High-performance CE: an effective method to study lactonization of alpha2,8-linked oligosialic acid

A sensitive and efficient method using high-performance CE (HPCE) and neuraminidase hydrolysis was developed to study the lactonization and hydrolysis of alpha2,8-pentasialic acid. Eleven lactone species of pentasialic acid formed in glacial acetic acid were detected and classified into three groups based on the number of carboxylic acids: monolactones with four carboxylic acids, dilactones with three carboxylic acids, and trilactones with two carboxylic acids. These lactones eluted between the original pentamer (with five carboxylic acids) and the fully lactonized species (with one carboxylic acid) in HPCE. Eight of the isomers were identified by hydrolysis with neuraminodase. Results obtained from previous reports and from this study together reveal a general rule for predicting the subtle difference in the acidity of each carboxylic acid in oligosialic acids: the closer the carboxylic acid is to the nonreducing end, the more acidic it is. Therefore, the elution order of lactone isomers having the same number of carboxylic groups can be predicted from the position of the free carboxylic groups in pentasialic acid. We used this principle and the results of hydrolysis with neuraminidase to identify hexamer lactone isomers separated by HPCE.     

Purification and dual-column HPLC determination of carboxylic acids in tissues,phloem and xylem saps of soybean plants

Summary A method for the determination of carboxylic acids in phloem sap, xylem sap and tissue extracts of soybean plants is reported. An easy and rapid procedure for the purification of the samples has been developed. Carboxylic acids were determined by isocratic HPLC. The separation of the first-eluting carboxylic acids and the unretained solutes have been improved by connecting an ion-exclusion column to the reversed-phase column. This chromatographic method also improved the separation of some carboxylic acids. The optimized method was applied to the determination of the carboxylic acids transported in xylem and phloem saps of soybean plants, or accumulated in their root tissues.     

高效钴氧化物催化羧酸可控加氢制醇（英文）

羧酸选择加氢是合成醇的重要方法,廉价高效的催化体系仍然在探索中.我们利用地球上储量丰富的钴氧化物作为催化剂,通过控制催化反应过程,进而实现高选择性地催化羧酸加氢制备醇.一系列含有不同官能团的羧酸可以被选择加氢至相应的醇类化合物,反应选择性可以满足工业生产要求.通过一系列的谱学表征以及理论计算,我们证实了钴氧化物在羧酸选择加氢反应中的优选活性位点位为氧化亚钴,从而建立了催化剂与反应活性之间的构效关系,为催化剂的理性设计提供指导.首先,我们选取硬脂酸加氢反应作为模型反应,通过对地球上储量丰富的氧化镍、四氧化三铁和四氧化三钴的催化活性对比发现,四氧化三钴催化剂活性最高,在473 K,2 MPa氢气条件下,反应速率可以达到1.2 mmol/(h·g).对四氧化三钴催化剂进行不同温度的预还原处理,我们发现催化剂的活性得到显著提高,其中573 K还原的样品活性最高,反应速率可以达到7.3 mmol/(h·g),要远远高于贵金属催化剂Pd/C(0.6 mmol/(h·g))和Pt/C(1.8 mmol/(h·g)).XRD结果表明,随着还原处理温度的不断升高,催化剂由四氧化三钴变为氧化亚钴,最终变为金属态的钴.当还原温度为573 K时,催化剂的组成为单一相氧化亚钴.XPS测试结果表明,当还原温度为573 K时,样品中只含有Co~(2+)的信号峰,并且Co/O的比例为1/1,进一步证明样品是纯态的氧化亚钴.从TEM照片中可以发现,在原始的四氧化三钴样品中观察到晶面间距为0.467和0.244 nm,分别对应四氧化三钴的(111)和(311)晶面.而对于573 K还原的样品只观察到一种晶面间距(0.246 nm),对应氧化亚钴的(111)晶面.结合表征手段和硬脂酸催化加氢活性结果,我们得出氧化亚钴是573 K还原样品催化羧酸加氢反应的活性位点.理论计算结果进一步证实了这个实验结论.理论计算结果表明,在氧化亚钴(111)晶面,硬脂酸加氢转换为十八醇是非常快速和高效的,然而,对于氢解C-C键和C-O键,需要耗费更高的能量,能垒约为1.2 e V.因为硬脂酸的吸附远远强于十八醇的吸附,硬脂酸的存在会抑制十八醇氢解形成烯烃的反应,只有当硬脂酸酸完全转化为十八醇,才会发生随后的氢解反应.通过控制催化反应过程,可以实现在氧化亚钴(111)晶面高选择性催化酸加氢至醇,也就是反应控制催化过程.基于氧化亚钴在硬脂酸加氢制备十八醇上的优异催化性能,我们进一步研究了一系列含有不同官能团的羧酸化合物的催化加氢,发现氧化亚钴表现出良好的官能团容忍度,可以实现高效、广谱的酸选择加氢至醇反应.     

Mild and efficient boronic acid catalysis of Diels-Alder cycloadditions to 2-alkynoic acids

The concept of boronic acid catalysis (BAC) for the activation of unsaturated carboxylic acids is applied to the Diels-Alder cycloaddition between 2-alkynoic acids as dienophiles and various dienes. These [4+2] cycloadditions produce cyclohexadienyl carboxylic acids, which can be oxidized in situ to produce polysubstituted aromatic carboxylic acids. The boronic acid catalyst is suspected to provide activation by a LUMO-lowering effect of the unsaturated carboxylic acid likely via a covalent, monoacylated hemiboronic ester intermediate.     

Silver‐Catalyzed Arylation of (Hetero)arenes by Oxidative Decarboxylation of Aromatic Carboxylic Acids

A long‐standing challenge in Minisci reactions is achieving the arylation of heteroarenes by oxidative decarboxylation of aromatic carboxylic acids. To address this challenge, the silver‐catalyzed intermolecular Minisci reaction of aromatic carboxylic acids was developed. With an inexpensive silver salt as a catalyst, this new reaction enables a variety of aromatic carboxylic acids to undergo decarboxylative coupling with electron‐deficient arenes or heteroarenes regardless of the position of the substituents on the aromatic carboxylic acid, thus eliminating the need for ortho‐substituted aromatic carboxylic acids, which were a limitation of previously reported methods.     

Resolution of carboxylic acids using copper(I)-promoted removal of propargylic esters under neutral conditions

A method for the optical resolution of carboxylic acids is described. Condensation of racemic carboxylic acids with chiral terminal propargyl alcohols gave separable diastereomeric esters. Chromatographic separation followed by heating the individual diastereomers in methanol with catalytic copper(I) halide regenerated the carboxylic acids in good yields and in enantiomeric ratios of ≥94%. This method is particularly useful for the resolution of carboxylic acids that are incompatible with conventional ester hydrolysis.     

Mass spectrometric analysis for carboxylic acids as viable markers of petroleum hydrocarbon biodegradation

The characterization of metabolites, which are considered markers of bacterial degradation of hydrocarbons, is gaining in importance. Over the years, carboxylic acids have served as useful indicators of aerobic and anaerobic hydrocarbon biodegradation. This interest has been accompanied by the extensive and robust development of analytical methods for monitoring, untargeted identification, and specific and sensitive determination of carboxylic acids in complex matrices. This review discusses critically the state-of-the-art of mass spectrometry as a reliable analytical technique to identify and quantify carboxylic acid metabolites. Attention is paid to sample pre-treatment, selective group pre-concentration, and gas and liquid chromatography preceding mass spectrometry to alleviate matrix effects and ionization discrimination. Recent specific applications of mass spectrometry in monitoring carboxylic acids for assessing hydrocarbon biodegradation are reviewed. Presently, no single technique is sufficient for holistic profiling of carboxylic acids. The direct characterization of carboxylic acids by mass spectrometry is the ultimate goal but despite recent significant developments, challenges persist.     

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.     

Enantioselective sensing of chiral carboxylic acids

A chiral 1,8-diacridylnaphthalene-derived fluorosensor has been prepared and used for enantioselective sensing of a broad variety of chiral carboxylic acids including amino acids, aliphatic acids, arylalkanoic acids, and halogenated carboxylic acids. Fluorescence titration experiments in acetonitrile gave linear Stern-Volmer plots for 1:1 and 1:2 complexes and enantioselectivities up to 4.5.     

Recent topics in the syntheses of β-keto carboxylic acids and the derivatives

β-Keto carboxylic acids are key intermediates in organic syntheses, used for the development of fine chemicals, natural products, and various biologically relevant molecules. Their utilities stem from the structural features and facile bond formations, e.g., asymmetric reduction of carbonyl groups for the synthesis of β-hydroxy carboxylic acids and conjugated addition reactions through decarboxylative enolate nucleophiles, which utilize the amphiphilic reactivity of β-keto carboxylic acids. Despite their versatility and utilities, development of efficient and straightforward synthetic methods for β-keto carboxylic acids has not attracted considerable attention owing to their instability. As efficient synthetic strategies for β-keto carboxylic acids and their derivatives, reactions of α-diazoesters, acylation of malonate anions, cross-coupling reactions, and CO₂ insertion reactions are summarized in this review.     

Convenient Synthesis of a Library of Discrete Hydroxamic Acids Using the Hydroxythiophenol (Marshall) Resin

Several resins have reportedly been used to synthesize hydroxamic acids except for the hydroxythiophenol (Marshall) resin. Herein, we report the use of the Marshall resin to synthesize hydroxamic acids from carboxylic acids and its application to convert a library of 14 discrete aliphatic and aromatic carboxylic acids including N-protected amino acids to their corresponding hydroxamic acids in good yields.     

Direct Ruthenium‐Catalyzed Hydrogenation of Carboxylic Acids to Alcohols

The “green” reduction of carboxylic acids to alcohols is a challenging task in organic chemistry. Herein, we describe a general protocol for generation of alcohols by catalytic hydrogenation of carboxylic acids. Key to success is the use of a combination of Ru(acac)₃, triphos and Lewis acids. The novel method showed broad substrate tolerance and a variety of aliphatic carboxylic acids including biomass‐derived compounds can be smoothly reduced.     

稀土氯化物催化丙烯直接环氧化反应研究

以氯化稀土为催化剂,以锌粉为还原剂,对不同羧酸和溶剂条件下的丙烯直接用氧气环氧化进行了研究,并对它的催化反应机理进行了初步探讨,实验结果表明,氯化稀土中有EuCl3对丙烯直接环氧化起催化作用,并且要在锌粉和羧酸共同存在下才有效,所用羧酸中丙酸的效果最佳,使用有机溶剂比不用溶剂效果更好,但不能用碱性物质作为反应体系的溶剂。反应气压力越高越有利于 环氧丙烷（PO）的生成,但反应温度不宜过高,在EuCl3、锌粉、羧酸催化体系中,EuCl3起电子传递的桥梁作用,锌粉提供电子,羧酸提供质子,推测的反应机理与实验结果吻合。     

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.     

O‐Arylation of Carboxylic Acids using (Phenyl)[2‐(trimethylsilyl)phenyl]iodonium Triflate as a Precursor of Arynes

Using (phenyl)[2‐(trimethylsilyl)phenyl]iodonium triflate as a precursor of arynes, Larock's method for O‐arylation of carboxylic acids and arynes was developed. A variety of acids including simple aliphatic carboxylic acids, aromatic carboxylic acids, allenoic acids, and p‐toluenesulfonic acid under mild reaction conditions could generate the aryl esters.     

Electron transfer reduction of carboxylic acids using SmI2-H2O-Et3N

The first general method for efficient electron transfer reduction of carboxylic acids has been developed. The protocol using SmI(2)-H(2)O-Et(3)N allows for reduction of a variety of carboxylic acids in excellent yields and provides an attractive alternative to processes mediated by reactive alkali metals, lithium aluminum hydride, and boron hydrides. Of broader significance, the method allows acyl radical equivalents to be generated from carboxylic acids under mild reaction conditions.     

A novel derivatization reagent possessing a bromoquinolinium structure for biological carboxylic acids in HPLC‐ESI‐MS/MS

A novel bromoquinolinium reagent, i.e. 1‐(3‐aminopropyl)‐3‐bromoquinolinium bromide (APBQ), was synthesized for the analysis of carboxylic acids. A simple and practical precolumn derivatization procedure using the APBQ in RP chromatography and MS (HPLC‐MS) has been developed using bile acids and free fatty acids, as the representative carboxylic acids in biological samples. The APBQ efficiently reacted with carboxylic acids at 60°C for 60 min in the presence of N,N‐dicyclohexylcarbodiimide and pyridine as the activation reagents. Because the APBQ possesses a bromine atom in the structure, the identification of a series of carboxylic acids was easily achieved due to the characteristic bromine isotope pattern in the mass spectra. The APBQ also has a quaternary amine structure, thus the positively charged derivatives are predominate for the highly sensitive detection of carboxylic acids. The APBQ was successfully applied to the selective determination of biological carboxylic acids in human plasma. The bile acids (chenodeoxycholic acid and deoxycholic acid) and several saturated (stearic acid and palmitic acid) and unsaturated free fatty acids (oleic acid and linoleic acid) were reasonably determined by HPLC‐MS under the proposed procedure. Based on the results of analyses of human plasma and saliva, the proposed procedure using APBQ seems to be applicable for the qualitative and quantitative analyses of a series of carboxylic acids in biological samples.     

Confirmation and determination of carboxylic acids in root exudates using LC-ESI-MS

Reversed-phase liquid chromatography with UV detection is of limited applicability in the separation and identification of carboxylic acids because of the column's poor separation efficiency and the non-selective nature of the UV detector. To address this issue, RP-LC with electrospray ionization mass spectrometry has been explored for the confirmation and determination of carboxylic acids in plant root exudates, with ESI-MS providing structural information, high selectivity, and high sensitivity. The separation of 10 carboxylic acids (pyruvic, lactic, malonic, maleic, fumaric, succinic, malic, tartaric, trans-aconitic, and citric acid) was performed on a C(18) column using an eluent containing 0.1% (v/v) acetic acid within 10 min, where the acidic eluent not only suppressed the ionization of the carboxylic acids to be retained on the column, but was also compatible with ESI-MS detection. In addition, an additional standard was used to overcome the matrix effect. The results showed that peak areas correlated linearly with the concentration of carboxylic acids over the range 0.05-10 mg/L. The detection limits of target acids (signal-to-noise S/N ratio of 3) ranged from 20 to 30 microg/L. Finally, the proposed method was used for the confirmation and determination of low-molecular-weight carboxylic acids in plant root exudates, and provided a simple analytical procedure, including sample processing, fast separation, and high specificity and sensitivity.     

Simultaneous determination of C2-C22 non-esterified fatty acids and other metabolically relevant carboxylic acids in biological material by gas chromatography of their benzyl esters

A method for the simultaneous determination of non-esterified short-, medium- and long-chain fatty acids and other types of metabolically relevant carboxylic acids such as hydroxy, keto, aromatic and dicarboxylic acids in biological material by capillary gas chromatography of benzyl ester derivatives is described. Sample preparation avoiding incomplete isolation of carboxylic acids consisted of deproteinization and extraction with ethanol, fixation of carboxylic acids as carboxylates, removal of interfering compounds such as neutral lipids by hexane extraction and amino acids, acyl carnitines and other cations by cation-exchange chromatography, derivatization of keto groups of ketocarboxylic acids into O-methyl oximes and benzyl ester formation by reaction of the potassium carboxylates with benzyl bromide via crown ether catalysis. The sample preparation conditions were investigated, showing the usefulness of this method for quantitative determinations. Chromatograms obtained from human serum, human urine and rat heart ventricle and concentrations of carboxylic acids in these specimens are presented.     

Preparation of Esters and Amides from Carboxylic Acids by Activation with Dialkyl Phosphite-Carbon Tetrachloride Mixture

A simple one pot phase transfer catalytic method is described for the synthesis of carboxylic amides and esters from carboxylic acids and amines or alcohols, respectively. For the activation of the carboxylic acids “in situ” generated phosphoric acid diester chlorides were applied.