Page 57 - Org 3 theoritical book 2024-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)
Moreover, because of the withdrawal of electrons from the ring-carbon atoms, the

ring is deactivated towards electrophilic reagents, resembling the effect of the
nitro group in nitrobenzene on the activity of the benzene ring. Therefore, pyridine

is one of the - deficient heteroaromatics.

Furthermore, in strong acid solution, pyridine is protonated, forming a pyridinium

ion, and so the positively charged nitrogen atom deactivates the ring even more

than the unprotonated nitrogen atom.

H + pyridinium ion
+ (highly unreactive)
N N
H

Therefore, pyridine is more reactive towards nucleophilic reagents than benzene

and the nucleophilic attack occurs preferentially at the 2-and 4-positions.

Reactions of pyridine:

I- Electrophilic rections

A) Addition to the nitrogen:

a) Protonation:

Pyridine is easily protonated with most inorganic acids forming crystalline pyridinium

salts.

HCl
+ - pyridinium chloride
N N Cl
H

b) Alkylation:

Alkyl halides and alkyl sulphates react readily with pyridine giving pyridinium salts

(quaternary salts), which on heating at 300 rearranged to alkylpyridines, e.g., pyridine
o
methiodide gives 2- and 4-methylpyridine upon heating.

CH 3
o
CH I 300 C
3
+ CH +
N N 3
I - N N
CH 3
1-methylpyridinium iodide
(pyridine methiodide)