Aromatic Heterocycles 2: Pyridine Chemistry Flashcards
Why can pyridine act as a base?
Because the lone pair on the nitrogen is not involved in the aromatic π-system, making it available to accept protons.
What happens when pyridine reacts with HCl?
It forms pyridinium chloride, where the nitrogen becomes positively charged after protonation.
Is the lone pair on pyridine’s nitrogen delocalized in the aromatic ring?
No, it resides in an sp² orbital orthogonal to the aromatic π-system, and doesn’t participate in delocalization.
Does the lone pair on nitrogen participate in resonance in pyridine?
No — it stays in an sp² orbital, not the p-orbital that overlaps in the aromatic π-system.
How does pyridine maintain aromaticity despite having a nitrogen atom?
The nitrogen’s lone pair is not in the conjugated system; only the π-electrons in the ring participate in aromaticity (6 π-electrons total).
Draw the resonance structures of pyridine and state if the lone pair on N is involved in electron delocalization. (Insert Picture - Slide 3)
Lone pair is not delocalized; resonance involves only the ring π-electrons.
Why is pyridine less reactive toward electrophilic substitution compared to benzene?
Nitrogen is electronegative and withdraws electron density from the ring, deactivating it toward electrophiles.
Where does electrophilic substitution typically occur on pyridine?
At the 3-position (meta to N) because it avoids placing a positive charge on nitrogen in resonance structures.
What happens when pyridine is treated with Br₂ at high temperatures?
Bromination occurs at the 3-position, forming 3-bromopyridine.
Why is substitution favored at the 3-position in pyridine? (Insert Picture - Slide 6)
Resonance structures at position 3 avoid placing a positive charge on nitrogen, unlike 2- or 4-substitutions.
How can pyridine be activated for electrophilic substitution?
By forming pyridine N-oxide, which donates electron density into the ring and increases reactivity.
Where does electrophilic substitution occur in pyridine N-oxide?
At the 4-position.
What happens to pyridine N-oxide upon reaction with PCl₃?
The N-oxide group is removed, regenerating pyridine.
Describe the mechanism of nitration of pyridine N-oxide. (Insert Picture - Slide 8)
EAS at 4-position, oxygen’s lone pairs stabilize intermediate, and PCl₃ removes the N-oxide group at the end.
How does pyridine act as a catalyst in bromination of benzene?
It forms an N-bromo-pyridinium ion that reacts with benzene; pyridine is regenerated.
Why is pyridine a good nucleophilic catalyst?
It’s a stronger nucleophile than benzene and forms reactive intermediates easily.
Why is pyridine reactive toward nucleophilic substitution?
Nitrogen’s electronegativity creates partial positive charges on ring carbons, especially at positions 2 and 4.
What positions are favored for nucleophilic substitution in pyridine and why?
Positions 2 and 4, due to resonance stabilization; position 3 is not favorable.
Draw the resonance-stabilized intermediate for 2-substitution in pyridine. (Insert Picture - Slide 9)
Show delocalization avoiding positive charge on nitrogen.
What makes 2-chloropyridine a good substrate for nucleophilic substitution?
The chlorine at position 2 is a good leaving group, and the nitrogen helps stabilize the intermediate.
What are some reagents that can undergo nucleophilic substitution on 2-chloropyridine?
NaOR, NaSR, RNH₂, hydrazine, etc. (Examples: PhONa, NH₂NH₂)
What is the synthetic route to 2-chloropyridine from 2-pyridone? (Insert Picture - Slide 10)
Chlorination with POCl₃, forming 2-chloropyridine via electrophilic substitution.
What is bipyridyl (bipy) and how is it formed from pyridine?
Bipyridyl (bipy), or 2,2’-bipyridyl, is a bidentate ligand formed by coupling two pyridine rings. It is a strong ligand for transition metals, especially Fe(II).
It is synthesized by treating pyridine with FeCl₂·4H₂O under high temperature and pressure. Only a small amount (~5%) of pyridine converts into the Fe(II) complex of bipy, while the rest returns to react again. The process likely proceeds via a radical mechanism involving Fe(II).
