Mechanochemical Ritter Reaction: A Rapid Approach to Functionalized Amides at Room Temperature

Abstract

A fast and efficient mechanochemical Ritter reaction between alcohols and nitriles under mild conditions is demonstrated. The reaction proceeds rapidly at room temperature in a solvent-free or low-solvent environment, utilizing a Brønsted acid catalyst. Its general application has been verified through a substrate screening investigation comprising a wide range of functionalized nitriles, as well as secondary and tertiary alcohols.

Mechanochemical Strecker Reaction: Access to α‐Aminonitriles and Tetrahydroisoquinolines under Ball‐Milling Conditions

“…Hence, the intrinsic properties of added auxiliaries should also be taken into account during the early planning stage of a mechanosynthesis. The successful synthesis of α‐aminonitriles in the ball mill now opens the possibility to explore the mechanochemical formation of α‐amino acids upon enzymatic or chemical hydrolysis of the nitrile group, and research along these lines is currently ongoing in our group.…”

Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1‐c][1,2,4]‐triazines and Pyrazolo[5,1‐c][1,2,4]triazines as Potential Antidiabetic Agents

“…In addition to the electrophilic carbon, the cyano group possesses a nucleophilic center, namely the nitrogen atom, and all nitriles are known to undergo the Ritter reaction with carbocations, thus giving N ‐substituted amides . Indeed, the reaction of cyanopyrazolotriazines 11a , b with tert ‐butanol in trifluoroacetic acid results in the formation of 3‐ tert ‐butylaminocarbonylpyrazolo[5,1‐ c ][1,2,4]triazines 16a , b .…”

Mechanochemistry for Organic Chemists: An Update

“…These strategies, although efficient and high‐yielding, usually rely on sacrificial coupling reactants, such as carbodiimides or 2,4,6‐trichloro‐1,3,5‐triazine, along with base activators such as carbonates or pyridines. Dokli and Gredičak described atom‐economic mechanochemical Ritter reactions between nitriles and alcohols, leading to functionalized amides in excellent yields, in the absence of stoichiometric bases or activators (Figure a).…”

“…(a) Mechanochemical Ritter reaction to make amide bonds, reported by Dokli and Gredičak . (b) Mechanoenzymatic formation of amide bonds with the aid of papain, reported by Hernández et al…”