Page 33 - Pharmaceutical Organic Chemmistry-3 (Theoritical book) 24-25

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

Five-Membered Heterocycles

1. Compounds with One Heteroatom

The most common five-membered heterocycles:

These heterocycles possess a considerable aromatic character resulting, from

delocalization of 4 -electrons (from the 4 C-atoms) and 2 paired electrons donated by

the heteroatom (4n + 2 = 6). This combination forms a sextet of delocalized electrons

similar to that in benzene.

The resonance stabilization associated with each of these rings is large enough so that

they have a closer resemblance to benzene. This is visualized by the following

resonance contributing forms:

Therefore, these five-membered heterocycles belong to the -excessive

heteroaromatics, actually all are more reactive than benzene towards electrophilic

substitution, which occurs mainly at the -position.

The extent of electron release will depend mainly on the electronegativity of the

heteroatom, in the following order: O > N > S.