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  • Open access
  • 15 Reads
Solvent-Controlled Switching of Cycloisomerization to Transposition in the Ag/Cu-Promoted Reaction of Terminal α-Allenols

In recent years, allenes (1,2-dienes) have evolved from a laboratory curiosity to a versatile and uniquely reactive functional group, allowing chemists to prepare a variety of compounds of chemical and biological interest.

Transition-metal catalyzed nucleophile addition to allenes is a very powerful tool for the synthesis of functionalized molecules containing heteroatoms in an atom efficient manner. The reaction on allenic systems has a benefit as the regiochemistry can be controlled by using different metals or by changing the substituents or the length of the chain between the allene and the heteroatom in the intramolecular case.

On the other hand, both non-aromatic oxacycles and quaternary α-substituted aldehydes are structural units that are extensively encountered in a number of biologically active natural products and functional molecules, and therefore their stereocontrolled synthesis remains an intensive research area.

We wish to report herein a study on the Ag/Cu-catalyzed reactivity of α-allenols. The focus was the development of new methodologies for cyclization and/or transposition of this moiety. By simple solvent switch, the divergent preparation of dihydrofurans and 3-halo-3-alkenals in a controlled manner has been reached.

  • Open access
  • 17 Reads
N-Terpenyl benzisoselenazolones - evaluation of the particular structure-bioactivity relationship

Different activity of compounds with the same molecular formula but possessing alternative bonding arrangement or orientation of atoms in space is a very important issue when constructing molecules that can selectively interact with certain domains of the biological target. Herein, we present the synthesis of new chiral benzisoselenazol-3(2H)-ones substituted on the nitrogen atom with three monoterpene moieties: p-menthane, pinane and carane. All derivatives were obtained by the reaction of appropriate amine with 2-(chloroseleno)benzoyl chloride. The applied terpenyl amines were first synthetized by a multistep procedure starting from corresponding alcohol (p-menthane system) or alkene (pinene and carene systems). Finally, all compounds were tested as antioxidants and antiproliferative agents on breast cancer MCF-7 and human promyelocytic leukemia cell line HL-60. The correlation between the structure of the obtained organoselenium compounds, representing examples of various isomers including enantiomers, diastereoisomers and regioisomers, and their bio-activity was thoroughly evaluated.

  • Open access
  • 19 Reads
Synthesis of di(benzotriazol-1-yl)methane derivatives by cobalt-catalyzed formation of C-C bonds

The first example of CoCl2-catalyzed reaction between 1,1'-carbonyldiazoles and carbonyl compounds was reported by Thé and Peterson in 1973, obtaining 2,2-di(pirazol-1-yl)propane from di(pyrazol-1-yl)methanone and acetone. The study was extended to several other ketones and aldehydes and to methyl-substituted di(pyrazol-1-yl)methanone derivatives, with the isolation of the corresponding di(pirazol-1-yl)alkanes by elimination of CO2. A reaction mechanism was subsequently proposed. The synthetic approach was then extended to functionalized aldehydes, with the aim of preparing pyrazole-based ligands to be applied in coordination, supramolecular, bioinorganic and organometallic chemistry.

To the best of our knowledge, the cobalt-catalyzed reaction was never applied for the synthesis of di(benzotriazol-1-yl)methane derivatives, despite the fact that benzotriazole is considered an ideal synthetic auxiliary in organic chemistry [4]. For instance, di(benzotriazol-1-yl)phenylmethane was obtained following different synthetic approaches with variable selectivity [5]. In this communication we report the straightforward preparation of di(benzotriazol-1-yl)phenylmethane and di(benzotriazol-1-yl)pyridin-2-ylmethane from di(benzotriazol-1-yl)methanone and the proper aldehyde, using CoCl2 as catalyst under neat conditions. The products were characterized spectroscopically and their solid structures were ascertained by single-crystal X-ray diffraction.

  • Open access
  • 67 Reads
1,3-Di(hetero)aryl-7-substituted pyrenes – an undiscovered area of important pyrene derivatives

Despite the pyrene derivatives have been covered extensively by scientists during the last years, many interesting properties and applications of pyrene derivatives have been presented, nowadays there are still areas of pyrenes’ chemistry that need to be fulfilled. Most of the described in literature pyrenes are 1,3,6,8-tetrasubstituted followed by 4,5,9,10-tetrasubstituted, 2,7-, and 1,6-, and 1,8-disubstituted pyrene derivatives. In the case of 1,3-di(hetero)aryl-7-substituted, there are only a few examples of derivatives containing at position 7 - tert-butyl group. In this work, the necessity of synthesis of 1,3-di(hetero)aryl-7-substituted pyrenes is presented based on the results of theoretical calculations by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) by using Gaussian 09 program with B3LYP exchange-correlation functional and 6-31G** basis set. What is more, the synthetic routes with feasible reagents and conditions are presented. As the starting material, 1,3-dibromo-7-nitropyrene will be used which can be synthesized based on the literature method starting from commercially available pyrene. This compound will be used in the next steps in the synthesis of 1,3-disubstituted by (hetero)aryl groups pyrene derivatives which will be also substituted at position 7 by various groups. It will be possible by exchange nitro group at position 7 on amine group followed by a further exchange on bromine group. Properly selected substituents (the part of target molecules containing at positions 1 and 3 heteroaryl groups suitable for the coordination of metal ions) will allow also to determine the application of new pyrene derivatives as NCN-cyclometalating ligands with various d-block metals.

  • Open access
  • 24 Reads
Hemiacetal formation from a Schiff base in the presence of dysprosium(III)

The formation of hemiacetals from aldehydes and alcohols is quite well known, as these are usually developed as intermediates in the preparation of acetals from aldehydes or ketones. Nevertheless, as far as we know, the examples of transformation of imines into hemiacetals are very scarce, and this reaction seems to be promoted by coordination to a metal ion. In this work, we describe the partial hydrolysis of a Schiff base, and its subsequent evolution to an hemiacetal donor in the presence of dysprosium(III) in an alcoholic medium. Full characterization of the final product, including single X-ray studies, is reported.

  • Open access
  • 21 Reads
Benzylidene as efficient corrosion inhibition of mild steel in acidic solution

New benzylidene derivative namely benzylidene-5-phenyl-1,3,4-thiadiazol-2-amine (BPTA), was successfully synthesized and characterized using Fourier Transform Infrared, Nuclear Magnetic Resonance and elemental analysis (CHN) techniques. The inhibition efficiency of BPTA on mild steel corrosion in 1.0 N HCl was tested at various temperatures. The methodological work was achieved by gravimetric method complemented with morphological investigation. The concentrations of inhibitor were 0.1, 0.2, 0.3, 0.4 and 0.5 mM at the temperatures 303, 313, 323 and 333 K. The BPTA, molecules as become superior corrosion inhibitor with 92% inhibition efficiency of mild steel coupon in the acidic environment. The inhibition efficiency increased with increasing concentrations of BPTA and the excellent efficiency was performed with the 0.5 mM concentration and followed with 0.4 mM. In acidic environment, the 0.5 and 0.4 mM gave the optimum performance with weight loss technique and scanning electron microscopy analysis. On the other hand, the inhibition efficiency decreased with the increase of temperature. Results of BPTA indicated mixed type inhibitor and the adsorption on the mild steels surface obeys the Langmuir adsorption isotherm. It was found that the BPTA performance depend on the concentration and the solution temperature. Quantum chemical calculations have been done to correlate the electronic characteristics of BPTA with the corrosive inhibitive impact. Experimental and theoretical results are in good agreement.

  • Open access
  • 20 Reads
Vaccines against drug abuse: morphine-hapten design and synthesis

Drugs of abuse are small molecules that typically do not induce an antibody response following injection or inhalation. To induce antibodies against small molecules, structural surrogates of the molecules, which were named “haptens”, must be coupled to immunogenic proteins, called “carriers”. These structural surrogates are typically drug-linker adducts, in which the linker has a terminal functional group that forms a covalent bond with the carrier. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant.

We designed N-substituted morphine compounds and for this purpose the normorphine-derivatives were required. (Dihydro)morphine, (dihydro)codeine, oxymorphone and oxycodone were N-demethylated with a-chloroethyl chloroformate to obtain the desired nor-compounds.

These six nor-molecules were reacted with ethyl acrylate and ethyl bromoacetate. After the synthesis of the specific esters we hydrolyzed them to receive the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives. The next step was the coupling phase with glycine ethyl ester, but the reactions didn’t work or the work-up process was not accomplishable. As an alternative route the normorphine-compounds were reacted with N-chloroacetyl glycine ethyl ester.

R1R2NH + Cl-CH2CONH-CH2COOEt ---> R1R2N-CH2CONH-CH2COOEt --- hydr. ---> R1R2N-CH2CONH-CH2COOH

After column chromatography purification the structures of the new compounds were elucidated by NMR and mass spectroscopy. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine sidechain, confirmed by NMR measurements. All of the glycine ester and the glycine carboxylic acid derivatives are under biological tests.

  • Open access
  • 19 Reads
Microwave assisted three component reaction conditions to obtain new thiazolidinones with different heterocyclic skeletons.

Taking into account previous results studied in our research group in the synthesis of 4-thiazolidinones selectively by a three-component reaction, we present here a new proposal for the “one pot” generation of new 4-thiazolidinones through a multicomponent reaction using aromatic and heteroaromatic amines, ethanol as a “green” solvent in order to minimize the environmental impact, and modifying the aldehyde group in the glycosidic residue, synthesized from D-mannitol. In the first place 1,2:5,6-di-O-isopropylidene-D-mannitol is obtained and then, the oxidative cleavage with NaIO4 gives 2,3-O-isopropiliden-D-glyceraldehyde. Thus, the new stereocenters in the target molecule may have an amplifying effect of the biological activity and reducing cytotoxicity. The study is focused in the variation of the irradiation times (period of 5, 10 and 30 minutes) and the concentration of thioglycolic acid (1 to 10 equivalents) in order to study the possibility of controlling the structure and / or stereochemistry of the products formed in the reaction. Thiazolidinones are obtained with a 62-95% yield for 30 minutes as the maximum time reaction. The generation of the corresponding intermediates and reaction products were monitored by TLC and CG-MS, taking reaction aliquots. The characterization of the intermediates and corresponding products were performed by 1H-, 13C, DEPT and HSQC- NMR spectroscopy.

  • Open access
  • 17 Reads
Ultrasound-assisted syntheses of chalcones: Experimental design and optimization

Chalcones are a group of compounds that belong to the flavonoid family and have a wide variety of uses, including a high therapeutic potential for multiple diseases, such as, anticancer, antifungal or antibacterial agents.

As is well known, chalcones are commonly synthesized by Claisen-Schmidt condensation, aldol condensation involving the appropriate aldehydes and ketones, in presence of acid or base as catalyst followed by dehydration reactions. However, under conventional conditions it is carried out with prolonged reaction times and requires expensive catalysts. For this reason, alternative source of energy, microwave or ultrasound, are employed.

On the other hand, in all chemical processes a considerable amount of variables (instrumental parameters, reagents, temperatures, times, etc.) take part so a large number of experiments must be carried out in order to define the optimal conditions. In addition, the experimental design technique -important tool- allows the optimization of conditions leading to better yields in shorter times. Here and in line with previous research, we explore the synthesis, assisted by ultrasound, of (E)-1,3-diphenyl-2-propen-1-one like a model reaction. Taguchi Design was the mathematical method employed to determine the best working condition.

In conclusion, the desired product is obtained quantitatively, without undesired by-products, and in short reaction times. Additionally, the reaction was used, as an alternative method, to monitor the ultrasound equipment using the control chart methodology (Shewhart chart), which allowed us to study how a process changes over time.

  • Open access
  • 11 Reads
Synthesis of novel and potential antimicrobial, antioxidant and anticancer chalcones and dihydropyrazoles bearing isoxazole scaffold

A series of isoxazole based (E)-1-(isoxazole-5-yl)-3-(substituted phenyl)-prop-2-en-1-ones (chalcones, 3a-3o) and 3-(isoxazol-5-yl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide (dihydropyrazoles, 4a-4o) were synthesized, characterized and evaluated for their antimicrobial, antioxidant and anticancer properties. Chalcones exhibited excellent antibacterial and antioxidant activities whereas the dihydropyrazoles showed superior antifungal and anticancer activities. The compound 3l containing 3,4,5-trimethoxy phenyl ring showed the potent antibacterial activity (MIC= 1 µg/mL) as well as the antioxidant activity (IC50= 5 µg/mL) whereas the dihydropyrazole, 4o (MIC= 0.5 µg/mL) bearing the 2-chloro-3,4-dimethoxyphenyl was the potent antifungal compound identified. The dihydropyrazoles 4n and 4h possessing 2-fluoro-3,4-dimethoxyphenyl and 3,4-dimethoxyphenyl substituents exhibited potent anticancer activity against prostate cancer cell line (DU-145) with MIC 2 and 4 µg/mL respectively. The structure-activity relationships had shown that there is a marked influence of both electron-withdrawing halogens and electron releasing methoxyl groups on the above biological activities. All the compounds were evaluated for toxicity on normal human cell lines (LO2) and found to be non-toxic. These studies could help to synthesize, explore and identify new isoxazole containing leads for antimicrobial, antioxidant and anticancer properties.

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