11.4: Characteristics of the SN2 Reaction
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Now that we know how SN2 reactions occur, we need to see how they can be used and what variables affect them. Some SN2 reactions are fast, and some are slow; some take place in high yield and others in low yield. Understanding the factors involved can be of tremendous value. Let’s begin by recalling a few things about reaction rates in general.
The rate of a chemical reaction is determined by the activation energy ∆G‡, the energy difference between reactant ground state and transition state. A change in reaction conditions can affect ∆G‡ either by changing the reactant energy level or by changing the transition-state energy level. Lowering the reactant energy or raising the transition-state energy increases ∆G‡ and decreases the reaction rate; raising the reactant energy or decreasing the transition-state energy decreases ∆G‡ and increases the reaction rate (Figure 11.6). We’ll see examples of all these effects as we look at SN2 reaction variables.
Steric Effects in the SN2 Reaction
The first SN2 reaction variable to look at is the structure of the substrate. Because the SN2 transition state involves partial bond formation between the incoming nucleophile and the alkyl halide carbon atom, it seems reasonable that a hindered, bulky substrate should prevent easy approach of the nucleophile, making bond formation difficult. In other words, the transition state for reaction of a sterically hindered substrate, whose carbon atom is “shielded” from the approach of the incoming nucleophile, is higher in energy and forms more slowly than the corresponding transition state for a less hindered substrate (Figure 11.7).
As Figure 11.7 shows, the difficulty of nucleophile approach increases as the three substituents bonded to the halo-substituted carbon atom increase in size. Methyl halides are by far the most reactive substrates in SN2 reactions, followed by primary alkyl halides such as ethyl and propyl. Alkyl branching at the reacting center, as in isopropyl halides (2°), slows the reaction greatly, and further branching, as in tert-butyl halides (3°), effectively halts the reaction. Even branching one carbon away from the reacting center, as in 2,2-dimethylpropyl (neopentyl) halides, greatly hinders nucleophilic displacement. As a result, SN2 reactions occur only at relatively unhindered sites and are normally useful only with methyl halides, primary halides, and a few simple secondary halides. Relative reactivities for some different substrates are as follows:
Vinylic halides () and aryl halides are not shown on this reactivity list because they are unreactive toward SN2 displacement. This lack of reactivity is due to steric factors: the incoming nucleophile would have to approach in the plane of the carbon–carbon double bond and burrow through part of the molecule to carry out a backside displacement.
The Nucleophile
Another variable that has a major effect on the SN2 reaction is the nature of the nucleophile. Any species, either neutral or negatively charged, can act as a nucleophile as long as it has an unshared pair of electrons; that is, as long as it is a Lewis base. If the nucleophile is negatively charged, the product is neutral; if the nucleophile is neutral, the product is positively charged.
A wide array of substances can be prepared using nucleophilic substitution reactions. In fact, we’ve already seen examples in previous chapters. For instance, the reaction of an acetylide anion with an alkyl halide, discussed in Section 9.8, is an SN2 reaction in which the acetylide nucleophile displaces a halide leaving group.
Table 11.1 lists some nucleophiles in the order of their reactivity, shows the products of their reactions with bromomethane, and gives the relative rates of their reactions. There are large differences in the rates at which various nucleophiles react.
Nu:– + CH3Br → CH3Nu + Br– | ||||
---|---|---|---|---|
Nucleophile | Product | Relative rate of reaction | ||
Formula | Name | Formula | Name | |
H2O | Water | CH3OH2+ | Methylhydronium ion | 1 |
CH3CO2– | Acetate | CH3CO2CH3 | Methyl acetate | 500 |
NH3 | Ammonia | CH3NH3+ | Methylammonium ion | 700 |
Cl– | Chloride | CH3Cl | Chloromethane | 1,000 |
HO– | Hydroxide | CH3OH | Methanol | 10,000 |
CH3O– | Methoxide | CH3OCH3 | Dimethyl ether | 25,000 |
I– | Iodide | CH3I | Iodomethane | 100,000 |
–CN | Cyanide | CH3CN | Acetonitrile | 125,000 |
HS– | Hydrosulfide | CH3SH | Methanethiol | 125,000 |
What are the reasons for the reactivity differences observed in Table 11.1? Why do some reactants appear to be much more “nucleophilic” than others? The answers to these questions aren’t straightforward. Part of the problem is that the term nucleophilicity is imprecise. The term is usually taken to be a measure of the affinity of a nucleophile for a carbon atom in the SN2 reaction, but the reactivity of a given nucleophile can change from one reaction to the next. The exact nucleophilicity of a species in a given reaction depends on the substrate, the solvent, and even the reactant concentrations. Detailed explanations for the observed nucleophilicities aren’t always simple, but some trends can be detected from the data of Table 11.1.
- Nucleophilicity roughly parallels basicity when comparing nucleophiles that have the same reacting atom. Thus, OH– is both more basic and more nucleophilic than acetate ion, CH3CO2–, which in turn is more basic and more nucleophilic than H2O. Since “nucleophilicity” is usually taken as the affinity of a Lewis base for a carbon atom in the SN2 reaction and “basicity” is the affinity of a base for a proton, it’s easy to see why there might be a correlation between the two kinds of behavior.
- Nucleophilicity usually increases going down a column of the periodic table. Thus, HS– is more nucleophilic than HO–, and the halide reactivity order is I– > Br– > Cl–. Going down the periodic table, elements have their valence electrons in successively larger shells where they are successively farther from the nucleus, less tightly held, and consequently more reactive. This matter is complex, though, and the nucleophilicity order can change depending on the solvent.
- Negatively charged nucleophiles are usually more reactive than neutral ones. As a result, SN2 reactions are often carried out under basic conditions rather than neutral or acidic conditions.