Alcohols are a very rich (chemically speaking) functional group. There are reactions of alcohols that allow you to convert alcohols into alkenes, halides, ketones, aldehydes, carboxylic acids, esters, and ethers. Reactions of alcohols are often a key step in many syntheses, so knowing chemistry of alcohols is important.
Acid-Base Properties of Alcohols
Alcohols can act as either Brønsted acids and bases depending on what they are reacting with. When alcohols are deprotonated (example 1 below), they form strong bases (alcoxides) that can also be good nucleophiles. The while protonated alcohols (example 2 below), however, are generally very acidic and will tend to yield a proton back into the solution.
Alcoxides as Bases and Nucleophiles
Deprotonated alcohols (alcoxides) are both good bases and good nucleophiles (depending on their size). Their nucleophilicity decreases with size while the basicity increases in the same direction.
Alcoxides are commonly used in two types of reactions:
- SN2 reaction called Williamson ether synthesis that yields simple non-sterically hindered ethers; and
- E2 reactions yielding alkenes or alkynes.
Acid-Catalyzed Dehydration of Alcohols
Alcohols undergo dehydration in acidic conditions. The reaction follows the E1 mechanism and can potentially cause skeletal rearrangements (via formation of carbocations) complicating the outcome of the reaction. Simple alcohols generally follow the Zaitsev Rule giving the alkene with more substituted (more stable) double bond.
E2 Dehydration with POCl3 in Pyridine
Dehydration of alcohols in acidic conditions can be problematic because it uses harsh conditions and can potentially cause rearrangements. A more gentle way to directly eliminate water from alcohol fiving a corresponding alkene is a reaction with POCl3 and pyridine (solvent/base). Hydroxyl group in this reaction is converted into a good leaving group and is eliminated via E2 mechanism using pyridine as the base for the reaction.
The reaction obeys all the rules and restrictions of E2 mechanism (e.g. antiperiplanar orientation of hydrogen and leaving group).
Substitution Reactions of Alcohols with Hydrogen Halides
Hydroxyl group of the alcohol can be replaced (substituted) with a halogen.
Reaction mechanism depends heavily on the type of the alcohol that was taken for the reaction along with the nature of the hydrogen halide. For instance the reactions with HBr or HI go relatively smoothly on their own, while a reaction with HCl often requires a use of a lewis acid catalyst.
Alcohol “Activation” via Sulfonyl Esters
Hydroxyl of an alcohol is a poor leaving group because it is a very strong nucleophile and it is unlikely that it will be replaced on its own. To enhance alcohol’s ability to go into SN2 and E2 reactions (which can be easily controlled), the hydroxyl group can be modified into a sulfonyl ester, which, upon dissociation, produces a good leaving group and a poor nucleophile.
Conversion of Alcohols to Alkyl Chlorides Using SOCl2, PCl3, or PCl5
Reaction of alcohols with hydrogen halides is not always desirable due to possible rearrangements and harsh(er) conditions. Alcohols can be selectively converted into corresponding alkyl halides using SOCl2, PCl3, or PCl5. This reaction generally follows the SN2 mechanisms.
Conversion of Alcohols to Alkyl Bromides Using PBr3, PBr5, or PPh2Br3
Similarly to conversion to alkyl chlorides, there are several common reactions of alcohols that convert those to alkyl bromides via SN2 mechanism.
Oxidative Cleavage of Vicinal Diols with HIO4
This reaction is specific to vicinal (1,2-) diols. It works best when the hydroxyl groups can be in the gauche or complete eclipsed conformation.
This reaction of alcohols can be used as an alternative to a reductive ozonolysis of alkenes.
Oxidation Reactions of Alcohols
Oxidation reactions of alcohols is a huge topic and includes many different reactions based on the type of alcohol being oxidized and the desired products. Here are some examples: