Mechanosynthesis of amides in the total absence of organic solvent from reaction to product recovery

Abstract

The synthesis of various amides has been realised avoiding the use of any organic solvent from activation of carboxylic acids with CDI to isolation of the amides. Mechanochemistry was the key point of the process allowing rapid formation of the amide bond and efficient water-based purification of the final products.

Comprehensive Study of the Organic‐Solvent‐Free CDI‐Mediated Acylation of Various Nucleophiles by Mechanochemistry

“…To give a global view of the substrate scope and limitations of this approach, preliminary results from a study that we published previously have been included in the following discussion 12. Application of this approach to other carboxylic acids and amines was realised on the 1.35 mmol scale in a 12 mL stainless‐steel jar containing fifty 5 mm diameter balls under planetary ball‐milling agitation.…”

“…[11] For our part, we have previously described the mechanosynthesis of amides from carboxylic acids and amine hydrochlorides by treatment with N,N'-carbonyldiimidazole (CDI) without using organic solvent from reaction to product recovery. [12] Pursuing our efforts to provide the organic chemistry community with as et of solutionse nabling to avoid the use of problematic solvents, [13] we herein describe ac omprehensive study of the organic-solvent-free CDI-mediated acylationo fN -, O-, S-and Cnucleophiles by mechanochemistry,i ncluding analysis, discussion and solutions to limitations relatedt o1 )the physical state and water solubility of the products and 2) contamination from wear.…”

Sterically Shielded Stable Carbenes and Biscarbenes of the 1,2,4‐Triazole Series: A New Method for the Preparation of 1,3,4‐Triaryl‐1,2,4‐triazol‐5‐ylidenes

“…The acylation reaction of phenylhydrazine can also be carried out without the use of acid halides; in particular under the action to phenylhydrazine of benzoic anhydride or benzoic acid in the presence of carbodiimides or other condensing agents (see, for example,). In the present paper a preparatory one‐reactor method was used for obtaining 2‐benzoyl‐1‐formylhydrazine from phenylhydrazine and benzoyl chloride in dimethoxyethane at 0–5 °C followed by further refluxing in formic acid.…”

CHAPTER 6. Amino Acids and Peptides in Ball Milling

“…38 In a first step, carboxylic acids were efficiently transformed into acylimidazoles by treatment with CDI as activating agent. Subsequent addition of amine in a ball-mill reactor furnished, through a highly stereoselective process, the amino acid derivatives 40 and 41 when using enantiopure HCl Á NH 2 -Phe-O t Bu or Boc-NH-Phe-OH, respectively (Scheme 6.11).…”

“…Organic solventfree recovery and purification have been a scarcely studied theme in fine organic chemistry, but promising methods have been published recently. 38,40,[48][49][50][51] Mechanochemical peptide syntheses would gain even more interest in the organic chemist's community if solutions addressing this challenge would emerge.…”