Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone
Abstract:In a kinetic experiment on the SN2 reaction of sodium p-nitrophenoxide with iodomethane in acetone-water mixed solvent, Humeres et al. (J. Org. Chem. 2001, 66, 1163) found that the reaction depends strongly on the medium, and the fastest rate constant was observed in pure acetone. The present work tries to explore why acetone can enhance the reactivity of the title reactions. Accordingly, we make a mechanistic study on the reactions of sodium p-nitrophenoxide with halomethanes (CH3X, X = Cl, Br, I) in acetone … Show more
“…Additionally, the properties of isolated ions can be substantially different from their solvated cluster structure. For example, the isolated (SO 4 ) 2ion is unstable in the gas phase as a dianion due to its very high Coulombic repulsion; the same is true [6] for PO 4 3-. However, these same ions become stable when microsolvated by a cluster of solvent molecules, or in the solid state [7,8].…”
Section: Introductionmentioning
confidence: 98%
“…The study of microsolvation of ions provides an important tool for understanding their structure, energetics, spectroscopic properties, and reaction mechanisms and kinetics in the solution phase as well as in the gas phase. For example, in an ion pair S N 2 reaction between sodium p-nitrophenoxide and halomethanes in acetone [4], the rate of reaction is found to be drastically affected by the microsolvation of anions by acetone molecules. As another example, the α-effect in an S N 2 reaction has been found [5] to be strongly affected by the microsolvation of anions by solvent molecules.…”
Various anions were surrounded by n molecules of CF 3 H, which was used as a prototype CH donor solvent, and the structures and energies studied by M06-2X calculations with a 6-31+G** basis set. Anions considered included the halides F-, Cl-, Brand I-, as well as those with multiple proton acceptor sites: CN-, NO 3-, HCOO-, CH 3 COO-, HSO 4-, H 2 PO 4-, and anions with higher charges SO 4 2-, HPO 4 2and PO 4 3-. Well structured cages were formed and the average H-bond energy decreases steadily as the number of surrounding solvent molecules rises, even when n exceeds 6 and the CF 3 H molecules begin to interact with one another rather than with the central anion. Total binding energies are very nearly proportional to the magnitude of the negative charge on the anion. The free energy of complexation becomes more negative for larger n initially, but then reaches a minimum and begins to rise for larger values of n.
“…Additionally, the properties of isolated ions can be substantially different from their solvated cluster structure. For example, the isolated (SO 4 ) 2ion is unstable in the gas phase as a dianion due to its very high Coulombic repulsion; the same is true [6] for PO 4 3-. However, these same ions become stable when microsolvated by a cluster of solvent molecules, or in the solid state [7,8].…”
Section: Introductionmentioning
confidence: 98%
“…The study of microsolvation of ions provides an important tool for understanding their structure, energetics, spectroscopic properties, and reaction mechanisms and kinetics in the solution phase as well as in the gas phase. For example, in an ion pair S N 2 reaction between sodium p-nitrophenoxide and halomethanes in acetone [4], the rate of reaction is found to be drastically affected by the microsolvation of anions by acetone molecules. As another example, the α-effect in an S N 2 reaction has been found [5] to be strongly affected by the microsolvation of anions by solvent molecules.…”
Various anions were surrounded by n molecules of CF 3 H, which was used as a prototype CH donor solvent, and the structures and energies studied by M06-2X calculations with a 6-31+G** basis set. Anions considered included the halides F-, Cl-, Brand I-, as well as those with multiple proton acceptor sites: CN-, NO 3-, HCOO-, CH 3 COO-, HSO 4-, H 2 PO 4-, and anions with higher charges SO 4 2-, HPO 4 2and PO 4 3-. Well structured cages were formed and the average H-bond energy decreases steadily as the number of surrounding solvent molecules rises, even when n exceeds 6 and the CF 3 H molecules begin to interact with one another rather than with the central anion. Total binding energies are very nearly proportional to the magnitude of the negative charge on the anion. The free energy of complexation becomes more negative for larger n initially, but then reaches a minimum and begins to rise for larger values of n.
“…Interestingly, the TS of such gas‐phase S N 2 reactions can be lower in energy than those of separate reactants. The double‐well PES gradually turns into a unimodal reaction profile with a positive reaction barrier as one adds more and more solvent molecules, going from the gas phase through microsolvation to bulk solvation (see Figure a) …”
The ion-pair SN 2 reactions of model systems MnF(n-1) +CH3Cl(M(+) =Li(+), Na(+), K(+), and MgCl(+); n=0, 1) have been quantum chemically explored by using DFT at the OLYP/6-31++G(d,p) level. The purpose of this study is threefold: 1) to elucidate how the counterion M(+) modifies ion-pair SN 2 reactivity relative to the parent reaction F(-) +CH3Cl; 2) to determine how this influences stereochemical competition between the backside and frontside attacks; and 3) to examine the effect of solvation on these ion-pair SN2 pathways. Trends in reactivity are analyzed and explained by using the activation strain model (ASM) of chemical reactivity. The ASM has been extended to treat reactivity in solution. These findings contribute to a more rational design of tailor-made substitution reactions.
“…Mechanistic studies of S N 2 reactions that take into account the effects of ion pairing are comparatively few ( Harder et al., 1995 ; Streitwieser et al. 1997 , 2008 ; Chen et al., 2009 ; Streitwieser and Jayasree, 2007 ; Zheng et al., 2010 ; Westaway, 2011 ; Li et al., 2015 ; Laloo et al., 2016 ). Scheme 2 Analysis of Nucleophilic Reactions Using the Concept of Transition-State Expansion (A) The transition state in an S N 2 reaction when the counter is ignored.…”
Section: Resultsmentioning
confidence: 99%
“…We assume TS-A should be bigger than the starting anion (Cl À ) (TSE). Mechanistic studies of S N 2 reactions that take into account the effects of ion pairing are comparatively few (Harder et al, 1995;Streitwieser et al 1997Streitwieser et al , 2008Chen et al, 2009;Streitwieser and Jayasree, 2007;Zheng et al, 2010;Westaway, 2011;Li et al, 2015;Laloo et al, 2016).…”
Summary
Ionic reactions are the most common reactions used in chemical synthesis. In relatively low dielectric constant solvents (e.g., dichloromethane, toluene), ions usually exist as ion pairs. Despite the importance of counterions, a quantitative description of how the paired 'counterion' affects the reaction kinetic is still elusive. We introduce a general and quantitative model, namely transition-state expansion (TSE), that describes how the size of a counterion affects the transition-state structure and the kinetics of an ionic reaction. This model could rationalize the counterion effects in nucleophilic substitutions and gold-catalyzed enyne cycloisomerizations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
