JNTU Pharm. D I Year PHARMACEUTICAL ORGANIC CHEMISTRY Previous Question Paper (February/March - 2023 - R08)

Free radical addition to conjugated dienes, such as 1,3-butadiene, typically involves the addition of a radical initiator (like a halogen or peroxide-derived radical) to the terminal carbon atoms. This process is governed by the stability of the resulting allylic radical intermediate.

When a radical adds to a terminal carbon (C1) of 1,3-butadiene, it generates an allylic radical at the C2 position. Due to resonance, this unpaired electron is delocalized between C2 and C4. Consequently, the second step of the addition can occur at either the C2 position (1,2-addition) or the C4 position (1,4-addition).

The orientation is primarily determined by the stability of the intermediate and the reaction conditions. 1,4-addition is generally favored at higher temperatures as it leads to a more substituted, and thus more stable, alkene product (thermodynamic control). Conversely, 1,2-addition is often favored at lower temperatures due to the proximity of the incoming reagent to the site of initial radical attack (kinetic control).

Keto-enol tautomerism is a type of structural isomerism where a compound exists in equilibrium between two forms, the keto form (containing a carbonyl group) and the enol form (containing a hydroxyl group attached to a carbon-carbon double bond). This interconversion occurs via the migration of an alpha-hydrogen atom.

For example, in acetone (propanone), the equilibrium lies heavily toward the keto form:

The keto form is generally more stable than the enol form because the carbon-oxygen double bond is significantly stronger than the carbon-carbon double bond, despite the resonance stabilization present in the enol form.