JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D I Year PHARMACEUTICAL ORGANIC CHEMISTRY Previous Question Paper (October/November - 2019 - R08)

Cycloalkanes can be synthesized through several key chemical methods:

1. From Dihalides (Wurtz-type reaction): Treatment of alpha,omega-dihalides with metallic sodium or zinc results in intramolecular cyclization. For example, 1,3-dibromopropane reacts with sodium to form cyclopropane.
2. From Aromatic Compounds: Catalytic hydrogenation of benzene or its derivatives under high pressure and temperature (using Ni, Pt, or Pd catalysts) yields cyclohexane and its substituted derivatives.
3. Dieckmann Condensation: Intramolecular Claisen condensation of dicarboxylic acid esters in the presence of a strong base (like sodium ethoxide) produces cyclic beta-keto esters, which can be further reduced to cycloalkanes.
4. Pyrolysis of Calcium or Barium Salts: Heating the calcium or barium salts of dicarboxylic acids (e.g., adipic acid) leads to the formation of cyclic ketones, which are subsequently reduced to cycloalkanes via Clemmensen or Wolff-Kishner reduction.

Bayer’s Strain Theory proposes that the stability of cycloalkanes depends on the deviation of their internal bond angles from the ideal tetrahedral angle of 109.5°. The theory suggests that any deviation creates angle strain, making the ring less stable and more reactive.

Where α is the internal bond angle of the cycloalkane. According to this theory, cyclopropane (60°) has high positive strain, cyclobutane (90°) has moderate strain, and cyclopentane (108°) is the most stable due to minimal deviation.

In terms of orbital pictures, the carbon atoms in small rings cannot achieve optimal sp3 hybridization overlap. Instead of the orbitals pointing directly at each other (sigma bond formation), they overlap at an angle, resulting in bent bonds or 'banana bonds'. This non-axial overlap is weaker than standard head-on overlap, leading to high potential energy and increased reactivity in small-membered rings.