title: Comprehensive study of the organic-solvent-free CDI-mediated acylation of various nucleophiles by mechanochemistry.
abstract: Acylation reactions are ubiquitous in the synthesis of natural products and biologically active compounds. Unfortunately, these reactions often require the use of large quantities of volatile and/or toxic solvents, either for the reaction, purification or isolation of the products. Herein we describe and discuss the possibility of completely eliminating the use of organic solvents for the synthesis, purification and isolation of products resulting from the acylation of amines and other nucleophiles. Thus, utilisation of N,N'-carbonyldiimidazole (CDI) allows efficient coupling between carboxylic acids and various nucleophiles under solvent-free mechanical agitation, and water-assisted grinding enables both the purification and isolation of pure products. Critical parameters such as the physical state and water solubility of the products, milling material, type of agitation (vibratory or planetary) as well as contamination from wear are analysed and discussed. In addition, original organic-solvent-free conditions are proposed to overcome the limitations of this approach. The calculations of various green metrics are included, highlighting the particularly low environmental impact of this strategy.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France). txmetro@univ-montp2.fr.
authors.forename: Thomas-Xavier
authors.initials: TX
authors.lastname: Métro
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France).
authors.forename: Julien
authors.initials: J
authors.lastname: Bonnamour
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France).
authors.forename: Thomas
authors.initials: T
authors.lastname: Reidon
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France).
authors.forename: Anthony
authors.initials: A
authors.lastname: Duprez
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France).
authors.forename: Jordi
authors.initials: J
authors.lastname: Sarpoulet
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France).
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Université de Montpellier, Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France). frederic.lamaty@univ-montp2.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamaty
keywords: acylation; amides; green chemistry; mechanochemistry; solvent-free synthesis