Swern

Swern oxidation is a method for oxidizing primary and secondary alcohols to aldehydes and ketones, respectively. It uses dimethyl sulfoxide (DMSO) activated by oxalyl chloride, with a base such as triethylamine, typically at very low temperatures. The procedure, named after Daniel Swern, was developed in the 1970s and has become a standard tool in organic synthesis for mild oxidation.

Mechanism and reagents: Oxalyl chloride reacts with DMSO to form the chlorodimethylsulfonium species, the active Swern reagent. The alcohol attacks to form an alkoxysulfonium intermediate, which is deprotonated by the amine to furnish the aldehyde or ketone, with dimethyl sulfide as a byproduct. Gas byproducts from oxalyl chloride (carbon monoxide and carbon dioxide) are evolved. Reactions are usually performed in dichloromethane at −60 to −78 °C.

Scope and procedure: Primary alcohols are oxidized to aldehydes, secondary alcohols to ketones; tertiary alcohols are generally unreactive. The method tolerates a variety of functional groups, including alkenes and acetals, but it is moisture- and air-sensitive and requires low temperature. Workup involves aqueous quenching and extraction, followed by purification by standard chromatographic methods.

Advantages and limitations: The Swern oxidation is chemoselective and avoids heavy-metal oxidants, often giving high yields under mild conditions. Disadvantages include the need for low temperature, the use of oxalyl chloride and DMSO, and the generation of malodorous dimethyl sulfide and gaseous byproducts, which complicate handling and waste disposal.

See also: Dess–Martin periodinane oxidation as an alternative mild oxidation method.