Formation Of Azine Research Articles

Energy-Barrier-less Synthesis of Hexaaza-trifuranacyclopentadecaphane-hexaene at Ambient Temperature.

A thermochemically stable furan-based hexaaza-trifuranacyclopentadecaphane-hexaene (AF-cpdp) as a π1212 cyclic-conjugated color enriched heterocycle has been synthesized at ambient temperature. An energy-barrier-less (EBL) dehydrative azine formation of 2,5-diformylfuran (DFF) with hydrazine hydrate (N2H4·H2O) followed by a single-arm heteroconjugation and ring formation at the final step under classical and mechanochemical approaches, avoiding external heating, was conducted for construction of a novel and highly stable cyclopentadecaphene (cpdp) conjugated system. The developed protocol is simple, energy-efficient, atom-economical, and easy to scale-up.

Unravelling the Unexpected: Mechanistic Insights and DFT Studies on the Formation of Azine from N-Acylhydrazones

Unravelling the Unexpected: Mechanistic Insights and DFT Studies on the Formation of Azine from N-Acylhydrazones

Azines of porphyrinoids. Does azine provide conjugation between chromophores?

A new approach to functionalize porphyrinoids was developed based on the Vilsmeier formylation followed by the azine formation and a new class of the compounds namely azines of porphyrinoids was obtained. Variously substituted azine porphyrins, chlorins and their dyads were synthesized, and their structural and electronic parameters were studied with X-ray diffraction analysis, electronic absorption and emission spectra, electrochemistry and DFT calculations. Azine represents a very peculiar bridge with an unclear conjugation ability affecting optical properties of chromophores. This work was aimed to reveal azine properties and the influence of the azine bridge on the chromophores linked. The results of investigation allowed to conclude that azine bridge can partly be regarded as a conjugation switch with a high threshold level of switching, where limited conjugation in the ground state can be greatly increased at higher energy states of the azine molecule.

Enantioselective Si-H Insertion Reactions of Diarylcarbenes for the Synthesis of Silicon-Stereogenic Silanes.

We report the first example of enantioselective, intermolecular diarylcarbene insertion into Si-H bonds for the synthesis of silicon-stereogenic silanes. Dirhodium(II) carboxylates catalyze an Si-H insertion using carbenes derived from diazo compounds where selective formation of an enantioenriched silicon center is achieved using prochiral silanes. Fourteen prochiral silanes were evaluated with symmetrical and prochiral diazo reactants to produce a total of 25 novel silanes. Adding an ortho substituent on one phenyl ring of a prochiral diazo enhances enantioselectivity up to 95:5 er with yields up to 98%. Using in situ IR spectroscopy, the impact of the off-cycle azine formation is supported based on the structural dependence for relative rates of diazo decomposition. A catalytic cycle is proposed with Si-H insertion as the rate-determining step, supported by kinetic isotope experiments. Transformations of an enantioenriched silane derived from this method, including selective synthesis of a novel sila-indane, are demonstrated.

Chemical modification of proteins with photocleavable groups.

In this work, we describe methods for synthesizing and incorporating a wide range of photocleavable groups into proteins. These are based on the di-methoxyl nitro phenyl ethyl (DMNPE) group. Using a common ketone starting material, we have modified the DMNPE core with different peptides and small molecules. We describe how these can be incorporated into DMNPE either by solution or solid phase methods. In addition, we show how the ketone group can be effectively converted into a hydrazone group and ultimately into a diazo. The potential pitfall of azine formation is also delineated, as are the strategies for avoiding this side product. We then show how these modified diazo groups can then be reacted with the carboxyl groups of the protein to make the final ester product. Finally, we show how the ultimate product can be purified, and the products identified using 280 and 345nm ratios, as well as ESI-MS characterization. The combined methods should allow the incorporation of many possible photocleavable groups into a range of proteins, and allow the ultimate properties of the modified protein to be subsequently toggled with light.

Formation of [2]- and [3]Rotaxanes through Bridging under Kinetic and Thermodynamic Control.

An efficient synthesis of a doubly stranded [3]rotaxane has been developed through bridging of a pseudo[3]rotaxane featuring two axle components. Reversible azine formation was effective as the bridging reaction. Kinetic and thermodynamic conditions provided the [2]- and [3]rotaxanes, respectively.

Copper-Catalyzed Cross-Dehydrogenative C–N Bond Formation of Azines with Azoles: Overcoming the Limitation of Oxidizing N–O Activation Strategy

Here, we report the copper-catalyzed C2 selective cross-dehydrogenative C–N bond formation of azines with azoles. This straightforward method enables us to address the key limitation of prior N–O activation strategy in C2 amination of azines. The wide substrate scope, high functional group tolerance, and ease of operation of the present method are expected to promote its potential application in synthetic chemistry.

Generation of semicarbazide from natural azine development in foods, followed by reaction with urea compounds

This paper proposes a mechanism to explain the trace levels of natural semicarbazide occasionally observed in foods. The analytical derivative of semicarbazide, 2-nitrobenzaldehyde semicarbazone, is often measured as a metabolite marker to detect the widely banned antibiotic nitrofurazone. However, this marker is not specific as semicarbazide may be present in foods for several reasons other than exposure to nitrofurazone. In some cases, an entirely natural origin of semicarbazide is suspected, although up until now there was no explanation about how semicarbazide could occur naturally. In this work, semicarbazide is proposed as being generated from natural food compounds via an azine intermediate. Hydrazine, in the form of azines or hydrazones, may be generated in dilute aqueous solution from the natural food compounds ammonia, hydrogen peroxide and acetone, following known oxidation chemistry. When this mixture was prepared in the presence of ureas such as allantoin, urea, biuret or hydroxyurea, and then analysed by the standard method for the determination of semicarbazide, 2-nitrobenzaldehyde semicarbazone was detected. 2-Nitrobenzaldehyde aldazine was also found, and it may be a general marker for azines in foods. This proposal, that azine formation is central to semicarbazide development, provides a convergence of the published mechanisms for semicarbazide. The reaction starts with hydrogen peroxide, peracetic acid, atmospheric oxygen or hypochlorite; generates hydrazine either by an oxaziridine intermediate or via the chlorination of ammonia; and then either route may converge on azine formation, followed by reaction with a urea compound. Additionally, carbamate ion may speculatively generate semicarbazide by reaction with hydrazine, which might be a significant route in the case of the hypochlorite treatment of foods or food contact surfaces. Significantly, detection of 2-nitrobenzaldehyde semicarbazone may be somewhat artefactual because semicarbazide can form during the acid conditions of analysis, which can free hydrazine in the presence of urea compounds.

Product Selectivity in Solar Photocatalytic Dehydrazonation of Aromatic Hydrazones by TiO2-Based Catalysts

Product selectivity of ketone and azine in the photocatalytic dehydrazonation of aromatic hydrazones with TiO2-based photocatalysts has been investigated using solar light. Product selectivity is dependent on the nature of the photocatalysts, substituents and the solvents. Loading of metals on TiO2-P25 selectively enhances the formation of azine from benzophenone hydrazone. Solvents such as dichloromethane, chloroform, ethanol, and 2-propanol enhance the formation of azine under solar irradiation. Structures of products have been established by FT-IR, 1H-NMR, 13C-NMR, and GC-MS spectrometry. Supplementary materials are available for this article. Go to the publisher's online edition of Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry to view the supplemental file.

Density Functional Study on the Mechanism of Nickel-Mediated Diazo Carbonylation

The mechanism of diazo activation as well as the carbonylation of the resulting carbene complexes has been investigated by means of DFT calculations at the PBE0/TZVP level of theory. The free energy profile of all elementary steps of the reaction, i.e., diazo coordination, dinitrogen extrusion, carbene–CO coupling, CO coordination, and ketene elimination, have been elucidated for diazomethane and ethyl diazoacetate as substrates and for Ni(CO)3, Ni(CO)2(PH3), and Ni(dtbpe)(CO) (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane) as precursors. The reaction rate is determined by the formation of the coordinatively unsaturated precursor followed by the dinitrogen extrusion, regardless of the initial diazo compound and the catalyst precursor. For the homoleptic precursor Ni(CO)3 the free energy of activation for diazomethane and ethyl diazoacetate (EDA) is 16.9 and 22.4 kcal/mol, respectively. The replacement of one carbonyl ligand with PH3 results in a decrease in the activation barrier, modifying the energies to 15.7 and 20.5 kcal/mol, respectively. The activation free energy of the diazo extrusion step promoted by Ni(dtbpe)(CO) is 24.3 kcal/mol for diazomethane and 28.1 kcal/mol for EDA. The formation of carbene complexes is slightly endergonic starting from the homoleptic precursor and exergonic for the phosphine-substituted complex. The carbene–CO coupling, resulting in coordinatively unsaturated ketene complexes, is a fast and highly exergonic process with reaction free energies between −32.3 and −42.1 kcal/mol, depending on the substituents. Under a carbon monoxide atmosphere the ketene complexes may uptake one CO, forming coordinatively saturated ketene complexes via low barriers in exergonic reactions. The final step, i.e., the dissociation of ketene or ethoxycarbonylketene from the saturated ketene complex, regenerates the corresponding nickel–carbonyl precursor. The azine formation side reaction for the simplest case between Ni(CO)3 and diazomethane has been also examined and found to be highly exergonic; however, the large free energy barrier prevents the formation of benzophenone-azine when CO is also present.

ChemInform Abstract: Copper‐Catalyzed Oxidative Alkynylation of Diaryl Imines with Terminal Alkynes: A Facile Synthesis of Ynimines.

AbstractIn all reactions carried out under conditions A), formation of azine by‐products is observed.

Product Selectivity in Semiconductor-Mediated Dehydrazonation of Benzophenone Hydrazone

Product selectivity in the dehydrazonation of benzophenone hydrazone by photocatalytic oxidation with various semiconductor photocatalysts has been investigated using ultraviolet-A light. TiO2-P25 shows greater product selectivity of benzophenone formation with 93.9% conversion. Doping of metals on TiO2 selectively enhances the formation of azine from hydrazone. Solvents such as dichloromethane, chloroform, and dichloroethane also enhance the formation of azine.

Supramolecular Photochirogenesis with Carbenes Entrapped in Cyclodextrins

AbstractTwo achiral diazirines 1a and 1b have been encapsulated in the inherently chiral cavity of α‐cyclodextrin (6‐Cy), β‐cyclodextrin (7‐Cy) and permethylated β‐cyclodextrin (TRIMEB) and photolyzed. Because of supramolecular photochirogenesis the generated carbenes afford intramolecular C–H insertion products not as a racemate but one enantiomer is slightly favored. With 1a@(6‐Cy)2 the ee of product 7a is doubled. To the best of our knowledge for the first time for carbene reactions, products are imprinted, though modestly, with handedness derived from Cys. The reaction of 1b is highly dependent on the molecular reactor used for inclusion. Whereas 7‐Cy is very efficient for favoring dimerization through azine formation, the use of TRIMEB permits exclusive formation of intramolecular insertion product 7b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Cloud point formation based on mixed micelle in the presence of electrolyte for extraction, preconcentration, and spectrophotometric determination of trace amounts of hydrazine in water and biological samples

A cloud point extraction process using mixed micelle of the anionic surfactant sodium dodecyl sulfate and the nonionic surfactant Triton X-114 to extract hydrazine from aqueous solutions was investigated. The method is based on the condensation reaction of hydrazine with p-(dimethylamino)benzaldehyde, azine formation, and mixed micelle-mediated extraction of azine in the presence of NaCl electrolyte as an inducing phase separation. An azine product was concentrated in surfactant-rich phase after separation. The optimal extraction and reaction conditions (e.g., surfactant, reagent and electrolyte concentrations, and centrifuge time) were studied and the analytical characteristics of the method (e.g., limit of detection, linear range, preconcentration, and improvement factors) were obtained. Linearity was obeyed in the range of 0.50–110 ng ml −1 of hydrazine and the detection limit of the method is 0.08 ng ml −1. The interference effect of some cations, anions, and organic compounds was also tested. The method was successfully applied to the determination of hydrazine in water and biological samples.

Facile formation of azines from reactions of singlet methylene and dimethylcarbene with precursor diazirines: theoretical explorations

The reactions of the singlet methylene (1a) and dimethylcarbene (1b), with their diazirine precursors, diazirine (2a), and dimethyldiazirine (2b), have been studied theoretically using ab initio and density functional theory. The reaction has no activation barriers for the parent system (1a + 2a) and proceeds via a reactive complex and a transition state with a small negative enthalpy of activation Δ Hnot =298 = -1.1 kcal mol-1, ΔSnot =298 = -34.4 cal mol-1 K-1, ΔG°298 = 9.2 kcal mol-1) for the dimethyl derivatives (1b + 2b). The formation of N-methylene diazirinium ylides (3a,b) is exothermic by 64-80 kcal mol-1. The isomer, 1,3-diazabicyclo[1.1.0]butane (4a), is more stable (5-12 kcal mol-1) than isomer 3a, but can neither be formed by direct thermal reaction of 1a with 2a nor undergo the direct rearrangement into formaldazine (5a). The rearrangement of ylides 3a,b into azines 5a,b proceeds by conrotatory C3-N1 ring opening. The predicted activation barrier of ca. 15 kcal mol-1 for the ring opening in ylide 3b is in excellent agreement with experimental data. The formation of pyridinium ylides from carbenes and pyridine is also studied.Key words: diazirinium ylide, ab initio MO (molecular orbital) theory, density functional theory, pyridinium ylide, CIS (singles configuration interaction) transition energies.

Facile formation of azines from reactions of singlet methylene and dimethylcarbene with precursor diazirines: theoretical explorations

The reactions of the singlet methylene (1a) and dimethylcarbene (1b), with their diazirine precursors, diazirine (2a), and dimethyldiazirine (2b), have been studied theoretically using ab initio and density functional theory. The reaction has no activation barriers for the parent system (1a + 2a) and proceeds via a reactive complex and a transition state with a small negative enthalpy of activation Δ Hnot =298 = -1.1 kcal mol-1, ΔSnot =298 = -34.4 cal mol-1 K-1, ΔG°298 = 9.2 kcal mol-1) for the dimethyl derivatives (1b + 2b). The formation of N-methylene diazirinium ylides (3a,b) is exothermic by 64-80 kcal mol-1. The isomer, 1,3-diazabicyclo[1.1.0]butane (4a), is more stable (5-12 kcal mol-1) than isomer 3a, but can neither be formed by direct thermal reaction of 1a with 2a nor undergo the direct rearrangement into formaldazine (5a). The rearrangement of ylides 3a,b into azines 5a,b proceeds by conrotatory C3-N1 ring opening. The predicted activation barrier of ca. 15 kcal mol-1 for the ring opening in ylide 3b is in excellent agreement with experimental data. The formation of pyridinium ylides from carbenes and pyridine is also studied.Key words: diazirinium ylide, ab initio MO (molecular orbital) theory, density functional theory, pyridinium ylide, CIS (singles configuration interaction) transition energies.

Synthesis, structure, electrostatic properties and spectroscopy of 3-methyl-4,5,6,7-tetrafluoro-1H-indazole. An experimental and ab initio computational study †

The azine of pentafluorobenzaldehyde had been previously prepared from pentafluorobenzaldehyde and hydrazine. However, the analogous reaction of 2,3,4,5,6-pentafluoroacetophenone 1 with hydrazine did not result in the formation of azine 3 but resulted instead in the formation of 3-methyl-4,5,6,7-tetrafluoro-1H-indazole, 4, via the hydrazone 2. The resulting indazole was characterized by high resolution mass spectroscopy and 1H-, 13C-, and 19F-NMR spectroscopy. The geometry and electrostatic properties of the parent indazole and its derivative, 4, were studied with ab initio quantum theory and density functional methods. Our optimized structure of the parent indazole computed at the MP2(fc)/6-311G** level is presumably more accurate than the structure derived from microwave measurements. The preferred conformer of 4 was determined from RHF/6-31G* energies and full normal mode analyses were used to characterize both conformers. The minimum structure of 4 was refined at the MP2(fc)/6-311G** level of theory and compared to the unsubstituted structure. The electrostatic properties of the parent indazole and 4 are discussed and compared to those of benzene and hexafluorobenzene calculated at the same level. Natural bond order (NBO) calculations were performed to rationalize the difference in direction of the dipole moments of the parent indazole and 4. The gauge-invariant atomic orbital (GIAO) method was employed to calculate atomic shielding tensors of the indazoles using density functional theory at the B3LYP/6-311+G(2d,p) level. The calculated chemical shifts were used to aid in assigning peaks in the NMR spectra.

Benzylfluorocarbene: Reactions and kinetics

Benzylfluorocarbene, generated from the corresponding diazirine, is accompanied by considerable azine formation. Its rearrangement to β-fluorostyrene isomers in tetrachloroethane is characterized by E a = 3.2 kcal/mol and log A = 9.5 s −1

Formation of diazoketones and azines by improved oxidation of ketohydrazones using Cu(acac) 2 as a catalyst

An efficient Cu(acac) 2-catalyzed oxidation of ketohydrazones afforded the corresponding α-diazoketones or ketazines in high yields depending on the reaction conditions. However, the reaction of benzophenone hydrazone gave benzophenone azine without affording diphenyldiazomethane. The formation of azines is explained by the intermediacy of carbenoid generated by the Cu(acac) 2-catalyzed decomposition of diazo compounds.

Alternatives to α-diazo ketones for tandem cyclization–cycloaddition and carbenoid–alkyne metathesis strategies. Novel cyclic enol–ether formation via carbonyl ylide rearrangement reactions

Attempts to form carbonyl ylides from free carbenes derived from diazirines or diazo compounds lacking electron-withdrawing substituents resulted in azine formation or Wolff rearrangement, respectively, lodonium ylides proved to be a possible alternative to α-diazo compounds for metallocarbenoid generation, similar reactivity being observed for both systems. Studies into the rearrangement chemistry of carbonyl ylides provided a novel cyclic enol–ether synthesis via a 1,4-hydrogen shift process.