Nitro Isomers Research Articles

Mononitro-monoperchlorylbenzenes - A DFT Treatment

Perchloryl derivatives, especially aromatic ones have some explosive character and decompose explosively when they are initiated. In the present study, ortho, meta and para nitro isomers of perchlorylbenzene have been considered within the framework of density functional theory at the level of B3LYP/6-311++G(d,p). The results have indicated that they are electronically stable such that the para isomer is more stable than the others whereas the ortho isomer is the least stable of all. Various quantum chemical properties of these isomers are harvested and discussed. The calculated UV-VIS spectra of the isomers have been obtained and the impact sensitivity order is estimated as meta < para < ortho. Also nucleus independent chemical shifts values for the isomers are calculated which yield the aromaticity order of ortho > meta > para.

Exploring Photoswitchable Properties of Two Nitro Nickel(II) Complexes with (N,N,O)-Donor Ligands and Their Copper(II) Analogues.

Two photoswitchable nickel(II) nitro coordination compounds and their copper(II) analogues are reported. In all these systems, the metal center is chelated by (N,N,O)-donor ligands containing either 2-picolylamine or 8-aminoquinoline fragments. The studied compounds were thoroughly investigated using crystallographic and spectroscopic techniques supplemented by computational analysis. They are easy to synthesize and stable, and all compounds undergo the nitro group isomerization reaction. Nevertheless, there are significant differences between the copper and nickel systems regarding their structural and switchable properties. According to the solid-state IR spectroscopy results, 400–660 nm light irradiation of the ground-state (η2-O,O′)-κ-nitrito copper(II) complexes at 10 K induces a rather moderate conversion to a metastable linkage isomer, which is visible only up to approximately 60–80 K. In turn, upon visible light irradiation (ca. 530 nm excitation wavelength), the ground-state nitro isomers of the examined nickel(II) complexes transform into the endo-nitrito forms. It was possible to achieve about 35% conversion for both nickel(II) systems and to determine the resulting crystal structures at 160 K in the case of single crystals after 30–45 min of exposure to LED light (crystals decayed with longer irradiation), and roughly 95% conversion was achieved for thin-film samples as indicated by the IR spectroscopy results. Traces of the endo-nitrito linkage isomers remained up to 200–220 K, and the isomerization reaction was proven to be fully reversible.

N-(4-Hy-droxy-2-nitro-phen-yl)acetamide.

The title compound, C8H8N2O4, differs in its degree of planarity from the 3-nitro isomer and also in its hydrogen-bonding pattern. Its NH group forms an intra-molecular hydrogen bond to a nitro oxygen atom, and its OH group forms an inter-molecular hydrogen bond to an amide oxygen atom, generating [10] chains in the crystal.

Nitro Fatty Acids (NO2-FAs): An Emerging Class of Bioactive Fatty Acids.

Unsaturated nitro fatty acids (NO2-FAs) constitute a category of molecules that may be formed endogenously by the reaction of unsaturated fatty acids (UFAs) with secondary species of nitrogen monoxide and nitrite anions. The warhead of NO2-FAs is a nitroalkene moiety, which is a potent Michael acceptor and can undergo nucleophilic attack from thiol groups of biologically relevant proteins, showcasing the value of these molecules regarding their therapeutic potential against many diseases. In general, NO2-FAs inhibit nuclear factorκ-B (NF-κB), and simultaneously they activate nuclear factor (erythroid derived)-like 2 (Nrf2), which activates an antioxidant signaling pathway. NO2-FAs can be synthesized not only endogenously in the organism, but in a synthetic laboratory as well, either by a step-by-step synthesis or by a direct nitration of UFAs. The step-by-step synthesis requires specific precursor compounds and is in position to afford the desired NO2-FAs with a certain position of the nitro group. On the contrary, the direct nitration of UFAs is not a selective methodology; thus, it affords a mixture of all possible nitro isomers.

Isomeric nitro substituted symmetrical benzamides: Crystal Structures, Hirshfeld surface analysis, 3D energy frameworks, DNA binding and cell line studies

Isomeric nitro substituted symmetrical benzamides, 2-nitro-N-(2-nitrobenzoyl)benzamide – ASP4 and 3-nitro-N-(3-nitrobenzoyl)benzamide – ASP5, were synthesized. Analysis of both crystals approved the structures of synthesized compounds as assigned from spectroscopic data. The intermolecular N–H···O and C–H···O hydrogen bonds linked the molecules, through the bifurcated hydrogen bonds, into three-dimensional architectures, in which they may be effective in the stabilizations of the structures. π–π interactions between the benzene rings of neighboring molecules further consolidated the crystal packings. Crystal structures by Hirshfeld surface (HS) analysis specified the substantial contributions for the crystal packing that are from H ... O/O ... H (46.4%) and H ... H (20.3%) (ASP4) and H ... O/O ... H (36.7%), H ... C/C ... H (19.9%) and H ... H (14.1%) (ASP5) interactions. The N–H···O and C–H···O hydrogen bond energies, by computational analysis, were found to be 71.0 and 50.5 kJ mol−1 (for ASP4) and 37.0, 36.9 and 26.0, 24.1 kJ mol−1 (for ASP5). The evaluations of the electrostatic, dispersion and total energy frameworks indicated that the stabilizations were dominated via the dispersion energy contributions in both compounds. DNA binding studies pointed that ASP4 has comparatively stronger interaction with DNA. Glioblastoma cancer (U87) and human embryonic kidney (HEK-293) cell lines studies of both the compounds revealed their promising anticancer drug candidacy. However, ASP4 showed less toxicity towards normal cells, hence comparatively safer than ASP5.

Binder-Free Modification of a Glassy Carbon Electrode by Using Porous Carbon for Voltammetric Determination of Nitro Isomers.

In this study, Liquidambar formosana tree leaves have been used as a renewable biomass precursor for preparing porous carbons (PCs). The PCs were produced by pyrolysis of natural waste of leaves after 10% KOH activation under a nitrogen atmosphere and characterized by a variety of state-of-the-art techniques. The PCs possess a large surface area, micro-/mesoporosity, and functional groups on its surface. A glassy carbon electrode modified with high PCs was explored as an efficient binder-free electrocatalyst material for the voltammetric determination of nitro isomers such as 3-nitroaniline (3-NA) and 4-nitroaniline (4-NA). Under optimal experimental conditions, the electrochemical detection of 3-NA and 4-NA was found to have a wide linear range of 0.2–115.6 and 0.5–120 μM and a low detection limit of 0.0551 and 0.0326 μM, respectively, with appreciable selectivity. This route not only enhanced the benefit from biomass wastes but also reduced the cost of producing electrode materials for electrochemical sensors. Additionally, the sensor was successfully applied in the determination of nitro isomers even in the presence of other common electroactive interference and real samples analysis (beverage and pineapple jam solutions). Therefore, the proposed method is simple, rapid, stable, sensitive, specific, reproducible, and cost-effective and can be applicable for real sample detection.

Synthesis and Reactivity of Fusion Product of 2-Methylthiazole Fragment to 2-(Furan-2-yl)benzimidazole

Reaction of 1,2-diamino-4-nitrobenzene with furan-2-carbaldehyde in the presence of copper sulfate afforded 2-(furan-2-yl)-5(6)-nitro-1H-benzimidazole. Its N-methylation provided 1-methyl-5(6)-nitro isomers. After reduction of isomers with tin in conc. HCl a pure 3-methyl-2-(furan-2-yl)benzimidazol-5-amine was obtained. The condensation of this amine with acetic anhydride led to the formation of N-[3-methyl-2-(furan-2-yl)benzimidazol-5-yl]acetamide whose treatment with excess P2S5 in anhydrous pyridine resulted in the corresponding thioamide. The latter was oxidized with K3[Fe(CN)6] in alkaline environment to obtain 2,8-dimethyl-7-(furan-2-yl)-8H-imidazo[4,5-g][1,3]benzothiazole. Its reactions of electrophilic substitution were studied: nitration, bromination, sulfonation, formylation, acylation. The substituent is introduced exclusively in the position 5 of the furan ring.

Antitubercular Nitroimidazoles Revisited: Synthesis and Activity of the Authentic 3-Nitro Isomer of Pretomanid.

A published study of structural features associated with the aerobic and anaerobic activities of 4- and 5-nitroimidazoles had found that the 3-nitro isomer of pretomanid, 8, displayed interesting potencies, including against nitroreductase mutant Mycobacterium tuberculosis. However, recent nuclear magnetic resonance analyses of two trace byproducts, isolated from early process optimization studies toward a large-scale synthesis of pretomanid, raised structural assignment queries, particularly for 8, stimulating further investigation. Following our discovery that the reported compound was a 6-nitroimidazooxazole derivative, we developed a de novo synthesis of authentic 8 via nitration of the chiral des-nitro imidazooxazine alcohol 26 in trifluoroacetic or acetic anhydride, and verified its identity through an X-ray crystal structure. Unfortunately, 8 displayed no antitubercular activity (MICs > 128 μM), whereas the second byproduct (3′-methyl pretomanid) was eight-fold more potent than pretomanid in the aerobic assay. These findings further clarify target specificities for bicyclic nitroimidazoles, which may become important in the event of any future clinical resistance.

Theoretical and conceptual density functional theory (DFT) study on selectivity of 4-hydroxyquinazoline electrophilic aromatic nitration

In common with other aza-heterocycles, 4-hydroxyquinazoline and their derivatives are important pharmacophores and versatile lead molecule used in several specific biological activities. The potency of these compounds depends on the nature and/or position of their substituents. In this paper, we report a theoretical study of the most probable nitration reaction centers of 4-hydroxyquinazoline for electrophilic attack, the mono and di-nitration was also discussed. In parallel, a computational study has been performed in gas by using the B3LYP/6311 G(d) level. The stability of the four nitro isomers is rationalized by means of the global index and local reactivity indices. Their molecular electrostatic potential (MEP) and Milliken charge were explored. Molecular geometries and NMR H spectra was examined. In addition, stationary points of reactant, transition state and intermediate were optimized in water condensed phase at the same level. The relative energies of the regioisomeric δ-complexes confirm that the substitution at C6 (6-nitro σ-complexes) is favored in these conditions, what was in agreement with our others calculating results (in gas).

N-[2,2-Bis(methoxy-NNO-azoxy)ethyl]pyrazoles

The reaction of 2,2-bis(methoxy-NNO-azoxy)ethanol nitrate with pyrazole, 3-nitropyrazole, 4-nitropyrazole, or 3,4-dinitropyrazole allowed to obtain the respective N-[2,2-bis(methoxy-NNO-azoxy)ethyl]pyrazoles. In the case of 3-nitropyrazole, only the 3-nitro isomer was formed, while alkylation of 3,4-dinitropyrazole led to a mixture of 3,4- and 4,5-dinitro isomers in 7:1 ratio, which was difficult to separate. The obtained pyrazoles were characterized by 1H, 13C, and 15N NMR spectroscopy. X-ray structural studies were performed for the synthesized 3-NO2, 4-NO2, and 3,4-(NO2)2 derivatives.

Nitrite-bonded nickel(II) complex of N-cyclohexyl-N-(2-pyridinylmethyl)amine; Synthesis, spectroscopic characterization, X-ray structure and DFT calculations

A combined experimental and computational investigation on a nickel(II) complex of N-cyclohexyl-N-(2-pyridinylmethyl)amine, L, was carried out. The compound [NiL2(ONO)]NO2·½CH3CN has been prepared by the addition of L to a suspension of K4[Ni(NO2)6]·H2O in methanol and structurally characterized by a combination of analytical, spectroscopic and crystallographic methods. The nickel(II) center in the complex is surrounded by two amine nitrogen and two oxygen atoms of the nitrite ion (η2-ONO) in the basal plane and two nitrogen atoms of pyridine moieties in apical positions, forming a distorted octahedral geometry. The relative stability of the geometrical isomers (cis and trans) and linkage isomers (η1-NO2, η2-ONO and η1-ONO) of the complex were investigated by density functional theory (DFT) calculations. In support of the X-ray structure, the calculated results verified that in all cases the cis-bidentate η2-ONO isomer is more stable than the other four-coordinated nitro isomers. A further theoretical analysis of the electronic structure of the complex has also been carried out to achieve deeper insight into the properties of the relevant molecular orbitals.

N-Alkylation and N-amination of isomeric nitro derivatives of 3-methyl-4-(1H-pyrazol-3(5)-yl)furazan

The reaction of bromoacetone and hydroxylamine-О-sulfonic acid with isomeric mono- and dinitropyrazoles containing a furazanyl moiety at position 3(5) gave pairs of regioisomeric products from pyrazole ring N-acetonylation and N-amination, respectively, that were characterized in detail by multinuclear NMR spectroscopy. X-ray structural study of the four synthesized N-amino derivatives indicated a non-planar structure, while the conformational analysis pointed to conformational lability of such molecules, and the role of intermolecular interactions in determining the crystal structure.

Continuous-Flow Nitration of o-Xylene: Effect of Nitrating Agent and Feasibility of Tubular Reactors for Scale-Up

Continuous-flow nitration of o-xylene has been studied with different nitrating agents over a wide range of conditions for different parameters such as temperature, residence time, and concentrations. A nitrating mixture comprising sulfuric acid and fuming nitric acid was seen to yield higher selectivity for the isomer 1,2-dimethyl-3-nitrobenzene over the isomer 1,2-dimethyl-4-nitrobenzene and also a non-negligible quantity of dinitro derivatives of o-xylene. With only fuming nitric acid as the nitrating agent, the reaction was selective for 1,2-dimethyl-4-nitrobenzene over 1,2-dimethyl-3-nitrobenzene. Impurities mainly come from nitration of mononitro derivatives, and this occurs more from nitration of the 3-nitro isomer because of its higher reactivity with nitric acid. An economic analysis of the continuous-flow reactor for the production of 1,2-dimethyl-4-nitrobenzene at 100 and 500 kg/h in a jacketed tubular reactor showed that numbering-up is a more economical approach for higher production capacity. A combination of large- and small-sized tubes depending upon the relative rates of heat generation during a reaction will achieve more profit and a shorter payback period than having the entire reactor made of a single tube size.

Molecular structure and nitrite-bonded study on copper(II) complexes of N,N-dialkyl,N′-benzyl-ethylenediamine; synthesis, spectroscopic characterization, X-ray structure, steric effect and density functional theory calculations

Presented here is an investigation on the geometric (molecular) structures, spectroscopic properties and electronic structures of copper(II)-nitrite complexes as a function of steric effects, utilizing a set of closely related co-ligands. The prepared complexes, with the general formula [CuLR(η2-ONO)2] where LR is N,N-dialkyl,N′-benzyl-ethylenediamine and R is methyl, ethyl or isopropyl moieties, were structurally characterized by physico-chemical and spectroscopic methods. An X-ray diffraction study on CuLMe(η2-ONO)2] and CuLEt(η2-ONO)2] reveals that the copper(II) center in both compounds is located in a distorted octahedral environment through coordination of two amine nitrogen atoms and four oxygen atoms of the nitrite ligands. Depending on the steric crowding of the co-ligand, the coordination mode is either symmetric or asymmetric bidentate, as is evident from X-ray crystallography and IR spectroscopy. The relative stability of linkage isomers of these compounds, along with a tert-butyl derivative complex, was investigated using density functional theory (DFT) calculations. The calculated results demonstrated that in all cases the bidentate η2-ONO isomer is more stable than the four-coordinated nitro isomer (η1-NO2). However, the differences in the relative stability decrease as the steric hindrance in the co-ligand increases. The vibrational spectra of the complexes were assigned using DFT calculations. In support with the X-ray structure, the results reveal that νas(N–O) splits into two bands, with the separation increasing from [CuLMe(η2-ONO)2] through to [CuLtert-buty(η2-ONO)2]. That is at least partially dictated by steric factors within the molecules, imposed by the alkyl groups of the co-ligand. The UV–Vis absorption spectra are presented and analyzed with the help of time-dependent density functional theory (TD-DFT) calculations.

Solid‐State Interconversions: Unique 100 % Reversible Transformations between the Ground and Metastable States in Single‐Crystals of a Series of Nickel(II) Nitro Complexes

The solid-state, low-temperature linkage isomerism in a series of five square planar group 10 phosphino nitro complexes have been investigated by a combination of photocrystallographic experiments, Raman spectroscopy and computer modelling. The factors influencing the reversible solid-state interconversion between the nitro and nitrito structural isomers have also been investigated, providing insight into the dynamics of this process. The cis-[Ni(dcpe)(NO2)2] (1) and cis-[Ni(dppe)(NO2)2] (2) complexes show reversible 100 % interconversion between the η1-NO2 nitro isomer and the η1-ONO nitrito form when single-crystals are irradiated with 400 nm light at 100 K. Variable temperature photocrystallographic studies for these complexes established that the metastable nitrito isomer reverted to the ground-state nitro isomer at temperatures above 180 K. By comparison, the related trans complex [Ni(PCy3)2(NO2)2] (3) showed 82 % conversion under the same experimental conditions at 100 K. The level of conversion to the metastable nitrito isomers is further reduced when the nickel centre is replaced by palladium or platinum. Prolonged irradiation of the trans-[Pd(PCy3)2(NO2)2] (4) and trans-[Pt(PCy3)2(NO2)2] (5) with 400 nm light gives reversible conversions of 44 and 27 %, respectively, consistent with the slower kinetics associated with the heavier members of group 10. The mechanism of the interconversion has been investigated by theoretical calculations based on the model complex [Ni(dmpe)Cl(NO2)].

Thermoanalytical study of linkage isomerism in coordination compounds. Part III: A DSC study on the effect of counterion on the solid state isomerization of nitro and nitrito linkage isomers of pentaamminecobalt(III) complexes

Solid state thermal interconversion of [Co(NH3)5NO2]X2 (nitro isomer) and [Co(NH3)5ONO]X2 (nitrito isomer) complexes (X=Cl−, Br−, I−, PF6−) was studied by DSC at several heating rates. The isomerization of pure sample of both isomers leads to an equilibrium stable state in which nitro and nitrito isomers are major and minor components, respectively. Change of the counterion affects thermodynamic parameters of the isomerization reaction, but the nitro isomer is always more stable than the nitrito one. The equilibrium constant (nitro to nitrito molar ratio) increases in the series Cl−≈Br−<PF6−<I−. The kinetic parameters of isomerization of both isomers were determined by Kissinger method. It was founded that the rate of interconversion of different salts of both isomers decreases in the series Cl−>Br−>PF6−>I−. The negative activation entropy supports an associative mechanism with a seven coordinate transition state in solid state.

Photoinduced linkage isomerization in new rhenium(I) tricarbonyl complexes coordinated to N-nitrite and O-nitrite

The ambidentate nitrite ion, NO2−, is a biologically relevant species that can be coordinated to transition metals via the nitrogen or oxygen atom. Most of its physiological effects involve metalloproteins so it is important to understand the factors that control the predominance of one or another isomer. In this work, we present the syntheses and characterization by spectroscopy, electrochemistry and DFT calculations of new rhenium(I) tricarbonyl complexes with different polypyridyl ligands in the coordination sphere and with the nitrite ion coordinated through either its N- or O-atom. For two of them we have determined their crystal structures by X-ray diffraction and we have found that in the solid when the ancilliary ligand is bpy the N-binding mode is the most stable, while dmb is the ligand, the –CH3 substituents imposed the C–H (methyl group)⋯O–NO (nitrito) interactions favoring the O-binding mode. However, at room temperature in CH2Cl2 the nitro isomer is the most stable for both complexes in agreement with DFT calculations. Both complexes exhibit photoinduced linkage isomerism which could be of interesting in the design of new materials. Although nitro complexes are precursors of nitrosyl compounds, in this work the synthesis of the nitrosyl complexes as solid could not be possible because there is higher π-backbonding from Re(I) to the carbonyl groups, or to the polypyridil ligands instead of to the NO group, which is π-acceptor, in consequence the nitrosyl complexes are unstable and decompose immediately to the solvate complexes.

β-Nitro-5,10,15-tritolylcorroles

Functionalization of the β-pyrrolic positions of the corrole macrocycle with -NO(2) groups is limited at present to metallocorrolates due to the instability exhibited by corrole free bases under oxidizing conditions. A careful choice of the oxidant can limit the transformation of corroles into decomposition products or isocorrole species, preserving the corrole aromaticity, and thus allowing the insertion of nitro groups onto the corrole framework. Here we report results obtained by reacting 5,10,15-tritolylcorrole (TTCorrH(3)) with the AgNO(2)/NaNO(2) system, to give mono- and dinitrocorrole derivatives when stoichiometry is carefully controlled. Reactions were found to be regioselective, affording the 3-NO(2)TTCorrH(3) and 3,17-(NO(2))(2)TTCorrH(3) isomers as the main products in the case of mono- and disubstitution, in 53 and 20% yields, respectively. In both cases, traces of other mono- and disubstituted isomers were detected, which were structurally characterized by X-ray crystallography. The influence of the β-nitro substituents on the corrole properties is studied in detail by UV-visible, electrochemical, and spectroelectrochemical characterization of these functionalized corroles. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations of the ground and excited state properties of these β-nitrocorrole derivatives also afforded significant information, closely matching the experimental observations. It is found that the β-NO(2) substituents conjugate with the π-aromatic system of the macrocycle, which initiates significant changes in both the spectroscopic and redox properties of the so functionalized corroles. This effect is more pronounced when the nitro group is introduced at the 2-position, because in this case the conjugation is, for steric reasons, more efficient than in the 3-nitro isomer.

Photocrystallographic identification of metastable nitrito linkage isomers in a series of nickel(ii) complexes

Single crystal photocrystallographic experiments and solid state Raman spectroscopy have been used to determine the low temperature, metastable structures of the nickel(ii) nitrito complexes [Ni(aep)(2)(η(1)-ONO)(2)] 1#O (aep = 1-(2-aminoethyl)piperidine), [Ni(aem)(2)(η(1)-ONO)(2)] 2#O (aem = 1-(2-aminoethyl)morpholine), and [Ni(aepy)(2)(η(1)-ONO)(2)] 3#O (aepy = 1-(2-aminoethyl)pyrrolidine and where the #O denotes the oxygen-bound nitrito metastable molecule). These linkage isomers of the equivalent nitro complexes [Ni(aep)(2)(η(1)-NO(2))(2)] 1, [Ni(aem)(2)(η(1)-NO(2))(2)] 2 and [Ni(aepy)(2)(η(1)-NO(2))(2)] 3 are formed by LED irradiation at temperatures below 120 K. The behavior of the three complexes upon irradiation is generally similar, but some subtle differences have been observed. From the crystallographic studies all three complexes 1-3 exhibit the endo-nitrito linkage isomer upon irradiation, however, for 3# (a crystal structure that contains components of both 3 and 3#O) an exo-nitrito isomer is also observed. Under conditions of 90-100 K, with blue light, the conversion percentages to the nitrito isomers, 1#O, 2#O and 3#O were 16%, 22% and 30%, respectively. At temperatures below 110 K all three nitrito isomers were stable for over four hours but while 2#O and 3#O could be detected at temperatures down to 30 K, at temperatures below 60 K the metastable structure 1#O appeared to be quenched and only the nitro isomer 1 was identified in the crystal. The solid state Raman spectra for 1#, 2# and 3# confirmed the photocrystallographic results with the nitrito isomers being identified from the O-N-O deformation vibrations.

Photo-induced isomerization of three nitrotoluene isomers: A matrix-isolation infrared spectroscopic and quantum-chemical study

The photo-induced isomerization reactions of ortho-, meta- and para-nitrotoluene molecules were investigated by matrix isolation infrared spectroscopy and quantum chemical calculations. Under UV irradiation of ortho-nitrotoluene in solid argon, the hydrogen atom transfer isomer was formed, as reported previously. It was found that the hydrogen atom transfer isomer is unstable and rearranged to its nitro isomer upon annealing. In addition, the nitrite isomer as well as its dissociation product tolyloxy radical was also formed. Only the nitrite isomers and the tolyloxy radicals were formed upon UV excitation of the meta- and para-nitrotoluene molecules. Infrared spectra and vibrational frequency assignments of the newly observed nitrite isomers and tolyloxy radicals are reported, which are supported by quantum chemical calculations.