Alcohols on their own cannot undergo nucleophilic substitution reactions. The leaving group (HO-) is too strong a base for that. The OH-group will need to be converted to a group that is more easily displaced. This can be done by (1) protonation of the OH-group and then replacing it by a weakly basic nucleophile in the presence of heat, (2) using (among others) phosphorus halides or (3) by converting the alcohol to a sulfonate ester. All three methods will be discussed below.
Protonation of the OH-group
The OH-group of an alcohol can be protonated by an acid. A protonated OH-group can be displaced from the molecule by a weakly basic nucleophile when heated. In this process a water molecule becomes the leaving group, as shown in the reaction below. In this reaction ethanol is first protonated by hydrogen bromide, after which the bromide-ion becomes available to displace the OH-group.
Note that when too strong of a base is used that this base will be protonated instead of the alcohol (and it will no longer be a good nucleophile). Also, a strong base will tend to dehydrate the alcohol (see below). The alkylhalide that is formed can be used in further reactions.
Alcohols can undergo both SN1 and SN2 reactions. Because primary carbocations are too unstable to form and SN1 reactions of alcohols have a carbocation intermediary, primary alcohols can only undergo SN2 reactions. Secondary and tertiary alcohols do undergo SN1 reactions, so watch out for hydride shifts. In the reaction below, between 3-methylbutan-2-ol and hydrogen bromide, the main product is 2-bromo-2-methylbutane and only a small amount of 2-bromo-3-methylbutane is formed because of the higher stability of the tertiary carbocation.
Phosphorus halides
Even though it is possible to convert an alcohol to an alkylhalide using a hydrogen halide, it is more efficient to let the alcohol react with a phosphorus halide or with thionyl chloride. This reaction has a higher yield and will also avoid rearrangements due to carbocations.
3 CH3CH2OH + PBr3 → 3 CH3CH2Br + H3PO3
This reaction starts as an SN2-reaction, where the OH-group of the alcohol attacks the phosphorus atom. This releases a bromide ion. The presence of a base such as pyridine is required, because the proton of the alcohol needs a place to go before the reaction can continue. The released bromide ion can displace the just created bromophosphite group to form the alkylhalide. The yield of these reactions for tertiary alcohols is low, because it can't effectively attack the alcohol due to steric hindrance.
A comparable reaction occurs with PCl5 or thionyl chloride. Note that the reaction with PCl5 is very explosive and the POCl3 that is created will react further with the alcohol. The side products of the reaction with thionyl chloride are all gases, which will automatically leave the reaction mixture.
Sulfonate esters
A third way to make alcohols suitable for further reaction is by using a sulfonyl chloride. The oxygen atom of the alcohol attacks the sulfur atom of the sulfonyl chloride in an SN2-reaction which displaces the chloride. This reaction also requires the presence of a base to temporarily accomodate the proton of the OH-group. The most commonly used sulfonyl chloride is para-toluenesulfonyl chloride (sometimes shortened to TsCl, short for tosylate chloride).
The sulfonate ester that is created is very suitable for further reaction with a nucleophile since the leaving group is very weakly basic and can be easily displaced (100 times easier than chloride for example, due to resonance stabilization). If a tertiary alcohol is used for this reaction, further reactions become impossible due to steric hindrance.
Practice