2318-82-3

We report a Cu(II)-catalyzed C-H amidation/cyclization of azomethine imines with dioxazolones as acyl nitrene transfer reagents under additive-and ligand-free conditions. An array of 1,2,4-triazolo[1,5-a]pyridine derivatives were afforded in moderate to good yields with excellent functional group tolerance. In addition, scale-up reaction and photoluminescence properties were discussed.

An cascade intramolecular 5-exo-dig cyclization of N-(2-iodophenyl)propiolamides and sequential amination/etherification (with N-hydroxybenzamides, phenyl hydroxycarbamate) protocol for the synthesis of amino- and phenoxy-substituted 3-methyleneindolinones using unexpensive Pd(PPh3)4 as catalyst has been developed. The protocol enables the assembly of structurally important oxindole cores featuring moderate functional group tolerance (particularly the halo group), affording a broad spectrum of products with diverse substituents in good to excellent yields. (Figure presented.).

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C-H bond amidation of unactivated alkenes. Due to the preference for five-membered nickelacycle formation, the chain-walking isomerization initiated by the NiH insertion to an alkene can be terminated at the γ-methylene site remote from the alkene moiety. By employing 2,9-dibutyl-1,10-phenanthroline as the ligand and dioxazolones as the reagent, the amidation occurs at the γ-C(sp3)-H bonds to afford the amide products in up to 90% yield (>40 examples) with remarkable regioselectivity (up to 24:1 rr).

The acyl nitroso Diels–Alder reaction of 1,3-dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro-induced decomposition could be suppressed in favour of the 1,2-oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3-dienes and hydroxamic acids, giving up to 96 % isolated yield.

A rhodium(III)-based catalytic system has been used to develop a C?H bond activation of benzaldehyde derivatives and subsequent functionalization with dioxazolones in order to afford imides. The importance of the nature of the directing group to perform selectively the aldehydic C?H bond activation has been highlighted. The scope investigation showed that this transformation could be applied to various dioxazolones and many benzaldehyde derivatives as well as an acrolein derivative. Derivatization reactions of the imide products demonstrated the synthetic utility of this rhodium-catalyzed aldehydic C?H amidation.

A highly novel and direct synthesis of benzoxazinones was developed via Cp*Co(III)-catalyzed C–H activation and [3 + 3] annulation between sulfoxonium ylides and dioxazolones. The reaction is conducted under base-free conditions and tolerates various functional groups. Starting from diverse readily available sulfoxonium ylides and dioxazolones, a variety of benzoxazinones could be synthesized in one step in 32%-75% yields.

The N-acyloxyamides were employed as effective N-acyl nitrene precursors in reactions with thioethers under the catalysis of a commercially available Ru(II) complex, from which a variety of sulfimides were synthesized efficiently and mildly. If an allyl group is contained in the thioether precursor, the [2,3]-sigmatropic rearrangement of the sulfimide occurs simultaneously and the N-allyl-N-(thio)amides were obtained as the final products. Preliminary mechanistic studies indicated that the Ru-nitrenoid species should be a key intermediate in the transformation.

An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.

A series of rhodium complexes bearing sterically and electronically tunable cyclopentadienyl ligands, prepared by utilizing Co2(CO)8-mediated [2+2+1] cyclization as a key step, were synthesized. In the presence of 2.5 mol% of CpmRh4, unprecedented enantioselective [4+1] annulation reaction of benzamides and alkenes was achieved with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio-and enantioselectivity (up to 94% yield, 97:3 er). Preliminary mechanistic studies suggest that the reaction involves an oxidative Heck reaction and an intramolecular enantioselective alkene hydroamination reaction.

Hydroxamic acids [R(CO)N(OH)R’] are flexible compounds for organic and inorganic analyses due to their frailer structures compared to the carboxylic acid. The syntheses and characterization of benzohydroxamic acid (BHA), its CH3–, OCH3/su

RhIII-catalyzed C?H functionalization reaction yielding isoindolinones from aryl hydroxamates and ortho-substituted styrenes is reported. The reaction proceeds smoothly under mild conditions at room temperature, and tolerates a range of functional groups. Experimental and computational investigations support that the high regioselectivity observed for these substrates results from the presence of an ortho-substituent embedded in the styrene. The resulting isoindolinones are valuable building blocks for the synthesis of bioactive compounds. They provide easy access to the natural-product-like compounds, isoindolobenzazepines, in a one-pot two-step reaction. Selected isoindolinones inhibited Hedgehog (Hh)-dependent differentiation of multipotent murine mesenchymal progenitor stem cells into osteoblasts.

A cobalt(III)-catalyzed C-8 selective C-H amidation of quinoline N-oxide using dioxazolone as an amidating reagent under mild conditions is disclosed. The reaction proceeds efficiently with excellent functional group compatibility. The utility of the current method is demonstrated by gram scale synthesis of C-8 amide quinoline N-oxide and by converting this amidated product into functionalized quinolines. Furthermore, the developed catalytic method is also applicable for C-7 amidation of N-pyrimidylindolines and ortho-amidation of benzamides.

A novel method for the Rh(III)-catalyzed oxime-directed C-H amidation of indoles with dioxazolones has been developed. This strategy provides an exclusive site selectivity and the directing group can be easily removed. This transformation features a wide substrate scope, good functional group tolerance and excellent yields, and may serve as a significant tool to construct structurally diverse indole derivatives for the screening of potential pharmaceuticals in the future. This journal is

In the present investigation, 6 compounds (E1-E6) were synthesized by reaction of ethyl esters of p-substituted benzoic acid with hydroxylamine. The chemical structures of the synthesized hydroxamic acids were verified on the basis of spectral analysis (IR, 1H NMR, 13C NMR and mass spectra). The benzohydroxamic acids were examined for potential local anesthetic activity using foot withdrawal reflex of the frog and benzocaine was used as standard drug. Compounds were tested at two different solvents; 5 % DMSO and 0.65 % NaOH, each solution was tested at three different concentration levels (40, 100 and 200 μg/mL). Local anesthetic activity of the compounds differed according to the concentration level and selected solvent. Compounds E4 and E5 were found to be the most active and were comparable to the standard drug in tested solvents at all investigated concentrations. All compounds displayed an enhanced activity in the the aqueous basic solutions.

A simple and effective Pd(ii)-catalyzed regioselective C(2)-H arylation of 6,5-fused heterocycles with dioxazolones as a masked ester surrogate under mild conditions is reported. The significance of the arylation is highlighted by the new reactivity demonstrated in dioxazolones via proximal C-H activation of the cyclic carbonate of the hydroxamic acid functionality under protic conditions.

A rhodium-catalyzed cascade reaction of benzoic acids with 1,4,2-dioxazol-5-ones was studied. The carboxyl group enabled a double C-H amidation followed by further intramolecular cyclization to afford 2,5-substituted benzoxazinones, which exhibited aggregation-induced emission (AIE) properties with a promising excited-state intramolecular proton-transfer (ESIPT) phenomenon.

An efficient and convenient cobalt-catalyzed ortho-C(sp2)-H amidation of benzaldehydes employing dioxazolones as the aminating reagent has been developed. The key feature of this protocol is the use of green and economic earth-abundant metals c

The Lossen rearrangement is a classic process for transforming activated hydroxamic acids into isocyanate under basic or thermal conditions. In the current report we disclosed a consecutive Lossen rearrangement/transamidation reaction in which unactivated hydroxamic acids were converted into N-substituted formamides in a one-pot manner under catalyst- and additive-free conditions. One feature of this novel transformation is that the formamide plays triple roles in the reaction by acting as a readily available solvent, a promoter for additive-free Lossen rearrangement, and a source of the formyl group in the final products. Acyl groups other than formyl could also be introduced into the product when changing the solvent to other low molecular weight aliphatic amide derivatives. The solvent-promoted Lossen rearrangement was better understood by DFT calculations, and the intermediacy of isocyanate and amine was supported well by experiments, in which the desired products were obtained in excellent yields under similar conditions. Not only monosubstituted formamides were synthesized from hydroxamic acids, but also N,N-disubstituted formamides were obtained when secondary amines were used as precursors.

An efficient and convenient ligand-free, rhodium-catalyzed ortho-C(sp2)-H amidation of benzaldehydes with dioxazolones using H2O as the key promoter is described. Using this protocol, a wide range of benzaldehyde substrates were selectively amidated in good to excellent yields with broad functional group compatibility. KIE experiments revealed that the C-H bond activation was likely the rate-limiting step. In addition, computational studies indicated that the catalyst precursor interacted with water and dioxazolones to generate the active catalytic species. Notably, the practicality and efficacy of this method were illustrated by a late-stage amidation of an estrone-derived molecule and further transformations of the amidated product.

An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

A one-pot synthesis of primary amines from carboxylic acids through a Lossen rearrangement of hydroxamic acid derivatives, which were in situ generated by the reaction of carboxylic acids with O-trimethylsilylhydroxylamine (NH2OTMS) and carbonyl diimidazole (CDI, 1.5 equiv) in dimethyl sulfoxide at room temperature, has been achieved. This one-pot method could be applied to various carboxylic acids such as aromatic, heteroaromatic, aliphatic, and optically active substrates.

A new class of Weinreb amides has been developed as directing groups for the ruthenium-catalysed regioselective oxidative C?H olefination. The new Weinreb amides successfully inhibit the N?O bond reductive cleavage usually associated with the cationic ruthenium system, thereby keeping intact the synthetic utility of Weinreb amides. Mechanistic studies reveal interesting aspects of the directing group capabilities of Weinreb amides when compared to simple amides of similar structures.

A variety of aromatic and aliphatic hydroxamic acids were converted to the corresponding primary amines via base-mediated rearrangement. This rearrangement could proceed with less than 1 equiv. of K2CO3 in polar solvents under thermal conditions with no external reagents. This rearrangement has several features including no external activating agents needed for promoting the rearrangement, less than one equivalent of a base is sufficient for the reaction, and a clean reaction in which only carbon dioxide is produced as a by-product. A self-propagating mechanism via an isocyanate intermediate is proposed and elementary reaction steps, namely, chain propagation reactions are supported by experiments.

A one-pot oxidative transformation of aldehydes into hydroxamic acids by the use of an aqueous solution of hydroxylamine is reported. The methodology gives high yields and makes use of cheap, abundant and easily available reagents.

The rhodium(III)-catalyzed ortho C-H alkynylation of non-electronically activated arenes is disclosed. This process features a straightforward and highly effective protocol for the synthesis of functionalized alkynes and represents the first example of merging a hypervalent iodine reagent with rhodium(III) catalysis. Notably, this reaction proceeds at room temperature, tolerates a variety of functional groups, and more importantly, exhibits high selectivity for monoalkynylation. Hot rhod: A rhodium-catalyzed, electronically reversed Sonogashira reaction between unbiased arenes and the hypervalent iodine reagent 1 proceeds through C-H activation. This reaction displays excellent functional-group tolerance and high efficiency, and thus opens a new synthetic pathway to access functionalized alkynes. Cp=C5Me5, DCE=1,2-dichloroethane, Piv=pivaloyl, TIPS=triisopropylsilyl.

A Rh(iii)-catalyzed oxidative [4 + 1] cycloaddition of benzohydroxamic acids and α-diazoesters is achieved to afford benzolactams in up to 93% yields. With the N-OAc amido moiety as a directing group, the ortho-C-H is selectively functionalized and the catalytic reaction exhibits excellent tolerance to different functional substituents. A notable rhodacyclic complex is isolated and structurally characterized, suggesting that C-H/N-H cyclometallation is a key step in the catalytic cycle. This journal is the Partner Organisations 2014.

An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.

A diverse collection of 40 derivatives of benzohydroxamic acid (BHAs) of various structural groups were synthesized and tested against hepatitis C virus (HCV) in full-genome replicon assay. Some of these compounds demonstrated an exceptional activity, suppressing viral replication at sub-micromolar concentrations. The compounds were inactive against key viral enzymes NS3, and NS5B in vitro assays, suggesting host cell inhibition target(s). The testing results were consistent with metal coordination by the BHAs hydroxamic group in complex with a target(s). Remarkably, this class of compounds did not suppress poliomyelitis virus (PV) propagation in RD cells indicating a specific antiviral activity of BHAs against HCV.

Reactions of acyl chlorides with hydroxylamine hydrochloride and NaHCO 3 generate the corresponding hydroxamic acid products in ethyl acetate and water at room temperature for 5 min. This is a simple and efficient method to synthesize a wide range of hydroxamic acids from carboxylic acids in excellent yield and high purity after simple post-treatment without chromatographic purification. In this process, the highlights are the simple separation of products and cheaply available reagents.

A new, highly efficient and environmentally benign catalytic variant of the Lossen rearrangement is described. Dimethyl carbonate (DMC) as green activation reagent of hydroxamic acids in presence of catalytic amounts of tertiary amine bases {1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 1,8-biazabicyclo 5.4.0 undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and triethylamine} and small quantities of methanol initiate the rearrangement. Methyl carbamates were obtained in good to moderate yields when aliphatic hydroxamic acids were employed in this catalytic Lossen rearrangement; under the same conditions aromatic hydroxamic acids yielded anilines. Notably, the mixture of DMC/methanol was recycled several times without observing decreased yields, thus minimizing the produced waste. Moreover, several other organic carbonates were successfully employed in the introduced catalytic Lossen rearrangement procedure. Copyright

A simple and convenient procedure has been developed for the synthesis of aromatic amine by a one-pot reaction of aromatic aldoxime with hypervalent iodine(III) reagent [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser's reagent), in an alkaline medium. The aldoxime reacts with Koser's reagent to form an intermediate hydroxamic acid, which then undergoes Lossen type rearrangement to produce the desired amine. Several amines have been prepared which otherwise are difficult to prepare, by the reduction of corresponding nitro compounds. The scopes and limitations of this transformation have been discussed. ARKAT-USA, Inc.

Treatment of various aliphatic and aromatic aldoximes with the hypervalent iodine(iii) reagents (diacetoxyiodo)benzene (DIB) or Koser's reagent [hydroxy(tosyloxy)iodo]benzene (HTIB) gave, respectively, N-acetoxy or N-hydroxy amides in good yields rather t

[Chemical Equation Presented] Carbonyldiimidazole (CDI) was found to mediate the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO 2 being the sole stoichiometric byproduct. Significant for large-scale application, the method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.

Without using activating agents, a variety of free aromatic hydroxamic acids could be rearranged to aromatic amines in the presence of base alone. The Royal Society of Chemistry 2009.

A serles of novel sterol analogs was prepared using nitroso Dlels-Alder reactions with ergosterol. Most cycloaddltlon reactions proceeded In an excellent reglo- and stereoselective fashion. Further N-O bond cleavage of cycloadducts generated compounds with biological activity In PC-3 and MCF-7 cancer cell lines

The synthesis and spectroscopic characterisation of novel mononuclear RuIII(edta)(hydroxamato) complexes of general formula [Ru(H 2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-Cl and 3-Me-phenylhydroxamato), as well as the first example of a Ru III-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)] ·H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear RuIII complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(μ-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with RuIII, are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru III involves initial formation of RuIII-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of RuIII-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids. The Royal Society of Chemistry.

Acid dissociation constant (pKa) of some para-substituted benzohydroxamic, 4-XC6H4CONHOH, and N-methyl para-substituted benzohydroxamic acids, 4- XC6H4CON(OH) CH3, where X = H, CH3, CH3O, NO2, Cl, have been determined spectrophotometrically by nucleophilic substitution reactions of p-nitrophenyl acetate with hydroxamate ions at 27± 0.1°C. All reactions in this study follow pseudo-first order kinetics under condition of excess nucleophile. Good correlation has been observed between pKa and substitutent constants pointing out the validity of the Hammett equation. The kinetics results have been discussed on the basis of pKa and α-effect of hydroxamic acids.

Angeli-Rimini's reaction has been performed for the first time on solid phase. A convenient one-step procedure for the synthesis of hydroxamic acids starting from aldehydes and solid-supported N-hydroxybenzenesulfonamide is reported. The hydroxamates are isolated in good to high yields and purities by simple evaporation of the volatile solvents, after treatment of the crude reaction mixture with sequestering agents.

Syntheses of a series of new C-3′ hydroxamate-substituted cephalosporin derivatives with potent antibacterial and media-dependent anti-TB activity are described. The Royal Society of Chemistry 2006.

As part of our investigations on the structure-reactivity relationships in protonation and hydrolysis of hydroxamic acids, we have now studied a series of 4-substituted benzohydroxamic acids (4-X-C6H4.CO.NH(OH), with X=H, Me, OMe, Cl, Br, F and NO2) in aqueous sulfuric acid. Good correlation was observed pointing out the validity of the Hammett equation. The protonation constant, ionization constant and rate constant for acid- and base-catalysed hydrolysis reactions seems are to be related in a linear free-energy (LEER) fashion.

A new method for the preparation of para-substituted benzohydroxamic acids from para-substituted benzoic acids by using hydroxylamine hydrochloride in the presence of triphenyl phosphine and N-bromosuccinimide under mild basic conditions is described.

In the dye-sensitized photooxygenation of C-aryl nitrones and hydrazones, short-lived peroxidic intermediates are observed. Their characterization, mechanisms leading to them, as well their decomposition pathways are discussed.

Aromatic and aliphatic nitriles are prepared in excellent yield from the corresponding hydroxamic acids and phosphorus tribromide in benzene solution.

The reactions of N-substituted hydroxylamines with alkenals serve as a method for the synthesis of the corresponding 2-substituted 3(5)-hydroxyisoxazolidines.The reaction pathway is determined by the nature of the substituent attached to the nitrogen atom.Ring-chain isomerism has been detected in these newly obtained compounds.