A Reaction of N-substituted Succinimides with Hydroxylamine as a Novel Approach to the Synthesis of Hydroxamic Acids

Abstract

We describe a new reaction for the synthesis of compounds with a hydroxylamide group (hydroxamic acids) which are widely known for their biological activity (histone deacetylase inhibitors, matrix metalloproteinases inhibitors and others). The reaction involves the interaction between N-substituted succinimides and hydroxylamine in aqueous solution. A novel two step approach to the synthesis of hydroxamic acids was developed based on the new reaction. The first stage is the synthesis of N-substituted succinimide via the reaction of aromatic amine or carboxylic acid hydrazide with succinic anhydride. The second step involves the imide ring opening reaction in the presence of hydroxylamine. For the both stages, universal synthetic methods have been developed that exclude additional purification stages for the target compounds. Sixteen hydroxamic acids were synthesized using the developed approach. Most of the compounds were obtained for the first time.

Design, Synthesis, and Biological Evaluation of Novel Hydroxamic Acid-Based Organoselenium Hybrids

“…Hydroxamic acid moiety has gained significant attention from research groups worldwide. Therefore, many hydroxamic derivatives have been synthesized and examined for their biological activities and chemistry applications [ 4 , 5 , 6 ].…”

A Reaction of N-Substituted Succinimides with Hydroxylamine as a Novel Approach to the Synthesis of Hydroxamic Acids

“…One more reaction that we believe can expand the possibilities for the synthesis of a broad number of new compounds with hydroxamic acid group is the five-membered imide cycle opening by ammonia derivatives [12][13][14]. Recently [15], based on the reaction of N-substituted succinimides with hydroxylamine, we developed a novel approach that features simple and mild conditions. Here, we report a detailed description of the developed approach, which consists of two steps: (i) the synthesis of N-substituted succinimides by the reaction of succinic anhydride with amines in chloroform in the presence of polyphosphate ester and (ii) the treatment of N-substituted succinimides by hydroxylamine aquatic solution.…”