Use of Carbodiimides In Condensation Reactions

1 Esterification of Acids using Carbodiimides. The formation of anhydrides from carboxylic acids, thiocarboxylic acids, sulfonic acids and phosphorous acids are discussed in Section 2.4.S.2. In this section only special cases of anhydride formation are described. Mixed anhydrides of amino acids and adenylic acid are produced from the corresponding acids using DCC as the condensation agent. ° Mixed anhydrides not containing amino acids, such as butyryl adenate, adenosine 5 -phosphosulfate and p-nitrophenyl-thymidine-5-phosphate are also obtained. 

Reaction of a mixture of carboxylic acid and an alcohol or thioalcohol with a carbodiimide at room temperature affords the corresponding ester 652 in high yield. The reaction is best conducted in methylenechloride as solvent, using DMAP (4-dimethylaminopyridine) as the catalyst.  

Even the sterically hindered 2,4,6-trimethylbenzoic acid is esterified with methanol under these conditions. Carboxylic acids containing a-halogen atoms are best esterified with DCC without a solvent or base.  

Long chain tu-hydroxy acids, such as 653, are converted to the corresponding macrolactones 654 in 95 % yield using DMAP hydrochloride.  

The 17 membered ring lactone is also obtained in 96 % yield, while shorter chains produce lower yields. Under similar conditions without DMAP hydrochloride, mixtures of the lactones and linear polymers are obtained.  

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