Methylene Reagents Research Articles

DBU-Catalyzed, facile and efficient method for synthesis of spirocyclic 2-oxindole derivatives with incorporated 6-amino-4 H-pyridazines and fused derivatives via [3+3] atom combination

3-Cyanomethylidene oxindole derivatives were prepared in excellent yields utilizing DBU-promoted Knoevenagel condensation of isatin derivatives with active methylene reagents. The isolated products were then reacted with azaenamines via a DBU-promoted Michael addition to yield spirocyclic 2-oxindole derivatives with incorporated 6-amino-4 H-pyridazines and their fused derivatives.

Electrochemical and Thermal Grafting of Alkyl Grignard Reagents onto (100) Silicon Surfaces

Passivation of (100) silicon surfaces using alkyl Grignard reagents is explored via electrochemical and thermal grafting methods. The electrochemical behavior of silicon in methyl or ethyl Grignard reagents in tetrahydrofuran is investigated using cyclic voltammetry. Surface morphology and chemistry are investigated using atomic force microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy (XPS). Results show that electrochemical pathways provide an efficient and more uniform passivation method relative to thermal methods, and XPS results demonstrate that electrografted terminations are effective at limiting native oxide formation for more than 55 days in ambient conditions. A two-electron per silicon mechanism is proposed for electrografting a single (1:1) alkyl group per (100) silicon atom. The mechanism includes oxidation of two Grignard species and subsequent hydrogen abstraction and alkylation reaction resulting in a covalent attachment of alkyl groups with silicon.

Ammonium salt catalyzed multicomponent transformation: simple route to functionalized spirochromenes and spiroacridines

The combination of isatin or acenaphthoquinone, an activated methylene reagent, and 1,3-dicarbonyl compounds in the presence of catalytic ammonium chloride was found to be a suitable and efficient method for the synthesis of the biologically important spirooxindoles.

Properties of Arsenite Efflux Permeases (Acr3) from Alkaliphilus metalliredigens and Corynebacterium glutamicum

Members of the Acr3 family of arsenite permeases confer resistance to trivalent arsenic by extrusion from cells, with members in every phylogenetic domain. In this study bacterial Acr3 homologues from Alkaliphilus metalliredigens and Corynebacterium glutamicum were cloned and expressed in Escherichia coli. Modification of a single cysteine residue that is conserved in all analyzed Acr3 homologues resulted in loss of transport activity, indicating that it plays a role in Acr3 function. The results of treatment with thiol reagents suggested that the conserved cysteine is located in a hydrophobic region of the permease. A scanning cysteine accessibility method was used to show that Acr3 has 10 transmembrane segments, and the conserved cysteine would be predicted to be in the fourth transmembrane segment.

D 1 -Like Receptors Regulate NADPH Oxidase Activity and Subunit Expression in Lipid Raft Microdomains of Renal Proximal Tubule Cells

NADPH oxidase (Nox)-dependent reactive oxygen species production is implicated in the pathogenesis of cardiovascular diseases, including hypertension. We tested the hypothesis that oxidase subunits are differentially regulated in renal proximal tubules from normotensive and spontaneously hypertensive rats. Basal Nox2 and Nox4, but not Rac1, in immortalized renal proximal tubule cells and brush border membranes were greater in hypertensive than in normotensive rats. However, more Rac1 was expressed in lipid rafts in cells from hypertensive rats than in cells from normotensive rats; the converse was observed with Nox4, whereas Nox2 expression was similar. The D(1)-like receptor agonist fenoldopam decreased Nox2 and Rac1 protein in lipid rafts to a greater extent in hypertensive than in normotensive rats. Basal oxidase activity was 3-fold higher in hypertensive than in normotensive rats but was inhibited to a greater extent by fenoldopam in normotensive (58+/-3.3%) than in hypertensive rats (31+/-5.2%; P<0.05; n=6 per group). Fenoldopam decreased the amount of Nox2 that coimmunoprecipitated with p67(phox) in cells from normotensive rats. D(1)-like receptors may decrease oxidase activity by disrupting the distribution and assembly of oxidase subunits in cell membrane microdomains. The cholesterol-depleting reagent methyl-beta-cyclodextrin decreased oxidase activity and cholesterol content to a greater extent in hypertensive than in normotensive rats. The greater basal levels of Nox2 and Nox4 in cell membranes and Nox2 and Rac1 in lipid rafts in hypertensive rats than in normotensive rats may explain the increased basal oxidase activity in hypertensive rats.

β‐Oxoanilides in heterocyclic synthesis: An expeditious synthesis of new polyfunctionally substituted pyridine and pyrazole derivatives

Abstractmagnified image3‐Oxo‐N‐{4‐[(pyrimidin‐2‐ylamino)sulfonyl]phenyl}butanamide 3 was condensed with (DMF‐DMA) in refluxing dry dioxane to yield branched structure 4 not its linear isomeric 5. Compound 4 readily reacted with active methylene to yield compounds 8a‐c, 14, 17 and 20 respectively. Also enaminone 4 reacted with phenyl hydrazine giving 24 and 25. In contrast, when compound 4 reacted with hydrazine hydrate in the same experimental conditions pyrazole derivative 27 was obtained. Furthermore, condensation of anilide 3 with triethylorthoformate in refluxing acetic anhydride afforded the ethoxy methylene derivative 28. On the other hand, compound 28 was reacted with active methylene reagents, and hydrazines to afford the products identical in all respects (mp., mixed mp., and spectral data) with those corresponding to compounds 6‐27 respectively. Similarly, compound 3 was reacted with hydrazine hydrate to afford the reaction product 29. Also, compound 3 reacted with cyanoacetamide in refluxing ethanolic pipridine solution to yield the pyridine derivative 30. Finally, 3 reacted with hydroxylamine hydrochloride in refluxing ethanol/sodium acetate solution to yield the acyclic oxime derivative 31.

Simple and rapid method for the determination of ethylenebisdithiocarbamate fungicides in fruits and vegetables using liquid chromatography with tandem mass spectrometry

A simple and rapid method for determining ethylenebisdithiocarbamates (EBDCs; mancozeb, maneb, and zineb) in fruits and vegetables is described. EBDCs are transformed into dimethylethylenebisdithiocarbamate (EBDC-dimethyl) by methylation after their decomposition with ethylenediaminetetraacetic acid (EDTA). These processes were performed simultaneously in this method. Dimethyl sulfate was used as the methylation reagent, and acetonitrile extracts obtained from partitioning with anhydrous magnesium sulfate and sodium chloride were subjected to dispersive solid-phase extraction with the primary secondary amine sorbent. Liquid chromatography with tandem mass spectrometry in the positive heated-electrospray ionization mode was used for the determination of EBDC-dimethyl produced from EBDCs. The method was validated at levels of 10, 50, and 100 ng g(-1) maneb as a representative EBDC. The recoveries of the present method were between 71 and 101%. The limits of detection and quantification were 0.24 and 0.8 ng g(-1) maneb, respectively.

Preparation of Methyl Ketones via Direct Coupling of Amides with CH2Cl2

A novel method for the preparation of methyl ketones from amides is described. Hereby, a highly nucleophilic titanium-methylene complex serves as methylenation reagent. The reaction is selective for amides and tolerates ester groups (CO2 t-Bu).

PY/GC/MS analyses of historical papers

The thermal degradation of cellulose is an important process in several fields such as the paper industry, biomass combustion, fire retardation, etc. Paper consists mostly of cellulose fibres. Although the fibre source has changed continiously from cotton or linen rags to wood, its nature is still vegetal. Pyrolysis in combination with gas chromatography and mass spectrometry has been used to identify the structures of thermal degradation products with the aim to characterize papers used in different centuries. Pyrolysis of cellulose has also been studied in the presence of the methylating reagent tetramethylammonium hydroxide (TMAH).

Methanethiolation of the Liberated Cysteine Residues of Human α2-Macroglobulin Treated with Methylamine Generates a Derivative with Similar Functional Characteristics as Native α2-Macroglobulin

The thiol-modifying reagent methyl methanethiosulfonate reacts with the cysteine residues of thiol esters released upon treatment of human α2-macroglobulin with methylamine. This methanethiolation generates a derivative of α2-macroglobulin, with an ‘open trap’ and slow mobility in non-denaturing PAGE, similar to native α2-macroglobulin. This similarity is further substantiated by surface hydrophobicity determinations and by the fact that neither the derivative nor native α2-macroglobulin are cleared from the circulation in mice. Cleavages of bait regions in the derivative and native α2-macroglobulin, however, result in electrophoretically fast forms which are cleared from the circulation in mice. In contrast to native α2-macroglobulin, which can bind 2 mol chymotrypsin/mol, α2-macroglobulin treated with methylamine and methylmethanethiosulfonate binds only 0.8 mol chymotrypsin/mol. Protection of trypsin against inhibition by soybean trypsin inhibitor is significantly better when α2-macroglobulin is modified by methylamine and methylmethanethiosulfonate than when it is modified by dinitrophenyl thiocyanate, which cyanylates the exposed thiol group. The methanethiolated derivative is also more stable than the corresponding cyanylated derivative in that it is transformed to an electrophoretically fast form with a half-life of 9 h as compared to a half-life of 7 h for the latter. The transformation to the fast form is not due to instability of the thiol modification.

A Simple and Efficient One-Pot Synthesis of Spirooxindoles in Water Under Microwave Irradiation Conditions

A simple and efficient method for the synthesis of spirooxindoles derivatives by one-pot reactions of isatins, activated methylene reagents and activated carbonyl compounds in water under microwave irradiation was reported. This protocol has the advantages of short reaction time, high yields, easy work-up procedure and environmentally benign characters. Keywords: Spirooxindoles, three-component synthesis, microwave irradiation, aqueous media

Microstructure and aggregation behavior of methylcelluloses prepared in NaOH/urea aqueous solutions

Three water-soluble methylcelluloses (MCs) were prepared through homogeneous reaction in NaOH/urea aqueous solution, using dimethyl sulfate as a methylation reagent. The microstructure of the MC samples was characterized by IR, GC/MS, NMR, while dilute solution properties were measured by SEC–LLS, DLS and viscometer. The total degrees of substitution (DS) of the MC samples were 1.09, 1.42 and 1.56, respectively. However, we found that the relative DS value varies with the position of the hydroxyl group, i.e., C-2 > C-3 ≈ C-6, indicating the difference of reaction activity of different hydroxyl groups. In aqueous solution, MC has a trendency to form aggregates and hard to form actual solution, even at low concentration and low temperature, which was confirmed by the SEC–LLS and DLS result that isolated MC chains and large aggregates coexisted in the dilute aqueous solution. MC aqueous solutions showed two-stage temperature dependence of hydrodynamic radius. In the first stage, i.e., the temperature ranges from 20 to 65 °C, the hydrodynamic radius of MC displayed bimodal distribution, corresponding to the single chains and large aggregates. While in the second stage, i.e., the temperature higher than 70 °C, only large aggregates appeared. The results also proved that the microstructure of MC had a great influence on its physical properties.

(Ethane-1,2-diyl)bis[bis(3-methoxypropyl)methylphosphonium] bis(tetraphenylborate) diethyl ether solvate

In the course of substitution studies on the iron dihydrogen complex trans-[Fe(DMeOPrPE)2(H2)H](BPh4) {DMeOPrPE = 1,2-bis­[bis­(methoxy­prop­yl)phosphino]ethane}, we discovered an unexpected transformation of the diphosphine ligand to a diphospho­nium dication without the use of any typical methyl­ating reagent. The P atoms in the dication of the title compound, C20H46O4P2 2+·2C24H20B−·C4H10O, have a distorted tetra­hedral coordination with P—C(Me) distances of 1.791 (2) and 1.785 (2) Å. The P—C—C—P torsion angle about the central dimethyl­ene bridge is −168.3 (1)°.

Studies with enaminonitriles: Synthesis and chemical reactivity of 2‐phenyl‐3‐piperidin‐1‐yl acrylonitrile under microwave heating

Abstractmagnified imageBenzyl cyanide reacts with triethylorthoformate and piperidine in DMF solution to yield the title compound 2. This reacted with aromatic amines to yield either aminoacrylonitriles or quinoline depending on reaction conditions and substitution pattern on the aromatic amine. The reaction of compound 2 with hydrazine hydrate could only be effected in the microwave oven and resulted in the formation of aminopyrazole 7. Diazotization of 7 and coupling with an active methylene reagent afforded pyrazolo[5,1‐c]‐[1,2,4]triazine derivatives.

Measurement and Implications of Nonphotochemically Generated Superoxide in the Equatorial Pacific Ocean

Superoxide, formed by the single electron reduction of oxygen, is important due to its ability to act as a mild reductant under typical environmental conditions. Using chemiluminescence detection with the reagent methyl Cypridina luciferin analog (MCLA), we have measured superoxide at picomolar concentrations in the water column of the Costa Rica Dome (CRD) seasonal upwelling region of the eastern equatorial Pacific Ocean. After 0.45 microm filtration, superoxide decayed in a pseudofirst order manner but more slowly than expected (rate constants varied from <10(-4) to 9.7 x 10(-3) s(-1)), which we hypothesize is due to complexation of metals that could otherwise scavenge superoxide, and the noncatalytic nature of superoxide decay at subnanomolar concentrations. Depth profiles revealed a particle-associated and nonphotochemically generated source of superoxide, implicating biological processes in its production. Superoxide in surface waters exhibited a diel cycle but concentrations were comparable to those in samples stored in the dark for at least 30 min, suggesting that the nonphotochemical source may dominate over abiotic photochemical superoxide production in the CRD. Elevated concentrations of superoxide in localized zones of the ocean may promote the reduction of several biologically important trace metals, thereby increasing their solubility and potential bioavailability.

Palladium-Catalyzed Methylation of Aryl C−H Bond by Using Peroxides

A novel Pd(OAc)2-catalyzed methylation reaction by dicumyl peroxide via aryl C−H bond activation was discovered. Various 2-phenylpyridine and acetanilides can be used as reactants in these reactions. Peroxide was used as both the methylating reagent and the hydrogen acceptor.

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and Thiazoles from 3-Aryl-1-(2-naphthyl)prop-2-en-1-ones

3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which were treated with ethyl chloroacetate to give the corresponding ester. Treatment of the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and benzoxazines. The hydrazides were reacted with benzaldehyde or phenylisothiocyanate to afford the corresponding hydrazone and thiosemicarbazide derivatives, which were cyclized with chloroacetic acid or thioglycolic acid to the corresponding thiazole derivatives. 3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were either condensed with malononitrile under different conditions to produce carbonitrile derivatives or treated with active methylene reagents to afford the substituted cyclohexene derivatives. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. Some of these compounds exhibited antimicrobial activities comparable to Ampicillin® as reference drug.

Exploring the Cooperativity of the Fast Folding Reaction of a Small Protein Using Pulsed Thiol Labeling and Mass Spectrometry

It has been difficult to obtain directly residue-specific information on side chain packing during a fast (ms) protein folding reaction. Such information is necessary to determine the extent to which structural changes in different parts of the protein molecule are coupled together in defining the cooperativity of the overall folding transition. In this study, structural changes occurring during the major fast folding reaction of the small protein barstar have been characterized at the level of individual residue side chains. A pulsed cysteine labeling methodology has been employed in conjunction with mass spectrometry. This provides, with ms temporal resolution, direct information on structure formation at 10 different locations in barstar during its folding. Cysteine residues located on the surface of native barstar, at four different positions, remain fully solvent-accessible throughout the folding process, indicating the absence of any ephemeral nonnative structure in which these four cysteine residues get transiently buried. For buried cysteine residues, the rates of the change in cysteine-thiol accessibility to rapid chemical labeling by the thiol reagent methyl methanethiosulfonate appear to be dependent upon the location of the cysteine residue in the protein and are different from the rate measured by the change in tryptophan fluorescence. But the rates vary over only a 3-fold range. Nevertheless, a comparison of the kinetics of the change in accessibility of the cysteine 3 thiol with those of the change in the fluorescence of tryptophan 53, as well as of their denaturant dependences, indicates that the major folding reaction comprises more than one step.

Unprecedented One‐Pot Stereoselective Synthesis of Knoevenagel‐Type Derivatives via in situ Condensation of N‐Methyleniminium Salts of Ethylenethiourea and Ethyleneurea with Active Methylene Reagents.

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Phenylacetone as Building Blocks in Heterocyclic Synthesis: Synthesis of Polyfunctionally-Substituted Pyridines, and fused Pyridines

Many pyridinethiones are biologically active. In view of our interest in developing efficient syntheses of polyfunctionally substituted heteroaromatics utilizing the readily obtainable enaminone 3 as starting materials. So, treatment of enaminone 3 with cyanothioacetamide or cyanoacetamide afforded the pyridinethione 5a and pyridone 5b. compound 5a reacted with α -halo- ketones in refluxing sodium ethoxide to give the thienopyridine derivatives 9a – e . Compound 5a reacted with methyl iodide to give 2-methylthiopyridine 10. Condensation of pyridinethione 5a with dimethylformamide-dimethylacetal gave the adduct 11 and with hydrazine hydrate afforded 12 . Compound 5a reacted with arylidenemalonitrile to give styryl derivatives 14a – d . Compound 14a – d also prepared from the condensation of 5a with the aromatic aldehydes under the same condition. Reflux of thienopyridine derivatives 9a – d with triethylorthoformat, acetic anhydride, carbon disulfide and sodium nitrite to give compounds 19 – 23 , respectively. The aminopyrazole 12 reacted with dimethylaminopropiophenone hydrochloride 24 or enaminone 30 in refluxing DMF to yield compound 26a – d . Treatment of 12 with 32 afforded 34 . Compound 34 can be also prepared from the reaction of 37 with aroylacetonitrile 31. Compound 12 reacted with DMF-DMA to give 37 , which reacted with compound 1 to give 38 prepared directly from reaction of 12 with enaminone 2 . Diazotization of 12 with nitrous acid followed by coupling with different active methylene reagents afforded the pyridothienotriazines 42a , b . Reaction of benzylideneacetophenone with 12 yielded the pyridopyrazolopyrimidine 44. Also, compound 12 reacted directly with active methylene to give the pyridopyrazolopyrimidine derivatives 46a , b .