Unsymmetrical Ureas Research Articles

A Fe3O4@SiO2/Schiff Base/Pd Complex as an Efficient Heterogeneous and Recyclable Nanocatalyst for One‐Pot Domino Synthesis of Carbamates and Unsymmetrical Ureas

A palladium‐catalyzed domino method for the direct synthesis of carbamates and ureas has been developed by using readily available and economical starting materials (aryl halide, carbon monoxide, sodium azide, amines and alcohols) in a one‐pot approach. The domino process underwent carbonylation, Curtius rearrangement, and nucleophilic addition. This protocol provides a step‐economical and highly efficient reaction to access the wide range of valuable carbamates, symmetrical and unsymmetrical ureas with high yields under remarkable mild reaction conditions that are important factors in pharmaceutical science, biochemistry and agricultural industries. Furthermore, the magnetically recoverable nanocatalyst (Fe3O4@SiO2/Pd(II)) can be conveniently and swiftly recycled using external magnet and reused at least for seven times without noticeable loss of its catalytic activity.

From Lossen Transposition to Solventless “Medicinal Mechanochemistry”

An environmentally friendly mechanochemical strategy for the preparation of unsymmetrical ureas and 3,5-disubstituted hydantoins by using safe starting materials in place of hazardous and toxic iso...

Pd/C‐Catalyzed Domino Synthesis of Urea Derivatives Using Chloroform as the Carbon Monoxide Source in Water

AbstractA Pd/C‐catalyzed domino synthesis of symmetrical and unsymmetrical ureas from aryl iodides, sodium azide, amines and CHCl3 in water has been developed. This reaction proceeds with sequential carbonylation, Curtius rearrangement and nucleophilic addition. CHCl3 serves as a convenient and safe alternation of CO gas in the presence of KOH. A series of urea derivatives were obtained in moderate to good yields with good functional group tolerance. Furthermore, the Pd/C catalyst could be readily recovered with slight decrease in the catalytic activity after six consecutive runs.magnified image

Sulfated‐Tungstate‐Catalyzed Synthesis of Ureas/Thioureas via Transamidation and Synthesis of Forchlorofenuron

AbstractN, N’‐Disubstituted ureas and thioureas have been efficiently and expeditiously synthesized by transamidation reaction between unsubstituted or monosubstituted ureas/thioureas and amines under solvent‐free condition using sulfated tungstate as a heterogeneous mild solid acid catalyst. This protocol offers several advantages such as wide substrate scope, providing both symmetrical and unsymmetrical ureas and thioureas, solvent‐free reaction, recyclability of the catalyst and a simple work‐up procedure. Application of the methodology is demonstrated through simple and one step synthesis of forchlorofenuron [1‐(2‐chloropyridine‐4‐yl)‐3‐phenylurea] (CPPU), an approved plant growth regulator.

A Palladium‐Catalyzed Domino Procedure for the Synthesis of Unsymmetrical Ureas

AbstractA palladium‐catalyzed carbonylative procedure for the synthesis of unsymmetrical ureas has been developed. This one‐pot one‐step cascade procedure is consisted by three individual processes: carbonylation, Curtius rearrangement, and nucleophilic addition. A series of unsymmetrical ureas were prepared from easily available aryl iodides and amines in moderate to excellent yields. This procedure provides a convenient and practical approach for unsymmetrical urea synthesis.magnified image

Pd/C-catalyzed reductive carbonylation of nitroaromatics for the synthesis of unsymmetrical ureas: one-step synthesis of neburon

A Pd/C catalyzed reductive carbonylation of nitroarenes for the synthesis of unsymmetrical ureas has been developed.

Metal-Free Synthesis of Unsymmetrical Ureas and Carbamates from CO2 and Amines via Isocyanate Intermediates

A mild and metal-free synthesis of aryl isocyanates from arylamines under an atmosphere of CO2 was developed. The carbamic acid intermediate, derived from the arylamine starting material and CO2 in the presence of DBU, is dehydrated by activated sulfonium reagents to generate the corresponding isocyanate. The latter can be detected by in situ IR and trapped by various amines and alcohols to make unsymmetrical ureas and carbamates, respectively. Dicarbamates can also be prepared in good yields via the mild dehydration of the corresponding dicarbamic acids.

"In-loop" [11 C]CO2 fixation: Prototype and proof of concept.

Carbon-11-labeled carbon dioxide is the most common feedstock for the synthesis of positron emission tomography radiotracers and can be directly used for 11 C-carbonylation. Herein, we report the development of an apparatus that takes advantage of "in-loop" technologies to facilitate robust and reproducible syntheses of 11 C-carbonyl-based radiotracers by [11 C]CO2 -fixation. Our "in-loop" [11 C]CO2 -fixation method is simple, efficient, and proceeds smoothly at ambient pressure and temperature. We selected model 11 C-carbonyl-labeled carbamates as well as symmetrical and unsymmetrical ureas based on their widespread use in radiotracer design and our clinical research interests for proof of concept. Utility of this method is demonstrated by the synthesis of a reversible radiopharmaceutical for monoamine oxidase B, [11 C]SL25.1188, and 2 novel fatty acid amide hydrolase inhibitors. These radiotracers were isolated and formulated (>3.5GBq; 100mCi) with radiochemical purities (>99%) and molar radioactivity (≥80GBq/μmol; ≥2162mCi/μmol).

Highly Efficient Curtius Rearrangement Approach for the Synthesis of Unsymmetrical Sulfonimidoyl Ureas

AbstractA highly efficient synthesis of unsymmetrical sulfoximine ureas is developed. The reaction unites simple NH‐sulfoximines and acyl azides by a formal Curtius rearrangement as the key step. This reaction could be easily scaled up to gram scale and omits the generation of hazardous byproducts, thus allowing a practical and environmentally benign path for the synthesis of medicinally important sulfonimidoyl unsymmetrical ureas.

β-oxalylamino-substituted O-ethyl N-arylcarbamates and N-ethyl-N′-arylureas encapsulated into micelles of vinylimidazole–vinylcaprolactam copolymer

Low-molecular-weight compounds—β-oxalylamino-substituted O-ethyl carbamates and unsymmetrical ureas showing biological activity—have been synthesized and encapsulated into micelles of vinylimidazole–vinylcaprolactam copolymers. Solubilization in micelles has provided a preparation of water-soluble colloidal formulation of these compounds suitable for practical application.

Scalable, One-Pot, Microwave-Accelerated Tandem Synthesis of Unsymmetrical Urea Derivatives.

We report a facile, microwave-accelerated, one-pot tandem synthesis of unsymmetrical ureas via a Curtius rearrangement. In this method, one-pot microwave irradiation of commercially available (hetero)aromatic acids and amines in the presence of diphenylphosphoryl azide enabled extremely rapid (1-5 min) construction of an array of unsymmetrical ureas in good to excellent yields. We demonstrate the utility of our method in the efficient, gram-scale synthesis of key biologically active compounds targeting the cannabinoid 1 and α7 nicotinic acetylcholine receptors.

Correction to Mechanochemical Preparation of 3,5-Disubstituted Hydantoins from Dipeptides and Unsymmetrical Ureas of Amino Acid Derivatives.

Correction to Mechanochemical Preparation of 3,5-Disubstituted Hydantoins from Dipeptides and Unsymmetrical Ureas of Amino Acid Derivatives.

Mechanochemical Preparation of 3,5-Disubstituted Hydantoins from Dipeptides and Unsymmetrical Ureas of Amino Acid Derivatives.

5-Substituted-3-(alkoxycarbonyl)alkyl-hydantoin derivatives were prepared by mechanochemistry from amino esters or dipeptides, via a 1,1'-carbonyldiimidazole-mediated one-pot/two-step cyclization reaction involving amino acid unsymmetrical urea A and carboxy-imidazolyl-dipeptide ester B intermediates. Comparative experiments in solution were also performed. The successful preparation of an antibacterial agent precursor was also investigated.

ChemInform Abstract: Pd/C Catalyzed Carbonylation of Azides in the Presence of Amines.

AbstractThis new methodology provides a facile and efficient approach from simple and cheap organoazides with amines under atmospheric CO conditions, obtaining unsymmetrical ureas with good functional group tolerance.

ChemInform Abstract: Ruthenium‐Catalyzed Urea Synthesis Using Methanol as the C1 Source.

AbstractThe novel highly atom‐economical reaction between various benzylic or aliphatic amines, including diamines, and methanol allows for the preparation of symmetrical and unsymmetrical ureas.

Pd/C Catalyzed Carbonylation of Azides in the Presence of Amines.

A facile and efficient Pd/C-catalyzed carbonylation of both aliphatic and aromatic azides in the presence of amines is reported. Serving as the widely existed fragments in an array of biological pharmaceuticals, functionalized unsymmetrical ureas were straightforwardly synthesized by using readily available and cheap azides with amines under CO atmosphere, with the extrusion of N2 as the only byproduct. It was found that not only aryl azides but also benzyl and alkyl azides were suited for this methodology. Another feature of this procedure was the employment of a highly efficient palladium charcoal catalytic system.

A Facile Method for the Preparation of Unsymmetrical Ureas Utilizing Zirconium(IV) Chloride

A facile synthetic method for the preparation of unsymmetrical ureas from amines is described. Carbamoyl imidazole compounds were prepared by the reaction of 1,1‐carbonyldiimidazole with primary or secondary amines, and further activation by treatment with zirconium(IV) chloride to generate the desired urea. This reaction protocol was applied to the synthesis of tri and tetrasubstituted ureas with high yields. This study provides an alternative guideline for the practical preparation of various unsymmetrical ureas.

Facile one-pot synthesis of unsymmetrical ureas, carbamates, and thiocarbamates from Cbz-protected amines.

A novel one-pot synthesis of unsymmetrical ureas, carbamates and thiocarbamates from Cbz-protected amines has been developed. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, isocyanates are generated in situ, which facilitate rapid reaction with amines, alcohols, and thiols to afford the corresponding ureas, carbamates and thiocarbamates in high yields.

A Facile and Efficient Method for the Formation of Unsymmetrical Ureas Using DABAL-Me3

A practical synthetic method for the formation of unsymmetrical-substituted ureas is described. The synthesis of the unsymmetrical ureas was readily performed from 2,2,2-trichloroethyl carbamate compounds by treatment of amines with bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane (DABAL-Me3). Using this reaction protocol, various trisubstituted and tetrasubstituted ureas were synthesized in high yields. This study offers a promising approach for the facile synthesis of a variety of unsymmetrical ureas from 2,2,2-trichloroethyl carbamates.

ChemInform Abstract: Synthesis of Unsymmetrical Ureas and S‐Thiocarbamates under Catalyst‐Free Conditions in a [BMIM]BF4 Ionic Liquid.

AbstractTitle compounds are synthesized by direct condensation of phenylurea with primary and secondary amines or thiols.