Carboxylic Acid Intermediates Research Articles

Mn-enhanced performance of the Ni-CaO/γ-Al2O3 dual function material for CO2 capture and in situ methanation

The CH4 yield over dual functional materials (DFMs) remains low and requires further improvement. In this work, we first examined the influence of Mn on the performance of the Ni-CaO/γ-Al2O3 DFM for CO2 capture and in situ methanation. Our results showed that the MnNi-DFM-3 (MnNi-CaO/γ-Al2O3 DFM) exhibited the best performance at 350 °C, with a CH4 yield of 0.56 mmol/g which is 4 times higher than that of the Ni-DFM-1 (Ni-CaO/γ-Al2O3 DFM) (0.14 mmol/g). Nanoscale characterization revealed that highly scattered Mn3O4 acted as a barrier preventing the agglomeration of Ni-based catalysts. Furthermore, our density functional theory (DFT) analysis demonstrated that the introduction of Mn enhanced the activation of CO2, promoted the dissociation of H2 and intermediates, and reduced the activation energy needed to produce carboxylic acid intermediates on the Ni catalyst. The prepared MnNi-DFM is promising to be a cheap efficient material for CO2 capture and in situ methanation. This work opens up a new pathway for enhancing the performance of DFMs using inexpensive transition metals.

Cascade CO2 Insertion in Carbanion Ionic Liquids Driven by Structure Rearrangement.

The CO2 chemisorption in state-of-the-art sorbents based on oxide/hydroxide/amine moieties is driven by strong chemical bonding formation in the carbonate/bicarbonate/carbamate products, which in turn leads to high energy input in sorbent regeneration. In addition, the CO2 uptake capacity was limited by the active sites' utilization efficiency, with each active site incorporating one CO2 molecule or less. In this work, a new concept and generation of sorbent was developed to achieve cascade insertion of multiple CO2 molecules by leveraging structure rearrangement as the driving force, leading to in situ generation of extra CO2-binding sites and significantly reduced energy input for CO2 release. The designed ionic liquids (ILs) containing carbanions with conjugated and asymmetric structure, deprotonated (methylsulfonyl)acetonitrile ([MSA]) anion, allowed the cascade insertion of two CO2 molecules via consecutive C-C and O-C bond formations. The proton transfer and structure rearrangement of the carboxylic acid intermediates played critical roles in stabilizing the first integrated CO2 and generating extra electron-rich oxygen sites for the insertion of the second CO2. The structure variation and reaction pathway were confirmed by operando spectroscopy, magnetic resonance spectroscopy (NMR), mass spectroscopy, and computational chemistry. The energy input in sorbent regeneration could be further reduced by harnessing the phase-changing behavior of the carbanion salts in ether solutions upon reacting with CO2, avoiding the energy consumption in heating the solvent. The fundamental insights obtained herein provide a promising approach to greatly improve the CO2 sorption performance via sophisticated molecular-scale structural engineering of the sorbents.

Accessing Diverse Azole Carboxylic Acid Building Blocks via Mild C-H Carboxylation: Parallel, One-Pot Amide Couplings and Machine-Learning-Guided Substrate Scope Design.

This manuscript describes a mild, functional group tolerant, and metal-free C-H carboxylation that enables direct access to azole-2-carboxylic acids, followed by amide coupling in one pot. This demonstrates a significant expansion of the accessible chemical space of azole-2-amides, compared to previously known methodologies. Key to the described reactivity is the use of silyl triflate reagents, which serve as reaction mediators in C-H deprotonation and stabilizers of (otherwise unstable) azole carboxylic acid intermediates. A diverse azole substrate scope designed via machine-learning-guided analysis demonstrates the broad utility of the sequence. Density functional theory calculations provide detailed insights into the role of silyl triflates in the reaction mechanism. Transferrable applications of the protocol are successfully established: (i) A low pressure (CO2 balloon) option for synthesizing azole-2-carboxylic acids without the need for high-pressure equipment; (ii) the use of 13CO2 for the synthesis of labeled compounds; (iii) isocyanates as alternative electrophiles for direct C-H amidation; (iv) and the use of the developed chemistry in a 24 × 12 parallel synthesis workflow with a 90% library success rate. Fundamentally, the reported protocol expands the use of heterocycle C-H functionalization from late-stage functionalization applications toward its use in library synthesis. It provides general access to densely functionalized azole-2-carboxylic acid building blocks and demonstrates their one-pot diversification.

Efficient and rapid electrocatalytic degradation of polyethylene glycol by ammonium jarosite

Polyethylene glycol (PEG) in an aqueous environment is a potential problem for water pollution treatment because of its high thermal stability, difficult hydrolysis, and high biocompatibility. This study achieved the efficient and rapid degradation of PEG with a high polymerization degree of PEG (Mn = 20,000 g/mol) in simulated wastewater by a heterogeneous electro-Fenton process using ammonium jarosite as a catalyst. The results showed that the COD removal rate of simulated wastewater and the removal rate of PEG reached 85.85% and 92.29% within 60 min, respectively, and the number average molecular weight (Mn) of PEG was reduced by 79.18% at 180 min under the conditions of 80 mg/L PEG, pH = 3, current density of 5 mA/cm2, ammonium jarosite dosing amount of 0.8 g/L and aeration rate of 1 L/min. The catalytic mechanism of ammonium jarosite was proved that highly oxidative hydroxyl radicals (·OH) in the heterogeneous electro-Fenton process were the most critical active species, which can efficiently and rapidly oxidize PEG molecules. The oxygen atom in the ether bond of PEG molecules has lone pairs of electrons, which interact with the hydroxyl groups on the surface of ammonium jarosite to weaken the ether bonds in the PEG molecules. Then the ether bond is easily to be broken under the attack of the hydroxyl radical. The breakage of the polymer chains during PEG degradation leads to a continuous decrease in the average relative molecular mass of PEG, accompanied by the formation of aldehyde and carboxylic acid intermediates, which are eventually oxidized to form CO2 and H2O as the degradation time increases.

The positive effect of water on acetaldehyde oxidation depended on the reaction temperature and MnO2 structure

The effect of H2O on acetaldehyde oxidation was studied and α-, γ-, δ-MnO2 can be affected by the H2O vapor, while β-MnO2 is hardly affected by the H2O vapor during acetaldehyde oxidation. The H2O vapor can facilitate the catalytic oxidation of acetaldehyde at moderate temperatures (ca. 70∼100 °C), with a negative effect observed at high temperatures (>100 °C). The stretching mode of the Mn−O−Mn chains in α-, γ-, δ-MnO2 allows the associatively adsorbed water to absorb on the surface prior to acetaldehyde. Afterwards, acetaldehyde can form hydrogen bonds with the associatively adsorbed water molecules, thus, producing the intermediate carboxylic acid species, which are easily degraded to CO2. The negative effect of H2O on the acetaldehyde oxidation at high temperatures is attributed to the difficulty in adsorbing acetaldehyde on MnO2 via hydrogen bonding with the adsorbed H2O. These findings reveal the role of water in the catalytic oxidation of acetaldehyde.

Development of Manufacturing Processes for the Carboxylic Acid Key Intermediate of Lusutrombopag: One-Pot Reaction Process of Formylation and the Horner–Wadsworth–Emmons Reaction

We describe the development of a one-pot preparation process of (E)-3,5-dichloro-4-(3-ethoxy-2-methyl-3-oxoprop-1-en-1-yl)benzoic acid (3), which is a key carboxylic acid intermediate of lusutrombopag. This one-pot reaction process is composed of lithiation of 3,5-dichlorobenzoic acid with lithium diisopropylamide (LDA), formylation using N-formylmorpholine, followed by olefination employing the Horner–Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate. This method enabled kilogram-scale manufacturing of carboxylic acid 3, a key intermediate of lusutrombopag with high purity, together with a reduced number of steps, improvement of yield, and avoidance of a cumbersome procedure for isolation of the intermediate.

Effective Removal and Mineralization of 8‐Hydroxyquinoline‐5‐sulfonic Acid through a Pressurized Electro‐Fenton‐like Process with Ni−Cu−Al Layered Double Hydroxide

AbstractNi−Cu−Al layered double hydroxide (Ni−Cu−Al LDH) was proposed as an electro‐Fenton‐like catalyst for 8‐hydroxyquinoline‐5‐sulfonic acid (8‐HQS) removal in water. The properties of the prepared catalysts were characterized by using X‐ray, SEM and EDAX analyses. The effect of numerous operative parameters on the removal of 8‐HQS and total organic carbon (TOC) was studied. Very high level removal of both 8‐HQS and TOC (87 and 79 %, respectively) were obtained by using a pressurized electro‐Fenton‐like process (PrEFL‐LDH) at P=10 bars, using a Ti/IrO2‐Ta2O5 anode for 6 h. The process presented good performances in a large range of pH (3–10) and gave better removals of 8‐HQS and TOC with respect to that achieved by both i) EF catalyzed by homogeneous (FeSO4) or natural heterogeneous catalysts (pyrite and chalcopyrite) and ii) anodic oxidation at a boron doped diamond anode. Ni−Cu−Al LDH retained its catalytic activity after four cycles. Moreover, the carboxylic acid intermediates were identified and analyzed by HPLC.

Occurrence and Degradation Potential of Fluoroalkylsilane Substances as Precursors of Perfluoroalkyl Carboxylic Acids.

Polyfluoroalkylsilanes (PFASis) are a class of artificial chemicals with wide applications in surface coating, which arouse attention due to their hydrophobic/oleophobic properties and potential biological effects. In this study, a robust high-resolution mass spectrometry method through direct injection into a Fourier transform ion cyclotron resonance instrument was established, with the aid of CF2-scaled Kendrick mass defect analysis and isotope fine structure elucidation. The occurrence of 8:2 polyfluoroalkyl trimethoxysilane (8:2 PTrMeOSi) and 8:2 polyfluoroalkyl triethoxysilane (8:2 PTrEtOSi), as well as their cationic adducts, solvent substitutions, and other compound analogues, were identified in commercial antifingerprint liquid products. In the hydroxyl radical-based total oxidizable precursor assay, differential molar yields of products were observed with regard to varied PFASi carbon-chain lengths and terminal groups. The yields of perfluoroalkyl carboxylic acids (PFCAs) from 8:2 PTrMeOSi conversion were the highest (92 ± 9%, n = 3), with the C ( n - 1) perfluoroheptanoic acid (PFHpA, 49 ± 11%, n = 3) as the dominating product. Distinct conversion of 8:2 PTrMeOSi in the simulated solar exposure experiments found that C ( n) perfluorooctanoic acid (PFOA, 0.6 ± 0.04 ‰, n = 3) was predominant, and 8:2 fluorotelomer carboxylic acid (8:2 FTCA, 0.59 ± 0.08‰, n = 3), 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA, 0.09 ± 0.00‰, n = 3) intermediates were also observed. To our knowledge, this is the first report regarding the occurrence and degradation potential of several fluoroalkylsilane substances as PFCA precursors.

Synthesis and kinetics of photochromic carboxy-substituted dithizonatophenylmercury(II)

With the aim of improving water-solubility and providing anchor points for follow-up reactions, the well-known intensely colored green analytical reagent, dithizone (H2Dz), was functionalized by two carboxylic acid substituents. Similarly, sulfacetamide and sulfonyl substituents were also employed, but its dithizone products decomposed in aqueous medium. The crystal structure of the nitroformazan carboxylic acid intermediate is reported. Its bent conformation is maintained by intramolecular hydrogen-bonding. Together with the two added dithizone carboxylate end groups the three spatially removed points are now available for complexation, eg. with phenylmercury(II) moieties. As opposed to the otherwise single-metal PhHgHDz(COOH)2 complex, added heavy mercury atoms in PhHgHDz(COOHgPh)2 inhibit photochromism in the tri-metallic complex. Kinetic studies of the photochromic return reaction of PhHgHDz(COOH)2 show the reaction rate to be linearly dependant on concentration and exponentially dependant on temperature, with rate constant of 0.0084 s−1 at 0 °C, i.e. four times faster than observed for the unsubstituted complex, PhHgHDz.

Deciphering the degradation/chlorination mechanisms of maleic acid in the Fe(II)/peroxymonosulfate process: An often overlooked effect of chloride

In recent years, a significant effort has been devoted into investigating the effects of chloride on the degradation kinetics of aromatic pollutants. The impact of chloride on the decomposition of short-chain carboxylic acid intermediates from aromatics degradation has often been overlooked. In this study the roles of chloride in the oxidation of maleic acid (MA) in the Fe(II)/peroxymonosulfate (PMS) process was investigated. Degradation efficiency, reaction intermediates, adsorbable organic halogen (AOX) accumulation and mineralization were examined. The chloride ion (Cl−) was found to have an overall negative impact on MA degradation and mineralization in the Fe(II)/PMS system. The presence of Cl− led to the formation of chlorinated by-products and a high production of AOX. The mineralization of MA was decreased with increasing Cl− concentrations. Kinetic modeling demonstrated the impact of various radicals largely depended on the concentration of Cl−. The significance of Cl2•- or Cl2 for MA destruction was enhanced with increasing Cl− content, and overwhelmed that of SO4•- when the Cl− concentration was over 5 mM. In the absence of Cl−, SO4•- was the primary radical responsible for MA oxidation. A possible degradation pathway is proposed (cis-trans isomerization, decarboxylation and halogenations processes). These results may help to understand the full oxidation pathways of refractory aromatic compounds and the mechanism of chlorinated by-products formation in industrial saline wastewater treatment.

Kirmse-Doyle- and Stevens-Type Rearrangements of Glutarate-Derived Oxonium Ylides.

A novel chemoenzymatic synthetic cascade enables the preparation of densely decorated tetrahydrofuran building blocks. Here, the lipase-catalyzed desymmetrization of 3-alkoxyglutarates renders highly enantioenriched carboxylic acid intermediates, whose subsequent activation and oxonium ylide rearrangement by means of rhodium or copper complexes furnishes functionalized O-heterocycles with excellent diastereoselectivity. The two-step protocol offers a streamlined and flexible synthesis of tetrahydrofuranones bearing different benzylic, allylic or allenylic side chains with full control over multiple stereogenic centers.

Mechanistic in-operando FT-IR studies for hydroprocessing of triglycerides

In-operando measurements were carried out for the first time to identify different intermediates and primary products formed during the conversion of lipids for catalytic as well as non-catalytic thermal hydroprocessing. Hydroprocessing of lipids was carried at 280–300 °C temperature, 40–60 bar pressure, 1500 Nl/L H2/Feed ratio and 1 h−1 space velocity in a fixed-bed tubular reactor. A high pressure metallic probe was used for collecting the FTIR spectra under these conditions. Under these conditions although the conversion of triglyceride molecules were complete, the deoxygenation reactions were less than 1%, with 6–7% carbon loss and 17–18% hydrogen loss into the gaseous phase corresponding to propane. In-operando FT-IR studies confirmed that depropanation (propane removal) is the primary reaction during catalytic hydroprocessing of triglycerides, along with formation of intermediates. For thermal hydroprocessing wide range of intermediates – alcohols, alkenes, ketones, anhydrides, ethers, acids, aldehyde and esters – were observed. Such intermediates indicate several undesirable coupling reactions such as CC bond formation, esterification, etherification and ketonization. For catalytic hydroprocessing only selective product intermediates were observed. Triglycerides hydroprocessing over Pd/Al2O3 catalyst predominantly produced carboxylic acid and aldehyde intermediates, along with very weak bands due to aromatics. Pd/C predominantly produced aldehydes with weak bands due to ketones. Sulfided CoMoP/Al2O3 catalyst also produced aldehydes predominantly, but also small quantities of carboxylic acids as intermediates, from trigycerides. IR bands due to alcohols, ethers, aromatics and cyclic ketones were observed at the later stage of reaction over CoMoP(S)/Al2O3 catalyst.

From 2- to 3-Substituted Ferrocene Carboxamides or How to Apply Halogen “Dance” to the Ferrocene Series

Two methods were compared to convert ferrocene into N,N-diisopropylferrocenecarboxamide, N,N-diethylferrocenecarboxamide, N,N-dimethylferrocenecarboxamide, and (4-morpholinocarbonyl)ferrocene, namely, deprotometalation followed by trapping using dialkylcarbamoyl chlorides and amide formation from the intermediate carboxylic acid. The four ferrocenecarboxamides were functionalized at C2; in the case of the less hindered and more sensitive amides, recourse to a mixed lithium–zinc 2,2,6,6-tetramethylpiperidino-based base allowed us to achieve the reactions. Halogen migration using lithium amides was next optimized. Whereas it appeared impossible to isolate the less hindered 3-iodoferrocenecarboxamides, 3-iodo-N,N-diisopropylferrocenecarboxamide proved stable and was converted to new 1,3-disubstituted ferrocenes by Suzuki coupling or amide reduction. DFT calculations were used to rationalize the results obtained.

Comparative electrochemical degradation of the herbicide tebuthiuron using a flow cell with a boron-doped diamond anode and identifying degradation intermediates

The electrochemical degradation of tebuthiuron (TBH; 100mgL−1) was carried out under enhanced mass transport conditions (using a flow cell with a BDD anode), while investigating the effect of solution pH, absence and presence of Cl− ions in the supporting electrolyte solution (0.1molL−1 Na2SO4), and current density (j=10, 30, 50mAcm−2) on the herbicide degradation and resulting oxidation intermediates. The enhanced mass transport conditions led to significantly improved performances, comparatively to previous results obtained with a common electrochemical cell. The solution pH or presence of Cl− ions did not affect the TBH removal rate. However, the COD removal rate, despite being independent of pH, was significantly faster in the presence of Cl− ions, most probably due to false results caused by organochlorinated intermediates. In the absence of Cl− ions in solution, the TBH removal rate increased with j, whereas the COD removal rate was not affected, but significantly increased removal rates were attained in the presence of Cl− ions, most probably because of increased formation of organochlorines. As expected, higher values of the general and mineralization current efficiencies as well as lower energy consumptions per unit TOC mass removed (ECTOC) were attained at 10mAcm−2; in the absence of Cl− ions, complete removal of TBH and 80% removal of TOC were attained with ECTOC=0.2kWhg−1 (less than 1/10 of those for electrolyses using a conventional electrochemical cell). From the identified intermediates, an initial TBH oxidation pathway like those of coupled processes involving photochemistry is expected. Most carboxylic acid intermediates were removed or being removed by the end of the electrolyses (except tartronic acid, which accumulated). As expected, organochlorinated intermediates were identified in the presence of Cl− ions, but were completely removed by the end of the electrolyses. In summary, the electrochemical degradation of TBH in the presence of Cl− ions is not advantageous; no significant improvement in the TBH and TOC removal rates, or in the energy expense, is achieved and the formation of organochlorines is a real possibility.

Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast.

The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combination of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic.

Photocatalytic degradation of terephthalic acid on sulfated titania particles and identification of fluorescent intermediates

Terephthalic acid (TA) is toxic and known as an endocrine disruptor. In this paper, the photocatalytic degradation of TA using sulfated titanium dioxide SO42−/TiO2 photocatalysts was investigated. The photocatalysts were prepared by sol–gel method and characterized by XRD, SEM, BET, ICP/MS and spectroscopic methods. Their activities were compared with bare TiO2 and Degussa P25. The effects of catalyst sulfur content, the initial TA concentration and pre-treatment conditions (O2, N2 or non-pretreated) were studied. O2 functions were also explored. Since there had been no comprehensive study of fluorescent intermediates reported yet, we investigated the intermediates and discovered 5 new intermediates (4 fluorescent and 1 non-fluorescent) which were identified by gas chromatography–mass spectrometry (GC/MS) and fluorescence spectroscopy. These intermediates are complementary to the previously identified carboxylic acid intermediates and might provide new insights to the mechanism of photocatalytic degradation of TA. Since TA is widely used as a probing molecule for photocatalytically generated ·OH radicals, the ratios of fluorescent intermediates of TA degradation may provide new clues to the photocatalytic activity and mechanism. Based on the results obtained, the possible destruction pathway of TA is also proposed.

Nucleophilic difluoro(trimethylsilyl)methylation of arylidene Meldrum's acids

A reaction of arylidene Meldrum's acids with difluoro(trimethylsilyl)methylzinc bromide in the presence of copper cyanide (10 mol%) is described. The primary addition products are hydrolized and decarboxylated followed by esterification of intermediate carboxylic acids affording β-Me3SiCF2-substituted esters. Protodesilylation of Me3SiCF2-group can be performed under mild conditions affording CHF2-fragment.

Synthesis and pharmacological evaluation of optically pure, novel carbonyl guanidine derivatives as dual 5-HT2B and 5-HT7 receptor antagonists

A series of 9-disubstituted N-(9H-fluorene-2-carbonyl)guanidine derivatives have been discovered as potent and orally active dual 5-HT2B and 5-HT7 receptor antagonists. Upon screening several compounds, N-(diaminomethylene)-4′,5′-dihydro-3′H-spiro[fluorene-9,2′-furan]-2-carboxamide (17) exhibited potent affinity for both 5-HT2B (Ki=5.1nM) and 5-HT7 (Ki=1.7nM) receptors with high selectivity over 5-HT2A, 5-HT2C, α1, D2 and M1 receptors. Optical resolution of the intermediate carboxylic acid 16 via the formation of diastereomeric salts using chiral alkaloids gave the optically pure compounds (R)-17 and (S)-17. Both enantiomers suppressed 5-HT-induced dural protein extravasation in guinea pigs in a dose-dependent manner and the amount of leaked protein was suppressed to near normal levels when orally administrated at 10mg/kg. (R)-17 and (S)-17 were therefore selected as candidates for human clinical trials.

Hydrodeoxygenation of palm oil to hydrocarbon fuels over Ni/SAPO-11 catalysts

Small particles of SAPO-11 with large surface area and mesoporosity were synthesized hydrothermally. Ni/SAPO-11 catalysts with different Ni loadings were prepared by incipient wetness impregnation, and their physicochemical properties were characterized by X-ray diffraction, scanning electron microscopy, N2 adsorption-desorption, NH3 temperature-programmed desorption, Thermogravimetric, and H2 chemisorption. In the Ni impregnation of SAPO-11, the mesopores of SAPO-11 accommodated the Ni particles and give good dispersions, but with the partial blocking of some micropores. In the hydrodeoxygenation of palm oil, the production of liquid alkanes depends on the competition between hydrodeoxygenation and decarbonylation pathways via the corresponding carboxylic acid intermediates. The weak and medium acidity of SAPO-11 and a good match of the Ni and SAPO-11 functions in the Ni/SAPO-11 catalysts decreased the cracking of primary long chain alkanes and gave a high liquid alkane yield of 70 wt% and isomerization selectivity of >80 mol%.

Diastereoselective synthesis of γ- and δ-lactams from imines and sulfone-substituted anhydrides.

Sulfone-substituted γ- and δ-lactams have been prepared in a single step with high diastereoselectivity. Sulfonylglutaric anhydrides produce intermediates that readily decarboxylate to provide δ-lactams with high diastereoselectivity. Substituents at the 3- or 4-position of the glutaric anhydride induce high levels of stereocontrol. Sulfonylsuccinic anhydrides produce intermediate carboxylic acids that can be trapped as methyl esters or allowed to decarboxylate under mild conditions. This method has been applied to a short synthesis of the pyrrolizidine alkaloid (±)-isoretronecanol.