Displacement reactions neighboring group effects

In its simplest form, the study of neighboring group effects notes that a heteroatom with a pair of nonbonding electrons can act as a nucleophile in an intramolecular displacement reaction, just as external nucleophiles can participate in intermolecu-lar S]v2 reactions. In an example we have seen (p. 317), oxiranes can be formed from halohydrins in base (Fig. 21.2). 

Whenever you see an unexpected stereochemical result (usually retention where inversion is expected), look for an intramolecular displacement reaction—a neighboring group effect. You will almost always find it. 

At least one of the clues to the operation of a neighboring group effect is present in this reaction. The stereochemistry of the product is the opposite to what one would expect from a simple displacement (clue 1). 

The formation of the wrong stereoisomer is the clue to the operation of a neighboring group effect in the reaction of Figure 21.21. The product is formed not with the inversion of configuration required by the mechanism, but with retention (clue 1). After the hydroxyl group is protonated, it is displaced not by an external bromide ion, but by the bromine atom lurking in the same molecule (Fig. 21.22). It is most important at this point to keep the stereochemical relationships clear. Displacement must be from the rear, as this is an intramolecular Sn2 reaction. 

Kinetic isotope effect for lysozyme. A secondary kinetic isotope effect is expected because a molecule with H in the number 1 position can be converted to the corresponding oxocarbenium ion somewhat more easily than the molecule with 2H in the same position (Eq. 12-13). For example, in the nonenzymatic acid-catalyzed hydrolysis of a methyl- glucoside, a reaction also believed to proceed through a carbocation intermediate,41 75 the ratio h / h, is 1.14 for the a anorner and 1.09 for the (3 anorner.53 In the base-catalyzed hydrolysis of the same compound, which is believed to occur by a double-displacement reaction involving participation of the neighboring OH group on C-2, the ratio /c1h / /c2h is 1.03. The corresponding ratio measured... 

The dependence of the rate of an intramolecular nucleophilic displacement on the size of the ring that is being formed is determined by the interplay of at least three quantities (1) the entropy loss on formation of the transition state, (2) the increase in strain energy on formation of the transition state, and (3) the electronic effects of the neighboring group and reaction group on one another. 

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