ORIGINAL PAPER Reactions of ketones with aromatics in acid media. The effect of trifluoromethyl groups and the acidity media. A theoretical study Ulises Jiménez Castillo & Mikhail G. Zolotukhin & Lioudmila Fomina & Daniel Romero Nieto & Lilian Olivera Garza & Serguei Fomine Received: 27 July 2012 / Accepted: 26 September 2012 # Springer-Verlag Berlin Heidelberg 2012 Abstract The reactions of acetone, 2,2,2-trifluoroacetone and hexafluoroacetone in methanesulfonic (MSA) and triflic acids (TFSA) with benzene have been studied at M06-2X/6- 311+G(d,p) level using cluster-continuum model, where the carbonyl group is explicitly solvated by acid molecules. The introduction of a trifluoromethyl group into the ketone struc- ture reduces the activation energy of the tetrahedral intermedi- ates formation due to an increase of the electrophilicity of the carbonyl group and raises the activation and the reaction energies of the C-O bond cleavage in formed carbinol due to the destabilization of the corresponding carbocation. The in- troduction of the second trifluoromethyl group inhibits the hydroxyalkylation reaction due to a very strong increase of the reaction and activation energies of the C-O bond cleavage which becomes the rate determining step. The most important catalytic effect of TFSA compared to MSA is not the proton- ation of the ketone carbonyl, but the reduction of the activa- tion and reaction energies of the carbinol C-O bond cleavage due to better protosolvation properties. Even for TFSA no complete proton transfer to carbonyl oxygen has been ob- served for free ketones. Therefore, the protonation energies of free ketones cannot be considered as a measure of ketone reactivity in the hydroxyalkylation reaction. Keywords DFT . Hydroxyalkylation . Protonation . Superacid . Trifluoromethyl group Introduction The reaction of ketones with aromatics in acid media is known as hydroxyalkylation reaction [1, 2]. Depending on the monomer structures and the reaction conditions, an alcohol, a diaryl-compound or a mixture of those can be obtained. Although this reaction is often limited to activated, electron-reach arenes, ketones bearing electron withdrawing groups may react with benzene and even deactivated arenes giving derivatives of tetrasubstituted methanes in high yield. Thus, Kray and Rosser reported on trifluoromethanesulfonic acid (TFSA) catalyzed condensation of 2,2,2-trifluoracetophe- none with aromatic substrates affording diaryl-derivatives with moderate yield [3]. The concept of superelectrophilic activation proposed by Nobel Prize winner Olah and co-workers to explain the high reactivities of electrophilic species in superacidic media [4], and its application for hydroxyalkylation reactions turned out to be remarkably successful. Numerous hydroxyalkylation reactions have been carried out using superacids, mostly (TFSA) as catalysts or as a reaction medium [5–8]. Non substituted and substituted trifluoromethyl ketones were found to react smoothly with benzene and substituted arenes in TFSA at room temperature to give diaryl compounds [9]. Klumpp recently reported on unusual chemo-, regio-, and stereoselectivities in TFSA catalyzed reactions of some tri- fluoromethylketones with aromatics [10]. High efficiency of polymer-forming superacid catalyzed polyhydroxyalkylations Electronic supplementary material The online version of this article (doi:10.1007/s00894-012-1610-1) contains supplementary material, which is available to authorized users. U. J. Castillo : M. G. Zolotukhin : L. Fomina : L. O. Garza : S. Fomine (*) Instituto de Investigaciones en Materiales Universidad Nacional Autonoma de Mexico, Apartado Postal 70-360, CU, Coyoacan, Mexico DF 04510, Mexico e-mail: fomine@servidor.unam.mx D. R. Nieto University of Trieste, Via Valerio 10, 34127 Trieste, Italy J Mol Model DOI 10.1007/s00894-012-1610-1