Summary
Highlights
Alcohols, particularly ethanol, are known from alcoholic beverages, but methanol can be toxic, causing blindness or death. Alcohols like ethanol, propanol, and isopropanol are also used in hand sanitizers to denature proteins in viruses and bacteria. In organic chemistry, alcohols are crucial building blocks for creating other oxygen-containing compounds such as ethers and epoxides.
Alcohols can be synthesized through various reactions. Acid-catalyzed hydration of alkenes adds water across a double bond, following Markovnikov's rule, or anti-Markovnikov with specific reagents. Substitution reactions, like mixing haloalkanes with sodium hydroxide, can also produce alcohols. Additionally, diols (double alcohols) can be formed by reacting alkenes with oxidizing agents like osmium tetroxide, resulting in syn diols where hydroxyl groups are added to the same side of the double bond.
While hydroxide ions are excellent nucleophiles, neutral alcohols are not. However, alcohols are weakly acidic, and deprotonating them forms alkoxides, which are highly nucleophilic. Alkoxides can be used in SN2 reactions to create ethers, compounds with an oxygen connected to two alkyl or aromatic carbons. For example, diethyl ether can be synthesized by deprotonating ethanol with sodium hydride to form ethoxide, which then reacts with an alkyl halide.
Ethers are remarkably stable compounds and generally unreactive. One way to break them down is through a substitution reaction with a strong acid. The acid protonates the ether, making the oxygen a better leaving group, and a nucleophile (like a halide ion) then attacks a carbon, breaking the C-O bond and regenerating an alkyl halide and an alcohol. With excess strong acid, the alcohol can also be converted to an alkyl halide.
Converting alcohols to alkyl halides is a valuable synthetic tool. Hydroxyl groups are poor leaving groups, but they can be made better by converting them into halides using reagents like hydrogen halides, phosphorus tribromide, or thionyl chloride. These reactions often proceed via SN2 mechanisms, leading to inversion of stereochemistry. Alternatively, alcohols can be converted into tosylates or mesylates using tosyl chloride or mesyl chloride, which retain the stereochemistry at the carbon attached to the hydroxyl group, offering different options for subsequent reactions.
Epoxides are cyclic ethers forming a three-atom ring with two carbon atoms and an oxygen. They can be formed from halohydrins. Unlike stable ethers, epoxides are highly reactive due to ring strain, making them useful in organic synthesis and in applications like epoxy glues. Epoxides can be opened in two ways: acid-catalyzed, where protonation occurs first and a nucleophile attacks the more substituted carbon, or base-catalyzed, where a nucleophile attacks the least substituted carbon in an SN2 reaction. These two methods can lead to different regioselectivity in the products.
Alcohol oxidation is defined as the loss of carbon-hydrogen bonds or gain of carbon-oxygen bonds. Primary alcohols can be oxidized by strong oxidizing agents like chromic acid to aldehydes and then further to carboxylic acids. Secondary alcohols oxidize to ketones. Tertiary alcohols cannot be oxidized because they lack the necessary hydrogen atoms on the carbon attached to the hydroxyl group. Weaker oxidizing agents like pyridinium chlorochromate (PCC) can be used to stop the oxidation of primary alcohols at the aldehyde stage. Chromium-based oxidants provide a color change indicating oxidation, but safer alternatives like Dess-Martin Periodinane (DMP) exist due to chromium's toxicity.