An Experimental and Theoretical Study on the Prototropic Equilibria of

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J. Org. Chem. 1997, 62, 5104-5109

An Experimental and Theoretical Study on the Prototropic Equilibria of the Four Carboline Isomers Gonzalo Angulo, Carmen Carmona, Rafael R. Pappalardo, Marı´a A. Mun˜oz, Pilar Guardado, Enrique Sa´nchez Marcos,* and Manuel Balo´n Departamento de Quı´mica Fı´sica, Universidad de Sevilla, 41012-Sevilla, Spain Received January 24, 1997X

We have determined the experimental pKas for the pyridine protonation and pyrrole deprotonation equilibria of the four isomeric (R-, β-, γ-, and δ-) carbolines (pyridoindoles) and for the deprotonation of their N-pyrido methylated derivatives. HF 6-31+G* ab initio calculations have been carried out to obtain theoretically the magnitudes of the prototropic equilibria in gas phase and in solution. A cavity model of solvation has been employed. To analyze the influence of annelation and tautomerism, prototropic equilibria of azaindole isomers and H-pyrido tautomers of carbolines, respectively, have also been theoretically studied. Equilibria involving tautomeric species are always energetically unfavored against those of the normal forms. Solvation differently affects the relative gas phase values among isomers within the series and between the same isomers of related series. Solvent damps the magnitude of the gap among azaindole or carboline isomers and can even reverse the acidity sequence. The acidity sequence of theoretical free energies for the pyridine nitrogen deprotonation (γ