Organic Chemistry Research Articles

Mild Photochemical Reduction of Alkenes and Heterocycles via Thiol-Mediated Formate Activation.

The reduction of alkenes to their respective alkanes is one of the most important transformations in organic chemistry, given the abundance of natural and commercial olefins. Metal-catalyzed hydrogenation is the most common way to reduce alkenes; however, the use of H2 gas in combination with the precious metals required for these conditions can be impractical, dangerous, and expensive. More complex substrates often require extremely high pressures of H2, further emphasizing the safety concerns associated with these hydrogenation reactions. Here we report a safe, cheap, and practical photochemical alkene reduction using a readily available organophotocatalyst, catalytic thiol, and formate. These conditions reduce a variety of di-, tri-, and tetra-substituted alkenes in good yield as well as dearomatize pharmaceutically relevant heterocycles to generate sp3-rich isosteres of benzofurans and indoles. These formal-hydrogenation conditions tolerate a broad range of functionalities that would otherwise be sensitive to typical hydrogenations and are likely to be important for industry applications.

Reform of Inorganic and Analytical Chemistry Course Teaching Model in Biology Major under the New Situations

Inorganic and analytical chemistry is a compulsory basic course for students majoring in biology. The goal of this course is to provide them with the necessary chemical knowledge and experimental skills and to lay the foundation for the subsequent professional courses. This study explores the teaching model reform of inorganic and analytical chemistry teaching for non-chemistry majors according to the current situation, hoping to explore a suitable course teaching model for biology majors by optimizing teaching content, stimulating students’ interest, and improving teaching methods.

Catalytic Aerobic Carbooxygenation for the Construction of Vicinal Tetrasubstituted Centers: Application to the Synthesis of Hexasubstituted γ-Lactones.

Strategic design for the construction of contiguous tetrasubstituted carbons represents a daunting challenge in synthetic organic chemistry. Herein, we report a combined experimental and computational investigation aimed at developing catalytic aerobic carbooxygenation, involving the intramolecular addition of tertiary radicals to geminally di-substituted-alkenes followed by aerobic oxygenation. This reaction provides astraightforward route to various α,α,β,β-tetrasubstituted γ-lactones, which can be readily transformed into hexasubstituted γ-lactones through allylation/translactonization. Computational analysis reveals that the key mechanistic foundation for achieving the developed aerobic carbooxygenation involves the design of endothermic (energetically uphill) C-C bond formation followed by exothermic (energetically downhill) oxygenation. Furthermore, we highlight a unique fluorine- induced stereoelectronic effect that stabilizes the endothermic stereo-determining transition state.

Revolutionizing Indole Synthesis: A Microwave‐Powered Approach

AbstractTempted by the unique medicinal and biological potential of indole‐containing heterocycles, chemists, especially those specializing in heterocycle synthesis and drug discovery, are actively pursuing their efficient construction. This review spotlights the latest advancements in microwave‐assisted (M. W.) synthesis of diverse indole‐based heterocyclic compounds. We systematically categorize the reported methods based on the specific indole substitution patterns. This review concise the microwave assisted synthesis of indole based‐pyridine derivatives, indole based‐pyrimidine, indole based‐oxindole, spiro‐oxindole, Fischer indole Heck‐isomerization derivatives, functionalized indole, substituted indoles, indolyl quinoline, indole triazole and indolylnicotinonitriles derivatives. Ultimately, this review aims to provide organic and medicinal chemists with a concise yet informative guide to recent methodologies employing indole derivatives in the microwave‐powered synthesis of heterocycles.

Recent Developments in the Ruthenium‐Catalyzed Azide Alkyne Cycloaddition (RuAAC) Reaction

AbstractThe ruthenium‐catalyzed azide‐alkyne cycloaddition (RuAAC) gives access to 1,5‐disubstitued triazoles in a single atom‐economical step and offers advantages compared to its copper‐catalyzed counterpart in that both terminal and internal alkynes can be employed. This review summarizes recent findings in this field during the last eight years, covering mechanistic investigations, synthetic developments, as well as applications in medicinal chemistry, polymer synthesis and physical organic chemistry.

Learning from Protein Engineering by Deconvolution of Multi-Mutational Variants.

This review analyzes a development in biochemistry, enzymology and biotechnology that originally came as a surprise. As part of directed evolution of stereoselective enzymes in organic chemistry, the concept of partial or complete deconvolution of selective multi-mutational variants was established and refined during the past 15 years. Early deconvolution experiments of stereoselective variants led to the finding that mutations can interact cooperatively or antagonistically with one another, not just additively. Later, this phenomenon was shown to be general. Molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) computations were performed in order to shed light on the origin of non-additivity at all stages of an evolutionary upward climb. Data of complete deconvolution can be used to construct unique multi-dimensional rugged fitness pathway landscapes, which provide more mechanistic insight than traditional fitness landscapes. Along a related line, biochemists have long tested the result of introducing two point mutations in an enzyme for mechanistic reasons, followed by a comparison of the respective double mutant in so-called double mutant cycles, which originally showed only additive effects, but more recently also uncovered cooperative and antagonistic non-additive effects.

Exploring the Inductive Effect through Computational Modeling: A General and Organic Chemistry Lab Experiment

Exploring the Inductive Effect through Computational Modeling: A General and Organic Chemistry Lab Experiment

Some transformations in a series of 4-amino-1,2,4-triazole-3-thion derivatives

The continuous improvement of synthesis methods enables the optimization of the process for developing and obtaining target products of chemical transformation. Derivatives of 1,2,4-triazole-3-thiol present a convenient object for chemical transformation, facilitating the creation of promising biologically active compounds. Combining the structure of this heterocyclic system with pharmacophore fragments of different natures allows for more effective work on the development of molecules with high pharmacological potential. To implement this strategy, 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones were utilized as starting structures. This molecule possesses three reaction centers, facilitating a wide range of chemical transformations involving these substances. The aim of the work was to create a series of 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones as a promising source for the preparation of biologically active substances. Materials and methods. The structure of the target compounds has been formed using well-known methods of organic chemistry. The starting materials used were 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones, which were previously obtained. The first stage of the work involved the temporary protection of the amino group with a tert-butoxycarbonyl group. The second stage of the work involved the realization of Mannich reactions involving primary and secondary amines. The reaction has been carried out with formalin in an alcohol-dioxane medium. The products of the chemical transformation have been recrystallized in methanol. The third stage of the work was based on the removal of Boc-protection, which was realized using hydrochloric acid in a dioxane medium. The structures of all synthesized substances have been determined by 1H NMR spectroscopy and elemental analysis. The individuality of the compounds has been confirmed by high-performance liquid chromatography. Results. The successful study of the mechanisms of Mannich reactions for 4-amino-1,2,4-triazole-3-thione derivatives allowed us to obtain 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones in quantitative yields. The studies made it possible to establish the favorable effect of protecting the amino group of the 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione of the tert-butyloxycarbonyl group on the course and direction of the reaction. Conclusions. The optimal conditions for the Mannich reactions involving 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione with intermediate Boc-protection of the amino group have been determined, which allowed us to create the theoretical basis for the successful use of Mannich reactions to expand the range of promising 4-amino-1,2,4-triazole-3-thione derivatives.

Mechanical-Force-Induced Non-spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst.

The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid-phase system under ball-milling conditions. This non-spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D-ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro.

Mechanical‐Force‐Induced Non‐spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst

AbstractThe development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid‐phase system under ball‐milling conditions. This non‐spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D‐ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro.

Stereoselective oxidative C3–N bond dehydrogenation and aromatization of 1-carboxyl substituted tetrahydroisoquinolines employing pipecolate oxidase

The dehydrogenation of C–N bond in 1,2,3,4-tetrahydroisoquinolines (THIQs), especially 1-substituted THIQs, is a type of fascinating transformation owing to its utility in synthetic organic chemistry. Yet, the existing reports are limitedly known as C1–N semi-dehydrogenation and dehydroaromatization. Herein, we describe a biocatalytic strategy for stereoselective oxidative C3–N dehydrogenation and aromatization of 1-substituted THIQs. This redox biotransformation enables the efficient kinetic resolution of a range of racemic 1-carboxyl substituted THIQs by employing a putative pipecolate oxidase from Schizosaccharomyces octosporus yFS286 (SoPIPOX), providing straightforward access to aromatized isoquinolines and unreacted (R)-enantiomers with excellent enantioselectivity and regioselectivity under mild conditions. Mechanistic studies reveal that the SoPIPOX-mediated successive dehydrogenation process proceeds via the initial unusual C3–N dehydrogenation followed by spontaneous further dehydrogenative aromatization of the resultant imine intermediate. This work lays the foundation for repurposing pipecolate oxidase for the synthesis of versatile N-heterocycles analogues.

Exploring the Trends and Patterns in Periodicity of Elements: from Mendeleev to Modern Periodic Table

Dmitri Mendeleev created the periodic table in 1869, and it has undergone significant modifications to become an essential tool in chemical science today. This abstract provides an informative summary of the evolution of periodic trends and patterns, from Mendeleev's work to the latest complexities in the current periodic table. The first step towards comprehending the periodicity of elements was Mendeleev's periodic table, which he offered as a means of classifying elements according to their atomic weights and chemical behaviours. The periodic table underwent additions and modifications during the ensuing decades as atomic theory and experimental methods advanced. Instead of focusing on atomic weights, the current periodic law is concerned with the precise atomic number. Henry Moseley's discovery of the atomic number altered the elemental positions. This modification allowed for a deeper examination of periodic trends between elements by clarifying elemental relationships. Periodic trend analysis takes into account several characteristics, such as atomic radius, ionisation energy, electron affinity, and electronegativity. This is evident from the fact that each group of elements, ranging from noble gases to alkali metals, has distinct tendencies in both physical and chemical properties. We gathered the necessary materials for this review from a variety of reliable sources, including physical chemistry by K. K. Sharma, inorganic chemistry by J. D. Lee, and other published works. In conclusion, Mendeleev's table's evolution to its current state demonstrates that scientists have been addressing the issue for many generations. The periodic table is still a vital tool for classifying and evaluating the wide range of elements and their characteristics, although there are still many uncharted territories in chemistry. Keywords: electronic configuration, group analysis, periodic trend, periodicity, atomic number, and quantum physics.

Vanadium (IV)oxo catalyzed One-Pot transformation of cinnamate to aromatic ester and its mechanistic aspects

Metal-catalyzed oxidative cleavage of unsaturated carbon–carbon bond is among the utmost valuable chemical transformations in synthetic organic chemistry. However, the direct transformation of cinnamate to benzoate remains an unsolved task in the series. Herein, we have developed an unprecedented one-pot strategy for the direct transformation of cinnamate esters to aromatic ester using V-catalyst [(L2)VIVO](ClO4) and green oxidant H2O2 in alcohol-reflux condition. The reaction on cinnamate proceeded via CC bond breaking to generate aldehyde intermediate, followed by oxidative esterification to yield two carbon less aromatic esters in 52–95% yields. Further, experimental and DFT studies confirmed the mechanism and in-situ aldehyde formation which consequently supported to the developed protocol.

Enantioselective Synthesis of Secondary Amines by Combining Oxidative Rearrangement and Biocatalysis in a One-Pot Process.

This contribution describes the development of chemoenzymatic one-pot processes, which combine an oxidative rearrangement and a biotransformation catalyzed by an imine reductase (IRED), for the synthesis of highly enantiomerically enriched secondary amines, such as an aryl-substituted pyrrolidine and a benzazepine. The benefits of this chemoenzymatic one-pot approach include high overall conversions (up to >99%), high enantiomeric excesses (up to >99% ee), and a straightforward synthetic approach toward secondary amines without the need to isolate the formed intermediate. For the initial chemical reaction, namely, the oxidative rearrangement, PhI(OAc)2 in methanol is used as a non-natural reagent, whereas the enzymatic step requires only stoichiometric amounts of d-glucose along with catalytic amounts of IRED, glucose dehydrogenase (GDH), and the cofactor NADPH. This methodology, demonstrating the compatibility of a "classic" organic synthesis using a non-natural, highly reactive reagent and a subsequent biocatalytic step, can be applied for different amines as substrates, thus making this concept a versatile tool in synthetic organic chemistry in general and for enantioselective synthesis of heterocyclic secondary amines in particular.

Stepping stones to success: A qualitative investigation of the effectiveness of adaptive stepped supporting tools for problem-solving in organic chemistry to design an intelligent tutoring system

ABSTRACT Supporting students in complex problem-solving tasks is intricate due to the variety of difficulties students face. Although adaptive support has proven effective in addressing various difficulties in different disciplines, its application and exploration in science education, particularly through intelligent tutoring systems (ITSs), is limited. This study aimed to investigate the effectiveness of adaptive support in fostering students’ problem-solving processes in organic chemistry, focusing on deriving insights for designing an ITS. Adaptive support, in the form of adaptive stepped supporting tools (ASSTs), was developed and implemented in problem-centred interviews with 19 undergraduate chemistry students. The analysis indicated that ASSTs generally supported students’ problem-solving processes effectively. Additionally, certain factors were identified that influenced the effective processing of ASSTs. The results suggest that an effective ITS should feature highly flexible support pathways, a prior knowledge assessment, the explicit communication of identified difficulties, a drop-out option, and discipline-specific task formats. However, the results also raise questions about the assumed extent of prior knowledge in adaptive support and the point at which the amount of required support becomes impractical.

Copper-Promoted Dimerization of Benzyl Thiocyanates to Access Functionalized Bibenzyls

AbstractThe synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper-promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions through a cascade C–S bond cleavage in one pot. Diverse substituents, including electron-withdrawing groups on the aryl ring, are well tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross-coupling product from two different electron-deficient benzyl thiocyanates.

Cyclization by metal-catalyzed hydrogen atom transfer/radical-polar crossover

Catalytic transformation of alkenes via the metal-hydride hydrogen atom transfer (MHAT) mechanism has notably advanced synthetic organic chemistry. This review focuses on MHAT/radical-polar crossover (MHAT/RPC) conditions, offering a novel perspective on generating electrophilic intermediates and facilitating various intramolecular reactions. Upon using cobalt hydrides, the MHAT mechanism displayed exceptional chemoselectivity and functional group tolerance, making it invaluable for the construction of complex biologically relevant molecules under mild conditions. Recent developments have enhanced regioselectivity and expanded the scope of MHAT-type reactions, enabling the formation of cyclic molecules via hydroalkoxylation, hydroacyloxylation, and hydroamination. Notably, the addition of an oxidant to traditional MHAT systems enables the synthesis of rare cationic alkylcobalt(IV) complexes, bridging radical mechanisms to ionic reaction systems. This review culminates with examples of natural product syntheses and exploration of asymmetric intramolecular hydroalkoxylation, highlighting the ongoing challenges and opportunities for future research to achieve higher enantioselectivity. This comprehensive study revisits the historical evolution of the MHAT mechanism and provides the groundwork for further innovations in the synthesis of structurally diverse and complex natural products. 1 Introduction 2 Intramolecular hydroalkoxylation and hydroacyloxylation reactions 3 Intramolecular hydroamination reactions 4 Intramolecular hydroarylation reactions 5 Deprotective cyclization 6 Asymmetric intramolecular hydroalkoxylation

Effect of Metal Coordination Environment on the Stability of Zinc Complexes and Their Reactivity with NaSH

AbstractMetal complexes with multidentate ligands are frequently used as model compounds to shed light on the (bio)‐inorganic chemistry of H2S. Zinc complexes bearing salen‐type ONNO ligands with different bridging groups are particularly relevant in this respect. Here, we describe the use of zinc complexes with the sulfur‐analogues of the ONNO ligands with the S‐donors replacing either the neutral nitrogen donors or the anionic oxygen atoms of the classical salen ligands. In addition, we studied a hexadentate cyclic ligand, with four neutral sulfur atoms and two anionic oxygens. Having two coordinative pockets this ligand is able to form a bimetallic zinc complex. We report how the different coordinative environments of the explored ligands influence the stability of the zinc complexes and their abilities to form the related hydrosulfide species.

An Exceptional Valorization of CuO Nanoparticles in Ionic Liquids as an Efficient Medium for the Electrophilic Substitution of Indole Towards the Formation of Bis(indolyl)methanes

Aim: Ionic liquids are promising green solvents with simple but unique structure-related physical properties such as negligible vapour pressure, exceptional thermal conductivity, remarkable thermal stability and their suitability and inertness towards a broad range of catalytic applications. CuO NPs have been addressed as a cost-effective and a reagent of a choice that necessitates only mild reaction conditions to offer a high yield of the desired products with exceptional selectivity in a short duration of time. Therefore, in the present work, attempts have been made to explore the catalytic potentials of CuO NPs in an ionic liquid medium to synthesize biologically important bis(indolyl)methanes. Background: Catalytic explorations of metal oxide nanoparticles in ionic liquids offers a cooperative effect that has a significant impact on the kinetics as well as on the outcome of the reaction. Therefore, such catalytic systems in the present times have seized the scientific community's interest from the perspectives of sustainable development in synthetic organic chemistry. The combination of metal oxide nanoparticles with highly tunable ionic liquids is not only used to synthesize simple organic molecules but also explored in the synthesis of complex organic molecules of high commercial and biological relevance. Objectives: The current work offers a rapid and robust protocol for synthesizing bis(indolyl)methanes via electrophilic substitution reaction between indole and various aldehydes in the presence of a CuO nanoparticles-ionic liquid system. The discussion focuses on the high tolerance of different functionalities by the catalytic system leading to the synthesis of bis(indolyl)methanes. Methods: CuO NPs have been synthesized via the co-precipitation method using ionic liquid. The applicability of metal oxide nanoparticles-IL matrix was further investigated in synthesizing bis(indolyl)methanes. Results: The FT-IR absorption below 600 cm-1 and the XRD pattern showing all the peaks in the diffraction diagram revealed the formation of CuO NPs. FESEM images show the flake-shaped morphology of CuO NPs and are found to be separated from the agglomerated clusters Conclusion: Ionic liquid-CuO NPs matrix reveals good to exceptional catalytic properties, and their advancements as a catalytic system at room temperature open new avenues for synthetic organic chemists.

Organic Chemistry and its Important Role in the Creation of Type: Novel Functional Materials

Organic Chemistry and its Important Role in the Creation of Type: Novel Functional Materials