Solvent-Free Synthesis of α-Amino Nitrile-Derived Ureas

Abstract

An efficient and environmentally friendly methodology for the solvent-free synthesis of -amino nitrile-derived ureas from -amino acid-based amino nitriles has been developed. At room temperature no epimerization was observed in the resulting ureas, but under MW heating, epimerization occurred at the chiral center bearing the cyano group.

A decade update on solvent and catalyst-free neat organic reactions: a step forward towards sustainability

“…Initially, 2-aminopyridine ( 172) and benzaldehyde (182) reacted to form the imine derivative 189, then, as a C-nucleophile, isocyanide (181) attacked the C-atom of the imine 189 and produced a nitrilium ion intermediate (190) followed by the final product being formed by the intramolecular cyclisation of intermediate 191.…”

“…Herranz and coworkers, in 2013, designed a method for the synthesis of α-amino nitrile-derived ureas (374). 190 In a screening reaction, α-amino nitrile (S)-371 was treated with 2 equiv. of phenyl isocyanate (373) under neat conditions using MW irradiation (Scheme 103).…”

Chameleonic reactivity of α-amino nitrile-derived ureas. Synthesis of highly functionalized imidazolidin-2-one and imidazolidine-2,4-dione derivatives

“…[11][12][13] In view of these precedents and in the context of a medicinal chemistry project focused on the search of antagonists of the thrombin receptor PAR1, 14,15 by exploring the use of -amino acid-derived amino nitriles as molecular diversity generators, 16 we have recently described a versatile solvent-free synthesis of basic amino acid-derived N-(cyanomethyl)ureas of general formula A. 17 Now, taking into account that hydantoins (imidazolidine-2,4-diones) are included among privileged scaffolds in medicinal chemistry, 18,19 natural products [20][21][22][23][24][25][26] and organic synthesis, 19,27 we have studied and report herein the cyclization of cyanomethylureas A to imidazolidin-2-one derivatives B (Scheme 1).…”

Efficient Synthesis of 1,5-Disubstituted Carbohydrazones Using K2CO3 As a Carbonyl Donor

“…CO 2 is often used in large excess under high pressure, thus complicating the process. Recently, alternative carbonyl group donors have been developed, such as organic carbonates, isocyanate, formamides, and carbonylimidazolium salts . Nevertheless, some of these reagents originate from phosgene or require costly multistep syntheses.…”