- 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 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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- 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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- Hydration of Nitriles to Amides by Thiolate-Bridged Diiron Complexes
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A series of nitrile-coordinating complexes [CpFe(μ-SEt)RCN]2[PF6]2 (1, R = alkyl, aryl, vinyl, amine) have been obtained by the reaction of [CpFe(μ-SEt)MeCN]2[PF6]2 (1a) with various nitriles in acetone. Complexes 1 can realize the hydration of a nitrile ligand under ambient conditions. Complexes [CpFe(μ-SEt)2(μ-η1:η1-NH(O)CR)FeCp][PF6] (2) were successfully isolated as intermediates during the hydration process, with 2b and 2e (R = CH2i = CH and Et2N) being characterized by spectrometry and X-ray crystallography. Treatment of 2 with HBF4·Et2O in the presence of nitriles released corresponding amides 3. At the same time, the structural features of the [Fe2S2] scaffold were retained. These results confirmed that the hydration of nitriles was realized by cooperative interaction on diiron centers. (Figure Presented).
- Tong, Peng,Yang, Dawei,Li, Yang,Wang, Baomin,Qu, Jingping
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p. 3571 - 3576
(2015/08/06)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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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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- 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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- KINETICS AND MECHANISM OF METHANOLYSIS OF BENZOYL DERIVATIVES OF SUBSTITUTED PHENYLUREAS AND PHENYLTHIOUREAS
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The methanolysis rate constants and dissociation constants have been measured of benzoyl derivatives of substituted phenylureas and phenylthioureas.The dissociation constants of the thio derivatives are higher by 1 order of magnitude and the rate constants are higher by 2 orders of magnitude than the respective values of the oxygen analogues.Logarithms of the rate and dissociation constants have been correlated with Hammett ? constant; the ρ constant of the methanolysis of the oxygen derivatives is almost 2 * higher than that of the thio derivatives, which is explained by a change in the rate-limiting step.Methylation of the phenyl nitrogen atom increases the acidity by almost 2 orders of magnitude.This effect is due obviously to steric hindrance to the conjugation with the adjacent carbonyl or thiocarbonyl group.
- Kavalek, Jaromir,El Bahaie, Said,Sterba, Vojeslav
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p. 2103 - 2110
(2007/10/02)
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- Some Extensions of von Braun (BrCN) Reaction on Organic Bases
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Some extensions of von Braun cyanogen bromide reaction have been undertaken on conessine, isoconessine and two simpler bases, dimethyl α-naphthyl amine and diethyl amine.The monocyanamides of conessine and isoconessine yielded acid amides, aminoderivatives (diamines) and guanido derivatives on careful hydrolysis, reduction and treatment with ammonia, respectively.The simpler bases also formed the acid amides and diamines but failed to give the guanido derivatives under the conditions employed for conessine series.Diamines of all these bases yielded carbinol amines on reaction with nitrous acid. - Key words: von Braun Cyanogen Bromide Reaction
- Siddiqui, Salimuzzaman,Siddiqui, Bina S.
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p. 1049 - 1052
(2007/10/02)
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