Microwave‐assisted synthesis of new regioisomeric 6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones

Novel 11‐amino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e] pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones 4a‐f were prepared regioselectively by the tricomponent reaction of 4,5,6‐triaminopyrimidine 1, 1,3‐indandione 2 and aromatic aldehydes 3a‐f. The bicomponent approach, using 2,4,5,6‐tetraaminopyrimidine 5 and 2‐aryl‐ideneindandiones 6a‐f as reagents, afforded 9,11‐diamino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b]‐[1,4]diazepin‐5(5aH)‐ones 7a‐f in good yields and the regioisomeric 8,10‐diamino derivatives 8a‐c in lower yields. Both, bi‐ and tricomponent approaches were performed by microwave irradiation and all products were fully characterized by detailed NMR measurements.     

Composition of three essential oils, and their mammalian cell toxicity and antimycobacterial activity against drug resistant-tuberculosis and nontuberculous mycobacteria strains

Tuberculosis (TB) is the most ancient epidemic disease in the world and a serious opportunistic disease in HIV/AIDS patients. The increase in multidrug resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) demands the search for novel antimycobacterial drugs. Essential oils (EOs) have been widely used in medicine and some EOs and their major components have been shown to be active against M. tuberculosis. The aim of this work was to evaluate the antimycobacterial and cell toxicity activities of three EOs derived from Salvia aratocensis, Turnera diffusa and Lippia americana, aromatics plants collected in Colombia. The EOs were isolated by hydrodistillation and analyzed by GC/MS techniques. The EOs were tested against 15 Mycobacterium spp using a colorimetric macrodilution method and against mammalian Vero and THP-1 cells by MTT. The activity was expressed as minimal concentration in microg/mL that inhibits growth, and the concentration that is cytotoxic for 50 or 90% of the cells (CC50 and CC90). The major components were epi-alpha-cadinol (20.1%) and 1,10-di-epi-cubenol (14.2%) for Salvia aratocensis; drima-7,9(11)-diene (22.9%) and viridiflorene (6.6%) for Turnera diffusa; and germacrene D (15.4%) and trans-beta- caryophyllene (11.3%) for Lippia americana. The most active EO was obtained from S. aratocensis, with MIC values below 125 microg mL(-1) for M. tuberculosis Beijing genotype strains, and 200 to 500 microg mL(-1) for nontuberculous mycobacterial strains. The EOs were either partially or non toxic to Vero and THP-1 mammalian cells with CC50 values from 30 to > 100 microg mL(-1), and a CC90 > 100 microg mL(-1). The EOs obtained from the three aromatic Colombian plants are an important source of potential compounds against TB. Future studies using the major EO components are recommended.     

Fast batch injection analysis of H(2)O(2) using an array of Pt-modified gold microelectrodes obtained from split electronic chips

A fast and robust analytical method for amperometric determination of hydrogen peroxide (H(2)O(2)) based on batch injection analysis (BIA) on an array of gold microelectrodes modified with platinum is proposed. The gold microelectrode array (n=14) was obtained from electronic chips developed for surface mounted device technology (SMD), whose size offers advantages to adapt them in batch cells. The effect of the dispensing rate, volume injected, distance between the platinum microelectrodes and the pipette tip, as well as the volume of solution in the cell on the analytical response were evaluated. The method allows the H(2)O(2) amperometric determination in the concentration range from 0.8 μmolL(-1) to 100 μmolL(-1). The analytical frequency can attain 300 determinations per hour and the detection limit was estimated in 0.34 μmolL(-1) (3σ). The anodic current peaks obtained after a series of 23 successive injections of 50 μL of 25 μmolL(-1) H(2)O(2) showed an RSD<0.9%. To ensure the good selectivity to detect H(2)O(2), its determination was performed in a differential mode, with selective destruction of the H(2)O(2) with catalase in 10 mmolL(-1) phosphate buffer solution. Practical application of the analytical procedure involved H(2)O(2) determination in rainwater of S?o Paulo City. A comparison of the results obtained by the proposed amperometric method with another one which combines flow injection analysis (FIA) with spectrophotometric detection showed good agreement.     

Four 7‐aryl‐substituted pyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones: similar molecular structures but different crystal structures

Molecules of 1,3‐dimethyl‐7‐(4‐methylphenyl)pyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione, C₁₆H₁₅N₃O₂, (I), are linked by paired C—H...O hydrogen bonds to form centrosymmetric R₂²(10) dimers, which are linked into chains by a single π–π stacking interaction. A single C—H...O hydrogen bond links the molecules of 7‐(biphenyl‐4‐yl)‐1,3‐dimethylpyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione, C₂₁H₁₇N₃O₂, (II), into C(10) chains, which are weakly linked into sheets by a π–π stacking interaction. In 7‐(4‐fluorophenyl)‐3‐methylpyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione, C₁₄H₁₀FN₃O₂, (III), an N—H...O hydrogen bond links the molecules into C(6) chains, which are linked into sheets by a π–π stacking interaction. The molecules of 7‐(4‐methoxyphenyl)‐3‐methylpyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione, C₁₅H₁₃N₃O₃, (IV), are also linked into C(6) chains by an N—H...O hydrogen bond, but here the chains are linked into sheets by a combination of two independent C—H...π(arene) hydrogen bonds.     

(E)‐N2‐{4‐[(E)‐2‐(4‐Chlorobenzoyl)ethenyl]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐yl}‐N1,N1‐dimethylformamidine: polarized molecules within sheets of π‐stacked hydrogen‐bonded chains

The molecules of the title compound, C₂₂H₂₁ClN₄O, are conformationally chiral, and in the space group P2₁2₁2₁ each crystal contains only one conformational enantiomer. The intramolecular dimensions provide evidence for polarization of the electronic structure. Molecules are linked by a single C—H...π(arene) hydrogen bond into chains, which are themselves weakly linked into sheets by an aromatic π–π stacking interaction.     

Scheduling jobs on a <Emphasis Type="Italic">k</Emphasis>-stage flexible flow-shop

We consider the problem of makespan minimization on a flexible flow shop with k stages and m _s machines at any stage. We propose a heuristic algorithm based on the identification and exploitation of the bottleneck stage, which is simple to use and to understand by practitioners. A computational experiment is conducted to evaluate the performance of the proposed method. The study shows that our method is, in average, comparable with other bottleneck-based algorithms, but with smaller variance, and that it requires less computational effort.     

9‐Benzoyl‐3,3,6,6‐tetramethyl‐1,2,3,4,5,6,7,8‐octahydroxanthene‐1,8‐dione: molecular conformation and supramolecular aggregation in xanthenediones

In the title compound, C₂₄H₂₆O₄, (I), the central ring of the fused tricyclic ring system adopts a shallow boat conformation, while the two outer rings adopt envelope conformations. The molecules are linked into C(9) chains by a single C—H...O hydrogen bond. The significance of this study lies in its comparison of the conformation and supramolecular aggregation of (I) with those of related compounds in the published literature.     

Solvent‐Free Microwave‐Assisted Synthesis of Novel 4‐Hetarylpyrazolo[1,5‐a][1,3,5]triazines

A series of novel 4‐hetaryl substituted pyrazolo[1,5‐a][1,3,5]triazines were synthesized by microwave assisted reaction between O,S‐diethyl hetaroylimidothiocarbonates and 5‐amino‐3‐aryl‐1H‐pyrazoles under solvent‐free conditions. This procedure led to the formation of mixtures of two new pyrazolotriazine derivatives in a 1:4 ratio, which were separated by column chromatography being their corresponding structures unambiguously established by spectroscopic and analytical techniques. Comparison of the reactions mediated by microwave irradiation and by conventional heating in solution of DMF showed that both procedures afforded the same mixtures of products, but the first approach required shorter reaction times and gave higher yields than the second one.     

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine are isostructural and form hydrogen‐bonded sheets of R22(8) and R66(32) rings

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine, C₁₃H₁₃ClN₄O, (I), and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine, C₁₃H₁₃ClN₄O₂, (II), are isostructural and essentially isomorphous. Although the pyrimidine rings in each compound are planar, the ring‐substituent atoms show significant displacements from this plane, and the bond distances provide evidence for polarization of the electronic structures. In each compound, a combination of N—H...N and N—H...O hydrogen bonds links the molecules into sheets built from centrosymmetric R₂²(8) and R₆⁶(32) rings. The significance of this study lies in its observation of the isostructural nature of (I) and (II), and in the comparison of their crystal and molecular structures with those of analogous compounds.     

Modeling reverse logistics process in the agro-industrial sector: The case of the palm oil supply chain

As today’s consumers are more and more concerned with the environmental impacts of products and services they buy, enterprises have been more and more concerned with “green operations”. One of the key aspects of green logistics management is reverse logistics. This paper shows how the potential of managing reverse logistics flows can be implemented in the agro-industrial sector. As an example, the palm oil supply chain is considered. This study is carried out under the focus of the “closed-loop supply chain (CLSC) framework” in which forward and backward product flows are considered simultaneously. A mathematical model is proposed in order to represent the dynamic interaction between flows. The objective function considers energy, cost and economic profits. Different implementation scenarios of recovery processes are proposed and interactions between direct and reverse flows in the chain are evaluated. Results are analyzed using proper statistical tools, showing that the simultaneous analysis of direct and reverse flows positively impact the net economic profits in this complex supply chain of the agro-industrial sector.