Strecker Reaction Research Articles

Stoichiometry-Regulated Synthesis of Three Adenine-Based Coordination Polymers for Catalytic Excellence through the Synergistic Amalgamation of Coordinative Unsaturation and Lewis Basic Sites.

Nucleobase adenine is a promising candidate for synthesizing fascinating coordination polymers (CPs) due to the presence of five potential metal-ion binding centers. In recent years, CPs have emerged as promising Lewis acid-base centers containing heterogeneous catalysts for a wide range of organic transformations. However, the crucial role of stoichiometric regulations of the starting materials and their consequential impact on catalytic performance are rarely studied. Herein, we have synthesized three adenine (Ad)-based cadmium CPs with 5-nitro isophthalic acid (H2NIPA) by a mixed linker approach by tuning the substrate's stoichiometric proportion. The single-crystal X-ray diffraction analysis of the synthesized CPs, SSICG-11, [Cd(Ad)(NIPA)(H2O)]·H2O; SSICG-12, [Cd(Ad)2(NIPA)(H2O)]; and SSICG-13, [Cd4(Ad)(NIPA)3]·H2O·DMF, reveals that these three compounds exhibit distinct asymmetric units, each reflecting varying precursor proportions. Due to their high chemical stability and the presence of both Lewis acidic-basic sites, SSICG-11-13 were employed as heterogeneous catalysts for Hantzsch and Strecker reactions. However, SSICG-12 is more efficient due to its capacity to form an open metal sites (OMSs) and the presence of a higher number of adenine moieties. Overall, this study demonstrated the stoichiometrically controlled synthesis of adenine-based CPs and dissected their efficiency as a heterogeneous catalyst by correlating their structures and compositions.

Robust Cd(4,5-Imdb)-MOF for Lewis-Acid Assisted Catalysis and Selective Sensing of 2,4,6-Trinitrophenol.

Developing multifunctional metal-organic frameworks (MOFs) for effective catalysis and sensing remains a significant challenge. This study presents the synthesis of an imidazole-based angular linker, 4,4'-(1-methyl-1H-imidazole-4,5-diyl)dibenzoic acid (4,5-H2Imdb), which is used in the synthesis of the Cd(4,5-Imdb)-MOF. This MOF demonstrates robust and recyclable properties, making it suitable for solvent-free Strecker synthesis and in the detection of the secondary explosive 2,4,6-trinitrophenol (TNP) molecule, with a limit of detection (LOD) of 7.5 ppb in methanol. The material's hydrolytic stability and reusability are thoroughly evaluated. Additionally, density functional theory (DFT) calculations provide insights into the selective detection mechanism of TNP. These findings highlight the potential of Cd(4,5-Imdb)-MOF in catalysis and sensing applications.

Synthesis of Aminonitriles by Asymmetric Strecker Reaction Using Organocatalysis

Synthesis of Aminonitriles by Asymmetric Strecker Reaction Using Organocatalysis

From Meteorite to Life's Building Blocks: A possible Electrochemical Pathway to Amino Acids and Peptide Bonds.

This study explores the electrochemical properties of the carbonaceous Allende CV3 meteorite, focusing on its potential as a Fe-based catalyst derived from Mackinawite iron sulfide for electrocatalytic reactions facilitating nitrogen (N2) fixation into ammonia. Through comprehensive analysis, we not only monitored the evolution of key compounds such as CN-, sulfur/H2S, H2 and carbonyl compounds, but also identified potential reagent carriers, indicating significant implications for the Strecker synthesis of amino acids in space environments. Initial examination revealed the presence of polypeptides, notably sequences including dimer Ala-α-HO-Gly, pentamer Gly3-Ala2, and hexamer Gly4-(HO-Gly)2. These discoveries greatly enhance our understanding of astrobiological chemistry, offering valuable insights into prebiotic processes and the potential presence of life-building blocks throughout the universe.

(Ga1-xAlx)4B2O9: controlled surface acid-base properties and catalytic behavior towards the Strecker reaction.

Solid bases are valuable catalysts for industrial syntheses. However, controlling the basicity of these catalysts remains a challenge. Ga4B2O9, due to μ3-O within its structure, could behave as a special solid base catalyst exhibiting intrinsic Lewis basicity. In this work, a sol-gel method was proposed to obtain continuously adjustable acidity and basicity of the metal borate catalyst (AlxGa1-x)4B2O9. According to the results of NH3-TPD, CO2-TPD, and the systematic experimental design, Lewis basic sites originating from GaO5 groups in (AlxGa1-x)4B2O9 boost the Strecker reaction rather than the Lewis acid sites related to unsaturated Al. This work illustrates the possible application of bulk-type solid solutions with simultaneous Lewis acid and base sites for the first time. A reaction mechanism has also been proposed based on the catalytic reaction results.

High‐Voltage Single‐Ion Covalent Organic Framework Electrolytes Enabled by Nitrile Migration Ladders for Lithium Metal Batteries

AbstractThe poor electrochemical stability window and low ionic conductivity in solid‐state electrolytes hinder the development of safe, high‐voltage, and energy‐dense lithium metal batteries. Herein, taking advantage of the unique electronic effect of nitrile groups, we designed a novel azanide‐based single‐ion covalent organic framework (CN−iCOF) structure that possesses effective Li+ transport and high‐voltage stability in lithium metal batteries. Density functional theory (DFT) calculations and molecular dynamics (MD) revealed that electron‐withdrawing nitrile groups not only resulted in an ultralow HOMO energy orbital but also enhanced Li+ dissociation through charge delocalization, leading to a high tLi+ of 0.93 and remarkable oxidative stability up to 5.6 V (vs. Li+/Li) simultaneously. Moreover, cyanation leveraging Strecker reaction transformed reversible imine‐linkage to a stable sp3‐carbon‐containing azanide anion, which facilitated contorted alignment of transport “ladders” along the one‐dimensional anionic channels and the ionic conductivity could reach 1.33×10−5 S cm−1 at ambient temperature without any additives. As a result, CN−iCOF allowed operation of solid‐state lithium metal batteries with high‐voltage cathodes such as LiNi0.8Mn0.1Co0.1O2 (NCM811), demonstrating stable lithium deposition up to 1,100 h and reversible battery cycling at ambient temperature up to 4.5 V, shedding light on the importance of discovering new functionality for forthcoming high‐performance batteries.

Synthesis of α-Aminonitriles via Ammonium-Catalyzed Reactions of Aminoacetonitrile.

α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N-arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters.

How to Experimentally Determine the Influence of the Weak Nuclear Force in Promoting Molecular Chirality via Heavy–Metal Promoted Autocatalytic Synthesis of Amino Acids

AbstractThe potential impact of the parity non‐conserving (PNC) weak nuclear interaction on the chirality of a nascent chiral carbon center has previously been examined in the context of evolutionary models for enantiomeric selectivity in the formation of natural amino acids and nucleic acids. Since the PNC effect is the only inherently handed property in nature, it is an obvious candidate to consider in those cases where there is a natural selectivity for a specific enantiomer, including the molecular building blocks of the molecules of life. Over geological timeframes, the potential impact of the PNC weak nuclear force on chiral preference appears feasible. Key requirements included an autocatalytic reaction cycle and involvement of metal‐ion catalysts. While prior studies offer no feasible path to experimentally test the hypothesis; the Z5‐dependence of the PNC interaction does suggest that catalysis by heavy elements could yield observable chiral preferences within an experimentally accessible timeframe. Calculations of the magnitude of the effect are presented for select heavy‐elements and it is shown that chiral preference could be observed within a time span of weeks to months when such metals are used to promote amino acid synthesis via an autocatalytic Strecker reaction.

An Overview of Various Applications of Cadmium Carboxylate Coordination Polymers.

This review highlights the most recent applications of Cd(II)-carboxylate-based coordination polymers (Cd(II)-CBCPs), such as sensors, catalysts, and storage materials, in comparison with those of Zn(II) counterparts. A wide range of species with luminescence properties were designed by using proper organic fluorophores, especially a carboxylate bridging ligand combined with an ancillary N-donor species, both with a rigid structure. These characteristics, combined with the arrangement in Cd(II)-CBCPs' structure and the intermolecular interaction, enable the sensing behavior of a plethora of various inorganic and organic pollutants. In addition, the Lewis acid behavior of Cd(II) was investigated either in developing valuable heterogeneous catalysts in acetalization, cyanosilylation, Henry or Strecker reactions, Knoevenagel condensation, or dyes or drug elimination from wastewater through photocatalysis. Furthermore, the pores structure of such derivatives induced the ability of some species to store gases or toxic dyes. Applications such as in herbicides, antibacterials, and electronic devices are also described together with their ability to generate nano-CdO species.

High-Voltage Single-Ion Covalent Organic Framework Electrolytes Enabled by Nitrile Migration Ladders for Lithium Metal Batteries.

The poor electrochemical stability window and low ionic conductivity in solid-state electrolytes hinder the development of safe, high-voltage, and energy-dense lithium metal batteries. Herein, taking advantage of the unique electronic effect of nitrile groups, we designed a novel azanide-based single-ion covalent organic framework (CN-iCOF) structure that possesses effective Li+ transport and high-voltage stability in lithium metal batteries. Density functional theory (DFT) calculations and molecular dynamics (MD) revealed that electron-withdrawing nitrile groups not only resulted in an ultralow HOMO energy orbital but also enhanced Li+ dissociation through charge delocalization, leading to a high tLi+ of 0.93 and remarkable oxidative stability up to 5.6 V (vs. Li+/Li) simultaneously. Moreover, cyanation leveraging Strecker reaction transformed reversible imine-linkage to a stable sp3-carbon-containing azanide anion, which facilitated contorted alignment of transport "ladders" along the one-dimensional anionic channels and the ionic conductivity could reach 1.33×10-5 S cm-1 at ambient temperature without any additives. As a result, CN-iCOF allowed operation of solid-state lithium metal batteries with high-voltage cathodes such as LiNi0.8Mn0.1Co0.1O2 (NCM811), demonstrating stable lithium deposition up to 1,100 h and reversible battery cycling at ambient temperature up to 4.5 V, shedding light on the importance of discovering new functionality for forthcoming high-performance batteries.

Synthesis of UiO-66-Pyca-CuO by a Simple and Novel Method: MOF-based Metal Thin Film as Heterogeneous Catalysts for the Synthesis of α-Aminonitriles.

Metal-organic frameworks (MOFs), particularly UiO-66-NH2, are employed as catalysts in many industrial catalyst applications. As converting catalysts into thin film significantly increases their catalytic properties, we report a general approach to synthesizing MOF thin films (UiO-66-Pyca-CuO). First, functionalization of UiO-66-NH2 was done with 3-pyridine carboxaldehyde by the postsynthesis method, and then, UiO-66-Pyca was entangled on the surface of copper oxide nanoparticles with a modern strategy (MOF thin film). The morphology and structure of the synthesized UiO-66-Pyca-CuO were determined by using X-ray diffraction, Fourier transform infrared, field-emission scanning electron microscopy, energy-dispersive analysis of X-ray, inductively coupled plasma-mass spectrometry, elemental analyses of CHNOS, temperature-programmed desorption of ammonia, Brunauer-Emmett-Teller, and X-ray photoelectron spectroscopy. We studied the catalytic action of the UiO-66-Pyca-CuO thin film in the synthesis of α-aminonitriles via Strecker reaction. Our studies show that this catalysis can be a suitable catalyst in the synthesis of α-aminonitriles because of having advantages such as using the solvent being environmentally friendly, easy separation of the catalyst (only by picking up the MOF thin film from inside the solution), the reaction at room temperature, high yield, and reusability.

Natural product synthesis by a nanoporous In-MOF Catalyst: Crystallographic insight by incorporating substrate inside its nanopores

Metal-organic frameworks (MOFs) are promising candidates as nanoporous heterogeneous catalysts over other solid catalysts. Herein, utilizing a new tetra-acid ligand and employing high-valent Indium metal source we have strategically developed a 3D robust nanoporous framework, IITKGP-53, which retained its crystallinity over a wide range of pH solutions (2–12). Considering the green synthesis approach IITKGP-53 was explored as a heterogeneous catalyst toward one-pot three-component Strecker reaction under solvent-free condition, with low catalyst loading for a broad range of substrates. Considering practical utility, biologically important natural product, Girgensohnine, was synthesized for the first time by using this catalyst with excellent conversion rate. The substrate binding sites inside the nanopores and host–guest interactions were verified crystallographically by obtaining a substrate inside nanopores of this MOF (aniline@IITKGP-53) and computational modeling. An in-depth theoretical investigation unveiled the most plausible transition states for the first time. This study inaugurates the usage of nanoporous MOFs as heterogeneous catalysts for natural product synthesis.

Inhibitory effects of cassiae semen extract on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) in model system.

2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines. To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC-MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine. The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass-charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde. Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.

Ultrasound-assisted Cu(II) Strecker-functionalized organocatalyst for green azide–alkyne cycloaddition and Ullmann reactions

A new aminonitrile-functionalized Fe3O4 has been synthesized via the Strecker reaction, the designed aminonitrile ligand on the surface of the magnetic core coordinated to copper(II) to obtain the final new catalyst. The fabricated nanocatalyst was characterized by Fourier transform Infrared (FT-IR), Field Emission Scanning Electron Microscopy (FESEM), Energy-Dispersive X-ray spectroscopy (EDX), Transmission Electron Microscopy (TEM), Vibrating-Sample Magnetometer (VSM), Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), and Thermogravimetric Analysis (TGA). The high tendency of nitrogens in the aminonitrile functional group to make a complex with Cu(II) has caused the practical activity of this nucleus in this catalyst. This nanocatalyst performance was investigated in azide–alkyne Huisgen cycloaddition (3 + 2) reaction for achieving to 1,4-disubstituted 1,2,3-triazoles in water as a green media at room temperature. In another try, Classic Ullmann Reaction was investigated for the synthesis of biaryls at 85 °C promoted by ultrasonic condition (37 kHz). The reaction scope was explored using different reactants and the results of using this developed catalytic system demonstrated its capacity to reduce the reaction time and enhance the reaction efficiency to provide good to excellent product yield. Conversely, the simple recycling and reusability of this catalyst for at least six times without any noticeable leaching of copper makes it a potential future catalyst for synthesizing such compounds.

Variation in Catalytic Efficacies of a 2D pH-Stable MOF by Altering Activation Methods.

Although it is well-known that the Lewis acidity of Metal-Organic Frameworks (MOFs) can effectively enhance their catalytic activity in organic transformations, access to these Lewis-acidic sites remains a key hurdle to widespread applications of Lewis-acidic catalysis by MOFs. Easy accessibility of strong Lewis acidic sites onto 2D MOFs by using proper activation methods can be a cornerstone in attaining desired catalytic performance. Herein, we report a new 2D chemically stable MOF, IITKGP-60, which displayed excellent framework robustness over a wide pH range (2-12). Benefiting from the abundant open metal sites (OMSs) and framework robustness, the catalytic activity of the developed material was explored in one-pot three-component Strecker reaction and Knoevenagel condensation reaction. Moreover, the developed catalyst is superior in catalyzing the reactions involving sterically hindered substrate (1-naphthaldehyde) with high turnover number. A comparative catalytic study was conducted using different activation methods (chloroform and methanol exchanged activated samples), highlighting the significant effect of activation methods on its catalytic performances. The sustainable synthetic pathway under solvent-free conditions for a broad scope of substrates using low catalyst loading and excellent recyclability made the developed pH-stable framework a promising heterogeneous catalyst.

Catalytic Asymmetric Synthesis of Chiral α,α-Dialkyl Aminonitriles via Reaction of Cyanoketimines.

Chiral aminonitriles not only are broadly useful building blocks but also increasingly appear as structural motifs in bioactive molecules and pharmaceuticals. The catalytic asymmetric synthesis of chiral aminonitriles, therefore, has been intensively investigated, as reflected in numerous reports of catalytic asymmetric Strecker reactions. Despite such great progress, the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles in a highly selective and efficient manner is still a formidable challenge. Here, we report a new approach for the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles via reaction of cyanoketimines with enals. We demonstrate that this reaction could be carried out with as low as 20 ppm catalyst loading.

Montmorillonite-Silica-Graphene oxide composite incorporating with chiral thiourea for the Strecker reaction

The present study has successfully intercalated graphene oxide (GO) nanosheets and silica into the montmorillonite (MMT) interlayer and deposited them onto its external surface to make montmorillonite, silica, and graphene oxide composite (MMT-silica-GO). The as-prepared composite demonstrates improved thermal stability compared to neat MMT and GO. It was followed by incorporating chiral thiourea (CTU) scaffold into MMT-silica-GO-based composite to establish chiral MMT-silica-GO-CTU-based heterogeneous system and tested over Strecker reaction, revealing high activity and selectivity. FTIR, Raman spectroscopy, powder X-ray diffraction, SAXS, XPS, BET, SEM, EDAX, and thermogravimetric analysis were used to characterize the samples. It was credited to the synergistic effect between the composite components that enhanced access to active sites and dispersion of catalyst. Across the board, the chiral MMT-silica-GO-CTU-based heterogeneous system appears to be a promising candidate for the Strecker reaction.

Alanine Formation in a Zero-Gap Flow Cell and the Role of TiO2/Ti Electrocatalysts.

The electrochemical synthesis of -amino acids at room temperature and pressure is a sustainable alternative to conventional methods like microbial fermentation and Strecker synthesis. A custom-built zero-gap flow electrolyzer was used to study the electrosynthesis of alanine via the electrocatalytic reductive amination (ERA) of the corresponding biomass-derivable -keto acid precursor - pyruvic acid (PA), and hydroxylamine (NH2OH) at very low pH. Non-toxic, abundant, and easy to prepare TiO2/Ti electrocatalysts were utilized as the cathode. Three TiO2/Ti felt electrodes with different oxide thicknesses were prepared and their characterization results were correlated with their respective electrochemical performance in terms of Faradaic efficiency , and partial current density . Cyclic voltammetry indicated a different electrocatalytic reduction process on hydrothermally treated electrodes, compared to thermally oxidized ones. Hydrothermally treated electrodes were also found to have the thickest porous anatase layer and achieved 50-75 % alanine conversion efficiencies. Optimization showed that the cell potential, reactant flow rate and the PA: NH2OH ratio were crucial parameters in determining the conversion efficiency. and were found to significantly decrease when an excess of is used and, an optimal alanine of 75 % was achieved at 2.0 V applied cell potential and 10 mL/h reactant flow rate.

An Electrochemically Driven Oxidative Strecker Reaction via the Unique Hydroxymethyl Radical Intermediate

AbstractAlfa‐aminonitriles are versatile and valuable intermediates in pharmaceutical chemistry. Until now, the Strecker reaction has remained the most efficient tool for synthesizing these compounds. Nevertheless, it is only applicable to aldehyde/imine systems and generally needs metal catalysts and external additives. Herein, an electrochemically driven oxidative Strecker reaction strategy was designed and accomplished for the synthesis of α‐aminonitriles with alcohol as the alkylation reagent. The strategy is environmentally friendly, scalable, and compatible with a wide range of functional groups, encompassing aromatic primary amines, secondary amines, and even alkylamine. Utilizing the merits of electro‐organic synthesis, it can be readily magnified from milligram to gram scale by simply adjusting the electrochemical parameters. Emphasized, it testified that a unique intermediate CH2*OH well‐established in fuel cells was involved in the reaction.

Humic Acid: A Promising and Green Bioorganic Catalyst in Organic Syntheses

AbstractThe growing pollution and threat to the environment demand green synthetic methods. Green chemistry mainly focuses on minimizing the waste and utilization of green solvents, energy sources, and catalysts and prefers one‐pot reactions. In this context, humic acid (HA), a natural bioorganic catalyst found in rivers, peat coal and sewage; is a high molecular weight macromolecule containing multifunctional groups, mainly contains quinone, phenolic OH, and COOH groups which make it acidic and activate carbonyl groups by protonation. Owing to its green aspect such as biodegradability, recyclability and reusability, humic acid is considered as sustainable bioorganic catalyst which meets the criteria for industrial requirements. The HA is mild acidic in nature, thus many functional groups tolerate in the HA catalyzed reactions. After few initial reports in 2001 and 2009, the HA catalyzed reactions gained much attention by the organic synthetic community from 2019 in aldol condensation, Knoevenagel condensation, Claisen‐Schmidt reaction, Michael addition, Strecker synthesis, tetrazole synthesis, Hantzsch dihydropyridine synthesis, hydrosilylation of terminal alkenes, hydrogenation, α‐aminophosphonate synthesis, cross coupling reactions such as Heck and Suzuki coupling reactions. Herein we report the comprehensive analysis on the role of HA in organic transformations providing diverse array of molecular scaffolds till date and future perspective.