International Journal of Mass Spectrometry 301 (2011) 151–158 Contents lists available at ScienceDirect International Journal of Mass Spectrometry journal homepage: www.elsevier.com/locate/ijms Mechanistic investigation of S N 2 dominated gas phase alkyl iodide reactions John M. Garver, Nicole Eyet 1 , Stephanie M. Villano, Zhibo Yang, Veronica M. Bierbaum ∗ Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, United States article info Article history: Received 8 April 2010 Received in revised form 16 July 2010 Accepted 12 August 2010 Available online 27 August 2010 Keywords: Gas phase Ion/molecule Mechanism Reactivity Transition state Barrier height abstract The competition between substitution (S N 2) and elimination (E2) has been studied for the reactions of methyl, ethyl, isopropyl, and tert-butyl iodide with Cl - , CN - , and HS - in the gas phase. Previous studies have shown a dominance of the S N 2 mechanism for sulfur anions and for some cyanide–alkyl iodide reactions. Although our results support this conclusion for the reactions studied, they reveal that compe- tition between the S N 2 and E2 pathways exists for the isopropyl reactions. Steric and electronic effects, upon alkyl group substitution, produce looser and less stable S N 2 transition states, however, they can favor the E2 process. These opposing effects on barrier heights produce E2/S N 2 competition as steric hin- drance increases around the -carbon, however the relative differences in intrinsic barrier heights lead to significantly different branching ratios. This interpretation is discussed in terms of reaction efficiencies, kinetic isotope effects, linear basicity–reactivity relationships, electrostatic models, and transition state looseness parameters. Published by Elsevier B.V. 1. Introduction Studies of bimolecular nucleophilic substitution (S N 2) and base-induced elimination reactions (E2) have made significant con- tributions to the fundamental knowledge of prototypical organic reactions [1,2] and the conceptual framework for understanding biological systems [3,4]. In these experimental [5–14] and theoret- ical investigations [15–20], wide-ranging relationships connecting structure and reactivity parameters to reaction rates and mech- anistic pathways have been established. These structure–energy relationships form the basis of efforts to predict and control the predominant reaction channel between the two competitive pro- cesses. Even within the current conceptual construct, transition state energetics [9,21] and solvent effects [22–25] produce excep- tions to expected reactivity and mechanistic selectivity. Of interest for our current research is the apparent dominance of the S N 2 mechanism for sulfur anions [9,21] and for some cyanide-alkyl iodide reactions [26] in the gas phase. By investigating the elec- tronic and structural properties of systems that deviate from typical reactivity patterns, valuable insight can be gained to provide a more detailed picture of kinetics, mechanisms, and product dis- tributions. Studies of ion-molecule reactions have shown competition between S N 2 and E2 mechanisms (Scheme 1) to be significantly ∗ Corresponding author. Tel.: +1 303 492 7081; fax: +1 303 492 5894. E-mail address: veronica.bierbaum@colorado.edu (V.M. Bierbaum). 1 Current address: Department of Chemistry, Saint Anselm College, 100 Saint Anselm Dr. #1760, Manchester, NH 03102, United States. influenced by the nature of the attacking group (X – ), leaving group abilities (Y), substrate properties, and solvent effects [9,27–29]. The most influential factors on the E2/S N 2 ratio are the pres- ence of -hydrogens, the degree of - and - branching, and the nucleophilicity versus basicity of the reactant anion. For an E2 elimination to occur, there must be periplanar -hydrogens allow- ing orbital overlap during double bond formation. This sp 3 to sp 2 transformation from reactants to products reduces steric strain between substituents producing a driving force for the E2 pro- cess in highly substituted systems. In contrast, increasing alkyl group substitution at the -carbon or on the attacking group hin- ders the approach of the nucleophile during the S N 2 process, thus increasing the activation barrier and decreasing contributions from this channel. Experimental investigations into substituent effects around the -carbon of alkyl halide substrates have shown a tran- sition from predominantly substitution products for primary alkyl halides to exclusively elimination products for tertiary alkyl halides [17,28,30]. In addition to structural influences, strong nucleophilic- ity (carbon cation affinity measured by kinetics) enhances the S N 2 pathway, while strong basicity (proton affinity measured by ther- modynamics) enhances the E2 pathway. Distinguishing between the relative nucleophilic or basic character of an attacking group is not straightforward due to a linear free-energy relationship between these properties. Rationalized in the context of Marcus theory, the intrinsic transition-state barrier height is lowered by the exothermicity of reaction [31,32]. Although gas-phase basicity is often an excellent predictive tool for S N 2 reactivity, deviations in the correlation between S N 2 and E2 barriers arise for attack- ing atoms outside the same row or group in the periodic table [9,29]. Alternative correlations utilizing transition state geome- 1387-3806/$ – see front matter. Published by Elsevier B.V. doi:10.1016/j.ijms.2010.08.008