On the behaviour of the (Z )-phenylhydrazones of some 5-alkyl-3-benzoyl-1,2,4-oxadiazoles in solution and in the gas phase: kinetic and spectrometric evidence in favour of self-assembly Antonella Fontana a , Susanna Guernelli b , Paolo Lo Meo c , Elisabetta Mezzina b , Stefano Morganti b , Renato Noto c, * , Egon Rizzato b , Domenico Spinelli b, * , Romina Zappacosta a a Dipartimento di Scienze del Farmaco, Universita ` ‘‘G. d’Annunzio’’, Via dei Vestini 31, 66013 Chieti, Italy b Dipartimento di Chimica Organica ‘‘A. Mangini’’, Universita ` di Bologna, Via San Giacomo 11, 40126 Bologna, Italy c Dipartimento di Chimica Organica ‘‘E. Paterno ` ’’, Universita ` di Palermo, Viale delle Scienze, Parco d’Orleans II, pad. 17, 90128 Palermo, Italy Received 6 September 2007; received in revised form 16 October 2007; accepted 1 November 2007 Available online 6 November 2007 Abstract Rate constants, k A,R , for the rearrangement of the (Z )-phenylhydrazones (1aee) of a series of 5-alkyl-3-benzoyl-1,2,4-oxadiazoles substituted at C(5) with linear alkyl chains of different length (from C 4 up to C 12 ) into the relevant 4-acylamino-2,5-diphenyl-1,2,3-triazoles (2aee) have been measured in dioxan/water in the base-catalyzed region (pS þ 10.5e12.6). For each substrate log k A,R are linearly related to pS þ . The significant decrease of the slopes of these straight lines (from 0.96 down to 0.78) upon increasing the length of the linear alkyl chain at C(5) and that of the reactivity (down to 14e26%) upon increasing the substrate concentration suggest a decrease of the polarity of the ‘actual’ reaction medium and provide indirect evidence of the tendency of the substrates (Z )-1aee to self-assemble. To confirm the above outcome direct evidence of the formation of self-assemblies in solution were obtained from 1 H NMR and spectrofluorimetry measurements while ESI-MS experiments point out the presence of aggregated substrates also in the gas phase. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction Our research group is involved by long time in the kinetic study of the mononuclear rearrangement of heterocycles (MRH) or BoultoneKatritzky reaction (BKR). 1,2 Our interest in this and in general in ring interconversion of azoles is based on both the intriguing mechanistic aspects of the rearrangement (depending on both the proton concentration and the structure of the investigated substrates) and the wide synthetic applicability of ring interconversion of 1,2,4-oxadi- azoles. 1e3 E.g., a strong electron-withdrawing substituent, such as a perfluoroalkyl, 3 favoured new irreversible ring- degenerate rearrangements 3a as well as new ANRORC-like (Addition of a Nucleophile followed by Ring Opening and Ring Closure) processes eventually associated with ring-enlar- gement. 3bef In order to extend the study of the reactivity in MRH of (Z )-phenylhydrazones of 3-benzoyl-1,2,4-oxadiazoles, we have synthesized a new series of 5-alkyl-substituted substrates with the aim of evaluating the effect of linear alkyl chains of differ- ent lengths (from C 4 up to C 12 ) on the rearrangement rates of (Z )-1aee into the relevant triazoles 2aee (Scheme 1). The presence of long linear alkyl chains at C(5) of the 1,2,4-oxadiazole ring could favour self-assembly and conse- quently could affect the course of the rearrangement. In this paper we will therefore investigate the supramolecular behav- iour of the title substrates by collecting evidence on their abil- ity to self-assemble both in solution (by using kinetics, * Corresponding authors. Tel.: þ39 091 596919 (R.N.); tel.: þ39 051 2095689; fax: þ39 051 2095688 (D.S.). E-mail addresses: rnoto@unipa.it (R. Noto), domenico.spinelli@unibo.it (D. Spinelli). 0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2007.11.014 Available online at www.sciencedirect.com Tetrahedron 64 (2008) 733e740 www.elsevier.com/locate/tet