Alcohols can be converted to haloalkames by reaction with HC., HBr, and HI, or PBrs \(50 C l_{2}\) or SOBr?. \- The HX reactions work hest for tertiary alcohols, where they involve a carbocation intermediate. \- \(\mathrm{PBr}_{3,} \mathrm{SOCl}_{2}\), or \(\mathrm{SOBr}_{2}\) react well with secondary and primary alcohols. These reactions involve an \(\mathrm{S}_{\mathrm{s}} 2\) displacement, so irversion of stereochemistry is seen when the DII group is bonded to a chiral center.

Nucleophilic substitution reactions are a type of organic reaction where a nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms to replace a leaving group. The nucleophile is a species that donates an electron pair to form a new chemical bond in the process of bond formation.

These reactions are particularly important in the conversion of alcohols to haloalkanes. For primary and secondary alcohols, the reaction proceeds via an SN2 mechanism. This involves a single concerted step where the nucleophile, typically a halide ion, attacks the electrophilic carbon atom from the opposite side of the leaving alcohol group (OH). The result is the departure of the leaving group and the simultaneous formation of a new bond between the nucleophile and the carbon atom, forming the haloalkane.

In SN2 reactions, the rate of the reaction is dependent on the concentration of both the nucleophile and the substrate (alcohol), because the reaction involves a transition state with both reactants. Factors affecting the rate include steric hindrance and the nucleophilicity and electrophilicity of the reactants engaged.

A carbocation intermediate is a highly reactive, positively charged species that has a carbon atom with only six electrons in its valence shell, making it electron-deficient. When tertiary alcohols undergo nucleophilic substitution reactions, especially with hydrogen halides (HX), they first form a carbocation intermediate.

In this process, the OH group of the alcohol is protonated to form a better leaving group, water. The loss of water then generates a carbocation. The stability of this cation is crucial and is enhanced by the presence of electron-donating alkyl groups. As a result, tertiary carbocations are more stable than secondary or primary carbocations due to hyperconjugation and the inductive effect of the surrounding alkyl groups.

This intermediate is central to the SN1 reaction mechanism, where the rate of the reaction is only dependent on the concentration of the substrate (the alcohol), because the formation of the carbocation is the rate-determining step. Once the carbocation is formed, the nucleophile can quickly react with it to form the final product.

Inversion of stereochemistry refers to a flip in the spatial arrangement of atoms around a stereocenter during a chemical reaction. This concept is particularly significant when dealing with chiral molecules—molecules that are not superimposable on their mirror images.

In the conversion of alcohols to haloalkanes through an SN2 reaction, the nucleophile attacks from the opposite side of the leaving group, leading to inversion of configuration at the carbon atom where the substitution occurs, akin to an umbrella turning inside out in the wind. This is because in an SN2 reaction, the bond formation with the nucleophile and the bond breaking of the leaving group occur simultaneously but from opposite sides of the planar intermediate, effectively resulting in the 'backside attack'.

This aspect is particularly crucial for understanding the stereochemical outcomes of chemical reactions involving chiral centers. It shows that the new molecule, if chiral, will be the enantiomer (non-superimposable mirror image) of the original molecule. In more complex molecules, predicting the outcome of SN2 reactions can be essential in the synthesis of a desired isomer.

The reactivity of an alcohol in substitution reactions is influenced by several factors, including its structure, which dictates whether a reaction will follow an SN1 or SN2 pathway. Primary alcohols, having only one alkyl group attached, are less sterically hindered, favoring an SN2 mechanism where the nucleophile must attack the central carbon atom directly.

Secondary alcohols are more reactive than primary alcohols but less reactive than tertiary alcohols. The presence of two alkyl groups can lead to intermediate steric hindrance and can sometimes allow for both SN1 and SN2 pathways, depending on conditions such as the nature of the nucleophile and solvent.

Tertiary alcohols are the most reactive toward nucleophilic substitution, especially with hydrogen halides, due to the added stability the additional alkyl groups confer to the carbocation intermediate formed during SN1 pathways. For this reason, tertiary alcohols rapidly form haloalkanes in the presence of strong acids without the need for a good nucleophile to assist in the removal of the leaving group.