Direct determination of tautomerism in purine derivatives by low-temperature NMR spectroscopy

Abstract

An investigation of the tautomerism of the purine derivatives N, N-dimethyl- N′-(7(9)- H-purin-6-yl)-formamidine 1 , 6-chloropurine 3 and 6-methoxy purine 5 at low temperatures by NMR spectroscopy has been carried out. Knowledge of tautomeric equilibria is important for predicting N-alkylation positions, hydrogen-bonding patterns, and interactions with biological targets. In the NMR spectra of 1 and 5 at 213 K we observed two sets of signals, whereas at laboratory temperature there was only a single set of signals, reflecting the time-averaged contribution of both components. Based on characteristic values of 13C and 15N chemical shifts and of vicinal 1H– 13C scalar coupling constants, the two components of 1 were determined to be the N7–H (71%) and N9–H (29%) tautomers and those of 5 as the N7–H (18%) and N9–H (82%) tautomers. The investigation of 3 revealed a substantial predominance of the N9–H tautomer without any separation of NMR signals at 213 K.