An efficient 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU)-mediated synthesis of 5-(trifluoromethyl)-N-alkyl-1-(3-phenylisoquinoline-1-yl)-1H-pyrazole-4-carboxamides

A series of 5-(trifluoromethyl)-N-alkyl-1-(3-phenylisoquinoline-1-yl)-1H-pyrazole-4-carboxamides 4 has been effectively achieved in high yield and purity from the reaction of pyrazole carboxylic acid 2 with amines 3 in the presence of TBTU as a catalyst and diisopropyl ethylamine as a base in acetonitrile at room temperature.     

Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling

A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction.     

Di-tert-butyl dicarbonate as an efficient coupling reagent for the immobilization of carboxylic acid moieties

We describe an efficient methodology for anchoring diverse carboxylic acids to hydroxymethylated resins using di-tert-butyl dicarbonate as coupling reagent. The reaction is equally effective for aromatic and aliphatic acids, and Fmoc-protected amino acids.     

(2-Alkyl-1,4-benzodioxan-2-yl)carboxylic acids as potential hypolipidemic agents

1,2-Diphenols reacted with 2-alkyl-3-chloro-1,2-epoxypropane to give a mixture of 1,4-benzodioxane, V, and 1,5-benzodioxepine, VII, alcohols. From potassium permanganate oxidation of benzodioxane compounds V the corresponding (2-alkyl-1,4-benzodioxan-2-yl)carboxylic acids II were obtained. In a preliminary pharmacological evaluation benzodioxane acids II did not show any effect on plasma cholesterol, while producing a moderate lowering of triglycerides.     

O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate-N-hydroxysuccinimide-CuCl2: a facile and reliable system for racemization-free coupling of peptides having a carboxy-terminal N-methylamino acid

Simultaneous use of N-hydroxysuccinimide (HOSu) and CuCl2 with a HOSu-based uronium coupling reagent, O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate, has been found to eliminate the racemization of the carboxy-terminal N-methylamino acid residue during the segment condensation.     

Copper(II) tetrafluoroborate as an extremely efficient catalyst for 1,3-dithiolane/dithiane formation from carbonyl compounds under solvent-free conditions at room temperature

Copper(II) tetrafluoroborate hydrate is a new and extremely efficient catalyst for 1,3-dithiolane/dithiane formation from aromatic, heteroaromatic and aliphatic aldehydes and cyclic saturated ketones in 1-5 min under solvent-free conditions at room temperature. The reaction is compatible with other functionalities such as ether, ester, hydroxyl, halide, nitro and cyano groups and exhibits excellent chemoselectivity. α,β-Unsaturated aldehydes/ketones lead to selective formation of 1,3-dithiolanes instead of Michael addition products. For substrates bearing an aldehyde and a ketone carbonyl group, chemoselective dithiolane formation takes place with the aldehyde.     

Identification and determination of carboxylic acids in food samples using 2-(2-(anthracen-10-yl)-1H-phenanthro[9,10-d]imidazol-1-yl)ethyl 4-methylbenzenesulfonate (APIETS) as labeling reagent by HPLC with FLD and APCI/MS

A new labeling reagent for carboxylic acids, 2-(2-(anthracen-10-yl)-1H-phenanthro[9,10-d]imidazol-1-yl)ethyl 4-methylbenzenesulfonate (APIETS) has been designed and synthesized. It was used to label eight fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, oleic acid, linoleic acid and linolenic acid) and four hydroxy pentacyclic triterpene acids (oleanolic acid, ursolic acid, betulinic acid and maslinic acid), successfully. APIETS could easily and quickly label carboxylic acids in the presence of K₂CO₃ catalyst at 85 °C for 35 min in N,N-dimethylformamide solvent. The carboxylic acids derivatives were separated on a C₈ reversed-phase column with gradient elution and fluorescence detection at λ_ex/λ_em = 315/435 nm. Identification of these derivatives was carried out by online mass spectrometry with atmospheric pressure chemical ionization in positive ion mode. The detection limits obtained were 13.37-30.26 fmol (signal-to-noise ratio of 3). The proposed method has been applied to the quantification of carboxylic acids in sultana raisin (Thompson seedless), hawthorn flake (Crataegus pinnatifida Bge.), Lycium barbarum seed oil and Microula sikkimensis seed oil with recoveries over 95.3%. It has been demonstrated that APIETS is a prominent labeling reagent for determining carboxylic acids with high performance liquid chromatography.     

2-Hydroxy-1,2,2-triphenylethanone as an efficient photolabile protecting group for carboxylic acids

The synthesis is reported of 2-hydroxy-1,2,2-triphenylethanone esters of carboxylic acids by the reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Photolysis of the esters occurs rapidly on irradiation with a medium-pressure mercury lamp through quartz or Pyrex to return the carboxylic acid. The side product of the photolysis is benzo[b]phenanthro[9,10-d]furan, formed through a tandem process involving initial generation of 2,3-diphenylbenzofuran, photochemical cyclisation and re-aromatisation by aerial oxidation.     

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature

Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.     

[Bmim]N3 as an efficient reagent for the Schmidt reactions of ketones,arylaldehydes and aromatic carboxylic acids

Schmidt reaction of arylaldehydes, ketones and aromatic carboxylic acids using task-specific ionic liquid, [bmim]N₃ in the presence of AcOH/H₂SO₄ proceeds at 50–60 °C within 2–4 h to give the corresponding products. Benzaldehydes containing electron releasing groups afforded to the related benzamide derivatives. Benzonitrile derivatives were formed from the reaction of benzaldehydes containing electron withdrawing groups under these conditions. High yields of the related amides and anilines were obtained from the reaction of a variety of ketones and aromatic carboxylic acids, respectively, utilizing this procedure.     

Repurposing n-butyl stannoic acid as highly efficient catalyst for direct amidation of carboxylic acids with amines

This is the first-time report on the repurposing n-butyl stannoic acid as a catalyst for direct amidation of carboxylic acids with amines. Notably, efficient amidation observed in comparison with all other catalytic methods reported up until now. The protocol has successfully applied to the synthesis of a variety of amides. Moderate reaction parameters, clean amidation with excellent yields of desired amides, ability to tolerate a variety of functional groups, easy product isolation; commercial availability and recyclability of the catalyst are key advantages of the current protocol.     

Synthesis of 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(2-cyclohexen-1-yl)- and 6-Methyl-4-(1-methyl-2-buten-1-yl)-2-(1-cyclohexen-1-yl)anilines

Alkenylation of 6-methyl-2-(2-cyclohexen-1-yl)- and 2-(1-cyclohexen-1-yl)anilines with piperylene in the presence of AlCl₃ and transformation of the resulting cyclohexenylanilines into carbazole structures were studied.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 441–443.Original Russian Text Copyright © 2005 by Gataullin, Ishberdina, Sotnikov, Abdrakhmanov.     

Direct electrochemical response of Myoglobin using a room temperature ionic liquid, 1-(2-hydroxyethyl)-3-methyl imidazolium tetrafluoroborate,as supporting electrolyte

Direct electrochemical response of Myoglobin (Myb) at the basal plane graphite (BPG) electrode was observed when a room temperature ionic liquid (RTIL), 1-(2-hydroxyethyl)-3-methyl imidazolium tetrafluoroborate ([HEMIm][BF₄]), was used as the supporting electrolyte. In a 0.17 M [HEMIm]BF₄ aqueous solution, a couple of well-defined redox peaks of Myb could be obtained, whose anodic and cathodic peak potentials were at −0.158 and −0.224 V (vs. Ag/AgCl), respectively. Both anodic and cathodic peak currents increased linearly with the potential scan rate. Compared with the supporting electrolyte of phosphate buffer, [HEMIm][BF₄] played an obvious promotion for the direct electron transfer between Myb and the BPG electrode. Further investigation suggested that Myb was adsorbed tightly on the surface of the BPG electrode in the presence of [HEMIm][BF₄] to form a stable, approximate monolayer Myb film. Myb adsorbed on the BPG electrode surface showed a remarkable electrocatalytic activity for the reduction of oxygen in a [HEMIm][BF₄] aqueous solution. Based on these, a third-generation biosensor could be constructed to directly detect the concentration of oxygen in aqueous solution with a limit of detection of 2.3 × 10⁻⁸ M.     

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.     

4-(4,6-di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium tetrafluoroborate. Triazine-based coupling reagents designed for coupling sterically hindered substrates

4-(4,6-Di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium tetrafluoroborate (DFET/NMM/BF(4)) was prepared and used as a reagent for coupling sterically hindered substrates. The formation of the appropriate triazine "superactive" ester in a reaction of DFET/NMM/BF(4) with carboxylic acids was confirmed. The efficiency of the reagent has been studied in the synthesis of Leu-enkephaline pentapeptide carried out on a Fmoc-RinkAmide-AM-PS resin, by systematically modifying the -Gly-Gly- fragment for N-methyl or α,α-disubstituted residues and compared with the efficiency of classic aminium salt 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) under a variety of reaction conditions. In syntheses of Aib-Aib (Aib: α-aminoisobutyric acid), MeVal-MeVal, and MeLeu-MeLeu, the considerably superior performance of enkephaline analogues was obtained for DFET/NMM/BF(4) relative to TBTU, regardless of reaction conditions. Analysis of the couplings involving triazine reagent suggests that factors controlling efficiency of coupling sterically hindered substrates are the structure of the leaving group permitting formation of the cyclic intermediate or cyclic transition state and the absence of strongly solvating solvents. It has to be considered as highly probable that the absence of strongly solvating milieu favors cyclic intermediates or the cyclic transition state. Arrangement of both components into the cyclic intermediate or cyclic transition state by accumulation of the geminal (vicinal) substituents effect (known as the Thorpe-Ingold effect) would compensate retardation of the coupling process caused by steric hindrance.     

Phenylsilane as an active amidation reagent for the preparation of carboxamides and peptides

The use of phenylsilane as a mild coupling reagent for amidation reactions is reported. Applicability to both solution- and solid-phase chemistry has been demonstrated for a variety of amines and carboxylic acids.     

Effective esterification of carboxylic acids using (6-oxo-6H-pyridazin-1-yl)phosphoric acid diethyl ester as novel coupling agents

(6-Oxo-6H-pyridazin-1-yl)phosphoric acid diethyl esters (3) are efficient and selective coupling agents for equimolar esterification of carboxylic acids and alcohols. Esterification of aliphatic and aromatic carboxylic acids with aliphatic and aromatic alcohols using 3 afforded the corresponding esters chemoselectively in good to excellent yield.     

Copper(II) tetrafluoroborate catalyzed ring-opening reaction of epoxides with alcohols at room temperature

[reaction: see text] Efficient ring opening of different epoxides by reaction with representative alcohols is presented. These processes were carried out at room temperature and rely on the usefulness of commercial copper tetrafluoroborate as catalyst.     

S-(2-pyridinyl)-1,1,3,3-tetramethylthiouronium hexafluorophosphate. A new reagent for the synthesis of 2-pyridinethiol esters

[reaction: see text] A new thiouronium-based reagent for the synthesis of 2-pyridinethiol esters under non-nucleophilic conditions from the corresponding carboxylic acids was developed. The resulting procedure enables the preparation of previously unavailable alpha,beta-unsaturated 2-pyridinethiol esters as well as their aliphatic and aromatic counterparts.