Quinazolines. VII. Synthesis of 1,3-Diamino-5,6-dihydrobenzo[f]quinazolines

Eighteen new 1,3-diamino-5,6-dihydrobenzo[f] quinazolines ( 6 , R. = alkyl, Cl, MeO) were synthesized via the condensation of appropriate 2-tetralones with cyanoguanidine under fusion conditions. Methods were developed for the preparation of a number of heretofore undescribed 2-tetralones as precursors. The final products can be viewed as conformationally rigid analogs of pyrimethamine ( 2 ), and are of interest as inhibitors of dihydrofolate reductase and as potential antimalarial and antitumor agents.     

Aromaticity of ortho and meta 8-Cycloparaphenylene and Their Dications: Induced Magnetic Field Analysis with Localized and Delocalized Orbitals in Strained Nanohoops

Dications of cycloparaphenyles ([n]CPPs) are known to exhibit in-plane global aromaticity, contained in a nanobelt structure. Recently synthesized ortho and meta isomers of [n]CPPs break the radial symmetry of π structure incorporating perpendicular oriented π orbitals. Herein we set to explore the aromaticity of neutral and dicationic ortho and meta isomers of [8]CPP by dissecting the induced magnetic field to contributions of the twofold radial/perpendicular π system using delocalized canonical molecular orbitals (CMO), and introducing the natural localized molecular orbitals (NLMO) analysis with DFT methods. The dications sustain a reduced global aromatic character of the radial π system under a perpendicular orientation of the external field which declines from ortho to meta isomer and reinforces local aromaticity of ortho ring while it destroys aromaticity of meta ring. Aromaticity variations are determined by symmetry governed rotational excitations of frontier π orbitals. The parallel orientation reveals a substantial reduction of local aromaticity verified with NICS_π analysis and electron delocalization indices.     

High-frequency vibration analysis of thin elastic plates under heavy fluid loading by an energy finite element formulation

An energy finite element analysis (EFEA) formulation for computing the high frequency behavior of plate structures in contact with a dense fluid is presented. The heavy fluid loading effect is incorporated in the derivation of the EFEA governing differential equations and in the computation of the power transfer coefficients between plate members. The new formulation is validated through comparison of EFEA results to classical techniques such as statistical energy analysis (SEA) method and the modal decomposition method for bodies of revolution. Good correlations are observed and the advantages of the EFEA formulation are identified.     

A note on the metric geometry of the unit ball

Denote by B ⁿ the unit ball in the Euclidean space ${\mathbb{R}^n}$ and define $$ M(B^n) = \sup \int_{B^n} \int_{B^n}\| x - y \| \, d\mu(x)d\mu(y),$$ where the supremum is taken over all finite signed Borel measures??? on B ⁿ of total mass 1. In this paper, the value of M(B ⁿ ) is computed explicitly for all n, and it is shown that for n >? 1 no measure exists that achieves the supremum defining M(B ⁿ ). These results generalize the work of Alexander (Proc Am Math Soc 64:317?C320, 1977) on M(B ³).     

On the harmonic continued fractions

The Ramanujan Journal - In this paper, we study the harmonic continued fractions. These form an infinite family of ordinary continued fractions with coefficients $$\frac{t}{1}, \frac{t}{2},...     

Methotrexate analogs. 7. Synthesis of two higher homologs and a positional isomer of methotrexate diethyl ester as potential antitumor agents

Analogs of methotrexate diethyl ester ( 1 ) were prepared, in which the distances separating the ester functions from each other and from the carboxamide function of the p-aminobenzoate moiety were varied via the use of methylene groups as “spacers”. The diethyl esters 3 and 4 , with D,L-α-aminoadipate and D,L-α-aminopimelate side chains in place of L-glutamate, displayed approximately the same order of activity as compound 1 against bacterial and mammalian cells in culture, and were inhibitors of the enzyme dihydrofolate reductase. When given intraperitoneally to L1210 1eukemic mice at a dose of 120 mg./kg. q3d 1,4,7, compound 4 produced a 67% increase in survival and no evidence of toxicity, whereas methotrexate diethyl ester ( 1 ) gave a 44% increase in survival at a dose of 45 mg./kg. q3d 1,4,7 but was toxic at higher doses. The positional isomer 2 was inactive.     

Solution phase synthesis of a library of tetrasubstituted pyrrole amides

An efficient strategy for the solution-phase parallel synthesis of a library of pyrrole-amides is described. Key reactions include functional homologation of beta-ketoesters with a set of aldehydes followed by oxidation to produce a series of differently substituted 1,4-dicarbonyl compounds. Rapid cyclization using a microwave-assisted Paal-Knorr reaction provided a set of 24 pyrrole esters that were further functionalized through a trimethylaluminum-mediated aminolysis to obtain a larger library of 288 diverse pyrrole-3-amides. The tetrasubstitution allows a good exploration of the chemical space around the central pyrrole core. The last step was entirely automated with a Bohdan Myriad personal synthesizer.     

Aromatic character of Oh-C24N24. A cavernous nitride fullerene bearing N4-macrocycle motifs

Spherical fullerenes offer noteworthy structures usually involving six- and five-membered faces, with application in technological issues. In this sense, cavernous spherical-like structures bearing larger holes provide interesting examples for further understanding of structure-properties relationship. Here, we explored the magnetic response of a proposed cavernous nitride fullerene, C₂₄N₂₄, which has a O_h-symmetry with six N₄-macrocyclic and eight 1,3,5-triazine faces displaying 48-π electrons. C₂₄N₂₄ exhibits a local aromatic behavior owing to the contrasting antiaromatic response of the N₄-macrocyclic faces and the aromatic character of the 1,3,5-triazine faces. Thus, the overall structure is ascribed as a local aromatic species, where the triazine faces exhibit the characteristic shielding cone for aromatic rings. Furthermore, the constructive combination of local shielding cones in C₂₄N₂₄ delivers a related shielding-cone response, as expected for a perfect aromatic cage. Hence, the local aromatic/nonaromatic/antiaromatic sections exhibit an additive or subtractive interaction, leading to a characteristic response inherent to the nature of the spherical cage. We expect that further study of the interplay between different aromatic and antiaromatic faces in fullerene-like cages can deliver interesting pseudo-aromatic or pseudo-antiaromatic spherical species.     

Fluid Penetration in a Deformable Permeable Web Moving Past a Stationary Rigid Solid Cylinder

We present an analysis for the process of fluid infiltration into a deformable, thin and permeable web that moves in close proximity over a rigid and stationary solid cylinder. While this is a process of significant interest in a range of coating, printing and composites pultrusion processes, its hydrodynamics have received limited attention in the open literature. The flow in the film separating the web from the cylinder is described by lubrication theory, while fluid transfer into the web is governed by Darcy’s law. The deformation of the web at each position is a linear function of the local gap pressure; this is consistent with the assumption of a thin and rigidly supported web. Our results indicate that the web/fluid interface is forced away from the cylinder surface as it approaches it and bounces back downstream from the minimum separation point. This behavior produces a non-symmetric gap between the adjacent surfaces, and this is shown to have critical influence on the final amount of penetrating fluid. The extent of fluid penetration is also found to be affected by the web elasticity (expressed by the dimensionless Ne number) and permeability (expressed in dimensionless form via \(\hat{{K}})\) where under a specific Ne and \(\hat{{K}}\) combination a maximum penetration depth is obtained. Finally, we derive a closed-form asymptotic solution for the final infiltration depth in the limit of Ne \(<<\) 1 and \(\hat{{K}}<<\)1 and test its predictions against the above-mentioned numerical results.