One‐Pot Synthesis of Amide, Dipeptide, Ester and Hydroxamate Using Oxyma and Thionyl Chloride (SOCl2)

An improved, one‐pot two‐step process is described to convert carboxylic acid to amides, dipeptides, esters, and hydroxamates using Oxyma and thionyl chloride. The addition of Oxyma to thionyl chloride in the presence of Hunig's base results in a mixture of probably Oxyma‐sulfinyl chloride and sulfinyl diOxyma, two new intermediates, which successfully converts the carboxylic acid into its Oxyma ester. Adding a nucleophile to the generated Oxyma ester leads to corresponding amide, ester, or hydroxamic acid formation at room temperature. The procedure is mild and well tolerant to various carboxylic acids, including N‐protected amino acids and different nucleophiles such as methyl esters of amino acids and alcohols. 32 examples with moderate to good yield (67–86 %) are reported. A rigorous mechanism investigation is performed using 1H and 13C‐NMR. By‐product Oxyma can be recovered and recycled. Thionyl chloride has been used for such coupling reactions in industries and academia for a few hundred years to date. Nevertheless, minimum racemization, side reaction, and waste generation make the addition of Oxyma (this methodology) a valuable improvement. A convenient methodology for synthesizing amide, hydroxamate, and ester using Oxyma and thionyl chloride is described here. A total of 32 examples, 19 amides, six hydroxamates, and seven esters, are reported with a 67 to 86 % yield. Recyclability and racemization suppression are the crucial features of this protocol. A detailed NMR‐based mechanistic study indicates the possibility of forming two novel intermediates, Oxyma sulfinyl chloride and sulfinyl diOxyma, during the process.