IMPROVING THE USE OF HYDROXYL PROTON RESONANCES IN STRUCTURE DETERMINATION AND NMR SPECTRAL ASSIGNMENT - INHIBITION OF EXCHANGE BY DILUTION

Hydroxyl resonances in NMR spectra potentially provide much structural information in the form of chemical shifts, J couplings. NOEs and iso tope shifts but this information is largely destroyed by intermolecula r exchange; these applications are briefly reviewed and the exchange m echanism is described. It is shown that exchange of the hydroxyl proto ns of alcohols in chloroform solution can be slowed simply by dilution of the alcohol because the rate-determining step for exchange require s a bimolecular encounter. When exchange is slow on the NMR chemical s hift and coupling timescales. separate signals are observed for each d ifferent hydroxyl site, allowing spectral and structural assignment by correlation techniques such as decoupling. COSY. and related techniqu es. In addition, the limiting chemical shifts and the concentrations r equired for fast exchange are characteristically different for protons which are intramolecularly hydrogen-bonded. It is shown that propane- 1,3-diol and ethane-1,2-diol are strongly hydrogen-bonded intramolecul arly in chloroform solution.