4.

12 Reaction of methyl and primary Alcohols With Hydrogen Halides: The S N2 Mechanism

Unlike tertiary and secondary carbocations, methyl and primary carbocations are too high in energy
to be intermediates in chemical reactions. However, methyl and primary alcohols are converted,
albeit rather slowly, to alkyl halides on treatment with hydrogen halides. Therefore, they must follow
a different mechanism, one that avoids carbocation intermediates. This alternative process is
outlined in mechanism 4.2 for the reaction of 1-heptanol with hydrogen bromide.

The first step of this new mechanism is exactly the same as that seen earlier for the reaction of tert-
butyl alcohol with hydrogen chloride-formation of an alkyloxonium ion by proton transfer from the
hydrogen halide to the alcohol. Like the earlier example, this is a rapid, reversible Bronsted acid-base
reaction.

The major difference between the two mechanism is the second step. The second step in the
reaction of tert-butyl alcohol with hydrogen chloride is the unimolecular dissociation of tert-
butyloxonium ion to tert-butyl cation and water. Heptyloxonium ion. However, instead of dissociating
to an unstable primary carbocation, reacts differently.

MECANISM 4.2 (CHEM-OFFICE)

It is attacked by bromide ion, which acts as a nucleophile. We can represent step 2 and its transition
state as:

TRANSITION STATE (CHEM-OFFICE)

Bromide ion forms a bond to the primary carbon by pushing off a water molecule. This step is
bimolecular because it involves both bromide and heptyloxonium ion. Step 2 is slower than the
proton transfer in step 1, so it is rate-determining. Using Ingolds terminology, we classify
nucleophilic substitutions that have a bimolecular rate-determining step by the mechanistic symbol
SN2.

It is important to note that although methyl and primary alcohols react with hydrogen halides by a
mechanism that involves fewer steps than the corresponding reactions of secondary and tertiary
alcohols, fewer steps do not translete to faster reaction rates. Remember, the observed order of
reactivity of alcohols with hydrogen halides is tertiary > secondary > primary. Reaction Rate is
governed by the activation energy of the slowest step, regardless of how many steps there are.

4.13 More on Activation Energy

In section 4.7. you saw that the reaction of 1-heptanol with hydrogen bromide requires elevated
temperature to proceed at a synthetically acceptable rate.

REACTION (CHEM-OFFICE)

A quantitative relationship between the energy of activation (E act), the rate constant (k) and
temperature (T) is expressed by the Arrhenius Equation:

k = Ae-Eact/RT

where R is the gas constant (R=8,314 x 10-3 kJ/K.mol or 1,987 x 10-3 kcal/K.mol). T is the temperature
in kelvins. And A is the preexponential, or frequency factor that is related to the collision frequency
and geometry. Because temperature appears in the denominator of the negative exponent, the rate
constant k increase with increasing temperature. In physical terms, raising the temperature increases
the average kinetic energy of the reacting molecules with the result that more of them have energies
greater than Eact. We can also see from this expression that small differences in E act result in large
differences in reaction rate. As Eact gets smaller e-Eact/RT gets larger and the rate constant increases
exponentially. The field of kinetics involves the study of the rates of chemical reactions and the
factors that influence reaction rate. Kinetics provides a quantitative understanding for many of the
structure-reactivity relationships that we encounter in organic chemistry.