Synthesis Of Urea Derivatives Research Articles

Direct additive-free N-formylation and N-acylation of anilines and synthesis of urea derivatives using green, efficient, and reusable deep eutectic solvent ([ChCl][ZnCl2]2)

In the current report, we introduce a simple, mild efficient and green protocol for N-formylation and N-acetylation of anilines using formamide, formic acid, and acetic acid as inexpensive, nontoxic, and easily available starting materials just with heating along stirring in [ChCl][ZnCl2]2 as a durable, reusable deep eutectic solvent (DES), which acts as a dual catalyst and solvent system to produce a wide range of formanilides and acetanilides. Also, a variety of unsymmetrical urea derivatives were synthesized by the reaction of phenyl isocyanate with a range of amine compounds using this benign DES in high to excellent yields. [ChCl][ZnCl2]2 showed good recycling and reusability up to four runs without considerable loss of its catalytic activity.

Synthesis of N,N-diethylaminopropylurea and Monosubstituted Urea Derivatives from Primary Amines and Potassium Cyanate

Abstract: Urea derivatives are an important class of pharmacologically-active compounds due to their ability to form hydrogen bonds with biological targets. Several synthetic pathways have been developed to access urea derivatives, such as the metal-free and metal-catalysed carbonylation reactions of amines and the Curtius, Hofmann, and Tiemann rearrangement reactions. This study aimed to synthesize urea derivatives from primary amines. The urea derivatives were synthesized from primary amines and potassium cyanate in 1M HCl aqueous solution under ambient conditions and were isolated, followed by characterization using FTIR, DSC, and NMR (1H and 13C). A new urea derivative, N, N-diethylaminopropylurea (6), together with N-phenylurea (1), para-tolylurea (2), orthomethoxyphenylurea (3), para-methoxyphenylurea (4), N-benzylurea (5), and N-butylurea (7), was successfully synthesized under acidic conditions. This work presents the synthesis and characterization data of a newly-reported urea derivative, N, N-diethylaminopropylurea (6), and extends the substrate scope to basic side chains in the synthesis of urea derivatives from primary amines and potassium cyanate in water.

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

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 aroyl azides, and nucleophilic addition of amines sequentially occur to afford the products in good to excellent yields. This protocol is operationally simple and displays a broad substrates scope.

Search for new anticancer drugs among new carbohydrate derivatives urea

Introduction . In recent years, the creation and use of drugs for antitumor therapy, which have improved the quality of life and survival of cancer patients, has become a crucial event in the development of oncology. It is known that urea derivatives are included in the class of drugs with anti-angiogenic properties. The addition of a carbohydrate residue to urea derivatives helps to improve the solubility, targeted drug deliveiy in the body (targeting), and the elimination of side effects. In order to search for new compounds with anti-angiogenic properties, we have synthesized a number of compounds, some of which are previously unknown urea derivatives. Purpose of the study — synthesis of urea derivatives based on sugary nitrosocarbamidetransamidation. To evaluate using in silico and in vitro methods, there is the ability to create new anticancer drugs based on new glycosidic urea derivatives. Materials and methods . Pre-experimental prediction of biological activity was performed using a computer system PASS. Cytotoxic activity was determined by the MTT method. For the MTT assay, cells were dropped into 198 µl of RPMI-1640 complete medium in 96-well plates. After one day, the test compounds were added to each well in concentration 100 µmol. After 72 hours, 20 µl of MTT solution was added to each well. The intensity of the medium staining was measured on a Multiskan EX photometric immunoassay analyzer at λ = 540 nm. Results . From the number of virtual compounds studied, for 5 compounds a high probability of antineoplastic activity and a low probability of cytotoxic activity in silico are predicted. Compounds were synthesized: N-(β-D-galactopyranosylcarbamoyl-l)-2-isonicotin-semicarbazide, l-[(N- β -D-galactopyranosyl)-carbamoyl]-3,5-dimethylpyrazoIe, N-( β -D -galactopyranosylcarbamoyl)-p-bromophenylurea, N-( β -D -galactopyranosyl)-p-chlorophenylurea, N-( β -D -glucopyranosyl)-p-chlorophenylurea. The compounds did not show cytotoxic activity in vitro. Conclusion . For the studied compounds, a tow probability of cytostatic activity manifestation (as confirmed experimentally) and a high probability of antitumor activity manifestation are virtually predicted.

Pivotal Role of the Basic Character of Organic and Salt Catalysts in C−N Bond Forming Reactions of Amines with CO2

AbstractOrganocatalysts promote a range of C−N bond forming reactions of amines with CO2. Herein, we review these reactions and attempt to identify the unifying features of the catalysts that allows them to promote a multitude of seemingly unrelated reactions. Analysis of the literature shows that these reactions predominantly proceed by carbamate salt formation in the form [BaseH][RR′NCOO]. The anion of the carbamate salt acts as a nucleophile in hydrosilane reductions of CO2, internal cyclization reactions or after dehydration as an electrophile in the synthesis of urea derivatives. The reactions are enhanced by polar aprotic solvents and can be either promoted or hindered by H‐bonding interactions. The predominant role of all types of organic and salt catalysts (including ionic liquids, ILs) is the stabilization of the carbamate salt, mostly by acting as a base. Catalytic enhancement depends on the combination of the amine, the base strength, the solvent, steric factors, ion pairing and H‐bonding. A linear relationship between the base strength and the reaction yield has been demonstrated with IL catalysts in the synthesis of formamides and quinazoline‐2,4‐diones. The role of organocatalysts in the reactions indicates that all bases of sufficient strength should be able to catalyze the reactions. However, a physical limit to the extent of a purely base catalyzed reaction mechanism should exist, which needs to be identified, understood and overcome by synergistic or alternative methods.

Pivotal Role of the Basic Character of Organic and Salt Catalysts in C-N Bond Forming Reactions of Amines with CO2.

Organocatalysts promote a range of C-N bond forming reactions of amines with CO2 . Herein, we review these reactions and attempt to identify the unifying features of the catalysts that allows them to promote a multitude of seemingly unrelated reactions. Analysis of the literature shows that these reactions predominantly proceed by carbamate salt formation in the form [BaseH][RR'NCOO]. The anion of the carbamate salt acts as a nucleophile in hydrosilane reductions of CO2 , internal cyclization reactions or after dehydration as an electrophile in the synthesis of urea derivatives. The reactions are enhanced by polar aprotic solvents and can be either promoted or hindered by H-bonding interactions. The predominant role of all types of organic and salt catalysts (including ionic liquids, ILs) is the stabilization of the carbamate salt, mostly by acting as a base. Catalytic enhancement depends on the combination of the amine, the base strength, the solvent, steric factors, ion pairing and H-bonding. A linear relationship between the base strength and the reaction yield has been demonstrated with IL catalysts in the synthesis of formamides and quinazoline-2,4-diones. The role of organocatalysts in the reactions indicates that all bases of sufficient strength should be able to catalyze the reactions. However, a physical limit to the extent of a purely base catalyzed reaction mechanism should exist, which needs to be identified, understood and overcome by synergistic or alternative methods.

Synthesis of Urea Derivatives from CO2 and Silylamines.

A series of thirty-three N,N'-diaryl, dialkyl, and alkyl-aryl ureas have been prepared in pyridine or toluene by reaction of silylamines with CO2 . This protocol is shown to provide facile access to 13 C-labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed through initial generation of the corresponding silylcarbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl ether.

Synthesis of Urea Derivatives from CO2 and Silylamines

AbstractA series of thirty‐three N,N′‐diaryl, dialkyl, and alkyl‐aryl ureas have been prepared in pyridine or toluene by reaction of silylamines with CO2. This protocol is shown to provide facile access to 13C‐labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed through initial generation of the corresponding silylcarbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl ether.

Synthesis of Urea Derivatives using Carbon Dioxide as Carbonylation Reagent in Ionic Liquids

Urea and its derivatives, which are usually generated through the carbonylation reaction between amines and carbonylation reagent, have been found widespread applications in agriculture and pharmaceuticals. Among the carbonylation reaction, it is the most appealing and promising strategy that employs CO2 as a green carbonylation reagent. However, CO2 inherent thermodynamic stability and kinetic inertness limit its application. Apart from being regarded as one of the green solvents, ionic liquid is also an efficient organocatalyst for CO2 capture or activation due to the interaction between CO2 with cation or anion of ionic liquid. In this mini-review, we have summarized representative synthetic methodologies of urea derivatives using carbon dioxide as a green carbonylation reagent and using ionic liquids as solvents and/or organocatalysts. Keywords: Activation, carbon dioxide, carbonylation, ionic liquid, organocatalyst, urea derivatives.

Synthesis of Urea Derivatives in Two Sequential Continuous-Flow Reactors

A continuous-flow system consisting of two sequential microreactors was developed for the synthesis of nonsymmetrically substituted ureas starting from tert-butoxycarbonyl protected amines. Short reaction times could be achieved under mild conditions. In-line FT-IR analytical technique was used to monitor the reaction, including the formation of the isocyanate intermediate, thus allowing optimization of the reagent ratios. The mechanistic role of the applied base was also clarified. The setup was successfully utilized for the synthesis of several urea derivatives including the active pharmaceutical ingredient cariprazine.

Synthesis of urea derivatives via reductive carbon dioxide fixation into contracted porphyrin analogues

Carbon dioxide from ammonium carbonate is trapped by the free base corroles which forms the N21,N22-carbamide-corrole derivatives.

Efficient Synthesis of Urea Derivatives via a Sequential One-Pot Nucleophilic Addition/Ugi Five-Component Reaction Under Solvent-Free Conditions

Urea polyfunctional derivatives were successfully synthesized via a one-pot, five-component nucleophilic addition/Ugi reaction sequence. Simplicity, solvent-free conditions, and good yields of products are advantages of this method.

ChemInform Abstract: Synthesis of Urea Derivatives from Amines and CO2 in the Absence of Catalyst and Solvent.

AbstractThis green process utilizes the captured carbon dioxide to prepare urea derivatives, avoiding the use of toxic or expensive substrates.

ChemInform Abstract: Synthesis of Urea Derivatives from CO2 and Amines Catalyzed by Polyethylene Glycol Supported Potassium Hydroxide Without Dehydrating Agents.

AbstractA simple catalyst is developed and efficiently used for the fixation of carbon dioxide as symmetrical urea derivatives.

Synthesis of urea derivatives from amines and CO2 in the absence of catalyst and solvent

Urea derivatives are obtained in mild to good yield from the reactions of primary aliphatic amines with CO2 in the absence of any catalysts, organic solvents or other additives. To optimize reaction conditions, experimental variables including temperature, pressure, the concentration of amine, reaction time etc. were studied. Satisfactory yields were obtained at the optimized conditions that are comparable to the presence of catalyst and solvent. The preliminary investigation of the reaction mechanism showed that alkyl ammonium alkyl carbamate was quickly formed as the intermediate, and then the final product was formed by the intramolecular dehydration.

ChemInform Abstract: Solvent‐Free Synthesis of Urea Derivatives from Primary Amines and Sulfur under Carbon Monoxide and Oxygen at Atmospheric Pressure.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Síntese e emprego do ciclometalado [Pd(dmba)(N3)(PPh3)] em processos catalíticos envolvendo a n-carbonilação redutiva de nitroarenos a carbamatos e na síntese de derivados da uréia

This work deals with the use of the cyclometallated compound [Pd(dmba)(N3)(PPh3)] in homogeneous catalytic processes comprising the reductive N-carbonylation of nitrobenzene and p-nitrotoluene to ethyl-phenylcarbamate and ethyl-4-methylphenylcarbamate, respectively. The cyclopalladated compound was also employed in the synthesis of urea derivatives by reacting p-nitrotoluene and m-nitrotoluene, respectively, with p-toluidine and and m-chloroaniline.

Synthesis of urea derivatives and their study as jet fuel additives

Synthesis of urea derivatives and their study as jet fuel additives