Montelukast 1 is a famous drug demonstrated for the chronic and prophylaxis therapy of asthma. It behaves as a selective antagonist of the leukotriene D₄ receptor which causes the decrease of broncho constriction and eventuates in less inflammation. Montelukast is prescribed orally once daily which gives a profit in contrast with other drugs for pulmonary diseases such as asthma. The low stability and complex synthesis of Montelukast 1 present multitude difficulties for its large-scale production. Our present study demonstrates a novel and the industrially scalable process for the preparation of sodium (S,E)-2-(1-(((1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-(2-(methoxycarbonyl)phenyl)propyl)thio)methyl)cyclopropyl)acetate which is one of the key intermediates of the Montelukast sodium synthesis process. We demonstrated a novel process that resolves multitude prior limitations and problems. Our modified process (see in scheme 2), which details are shown in this paper, is appropriate for large-scale production of the active pharmaceutical ingredient (API) with many benefits generally known as Montelukast.

In this study, the new mononuclear complexes, K₂ [Ni (L)₂ Cl₂]. 2H₂O (C1), K₂ [Co (L)₂ Cl₂]. H₂O (C2) and K₂ [Fe (L)₂ Cl₂]. 4H₂O (C3), was L is the 2-(2-hydroxyaryl)-1H-benzimidazole, have been synthesized and characterized. The structures of these compounds were confirmed on the basis of FT-IR, UV-Vis, ¹H-, ³C-NMR, TGA, DTA, DTG measurements, conductivity, ICP and elemental analyses (C, H and N). The purity of the compounds was ascertained by melting point (m.p.) and TLC. According to the analysis used, in all of the complexes, the ligand coordinated as bidentate, via one imine nitrogen atom and phenolate oxygen atom. The coordination for all of the complexes is completed with two chloride ions adopting a six-coordinated octahedral geometry. The geometry optimization and vibrational frequency calculations of the compounds were carried out in Gaussian 09 program using B3LYP/TZVP level of theory. Based on the combined experimental and theoretical studies, all complexes showed six-coordinated octahedral structures.

Paralytic Shellfish Toxins (PSTs) are polar analytes, most of them with positive charges resulting in a charge-induced dipole at the graphene surface when they approach to it. Graphene is a novel material with great potentials to be used as sorbent due to its ultrahigh surface area. Herein, we perform the simulation about the retention mechanism of PSTs on the graphene through Merck Molecular Force Field (MMFF94) minimizations. The overall retention on graphene is a combination of two mechanisms:

- Adsorption: The strength of analyte interactions with graphene is largely dependent on the molecular area in contact with the graphene surface, and also on the type and positioning of the functional groups in relation to the graphene surface at the points of contact.

- Charge induced interactions of a polar analyte with the polarizable surface of graphene: when the polar group with apermanent dipole approaches the surface, an induced dipole is formed, increasing the attraction between the analyte and graphene surface.

Computational results were compared with those obtained after elution using a HPLC-Hypercarb column: they showed a good correlation pattern where it was seen that the theoretical model exhibited the potential of graphene as an excellent sorbent material for saxitoxin and analogues.

Hypercarb model: elution order: (shorter retention time) dcSTX < NEO < STX < GTX5 < GTX3 < C2 < GTX2 < C1 (longer retention time).

Merck Molecular Force Field (MMFF94) model, interaction energy values order: (minor complex energy) dcSTX < STX < NEO < GTX5 < GTX3 < GTX2 < C2 < C1 (mayor complex energy)

In this work, we succeeded to synthesis enol carbamates using modified MOFs in short times and excellent yields. In this procedure we utilized 1, 3- dicarbonyl compounds, DMF, TBHP as oxidant and MOFs as catalyst. Products were obtained with excellent yield and in short times.

New series of manganese(II), cobalt(II), nickel(II), copper(II) and cadmium(II) complexes with L1 and L2 bi dentate ligands of 3-acetylcoumarine were prepared and fully characterized by elemental analyses, FT-IR, UV-Visible as well as the magnetic moments and molar conductivity measurements were carried to conclude the geometry of the prepare complexes. The results obtained from H NMR and 13C NMR for the freee ligands and their Cd(II) complexes suggested the coordination sites of the new ligands via two nitrogen atoms of imine moiety and carbonyl of L1 and two nitrogen atoms of thiocyane and pyrazine moeity respectively. The octahedral configuration of aal complexes has revealed on the basis of the elemental analyses and spectral data whereas the Cd(II) complexes were tetrahedral. However, the thermal analyses (TG-DTA and DSC) have carried for some selected metal complexes to approve the thermal stability of complexes formation and to confirm their formula structures.

3-Benzoyl[b]benzofurans are structural cores to a host of bioactive molecules in pharmaceutical use or development. Representative examples include amiodarone, a clinically used drug for controlling intractable cardiac arrhythmias, LY 320135, a potent cannabinoid CB₁ receptor antagonist, and benzbromarone, an uricosuric agent.

Numerous approaches to the benzofurane scaffold have been disclosed in the literature. Most synthetic approaches to 2,3-disubstituted benzofurans introduce the C3-substituent on the preformed benzo[b]furan ring at the end of the synthesis. Traditionally, the simple and straightforward method for the C3 acylation of benzofurans appeared to be the Friedel-Craft reaction using acylchlorides. However this method suffer from some limitations e.g. the poor regioselectivity, especially when strongly deactivated acylchloride are used.

In the course of our program directed at the synthesis of novel MAO inhibitors, we planned to synthesize 2-phenylbenzofuranes using the intramolecular Wittig procedure due to its ease and simplicity.

Using this procedure, we found that the GC/MS analysis of the crude reaction mixture revealed, together with the desired product of cyclization (2-phenylbenzofuran), one unexpected side product, which, after extensive analysis by NMR and mass spectrometry, turned out to be the 2-phenyl-3-benzoyl benzofurane.

In this scenario, our findings could be extended to design and develop new potentially therapeutic molecules, especially useful in neurodegenerative diseases.

Abstract

Development of new multicomponent reactions (MCRS) is an area of considerable interest due to the fact that the products are formed in a single step and also the variety could be achieved only by changing the reaction components. Imidazole derivatives are in a very interesting class of heterocyclic compounds, because they have many pharmacological properties and play important roles in biological processes. The imidazole compounds are known to possess NO synthase inhibition and antifungal, antimycotic, antitumor, antibiotic, antibacterial, antiulcerative, and CB1 receptor antagonistic activities. Various substituted imidazoles act as B-Raf kinase, glucagon receptors, inhibitors of p38 MAP kinase, plant grown regulators, therapeutic agents, and pesticides [1,2]. These propellants have engendered considerable interest among synthetic organic and medicinal chemists in recent years. Accordingly, a number of synthetic methods have been reported for the synthesis of 2,4,5-trisubstituted imidazoles. These methods involve condensation of benzil or benzoin, aryl aldehydes and ammonium acetate by using various catalytic systems [3]. But, some of these synthetic methods are associated with one or more drawbacks such as using expensive reagents, long reaction times, purifications, complex work-up, generation of large amount of toxic wastes, strongly acidic conditions, high temperature, poor yields and occurrence of side reactions [4,5]. Owing to the wide range of pharmacological and biological activities, the development of effective, high yielding, economical, clean and mild environmental benign protocols is still desirable and is in demand. Moreover, the design of valuable, effective and recoverable catalysts is important for the both environmental and economic point of view. Owing to the wide range of pharmacological and biological activities, the development of effective, high yielding, economical, clean and mild environmental benign protocols is still desirable and is in demand. Moreover, the design of valuable, effective and recoverable catalysts is important for the both environmental and economic point of view. Herein we wish to report a new efficient and practical route for the synthesis of trisubstituted imidazoles by the condensation reaction of benzil or benzoin, aryl aldehydes and ammonium acetate catalyzed by novel BiFeO₃/CuWO₄ heterojunction nanoparticles. To the best of our knowledge, this is the first report of design, preparation, and characterization of BiFeO₃/CuWO₄ heterojunction and its application as a heterogeneous catalyst in organic reactions. This novel approach has several superiorities as compared with the previous reports for the synthesis of substituted imidazole derivatives and opens an important area to the use of environmentally benign and recoverable heterogeneous nanocatalyst in the synthesis of pharmaceutically important heterocyclic compounds.

References 

[1] A. D¨omling, W. Wang and K. Wang, Chem. Rev., 2012, 112, 3083.

[2] D. Kumar, D. N. Kommi, N. Bollineni, A. R. Patel and A. K. Chakraborti, Green Chem., 2012, 14, 2038.

[3] V. S. V. Satyanarayana and A. Sivakumar, Chem. Pap., 2011, 65, 519.

[4] D. I. MaGee, M. Bahramnejad and M. Dabiri, Tetrahedron Lett., 2013, 54, 2591.

[5] A. Keivanloo1, M. Bakherad, E. Imanifar and M.Mirzaee, Appl. Catal., A, 2013, 467, 291.

The design and synthesis of new chemosensors for the detection of trivalent cations represent a high interest area into the supramolecular chemistry. The detection and quantification of metallic ions is applied to many fields. In that direction, two derivatives of the bis-vainilline condensed in positions 3- and 3’- with hydralazine and isoniazide respectively, have been analyzed as potential sensors of trivalent cations. The structural geometry and the stability of both substances was determined using the DFT theory. In presence of Al³⁺ the structural differences between both compounds have a great influence in its fluorescents properties which can be explained with to the decrease in the dihedral angle. Moreover, the ΔE values as a consequence of the coupling with the cation Al³⁺ indicate that the energy difference between the HOMO and the LUMO declines, improving the stability of these systems. In the other hand, both compounds display a strong improvement of the signal intensity when Cr³⁺ was used, while when Fe³⁺ was employed with the first ligand a quenching effect was observed. Finally, it is necessary to consider that a mixture of both substances can be used to discriminate between Fe³⁺, Al³⁺, and Cr³⁺.

Iminophosphoranes are organic compounds of general composition R₃P=NR and can be considered as nitrogen analogues to phophorus ylides. They can be obtained by the Staudinger[1] and Kirsanov[2] reactions. This compounds have multiple applications: they can be used as intermediates in reactions such as the Aza-Wittig[3], as a protecting group for amines or as a ligands for coordinated or cyclometallated compounds[4].

The P=N bond is highly polarized, so that the nitrogen bears a partial negative charge. This feature makes them act as σ-donors with only minor π-acceptor properties, so when forming coordination compounds they can be displaced by other ligands[5].

Acknowledgments

We wish to thank the financial support received from the Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme Projects GRC2015/009.

[1] H Staudinger, J Meyer, Helv. Chim. Acta 2 (1): 635  

[2] A.V. Kirsanov, Izv. Akad. Nauk. SSSR, Ser. Khim. (1950) 426-437

[3] F. Palacios, C. Alonso, D. Aparicio, G. Rubiales, J.M. de los Santos, Tetrahedron 63 (2006) 523-575;

[4] Pingrong Wei, Katie T. K. Chan and Douglas W. Stephan Dalton Trans. 2003, 3804–3810

[5] M. Fukui, K. Itoh, Y. Ishii, Bull. Chem. Soc. Jpn. 48 (1975) 2044- 2046

In our group, we have synthesized indium nanoparticles (InNPs) of 4.0±0.5 nm, through the reducing system InCl₃-Li-DTBB(cat.) in THF at room temperature and in the absence of any additives or anti-caking ligand. The catalytic efficiency of these InNPs was evaluated by the allylation reaction of carbonyl compounds, giving excellent yields of the corresponding homoallylic alcohols. The reagents were selected rationally in order to complete an appropriate mechanistic knowledge of the system. Substituted allyl bromides used enabled us to establish that the reaction products come from a γ-coupling, via a six members cyclic transition state, type Zimmerman-Traxler.¹

Based on this, and in order to give an explanation to the experimental results, we started a computational theoretical study using the Gaussian09 program. The initial conformational analysis was performed using the semiempirical PM3 method, then we work with the B3LYP functional, applying the LANL2DZ pseudopotential for the indium and the 6-31+G* basis set for all the other atoms and the solvent effect was evaluated with the PCM model.

Regarding the reactivity, the allylation of benzaldehyde with allyl bromide gave 98% of product after 1 h reaction time, while the allylation of acetophenone, after 20 h, gave 67% yield. The computational modeling showed a very good agreement with the experimental results: the activation energy (Ea) for the first process (exothermic in 3.4 kcal/mol) was 6.9 kcal/mol, while the Ea for the allylation of acetophenone was 10.8 kcal/mol, being an endothermic process (+0.9 kcal/mol). Furthermore, the allylation of benzaldehyde with prenyl bromide, gave 93% of product, after 4 h reaction time. The reaction is slow because of the high Ea, 11.4 kcal/mol, and the endothermicity of 3.6 kcal/mol.

Relative the selectivity, when using crotyl bromide as allylating agent, a mixture of diastereomer alcohols was obtained, with a higher proportion of syn regarding to anti (67:33). The computational analysis is agreed with these results, being the Eas 8.0 and 9.6 kcal/mol respectively. Besides, the allylation with crotyl bromide of ortho substituted benzaldehydes showed syn selectivity. For example, for the ortho-Cl derivative, the computational modeling indicates that 8.1 kcal/mol are required to give the anti diastereomer while only 5.7 kcal/mol for the syn product; moreover, the first process is less exothermic than the second (-2.7 vs -4.0 kcal/mol respectively).

We appreciate the support received from SGCyT-UNS, CONICET and ANPCyT.

¹ Dorn, V., Chopa. A., Radivoy, G. RSC Advances, 2016, 6, 23798-23803.