Cyclodehydration

Cyclodehydration is an intramolecular dehydration process in which a diol or an amino alcohol loses a molecule of water to form a cyclic ether or a related ring system. The reaction is typically promoted by acid or Lewis acid catalysts and requires conditions that favor cyclization over intermolecular dehydration or other side reactions. The resulting rings are usually oxacycles, such as tetrahydrofuran (THF) or tetrahydropyran (THP), depending on the spacing of the reacting hydroxyl groups.

Mechanistically, protonation of a hydroxyl group makes water a good leaving group, generating an oxocarbenium-type intermediate. The remaining hydroxyl or alkoxide then attacks intramolecularly, closing the ring and yielding the cyclic ether after deprotonation. Ring size is governed by the relative positions of the functional groups; common products include five-membered rings from suitably spaced diols (for example, 1,4-diols giving THF) and six-membered rings from longer diols. Conditions often involve strong or concentrated acids (such as sulfuric acid or polyphosphoric acid) or specialized catalytic systems, with removal of water driving the equilibrium toward cyclization.

Applications and scope include synthesis of cyclic ethers used as solvents, intermediates in organic synthesis, and, in some contexts, protective-group strategies in carbohydrate and natural product chemistry. Cyclodehydration can also apply to amino alcohols to form azacyclic structures under analogous conditions. Limitations include competition with dehydration to alkenes, polymerization of highly reactive substrates, and sensitivity of certain substrates to strong acids. Reaction efficiency depends on substrate structure, ring size, and catalyst choice.