Neopentyl bromide, reactivity

The low Sn2 reactivity of 1°-alkyl bromide, 2,2-dimethyl-1-bromopropane (neopentyl bromide, 2.5), is explained by steric hindrance to the required 180° alignment of reacting orbitals. However, under Sn 1 conditions, neopentyl bromide (2.5) reacts at roughly the same rate as other 1°-alkyl halides such as ethyl bromide. Ionization of alkyl halides to carbocation in SnI is the rate-determining step. Although the product from ethyl bromide is ethanol as expected, neopentyl bromide (2.5) yields 2-methyl-2-butanol (2.6) instead of the expected 2,2-dimethyl-1-propanol (neopentyl alcohol) (2.7). This is because once formed the ethyl carbocation can only be transformed by a substitution or elimination process. In the case of the neopentyl carbocation, however, the initially formed l°-carbocation may be converted... 

The rate of an Sn2 reaction depends not only on the number of alkyl groups attached to the carbon that is undergoing nucleophilic attack, but also on their size. For example, while ethyl bromide and propyl bromide are both primary alkyl halides, ethyl bromide is more than twice as reactive in an Sn2 reaction because the bulkier propyl group provides more steric hindrance to back-side attack. Also, although neopentyl bromide is a primary alkyl halide, it undergoes Sn2 reactions very slowly because its single alkyl group is unusually bulky. 

None of these compounds has structural features necessary to promote SnI (not even the third notice that the bromine is attached to a primary carbon, even though there is a tert-butyl group in the molecule), so we need to think about Sn2 reactivity only. In general, steric hindrance slows dovm Sn2 reactions, so we can start by saying that methyl bromide > -butyl bromide > cyclohexyl bromide. But how do the other two fit into the scale An adjacent carbonyl group accelerates Sn2 reactions enormously, so the ketone will react even faster than methyl bromide. On the other hand, a bulky tert-butyl group adjacent to a reaction centre leads to very slow substitution, so this compound ( neopentyl bromide ) goes at the bottom of the scale. 

The physical explanation for this order of reactivity is suggested by the information in Table 6-5. All the slow-reacting compounds have one property in common The back side of the electrophilic carbon atom is crowded by the presence of bulky groups. Tertiary halides are more hindered than secondary halides, which are more hindered than primary halides. Even a bulky primary halide (like neopentyl bromide) undergoes 8f.j2 reaction at a rate similar to that of a tertiary halide. The relative rates show that... 

The second-order rate constants for the substitution reactions of alkyl halides generally decrease as the aUcyl halide varies from methyl to 1° to 2° to 3°. This trend is illustrated in Table 8.9, which summarizes kinetic data for alkyl bromides (R-Br) reacting with bromide ion. ° This trend is usually ascribed to increasing steric hindrance to back-side attack of the nucleophile as hydrogens bonded to the C—Br carbon atom are replaced with larger alkyl groups. Theoretical calculations and gas phase studies have provided support for this explanation. It is notable that neopentyl bromide is less reactive than... 

The rate of reaction shows first order dependence on the concentration of iron and ethyl bromide, but is independent of the concentration of ethylmagnesium bromide. The rate, however, varies with the structure of the Grignard reagent, and disproportionation usually results except when the alkyl group is methyl, neopentyl or benzyl which possess no g-hydrogens. The reactivities of the alkyl bromides (t-butyl >i-propyl >n-propyl) as well as the kinetics are the same as the silver-catalyzed coupling described above and suggest a similar mechanism ... 

Oxidative addition can also occur to two metal centers of dinuclear complexes that lack a metal-metal bond. For example, the dinuclear Au(I) complex containing phosphorus ylide ligands in Equation 7.29 undergoes oxidative addition of CH I in a transannular fashion. " The reactivity of CHjX, PhCH Br, and EtBr, but not neopentyl or adamantyl bromide, suggests that this reaction occurs by an Sj 2 mechanism. 

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