Improving the use of hydroxyl proton resonances in structure determination and NMR spectral assignment: inhibition of exchange by dilution

Abstract

Hydroxyl resonances in NMR spectra potentially provide much structural information in the form of chemical shifts, J couplings, NOES and isotope shifts but this information is largely destroyed by intermolecular exchange; these applications are briefly reviewed and the exchange mechanism is described. It is shown that exchange of the hydroxyl protons of alcohols in chloroform solution can be slowed simply by dilution of the alcohol because the rate-determining step for exchange requires a bimolecular encounter. When exchange is slow on the NMR chemical shift and coupling timescales, separate signals are observed for each different hydroxyl site, allowing spectral and structural assignment by correlation techniques such as decoupling, COSY, and related techniques. In addition, the limiting chemical shifts and the concentrations required 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 intramolecularly in chloroform solution.