Palladium‐Catalyzed Synthesis of Symmetrical and Unsymmetrical Ureas Using Chromium Hexacarbonyl as a Convenient and Safe Alternative Carbonyl Source

Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as soaps, toothpaste and shampoo. In September 2016, the U.S. FDA banned nineteen antimicrobial ingredients, including TCC, in over-the-counter consumer antiseptic wash products, due to their toxicity. Withdrawal of TCC has prompted efforts to search for new antimicrobial compounds. In this paper, we present the synthesis and biological evaluation, as antibiotic and non-cytotoxic agents, of a series of diarylureas, analogues of TCC. These compounds are characterized by an intriguingly simple chemistry and can be easily synthesized. Among the synthesized compounds, 1ab and 1bc emerge as the most interesting compounds as they show the same activity of TCC (MIC = 16 µg/mL) against Staphylococcus aureus, and a higher activity than TCC against Enterococcus faecalis (MIC = 32 µg/mL versus MIC = 64 µg/mL). Moreover, 1ab and 1bc show no cytotoxicity towards the human mammary epithelial cells MCF-10A and embryonic kidney epithelial cells Hek-293, in opposition to TCC, which exhibits a marked cytotoxicity on the same cell lines and shows a good antitumor activity on a panel of cell lines tested.

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“…1-(2-Methylphenyl)-3-(4-methylphenyl)urea ( 1ag ) [ 35 ]. Prepared from p -toluidine and o -methylphenyl isocyanate.…”

Section: Methodsmentioning

confidence: 99%

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

et al. 2021

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“…The aforementioned importance of urea leads to substantial experimental research which has been done on the synthesis of symmetrical and unsymmetrical urea. A literature survey revealed that there are numerous advanced methods have been developed for the synthesis of urea molecules including triazene‐linked amine, [13] modified Curtius rearrangement with acid halide, [14] palladium with chromium carbonyl, [15] Staudinger‐aza‐Wittig reaction, [16] and tandem urea synthesis by using DPPA [17] (Scheme 1). In addition to these, there were several approaches had been developed with CDI by using methyl sulphonic acid, [18] triethyl amine, [19] and polymer‐linked amines [20] .…”

Section: Introductionmentioning

confidence: 99%

Zinc Promoted Urea Synthesis Using Carbonyldiimidazole as Carbonyl Source and Its Application for the Synthesis of Cariprazine

et al. 2023

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“…The first route includes reactions in which the carbonyl group is introduced from the outside. These are palladium‐catalyzed cross‐coupling of aryl chlorides and triflates with sodium cyanate, [48] catalytic reduction of nitro compounds at the presence of CO, [49] catalytic carbonylation of amines by carbon monoxide, [50–52] carbon dioxide, [53,54] and metal carbonyls [55] . As alternative to amines, the azides carbonylation protocol was developed by Zhang and co‐workers [56,57] .…”

Section: Introductionmentioning

confidence: 99%

“…These are palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate, [48] catalytic reduction of nitro compounds at the presence of CO, [49] catalytic carbonylation of amines by carbon monoxide, [50][51][52] carbon dioxide, [53,54] and metal carbonyls. [55] As alternative to amines, the azides carbonylation protocol was developed by Zhang and co-workers. [56,57] Latter this method has been recon-ceptualized in terms of the multicomponent chemistry.…”

Section: Introductionmentioning

confidence: 99%

“Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents

et al. 2022

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A protocol for the synthesis of unsymmetrical ureas substituted by pyridyl/quinolinyl moiety has been developed. This method concluded in metal‐ and base‐free reamination of N,N‐dimethyl‐N‘‐hetaryl ureas with a wide range of aryl and alkyl amines. The isolated yields vary from 40 to 96% depending on the nucleophilicity of the amines. The scope of this method includes more than 50 examples. The reaction is not hindered by either donor or acceptor groups as well as diverse functionalities. The synthesis can be easily scaled to gram quantities. Theoretical calculations supported by experimental data allowed us to propose a plausible mechanism for the process. This reaction takes place through the intermediate formation of hetaryl isocyanate.

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Palladium‐Catalyzed Synthesis of Symmetrical and Unsymmetrical Ureas Using Chromium Hexacarbonyl as a Convenient and Safe Alternative Carbonyl Source

Abstract: Pd-catalyzed synthesis of urea derivatives from aryl iodides and different aliphatic and aromatic amines using sodium azide and chromium hexacarbonyl is described. In this process, carbonylation of aryl iodides, Curtius rearrangement of [a]

Cited by 8 publications

References 53 publications

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

Zinc Promoted Urea Synthesis Using Carbonyldiimidazole as Carbonyl Source and Its Application for the Synthesis of Cariprazine

“Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents

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