Reactions Of Carbonyl Compounds Research Articles

Efficient Radical-Mediated Intermolecular α-Alkylation Reactions of Carbonyl Compounds with Nonactivated Alkenes.

Alkylation reactions are fundamental carbon-carbon bond-forming reactions in synthetic organic chemistry. Among them, intermolecular α-alkylation reactions of carbonyl compounds with alkenes are important because they are more atom-economical than the equivalent processes using alkyl halides. However, intermolecular reactions with nonactivated alkenes such as 1-hexene, which can allow the use of a wide range of valuable substrates, have been considered to be very challenging for a long time. In this review, radical-mediated intermolecular α-alkylation reactions of carbonyl compounds with nonactivated alkenes are discussed. The examples are grouped into three types of reactions: peroxide-mediated reactions, metal-oxidant-mediated reactions, and photoactivated reactions. Photoredox-catalyzed alkylation reactions under visible-light irradiation are discussed as a particularly promising recent hot topic. This review provides brief history and new prospects on the α-alkylation process with nonactivated alkenes using α-carbonyl radical species.

NHC-Mediated Photochemical/Electrochemical Synthesis of Carbonyl Compounds

AbstractGreat progress has been made in the photochemical/electrochemical reactions of carbonyl compounds catalyzed by N-heterocyclic carbenes (NHCs), allowing for many incredible reactions. The form of active intermediates hugely varies in different reactions. Under light or electricity, different active intermediates can be generated during NHC-catalyzed reactions depending on their interaction with different substrates and the reaction conditions. Intermediates can be converted into α,β-unsaturated acylazoliums, Breslow intermediates, homoenolates, and acylazoliums and subsequently undergo single- or double-electron conversions. This study reviews the different active intermediates formed by NHC in photochemical/electrochemical catalysis.1 Introduction2 NHC-Mediated Photoreactions3 NHC-Mediated Electrochemical Reactions4 Conclusion and Prospects

A Simple and Efficient Method for the Nickel‐Catalyzed Synthesis of Azines from Aldehydes and Hydrazines

AbstractAzines are organic molecules with a C=N−N=C functional range of applications. But the conventional azines synthesis process requires a high reaction temperature and long reaction time combined with complex reaction facilities, so the synthesis process needs to be further improved in terms of economic efficiency and process simplification. Here, we demonstrate a structurally well‐defined inorganic ligand Ni compound, (NH4)4[NiMo6O18(OH)6](Ni‐POMs). The catalysts show good activity towards the reaction of carbonyl compounds, and the corresponding products can be obtained in yields up to about 90 %. In this condition, the majority of the aldehydes (aromatic and aliphatic) can be reacted, and the products are obtained in high yields. Density functional theory (DFT) looked into the process by which benzaldehyde and hydrazine hydrate reacted on the surface of Ni‐POMs. It was calculated that the whole reaction goes through two stages and the activation energy of the whole reaction is −6.72 kcal/mol. Thus, from experiment to calculation, a complete structure of the catalytic reaction cycle has been constructed.

Application of α-bromination reaction on acetophenone derivatives in experimental teaching: a chemical innovation experiment engaging junior undergraduates

The α-bromination reaction of carbonyl compounds is a significant topic in the field of organic chemistry. However, due to the lack of suitable brominating reagents, the application of this reaction in undergraduate organic chemistry experiments is limited. In this study, three junior undergraduates successfully conducted an innovative experiment under the guidance of teachers. The bromination of various acetophenone derivatives was investigated by employing pyridine hydrobromide perbromide as the brominating agent, with a focus on exploring the effects of reaction time, reaction temperature, and dosage of the brominating agent. The results demonstrated that 4-chloro-α-bromo-acetophenone could be synthesized at 90 ℃ using 4-chloroacetophenone as a substrate and acetic acid as a solvent with a molar ratio of substrate to brominator being 1.0:1.1. Through the experimental teaching of 18 junior undergraduates, it was observed that all the students successfully completed the experiment within a time frame of 4–5 h, with a notable achievement yield exceeding 80% observed in 14 students. This innovative experiment exhibits significant advantages in terms of safety, high yield, cost-effectiveness, and repeatability. Furthermore, while reinforcing fundamental skills in chemistry experimentation among students, it enhances their scientific literacy levels and fosters innovation consciousness as well as practical aptitude. Consequently, this approach is highly suitable for widespread implementation and integration into undergraduate experimental pedagogy.

Truly Catalytic Gewald Synthesis of 2-Aminothiophenes Using Piperidinium Borate (Pip Borate), a Conjugate Acid–Base Pair

AbstractThe Gewald reaction has been well-known for more than half a century as an excellent method to provide bioactive 2-aminothiophene heterocycles from the reaction of carbonyl compounds, α-cyanoacetates, and elemental sulfur, in the presence of amines, in stoichiometric amounts. This work describes the use of salts of boric acid as conjugate acid-base pairs in a truly catalytic amount for the cyclocondensation of ketones with active methylenes such as malononitrile, ethyl cyanoacetate, and benzoyl acetonitrile with sulfur to give 2-aminothiophenes via the Gewald reaction. The present protocol is also applied for synthesizing Tinoridine, an anti-peroxidative NSAID, with excellent yield. Additionally, the catalyst has great recyclability and reusability.

Photoinduced Efficient Catalytic α-Alkylation Reactions of Active Methylene and Methine Compounds with Nonactivated Alkenes.

In catalytic α-alkylation reactions of carbonyl compounds, although SN2-type substitution reactions of enolates with alkyl halides are a conventional methodology, addition reactions with alkenes are more desirable because of their atom-economical character; however, reactions with nonactivated alkenes are challenging. Here, we developed highly efficient catalytic α-alkylation reactions of active methylene and methine compounds with nonactivated alkenes such as 1-decene using an organophotocatalyst and lithium thiophenoxide as a Lewis acid/Brønsted base/hydrogen atom transfer (HAT) multifunctional catalyst under blue-light irradiation. The reaction was also performed with a higher degree of efficiency under a continuous-flow system to obtain the products in multigram scales. The present reaction system enables highly efficient and practical α-alkylation reactions of active methylene and methine compounds to be achieved.

Formation, Evolution, and Antioxidant Activity of Melanoidins in Black Garlic under Different Storage Conditions.

Melanoidins (MLDs) are formed through the reaction of carbonyl compounds and amino compounds in the Maillard reaction (MR) during the heating or storage of food. In this study, the formation, chemical composition, and structural characteristics of black garlic (BG) MLDs stored at different temperatures (4 °C, 20 °C, and 35 °C) over a period of 6 months were investigated. The initial products of the MR formed more often at 4 °C and 20 °C, while higher temperatures (35 °C) promoted the reaction in the middle and late stages of the MR. The higher temperature promoted an increase in molecular weight and MLD content, which can be attributed to the increase in protein and phenolic content. Elemental analysis confirmed an increase in nitrogen (N) content and the continuous incorporation of nitrogen-rich substances into the skeleton. Amino acids, particularly aspartic acid and threonine, were the primary N-containing compounds involved in MLD formation. Additionally, the infrared analysis revealed that the changes in MLDs during storage were characterized by amide I and amide II groups. The MR enhanced the yields of heterocyclic compounds (from 56.60% to 78.89%), especially that of O-heterocyclic compounds, at the higher temperature according to Py-GC-MS analysis. Furthermore, the higher temperature enhanced the molecular weight, maximum height, and roughness of MLDs compared to the control. The antioxidant ability of MLDs was positively correlated with storage temperatures. In summary, temperature had an impact on the formation, evolution, and antioxidant activity of MLDs.

Chemoselectivity change in catalytic hydrogenolysis enabling urea-reduction to formamide/amine over more reactive carbonyl compounds

The selective transformation of a less reactive carbonyl moiety in the presence of more reactive ones can realize straightforward and environmentally benign chemical processes. However, such a transformation is highly challenging because the reactivity of carbonyl compounds, one of the most important functionalities in organic chemistry, depends on the substituents on the carbon atom. Herein, we report an Ir catalyst for the selective hydrogenolysis of urea derivatives, which are the least reactive carbonyl compounds, affording formamides and amines. Although formamide, as well as ester, amide, and carbamate substituents, are considered to be more reactive than urea, the proposed Ir catalyst tolerated these carbonyl groups and reacted with urea in a highly chemoselective manner. The proposed chemo- and regioselective hydrogenolysis allows the development of a strategy for the chemical recycling of polyurea resins.

Recent Advances in Ynenamine Chemistry.

Enamines are formed by reacting a carbonyl compound with an amine under dehydration conditions. A vast array of transformations has been achieved via preformed enamine chemistry. Recently, by introducing conjugating double bonds to the enamine functionality, dienamines, and trienamines have propelled the discovery of several previously unattainable remote-site functionalization reactions of carbonyl compounds. Comparatively, alkyne-conjugating enamine analogues have recently shown high potential in multifunctionalization reactions while remaining underexplored. In this account, we systematically summarized and discussed recent advances in synthetic transformations based on ynenamine-containing compounds.

Comparative characteristics of oxidative modification intensity of proteins in infant milk formulas

Cow's milk is mainly used in the production of infant milk formulas. However, the protein composition of cow's milk differs significantly from the proteome of breast milk. In addition, various technological factors significantly affect the properties and structure of proteins, susceptibility to oxidative processes. This article uses a method of complex evaluation of the products of oxidative modification of proteins to characterize the total level of carbonyl compounds with the analysis of the ratio of aldehyde-dinitrophenylhydrazones (ADNPH) and ketone-dinitrophenylhydrazones (CDNPH), which increases the possibility of determining the severity of protein damage. The purpose of the study was to compare the level of indicators of oxidative modification of proteins in adapted milk infant formulas. Material and methods. The research objects were 4 dry adapted milk infant formulas, as well as ultra-pasteurized cow's milk. The intensity of oxidative modification of milk proteins was determined spectrophotometrically by the reaction of carbonyl compounds with dinitrophenylhydrazine (DNFG). Results. With spontaneous oxidation in infant formula, the total area of carbonyl derivatives of proteins (Sомб) was increased compared to the indicators of ultra-pasteurized cow's milk. The greatest change occurred in relation to ADNFG indicators (SАДНФГ), the level of which increased in 3 formulas by 48.6-59.4%. The content of ketone derivatives (SКДНФГ) did not differ significantly in the studied mixtures from milk indicators. The level of carbonyl derivatives of proteins in milk infant formulas was even more elevated during the induction of oxidation by the addition of iron ions and hydrogen peroxide to the incubation medium. The content of both total and various fractions of carbonyl compounds exceeded the corresponding indicators of cow's milk by 2.0-2.6 times. Conclusion. The results of the study indicate a greater susceptibility to oxidative damage of proteins in milk infant formulas, compared with cow's milk.

Synthetic approaches of medicinally important Schiff bases: An updated Review

The Schiff base defined by an imine or azomethine (-CH= N-) group, is mostly synthesized by the condensation reaction of carbonyl compounds (Aldehyde or Ketone) with compounds consisting of amine moiety. Schiff bases are among the most chiefly used organic compounds, revealing a wide range of applications, such as electroluminescent effects, fluorescence properties, nonlinear optical and chemosensory properties. The typical Schiff bases are crystalline solids that are basic, although at least some of them combine with strong acids to generate insoluble salt. Schiff bases are widely used in the pharmaceutical, electronic, cosmetic and polymer industries. Schiff bases use various alpha-amino acids and aldehydes in acidic or basic conditions. Schiff bases form a new class of drugs that can strengthen the immune system and also be used in the treatment of various ailments. The C=N imine bond's electrophilic carbon and nucleophilic nitrogen offer great binding chances with many nucleophiles and electrophiles, which can be used to suppress specific diseases, enzymes or DNA replication. These Schiff bases are synthesized from various aldehydes or ketones and amines under stirring conditions, catalyst-free, reflux conditions, conventional methods, microwave irradiation and ultrasonic conditions. Thus, Schiff bases and their derivatives can be synthesized using various techniques and may be further used for enormous biological applications with potent effects.

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis.

Photocatalysis opens up a new window for carbonyl chemistry. Despite a multitude of photochemical reactions of carbonyl compounds, visible light-induced catalytic asymmetric transformations remain elusive and pose a formidable challenge. Accordingly, the development of simple, efficient, and economic catalytic systems is the ideal pursuit for chemists. Herein, we report an enantioselective radical photoaddition to ketones through a Lewis acid-enabled photoredox catalysis wherein the in situ formed chiral N,N'-dioxide/Sc(III)-ketone complex serves as a temporary photocatalyst to trigger single-electron transfer oxidation of silanes for the generation of nucleophilic radical species, including primary, secondary, and tertiary alkyl radicals, giving various enantioenriched aza-heterocycle-based tertiary alcohols in good to excellent yields and enantioselectivities. The results of electron paramagnetic resonance (EPR) and high-resolution mass spectrum (HRMS) measurements provided favorable evidence for the stereocontrolled radical addition process involved in this reaction.

Exploring aging kinetic mechanisms of bio-oil from biomass pyrolysis based on change in carbonyl content

Bio-oil from biomass pyrolysis offers a wide range of applications such as transport fuels, value-added chemicals, materials, or heat and power generation. However, fresh bio-oil is unstable due to its physicochemical properties, chemical composition, and multiphase behaviors changing with time. The bio-oil aging kinetic model based on the change in carbonyl content was developed, and the pattern search method was proposed to optimize the model parameters. The accelerated and long-term aging kinetic behaviors of two bio-oil samples could be described accurately by the carbonyl-based aging kinetic model. The reaction rate constant values for the long-term and accelerated aging of bio-oil 1 were 1.694 × 10−4 and 4.589 × 10−2 h−1, whereas 3.084 × 10−4 h−1 and 1.329 × 10−1 h−1 were reported for bio-oil 2, respectively. The reaction order values of the long-term aging (2.452 for bio-oil 1 and 3.973 for bio-oil 2) were higher than that of the accelerated aging (0.943 for bio-oil 1 and 1.000 for bio-oil 2). Two bio-oil samples showed different aging kinetic characteristics due to different raw materials, pyrolysis reactor types and conditions, and bio-oil phases for aging tests. The hydration, hemiacetal, acetal and polymerization reactions of carbonyl compounds were the primary mechanisms for the change in carbonyl content during bio-oil aging.

Biocatalytic hydrogen-transfer to access enantiomerically pure proxyphylline, xanthinol, and diprophylline

Alcohol dehydrogenases (ADHs; EC 1.1.1.1) have been widely used for the reversible redox reactions of carbonyl compounds (i.e., aldehydes and ketones) and primary or secondary alcohols, often resulting in optically pure hydroxyl products with high added value. In this work, we report a concise chemoenzymatic route toward xanthine-based enantiomerically pure active pharmaceutical ingredients (API) – proxyphylline, xanthinol, and diprophylline employing various recombinant short-chain ADHs with (R)- or (S)-selectivity as key biocatalysts. By choosing the appropriate ADH, the (R)- as well as the (S)-enantiomer of proxyphylline was prepared in excellent enantiomeric excess (99–99.9% ee), >99% conversion, and the isolated yield ranging from 65% to 74%, depending on the used biocatalyst (ADH-A from Rhodococcus ruber or a variant derived from Lactobacillus kefir, Lk-ADH-Lica). In turn, E. coli/ADH-catalyzed bioreduction of the carbonylic precursor of xanthinol and diprophylline furnished the corresponding (S)-chlorohydrin in >99% ee, >99% conversion, and 80% yield (in the case of Lk-ADH-Lica); while the (R)-counterpart was afforded in 94% ee, 64% conversion, and 41% yield (in the case of SyADH from Sphingobium yanoikuyae). After further chemical functionalization of the key (S)-chlorohydrin intermediate, the desired homochiral (R)-xanthinol (>99% ee) was obtained in 97% yield and (S)-diprophylline (>99% ee) in 90% yield. The devised biocatalytic method is straightforward and thus might be considered practical in the manufacturing of title pharmaceuticals.

Nitrogen-Doped Carbon-Incarcerated Zinc Electrodes as Heterogeneous Catalysts for Electrochemical Allylation of Carbonyl Compounds.

Electrochemical allylation reactions of carbonyl compounds using cathodes prepared from nitrogen-doped carbon (NDC)-incarcerated zinc catalysts have been developed. A range of aldehydes and ketones afforded the desired allylic alcohols in high yields with <10 mol % zinc leaching, and the heterogeneous nature of the active species was suggested. Compared with bulk zinc electrodes, NDC-stabilized zinc nanoparticle species were compatible with a broader range of heteroaromatic substrates and enabled the use of an undivided cell.

ZnCl2-mediated stereo- and chemoselective synthesis of vinylphosphonates.

A highly chemo- and stereoselective synthesis of diethyl (E)-2-(alkylidene)-2-phosphonoacetonitriles via the Knoevenagel condensation reaction of carbonyl compounds with diethyl cyanomethylphosphonate in the presence of zinc chloride has been achieved. By the presented method, various E-isomers of arylmethylidene phosphonates rather than Horner-Wadsworth-Emmons olefination products were obtained in good to excellent yields. Their E configurations were determined by X-ray diffraction and NMR analyses. In addition, DFT calculations provided insights into the chemo- and stereoselectivity of the reaction.

A novel and efficient N-doping carbon supported cobalt catalyst derived from the fermentation broth solid waste for the hydrogenation of ketones via Meerwein–Ponndorf–Verley reaction

Most of the non-noble metal catalysts used for the Meerwein–Ponndorf–Verley (MPV) reaction of carbonyl compounds rely on the additional alkaline additives during preparation to achieve high efficiency. To solve this problem, in this work, we prepared a novel N-doped carbon supported cobalt catalyst (Co@CN), in which the carriers were derived from the nitrogen-rich organic waste, i.e., oxytetracycline fermentation residue (OFR, obtained from oxytetracycline refining workshop). No additional nitrogen sources were used during preparation. The results showed that inherent nitrogen in OFR could provide N-containing basic sites, and formed Co-N structures via coordinating with cobalt. The Co-N sites together with the coexisting Co(0) cooperated to catalyze the conversion of ethyl levulinate (EL) to γ-valerolactone (GVL) by MPV reaction. Co(0) dominated the activation of H in isopropanol, while Co-N dominated the formation of the six-membered ring transition state.

Concentration and Reactivity of Carbonyl Compounds in the Atmosphere of North China

To reveal the characteristics of photochemical pollution in North China, adsorbing columns with 2, 4-dinitrophenylhydrazine(DNPH) were used to sample carbonyl compounds in Shijiazhuang and Xinglong between May 2018 and April 2019. The samples were analyzed by high-performance liquid chromatography to understand the composition, volume fraction, source, ·OH loss rate, and ozone formation potential of the carbonyl compounds. A total of 13 carbonyl compounds containing carbonyl groups were determined, of which acetone, formaldehyde, and acetaldehyde were highest at(6.46±5.25)×10-9, (3.76±2.29×10-9), and(2.65±1.74)×10-9 in Shijiazhuang compared to(1.85±1.27)×10-9, (1.29±1.02)×10-9, and(0.72±0.48)×10-9 in Xinglong, respectively. The estimated maximum ozone formation potential(OFP) of formaldehyde was much higher than that of acetaldehyde; the C1/C2 and C2/C3 ozone formation potential(OFP) of formaldehyde was much higher than that of acetaldehyde; and the C1/C2 and C2/C3 values showed that vehicle exhaust and fossil fuel combustion were the main sources in Shijiazhuang in association with the higher level of industrialization. In Xinglong, the carbonyl compounds mainly originated from natural sources. Acetaldehyde(1.77 s-1), formaldehyde(1.57 s-1), and butyraldehyde(0.42 s-1) contributed most to L·OH in Shijiazhuang, and formaldehyde(0.53 s-1), acetaldehyde(0.47 s-1), and butyraldehyde(0.12 s-1) were the three main contributors to L·OH in Xinglong. The carbonyl compounds contributing most to O3 production were formaldehyde and acetaldehyde at(34.61×10-9 O3) and (16.73×10-9 O3) in Shijiazhuang, compared to (11.77×10-9 O3) and (4.47×10-9 O3) in Xinglong, respectively.

Kinetics of the Reactions of CH2OO with Acetone, α-Diketones, and β-Diketones

Rate constants for the reactions between the simplest Criegee intermediate, CH2OO, with acetone, the α-diketones biacetyl and acetylpropionyl, and the β-diketones acetylacetone and 3,3-dimethyl-2,4-pentanedione have been measured at 295 K. CH2OO was produced photochemically in a flow reactor by 355 nm laser flash photolysis of diiodomethane in the presence of excess oxygen. Time-dependent concentrations were measured using broadband transient absorption spectroscopy, and the reaction kinetics was characterized under pseudo-first-order conditions. The bimolecular rate constant for the CH2OO + acetone reaction is measured to be (4.1 ± 0.4) × 10-13 cm3 s-1, consistent with previous measurements. The reactions of CH2OO with the β-diketones acetylacetone and 3,3-dimethyl-2,5-pentanedione are found to have broadly similar rate constants of (6.6 ± 0.7) × 10-13 and (3.5 ± 0.8) × 10-13 cm3 s-1, respectively; these values may be cautiously considered as upper limits. In contrast, α-diketones react significantly faster, with rate constants of (1.45 ± 0.18) × 10-11 and (1.29 ± 0.15) × 10-11 cm3 s-1 measured for biacetyl and acetylpropionyl. The potential energy surfaces for these 1,3-dipolar cycloaddition reactions are characterized at the M06-2X/aug-cc-pVTZ and CBS-QB3 levels of theory and provide additional support to the observed experimental trends. The reactivity of carbonyl compounds with CH2OO is also interpreted by application of frontier molecular orbital theory and predicted using Hammett substituent constants. Finally, the results are compared with other kinetic studies of Criegee intermediate reactions with carbonyl compounds and discussed within the context of their atmospheric relevance.

Metal‐Free One‐Pot Synthesis of 2‐(2‐Hydrazinyl) Thiazole Derivatives Using Graphene Oxide in a Green Solvent and Molecular Docking Studies

AbstractAn efficient, one‐pot three‐component reaction in the synthesis of a wide range of 2,4‐disubstituted hydrazinyl thiazole scaffolds in ethanol at room temperature has been developed by the reaction of carbonyl compounds, phenacyl bromides, and thiosemicarbazide, using graphene oxide (GO) as a catalyst. The present catalytic method has many significant advantages such as shorter reaction time, broad substrate scope, low catalyst loading, environmentally benign solvent media, easy handling, and operational simplicity at room temperature. The products are identified based on their various spectroscopic data. The GO catalyst has a high reusability rate and is simple to recover. A mechanistic study suggests that the reaction takes placeviaa thiosemicarbazone intermediate, which is isolated and confirmed in this study using spectroscopic techniques. Thereafter, a molecular docking study has been performed to evaluate the binding affinity of hydrazinyl thiazole derivative as a possible inhibitor on the protein active site of human α‐amylase and glucosamine 6‐phosphate synthase