O-methyl Oxime Research Articles

Catalytic Behavior of Cobalt Complexes Bearing Pyridine-Oxime Ligands in Isoprene Polymerization.

Several cobalt(II) complexes Co1-Co3 bearing pyridine-oxime ligands (L1 = pyridine-2-aldoxime for Co1; L2 = 6-methylpyridine-2-aldoxime for Co2; L3 = phenyl-2-pyridylketoxime for Co3) and picolinaldehyde O-methyl oxime (L4)-supported Co4 were synthesized and well characterized by FT-IR, mass spectrum and elemental analysis. The single-crystal X-ray diffraction of complex Co2 reveals that the cobalt center of CoCl2 is coordinated with two 6-methylpyridine-2-aldoxime ligands binding with Npyridine and Noxime atoms, which feature a distorted octahedral structure. These Co complexes Co1-Co4 displayed extremely high activity toward isoprene polymerization upon activation with small amount of AlClEt2 in toluene, giving polyisoprene with high activity up to 16.3 × 105 (mol of Co)-1(h)-1. And, the generated polyisoprene displayed high molecular weights and narrow molecular distribution with a cis-1,4-enriched selectivity. The type of cobalt complexes, cocatalyst and reaction temperature all have effects on the polymerization activity but not on the microstructure of polymer.

Mechanistic insights to define the directional role of hydrogen-bonding network between aryl oximes and propargyl alcohols in Rh(III) catalysis

The mechanism of the Cp*Rh(OAc)2-catalyzed C−H activation/annulation of acetophenone oxime and secondary propargyl alcohol was studied theoretically. Four elementary steps are involved as follows: C−H activation via concerted-metalation-deprotonation (CMD) mechanism, regioselective alkyne insertion, β-OH elimination and metal-free 6π electrocyclization. Importantly, density functional theory (DFT) calculations reveal that β-H elimination is inferior to β-OH elimination that is assisted by the directional hydrogen-bonding network between the two hydroxyl groups of the substrates. This noncovalent interaction also contributes to tuning the regioselectivity of alkyne insertion. Furthermore, the metal-free 6π electrocyclization rather than Rh-assisted cyclization gave the final product, isoquinoline N-oxides. The computationally supported mechanistic features were further validated by exploring substrate effects via replacing acetophenone oxime with O-methyl oxime and secondary propargyl alcohol with allyl alcohol, allenol and tertiary propargyl alcohol, respectively.

Synthesis of (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-ones from (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oximes and iodobenzenes via a palladium-catalyzed dearomative arylation/oxidation reaction.

A new method has been successfully developed that offers a facile and reliable approach for synthesizing (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-one, providing 28 compounds. This optimized process enables efficient preparation of a wide range of compounds using readily available (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oxime and iodobenzene, and provides alternative ideas for the structural modification of benzofuran ketones.

Synthesis, Characterization and Catalytic Property Studies for Isoprene Polymerization of Iron Complexes Bearing Unionized Pyridine-Oxime Ligands.

Iron complexes of the types [Fe(HL)2Cl2] (Fe1: HL1 = pyridine-2-aldoxime; Fe2: HL2 = 6-methylpyridine-2-aldoxime; Fe3: HL3 = phenyl-2-pyridylketoxime; Fe4: HL4 = picolinaldehyde O-methyl oxime) were prepared and characterized by elemental analysis and IR spectroscopy. The crystal structure of Fe2, determined by single-crystal X-ray diffraction, featured a distorted octahedral coordination of the iron center binding with two ligands of HL2. The X-ray structure and infrared spectral data indicated that pyridine-oxime ligands act as unionized bidentate ligand by coordinating with Npyridine and Noxime. The catalytic performance for isoprene polymerization, catalyzed by these pyridine-oxime-ligated iron complexes, was examined. For a binary catalytic system combined with MAO, complexes Fe1, Fe3 and Fe4 were found to be highly active (up to 6.5 × 106 g/mol·h) in cis-1,4-alt-3,4 enchained polymerization, with average molecular weights in the range of 60–653 kg/mol and narrow PDI values of 1.7–3.5, even with very low amounts of MAO (Al/Fe = 5). Upon activation with [Ph3C][B(C6F5)4]/AlR3 for the ternary catalytic system, theses complexes showed extremely high activities, as well about 98% yield after 2 min, to afford cis-1,4-alt-3,4-polyisoprene with a molecular weight of 140–420 kg/mol.

Synthesis and antibacterial and antifungal activities of novel thiochroman-4-one derivatives incorporating oxime ether and 1,3,4-oxadiazole thioether moieties

In this study, 18 novel thiochroman-4-one derivatives incorporating oxime ether and 1,3,4-oxadiazole thioether moieties were synthesized and their structures analyzed by 1H NMR, 13C NMR, and HRMS. Their in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) as well as antifungal activities against Botrytis cinerea (B. cinerea), Verticillium dahliae (V. dahliae), and Fusarium oxysporum (F. oxysporum) were determined. Bioassay results showed that compound 6-chloro-2-(5-(methylthio)-1,3,4-oxadiazol-2-yl)thiochroman-4-one O-methyl oxime (7a) was found to be the most active against Xoo and Xac, with the median effective concentration values (EC50) of 17 and 28 μg/mL, respectively, which were even better than those of Bismerthiazol and Thiodiazole copper. Meanwhile, compound 2-(5-(ethylthio)-1,3,4-oxadiazol-2-yl)-6-methylthiochroman-4-one O-methyl oxime (7j) showed better in vitro antifungal activity against B. cinerea, with the inhibition rate of 79%, than that of Carbendazim. As far as we know, this paper is the first report on the synthesis and antibacterial and antifungal activities of this series of novel thiochroman-4-one derivatives incorporating oxime ether and 1,3,4-oxadiazole thioether moieties.

Iterative synthesis of nitrogen-containing polyketide via oxime intermediates.

Typical polyketides consist of C, H, and O atoms, whereas several types of N-containing polyketides are known to show intriguing properties. Because conventional synthetic approaches for such compounds focus on only specific structures, a more general method is desirable. Here, we have developed an iterative synthesis of nitrogen-containing polyketide. Chain elongation of carboxylic acid via decarboxylative Claisen condensation with malonic acid half thioester was iteratively performed to construct carbon frameworks. β-Keto groups formed by the chain elongation were appropriately converted to O-methyl oximes for incorporation of nitrogen atoms. Cyclization of the resulting oxime intermediates followed by reductive N–O cleavage afforded structurally diverse nitrogen-containing polyketides such as 2-pyridone, 4-aminopyrone, and 4-aminosalicylate. This method was finally applied to the synthesis of (R)-6-aminomellein, which is a nitrogen-substituted derivative of bioactive compound, (R)-6-methoxymellein. The versatility of the present method would enable the synthesis of diverse polyketides with nitrogen functional groups, which can be potentially utilized for the development of novel bioactive compounds.

Design, Synthesis and Fungicidal Activity of New 1,2,4-Triazole Derivatives Containing Oxime Ether and Phenoxyl Pyridinyl Moiety.

A series of novel 1,2,4-triazole derivatives containing oxime ether and phenoxy pyridine moiety were designed and synthesized. The new compounds were identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). Compound (Z)-1-(6-(4-nitrophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-methyl oxime (5a18) was further confirmed by X-ray single crystal diffraction. Their antifungal activities were evaluated against eight phytopathogens. The in vitro bioassays indicated that most of the title compounds displayed moderate to high fungicidal activities. Compound (Z)-1-(6-(4-bromo-2-chlorophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-methyl oxime (5a4) exhibited a broad-spectrum antifungal activities with the EC50 values of 1.59, 0.46, 0.27 and 11.39 mg/L against S. sclerotiorum, P. infestans, R. solani and B. cinerea, respectively. Compound (Z)-1-(6-(2-chlorophenoxy)pyridin-3-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one O-benzyl oxime (5b2) provided the lowest EC50 value of 0.12 mg/L against S. sclerotiorum, which were comparable to the commercialized difenoconazole. Moreover, homologous modeling and molecular docking disclosed possible binding modes of compounds 5a4 and 5b2 with CYP51. This work provided useful guidance for the discovery of new 1,2,4-triazole fungicides.

Palladium-Catalyzed β-Arylation of Cyclic α,β-Unsaturated O-Methyl Oximes with Aryl Iodides.

We report a Pd-catalyzed β-arylation of cyclic α,β-unsaturated O-methyl oximes with aryl iodides. This reaction shows complete regioselectivity and excellent functional group tolerance. β-Arylation of 2-cyclohexen-1-one O-methyl oxime (existing as 2 : 1 E/Z mixture) with certain aryl iodides such as 4-iodoanisole affords only β-arylated (E)-O-methyl oximes.

Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44 b displaying the best in vitro pharmacological profile. Compound 44 b acted as a very potent full PPARγ agonist and a weak partial agonist on the PPARα receptor subtype. Compound 44 b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPARγ modulator (SPPARγM).

A new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antibacterial agents: Design, synthesis and evaluation acting on microbes, DNA, HSA and topoisomerase IV

This work did a new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antimicrobial agents. A class of novel hybrids of quinolone, aminothiazole, piperazine and oxime fragments were designed for the first time, conveniently synthesized as well as characterized by 1H NMR, 13C NMR and HRMS spectra. Biological activity showed that some of the synthesized compounds exhibited good antimicrobial activities in comparison with the reference drugs. Especially, O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively. Further studies indicated that the highly active compound 10b showed low toxicity toward BEAS-2B and A549 cell lines and no obvious propensity to trigger the development of bacterial resistance. Quantum chemical studies have also been conducted and rationally explained the structural features essential for activity. The preliminarily mechanism exploration revealed that compound 10b could not only exert efficient membrane permeability by interfering with the integrity of cells, bind with topoisomerase IV–DNA complex through hydrogen bonds and π-π stacking, but also form a steady biosupramolecular complex by intercalating into DNA to exert the efficient antibacterial activity. The supramolecular interaction between compound 10b and human serum albumin (HSA) was a static quenching, and the binding process was spontaneous, where hydrogen bonds and van der Waals force played vital roles in the supramolecular transportation of the active compound 10b by HSA.

Complementary regioselective synthesis of 3,5-disubstituted isoxazoles from ynones

Two regioselective synthetic routes towards 3,5-disubstituted isoxazoles from ynones are reported. One route takes place via first converting the ynones to ynone O-methyl oximes, followed by a palladium-catalyzed intramolecular cyclization. The other involves the formation of 5-hydroxy-4,5-dihydroisoxazoles by a cyclocondensation between ynones and hydroxylamine, and subsequent acid mediated dehydration. The two routes are not only both highly regioselective, but also complementary to each other as a pair of regioisomeric 3,5-disubstituted isoxazoles are readily prepared from one single ynone substrate. The efficiency of the two routes are further evaluated and demonstrated in the synthesis of three representative 3,5-disubstituted isoxazoles.

A Convergent Continuous Multistep Process for the Preparation of C4-Oxime-Substituted Thiazoles

We report a strategy designed for the rapid and convergent assembly of C4-oxime substituted thiazoles. Our approach relied on 3-bromo-2-oxopropanal O-methyl oxime 7 as a key building block. A three-step sequence to 7 was designed, which, for safety concerns, could only be operated in batch mode on limited scales (≪100 g). We describe herein how we addressed such a limitation, by designing a multistep continuous synthesis of this intermediate and further demonstrate the advantages of flow reactor configuration upon scaling up.

From the Studies of Hydration and Hydrolysis Reactions to the Discovery of a New Organocatalyst and Its Further Applications in Acetalization and Glycosylation

AbstractCyanuric chloride activated dimethyl sulfoxide (DMSO) was found to catalyze the hydration of glycals and the hydrolysis of enol ethers, esters, oximes, O‐methyl oximes, and hydrazones. Overall, 68 examples of these 6 types of substrates were efficiently transformed into 2‐deoxysugars, phenols, and carbonyl compounds. Methyl methylene sulfonium chloride (a bulky weak Lewis acid) is presumed to be the active catalytic species. This assumption is strongly supported by the fact that the same reactions catalyzed by chloromethyl methyl sulfide/KI gave similar results to those catalyzed by the cyanuric chloride activated DMSO. We further employed the chloromethyl methyl sulfide/KI precatalyst to carbohydrate benzylidenations, decanal acetalizations, and the stereoselective transformations of 2‐deoxy‐2‐iodo‐α‐d‐mannopyranosyl acetate into 2,3‐unsaturated O‐glycosides. Key features of this precatalyst include that it is water tolerant, cost‐effective, and easily removed during workup.

Novel Catalytic Three-Component Reaction between a Terminal Alkyne, Sulfonyl Azide, and O-Methyl Oxime

O-Methyl oximes have been employed as nucleophiles in reactions with ketenimines derived from sulfonyl azides and terminal alkynes to form N-alkylidene N′-tosylacetimidamide derivatives. The optimized conditions involved the use of CuPF6 and i-Pr2NEt in MeCN at 65 °C. Both O-methyl aldoximes and ketoximes were tolerated under the optimum conditions.

Stereoselective intramolecular coupling of barbituric acids with aliphatic ketones and O-methyl oximes by electroreduction: radical cyclization mechanism supported by DFT study

The electroreductive intramolecular coupling of barbituric acids with aliphatic ketones gave five- and six-membered cyclized products stereospecifically. When the same reactions were carried out with SmI2, only a five-membered cyclized product was formed as the single stereoisomer different from that obtained by the electroreduction. The cyclized products were stereospecifically transformed to the corresponding deoxygenated compounds by reduction with Et3SiH–BF3·Et2O. Similarly, the electroreductive intramolecular coupling of barbituric acids with O-methyl oximes gave five- and six-membered cyclized products. The DFT calculations suggested that the electroreductive intramolecular coupling proceeds through the protonated radical generated by one-electron transfer and subsequent protonation to the barbituric acid moiety.

ChemInform Abstract: Palladium‐Catalyzed One‐Pot 2‐Arylquinazoline Formation via Hydrogen‐Transfer Strategy.

The palladium catalytic system was first applied to 2-arylquinazoline synthesis via hydrogen transfer methodology. Various (E)-2-nitrobenzaldehyde O-methyl oximes reacted easily with alcohols or benzyl amines to provide N-heterocyclic compounds in good to high yields. Similarly, the heterocyclic products could be prepared by the reaction of 1-(2-nitrophenyl)ethanone, urea and benzyl alcohols. In these reactions, the nitro group was reduced in situ by hydrogen generated from the alcohol dehydrogenation step.

Palladium-catalyzed one pot 2-arylquinazoline formation via hydrogen-transfer strategy.

The palladium catalytic system was first applied to 2-arylquinazoline synthesis via hydrogen transfer methodology. Various (E)-2-nitrobenzaldehyde O-methyl oximes reacted easily with alcohols or benzyl amines to provide N-heterocyclic compounds in good to high yields. Similarly, the heterocyclic products could be prepared by the reaction of 1-(2-nitrophenyl)ethanone, urea and benzyl alcohols. In these reactions, the nitro group was reduced in situ by hydrogen generated from the alcohol dehydrogenation step.

Direct synthesis of 4-fluoroisoxazoles through gold-catalyzed cascade cyclization-fluorination of 2-alkynone O-methyl oximes.

A tandem protocol for the synthesis of fluorinated isoxazoles has been developed via catalytic intramolecular cyclizations of 2-alkynone O-methyl oximes and ensuing fluorination. The reactions proceed smoothly at room temperature in the presence of 5 mol % of (IPr)AuCl, 5 mol % of AgOTs, 2.5 equiv of Selectfluor, and 2 equiv of NaHCO3. This process features an efficient one-pot cascade route to fluoroisoxazoles with high yields and high selectivity under mild reaction conditions.

A New Route to α-Carbolines Based on 6π-Electrocyclization of Indole-3-alkenyl Oximes

Indoles are converted into α-carbolines in four steps by acylation at C-3, Boc-protection, olefination of the resulting 3-indolyl aldehydes or ketones to give N-Boc-3-indolyl alkenyl oxime O-methyl ethers, which upon heating to 240 °C under microwave irradiation undergo loss of the Boc-group, and 6π-electrocyclization to α-carbolines, following aromatization by loss of methanol (11 examples, 30–90% yield).

Synthesis and antibacterial activities of para-alkoxy phenyl-β-ketoaldehyde derivatives

A series of para-alkoxy phenyl-β-ketoaldehyde derivatives were synthesized and evaluated for antimicrobial activities. Preliminary results showed that some compounds had moderate antibacterial activities, especially, 3-(4-methoxyphenyl)-3-oxopropanal O-methyl oxime (4) showed more potent antibacterial activity against Staphylococcus aureus and resistant Helicobacter pylori than the other compounds. Compound 4 showed more active antibacterial activities against methicillin-resistant S. aureus than Houttuynin and levofloxacin. Compound 4 was also investigated and its antibacterial activities against the strains clinical separated of Staphylococcus aureus. The preliminary structure–activity relationships were obtained. The maximum tolerance dose value for acute toxicity of compound 4 was 5,000 mg/kg. It indicated that compound 4 should be safe in clinical treatment. A series of para-alkoxy phenyl-β-ketoaldehyde derivatives were designed, synthesized and evaluated for antimicrobial activities. 3-(4-Methoxyphenyl)-3-oxopropanal O-methyl oxime (4) showed more potent antibacterial activities against Staphylococcus aureus and resistant Hp than the other compounds. The maximum tolerance dose values for acute toxicity of compound 4 was 5,000 mg/kg. It indicated that compound 4 should be safe in clinical treatment.