Synthesis of ortho-substituted cyanopyridines through lithio intermediate trapping

Ortholithiation of 4-cyanopyridine using 2,2,6,6-tetramethylpiperidide (LiTMP) and trapping the lithio intermediate with electrophiles represents an efficient and straightforward access to ortho-substituted-4-cyanopyridines. The cyano group can be used as an ortho-directing group and allows the preparation of 3-halogeno-4-cyanopyridines. Reactivity of 2- and 3-cyanopyridines is also investigated and seems to give similar results.     

Characterization of Autocatalytic Reactions in Modified Cellulose/NMMO Solutions by Thermal Analysis and UV/VIS Spectroscopy

The thermal stability of cellulose/N-methylmorpholine-N-oxide (NMMO) solutions were investigated using UV/VIS spectrometry with a temperature programming cuvette and caloric measurements by means of the Systag calorimeter RADEX (mini-autoclave). Both analytical methods allow to characterize the influences of stabilizers and additives. With the temporal course of the optical density, temperature and pressure thermal runaway reactions with gas evolution and accumulation of chromophoric degradation products were recognized. Kinetic model calculations compared with UV/VIS measurements demonstrate the existence of autocatalytic reactions in cellulose/NMMO solutions. Varying the heating rate autocatalysis can be proved by dynamic caloric measurements as well.     

Proof of the Fukui conjecture via resolution of singularities and related methods. II $$^{\star}$$

The present article is a direct continuation of the first part of this series. We reduce a proof of the Fukui conjecture (concerning the additivity problem of the zero-point vibrational energies of hydrocarbons) to that of a proposition related to the theory of algebraic curves, so that we can focus on the key mechanism of the additivity phenomena. Namely, by establishing what is called the Basic Piecewise Monotone Theorem (BPMT), we reduce a proof of the Fukui conjecture to that of a proposition, called the Local Analyticity Proposition, Version 1 (LAP1), which admits a proof via resolution of singularities. By LAP1, the essential part of the mechanism of the asymptotic linearity phenomena is extracted and is elucidated by using tools from the mathematical theory of algebraic curves, whose language is of vital importance in analyzing the crux of the additivity mechanism. Dedicated to the memory of Prof. Kenichi Fukui (1918–1998).     

Protease sensors for bioimaging

Optical imaging of specific molecular targets and pathways in vivo has recently become possible through continued developments in imaging equipment, reconstruction algorithms, and more importantly the availability of imaging reporter molecules. These reporter molecules encompass photoproteins expressed in vivo and exogenously administered probes detectable by fluorescence and/or bioluminescence imaging. One particularly enticing aspect of optical imaging is the ability to design activatible probes with inherent amplification. This review summarizes our experience in developing novel near-infrared fluorescent (NIRF) imaging agents that report on protease activities. These agents are designed to be biocompatible, highly activatible, and able to produce bright NIRF following protease cleavage.     

Cyclization of Nitrospirobenzopyrans to Bridged Benzoxazepino[3,2-a]indoles

Condensation of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with 5-nitrosalicylaldehyde afforded 1′-[(N-monosubstituted carbamoyl)methyl]indoline nitrospirobenzopyrans. Treatment of the latter with strong base led to the formation of a mixture of cis/trans-5a,13-methano-1,3-benzoxazepino[3,2-a]indoles. Results of semiempirical calculations gave evidence that such a transformation of nitrospirobenzopyrans to bicyclic indole derivatives could proceed via a single transition state, where the negatively charged carbon atom attacks the vinylic double bond of the spiropyran system.     

Synthesis and antibacterial activity of 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid

The synthesis of the quinolone, 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid 4 was accomplished utilizing the Gould-Jacobs dependent route. The compound had very weak in vitro activity as compared to nalidixic acid versus E. coli, P. aeruginosa, K. pnuemoniae, S. aureus and P. mirabilis.     

An efficient synthesis of 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid and some carbonyl derivatives of it and its 6-acetyl homologue

Starting with 1,1-dimethoxy-2-propanone ( 1 ), 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5a ) has been prepared in large quantities by a highly efficient, 4-step synthesis. This compound, along with its one carbon homologue, 6-acetyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5b ) has been reacted with several carbonyl derivative forming reagents to provide a series of side chains for β-lactams. Among these carbonyl derivatives are styrylamides which were prepared from Wittig and Horner-Emmons reagents. The preparation of the phosphonium salts and phosphonate esters is also described.     

A CONVENIENT IRRADIATION CELL FOR FERRIOXALATE ACTINOMETRY

Abstract— A calibrated volumetric optical cuvette is described which both simplifies the technique and improves the precision of potassium ferrioxalate actinometry. The cuvette is used both for irradiation of the actinometer solution and for in situ dilution and chemical developing of the irradiated aliquot. The technique permits all but one manipulation to be carried out in total darkness, thus protecting the actinometer solutions from ambient light. The method can be extended to any actinometric procedure and the volumetric cuvettes are very useful in a variety of other spectrophotometric applications.     

Design and characterization of flow-through coulometric cells with porous working electrodes made of crushed vitreous carbon

Summary Three types of flow-through, three-electrode cells with porous working electrodes made of crushed vitreous carbon were tested. The electrochemical properties of the cells were studied by hydrodynamic and cyclic voltammetry using potassium ferrocyanide test solutions. Depending on the volume of the porous working electrode, Nernstian behaviour and electrochemical yields up to 100% were observed for flow rates 1 to 7 ml/min. In the stopped-flow regime the cells exhibit thin-layer cell properties. The utility of the cells is demonstrated for on-line coulometric detection, continuous removal of impurities and dissolved oxygen and for anodic stripping coulometry of trace copper.On leave from: Department of Analytical Chemistry, Slovak Technical University, CS-812 37 Bratislava, Czechoslovakia     

Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated ketones: construction of a key intermediate for the total synthesis of zoanthamine

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.