Trifluoroacetic Acid Solution Research Articles

Scale-Up of the Nitration of 1-Acetyl-3,4-dichloro-1,2-(ethylenedioxy)benzene Using Nitric Acid/Trifluoroacetic Acid

The process development of the nitration of 3-acetyl-4,5-dichloro-1,2-(ethylenedioxy)benzene (1) to 3-acetyl-4,5-dichloro-1,2-(ethylenedioxy)-6-nitrobenzene (2) led to two potential scale-up processes. The two nitration processes were a solids addition to nitric acid and nitric acid addition to a trifluoroacetic acid solution. The detailed hazards safety evaluation of the two processes was carried out using abuse studies, CHETAH calculations, the reactive system screening tool, accelerating rate calorimetry, and differential scanning calorimetry. The nitric acid addition to a trifluoroacetic acid solution process was chosen because of the better safety profile. This process was successfully scaled up in a pharmaceutical pilot plant.

Oxidative rearrangement of imines to formamides using sodium perborate

Abstract Oxidation of C-aryl or alkyl-N-arylaldimines 6 or 20 by sodium perborate tetrahydrate (SPB) in trifluoroacetic acid solution gives rearranged N,N-disubstituted formamides 9 and 21. Yields are variable and solvent dependant with the best yields (50–60%) being obtained for electronically neutral C-aryl substituents or C-s-alkyl substituents. Product formation is rationalised in terms of an intermediate oxaziridine 5 that rearranges via acid catalysed ON bond cleavage. An alternative CO bond cleavage of these intermediates accounts for the formation of aldehydes, which are common by-products. Rearrangement appears to be favoured by N-aryl substituents and by C-substituents that do not stabilise a developing positive charge on carbon. Further support for an oxaziridine intermediate 5 is provided by the observation that MCPBA oxidation of benzaldehyde phenylimine gives rearranged N,N-diphenylformamide. Under the conditions of the SPB oxidative rearrangements, oxaziridine formation may well occur by initial formation of trifluoroperacetic acid. Stereochemical aspects of this novel rearrangement of aldimines 1 → 2 have been investigated using trans- and cis-myrtanal 25 and 30. The observed epimerisation using the N-4-tolyl imine of trans-myrtanal 26 is believed to arise from equilibration of the precursor imine 26 with the tautomeric enamine 35b.

Two-mode Analysis by High-performance Liquid Chromatography ofρ-Aminobenzoic Ethyl Ester-derivatized Monosaccharides

ρ-Aminobenzoic ethyl ester (ABEE)-derivatized monosaccharides were separated by HPLC with a trifluoroacetic acid (TFA) solution or borate buffer as the eluent. In the case of the TFA solution, ABEE-derivatized monosaccharides of the neutral and amino sugars found in animal glycoproteins were separated in a simultaneous analysis. In the case of the borate buffer, ABEE-derivatized monosaccharides of identical molecular weights such as ABEE-Gal, -Glc, and -Man were separated as stereoisomers. Glucuronic acid and galacturonic acid were detected and separated within 8 min. The relationship between the peak areas and the amounts of ABEE-derivatized monosaccharides was linear in the range of 1 to 1000 pmol.

High-performance liquid chromatography of peptides on a microspherical carbon column

The properties of a microspherical carbon column for the separation of peptides and proteins are described. One hundred and thirty-three peptides, with from 1 to 148 amino acid residues, were applied on a carbon column and eluted with a linear gradient of acetonitrile [10–70% (v/v), 30 min] in 0.1% (v/v) trifluoroacetic acid solution. The elution behaviour of the peptides on the carbon column and on an octadecylsilica (ODS) column were compared under the same elution conditions. Relationships between the logarithm of the hydrophobicity of peptides and their capacity factors were approximately linear on both columns, but some exceptions were observed with peptides with aromatic residues, indicating stronger adsorption on the carbon than on the ODS column. These results suggest that the major factor for the separation of peptides on both the carbon and ODS columns is hydrophobic interactions. The stronger adsorption of aromatic side-chains in peptides on the carbon column could be understood by an interaction based on the aromatic of graphitic nature of the surface of the microspherical carbon packings.

High-performance liquid chromatographic analysis of ( S)- α-amino-5-phosphonomethyl[1,1′-biphenyl]-3-propanoic acid (EAB 515) in brain and blood microdialysate (on-line) and in plasma ultrafiltrate of freely moving rats

( S)- α-Amino-5-phosphonomethyl[1,1′-biphenyl]-3-propanoic acid (EAB 515, I), a competitive antagonist of the N-methyl- d-aspartate receptor, has significant pharmacological activity in the central nervous system (CNS). An extremely sensitive and selective analytical method was developed for the simultaneous analysis of I and its hydroxylated analog (RDC, II) in the microdialysate (MD) and plasma ultrafiltrate (UF) of rats. Microdialysis was used for in vivo sampling of unbound drug in the CSF, cortical extracellular fluid and in the blood of freely moving rats. Compound II was used for retrodialysis-based in vivo calibration of microdialysis probes to estimate the recovery of I. Compound I, being extremely hydrophilic with a high degree of ionization at the physiological pH of 7.4, has limited access to the brain regions. This, combined with its low microdialysis recovery, made the estimation of low brain concentrations of I a challenge. The analytes in MD and UF were separated (within 5 min) by reversed-phase HPLC on a 250×4.6 mm I.D. Maxsil 5 μm RP-2 column, and fluorescence of the eluent was monitored at 255 nm ( λ ex) and 320 nm ( λ em). A 0.09% (v/v) aqueous solution of trifluoroacetic acid (1 ml/min) was used as the mobile phase. The response for I in MD and UF samples was linear from 5 to 2000 ng/ml and from 20 to 10 000 ng/ml, respectively. The between-run ( n=6) and within-run ( n=3) variability of the assay was <15%. Plasma-protein binding of I ( f u=0.68) was determined to be linear from 0.1 to 10 μg/ml. The analytical sensitivity, precision and accuracy of this method was suitable for the characterization of the pharmacokinetics and the CNS distribution of I, following administration of intravenous (i.v.) infusion, single i.v. bolus and multiple i.v. bolus doses of I to freely moving rats, with continuous microdialysate sampling of multiple tissues and simultaneous on-line HPLC analysis. Pharmacokinetic parameters for I, as determined from concentrations in blood MD samples with on-line analysis, were in good agreement with those estimated from concentrations in the UF of plasma samples obtained by conventional sampling.

Signal enhancement for gradient reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol

Trifluoroacetic acid (TFA) and other volatile strong acids, used as modifiers in reverse-phase high-performance liquid chromatography, cause signal suppression for basic compounds when analyzed by electrospray ionization mass spectrometry (ESI-MS). Evidence is presented that signal suppression is caused by strong ion pairing between the TFA anion and the protonated sample cation of basic sample molecules. The ion-pairing process "masks" the protonated sample cations from the ESI-MS electric fields by rendering them "neutral. " Weakly basic molecules are not suppressed by this process. The TFA signal suppression effect is independent from the well-known spray problem that electrospray has with highly aqueous solutions that contain TFA. This previously reported spray problem is caused by the high conductivity and surface tension of aqueous TFA solutions. A practical method to enhance the signal for most basic analytes in the presence of signal-suppressing volatile strong acids has been developed. The method employs postcolumn addition of a solution of 75% propionic acid and 25% isopropanol in a ratio 1:2 to the column flow. Signal enhancement is typically 10-50 times for peptides and other small basic molecules. Thus, peptide maps that use ESI-MS for detection can be performed at lower levels, with conventional columns, without the need to use capillary chromatography or reduced mass spectral resolution to achieve satisfactory sensitivity. The method may be used with similar results for heptafluorobutyric acid and hydrochloric acid. A mechanism for TFA signal suppression and signal enhancement by the foregoing method, is proposed.

Synthesis of a novel optically active nylon‐1 polymer: Anionic polymerization of L‐leucine methyl ester isocyanate

AbstractSynthesis and anionic polymerization of the isocyanate of L‐leucine methyl ester (LeuMI) were carried out. LeuMI was prepared by the reaction of L‐leucine methyl ester hydrochloride with phosgene. Anionic polymerization of LeuMI was carried out at –50°C in dimethyl‐formamide (DMF) using sodium methoxide, potassium tert‐butoxide, methyllithium, or sodium cyanide under a nitrogen atmosphere. The obtained polymers were insoluble in common organic solvents such as DMF, tetrahydrofuran, chloroform, and dimethyl sulfoxide, but were soluble in trifluoroacetic acid. Further, anionic copolymerization of LeuMI with n‐butyl isocyanate (BI) was also carried out to observe that the smaller the content of LeuMI unit in the copolymer was, the larger the specific rotation of the polymer. From the circular dichroic spectral analyses of the polymers it was confirmed that the capability of helix formation of poly (LeuMI) was smaller than poly(BI). The relaxation of the helical structure of the polymer in trifluoroacetic acid solution was observed, and the smaller the content of LeuMI unit in the copolymer was, the faster the relaxation of the helical structure. © 1995 John Wiley &amp; Sons, Inc.

Multinuclear NMR study of protonation in some indolizine systems

Abstract1H, 13C and 15N NMR data are presented for seven indolizine derivatives in solutions of dimethyl sulphoxide and trifluoroacetic acid (TFA). The TFA solutions contain species protonated at position N‐1 in all cases. The most definitive evidence for the site of protonation is provided by the 15N results.

Preparation, characterization, and mesophase formation of esters of ethylcellulose and methylcellulose

AbstractA range of mixed ether‐esters of cellulose was prepared from partially substituted ethylcellulose and methylcellulose. The 13C‐NMR analysis of ethylcellulose with a DS of 2.5 indicated that the hydroxyl groups at carbon six of anhydroglucose units were completely substituted. Acetylation of the ethylcellulose under different conditions yielded (acetyl) (ethyl) cellulose (AEC) samples with acetyl degree of substitution ranging from 0 to 0.5. Fully substituted (propionyl) (ethyl) cellulose (PEC) and (acetyl) (methyl) cellulose (AMC) were also prepared. Chiral nematic liquid crystals were formed in these mixed ester/ethers of cellulose in concentrated solutions of acidic solvents. The critical concentration for the phase separation of the cellulosic solutions depended on the nature of the substituent, the degree of substitution, and the solvent at a given temperature. Methylcellulose solutions in trifluoroacetic acid and dichloroacetic acid form chiral nematic liquid crystals with a left‐handed helicoidal structure. The acetylated methyl cellulose samples did not show the reversal of handedness with increasing acetyl content that was previously observed for the corresponding ethylcellulose samples. © 1994 John Wiley &amp; Sons, Inc.

Structural study of compounds modelling elementary polymer units, 6. X‐ray structural and quantum‐chemical investigation of the cis‐ and trans‐isomeric models of the polynaphthoylenebenzimidazole elementary units

AbstractThe X‐ray structural investigation of the naphthoylenebis‐(benzimidazole) (1) cis‐ and trans‐isomers as models for the cis and trans elementary units of the corresponding poly(naphthoylene‐benzimidazoles) (PNBI) was carried out. The correctness of the previous identification of the isomers was confirmed, and exact geometrical parameters of the PNBI elementary units (required, in particular, for the calculation of the Kuhn segment of PNBI) were determined. Quantum‐chemical semi‐empirical calculations of the ground and excited electronic states of the isomers were carried out. Both experimental and theoretical data confirm a larger stability of the planar π‐conjugated structure of the trans‐isomer in comparison with the cis‐isomer in the ground as well as in the excited electronic state. Crystals of the cis‐ and trans‐isomers obtained from trifluoroacetic acid solutions are the solvates of bis(trifluoroacetates) of diprotonated 1 with an extremely high content of the solvating trifluoroacetic acid. This peculiarity is favourable for modelling the main characteristics of the interaction between PNBI and protonic polar solvent molecules, viz. preferred types of H‐bonding and a possibility of interaction of the electronic lone pairs of the solvent molecules with the π‐electronic systems of the elementary units of PNBI by charge transfer complexes.

Ring-chain tautomerism of thiosemicarbazones of salicylaldehyde and pyridinecarbaldehyde in acidic media

On the basis of NMR spectroscopic data, it has been found that 4-substituted thosemicarbazones of salicylaldehyde and α-, β-, and γ- pyridinecarbaldehydes in solutions of trifluoroacetic acid are tautomeric mixtures of protonated linear and cyclic 1, 3, 4-thiadiazolidine-2-imine forms, the linear tautomer having an azinethiol structure with localization of the proton on the N(2) nitrogen atom.

An influence of a basic side chain moiety on the tautomer ratio between the enamine and methylene imine forms in azole condensed quinoxalines

AbstractThe reaction of 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)tetrazolo[1,5‐α]quinoxaline 2a with 4‐aminopyridine, p‐toluidine or p‐aminophenol gave 7‐chloro‐4‐(4‐pyridylcarbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]‐quinoxaline 7a, 7‐chloro‐4‐(p‐tolylcarbamoylmethylene)4, 5‐dihydrotetrazolo[1,5‐α]quinoxaline 8a or 7‐chloro‐4‐(p‐hydroxyphenylcarbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 9a, respectively. The reaction of 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)‐1,2,4‐triazolo[4,3‐α]quinoxaline 2b with 4‐aminopyridine, p‐toluidine or p‐aminophenol afforded 7‐chloro4‐(4‐pyridylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo‐[4,3‐α]quinoxaline 7b, 7‐chloro‐4‐(p‐tolylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo[4,3‐α]quinoxaline 8b or 7‐chloro‐4‐(p‐hydroxyphenylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo[4,3‐α]quinoxaline 9b, respectively. The reaction of compound 2a with 2‐aminopyridine or 3‐aminopyridine provided 7‐chloro‐4‐(2‐pyridyl‐carbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 10 or 7‐chloro‐4‐(3‐pyridyl‐carbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 11, respectively. Compounds 7a,b(4‐pyridylcarbamoyl) predominated as the enamine tautomer A in a trifluoroacetic acid solution, while compounds 8a,b (p‐tolylcarbamoyl) and compounds 9a,b (p‐hydroxyphenylcarbamoyl) coexisted as the enamine A and methylene imine B tautomers in a trifluoroacetic acid solution. Moreover, the ratio of the enamine tautomer A elevated in an order of compound 11 (3‐pyridylcarbamoyl), compound 10 (2‐pyridylcarbamoyl) and compound 7a (4‐pyridylcarbamoyl), reflecting an order of the increase in the pKa values of the aminopyridine side chain moieties. In general, the ratio of the enamine tautomer A was higher in the basic carbamoyl derivatives 7–11 than in the neutral ester derivatives 3a,b. From these results, the basic side chain moiety of the tetrazolo[1,5‐α]quinoxalines 7a‐11 or 1,2,4‐triazolo[4,3‐α]quinoxalines 7b‐9b was found to increase the ratio of the enamine tautomer A in trifluoroacetic acid media.

Cl . atom electrosorption and recombination at oxide-free and oxide-covered surfaces of Pt anodes, evolving Cl 2 in CF 3· COOH

In anhydrous trifluoroacetic acid (TFA), it has been shown that anodic Cl 2 evolution from dissolved RbCl arises from discharged Cl − and recombination of the resulting adsorbed Cl . radicals on an oxide-free surface of Pt, which is in contrast to the situation from aqueous Cl − solutions, where coadsorbed Cl, and OH and O species provide the electrocatalytic surface on which Cl . recombination to Cl 2 takes place. By means of recording and analysis of potential-relaxation transients, coupled with impedance spectroscopy studies, the adsorption behaviour of the Cl . intermediate at the oxide-free Pt surface in TFA has been determined in relation to the Cl . recombination kinetic step, which is indicated as the rate-controlling Cl . desorption pathway. The Cl . adsorption and kinetic behaviour at preoxidized Pt electrodes, also in TFA solutions of Cl −, are examined and discussed comparatively. Although in anhydrous TFA solution the Cl 2 evolution reaction demonstrably takes place on a completely oxide-free surface, Cl . recombination-controlled kinetics are also found for oxide-covered Pt, both in TFA and aqueous Cl − solutions. However, the coverage by the Cl . adsorbed intermediate remains relatively small, even towards the limiting current; this is attributed to strong competitive adsorption of the TFA solvent molecule.

Ring-Chain Tautomerism of N-Substituted Thiosemicarbazones

The condensation products from 4,4-dimethyl- and 2,4,4-trimethylthiosemicarbazides and aldehydes or ketones, as well as those from 2-methyl- and 2,4-disubstituted thiosemicarbazides and aldehydes have the thiosemicarbazone structure, while ketones react with 2-methyl- or 2,4-dialkylthiosemicarbazides to form 1,2,4- triazolidine-3-thiones. Both thiosemicarbazones and 1,2,4- triazolidine-3-thiones in trifluoroacetic acid solution yield 1,3,4-thiadiazolidine-2-iminium salts. Their deprotonation by pyridine leads to thiosemicarbazones, including otherwise inaccessible 2-methyl- and 2,4-disubstituted ketone thiosemicarbazones. The mass-spectrometric investigation of these compounds also suggests presence of their tautomers in the gas phase.

Dissolving states of cellulose and chitosan in trifluoroacetic acid

AbstractChemical structures of cellulose and chitosan dissolved in trifluoroacetic acid (TFA) and those of cellulose and chitosan films cast from their TFA solutions were studied by 13C‐NMR and infrared (IR) spectroscopy. Cellulose is trifluoroacetylated selectively at the C6–hydroxyl groups in the TFA solution, and chitosan is dissolved in TFA by forming amine salts with TFA at the C2–amine groups. IR analyses of cellulose films cast from its TFA–acetic acid solutions showed that partly trifluoroacetylated cellulose in the solution state turns to partly acetylated cellulose in the solid state during evaporation of the solvents in air by the ester interchange. Chitosan films cast from its TFA–acetic acid solutions still have the amine salts with TFA. These acetyl groups in cellulose films and TFA in chitosan films are removable by soaking the films in 1N NaOH at room temperature for 1 day.

Thermal and structural study of the phase transitions in liquid crystalline poly(heptamethylene terephthaloyl-bis-4-oxybenzoate)

The structure and thermal transitions of liquid crystalline poly(heptamethylene terephthaloyl-bis-4-oxybenzoate) have been studied by differential scanning calorimetry, X-ray diffraction and optical microscopy. A very important influence of different thermal treatments in the formation of crystal and mesophase has been found. The sample originating from the synthesis has a crystalline and a liquid crystalline phase at room temperature. However, by evaporation of trifluoroacetic acid solution, it is possible to obtain only the crystalline phase. By quenching the sample from the liquid crystal state into liquid nitrogen, the smectic mesophase can be ‘frozen in’.

Alkane activation by homogeneous palladium complexes

AbstractThe conversion of adamantane exclusively to 1‐adamantyl trifluoroacetate in a refluxing trifluoroacetic acid solution of palladium acetate at 1 atm of air or nitrogen was confirmed. The conversion can be made quantitative. The 1‐adamantyl trifluoroacetate was hydrolysed to yield 1‐adamantanol in 90% isolated yield. The adamantane functionalization is accompanied by concomitant formation of a palladium mirror.

Oxidation of ethane and propane with cobalt(II) catalyst: unexpected formation of 1,2-diol esters and C–C bond cleavage

Ethane reacts with both cobalt(III) and O2–cobalt(II) in trifluoroacetic acid solution to form ethyl trifluoroacetate and 1,2-bistrifluoroacetoxyethane in successive reactions, along with the products of C–C bond cleavage; propane undergoes similar oxidative reactions.

High-performance liquid chromatographic method for the determination of prolyl peptides in urine

A rapid and accurate method is described for the determination of prolyl peptides in urine, with specific reference to the dipeptide prolylhydroxyproline, and free hydroxyproline and proline. Free amino acids and peptides were isolated from urine on cation-exchange minicolumns, and free imino acids and prolyl-N-terminal peptides were selectively derivatized with 4-chloro-7-nitrobenzofurazan, after reaction of amino acids and N-terminal aminoacyl peptides with o-phthalaldehyde. The highly fluorescent adducts of imino acids and prolyl peptides were separated on a Spherisorb ODS 2 column by isocratic elution for 12 min using as mobile phase 17.5 m M aqueous trifluoroacetic acid solution containing 12.5% acetonitrile (eluent A), followed by gradient elution from eluent A to 40% of 17.5 m M aqueous trifluoroacetic acid solution containing 80% acetonitrile in 20 min. Analytes of interest, in particular the dipeptide prolylhydroxyproline, can be easily quantified by fluorimetric detection (ε ex = 470 nm, ε em  530 nm) without interference from primary amino-containing compounds.

ChemInform Abstract: Ozonization of Perfluoroolefins in Trifluoroacetic Acid Solution.

ChemInformVolume 21, Issue 5 Preparative Organic Chemistry ChemInform Abstract: Ozonization of Perfluoroolefins in Trifluoroacetic Acid Solution. N. I. MOISEEVA, N. I. MOISEEVA Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorA. E. GEKHMAN, A. E. GEKHMAN Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorE. S. RUMYANTSEV, E. S. RUMYANTSEV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorV. I. KLIMANOV, V. I. KLIMANOV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorI. I. MOISEEV, I. I. MOISEEV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this author N. I. MOISEEVA, N. I. MOISEEVA Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorA. E. GEKHMAN, A. E. GEKHMAN Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorE. S. RUMYANTSEV, E. S. RUMYANTSEV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorV. I. KLIMANOV, V. I. KLIMANOV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this authorI. I. MOISEEV, I. I. MOISEEV Inst. obshch. i neorg. khim. im. Kurnakova AN SSSR, MoskvaSearch for more papers by this author First published: January 30, 1990 https://doi.org/10.1002/chin.199005098Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue5January 30, 1990 RelatedInformation