Benzoylformate Research Articles

Pathways in permanganate oxidation of mandelic acid: reactivity and selectivity of intermediate manganese species.

We report a comprehensive kinetic and product study of the oxidation of mandelic acid (MA) by permanganate in the pH range of 1-13, including a full account of total oxidizing equivalents (five and three-electron change in acidic and basic media, respectively). In the entire pH range, the reaction shows a primary kinetic deuterium isotope effect (kH/kD ≥8-9), indicating rate-limiting hydride transfer. The deuterium label in α-deutero-mandelic acid is retained in benzaldehyde. Benzaldehyde (BZ) is formed in post-rate limiting steps due to reactions involving manganese intermediates. In alkaline pH (≥13), in the presence of barium acetate, Mn(VI) is removed as insoluble blue barium manganate; the stoichiometry of the first step of reduction was found to be: MA + 2Mn(VII) → PGA + 2Mn(VI). Manganate, MnO42-, is directly reduced to MnO2 giving an additional mole of phenylglyoxylic acid (PGA). The experimentally observed ratio of benzaldehyde to phenylglyoxylic (BZ/PGA) provides a basis for discrimination between mechanistic choices that include direct reduction of Mn(V) to Mn(III) (in an acidic medium), disproportionation to Mn(IV) and Mn(VI) or oxidation to Mn(VI) by a second mole of permanganate. Interestingly, at pH 4, a stoichiometric, soluble Mn(IV) is observed for the first time for hydroxy-acid oxidation, reminiscent of the Guyard reaction. Because of the widespread use of permanganate as an environmentally green oxidant, results from mandelic acid oxidation have implications for the remediation of dissolved organic matter (DOM) including hydrocarbons and nitroaromatics in waste and groundwater.

Exposure assessment of wastewater treatment plant employees to BTEX: a biological monitoring approach

To monitor employees' work safety and exposure against air contaminants, Trans, trans-muconic acid, Hippuric acid, Methyl hippuric acid, Mandelic acid and Phenylglyoxylic acid can be used as reliable biomarkers of exposure to benzene, toluene, ethylbenzene, and xylene (BTEX) compounds. This study aims to determine the level of urinary metabolites of BTEX compounds using biological monitoring in the employees of a wastewater treatment plant (WWTP) in the south of Iran. The study was performed on 56 employees of the WWTP of one of the southern cities of Iran in 2020. Urine samples (n total = 112) consisting of 60 samples of employees working in the operation section (exposed group) and 52 samples of employees working in the administrative section (control group) in the WWTP were collected before and at the end of their shift. The mean concentration of urinary metabolites of BTEX of both groups ranged from 546.43 (μg/g cr) for trans, trans-muconic acid to 0.006 (μg/g cr) for methyl hippuric acid, which indicates that most of the evaluated metabolites showed a higher concentration than their occupational threshold limit value urine (p < 0.05). Regression analysis results showed a significant correlation (p < 0.05) between age and utilization of flame heaters with changes in the measured BTEX metabolites in the urine. The results of this study illustrate that WWTPs should be considered as one of the workplaces with potential sources of BTEX exposure for employees. Future investigations are recommended to perform itemized appraisals of BTEX intake sources, particularly in employees of the operational sections of WWTP.

C‐H Activation of 2‐Arylbenzoxazinones in Aqueous Medium: Synthesis of Fused Isoindolinones Using a Heterogeneous Magnetic Pd‐Catalyst

AbstractWe have developed a C−H activation protocol of 2‐arylbenzoxazinones in aqueous medium under open aerial atmosphere at close to room temperature (40 °C) using magnetic Pd‐catalyst. 2‐Arylbenzoxazinones react with phenylglyoxylic acidsviadecarboxylative C−H acylation followed by cyclization reaction to produce the isoindolinone compounds. The reaction can be arrested at the intermediate step to obtain theortho‐acylated derivative at a certain lower temperature. The heterogeneous Pd‐catalyst is easy to separate magnetically and shows good recyclability.

Pyrolysis properties and kinetics of photocured waste from photopolymerization-based 3D printing: A TG-FTIR/GC–MS study

The emerging photopolymerization-based 3D printing industry has led to a growing concern for the disposal of photocured waste (PCW), which is inevitably generated during the life cycle of photopolymerization-based 3D printing. In order to shed light on suitable thermochemical treatment and utilization approaches of PCW, this work comprehensively investigated the properties and kinetics during PCW pyrolysis via TG-FTIR/GC–MS analysis. The results demonstrated that the main decomposition of PCW sample happened in the range 320–550 °C with a total weight loss of 93.34 wt%. According to the result of four kinetic models, the activation energy of PCW sample was approximately 228.58–245.05 kJ/mol. Finally, the FTIR and GC–MS results manifested that the main components of volatiles released at different heating rates were the same. The volatiles mainly include (S)-(+)-2-hydroxy-2-phenylprop, benzaldehyde, benzophenone (photo-initiator), benzoic acid, benzoylformic acid etc., which have a multitude of potential applications. However, these volatiles produced by PCW pyrolysis have a certain toxicity and potential hazard. This study demonstrates insightful fundamentals for thermochemical disposal of PCW, which appears to be potentially valuable with the rapid development of the photopolymerization-based 3D printing industry.

Comprehensive Analysis of the Relationships Between the Gut Microbiota and Fecal Metabolome in Individuals With Primary Sjogren's Syndrome by 16S rRNA Sequencing and LC-MS-Based Metabolomics.

The gut microbiota has been associated with primary Sjogren’s syndrome (pSS), yet the biological implications of these associations are often elusive. We analyzed the fecal microbiota through 16S rRNA gene amplification and sequencing in 30 patients with pSS and 20 healthy controls (HCs); At the same time, the fecal metabolome was characterized by ultrahigh-performance liquid chromatography–mass spectrometry. In addition, correlation analyses of microbiota and metabolome data were performed to identify meaningful associations. We found that the microbiota composition of pSS patients was significantly different from that of HCs. The pSS gut microbiota is characterized by increased abundances of proinflammatory microbes, especially Escherichia-Shigella, and decreased abundances of anti-inflammatory microbes. Concerning the metabolome, a multivariate model with 33 metabolites efficiently distinguished cases from controls. Through KEGG enrichment analysis, we found that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. The correlation analysis indicated that there were certain correlations between the microbiota and metabolism in pSS patients. In addition, an abundance of Escherichia-Shigella was found to be correlated with high levels of four metabolites (aflatoxin M1, glycocholic acid, L-histidine and phenylglyoxylic acid). Our research suggests that in pSS patients, the gut microbiota is characterized by a specific combination of proinflammatory changes and metabolic states. Escherichia-Shigella is a factor related to gut dysbiosis, which may promote intestinal damage and affect amino acid metabolism.

Flos Carthami Exerts Hepatoprotective Action in a Rat Model of Alcoholic Liver Injury via Modulating the Metabolomics Profile.

This study was intended to identify the shifts in the metabolomics profile of the hepatic tissue damaged by alcohol consumption and verify the potential restorative action of flos carthami (the flowers of Carthamus tinctorius, FC) in the protection of alcohol-induced injury by attenuating the level of identified metabolites. Rats were treated with FC and subsequently subjected to alcohol administration. The serum samples were subjected to liquid chromatography-mass spectrometry (LC-MS)-based metabolomics followed by statistical and bioinformatics analyses. The clustering of the samples showed an obvious separation in the principal component analysis (PCA) plot, and the scores plot of the orthogonal partial least squares-discriminant analysis (OPLS-DA) model allowed the distinction among the three groups. Among the 3211 total metabolites, 1088 features were significantly different between the control and alcohol-treated groups, while 367 metabolites were identified as differential metabolites between the alcohol- and FC-treated rat groups. Time series clustering approach indicated that 910 metabolites in profile 6 were upregulated by alcohol but subsequently reversed by FC treatment; among them, the top 10 metabolites based on the variable importance in projection (VIP) scores were 1-methyladenine, phenylglyoxylic acid, N-acetylvaline, mexiletine, L-fucose, propylthiouracil, dopamine 4-sulfate, isoleucylproline, (R)-salsolinol, and monomethyl phthalate. The Pearson correlation analysis and network construction revealed 96 hub metabolites that were upregulated in the alcohol liver injury model group but were downregulated by FC. This study confirmed the hepatoprotective effects of FC against alcohol-induced liver injury and the related changes in the metabolic profiles, which will contribute to the understanding and the treatment of alcohol-induced acute liver injury.

A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light.

This work presents a palladium-catalyzed oxime ether-directed ortho-selective benzoylation using benzoylformic acid as the acyl source with a palladium catalyst and 4CzIPN as the co-catalyst under light. Various non-symmetric benzophenone derivatives were obtained in moderate to good yields. A preliminary mechanism study revealed that the reaction proceeds through a free radical pathway.

Reactions of α-Phenylglyoxylic Acids with ortho-Functionalized Anilines in Deep Eutectic Solvents: Selective Syntheses of 3-Aryl-2H-benzo[b][1,4]oxazin-2-ones, 2-Arylbenzothiazoles, and 3-Arylquinoxalin-2(1H)-ones

Abstractα-Phenylglyoxylic acid is a novel cyclization reagent. In this study, three cyclization products were synthesized by the reaction of α-phenylglyoxylic acids with ortho-functionalized anilines in deep eutectic solvents (DES). The five-membered-ring-formation products, the 2-arylbenzothiazoles, with a highest yield of 88%, were obtained by the reaction between 0.30 mmol of an o-aminothiophenol and 0.30 mmol of an α-phenylglyoxylic acid in choline chloride (ChCl)/d-(–)-tartaric acid DES at 60 °C for 0.5 h. The six-membered-ring-formation products, 3-aryl-2H-benzo[b][1,4]oxazin-2-one derivatives, were obtained in yields up to 99% by the reaction between 0.30 mmol of an o-aminophenol and 0.60 mmol of an α-phenylglyoxylic acid in ChCl/urea DES at 80 °C for 2.0 h. In the reaction between 0.30 mmol of o-phenylenediamine and 0.45 mmol of an α-phenylglyoxylic acid in ChCl/anhydrous tin(II) chloride DES at 70 °C for 1.5 h, the six-membered-ring-formation products, 3-arylquinoxalin-2(1H)-one derivatives, were synthesized, with a highest yield of 96%. This cyclization reaction occurred without the addition of other catalysts, and the title compounds were obtained with good yields under mild conditions.

A Unified Mechanism for the PhCOCOOH-mediated Photochemical Reactions: Revisiting its Action and Comparison to Known Photoinitiators.

Since 2014, we have introduced in literature the use of phenylglyoxylic acid (PhCOCOOH), a small and commercially available organic molecule, as a potent promoter in a variety of photochemical processes. Although PhCOCOOH has a broad scope of photochemical reactions that can promote, the understanding of its mode of action in our early contributions was moderate. Herein, we are restudying and revisiting the mechanism of action of PhCOCOOH in most of these early contributions, providing a unified mechanism of action. Furthermore, the understanding of its action as a photoinitiator opened a new comparison study with known and commercially available photoinitiators.

A Four-Step Enzymatic Cascade for Efficient Production of L-Phenylglycine from Biobased L-Phenylalanine.

Enantiopure amino acids are of particular interest in the agrochemical and pharmaceutical industries. Here, we report a multi-enzyme cascade for efficient production of L-phenylglycine (L-Phg) from biobased L-phenylalanine (L-Phe). We first attempted to engineer Escherichia coli for expressing L-amino acid deaminase (LAAD) from Proteus mirabilis, hydroxymandelate synthase (HmaS) from Amycolatopsis orientalis, (S)-mandelate dehydrogenase (SMDH) from Pseudomonas putida, the endogenous aminotransferase (AT) encoded by ilvE and L-glutamate dehydrogenase (GluDH) from E. coli. However, 10 mM L-Phe only afforded the synthesis of 7.21±0.15 mM L-Phg. The accumulation of benzoylformic acid suggested that the transamination step might be rate-limiting. We next used leucine dehydrogenase (LeuDH) from Bacillus cereus to bypass the use of L-glutamate as amine donor, and 40 mM L-Phe gave 39.97±3.84 mM (6.04±0.58 g/L) L-Phg, reaching 99.9 % conversion. In summary, this work demonstrates a concise four-step enzymatic cascade for L-Phg synthesis from biobased L-Phe, with a potential for future industrial applications.

Water-soluble benzoylformic acid photoinitiators for water-based LED-triggered deep-layer photopolymerization

This paper reports a series of water-soluble benzoylformic acid cleavage photoinitiators (BFAs) for LED-triggered photopolymerization based computer simulating. The photolysis mechanism of BFAs under 405 nm LED was investigated by steady-state photolysis, high resolution mass spectrometer, and electron spin resonance. The as-reported water-soluble photoinitiators BFAs can efficiently initiate free radical photopolymerization of oil-based and water-based acrylate monomers under 405 nm LED irradiation, and final double bond conversions reached about 80%. Remarkedly, BAFs exhibited an excellent ability to initiate water-based LED-triggered deep-layer photopolymerization, and the polymerization depth achieved 6.7 cm after 405 nm LED irradiation for 40 s. This study also affords the valuable reference for design and development of photoinitiators for water-based LED-triggered deep-layer photopolymerization.

Two novel zinc-based MOFs as luminescence sensors to detect phenylglyoxylic acid.

Automobile exhaust gases, plastic pollutants, smoking, and other harmful substances can cause serious harm to human beings and the environment. Styrene, as a common airborne toxin, enters the human body through breathing or the skin and is discharged in the form of phenylglyoxylic acid (PGA). Therefore, specific, sensitive and trace detection of PGA is particularly important. Here, two zinc-based metal-organic frameworks {[Zn2L1(DMF)2H2O](DMF)2H2O}n, {[Zn4(L2)2(DMF)2(H2O)3](DMF)8}n (L1 = 2,5-bis((3-carboxylphenyl)amino)terephthalic acid, L2 = 2,5-bis((4-carboxyphenyl)amino)terephthalic acid) have been reported as 1 and 2, respectively. Both 1 and 2 present 3D structures, which can both be simplified as 4,4,4-c net topology. It is worth mentioning that 2 has two different kinds of Zn SBUs as connecting nodes in the structure. Besides, compared with the other materials for the detection of PGA, 1 and 2 exhibit relatively low detection limits (LODs), both in water and in urine (where the LODs for 1 in water and urine were 0.33 μM and 0.43 μM in the range of 0-0.39 mM, and those for 2 were 0.28 μM and 0.49 μM in the range of 0-0.59 mM, respectively). In addition, the sensors have excellent anti-interference ability, high stability, rapid response, and can easily distinguish between different concentrations of PGA with the naked eye. The developed paper probes were suitable for practical sensing applications for portable detection of PGA in urine.

Photochemical C-H acetalization of O-heterocycles utilizing phenylglyoxylic acid as the photoinitiator.

A novel, mild, metal-free and easy-to-execute procedure for the C-H acetalization of O-heterocycles via visible light activation is presented, utilizing phenylglyoxylic acid as the photoinitiator. Biomass-derived O-heterocycles, like THF, can be employed, while primary, secondary alcohols and alcohols bearing a variety of functionalities were succesfully employed, affording the desired acetals in high yields. Facile acidic deprotection was also performed.

Directed evolution of formate dehydrogenase and its application in the biosynthesis of L-phenylglycine from phenylglyoxylic acid

Formate dehydrogenase (FDH) is a d-2‑hydroxy acid dehydrogenase, and catalyzes the oxidation of formate to carbon dioxide, coupled with reduction of NAD+ to NADH that plays a key role in the process of NADH regeneration. In order to obtain high activity formate dehydrogenase mutants, the formate dehydrogenase CbFDHC23S was used as the parent to conduct two rounds of directed evolution, and a mutant M2 was obtained which specific activity was about 4 times more than the parent and was more suitable for coenzyme regeneration under physiological conditions. Then, the molecular mechanism of temperature characteristic and catalytic efficiency change was preliminarily elucidated by computer-aided method. Finally, an engineered E. coli strain was established to co-express formate dehydrogenase and l-leucine dehydrogenase and enantioselectively transform phenylglyoxylic acid to give l- phenylglycine (e.e. >99%), the yield and space-time yield of l- phenylglycine can reach 90.46% and 82.07 g·L−1·d−1. This study laid a theoretical foundation for the green biosynthesis of food additives such as chiral alcohols and amino acid derivatives catalyzed by FDH coupling to enhance the regeneration capacity of NADH, reduce the regeneration cost of NADH, and achieve high efficiency and low cost.

Ultrastable Tb-Organic Framework as a Selective Sensor of Phenylglyoxylic Acid in Urine.

Industrial pollution and harmful chemicals seriously affect environment and human health. Styrene is a common air toxicant with widespread exposure sources, including smoking, automobile exhaust, and plastic pollutants. Phenylglyoxylic acid (PGA) is a typical biomarker for exposed styrene. Therefore, it is crucial to quickly identify and quantitatively detect PGA. Herein, an ultrastable terbium metal-organic framework (Tb-MOF 1) was developed, and the luminescence film (1/PLA) consisting of polylactic acid (PLA) and 1 was fabricated as a sensor for rapid detection of PGA. The sensor possesses the advantages of efficient detection [limit of detection (LOD) is 1.05 × 10-4 mg/mL] and rapid response speed (less than 10 s) for PGA in urine. Furthermore, this sensor exhibits high stability, outstanding anti-interference ability, and excellent recyclability. Based on this film technology, a paper-based probe was then developed for portable and convenient detection. The probe could easily distinguish different concentrations of PGA under the naked eye toward practical sensing applications. Meanwhile, photoinduced electron transfer was demonstrated to be responsible for the luminescence sensing. Hence, this study indicates that Tb-MOF is a promising material to detect PGA for evaluating the effect of styrene on the body.

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole Derivatives.

An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido[1,2-b][1,2,4]triazine and pyrido[1′,2′:2,3][1,2,4]triazino[5,6-b]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under high-pressure conditions. In addition, trifluoroacetic acid was used to induce this transformation. In this research, conducting the targeted reactions under high pressure using the Q-tube reactor was found to be superb in comparison to that under the traditional refluxing conditions. X-ray single-crystal analysis was utilized in this study to authenticate the structure of the synthesized products.

Petroleum and Chlorinated Solvents in Meconium and the Risk of Hypospadias: A Pilot Study.

Background: Hypospadias is a male congenital malformation that occurs in ~2 of 1,000 births. The association between hypospadias and fetal exposure to environmental chemicals has been studied, but the results are inconsistent. Although several petroleum and chlorinated solvents are suspected to have teratogenic effects, their role in the occurrence of hypospadias has been little studied and never using biomarkers of exposure. We aimed to evaluate the association between fetal exposure to petroleum and chlorinated solvents measured in meconium and the occurrence of hypospadias.Methods: We conducted a pilot case-control study in the maternity of the University Hospital of Rennes (France). Eleven cases of hypospadias and 46 controls were recruited between October 2012 and January 2014. Data from hospital records and maternal self-reported questionnaires, including socio-demographic characteristics and occupational and non-occupational exposure to chemicals, were collected. Meconium samples were collected using a standardized protocol. Levels of petroleum solvents (toluene, benzene, ethylbenzene, and p, m, and o xylene), certain metabolites (mandelic acid, hippuric acid, methylhippuric acid, S-phenylmercapturic acid, S-benzylmercapturic acid, and phenylglyoxylic acid), and two chlorinated solvents (trichloroethylene and tetrachloroethylene) were measured in meconium by gas and liquid chromatography, both coupled to tandem mass spectrometry. Associations between the concentration of each chemical and the occurrence of hypospadias were analyzed using exact logistic regressions adjusted for maternal age, educational level, pre-pregnancy body mass index, and alcohol, and tobacco consumption during pregnancy. Results are presented with odds ratios (ORs) and their 95% confidence intervals (CIs).Results: Quantification rates for petroleum and chlorinated solvents or metabolites ranged from 2.2% (for methylhippuric acid) to 77.1% (for trichloroethylene) of the meconium samples. We found a significant association between the quantification of phenylglyoxylic acid (metabolite of styrene and ethylbenzene) in the meconium and a higher risk of hypospadias (OR = 14.2, 95% CI [2.5–138.7]). The risk of hypospadias was non-significantly elevated for most of the other solvents and metabolites.Conclusion: This exploratory study, on a limited number of cases, suggests an association between petroleum solvents and hypospadias. Additional studies are needed to confirm these results and identify the determinants for the presence of these solvents in meconium.

K2S2O8 mediated synthesis of 5-aryldipyrromethanes and meso-substituted A4-tetraarylporphyrins

The synthesis of dipyrromethanes from pyrrole and arylglyoxylic acids in the presence of K2S2O8at 90 [Formula: see text]C is reported affording dipyrromethanes in very good yields. Unlike an excess pyrrole traditionally used in dipyrromethane synthesis, the current method uses a stoichiometric amount of pyrrole avoiding any use of Brønsted or Lewis acid. A gram scale synthesis of 5-phenyldipyrromethane is also achieved demonstrating potential scale up of dipyrromethanes using this method feasible. Subsequently, dipyrromethanes were converted to A4-tetraarylporphyrins also in the presence of K2S2O8at 90[Formula: see text]C. A direct synthesis of A4-tetraphenylporphyrin from excess pyrrole and phenylglyoxylic acid in the presence of K2S2O8 at 90[Formula: see text]C is also reported.

Metal‐free Photochemical Atom Transfer Radical Addition (ATRA) of BrCCl3 to Alkenes

AbstractA simple, photochemical, and metal‐free protocol for the atom transfer radical addition (ATRA) of bromotrichloromethane onto various alkenes is described. Among a range of organic molecules, phenylglyoxylic acid proved to be the most suitable photoinitiator to promote a sustainable process for the addition of bromotrichloromethane to olefins. This photochemical atom transfer radical protocol can be expanded into a wide substrate scope of aliphatic olefins bearing various functional groups, leading to the corresponding products in good to excellent yields.

Luminescent sensors based on coordination polymers with adjustable emissions for detecting biomarker of pollutant ethylbenzene and styrene

Sensitive luminescent probes for phenylglyoxylic acid (PGA), which is a biomarker of ethylbenzene and styrene (EB/S) representing the internal dose of EB/S exposure, have been constructed on the basis of newly designed luminescent coordination polymers (LCPs). Three isostructural LCPs with different lanthanide centers were solvothermally synthesized and fully characterized. All the LCPs 1–3 display strong regulated emissions by the adjustable metal–organic coordination interactions. Among LCPs 1–3, the fabricated LCP 2 can quantitatively detect PGA with the highest sensitivity in physiologically relevant ranges. The mechanism study of luminescent responses toward PGA further explains the excellent sensitivity and selectivity of LCP 2 for sensing PGA. The facile, accurate, fast, and recyclable sensing system relying on LCP materials provides a convenient approach for developing sensing platforms with adjustable emissions for assessment of the intoxication level of EB/S.