- C-N bond formation followed by N-Cl bond breaking. One more and unexpected case of the formation of a hydroxamic group via heterolytic bond cleavage
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An unexpected and previously unknown reaction sequence in the interactions of the acyl halides with nitrosobenzenes, which involves carbon-nitrogen bond formation followed by heterolytic nitrogen-chlorine bond cleavage giving the corresponding unsubstituted N-phenylalkylhydroxamic acids (or N-phenylarylhydroxamic acids) and chlorine as the products has been observed. The kinetic and other evidence obtained suggest that the carbon-nitrogen bond formation is the consequence of a nucleophilic interaction of an N-phenylchlorohydroxylamine intermediate, formed in the first reaction step, with the acyl halide in the second step of the complex sequence, which leads to an N-acyl-N-chlorophenylhydroxylamine cation intermediate. The key reaction step involves the interaction of an N-acyl-N-chlorophenylhydroxylamine cation intermediate with chloride ion, which leads to the N-Cl heterolytic bond cleavage and the final formation of the hydroxamic group and a molecule of chlorine.
- Vinkovi? Vr?ek, Ivana,Pilepi?, Viktor,Ur?i?, Stanko
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Read Online
- Transketolase Catalyzed Synthesis of N-Aryl Hydroxamic Acids
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Hydroxamic acids are metal-chelating compounds that show important biological activity including anti-tumor effects. We have recently engineered the transketolase from Geobacillus stearothermopilus (TKgst) to convert benzaldehyde as a non-natur
- Fúster Fernández, Inés,Hecquet, Laurence,Fessner, Wolf-Dieter
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supporting information
p. 612 - 621
(2021/12/08)
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- Catalyst-free generation of acyl radicals induced by visible light in water to construct C-N bonds
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We describe herein a catalyst-free and redox-neutral photochemical strategy for the direct generation of acyl radicals from α-diketones, and its selective conversion of nitrosoarenes to hydroxyamides or amides with AcOH or NaCl as an additive. The reaction was carried out under mild conditions in water with purple LEDs as the light source. A broad scope of substrates was demonstrated. Mechanistic experiments indicate that α-diketones cleave to give acyl radicals, with hydroxyamides being further reduced to amides.
- Ran, Maogang,He, Jiaxin,Yan, Boyu,Liu, Wenbo,Li, Yi,Fu, Yunfen,Li, Chao-Jun,Yao, Qiuli
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supporting information
p. 1970 - 1975
(2021/03/16)
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- Hydroxamic Acids as Chemoselective (ortho-Amino)arylation Reagents via Sigmatropic Rearrangement
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The use of readily available hydroxamic acids as reagents for the chemoselective (ortho-amino)arylation of amides is described. This reaction proceeds under metal-free, mild conditions, displays a very broad scope, and constitutes a direct approach for the metal-free attachment of aniline residues to carbonyl derivatives.
- Shaaban, Saad,Tona, Veronica,Peng, Bo,Maulide, Nuno
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supporting information
p. 10938 - 10941
(2017/08/30)
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- TRIFLUOROMETHOXYLATION OF ARENES VIA INTRAMOLECULAR TRIFLUOROMETHOXY GROUP MIGRATION
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The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: (I), wherein A is an aryl or heteroaryl, each with or without subsutitution; and R1 is -H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), - (alkylaryl), - (alkylheteroaryl), -NH-(alkyl), -N(alkyl)2, -NH-(alkenyl), -NH-(alkynyl) -NH-(aryl), -NH-(heteroaryl), -O-(alkyl), -O-(alkenyl), -O-(alkynyl), -O-(aryl), -O-(heteroaryl), -S-(alkyl), -S- (alkenyl), -S-(alkynyl), -S-(aryl), or -S-(heteroaryl), comprising: (a) reacting a compound having the structure: (II), with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: (III); and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: (I).
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Page/Page column 70-71
(2016/05/02)
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- Mechanistic studies on intramolecular C-H trifluoromethoxylation of (hetero)arenes via OCF3-migration
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The one-pot two-step intramolecular aryl and heteroaryl C-H trifluoromethoxylation recently reported by our group has provided a general, scalable, and operationally simple approach to access a wide range of unprecedented and valuable OCF3-containing building blocks. Herein we describe our investigations to elucidate its reaction mechanism. Experimental data indicate that the O-trifluoromethylation of N-(hetero)aryl-N-hydroxylamine derivatives is a radical process, whereas the OCF3-migration step proceeds via a heterolytic cleavage of the N-OCF3 bond followed by rapid recombination of a short-lived ion pair. Computational studies further support the proposed ion pair reaction pathway for the OCF3-migration process. We hope that the current study would provide useful insights for the development of new transformations using versatile N-(hetero)aryl-N-hydroxylamine synthons.
- Lee, Katarzyna N.,Lei, Zhen,Morales-Rivera, Cristian A.,Liu, Peng,Ngai, Ming-Yu
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supporting information
p. 5599 - 5605
(2016/07/06)
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- Rhodium(III)-catalyzed internal oxidative coupling of N-hydroxyanilides with alkenes via C-H activation
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Abstract Described herein is an efficient new method for ortho-olefination of anilides in the presence of AgSbF6 and NaOAc via rhodium(III)-catalyzed internal oxidative C-H bond activation based on hydroxyl as directing and oxidative group. A range of alkenes and functional groups on acetanilides is supported and a possible mechanism is proposed according to the experimental results.
- Wen, Jing,Wu, An,Chen, Pei,Zhu, Jin
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supporting information
p. 5282 - 5286
(2015/08/26)
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- Trifluoromethoxylation of arenes: Synthesis of ortho- Trifluoromethoxylated aniline derivatives by OCF3 migration
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Aryl trifluoromethoxylation by a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxylamine derivatives and intramolecular OCF3 migration is presented. This protocol allows easy access to a wide range of synthetically useful ortho-OCF3 aniline derivatives. In addition, it utilizes bench-stable reagents, is operationally simple, shows high functional-group tolerance, and is amenable to gram-scale as well as one-pot synthesis.Areaction mechanism of a heterolytic cleavage of the N-OCF3 bond followed by recombination of the resulting nitrenium ion and trifluoromethoxide is proposed for the OCF3-migration reaction.
- Hojczyk, Katarzyna N.,Feng, Pengju,Zhan, Chengbo,Ngai, Ming-Yu
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supporting information
p. 14559 - 14563
(2015/01/09)
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- Reaction of aromatic nitroso compounds with chemical models of 'thiamine active aldehyde'
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Aromatic nitroso compounds in the presence of base and 2-(α-hydroxyalkyl)-3,4-dimethylthiazolium trifluoromethanesulfonate and related salts furnish in variable yields O- and N-acyl-aryl hydroxylamines and 3,4-dimethylthiazolium trifluoromethanesulfonate. A primary kinetic isotope effect of 4.9, obtained for the appropriate 2α-deuterated thiazolium salt, points to the C2α-H bond cleavage as the rate determining step. Radical species detected by ESR were unambiguously identified as phenylhydronitroxide, but attempted trapping of the corresponding C-heterocyclic radicals by TEMPO was not successful, and substrates incorporating a potential cyclopropyl radical clock gave products with the cyclopropyl ring intact. Theoretical calculations revealed a large activation energy for such reaction, which thus cannot per se exclude the intervention of such radical species. Evidence for the likely operation of two concurrent mechanisms, a radical and a preponderant ionic pathway, involving the conjugate base of the thiazolium salt, as the chemical model for 'active thiamine', and ArNO is presented for the formation of the products of the reaction.
- Ferreira, Luísa M.,Marques, M. Manuel B.,Glória, Paulo M.C.,Chaves, Humberto T.,Franco, Jo?o-Pedro P.,Mourato, Isabel,Antunes, José-Rafael T.,Rzepa, Henry S.,Lobo, Ana M.,Prabhakar, Sundaresan
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p. 7759 - 7770
(2008/12/21)
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- An unusual case of carbon-nitrogen bond formation. Reactivity of a C-nitroso group toward acyl chlorides
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Acyl chlorides react with nitrosobenzene in 99.9% acetonitrile and in the presence of catalytic amounts of HCl giving the corresponding N-p-chlorophenylhydroxamic acids. The spectroscopic and kinetic evidence obtained indicates that the reaction is initia
- Pilepi?, Viktor,Lovrek, Monika,Viki?-Topi?, Dra?en,Ur?i?, Stanko
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p. 8519 - 8522
(2007/10/03)
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- N-Arylhydroxamic Acids: Reaction of Nitroso Aromatics with α-Oxo Acids
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A practical and high-yielding route to N-arylhydroxamic acids from nitroso aromatics and α-oxo acids 1a-d is desctibed.In aqueous and acetic acid containing media, the reactions exhibit second-order reaction kinetics overall.In the aqueous medium, the rate constant (kobsd) for N-phenylacetohydroxamic acid (8b) formation increased with increasing +>, though there were some side pathways involving azoxybenzene formation.In general, kobsd for the reaction in the acetic acid containing medium was about one-tenth of that in HCl at pH 0.6.On a preparative scale, acetic acid is better than HCl, in that both reactants showed sufficient solubilities in acetic acid for a high reaction velocity and no side reaction was detected.With this method, the proximate carcinogens, N-(4-biphenylyl)acetohydroxamic acid (12b) and N-(2-fluorenyl)acetohydroxamic acid (13b), could be easily prepared.Under both conditions, the order of kobsd for the reactions of nitrosobenzene (2) with α-oxo acids 1a-d was glyoxylic (1a) > pyruvic (1b) 2-oxobutyric (1c) > benzoylformic (1d) acid.For the reactions of substituted nitrosobenzenes 3-6 with pyruvic acid (1b), the order of kobsd was p-phenyl (6) > unsubstituted (2) > p-chloro (5) > m-chloro (4) >> o-chloro (3) nitrosobenzene.The negative Hammett reaction constant value obtained indicates that an electron-donating substituent is preferable for the reaction.The reaction mechanism and other factors affecting N-arylhydroxamic acid formation are also descussed.
- Sakamoto, Yasuko,Yoshioka, Tadao,Uematsu, Takayoshi
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p. 4449 - 4453
(2007/10/02)
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- Solvolysis of N-Sulfonoxyacetanilides in Aqueous and Alcohol Solutions: Generation of Electrophilic Species
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A series of ring-substituted N-sulfonoxyacetanilides (1a-f) were synthesized, and their solvolysis reactions in aqueous and alcohol solvents were studied.These compounds serve as models for the carcinogenic metabolites of polynuclear aromatic amides.Kinetic and product studies yielded evidence for solvolysis via N-O bond cleavage in aqueous solution with generation of tight ion pairs and solvent-separated ion pairs.The tight ion pairs, which cannot be trapped by nucleophiles or reducing agents, give rise to o-sulfonoxyacetanilides, while the solvent-separated ion pairs can be trapped by these reagents to yield ring-substituted compounds and reduction products.The para-substituted N-sulfonoxyacetanilides yield substantial amounts of highly electrophilic p-benzoquinone imine derivatives such as 10 during solvolysis in aqueous media.In ethanol these esters solvolyze exclusively via S-O bond cleavage with apparent production of SO3.This study demonstrates that electrophilic species other than nitrenium ions can be generated during the solvolysis of N-sulfonoxy-N-arylamides.These species may play a role in the in vivo activity of these metabolites.
- Novak, Michael,Pelecanou, Maria,Roy, Ajit K.,Andronico, Anthony F.,Plourde, Francine M.,et al.
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p. 5623 - 5631
(2007/10/02)
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- Kinetics, mechanism, and thermodynamics of aqueous iron(III) chelation and dissociation: Influence of carbon and nitrogen substituents in hydroxamic acid ligands
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Thermodynamic and kinetic studies were performed to investigate the complexation of aqueous high-spin iron(III) by 12 bidentate hydroxamic acids, R1C(O)N(OH)R2, (R1 = CH3, C6H5, 4-NO2C6H4, 4-CH3C6H4, 4-CH3OC6H4; R2 = CH3, C6H5, 4-CH3C6H4, 4-ClC6H4, 4-IC6H4, 3-IC6H4, 4-NCC6H4, 3-NCC6H4, 4-CH3C(O)C6H4), in acid medium. Both complex formation and dissociation (aquation) reactions were investigated by stopped-flow relaxation methods over a range of [H+] and temperatures. A two-parallel-path mechanism without proton ambiguity is established for the reaction of Fe(H2O)63+ and Fe(H2O)5OH2+ with R1C(O)N(OH)R2 to form Fe(H2O)4(R1C(O)N(O)R2)2+. Equilibrium quotients, ΔH° and ΔS° values, rate constants, and ΔH≠ and ΔS≠ values for both reaction paths in the forward and reverse directions are reported. ΔH≠ and ΔS≠ values are found to be linearly related and compensating. On the basis of an analysis of the equilibrium quotients, rate constants, and activation parameters for the reaction in both directions, an associative interchange (Ia) mechanism is proposed for hydroxamic acid ligand substitution at Fe(H2O)63+. Similar trends for these parameters are observed for the reaction at Fe(H2O)5OH2+, suggesting an associative interchange character for this reaction path also. However, coordinated water dissociation appears to be dominant, and some associative character for this path may be the result of H-bonding interactions between the undissociated hydroxamic acid and coordinated -OH. Electron-donating and -withdrawing R1 and R2 substituents were selected in order to determine the relative influence of the C and N substituent on the hydroxamic acid and to determine the optimum hydroxamic acid structure for kinetic and thermodynamic stability of the iron(III) chelate. Kinetic and thermodynamic chelate stabilization are enhanced by increasing electron density on the carbonyl oxygen atom, which is promoted by electron donors in the R1 position and delocalization of the N atom lone pair of electrons into the C-N bond. The influence of the R2 substituent appears to be dominant with an electron-releasing alkyl group as the preferred R2 substituent for kinetic and thermodynamic stability. The optimum hydroxamic acid ligand for kinetic and thermodynamic stability of the iron(III) chelate was found to be 4-CH3OC6H4C(O)N(OH)CH3.
- Brink, Christina Poth,Crumbliss, Alvin L.
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p. 4708 - 4718
(2008/10/08)
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- Temperature-Dependent Acid Dissociation Constants (Ka, ΔHa, ΔSa) for a Series of Nitrogen-Substituted Hydroxamic Acids in Aqueous Solution
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The acid dissociation constants (Ka) of a series of eight substituted N-phenylacetohydroxamic acids, CH3C-(O)N(OH)C6H4X (X=H, 4-CH3, 4-Cl, 4-I, 3-I, 3-CN, 4-CN, 4-C(O)CH3), have been determined in aqueous solution (I=2.0) for a range of temperatures.The pKa data at 25 deg C exhibit a small variation with the substituent X in the direction expected according to their Hammett substituent constants (ρ ca. 0.1).These small variations in pKa values are due to compensating trends in ΔHa and ΔSa, which show significant variation with substituent.These results are discussed in terms of the substituent's influence on hydroxamate anion-solvent interactions and the relative influence on pKa of a substituted phenyl group attached to the C or N end of the hydroxamate moiety.
- Poth Brink, Christina,Crumbliss, Alvin L.
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p. 1171 - 1176
(2007/10/02)
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