J. Carbajo

Voltammetric studies of aromatic nitro compounds: pH-dependence on decay of the nitro radical anion in mixed media

Abstract In this report we have chosen ethyl- m -nitrobenzoate (EMNB) as a prototype of a nitroaromatic compound in order to carry out a detailed cyclic voltammetric study focused on the coupled chemical reaction of the generated nitro radical anion. The study was carried out in mixed media (water+DMF) at different DMF contents and several pH values on both mercury and carbon electrodes. In order to study the coupled chemical reaction it was necessary to choose a narrow pH range between 8 and 10. The coupled chemical reaction follows second order kinetics and we have used Olmsteads procedure to calculate the second order rate constant k 2 . The k 2 values are strongly pH dependent. Typical values of k 2 =are 1.68×10 4 l mol −1 s −1 and 1.15×10 4 l mol −1 s −1 for 60% DMF, pH 9.5 on mercury and GCE, respectively. Considering an EMNB concentration of 0.1 mM the corresponding half life time values were 0.59 s and 0.86 s.

Free Radical Formation and Characterization of Nitroanisole Isomer Reduction in Different Media

A comprehensive study of the electrochemical characteristics of 2-, 3-, and 4-nitroanisole isomers in three different electrolytic media has been carried out. Furthermore, kinetic characterization of the one-electron reduction product from these isomers in these media is also reported. Also, free radicals were characterized in aprotic media by electron paramagnetic resonance through their corresponding hyperfine splitting constants. In protic media (30% ethanol/0.1 M Britton-Robinson buffer pH 2-12) 2-, and 3-nitroanisole isomers gave an irreversible well-defined peak over the entire pH range on Hg in a reaction involving four electrons to give the hydroxylamine derivative. However, in the case of 4-nitroanisole the kinetic characterization of the corresponding nitro radical anion was successfully achieved in this medium at pH 10.5, exhibiting a k 2disp value of 19,000 (M s) -1 . In this medium the ease of reduction at pH 7 was 2-nitroanisole (2-NA) > 3-nitroanisole (3-NA) > 4-nitroanisole (4-NA). In mixed aqueous-organic media [0.015 M aqueous citrate dimethylformamide (DMF): 60:40, 0.3 M KCl, and 0.1 M tetrabutylammonium iodide (TBAI) at pH ≥ 10.5 the isolation of the couple by cyclic voltammetry and the electrochemical characterization of the nitro radical anion corresponding to the three compounds were achieved. Calculated disproportionation second-order rate constants, k 2disp , had an average value of 10,900 ± 930 (M s) 1 , 2400 ± 400 (M s) -1 , and 5000 ± 600 (M s) -1 for 2-NA 3-NA, and 4-NA, respectively. Also, the reactivity of the radicals toward glutathione was quantitatively assessed through the calculation of the respective apparent interaction rate constants. In aprotic media (0.1 M TBAI in DMF) the nitro radical anions were more stable than in the mixed media, with the following second-order decay rate constant, k 2dim , values: 1100 ± 100(M s) -1 , 1600 ± 150 (M s) -1 , and 650 ± 70 (M s) -1 for 2-NA, 3-NA, and 4-NA, respectively.

Electroreduction of Nitroaryl‐1,4‐dihydropyridines on a Mercury Pool Electrode in Mixed Media Analysis of the Reaction Products and Their Reactivity with Biomolecules

The electroreduction of a series of nitroaryl-1,4-dihydropyridines has been studied in mixed media. Controlled potential electrolyses using a mercury pool electrode at three different reduction potentials were carried out. Voltammetric (polarography and cyclic voltammetry) and chromatographic studies, showed that these nitro compounds were transformed into their corresponding hydroxylamine derivatives at the end of the electrolysis. On the other hand, early in the electrolysis it was possible to detect the formation of the nitro radical anion in the bulk solution which through a dismutation reaction produces the nitroso compound which is reduced to the final product, a hydroxylamine derivative. When different biomolecules like glutathione, cysteamine, adenine, and uracil were added, a direct reaction with the nitro radical anion derivative was detected. The parent nitro compound and the final product, the hydroxylamine derivative, did not react with the biomolecules.

Synthesis of Some C‐3,4,5‐Substituted 2,6‐Dimethyl‐1,4‐dihydropyridines (4‐DHPs)

Abstract A series of C‐3,4,5‐substituted 2,6‐dimethyl‐1,4‐dihydropyridines (1,4‐DHPs) with pharmacological properties were prepared by a variation from the classical Hantzsch synthesis. The procedure involves treatment of the respective aldehyde with either ethyl‐3‐aminocrotonate or 3‐aminocrotonitrile in anhydrous acetic acid at temperatures not exceeding 60°C, thus minimizing by‐product formation. The structures of title compounds were elucidated by 1H NMR, 13C NMR, FTIR, and elemental analysis.

Electrochemical Reduction of 2-Nitroimidazole in Aqueous Mixed Medium

A detailed investigation of the electrochemical reduction of 2-nitroimidazole (2-NIm) in a mixed aqueous medium was carried out by means of cyclic voltammetry (CV) at a mercury electrode. The voltammetric behavior of 2-NIm in 60% dimethylformamide (DMF) (0.1 M tetrabutyl ammonium perchlorate, TBAP)/40% aqueous buffer (0.3 M KCl + 0.015 M citric acid + 0.03 M boric acid) is pH-dependent, changing from one irreversible reduction peak at acid pHs to two reduction peaks at alkaline pHs. At pH 2.5 it is possible to obtain a voltammetric pK which is due to the protonation-deprotonation equilibrium produced by the hydroxylamine derivative formed from the reduction of 2-NIm. This indicates that 2-NIm is reduced to the unprotonated hydroxylamine derivative above pH 2.5 and to its protonated form below it. At pH > 7 it is possible to observe a cyclic voltammetric couple due to the one-electron reduction of 2-NIm to produce the corresponding nitro radical anion. Furthermore, the nitro radical anion disproportionates with a rate constant, k 2 , of 6.78 X 10 5 M s -1 and a half-life, t 1/2 , of 1.5 ms for the first half-life. The voltammetric behavior of 2-NIm in aqueous mixed medium is substantially different from that described in nonaqueous medium; in fact, only in the aqueous medium is it possible to study in isolation the nitro radical anion.

The use of digital simulation to improve the cyclic voltammetric determination of rate constants for homogeneous chemical reactions following charge transfers

Cyclic voltammetry (CV) is a very useful electrochemical tool used to study reaction systems that include chemical steps that are coupled to electron transfers. This type of system generally involves the chemical reaction of an electrochemically generated free radical. Published methods exist that are used to determine the kinetics of electrochemically initiated chemical reactions from the measurements of the peak current ratio (i(pa)/i(pc)) of a cyclic voltammogram. The published method requires working curves to relate a kinetic parameter to the peak current ratio. In the presented work, a digital simulation package was used to obtain improved working curves for specific working conditions. The curves were compared with the published results for the first- and second-order chemical reactions following the charge transfer step mechanisms. According to the presented results, the previously published working curve is reliable for a mechanism with a first-order chemical reaction; however, a change in the switching potential requires a recalculation of the curve. In the case of mechanisms with a second-order step (dimerisation and disproportionation), several different views exist on how the second-order chemical term should be expressed so that different values of the constant are obtained. Parameters such as electrode type, electrode area, electroactive species concentration, switching potential, scan rate and method for peak current ratio calculation modify the working curves and must always be specified. We propose a standardised method to obtain the most reliable kinetic constant values. The results of this work will permit researchers who handle simulation software to construct their own working curves. Additionally, those who do not have the simulation software could use the working curves described here. The revelations of the presented experiments may be useful to a broad chemistry audience because this study presents a simple and low-cost procedure for the study of free radicals that otherwise should be studied with more sophisticated and expensive techniques, such as ESR or pulse radiolysis.

Substituent Effect of 4-Nitroimidazole Derivatives: Acidic Hydrogen as Modulator of the Nitro Radical Kinetic Stability

The electrochemical reduction of l-methyl-4-nitro-2-carboxyimidazole (RNO 2 COOH) in a nonaqueous medium produced two reduction signals, which were influenced by the dissociation of the compound. The first reduction signal was caused by the reduction of the acidic species, and the second signal was a quasi-reversible couple caused by the reduction of the conjugate base to the radical dianion. According to the theory developed by Nicholson for the study of the electrode reaction kinetics, we have obtained the heterogeneous rate constant, k° = (9.74 ± 0.052) X 10 -3 cm s -1 , for the reduction of the conjugate base to the radical dianion. The voltammetric behavior of RNO 2 COOH and its comparison with the behavior of another related compound such as 1-methyl-4-nitro-2-hydroxymethylimidazole is a good example to show the applicability of the general theory about the mechanism of self-protonation reactions in organic electrochemical processes to the specific case of nitroimidazole derivatives. According to the presented results, the presence of acidic hydrogen as a substituent in the nitroimidazole moiety would permit the modulation of the nitro radical anion stability, thus affecting its potential biological activity.

Stereoselective Electrochemical Reduction of Imazapyr in Aqueous Media Without Chiral Auxiliaries

The electrochemical reduction of imazapyr at the static mercury drop electrode was studied by cyclic voltammetry as a function of pH in aqueous buffered media. The process leads to the 2,3-C=N double bond reduction in the imidazoline moiety in all media. The products have been isolated by controlled-potential electrolyses and identified by high performance liquid chromatography-tandem mass spectrometry measurements and 1 H-NMR, 13 C-NMR, and IR spectra. Although no chiral auxiliary was used, a moderate diasteroisomeric excess was observed. The diasteromeric ratio depends on pH of the electrolyses.

NITRORADICAL ANION FORMATION FROM NITROFURANTOIN IN CARBON ELECTRODES

La formacion electroquimica del nitro anion radicalde nitrofurantoina ha sido estudiada sobre electrodos de carbonovitreo y pasta de carbono. Se encontro que sobre ambos tipos de electrodos, existe un proceso monoelectronico reversible correspondientea la cupla redox ArNO2/ArNO2.-, seguido de un pico irreversible correspodiente a la reduccion viatres electrones del anion radical a la correspondiente hidroxilamina.De acuerdo a los resultados obtenidos, el proceso de reduccion ocurrea traves de un mecanismo EC, donde los valores de k2 encontrados, indican que el anion radical nitro es mejor estabilizadosobre electrodos de pasta de carbono