Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane

Spontaneous S-alkylation of methimazole (1) with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1H-imidazole-2-yl)thio]ethane (2), that we have described recently, opened the question about its formation pathway(s). Results of the synthetic, NMR spectroscopic, crystallographic and computational studies suggest that, under given conditions, 2 is obtained by direct attack of 1 on the chloroethyl derivative 2-[(chloroethyl)thio]-1-methyl-1H-imidazole (3), rather than through the isolated stable thiiranium ion isomer, i.e., 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium chloride (4a, orthorhombic, space group Pnma), or in analogy with similar reactions, through postulated, but unproven intermediate thiiranium ion 5. Furthermore, in the reaction with 1, 4a prefers isomerization to the N-chloroethyl derivative, 1-chloroethyl-2,3-dihydro-3-methyl-1H-imidazole-2-thione (7), rather than alkylation to 2, while 7 further reacts with 1 to form 3-methyl-1-[(1-methyl-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8, monoclinic, space group P 2₁/c). Additionally, during the isomerization of 3, the postulated intermediate thiiranium ion 5 was not detected by chromatographic and spectroscopic methods, nor by trapping with AgBF₄. However, trapping resulted in the formation of the silver complex of compound 3, i.e., bis-{2-[(chloroethyl)thio]-1-methyl-1H-imidazole}-silver(I)tetrafluoroborate (6_, monoclinic, space group P 2₁/c), which cyclized upon heating at 80 °C to 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium tetrafluoroborate (4b, monoclinic, space group P 2₁/c). Finally, we observed thermal isomerization of both 2 and 2,3-dihydro-3-methyl-1-[(1-methyl-1H-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8), into 1,2-bis(2,3-dihydro-3-methyl-1H-imidazole-2-thione-1-yl)ethane (9), which confirmed their structures.     

Comparison of isothermal and non-isothermal chemiluminescence and differential scanning calorimetry experiments with benzoyl peroxide

Difference in the kinetics of chemiluminescence (CL) and differential scanning calorimetry records for decomposition of originally solid benzoyl peroxide continuing as a melt reaction was outlined. While the main portion of heat measured by DSC is released in the spontaneous decomposition of benzoyl peroxide starting as a homolytic scission of peroxidic bonds, the CL light emission in oxygen comes presumably from the subsequent disproportionation reaction of polyphenyl peroxyl radicals and monitors the induced decomposition of peroxide. Thermogravimetry revealed that oxygen remains partially bound to the products of benzoyl peroxide decomposition.     

Synthesis,structure and properties of eight novel molybdenum(VI) complexes of the types: [MoO2LD] and [{MoO2L}2D] (L = thiosemicarbazonato ligand,D = N-donor molecule)

Eight new molybdenum(VI) complexes with 4-(diethylamino)salicylaldehyde and 2-hydroxy-3-methoxybenzaldehyde thiosemicarbazones have been prepared. They were characterized as mononuclear [MoO₂LD] or dinuclear [{MoO₂L}₂D] complexes. In all the compounds the MoO₂²⁺ core is coordinated by a tridentate ONS thiosemicarbazonato ligand and by the N-donor molecule (imidazole, pyridine or γ-picoline). All the complexes were characterized by chemical analysis, IR spectroscopy and thermogravimetry. Three of the mononuclear complexes, dioxo[(2-hydroxy-3-methoxybenzaldehyde thiosemicarbazonato)(pyridine)]molybdenum(VI), dioxo[(2-hydroxy-3-methoxybenzaldehyde thiosemicarbazonato)(γ-picoline)]molybdenum(VI) and dioxo[(2-hydroxy-3-methoxybenzaldehyde thiosemicarbazonato)(imidazole)]molybdenum(VI) were also characterized by single-crystal X-ray structural analysis. A spectrophotometric method for the determination of molybdenum based on extraction of ion-pairs formed by the cationic surfactant and the [MoO(SCN)₄]⁻ anion is described.     

Lepidium graminifolium L.: Glucosinolate Profile and Antiproliferative Potential of Volatile Isolates

Glucosinolates (GSLs) from Lepidium graminifolium L. were analyzed qualitatively and quantitatively by their desulfo-counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown products-isothiocyanates (ITCs) using GC-MS analysis. Thirteen GSLs were identified with arylaliphatic as the major ones in the following order: 3-hydroxybenzyl GSL (glucolepigramin, 7), benzyl GSL (glucotropaeolin, 9), 3,4,5-trimethoxybenzyl GSL (11), 3-methoxybenzyl GSL (glucolimnanthin, 12), 4-hydroxy-3,5-dimethoxybenzyl GSL (3,5-dimethoxysinalbin, 8), 4-hydroxybenzyl GSL (glucosinalbin, 6), 3,4-dimethoxybenzyl GSL (10) and 2-phenylethyl GSL (gluconasturtiin, 13). GSL breakdown products obtained by hydrodistillation (HD) and CH₂Cl₂ extraction after hydrolysis by myrosinase for 24 h (EXT) as well as benzyl ITC were tested for their cytotoxic activity using MTT assay. Generally, EXT showed noticeable antiproliferative activity against human bladder cancer cell line UM-UC-3 and human glioblastoma cell line LN229, and can be considered as moderately active, while IC₅₀ of benzyl ITC was 12.3 μg/mL, which can be considered as highly active.     

Desmotropy, polymorphism, and solid-state proton transfer: four solid forms of an aromatic o-hydroxy Schiff base

The Schiff base derived from salicylaldehyde and 2-amino-3-hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol-imino (D1?a and D1?b) and keto-amino (D2?a and D2?b) desmotropes. The isolated phases, identified by IR spectroscopy, X-ray crystallography, and (13)C cross-polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O-H???N (D1) or N-H???O (D2) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent-free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form (D1?a) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature-resolved powder X-ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

Desmotropy,Polymorphism, and Solid‐State Proton Transfer: Four Solid Forms of an Aromatic o‐Hydroxy Schiff Base

The Schiff base derived from salicylaldehyde and 2‐amino‐3‐hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol‐imino ( D1 a and D1 b ) and keto‐amino ( D2 a and D2 b ) desmotropes. The isolated phases, identified by IR spectroscopy, X‐ray crystallography, and ¹³C cross‐polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O? H???N ( D1 ) or N? H???O ( D2 ) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent‐free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form ( D1 a ) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature‐resolved powder X‐ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

Synthesis, NMR and X-ray structure analysis of macrolide aglycons

Macrolide aglycons (E)-9-hydroxyimino-6-O-methylerythronolide A (4), 9a-aza-9-deoxo-9,9-dihydro-9a,11-O-dimethyl-9a-homoerythronolide A (5) and 9a-aza-9-deoxo-9,9-dihydro-9a-homoerythronolide A (6) were prepared by multistep syntheses. A conformational study of these new macrolide aglycons was performed using single crystal X-ray crystallography to gain information about the solid state, while a combination of NMR spectroscopy and molecular modelling was employed to study the solution structures. The crystal structures were found to be stabilised by a complex network of hydrogen bonds and van der Waals interactions. To some extent, the same building motif of infinite molecular chains held together by O?CH···O hydrogen bonds was present in the crystal structure of all three compounds. Thorough analysis and comparison of the obtained solid state structures with their solution counterparts showed no significant differences between them, confirming the constrained flexibility of the macrocyclic ring. Moreover, in all three compounds, in both solution and solid state, the macrolactone ring adopts energetically more favoured folded-out conformations.     

Poly(2‐oxazoline) hydrogels crosslinked with aliphatic bis(2‐oxazoline)s: Properties,cytotoxicity, and cell cultivation

A series of hydrogels from 2‐ethyl‐2‐oxazoline and three bis(2‐oxazoline) crosslinkers—1,4‐butylene‐2,2′‐bis(2‐oxazoline), 1,6‐hexamethylene‐2,2′‐bis(2‐oxazoline), and 1,8‐octamethylene‐2,2′‐bis(2‐oxazoline)—are prepared. The hydrogels differ by the length of aliphatic chain of crosslinker and by the percentage of crosslinker (2–10%). The influence of the type and the percentage of the crosslinker on swelling properties, mechanical properties, and state of water is studied. The equilibrium swelling degree in water ranges from 2 to 20. With a proper selection of the crosslinker, Young's modulus can be varied from 10 kPa to almost 100 kPa. To evaluate the potential for medical applications, the cytotoxicity of extracts and the contact toxicity toward murine fibroblasts are measured. The hydrogels with the crosslinker containing a shorter aliphatic exhibit low toxicity toward fibroblast cells. Moreover, the viability and the proliferation of pancreatic β‐cells incubated inside hydrogels for 12 days are analyzed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1548–1559     

Mostar index

We propose and investigate a new bond-additive structural invariant as a measure of peripherality in graphs. We first determine its extremal values and characterize extremal trees and unicyclic graphs. Then we show how it can be efficiently computed for large classes of chemically interesting graphs using a variant of the cut method introduced by Klav?ar, Gutman and Mohar. Explicit formulas are presented for several classes of benzenoid graphs and Cartesian products. At the end we state several conjectures and list some open problems.     

Slater orbital molecular integrals with numerical fourier transform methods. I. (coplanar) multicenter exchange integrals over 1s orbitals

Slater orbital r₁₂^?1 integrals are calculated with a numerical Fourier-transform method based on a formulation first given by Bonham, Peacher and Cox. Spherical wave expansions are introduced that decouple the Feynman integrations for the charge distribution Fourier transforms. The Feynman integrals are evaluated semianalytically, and their properties are analyzed in detail. The final computational step involves a numerical integration over charge distribution quantities. Results for (coplanar) multicenter exchange integrals over 1s orbitals are given. As long as the charge distributions are overlapping considerably, the method gives good results, even when these distributions are highly asymmetric. The method as presently implemented fails when highly disconnected charge distributions are involved.