A colourful azulene-based protecting group for carboxylic acids

An intensely blue-coloured protecting group for carboxylic acids has been developed. The protecting group is introduced through a Steglich esterification that couples 6-(2-hydroxyethyl)azulene (AzulE) and the carboxylic acid substrate. Deprotection is effected under basic conditions by the addition of the amidine base DBU, whereupon cleavage occurs, accompanied by a colour change. A two-step deprotection methodology comprising activation with oxalyl chloride and deprotection with a very mild base was developed for use with base-sensitive substrates. The AzulE esters were found to be compatible with other commonly employed protecting groups – silyl ethers, MOM acetals – by studying their orthogonal and concomitant deprotections. The stability of the new protecting group towards various synthetic processes – oxidation, reduction, cross-coupling, olefination and treatment with base – provided the basis of a versatility profile. This indicated that AzulE esters are sensitive to strongly oxidising and basic agents while being compatible with reducing conditions and selected other reactions. The convenience of a highly coloured protecting group for tracking material (and avoiding loss of compound) through laboratory processes warrants further investigation of this and/or related species.     

A direct conversion of carboxylic acids to methylthiomethyl esters using a microwave-assisted pummerer rearrangement with dimethylsulfoxide

A simple microwave-assisted method for the conversion of carboxylic acids to MTM esters is presented. This new process allows for rapid introduction of an MTM ester protecting group to a variety of carboxylic acids including alkyl, electron-rich aromatic, and long chain unsaturated carboxylic acids. The products isolated from this reaction are very pure after a simple extraction, which eliminates the need for further purification. The reaction has also been carried out on 1.50 g without deterioration of product yields or purity.     

Fe-exchanged montmorillonite K10--the first heterogeneous catalyst for acylation of sulfonamides with carboxylic acid anhydrides

Fe-exchanged montmorillonite K10 catalyzes a highly efficient reaction between sterically and electronically diverse sulfonamides and carboxylic acid anhydrides to furnish N-acylsulfonamides in excellent yield and high selectivity. The catalyst can also be reused several times.     

A 4-OTBS benzyl-based protective group for carboxylic acids

Reported herein is a novel 4-OTBS benzyl-based protective group for carboxylic acids. This protective group can be removed in the presence of TBAF or TFA with high efficiency, which makes it compatible with base-sensitive or acid-sensitive substrates. With this protective group, a near-infrared fluorogenic probe for the detection of γ-glutamyltranspeptidase activities was readily prepared.     

Gas chromatographic analysis of the carboxylic acid composition of valeriana extracts

Summary The gas chromatographic analysis for the qualitatived and quantitative analysis of carboxylic acids present in valeriana extracts in the form of their n-butyl and trifluoroacetylated n-butyl esters is presented. On the basis of the proposed method the amount of four valtrate species, as well as the free carboxylic acid content of valeriana tinctures can be calculated. It is shown that extracts of Valeriana officinalis obtained by using ethanol, acetone, or chloroform as the solvent contain the same carboxylic acids. The determined components, are: formic, acetic, propionic, isobutyric, n-butyric, lactic, isovaleric, n-valeric, 2-hydroxy-isovaleric, isocaproic, n-caproic, caprylic, malic, capric, lauric, myristic, valerenic, palmitic, stearic, arachic, behenic, erucic and lignoceric acids.     

Phenyl-EDOTn derivatives as super acid labile carboxylic acid protecting groups for peptide synthesis

A series of new 3,4-ethylenedioxy-2-thenyl (EDOTn) derived alcohols have been synthesized and evaluated as super acid labile carboxylic acid protecting groups. All the derivatives are labile to very low concentrations of TFA (0.01-0.5%).     

Novel non-aggregated soluble metallophthalocyanines bearing carboxylic acid groups

Synthesis and characterization of zinc and cobalt phthalocyanines substituted with biphenylmethylpropionic acids, methyl-o-tolylpropionic acids, and methyl-p-tolylpropionic acids are described in this study. The new compounds have been characterized by elemental analyses, FT-IR, UV-Vis, MALDI-TOF, and ¹H NMR spectroscopy. All new compounds are soluble in THF, DMF, DMSO, and dilute sodium hydroxide solution. The influence of the carboxylic acid and bulky biphenyl, ortho-methylbenzyl and para-methylbenzyl groups on the spectroscopic properties has been investigated. UV-Vis experiments suggest that the tendency of phthalocyanines to aggregate in polar solvents is significantly reduced owing to the carboxylic acid groups and bulky peripheral substituents.     

Application of zirconium-modified silica gel as a stationary phase in the ion-exclusion chromatography of carboxylic acids II. Separation of aliphatic carboxylic acids with pyromellitic acid as eluent and with suppressed conductimetric detection

The application of zirconium-modified silica gels (Zr-Silica) as stationary phases for ion-exclusion chromatography with conductimetric detection (IEC–CD) for C₁–C₈ aliphatic carboxylic acids (formic, acetic, propionic, butyric, valeric, caproic, heptanoic and caprylic acids) was carried out using pyromellitic acid as the eluent. Zr-Silicas were prepared by the reaction of the silanol group on the surface of silica gel with zirconium tetrabutoxide [Zr(OCH₂CH₂CH₂CH₃)₄] in ethanol solution. An ASRS-Ultra anion self-regenerating suppressor in the K⁺ form was used for the enhancement of conductimetric detector response of these aliphatic carboxylic acids. A Zr-Silica adsorbed on 10 mg zirconium g⁻¹ silica gel was the most suitable stationary phase in IEC–CD for the separation of these aliphatic carboxylic acids. Excellently simultaneous separation and highly sensitive detection for these aliphatic carboxylic acids were achieved in 25 min by IEC–CD with the Zr-Silica column (250×4.6 mm I.D.) and a 0.2 mM pyromellitic acid containing 0.15% heptanol as the eluent.     

Hydrophilic [60]fullerene carboxylic acid derivatives retaining the original 60π electronic system

Water-soluble carboxylic acid derivatives of [60]fullerene retaining the original 60π electronic configuration are prepared from a tetra-tert-butyl ester of bis(fulleroid).     

Determination of low-molecular-mass carboxylic acids in atmospheric aerosol and vehicle emission samples by capillary electrophoresis

A method is developed for the determination of a large number of airborne and vehicle-emitted low-molecular-mass mono- and dicarboxylic acids using capillary electrophoresis with indirect UV detection. A background electrolyte (BGE) consisting of 2,6-naphthalenedicarboxylic acid and tetradecylmethylammonium bromide, adjusted to pH 6.2 with 2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol, is employed. Separations are robust using the buffered BGE, proper rinse steps, and constant current mode with migration time variations less than 3% RSD on a day-to-day basis, using different capillaries and performed by different analysts. Detection limits are at the tens of μg/l level using pressure injection. A comparison of the CE method with ion chromatography is also made.     

Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides

A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.     

A simple synthesis of ketone from carboxylic acid using tosyl chloride as an activator

An effective process for the conversion of carboxylic acid to ketone has been discovered. In this process, carboxylic acid has been activated using p-toluene sulphonyl group. Under the optimized condition, aromatic, aliphatic heteroaromatic carboxylic acids have been proved to be good substrates for this methodology. The byproduct of this reaction can be removed very easily during work up process. Also, one equivalent of organometallic reagent is sufficient to complete this transformation.     

Total synthesis of (+)-bongkrekic acid

Total synthesis of bongkrekic acid, an important apoptosis inhibitor, has been accomplished. The strategy includes inexpensive starting materials, asymmetric alkylation, anionic allyl coupling and oxidative manipulations. This process would provide a sufficient amount of bongkrekic acid and its analogues.     

A novel synthesis of (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes and their conversion into carboxylic acids

A novel procedure for preparing heterocyclic compounds such as (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes based on 1-trimethylgermyl-1-alkynes is described. 1-Trimethylgermyl-1-alkynes easily obtainable by deprotonation of 1-alkynes with n-butyllithium followed by treatment with trimethylgermanium chloride, are readily hydroborated in n-pentane in the presence of boron trichloride in hexane at 0 °C for 3 h. The resulting supernatant clear solution was separated from boron trichloride-methyl sulfide complex. It was then reacted with 1,3-propane diol at 0 °C for 0.5 h. The resulting representative (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes were isolated in good yields (65-86%) and in high stereochemical purities (>98%) as evidenced by NMR spectral data. The carbon skeletons present in these intermediates were confirmed by alkaline hydrogen peroxide oxidation to the corresponding carboxylic acids.     

A novel system for the synthesis of nitriles from carboxylic acids

A simple, mild and high yielding method for the conversion of various carboxylic acids to nitriles has been developed using diphosphorus tetraiodide in combination with ammonium carbonate at room temperature.     

A mild and efficient reaction for conversion of carboxylic acids into acid bromides with ethyl tribromoacetate/triphenylphosphine under acid-free conditions

Acid bromides were prepared efficiently from carboxylic acids with readily available ethyl tribromoacetate and triphenylphosphine at room temperature under neutral conditions. The present process is applicable to the preparation of various acid bromides from aromatic and aliphatic carboxylic acids. Aromatic carboxylic acids were found to be more reactive than aliphatic carboxylic acids under reaction conditions.     

Facile synthesis of diphenylmethyl esters from 2-diphenylmethoxypyridine using catalytic boron trifluoride·diethyl etherate

A practical method for the direct preparation of diphenylmethyl (DPM) esters from 2-diphenylmethoxypyridine is described. The reaction was readily performed in the presence of a catalytic amount of boron trifluoride-diethyl etherate at room temperature. Using this reaction protocol, various carboxylic acids were converted to DPM esters with high yields. This method is highly effective for the protection of carboxylic acids and the synthesis of DPM esters, and offers a promising approach for facile esterification of a variety of carboxylic acids.     

α-(1H-Imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters as prodrugs of carboxylic acid containing drugs

Synthesis of α-(1H-imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters have been reported in 2-3 simple steps. α-(1H-Imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters were found to be chemically labile and thus serve as novel prodrugs of carboxylic acids.     

Dansylation of aromatic, aliphatic, and medicinal carboxylic acid compounds in 1 M Na2CO3 buffer

Dansyl chloride (DNS-Cl) is a sulfonyl chloride compound which is utilized as a fluorescent probe for quantitative analysis or structural studies of complex molecules. The fluorescent emission was sufficiently strong to permit detection of less than 10 μg of the carboxyl compounds studied here. The dansylation of aromatic carboxyl compounds (i.e. aspirin), aromatic primary amines, and aliphatic carboxyl compounds was accomplished in 1 M Na₂CO₃ buffer at pH 11. The fluorescent labeled analytes were then isolated by thin layer chromatography (TLC) or the aqueous mixture was pre-extracted with proline (or glycine) to eliminate back-ground emission originating from the hydrolized or sulfonic acid form of DNS-Cl. Fluorescent labeled analytes are clearly discerned under ultraviolet light. Limits of detection for dansylated carboxyl compounds was 1-5 μg, however for amines it was approximately 1 μg. Dansylation of aromatic primary amines proceeded much faster (15 min) than that of carboxyl compounds (≥1.5 h) at 25 °C. Despite the aqueous solubility of analytes, which ranged from less than 0.004-5.30 mg/ml, the dansylation of carboxyl compounds was effective. Various organic solvents for extracting derivatives from aqueous mixture were evaluated.     

Efficient and one-pot synthesis of novel sulfamates from carboxylic acids

Effective synthesis of novel sulfamates from various carboxylic acids has been developed in the presence of chlorosulfonyl isocyanate (CSI) in mild conditions. Several acids, bases and solvents effects were investigated for one-pot synthesis sulfamates as a catalyst. Finally, triflic acid was found to possess efficiently under optimized conditions in acetonitrile. This method is easy, fair price and practical. It can be synthesized on grams and milligrams scale.