Mechanochemical Synthesis of N-Aryl Amides from O-Protected Hydroxamic Acids

Lloyd, Gareth O., Broumidis, Emmanouil, Jones, Mary C. and Vilela, Filipe (2020) Mechanochemical Synthesis of N-Aryl Amides from O-Protected Hydroxamic Acids. ChemPlusChem, 85 (8). pp. 1754-1761. ISSN 2192-6506

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Mechanochemically Mediated Synthesis of N‐Aryl Amides from O‐protected Hydroxamic Acids
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Two robust and efficient mechanochemical protocols for the synthesis of an array of N-arylamides have been developed. This was achieved by a C-N cross-coupling between O-pivaloyl hydroxamic acids and aryl iodides or aryl boronic acids, in the presence of a stoichiometric amount of a copper mediator. The effectiveness of this method is highlighted by the high-yielding (up to 94%), scalable (up to 8 mmol), and rapid (20 minutes) synthesis of N-aryl amides (15 examples), using a variety of deactivated and sterically encumbered substrates, whilst employing mild conditions and in the absence of solvents. In addition, it was determined that whilst the O-pivaloyl hydroxamic acid precursors can be synthesised mechanochemically, iron contamination originating from the steel jars was found to occur which can hinder the efficacy of this process. Furthermore, 3D printing was used to produce custom milling jars that could successfully accommodate a scaled-up version of the two protocols.

Keywords:Amidation, Cross-coupling, Mechanochemistry, Solvent-free synthesis, Sustainable chemistry, Green chemistry
Subjects:F Physical Sciences > F160 Organic Chemistry
F Physical Sciences > F190 Chemistry not elsewhere classified
F Physical Sciences > F100 Chemistry
Divisions:College of Science > School of Chemistry
ID Code:42046
Deposited On:12 Aug 2020 10:10

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