Synthesis of Amides from Alcohols and Amines Through a Domino Oxidative Amidation and Telescoped Transamidation Process

Abstract

The amide bond formation is of paramount importance in organic synthesis, both within academic research and industrial development and manufacturing of pharmaceutical chemicals and other biologically active compounds. Despite this fact, as well as the ever‐increasing treatment costs of side streams and other environmental concerns regarding handling and transportation of hazardous reagents, contemporary synthesis has elicited few new reactions and methods for the preparation of amides. Herein, we reveal a high yielding and expedite two‐step telescoped synthetic process that comprises a domino oxidative amidation and transamidation for the creation of amides. The process utilizes alcohols and amines as reaction pairs with TEMPO and Fe ions as catalytic system and 1,3‐dichloro‐5,5‐dimethyl hydantoin as a terminal oxidant. The oxidative amidation and transamidation process is conducted under benign reaction conditions and short reaction time (≈ 30 min.) in a two‐step telescoped fashion by means of a multi‐jet oscillating disk (MJOD) continuous‐flow reactor platform. The disclosed process integrates alcohol oxidation and amide formation to afford target amide in yields up to 90 %. The method operates with both primary and secondary amines together, but was hampered when bulky amines and/or alcohols were used as reagent/substrate.

Amino‐TEMPO Grafted on Magnetic Multi‐Walled Nanotubes: An Efficient and Recyclable Heterogeneous Oxidation Catalyst

“…At the outset of the investigation of the pre‐catalyst 6 , we believed that a Montanari‐type oxidation following a mechanism as outlined in Scheme could be conducted with 1,3‐dichloro‐5,5‐dimethylhydantoin (DCH) as the terminal oxidant. This because we recently developed an efficient and high yielding method based on TEMPO with DCH that was successfully adapted and used in telescoped processes for the preparation of amides from amines and alcohols and nitriles from alcohols . Based on the disclosed processes, we embarked on to exploit similar reaction conditions for novel applications using the MWCNT–{(CH 2 ) 3 –CO–NH–TEMPO} n 6 as the pre‐catalyst.…”

Transition‐metal‐catalyzed dehydrogenative coupling of alcohols and amines: A novel and atom‐economical access to amides

“…[56] Recently, Bjørsvik established an interesting domino oxidative amidation and transamidation process for the fabrication of tertiary amides 50 that is based on initial Fe/TEMPO-catalyzed amidation of alcohols 48 with 1,3-dichloro-5,5-dimethylhydantoin (DCH) and subsequent reaction of the generated 5,5-dimethyl-3-alkanoyl/ aroyl-imidazolidine-2,4-diones A with N,N-diethylamine 49 (Scheme 22). [57] Both benzyl and alkyl alcohols were tolerated under the catalytic conditions. The catalyst was, however, not effective for heterobenzylic alcohols as well as bicyclic benzylic alcohols.…”

Fe3O4@SiO2@SBA-3@CPTMS@Arg-Cu: preparation, characterization, and catalytic performance in the conversion of nitriles to amides and the synthesis of 5-substituted 1H-tetrazoles

“…In contrast, amides are an important key intermediate in many organic transformations that are widely applied in medicine, 36,37 biochemistry, 38 and materials science. 39 Various approaches have been used to synthesize amides, such as condensation of carboxylic acid and esters with amines, 40 reaction between alcohols/aldehydes with amines, 41 and hydroamination of unsaturated hydrocarbons. 42 Besides these methods, a practical method to form amides is the hydration of nitriles.…”