Sn2 ion-molecule reactions

The study of reactions of isolated ions and molecules in the gas phase without interference from solvents has led to very surprising results. Gas-phase studies of proton-transfer and nucleophilic substitution reactions permit the measurement of the intrinsic properties of the bare reactants and make it possible to distinguish these genuine properties from effects attributable to solvation. Furthermore, these studies provide a direct comparison of gas-phase and solution reactivities of ionic reactants. It has long been assumed that solvation retards the rates of ion-molecule reactions. Now, using these new techniques, the dramatic results obtained make it possible to show the extent of this retardation. For example, in a typical Sn2 ion-molecule reaction in the gas phase, the substrates react about 10 times faster than when they are dissolved in acetone, and about 10 ( ) times faster than in water cf. Table 5-2 in Section 5.2). 

Table 5-3. Comparison of the activation energies and specific rate constants for the bimolecular Sn2 ion-molecule reaction HO -f- CH3—Br — HO—CH3 -f Br in the gas phase and at various degrees of hydration of the hydroxide ion at ca. 23 °C [485],...

Fig. 17. The potential energy along the reaction coordinate for the exoergic Sn2 ion-molecule reaction Cl + CHsBr — Br -(- CH3CI. Adapted from Refe. 295-297.

Ions are extensively used as reagents and as catalysts because they are highly reactive. In solution, ions have a strong interaction with the solvent and, as we discuss in Chapter 11, this behavior leads to essential modifications of the dynamics. Therefore, to study their intrinsic behavior we examine here ion-molecule reactions in the gas phase, continuing from the discussion in Section 3.2.6. Specifically, we consider nucleophilic displacement reactions of the type X + RY XR + Y . Such gas-phase Sn2 ion-molecule reactions proceed with reaction rate constants that vary from almost capture-controlled to so slow that they can barely be detected. Moreover, the rate constant exhibits an inverse temperature dependence, that is, the rate of nucleophilic displacement slows down with increasing temperature. This behavior is in marked contrast to the predictions of the Arrhenius equation. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

Gas-phase ion chemistry is a broad field which has many applications and which encompasses various branches of chemistry and physics. An application that draws together many of these branches is the synthesis of molecules in interstellar clouds (Herbst). This was part of the motivation for studies on the neutralization of ions by electrons (Johnsen and Mitchell) and on isomerization in ion-neutral associations (Adams and Fisher). The results of investigations of particular aspects of ion dynamics are presented in these association studies, in studies of the intermediates of binary ion-molecule Sn2 reactions (Hase, Wang, and Peslherbe), and in those of excited states of ions and their associated neutrals (Richard, Lu, Walker, and Weisshaar). Solvation in ion-molecule reactions is discussed (Castleman) and extended to include multiply charged ions by the application of electrospray techniques (Klassen, Ho, Blades, and Kebarle). These studies also provide a wealth of information on reaction thermodynamics which is critical in determining reaction spontaneity and availability of reaction channels. More focused studies relating to the ionization process and its nature are presented in the final chapter (Harland and Vallance). 

Introduction 198 Experimental techniques 200 Ion cyclotron resonance spectrometry 201 Flowing afterglow 203 High pressure mass spectrometry 204 General features of gas-phase ion-molecule reactions 204 Gas-phase SN2 reactions involving negative ions 206 Thermochemical considerations 206 General aspects of gas-phase SN2 reactions 207 Stereochemistry 209... 

Despite this information, the question remains as to the exact structure of the associated ions and their possible electronic resemblance to an SN2 transition state. An icr experiment (Riveros et al., 1973) generated a CH3C12 species of mixed isotopic composition from the ion-molecule reaction (33). 

A typical example of such reactions is the exothermic Sn2 nucleophilic displacement reaction Cl -I- CH3—Br Cl—CH3 - - Br . Table 5-2 provides a comparison of Arrhenius activation energies and specific rate constants for this Finkelstein reaction in both the gas phase and solution. The new techniques described above cf. Sections 4.2.2 and 5.1) have made it possible to determine the rate constant of this ion-molecule reaction in the absence of any solvent molecules in the gas phase. The result is surprising on going from a protic solvent to a non-HBD solvent and then further to the gas phase, the ratio of the rate constants is approximately 1 10 10 The activation energy of this Sn2 reaction in water is about ten times larger than in the gas phase. The suppression of the Sn2 rate constant in aqueous solution by up to 15 orders of magnitude demonstrates the vital role of the solvent. 

In conclusion, these gas-phase measurements provide new elues to the role of solvation in ion-moleeule reaetions. For the first time, it is possible to study intrinsie reactivities and the extent to which the properties of gas-phase ion-moleeule reaetions relate to those of the eorresponding reactions in solution. It is clear, however, that gas-phase solvated-ion/moleeule reaetions in which solvent moleeules are transferred into the intermediate elusters by the nucleophile cannot be exaet duplieates of solvated-ion/ molecule reactions in solution in which solvated reactants exchange solvent molecules with the surrounding bulk solvent [743]. For a selection of more recent experimental [772] and theoretical studies of Sn2 reactions in gas phase and solution by classical trajectory simulations [773], molecular dynamics simulations [774, 775], ab initio molecular orbital calculations [776, 777], and density functional theory calculations [778, 779], see the references given. For studies of reactions other than Sn2 ion-molecule processes in the gas phase and in solution, see reviews [780, 781]. 

DePuy and coworkers have studied the gas-phase ion-molecule reactions of the phosphide ion. A number of reactions were observed which result in phosphorus-carbon bond formation, including Sn2 reactions (equation 60), adduct formation (equation 61) and the formation of the low-valent ions PCO (equation 62) and PCS (equation 63). The latter ion is also formed in a reaction between HP=F and CS2, for which the mechanism shown in Scheme 2 has been proposed ... 

Typical ion/molecule reactions between anions and neutral molecules [7, 9,152-155] can be classified as displacement (Scheme 2.1, Eq. (2.5)), proton transfer (Scheme 2.1, Eq. (2.6)), charge exchange (Scheme 2.1, Eq. (2.7)) and association (Scheme 2.1, Eq. (2.8)). Among these, the displacement reaction has been studied extensively in the gas phase [156,157], and the prototypical example is an anionic Sn2 reaction studied by Brauman [156]. In addition, interactions between a neutral molecule and an electron involving electron capture [158] and dissociative electron capture [159], are also important types of ion/molecule reactions in the gas phase. A molecule M vhth a positive electron affinity can form a stable anion M by capturing a thermal electron. In the case of dissociative electron capture, capture of an electron by a compound MX leads to a repulsive state of MX, which dissociates to form M and X vhth excess internal and/or translational energy. 

Le Meillour, S. Tabet, J. C. Ion-molecule reactions in the gas phase. Xl(l) regioselective SN2 induced by ammonia on the [M + NHJ adduct ions of the 4-hydroxy-4-methylcyclohexyl benzoate isomers. Spectroscopy 1988, 5, 135-148. 

The hydrolysis of an ester to alcohol and acid (1) and the esterification of a carboxylic acid with an alcohol (2) are shown here as an example of the Sn2 mechanism. Both reactions are made easier by the marked polarity of the C=0 double bond. In the form of ester hydrolysis shown here, a proton is removed from a water molecule by the catalytic effect of the base B. The resulting strongly nucleophilic OH ion attacks the positively charged carbonyl C of the ester (la), and an unstable sp -hybridized transition state is produced. From this, either water is eliminated (2b) and the ester re-forms, or the alcohol ROH is eliminated (1b) and the free acid results. In esterification (2), the same steps take place in reverse. 

Nevertheless, important features of real solvent reactions were reproduced by microsolvation. The role of ion-molecule complexes, important in the gas phase, decreased rapidly with introduction of solvent molecules, the reaction profile becoming nearly unimodal (see Continuum solvation, below). Activation energies for both E2 and SN2 processes increased due to stronger solvation of reactants than of transition states (although in this work, because of imposed geometric... 

The chemistry involved in nucleophilic aromatic substitution is well reflected in the reactions of a variety of nucleophiles with methyl penta-fluorophenyl ether (Ingemann et al 1982a). For most of the nucleophiles such as alkoxide, thiolate, enolate and (un)substituted allyl anions, the dominant reaction channel is the attack upon the fluoro-substituted carbon atoms, as is the case for OH-. The latter ion reacts approximately 75% by attack upon the fluoro-substituted carbon atoms and the remaining 25% by Sn2 (20%) and ipso (5%) substitution as summarized in (41). In the attack upon the fluorinated carbon atoms, the interesting observation is made that a F- ion is displaced via an anionic o-complex to form a F- ion/molecule complex, which is not observed to dissociate into F- as a free ionic product. 

Instead, the displaced F- ion re-attacks the newly formed molecule within the complex, leading eventually to the products shown in (42). Although the lifetime of the F- ion/molecule complexes is not known, they must live sufficiently long to allow secondary reactions to occur. Depending upon the nature of the original nucleophile, the re-attack by the displaced F- ion can involve proton transfer, SN2 substitution and E2 elimination. Proton transfer to the displaced F" ions (43) is the dominant reaction if the neutral in the complex is more acidic than HF. This is the case when the primary... 

These results clearly show that the potential energy surface can contain a series of minima. The fact that selectivity in re-attack by the F ions can be observed indicates that the differences between the energy barriers for the secondary reactions control the distribution of the final products. The multistep character of these processes is further illustrated by the reactions observed when enolate anions are used as reactant ions. The ambident enolate anions may react with methyl pentafluorophenyl ether at the carbon or the oxygen site. If they react with the carbon site at the fluorine-bearing carbon atoms, then the molecule in the F ion/molecule complex formed contains relatively acidic hydrogen atoms so that proton transfer to the displaced F ion may occur. An example is given in (47) where the enolate anion, generated by HF loss, is not observed. An intramolecular nucleophilic aromatic substitution occurs instead and leads to a second F ion/ molecule complex. The F" ion in this complex then re-attacks the substituted benzofuran molecule formed, either by proton transfer or SN2 substitution. 

These results, obtained on a FT-ICR mass spectrometer, led to the proposal that these reactions proceed through long-lived ion-molecule collision complexes which can undergo secondary reactions within the complex. The mechanism, sketched in Scheme 41, predicts the formation of products originating from attack of F on the neutral by proton transfer, SN2 or elimination reactions. 

In the absence of solvent, the gas-phase SN2 reaction is different, but it still takes place with inversion of stereochemistry. There is a double well in the energy surface the nucleophile and the alkyl halide combine exothermically with no energy barrier to give an ion-molecule complex. In a sense the naked nucleophile is solvated by the only solvent available, the alkyl halide. The Sn2 reaction then takes place with a low barrier, and the product ion-molecule complex dissociates endothermically to give the products. 

The unexpected gas-phase double-minimum diagram can be best explained as follows As the reactants approach one another, long-range ion-dipole and ion-induced dipole interactions first produce loose ion-molecule association complexes or clusters. This is related to a decrease in enthalpy prior to any chemical barrier produced by orbital overlap between the reactants. For reasons of symmetry, an analogous drop in enthalpy must exist on the product side. Because the neutral reactant and product molecules will, in general, have different dipole moments and polarizabilities, the two minima will also be different. Only in the case of degenerate identity Sn2 reactions (X + CH3—X —> X—CH3 + X ) will the enthalpy of the two minima be equal. 

Fig. 5-5. Schematic one-dimensional relative enthalpy diagram for the exothermic bimolecular displacement reaction HO + CH3—Br —> HO—CH3 + Br in the gas phase and at various degrees of hydration of the hydroxide ion [485]. Ordinate standard molar enthalpies of (a) the reactants, (b, d) loose ion-molecule clusters held together by ion-dipole and ion-induced dipole forces, (c) the activated complex, and (e) the products. Abscissa not defined, expresses only the sequence of (a). .. (e) as they occur in the chemical reaction. The barrier heights ascribed to the activated complex at intermediate degrees of hydration were chosen to be qualitatively consistent with the experimental rate measurements cf. Table 5-3 [485]. Possible hydration of the neutral reactant and product molecules, CH3—Br and HO—CH3, is ignored. The barrier height ascribed to the activated complex in aqueous solution corresponds to the measured Arrhenius activation energy. A somewhat different picture of this Sn2 reaction in the gas phase, which calls into question the simultaneous solvent-transfer from HO to Br , is given in reference [487].

The prototypical SN2 reaction studied in this work (see figure 1) presents in the gas phase a double-well PES with two equivalent local minima corresponding to the formation of a pre- and a post-reaction ion-molecule complex (Cl- CH3C1) and a transition state (TS) of D3h symmetry ([Cl CH3 - - Cl]-). Owing to the overall symmetry of the reaction, we will restrain our study to a reaction path from the transition state to one of the equivalent minima. 

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