Strong Electron-withdrawing Nitro Group Research Articles

Introducing the azocinnamic acid scaffold into bent-core liquid crystal design: A structure–property relationship study

A series of bent-core liquid crystals possessing the azocinnamoyl unit in both elongating side arms was synthesized. The chain length was kept fixed for each molecule (C12H25), whereas the substituents at the central and outer rings were varied. The LC phases were assigned by polarizing optical microscopy, differential scanning calorimetry and X-ray diffraction. The investigated compounds are suitably diverse to reveal some aspects of the relationship between molecular structure and the mesomorphic properties. Namely, non-substituted parent compound is crystalline only and the methyl group in position 2 or the chlorine atom in position 4 of the central ring suppresses LC phase formation. Introduction of the strong electron-withdrawing nitro group between the side arms on the central ring leads to a B7 phase. Compounds possessing a bromine atom or two chlorine atoms in the neighbourhood of the ester groups form LC phases typical for rod-like molecules, namely a nematic – smectic phase sequence. The results are compared with those reported for the azobenzoyl analogues.

Synthesis of Ag-Cu co-doping sponge iron-based trimetal for boosting simultaneous degradation of combined pollutants

To date, zero-valent iron (ZVI)-based technique has encountered a baffle, challenging simultaneous detoxification of refractory rhodamine B (RhB) and p-nitrophenol (PNP) possessing strong electronwithdrawing nitro-group. In this study, we synthesized Ag-Cu decorated sponge iron (s-Fe0)-based trimetal for simultaneous degradation of RhB and PNP. The results show that Cu-Ag co-doping s-Fe0 (s-Fe0-(Cu-Ag)) achieves approx. 90.6 % of maximized removal of RhB; the preferred s-Fe0-(5 wt%Cu-1 wt%Ag) assisted with 6 L/min aeration rate simultaneously declines RhB and PNP within 10 recycling tests; non-aeration process obtains a complete reduction of PNP as well as merely approx. 23.9 % removal of RhB. Moreover, the Cu-Ag microstructure covering s-Fe0-(Cu-Ag) has been characterized in detail. Furthermore, the electron spin resonance (ESR) spectra have been applied to investigate simultaneous generation of reactive oxygen species (ROSs) and hydrogen radicals ([H]abs) over s-Fe0-(Cu-Ag). To our best knowledge, this is the first study reporting the enhanced bifunctional catalysis of s-Fe0-(Cu-Ag)/O2 for simultaneous degradation of RhB and PNP.

Asymmetric Henry reaction using a double fluorous-tagged Co–salen complex

A highly stereoselective asymmetric Henry reaction using a double fluorous-tagged Co–salen complex was conducted. The introduction of two fluorous tags into the Co–salen complex was found to be more effective in terms of improving stereoselectivity than the introduction of a strong electron-withdrawing nitro group into the same position of the salen ligand. The observed stereoselectivity was significantly higher than that when using a Jacobsen-type Co–salen complex bearing the same asymmetric source.

Michael addition of amines to sterically crowded ortho-benzoquinone completed with unprecedented 1,2-shift of a tert-butyl group

A strong electron-withdrawing nitro group introduced into the 6-position of 3,5-di-( tert -butyl)-1,2-benzoquinone provides for activation of the sterically blocked Michael addition reaction channel. Addition of amines to the quinone is followed by a concerted 1,2-migration of a tert -butyl group to afford derivatives of 4-amino-3-nitrocyclohexa-3,5-diene-1,2-dione system. The multistep reaction mechanism was examined using DFT computational methods. • Michael addition reaction channel blocked in sterically crowded o-quinones is activated. • 3,5-di-( tert -butyl)-6-nitro-1,2-benzoquinone reacts with amines to give cyclohexadienones. • The addition reaction is accompanied by 1,2-shift of a tert- butyl group along the ring. • The multistep mechanism of the reaction is unveiled by the DFT study.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Nickel‐Catalyzed C‐O Cross‐Coupling Reaction at Low Catalytic Loading with Weak Base Participation

Herein, we report a nickel‐catalyzed crossing‐coupling reaction for the synthesis of diaryl ethers. The desired products are achieved by coupling heterocyclic alcohols with aryl bromides bearing strong electron withdrawing nitro group under the catalyst system of NiCl2(PPh3)2 and weak base KHCO3. This mild reaction exhibits a broad functional group tolerance. Compound 4 as an important intermediate is suitable for further structural modification of MALT1 inhibitor MI‐2.

Derivatization of Natural Compound β-Pinene Enhances Its In Vitro Antifungal Activity against Plant Pathogens.

Background: The development of new antifungal agents has always been a hot research topic in pesticide development. In this study, a series of derivatives of natural compound β-pinene were prepared, and the antifungal activities of these derivatives were evaluated. The purpose of this work is to develop some novel molecules as promising new fungicides. Methods: Through a variety of chemical reactions, β-pinene was transformed into a series of β-pinene-based derivatives containing amide moieties and acylthiourea moieties. The antifungal activities of these derivatives against five plant pathogens including Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana, Phomopsis sp. and Phytophthora capsici were tested; preliminary structure–activity relationship was discussed. Results: Some derivatives exhibited moderate or significant antifungal activity due to the fusion of the amide moiety or the acylthiourea moiety with the pinane skeleton. The structure–activity relationship analysis showed that the fluorine atom and the strong electron withdrawing nitro group, or trifluoromethyl group on the benzene ring of the derivatives had a significant effect on the improvement of the antifungal activity against Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana and Phomopsis sp. Meanwhile, the introduction of an ethyl group at the meta-position on the benzene ring of the derivatives could improve the antifungal activity against Phytophthora capsici. Compounds 4e, 4h, 4q, 4r exhibited broad-spectrum antifungal activity against the tested strains. Compound 4o had significant antifungal activity against Phytophthora capsici (IC50 = 0.18 μmol/L). These derivatives were expected to be used as precursor molecules for novel pesticide development in further research.

Design, molecular docking and synthesis of novel 5,6-dichloro-2-methyl-1H-benzimidazole derivatives as potential urease enzyme inhibitors

A novel series of 5,6-dichloro-2-methyl-1H-benzimidazole derivatives was synthesized and then screened for their urease inhibitory activity. All compounds showed more potent inhibitory activity in the range of IC50 = 0.0294 ± 0.0015–0.1494 ± 0.0041 µM than thiourea (IC50 = 0.5117 ± 0.0159 µM), as a reference inhibitor. Among all the tested compounds, the compound 15 (IC50 = 0.0294 ± 0.0015 µM) having strong electron-withdrawing nitro group on the phenyl ring was recorded as the most potent inhibitor of urease. All compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes.

Synthesis, anionophoric activity and apoptosis-inducing bioactivity of benzimidazolyl-based transmembrane anion transporters

In this paper we show that a series of 1,3-bis(benzimidazol-2-yl)benzene (m-Bimbe) derivatives exhibit excellent performance as transmembrane anion transporters with anticancer activity. The transport efficiency of m-Bimbe and its derivatives has been firstly optimized by adding a strong electron-withdrawing nitro group at the 5-position of the central phenyl subunits to enhance the CH···anion interactions. Evidences for the interactions were obtained from ESI MS, spectrophotometric and 1H NMR titrations. These compounds exhibit potent anionophoric activity in both liposomal models and live cells. In particular, the 5-nitrated derivatives having nitro or trifluoromethyl groups at the benzimidazoloyl subunits exhibit 2370- and 1721-fold enhanced anionophoric activity with the EC50 values as low as 36 and 50 nM, respectively. These compounds can disturb the cellular homeostasis of chloride anions, modify the intracellular pH and induce the basification of acidic organelles. Most of this series of m-Bimbe derivatives exhibit potent cytotoxicity toward the tested human solid tumor cell lines, and the 5-nitrated derivative bearing trifluoromethyl groups at the benzimidazoloyl subunits is the most active with the IC50 value in the low micromolar range. Mechanistic studies suggest that the transport of chloride anions across the cellular membranes plays a critical role in the cytotoxic effect and these compounds induce cell death probably via an apoptotic process.

Two Phenanthrenequinone-Based Compound Cathode Materials for Lithium Ion Batteries

Two phenanthrenequinone (PQ)-based compounds 2,7-dinitro-9,10-phenanthrenequinone (DNPQ) and 2,7-diamino-9,10-phenanthrenequinone (DAPQ) were prepared by introducing a strong electron-withdrawing nitro group or an electron-donating amino group at 2,7-positions of PQ. CR2430 coin-type cells were assembled using these compounds as cathode active materials and lithium metal as an anode. For comparison, the electrochemical performance of pristine PQ under the same condition was tested. The initial discharge specific capacity of DNPQ is 221 mAh g−1 which is higher than pristine PQ and PAPQ, because the nitro group is electrochemically active and can reversibly insert/deinsert lithium. Due to the lower solubility in the electrolyte, PNPQ has better cycling stability than PQ. This study shows that the introduction of nitro group in phenanthrenequinone can increase its specific capacity and cycle stability.

Synthesis, molecular docking and α-glucosidase inhibition of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides

A novel series of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides 5a–5q have been synthesized and evaluated for their α-glucosidase inhibitory activity. All newly synthesized compounds exhibited potent α-glucosidase inhibitory activity in the range of IC50=12.46±0.13–72.68±0.20μM, when compared to the standard drug acarbose (IC50=817.38±6.27μM). Among the series, compound 5j (12.46±0.13μM) with strong electron-withdrawing nitro group on the arylacetamide moiety was identified as the most potent inhibitor of α-glucosidase. Molecular docking study was carried out to explore the binding interactions of these compounds with α-glucosidase. Our study identifies a novel series of potent α-glucosidase inhibitors for further investigation.

Theoretical Characterization of the H-Bonding and Stacking Potential of Two Nonstandard Nucleobases Expanding the Genetic Alphabet.

We report a quantum chemical characterization of the non-natural (synthetic) H-bonded base pair formed by 6-amino-5-nitro-2(1H)-pyridone (Z) and 2-aminoimidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). The Z:P base pair, orthogonal to the classical G:C base pair, has been introduced into DNA molecules to expand the genetic code. Our results indicate that the Z:P base pair closely mimics the G:C base pair in terms of both structure and stability. To clarify the role of the NO2 group on the C5 position of the Z base, we compared the stability of the Z:P base pair with that of base pairs having different functional groups at the C5 position of Z. Our results indicate that the electron-donating/-withdrawing properties of the group on C5 have a clear impact on the stability of the Z:P base pair, with the strong electron-withdrawing nitro group achieving the largest stabilizing effect on the H-bonding interaction and the strong electron-donating NH2 group destabilizing the Z:P pair by almost 4 kcal/mol. Finally, our gas-phase and in-water calculations confirm that the Z-nitro group reinforces the stacking interaction with its adjacent purine or pyrimidine ring.

Stereoselective tandem synthesis of thiazolo fused naphthyridines and thienopyridines from o-alkynylaldehydes via Au(iii)-catalyzed regioselective 6-endo-dig ring closure

An operationally simple approach for the stereoselective tandem synthesis of novel thiazolo fused naphthyridines and thienopyridines by the reaction of o-alkynylaldehydes with L-cystine methyl ester hydrochloride via Au(III)-catalyzed regioselective 6-endo-dig ring closure under mild reaction conditions is described. It is noteworthy that alkynes bearing an alkyl and a strong electron-withdrawing nitro group successfully afforded the desired products in good yields.

The prototropic tautomerism and substituent effect through strong electron-withdrawing group in (E)-5-(diethylamino)-2-[(3-nitrophenylimino)methyl]phenol

The prototropic tautomerism in o-Hydroxy Schiff bases results in two forms called phenol-imine and keto-amine. The preference of a particular form by the compound changes in the solid and solvent media. The choice can also be regulated by a substituent with a different electron-donating or withdrawing group. In the present study, the above-mentioned factors are considered in the investigation of (E)-5-(diethylamino)-2-[(3-nitrophenylimino)methyl]phenol compound (an o-Hydroxy Schiff basis) by experimental (XRD, FT-IR and UV–vis) and computational (DFT and TD-DFT) methods. The results show that the title compound adopts only phenol-imine form in the solid and solvent media. This was attributed to the substituent effect through strong electron-withdrawing nitro group.

Synthetic, structural and spectroscopic studies on mono- and bi-arylimido functionalized hexamolybdates bearing the strong electron-withdrawing nitro group, (Bu 4N) 2[Mo 6O 18( [tbnd]NAr)] and (Bu 4N) 2[Mo 6O 17( [tbnd]NAr) 2] (Ar [dbnd]o-NO 2–C 6H 4)

Two novel mono- and bi-functionalized organoimido derivatives of hexamolybdates bearing the strong electron-withdrawing nitro group, (Bu 4N) 2[Mo 6O 17( NAr) 2] ( 1) and (Bu 4N) 2[Mo 6O 18( NAr)] ( 2) (Ar o-NO 2–C 6H 4) have been synthesized for the first time via the reaction of hexamolybdate ions and 2 equivalent of aromatic amines with an excessive dehydrating agent N, N′-dicyclohexylcarbodiimide (DCC). By controlling the amount of DCC, such two derivatives can be selectively prepared in reasonable yields, which have been characterized with UV/vis, IR, 1H NMR, ESI-mass spectrometry and single-crystal X-ray diffraction techniques. The influences of [NAr] ligands and [NAr] incorporation number on properties and supermolecular assembly of such two derivatives have been systematically investigated.

Reaction of N,N-dimethylaniline with N-cyanoazoles according to electrophilic aromatic substitution pattern

N-Cyanoazoles are highly reactive organic compounds and important intermediate products in the synthesis of numerous derivatives containing an azole ring. Owing to high polarity of the cyano group, N-cyanoazoles are capable of acting as electrophilic reagents in electrophilic aromatic substitution reactions. In the present communication we report on the synthesis of some imines via electrophilic aromatic substitution of hydrogen in N,N-dimethylaniline by N-cyanoimidazole, N-cyanobenzimidazole, N-cyano-1,2,3benzotriazole, and N-cyano-2-methylimidazoles. Initial N-cyanoazoles Ia–Id were prepared according to standard procedures. We were the first to demonstrate that the above listed N-cyanoazoles react with N,N-dimethylaniline in the presence of anhydrous aluminum bromide to give para-substituted imines in good yields (65–74%). Azole-containing imines IIa–IId were characterized by sharp melting points and Rf values, and their structure was confirmed by elemental analyses and H NMR spectra. Nitrobenzene was found to be appropriate solvent for carrying out reactions of N-cyanoazoles Ia–Id with N,N-dimethylaniline. High polarity and dissolving power of nitrobenzene ensure homogeneity of the reaction mixture throughout the process. On the other hand, nitrobenzene itself is not involved in the reaction because of the presence of a strong electron-withdrawing nitro group in its molecule. N,N-Dimethyl-4-[azolyl(imino)methyl]anilines IIa–IId (general procedure). Anhydrous aluminum bromide, 4 g, was dissolved in 50 ml of anhydrous nitrobenzene on cooling in an ice–salt bath, and a solution of 15 mmol of N-cyanoazole Ia–Id in 20 ml of anhydrous nitrobenzene was slowly added dropwise under stirring at 6°C. The mixture turned yellow– orange. It was stirred for 1 h, and a solution of 1.9 ml (1.82 g, 15 mmol) of N,N-dimethylaniline in 15 ml of anhydrous nitrobenzene was added. The mixture turned red or blue and was stirred for 4 h, the solvent was distilled off under reduced pressure (3 mm), and the tarry residue was extracted with anhydrous chloroform. The solvent was distilled from the extract on a rotary evaporator under reduced pressure (water-jet pump) at a bath temperature not exceeding 40°C. The crystalline product was stored in a vacuum desiccator over calcium chloride. 4-[1H-Imidazol-1-yl(imino)methyl]-N,N-dimethylaniline (IIa). Yield 2.12 g (66%), mp 186°C (from benzene), Rf 0.56. H NMR spectrum, δ, ppm: 3.2 br.s (6H, NMe2), 5.9 s (1H, NH), 7.2 d (2H, o-H), 7.5 m (2H, 4-H, 5-H), 7.8 m (2H, m-H), 8.1 br.s (1H, 2-H). Found, %: C 67.38; H 6.48; N 26.14. C12H14N4. Calculated, %: C 67.29; H 6.54; N 26.17. 4-[Imino(2-methyl-1H-imidazol-1-yl)methyl]N,N-dimethylaniline (IIb). Yield 2.22 g (65%), mp 168°C (from benzene), Rf 0.65. H NMR spectrum, δ, ppm: 2.5 s (3H, 2-CH3), 3.2 br.s (6H, NMe2), 6.2 s (1H, NH), 7.2 d (2H, o-H), 7.5 m (2H, 4-H, 5-H), 7.6– 7.7 m (2H, m-H). Found, %: C 68.53; H 6.97; N 24.50. C13H16N4. Calculated, %: C 68.42; H 7.02; N 24.56. 4-[1H-Benzimidazol-1-yl(imino)methyl]-N,N-dimethylaniline (IIc). Yield 2.12 g (74%), mp 205°C (from benzene), Rf 0.73. H NMR spectrum, δ, ppm: 3.2 br.s (6H, NMe2), 5.9 s (1H, NH), 7.2 d (2H, o-H), Ht = 1H-imidazol-1-yl (a), 2-methyl-1H-imidazol-1-yl (b), 1H-benzimidazol-1-yl (c), 1H-1,2,3-benzotriazol-1-yl (d). ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 3, pp. 459–460. © Pleiades Publishing, Ltd., 2010. Original Russian Text © A.O. Chunaev, E.A. Stepanov, P.P. Purygin, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 3, pp. 463–464.

A new class of functionalized polyoxometalates: synthesis, structure and preliminary antitumor activity studies of three arylimido substituted hexamolybdates bearing a strong electron-withdrawing nitro group, (Bu4N)2[Mo6O18(NAr)] (Ar = 3-NO2-C6H4, 2-CH3-4-NO2-C6H3, 2-CH3-5-NO2-C6H3)

Three novel mono-functionalized arylimido derivatives of hexamolybdate bearing the strongest electron-withdrawing nitro group, (Bu(4)N)(2)[Mo(6)O(18)([triple bond]NAr)] (1, 2 and 3), have been synthesized for the first time by an improved reaction of octamolybdate ion and 3-nitroaniline hydrochloride, 2-methyl-4-nitroaniline hydrochloride and 2-methyl-5-nitroaniline hydrochloride respectively with DCC (N,N'-dicyclohexylcarbodiimide) as a dehydrating agent. Complete assignments were achieved for the title compounds by elemental analysis, IR, (1)H NMR, UV/visible and single-crystal X-ray diffraction analyses. The preliminary antitumor activity test indicated that the title compounds have some effects on the cellular growth inhibition of K562 cells.

Application of a Microfluidic Reactor for Screening Cancer Prodrug Activation Using Silica-Immobilized Nitrobenzene Nitroreductase

The nitroreductase-catalyzed conversion of a strong electron-withdrawing nitro group to the corresponding electron-donating hydroxylamine is useful in a variety of biotechnological applications. Activation of prodrugs for cancer treatments or antibiotic therapy are the most common applications. Here, we show that a bacterial nitrobenzene nitroreductase (NbzA) from Pseudomonas pseudoalcaligenes JS45 activates the dinitrobenzamide cancer prodrug CB1954 and the proantibiotic nitrofurazone. NbzA was purified by affinity chromatography and screened for substrate specificity with respect to prodrug activation. To facilitate screening of alternate potential prodrugs, polyethyleneimine-mediated silica formation was used to immobilize NbzA with high immobilization yields and high loading capacities. Greater than 80% of the NbzA was immobilized, and enzyme activity was significantly more stable than NbzA in solution. The resulting silica-encapsulated NbzA was packed into a microfluidic microreactor that proved suitable for continuous operation using nitrobenzene, CB1954, and the proantibiotic nitrofurazone. The flow-through system provides a rapid and reproducible screening method for determining the NbzA-catalyzed activation of prodrugs and proantibiotics.

Photochemical and thermal decomposition of diphenylamine diazonium salts

The photochemical and thermal decomposition of diphenylamine-4-diazonium salt (DDS), N-methyl diphenylamine-4-diazonium salt (NMDDS), 3-methoxy diphenylamine-4-diazonium salt (MDDS), carbazole-3-diazonium salt (CDS) in ethanol and N-methyl-2-nitrodiphenylamine-4-diazonium salt (MNDDS) in water were studied. It was found that, in photochemical decomposition in ethanol, the major products (>70% of the total product) obtained for DDS, CDS, MDDS and NMDDS are diphenylamino-4-ethyl ether, carbazole-3-ethyl ether and the corresponding substituted diphenylamino-4-ethyl ethers. In thermal decomposition, the diphenylamine (DA), carbazole (CZ) and substituted DA were obtained as only one product in each case. For the decomposition of MNDDS, which has a strong electron-withdrawing nitro group on benzene nuclear at the meta site of the diazonium group, the decomposition products are identical, both in photochemical and in thermal decomposition. The mechanisms of photochemical and thermal decomposition for DDS, CDS and substituted DDS are discussed.

Nitroreductase-dependent mutagenicity of p-nitrophenylhydroxylamine and its N-acetyl and N-formyl hydroxamic acids.

p-Nitrophenylhydroxylamine (NPH) and two hydroxamic acids derived from it were synthesized and subjected to mutagenicity testing in Salmonella typhimurium strains TA98, TA98NR, TA1538 and TA1538NR. In addition, p-dinitrobenzene (DNB), p-nitroaniline (NA) and p-nitroacetanilide (AcNA) were simultaneously examined for mutagenic action against these four tester strains. NPH, its N-acetyl (AcNPH) and N-formyl (FoNPH) derivatives, and also DNB displayed strong mutagenic action to the nitroreductase-containing strains, TA98 and TA1538. NPH was the most potent chemical in this series against both of these strains, while the two hydroxamic acids AcNPH and FoNPH, and also DNB displayed approximately the same degree of mutagenicity. In the nitroreductase-deficient strains, TA98NR and TA1538NR, the mutagenicity of these four compounds was markedly reduced. The necessity for nitroreduction in order to activate these promutagens is fairly certain; however, the lack of mutagenicity of NA and AcNA towards all four tester strains made the interpretation of these data somewhat more complicated. Several possible bioactivation pathways were presented, with one mechanism in particular being proposed. This mechanism requires only that the strong electron-withdrawing nitro group be converted to an electron-donating group by bacterial nitroreductase. Such a mechanism is unique for the bioactivation of nitro aromatics by nitroreductase, since the enzymatic reduction need not produce the intermediary hydroxylamine metabolite.