Synthesis and stereochemistry of trans- and cis-2,3-difluoro-2,3-dihydrobenzofuran

The geometrical isomers of 2,3-difluoro-2,3-dihydrobenzofuran have been prepared and their structure assigned on the basis of the nmr spectra. Some suggestions on the conformational situation of two adducts are also reported.     

Catalysis of the beta-elimination of HF from isomeric 2-fluoroethylpyridines and 1-methyl-2-fluoroethylpyridinium salts. Proton-activating factors and methyl-activating factors as a mechanistic test to distinguish between concerted E2 and E1cb irreversible mechanisms

Second-order rate constants, k(OH)(N), M(-)(1) s(-)(1), for the beta-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH(-)/H(2)O, at 50 degrees C and mu = 1 M KCl, are = 0.646 x 10(-)(4) M(-)(1) s(-)(1), = 2.97 x 10(-)(6) M(-)(1) s(-)(1), and = 5.28 x 10(-)(4) M(-)(1) s(-)(1), respectively. When compared with the second-order rate constants for the same processes with the nitrogen-methylated substrates 1-methyl-2-(2-fluoroethyl)pyridinium iodide (5), 1-methyl-3-(2-fluoroethyl)pyridinium iodide (6), and 1-methyl-4-(2-fluoroethyl)pyridinium iodide (7), the methyl-activating factor (MethylAF) can be calculated from the ratio k(OH)(NCH)3/, and a value of 8.7 x 10(5) is obtained with substrates 5/2, a value of 1.6 x 10(3) with 6/3, and a value of 2.1 x 10(4) with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (A(N)D(E) + D(N)) for substrates 5 and 7 and with the high stability of the intermediate carbanion related to its enamine-type structure. In acetohydroxamate/acetohydroxamic acid buffers (pH 8.45-9.42) and acetate/acetic acid buffers (pH 4.13-5.13), the beta-elimination reactions of HF, with substrates 2 and 4, occur at NH(+), the substrates protonated at the nitrogen atom of the pyridine ring, even when the [NH(+)] is much lower than the [N], the unprotonated substrate, due to the high proton-activating factor (PAF) value observed: 3.6 x 10(5) for 2 and 6.5 x 10(4) for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (A(N)D(E)D(N)) mechanism. Finally, the rate constant for carbanion formation from NH(+) with 2 is k(B)(NH)+ = 0.35 M(-)(1) s(-)(1), which is lower than when chlorine is the leaving group ( = 1.05 M(-)(1) s(-)(1); Alunni, S.; Busti, A. J. Chem. Soc., Perkin Trans. 2 2001, 778). This is direct experimental evidence that some lengthening of the carbon-leaving group bond can occur in the intermediate carbanion. This is a point of interest for interpreting a heavy-atom isotope effect.     

Fluorine-Containing Drugs Approved by the FDA in 2018

Over the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine-containing drugs approved by the food and drug administration (FDA) in 2018. The newly approved pharmaceuticals feature several types of aromatic F and CF₃, as well as aliphatic (CF₂) substitution, offering advances in the treatment of various diseases, including cancer, HIV, malarial and smallpox infections.     

Multistability in an electrically actuated carbon nanotube: a dynamical integrity perspective

This study deals with a slacked carbon nanotube, which is electrostatically and electrodynamically actuated. After introducing a reduced-order model, we investigate the overall scenario of the device response when both the frequency and the electrodynamic voltage are varied. Extensive numerical simulations are performed. The nanostructure exhibits several competing attractors with different characteristics. We examine the multistability in detail, based on numerical integration of the equation of motion in time, since it leads to a considerable versatility of behavior, which may be desirable in applications. Nevertheless, these results do not take into account the presence of disturbances, which are unavoidable under realistic conditions. To extend them to the practical case where disturbances exist, we develop a dynamical integrity analysis. This is performed via the combined use of several dynamical integrity tools. Analyzing the potential well, we observe that the device may be vulnerable to pull-in considerably before the theoretical inevitable escape. Focusing on the safe range, the main attractors are examined to investigate the practical probability to catch them and the practical disappearance of the main ones. Special attention is devoted to the practical final response, to detect where the safe jump to another attractor may be ensured and where instead dynamic pull-in may arise. We build the integrity charts, which are able to illustrate if and in which parameter range the theoretical predictions can be guaranteed in practice. They may be used to establish safety factors to effectively operate the device according to the desired outcome, depending on the expected disturbances.     

The Torsional Barriers of 2‐Hydroxy‐ and 2‐Fluorobiphenyl: Small but Measurable

By making use of a novel diastereotopicity probe, namely C(CF₃)₂OH, it has been possible to measure by very low temperature ¹⁹F NMR spectroscopy the elusive aryl–aryl rotation barriers of biphenyls bearing an OH or F group in one ortho position. The experimental values (5.4 and 4.4 kcal mol^?1, respectively) are matched by those from ab initio calculations (5.3 and 4.3 kcal mol^?1, respectively).