Fluorine atoms, in molecules

Does a fluorine-substituent stabilize carbocation is an interesting question to be clarified in this section. In spite of the strong electron-withdrawing nature of a fluorine atom in molecules, the fluorine atom stabilizes a-carbocation by releasing its lone-pair electrons to the vacant p-orbital of the carbocation. However, it destabilizes (3-carbocation because of its strong electron-withdrawing nature (Scheme 1.53). 

The evidence for fluorine hyperconjugation derived from nmr measurements available in 1970 was not deflnitive (3,4). Taft and his associates had originally argued that the fluorine substituent chemical shifts (SCS) of p-fluorine atoms in molecules with substituents which are capable of resonance interactions, for example the nitro group, exhibited a special solvent dependence and shifted to lower field as the polar character of the solvent was increased (38,39). The fluorine substituent chemical shift for the aromatic fluorine atom in 4-fluo-robenzotrifluoride, indeed, exhibits a small downfleld shift from 4.95 in 3-methylpentane to 5.75 in nitromethane to 6.05 in 75% aqueous methanol. For comparison, the substituent chemical shift for the fluorine atom in 4-fluoroni-trobenzene exhibits a shift from 9.00 in 3-methylpentane to 10.55 in nitromethane to 11.20 in 75% aqueous methanol (39). Holtz concluded on these grounds that fluorine hyperconjugation, structure XVC, might contribute to the determination of the substituent chemical shift. However, Brownlee, Dayal, and Taft subsequently showed that the effects of dipolar aprotic solvents on the... 

Existence of three nitrogen atoms in a ring and such substituents as fluorine atoms in molecules of considered group of compounds does the most informative for the analysis of structure and properties NMR C and F spectroscopy. 

As an example, we look at tire etching of silicon in a CF plasma in more detail. Flat Si wafers are typically etched using quasi-one-dimensional homogeneous capacitively or inductively coupled RF-plasmas. The important process in tire bulk plasma is tire fonnation of fluorine atoms in collisions of CF molecules witli tire plasma electrons... 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

These reactions differ from those of sulfur tetrafluoride with carbonyl compounds in that a formal oxidation-reduction of the sulfur atoms m the thiocarbonyl compound and sulfur tetrafluoride molecule occurs, resulting in the formation of free sulfur and the complete utilization of the fluorine atoms in sulfur tetrafluoride. 

Polarizability (Section 4.6) A measure of the ease of distortion of the electric field associated with an atom or a group. A fluorine atom in a molecule, for example, holds its electrons tightly and is very nonpolarizable. Iodine is very polarizable. 

These three frameworks and the framework for glycine in Figure 9 illustrate an important point about Lewis structures. Although Lewis structures show how atoms are connected to one another, a Lewis structure is not intended to show the actual shape of a molecule. Silicon tetrachloride is not flat and square, SO2 is not linear, and the fluorine atoms in CIF3 are not all equivalent. We describe how to use Lewis structures to determine the shapes of molecules later in this chapter. 

The six positions around an octahedron are equivalent, as Figure 9-25 demonstrates. Replacing one fluorine atom in SFg with a chlorine atom gives SF5 Cl. No matter which fluorine is replaced, the SF5 Cl molecule has four fluorine atoms in a square, with the fifth fluorine and the chlorine atom on opposite sides, at right angles to the plane of the square. 

There are not therefore three lone pair nonbonding domains but a nonbonding domain containing six electrons having the form of a torus around the fluorine atom. This is the situation for all atoms, except hydrogen atoms, in any diatomic molecule, as we have seen for the fluorine atom in HF, and for any singly bonded ligand. 

In order to determine whether this increase in toxicity was necessarily bound up with the presence of two fluorine atoms in the molecule, a series of structurally related esters was prepared and examined.1... 

It is a prominent problem whether a negative quark can be transferred from one atom to another. If the low radii of quark 1 s orbitals are considered, the exceedingly low overlap integrals (16) would not permit transfer in times far in excess of 1010 years, unless some higher-order electrodynamic effect is of assistance. Already the motion of a F 1 s hole between two adjacent fluorine atoms in a molecule (36) takes more than 10-8 sec, i.e., many million times the lifetime of the ionized system... 

The introduction of fluorine atoms in a molecule can be used to modify the processes and the rates of metabolism of the drug, in order to extend the plasma half-life or to avoid the formation of toxic metabolites. Because of the properties of fluorine atom, in particular its electronic effects, it may interact differently on the bio-transformation steps, according to the type of processes involved... 

Most of the effects induced by the presence of fluorine atoms in a molecule come from both the structure and the fundamental atomic properties of the fluorine atom (Table 1.1). Because of its electronic structure ls 2s 2p, fluorine has very specific properties, as indicated by the extreme values of the atomic parameters given in Table 1.1. ... 

In the case of fluorinated molecules, it is important to differentiate the lipophilic character from the hydrophobic character. Both these characters are in tune for nonfluorinated molecules, but they diverge when the number of fluorine atoms increases in a molecule. It is generally recognized that fluorination induces an increase in the lipophilicity. However, this has only been demonstrated for aromatic compounds, and more specifically when fluorine atoms are in the a position of atoms, or groups bearing n electrons (Table 1.8)." Conversely, the presence of fluorine atoms in an aliphatic molecule provokes a decrease in the lipophilicity, while it can enhance the hydrophobicity. This phenomenon is so important that highly fluorinated molecules are not soluble in organic solvents or in water and constitute a third phase. 

Modifications of the chemical reactivity generated by the presence of fluorine atoms in a molecule are connected to three main factors the strength of the C— F bond, the electron-withdrawing character of the fluorinated substituents, and the possible loss of a fluoride ion or of HF in the processes of )S-elimination. On these bases and taking into account the ability of fluoro-substituents to sterically or electronically mimic other... 

By far, 2-fluoro-2-deoxyfuranoses have been the most studied compounds. Indeed, at a structural level they are the closest analogues of 2-deoxynucleosides. Due to its electronic effect, the fluorine atom in the 2 position inhibits development of a positive charge on the anomeric carbon (which is responsible for the hydrolytic cleavage of nucleosides). In order to enhance the stability of 2-deoxynucleosides in acidic medium, and thus make oral administration of an antiviral compound easier, introduction of a fluorine atom in the 2 position is a commonly used strategy. The resulting protective effect toward proteolysis has been well demonstrated, as exemplified by the fluorinated analogues of ddl and ddA (cf. Chapter 3, Figure 3.13). However, the presence of this fluorine atoms often induces modifications in the antiviral properties of the molecule. ... 

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