Phenyl rings fluorinated

Dendrimers made up of fluorinated phenyl rings were s)mthesized by a similar sequence of reactions. The solubility and thermal properties of these dendritic polyphenylenes have been evaluated. The largest hydrocarbon dendrimer was, for instance, soluble in toluene and stable up to 500°C [26]. 

The hard sphere exclusion distances for this system were chosen as follows nonbonded backbone carbons, 4.60 R (twice the C-H bond distance plus van der Waals radius for H) non-neighboring fluorines, 2.70 R (twice van der Waals radius for F) neighboring fluorines, 6.39 R (distance across phenyl ring using dimensions of Table I and van der Waals radius for Hof... 

Figure 6. Effect of using a special near-neighbor fluorine-fluorine excluded volume to account for the steric effects of the phenyl ring. This serves the same purpose as dyad weights which discriminate against certain sterically forbidden conformations.

Fluorine has been used to modulate the basicity of amines which may lead to an improvement in brain exposure. Recently, the discovery of a series of a4(32 nicotinic acetylcholine receptor (nAChR) potentiators as possible treatment for Parkinson s disease and schizophrenia was were disclosed [40]. Optimization of isoxazole 40 included the bioisosteric replacement of the central amide by an imidazole ring. Introduction of a fluorine at the 6-position of the phenyl ring provided compound 41. This compound had excellent potency but was determined to be a substrate for P-gp (efflux ratio >10). In an attempt to reduce amine basicity and decrease the efflux propensity, the 4-fluoropiperidine 42 was identified which retained potency and had significantly reduced P-gp efflux liability (efflux ratio 1). CNS penetration of 42 was observed in rodents following intraperitoneal (IP) treatment at 5mg/kg and showed a brain concentration of 6.5 gM. 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

In 1998, Yang and coworkers reported a series of (7 )-carvone derived ketones (63) containing a quaternary center at and various substituents at (Fig. 22) [119]. The ees of fran -stilbene oxide varied with different para and meta substituents when 63b was used as the catalyst. The major contribution for the observed ee difference is from the n-n electronic repulsion between the Cl atom of the catalyst and the phenyl group of the substrate. The substitution at also influences the epoxidation transition state via an electrostatic interaction between the polarized C -X bond and the phenyl ring on franx-stilbene (Table 6, entries 3-7, 10-14). In 2000, Solladie-Cavallo and coworkers reported a series of fluorinated carbocyclic ketones... 

Regarding other fluorine positions on the phenyl ring it is observed that ortho-fLuorine atoms give the largest and most sensitive values some reported values<1966,19) are shown in Table XXIII. For the purposes of comparison the data of Nichols<1969,121) shown in Table XXIV is of interest. 

Although for the parent /3,/3-dimethyl styrene 20, the cation binds approximately in the middle and on top of the phenyl ring, for the P-CF3 substituted styrene 143, binding occurs in between the middle of the aryl ring and the fluorine atoms (Figure 4). For the 0-CF3 substituted styrene 145, however, the binding site changes dramatically, and resides closely to the alkene double bond. 

Thioxanthenes lack the ring nitrogen of phenothiazine, and the side chain is attached by a double bond. In all cases, the cis isomer (relative to the substituted phenyl ring) is more active. Electron-attracting substituents seem to have a cumulative effect. For instance, pifluthixol (4.89), with a fluorine and a trifluoromethyl substituent, is 5-10 times more potent than its parent flupenthixol (4.90), and has an inhibitory effect (IC50 = 9.7 X 10 ° M) on the DA-sensitive adenylate cyclase of the striatum. 

In the reactions of various hydroxyalkyl-substituted benzene derivatives, which depend on the substituent attached to the phenyl ring, oxidation, ring fluorination. the addition process and substitution of a hydroxyalkyl group are all observed.22... 

Complexes of platinum(II) with /J-monothiodiketonates, derived by deprotonation of the parent acid (207), can be prepared from PtCl -. The dark red complex Pt(C3H(Ph)2SO 2 (R = R = Ph) shows IR bands at 1535 cm-1 [v(C=C)], 1410 cm-1 [v(O O)] and 1270 cm-1 [v(O S)].1824 Electronic spectra and dipole moment data for these complexes have been compared with the O.O -diketonate complexes.182s 1826 The structure of the phenyl derivative has been confirmed by X-ray crystallography.1827 Detailed dipole moment measurements using static polarization have been made with fluorinated jS-monothiodiketone complexes. Variations with substituent depend on the magnitude and vector directions of the Ph—X bond moments (aryl substituents), the inductive effect of the meta and para substituent on the phenyl ring, and the mesomeric effect of the substituent X.1828 A useful separation method for bis(monothiotrifluoroacetylacetonates) of platinum(II) is gas chromatography.1829... 

---