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Electricity

The Chemical Bond

Thermochemistry

Chemical Kinetics

Solutions

Acids and Bases

Reactions of Alkyl Halides

Substitution versus elimination is a classic problem of the organic chemistry lecture course, and it is important for the MCAT. The major product of the reaction of an alkyl halide and a Lewis base depends on whether the dominant reaction pathway is SN1, SN2, E1, or E2. The main determinants are the structure of the alkyl halide and the basicity of the anion, although the solvent is also important.

If the substrate is a primary alkyl halide, the reaction that occurs will be SN2 unless there is significant steric hindrance due to a bulky anion such as tert-butoxide or crowding on carbons adjacent to the halide substituent, in which case E2 would be increasingly favored. Because primary carbocations are so unstable, E1 and SN1 will not occur with primary alkyl halides.

If the alkyl halide is not primary, the path depends on whether the anion is a strong base. For secondary and tertiary alkyl halides reacting with a strong base, the E2 mechanism predominates.

For secondary alkyl halides in the presence of nucleophiles that are weak bases, the solvent plays a major roll in determining the reaction pathway. A polar, aprotic solvent, such as DMSO, while good for stabilizing the charge separations in transition states and for stabilizing cations, lacking hydrogen bonding capability, does not stabilize anions. Therefore, the nucleophilicity of anions is substantially enhanced in polar aprotic solvents, increasing the tendency for SN2 substitution to occur. Protic solvents, on the other hand, greatly enhance the rate of solvolysis (carbocation formation) by lowering the activation energy of ionization, so secondary a alkyl halide with a weak base in protic solvents generally reacts to form E1, SN1 mixtures.

With tertiary alkyl halides, the picture is not complicated by the possibility of SN2, so if the base is strong, the predominant reaction is E2, if the base is weak, then the reaction path is E1 or E1/SN1 in mixture.




Electricity

Stereochemistry

Thermochemistry

Solutions

Acids and Bases

Reactions of Alkyl Halides

Read for comprehension. SN1 substitution is not generally useful for synthetic organic chemistry, except in ideal solvolysis. The hindered substrates upon which it occurs are generally even more prone to elimination.

Modifications of the mechanism, which occur in a majority of mechanisms include the case of assistance by the solvent in ionization and the case of the nucleophile attacking the carbocation-leaving group pair, which places the mechanism between SN1 and SN2. The same solvent might facilitate carbocation formation through solvolysis stabilization and through its nucleophilicity, the former action involving the weakening of the electric field of separating charges as a dielectric, the latter action involving the weakening of the electric field of the separating charges by the partial donation of an electron pair. In most SN1 reactions the carbocation never becomes electrostatically independent of its leaving group; rather the nucleophile attacks an ion pair, evidence being the dependence of product distribution on the leaving group, the tendency in allylic systems to favor the unrearranged product, and in some cases, product that is only partially racemized. Substitution can occur on all three types of carbocation, the contact ion pair, the solvent separated ion pair, and the free carbocation.








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