- Catalytic hydration of cyanamides with phosphinous acid-based ruthenium(ii) and osmium(ii) complexes: scope and mechanistic insights
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The synthesis of a large variety of ureas R1R2NC(O)NH2 (R1 and R2 = alkyl, aryl or H; 26 examples) was successfully accomplished by hydration of the corresponding cyanamides R1R2NCN using the phosphinous acid-based complexes [MCl2(η6-p-cymene)(PMe2OH)] (M = Ru (1), Os (2)) as catalysts. The reactions proceeded cleanly under mild conditions (40-70 °C), in the absence of any additive, employing low metal loadings (1 molpercent) and water as the sole solvent. In almost all the cases, the osmium complex 2 featured a superior reactivity in comparison to that of its ruthenium counterpart 1. In addition, for both catalysts, the reaction rates observed for the hydration of the cyanamide substrates were remarkably faster than those involving classical aliphatic and aromatic nitriles. Computational studies allowed us to rationalize all these trends. Thus, the calculations indicated that the presence of a nitrogen atom directly linked to the CN bond depopulates electronically the nitrile carbon by inductive effect when coordinated to the metal center, thus favouring the intramolecular nucleophilic attack of the OH group of the phosphinous acid ligand to this carbon. On the other hand, the higher reactivity of Os vs. Ru seems to be related with the lower ring strain on the incipient metallacycle that starts to form in the transition state associated with this key step in the catalytic cycle. Indirect experimental evidence of the generation of the metallacyclic intermediates was obtained by studying the reactivity of [RuCl2(η6-p-cymene)(PMe2OH)] (1) towards dimethylcyanamide in methanol and ethanol. The reactions afforded compounds [RuCl(η6-p-cymene)(PMe2OR)(NCNMe2)][SbF6] (R = Me (5a), Et (5b)), resulting from the alcoholysis of the metallacycle, which could be characterized by single-crystal X-ray diffraction. This journal is
- álvarez, Daniel,Cadierno, Victorio,Crochet, Pascale,González-Fernández, Rebeca,López, Ramón,Menéndez, M. Isabel
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p. 4084 - 4098
(2020/07/09)
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- A Straightforward Synthesis of N-Substituted Ureas from Primary Amides
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A direct and convenient method for the preparation of N-substituted ureas is achieved by treating primary amides with phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH 3 or ammonium carbamate) in MeOH. The use of 2,2,2-trifluoroethanol (TFE) as the solvent increases the electrophilicity of the hypervalent iodine species and allows the synthesis of electron-poor carboxamides. This transformation involves a nucleophilic addition of ammonia on the isocyanate intermediate generated in situ by a Hofmann rearrangement of the starting amide.
- Franck, Xavier,Glachet, Thomas,Ibert, Quentin,Lohier, Jean-Fran?ois,Reboul, Vincent,Saraiva Rosa, Nathalie
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p. 2099 - 2105
(2020/07/13)
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- 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
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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.
- Basu, Priyanka,Dey, Tusar Kanto,Ghosh, Aniruddha,Biswas, Surajit,Khan, Aslam,Islam, Sk. Manirul
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p. 2630 - 2643
(2020/02/20)
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- Synthesis and Structure of 1-Substituted Semithioglycolurils
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Two methods for the synthesis of previously unavailable 1-substituted semithioglycolurils were developed. These methods consist of the cyclocondensation of 1-substituted ureas with 4,5-dihydroxy- or 4,5-dimethoxyimidazolidine-2-thione or glyoxal, followed by the reaction of the resulting 1-substituted 4,5-dihydroxyimidazolidine-2-ones with HSCN in a two-step one-pot procedure. Two of the desired semithioglycolurils were obtained as conglomerates.
- Baranov, Vladimir V.,Galochkin, Anton A.,Kravchenko, Angelina N.,Makhova, Nina N.,Nelyubina, Yulia V.
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p. 2563 - 2571
(2020/09/07)
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- A Physical Organic Approach to Tuning Reagents for Selective and Stable Methionine Bioconjugation
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We report a data-driven, physical organic approach to the development of new methionine-selective bioconjugation reagents with tunable adduct stabilities. Statistical modeling of structural features described by intrinsic physical organic parameters was applied to the development of a predictive model and to gain insight into features driving the stability of adducts formed from the chemoselective coupling of oxaziridine and methionine thioether partners through Redox Activated Chemical Tagging (ReACT). From these analyses, a correlation between sulfimide stabilities and sulfimide ν (C=O) stretching frequencies was revealed. We exploited the rational gains in adduct stability exposed by this analysis to achieve the design and synthesis of a bis-oxaziridine reagent for peptide stapling. Indeed, we observed that a macrocyclic peptide formed by ReACT stapling at methionine exhibited improved uptake into live cells compared to an unstapled congener, highlighting the potential utility of this unique chemical tool for thioether modification. This work provides a template for the broader use of data-driven approaches to bioconjugation chemistry and other chemical biology applications.
- Christian, Alec H.,Jia, Shang,Cao, Wendy,Zhang, Patricia,Meza, Arismel Tena,Sigman, Matthew S.,Chang, Christopher J.,Toste, F. Dean
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supporting information
p. 12657 - 12662
(2019/09/04)
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- Direct conversion of carboxylic acids to various nitrogen-containing compounds in the one-pot exploiting curtius rearrangement
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Herein we report, a single-pot multistep conversion of inactivated carboxylic acids to various N-containing compounds using a common synthetic methodology. The developed methodology rendered the use of carboxylic acids as a direct surrogate of primary amines, for the synthesis of primary ureas, secondary/tertiary ureas, O/S-carbamates, benzoyl ureas, amides, and N-formyls, exploiting the Curtius reaction. This approach has a potential to provide a diversified library of N-containing compounds, starting from a single carboxylic acid, based on the selection of the nucleophile.
- Kumar, Arun,Kumar, Naveen,Sharma, Ritika,Bhargava, Gaurav,Mahajan, Dinesh
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p. 11323 - 11334
(2019/09/10)
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- Novel synthesis and biological evaluations of N,N’-disubstituted-3,6-bis(substitutedphenyl)-1,2,4,5-tetrazine-1,4-dicarboxamide
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A series of novel N,N’-disubstituted-3,6-bis(substitutedphenyl) -1,2,4,5-tetrazine-1,4-dicarboxamides were prepared using the intermolecular cyclization reaction of N-substituted-N’-(α-chloro-substitutedbenzylidene) hydrazinecarboxamide and triethylamine by the modification of solvent polarity. The structures of all the new compounds were characterized by IR, 1H-NMR, MS and elemental analysis. Their cytostatic effects were screened in vitro by the SRB method for A-549 cell and the MTT method for P-388 cell. The results showed that several compounds demonstrate potential antitumor activities against P-388. The substituents have clearly effect on their antitumor activity.
- Tong, Guo-Tong,Lv, Lu-Ping,Tang, Ping,Li, Wei-Wei
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p. 335 - 342
(2018/06/06)
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- A practically simple, catalyst free and scalable synthesis of: N -substituted ureas in water
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A practically simple, mild and efficient method is developed for the synthesis of N-substituted ureas by nucleophilic addition of amines to potassium isocyanate in water without organic co-solvent. Using this methodology, a variety of N-substituted ureas (mono-, di- and cyclic-) were synthesized in good to excellent yields with high chemical purity by applying simple filtration or routine extraction procedures avoiding silica gel purification. The developed methodology was also found to be suitable for gram scale synthesis of molecules having commercial application in large volumes. The identified reaction conditions were found to promote a unique substrate selectivity from a mixture of two amines.
- Tiwari, Lata,Kumar, Varun,Kumar, Bhuvesh,Mahajan, Dinesh
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p. 21585 - 21595
(2018/06/26)
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- Iron-catalyzed reaction of urea with alcohols and amines: A safe alternative for the synthesis of primary carbamates
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A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N-unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamat, without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono-and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(Icatalyst.
- Pe?a-López, Miguel,Neumann, Helfried,Beller, Matthias
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p. 2233 - 2238
(2017/07/25)
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- One-pot, solvent-free access to unsymmetrical ureas by palladium-catalysed reductive alkylation using molecular hydrogen
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Palladium-catalysed reductive alkylation of monosubstituted ureas has been studied in the presence of aldehydes and using molecular hydrogen as a clean reductant. Unsymmetrical N,N′-disubstituted ureas were formed in good to excellent isolated yields (60-93 %) without the production of salt waste. This reaction was incorporated to a one-pot, solvent-free sequence involving the alkylation of monosubstituted ureas generated in situ from the corresponding amines. Unsymmetrical N,N′-disubstituted ureas were prepared in 60-93 % isolated yield by palladium-catalysed reductive alkylation of monosubstituted ureas using aldehydes as alkylating agents and molecular hydrogen as a clean reductant. A one-pot, solvent-free sequence was also developed from the corresponding amines. Copyright
- Mohy El Dine, Tharwat,Chapron, Simon,Duclos, Marie-Christine,Duguet, Nicolas,Popowycz, Florence,Lemaire, Marc
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p. 5445 - 5454
(2013/09/02)
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- Carboxylic acid-catalyzed one-pot synthesis of cyanoacetylureas and their cyclization to 6-aminouracils in guanidine ionic liquid
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A novel, one-pot, carboxylic acid-catalyzed synthesis of cyanoacetylureas via in situ generated ureas and their cyclization to 6-aminouracils in the presence of the guanidine-based ionic liquid 1,1,3,3-tetramethylguanidine lactate [TMG][Lac] is described. The ureas were synthesized from amines and potassium cyanate, which on reaction with cyanoacetic acid in the presence of acetic anhydride in the same pot afforded cyanoacetylureas, which undergo cyclization in [TMG][Lac] as solvent as well as catalyst to afford 6-aminouracils. One-pot synthesis of cyanoacetylureas, efficient and rapid cyclization, better yield, shorter reaction time, easy workup procedure, and recyclability of the ionic liquid are some advantages of this procedure.
- Chavan, Sunil S.,Shelke, Rupesh U.,Degani, Mariam S.
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p. 399 - 403
(2013/05/21)
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- An improved method for the preparation of alkyl/arylurea derivatives using chlorocarbonylsulfenyl chloride as carbonylating agent
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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.
- Manidhar,K. Uma Maheswara Rao,C. Suresh Reddy,Ch. Syamasunder,Adeppa,Misra, Krishna
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p. 2479 - 2489
(2013/03/13)
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- Preparation of mono-, di-, and trisubstituted ureas by carbonylation of aliphatic amines with S,S-dimethyl dithiocarbonate
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General procedures are reported to prepare N-alkylureas, N,N′-dialkylureas (both symmetrical and unsymmetrical), and N,N,N′-trialkylureas by carbonylation of aliphatic amines, employing S,S-dimethyl dithiocarbonate (DMDTC) as a phosgene substitute. All reactions were carried out in water. Symmetrical disubstituted ureas were prepared directly working at 60°C with a molar ratio of DMDTC:amine = 1:2, preferably under nitrogen. Unsymmetrical ureas were prepared in two steps via S-methyl N-alkyl-thiocarbamate intermediates, which are formed selectively in the first step at room temperature. These intermediates react in the second step with ammonia or various aliphatic amines, both primary and secondary, at temperatures varying between 50 and 70°C. All the target ureas were obtained in high yields (28 examples, average yield 94%) and with very high purity (generally >99.2%). Also to be noted is the recovery of a co-product of industrial interest, methanethiol, in an amount of two moles for each mole of DMDTC, with complete exploitation of the reagent. Georg Thieme Verlag Stuttgart.
- Artuso, Emma,Degani, Iacopo,Fochi, Rita,Magistris, Claudio
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p. 3497 - 3506
(2008/09/19)
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- THE CLAIMED INVENTION RELATES TO NOVEL 4-PIPERIDINECARBOXAMIDE AND THE USE THEREOF FOR THE PREPARATION OF MEDICAMENTS AGAINST 5-HT2A RECEPTOR-RELATED DISORDERS
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The present invention relates to compounds of Formula (I) wherein R and R′ are as described herein, processes for preparing the compounds, pharmaceutical compositions comprising the compounds, and use of the compounds and compositions in the prophylaxis or treatment of a 5-HT2A receptor-related disorder.
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Page/Page column 14-15
(2008/06/13)
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- Process to prepare alkyl-ureas from O,S-dimethyl dithiocarbonate
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The present invention relates to the preparation of alkyl-ureas, starting from O,S-dimethyl dithiocarbonate, which provides the following steps: A) causing the O,S-dimethyl dithiocarbonate to react with a primary amine of general formula R1NH2in order to obtain an O-methyl thiocarbamate; B) isomerising the O-methyl thiocarbamate in order to obtain an S-methyl thiocarbamate; C) causing the S-methyl thiocarbamate with a compound of general formula R′R″NH, wherein R′ and R″ may be equal or different one in respect of the other and of R1and may be H, R2or R3, in order to obtain one of the alkyl-ureas of formula (4), (5) or (6).
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Page column 8
(2010/02/06)
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- Novel aminobenzoephenones
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The invention relates to a novel class of aminobenzophenones derivatives, to pharmaceutical preparations comprising said compounds, to dosage units of such preparations, to methods of treating patients comprising administering said compounds, and to the use of said compounds in the manufacture of pharmaceutical preparations.
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- A simple conversion of amines into monosubstituted ureas in organic and aqueous solvents
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A versatile and highly efficient synthesis of monosubstituted ureas is described. The reaction of an amine with 4-nitrophenyl-N-benzylcarbamate, followed by hydrogenolysis, provides the corresponding urea in high yield and purity. This carbamate can also be employed for the derivatization of water-soluble polyamines (e.g. aminoglycoside antibiotics), while other reagents (e.g. benzylisocyanate) fail to give the desired products in any significant yield.
- Liu, Qi,Luedtke, Nathan W.,Tor, Yitzhak
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p. 1445 - 1447
(2007/10/03)
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- Spontaneous Lossen Rearrangement of (Phosphonoformyl)hydroxamates. The Migratory Aptitude of the Phosphonyl Group
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(i-PrO)2P(=O)COSEt (1) reacted with NH2OH in pyridine at room temperature to give mainly (i-PrO)2P(=O)NH2 (4). The formation of 4 was interpreted in terms of a spontaneous Lossen rearrangement of (i-PrO)2P(=O)CONHOH (2a) formed in the reaction. A transient 31P NMR signal appearing in the reaction mixture at δ-1.8 was assigned to 2a. Trapping of (i-PrO)2P(=O)N=C=O (5), formed in the reaction of 1 and NH2OH, by cyclohexylamine gave (i-PrO)2P(=O)NHCONHC6H11 (6). Attempted isolation of 6 gave the hydrolyzed product N-cyclohexylurea (7). The reaction of 1 with NH2OMe proceeded slower than that with NH2OH and gave the expected (i-PrO)2P(=O)-CONHOMe (2b), which was isolated and identified. 2b converts slowly to 4 in pyridine at room temperature. In contrast, MeNHOH reacted rapidly with 1 and gave the stable crystalline (i-PrO)2P(=O)CON(Me)OH (2c). The structure of hydroxamates 2 were assigned on the basis of 1H, 13C, and 31P NMR spectral data. This facile Lossen rearrangement is discussed in terms of the unusually high migratory aptitude of the phosphonyl group.
- Salomon, Claudio J.,Breuer, Eli
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p. 3858 - 3861
(2007/10/03)
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- Process for the preparation of asymmetrically substituted ureas, carbamates or thiocarbamates
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Process for the preparation of asymmetrically substituted ureas, carbamates, thiocarbamates or substituted isocyanates by reaction of an adduct of isocyanic acid and a tertiary amine with a primary and secondary amine, an alcohol, a thiol or a compound having one or two non-cumulated olefinic double bonds, and a process for the preparation of N-mono- or N,N-disubstituted ureas by reaction of ammonium isocyanate with a primary or secondary amine in a diluent.
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- USE OF ISOCYANIC ACID FOR THE PREPARATION OF SUBSTITUTED UREAS
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A thermogravimetric study was carried out on the thermolysis of cyanuric acid and conditions were found for carrying out this reaction to give gaseous isocyanic acid.Dosing this acid in the vapor of inert organic solvents gave systems used for the selective synthesis of monosubstituted ureas.The reaction of gaseous isocyanic acid with amine vapor selectively gave highly pure N-cyclohexylurea and N,N'-bis(3-trifluoromethylphenyl)urea.
- Kirpichev, V. P.,Karachinskii, S. V.,Dragalov, V. V.,Peshkova, O. Yu.
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p. 1651 - 1653
(2007/10/02)
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- Process for the preparation of substituted isocyanates
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Process for the preparation of asymmetrically substituted ureas, carbamates, thiocarbamates or substituted isocyanates by reaction of an adduct of isocyanic acid and a tertiary amine with a primary and secondary amine, an alcohol, a thiol or a compound having one or two non-cumulated olefinic double bonds.
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- Process for the preparation of asymmetrically substituted ureas
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Process for the preparation of asymmetrically substituted ureas by reaction of a gaseous mixture of isocyanic acid and ammonia having a temperature of 260° to 600° C. with a primary or secondary amine.
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- Process for the preparation of monocyclohexylurea
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Monocyclohexylurea can be prepared particularly selectively if 100 parts by weight of cyclohexylamine are reacted with 70 to 300 parts by weight of urea in the presence of water in the boiling range of water.
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- Reaction of Ethyl 3,3-Diaminopropenoate with Isocyanates and Isothiocyanates
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The title compound 1 reacts with alkyl(or phenyl) isocyanates 2 in a molar ratio of 1:1 to give the N-monoadducts 3 which cyclize readily to yield the 6-aminouracils 4, whereas in a molar ratio of 1:2 mainly N,N'-bisadducts 6 and, in two cases, small amounts of C,N-bisadducts 5 are formed.The N,N'-bisadducts 6 are extremely sensitive to water giving the ureido esters 7, but can be converted into substituted uracils 8 under basic conditions.The addition of 1 to isothiocyanates 9 yields mainly the C-monoadducts 10 and, as minor products, the 6-amino-2-thiouracils 11.
- Sulay, Piroshka B.,Ivanov, Ivo C.
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p. 1101 - 1106
(2007/10/02)
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- Some Extensions of von Braun (BrCN) Reaction on Organic Bases, Part IV
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Extensions of von Braun cyanogen bromide reaction have been undertaken on some aliphatic and heterocyclic amines.Monocyanamides of all these bases yielded their respective urea and carboxamide derivatives on hydrolysis with dilute hydrochloric acid.They also gave the amido derivatives on reaction with Zn/HCl, as in the case of diisobutyl and di-2-butyl cyanamides. - Key words: von Braun Cyanogen Bromide Reaction
- Siddiqui, Salimuzzaman,Haider, S. Imtiaz,Ahmad, S. Salman,Siddiqui, B. Shaheen
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p. 546 - 549
(2007/10/02)
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- Amidomercuriation: A General Addition of Amides and Related Compounds to Olefins
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The addition of different carboxamides and related compounds such as urethane or urea to olefins using mercury(II) nitrate followed by sodium borohydride reduction to give the corresponding N-substituted amides, urethanes, or ureas, respectively, is described.The monoalkylated ureas, through the same amidomercuriation-demercuriation procedure, yield symmetrical and unsymmetrical N,N'-disubstituted ureas.This amidomercuriation-demercuriation process provides a new, convenient, and general method for the Markovnikov amidation of carbon-carbon double bonds.
- Barluenga, Jose,Jimenez, Carmen,Najera, Carmen,Yus, Miguel
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p. 591 - 593
(2007/10/02)
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- The Dehydration of Ureas by Two-Phase Dichlorocarbene Reaction, a Synthetic Access to Substituted Cyanamides
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A wide variety of N,N-disubstituted ureas are dehydrated in the CHCl3/NaOH catalytic two-phase system under mild conditions.The sequence of urea-transamidation and dehydration thus offers a profitable approach to aprotic cyanamides.Among various tested PT-catalysts tertiary amines prove to be the most efficient and favourable ones.Tertiary amines may also be used advantageously in the transformation of carboxylic amides and thioamides to the corresponding nitriles.The application of the same technique is less suitable in the case of N-mono-substituted ureas, N,N'-disubstituted ureas as well as N(dialkylaminomethylidene)ureas, because consequent reactions of the primarily formed cyanamides predominate.Problems concerning the dehydration mechanism are elucidated in terms of HMO-perturbation theory.
- Schroth, W.,Kluge, H.,Frach, R.,Hodek, W.,Schaedler, H. D.
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p. 787 - 802
(2007/10/02)
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- Reactivity of 1,3-Diimines. Reaction with Heterocumulenes
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1,3-Diimines 1 react with isocyanates and isothiocyanates 2 to give, as the major products, different 2-oxo- and 2-thiopyrimidines 9 and 10.The formation of these products can be explained by two different reaction paths that involve an addition reaction followed by an electrocyclic ring closure.The nature of the group R1 in 1 plays a basic role in the result of the process.Open-chain intermediate products 3 have been isolated and characterized for the first time in a cyclization reaction with diimines 1.
- Barluenga, Jose,Rubio, Victor,Gotor, Vicente
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p. 2592 - 2596
(2007/10/02)
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- Isoxazole derivatives
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Isoxazole derivatives represented by the formula: STR1 are prepared; wherein R1 and R2 each is hydrogen atom, alkyl group of 1 to 8 carbon atoms, or cycloalkyl group of 3 to 10 carbon atoms; R3 and R4 each is hydrogen atom, alkyl group of 1 to 8 carbon atoms, cycloalkyl group of 3 to 10 carbon atoms, or phenyl group; or the group Is morpholino group; and Y is oxo group, thioxo group or imino group; being useful as a hypoglycemic and/or a blood free-fatty-acid normalizing antidiabetic agent.
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