Solvent-induced syn-anti rotamerization of 2-(2'-pyridyl)indole and the structure of its alcohol complexes

Conformational changes caused by specific interactions with protic solvents were studied for 2-(2'pyridyl)indole and related compounds. Both syn and a nti rotameric forms are possible for 2-(2'-pyridyl)indole. Only the syn con formers are able to form cyclic, doubly hydrogen-bonded complexes with prot ic solvents. These cyclic solvates undergo efficient fluorescence quenching due to photoinduced double proton transfer and internal conversion. This f eature makes it possible to distinguish between the two rotamers and to det ermine their relative abundance. In aprotic solvents, only the syn form is detected. On the contrary, fluorescence measurements reveal that in alcohol s about 80% of the excited-state population are due to the anti conformer. Similar results are obtained for the ground state from NMR NOE experiments, which imply that no interconversion between the two forms occurs in the ex cited state. Ab initio calculations predict that the syn form should be mor e stable by about 4.3 kcal/mol. Therefore, the data obtained in alcohol sol vents show that the reversal of the syn/anti relative stability is due to h ydrogen bonding to the solvent. These conclusions are confirmed by experime nts performed for the N-methylated derivative, for bridged 2-(2'-pyridyl)in doles which can only exist in the syn form, and for 2-(4,6-dimethyl-2'-pyri midyl)indole, when syn and anti conformers are identical. In bulk water sol utions no evidence for spn --> anti rotamerization was found. However, the process was detected in acetonitrile/water mixtures.