Mechanisms of the Reactions of Alcohols with HX

Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation, in an SN1 reaction with the protonated alcohol acting as the substrate.

The SN1 mechanism is illustrated by the reaction tert-butyl alcohol and aqueous hydrochloric acid (H3O+, Cl− ). The first two steps in this Sn1 substitution mechanism are protonation of the alcohol to form an oxonium ion. Although the oxonium ion is formed by protonation of the alcohol, it can also be viewed as a Lewis acid-base complex between the cation (R+) and H2O. Protonation of the alcohol converts a poor leaving group (OH-) to a good leaving group ()H_2O\_), which makes the dissociation step of the SN1 mechanism more favorable.

In step 3, the carbocation reacts with a nucleophile (a halide ion) to complete the substitution.

When we convert an alcohol to an alkyl halide, we carry out the reaction in the presence of acid and in the presence of halide ions, and not at elevated temperature. Halide ions are good nucleophiles (they are much stronger nucleophiles than water), and since halide ions are present in high concentration, most of the carbocations react with an electron pair of a halide ion to form a more stable species, the alkyl halide product. The overall result is an Sn1

reaction.

Not all acid-catalyzed conversions of alcohols to alkyl halides proceed through the formation of carbocations. Primary alcohols and methanol react to form alkyl halides under acidic conditions by an S_N2 mechanism.

In these reactions the function of the acid is to produce a protonated alcohol. The halide ion then displaces a molecule of water (a good leaving group) from carbon; this produces an alkyl halide:

Again, acid is required. Although halide ions (particularly iodide and bromide ions) are strong nucleophiles, they are not strong enough to carry out substitution reactions with alcohols themselves. Direct displacement of the hydroxyl group does not occur because the leaving group would have to be a strongly basic hydroxide ion:

We can see now why the reactions of alcohols with hydrogen halides are acid-promoted.

Carbocation rearrangements are extremely common in organic chemistry reactions are are defined as the movement of a carbocation from an unstable state to a more stable state through the use of various structural reorganizational "shifts" within the molecule. Once the carbocation has shifted over to a different carbon, we can say that there is a structural isomer of the initial molecule. However, this phenomenon is not as simple as it sounds.

The most common methods for converting 1º- and 2º-alcohols to the corresponding chloro and bromo alkanes (i.e. replacement of the hydroxyl group) are treatments with thionyl chloride and phosphorus tribromide, respectively. These reagents are generally preferred over the use of concentrated HX due to the harsh acidity of these hydrohalic acids and the carbocation rearrangements associated with their use.

Synthetic organic chemists, when they want to convert an alcohol into a better leaving group, have several methods to choose from. One common strategy is to convert the alcohol into an alkyl chloride or bromide, using thionyl chloride or phosphorus tribromide:

Despite their general usefulness, phosphorous tribromide and thionyl chloride have shortcomings. Hindered 1º- and 2º-alcohols react sluggishly with the former, and may form rearrangement products, as noted in the following equation.

Below, an abbreviated mechanism for the reaction is displayed. The initially formed trialkylphosphite ester may be isolated if the HBr byproduct is scavenged by base. In the presence of HBr a series of acid-base and S_N2 reactions take place, along with the transient formation of carbocation intermediates. Rearrangement (pink arrows) of the carbocations leads to isomeric products.

Reaction of thionyl chloride with chiral 2º-alcohols has been observed to proceed with either inversion or retention. In the presence of a base such as pyridine, the intermediate chlorosulfite ester reacts to form an "pyridinium" salt, which undergoes a relatively clean S_N2 reaction to the inverted chloride. In ether and similar solvents the chlorosulfite reacts with retention of configuration, presumably by way of a tight or intimate ion pair. This is classified as an S_Ni reaction (nucleophilic substitution internal). The carbocation partner in the ion pair may also rearrange. These reactions are illustrated by the following equations. An alternative explanation for the retention of configuration, involving an initial solvent molecule displacement of the chlorosulfite group (as SO₂ and chloride anion), followed by chloride ion displacement of the solvent moiety, has been suggested. In this case, two inversions lead to retention.