Oxallyl chloride

Another superior reagent for the preparation of acid chlorides is oxallyl chloride in methylene chloride. Addition of a carboxylic acid leads to the smooth evolution of gas (CO2, CO, HC1) which can be used as a crude monitor of the reaction progress. The acid chloride is very easily purified since oxallyl chloride boils at 62°C and is easily evaporated from the product. In many instances, the crude product is sufficiently pure to be used directly. 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

Scheme 5. Preparation of asymmetric TB derivatives. Reaction conditions (i) EtOH, reflux (ii) DCC, DMF (iii) benzene, oxallyl chloride (iv) DMF, pyridine, rt (v) BH3-THF, reflux (vi) Pt02 or Pd, H2, MeOH (vii) LiAlH4, THF or Et20, reflux (viii) HCHO, HC1...

In this book, there have been many references to oxidation and reduction reactions. While these reactions are not within the scope of the discussions of this book, their mechanisms do involve the processes presented herein. In the case of the Swem oxidation, the first step is an addition-elimination reaction between dimethyl sulfoxide and oxallyl chloride. This process, illustrated below using arrow pushing, involves addition of the sulfoxide oxygen to a carbonyl with subsequent elimination of a chloride anion. 

Stable alkyl amino carbenes are still unknown. In contrast to the difficulties met in the synthesis of the precursor for the deprotonation method, the corresponding chloro iminium salt was readily available by chlorination of terf-butyl diisopropylamide with oxallyl chloride. 

The second stage of the Swem oxidation, illustrated below, involves a nucleophilic displacement of the oxallyl group from the sulfur. In this step, the nucleophile is a chloride anion, and the reaction is facilitated by the decomposition of the leaving group into carbon dioxide gas, carbon monoxide gas, and a chloride anion. 

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