Trifluoroacetic Acid In Dichloromethane Research Articles

Polymethylhydrosiloxane (PMHS)/trifluoroacetic acid (TFA): a novel system for reductive amination reactions

Polymethylhydrosiloxane (PMHS)/trifluoroacetic acid (TFA) was discovered as a novel metal-free system for reductive amination reactions. A variety of (het)aryl amines as well as a representative carbamate and urea were successfully alkylated by benzaldehyde in the presence of PMHS and TFA in dichloromethane at room temperature in moderate to excellent yields (28–87%). Furthermore, this reaction protocol was successfully applied to the alkylation of p-nitroaniline with a wide range of aldehydes, ketones, and a representative acetal to obtain the alkylated products in yields ranging from 40% to 92%. The current work represents one of the very few examples of PMHS being activated by a Brønsted acid.

Three-component synthesis of 2-aryl-4-arylthio-tetrahydro-2 H-pyrans via the Prins-cyclization

A three-component coupling of aldehyde, homoallylic alcohol and aryl thiol has been achieved in the presence of trifluoroacetic acid in dichloromethane at room temperature to produce 4-arylthiotetrahydropyrans in good yields with all cis-selectivity. This method is simple, selective and convenient for introducing a thiol group on a tetrahydropyran ring.

In-situ growth of titania nanoparticles in electrospun polymer nanofibers at low temperature

In-situ growth of titania nanoparticles in poly (ethylene terephthalate) (PET) nanofibers has been successfully achieved by combining sol–gel method and electrospinning process. Titania precursor, tetra-n-butyl titanate (TBT), was firstly hydrolyzed in trifluoroacetic acid (TFA), and then blend with a solution of PET in mixture of trifluoroacetic acid/dichloromethane (TFA/DCM) to form a homogeneous solution for electrospinning. Titania nanoparticles in-situ generated in the electrospun nanofibers via a hydrothermal treatment process at 70 °C–90 °C. The morphology and crystallinity of PET/TiO 2 hybrid nanofibers were investigated using TEM and DSC. The results showed that titania nanoparticles of anatase phase with an average diameter of about 10 nm in-situ generated both inside and on the surface of PET electrospun nanofibers. The reversible networks formed between titania nanoparticles and PET macromolecular chains led to considerable decrease of PET crystallinity.

Anionic Ring-Opening Copolymerization of L-Lactide with a Five-Membered Cyclic Carbonate Having a Glucopyranoside Structure

The anionic ring-opening copolymerization of L-lactide (LL) with a five-membered cyclic carbonate having the glucopyranoside structure, methyl 4,6-O-benzilidene-2,3-O-carbonyl-α-D-glucopyranoside (MBCG), was carried out using potassium tert-butoxide (t-BuOK) as the initiator and tetrahydrofuran (THF) as the solvent at 30°C for 12h. The mole fractions of LL in the copolymer (fLL) of all copolymers were nearly equal to the corresponding mole fraction of LL in the feed (FLL). Deprotection of the copolymer was performed using trifluoroacetic acid in dichloromethane. 1H NMR spectra of the resulting product indicated that deprotection was completely achieved due to the absence of the aromatic proton signals.

Metal-Free Hydroarylation of Alkynes: A Very Convenient, Simple Procedure for Substituted Arylalkenes

Hydroarylation of aryl-substituted alkynes with simple and substituted arenes was conducted in the presence of trifluoroacetic acid in dichloromethane without any metal catalysts or additives. Electron-rich arenes coupled with aryl-substituted alkynes to give 1,1-diarylalkenes in good to high yields.

Solvent and concentration effects on the properties of electrospun poly(ethylene terephthalate) nanofiber mats

AbstractThis study describes the preparation and characterization of nanofibrous mats obtained by electrospinning poly(ethylene terephthalate) (PET) solutions in trifluoroacetic acid/dichloromethane (TFA/DCM). Special attention was paid to the effect of polymer concentration and solvent properties on the morphology, structure, and mechanical and thermal properties of the electrospun nonwovens. The results show that the spinnable concentration of PET solution in TFA/DCM solvents is above 10 wt %. Mats have nanofibrous morphology with fibers having an average diameter in the range of 200–700 nm (depending on polymer concentration and solvent composition) and an interconnected pore structure. Higher solution concentration favors the formation of uniform fibers without beads and with higher diameter. Morphology and fiber assembly changed with the solvent properties. Solvent mixtures rich in TFA, i.e., those with higher dielectric constant and lower surface tension, originated fibers with small diameter. However, due to the lower volatility, those solvent mixtures also produced more branched and crosslinking fibers, with less morphologic uniformity. Mechanical properties (Young's modulus, ultimate strength, and elongation at break) and thermal properties (glass transition, crystallization, and melting) have been studied for the PET electrospun nanomats and compared with those of the original polymer. Solvent effect on fiber crystallinity was not significant, but a complex effect was observed on the mechanical properties of the electrospun mats, as a consequence of the different structural organization of the fibers within the mat network. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 460–471, 2008

A diastereoselective synthesis of 4-azidotetrahydropyrans via the Prins-cyclization

A three component coupling of aldehydes, homoallylic alcohols and sodium azide is achieved in the presence of trifluoroacetic acid in dichloromethane to produce 4-azidotetrahydropyran derivatives in high yields with all cis-selectivity. The use of trifluoroacetic acid makes this procedure simple and cost-effective.

The mechanism of the Baeyer–Villiger rearrangement: quantum chemistry and TST study supported by experimental kinetic data

The mechanism of the Baeyer-Villiger rearrangement is modelled for the reaction of propanone with trifluoroperacetic acid, catalyzed by trifluoroacetic acid in dichloromethane, using three DFT methods (B3LYP, BH&HLYP and MPWB1K) and MP2. These results are refined and used to calculate the overall reaction rate coefficient using conventional Transition State Theory. The excellent agreement between the calculated (1.00 x 10(-3) L mol(-1) s(-1)) and the experimental (1.8 x 10(-3) L mol(-1) s(-1)) rate coefficients at the MPWB1K level strongly supports the mechanism recently proposed by our group. This DFT method is then used to study the mechanism of a larger system: cyclohexanone + trifluoroperacetic acid, for which a very good agreement between the calculated and the experimental rate coefficients is also found (1.37 and 0.32 L mol(-1) s(-1), respectively). The modelled mechanism is not ionic but neutral, and consists of two concerted steps. The first one is strongly catalyzed while the second one, the migration step, seems not to be catalyzed for the systems under study. The results of this work could be of interest for understanding other reactions in non-polar solvents for which ionic mechanisms have been assumed.

Synthesis of per-6-guanidinylated cyclodextrins

Reaction of per(6-amino-6-deoxy-2,3-di- O-methyl)-α-, β- and γ-cyclodextrins with N, N′-bis( tert-butoxycarbonyl)- N″-triflylguanidine and triethylamine in tetrahydrofuran gave per[6- N, N′-bis( tert-butoxycarbonyl)guanidino-6-deoxy-2,3-di- O-methyl]-α-, β- and γ-cyclodextrins, respectively. Subsequent cleavage of the protective groups with trifluoroacetic acid in dichloromethane afforded per(6-deoxy-6-guanidino-2,3-di- O-methyl)-α-, β- and γ-cyclodextrins in very good overall yields.

A Novel TFA‐Mediated cyclo‐Dimerization of 1‐Substituted 3‐Alkenylindole Derivatives to Cyclopent[b]indoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A novel TFA-mediated cyclo-dimerization of 1-substituted 3-alkenylindole derivatives to cyclopent[ b]indoles

Reaction of 1-substituted 3-alkenyl-1 H-indoles with an equimolar amount of trifluoroacetic acid in dichloromethane gave cyclic dimers, 1,3- trans- N, N′-disubstituted cyclopent[ b]indoles, in 53–84% yields as sole products through an acid-mediated stereoselective cyclo-dimerization process. The structure of the cyclic dimer derived from 3-cyclopentylidenemethyl-1-methyl-1 H-indole was elucidated by X-ray crystallographic analysis.

Novel Cyclo‐Dimerization of 1‐tert‐Butoxycarbonyl‐3‐alkenylindole Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel cyclo-dimerization of 1- tert-butoxycarbonyl-3-alkenylindole derivatives

Reaction of 1- tert-butoxycarbonyl-3-cyclopentylidenemethyl-1 H-indole with an excess of trifluoroacetic acid in dichloromethane at room temperature gave a cyclic dimer, 13-cyclopentyl-6,7,12,13-tetrahydrospiro[5 H-cyclohepta[1,2- b:4,5- b′]diindole-6,1′-cyclopentane] in 73% yield as the sole product through a novel cyclo-dimerization process. Structure of the cyclic dimer derived from 5-bromo-1- t-butoxycarbonyl-3-cyclopentylidenemethyl-1 H-indole was elucidated by X-ray crystallographic analysis.

Solid-phase synthesis of 5-aminotetrazoles

A solid-phase synthesis of 5-aminotetrazoles is described. Resin-bound thioureas were displaced by sodium azide in the presence of HgCl 2 and following nucleophilic cyclization produced the resin-bound products. The desired 5-aminotetrazoles were cleaved from the resin using 95% trifluoroacetic acid in dichloromethane in good yield and purity.

Study of acid-base interactions of mono- and diazaporphyrin indium complexes with acetic and trifluoroacetic acids by 1H NMR and electronic spectroscopy

Indium complex of 13,17-dibutyl-2,3,7,8,12,18-hexamethyl-5-azaporphyrin (Cl)InMAP was synthesized, and acid-base interactions of the meso-nitrogen atoms in (Cl)InMAP and its diaza analog (Cl)InDAP with acetic and trifluoroacetic acids were studied by 1H NMR and electronic spectroscopy. Depending on the medium, the complexes and proton-donor species HA give rise to acid solvates >N⋅⋅⋅(HA)n which are converted to final acid-base interaction products, H-complexes >N⋅⋅⋅H+⋅⋅⋅A−(HA)m or ionic associates >NH+⋅⋅⋅A−(HA)l , as the acidity of the medium rises. In acetic acid solution, the acid solvates derived from more basic (Cl)InMAP exist in equilibrium with the H-associates (pK a1 = 4.45±0.03). From (Cl)InDAP, the corresponding H-associates are formed only in the presence of H2SO4 (pK a1 = 2.10±0.03). In more polar media (solutions of trifluoroacetic acid in methylene chloride), ionic associates are formed, which involve one [(Cl)InMAP, pK 1 = 2.46±0.02] or two meso-nitrogen atoms [(Cl)InDAP, pK 1 = 2.11±0.03, pK 2 = 0.41±0.04).

Multivalent Contrast Agents Based on Gadolinium−Diethylenetriaminepentaacetic Acid-Terminated Poly(propylene imine) Dendrimers for Magnetic Resonance Imaging

A convenient methodology has been developed for the synthesis of gadolinium−diethylenetriaminepentaacetic acid (Gd−DTPA)-terminated poly(propylene imine) dendrimers as contrast agents for magnetic resonance imaging (MRI). In our strategy, isocyanate-activated, tert-butyl-protected DTPA analogues were coupled to different generations of poly(propylene imine) dendrimers. Deprotection of the tert-butyl esters with trifluoroacetic acid in dichloromethane and extensive dialysis afforded gadolinium-chelating poly(propylene imine) dendrimers. The corresponding Gd−DTPA-based dendritic contrast agents were prepared from GdCl3 in either water or citrate buffer. Atomic force microscopy and cryogenic transmission electron microscopy experiments of the fifth-generation Gd−DTPA based dendritic contrast agent in citrate buffer demonstrated the presence of well-defined spherical particles with nanoscopic dimensions (5−6 nm), and no self-aggregation of dendrimers was observed. The efficiencies of these dendritic contrast agents in MRI, expressed in terms of longitudinal (r1) and transverse (r2) relaxivities, were determined at 1.5 T at 20 °C. The r1 and r2 values increase considerably with increasing generation of Gd−DTPA-terminated dendrimer. The fifth-generation dendritic contrast agent displays the highest ionic relaxivities (per gadolinium), r1 = 19.7 mM-1 s-1 and r2 = 27.8 mM-1 s-1, which are substantially higher than the ionic relaxivities of parent Gd−DTPA. Moreover, a series of combined gadolinium and yttrium complexes of the fifth-generation dendrimer are prepared, resulting in well-defined dendritic contrast agents with tunable molecular relaxivities.

Solid-phase synthesis of an oxalic acid amide library.

Monoamides of oxalic acid are of interest as bioisosteric replacements for phosphate groups in the design of new enzyme inhibitors. Here, we have demonstrated the use of oxalic acid as a linker to the Wang resin to synthesize individual or libraries of phosphate biosteres. The highly reactive resin-bound acid chloride reacts with arylamines to yield resin-bound N-aryloxamic acids (oxanilic acids). This methodology is especially useful for the rapid synthesis of 2-(oxalylamino)benzoic acids (OBAs), because it can be utilized for library synthesis and eliminates the intermediate purification step necessary in solution-phase reactions. The products are cleaved off the resin with trifluoroacetic acid in dichloromethane in good yields.

Solid‐Liquid Biphasic Hydroformylation of Olefins Catalyzed by Rhodium Carbonyl Complexes

AbstractSome polymer‐anchored alkenes have been hydroformylated by carrying out the reaction in a high‐pressure reactor equipped with a suitably designed vial. The solid substrates are converted to the corresponding oxo‐aldehydes in high yields. In all cases the regioselectivity was strongly shifted towards the linear aldehyde when the rhodium carbonyl complex was modified with xantphos (3 : 1 or 4 : 1 P/Rh molar ratio). Treatment with 5% of trifluoroacetic acid in dichloromethane at room temperature removed quantitatively the oxo‐product from the polymer support, which can be purified and reused.

Solid-phase parallel synthesis of 17alpha-substituted estradiol sulfamate and phenol libraries using the multidetachable sulfamate linker.

We report an application of the multidetachable sulfamate linker in the synthesis of two model libraries of N-derivatized 17alpha-piperazinomethyl estradiols (phenols and sulfamates) by solid-phase parallel chemistry. The solid-phase precursor, a 3-sulfamoyl-17alpha-(N-trifluoroacetyl-piperazinomethyl) estradiol, was synthesized in solution from estrone and loaded efficiently onto trityl chloride resin as polymeric support. After cleavage of the trifluoroacetyl protecting group, sequential acylation reactions with five Fmoc-protected amino acids and five carboxylic acids were performed to introduce two levels of molecular diversity. Finally, the resins were split into two parts, and acidic (5% trifluoroacetic acid in dichloromethane) and nucleophilic (piperazine in tetrahydrofuran) cleavages were used to generate libraries A (5 x 5 sulfamates) and B (5 x 5 phenols) members in overall yields of 18-66% and high HPLC purities (87-96%) without purification steps. A preliminary screening test for inhibition of steroid sulfatase showed that the phenols were clearly weaker inhibitors, as compared to their sulfamate analogues. The most potent inhibitors were those with suitable hydrophobic amino acid and carboxylic acid substituents. Thus, compounds with a phenylalanine residue as the first element of diversity inhibited over 90% of steroid sulfatase activity at a concentration of 1 nM in homogenates of HEK-293 transfected cells, being as potent as the leading inhibitor 17alpha-tert-butylbenzyl estradiol 3-O-sulfamate previously reported. These results suggest that the steroid sulfatase inhibitory potency of estradiol derivatives, sulfamoylated or not, can be increased by the hydrophobic effect of a suitable substituent introduced in the proximity of the D ring of the steroid. The present work also demonstrated the efficiency and the cleavage versatility of the sulfamate linker to generate libraries of compounds with relevant biological importance, phenols and sulfamates.

Efficient Epimerization of Pyrene and Other Aromatic C‐Nucleosides with Trifluoroacetic Acid in Dichloromethane.

AbstractFor Abstract see ChemInform Abstract in Full Text.