PYRIDINES

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PYRIDINES
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
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PYRIDINES

• Reaction with electrophiles - react. on N
• Protonation
• Nitration
• Sulfonation
• Amination
• Halogenation
• Alkylation
• Acylation

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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.
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Nitration
Bakke
1,5-sigmatropic rearrang.
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Sulfonation
Possible intermediates
Halogenation
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Reaction with Nucleophiles

• XH, 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)

• XLG, Displacement of good leaving group
• X Halogen (FgtgtCl,gtBr,gtI), -OSO2R, -NO2, -OR

Via Pyridyne
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Metallation and Reactions with Electrophiles
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Direct Reactions with Electrophiles Additions,
Substitutions
Some examples (c.f. react. with ArLi)
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Pd-Catalyzed Coupling reactions
a) On metallated pyridines
b) On halopyridines
Reactivity
XIgtXBr/OTfgtXCl
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Radical Reactions
a) Reactions with C-radicals Minisci React.
b) Generation of / Reaction on pyridylradicals
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Reductions
Photochemistry
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Oxy-, Thio- and Aminopyridines
Structure - Tautomerism
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Reactions on Pyridones - With Electrophiles
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Reactions on Pyridones - Deprotonation - O or
N-substitution
Reactions on Pyridones - Replacement of Oxygen
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Thiopyridones
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Aminopyridines
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Alkyl- and Vinylpyridines
Quartenary Pyridinium Salts
Add of -hydrides -dithionite
-organometallics -stab.
carbanions etc. etc.
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Co-enz. NAD
Hydride add. to NAD, SubH2 oxidized
Nicotine amide Vit. B3 Adenine Vit. B4
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Pyridine N-oxides
More activated for electrophilic and
nucleophilic attack
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Electrophilic Ar. subst
Rearrangements