Page 56 - Org 3 theoritical book 2024-25

Clinical Pharmacy PharmD - 2024/2025 Level 2 Pharmaceutical Organic Chemistry-3 (PC 305)

CH CH NH 3

H C CH 2 - 2H O
O O C H 2 N
glutaconic dialdehyde

2) From 1, 3-dicarbonyl compound, ammonia and an aldehyde (Hantzsch

Synthesis):

It involves the condensation of a 1,3-dicarbonyl compound containing an active

methylene group (2 equivalents) with an aldehyde and ammonia ( 1 equivalent each),

whereby a 1,4-dihydropyridine derivative is obtained, which is easily oxidized by

nitric acid to a pyridine derivative.

R
O O O O H
H H R O O R O
H + H [O]
O O - 3H O -2H
2
NH 3 N N
1,3-dicarbonyl H H
compound 1,4-dihydro-
pyridine derivative

Substitution of pyridine:
The π-electron densities at various positions of the pyridine ring are not all the same.

As there is a considerable drift of electrons from the ring towards the more

electronegative nitrogen atom.

+

+ +
N N N N N

Kekule structures charged structures

S N

S E S E

S N N S N