones - With Electrophiles

14. Reactions on Pyridones - Deprotonation - O or N-substitution
Reactions on Pyridones - Replacement of Oxygen

15. Thiopyridones

16. Aminopyridines

17. Alkyl- and Vinylpyridines
Quartenary Pyridinium Salts
Add of: -hydrides
-dithionite
-organometallics
-stab. carbanions
etc. etc.

18. Co-enz. NAD+ Hydride add. to NAD+, SubH2 oxidized
Nicotine amide: Vit. B3
Adenine: Vit. B4

19. Pyridine N-oxides More activated for electrophilic
and nucleophilic attack

20. Electrophilic Ar. subst
Rearrangements