76-05-1

Alkenes undergo a rapid reaction with trifluoroacetic acid containing 0.25 M trifluoroacetic anhydride in the presence of a strong acid catalyst.The enthalpies of trifluoroacetolysis of the five n-hexenes were determined and were corrected to the enthalpies corresponding to the formation of the equilibrium mixture of 2-hexyl trifluoroacetate and 3-hexyl trifluoroacetate.The enthalpy difference between the latter was determined by measuring the equilibrium constant as a function of temperature.The trifluoroacetolysis data may be combined with the measured enthalpies of formation of the alkenes to derive more precise values for the latter.The enthalpies of reaction of water, 2-hexanol, and 3-hexanol with the reaction solvent were determined, and when combined with the other data lead to enthalpies of hydration of the alkenes and the enthalpies of formation of the alcohols.

The heterogeneous chemistry, on aqueous surfaces, of a series of acid halides, COF2, CF3COF, and CF3-COCl, was studied. The technique used consists of a low-pressure flow tube reactor in which a stream of monodisperse droplets interacts with the gaseous acid halide. The experiments, which were performed as a function of the initial pH of the droplets, temperature, and gas/liquid interaction time, yield low uptake coefficients in the range 5 × 10-4 to 5 × 10-3 and allow estimation of the product H.√k, where H is the Henry's law constant and k is the hydrolysis rate constant. The values reported here are 60, 60, and 350 M-atm-1 s- 1/2 for CF3COCl, CF3COF, and COF2, respectively, at 273 K. Separate values of H and k are also reported. The results show slightly different behavior between the chloride and the fluorides as a function of temperature. This study shows Henry's law and hydrolysis rate constants large enough that heterogeneous reactions on aqueous surfaces will limit the residence time of these species in the atmosphere.

The hitherto unknown trifluoroselenoacetic acid was prepared through the reaction of trifluoroacetic acid with Woollins' reagent. The compound was fully characterized by mass spectrometry, 1H, 19F, 77Se, and 13C NMR, UV-visible, IR and Raman spectroscopy, and the boiling point at 46 °C was estimated from the vapor pressure curve. An IR matrix isolation study revealed the presence of two different syn-anti and anti-syn conformers. The IR spectra of the two stereoisomers have been assigned, aided by DFT, and ab initio calculations. The UV photolysis of Ar matrix isolated CF3C(O)SeH yielded CO, OCSe, CF3SeH, and CHF3. Apart from CF3SeH, these products were also obtained by vacuum flash-pyrolysis (310 °C) of gaseous CF3C(O)SeH. Instead of CF3SeH, CF2Se, and HF were detected among the pyrolysis products. The different decomposition pathways of CF 3C(O)SeH are discussed.

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Dynamic NMR measurements of 8-(dimethylamino)-1-acetonaphthone 1 in neutral solutions reveal a solvent dependency of the barrier to NMe group interchange similar to that reported for N,N-dimethylacetamide. Titrating 1 with TFA in solvents of varying donicities gives rise to equilibrium mixtures of N-protonated aminoketone 2 and the O-protonated transannular addition product 3, the interconversion rate of which is slow on the NMR time scale at ambient temperature. The preference for O- or N-protonation is medium-dependent, the amount of N-protonated 2 increasing with a decrease in the nucleophilicity of the solvent. The set of equilibria which govern the interconversion of 2 and 3 in the titration mixtures are identified and their equilibrium constants evaluated from the NMR data. X-ray analysis of the crystalline trifluoroacetate salt of O-protonated 3 indicates that the transannular N···CO bond of 3 is formed to an extent of only 80%. The equilibrium distribution of 2 and 3, paired with the tetrafluoroborate anion, depends on both the nucleophilicity and the polarity of the solvent. In PhNO2 the enthalpy change 3 → 2 amounts to 2.6 kcal/mol.

TiO2 photocatalysis and ultrasound are emerging technologies for the mineralization of pollutants in water. To further investigate these technologies and to assess whether advantages and synergy can be expected from their differences, phenyltrifluoromethylketone (PTMK) was selected as a test compound for pollutants generating CF3COOH, an undesirable final product. The PTMK first-order removal rate constant k was ca. 14 times higher when the ultrasound frequency was 515 kHz instead of 30 kHz for the same energy, and ca. 2.5 times higher when a TiO2 sample we synthesized was used instead of TiO2 Degussa P25. On simultaneous photocatalytic and ultrasonic treatment an increase in k by a factor between 1.4 and 1.9, depending on the TiO2 sample, was observed at 30 kHz but not at 515 kHz. On the basis of catalase enzymatic effect upon k, these observations are tentatively explained by a photocatalytic OH radical production from sonochemically formed H2O2, provided that the H2O2 residence time on TiO2 is sufficient. PTMK ultrasonic pyrolysis was demonstrated by product analysis. The amount of CF3COOH was ca. 8 times lower in sonicated solutions than in UV-irradiated TiO2 suspensions, for both frequencies and both TiO2 samples. Therefore, because of a higher k value, a high frequency ultrasonic (pre)treatment is preferable to minimize CF3COOH formation.

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.

Fluoroalkyl alcohols are effectivity oxidized to the corresponding fluoroalkyl carbonyl compounds by reaction with sodium hypochlorite pentahydrate in acetonitrile in the presence of acid and nitroxyl radical catalysts. Although the reaction proceeded slower under a nitroxyl radical catalyst- free condition, the desired carbonyl compounds were obtained in high yields. For the reaction with fluoroalkyl allylic alcohols, the corresponding α,β-epoxyketone hydrates were obtained in high yields.

A method for producing a methanol precursor, methyl trifluoroacetate, having high-purity includes the steps of (a) preparing methyl bisulfate by mixing a catalyst with an acid solution comprising a sulfur-containing acid to provide a first mixture and supplying methane gas to the first mixture to prepare the methyl bisulfate; and (b) preparing methyl trifluoroacetate (CF3CO2CH3) by adding trifluoroacetic acid (CF3CO2H) to the first mixture including the methyl bisulfate to provide a second mixture and distilling the second mixture under heating to prepare, separate and purify the methyl trifluoroacetate (CF3CO2CH3). Methanol may be produced by adding water to the methyl trifluoroacetate (CF3CO2CH3). A methyl ester represented by Formula 2 below may be produced by adding a carboxylic acid represented by Formula 1 below to the methyl trifluoroacetate (CF3CO2CH3): R1CO2H??(1),where R1 is selected from C1-C10 alkyl groups, R1CO2CH3??(2),where R1 is as defined in Formula 1.

In the reactions with aqueous K2CO3, perfluorinated benzocyclobuten-1-one, 3-R-indan-1-ones and 4-R-tetralin-1-ones (R = F, C2F5) undergo selective cleavage of the СO–С(Ar) bond to yield (2,3,4,5-tetrafluorophen

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.

The present invention concerns a method for preparing an oxysulphide and fluorinated derivative of formula (III) Ea-SO3R (III) that comprises bringing a compound of formula (II) Ea-SOOR (II)—Ea representing the fluorine atom or a group having 1 to 10 carbon atoms chosen from the fluoroalkyls, the perfluoroalkyls and the fluoroalkenyls; and—R representing hydrogen, a monovalent cation or an alkyl group; into contact, in the presence of a polar aprotic organic solvent, with an oxidising agent.

The present invention relates to novel binder-prodrug conjugates (APDCs) where binders are conjugated with inactive precursor compounds of kinesin spindle protein inhibitors, and to antibody-drug conjugates ADCs and to processes for producing these APDCs and ADCs.

Equilibrium constants for the proton transfer reaction between pyridines and trifluoroacetic acid were measured in room-temperature ionic liquids (ILs) of different cation–anion compositions. The experimental equilibrium constants for ion-pair formation were corrected according to the Fuoss equation. The calculated equilibrium constants for the formation of free ions were taken as a quantitative measure of the base strength in IL solutions and compared with the relative constants in water. The effect of IL composition is discussed for a series of fixed IL anions and fixed IL cations. Finally, the sensitivity of the proton transfer reaction to the electronic effects of the substituent groups on the pyridine ring was quantified by applying the Hammett equation. A more marked levelling effect on the base strength was observed in ILs than in water. The Hammett reaction constants ρ were then correlated with solvent parameters according to a multi-parametric analysis, which showed that both specific hydrogen-bond donor/acceptor and non-specific interactions play an important role, with α and permittivity being the main parameters affecting the ability of the IL to differentiate the strength of the base.

The luminescent dye EuropiumIII(thenoyltrifluoroacetone)(4′-(4-methylphenyl)-2,2′:6′,2′′-terpyridine) (EuIII(TTFA)3(MePhTerpy)) has been proposed as a probe molecule for a fast photocatalytic test of TiO2-materials. For an industrial application of this test method the underlying photocatalytic reaction mechanism and the degradation products of the dye need to be known. Hence, in this study the adsorption and the photocatalytic degradation of the luminescent dye on the TiO2 surface were investigated by means of ATR-FTIR spectroscopy and GC/MS analysis. The dye is adsorbed by the thenoyltrifluoroacetone (TTFA) ligand on the TiO2 surface as evinced by the respective ATR-FTIR spectra. It is assumed that TTFA and TiO2 form hydrogen bonds. Upon UV illumination the ATR-FTIR spectra reveal a degradation of the TTFA ligand forming trifluoroacetic acid (TFAA) and 2-thiophenecarboxylic acid (TCA). GC/MS analysis confirms the ATR-FTIR results because TCA and TFAA are also detected here. Additionally, 2-thiophenecarboxaldehyde is observed, which is proposed to be an intermediate that is further oxidized to TCA.

The hydrolysis rate constant of 2,2,2-trifluoro-3-(trifluoromethyl)oxirane (hexafluoropropene oxide; HFPO), a versatile precursor of fluorinated chemicals, was determined at 279–307 K, and the rate of hydrolysis was used to estimate the tropospheric lifetime of HFPO with respect to hydrolysis in clouds or uptake by the ocean. The low solubility of HFPO in water made it difficult to determine the hydrolysis rate constant because of mass-transfer limitation between the gas and liquid. A closed-circulation reactor was used to measure the rate of decrease of the partial pressure of HFPO while an HFPO-air mixture flowed over a stirred test solution under various experimental conditions. The rate of hydrolysis increased as the OH? concentration increased in an aqueous NaOH solution but was almost independent of the H2SO4 concentration in aqueous H2SO4 solutions. Much scissioning of C–C bonds in HFPO produced carbon monoxide and trifluoroacetate in aqueous NaOH, but similar scissioning did not in water or aqueous H2SO4. The first-order rate constant for the pH-independent hydrolysis (kwater in s?1), the bimolecular rate constant for the hydroxide-catalyzed hydrolysis, and the temperature dependence of these parameters were estimated by simultaneously fitting equations based on a two-film model to the time series of HFPO partial pressures under different experimental conditions. The equations included the rate constants as common parameters. The product of kwater and the Henry's law constant, KH (M Pa?1), at a temperature of T (K) was determined to be kwater × KH = 3.7 × 10?11 exp[?3300 × (T?1 ? 1/298.2)]. The tropospheric lifetime of HFPO estimated using this equation indicates that removal of HFPO via hydrolysis in clouds is probably not a substantial sink of HFPO and suggests that, in the absence of other atmospheric sinks of HFPO, hydrolysis of HFPO in the ocean would be the major sink of HFPO.

The present invention provides a method for producing a diol having a specific structure in high yields while keeping high selectivity. Provided is a method for producing a diol having a specific structure by oxidizing an olefin having a specific structure in the presence of a ruthenium compound.

The invention discloses a preparation method of trifluoroacetic acid. The preparation method comprises the following steps: (1), vaporizing 1,1,1-trifluoro-2-chloroethane and chlorine gas, then enabling the 1,1,1-trifluoro-2-chloroethane and chlorine gas to enter a fixed bed reactor with a catalyst, and performing a gas phase chlorination reaction to synthesize 1,1,1-trifluoro-2,2-dichloroethane;(2), vaporizing the 1,1,1-trifluoro-2,2-dichloroethane and oxygen, then performing an oxidation reaction under the action of a light source to obtain trifluoroacetyl chloride, condensing the unreacted1,1,1-trifluoro-2,2-dichloroethane, and then enabling the unreacted 1,1,1-trifluoro-2,2-dichloroethane to return to the reactor; (3), hydrolyzing the trifluoroacetyl chloride to obtain the trifluoroacetic acid. The preparation method has the advantages of a simple technology, high yield, few three wastes and the like; in addition, by the preparation method, the reaction conversion rate is high, the selectivity is high, the reaction production is continuous, and the safety and the environment friendliness are achieved.

The invention belongs to the field of chemical synthesis, in particular to a halogenated acetic acid or a halogenated acetic acid ester compound preparation method; halogenated ethane (type I) by ozone oxidation after the reaction, the reaction with water or alcohol to obtain a halogenated acetic acid or halogenated acetate (type II). (by machine translation)

A study was carried out on the hydrolysis of phenyl trifluoroacetate (PTFA) in AOT/n-heptane/water reverse micelles. The results obtained have been interpreted by taking into account the distribution of the PTFA using a kinetic model based on the pseudophase concept and, it is demonstrated that the reaction takes place in the water pool of the reverse micelles. Moreover, it is established that the water molecules involved in the hydration of the interface do not react with PTFA or they do it at much slower rate compared with the water molecules that form the pool. The value of the second order rate constant in the water pool, kw-MI, is of the same order of magnitude as that in pure water but is greater (500 times) than those obtained in water-acetonitrile mixtures with low water content. We performed kinetic solvent isotopic effect (KSIE) and proton inventory experiments (PI) and we concluded that the water is acting as a general-base catalyst and the water sequestered in the water pool is pre-organized favoring the activation process, in contrast to what happened in water-acetonitrile mixtures.

Rapid and selective formal hydrogenolysis of aliphatic ester RC(O)O-R′ linkages is achieved by a tandem homogeneous metal triflate + supported palladium catalytic system. The triflate catalyzes the mildly exothermic, turnover-limiting O-R′ cleavage process, whereas the exothermic hydrogenation of the intermediate alkene further drives the overall reaction to completion.

The influence of oxygen in the photocatalytic oxidation of perfluorooctanoic acid (PFOA) promoted by a commercial nano-sized titanium dioxide was studied by testing the reaction in different conditions: static air, oxygen flux, nitrogen flux and pre-saturated nitrogen flux. The reaction was monitored by Total Organic Carbon (TOC) analysis and Ionic Chromatography (IC). Shorter chain perfluorocarboxylic acids (PFCAs; Cn, n = 1-7) intermediate degradation products were quantitatively determined by High-Performance Liquid Chromatography combined with Mass Spectrometry (HPLC-MS) analysis. The presence of shorter chain PFCAs in solution was also monitored by 19F NMR. The experimental findings are in agreement with two major oxidative pathways: Cn → Cn-1 photo-redox and β-scissions routes mediated by COF2 elimination. Depending on the experimental conditions, the mutually operating mechanisms could be unbalanced up to the complete predominance of one pathway over the other. In particular, the existence of the β-scissions route with COF2 elimination was corroborated by the isolation and characterization of carbonyl difluoride, a predicted fluorinated decomposition by-product.

The present application relates to new derivatives, substituted on the N terminus by a carboxyalkyl group, of monomethylauristatin E and monomethylauristatin F, to processes for preparing these derivatives, to the use of these derivatives for treating and/or preventing diseases, and to the use of these derivatives for producing medicaments for treating and/or preventing diseases, more particularly hyperproliferative and/or angiogenic disorders such as cancer disorders, for example. Such treatments may be applied as a monotherapy or else in combination with other medicaments or further therapeutic measures.

A method for preparing a fluorinated organic compound (II) from an organic compound (I) comprising at least one nucleofugal group Nu, and also a preparation of different specific organic compounds, in particular a fluoro-methylpyrazole compound. The method comprises: a reaction, in the presence of water, of the organic compound (I) and at least one salt providing at least one fluoride anion; and a replacement of at least one nucleofugal group Nu of the compound (I) with a fluorine atom, in order to obtain the fluorinated organic compound (II).

The ionic liquid choline bis(trifluoromethylsulfonyl)imide, [Chol][Tf 2N], was used for the extraction of neodymium(iii), in combination with choline hexafluoroacetylacetonate, [Chol][hfac], as the extractant. The binary mixture of [Chol][Tf2N] and water shows temperature-dependent phase behavior, with an upper critical solution temperature of 72 °C. A novel extraction technique, homogeneous liquid-liquid extraction (HLLE), was applied to this solvent system. HLLE is based on the use of thermomorphic solvent mixtures and has the advantage of forming a homogeneous phase during mixing. Extraction is not kinetically hindered by an interface and the extraction equilibrium is reached faster than in the case of heterogeneous mixing in conventional solvent extraction. Several extraction parameters were studied for the extraction of neodymium(iii) with [Chol][hfac]: temperature, pH, extractant concentration and loading of the ionic liquid phase. A speciation study was performed to determine the stoichiometry of the extracted neodymium(iii) complex and a plausible extraction mechanism is proposed. Neodymium is extracted as a tetrakis hexafluoroacetylacetonate complex with one choline cation as counter ion. The crystal structure of the extracted complex showed the presence of a coordination bond between the choline counter ion and the neodymium(iii) center, resulting in a coordination number of nine. The stripping of the loaded neodymium and the influence of acid and extractant concentrations on the phase behavior of the [Chol][Tf2N]-H 2O system were investigated. This journal is the Partner Organisations 2014.

The invention pertains to a method for making a fluoropolymer comprising an aqueous emulsion polymerization of one or more fluorinated monomers wherein said aqueous emulsion polymerization is carried out in the presence of at least one cyclic fluorocompound of the following formula (I): wherein X1, X2, X3, equal or different from each other are independently selected among H, F, and C1-6 (per)fluoroalkyl groups, optionally comprising one or more catenary or non-catenary oxygen atoms; L represents a bond or a divalent group; RF is a divalent fluorinated C1-3 bridging group; Y is a hydrophilic function selected among anionic functionalities, cationic functionalities and non-ionic functionalities.

Carbon-fluorine bonds are the strongest single bonds in organic chemistry, making activation and cleavage usually associated with organometallic and reductive approaches particularly difficult. We describe here an efficient defluorination of poly- and perfluorinated aromatics under oxidative conditions catalyzed by the μ-nitrido diiron phthalocyanine complex [(Pc)Fe III(μ-N)FeIV(Pc)] under mild conditions (hydrogen peroxide as the oxidant, near-ambient temperatures). The reaction proceeds via the formation of a high-valent diiron phthalocyanine radical cation complex with fluoride axial ligands, [(Pc)(F)FeIV(μ-N)FeIV(F) (Pc+?)], which was isolated and characterized by UV-vis, EPR, 19F NMR, Fe K-edge EXAFS, XANES, and Kβ X-ray emission spectroscopy, ESI-MS, and electrochemical techniques. A wide range of per- and polyfluorinated aromatics (21 examples), including C6F6, C6F5CF3, C6F5CN, and C6F5NO2, were defluorinated with high conversions and high turnover numbers. [(Pc)FeIII(μ-N)Fe IV(Pc)] immobilized on a carbon support showed increased catalytic activity in heterogeneous defluorination in water, providing up to 4825 C-F cleavages per catalyst molecule. The μ-nitrido diiron structure is essential for the oxidative defluorination. Intramolecular competitive reactions using C6F3Cl3 and C6F3H 3 probes indicated preferential transformation of C-F bonds with respect to C-Cl and C-H bonds. On the basis of the available data, mechanistic issues of this unusual reactivity are discussed and a tentative mechanism of defluorination under oxidative conditions is proposed.

The leaving group ability (nucleofugality) of fluoroacetate, chloroacetate, bromoacetate, dichloroacetate, trifluoroacetate, trichloroacetate, heptafluorobutyrate, formate, isobutyrate, and pivalate have been derived from the solvolysis rate constants of the corresponding X,Y-substituted benzhydryl carboxylates in 60 % and 80 % aqueous acetonitrile and 60 % aqueous acetone, applying the LFER equation: log k = sf(Ef + Nf). The experimental barriers (ΔG?,exp) for solvolyses of 11 reference dianisylmethyl carboxylates in these solvents correlate very well (r = 0.994 in all solvents) with ΔG?,model of the model σ-assisted heterolytic displacement reaction of cis-2,3-dihydroxycyclopropyl trans-carboxylates calculated earlier. Linear correlation observed between the log k for the reference dianisylmethyl carboxylates and the sf values enables estimation of the reaction constant (sfestim). Using the ΔG?,exp vs. ΔG?,model correlation, and taking the estimated sfestim, the nucleofugality parameters for other 34 aliphatic carboxylates have been determined in 60 % and 80 % aqueous acetonitrile and 60 % aqueous acetone. The most important variable that determines the reactivity of aliphatic carboxylates in aprotic solvent/water mixtures is the inductive effect of the group(s) attached onto the carboxylate moiety.

By combining two green and efficient catalysts, such as the commercially available enzyme laccase from Trametes versicolor and the stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), the oxidation in water of some primary alcohols to the corresponding carboxylic acids or aldehydes and of selected secondary alcohols to ketones can be accomplished. The range of applicability of bio-oxidation is widened by applying the optimized protocol to the oxidation of enantiomerically pure 2-arylpropanols (profenols) into the corresponding 2-arylpropionic acids (profens), in high yields and with complete retention of configuration.

The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

A ruthenium catalyst supported on glucose-derived carbon spheres was prepared and characterized by TEM, XPS, FTIR TG-DTG and XRD. The Ru/CSP catalyst showed an excellent catalytic performance for the hydrogenation of ethyl lactate to 1, 2-propanediol in water. The catalyst was recycled for six times without the marked loss in both the activity and selectivity. The steric hindrance and electronic effects of substrates on the hydrogenation were tested. It is postulated that the high performance of this novel catalyst system is related to the cooperation between the hydroxyl groups of support surface and water as a solvent.

The present invention relates to a method for preparing a highly pure trifluoromethanesulphinic acid. The method of the invention for preparing a highly pure trifluoromethanesulphinic acid, starting from an aqueous mixture comprising a trifluoromethanesulphinic acid salt, a trifluoroacetic acid salt and saline impurities resulting from the method for preparing same, is characterized in that said mixture is subjected to the following operations:- acidification such that the trifluoroacetic acid salt and the triflinic acid salt are released in an acid form,- separation of the trifluoroacetic acid and trifluoromethanesulphinic acid by distillation enabling the trifluoroacetic acid to be recovered at the top of the distillation and the trifluoromethanesulphinic acid to be recovered at the bottom of the distillation,- separation by distillation of the trifluoromethanesulphinic acid present in the distillation residue previously obtained.

The heating of perfluoro-3,3-diethylindan-1-one with SbF5 at 180°C after treatment of the reaction mixture with anhydrous HF afforded perfluoro-1,3-dimethyl-4-ethylisochromen, and after hydrolysis, perfluoro-1,3-dimethyl-4-ethyl-1H-isochromen-1-ol. The latter under the action of NaHCO3 converted into 5,6,7,8-tetrafluoro-1,3-bis(trifluoromethyl) -1H-isochromen-1-ol. Both isochromenols reacted with SOCl2 gave the corresponding polyfluoro-1-chloro-1H-isochromens. On dissolving isochromenols in CF3SO3H and isochromens in SbF5 perfluoro-1,3-dimethyl-4-ethylisochromenyl and 5,6,7,8-tetrafluoro-1,3- bis(trifluoromethyl)isochromenyl cations were generated which by hydrolysis were converted into the corresponding isochromenols.

The present invention relates to a PYY or PP peptide derivative or analogue thereof derivatised with one or more serum albumin binding side chains comprising a dis-tal tetrazole or carboxylic acid group. Moreover, the invention relates to compositions hereof and methods of treatment of conditions responsive to Y receptor modulation.

Figure presented The equilibrium constants for ion pair formation of some pyridines have been evaluated by spectrophotometric titration with trifluoroacetic acid in different ionic liquids. The basicity order is the same in ionic liquids and in water. The substituent effect on the equilibrium constant has been discussed in terms of the Hammett equation. Pyridine basicity appears to be less sensitive to the substituent effect in ionic liquids than in water.

A systematic investigation into the Lewis base catalyzed, asymmetric, intramolecular selenoetherification of olefins is described. A critical challenge for the development of this process was the identification and suppression of racemization pathways available to arylseleniranium ion intermediates. This report details a thorough study of the influences of the steric and electronic modulation of the arylselenenyl group on the configurational stability of enantioenriched seleniranium ions. These studies show that the 2-nitrophenyl group attached to the selenium atom significantly attenuates the racemization of seleniranium ions. A variety of achiral Lewis bases catalyze the intramolecular selenoetherification of alkenes using N-(2-nitrophenylselenenyl)succinimide as the electrophile along with a Bronsted acid. Preliminary mechanistic studies suggest the intermediacy of ionic Lewis base-selenium(II) adducts. Most importantly, a broad survey of chiral Lewis bases revealed that 1,1′-binaphthalene-2,2′-diamine (BINAM)-derived thiophosphoramides catalyze the cyclization of unsaturated alcohols in the presence of N-(2-nitrophenylselenenyl)succinimide and methanesulfonic acid. A variety of cyclic seleno ethers were produced in good chemical yields and in moderate to good enantioselectivities, which constitutes the first catalytic, enantioselective selenofunctionalization of unactivated olefins.

The 9.24 eV ionization energy often quoted in photoelectron spectroscopic investigations of benzyne is not due to benzyne 1 but to benzene, C 6H6. The 8.9 eV ionization is not due to benzyne either but to cyclopentadienylideneketene 12 when a 10.2 eV band is also present, or to biphenylene 5 when a 7.6 eV band is simultaneously present. Cyclopentadienylideneketene 12 has been generated by flash vacuum thermolysis of four different precursors, which permit a linking of infrared, mass, and photoelectron spectroscopic observations.

Polyfluoroalkyl esters of phosphoric, alkylphosphonic and 1-hydroxypolyfluoroalkylphosphonic acids exhibited significant antiesterase activity against various esterases of animal and microbial origin. Moreover, with some compounds reversible inhibition of enzymes was observed due to the specific influence of hydrophobic fragments of the target products.

A former studied reaction of acetylation of pyrrole was revisited and this allowed the identification of new compounds and the isolation and characterization of a very stable solid (2,2′,2″-(2,2,2-trifluoroethane-1,1,1-triyl)tris(1H-pyrrole)). All these m

Disclosed are Tetrahydro-isoquinoline derivatives such as structural formula (I), pharmaceutical compositions comprising them and methods of treating bacterial infections. The disclosed compounds are inhibitors of PPAT (phosphopantetheine adenyl transferase), and are useful in the treatment and prevention of diseases caused by bacteria, particularly bacteria dependent on PPAT, for example, species such Escherichia coli, Helicobacter pylori, Staphyloccocus aureus, and the like. Description of the variables in structural formula (I) are provided herein.

Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the O 2-dependent cleavage of the carbon-carbon bond of 2-hydroxyethylphosphonate (2-HEP) to afford hydroxymethylphosphonate (HMP) and formate without input of electrons or use of any organic

Reactions of 4-aryl-1H-pyrazol-5(3)-amines with 2-acylcycloakanones and 2-acyl-5,5-dimethylcyclohexane-1,3-diones led to the formation of regioisomeric 6,7,8,9-tetrahydropyrazolo[1,5-a]quinazoline, 5,6,7,8-tetrahydropyrazolo[5,1-b] quinazoline, and 7,8-di

The invention provides compounds of Formula (1) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating mammals suffering from the condition of being overweight.

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds having the general formula U1 - M - U2 wherein M is a linking group covalently joining R2, R3, R4 or R5 of U1 to an R2, R3, R4 or R5 group of U2; U1 and U2 have the general formula (I) and G, X1, X2, R2, R3, R3', R4, R4' and R5, are as described herein.

(1,1-Dihydroperfluoroalkyl)phenyliodonium N,N-bis(trifluoromethylsulfonyl)imides (4, n = 0-2) were synthesized and used to transfer the corresponding 1,1-dihydroperfluoroalkyl groups to the α-amino group of (l)tyrosine. The obtained Nα-2,2,2-trifluoroethylated (l)tyrosine (6, n = 0) was further used as the N-terminus in the solid phase peptide synthesis of leucine enkephalin analogue. The lipophilicity of the Nα-1,1-dihydroperfluoroalkylated (l)tyrosines (6, n = 0-2) and N-terminus-2,2,2-trifluoroethylated leucine enkephalin analogue (7), as well as the corresponding parent compounds, was measured.

A compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O), S(O)2 or NR6 where R6 is hydrogen of C1-6alkyl; R5 is an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R1, R2, R3, R4 are independently selected from halogeno, cyano, nitro, C1-3alkylsulphanyl, —N(OH)R7— (wherein R7 is hydrogen, or C1-3alkyl), or R9X1— (wherein X1 represents a direct bond, —O—, —CH2—, —OC(O), —C(O)—, —S—, —SO—, —SO2—, —NR10C(O)—, —C(O)NR11—, —SO2NR12—, —NR13SO2— or NR14— (wherein R10, R11, R12, R13 and R14 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R9 is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; provided that at least one of R2 or R3 is other than hydrogen. These compounds inhibit aurora 2 kinase and are useful in the preparation of medicaments for the treatment of proliferative disease such as cancer.

The present invention relates to bicyclic heterocycles of general formula their tautomers, their stereoisomers, their mixtures and their salts, in particular their physiologically acceptable salts with inorganic or organic acids, which have valuable pharmacological properties, in particular an inhibitory action on the signal transduction mediated by tyrosine kinases, their use for the treatment of illnesses, in particular of tumoral diseases and of benign prostatic hyperplasia (BPH), of diseases of the lung and of the airways, and the preparation thereof.

The synthesis of trifluoroacetaldehyde by vapor-phase oxidation of 2,2,2-trifluoroethanol using supported vanadium catalysts was studied. Significant differences were observed in the reaction outcomes resulting from different types of catalysts. The ZrO2- and Al2O3-supported catalyst demonstrated both high catalytic activity and selectivity. The addition of co-catalysts such as MoO3 or SnO2 improved catalytic performance (Selectivity: up to 91%; S.T.Y.: >200 g L-1 h-1). The experimental results on catalyst lifetime showed a marked decrease in the activity of the Al2O3-supported catalyst within tens of hours, while the ZrO2-supported catalyst showed little, if any, performance alterations for 2000 h.

Electrochemical perfluorination (ECPF) of the title compounds containing primary, secondary and tertiary carbon atoms was carried out in anhydrous hydrofluoric acid (AHF). Detailed analysis of major and minor products suggest that carbon chain isomerisation involving cyclo-propane intermediate is more prevalent during ECPF of i-butyryl chloride when compared to n-butyryl chloride. Simple statistical probability involving free radical intermediates also support this observation. ECPF involving cyclo-propane intermediate is even more prevalent in pivaloyl chloride containing three methyl substituents. In this case, perfluorinated cyclo-propane intermediates were also observed in the product sample. Distribution of minor perfluorinated and partially fluorinated products also suggest the predominant role of normal free radical pathway involving single-electron transfer.

A fullerene mixture comprising any two or more of C60, C70 and higher fullerenes having greater than 70 carbon atoms is brought into contact with an amine having two or more nitrogen atoms, especially an amine having an amidine structure, in a solvent to form a complex of a specific fullerene contained in the fullerene mixture and the amine, and the complex is separated from a solution in which fullerenes not forming the complex are dissolved. Consequently, a method of fullerene separation, by which the specific fullerene is separated from the fullerene mixture with ease and at low cost, and the complex having the fullerene can be provided.

Reaction of α-methoxyacetic acid with aromatic compounds in the presence of trifluoroacetic anhydride and Lewis acid has been found to give diarylmethanes. Some of the intermediates in this transformation have been identified via direct observation by 1H and 13CNMR spectroscopy. The reaction route has been clarified as follows: a mixed acid anhydride is formed from α-methoxyacetic acid and trifluoroacetic anhydride, which gives a hemiacylal type intermediate via decarbonylation followed by successive double electrophilic aromatic substitutions yielding diarylmethanes. Copyright

The present invention provides a metastin derivative having excellent blood stability and exhibiting cancer metastasis inhibiting action or cancer growth inhibiting action. Specifically, the present invention the metastin derivative (I), which is represented by formula: [wherein, Z1, Z3, Z5 and Z7 represent H or a C1-3 alkyl group; Z2, Z4, Z6 and Z8 represent H, O or S; R1 represents (1) H, or (2) a C1-8 alkyl group optionally substituted with a substituent selected from the group consisting of a carbamoyl group, a hydroxyl group and a aromatic cyclic group; R2 represents (1) H or (2) a cyclic or linear C1-10 alkyl group, or (3) a C1-10 alkyl group consisting of a cyclic alkyl group and a linear alkyl group; R3 represents a C1-8 alkyl group having a basic group, an aralkyl group having a basic group, a C1-4 alkyl group having a non-aromatic cyclic hydrocarbon group of carbon atoms not greater than 7 having a basic group, or a C1-4 alkyl group having a non-aromatic heterocyclic group of carbon atoms not greater than 7 having a basic group; R4 represents a C1-4 alkyl group, which may optionally be substituted with a substituent selected from the group consisting of a C6-12 aromatic hydrocarbon group, an aromatic heterocyclic group, a C8-14 aromatic fused-ring group, an aromatic fused heterocyclic group, a non-aromatic cyclic hydrocarbon group, and a non-aromatic heterocyclic group having carbon atoms not greater than 7; X represents a group shown by formula: -NHCH(Q1)YQ2C(=Z9)- (wherein, Q1 represents a C1-4 alkyl group, which may optionally be substituted with a substituent selected from the group consisting of an aromatic hydrocarbon group, an aromatic heterocyclic group, a C8-14 aromatic fused-ring group, an aromatic fused heterocyclic group, a non-aromatic cyclic hydrocarbon group having carbon atoms not greater than 7, and a non-aromatic heterocyclic group having carbon atoms not greater than 7; Q2 represents CH2, NH or O; Y represents -CONH-, -CSNH-, -CH2NH-, -NHCO-, -CH2O-, -CH2S- or -CH2CH2-; Z9 represents H, O or S); and P represents (1) H; (2) an optional amino acid residue continuously or discontinuously bound from the C-terminal end of the 1-48 amino acid sequence in the amino acid sequence represented by SEQ ID NO: 1; (3) a group represented by formula: J1-J2-C(J3)(Q3)Y1C(J4)(Q4)Y2C(J5)(Q5)Y3C(J6)(Q6)C(=Z10)-(wherein, J1 represents (a) H or (b) (i) a C1-15 acyl group, (ii) a C1-15 alkyl group, (iii) a carbamoyl group, (iv) a C1-15 alkylcarbamoyl group, (v) a C1-15 alkanoylcarbamoyl group, (vi) an aminocarbamoyl group, (vii) a C1-15 alkylaminocarbamoyl group, (viii) an oxycarbonyl group, (ix) a C1-15 alkoxylcarbonyl group, (x) a sulfonyl group, (xi) an amidino group, (xii) a C1-15 alkylamidino group, (xiii) a C1-15 acylamidino group, (xiv) a C1-15 alkylsulfonyl group, or (xv) a oxaryl group, which group may optionally be substituted with cyclic group; J2 represents NH, CH2, O or S; J3 through J6 represent H or a C1-3 alkyl group; Q3 through Q6 represent a C1-4 alkyl group, which may optionally be substituted with a substituent selected from the group consisting of a C6-12 aromatic hydrocarbon group, an aromatic heterocyclic group, a C8-14 aromatic fused-ring group, an aromatic fused heterocyclic group, a non-aromatic cyclic hydrocarbon group having carbon atoms not greater than 7, a non-aromatic heterocyclic group having carbon atoms not greater than 7, an amino group, a guanidino group, a hydroxyl group, a carboxyl group, a carbamoyl group, and a sulfhydryl group, or H; J3 and Q3, J4 and Q4, J5 and Q5 or J6 and Q6 may be combined together, or, J2 and Q3, Y1 and Q4, Y2 and Q5, or Y3 and Q6 may be combined together, to form a ring; Y1 through Y3 represent a group represented by formula: -CON(J13)-, -CSN(J13)-, -C(J14)N(J13)- or -N(J13)CO- (wherein J13 and J14 represent H or a C1-3 alkyl group); and Z10 represents H, O or S); (4) a group represented by formula: J1-J2-C(J7)(Q7)Y2C(J8)(Q8)Y3C(J9)(Q9)C(=Z10)- (wherein, J1 and J2 have the same significance as described above; J7 through J9 have the same significance as J3; Q7 through Q9 have the same significance as Q3; Y2 and Y3 have the same significance as described above; Z10 has the same significance as described above; J7 and Q7, J8 and Q8 or J9 and Q9 may be combined together, or, J2 and Q7, Y2 and Q8 or Y3 and Q9 may be combined together, to form a ring); (5) a group represented by formula: J1-J2-C(J10)(Q10)Y3C(J11)(Q11)C(=Z10)- (wherein, J1 and J2 have the same significance as described above represents; J10 and J11 have the same significance as J3; Q10 and Q11 have the same significance as Q3; Y3 has the same significance as described above; Z10 has the same significance as described above; and J10 and Q10 or J11 and Q11 may be combined together, or J2 and Q10 or Y3 and Q11 may be combined together, to form a ring); (6) a group represented by formula: J1-J2-C(J12)(Q12)C(=Z10)- (wherein, J1 and J2 have the same significance as described above; J12 has the same significance as J3; Q12 has the same significance as Q3; Z10 has the same significance as described above; and J12 and Q12 may be combined together, or J2 and Q12 may be combined together, to form a ring); or (7) a group represented by formula: J1- (wherein, J1 has the same significance as described above)], or a salt thereof.

In one embodiment, the present application relates to a process of making a compound of Formula (I); and to certain intermediate compounds that are made within the process of making the compound Formula (I).

Barbier-type reductive alkylation of perfluorocarboxylic acid esters (I) with CFCl3 and activated Al was successfully performed to give α,α-dichloroperfluoroketones (II). A similar reaction of CF 3COOEt with CCl4 and Al provided a convenient synthesis of CF3COCCl3. Ketones (II) were fluorinated further with SbF5 to form higher linear perfluoroketones (IX). An alternative approach to the synthesis of ketones (IX) was proposed by reductive perfluoroalkylation of esters (I) under the action of RFI and Al.

The present invention relates to DNA-targeted 1,2,4-benzotriazine- 1,4-dioxides and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.