Electrochemical Study of 4‐Substituted Analogues of Megazol

The electrochemical behavior of three different megazol analogues substituted at position 4 and their comparison with the parent compound megazol in protic and aprotic media by cyclic voltammetry, Tast and differential pulse polarography was studied. All the compounds were electrochemically reducible in both media with the reduction of the nitroimidazole group the main voltammetric signal. The one‐electron reduction couple due to the nitro radical anion formation was visualized only in aprotic media for all these compounds. By applying cyclic voltammetric methodology we have calculated the dimerization reaction decay constants (k₂) of the corresponding nitro radical anions in aprotic media. The nitro radical anion obtained from the synthesized nitroimidazole compound having a bromine substituent in 4‐position (GC‐141) was significantly more stable than the corresponding radical formed from the compound lacking of the substituent in 4‐position, megazol.     

The effect of charge on hydroxyl loss from ortho-substituted nitrobenzene ions

An abundant loss of hydroxyl in decompositions of ortho-substituted nitroarene cations is commonly observed when the substituent contains one or more labile hydrogen atoms. The major loss of hydroxyl also takes place from many but not all of the corresponding molecular anions. Data are reported for the collisionally activated decompositions of the cations and anions of o-nitrotoiuene, o-nitrophenol and o-nitroaniline. Data for some dinitro ions are also reported. The results can be rationalized on the basis of a greater degree of charge developed at the substituent in the transition state of the anions that leads to a rearranged ion. It is from this structure tint hydroxyl is lost via simple bond cleavage. This can be viewed most simply as a proton transfer from the substituent to the nitro group in the anion as opposed to hydrogen transfer in the analogous step for the cation. The degree to which hydroxyl loss occurs is therefore largely determined by the tendency for hydrogen (cations), or proton (anions), transfer from the substituent to the nitro group.     

Out-of-Plane Distortions of Chlorinated Nitrobenzene Radical Anions

According to UHF/INDO calculations of the model conformations of the chlorinated nitrobenzene radical anions, the rotation of the nitro group relative to the plane of the benzene ring is accompanied by its pyramidal deformation caused by the pseudo-Jahn–Teller effect. The degree of the structural distortions of the chlorinated nitrobenzene radical anions depends on the arrangement of the chlorine atoms in the benzene ring and on the solvent, increasing from DMF to its mixtures with water. The isotropic hyperfine coupling constants and their dependence on the water content in a binary mixture of solvents are interpreted for a number of chlorinated nitrobenzene radical anions.     

Out-of-Plane Distortions in Fluorinated Nitrobenzene Radical Anions

According to the data of UHF/INDO calculations of the model conformations of fluorinated nitrobenzene radical anions, rotation of the nitro group relative to the plane of the benzene ring is accompanied by a pyramidal distortion of the group, which is of pseudo-Jahn–Teller nature. The degree of structural distortions depends on the position of the fluorine atoms in the benzene ring and on the solvent, increasing from DMF to DMF–water mixtures. The values of isotropic hyperfine interaction constants are interpreted in the series of fluorinated nitrobenzene radical anions, and the effects of water content in binary mixtures of solvents are discussed.     

Indo study of the angular dependences of isotropic hyperfese interaction constants in the model conformations of the nitrobenzene radical anion

The UHF/INDO calculations of the model conformations of the nitrobenzene radical onion show that rotation of the nitro group relative to the plane of the benzene ring is accompanied by a pyramidal distortion of the group caused by the pseudo-Jahn-Teller effect (vibronic interaction between the ground n and totally symmetric lowest excited σ states). The angular dependences of the¹⁴N,¹³C,¹H, and¹⁷O Isotropic hyperfine interaction constants are analyzed. Experimental ESR data are interpreted for the radical anions of nitrobenzene derivatives with ortho-alkyl groups. Translated fromZhumal Strukturnoi Khimii, Vol. 41, No. 3, pp. 457-467, May-June, 2000.     

Unimolecular and collision-induced fragmentation of protonated nitroarenes

The unimolecular fragmentation reactions of 28 protonated nitroarenes, occurring on the metastable ion time-scale, are reported. In addition, the collision-induced fragmentation of the same species have been studied at 10 eV and at 50 eV collision energy. When an OH, COOH or NH₂ substituent is ortho to the nitro function, the dominant fragmentation involves loss of H₂O, for both unimolecular and collision-induced reactions. When there is an electron-releasing substituent ortho or para to the litro group, loss of OH is the dominant fragmentation reaction both on the metastable ion time-scale and for ions activated by collision. When the electron-releasing substituent is meta to the nitro group, loss of NO₂ is the dominant low-energy unimolecular fragmentation reaction while loss of HNO₂ is the most important fragmentation for ions activated by 50 eV collisions. Elimination of NO from [MH]⁺ occurs to a significant extent in the unimolecular fragmentation of protonated nitrobenzene and those protenated nitrobenzenes containing electron- attracting substituents. In the collision-induced dissociation of these species loss of HNO₂ occurs at the expense of loss of NO. The results are consistent with protonation predominantly at the nitro group. The results are discussed in terms of the use of neutral loss scans in tandem mass spectrometry to monitor complex mixtures for nitroarenes.     

Voltammetric Study of Nitro Radical Anion Generated from Some Nitrofuran Compounds of Pharmacological Significance

The electrochemical behavior of 2‐(5‐amino‐ 1,3,4‐oxadiazolyl)‐5‐nitrofuran (NF359) and its comparison with well‐known drugs such as nifurtimox (NFX) and nitrofurazone (NFZ) in protic, mixed and aprotic media by cyclic voltammetry, tast and differential pulse polarography was studied. All the compounds were electrochemically reducible in all media being the reduction of the nitrofuran group the main voltammetric signal. The one‐electron reduction couple due to the nitro radical anion formation was visualized in mixed (for NF359 and NFZ) and aprotic media (for all compounds). By applying a cyclic voltammetric methodology we have calculated the decay constants (k₂) of the corresponding nitro radical anions in mixed and aprotic media. In mixed medium data fit well with a disproportionation reaction of the nitro radical anion but in aprotic medium fit better with a dimerization reaction. Also, considering cyclic voltammetric measurements in aprotic media we have estimated the reduction potential of the RNO₂/RNO₂^.? couple in aqueous medium, pH 7 (E¹₇ values) finding very good correlation with E¹₇ values obtained by pulse radiolysis. Furthermore we have calculated the equilibrium constants from the electron transfer from nitro radical anion to oxygen (k_O2) finding that nitro radical anion from NF359 is thermodynamically favored to react with oxygen in respect to both NFZ and NFX.     

Chemical ionization mass spectra of mononitroarenes

The H₂ and CH₄ chemical ionization mass spectra of a selection of substituted nitrobenzenes have been determined. It is shown that reduction of the nitro group to the amine is favoured by high source temperatures and the presence of water in the ion source. The H₂ chemical ionization mass spectra are much more useful for distinguishing between isomeric compounds than the CH₄ CI mass spectra because of the more extensive fragmentation. For ortho substituents bearing a labile hydrogen abundant [MH ? H₂O]⁺ fragments are observed. When the substituent is electron-releasing both ortho and para substituted nitrobenzenes show abundant [MH? OH]⁺ fragment ions while meta substituted compounds show abundant loss of NO and NO₂ from [MH]⁺. The latter fragmentation is interpreted in terms of protonation para to the substituent or ortho to the vitro function, while the first two fragmentation routes arise from protonation at the nitro group. When the substituent is electron-attracting the chemical ionization mass spectra of isomers are very similar except for the H₂O loss reaction for ortho compounds.     

Electron spin resonance studies of several anion radicals of nitro-substituted thioacylpiperidines and morpholines

The radical anions of m- and p- nitro-substituted derivatives of several classes of N-(thioacyl)-piperidines and -morpholines have been studied by ESR spectroscopy. The anion radicals were found to be centred on the nitro group, and the distribution of the unpaired electron was found to be dependent on the extent of conjugation between the thiocarbonyl group and the aromatic moiety of the molecule. The hfs constants were discussed in terms of the spin densities calculated by the McLachlan procedure.     

Characterization of multiple fragmentation pathways initiated by collision‐induced dissociation of multifunctional anions formed by deprotonation of 2‐nitrobenzenesulfonylglycine

The correlation of anion structure with the fragmentation behavior of deprotonated nitrobenzenesulfonylamino acids was investigated using tandem mass spectrometry, isotopic labeling and computational methods. Four distinct fragmentation pathways resulting from the collision‐induced dissociation (CID) of deprotonated 2‐nitrobenzenesulfonylglycine (NsGly) were characterized. The unusual loss of the aryl nitro substituent as HONO was the lowest energy process. Subsequent successive losses of CO, HCN and SO₂ indicated that an ortho cyclization reaction had accompanied loss of HONO. Other pathways involving rearrangement of the ionized sulfonamide group, dual bond cleavage and intramolecular nucleophilic displacement were proposed to account for the formation of phenoxide, arylsulfinate and arylsulfonamide product ions at higher collision energies. The four distinct fragmentation pathways were consistent with precursor–product relationships established by CID experiments, isotopic labeling results and the formation of analogous product ions from 2,4‐dinitrobenzenesulfonylglycine and the Ns derivatives of alanine and 2‐aminoisobutyric acid. The computations confirmed a low barrier for ortho cyclization with loss of HONO and feasible energetics for each reaction step in the four pathways. Computations also indicated that three of the fragmentation pathways started from NsGly ionized at the carboxyl group. Overall, the pathways identified for the fragmentation of the NsGly anion differed from processes reported for anions containing a single functional group, demonstrating the importance of functional group interactions in the fragmentation pathways of multifunctional anions. Copyright © 2014 John Wiley & Sons, Ltd.     

ESR. Spectra of the Radical Anions of Cycloalkylbenzenes

Radical anions of five cycloalkylbenzenes (alkyl = propyl, butyl, pentyl, hexyl, or heptyl) have been studied by ESR. spectroscopy at ?90°C. In the case of cyclopropylbenzene, no reliable experimental data could be obtained, because of the instability of its radical anion. The spectra of the radical anions of the four higher homologues have been analysed by means of a computer program. The assignment of the coupling constants to the α-protons in the para position of the benzene ring and to the cycloalkyl ß-protons has been based on the spectra of specifically deuterated derivatives. The experimental data of the radical anion of cycloalkylbenzenes have been compared with those of the radical anions of five alkylbenzenes (alkyl = methyl, ethyl, n-propyl, isopropyl, or t-butyl), the spectra of the latter being reexamined at ?90°C. In the cycloalkyl series the degeneracy of the two benzene-type lowest antibonding orbitals is the more effectively removed the larger the substituent, whereas the reverse relation holds for the non-cyclic series. The preferred conformation of the substituents is that in which the alkyl or cycloalkyl ß-proton is near to the nodal plane of the benzene π-system, and this preference is accentuated with the increasing size of the substituent group.     

Competing oxygen migrations in ortho nitro aromatic thioamides on electron impact

Interesting competitive oxygen migrations from the nitro group to the nitrogen and to the sulfur have been noticed during the mass spectral decomposition of ortho nitro aromatic thioamides on electron impact. The migration of the oxygen to the nitrogen of the thioamide function results in the formation of stable o-nitrosothiobenzoyl cation. The other novel ortho effect noticed in the ortho isomers is the transfer of an oxygen from the nitro group to the sulfur followed by the ejection of SO from the molecular ions. A mechanism involving the initial oxygen migration to the sulfur through a favourable 6-membered transition state followed by cyclization with the concomitant expulsion of SO is proposed for this process. Other interesting decomposition processes occurring as a consequence of this ortho effect have also been noticed. The proposed mechanisms for these processes are supported by mass analysed ion kinetic energy spectra and high voltage scans.     

Nitroradical Anion Formation from some Iodo‐Substituted Nitroimidazoles

The electrochemical behavior of iodo nitroimidazole derivatives such as 1‐methyl‐4‐iodo‐5‐nitroimidazole (M‐I‐NIm) and 1‐methyl‐2,4‐diiodo‐5‐nitroimidazole (M‐I₂‐NIm) and the parent compound 1‐methyl‐5‐nitroimidazole (M‐NIm), was studied in protic, mixed and non‐aqueous media. The electrochemical study was carried out using Differential Pulse Polarography (DPP), Cyclic Voltammetry (CV), Differential Pulse Voltammetry (DPV) and coulometry and as working electrodes mercury and glassy carbon were used. As can be expected, in all media, the effect of introduce iodo as substituent in the nitroimidazole ring produced a decrease of the energy requirements of the nitro group reduction. Certainly, this fact can be explained by the electron withdrawing character of the iodo substituent that acts diminishing the electronic density on the nitro group thus facilitating their reduction. In all the studied media the reduction of M‐NIm produced a detectable signal for a nitro radical anion derivative. In the case of M‐I‐NIm the nitro radical anion was only detectable in both mixed and non‐aqueous media. On the other hand the nitro radical anion for the M‐I₂‐NIm was detected only in non‐aqueous medium. When glassy carbon electrode was used as the working electrode in a mixed medium a detectable nitro radical anion derivative appeared for all compounds, thus permitting an adequate comparison between them. The obtained values of k₂ for M‐NIm, M‐I‐NIm and M‐I₂‐NIm in non‐aqueous medium were 5.81×10², 132×10² and 1100×10² M^?1 s^?1, respectively. From the obtained k₂ and t_1/2 values in this medium, it is concluded that there is a direct dependence between the presence of iodo substitution in the nitroimidazole ring with the stability of the nitro radical anion.     

Use of two-parameter correlations for studying the radical reactivity of aromatic compounds

Two-parameter equation correlations are reported for radical reactions of aromatic compounds. In these correlations polar and resonance substituent constants identical with the substituent constants of aliphatic compounds were used. The equations correlate the rate constants for H abstraction reactions and for the addition of a variety of free radicals to the ortho-, meta-, and para-substituted aromatic compounds. Besides, they correlate parameters of the spectra for substituted aromatic radicals. The correlations show that the effects of para substituents on the reactions studied are nearly entirely resonance effects, whereas for the meta- and ortho-substituted compounds polar (inductive) effects become essential. Application of the two-parameter correlations permits also to determine the structure of transition states (σ or π-complex) in free-radical reactions.     

Pyramidal distortion of the NO<Subscript>2</Subscript> group in the radical anion of 2,4,6-trimethoxynitrobenzene

Electrochemical reduction in DMF is used to produce the radical anion of 2,4,6-trimethoxynitrobenzene with an EPR spectrum that shows hyperfine splitting for ¹⁵N nuclei of the nitro group and ¹³C nuclei of the benzene ring given the natural abundance of the isotopes. According to UB3LYP/6-31+G* quantum chemical calculations considering solvation in the PCM model, the nitro group in the equilibrium conformation of the RA of 2,4,6-trimethoxynitrobenzene is rotated relative to the benzene ring plane by an angle close to 90° and has a pyramidal structure. The calculated isotropic hyperfine coupling constants for this conformation are closest to the experimental results.     

Photochromic Properties of ortho-Methylnitrobenzothiazoles in Solution

Isomeric benzothiazoles having the nitro and methyl groups ortho to each other are converted into tautomeric aci-nitro derivatives on irradiation in heptane solution; in water, the corresponding more deeply colored anions are formed. The efficiency of photochromic transformations strongly depends on the position of the nitro and methyl groups in the benzene ring of the benzothiazole molecule.     

Dibenz[b,f]oxepin and thiepin radical anions. Conjugative properties of sulfur in its different oxidation states

The radical anion of dibenz[b,f]oxepin has been investigated by esr spectroscopy and the relative coupling constants compared with dibenzo[b,f]thiepin. In both cases assignments were obtained using a theoretical method (INDO). In addition radicals from dibenzo[b,f]thiepin sulfoxide and sulfone could be detected and, unusually, the free electron density on carbon atoms of the radical anion containing a sulfonyl group is larger than that on carbons of radical anions containing a sulfide or a sulfoxide group.     

Electron-impact studies. LXXXVII—ortho effects in the negative ion mass spectra of salicylates and anthranilates

The molecular anions of the methyl and phenyl esters of 4-nitrosalicylic acid and 5-nitroanthranilic acid eliminate ROH (R ? Me or Ph) by an ortho rearrangement. The molecular anions of phenyl 3-hydroxy-5-nitrobenzoate and phenyl 3-amino-5-nitrobenzoate lose PhOH to a lesser extent, and a study of the pressure dependence of these eliminations indicates the operation of simultaneous two-stage cleavage reactions. The competitive ortho effects observed when the nitro group is adjacent to either the ester or hydroxyl functions are described.     

A theoretical study of α-substituted isopropyl and cyclopropyl anions

Ab initio molecular orbital theory has been used to probe the effect of the substituent X on the structures, strain energies, stabilization energies, inversion barriers, and proton affinities of carbanions CH₃CX CH and cis-C₃H₄X^?, where X = H, F, CN, and NC. All geometries have been optimized with a 3-21G basis set, and the parent anions (X = H) were also optimized with the same basis set with a diffuse function added (i.e. the 3-21 + G basis set). The anions, with the exception of the α-cyanoisopropyl anion, are pyramidal. The out-of-plane angle, α, for the pyramidal anions decreases in the order F > H ≈ NC > CN, and the barriers to inversion follow the same order with the cyclopropyl anions consistently having higher barriers than the isopropyl anions. The substituents strongly stabilize the anions with the stabilization energy following the order CN > NC > F. The cyano group slightly reduces the strain energy of cyclopropane, but the isocyano and fluoro substituents are weakly and strongly destabilizing, respectively. The pyramidal cyclopropyl anions are less strained than the cyclopropanes except when the substituent is a cyano group where the strain energies are reversed but are very similar. The planar anions all have higher strain energies than the cyclopropanes.     

Phototransformations of 6-X-5-Nitroquinoxalines

Photophysical properties and photochemical activity of 6-X-5-nitroquinoxalines with electron-donor substituents (X = H, CH₃, Cl, OC₂H₅, NH₂) ortho to the nitro group were studied. The quantum yield of the formation of 5-hydroxyquinoxaline from the corresponding nitro derivative depends on the nature of the substituent and irradiation conditions. Phototransformations can go through nitro-nitrite rearrangement with the participation of two alternative T(n*) levels, depending on the size and electronic effects of the substituent. The latter factor is largely determined by the population on excitation of different charge-transfer states involving the nitro group.