Substitution Of Fluorine Atom Research Articles

Polynucleotides and their components in the process of aromatic nucleophilic substitution. I. Chemistry and dynamics of nucleotide arylation with pentafluoropyridine. Intermediate product ofr molecular design of nucleic acid analogs

Pentafluoropyridine reacts with thymidine, adenosine, and uridine hydroxy groups to give quantitative yields of the corresponding nucleoside di- and triaryl ethers. The nucleophilic substitution reactions proceed successively and in parallel, with the slowest step being the nucleophilic substitution of the nucleoside secondary hydroxyls. The resulting ethers contain tetrafluoropyridyl moieties, which could be smoothly modified by nucleophilic substitution of fluorine atoms. The ethers are useful intermediate synthons (both isolated and in situ) for molecular design of oligonucleotide analogues. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.

Electron collisions with tetrafluoroethylene(C2F4)and ethylene(C2H4)molecules

Absolute total cross sections (TCSs) for 0.6-370 eV electrons scattered by tetrafluoroethylene (C{sub 2}F{sub 4}) molecules have been measured using a linear transmission method. The TCS energy function for C{sub 2}F{sub 4} shows one very broad enhancement with the maximum value of 30x10{sup -20} m{sup 2} located around 30 eV. On the low-energy slope of the TCS curve some weak features near 2.8, 9.5, and 16 eV are discernible. Above 50 eV the present TCS agrees well with theoretical predictions. Absolute TCS for ethylene (C{sub 2}H{sub 4}) has also been measured and compared with the TCS for C{sub 2}F{sub 4}. Effect of substitution of fluorine atoms for hydrogen (perfluorination effect) was indicated and discussed. The reported TCS for C{sub 2}H{sub 4} is distinctly higher than experimental data existing so far.

Reactions of Polyhalopyridines. 16. Synthesis and Reactions of 2,3,5,6-Tetrafluoro-4-perfluoroalkylthiopyridines

Identical reaction products, viz. 2,3,5,6-tetrafluoro-4-perfluoroalkylthiopyridines 3a-c, were obtained on thermal decomposition of Xe(II) bisperfluoroalkylcarboxylates in the presence of mercaptotetrafluoropyridine and bis(2,3,5,6-tetrafluoro-4-pyridyl) disulfide. Compounds 3a-c readily interact with N-, O-, and S-containing nucleophiles, though with the first two types of reactant only with substitution of fluorine atoms in position 2 of the pyridine ring. In the latter case products are obtained both with retention of the perfluoroalkylthio group on interaction with sodium N,N-dimethyldithiocarbamate, and with total fission of that group in the case of alkali metal methanethiolate and toluenethiolate.

Architecture and optical properties of two-dimensional perovskite compounds containing fluoroamines

Aromatic ammonium-based perovskites and fluorine substituted analogues were prepared. The effects of the electronic structures of aromatic ammonium containing fluorine on the optical properties of layered perovskites were investigated by the XRD, UV-Vis absorption, and fluorescence spectrum measurements. The absorption peaks were shifted by the substitution of fluorine atoms in organic ammonium compounds. It became clear that the optical properties of two-dimensional perovskite compounds were controlled by the substitution of fluorine atoms.

15 and 30-Membered polyolefinic macrocycles. Periphery modification by aromatic nucleophilic substitution of fluorine

Tris[(4-fluorophenyl)sulfonyl]-1,6,11-triazacyclopentadeca-3,8,13-triene is a pivotal 15-membered triolefinic macrocycle from which a vast array of different derivatives are prepared by substitution of fluorine atoms.

DNA cleavage by pentadentate iron(II) complexes containing fluoro-substituted phenyl groups

Four pentadentate iron(II) complexes containing non- or fluoro-substituted phenyl group ( 2b– 2e) were synthesized and cleaving activity of them to pUC19 DNA was evaluated in the presence of hydrogen peroxide. DNA cleavage activity increased with the number of substituted fluorine atoms on the phenyl group of 2b.

Photofragment Translational Spectroscopy of 1-Bromo-3-fluorobenzene and 1-Bromo-4-fluorobenzene at 266 nm

The ultraviolet photodissociation of 1-bromo-3-fluorobenzene and 1-bromo-4-fluorobenzene at 266 nm has been performed on a universal crossed molecular beams machine combined with the photofragment translational spectroscopy (PTS) detection technique. The time-of-flight (TOF) spectra of Br and FC6H4 photofragments have been measured. The observed translational energy distributions P(E-t) of photofragments revealed that about 46.8 +/- 3.3% and 41.7 +/- 3.0% of the available energy are partitioned into translational energy and the anisotropy parameter beta is 0.7 +/- 0.1 and -0.4 +/- 0.1 for 1-bromo-3-fluorobenzene and 1-bromo-4-fluorobenzene, in accord with that of bromobenzene (-0.7), indicating significant change caused by the fluorine atom substitution. To better interpret the experimental results, ab initio calculations have been performed and the calculation results are in good agreement with the experimental results. A plausible photodissociation mechanism is suggested, and the substitution effect of the fluorine atom is discussed.

Unexpected Photoreactions of Some 7-Amino-6-fluoroquinolones in Phosphate Buffer

The products of irradiation of some 6-fluoro-7-piperazino-4-quinolone-3-carboxylic acids in phosphate buffer arise from a combination of reductive defluorination of the heteroaryl ring and oxidative fragmentation of the piperazine side chain. This unusual reaction contrasts with the fluorine atom substitution observed in neat water. The results of steady-state and time-resolved experiments are consistent with initiation of the process by electron-transfer quenching of the triplet state of these heterocycles by the phosphate anion. For one of the compounds, a transient band (λmax = 670 nm), previously attributed to the defluorinated cation, must now be reassigned to the radical anion. This intermediate undergoes inefficient reductive defluorination of the ring. In the process, a phosphate radical anion is expected to be formed and to abstract a hydrogen atom from the piperazine group, leading to degradation of the latter.

19F NMR Study of the Heme Orientation and Electronic Structure in a Myoglobin Reconstituted with a Ring-Fluorinated Heme

Abstract 13,17-Bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12,18-trimethylporphyrinatoiron(III) was reconstituted with sperm-whale apomyoglobin to investigate the molecular and electronic structures of the heme-active site by 19F NMR spectroscopy. The detection of the nuclear Overhauser effect between the substituted fluorine atom for a heme side-chain and an amino acid side-chain proton in the reconstituted myoglobin unequivocally determines the heme orientation relative to the protein matrix. The orientation of this fluorinated hemin in the protein was found to differ by a 180° rotation of the heme plane about its C2-axis from that of structurally analogous mesohemin in the active site of myoglobin. Thus, the difference between the methyl group and fluorine atom as the peripheral side-chain at the 2-position of the porphyrin is a critical determinant for the thermodynamical stability of the heme orientational isomers. The effects of the heme orientation on the electronic structure of the active site of myoglobin in a variety of iron oxidation, spin, and ligation states were characterized by 19F NMR spectroscopy. The present study demonstrated that the 19F NMR signals observed for hemoprotein reconstituted with fluorinated hemin provides useful information on the relationship between the heme orientation relative to the protein and its electronic structure in all accessible oxidation/spin states of the protein, that can be hardly obtained by 1H NMR spectroscopy.

The syntheses of nonnucleoside, HIV-1 reverse transcriptase inhibitors containing a CF 2 group : The S RN1 reactions of 2-(bromodifluoromethyl)benzoxazole with the anions derived from heterocyclic thiols and phenolic compounds

In an effort to prepare new fluorine-containing compounds which are active against HIV, the S RN1 reactions of 2-(bromodifluoromethyl)benzoxazole ( 5) with the anions of heterocyclic thiols and phenolic compounds were carried out. The products ( 6a–j and 7a–f), which all have a CF 2 group, were tested for activity against HIV, and several were found to be active, including 6f which was very active. By comparing the activity of 6e, which contains a CF 2 group, to that of 10, where the CF 2 is replaced by a CH 2 group, it was demonstrated that fluorine atom substitution produces a 10-fold increase in activity against HIV-1.

酵素反応を利用した強誘電性液晶材料の開発

With the increase of interest in the electrooptical devices using ferroelectric liquid crystals, there has been a considerable amount of efforts in the synthesis and evaluation of many compounds exhibiting Sc* phase. Particularly, the wide range of temperature and the low rotational viscosity are needed for the practical use. In order to solve these problems, it is important to design the liquid crystal that has a properly designed size of molecule and a suitable chiral center. It is particularly effective to introduce methylene chain linkage between a chiral carbon atom and core part. We also study the effect of the substitution of fluorine atoms on the benzene ring and the chiral part. We established the method for the synthesis of these kinds of liquid crystals utilizing the enzymatic method in high optical yield.

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.

Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6- fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB20304).

New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C5-NH2) > F (C5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C5-NH2) > naphthyridine = F (C5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (microgram/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Actinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

Ultrafast optical probes of excited states in poly(1,4-phenylene vinylene) and poly(2-fluoro-1,4-phenylene vinylene)

We have investigated the photoexcitation dynamics of poly(1,4-phenylene vinylene) (PPV) and poly(2-fluoro-1,4-phenylene vinylene) (PFPV) by using the femtosecond transient absorption spectroscopic technique. It was demonstrated that photoinduced absorption originates from nonemissive indirect polaron pairs which are more efficiently produced in PFPV than in PPV. The decay processes of polaron pairs are mainly contributed by collisional annihilation and internal conversion by phonon emission in PFPV and PPV, respectively. The differences in photoexcitation dynamics between PPV and PFPV are believed to be caused by the strong electronegativity of substituted fluorine atom.

Modification of the carcinogenic potency of quinoline, a hepatocarcinogen, by fluorine atom substitution: evaluation of carcinogenicity by a medium-term assay.

The potent mutagen, 5-fluoroquinoline (5-FQ), and non-mutagenic 3-fluoroquinoline (3-FQ) were tested for hepatocarcinogenicity using a medium-term assay system employing quinoline, a moderately mutagenic hepatocarcinogen, as a reference. F344 male rats were given a single i.p. injection of a submanifestational dose of diethylnitrosamine (DEN, 200 mg/kg). Then, quinoline, 3-FQ, or 5-FQ at two doses (0.1%, and 0.05%) was added to their diet for a period of 6 weeks, starting from 2 weeks after the DEN injection. Control groups were administered DEN alone. All rats were subjected to a partial (two-thirds) hepatectomy at the end of week 3 and sacrificed at the end of week 8. The number and areas of GST-P (placental glutathione S-transferase)-positive foci induced in the liver increased significantly as a result of treatment with 0.1% quinoline, and this increase was dramatic with 5-FQ at both doses, whereas no increases were noted with 3-FQ at either dose. Thus, the results of the medium-term carcinogenicity assay predicted that quinoline, a hepatocarcinogen, would be deprived of carcinogenicity by fluorine atom substitution at position 3, and would conversely be endowed with a higher carcinogenic capacity by substitution at position 5. A semi-quantitative relationship was demonstrated between carcinogenic and mutagenic potencies.

Interaction of hexafluoropropene trimers with ammonia and primary amines

Hexafluoropropene trimers (HFPT) react with primary amines to form the corresponding enamines and enimines, i.e. products arising from the indirect substitution of fluorine atoms. The adduct with HFPT has been obtained for the first time in the reaction with ammonia. The intramolecular cyclization of the compounds synthesized to give azetines and azetidines has been studied. Specific features of the 19F NMR spectra of the enimines obtained have been considered.

Ferroelectric behavior in fluoro-nylons

Ferroelectric behavior was investigated in two fluoro-polyamides (fluoro-nylon) [-NH(CH2)mNHCO(CF2)nCO-]x=m,n+2F. The fluoro-nylons (7,5F, 9,5F) were synthesized by interfacial polycondensation between alkyldiamines and perfluoroglutrichloride. Quenched samples of these polyamides exhibited D−E hysteresis loops with remanent polarization in the range of 29–33 mC/m2 close to the room temperature. After crystallization by annealing near the melting temperature, no ferroelectric behavior was observed. The dipole rotation is considered to be influenced by the substitution of fluorine atoms behalf on hydrogen atoms in the polymers.

Scanning Tunneling Microscopy Imaging of Single Fluorine Atom Substitution in Stearic Acid

In this paper we report on the effect that a single fluorine substitution in a hydrocarbon chain of stearic acid has on the molecular ordering of the material and, in addition, the effect that the fluorines have on the scanning tunneling microscopy (STM) contrast of an alkyl chain physisorbed on graphite. The area demand due to a single fluorine substitution is increased by only approximately 1%, demonstrating a very similar steric impact of hydrogen and fluorine. The required accuracy in the measurement is achieved by evaluating the moire pattern due to the adsorbate and substrate lattices. The predicted change in theSTM contrast caused by the fluorine atom was observed for the first time

Catalytic Activation of Carbon-Fluorine Bonds by a Soluble Transition Metal Complex

Homogeneous catalytic activation of the strong carbon-fluorine bonds under mild conditions was achieved with the use of rhodium complexes as catalysts. The catalytic reactions between polyfluorobenzenes and hydrosilanes result in substitution of fluorine atoms by hydrogen atoms and are chemo- and regioselective. With individual stoichiometric steps observed and combined, and with intermediates isolated and fully characterized (including crystal structures), these systems demonstrate the effectiveness of a rational approach to catalytic design.

Thin film characteristics of fluorine-substituted monolayers prepared by chemical adsorption from solution

Monolayers containing a fluorine-substituted carbon chain were prepared by the chemical adsorption (CA) technique. Characteristics of the monolayers were evaluated by spectroscopy, copper decoration technique, current-voltage characteristics (current density and resistivity), measurement of the contact angle, and friction tests. By the copper decoration technique, the CA monolayer was more pinhole free and uniform than a Langmuir-Blodgett film. The characteristics (such as the leakage current density, resistivity, critical surface tension and coefficient of kinetic friction) of the fluorine-substituted monolayers depended markedly on the number of substituted fluorine atoms.