4-nitrobenzyl Alcohol Research Articles

Cyanine fluorophore derivatives with enhanced photostability

Fluorescence applications requiring high photostability often depend on the use of solution additives to enhance fluorophore performance. Here we demonstrate that the direct or proximal conjugation of cyclooctatetraene (COT), 4-nitrobenzyl alcohol (NBA) or Trolox to the cyanine fluorophore Cy5 dramatically enhanced fluorophore photostability without otherwise affecting its native spectral characteristics. Such conjugation is a powerful means of improving the robustness of fluorescence-based applications demanding long-lived, nonblinking fluorescence emission.

Derivatization of carboxyl-terminated polybutadiene for determining relative functionality distribution

A new and highly efficient method for determining relative carboxyl group distribution in carboxyl-terminated polybutadiene has been developed using practical synthetic and analytical techniques. Using oxalyl chloride, samples of carboxyl-terminated polybutadiene were rapidly transformed to acid chlorides that were then chemically derivatized with benzyl alcohol, 4-nitrobenzyl alcohol, and 3,5-dinitrobenzyl alcohol. This provided quick and quantitative conversion to the corresponding benzyl ester derivatives. Each new derivative was fully characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. The benzyl ester modified polymers were investigated in detail to determine their relative carboxyl group concentrations. To do this, gel permeation chromatography combined with ultra violet/refractive index dual detection was employed. The 4-nitrobenzyl ester, having the highest extinction factor at 270 nm provided the best UV data for analysis. The ultra violet/refractive index data of four separate polymer samples were plotted as a function of molecular weight. The data were compared with a theoretical plot (carboxyl group = two for all molecular weights) to illustrate the relative carboxyl concentration over the entire molecular weight range. Supplemental characterization of the 4-nitrobenzyl modified polymer was carried out using matrix-assisted laser desorption ionization coupled with time of flight mass spectrometry. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Synthesis of 2-Nitrobenzaldehyde in the Presence of Ionic Liquids

A method for synthesizing of 2-nitrobenzaldehyde from 2-nitrobenzyl alcohol using ionic liquids (ILs) has been developed. The conversion of 2-nitrobenzyl alcohol and the selectivity of 2-nitrobenzaldehyde in the ionic liquids are higher than those in the traditional dichlorethane solvent. In addition, a reaction mechanism for the oxidation of 2-nitrobenzyl alcohol to 2-nitrobenzaldehyde is proposed.

ChemInform Abstract: Oxidation-Reduction Reactions Involving Nitro Groups in Trifluoromethanesulfonic Acid. Part 3. The Reactions of 2-Nitrobenzyl Alcohol and Related Compounds.

2-Nitrobenzyl alcohol reacts with trifluoromethanesulfonic acid (99%) at 90 °C to give a 66% yield of 4-amino-3-carboxyphenyl trifluoromethanesulfonate 4. The reaction occurs through the intermediate formation of the C-protonated conjugate acid of anthranil N-oxide 7 and then probably involves the mono- and di-protonated forms of 2-nitrosobenzaldehyde. Under the same conditions, 2-nitrobenzyl chloride and 2-nitrosobenzaldehyde react to give the same product in essentially the same yield. Low temperature reactions in trifluoromethanesulfonic acid permit the conversion of N-phenylhydroxylamine into 4-aminophenyl trifluoromethanesulfonate in a yield of 78%.

Supercritical carbon dioxide, a new medium for aerobic alcohol oxidations catalysed by copper-TEMPO

The copper catalysed aerobic oxidation of selected alcohol substrates in supercritical carbon dioxide (scCO(2)), employing a range of simple copper(II) catalyst compounds, is here described. The copper acetate complex of polydimethylsiloxane (PDMS) functionalised pyridine (1), compound 2, has previously been synthesised and characterised by us and its solubility in scCO(2) demonstrated. Due to this solubility we anticipated that the selective aerobic oxidation of alcohols to aldehydes could be homogeneously catalysed by this compound in scCO(2) in combination with the co-catalyst 2,2,6,6-tetramethylpiperidin-1-yloxy free radical (TEMPO). Our initial results showed that complete oxidation of 4-nitrobenzyl alcohol was achieved within 4 h of reaction. However, the activities of analogous copper derivatives containing simpler pyridine substituents, [Cu(AcO)(2)(py)](2) and [Cu(AcO)(2)(4VP)](2) (4VP = 4-vinylpyridine), were shown to be similar, in spite of their negligible solubility in scCO(2). When we repeated the reactions in highly non-polar hexane rather than scCO(2) similar observations were made. In both cases, as 2 is soluble and the pyridine analogues are not, a much higher reaction rate was anticipated for 2 as it is the only compound capable of homogeneous catalysis. However, in some cases slightly better activities were observed for [Cu(AcO)(2)(py)](2) rather than for the PDMS functionalised analogue, 2. Thus, despite poor catalyst solubility typically being very inhibitory in this type of catalytic process, in this system solubilisation of the catalyst is not necessary. In continuation the activity of silica supported copper complexes was therefore investigated. Employing such catalysts the 4-nitrobenzyl and benzyl alcohol substrates were completely oxidised to the corresponding aldehydes in scCO(2), this time employing lower catalyst loadings. Other types of alcohol substrate showed more limited conversions however. To conclude, alcohol oxidation in the non-conventional green solvent scCO(2), with the benign terminal oxidant, dioxygen, and simple, cheap, easily prepared metal catalyst compounds was demonstrated. This is the first copper-TEMPO catalysed alcohol oxidation system in scCO(2) to be described.

Isolation and Characterization of a 4-Nitrotoluene-Oxidizing Enzyme from Activated Sludge by a Metagenomic Approach

To isolate a biocatalytic enzyme, metagenomic libraries were constructed in fosmids from samples of activated sludge used to treat coke plant wastewater. Six indigo-producing clones were isolated from approximately 40,000 metagenomic clones in the search for the oxygenase responsible. In vitro mutagenesis and whole-sequencing revealed one open reading frame to be responsible for the production of indigo in the fosmid clones. The deduced sequence of the gene product showed 60% identity with 2-naphthoate monooxygenase from Burkholderia sp. JT1500. Subclones carrying this open reading frame (icpA) retained indigo production, and indigo-producing enzymes expressed from subclones catalyzed the oxidization of 4-nitrotoluene to form 4-nitrobenzyl alcohol. These results suggested that the icp product is an enzyme involved in catalyzing 4-nitrotoluene's oxygenation.

Selective photocatalytic oxidation of benzyl alcohol and its derivatives into corresponding aldehydes by molecular oxygen on titanium dioxide under visible light irradiation

The photocatalytic oxidation of benzyl alcohol and its derivatives, such as 4-methoxybenzyl alcohol, 4-chlorobenzyl alcohol, 4-nitrobenzyl alcohol, 4-methylbenzyl alcohol, 4-(trifluoromethyl)benzyl alcohol, and 4- tertiary-butylbenzyl alcohol, into corresponding aldehydes proceeded at high conversion and selectivity on a TiO 2 photocatalyst under O 2 atmosphere. The reaction was confirmed to proceed under irradiation with both UV-light and visible light. In particular, the visible light response was observed to be attributed to a characteristic surface complex formed by the adsorption of a benzyl alcoholic compound on the TiO 2 surface. Here, the properties of the surface complex as the active center for this selective photocatalytic oxidation and the mechanism behind the reaction have been investigated.

Mitigating Unwanted Photophysical Processes for Improved Single-Molecule Fluorescence Imaging

Organic fluorophores common to fluorescence-based investigations suffer from unwanted photophysical properties, including blinking and photobleaching, which limit their overall experimental performance. Methods to control such processes are particularly important for single-molecule fluorescence and fluorescence resonance energy transfer imaging where uninterrupted, stable fluorescence is paramount. Fluorescence and FRET-based assays have been carried out on dye-labeled DNA and RNA-based systems to quantify the effect of including small-molecule solution additives on the fluorescence and FRET behaviors of both cyanine and Alexa fluorophores. A detailed dwell time analysis of the fluorescence and FRET trajectories of more than 200,000 individual molecules showed that two compounds identified previously as triplet state quenchers, cyclooctatetraene, and Trolox, as well as 4-nitrobenzyl alcohol, act to favorably attenuate blinking, photobleaching, and influence the rate of photoresurrection in a concentration-dependent and context-dependent manner. In both biochemical systems examined, a unique cocktail of compounds was shown to be optimal for imaging performance. By simultaneously providing the most rapid and direct access to multiple photophysical kinetic parameters, smFRET imaging provides a powerful avenue for future investigations aimed at discovering new compounds, and effective combinations thereof. These efforts may ultimately facilitate tuning organic dye molecule performance according to each specific experimental demand.

Electrochemistry and Reactivity of Surface-Confined Catechol Groups Derived from Diazonium Reduction. Bias-Assisted Michael Addition at the Solid/Liquid Interface

We have designed a novel catechol-modified electrode that could be used for bias-assisted Michael addition at the solid/liquid interface. The glassy carbon electrode was modified by the electrochemical reduction of a catechol para-substituted phenyldiazonium salt. The electrochemistry of surface-confined catechol moieties was investigated by cyclic voltammetry. The transfer coefficient and apparent surface standard electron-transfer rate constant were obtained using Laviron's theory. We demonstrate that o-quinone moieties linked to the surface remain quite reactive with nucleophilic species by Michael addition at the solid/liquid interface. To demonstrate the versatility of this procedure, 4-nitrobenzyl alcohol, (4-nitrobenzyl)amine, and a ferrocenealkylamine were chosen as nucleophile models due to their well-known redox properties. Electrochemically triggered Michael addition was validated, leading to redox headgroup-tethered surfaces.

Substituted 2-nitrobenzyltrichloroacetate esters for photodirected oligonucleotide detritylation in solid films

Oligonucleotide microarray fabrication by chemical synthesis using photoacid generators in solid films could have advantages over existing methods, but has not matched the accuracy of conventional synthesis where detritylation is performed with acid solutions. To address this problem, we explored the kinetics and equilibria of nucleoside detritylation in solid films, using trichloroacetic acid (TCA) generated by photolysis from its esters with substituted 2-nitrobenzyl alcohols. We synthesised 25 such esters, all alpha-phenyl substituted, and assessed their potential as solid film photoacid generators. They included sets with (i) mono- or dimethoxy-, (ii) 5-halo-, (iii) alkyl- or aryl-substituted 5-amino-, or (iv) 5-aryl-substituents in the 2-nitro- or 2,6-dinitrobenzyl ring. Absorption maxima of their UV spectra ranged from 230 to 410 nm, with quantum yields at 365 nm from < 0.01 to nearly 1.0. The esters formed optically clear solid films on glass slides without added polymer. Kinetics of intrafilm photoacid generation, proton activity changes and detritylation were measured in situ. The most effective esters for light sensitivity and detritylation were 5-chloro-, 5-bromo-, 4,5-dimethoxy-, and 4- or 5-aryl-substituted 2,6-dinitrobenzyl esters. Photoacid-induced increases in proton activity and detritylation were severely inhibited by polymers containing electronegative heteroatoms, but not by polymers lacking them. In solid films, intrafilm detritylation with photogenerated TCA was fast, but stopped at an equilibrium well short of completion. Both experiment and theory emphasise the inadequacy of attempting to force detritylation with high intrafilm acid activity.

Efficient, recoverable, copper-catalyzed aerobic oxidation of alcohols under FBS and thermomorphic mode

A series of fluorinated bipyridine derivatives, (4,4′-bis(R fCH 2OCH 2)-2,2′-bpy) {R f = n-C 8F 17 ( 1a), n-C 9F 19 ( 1b), n-C 10F 21 ( 1c), n-C 11F 23 ( 1d)} have been successfully synthesized using 4,4′-bis(bromomethylene)-2,2′-bpy and fluorinated alkoxides. Bpy 1a– d have been characterized by multi-nuclei ( 1H, 19F, and 13C) NMR, GC/MS and FTIR. The Cu complexes 2a– d could be generated in situ by stirring ligands 1a– d with CuBr·Me 2S at room temperature, respectively. The 3-component systems 3c– d, CuBr·Me 2S/Bpy ( 1c– d)/2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO), were successfully used to the aerobic oxidation of alcohols under the fluorous biphasic system (FBS). The resulting products from FBS could be easily recovered by two phase separation with high yields up to 8 runs (>90%). In order to avoid using the expensive fluorous solvents, systems 3a– d, CuBr·Me 2S/Bpy ( 1a– d)/TEMPO, were also successfully shown to catalyze the aerobic alcohol oxidation under the thermomorphic condition (in C 6H 5Cl), and the yields of oxidation of 4-nitrobenzyl alcohol were close to 100% even after 8 runs. In particular, 3a was most effective under the thermomorphic mode in the chemoselectivity of aerobic oxidation of aliphatic primary alcohols to aldehydes without any overoxidized acids.

Voltammetric and X-ray photoelectron spectroscopic fingerprinting of carboxylic acid groups on the surface of carbon nanotubes via derivatisation with arylnitro labels

4-Nitrophenol (4-NP)or 4-nitrobenzyl alcohol (4-NBA) are used as voltammetric and X-ray photoelectron spectroscopic (XPS) labels for carboxylic acid groups on the surface of single-walled carbon nanotubes, “bamboo-like” and “hollow-tube” multi-walled carbon nanotubes. The surface carboxyl groups are first converted to the corresponding acyl chlorides, and coupled to the labels via the formation of an ester linkage. The voltammetric reduction of the arylnitro label allows the number of carboxyl groups on the surface to be estimated. Alternatively the percentage of the elemental surface composition corresponding to the carboxyl groups can be measured using XPS via the emission from the N1s level of the label. The number of electroactive quinonyl groups present on the surface relative to the number of carboxyl groups can also be determined voltammetrically by measuring the area under the voltammetric wave corresponding to the surface quinone groups. By combining these voltammetric and XPS results the relative percentages of the O1s spectral peak, which correspond to carboxyl and quinonyl groups, can then be determined, which also allows, by difference, an estimate of the percentage elemental surface composition of total other oxygen-containing functionalities present such as lactones, ethers, aliphatic ketones etc. The effect of standard acid pre-treatments used to introduce carboxyl groups onto the CNT surface (such as stirring in relatively concentrated mixtures of nitric and sulfuric acids) on the number of each type of oxygen functionality is compared. In all cases the number of carboxyl groups is found to increase, but the number of quinonyl and other oxygen-containing functionalities is also found to increase, often to a greater extent than the carboxyl groups.

Heterogeneous Method for the Oxidation of Alcohols under Mild Conditions with Zinc Dichromate Adsorbed on Alumina

Chromate salts and other chromium (VI) oxides have been widely used as oxidizing agents for a variety of substrates including alcohols. These oxidants are frequently used in large excess but can also be used catalytically in conjunction with secondary oxidants. Problems in the use of chromium (VI) complexes as oxidation reagents include the lack of selectivity in oxidations, safety hazards associated with the use of large quantities of toxic compounds, cumbersome preparation and potential danger (ignition) in handling its complexes, difficulties in terms of product isolation and waste disposal and the need for aqueous acidic or basic conditions for reactions of chromate salts. These problems could be eliminated by reagents on solid supports. Many oxidants, especially the older and stronger chromium oxidizing agents, may have their reactivity and selectivity modified by adsorption onto inert supports. There were many chromium oxidants on inert inorganic supports such as: pyridinium chlorochromate on alumina, pyridinium chromate on silica, chromic acid on alumina and silica, chromyl chloride on silica – alumina and resin, poly(vinyl pyridinium chlorochromate (PVPCC) and poly(vinyl pyridinium dichromate, chromium VI oxide prepared and used for the oxidation of organic compounds. In this paper, we wish to report the utilization of zinc dichromate onto alumina as a convenient, efficient and economical reagent for the oxidation of alcohol to carbonyl compounds in CH3CN, H2O and solvent–Free conditions. (Table 1, Scheme 1) The rate of oxidation and yield of product depended on the nature of the substrate and reaction condition. Oxidation of benzylic alcohols proceeded more rapidly than the oxidation of aliphatic alcohols (Table 1). In the oxidation of benzyl alcohols to benzaldehyde, when there is an electron releasing group, the rate and yield of the reaction increased (Entry 1-3). 4-Nitro benzyl alcohol is oxidized to its corresponding aldehyde within a longer time and 80-85% yield. Primary and secondary aliphatic alcohols (Entry 1012) are oxidized to the corresponding carbonyl compounds under these conditions. Reaction in solvent–Free conditions is of a high yield and faster than reactions in water and acetonitrile. The reactions are relatively clean with no tar formation and no over oxidation to carboxylic acids. The reaction of cinnamyl alcohol gave cinnamaldehyde with a high yield without cleavage of benzylic double bond. (Entry 9) The acidity of zinc dichromate/Alumina (pH of 0.01 molar solution: 4.65) is less pronounced than those reported for pyridinium chlorochromate (pH of a 0.01 molar solution: 1.75) and pyridinium fluorochromate (pH of a 0.01 molar solution: 2.45). This reaction has several interesting features: 1) Yields are satisfactory. 2) The reaction is specific, avoiding over oxidation of aromatic aldehyde into acid. 3) The reagent is cheap and easy to prepare. 4) The reaction is performed under mild conditions, in CH3CN, H2O and solvent-free at room temperature. 5) The experimental set-up and work-up are exceedingly simple.

Effects of 4,5-dimethoxy groups on the time-resolved photoconversion of 2-nitrobenzyl alcohols and 2-nitrobenzaldehyde into nitroso derivatives

The photoinduced conversion of the aci-nitro in the nitroso form was studied with four compounds containing the o-nitrobenzyl moiety in solution at ambient temperature using time-resolved UV-vis spectroscopy. For 4,5-dimethoxy-2-nitrobenzyl alcohol (2) and 4,5-methylenedioxy-2-nitrobenzyl alcohol (3) the absorption spectra are red-shifted and, in contrast to the parent 2-nitrobenzyl alcohol (1), a triplet state with CT character was detected after the 308 nm laser pulse. The other photochemical properties of 1-3 are similar. The aci-nitro form of 1-3 in acetonitrile or ethanol is quenched by water, the rate constant is (0.3-1.7) x 10(5) M(-1) s(-1). A CT triplet state and the nitroso product but no aci-nitro form were observed for 4,5-methylenedioxy-2-nitrobenzaldehyde (4). The conversion of the aci-nitro into the nitroso monomer and eventual dimer formation were studied by FTIR spectroscopy. The common features and specific differences in the photoreaction mechanisms of 1-4 are discussed.

Photochemical reaction mechanisms of 2-nitrobenzyl compounds: 2-Nitrobenzyl alcohols form 2-nitroso hydrates by dual proton transfer

Irradiation of 2-nitrobenzyl alcohol (1, R = H) and 1-(2-nitrophenyl)ethanol (1, R = Me) in various solvents yields 2-nitroso benzaldehyde (4, R = H) and 2-nitroso acetophenone (4 R = Me), respectively, with quantum yields of about 60%. The mechanism of this reaction, known since 1918, was investigated using laser flash photolysis, time-resolved infrared spectroscopy (TRIR), and 18O-labeling experiments. The primary aci-nitro photoproducts 2 react by two competing paths. The balance between the two depends on the reaction medium. Reaction via hydrated nitroso compounds 3 formed by proton transfer prevails in aprotic solvents and in aqueous acid and base. In water, pH 3-8, the classical mechanism of cyclization to benzisoxazolidine intermediates 5, followed by ring opening to carbonyl hydrates 6, predominates. The transient intermediates 3 and 6 were identified by TRIR. Potential energy surfaces for these reactions were mapped by density functional calculations.

Bioreduction activated prodrugs of camptothecin: molecular design, synthesis, activation mechanism and hypoxia selective cytotoxicity

Several water-soluble derivatives (CPT3, CPT3a-d) of camptothecin (CPT) were synthesized, among which CPT3 bearing an N,N'-dimethyl-1-aminoethylcarbamate side-chain was further conjugated with reductively eliminating structural units of indolequinone, 4-nitrobenzyl alcohol and 4-nitrofuryl alcohol to produce novel prodrugs of camptothecin (CPT4-6). All CPT derivatives were of lower cytotoxicity than their parent compound of CPT. In contrast, CPT4 and CPT6 showed higher hypoxia selectivity of cytotoxicity towards tumor cells than CPT. A mechanism by which a representative prodrug CPT4 is activated in the presence of DT-diaphorase to release CPT was also discussed. The bioreduction activated CPT prodrugs including CPT4 and CPT6 are identified to be promising for application to the hypoxia targeting tumor chemotherapy.

A New Synthetic Method of 1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐ones: Selenium‐Catalyzed Reductive Carbonylation of Aromatic Nitro Compounds with Carbon Monoxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Fungal cytochrome P450s catalyzing hydroxylation of substituted toluenes to form their hydroxymethyl derivatives

The degradation of a series of nitroaromatic compounds by the lignin-degrading fungus Phanerochaete chrysosporium was examined. From 4-nitrotoluene (4-NT), several metabolic intermediates were identified. Initially, 4-NT was converted to 4-nitrobenzyl alcohol (4-NBA), followed by the oxidation reactions to form 4-nitrobenzaldehyde and 4-nitrobenzoic acid, albeit slowly. Exogenously added 4-nitrobenzaldehyde and 4-nitrobenzoic acid were predominantly reduced to 4-NBA. The fungal formation of 4-NBA was inhibited by piperonyl butoxide, a cytochrome P450 inhibitor, suggesting the involvement of cytochrome P450 in the hydroxylation of the methyl group. Similarly, 2-, and 3-nitrotoluenes and 4-chlorotoluene were converted to the corresponding arylalcohols by P. chrysosporium. On the other hand, toluene and 4-methoxytoluene were not converted. Thus, P. chrysosporium possesses an alkyl hydroxylation activity against aromatic compounds substituted with a strong electron-withdrawing group.

A New Synthetic Method of 1,4-Dihydro-2H-3,1-benzoxazin-2-ones: Selenium-Catalyzed Reductive Carbonylation of Aromatic Nitro Compounds with Carbon Monoxide

It was confirmed that selenium catalyzed the reaction of 2-nitrobenzyl alcohols with carbon monoxide to afford 1,4-dihydro-2H-3,1-benzoxazin-2-ones in good yields. Similarly, seven-membered cyclic carbamate was prepared by the reaction of 2-(2-nitrophenyl)ethanol with carbon monoxide.

Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease

A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-yl)-acetic acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised lipase enzyme and a palladium-catalysed aminocarbonylation reaction.