We are reporting for the first time, rapid N-chloroacetylation of anilines and amines in phosphate buffer within 20 min. Primary and secondary amino derivatives (amines, anilines) were efficiently condensed with various acid chlorides (containing aliphatic, aromatic, cyclic and heteroaromatic units). We have also shown that the modification of the electrophilic nature of the substituents on the acid chloride did not affect the product formation and the required amides are formed in high yields. The major advantage of this process is highlighted by the ease of product isolation (simple filtration/precipitation). This process represents the first example of a metal-free, green chemical synthesis under neutral conditions to provide an eco-friendly, easily scalable and robust process for the preparation of amides that expands the scope, utility and applicability of acid chlorides.

We are reporting for the first time, efficient, highly chemoselective N-chloroacetylation of amino compounds (amino alcohols, amino acids) by chloroacetyl chloride, without compromising its high reactivity, to give chloroacetamides in phosphate buffer within 20 min. We have systematically studied the effects of buffers, metal salts and HCl scavengers to optimize the reaction conditions. We have carried out intermolecular competitive reactions and shown that anilines and aliphatic amines can be selectively N-chloroacylated in the presence of alcohols and phenols. The acylated products are obtained in high yields and can be easily isolated without chromatographic separation. This reaction represents the first example of a metal-free biocompatible synthesis under neutral conditions. This method is eco-friendly, easily scalable and robust. We have further studied the intramolecular competitive reactions of aminoalcohols and prepared various N-chloroacetamides in very good yields. Finally, this protocol was conveniently extended to ceramides synthesis as well.