Some observations on the spectrophotometric determination of amino acids via interaction with p-benzoquinone

Spectrophotometric quantitative determination of amines and sulfa drugs via interaction with p-benzoquinone was extended to determination of amino acids, whereby the colored products obtained display maximum absorption at λ = 490–500 nm, E₁ cm^1% in the range 160–480, and a concentration range of 1.5–34.0 μg/ml. The effects of time, concentration, temperature, and cooling on the nature of the reaction product were investigated. The reaction proved to be irreversible. A monosubstituent compound is more easily formed in the presence of excess p-benzoquinone. A linear relation between the formation constant (K_f) and pK_α for the tested amino acids has been observed. Determination of adrenaline by this method is considered to offer an indirect means of determination of tyrosine.     

Determination of C1−C4 fatty acids as p-bromophenacyl esters using glass-capillary gas chromatography and electron-capture detection

Summary A method for the determination of low relative molecular mass carboxylic acids (C₁–C₄) in water is reported. The acids are converted to p-bromophenacyl esters prior to a glass-capillary gas chromatographic separation. By utilizing electron-caputre detection the detectability is substantially improved compared to flame-ionization detection. A comparison of three different ways to treat the water samples and to produce the derivatives is made. It is shown that the , p-dibromoacetophenone reagent decomposes to a small extent which limits the utility of the reagent. Nevertheless a detection limit for formic acid of approximately 2.5 mgl^–1 is obtained. The method is applied to the determination of formic and acetic acids in a paper kraft water sample.     

Reagent peak-free liquid chromatography–fluorescence analysis of carboxylic acids using a fluorous scavenging–derivatization method

We developed a fluorous scavenging–derivatization method for reagent peak-free liquid chromatography (LC)–fluorescence analysis of carboxylic acids. In this method, carboxylic acids were fluorescently derivatized with 1-pyrenemethylamine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxy-1H-benzotriazole. Residual excess unreacted reagent was tagged with 2-(perfluorooctyl)ethyl isocyanate and could be selectively removed by microfluorous solid-phase extraction before LC analysis. With use of this method, eight fluorescent derivatives of linear aliphatic carboxylic acids (C₁–C₈) can be separated within 30 min by reversed-phase LC with gradient elution. In the chromatogram obtained, the fluorous-tagged unreacted reagent peak is greatly decreased after microfluorous solid-phase extraction and does not interfere with the quantification of each acid. With use of microfluorous solid-phase extraction with 80% (v/v) aqueous methanol elution, over 99.9% of the unreacted fluorescent reagent was removed. The detection limits (signal-to-noise ratio of 3) for the carboxylic acids examined are 2.3–8.0 fmol per 10-μL injection. We also applied this method successfully to the analysis of highly polar carboxylic acids such as α-keto acids and tricarboxylic acid cycle metabolites.     

Thermodynamic Estimate of pKa Values of the Carboxylic Acids in Aqueous Solution with the Density Functional Theory

The 96 pK_a values of 85 carboxylic acids in aqueous solution were calculated with the density functional theory method at the level of B3LYP/6‐31+G(d,p) and the polarizable continuum model (PCM) was used to describe the solvent. In the calculations of pK_a values, the dissociation Gibbs free energies were directly calculated using carboxylic acid dissociation reactions in aqueous solution, i. e., no thermodynamic cycle was employed, which is different from the previous literatures. A highly significant correlation of R²=0.95 with a standard deviation (SD) of 0.36 between the experimental pK_a values and the calculated dissociation Gibbs free energies [ΔG(calc.)] was found. The slope of pK_a vs. (G(calc.)/(20303RT) is only 47.6% of the theoretically expected value, which implies that the ΔG(calc.) value from the theoretical calculation is larger than the actual one for all 85 carboxylic acids studied. Thus, by adding the 0.476 scaling‐factor into the slope, we can derive a reliably procedure that can reproduce the experimental pK_a values of carboxylic acids. The pK_a values furnished by this procedure are in good agreement with the experimental results for carboxylic acids in aqueous solution.     

Determination of C<Subscript>1</Subscript>-C<Subscript>3</Subscript> carboxylic acids in air using a sensor

The adsorption of C₁-C₃ carboxylic acids on modified films of different natures and polarities is studied in exposuring piezoelectric sensors to acid vapors. The method of film fabrication and the ratio of components in the mixed films are optimized; the sensitivity and selectivity of films are calculated; piezoelectric sensors are proposed for the separate determination of acids in air; and equations for calculating their concentrations are derived.     

Polarographic determination of picolinaldehyde in the presence of some related compounds

A d.c. polarographic method is described for the determination of picolinaldehyde (1.5 × 10^?5–2.9 × 10^?4 M), based on the in situ formation of its Girard-P derivative in aqueous solution. A mechanism of reduction (E_1/2 = ?0.71 V at pH 3.5) is proposed. The applicability of this method is checked in synthetic samples containing pyridine, picoline and pyridine carboxylic acids.     

Synthesis of derivatives of prenylacetic acids by reactions of alkyl malonate, cyanoacetate, and acetoacetate with alkylating reagents in ionic liquids

A method for the synthesis of carboxylic acid derivatives containing one or two —CH₂CH _n (Me)CH _n+1CH₂— fragments (n = 0, 1) was developed. The method is based on the alkylation of (di)alkyl malonates, cyanoacetates, and acetoacetates with acyclic prenyl halides in ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate and tetrafluoroborate. For the ambident ethyl acetoacetate anion, the reactions with prenyl halides devoid of a double bond in the allylic position relative to the halogen atom carried out in the ionic liquids give mixtures of C- and O-alkylation products, while in the case of allylic prenyl halides, only C-alkylation products are formed. The reactions of ethyl 2-geranylmalonate and 2-geranylacetoacetate with bromocyclohexane and 1-chloro-3-dimethylaminopropane in ionic liquids provided derivatives of pharmacologically active geranylacetic acids. The product yields are higher than those in molecular organic solvents. The ionic liquids were recovered and reused in the alkylation.     

A simple and rapid visual method for the determination of ammonia nitrogen in environmental waters using thymol

Simple visual and spectrophotometric methods for the determination of ammonia nitrogen in water are proposed, based on the color development of indothymol blue formed between ammonia and thymol. The color development was accelerated by nitroprusside to complete in 3 min. This color development is remarkably rapid compared with that of the other conventional methods with indothymol blue and indophenol blue. The concentration range of ammonia nitrogen spectrophotometrically determined was 0.04–1.2 mg/L NH₄-N. The absorbance per 1 μg NH₄-N was 0.0215 (molar absorptivity = 1.51 × 10⁴) at 690 nm. The visual method not using any instrument as an in situ method in field works was developed based on the optimum conditions for the established spectrophotometric method. This visual method was successfully applied to the determination of ammonia nitrogen in environmental waters. Received: 21 December 1998 / Revised: 31 May 1999 / /Accepted: 4 June 1999     

Nickel‐Catalyzed Cross‐Coupling of Redox‐Active Esters with Boronic Acids

A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross‐coupling between alkyl‐carboxylic acids and boronic acids is described. This Ni‐catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox‐active ester derivatives, specifically N‐hydroxy‐tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl₂?6 H₂O—$9.5 mol^?1, Et₃N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption.     

N-Boc-Protected α-Amino Acids by 1,3-Migratory Nitrene C(sp3)−H Insertion

N-Boc-protected α-amino acids are synthesized in two steps from linear or branched carboxylic acid feedstocks. In the first step, the carboxylic acid is coupled with tert-butyl aminocarbonate (BocNHOH) to generate azanyl ester (acyloxycarbamate) RCO₂NHBoc. In the second step, this azanyl ester undergoes a stereocontrolled iron-catalyzed 1,3-nitrogen migration to generate the N-Boc-protected non-racemic α-amino acid. This straightforward protocol is applicable to the catalytic asymmetric synthesis of α-monosubstituted α-amino acids with aryl, alkenyl, and alkyl side chains. Furthermore, α,α-disubstituted α-amino acids are accessible in an enantioconvergent fashion from racemic carboxylic acids. The new method is also advantageous for the synthesis of α-deuterated α-amino acids. N-Boc-protected α-amino acids synthesized using this two-step protocol are ready-to-use building blocks.     

Absolute Configuration Assignment from Optical Rotation Data by Means of Biphenyl Chiroptical Probes

A non-empirical approach for the assignment of the absolute configuration of chiral 2-alkyl-substituted carboxylic acids and primary amines by [α]_D measurements has been developed. The method requires the conversion of the chiral acids or amines into the corresponding 4,4′-disubstituted biphenylamides or biphenylazepines, respectively. In these derivatives a central-to-axial chirality transfer induces a preferred torsion in the biphenyl moiety revealed by the sign of the biphenyl A band in the ECD spectrum. By 4,4′-substitution on the biphenyl moiety a redshift of the A band is obtained, leading to an increase of its relative contribution to optical rotation. This allows to reliably establish a direct correlation between the [α]_D sign, the biphenyl twist and, then, the substrate absolute configuration. This approach thus constitutes a really practical and reliable method to assign the absolute configuration of chiral carboxylic acids and primary amines by simple and straightforward [α]_D measurement, readily obtainable by a routine instrumentation like the polarimeter.     

Estimation of pKa for organic oxyacids using calculated atomic charges

A method for the estimation of pK_a from empirically calculated atomic charges has been developed and tested on a diverse set of organic oxyacids. The approach involves a comparison of the atomic charges calculated for both the acid and the negative ion that is formed after loss of the acidic proton. These charges have been used in conjunction with the familiar concepts of induction and resonance to develop an accurate formula to predict pK_a. Results for a set of 135 compounds, including alcohols, phenols, and carboxylic acids, yielded a fit of pK_a with r = 0.993 and an rms error of 0.455. © John Wiley & Sons, Inc.     

α- and β-cyclodextrin complexes with n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates. A molecular mechanics study of 1:1 and 1:2 associations

Molecular mechanics (MM) methods were employed to evaluate stabilization upon formation of inclusion compounds between two different guest molecules and α- and β-cyclodextrins (CDs) for two different stoichiometries 1:1 and 1:2. The two guest molecules studied were n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates with variety of chain lengths. The computed stability for the inclusion compounds between α-CDs and n-alkyl carboxylic acids reproduced experimental data reported in the literature. The transition between 1:1/1:2 complexes occurred at an alkyl chain length of n_C=9. It was previously demonstrated by diffusion coefficients measures that a stable 1:2 stoichiometry inclusion compound could be formed between n-alkyl p-hydroxy benzoates and α-CD for the chain length n_C>4. The computed results reproduced the experimental ones. The combination between OPLS and GB/SA resulted in better agreements with experiments than those obtained with MM2 and MM3.     

Difference between Extra‐ and Intracellular T1 Values of Carboxylic Acids Affects the Quantitative Analysis of Cellular Kinetics by Hyperpolarized NMR

Incomplete knowledge of the longitudinal relaxation time constant (T₁) leads to incorrect assumptions in quantitative kinetic models of cellular systems, studied by hyperpolarized real‐time NMR. Using an assay that measures the intracellular signal of small carboxylic acids in living cells, the intracellular T₁ of the carboxylic acid moiety of acetate, keto‐isocaproate, pyruvate, and butyrate was determined. The intracellular T₁ is shown to be up to four‐fold shorter than the extracellular T₁. Such a large difference in T₁ values between the inside and the outside of the cell has significant influence on the quantification of intracellular metabolic activity. It is expected that the significantly shorter T₁ value of the carboxylic moieties inside cells is a result of macromolecular crowding. An artificial cytosol has been prepared and applied to predict the T₁ of other carboxylic acids. We demonstrate the value of this prediction tool.     

Determination of hydrazides and 1,2-diacylhydrazines of aliphatic carboxylic acids by conductometric titration

A procedure is developed for the conductometric titration of hydrazides and 1,2-diacylhydrazines of aliphatic carboxylic acids with HCl or KOH in nonaqueous and water-alcohol solutions. The procedure is suitable for the determination of the major substance in hydrazides of C₅H₁₁-C₁₂H₂₅ aliphatic carboxylic acids and CH₃-C₇H₁₅ 1,2-diacylhydrazines and for the analysis of reaction mixtures containing N₂H₄, RCOOH, and RCOOH · N₂H₄ along with the major substance.     

Density functional theoretical study of pKa of RCOOH (RH,CH3, and C2H5) using the combination of the extended clusters‐continuum model

The accurate pK_a determinations for three carboxylic acids have been investigated using the combination of the extended clusters‐continuum model at B3LYP/6‐31+g(d,p) and B3LYP/6‐311++g(d,p) levels. To take into account of the effect of the water combined with carboxylic acids in different positions, eleven molecular clusters were considered. Among these clusters, the one involving the carboxylic acid wrapped up with water molecules and saturated with hydrogen bonds (four hydrogen bonds around ? COOH) leads to the best B3LYP pK_a results compared to the experimental data. For those clusters saturated with hydrogen bonds, when n = 3 (the number of water molecules), the average absolute errors between the calculated pK_a results and experimental data of these three carboxylic acids were 0.19 (0.23) and 0.12 (0.22) pK_a at B3LYP/6‐31+g(d,p)//PCM (IEFPCM) and B3LYP/6‐311++g(d,p)//PCM (IEFPCM) levels, respectively; when n = 4, they are 0.53 (1.23) and 1.09 (1.03) pK_a, respectively. On the basis of the above results, the molecular cluster saturated with four hydrogen bonds formed by three waters and one carboxylic acid molecule was the chief existence in the carboxylic acid solution. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

A Short Synthesis of Allene- and [3] Cumulenecarboxylates

It is shown that carboxylic acids, in the presence of Bu₃N and 2-chloro-1-methylpyridinium iodide in toluene or CH₂Cl₂, react with [(alkoxycarbonyl)methylidene]phosphoranes to yield the corresponding esters of allene carboxylic acids (ef. Scheme 1 and Table 1). This procedure can also be applied to cinnamic acids which form [3]cumulenecarboxylates in low yield (Table 3). Under the same conditions 4-methyl-2-pentynoic acid can be transformed into (2E)-4-chloro-2,6-dimethylhepta-2,4,5-trienoate (Scheme 4).     

Determination of trans-fatty acids in food samples based on the precolumn fluorescence derivatization by high performance liquid chromatography

Trans-fatty acids are unsaturated fatty acids that are considered to have health risks. 1,3,5,7-Tetramethyl-8-butyrethylenediamine-difluoroboradiaza-s-indacene is a highly sensitive fluorescent labeling reagent for carboxylic acids developed by our lab. In this study, using this precolumn fluorescent derivatization reagent, a rapid and accurate high-performance liquid chromatography with fluorescence detection method was developed for the determination of two trans-fatty acids in food samples. Under the optimized derivative conditions, two trans-fatty acids were tagged with the fluorescent labeling reagent in the presence of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide at 25°C for 30 min. Then, the baseline separation of trans- and cis-fatty acids and their saturated fatty acid with similar structures was achieved with less interference using a reversed-phased C₁₈ column with isocratic elution in 14 min. With fluorescence detection at λ_ex/λ_em = 490 /510 nm, the linear range of the TFAs was 1.0-200 nM with low detection limits in the range of 0.1–0.2 nM (signal-to-noise ratio = 3). In addition, the proposed approach was successfully applied for the detection of trans-fatty acids in food samples, and the recoveries using this method ranged from 96.02 to 109.22% with low relative standard deviations of 1.2–4.3% (n = 6).     

Hydrocarbomethoxylation of C5-C9 olefins with formic acid and methanol under conditions of catalysis with phosphoric acid

Conclusions The methyl esters of branched carboxylic acids containing quaternary and tertiary C atoms in the-position, together with a small amount of the corresponding carboxylic acids, are formed during the hydrocarbomethoxylation of the straight-chain C₅-C₉ olefins at atmospheric pressure in the presence of concentrated H₃PO₄.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 454–456, February, 1973.     

An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator

A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propanephosphonic acid cyclic anhydride (T3P) and subsequent reduction using NaBH₄ yield the alcohol in excellent yields with good purity. Reduction of several alkyl/aryl carboxylic acids and N^α-protected amino acids/peptide acids as well as N^β-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields. All the products were fully characterized by ¹H NMR and mass spectral analyses. The procedure is mild, simple and the isolation of the products is easy.