The Effect of Deoxyfluorination on Intermolecular Interactions in the Crystal Structures of 1,6-Anhydro-2,3-epimino-hexopyranoses

The effect of substitution on intermolecular interactions was investigated in a series of 1,6-anhydro-2,3-epimino-hexopyranoses. The study focused on the qualitative evaluation of intermolecular interactions using DFT calculations and the comparison of molecular arrangements in the crystal lattice. Altogether, ten crystal structures were compared, including two structures of C4-deoxygenated, four C4-deoxyfluorinated and four parent epimino pyranoses. It was found that the substitution of the original hydroxy group by hydrogen or fluorine leads to a weakening of the intermolecular interaction by approximately 4 kcal/mol. The strength of the intermolecular interactions was found to be in the following descending order: hydrogen bonding of hydroxy groups, hydrogen bonding of the amino group, interactions with fluorine and weak electrostatic interactions. The intermolecular interactions that involved fluorine atom were rather weak; however, they were often supported by other weak interactions. The fluorine atom was not able to substitute the role of the hydroxy group in molecular packing and the fluorine atoms interacted only weakly with the hydrogen atoms located at electropositive regions of the carbohydrate molecules. However, the fluorine interaction was not restricted to a single molecule but was spread over at least three other molecules. This feature is a base for similar molecule arrangements in the structures of related compounds, as we found for the C4-Fax and C4-Feq epimines presented here.

Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines

Abstract2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp3-F bond cleavage.

(4-Benzyl-1-methyl-1,2,4-triazol-5-ylidene)[(1,2,5,6-η)-cycloocta-1,5-diene](triphenylphosphane-κP)iridium(I) tetrafluoridoborate

A new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetrafluoridoborate counter-anion, [Ir(C10H11N3)(C8H12)(C18H15P)]BF4, has been synthesized and structurally characterized. The cationic complex exhibits a distorted square-planar environment around the IrI ion. One significant non-standard hydrogen-bonding interaction exists between a hydrogen atom on the N-heterocyclic carbene ligand and a fluorine atom from the counter-ion, BF4 −. In the crystal, π–π stacking interactions are observed between one of the phenyl rings and the triazole ring. Both intermolecular and intramolecular C—H...π(ring) interactions are also observed.

Design and Synthesis of Fluoro Analogues of Vitamin D

The discovery of a large variety of functions of vitamin D3 and its metabolites has led to the design and synthesis of a vast amount of vitamin D3 analogues in order to increase the potency and reduce toxicity. The introduction of highly electronegative fluorine atom(s) into vitamin D3 skeletons alters their physical and chemical properties. To date, many fluorinated vitamin D3 analogues have been designed and synthesized. This review summarizes the molecular structures of fluoro-containing vitamin D3 analogues and their synthetic methodologies.

Recent Innovations of Organo-Fluorine synthesis and pharmacokinetics

: The fluorinated compounds have significance in medicinal chemistry and pharmaceuticals research. The introduction of fluorine atom in the heterocyclic compounds increases biological activity, develops favourable physiochemical interaction. Combination of the heterocycles and fluorine substituent having large scope in the research work of the different drugs molecules. The compounds not only show biological activity but also show unique physical and chemical properties that open the doors of multidisciplinary research areas. Fluorine atom tolerance towards maximum functional groups, simplicity in operation, replacing hydrogen with fluorine of bioactive molecules are more efficient for the production at the commercial level. The fluorine substitution also increases the binding affinity to the targeted protein. Also, incorporation of fluorine into the drug helps to increase the polarity hence to increase the rate of drug metabolism and improves the metabolic stability. The pharmacokinetic study plays an important role in clinical research, since 1996, researcher Whitford discover that the pharmacokinetic of fluorine is depend on its pH and amount in the bone. pH of organofluoride governs the absorption, distribution and excretion of fluoride. It also increases the stability when binding with carbon atom and resulting in an increase in bioactivity. This is the main reason that around 25% of present active drugs on various diseases, including cancer, diabetes, HIV, etc. have fluorine as important content. Not only pharmacokinetic property but also the physical property of the drug can be enhanced or altered by selective insertion at the key place of the fluorine atom in the drug compound. In this report, we have summarized the interesting research article reported since 2000 for the synthesis of low fluorine substituted organic compounds for medicinal research and pharmacokinetic study of fluorine molecules in neurological diseases, cancer, and tuberculosis research.

Adsorption of Rare Earth Ce3+ and Pr3+ Ions by Hydrophobic Ionic Liquid

This study reports the use of hydrophobic ionic liquid (IL) based on D-galactose for the recovery of Ce (III) and Pr (III) ions from solutions. The equilibrium data were obtained by optimization of batch parameters, and various isotherms and kinetic models were utilised to predict the mechanistic process of sequestration of ions. The Arrhenius activation energies are found to be between 5–40 kJ, suggesting the physisorption process of ions onto IL. The present process is understood to be rapid and exothermic in nature according to thermodynamic experiments. The loading capacity was found to be 179.3 g L−1 and 141.5 g L−1, respectively, for Ce (III) and Pr (III) ions at pH 5 with a contact time of 30 min and dose being 0.1 g L−1. The higher uptake capacity is attributed to the presence of a highly electronegative fluorine atom in the IL. These results highlight the potential application of IL in the sequestration of Ce (III) and Pr (III) ions from any water sources.

New-Generation Liquid Crystal Materials for Application in Infrared Region

This study presents 13 new organic compounds with self-assembling behavior, which can be divided into two groups. The first synthesized group includes compounds based on 4′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl-4-(trifluoromethoxy) benzoate core, and the second includes compounds based on 4-((4-(trifluoromethoxy)phenyl)ethynyl)phenyl-4-(trifluoromethoxy) benzoate core. They differ in the number and location of the fluorine atom in the lateral position. Mesomorphic properties, phase transition enthalpies, refractive indices, birefringence, and MWIR (mid-wavelength infrared) spectral properties of the compounds were investigated, and the results were compared with currently used materials. The influence of the length of the core as well as type and position of substituents in the molecular core was analyzed. The lack of aliphatic protons in the molecular structure generated unique infrared properties.

Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.

The Effects on Lipophilicity of Replacing Oxygenated Functionality with Their Fluorinated Bioisosteres

The replacement of oxygenated functionality (hydroxy, alkoxy) with a fluorine atom is a very commonly used bioisosteric replacement in medicinal chemistry. In this paper we use a Molecular Matched Pair Analysis approach to better understand the effects of this bioisosteric replacement on the physicochemical properties of compounds, particularly in terms of lipophilicity. We observe that the presence of electron-donating groups on an aromatic ring generally increase the difference in lipophilicity between an oxygenated compound and its fluorinated analogue.