Reductive dimerization of dithianylium salts and fluorodesulfuration: a new synthetic approach to tetrafluoroethylene substructures

The reductive dimerization of dithianylium ions, followed by oxidative fluorodesulfuration, opens a convenient access to a variety of 1,2-disubstituted tetrafluoroethylene derivatives. A similar method leads to hexafluorodiacetyl, a potential building block for fluorinated heterocycles.     

TEMPO-catalyzed oxidative dimerization and cyanation of indoles for the synthesis of 2-(1H-indol-3-yl)-3-oxoindoline-2-carbonitriles

A method for the combinative oxidative homo dimerization and cyanation of free indole derivatives catalysed by TEMPO along with silver carbonate was demonstrated for the first time This new methodology is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2-(1H-indol-3-yl)-3-oxoindoline- 2-carbonitriles in moderate to excellent yields. Furthermore, selected compounds 6b and 6g exhibit moderate to good anti-schistosomicidal activities.     

N,N'-Linked biazoles : Part 7. Oxidative dimerization of n-unsubstituted tetrahydroindazolones

The structure of the products obtained by oxidative dimerization of tetrahydroindazolones was established as being N(1)-C(3a') dimers. In one case a C(3a)-C(3a') dimer was also isolated, but N-N'-Linked dimers were never found, contrary to a previous report in the literature. A complete 13-carbon nmr study of the monomers and their fixed methylated derivatives was performed to determine the most abundant tautomer in each case, since the tautomerism study of tetrahydroindazolone and of its 4-ethoxycarbonyl derivative was needed to fully determine the structure of the dimers.     

Scandium ion-enhanced oxidative dimerization and N-demethylation of N,N-dimethylanilines by a non-heme iron(IV)-oxo complex

Oxidative dimerization of N,N-dimethylaniline (DMA) occurs with a nonheme iron(IV)-oxo complex, [Fe(IV)(O)(N4Py)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), to yield the corresponding dimer, tetramethylbenzidine (TMB), in acetonitrile. The rate of the oxidative dimerization of DMA by [Fe(IV)(O)(N4Py)](2+) is markedly enhanced by the presence of scandium triflate, Sc(OTf)(3) (OTf = CF(3)SO(3)(-)), when TMB is further oxidized to the radical cation (TMB(?+)). In contrast, we have observed the oxidative N-demethylation with para-substituted DMA substrates, since the position of the C-C bond formation to yield the dimer is blocked. The rate of the oxidative N-demethylation of para-substituted DMA by [Fe(IV)(O)(N4Py)](2+) is also markedly enhanced by the presence of Sc(OTf)(3). In the case of para-substituted DMA derivatives with electron-donating substituents, radical cations of DMA derivatives are initially formed by Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), giving demethylated products. Binding of Sc(3+) to [Fe(IV)(O)(N4Py)](2+) enhances the Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), whereas binding of Sc(3+) to DMA derivatives retards the electron-transfer reaction. The complicated kinetics of the Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+) are analyzed by competition between binding of Sc(3+) to DMA derivatives and to [Fe(IV)(O)(N4Py)](2+). The binding constants of Sc(3+) to DMA derivatives increase with the increase of the electron-donating ability of the para-substituent. The rate constants of Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), which are estimated from the binding constants of Sc(3+) to DMA derivatives, agree well with those predicted from the driving force dependence of the rate constants of Sc(3+) ion-coupled electron transfer from one-electron reductants to [Fe(IV)(O)(N4Py)](2+). Thus, oxidative dimerization of DMA and N-demethylation of para-substituted DMA derivatives proceed via Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+).     

Synthesis of Cytotoxic Iron-Containing Macrocycles Through Unexpected C(sp2)−C(sp2) Bonds Formation

In previous reports, it has been demonstrated that cyclometalated iron(II/III) complexes can be prepared by reacting iron(0) precursors and mercurated or brominated derivatives. However, in this report, the reaction between [Fe₃(CO)₁₂] and mercurated 6-phenyl-2,2′-bipyridine or brominated 2,6-diphenyl-pyridine pincer derivatives led to compounds in which C(sp²)−C(sp²) bonds have been formed between two ligands. A 16-electron iron(II) complex ( 1Cl ) bearing a tetradentate ligand originating from the dimerization of 6-phenyl-2,2′-bipyridine was isolated, while a protonated 14-membered macrocycle with [FeBr₄]⁻ as counterion ( 2 ) was obtained from 2,6-diphenyl-pyridine. Studies by X-ray diffraction crystallography, NMR, UV-vis and cyclic voltammetry confirmed the structures. Additionally, the cytotoxicity of the new compounds toward gastric cancer cell lines was evaluated, and it was established that the presence of the iron(II) center was crucial for an elevated activity.     

3-Cyclobutenyl-1,2-dione-substituted porphyrins. 2. A simple and general entry to quinone-porphyrin-porphyrin-quinone tetrads and related molecules

The synthesis of meso-linked quinone-porphyrin-porphyrin-quinone tetrads has been accomplished by the simple treatment of a CH2Cl2 solution of zincated 5-substituted-10,20-diphenylporphyrins (where the substituent = 3-cyclobutenyl-1,2-dione, various quinonyl derivatives, and p-anisyl) with 2,3-dichloro-5,6-dicyanoquinone (DDQ). The zincated porphyrinic quinones were synthesized from 5-(3-cyclobutenyl-1,2-dione)-10,20-diphenylporphyrin(Zn). The meso-linked dimer of 5-(3-cyclobutenyl-1,2-dione)-10,20-diphenylporphyrin(Zn) was also shown to be a useful precursor to meso-linked quinone-porphyrin-porphyrin-quinone tetrads. This DDQ-based oxidative dimerization appears to be general and effective for various zincated 5-substituted-10,20-diphenylporphyrins bearing both electron-withdrawing and -donating substituents. The oxidative dimerization was very sensitive to the reaction solvent (dimerization occurred in CH2Cl2, not in THF) and required the zincated porphyrins (the corresponding free base porphyrins did not undergo dimerization). When this solvent effect was applied to the reaction of I2/AgO2CCF3 with zincated porphyrins, either the dimeric porphyrins or iodoporphyrins could be selectively prepared simply by selecting methylene chloride or THF as the reaction solvent, respectively.     

Use of isothermal microcalorimetry for prediction of oxidative stability of several amino acids

Isothermal microcalorimetry has been applied as a method for predicting (in)stability of ascorbic acid and several amino acids that undergo oxidative degradation in aqueous media. The fast and simple method involved the addition of different amounts of hydrogen peroxide. The appearance of the heat flow curves gave a clear general indication of how stability was influenced. The accuracy of the microcalorimetric result was investigated by comparing it with an HPLC assay and a good agreement between the results of both methods was demonstrated. It was also established that susceptibility to oxidative degradation decreases in the following order: cysteine, methionine, ascorbic acid, tyrosine and tryptophan.     

Identification of oxidation products and free radicals of tryptophan by mass spectrometry

New oxidation products and free radicals derived from tryptophan (Trp) oxidation under Fenton reaction conditions were identified using mass spectrometry. After the oxidation of tryptophan using hydrogen peroxide and iron (II) system (Fenton reaction), mono- and dihydoxy tryptophans and N-formylkynurenine were identified using electrospray mass spectrometry (ES-MS) and ES-MS/MS. Besides these products, new products resulting from the reaction of tryptophan and oxidized tryptophan and 3-methyl indole derivatives were also identified. The 3-methyl indole derivatives resulted, most probably, from the oxidation process and not from in-source processes. A dimer formed by cross-linking between two Trp radicals (Trp-Trp), similar to the previously described tyrosine dimer was observed, as well as the corresponding monohydroxy-dimer (Trp-Trp-OH). Tandem mass spectrometry was used to identify the structures of these new oxidation products. Free radicals derived from tryptophan oxidation under Fenton reaction were detected using as spin trap the DMPO. The free radical species originated during the oxidation reaction formed stable adducts with the spin trap, and these adducts were identified by ES-MS. New adducts of oxidized tryptophan radicals, namely monohydroxy-tryptophan and dihydroxy-Trp dimer radicals, with one and two DMPO spin trap molecules where identified. Tandem mass spectrometry was used to confirm the proposed structure of the observed adducts.     

Oxidative dimerization of azoles via copper(II)/silver(I)-catalyzed CH homocoupling

When several azole derivatives such as imidazole, thiazole, and oxazole are treated with a catalyst system of copper(II)/silver(I) under oxygen atmosphere, oxidative dimerization at the CH bond of the 2-position takes place to afford the corresponding bisazoles up to 86% yield.     

Synthesis of 2-iminothiazoline derivatives by sequential conjugate addition/annulation/ring-opening reactions

1,2-Diaza-1,3-butadienes reacted with rhodanine affording 2-(mercaptoacetyl)iminothiazoline derivatives through conjugate addition/annulation/ring-opening/oxidative dimerization. The hypothesized ring-closure and ring-opening mechanism was supported by X-ray crystal structure analysis of a compound obtained by reaction of the same reagents with a chiral 1,3-oxazolidine-2-thione derivative.     

Ru‐Catalysed CH Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies

The Ru‐catalysed C2?H arylation of indoles and pyrroles by using boronic acids under oxidative conditions is reported. This reaction can be applied to tryptophan derivatives and tolerates a wide range of functional groups on both coupling partners, including bromides and iodides, which can be further derivatised selectively. New indole‐based ruthenacyclic complexes are described and investigated as possible intermediates in the reaction. Mechanistic studies suggest the on‐cycle intermediates do not possess a para‐cymene ligand and that the on‐cycle metalation occurs through an electrophilic attack by the Ru centre.     

Flow-injection photometric determination of nanogram levels of iron based on the catalysis of oxidative coupling of N-phenyl-p-phenylenediamine with m-phenylenediamine in a micellar medium

A highly sensitive photometric flow-injection method is described for the determination of iron(II, III) based on the catalytic action on the oxidative coupling of N-phenyl-p-phenylenediamine with m-phenylenediamine in the presence of hydrogen peroxide. The sensitivity of the method was enhanced by the addition of Tween 80 as a surfactant. The dynamic range was 0.5-30 ng/ml of iron(II, III) with the relative standard deviations below 3% at a sampling rate of 30 h(-1). The proposed method was subject to few interferences from coexisting metal ions and was successfully applied to the determination of iron in natural water samples.     

Bis(imino)pyridine iron alkyls containing beta-hydrogens: synthesis, evaluation of kinetic stability, and decomposition pathways involving chelate participation

Bis(imino)pyridine iron alkyl complexes bearing beta-hydrogens, ((iPr)PDI)FeR (((iPr)PDI = 2,6-(2,6-(i)Pr2-C6H3N=CMe)2C5H3N; R = Et, (n)Bu, (i)Bu, CH2 (cyclo)C5H 9; 1-R), were synthesized either by direct alkylation of ((iPr)PDI)FeCl (1-Cl) with the appropriate Grignard reagent or more typically by oxidative addition of the appropriate alkyl bromide to the iron bis(dinitrogen) complex, ((iPr)PDI)Fe(N2)2 (1-(N2)2). In the latter method, the formal oxidative addition reaction produced ((iPr)PDI)FeBr (1-Br), along with the desired iron alkyl, 1-R. Elucidation of the electronic structure of 1-Br and related 1-R derivatives by magnetic measurements, structural studies and NMR spectroscopy established high spin ferrous compounds antiferromagnetically coupled to chelate radical anions. Thus, the formal oxidative process is bis(imino)pyridine ligand-based (one electron is formally removed from each chelate, not the iron) during oxidative addition. The kinetic stability of each 1-R compound was assayed in benzene-d6 solution and found to produce a mixture of the corresponding alkane and alkene. The kinetic stability of the iron alkyl complexes was inversely correlated with the number of beta-hydrogens present. For example, the iron ethyl complex, 1-Et, underwent clean loss of ethane over the course of three hours, whereas the corresponding 1-(i)Bu compound had a half-life of over 12 h under identical conditions. The mechanism of the decomposition was studied with a series of deuterium labeling experiments and support a pathway involving initial beta-hydrogen elimination followed by cyclometalation of an isopropyl methyl group, demonstrating an overall transfer hydrogenation pathway. The relevance of such pathways to chain transfer in bis(imino)pyridine iron catalyzed olefin polymerization reactions is also presented.     

Formation of tryptanthrin compounds upon Oxone-induced dimerization of indole-3-carbaldehydes

Tryptanthrin is a natural product with numerous important pharmacological properties. Tryptanthrin and its analogs are commonly prepared by condensation of isatoic anhydride and isatin. In this Letter we investigate the formation of tryptanthrin derivatives upon Oxone-induced oxidative dimerization of indole-3-carbaldehydes.     

Chiral resolution of tryptophan derivatives by CE using canine serum albumin and bovine serum albumin as chiral selectors

This work deals with the application of BSA and canine serum albumin (CSA) for enantioseparation of tryptophan derivatives with CE. The aim of this work was the investigation of the influence of different functional groups of tryptophan derivatives on enantioseparation. CSA as a chiral selector was tested to compare its selector properties with those of BSA. The enantiomers of the tryptophan derivatives were separated by adding BSA or CSA to the BGE. The influence of pH, temperature, BSA and CSA concentration and organic modifiers was investigated. It was found that the stereoselectivity for the different tryptophan derivatives is dependent on the albumin species. It turned out that the different functional groups of the derivatives showed a significant influence on stereoselectivity.     

Oxidative dimerization of vinylbornylacetylenes under the action of mercuric acetate

Vinylbornylacetylenes and their trimethylsilyl derivatives undergo oxidative dimerization in the presence of an Hg(OAc)₂—HgO system in MeOH to give the corresponding diacetylenes.     

An electron paramagnetic resonance study of the influence of spermine on the photophysical reactions of tryptophan in aqueous solution at 77–200 K

The influence of the antioxidant spermine of the UV-induced formation of free radicals from tryptophan in frozen aqueous solutions was studied by electron paramagnetic resonance (EPR) instrumentation, and the stability of the radicals was investigated in the range 95–200 K. Without spermine, the tryptophan cation and neutral tryptophan radical were stabilized at 77 K; cations were formed by electron ejection from an excited singlet state, and neutral radicals by hydrogen donation from tryptophan in the triplet state. When present, spermine trapped the ejected photoelectrons; the rates of the two photoreactions of tryptophan were also influenced by spermine. Firstly, at low tryptophan concentrations, the yield of cations was reduced, due to diminished charge transfer from the excited singlet state to the solvation shell. Secondly, at high concentrations, minute additions of spermine enhanced intersystem crossing (which is quenched, in the absence of spermine, by dimerization) and, consequently, the yield of neutral radicals was increased. At 180 K, the electrons trapped by spermine were released and reacted with molecular oxygen to form the superoxide radical; at 190 K, the tryptophan radicals were thermally annealed.     

Synthesis and Molecular Structure Characterization of Novel 1,6-Diazahexatrienes

Novel 1,6-diazahexatrienes (1a–d) are a type of aza-conjugated hexatriene containing N,N-diamino moieties. We present the oxidative dimerization of 1,1,2-trisubstituted hydrazines as a synthetic approach to 1,6-diazahexatriene derivatives, rather than the expected pyrazine and pyridazine. The proposed mechanism for formation of 1a–d involves oxidative dimerization of 1,1,2-trisubstituted hydrazines via their hydrazones. The structures of 1a–d were characterized by ¹H NMR, ¹³C NMR, and mass spectroscopy. A detailed discussion regarding the character of the three-dimensional structure of 1 is based on x-ray crystallography.     

SPECTRAL CHARACTERISTICS AND MECHANISM OF CHEMILUMINESCENCE FROM TRYPTOPHAN SOLUTIONS INDUCED BY UV-IRRADIATION

The spectral distribution of the chemiluminescence, fluorescence and phosphorescence of tryptophan aqueous solutions irradiated with high and low pressure mercury lamps has been measured. The blue emission bands in the region of 380–520 nm observed both in the chemi- and photoluminescence, as well as an absorbance increase at 230 and 330 nm, indicate oxidative degradation of tryptophan leading to the formation of derivatives of N-formylkynurenine, xanthurenic and anthranilic acids. Red emission bands at 630 and 705 nm in the spectrum of the chemiluminescence, an enhancement of light intensity by D₂O and its decrease by NaN₃ and DABCO suggest a partial contribution of O₂(¹Δ_g) to the photooxidation and chemiluminescence of tryptophan. The enthalpy of the exergonic reactions, leading to the formation of luminescing products, was calculated to average -270 kJ-mol.     

Oxidative dimerization of heterocyclic nitrones,derivatives of pyrroline and imidazoline

The oxidation of -oxonitrones, derivatives of pyrroline and imidazoline, afforded symmetric dimers with a C-C bond and dehydrodimers with a C=C bond. Oxidation of the trifluoroacetyl imidazoline derivative afforded an asymmetric dimer. The oxidative dimerization of endocyclic -oxonitrones, derivatives of pyrroline, proceeded much faster than that of exocyclic -oxonitrones, derivatives of imidazoline. Imidazoline derivatives containing a perfluorophenyl or cyano group at the -carbon atom on the nitrone group also underwent oxidative dimerization.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1398–1404, June, 1990.