- The Solvolysis of N-Acetoxy-2-acetylaminofluorene and N-Acetoxy-4-acetylaminobiphenyl: Delicate Balance between Nitrenium Ion Formation and Hydrolysis
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The solvolysis of N-acetoxy-2-acetylaminofluorene in aqueous acetone at neutral pH proceeds exclusively with nitrenium ion formation while under the same conditions, the 4-aminobiphenyl analogue undergoes exclusive acyl-oxygen scission.
- Underwood, Graham R.,Kirsch, Robert B.
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Read Online
- Reduction of Nitrosobenzene by 2-(α-Hydroxyethyl)-3,4-dimethylthiazolium Salts
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Nitrosobenzene in a basic medium is reduced by 2-(α-hydroxyethyl)- or 2-(α-hydroxybenzyl)-3,4-dimethylthiazolium trifluoromethanesulfonate to yield the intermediate hydroxylamine and 2-acyl-3,4-dimethylthiazolium trifluoromethanesulfonate, with acylation of the former by the latter giving the final products.
- Ferreira, Luisa M.,Chaves, Humberto T.,Lobo, Ana M.,Prabhakar, Sundaresan,Rzepa, Henry S.
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Read Online
- Enzymatic and mechanistic studies on the formation of N- phenylglycolohydroxamic acid from nitrosobenzene and pyruvate in spinach leaf homogenate
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The biotransformation mechanism of an unknown metabolite formed enzymatically from nitrosobenzene (NOB) and pyruvate in spinach (Spinacea oleracea L.) was investigated using spinach leaf homogenate. The unknown metabolite was identified as N-phenylglycolo
- Tatsunami, Ryosuke,Yoshioka, Tadao
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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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- Redox-Neutral Selenium-Catalysed Isomerisation of para-Hydroxamic Acids into para-Aminophenols
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A selenium-catalysed para-hydroxylation of N-aryl-hydroxamic acids is reported. Mechanistically, the reaction comprises an N?O bond cleavage and consecutive selenium-induced [2,3]-rearrangement to deliver para-hydroxyaniline derivatives. The mechanism is studied through both 18O-crossover experiments as well as quantum chemical calculations. This redox-neutral transformation provides an unconventional synthetic approach to para-aminophenols.
- Chuang, Hsiang-Yu,Schupp, Manuel,Meyrelles, Ricardo,Maryasin, Boris,Maulide, Nuno
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supporting information
p. 13778 - 13782
(2021/03/31)
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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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- Synthesis method of N-acylhydroxylamine
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The invention relates to a synthesis method of N-acylhydroxylamine, which comprises the following steps: starting from o-diketone and a nitroso compound, and adding an acid thereby efficiently obtaining the structure of N-acylhydroxylamine under the irradiation of visible light or ultraviolet light, wherein a part of the obtained product is an important biomedical chemical intermediate. Accordingto the method, the o-diketone and the nitroso compound which are cheap and easy to obtain are used as raw materials, only visible light or ultraviolet light irradiation is needed, cheap acid is addedin the reaction process, a catalyst or a metal compound is not needed, and only water can be used as a solvent in mass production. The whole production process is environmentally friendly, economical,efficient and low in cost, and has very remarkable advantages compared with the conventional production process.
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Paragraph 0020-0040; 0062-0076
(2020/09/30)
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- Regioselective installation of fluorosulfate (-OSO2F) functionality into aromatic C(sp2)-H bonds for the construction of: Para-amino-arylfluorosulfates
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The construction of para-amino-arylfluorosulfates was achieved through installation of fluorosulfate (-OSO2F) functionality into aromatic C(sp2)-H bonds by the reaction of N-arylhydroxylamine with sulfuryl fluoride (SO2Fs
- Fang, Wan-Yin,Zha, Gao-Feng,Zhao, Chuang,Qin, Hua-Li
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supporting information
p. 6273 - 6276
(2019/06/07)
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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 67-68
(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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- Synthesis of site-specific damaged DNA strands by 8-(acetylarylamino)- 2′-deoxyguanosine adducts and effects on various DNA polymerases
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Beside the predominately found 8-(arylamino)-2′-dG, 8-(acetylarylamino) damages within DNA-strands may also play an important role in the induction of chemical carcinogenesis. A synthesis pathway leading to these 8-(acetylarylamino)-dG adducts using different aromatic amines has been optimized. The 8-modified dGs were converted into the corresponding phosphoramidites and site-specifically incorporated into different oligonucleotides leading to DNA strands. Lesion-bearing hybrids of these damaged DNA-strands with complementary oligonucleotides were used to study their melting properties and their circular dichroism spectra. It was shown that no EcoRI restriction took place with the damage inside the cleavage site. Finally, three different DNA polymerases were used for primer extension studies. C8-NAc-Arylamine adducts of 2′-deoxyguanosine with various aromatic amines were synthesized by using cross-coupling reactions and converted into 3′-phosphoramidites. Site-specific damaged NarI-, EcoRI- and 20mer-oligonucleotides were prepared by automated DNA-synthesis. Biophysical properties, restriction endonuclease studies and DNA-polymerase assays were performed. Copyright
- Krueger, Sarah,Meier, Chris
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p. 1158 - 1169
(2013/04/10)
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- Interrupted fischer-indole intermediates via oxyarylation of alkenyl boronic acids
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The oxyarylation of alkenyl boronic acids with N-arylbenzhydroxamic acids has been achieved under both copper-mediated and copper-catalyzed conditions to provide access to interrupted Fischer-indole intermediates. This transformation is believed to proceed through a copper-promoted C-O bond forming event followed by a [3,3] rearrangement. The scope of the method is described and mechanistic experiments are discussed.
- Wang, Heng-Yen,Anderson, Laura L.
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supporting information
p. 3362 - 3365
(2013/07/26)
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- DXP synthase-catalyzed c-n bond formation: Nitroso substrate specificity studies guide selective inhibitor design
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1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the first step in the nonmammalian isoprenoid biosynthetic pathway to form DXP from pyruvate and D-glyceraldehyde 3-phosphate (D-GAP) in a thiamin diphosphate-dependent manner. Its unique structure and mechanism distinguish DXP synthase from its homologues and suggest that it should be pursued as an anti-infective drug target. However, few reports describe any development of selective inhibitors of this enzyme. Here, we reveal that DXP synthase catalyzes C-N bond formation and exploit aromatic nitroso substrates as active site probes. Substrate specificity studies reveal a high affinity of DXP synthase for aromatic nitroso substrates compared to the related ThDP-dependent enzyme pyruvate dehydrogenase (PDH). Results from inhibition and mutagenesis studies indicate that nitroso substrates bind to E. coli DXP synthase in a manner distinct from that of D-GAP. Our results suggest that the incorporation of aryl acceptor substrate mimics into unnatural bisubstrate analogues will impart selectivity to DXP synthase inhibitors. As a proof of concept, we show selective inhibition of DXP synthase by benzylacetylphosphonate (BnAP).
- Morris, Francine,Vierling, Ryan,Boucher, Lauren,Bosch, Juergen,Freel Meyers, Caren L.
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p. 1309 - 1315
(2013/08/23)
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- Photoacid generators (PAGs) based on N-acyl-N-phenylhydroxylamines for carboxylic and sulfonic acids
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Simple and efficient photoacid generators (PAGs) for carboxylic and sulfonic acids based on N-acyl-N-phenylhydroxylamines have been demonstrated. Irradiation of o-carboxylates and thermally rearranged o-arenesulfonates of N-acyl-N-phenylhydroxylamines using UV light (≥254 nm) in aqueous methanolic solution resulted in efficient generation of carboxylic and sulfonic acids, respectively. The carboxylic acid generation ability of N-acyl-N- phenylhydroxylamines was found to be dependent on their N-acyl substituents. Further, polymer bearing o-arenesulfonates of N-acyl-N-phenylhydroxylamine was synthesized and demonstrated as PAG for sulfonic acids.
- Ikbal, Mohammed,Jana, Avijit,Singh, N.D. Pradeep,Banerjee, Rakesh,Dhara, Dibakar
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scheme or table
p. 3733 - 3742
(2011/06/21)
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- Benzaldehyde lyase-catalyzed direct amidation of aldehydes with nitroso compounds
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Benzaldehyde lyase from the Pseudomonas fluorescens catalyzes the reaction of aromatic aldehydes with nitroso compounds and furnishes N-arylhydroxamic acids in high yields. Aromatic aldehydes and benzoins are converted into enamine-carbanion-like intermediates prior to their reaction with nitroso compounds. The kinetic resolution of rac-2-hydroxy-1,2-diphenylethanones furnished (S)-benzoins and arylhydroxamic acids with high enantioselectivities and conversions.
- Ayhan, Peruze,Demir, Ayhan S.
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supporting information; experimental part
p. 624 - 629
(2011/04/24)
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- Laccase Variants
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The present invention relates to variants of a parent laccase. The present invention also relates to polynucleotides encoding the variant laccases and to nucleic acid constructs, vectors, and host cells comprising the polynucleotides, and methods of using the variant enzymes.
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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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- A new short and efficient synthetic route to C8-N-acetylarylamine 2′-deoxyguanosine phosphoramidites
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In addition to their C8-NH-arylamine-dG counterparts, C8-N-acetylarylamine adducts of 2′-deoxyguanosine (2′-dG) play an important role in the possible induction of chemical carcinogenesis. A new synthetic pathway of this adduct type using different aromatic amines has been developed following most probably an electrophilic amination reaction. These adducts can be converted into the corresponding phosphoramidites for incorporation into oligonucleotides. Georg Thieme Verlag Stuttgart.
- Boege, Nicolas,Krueger, Sarah,Schroeder, Marcus,Meier, Chris
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p. 3907 - 3914
(2008/09/18)
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- 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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p. 699 - 702
(2007/10/03)
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- ANTIMICROBIAL COMPOSITION CONTAINING AN OXIDOREDUCTASE AND AN ENHANCER OF THER N-HYDROXYANILIDE-TYPE
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The present invention relates to an enzymatic composition capable of killing or inhibiting microbial cells or micro-organisms, e.g. in laundry, on hard surfaces, in water systems, on skin, on teeth or on mucous membranes. The present invention also relate
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- Salt effects and kinetic isotope effects interconnected. Evidence for the involvement of chloride ion in the C-H bond breaking in aqueous solution?
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An unusual change of the primary kinetic isotope effect in the formation of hydroxamic acid from nitrosobenzene and formaldehyde in mixed solvents on addition of very small quantities of salts and at higher salt concentration in water was observed and interpreted in terms of ion pairing and hydrogen bonding phenomena in the reaction.
- Ursic, Stanko,Lovrek, Monika,Vrecek, Ivana Vinkovic,Pilepic, Viktor
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p. 1295 - 1297
(2007/10/03)
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- Reactions of the Carbonyl Group with Nitroso Compounds. The Cases of Pyruvic Acid and Acetaldehyde
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Pyruvic acid and acetaldehyde react with substituted nitrosobenzenes to give the corresponding N-phenylacetohydroxamic acids.A mechanism for these reactions involving three sequential steps is proposed.The first step is the nucleophilic attack of the nitr
- Ursic, Stanko,Pilepic, Viktor,Vrcek, Valerije,Gabricevic, Mario,Zorc, Branka
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p. 509 - 514
(2007/10/02)
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- A Novel Conversion of N-Aryl-N-methoxyamides into N-Arylhydroxamic Acids Using AlCl3/Thiol System
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Treatment of N-aryl-N-methoxyamides with AlCl3 in EtSH (or Me2S) generates the corresponding N-aryl-N-hydroxyamides in high yields.
- Kawase, Masami,Kitamura, Takahiro,Shimada, Masahiro,Kikugawa, Yasuo
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p. 887 - 892
(2007/10/02)
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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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- Glycosides of N-Hydroxy-N-arylamine Derivatives. Part 1. Synthesis and Mutagenicity of O-Glycosides of N-Hydroxy-N-arylamines and their Acetohydroxamic Acids
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N-Acetyl-N-arylamino β-D-glucopyranosides (7a-d) were synthesized by the orthoester glycosylation method via N-arylamino β-D-glucopyranosides (6a-d), and the N-acetyl amides, having an N-O-C-1 linkage in their molecules, were characterized by chemical, enzymatic, and spectral analyses.In the mutation assay using Salmonella typhimurium TA100 strain with or without various intracellular fractions of guinea pig liver, these glucosides (7a-d) were non-mutagenic per se, but showed mutagenic activity in the presence of the post-mitochondrial supernatant (S9) or the microsomal fraction (Ms), except for the glucoside (7a).Of the glucosides (7b-d), the compounds having fewer chlorine atoms were more effective in inducing mutations than were those having multiple chlorines.No mutagenic activity was observed in the presence of the soluble supernatant fraction (S10.5).The mutagenecity of the glucosides (7b-d) seemed to be due to the corresponding N-deacetylated compounds (6b-d) formed through hydrolysis by a microsomal deacetylase(s).The pathway of the metabolic activation of the glucosides (7b-d) is discussed.
- Yoshioka, Tadao,Uematsu, Takayoshi
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p. 1261 - 1270
(2007/10/02)
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- NAD(P)H and Acetyl-CoA Models: Part I - Reaction of Nitrosobenzene with 1,1'-Diacetyl-1,1',4,4'-tetrahydro-4,4'-bipyridine
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In vivo metabolic conditions of coenzymes NAD(P)H and acetyl-CoA may be simulated in 1,1'-diacetyl-1,1',4,4'-tetrahydro-4,4'-bipyridine (DTB) loosing hydride ion with concomitant loss of acetyl cation.This is illustrated by the formation of almost same products on treatment of nitrosobenzene with DTB as formed in vivo.The simultaneous loss of hydride and acetyl cation by DTB converts nitrosobenzene to activated labile intermediate O-acetylphenylhydroxylamine (12) which has been considered responsible for the origin of majority of products.
- Juneja, T. R.,Ojha, Anil,Gupta, R. L.
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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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- Novel Reactions: Part I - Facile Synthesis of Substituted ortho-Chloranilines from Nitrobenzene Derivatives
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N-Substituted benzo and acetohydroxamic acids (5), prepared from N-arylhydroxylamines and benzoyl or acetyl chloride, react readily with thionyl chloride at low temperature to give ortho-chloroanilide derivatives (6) in good yield.The latter (6) on hydrolysis give ortho-chloroanilines (10).Since the N-arylhydroxylamines are obtained from nitroarenes by partial reduction, the overall reaction amounts to the preparation of 10 from nitroarenes.
- Ayyangar, N. R.,Kalkote, U. R.,Nikrad, P. V.
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p. 872 - 877
(2007/10/02)
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- Arylhydroxamic acid N,O-acyltransferase substrates. Acetyl transfer and electrophile generating activity of N-hydroxy-N-(4-alkenyl-, and 4-cyclohexylphenyl)acetamides
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Arylhydroxamic acid N,O-acyltransferase (AHAT) is an enzyme system that is capable of converting many N-arylhydroxamic acids into reactive electrophilic species. As part of an investigation into the influence of the structure of the aryl group upon the ability of N-arylhydroxamic acids to serve as substrates for AHAT, a series of N-hydroxy-N-(4-alkyl-, 4-alkenyl-, and 4-cyclohexylphenyl) acetamides was prepared and evaluated in vitro with partially purified rat and hamster hepatic AHAT. The nature of the 4-substituent markedly influenced the ability of the hydroxamic acids to serve as acetyl donors in the AHAT-catalyzed transacetylation of 4-aminoazobenzene (AAB). As the length of the 4-substituent was increased from methyl to pentyl, the compounds became increasingly more effective substrates. The compounds containing vinyl, propenyl, and 2-methylpropenyl 4-substituents were more effective acetyl donors than the corresponding compounds containing saturated 4-substituents. The three most effective AHAT substrates in the AAB transacetylation assay were N-hydroxy-N-(4-pentylphenyl)- (7), N-hydroxy-N-(4-propenylphenyl)- (10), and N-hydroxy-N-[4-(2-methylpropenyl)phenyl]acetamide (11), each of which was approximately as active as the standard compound, N-hydroxy-4-acetamidobiphenyl (1), with rat hepatic AHAT and approximately 60% as active as 1 with hamster hepatic AHAT. Both 1 and N-hydroxyl-N-(4-cyclohexylphenyl)acetamide (8) were activated by hamster hepatic AHAT to yield electrophilic intermediates that formed adducts with 2-mercaptoethanol. The 2-mercaptoethanol adducts were characterized by mass spectrometry and were identified as 4-phenyl-2-[(2-hydroxyethyl)thio]aniline (22) and 4-cyclohexyl-2-[(2-hydroxyethyl)thio]aniline (21). The structure of compounds 21 and 22 were confirmed by an unambiguous chemical synthesis. Both compounds 1 and 8 irreversibly inactivated hamster hepatic AHAT by a time-dependent process. The results of the inactivation experiments confirmed that 1 inactivates AHAT primarily via a suicide substrate mechanism and revealed that 8 inactivates the enzyme by a process consisting primarily of a pathway in which electrophiles are released into the medium and subsequently react with nucleophiles present on AHAT.
- Mangold,Hanna
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p. 630 - 638
(2007/10/02)
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- Meldrum's Acid in Organic Synthesis. VI. Synthesis of 2-Substituted Indoles from Acyl Meldrum's Acids and Phenylhydroxylamine via Sigmatropic Rearrangement
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Phenylhydroxylamine (13) oxalate was quite easily acylacetylated by heating with an equimolar amount of acyl Meldrum's acid (4) in acetonitrile to give an N-acylacetylphenylhydroxylamine (14) in high yield.When 14 was treated with another equimolar amount of the same 4 in refluxing toluene, a series of reactions, O-acylacetylation, 1-aza-1'-oxasigmatropic rearrangement, decarboxylation, dehydrative cyclization, and deacylation, occured consecutively to give a 2-substituted indole (16) in fair yield, though sometimes accompanied by the formation of a 5-substituted 4-isoxazolin-3-one (17).N-Benzoyl, N-acetyl, and N-benzyloxycarbonyl derivatives of phenylhydroxylamine (18) were treated with phenylacetyl Meldrum's acid (4i) in refluxing benzene containing copper powder to give readily rearranged ortho alkylation products (19), which were converted to the corresponding N-acyl-2-benzylindoles (20) by treatment with hydrochloric acid in boiling ethanol or with anhydrous p-toluenesulfonic acid in benzene at room temperature.Keywords - acyl Meldrum's acid; phenylhydroxylamine; N-acylacetylphenylhydroxylamine; 2-substituted indole; 1-aza-1'-oxasigmatropic rearrangement; acid-catalyzed cyclization
- Mohri, Kunihiko,Oikawa, Yuji,Hirao, Ken-ichi,Yonemitsu, Osamu
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p. 3097 - 3105
(2007/10/02)
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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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- Acid Dissociation Constants (Ka) and Their Temperature Dependencies (ΔHa, ΔSa) for a Series of Carbon- and Nitrogen-Substituted Hydroxamic Acids in Aqueous Solution
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The acid dissociation constants (Ka) of a series of six C- and N-substituted hydroxamic acids, R1C(O)N(OH)R2 (R1 = CH3, C6H5; R2 = H, CH3, C6H5), have been determined in aqueous solution (I = 2.0) for
- Monzyk, Bruce,Crumbliss, Alvin L.
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p. 4670 - 4675
(2007/10/02)
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