A Gas-Phase Study of the Ionic Alkylation of Benzocycloalkenes Barbara Chiavarino, Maria Elisa Crestoni, and Simonetta Fornarini* Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente AttiVe UniVersita ` di Roma “La Sapienza” P.le A. Moro 5, I-00185 Roma, Italy ReceiVed January 18, 2000 Since the early finding by Mills and Nixon of enhanced positional selectivities in the bromination of indan and tetralin derivatives, 1 the properties of benzocycloalkenes have been the subject of considerable interest. A small fused carbocyclic ring was found to direct the electrophilic substitution of the benzene nucleus to the -position. 1,2 The effect (MN effect) was ascribed to partial π-electron localization resulting from the fusion of an angular strained ring. 3 Accordingly, the bond common to both rings was proposed to have a reinforced single-bond character. This concept has stimulated extensive experimental 4 and theoreti- cal 5 investigations. Their conclusions were found either to support the manifestation of the MN effect 6 or to cast doubts on its existence. 7 The major focus of recent research has addressed the design and the structural elucidation of molecular frameworks where a mono-, bis-, or tris-annelated benzene nucleus was expected to display aromatic bond alternation. 8 Thus, in recent investigations the issue of the effect of a small ring on the structural features of a fused aromatic ring has superseded the original interest on the reactivity of the benzene nucleus. We turn to this latter point with the present report, although using a quite different approach. It may be noted that the operation of the MN effect has been discussed in relation to either positional selectivities in electro- philic aromatic substitution reactions in solution or structural analysis in a crystal packing. In both cases there may be a major role played by the environment in affecting intrinsic molecular properties. In a series of studies we have obtained valuable insights into the reactivity of aromatic compounds toward ionic electro- philes by utilizing a radiolytic technique for the investigation of gaseous systems at atmospheric pressure. 9 In this environment, the lack of solvents, catalysts and counterions allows one to unveil the intrinsic features of the reaction under scrutiny by experimental means relying on the characterization of the neutral end products. By this methodology the reactivity of a benchmark substrate for the MN effect, benzocyclobutene (1), was studied in relation to the higher homologues, 2, 3, and 4, using simple aromatic compounds, such as o-xylene (5) and mesitylene (6), as reference substrates. 10 Me 2 Cl + and Me 3 C + were chosen as model reagents, both ions being known to promote an electrophilic aromatic substitution reaction in the gas phase. Me 2 Cl + , from the radiation induced ionization of MeCl and subsequent ion-molecule reactions, behaves as a selective methylating agent where the displacement of MeCl by the aromatic π system involves significant activation energies. 11 Me 3 C + , from the ionization/fragmentation of isobutane, is a mild electrophile, reacting as a Lewis acid with aromatic compounds. 12 The positional selectivity for the electrophilic substitution by Me 3 C + is known to be highly sensitive to steric effects, inhibiting, to a large extent, the attack at a ring carbon that is ortho to a methyl group. The yields of the substitution products from the selected substrates are summarized in Table 1, where R and  denote the site of the entered alkyl group (Me or Me 3 C) on the aromatic ring with respect to the cyclic alkyl substituent in the substitution products. The formation of the alkylation products is ascribed to a stepwise reaction pattern (1) Mills, W. H.; Nixon, I. G. J. Chem. Soc. 1930, 2510. (2) Taylor, R. Electrophilic Aromatic Substitution; Wiley: New York, 1990. (3) Maksic, Z. B.; Eckert-Maksic, M.; Mo, O.; Yanez, M. In Pauling’s Legacy - Modern Modeling of the Chemical Bond; Maksic, Z. B., Orville- Thomas, W. J. Eds.; Vol. 6 of the series Theoretical and Computational Chemistry; Elsevier: Amsterdam, 1999. (4) (a) Jemmis, E. D.; Kiran, B. J. Org. Chem. 1996, 61, 9006. (b) Rathore, R.; Lindeman, S. V.; Kumar, A. S.; Kochi, J. K. J. Am. Chem. Soc. 1998, 120, 6012. (c) Martinez, A.; Jimeno, M. L.; Elguero, J. New J. Chem. 1994, 18, 269. (d) Siegel, J. S. Angew. Chem., Int. Ed. Engl. 1994, 33, 1721. (e) Anthony, I. J.; Wege, D. Aust. J. Chem. 1996, 49, 1263. (f) Gescheidt, G.; Prinzbach, H.; Davies, A. G.; Herges, R. Acta Chem. Scand. 1997, 51, 174. (g) Apeloig, Y.; Boese, R.; Halton, B.; Maulitz, A. H. J. Am. Chem. Soc. 1998, 120, 10147 and references therein. (5) (a) Stanger, A. J. Am. Chem. Soc. 1991, 113, 8277. (b) Miller, I. J. Aust. J. Chem. 1997, 50, 795. (c) Koch, W.; Eckert-Maksic, M.; Maksic, Z. B. J. Chem. Soc., Perkin Trans. 2 1993, 2195. (d) Mo, O.; Yanez, M.; Eckert- Maksic, M.; Maksic, Z. B. J. Org. Chem. 1995, 60, 1638. (e) Maksic, Z. B.; Eckert-Maksic, M.; Pfeifer, K.-H. J. Mol. Struct. 1993, 300, 445. (f) Hiberty, P. C.; Danovich, D.; Shurki, A.; Shaik, S. J. Am. Chem. Soc. 1995, 117, 7760. (g) Howard, S. T.; Krygowski, T. M.; Ciesielski, A.; Wisiorowski, M. Tetrahedron 1998, 54, 3533 and references therein. (6) (a) Eckert-Maksic, M.; Maksic, Z. B.; Klessinger, M. Int. J. Quantum Chem. 1994, 49, 383. (b) Eckert-Maksic, M.; Maksic, Z. B.; Klessinger, M. J. Chem. Soc., Perkin Trans. 2 1994, 285. (7) (a) Boese, R.; Bla ¨ser, D.; Billups, W. E.; Haley, M. M.; Maulitz, A. H.; Mohler, D. L.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1994, 33, 313. (b) Bu ¨rgi, H.-B.; Baldridge, K. K.; Hardcastle, K.; Frank, N. L.; Gantzel, P.; Siegel, J. S.; Ziller, J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1454. (c) Apeloig, Y.; Arad, D. J. Am. Chem. Soc. 1986, 108, 3241. (d) Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 1992, 114, 9583. (8) (a) Cossu, S.; De Lucchi, O.; Lucchini, V.; Valle, G.; Balci, M.; Dastan, A.; Demirci, B. Tetrahedron Lett. 1997, 38, 5319. (b) Cardullo, F.; Giuffrida, D.; Kohnke, F. H.; Raymo, F. M.; Stoddard, J. F.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 339. (9) (a) Cacace, F. Acc. Chem. Res. 1988, 21, 215. (b) Fornarini, S.; Crestoni, M. E. Acc. Chem. Res. 1998, 31, 827. (c) Fornarini, S. Mass Spectrom. ReV. 1996, 15, 365. (10) Gaseous samples of known composition were prepared in sealed 0.13-L Pyrex vessels according to a well-established procedure. Typical components were as follows: 600-650 Torr of a bulk gas (MeCl to form Me2Cl + , or isobutane as the precursor of Me3C + ), 10 Torr O2 (a radical scavenger), 0.5-2 Torr of the aromatic substrate(s). TEA (0.7-1.0 Torr) was added in all experiments run in isobutane and in several experiments run in MeCl. Irradiations were performed in a 220 Gammacell (Nuclear Canada Ltd.) at the dose rate of ∼5 × 10 3 Gy h -1 for 3 h in a thermostated device. The radiolytic products were extracted from the vessel utilizing ethyl acetate as the solvent by repeated freeze-thaw cycles and analyzed by GC-MS using a Hewlett-Packard 5890 series II gas chromatograph in line with a quadrupole mass spectrometer, HP 5989B. The capillary columns and gas-chromatographic conditions were the following: (i) a 50-m long, 0.20-mm i.d. fused silica capillary column, coated with a 0.5-µm cross-linked methylsilicone film (HP PONA column), operated isothermally at 60 °C for 5 min and then heated at the rate of 3 deg min -1 to 120 °C and subsequently at 16 deg min -1 to 240 °C.; (ii) a 60-m long, 0.20-mm i.d. bonded-phase capillary column, coated with a 0.2-µm poly(ethylene glycol) film (Supelcowax 10M from Supelco Co.), operated at 100 °C for 2 min and then heated at the rate of 5 deg min -1 to 250 °C. MeCl, i-C4H10, and O2 were research grade gases from Matheson Gas Products Inc. with a stated purity in excess of 99.95 mol %. 1 was obtained from 2-(2′-bromophenyl)ethyl bromide according to (a) Brewer, P. D.; Tagat, J.; Hergrueter, C. A.; Helquist, P. Tetrahedron Lett. 1977, 52, 4573 and (b) Parham, W. E.; Jones, L. D.; Sayed, Y. A. J. Org. Chem. 1976, 41, 1184. Other compounds used as additives, as substrates or as reference compounds for GC-MS analyses were obtained from commercial sources or prepared according to established methods. (11) Sen Sharma, D. K.; Kebarle, P. J. Am. Chem. Soc. 1982, 104, 19. (12) (a) Sen Sharma, D. K.; Ikuta, S.; Kebarle, P. Can. J. Chem. 1982, 60, 2325. (b) Stone, J. M.; Stone, J. A. Int. J. Mass Spectrom. Ion Processes 1991, 109, 247. (c) Crestoni, M. E.; Fornarini, S. J. Am. Chem. Soc. 1994, 116, 5873. 5397 J. Am. Chem. Soc. 2000, 122, 5397-5398 10.1021/ja000164f CCC: $19.00 © 2000 American Chemical Society Published on Web 05/18/2000