A Green Suzuki-Miyaura Cross-coupling Reaction of N-(4-Bromophenyl) Ureas with Phenylboronic Acid using Palladium Nanoparticles as a Catalyst.

Abstract

INTRODUCTION: The N-biphenyl urea framework is of particular importance due to its relevant pharmacological activities, such as antitumour, antithrombotic, and herbicidal activities. Here, we present our results on the preparation of N-biphenyl ureas using a green Suzuki-Miyaura cross-coupling reaction of N-(4-bromophenyl) ureas with phenylboronic acid. METHODS: Several N-(4-bromophenyl) ureas with different substitution patterns were prepared in excellent yields by the reaction of 4-bromophenylisocyanate with primary and secondary amines in hexane at room temperature. Their Suzuki-Miyaura cross-coupling reaction with phenylboronic acid was accomplished at room temperature in aqueous ethanol using a catalytic system composed of Na2PdCl4 (2 mol%) as a source of palladium and 2-hydroxypropyl-β-cyclodextrin as a reductant/ stabiliser of palladium nanoparticles. RESULTS: The Suzuki-Miyaura cross-coupling reaction of N-(4-bromophenyl) and N-(4- bromobenzyl) ureas with phenylboronic acid, catalysed by palladium nanoparticles, gave the corresponding N-biphenyl ureas in up to 93% yield. DISCUSSION: We have developed a convenient synthesis of N-4-biphenyl ureas from the corresponding N-(4-bromophenyl) or N-(4-bromobenzyl) ureas and phenylboronic acid using palladium nanoparticles as a catalyst. The methodology also proved suitable for the Suzuki-Miyaura crosscoupling reaction using N-(4-bromobenzyl)-N'-butylurea as the substrate. The reaction conditions are mild and consistent with the principles of green chemistry. CONCLUSION: N-biaryl ureas are potentially pharmacologically active, and our approach opens the possibility for the preparation and study of new substances.

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