Trifluoroacetyl Group Research Articles

Aluminium oxide-mediated cross-coupling of pyrroles with 1-bromo-2-(trifluoroacetyl)acetylene: a quantum-chemical insight

Cross-coupling of NH-pyrroles with 1-bromo-2-(trifluoroacetyl) acetylene in the Al2O3 medium affords (E)-4-bromo-1,1,1-trifluoro-4-(pyrrol-2-yl)but-3-en-2-ones instead of the expected 2-ethynylated products. Quantum-chemical analysis shows strong intramolecular hydrogen bonding between NH and trifluoroacetyl groups, higher NH acidity and deeper charge transfer to the ethenyl moiety, which determines the reaction pathway.

Molecular Recognition of Azelaic Acid and Related Molecules with DNA Polymerase I Investigated by Molecular Modeling Calculations.

Molecular recognition has central role on the development of rational drug design. Binding affinity and interactions are two key components which aid to understand the molecular recognition in drug-receptor complex and crucial for structure-based drug design in medicinal chemistry. Herein, we report the binding affinity and the nonbonding interactions of azelaic acid and related compounds with the receptor DNA polymerase I (2KFN). Quantum mechanical calculation was employed to optimize the modified drugs using B3LYP/6-31G(d,p) level of theory. Charge distribution, dipole moment and thermodynamic properties such as electronic energy, enthalpy and free energy of these optimized drugs are also explored to evaluate how modifications impact the drug properties. Molecular docking calculation was performed to evaluate the binding affinity and nonbonding interactions between designed molecules and the receptor protein. We notice that all modified drugs are thermodynamically more stable and some of them are more chemically reactive than the unmodified drug. Promise in enhancing hydrogen bonds is found in case of fluorine-directed modifications as well as in the addition of trifluoroacetyl group. Fluorine participates in forming fluorine bonds and also stimulates alkyl, pi-alkyl interactions in some drugs. Designed drugs revealed increased binding affinity toward 2KFN. A1, A2 and A3 showed binding affinities of -8.7, -8.6 and -7.9kcal/mol, respectively against 2KFN compared to the binding affinity -6.7kcal/mol of the parent drug. Significant interactions observed between the drugs and Thr358 and Asp355 residues of 2KFN. Moreover, designed drugs demonstrated improved pharmacokinetic properties. This study disclosed that 9-octadecenoic acid and drugs containing trifluoroacetyl and trifluoromethyl groups are the best 2KFN inhibitors. Overall, these results can be useful for the design of new potential candidates against DNA polymerase I.

Radical Stability as a Guideline in C–H Amination Reactions

AbstractThe stability of N‐centered radicals and radical cations of potential relevance in C–H amidation reactions has been quantified using highly accurate theoretical methods. Combination with available C–H bond energies for substrate fragments allows for the prediction of reaction enthalpies in 1,5‐hydrogen atom transfer (HAT) steps frequently encountered in reactions such as the Hofmann–Löffler–Freytag (HLF) reaction. Protonation of N‐radicals is found to be essential in classical HLF reactions for thermochemically feasible HAT steps. The stability of neutral N‐radicals depends strongly on the type ofN‐substituent. Among the electron‐withdrawing substituents, the trifluoroacetyl (TFA) group is the least and the toluenesulfonyl (tosyl) group the most stabilizing. This implies that TFA‐aminyl radicals have the broadest and tosyl‐aminyl radicals the smallest window of synthetic applicability. In how far the intramolecular C–H amidation reactions compete with hydrogen abstraction from common organic solvents can be judged based on a comparison of reaction thermodynamics.magnified image

The rearrangement of trifluoroacetylchromenes to trifluoromethylchromenols

The reaction of o-phenylenediamine with condensed 4H-pyrans containing a trifluoroacetyl group at the β-position relative to the oxygen atom led to 2-(trifluoromethyl)chroman-2-ols and 3-(trifluoromethyl)-2,3-dihydro-1H-benzo[f]chromen-3-ols via a cascade process that was initiated by a Michael reaction.

Unusual reaction of bromoalkyl trifluoromethyl ketones with symmetrically disubstituted ethylenediamines. Theoretic investigation applying methods of density functional and multiparticle perturbation theory МР-2

Mechanism of a multistage reaction between α-bromotrifluoromethylenones and N,N′-dialkylethylenediamines was examined in detail using quantum chemical methods of density functional (non-empirical functional РВЕ, extended split TZp-basis) and multiparticle perturbation theory МР-2, basis 6-311+G(d,p), in the gas phase approximation, and also including solvents molecules (water and 2,2,2-trifluoroethanol). The specific solvation of transition states owing to the hydrogen bonds formation with solvent molecules is the main factor governing the direction of the reaction. Trifluoroethanol forms a strong H-bond with the carbonyl oxygen atom of the trifluoroacetyl group increasing its electrophilicity. It also solvates the departing bromide anion facilitating the occurrence of the S N 2-substitution reaction. An essential but less important factor is the ability of trifluoroethanol to play the role of a nucleophilic partner by forming hydrogen bonds at the expense of the unshared electron pair of the hydroxyl oxygen facilitating the proton abstraction from the nitrogen atom of the diamine attacking the carbon atom in the course of S N 2-substitution.

Aminohydroxylation of olefins with iminopyridinium ylides by dual Ir photocatalysis and Sc(OTf)3 catalysis

We have developed a new strategy for catalytic aminohydroxylation of olefins with an N-protected iminopyridinium ylide as the amine source. Iminopyridinium ylides N-protected with TFAc (trifluoroacetyl), Boc (tert-butoxycarbonyl), Troc (2,2,2-trichloroethoxycarbonyl), and Alloc (allyloxycarbonyl) groups serve as N-centered radical precursors when combined with fac-[Ir(ppy)3] photocatalysis and Sc(OTf)3 catalysis. The dual Ir photoredox/Sc(OTf)3 catalysis proves to be effective for aminohydroxylation of olefins under mild reaction conditions to provide 2-aminoalcohol derivatives bearing a primary amino group.

ChemInform Abstract: Selective Introduction of a Trifluoroacetyl Group onto 4‐Vinylpyridines Through Magnesium‐Promoted Reduction.

Abstract Magnesium-promoted reductive coupling of 4-vinylpyridines and ethyl trifluoroacetate in the presence of chlorotrimethylsilane in N-methyl-2-pyrrolidone resulted in selective formation of the trifluoroacetylated compounds at the β-olefinic carbon of the pyridine ring, the electron deficient carbon in good yields. In particular, 4-vinylpyridine with an aromatic ring at the β-olefinic position of the pyridine ring gave higher yield of the trifluoroacetylated compound. The nitrogen atom of the pyridine ring may play an important role in the regioselectivity of the product.

Direct trifluoroacetylation of mono- and disubstituted thiophene derivatives

Abstract A convenient “one-pot” Friedel–Crafts reaction of mono -, bi - and tert -thiophenes with trifluoroacetic acid anhydride (TFAA) as an acylating agent and magnesium perchlorate dihydrate (anhydron) as catalyst affords trifluoroacetyl-substituted products in high yields. This method provides a novel approach for the synthesis of thiophene based derivatives bearing trifluoroacetyl group. The mechanism of this reaction is suggested.

Synthesis and reactivity of 8-aza-5,7-dimethyl-2-trifluoroacetylchromone

Claisen condensation of 3-acetyl-4,6-dimethyl-2-pyridone with methyl 2-methoxytetrafluoropropionate in the presence of LiH in refluxing dioxane gave the corresponding 1,3-diketone, further converted by treatment with conc. H2SO4 to 5,7-dimethyl-2-(1-methoxytetrafluoroethyl)-8-azachromone and 5,7-dimethyl-2-trifluoroacetyl-8-azachromone, which was isolated as hydrate. The first of these azachromones reacted with dinucleophiles at the С-2 atom and the pyrone carbonyl group, while the second reacted at the С-2 atom and trifluoroacetyl group. Based on these compounds, we obtained new trifluoromethylated heterocyclic systems containing a 2-pyridone ring, as well as (8-azachromon-2-yl)(indol-3-yl)carbinols.

Selective introduction of a trifluoroacetyl group onto 4-vinylpyridines through magnesium-promoted reduction

Magnesium-promoted reductive coupling of 4-vinylpyridines and ethyl trifluoroacetate in the presence of chlorotrimethylsilane in N-methyl-2-pyrrolidone resulted in selective formation of the trifluoroacetylated compounds at the β-olefinic carbon of the pyridine ring, the electron deficient carbon in good yields. In particular, 4-vinylpyridine with an aromatic ring at the β-olefinic position of the pyridine ring gave higher yield of the trifluoroacetylated compound. The nitrogen atom of the pyridine ring may play an important role in the regioselectivity of the product.

New oleyl glycoside as anti-cancer agent that targets on neutral sphingomyelinase

We designed and synthesized two anomeric oleyl glucosaminides as anti-cancer agents where the presence of a trifluoroacetyl group close to the anomeric center makes them resistant to hydrolysis by hexosaminidases. The oleyl glycosides share key structural features with synthetic and natural oleyl derivatives that have been reported to exhibit anti-cancer properties. While both glycosides showed antiproliferative activity on cancer cell lines, only the α-anomer caused endoplasmic reticulum (ER) stress and cell death on C6 glioma cells. Analysis of sphingolipids and glycosphingolipds in cells treated with the glycosides showed that the α-anomer caused a drastic accumulation of ceramide and glucosylceramide and reduction of lactosylceramide and GM3 ganglioside at concentrations above a threshold of 20μM. In order to understand how ceramide levels increase in response to α-glycoside treatment, further investigations were done using specific inhibitors of sphingolipid metabolic pathways. The pretreatment with 3-O-methylsphingomyelin (a neutral sphingomyelinase inhibitor) restored sphingomyelin levels together with the lactosylceramide and GM3 ganglioside levels and prevented the ER stress and cell death caused by the α-glycoside. The results indicated that the activation of neutral sphingomyelinase is the main cause of the alterations in sphingolipids that eventually lead to cell death. The new oleyl glycoside targets a key enzyme in sphingolipid metabolism with potential applications in cancer therapy.

Base-promoted transformation of 2-C(O)R-1,8-bis(dimethylamino)naphthalenes into benzo[g]indole derivatives

1,8-Bis(dimethylamino)naphthalenes bearing 2-positioned trifluoroacetyl or ethoxycarbonyl group on treatment with 2-lithio-1,8-bis-dimethylamino)naphthalene undergo base-promoted transformation into benzo[g]indole derivatives in small to moderate yield, representing previously unknown mode of the pyrrole ring closure which proceeds via deprotonation of the NMe group.

Ultrathin and nanofibers via room temperature electrospinning from trifluoroacetic acid solutions of untreated lignocellulosic sisal fiber or sisal pulp

ABSTRACTLignocellulosic sisal fiber (LSF) and sisal pulp (SP) were electrospun at room temperature from solutions in trifluoroacetic acid (TFA) prepared at concentrations of 2 × 10−2g mL−1and 3 × 10−2g mL−1, respectively. Scanning electron microscopy images of the electrospun LSF showed fibers with diameters ranging from 120 to 510 nm. The presence of defects decreased along with increasing the flow rate of the SP solution, which generated nanofibers and ultrathin fibers with diameters in the range of 40–60 (at 5.5 µL min−1) up to 90–200 nm (at 65.5 µL min−1). Despite the known ability of TFA to esterify the hydroxyl groups present in the starting materials, the Fourier transform infrared spectra indicated the absence of trifluoroacetyl groups in the electrospun samples. The thermal stability of the final materials proved suitable for many applications even though some differences were observed relative to the starting materials. This study demonstrated a feasible novel approach for producing nano/ultrathin fibers from lignocellulosic biomass or its main component, which allows for a wide range of applications for these materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41826.

Microwave-assisted synthesis of HYNIC protected analogue for 99mTc labeled antibody.

We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates. The NHS-HYNIC-Tfa derivate allowed better labeling yields during longer times of preservation of the conjugated antibody.

High-performance liquid chromatography for analytical and small-scale preparative separation of (R,S)-mexiletine using (S)-(—)-(N)-trifluoroacetyl-prolyl chloride and (1S)-(—)-camphanic chloride and recovery of native enantiomer by detagging

A reversed phase high-performance liquid chromatographic method has been established for enantioseparation of (R, S)-mexiletine. Two volatile and thermally stable acyl chlorides, viz., (S)-(—)-(N)-trifluoro acetyl prolyl chloride and (1S)-(—)-camphanic chloride, were used as chiral derivatizing reagents. Binary composition of aqueous trifluoroacetic acid (0.1%)-acetonitrile as mobile phase was successful with ultraviolet (UV) detection at 210 nm. The method was optimized and validated for accuracy, precision, and limit of detection. The limit of detection was found to be 45 ng mL−1 and 80 ng mL−1 for the two types of diastereomers. Besides, kinetic resolution was achieved, and the experimental conditions optimized for this purpose provided diastereomeric excess up to 74% for (R)-isomer. On achieving a resolution value greater than 2, the optimized method for analytical enantioseparation was scaled-up to smallscale preparative level, and the native (R)-mexiletine was recovered by acid hydrolysis of the diastereomer.

ChemInform Abstract: Transition from π Radicals to σ Radicals: Substituent‐Tuned Cyclization of Hydrazonyl Radicals.

AbstractHydrazonyl radicals, generally possessing π‐electronic structures, can be tuned to σ radicals by attaching a trifluoroacetyl or trichloroacetyl group to the N‐1 atom.

GC/MS によるメチルアンフェタミン類の位置異性体識別

Methylamphetamines (methylamphetamine (Me-AP) and methylmethamphetamine (Me-MA)) have three ringpositional isomers. Among them, 4-Me-AP has been controlled as a designated substance (Shitei-Yakubutsu) in Japan since November 2012. Furthermore, Me-APs are a structural isomer of methamphetamine (MA), controlled as a stimulant. Because of the increasing number of structural isomer of designer drugs encountered in forensic science laboratories, analytical differentiation of structural isomers is a significant issue. In this study, a method for differentiation of methylamphetamines using gas chromatography/mass spectrometry (GC/MS) was developed. DB-1ms and DB-5ms columns could not separate free bases and trifluoroacetyl (TFA) derivatives of methylamphetamines while the columns incompletely separated their trimethylsilyl (TMS) derivatives. On the other hand, the mid-polar DB-17ms column separated free bases, TFA and TMS derivatives of 6 methylamphetamines though peak shapes of the free bases were tailing. The best separation was obtained from the analysis of the TMS derivatives on DB-17ms column. The mass spectra showed a little difference between the 2-, 3-Me-AP and 4-Me-AP after TFA derivatization. Also the structural isomers of Me-AP and MA could be differentiated by their EI mass spectra. The results indicated that differentiation of regioisomeric methylamphetamines could be accomplished well by GC/MS of their TMS derivatives on the mid-polar capillary column.

Molecular Recognition of Aliphatic Diamines by 3,3′-Di(trifluoroacetyl)-1,1′-bi-2-naphthol

The fluorescent responses of 3,3'-di(trifluoroacetyl)-1,1'-bi-2-naphthol toward a variety of amines have been studied. It was found that the aliphatic primary 1,2- and 1,5-diamines can greatly enhance the fluorescence of this compound, but under the same conditions, primary, secondary, and tertiary monoamines cannot turn on the fluorescence of this compound. In addition, this compound was shown to be an enantioselective and diastereoselective fluorescent sensor for chiral diamines. UV absorption and NMR spectroscopic methods have been used to study the interaction of the sensor with amines. These studies have demonstrated that the intramolecular OH···O═C hydrogen bonding of the sensor is important for both the reactivity of its trifluoroacetyl group with the amines and its fluorescent responses. The interaction of both of the two amine groups of a diamine molecule with the sensor is essential for the observed fluorescent sensitivity and selectivity.

Synthesis of carboxyl cellulose sulfates with regioselective sulfation and regiospecific oxidation using cellulose trifluoroacetate as intermediates

Synthesis of cellulose sulfates (CSs) and carboxyl cellulose sulfates (COCSs) with regioselectively or regiospecifically distributed functional groups within anhydroglucose units was reported. CS with regioselectively distributed sulfate groups at 2,3-O- or 2,6-O-position were homogeneously synthesized and cellulose trifluoroacetate (CTFA) was used as intermediates. The trifluoroacetyl groups were detected primarily at 6-O-position and their distributions could be altered by changing the amount of trifluoroacetyl anhydride (TFAA). Various sulfating agents were used for further homogeneous sulfation of CTFA. The total degree of sulfation (DSS) and the distribution of sulfate groups within the repeating units were affected by the amount of TFAA, the type and amount of sulfating agents. Subsequent homogenous 4-acetamide-TEMPO or TEMPO-mediated oxidation of CS led to COCS with carboxyl groups regiospecifically distributed at C6 position, which may be interesting structural mimics for natural occurring heparin.

19-Fluorine nuclear magnetic resonance chemical shift variability in trifluoroacetyl species

19-Fluorine nuclear magnetic resonance chemical shift variability in trifluoroacetyl species Joseph C SloopSchool of Science and Technology, Georgia Gwinnett College, Lawrenceville, GA, USAAbstract: This review examines the variability of chemical shifts observed in 19-fluorine (19F) nuclear magnetic resonance spectra for the trifluoroacetyl (TFA) functional group. The range of 19F chemical shifts reported spectra for the TFA group varies generally from −85 to −67 ppm relative to CFCl3. The literature revealed several factors that impact chemical shifts of the TFA moiety - substrate topology, electronic environment, solvent polarity, and concentration effects. Often these effects conspire to cause deshielding of the TFA group by up to 15 ppm. These factors will be examined for a series of TFA-functionalized acyclic, cyclic, aromatic, and heterocyclic molecules.Keywords: 19F NMR, chemical shift, shielding, trifluoroacetyl group, fluorinated diketones, triketones