Microwave-Assisted Synthesis of N-Monosubstituted Urea Derivatives

Abstract

An easy and rapid procedure for the preparation of Nmonosubstituted ureas via reaction between potassium cyanate and a wide range of amines is described. The procedure was performed under microwave irradiation using water as solvent. This methodology is particularly attractive since it provides ureas in high yield and purity.

Straightforward preparation of labeled potassium cyanate by ozonation and application to the synthesis of [13C] or [14C]ureidocarboxylic acids

“…They are also useful precursors of hydantoins and amino acids . As they can be readily prepared from α‐amino acids and potassium cyanate by conventional heating or microwave irradiation, we chose this reaction to test our [ 13 C] or [ 14 C]cyanate as labeling reagent (Scheme ).…”

One-Pot Assembly towards ω-Substituted Arylbiurets from ­Aromatic Amines, Potassium Cyanate, and Glacial Acetic Acid

“…If KOCN reacts with amines, N-monosubstituded ureas could be generated. 10 In addition, according to Davis and Blanchard, 11 HOCN dimerizes in solution to form dicyanic acid, with one molecule of HOCN functioning in the usual manner in urea formation and the second as an ammonia derivative. Inspired by these two observations, we hypothesized that the use of dicyanic acid to react with amine may lead to ω-substituted biuret.…”

“…Based on the results of the validation experiments described above, as well as on previous reports, we propose a plausible mechanism for this one-pot reaction, as depicted in Scheme 4. 10,12 Initially, the reaction of AcOH with an excess of KOCN gives cyanic acid I. The negative charge on the nitrogen of KOCN attacks the carbon atom of the carbonyl group to give the adduct II.…”

“…Protonation of this salt produces the zwitterionic intermediate III, which can be isomerized to more stable dicyanic IV. 10,13 The nitrogen atom attacks the cyanic acid fragment to form a dipolar intermediate V. A simple proton-transfer enables the conversion of the zwitterionic intermediate V into the uncharged biuret product. This pathway is consistent with our previous results obtained using excessive AcOH.…”

Acyclic and Cyclic Ureas (Update 2013)

“…To increase the yield and accelerate the conversion, the use of microwave irradiation can be beneficial. [32] A palladium-catalyzed cross-coupling reaction that provides a facile and highly versatile access to isocyanates represents an important new method of urea synthesis, because the initially formed products can easily be converted into unsymmetrical ureas 9 by reaction with amines in a one-pot procedure (Scheme 5). [33] The first step of the reaction sequence involves cross coupling of aryl chlorides or trifluoromethanesulfonates and a cyanate salt in the presence of a palladium(0) complex.…”