Configuration in the SN2 Reaction

CHAPTER 7 Inversion of Configuration in the Sn2 Reaction 244 Racemization in the Sn1 Reaction 252 Hydride Shift in an Sn1 Reaction 253 Methyl Shift in an Sn1 Reaction 254 Rearrangement in an E1 Reaction 261 Dehydrohalogenation by the E2 Mechanism 304 Stereochemistry of the E2 Reaction 306 E2 Debromination of a Vicinal Dibromide 310... 

We can also explain inversion of configuration in the Sn2 reaction by looking at the frontier orbitals, but it is a much weaker explanation. The appropriate frontier orbitals will be the HOMO of the nucleophile and the LUMO of the electrophile. Taking the orbitals of methyl chloride in Figs 1.45 and 1.47, we can see the LUMO is the [Pg.155]

The chiral malic acid figures strongly in the original discovery of inversion of configuration in the Sn2 reaction. Malic acid is sometimes called apple acid because of its high concentration in apples, nectarines, and some other fruits. In fact, it was first isolated from apple juice as early as 1785. It functions as a molecular carrier of the carbon dioxide absorbed by plants. The CO2 appears in the CHjCOOH group of malic acid. The principal actor in the early mechanistic work on the S>j2 reaction was Paul Walden, a chemist born in 1863 in what is... 

The reaction of an alkyl halide or los3 late with a nucleophiJe/base results eithe in substitution or in diminution. Nucleophilic substitutions are of two types S 2 reactions and SN1 reactions, in the SN2 reaction, the entering nucleophih approaches the halide from a direction 180° away from the leaving group, result ing in an umbrella-like inversion of configuration at the carbon atom. The reaction is kinetically second-order and is strongly inhibited by increasing stork bulk of the reactants. Thus, S 2 reactions are favored for primary and secondary substrates. 

Exercise 8-7 Equations 8-3 through 8-5 show how Kenyon and Phillips established that inversion of configuration accompanies what we now recognize to be SN2 substitutions. For each reaction, we indicate whether R—0 or O—H is broken by an appropriately placed vertical line. Explain how the sequence of steps shows that inversion occurs in the SN2 reaction of Equation 8-5. The symbols (+) or (—) designate for each compound the sign of the rotation a of the plane of polarized light that it produces. 

The product has the opposite configuration from the starting materials, as in the Sn2 reaction, but this time there is a loss in optical purity. Optically pure bromide yields alcohol that is only about two-thirds optically pure. Optically pure starting material contains only the one enantiomer, whereas the product clearly must contain both. The product is thus a mixture of the inverted compound and the racemic modification, and we say that the reaction has proceeded with partial racemization. How can we account for these stereochemical results ... 

To calculate reactive trajectories, Keirstead et al. began with f-butyl chloride configurations constrained at the transition state as found from their free energy calculations. They released this constraint and followed the dynamics for 1 ps both forward and backward in time. From these trajectories, they calculated a transmission coefficient of 0.53, which was found to be in excellent agreement with both Grote—Hynes theory and the frozen solvent nonadiaba-tic solvation model discussed above in connection with the Sn2 simulations.Thus, as in the Sn2 reaction, it is an excellent approximation to... 

The alternative mechanism, the Sn2 reaction, is a concerted reaction in which the nucleophile approaches from the side of the R groups as the other group (Cl in the example) leaves. In this case the configuration of the molecule is inverted. If the original molecule is optically active, the product has the opposite activity, an effect known as Walden Inversion. The notations SnI and Sn2 refer to the kinetics of the reactions. In the SnI mechanism, the slow step is the first one, which is unimolecular (and first order in CR3CI). In the Sn2 reaction, the process is bimolecular (and second order overall). 

A mechanism that accounts for both the inversion of configuration and the second-order kinetics that are observed with nucleophilic substitution reactions was suggested in 1937 by E. D. Hughes and Christopher Ingold, who formulated what they called the SN2 reaction—short for substitution, nucleophilic, birnolecu-lar. (Birnolecular means that two molecules, nucleophile and alkyl halide, take part in the step whose kinetics are measured.)... 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

In the MOVB method, we use one Slater determinant with block-localized molecular orbitals to define individual VB configuration, called diabatic state. For example, the reactant state of the Sn2 reaction between HS- and CH3CI is defined as the Lewis bond structure of the substrate CH3CI ... 

Many theories have been put forward to explain the mechanism of inversion. According to the accepted Hugles, Ingold theory aliphatic nucleophilic substitution reactions occur eigher by SN2 or SN1 mechanism. In the SN2 mechanism the backside attack reduces electrostatic repulsion in the transition state to a minimum when the leaving meleophile leaves the asymmetric carbon, naturally an inversion of configuration occurs at the central carbon atom. 

We noted above that the inversion of configuration that accompanied Sn2 reactions was particularly apparent in cyclic systems, and that cis derivatives would be converted into trans products in disubsti-tuted rings, and vice versa (see Section 6.1.5). Should... 

A reaction described as Sn2, abbreviation for substitution, nucleophilic (bimolecular), is a one-step process, and no intermediate is formed. This reaction involves the so-called backside attack of a nucleophile Y on an electrophilic center RX, such that the reaction center the carbon or other atom attacked by the nucleophile) undergoes inversion of stereochemical configuration. In the transition-state nucleophile and exiphile (leaving group) reside at the reaction center. Aside from stereochemical issues, other evidence can be used to identify Sn2 reactions. First, because both nucleophile and substrate are involved in the rate-determining step, the reaction is second order overall rate = k[RX][Y]. Moreover, one can use kinetic isotope effects to distinguish SnI and Sn2 cases (See Kinetic Isotope Effects). 

Two-configuration substitution reactions. Methyl derivatives The Sn2 reaction profile of methyl derivatives may in simplest terms, be considered as resulting from the avoided crossing of reactant [20] and product... 

In conclusion, for the SN2 reactions of primary alkyl derivatives, the author is of the view that the Bronsted parameter a does not constitute measure of transition state charge development, and is unlikely to represent a meaningful measure of transition state geometry. As we shall see in the following section, however, for reactions described by three or more configurations, the Bronsted parameter or Hammett p parameter may provide a relative measure of transition state charge development (Pross, 1984). 

Let us now consider the effect on an SN2 reaction of stabilizing the car-banion configuration. If the carbanionic configuration [23] is the one that is stabilized - for example, by an a-carbonyl group - then the transition state is expected to take on carbanionic character. This is indeed what is observed for the Sn2 reaction of a family of a-carbonyl derivatives indicated in (86)... 

In CM terms the proton transfer reaction is very similar to the SN2 reaction of methyl derivatives. The two key configurations which are involved are the reactant and product configurations, [40] and [41]. The arguments that were applicable to methyl transfer reactions now may be utilized for proton transfer reactions. These may be summarized as follows ... 

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