Acid-catalysed dehydration of heterocyclic ring hydrates of benzofuran, benzothiophene, chromene and thiochromene

Rate constants and equilibrium constants have been measured for acid-catalysed dehydration of hydrates of benzo-fused five- and six-membered heterocyclic and carbocyclic rings. Substrates studied include 2- and 3-hydroxy-2,3-dihydrobenzofuran, 3-hydroxy-2,3-dihydrobenzothiophene, 1-indanol, 4-chromanol, 4-thiochromanol and 1-tetralol. For the benzofuran-3-hydrate (3-hydroxy-2,3-dihydrobenzofuran), 1-indanol and 1-tetralol rate constants have also been measured for the acid-catalysed racemisation of optically active substrates. These are believed to represent carbocation formation, and this supposition is confirmed by measurements of product partitioning between benzofuran and benzofuran hydrate products from solvolysis of the chloroacetate ester of the 3-hydrate. A surprising observation is that, in the five-membered ring series, heterocyclic oxygen and sulphur atoms have very small accelerating effects on rates of carbocation formation (1.3 and 2.5-fold, respectively, relative to indanol) despite the possibility of direct resonance between the heteroatom and carbocation centre. For dehydration of the corresponding six-membered rings indeed the heteroatoms slow the reaction:in the case of oxygen (4-chromanol) by 100-fold. The possibility that this behaviour arises from adverse inductive or stereoelectronic effects is discussed.