Solvent-Induced <i>s</i><i>yn</i><i>−</i><i>a</i><i>nti</i> Rotamerization of 2-(2‘-Pyridyl)indole and the Structure of its Alcohol Complexes

Abstract

Conformational changes caused by specific interactions with protic solvents were studied for 2-(2‘-pyridyl)indole and related compounds. Both syn and anti rotameric forms are possible for 2-(2‘-pyridyl)indole. Only the syn conformers are able to form cyclic, doubly hydrogen-bonded complexes with protic solvents. These cyclic solvates undergo efficient fluorescence quenching due to photoinduced double proton transfer and internal conversion. This feature makes it possible to distinguish between the two rotamers and to determine their relative abundance. In aprotic solvents, only the syn form is detected. On the contrary, fluorescence measurements reveal that in alcohols 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 excited state. Ab initio calculations predict that the syn form should be more stable by about 4.3 kcal/mol. Therefore, the data obtained in alcohol solvents show that the reversal of the syn/anti relative stability is due to hydrogen bonding to the solvent. These conclusions are confirmed by experiments performed for the N-methylated derivative, for bridged 2-(2‘-pyridyl)indoles which can only exist in the syn form, and for 2-(4,6-dimethyl-2‘-pyrimidyl)indole, where syn and anti conformers are identical. In bulk water solutions no evidence for syn → anti rotamerization was found. However, the process was detected in acetonitrile/water mixtures.