Synthesis of phosphonium salts under microwave activation — Leaving group and phosphine substituents effects Ján Cvengros, Stefan Toma, Sylvain Marque, and André Loupy Abstract: The specific nonpurely thermal effects of microwaves were evidenced according to neutral or charged leav- ing groups during nucleophilic substitution of benzylic electrophiles with triphenylphosphine and tributylphosphine. Mi- crowave (MW) irradiation considerably enhanced the reactions with charged alkylating agents, especially under solvent- free conditions. Results are interpreted considering the magnitude of MW effects according to the position of the tran- sition state along the reaction coordinates. Key words: microwave irradiation, specific effects, phosphonium salts, leaving group effects. Résumé : Des effets spécifiques non purement thermiques des micro-ondes ont été mis en évidence. Ils dépendent de la nature neutre ou chargée des groupes partants au cours de la substitution nucléophile par la triphénylphosphine ou la tributylphosphine sur des agents benzylants. L’irradiation micro-onde augmente considérablement les vitesses de réac- tion avec les agents alkylants chargés, particulièrement dans des conditions sans solvant. Les résultats sont interprétés en considérant les effets des micro-ondes en fonction de la position de l’état de transition sur les coordonnées réaction- nelles. Mots clés : irradiation aux micro-ondes, effets spécifiques, sels de phosphonium, effets de groupes partants. [Traduit par la Rédaction] Cvengros et al. 1371 Introduction Application of microwave (MW) irradiation in organic synthesis is well documented (1–10). Most of the publica- tions describe significant accelerations for a wide range of organic reactions especially when carried out under solvent- free conditions. They can find their origins in either thermal effects and (or) specific nonpurely thermal effects. There- fore, a vivid discussion was going on the possible interven- tion of any specific microwave effect resulting from decrease in the free energy of activation or if the enhancement of the reactions is due to a local overheating of the reaction mix- ture (11–13) (a hot spot effect as advocated in sonochem- istry) (14). Microwaves consist of electromagnetic waves generated by an alternating electric field of high frequency. The energy associated with a MW photon (1 J mol –1 by application of Planck’s law E = hν with ν = 2450 MHz) is by far too small to induce any excitation of molecules. It can, however, pro- voke thermal effects because of some internal friction among polar molecules during their changes in orientation with each alternation of the electric field. In addition, they can induce some electrostatic interactions with polar materi- als by dipole–dipole interactions, rather similar to the behav- iour of a dipolar solvent. It was, for instance, shown that the regioselectivity of phenacylation of 1,2,4-triazole is the same under conventional heating in a dipolar aprotic solvent (DMF) and under MW irradiation in a non-polar medium (xylene), or even in the absence of any solvent (15). By analogy and extension of the interpretation of solvent ef- fects, the carbon–halogen bond breaking in S N 2 reactions can be facilitated by an increase in the polarity of the system during the reaction progress from the ground state to its transition state and could depend on the leaving group abil- ity. A working hypothesis was therefore advanced very re- cently according to which it is possible to predict (according to the type of reaction) if a significant specific (non-purely thermal) MW effect can be observed (15, 16). It considers medium and mechanism influences on the MW-assisted re- actions. MW stabilizations by electrostatic dipole–dipole in- teractions between materials and the electromagnetic field are foreseen to be increased if the polarity of the systems are increased when the reaction is progressing. From a reactivity point of view, a decrease in the energy of activation by ex- tending stabilization from the ground state can be expected towards the transition state can be expected (15–17). It would be the case when polar mechanisms are concerned, i.e., when there is a development of charge during the course of the reaction. It would also be the case if the position of Can. J. Chem. 82: 1365–1371 (2004) doi: 10.1139/V04-103 © 2004 NRC Canada 1365 Received 20 February 2004. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 23 October 2004. J. Cvengros and S. Toma. Faculty of Natural Sciences, Comenius University, SK-842 15 Bratislava, Slovakia. S. Marque and A. Loupy. 1 Laboratoire des Réactions Sélectives sur Supports, Université de Paris-Sud, Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS UMR 8615, building 410, F-91405, Orsay, France. 1 Corresponding author (e-mail: aloupy@icmo.u-psud.fr).