My commentary on the mechanism of a Swern oxidation, a widely used transformation in organic chemistry. I also outline my favourite sneaky use of the mechanism when oxidising 1,5diols to 1,5dicarbonyls.

#chemistry #orgo #ochem #mechanism #synthesis

The Swern oxidation is a mild oxidation reaction commonly used in organic chemistry and general organic synthesis. The Swern oxidation will convert a primary alcohol into an aldehyde, and a secondary alcohol into a ketone. The conditions are mild and broadly tolerant of other functional groups, whereas many other classic oxidation methods are not.

Firstly, oxalyl chloride ((COCl)2) is mixed with DMSO (dimethylsulfoxide, Me2SO) to form a reactive sulfonium intermediate. This occurs with the loss of both carbon dioxide and carbon monoxide gases, which is a massive increase in entropy associated with that mechanistic step. Then, the hydroxyl group of an alcohol can attach the electrophilic sulfur species using its oxygen lone pairs, to transfer the higher oxidation state sulfur atom to the substrate that is to be oxidised.

Next, the activated alcohol is treated with triethylamine (Et3N, TEA), being a weak amine base, and the alpha proton to the positively charged sulfur atom is abstracted. This mechanism generates a sulfur ylid (sulfur ylide). An ylid (ylide) inherently is quite basic or nucleophilic at its carbon atom due to weak pi bonding between atoms in the second and third rows of the Periodic Table (Period 2 and Period 3 in the pblock). Ylids (ylides) are, perhaps, more commonly encountered in reactions such as the Wittig reaction when learning about organic chemistry, but they have more uses for sneaky transformations and curly arrow mechanisms.

The sulfur ylid (ylide) can participate in a pericyclic reaction (group transfer reaction) where a nearby hydrogen atom can be transferred to the location adjacent to the sulfur. The curly arrow mechanism shows that, as a consequence, a new carbonoxygen double bond (an aldehyde or ketone functional group) is formed and dimethylsufide (Me2S, DMS) is released. So overall the DMSO is reduced and the alcohol is oxidised so this is a redox reaction by the usual definitions. This mechanism can also be viewed as an intramolecular elimination reaction.

My favourite trick with the Swern oxidation is when I want to oxidise a 1,5diol to a 1,5dicarbonyl. Because the first step of the curly arrow mechanism of the Swern oxidation involves waiting to preactivate the hydroxyl groups, it is possible to prevent e.g. lactone formation by intramolecular cyclisation then oxidation if one hydroxyl group is more prone to oxidation than the other.