538-32-9Relevant academic research and scientific papers
Kinetics and mechanism of the aminolysis of aryl thiocarbamates: Effects of the non-leaving group
Oh, Hyuck Keun,Jin, Young Cheul,Sung, Dae Dong,Lee, Ikchoon
, p. 1240 - 1244 (2005)
The kinetics of the aminolysis of aryl thiocarbamates [ATC: H 2NC(=O)SC6H4Z] with benzylamines (XC 6H4CH2NH2) in acetonitrile at 10.0°C have been studied. The rate order with variation of the non-leaving amino group, RNH, in RNHC(=O)SC6H4Z is NH2 s) effects of the RNH group are insignificant, and the strength of push to expel the leaving group in the tetrahedral transition state is the sole, important effect. The strong push provided by the NH2 group, the negative ρxz (-0.38) value, the size of βz (-0.54), and failure of the reactivity-selectivity principle are all consistent with the concerted mechanism. The kinetic isotope effects involving deuterated amine nucleophiles (XC6H4CH2ND2) are normal (kH/kD ≈ 1.40-1.73) suggesting a hydrogen-bonded cyclic transition state. The Royal Society of Chemistry 2005.
An improved method for the preparation of alkyl/arylurea derivatives using chlorocarbonylsulfenyl chloride as carbonylating agent
Manidhar,K. Uma Maheswara Rao,C. Suresh Reddy,Ch. Syamasunder,Adeppa,Misra, Krishna
, p. 2479 - 2489 (2012)
A convenient procedure has been developed for preparation of aminesubstituted or monomethylamine-substituted alkyl/arylurea derivatives. The method comprises two steps-reaction of an alkyl/aryl amine with chlorocarbonylsulfenyl chloride in a non-polar solvent to produce an alkyl/arylcarbonylsulfenyl chloride, then reaction of this alkyl/ arylcarbonylsulfenyl chloride with ammonia or monomethylamine in a two-phase reaction with a phase-transfer catalyst, to produce the corresponding alkyl/aryl-substituted urea. Springer Science+Business Media B.V. 2012.
Degradation kinetics and mechanism of an oxadiazole derivative, design of a stable drug product for BMS-708163, a γ-secretase inhibitor drug candidate
Hartley, Ruiling F.,Huang, Yande,Cassidy, Michael,Razler, Thomas M.,Qian, Feng,Hussain, Munir A.
, p. 3124 - 3133 (2012)
The stability of a 1,2,4-oxadiazole derivative, BMS-708163, A, was studied in the cosolvent mixture of acetonitrile-water at various pH values, in the solid state and in the presence of various excipients. The objective of this study was to develop a deep understanding of the stability of compound A based on its degradation kinetics and mechanism to enable design of a robust drug product. A series of isotopically 13C- and 15N-labeled compounds were synthesized and their degradation was studied by liquid chromatography-mass spectrometry and nuclear magnetic resonance to prove the degradation mechanism. Compound A exhibited maximum stability at a pH range of 3-5. In forced degradation studies, higher or lower pH resulted in an increase in degradation rate. At low pH, the N-4 atom on the 1,2,4-oxadiazole ring is protonated, followed by nucleophilic attack on the activated methine carbon to cause ring opening to form aryl nitrile degradation product, compound B. At high pH, the nucleophilic attack occurs on the methine carbon to generate an anion on N-4. Subsequent proton capture from a proton donor, such as ambient water, facilitates ring opening to generate compound B. In the absence of a proton donor, such as in dry acetonitrile, anion on N-4 will go back to compound A. Therefore, compound A is stable in absence of proton donor. This study defines the package condition and microenvironmental pH under which compound A can be formulated into a stable product.
Indium(III)-Catalyzed Synthesis of Primary Carbamates and N-Substituted Ureas
Jain, Isha,Malik, Payal
supporting information, p. 93 - 97 (2021/11/26)
An indium triflate-catalyzed synthesis of primary carbamates from alcohols and urea as an ecofriendly carbonyl source has been developed. Various linear, branched, and cyclic alcohols were converted into the corresponding carbamates in good to excellent yields. This method also provided access to N-substituted ureas by carbamoylation of amines. All the products were obtained by simple filtration or crystallization, without the need for chromatographic purification. Mechanistic investigations suggest that the carbamoylation reaction proceeds through activation of urea by O-coordination with indium, followed by nucleophilic attack by the alcohol or amine on the carbonyl center of urea. The inexpensive and easily available starting materials and catalyst, the short reaction times, and the ease of product isolation highlight the inherent practicality of the developed method.
Synthesis of Biuret Derivatives as Potential HIV-1 Protease Inhibitors Using (LDHs-g-HMDI-Citric Acid), as a Green Recyclable Catalyst
Ghiasifar, Zahra,Salehabadi, Hafezeh,Adibpour, Neda,Alipour, Eskandar,Kobarfard, Farzad,Shoushizadeh, Mohammad Reza
, p. 48 - 59 (2020/12/07)
In this study, a novel catalyst based on layered double hydroxides (LDHs) attached by hexamethylene-1,6-diisocyanate (HMDI) and citric acid (LDHs-g-HMDI-Citric acid) is reported and used to increase the yield of biurets synthesis. Biuret derivatives 5a–n were prepared by reaction of several phenyl allophanates (3a–d), which prepared from the reaction of phenyl chloroformate and urea derivatives (2a–d), with variously substituted amines (4a–g) in the presence of LDHs-g-HMDI-Citric acid as a reusable heterogeneous catalyst at reflux condition for 60–180 min. These biurets (5a–n) were evaluated for human immunodeficiency virus type-1 (HIV-1) protease inhibitory activity by HIV-1 p24 antigen ELISA kit and six of them (5n, 5i, 5j, 5 m, 5f, and 5a) showed moderate activity on HIV-1 virus with IC50 values ranging from 55 to 100 μM compared with the azidothymidine as the reference drug (IC50 = 0.11 μM). Results of the in vitro test and docking study were in good correlation.
Ammonium Chloride-Promoted Rapid Synthesis of Monosubstituted Ureas under Microwave Irradiation
Lan, Chunling Blue,Auclair, Karine
supporting information, p. 5135 - 5146 (2021/10/19)
Monosubstituted ureas are important scaffolds in organic chemistry. They appear in various biologically active compounds and serve as versatile precursors in synthesis. Monosubstituted ureas were originally prepared using toxic and hazardous phosgene equivalents. Modern methods include transamidation of urea and nucleophilic addition to cyanate salts, both of which suffer from a narrow substrate scope due to the need for a strong acid and prolonged reaction times. We hereby report that ammonium chloride can promote the reaction between amines and potassium cyanate to generate monosubstituted ureas in water. This method proceeds rapidly under microwave irradiation and tolerates a broad range of functional groups. Unlike previous strategies, it is compatible with other nucleophiles, acid-labile moieties, and most of the common protecting groups. The products precipitate out of solution, allowing facile isolation without column chromatography.
Green and efficient synthesis of thioureas, ureas, primary: O -thiocarbamates, and carbamates in deep eutectic solvent/catalyst systems using thiourea and urea
Bagherzadeh, Nastaran,Sardarian, Ali Reza,Inaloo, Iman Dindarloo
supporting information, p. 11852 - 11858 (2021/07/12)
An efficient and general catalysis process was developed for the direct preparation of various primary O-thiocarbamates/carbamates as well as monosubstituted thioureas/ureas by using thiourea/urea as biocompatible thiocarbonyl (carbonyl) sources. This procedure used choline chloride/tin(ii) chloride [ChCl][SnCl2]2 with a dual role as a green catalyst and reaction medium to afford the desired products in moderate to excellent yields. Moreover, the DES can be easily recovered and reused for seven cycles with no significant loss in its activity. Besides, the method shows very good performance for synthesizing the desired products on a large scale.
Enzyme-Inspired Lysine-Modified Carbon Quantum Dots Performing Carbonylation Using Urea and a Cascade Reaction for Synthesizing 2-Benzoxazolinone
Hasani, Morteza,Kalhor, Hamid R.
, p. 10778 - 10788 (2021/09/08)
Catalysts as the dynamo of chemical reactions along with solvents play paramount roles in organic transformations in long-lasting modes. Thus, developing effective and biobased catalysts in nontoxic solvents is highly in demand. In this report, carbon quantum dots (CQDs) functionalized with-lysine (Lys-CQDs) were generated from entirely nature-derived materials; they were demonstrated to be a promising catalyst for C-N bond formation in choline chloride urea (ChCl/U), a natural deep eutectic solvent (NADES). Among a number of synthesized CQDs, Lys-CQD turned out to be a powerful catalyst in the model reaction with aniline to afford phenyl urea. This type of transformation is important because aniline as a nucleophile has low activity, and urea is a very weak electrophile but an abundant natural source of the carbonyl moiety at the same time. The optimized reaction was performed under a highly desirable condition without using tedious and toxic workup processes at a low temperature (37 °C for aliphatic amines and 60 °C for aniline derivatives), as well as by embracing the broad scope of products in good to high yields even with weak nucleophiles such as aniline. A proposed acid-activated mechanism was suggested for the model reaction that was further confirmed by detecting ammonia as the leaving group. To show further multifunctionality of the catalyst, a cascade catalysis approach was developed for synthesizing 2-benzoxazolinone, which was furnished in a two-step transformation, starting from 2-aminophenol. Using X-ray crystallography, the structure of the final product in the cascade reaction was also determined. The catalyst was characterized using various analytical techniques including SEM, TEM, AFM, XRD, IR spectroscopy, UV-vis spectroscopy, DLS, and fluorescence spectroscopy. Measuring the acid/base sites by back titration, the catalyst was shown to be highly functionalized by the lysine functional group. The size of the catalyst was determined to be in the range of 1-8 nm, having a well-dispersed surface. In all, Lys-modified CQD, as a metal-free catalyst, was synthesized, characterized, and optimized for carbonylation, as well as a cascade reaction, under mild conditions. The whole process including catalyst synthesis and organic transformations is economically competitive and fulfills all requirements toward viability.
An efficient one-pot synthesis of industrially valuable primary organic carbamates and: N -substituted ureas by a reusable Merrifield anchored iron(ii)-anthra catalyst [FeII(Anthra-Merf)] using urea as a sustainable carbonylation source
Basu, Priyanka,Dey, Tusar Kanto,Ghosh, Aniruddha,Biswas, Surajit,Khan, Aslam,Islam, Sk. Manirul
, p. 2630 - 2643 (2020/02/20)
An efficient synthesis of primary carbamates and N-substituted ureas is explored with a newly developed heterogeneous polymer supported iron catalyst in the presence of a sustainable carbonylation source. The Merrifield anchored iron(ii)-anthra catalyst [FeII(Anthra-Merf)] was synthesized by functionalization of Merrifield polymer followed by grafting of iron metal. The catalyst [FeII(Anthra-Merf)] was characterized by several techniques, like SEM, EDAX, TGA, PXRD, XPS, FTIR, CHN, AAS and UV-Vis analysis. The designed polymer embedded [FeII(Anthra-Merf)] complex is a remarkably successful catalyst for the synthesis of primary organic carbamates and N-substituted ureas by using safe carbonylation agent urea with different derivatives of alcohols and amines, respectively. The reported catalyst is a potential candidate towards contributing a satisfactory yield of isolated products under suitable reaction conditions. The catalyst is recyclable and almost non-leaching in nature after six runs with an insignificant drop in catalytic activity. Thus we found an economical and viable catalyst [FeII(Anthra-Merf)] for primary carbamates and N-substituted urea synthesis under moderate reaction conditions.
MONOSUBSTITUTED UREA DERIVATIVES AS A SELF-TANNING SUBSTANCE
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Paragraph 0160; 0161; 0162; 0163, (2020/02/20)
The present invention relates to the use of monosubstiuted urea derivatives of the formula I as self-tanning substance, for increasing melanin synthesis, for improving melanin transport and/or improving the distribution of melanin in suprabasal layers, and to preparations comprising these urea derivatives.
