ringclosure

Ringclosure is the process by which a linear or open-chain precursor undergoes an intramolecular reaction to form a cyclic product. In organic synthesis, ring closure is driven by a combination of enthalpic stabilization of the cyclic bond and entropic considerations related to tethering reactive ends. Ring-closed products include lactones, lactams, cyclic ethers and various heterocycles, and ring closure is a common strategy in the synthesis of natural products and functional materials.

Mechanisms include radical cyclizations, intramolecular nucleophilic or electrophilic cyclizations, and ring-closing metathesis. The choice of mechanism is influenced by the nature of the tether, functional groups, and the desired ring size. Baldwin's rules describe preferred modes for cyclization, with five-, six-, and seven-membered rings generally favored over highly strained smaller rings or very large macrocycles. Ring closure can be consecutive steps in a cascade or a key step in a convergent synthesis, and may proceed thermodynamically or kinetically depending on conditions.

Several factors influence ring closure: ring size and strain, tether length and flexibility, preorganization of reacting groups, choice of catalyst or initiator, solvent, temperature, and dilution (especially for macrocyclizations). Shorter tethers may prefer rapid, unselective closures, while properly designed tethers promote selective cyclization. Macrocyclizations often require high dilution to suppress intermolecular polymerization.

Applications span organic synthesis, medicinal chemistry, and materials science. Ring-closure strategies enable construction of libraries of cyclic compounds, cyclic peptides, and macrocycles used in drug discovery. They also underpin methods such as ring-closing metathesis and related catalytic approaches. In mathematics, related uses of the term describe a different type of closure, such as the smallest subring containing a given set.