Absence Of Trifluoroacetic Acid Research Articles

Isolation and Purification of Harpagogenin as an Nrf2-ARE Activator from the Tubers of Chinese Artichoke (Stachys sieboldii).

Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics. Hot water extracts exhibited relatively high ARE activity. ARE activity was observed in two fractions when the hot water extracts were separated in the presence of trifluoroacetic acid using HPLC. Conversely, the highly active fraction disappeared when the hot water extracts were separated in the absence of trifluoroacetic acid. These results indicate that acidic degradation produces active ingredients. The structural analysis of the two active fractions identified harpagide, which is an iridoid glucoside, and harpagogenin. In vitro experiments revealed that harpagide was converted into harpagogenin under acidic conditions and that harpagogenin, but not harpagide, had potent ARE activity. Therefore, this study identified harpagogenin, which is an acid hydrolysate of harpagide, as an ARE activator and suggests that Nrf2-ARE pathway activation by Chinese artichoke contributes to the antioxidative effect.

O-Acylbenzonitriles: Synthesis and Heterocyclization under Acid Hydrolysis of the Cyano Group

2-Cyanobenzophenones were synthesized by reaction of 2-bromobenzophenones with copper(I) cyanide in DMF, and their transformations involving acid hydrolysis of the cyano group were studied. Reactions of o-benzoylbenzonitriles with trifluoroacetic acid in the presence or in the absence of sulfuric acid afforded 3-hydroxyphthalimidines in high yields. Under analogous conditions, benzonitriles having no acyl group in the ortho position were converted to the corresponding benzamides. 2-Cyanobenzophenones reacted with sulfuric acid in the absence of trifluoroacetic acid to give only substituted anthraquinones.

Stereo- and Regioselective Addition of Arene to Alkyne Using Abnormal NHC Based Palladium Catalysts: Elucidating the Role of Trifluoroacetic Acid in Fujiwara Process

Hydroarylation of alkyne was reported by Fujiwara nearly two decades back. Interestingly, this reaction does not proceed in the absence of trifluoroacetic acid; however, the exact role of TFA has not been unambiguously established, in particular with the support of X-ray crystallography by isolating the TFA-involved catalytically active species. In this work, abnormal N-heterocyclic carbene (aNHC) based Pd catalysts have been used for the efficient hydroarylation of aromatic C–H bonds leading to new C–C bond formation through regio- and stereoselective addition to alkynes. The addition reaction has been realized by a catalytic amount of Pd (II) compound (0.5 mol %) in trifluoroacetic acid (TFA) under ambient conditions. Various arenes undergo transhydroarylation selectively across the triple bond (containing functional groups CO2Me, CO2Et, and CO2H), affording the kinetically controlled cis adduct predominantly in good yields. A simple reaction condition through an intermolecular reaction has been outline...

Hydrogen atom transfer from 1,n-alkanediamines to the cumyloxyl radical. Modulating C-H deactivation through acid-base interactions and solvent effects.

A time-resolved kinetic study on the effect of trifluoroacetic acid (TFA) on the hydrogen atom transfer (HAT) reactions from 1,n-alkanediamines (R2N(CH2)nNR2, R = H, CH3; n = 1-4), piperazine, and 1,4-dimethylpiperazine to the cumyloxyl radical (CumO(•)), has been carried out in MeCN and DMSO. Very strong deactivation of the α-C-H bonds has been observed following nitrogen protonation and the results obtained have been explained in terms of substrate basicity, of the distance between the two basic centers and of the solvent hydrogen bond acceptor ability. At [substrate] ≤ 1/2 [TFA] the substrates exist in the doubly protonated form HR2N(+)(CH2)nN(+)R2H, and no reaction with CumO(•) is observed. At 1/2 [TFA] < [substrate] ≤ [TFA], HAT occurs from the C-H bonds that are α to the nonprotonated nitrogen in R2N(CH2)nN(+)R2H. At [substrate] > [TFA], HAT occurs from the α-C-H bonds of R2N(CH2)nNR2, and the mesured kH values are very close to those obtained in the absence of TFA. Comparison between MeCN and DMSO clearly shows that in the monoprotonated diamines R2N(CH2)nN(+)R2H remote C-H deactivation can be modulated through solvent hydrogen bonding.

Detailed Electrochemical Analysis of the Redox Chemistry of Tetrafluorotetracyanoquinodimethane TCNQF4, the Radical Anion [TCNQF4]•–, and the Dianion [TCNQF4]2– in the Presence of Trifluoroacetic Acid

The electrochemistry of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (TCNQF(4)), [TCNQF(4)](•-), and [TCNQF(4)](2-) have been studied in acetonitrile (0.1 M [Bu(4)N][ClO(4)]). Transient and steady-state voltammetric techniques have been utilized to monitor the generation of [TCNQF(4)](•-) and [TCNQF(4)](2-) anions as well as their reactions with trifluoroacetic acid (TFA). In the absence of TFA, the reduction of TCNQF(4) occurs via two, diffusion controlled, chemically and electrochemically reversible, one-electron processes where the reversible formal potentials are 0.31 and -0.22 V vs Ag/Ag(+). Unlike the TCNQ analogues, both [TCNQF(4)](•-) and [TCNQF(4)](2-) are persistent when generated via bulk electrolysis even under aerobic conditions. Voltammetric and UV-vis data revealed that although the parent TCNQF(4) does not react with TFA, the electrochemically generated radical anion and dianion undergo facile protonation to yield [HTCNQF(4)](•), [HTCNQF(4)](-) and H(2)TCNQF(4) respectively. The voltammetry can be simulated to give a complete thermodynamic and kinetic description of the complex, coupled redox and acid-base chemistry. The data indicate dramatically different equilibrium and rate constants for the protonation of [TCNQF(4)](•-) (K(eq) = 3.9 × 10(-6), k(f) = 1.0 × 10(-3) M(-1) s(-1)) and [TCNQF(4)](2-) (K(eq) = 3.0 × 10(3), k(f) = 1.0 × 10(10) M(-1) s(-1)) in the presence of TFA.

Observation of optical activity in polythiourethane obtained by the controlled cationic ring‐opening polymerization of chiral cyclic thiourethane derived from serine

AbstractThe secondary structure of an optically active polythiourethane [(CH2C*H(CO2Me)NHCOS)n] was evaluated with 1H NMR, IR, and circular dichroism (CD) spectroscopy. Hydrogen bonds between the carbonyl and NH groups in the thiourethane group constrained the main chain of the chiral polythiourethane precisely under the direction of chirality in the main chain, whereas the racemic polymer was also constrained but randomly. The secondary structure of the polythiourethane in CHCl3 changed noticeably in the presence or absence of trifluoroacetic acid, which eliminated constraining intramolecular hydrogen bonds. IR spectroscopy suggested that the secondary structure was almost identical in solid and solution states. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1554–1561, 2005

A Convenient Synthesis of 2‐Substituted Thiazole‐5‐carboxylates.

The photolysis of ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate in acetonitrile containing 0.5% tri- fluoroacetic acid in the presence of thioamides gives moderate (40–60%) yields of thiazole-5-carboxylate esters. In the absence of trifluoroacetic acid, the intermediate vinyl thioesters can be isolated. That addition of the thioamide to the first formed carbene was, through sulfur, confirmed by X-ray crystal structures of 2-methylthiazole-5-carboxylic acid and a byproduct.

A Convenient Synthesis of 2-Substituted Thiazole-5-carboxylates

The photolysis of ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate in acetonitrile containing 0.5% tri- fluoroacetic acid in the presence of thioamides gives moderate (40–60%) yields of thiazole-5-carboxylate esters. In the absence of trifluoroacetic acid, the intermediate vinyl thioesters can be isolated. That addition of the thioamide to the first formed carbene was, through sulfur, confirmed by X-ray crystal structures of 2-methylthiazole-5-carboxylic acid and a byproduct.

Synthesis and characterization of the anionic fluorocarboranes 6,7,8,9,10-CB 9H 5F 5 −, 6,7,8,9-CB 9H 5F 4-10-OH −, and 6,7,8,9-CB 9H 5F 4-10-NHCOCH 3 −

The reactions of salts of the 6,7,8,9-CB 9H 6F 4 − and CB 9H 10 − anions with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA) in acetonitrile in the presence or absence of trifluoroacetic acid were studied. The addition of trifluoroacetic acid to the reaction mixture significantly changed the concentration ratio of the two pentafluoro isomers produced in the reactions, [6,7,8,9,10-CB 9H 5F 5 −]/[2,6,7,8,9-CB 9H 5F 5 −]. The ratio increased from 0.6 to >23 when the solvent was changed from neat acetonitrile to a 20% solution of trifluoroacetic acid in acetonitrile while simultaneously raising the temperature from 25°C to 60°C. The synthesis and 11B and 19F NMR spectroscopic characterization of the 6,7,8,9,10-CB 9H 5F 5 − anion are reported here for the first time. Chromatographic separation of the reaction mixtures led to the isolation of salts of two additional new anions, 6,7,8,9-CB 9H 5F 4-10-NHCOCH 3 − and 6,7,8,9-CB 9H 5F 4-10-OH −. The structure of [PPh 4][6,7,8,9-CB 9H 5F 4-10-NHCOCH 3] was determined by X-ray crystallography: monoclinic, space group P2 1/ n, a=7.5169(3), b=23.2793(10), c=16.6170(7) Å, Z=4, T=−113°C, least-squares refinement on F 2, R 1 ( I>2 σ( I))=0.0805, wR 2 (all data)=0.1922.

2-Cyanoacrylates in the conjugate addition of trifluoroacetic acid and nucleophilic reagents

In the presence of trifluoroacetic acid, ethyl 2-cyanoacrylate readily reacts with nucleophilic reagents, such as 2-chloro-1,3,2-benzodioxaphosphole, (EtO)3P, (EtO)2PCl, Ph2PCl, Ph3P, and thiourea. In these reactions the acid proton enters position 2 of the cyanoacrylate, whereas the nucleophilic component enters position 3, in accordance with the electron density distribution in the acrylate. In the absence of trifluoroacetic acid the above reagents, except 2-chloro-1,3,2-benzodioxaphosphole, cause ethyl 2-cyanoacrylate polymerization. The interaction of ethyl 2-cyanoacrylate with 2-chloro-1,3,2-benzodioxaphosphole and trifluoroacetic acid is the first example of a 2-cyanoacrylate taking part in the acid-initiated electrophilic conjugate addition of a weak nucleophile.

Electrophilic aromatic N-substitution by ethoxycarbonylnitrenium ion generated from ethyl azidoformate in the presence of trifluoroacetic acid

Thermal reactions of ethyl azidoformate with aromatic compounds in the presence of trifluoroacetic acid (TFA) gave ethyl N-arylcarbamates. Toluene, nitrobenzene, or naphthalene was selectively attacked on the ortho- and para-positions, on the ortho- and meta-positions, or on the 1- and 2-positions, respectively. The yields were ca. twice as high as those for thermolysis (a nitrene–azepine route) in the absence of TFA with the subsequent addition of TFA at room temperature. The positional selectivities for toluene and naphthalene were lower for the former thermolysis than for the latter. The reactivity of cyclohexane or toluene relative to benzene was greater in the latter thermolysis than the former. A Hammett plot with ρ–1.7 was obtained for the formation of ethyl N-arylcarbamates in the former thermolysis in TFA–nitrobenzene (8 : 2 v/v); the value was more negative than that (–1.32) for the disappearance of substituted benzenes in the reaction with ethoxycarbonylnitrene. The results suggest that the thermolysis in the presence of TFA involves an electrophilic aromatic N-substitution by ethoxycarbonylnitrenium ion.

Studies on sulfenamides. VI. Cyclic voltammetry and controlled potential electrolysis of 4'-substituted 2-nitrobenzenesulfenanilides in the presence of trifluoroacetic acid or pyridine.

Anodic oxidation of 4'-substituted 2-nitrobenzenesulfenanilides (4'-OMe (1a), 4'-Me (1b), 4'-H (1c), 4'-Cl (1d), 4'-COOEt (le), 4'-COCH3 (1f), 4'-NO2 (1g)) and 4'-ethoxycarbonyl-N-methyl-2-nitrobenzenesulfenanilide (1h) was investigated by cyclic voltammetry and controlled potential electrolysis at a glassy-carbon or a reticulated vitreous carbon anode in acetonitrile containing 1% trifluoroacetic acid (TFA) or 1% pyridine. The peak potentials of 1a-g in acetonitrile containing TFA were 0.23-0.55 V more positive than those in acetonitrile containing pyridine. On the other hand, the peak potential of 1h was not affected by addition of TFA or pyridine. This suggests that 1a-g partially dissociate into the sulfenamide anions in the presence of pyridine. Electrolysis of 1a, 1b, and 1d in the presence of TFA gave the corresponding 2, 7-disubstituted phenazines in higher yields than that in the absence of TFA. Although electrolysis of 1e and 1f did not give the corresponding phenazines in the absence of TFA, in the presence of TFA it did. Electrolysis of 1c and 1g did not give the corresponding phenazines in the presence or absence of TFA. Electrolysis of 1a-d in the presence of pyridine gave the corresponding pyridinated sulfenanilides, and that of 1e and 1f gave the corresponding 4, 4'-disubstituted azobenzenes. Electrolysis of 1g gave p-nitroaniline both in the absence and presence of pyridine. The variation of yields of the phenazines and species of the products was explained in terms of the extent of dissociation of the dication intermediate, which in turn depends on the 4'-substituent. The nitrenium ions and nitrenes are suggested to be intermediates in the formation of the corresponding phenazines and the primary amines, respectively. The azobenzenes are considered to be oxidation products of the primary amines.

Aroyl Arenesulfonyl Peroxides IV. The Mechanism of Carboxy-inversion of Benzoyl p-Toluenesulfonyl Peroxide

Abstract Benzoyl p-toluenesulfonyl peroxide (BTP) with 18O-labeled carbonyl oxygen and 18O-labeled sulfonyl oxygen were prepared. They were decomposed in benzene in the presence or in the absence of trifluoroacetic acid,and the phenyl p-toluenesulfonyl carbonate (PTC)-18O produced was isolated and analyzed. It was found that the carbonyl oxygen-18 of BTP was retained as the carbonyl oxygen of PTC, whereas the sulfonyl oxygen-18 of BTP was equilibrated with the peroxidic oxygen. The mechanism of the carboxy-inversion was discussed.

Ionic Decomposition of Phenylazotriphenylmethane in Trifluoroacetic Acid

Abstract Acid-catalyzed decomposition of phenylazotriphenylmethane was studied in mixtures of benzene and large excess concentration of trifluoroacetic acid. The decomposition was of first order and the rate was much faster than that in pure aromatic solvents. The values of activation energy (Ea=22.3 kcal/mol) and activation entropy (ΔS\eweq=−5.2 e.u) fit the isokinetic relationship established for the ionic decomposition of benzenediazonium tetrafluoroborate in aprotic polar solvents and of phenylazo p-tolyl sulfone in mixtures of benzene and trifluoroacetic acid. The reaction products were benzene, biphenyl, benzophenone, triphenylmethane, triphenylmethyl alcohol and nitrogen. Orientations and partial rate factors for the phenylation of monosubstituted benzenes indicated that not phenyl radical but phenyl cation was produced as an intermediate. Further, the UV spectrum of PAT in benzene and trifluoroacetic acid shows λmax at 403 mμ (logε 4.48) and λmax at 427 mμ (logε 4.48). However, the UV spectrum of PAT in benzene and in the absence of trifluoroacetic acid has no absorption in this range. The formation of triphenylmethyl alcohol and the UV spectra of PAT in acid solution indicate that triphenylmethyl cation was formed as an intermediate. A plausible mechanism was discussed.