Chapter 11: Reactions of Alkyl Halides: Nucleophilic Substitution and Elimination
Four reactions, two outcomes, one substrate
The reactions in this chapter connect a single functional group, the alkyl halide, to four mechanisms that recur throughout organic chemistry. Two of them are substitutions, in which a nucleophile takes the place of the halide on carbon, and two are eliminations, in which a base removes a beta hydrogen while the halide leaves and a carbon-carbon double bond forms. The product tells the families apart at a glance: substitution keeps the carbon skeleton saturated and installs a new group where the halogen was, whereas elimination introduces unsaturation. Within each family the distinction is…
One step, backside attack, and inversion
The defining feature of the SN2 reaction is that everything happens at once. There is no intermediate; bond formation to the nucleophile and cleavage of the carbon-halogen bond are concerted, reaching a maximum together in one transition state. That transition state contains both partners, and this is why the observed kinetics are second order, first order in the substrate and first order in the nucleophile. Doubling either concentration doubles the rate, a direct experimental fingerprint of a bimolecular rate-determining step, which is what the name, substitution nucleophilic bimolecular,…
Steric access, nucleophile, leaving group, and solvent
The SN2 reaction is controlled first and foremost by steric access to the electrophilic carbon. Since the nucleophile must approach along the axis opposite the leaving group, any alkyl group attached to that carbon obstructs the trajectory. The result is a sharp reactivity order, methyl greater than primary greater than secondary, with tertiary substrates so crowded that the SN2 pathway is closed to them; they react, if at all, by the stepwise routes. Branching one carbon away, at the beta position, slows the reaction as well, which is why neopentyl halides are notoriously sluggish despite…
Ionize, then capture: two steps and racemization
The SN1 reaction separates the events that the SN2 reaction fused. The first step is a unimolecular ionization: the carbon-halogen bond breaks on its own to give a carbocation and a halide ion. This step is difficult and slow, and it alone determines the rate. The kinetics are therefore first order, depending only on the concentration of the substrate; the nucleophile does not appear in the rate law because it takes part only after the rate-determining step is over. The name records this, substitution nucleophilic unimolecular. The second step is fast. The nucleophile adds to the…
What favors ionization: cation stability, leaving group, and protic solvent
Every factor that governs the SN1 reaction traces back to a single slow event, the formation of a carbocation. Anything that stabilizes that cation lowers the barrier to the rate-determining step and speeds the reaction. Substrate structure is therefore read through the lens of cation stability: a tertiary halide ionizes to a stabilized tertiary cation and reacts readily, a secondary halide reacts more slowly, and primary and methyl halides effectively do not react by this pathway because the corresponding cations are prohibitively high in energy. This ordering, tertiary greater than…
Concerted elimination, anti-periplanar geometry, and Zaitsev
The E2 reaction removes the elements of H and X from adjacent carbons in a single concerted step, and it is the elimination analog of the SN2 reaction in both mechanism and kinetics. A base attacks a beta hydrogen, the C-H bond breaks, its electrons form a new pi bond between the alpha and beta carbons, and the leaving group departs, all at the same time. Because both the substrate and the base are present in this one rate-determining transition state, the reaction is second order, first order in each. The name, elimination bimolecular, records this. Geometry is the feature that most…
Stepwise elimination through a carbocation, and the SN1 partnership
The E1 reaction is the elimination that branches off the SN1 pathway. Its first step is identical to that of the SN1 reaction: the carbon-halogen bond ionizes to give a carbocation and a halide ion, slowly and rate-determiningly. The rate is therefore first order in the substrate alone, and, as in the SN1 reaction, the base does not appear in the rate law. What differs is the fate of the carbocation. Rather than being captured by a nucleophile at carbon, it loses a proton from an adjacent carbon; a base, frequently just the solvent or the departed halide, removes a beta hydrogen, and the…
Building the decision grid
Predicting which of the four pathways dominates is the synthesis of the whole chapter, and it cannot be done from any one variable in isolation. The reliable procedure is to read four inputs in a fixed order: the substrate class, the reagent's character as nucleophile and as base, the solvent, and the temperature. Substrate class sets the outer bounds. Methyl and primary halides react overwhelmingly by the SN2 reaction with essentially any nucleophile, because backside attack is unobstructed and the corresponding carbocations are too unstable to form; the only way to make a primary substrate…
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