Reactivity in Sn2 reactions

Simple alkyl halides show the following general order of reactivity in SN2 reactions ... 

A number of nucleophilic agents, which are very reactive in SN2 reactions, are of the type X-Y, where both atoms have unshared electron pairs. Examples include HOO , H2NO , CIO , and H2NNH2, all of which are more reactive than the closely related nucleophiles HO and NH3. 

The important chemistry of alkyl halides, RX, includes the nucleophilic (SN) displacement and elimination (E) reactions discussed in Chapter 8. Recall that tertiary alkyl halides normally are reactive in ionization (SN1) reactions, whereas primary halides, and to a lesser extent secondary halides, are reactive in Sn2 reactions, which occur by a concerted mechanism with inversion of configuration (Sections 8-4 to 8-7). 

This step should work very well, since the substrate is a primary benzylic halide, cannot undergo elimination, and is very reactive in SN2 reactions. 

The second approach for the nucleophilic animation reactions to be considered here will be reactions of allyl halides and allyl acetates leading to allyl amines. Allyl halides are normally very reactive in SN2 reactions, but the direct coupling of allyl halides with nitrogen nucleophiles has been performed with limited success [4], as di- and trialkylated by products often predominate. The application of the Gabriel synthesis can to a certain extent eliminate the problem with polyalkylation of amines using, e.g., the stabilized phthalimide anion 19 as the nucleophile. The allyl amine 20... 

The reactivity of RX toward C6o is found to be insensitive to the steric hindrance of the alkyl group of RX. This is however in contrast to the normal reactivity in Sn2 reactions [162]. For example, the largest rate constant is seen for a sterically hindered CCU, while the also sterically hindered /-Bui gives rise to a larger kobs value (4.7 x 10 m s ) than the much less sterically hindered Mel (3.5 X 10 M s ) [161]. Such an insensitivity of the rate on the steric hindrance... 

A breakthrough came when Swain and Scott (5) proposed a two-parameter equation that calibrated the reactivity of nucleophiles by reference to their rate of reaction toward methyl iodide, taken to be a standard electrophile. This equation was based, in effect, on the well-known order of reactivity in SN2 reactions I- > Br-, Cl- > F- and on the work of Foss (6),... 

Parenthetically, it should also be noted that allylic and benzylic substrate are particularly reactive in SN2 reactions as well as in SN1 reactions. Allvli. and benzylic C-X bonds are about 50 kJ/mol (12 keal/mol) weaker than tl corresponding saturated bonds and are therefore more easily broken. 

Benzyl ethers are commonly used to protect hydroxyl groups in sugars. Benzyl halides are easily introduced because they are highly reactive in Sn2 reactions. Sodium or potassium hydride is typically used as the base in an aprotic solvent such as DMF or DMSO. The benzyl groups can later be easily removed by hydrogenolysis using a palladium catalyst. 

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