Neopentyl systems, nucleophilic substitution reactions

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleophilic substitution reactions. They are primary and do not form carbocation intermediates moreover the r-butyl substituent hinders back-side displacement. The rate of reaction of neopentyl bromide with iodide ion is 470 times less than that of n-butyl bromide. Under solvolysis conditions the neopentyl system usually reacts with rearrangement to the... 

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleophilic substitution reactions. They are primary and do not form carbocation intermediates, but the /-butyl substituent effectively hinders back-side attack. The rate of reaction of neopentyl bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, the neopentyl system reacts with rearrangement to the /-pentyl system, although use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary benzyl system in entry 3 exhibits high, but not complete, inversion. This is attributed to racemization of the reactant by ionization and internal return. 

The extent to which rearrangement occurs depends on the structure of the cation and foe nature of the reaction medium. Capture of carbocations by nucleophiles is a process with a very low activation energy, so that only very fast rearrangements can occur in the presence of nucleophiles. Neopentyl systems, for example, often react to give r-pentyl products. This is very likely to occur under solvolytic conditions but can be avoided by adjusting reaction conditions to favor direct substitution, for example, by use of an aptotic dipolar solvent to enhance the reactivity of the nucleophile. In contrast, in nonnucleophilic media, in which fhe carbocations have a longer lifetime, several successive rearrangement steps may occur. This accounts for the fact that the most stable possible ion is usually the one observed in superacid systems. 

Neopentyl halides are among the most unreactive substrates in polar nucleophilic substitution reactions118. Due to the fact that the halogens are on a primary carbon atom, neopentyl halides seldom react by the S l mechanism. Beacuse of the steric hindrance by the t-butyl group to backside attack, the S 2 reaction in the neopentyl system is notoriously slow. However, with nucleophiles that are good electron donors, the ET reaction competes with the polar mechanism. 

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