An Alternative Method for the Selective Synthesis of Ortho-nitro Anilines Using Bismuth Nitrate Pentahydrate.

BACKGROUND: Nitroaromatic compounds are important scaffolds used for the syn-thesis of a variety of compounds, such as explosives, herbicides, dyes, perfumes and phar-maceuticals. Bismuth nitrate pentahydrate is a widely used reagent in organic synthesis; how-ever, its utility as a nitrating agent for anilines is underexplored. OBJECTIVE: The aim of this work is to propose and find the proper reaction conditions of an alternative nitrating agent constituted by a mixture of bismuth nitrate / acetic anhydride in DCM with a series of substituted anilines under mild reflux. METHODS: Several anilines having both activating and deactivating substituents in the ortho, meta and para positions were the substrate for the nitration reaction. Experimental conditions were performed in "one-pot" conditions before product purification. RESULTS: Bi(NO3)3•5H2O demonstrated to be effective and somehow regioselective when it came to the nitration of anilines in the ortho position. Although other products were also identified under these conditions, in most cases, the ortho derivative was the major or even the only product obtained with moderate to high yields in the range of 50% - 96%. CONCLUSION: Bi(NO3)3•5H2O is an efficient and safe nitrating agent since the use of concen-trated and corrosive acids like sulfuric and nitric is avoided; furthermore, bismuth nitrate is low-priced and no special care nor equipment is required.

Expanding the scope of bis(catecholato)germane catalysis: hydrosilylation, hydroboration, Friedel-Crafts alkylation and oligomerization.

Various applications of bis(catecholato)germanes in catalysis were examined. The hydrosilylation of benzaldehydes, hydroboration of phenylacetylene derivatives, and Friedel-Crafts alkylation using arylalkenes and either diphenylamine or anisole was achieved. Furthermore, the recently reported oligomerization of α-methylstyrene catalyzed by bis(catecholato)germanes with weak donor ligands was examined further. The formation of a trimer species was observed in DCM. VTNA and Hammett analyses of the oligomerization reaction were conducted and an updated mechanism for bis(catecholato)germane catalysis is proposed.

On the Stereochemistry of the NH Bond Activation of Ammonia or Amines by Disilenes: Predictability.

The stereochemistry of the addition of NH3 to the stereoisomers of 1,2-di-tert-butyl-1,2-bis(2,4,6-triisopropylphenyl)disilene (Z-5 or E-5) is 100 % stereospecific giving two isomeric disilylamines 6 and 7, respectively, derived from syn-addition to the stereoisomeric disilenes. Variable time normalization analysis studies of the reaction of tetramesityldisilene (3) with isopropylamine (i PrNH2 ) revealed that the order in both amine and disilene is 1. The kinetic isotope effect for the addition of i PrNH2 /i PrND2 to tetramesityldisilene was determined to be 3.04±0.06 at 298 K, a primary KIE, indicating that the proton is transferred in the rate determining step. Competition studies between the addition of PrNH2 and i PrNH2 to tetramesityldisilene resulted in the exclusive formation of the PrNH2 adduct consistent with a nucleophilic addition. Computational studies of the mechanism of the addition of ammonia to E-5 revealed the lowest energy pathway involves the formation of the donor adduct derived from syn-addition, followed by intramolecular syn-transfer of the proton. The formation of the donor adduct is the rate determining step. The results of this study, together with previous studies on the addition of ammonia and amines to disilenes, allow for a refinement of our understanding of the mechanism of this important fundamental reaction in disilene chemistry, and allow us to understand our ability to reliably predict the stereochemical outcomes of future NH σ-bond activation reactions.

Novel ciprofloxacin and norfloxacin-tetrazole hybrids as potential antibacterial and antiviral agents: Targeting S. aureus topoisomerase and SARS-CoV-2-MPro.

This study was designed to synthesize hybridizing molecules from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining suitable statistical parameters ( R 2 = 87.00 , Q L M O 2 = 71.67 , and Q E X T 2 = 73.49 ) to support our results. The binding interaction of our compounds with CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds.

NH bond activation of ammonia and amines by ditetrelenes: key insights into the stereochemistry of nucleophilic addition.

The NH bond activation of ammonia, primary and secondary amines by tetramesityldisilene and -digermene was investigated. In each case, a disilyl- or digermylamine was formed as the only product of amine addition. The mechanism of the addition of ammonia to tetramesityldisilene was computed and revealed a three-step reaction pathway: formation of the anti-ammonia-disilene adduct, inversion at the ß-silicon, and syn-transfer of the proton to give the syn-product, where each step follows a distinct stereochemical course. Examination of the reaction landscape also revealed several additional insights: (a) that, in the initial step, the formation of the anti-oriented zwitterionic intermediate is kinetically more preferable than formation of the syn-oriented zwitterionic intermediate, (b) that intermolecular transfer of a proton is not energetically feasible in non-polar solvents, and (c) that the bulk of the substituents can have a profound effect on the stereochemical course of the reaction. With this detailed understanding, nucleophilic additions to ditetrelenes can be exploited in the future.

Selective dimerization of α-methylstyrene by tunable bis(catecholato)germane Lewis acid catalysts.

The synthesis of a variety of bis(catecholato)germanes is reported. The Lewis acidity of the bis(catecholato)germanes was assessed using the experimental Gutmann-Beckett method and computational FIA and GEI methods. The oligomerization of alkenes using bis(catecholato)germanes demonstrates the use of these complexes in catalysis. The use of donor additives in the dimerization of α-methylstyrene resulted in selectivity control comparable to transition metal catalyst systems.

Synthesis and Reactivity of Cationic Gallium(I) [12]Crown-4 Complexes.

The synthesis and reactivity of a gallium(I) cationic complex using [12]crown-4 as a stabilizing ligand were explored. The synthesis of [Ga([12]crown-4)][GaCl4] was achieved in one step from commercially available starting materials. Anion exchange was utilized to replace the reactive tetrachlorogallate anion for the perfluorophenylborate anion. [Ga([12]crown-4)][B(C6F5)4] was analyzed using XPS, which allowed for the classification of the gallium(I)-crown ether complex as electron-deficient. Reactions of the gallium(I)-crown ether complex with Cp*K and cryptand[2.2.2] demonstrated the facile synthesis of a known gallium(I) compound as well as the generation of new gallium(I) complexes, highlighting the use of the gallium(I)-crown ether complex as an effective starting material for new gallium(I) complexes.

Chlorine-35 Solid-State Nuclear Magnetic Resonance Spectroscopy as an Indirect Probe of the Oxidation Number of Tin in Tin Chlorides.

Ultrawideline 35Cl solid-state nuclear magnetic resonance (SSNMR) spectra of a series of 12 tin chlorides were recorded. The magnitude of the 35Cl quadrupolar coupling constant (CQ) was shown to consistently indicate the chemical state (oxidation number) of the bound Sn center. The chemical state of the Sn center was independently verified by tin Mössbauer spectroscopy. CQ(35Cl) values of >30 MHz correspond to Sn(IV), while CQ(35Cl) readings of <30 MHz indicate that Sn(II) is present. Tin-119 SSNMR experiments would seem to be the most direct and effective route to interrogating tin in these systems, yet we show that ambiguous results can emerge from this method, which may lead to an incorrect interpretation of the Sn oxidation number. The accumulated 35Cl NMR data are used as a guide to assign the Sn oxidation number in the mixed-valent metal complex Ph3PPdImSnCl2. The synthesis and crystal structure of the related Ph3PPtImSnCl2 are reported, and 195Pt and 35Cl SSNMR experiments were also used to investigate its Pt-Sn bonding. Plane-wave DFT calculations of 35Cl, 119Sn, and 195Pt NMR parameters are used to model and interpret experimental data, supported by computed 119Sn and 195Pt chemical shift tensor orientations. Given the ubiquity of directly bound Cl centers in organometallic and inorganic systems, there is tremendous potential for widespread usage of 35Cl SSNMR parameters to provide a reliable indication of the chemical state in metal chlorides.

The Diverse Reactivity of Disilenes Toward Isocyanides.

The addition of 2,6-dimethylphenyl isocyanide and t-butyl isocyanide to tetramesityldisilene was examined. In both cases, the initially formed product is an iminodisilirane; however, the iminodisiliranes are unstable under the reaction conditions and react with a second equivalent of the isocyanide to give either a 3-silaazetidine or a novel bicyclic double enamine, respectively. Taken together with the previous examples in the literature, the results demonstrate that subtle differences in the steric bulk of the disilene or the electronic effects of the isocyanide can lead to dramatic differences in the reaction pathway.

Reactivity of sulfonyl-containing compounds with ditetrelenes.

The addition of a variety of sulfones and a sulfoxide to ditetrelenes (a disilene and a digermene) was examined. The reaction of benzenesulfonyl chloride with tetramesityldisilene or tetramesityldigermene results in the formation of the 1,2-addition products, 2-chlorotetramesityldisilyl- or digermylbenzenesulfinate. The addition of p-toluenesulfonyl chloride to the disilene gave the analogous product, 2-chlorotetramesityldisilyl p-toluenesulfinate. In contrast, benzenesulfonyl fluoride, diphenyl and dimethyl sulfone did not react with either the disilene or the digermene. The unprecedented formation of the sulfinates reveals a selective 2-electron reduction of the sulfur centres using ditetrelenes. The addition reactions of sulfonyl compounds illustrates the potential of ditetrelenes to serve as reducing agents which react rapidly, at room temperature under mild conditions. The reaction of tetramesityldisilene with diphenyl sulfoxide resulted in the formation of tetramesityloxadisilirane and with benzene sulfonic acid resulted in the formation of 1,1,2,2-tetramesityldisilyl benzenesulfonate.

A chlorine-free protocol for processing germanium.

Replacing molecular chlorine and hydrochloric acid with less energy- and risk-intensive reagents would markedly improve the environmental impact of metal manufacturing at a time when demand for metals is rapidly increasing. We describe a recyclable quinone/catechol redox platform that provides an innovative replacement for elemental chlorine and hydrochloric acid in the conversion of either germanium metal or germanium dioxide to a germanium tetrachloride substitute. Germanium is classified as a "critical" element based on its high dispersion in the environment, growing demand, and lack of suitable substitutes. Our approach replaces the oxidizing capacity of chlorine with molecular oxygen and replaces germanium tetrachloride with an air- and moisture-stable Ge(IV)-catecholate that is kinetically competent for conversion to high-purity germanes.

Beyond Oxidation States: Distinguishing Chemical States of Gallium in Compounds with Multiple Gallium Centers.

The electronic structures of a series of gallium complexes are examined using X-ray absorption spectroscopy (XAS) in combination with ab initio calculations. The chemical states of Ga are strongly affected by the ligands and the bonding environment. For complexes containing multiple gallium sites, we demonstrate that XAS can identify the chemical state of each unique gallium center. A reliable understanding of the chemical nature of the core element in a coordination complex with strong core-ligand interaction can be obtained only when both experimental and theoretical approaches are combined.

Addition of Isocyanides to Tetramesityldigermene: A Comparison of the Reactivity between Surface and Molecular Digermenes.

The reaction of benzyl isocyanide, tert-butyl isocyanide, and 2,6-dimethylphenyl isocyanide with tetramesityldigermene (Mes2 Ge=GeMes2 ) was examined. Whereas the addition of benzyl isocyanide gave the C-NC activation product, Mes2 Ge(CH2 Ph)Ge(CN)Mes2 , tert-butyl isocyanide, and 2,6-dimethylphenyl isocyanide did not give stable adducts, rather the rate of conversion of the digermene to the corresponding cyclotrigermane was accelerated. A comparison between the reactivity of the isocyanides with Mes2 Ge=GeMes2 and the Ge(100)-2×1 surface was made and some insights into the surface chemistry are offered.

Chemical state determination of molecular gallium compounds using XPS.

A series of molecular gallium compounds were analyzed using X-ray photoelectron spectroscopy (XPS). Specifically, the Ga 2p3/2 and Ga 3d5/2 photoelectron binding energies and the Ga L3M45M45 Auger electron kinetic energies of compounds with gallium in a range of assigned oxidation numbers and with different stabilizing ligands were measured. Auger parameters were calculated and used to generate multiple chemical speciation (or Wagner) plots that were subsequently used to characterize the novel gallium-cryptand[2.2.2] complexes that possess ambiguous oxidation numbers for gallium. The results presented demonstrate the ability of widely accessible XPS instruments to experimentally determine the chemical state of gallium centers and, as a consequence, provide deeper insights into reactivity compared to assigned oxidation and valence numbers.

Addition of alkynes to digermynes: experimental insight into the reaction pathway.

The addition of an alkynyl cyclopropyl mechanistic probe to a digermyne did not lead to any ring-opened rearrangement products indicating that the reaction pathway does not involve any vinylic radicals or cations and providing experimental insight into the addition of alkynes to digermynes.

Cycloaddition of carbonyl compounds and alkynes to (di)silenes and (di)germenes: reactivity and mechanism.

The chemistry of silenes, germenes, disilenes and digermenes has been extensively studied over the last 35 years; however, not much is known about the mechanisms of many of the fundamental reactions of this class of compounds, including cycloadditions. This review describes the current understanding of the reaction pathways for the cycloaddition of carbonyl compounds and alkynes to (di)tetrelenes. The question of whether or not the cycloaddition reactions of (di)tetrelenes follow the Woodward-Hoffman rules, established for alkenes and alkynes, is addressed.

Synthesis and Characterization of Cationic Low-Valent Gallium Complexes of Cryptand[2.2.2].

The synthesis and characterization of two bimetallic, cationic low-valent gallium-cryptand[2.2.2] complexes is reported. The reaction of cryptand[2.2.2] with Ga2Cl4 gave two different cations, [Ga3Cl4 (crypt-222)](+) (1) or [Ga2Cl2 (crypt-222)](2+) (2), depending on whether or not trimethylsilyl triflate (Me3SiOTf) was added as a co-reagent. Complexes 1 and 2 are the first examples of bimetallic cryptand[2.2.2] complexes, as well as the first low-valent gallium-cryptand[2.2.2] complexes. Computational methods were used to evaluate the bonding in the gallium cores.

The addition of nitriles to a molecular digermene: reversible addition and comparison to surface reactivity.

The addition of acetonitrile, propionitrile, and acrylonitrile to tetramesityldigermene was investigated and compared to the addition of acetonitrile and acrylonitrile to germanium dimers on the Ge(100)-2×1 surface. In each case, a 1,2,3-azadigermetine was formed as the major product. As on the surface, the addition of nitriles to digermenes was found to be reversible, providing the first example of a reversible cycloaddition of a ditetrelene. No evidence for a six-membered cyclic ketenimine was observed as noted in the surface chemistry, suggesting that the surface ketenimine might only form between two adjacent dimers rather than on a single dimer. The comparative chemistry provides important insights that are not possible by the independent study of each system.

Addition of nitromethane to a disilene and a digermene: comparison to surface reactivity and the facile formation of 1,3,2-dioxazolidines.

The addition of nitromethane to tetramesityldisilene and tetramesityldigermene leads to the formation of the novel 1,3,2,4,5-dioxazadisil- and digermolidine ring systems, respectively. The 1,3,2,4,5-dioxazadisilolidine isomerizes to the 1,4,2,3,5-dioxazadisilolidine ring system, whereas the 1,3,2,4,5-dioxazadigermolidine undergoes ring opening to the isomeric oxime. The preferential formation of the 1,3,2,4,5-dioxazadisilolidine, and its rearrangement to a 1,4,2,3,5-dioxazadisilolidine, provides support for the suggested reaction pathway between nitromethane and the Si(100) 2×1 reconstructed surface.

The addition of nitriles to tetramesityldisilene: a comparison of the reactivity between surface and molecular disilenes.

The addition of acetonitrile, propionitrile, and phenylacetonitrile to tetramesityldisilene (Mes2 Si=SiMes2 ) was examined. In general, 1,2,3-azadisiletines and the tautomeric enamines were formed, although a ketenimine was formed as the major product in the addition of phenylacetonitrile to the disilene. In the presence of LiCl, the mode of addition changed for both acetonitrile and propionitrile: insertion into the α-CH bond of acetonitrile and/or formation of the formal HCN adduct was observed. Preliminary investigations of the reactivity of the nitrile adducts are also reported. A comparison between the reactivity of nitriles with Mes2 Si=SiMes2 and the Si(100)-2×1 surface was made both in terms of the types of adducts formed and their reactivity. Some insights into the surface chemistry are offered.