Fluorine Atom In Position Research Articles

MNDO Study of the (Anti)aromaticity of Fluorine-Containing Cyclopentadienyl, Indenyl, and Cyclopenta[b]naphthyl Cations

MNDO calculations were performed to estimate the aromaticity (antiaromaticity) of a series of fluorine-containing cyclopentadienyl, indenyl, and cyclopenta[b]naphthyl cations in terms of the Dewar-Breslow criterion which utilizes the difference in the enthalpies of formation of isomeric cations with closed and open π-systems as aromaticity index. The aromaticity is strongly determined by both the structure of the carbon skeleton and the number and position of fluorine atoms. A linear correlation was revealed between the aromaticity index and the energy of the lowest singlet-singlet excitation for cations having a cyclic π-system.

A new series with smectic blue phases and SmC*-BPSm2 direct transition

A series of trifluoro-substituted benzoate derivatives: (R)-1-methylheptyl 4-[4-(4-alkyloxy3-fluorobenzoyloxy)-3-fluorobenzoyloxy]-3-fluorobenzoates is reported. The short chain members (n = 8 to 12) display the phase sequence Cr-SmC*-TGBC-TGBA-BPSm-I (except for n = 8, 9 where there is no TGBC phase), whereas for the longer ones (n = 13, 14, 16) a direct SmC*-BPSm2 transition is observed for the first time. We observe for n = 8 to 10, BPSm1 and BPSm3; for n = 11, the full set of three BPSm phases, and for n > 11, only BPSm2 and BPSm3 phases. The mesomorphic properties were studied by optical microscopy, DSC, and electrooptical, optical rotatory power and X-ray scattering measurements. The effect of the positions of fluorine atoms and their influence over mesomorphic behaviour are discussed.

Conformational analysis. 23: A gas-phase electron-diffraction and ab initio molecular orbital investigation of 3-fluoropropan-1-ol. Is there significant internal hydrogen bonding?

There are 14 possible rotational conformers of 3-fluoropropan-1-ol, based on the assumption of three potential minima for rotation about single bonds. Of these, only the gG−G form (g,G=gauche, a,A=anti) where the sequence indicates rotation around the C–O, the CO–C, and the C–CF bonds, with the minus sign indicating clock-wise rotation has the hydrogen and fluorine atoms in position for formation of a hydrogen bond. Analysis of gas-phase electron-diffraction data obtained at a sample temperature of 20°C indicates the dominant form to be aGG (41 (2σ=19)% of the sample). The hydrogen-bonded form gG−G comprises 2 (19)% of the sample. These values reflect the assumption that the amounts of the remaining components of the system exist in proportions given by the results of ab initio (B3LYP/6-311+G(3d,2p)//B3LYP/6-31G(d)) calculations. Weighted average parameter values (rg/Å, ∠g/deg) for all forms are r(C–C)=1.528(3), r(C1–C2)− r(C2–C3)=0.066(12), r(C–H)=1.115(4), r(C–O)=1.380(8), r(C–F)=1.450(6), ∠(COH)=105.9(assumed), ∠(CCF)=109.7(8), 〈∠(CCC), ∠(CCO)〉=111.8(6), ∠(COH)−∠(COH)=3.1(assumed), ∠(CCH)=109.4(7). Torsion-angle parameters could not be refined. Weighted average theoretical torsion angles for conformers with G or G− orientations are ∠(OCCC)=63.2(3), and ∠(CCCF)=61.0(3). Ab initio calculations at several levels of theory with several basis sets predicted substantially different amounts of the gG−G form. Best agreement with experiment was given by the B3LYP/6311++G(3d,2p)//B3LYP/6-31G(d) calculations.

Reductive Transformations of Organofluorine Compounds: III. Hydrodefluorination of Perfluoroalkylbenzenes Effected by Zn(Cu). The Unusual Behavior of Compounds Containing Perfluorinated tert-Butyl Group

Perfluoroalkylbenzenes under a treatment of a system Zn(Cu)-DMF-H2O-electrolyte give rise in high yield to products of fluorine substitution by hydrogen in position 4. In perfluoro-tert-butylbenzene are substituted by hydrogen the fluorine atoms in positions 2 and 4; here the DMF-water ratio affects the regioselectivity of the process. In the perfluoro-4-tert-butyltoluene is mainly substituted the fluorine in the ortho-position to the C(CF3)3 group.

Acetylcholinesterase inhibitors for potential use in Alzheimer's disease: molecular modeling, synthesis and kinetic evaluation of 11H-indeno-[1,2-b]-quinolin-10-ylamine derivatives

Continuing our work on tetracyclic tacrine analogues, we synthesized a series of acetylcholinesterase (AChE) inhibitors of 11H-indeno-[1,2-b]-quinolin-10-ylaminic structure. Selected substituents were placed in synthetically accessible positions of the tetracyclic nucleus, in order to explore the structure–activity relationships (SAR) and the mode of action of this class of anticholinesterases. A molecular modeling investigation of the binding interaction of the lead compound (1a) with the AChE active site was performed, from which it resulted that, despite the rather wide and rigid structure of 1a, there may still be the possibility to introduce some small substituent in some positions of the tetracycle. However, from the examination of the experimental IC50 values, it derived that the indenoquinoline nucleus probably represents the maximum allowable molecular size for rigid compounds binding to AChE. In fact, only a fluorine atom in position 2 maintains the AChE inhibitory potency of the parent compound, and, actually, increases the AChE-selectivity with respect to the butyrylcholinesterase inhibition. By studying the kinetics of AChE inhibition for two representative compounds of the series, it resulted that the lead compound (1a) shows an inhibition of mixed type, binding to both the active and the peripheral sites, while the more sterically hindered analogue 2n seems to interact only at the external binding site of the enzyme. This finding seems particularly important in the context of Alzheimer's disease research in the light of recent observations showing that peripheral AChE inhibitors might decrease the aggregating effects of the enzyme on the β-amyloid peptide (βA).

Selective reductive dehalogenation at position 8 in 8-chloro-1,2,3,4,8-pentafluorobicyclo[2.2.2]octa-2,5-dienones

The reduction of 8-chloro-1,2,3,4,8-pentafluorobicyclo-[2.2.2]octa-2,5-dienones I having aryl and alkyl substituents at the double bond with zinc in acetic acid leads to successive displacement of chlorine and fluorine atoms in position 8 by hydrogen.

Synthesis of polyfunctionally substituted benzothiazines based on vinylthionahlobenzenes and 2-mercaptoethylamine

Regioselective nucleophilic substitution of the fluorine atoms in positions 2 and 5 of the benzene ring takes place in the reaction of 3,6-bis(vinylthio)-1,2,4,5-tetrafluoro- and 3-vinylthio-6-chloro-1,2,4,5-tetrafluorobenzenes with 2-mercaptoethylamine in isopropyl alcohol-water-dimethylformamide mixture at 40–45°C in the presence of KOH. The products of disubstitution obtained are converted into 1,4-benzothiazines on heating to 100°C in dimethylformamide in the presence of K2CO3 as a result of intramolecular substitution.

Quantum chemical and x-ray spectral studies of the structures of superstoichiometric fluorocarbons

The possibility of hole formation in the structures of superstoichiometric fluorocarbons is studied. Different geometries are modeled by removing one, two, or six CF groups from the stoichiometric fluorocarbon lattice. The positions of fluorine atoms in the internal CF2 groups are optimized using the semiempirical MNDO method. The quantum chemical calculations of fluorocarbon clusters containing holes of different geometries suggest the preferential formation of six-center hole structures in fluorocarbon lattices. The X-ray emission CKα-spectra of the superstoichiometric CFx (x=1.20 and 1.33) samples are obtained. Based on the cluster calculations, theoretical CKα-spectra of CFx are constructed. A comparison of the theoretical and experimental results shows that the spectra of the superstoichiometric fluorocarbons are characterized by a short-wave maximum, whose intensity increases with x.

The pyrethrins and related compounds. Part XXXVIII—optimisation of insecticidal activity in 3‐[(alkoxyimino)methyl]‐4‐fluorobenzyl esters

AbstractOptimisation of activity in 3‐[(alkoxyimino)methylbenzyl] esters has been investigated by introducing an α‐cyano group and a fluorine atom in position 4 of the benzylic moiety in conjunction with varying the length and nature of the side chain. Of the five side‐chain variations investigated, the 3‐methoxyiminomethyl was more effective than others. Introduction of fluorine in position 4 of the benzylic moiety generally increased activity, particularly against mustard beetles, as in previous instances. Surprisingly, the effect on insecticidal activity of introducing an α‐CN group ranged from positive to negative depending upon the nature of the alkoxyimino substituent, an effect not observed previously. The most effective esters were derived from α‐cyano‐4‐fluoro‐3‐[(methoxyimino)methyl]benzyl alcohol, which was synthesised from 2‐{4‐fluoro‐3‐[(hydroxyimino)methyl]phenyl}‐1,3‐dioxolane.

Metabolism, pharmacokinetics, and activity of a new 6-fluoro analogue of ursodeoxycholic acid in rats and hamsters

Background/Aims : The effectiveness of ursodeoxycholic acid in treating biliary liver diseases is limited by low bioavailability and moderate activity. A new analogue of ursodeoxycholic acid was synthesized with a fluorine atom in position 6 because this should have resulted in an analogue more hydrophilic than ursodeoxycholic acid but with similar detergency. Methods : After synthesis, detergency, solubility, and lipophilicity of the 6-fluoro analogue in aqueous solution were determined and compared with those of natural analogues. Stability toward 7-dehydroxylation was assessed in human stools, pharmacokinetics and metabolism were evaluated in bile fistula rats and hamsters, accumulation in bile with long-term feeding was assessed in the hamsters, and the ability to prevent the hepatotoxic effects of taurochenodeoxycholic acid was evaluated in bile fistula rats after intraduodenal coinfusion. Results : 6-Fluoro-ursodeoxycholic acid was more stable than its parent molecule toward 7-dehydroxylation, it was efficiently secreted in bile, and its total recovery was very high. With long-term administration of 6-fluoro-ursodeoxycholic acid, taurine and glycine amidates accounted for more than 60% of the total biliary bile acids (15% ursodeoxycholic acid). The 6-fluoro analogue prevented the hepatotoxic effects of taurochenodeoxycholic acid. Conclusions : The results suggest that 6-fluoro-ursodeoxycholic acid has considerable potential as a pharmaceutical agent in the treatment of cholestatic liver disease.

Synthesis and Some Physical Properties of Bicyclohexanes Having Fluoro Substituted Alkyl Moiety

Abstract The influence of introducing fluorine, atoms into alkyl chains of dialkylbicyclohexanes on their physical properties has been investigated. Wide mesophase ranges of the bicyclohesanes were induced by the fluorine atoms. Their viscosity changed depending on the position of fluorine atoms on the alkyl chains and some of the fluorinated bicyclohexanes showed low viscosity. Also dielectric anisotropy and birefringence increased by introducing fluorine atoms. By using the fluorinated compounds mixtures for TFT and STN applications having attractive properties; a wide mesophase range, lower viscosity and higher specific resistivity could be obtained.

Hybrid character of the 0 00 band of the S1- S0 269-nm absorption spectrum of 1,2,4-trifluorobenzene by rotational band contour analysis

A rotational contour analysis of the 0 0 0 band of the 269-nm S 1- S 0 band system of 1,2,4-trifluorobenzene has been carried out by computer simulation. The band is a type A B hybrid which shows that the electronic transition is of the π ∗-π type polarized in the plane of the molecule. The fact that there is 75 ± 5% type B character shows that the transition moment is at 60 ± 4° to the a inertial axis, probably inclined toward the fluorine atom in position 4.

Fluorine effect on stretching vibration intensities in Raman spectraof polyfluoroaromatic compounds

To reveal the general tendencies of benzene fluorine effect on spectral data of polyfluoroaromatic compounds, The stretching vibration intensities of the benzene ring and multiple bonds have been measured for compounds of type ArX and ArYAr with different number and position of fluorine atoms in the ring (X=CH 3, OH, Hal, NH 2, NO 2, CN, NSO; Y NN, N(O)N). The intensities measured were compared to those in the Raman spectra of the non-fluorinated compounds. It has been shown that introduction of fluorine atoms into the ring leads to the decreased intensity of the bands in the Raman spectra. It has been found on the basis of calculations in valence force approximation for fluorobenzenes, octafluoroazo- and azoxybenzenes that introduction of fluorine atoms produces a minor effect on benezene ring vibrations in these compounds. The reasons are discussed for the decreased stretching vibration intensities in the spectra of polyfluoroaromatic compounds as compared with the non-fluorinated analogues and the fluorine effect on the efficiency of conjugation of benzene π-systems with unsaturated bonds of functional groups. The data obtained are compared with ionization potentials and maximum positions in the UV absorption spectra of compounds under study. For assignment vibrations in the Raman spectra of azo- and azoxybenzenes, 15N-labelled samples were used, and comparison has been made with the spectra of complexes of these compounds with SbCl 5. Based on the IR and 15N NMR spectra, conclusions have been made about complexation centres of NN and NN(O) groups with SbCl 5. The effect of the accepting nature of aryl fragment on the complexation centre has been investigated.

Thiokynurenates: a new group of antagonists of the glycine moduiatory site of the NMBA receptor

Several substituted derivatives of kynurenic acid were tested on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex present in the guinea pig myenteric plexus, on the binding of [ 3H]glycine and of [3H]N-[M2-thienyl)cyclohexyl]piperidine ([ 3H]TCP) to rat cortical membranes and on the depolarization of mice cortical wedges induced by NMDA or quisqualic acid (QA). Kynurenic acid derivatives, having a chlorine (CO or a fluorine atom in position 5 or 7 but not in position 6 or 8 had significantly lower IC 50s than the parent compound when tested on the antagonism of glutamate-induced ileal contraction and in the glycine binding assay. A further significant increase in potency was obtained by substituting a thio group for the hydroxy group in position 4 of kynurenic acid: the IC 50 was 160 ± 20 μM of kynurenic acid and 70 ± 15 μM of thiokynurenic acid in the myenteric plexus whereas these IC 50s for glycine binding were 25 ± 3 and 9 ± 2 μM respectively. Several thiokynurenic acid derivatives were synthetized and showed an increased affinity for the glycine recognition site over the corresponding kynurenic acid derivatives. Glycine competitively antagonized the actions of the thiokynurenates in the ileum, in cortical wedges and on [ 3H]TCP binding. In this preparation, 7-Cl-thiokynurervc acid had an IC 50 of 8 μM for antagonizing 10 /iM NMDA-induced depolarization while 50% of the 10 μM QA depolarization was antagonized at 300 μM. Thus thiokynurenic acid derivatives seem to be a new group of potent and selective antagonists of strychnine-insensitive glycine receptors.

Mechanisms of Diffusion of a Small Impurity in Noble Gas Crystals

AbstractMechanisms of diffusion of fluorine in noble gas crystals are analyzed. By numerical simulation of the fluorine atom interstitial diffusion jump in a crypton crystal the profile of the system potential energy is obtained along the jump coordinate. The most energy‐beneficial way for the fluorine atom transition between neighbouring octahedral interstices is shown to pass through a tetrahedral interstice in which the position of fluorine atom is unstable (the octa‐tetra‐octa jump). The theory of such transitions is developed, taking into account the change in phonon spectrum of a disturbed crystal in the process of diffusion jump. The fluorine atom diffusion coefficient is obtained.

On the reactivity of some polyfluorinated organic compounds in a glow discharge

The polymerizing reactivity of fluorobenzenes C 6 H n F 6−n (n = 1−6), perfluoromethylbenzenes, polyfluorostyrenes, perfluorinated cyclo- and benzocyclo-alkenes has been studied in a glow discharge. The reactivity of each of these compounds is found to be dependent on the number and position of fluorine atoms in the ring and on the kind of substituent, the highest reactivity being exhibited by compounds with the fluorinated vinyl group and by o -substituted compounds (perfluoro- o -xylene, perfluorocyclobutene). The discussion of possible ways of polymerization is based on kinetic data, infrared spectra, the amount of fluorine atoms and other groups in polymers.

Partially flourinated heterocyclic compounds. Part 19 [1]. The formation of fischer indole products from a series of hydrozones derived from pentaflourophenylhydrazine and 1,3,4,5,6,7,8-heptaflouro-2-naphthylhydrazine. The surprising loss of o-flourine

Abstract The pentafluorophenyl and 1,3,4,5,6,7,8-heptafluoro-2-naphthylhydrazones of a variety of aldehydes and ketones give 4,5,6,7-tetrafluoroindole and 4,5,6,7,8,9-hexafluorobenz[e]indole derivatives when heated under reflux in tetralin. These products are typical Fischer indole products — yet the substrates all have fluorine atoms in positions ortho to the nitrogen rather than hydrogen which is a pre-requisite in the conventional reaction. Acetaldehyde (10) and cyclohexanone(11) pentafluorophenylhydrazones give 4,5,6,7-tetrafluoroindole(8) (1.5%) and 5,6,7,8-tetrafluoro-1,2,3,4-tetrahydrocarbazole(9) (18%) respectively. 4-Methylacetophenone- (12) , propiophenone- (13) , 1,2-diphenylethanone- (14), acetone-(15) and phenylacetaldehyde-1,3,4,5,6,7,8-heptafluoro-2-naphthylhydrazones give 4,5,6,7,8,9-hexafluoro-2-(4-methylphenyl)- (16)(41%), -2-phenyl-3-methyl-(17) (34%), -2,3-diphenyl-(18) (42%), -2-methyl-(19) (20%), and-3-phenyl-(20) (24%) -benz[e]indoles respectively.

A study of 8-mercaptoquinoline (thiooxine) and its derivatives

The absorption spectra of 5-fluoro-8-mercaptoquinoline in aqueous solutions at various pH values have been studied. The emax values of the 5-fluoro-8-mercaptoquinolinium ion and also of the 5-fluoro-8-mercaptoquinolate ion, and the apparent molar absorption coefficient of the hydrated form have been determined. In the hydrated form, a molecule of water is connected by hydrogen bonds both with the nitrogen and with the mercapto group. The presence of the fluorine atom in positions 5 of the molecule of the 8-mercaptoquinoline increases the acidic properties of the mercapto group and decreases the basic properties of the nitrogen, in comparison with those in 8-mercaptoquinoline. The dissociation constants of 5-fluoro-8-mercaptoquinoline are pKSH=7.49 ± 0.02 (thermodynamic) and pKNH= 1.97 ±0.02 (concentration). The isoelectric point is at pH 4.70.

Polyfluoroheterocyclic compounds—X : 2,3,5,6-tetrafluoro-4-methylpyridine and related compounds

The hydrogen atoms of the Me group in tetrafluoro-4-methylpyridine (I) are much less acidic than those of 4-picoline because of the Iπ effect of the fluorine atoms in positions 3 and 5. Free radical halogenation of the side chain of I occurs less readily than for 4-picoline and the resulting di- and trichloromethyl-tetrafluoropyridines can be hydrolysed to the corresponding aldehyde and acid.