FULL PAPER DOI: 10.1002/ejoc.200900818 3-(Pyridin-2-yl)[1,2,3]triazolo[1,5-a]quinoline: A Theoretical and Experimental Analysis of Ring-Chain Isomerisation Rafael Ballesteros-Garrido, [a] Fernando Blanco,* [b] Rafael Ballesteros,* [c] Frédéric R. Leroux,* [a] Belén Abarca,* [c] Françoise Colobert,* [a] Ibon Alkorta, [b] and José Elguero [b] Keywords: Heterocycles / Isomerization / Metalation / Density functional calculations In the course of the synthesis of new fluorophores for molecu- lar recognition an experimental ( 1 H NMR) and theoretical (DFT) study of the ring-chain isomerism of 3-(pyridin-2-yl)- [1,2,3]triazolo[1,5-a]quinoline derivatives (A) into 2-([1,2,3]- triazolo[1,5-a]pyridin-3-yl)quinoline derivatives (B) has been Introduction The chemistry of [1,2,3]triazolo[1,5-a]pyridines [1] in- cludes the existence of ring-chain isomerism between the closed form of the triazole ring and the open form of the diazo compound. [2–4] Previously, some of us determined the mechanism of this ring-chain isomerism, both experimental and theoretically, in the case of substituted 3-(pyridin-2- yl)[1,2,3]triazolo[1,5-a]pyridines (1), [3] which indicated the existence of two different compounds: either 1A or 1B as depicted in Scheme 1. Scheme 1. Triazole ring-chain isomerisation. [a] Laboratoire de Stéréochimie, CNRS, Université de Strasbourg (ECPM), 25 rue Becquerel, 67087 Strasbourg, France Fax: +33-3-68-85-27-42 E-mail: frederic.leroux@unistra.fr francoise.colobert@unistra.fr [b] Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain E-mail: fblanco@iqm.csic.es [c] Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain E-mail: belen.abarca@uv.es Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.200900818. Eur. J. Org. Chem. 2009, 5765–5778 © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 5765 carried out. The rearrangement is influenced by steric and electronic effects of the substituents present on the quinoline ring. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) This equilibrium can be efficiently used for the prepara- tion of 2,6-disubstituted pyridines [5,6] or of indolizines and imidazopyridines. [7] It is worth mentioning that such ring- chain isomerism is an important property of many hetero- cyclic systems. [8–10] The ring-chain-ring isomerisation between structures A and B was found to be essentially dependent on the elec- tronic properties of the R substituent. In general, A-type compounds are obtained with electron-donating substitu- ents, whereas B-type compounds are formed with electron- withdrawing groups. Moreover, we have also shown how this isomerisation can be controlled by the presence of different phosphorus substituents (R = PX 2 ) bound to the triazolo- pyridine ring, [11] providing mixtures of A- and B-type struc- tures in different proportions depending on the accepting/ donating characters of the substituents on phosphorus (X). We have quite recently reported on the fluorescence properties of compounds 1. [12] We obtained good yields of various fluorescent tridentate ligands [13–15] that proved ef- ficient in the detection of anions and cations. [16] From these results, we came to believe that it might be possible to de- velop new ligands with different electron densities as fluo- rescence sensors through the employment of the 3-(pyridin- 2-yl)[1,2,3]triazolo[1,5-a]quinoline moiety, a benzo deriva- tive of 3-(pyridin-2-yl)triazolopyridine, as fluorophore. So far, only some aspects of the synthesis and reactivity of [1,2,3]triazolo[1,5-a]quinolines have been reported by us and others. [17–20] Although 3-(pyridin-2-yl)[1,2,3]triazolo- [1,5-a]quinoline was a unknown compound, we believed that it should show an isomerisation equilibrium similar to that observed for triazolopyridine 1 (Scheme 2). The ring-chain equilibrium should be governed by the substitution pattern on the condensed heterocyclic ring, similarly to what has been described in our work on tri-