Recent Catalysts Used in the Synthesis of 1,4-Disubstituted 1,2,3-Triazoles by Heterogeneous and Homogeneous Methods

1,2,3-triazoles are popular heterocycles employed in material sciences and medicinal chemistry as they show antiviral, antibacterial, anti-HIV, antitubercular, and antifungal activities. Triazoles are appealing due to their stability and interesting click chemistry properties. The Cu(I) catalyzed reaction between azides and alkynes affords the 1,4- disubstituted derivative exclusively becoming a useful synthetic tool. However, one of the main drawbacks of the catalyzed reaction is the need to use Cu(I), which is unstable at standard conditions and rapidly oxidizes to the non-active Cu(II). The most common approach when synthesizing 1,4-disubstituted-1,2,3-triazoles is to reduce Cu in situ employing inorganic Cu salts and a reducing agent. The resulting Cu(I) needs to be further stabilized with organic ligands for the reaction to take place. The aim of homogeneous catalysis is to produce a ligand with a dual function both in reducing and stabilizing Cu(I) without interfering in the overall reaction. Instead, heterogeneous catalysis offers more options when supporting Cu on nanoparticles, complexes, and composites yielding the desired 1,2,3-triazoles in most cases without the need of a reducing agent under green solvents such as ethanol and water. The catalytic activity of Ag, Ru, and Ce is also discussed. This review exemplifies how the use of homogeneous and heterogeneous catalysts offers new and green methodologies for the synthesis of 1,2,3-triazole derivatives. The materials supporting Cu show catalytic properties like high surface area, acid-base sites or phase transfer. Although there is no ideal catalyst, Cu remains the most effective metal since it is economical, abundant and readily available.

INVESTIGATING EFFECTS OF 7,8-DISUBSTITUTED DERIVATIVE OF THEOPHYLLINE (BENOPHYLLINE) ON FREE-RADICAL OXIDATION IN RENAL INJURY OF RATS

This article highlights the pharmacological study of new 7,8-disubstituted derivative of theophylline, the substance conditionally named benophylline. Based on the literature data and previous studies of compounds of this class, it has been concluded that studying the effect of benophylline on the pro-antioxidant system under simulated pathologies is of great interest and importance. The study of antihypoxic action of 7,8-disubstituted theophylline in rats was carried out under modelled normobaric hypoxia with hypercapnia (in an enclosed space). It has been found out the application of 7-n-methylbenzyl-8-substituted polyphosphonates increases the longevity of rats in the conditions described above that evidences the improvement of metabolic processes in mitochondrial respiratory chain. Based on the results of screening studies, we selected 7,8-disubstituted derivative of theophylline (benophylline) as a leading substance for further investigation. The purpose of the study was to evaluate the efficacy of benophylline for the pharmacological correction of free radical processes in experimental renal damage in rats based on the evaluation of the expression of lipid peroxidation and antioxidant protection. Materials and methods: blood serum, homogenate and rat kidney tissues were the study materials. The study of the protective effect of benophylline on the functional state of the kidneys was investigated on experimental model of acute renal injury by introducing 50% water solution of glycerol (myoglobin nephropathy). Pathogenesis of this model was described in the methodological recommendations by C. Yu. Shtrygol, V. M. Lysovoi, I. A. Zupanetz et al. in «Methods of experimental modeling of kidney damage for pharmacological research». The content of TBK-R was determined spectrophotometrically by reaction with thiobarbituric acid. Glutathione recovered activity was determined spectrophotometrically in reaction with Elman's reagent using the method of Beutler E. D. et al. The catalase activity was assessed by the method of M.A. Koroluk et al. The influence of benophylline on the morphological state of the renal parenchyma was assessed on the modeled myoglobin nephropathy. The activity of gamma-glutamyltranspeptidase in serum was evaluated photometrically using a reagent test kit (“Filisit”). Statistical processing of the results was performed using the STATISTICA 8.0 software package, with the mean value, standard error of the mean confidence interval (p≤0.05). The microscopic study of microproducts was performed under the Granum microscope. Micrographs were taken with a Granum DMC 310 digital camera. The images were processed on a Pentium 2.4 GHz computer using Toup View software. Research results: Under the influence of benophylline, the processes of LPO and AOP became normalized, the expressiveness of degradation of the nephrocytes decreased, the microscopic picture of renal excretion in all rats got normalized. At the same time, 62.5% of the rats had the morphological condition of kidneys close to the intact control, and 37.5% of the animals were noticed to demonstrate a significant decrease in the dyscirculatory abnormalities, inflammatory manifestations and signs of nephrocyte regeneration. Conclusions: The ability of benophylline to inhibit the processes of free radical oxidation and to enhance antioxidant protection has been found out. The study has shown benophylline enhances regenerative effect kidney tissues.

Synthesis and Density Functional Theory Studies of Azirinyl and Oxiranyl Functionalized Isoindigo and (3Z,3’Z)-3,3’-(ethane-1,2-diylidene)bis(indolin-2-one) Derivatives

The design and synthesis of functionalized isoindigo compounds by reaction of isoindigo with (S)-glycidyl tosylate, epibromohydrin, 2-(bromomethyl)-1-(arylsulfonyl)aziridine, and 2-(bromomethyl)-1-(alkylsulfonyl)aziridine in the presence of MeONa proceed under mild conditions in moderate yields. (3Z,3’Z)-3,3’-(Ethane-1,2-diylidene)bis(1-(oxiran-2-ylmethyl)indolin-2-one), with an extended central olefin π-conjugated moiety was also reacted with methyl-oxiranes to give the corresponding N,N’-disubstituted derivative. Calculations with DFT and TD-DFT of hypothetical isoindigo-thiophene DA molecules with various electron withdrawing substituents, including aziridine, oxirane, nitrile, carbonyl, and sulfonate, indicated that the proximity and strength of the functional group have a significant effect on the HOMO, LUMO, vertical excitation energy, and oscillator strength of the π–π* transitions.

Sonochemical synthesis of 5-substituted 1H-tetrazoles catalyzed by ZrP2O7 nanoparticles and regioselective conversion into new 2,5-disubstituted tetrazoles

The ultrasound-assisted preparation of 2-(1H-tetrazol-5-yl) acrylonitrile derivatives via a one-pot multi-component method is described successfully using ZrP2O7 nanoparticles as a catalyst. Readily available tetrazoles can be transformed into the corresponding 1,5- and 2,5-disubstituted tetrazoles. 2,4′-Dibromoacetophenone gave the corresponding 2,5-disubstituted derivative as the only isomer. Synthesis of tetrazole derivatives with excellent yields in short times, a wide range of products under ultrasound irradiation, environmental benignity and a simple work-up procedure are some of the important features of this protocol.

Wechselwirkungen in Molekülkristallen, 127 [1] Die unterschiedlichen Strukturen des im Kristall verdrillten 1,4-Bis(tricyanvinyl)- benzols sowie des eingeebneten 1-Tricyanvinylbenzols, Dichtefunktional- Berechnungen und cyclovoltammetrisch sowie ESR/ENDOR-spektroskopisch charakterisiertes Reduktionsverhalten / Interactions in Molecular Crystals, 127 [1]The Different Structures in the Crystal of Twisted 1,4-Bis(tricyanovinyl)benzene as well as of Planar 1-Tricyanovinyl-benzene, Density Functional Calculations and Reduction Behaviour Studied by Cyclovoltammetry and ESR/ENDOR Spectroscopy

The attempted crystal growth of 1,4-bis(tricyanovinyl)benzene dianion salts, although without success so far, has provided information of general interest. The crystal structures of the related mono and 1,4-bis(tricyanovinyl)benzene derivatives differ considerably in their substituent group twisting angles: The two tricyanovinylbenzenes in split-positions exhibit dihedral angles of only 6° or 11°, whereas the two C2(CN)3 groups of the disubstituted benzene are conrotationally twisted by 48° out of the benzene plane. Density functional calculations with 6 - 311++G** basis sets, however, predict identical values of 32° for both compounds and, therefore, their crystal arrangements are discussed in detail for packingenforced additional interactions. Cyclovoltammetric and ESR/ENDOR-measurements provide information on the redox behaviour, a prerequisite for attempts to crystallize molecular anion salts: The 1,4-disubstituted derivative with a cyclovoltammetrically determined halfwave reduction potential of +.14 V in aprotic THF solution proves to be one of the strongest polycyano-substituted π-acceptors and its radical anion can be selectively generated by T1 metal reduction as confirmed by its ESR/ENDOR spectra.

New investigation of the reaction of 2-amino-2-oxazolines with isocyanates and isothiocyanates. Evidence of a transposition during the second step

The reaction of some 2-amino-2-oxazolines with isocyanates and arylisothiocyanates yields 3-monosubstituted or 2,3-disubstituted 2-iminooxazolidines depending on the experimental conditions and on the nature of the electrophile reactants. The structures of a mono- and a disubstituted derivative were established by X-ray analysis. The chemical behaviour of the compounds was investigated by molecular and quantum mechanics calculations. An intramolecular transposition during the second step of the reaction was found. Key words: 2-amino-2-oxazolines, iso(thio)cyanates, transposition. X-ray structure, MOPAC calculations.

The reaction of rabbit muscle creatine kinase with diethyl pyrocarbonate

The reaction of rabbit muscle creatine kinase with diethyl pyrocarbonate was studied. It was found that up to five of the sixteen histidine groups per enzyme subunit could be modified, and under the conditions employed, there was no evidence for formation of the disubstituted derivative of histidine. Evidence was obtained for small but significant amounts of modification of lysine and cysteine groups; tyrosine groups were not modified. Modification of the enzyme led to inactivation; this could be protected against by inclusion of substrates or, more effectively, by inclusion of the combination MgADP plus creatine plus nitrate, which is thought to produce a ‘transition-stage-analogue’ complex. Analysis of data on the rates of inactivation and the stoicheiometry of modification suggested that there was one essential histidine group per enzyme subunit, modification of which led to inactivation.