Applications In Organic Synthesis Research Articles

Iridium-catalyzed selective para-C-alkylation of anilines/phenols with aryl alkynes

The general protocol for site-specific alkylation of anilines and phenols would provide an ideal strategy for affording densely functionalized aniline and phenol derivatives. Herein, we disclose a new iridium-catalyzed and acid-promoted process for selective para-alkylation of anilines and phenols using aryloxy or alkoxy aryl alkynes as the alkylated sources, delivering a wide range of para-C-alkylated phenols and anilines in good to excellent yields. The low catalyst loading (up to 0.05 mol%), scale-up of synthesis, operation under air conditions, as well as recycling of catalyst (5 times without deactivation) evidenced the promising application in organic synthesis.

LANTHANIDE CONTRACTION IN CHELATES OF ETHYLENEDIAMINETETRAACETIC ACID BASED ON CRYSTALLOGRAPHIC DATA: A SHORT REVIEW

The lanthanide (Ln) series has been attracted so much attention not only for its physical properties but also for its applications in organic synthesis and biomedical engineering. In the lanthanide chemistry, lanthanide contraction is a crucial concept meaning the gradual decrease in ionic radii as the atomic number of the Ln series increases. As a prominent chelator, ethylenediaminetetraacetic acid (EDTA) has been well-known to give stable complexes with various metals including Ln ions, resulted in forming (EDTA−4H)4− anion by deprotonation; over 100 kinds of Ln-EDTA complexes have hitherto been synthesized and structurally characterized using X-ray crystallography. While the lanthanide contraction phenomenon has been extensively studied in certain complexes of Ln, systematization on the Ln-EDTA remains inadequate though the chelates of EDTA are commonly used. Thus, this study presents a comprehensive analysis based on the data from the Cambridge Crystallographic Data Centre (CCDC). In mononuclear EDTA complexes X[Ln(EDTA−4H)(H2O)m]·nH2O (X+ = NH4+and its analogues) systematic lanthanide contraction depending on their coordination number are presented except for a few cases. However, in the case of non-mononuclear complexes or coordination polymers, the compositions become more complicated, and a greater variation in atomic bond length occurs, which is unusual for the lanthanide contraction studies in previous research. These varieties are considered to be influenced by different types of counter-cations, inorganic anions, solvent molecules and bridging O atoms from another EDTA anions. This suggests the flexibility and versatility of EDTA as a ligand. Such findings in the Ln-EDTA complexes could potentially provide us further development of a novel function in the future.

β‐Silylacrylate as a Multipurpose Reagent in Organic Synthesis

AbstractAcrylates are well known electrophilic alkenes having multitude of applications in organic synthesis. They are very good acceptors in Michael addition reactions and are good enophile/dienophile/dipolarophile partners in cycloaddition reactions. Replacing the β‐alkyl/aryl groups in acrylates by a silicon group would be interesting. In addition to the conventional reactions displayed by acrylates, β‐silylacrylates (β‐SAs) can show reactivity specifically related to the silicon group. Many conventional organic reactions such as hydrodimerization, organocatalytic asymmetric Michael additions, inter‐ and intra‐molecular Diels–Alder reactions, and asymmetric 1,3‐dipolar cycloadditions have been used to generate the complex chemical entities from β‐SAs. Some of the reaction outcomes were vastly influenced by the silicon substituent. This review describes the practical synthesis β‐SAs and their use as starting point in complex molecule generation including total synthesis of some natural products/bioactive molecules.

Coordination-Induced Radical Generation: Selective Hydrogen Atom Abstraction via Controlled Ti-C σ-Bond Homolysis.

A method for the generation of transient alkyl radicals via homolytic Ti-C bond cleavage was developed by employing a tailor-made organotitanium half-cage complex. In contrast to established metal-mediated radical initiation protocols via thermal or photochemical M-C σ-bond homolysis, radical formation is triggered solely by coordination of a solvent molecule (thf) to a titanium(IV) center. During the reaction, the nonstabilized alkyl radical is formed along with a persistent titanium(III) metalloradical, thus taming the former transient radical (persistent radical effect). Radical coupling and hydrogen atom abstraction (HAT) reactions have been explored not only experimentally but also computationally and by means of kinetic analysis. Exploiting these findings led to the development of selective HAT transformations, for example, with 9,10-dihydroanthracene. Deuterium labeling studies using selectively deuterated alkyls and 9,10-dihydroanthracene-d4 confirmed a radical pathway, which was underpinned by developing a radical-radical cross-coupling reaction for transferring the alkyl radical to a stable Sn-centered radical. To set the stage for an application in organic synthesis, a 5-endo-trig radical cyclization based on our methodology was established, and a dihydroxylated sesquiterpene was thus prepared in high diastereomeric excess.

Recent developments in the organic synthesis using nano-NiFe2O4 as reusable catalyst: A comprehensive synthetic & catalytic reusability protocol

Due to the alarming environmental hazards of the production of fine chemicals, medicines, and various kinds of compounds and minerals, the development of environmentally-friendly catalytic techniques has recently become of special interest. Accordingly, intensive research work was carried out in pursuit of abundant and sustainable catalysts that are eco- friendly. In particular, the employment of nano-nickel ferrite as a catalyst mitigates the waste impact of the and provides affordable synthetic approaches. This review paper addresses the recent advancements in synthetic organic processes that use nano-nickel ferrites as eco-friendly catalysts. In this review, we go over a number of frequently performed chemical reactions with nano-nickel ferrite acting as a catalyst. These include C-C and C-X (X = N, O, S) cross-coupling, cycloaddition, C-H annulation/functionalization, hydrogenation, aldehyde/ketone alkylation, oxidation, functional group removal and synthesis of heterocycles etc. The review paper also highlights the mechanistic course of reactions, recyclability protocols, synthetic processes, and their applications in organic synthesis.

Green oxidative cyclization to access 2,5-disubstituted-1,3,4-oxadiazoles from aldehydes and hydrazide derivatives using FeBr3 catalyst and hydrogen peroxide

2,5-disubstituted-1,3,4-oxadiazoles Oxidative cyclization of aldehydes and hydrazide derivatives to access 2,5-disubstituted-1,3,4-oxadiazoles has been developed using a catalytic amount of FeBr3 in the presence of aqueous hydrogen peroxide as an oxidant. By synthesizing 35 examples of 2,5-disubstituted 1,3,4-oxadiazoles, this approach was demonstrated to have good features including broad scope, mild conditions, air/water tolerance, and simple operation. More importantly, it can be expected to find wide applications in organic synthesis.

Some sulphur - containing double combination reagents

Research and development of new reagents are very important for organic synthesis. In recent years, some new reagents with universal applicability have been reported, but new reagents of sulphur-containing are rarely reported. Wang’s group has developed several new sulphur-containing reagents which are called as Wang reagents: Sodium dithionite - tert-Butyl hydroperoxide (Na2S2O4-TBHP). The paper presents the reactions involved in the reagents obtaining and the associated mechanisms. Na2S2O4-TBHP is a new reagent for selective oxidation of aromatic alcohols to aldehydes. Wang reagents have universal applicability in organic synthesis.

Graphite-Catalyzed Electro-Oxidation of Hydrazine Derivatives Using Sodium Chloride under Green and Sustainable Chemistry

The development of efficient and environmentally friendly catalysts for the electro-oxidation of hydrazine derivatives is of great importance in various industrial applications. In this study, we report the utilization of graphite-based catalysts for the electro-oxidation of hydrazine derivatives, using sodium chloride as a green and sustainable chemical approach. Graphite, a two-dimensional carbon material with exceptional properties, offers numerous advantages as a catalyst, including its high surface area, excellent electrical conductivity, and chemical stability. These characteristics make graphite an ideal candidate for promoting electrochemical reactions. Sodium chloride (NaCl), a readily available and cost-effective salt, serves as a green alternative to traditional oxidants used in hydrazine oxidation processes. By replacing conventional oxidizing agents with NaCl, we aim to reduce the environmental impact associated with the production and disposal of hazardous chemicals. This process enables the transformation of the HN-NH bond within hydrazines, leading to the formation of azo compounds (N = N). Azo compounds are important organic molecules with diverse applications in organic synthesis. This novel approach has successfully showcased the efficacy of utilizing various azo compounds in 13 different examples, yielding excellent or moderate to good results. The method capitalizes on electricity as the final oxidizing agent, providing an environmentally friendly oxidation strategy. Its high efficiency and gentle reaction conditions make this technique valuable for synthesizing azo derivatives, even when working with hydrazines containing diverse functional groups, resulting in yields ranging from moderate to excellent. Through systematic experiments, we evaluated the catalytic performance of graphite-based catalysts in the electro-oxidation of hydrazine derivatives. The catalysts demonstrated remarkable catalytic activity due to their efficient conversion of hydrazine derivatives into desired products. Moreover, the system exhibited good stability and recyclability, suggesting its suitability for practical applications.

T-BuOOH/TiO2 Photocatalytic System as a Convenient Peroxyl Radical Source at Room Temperature under Visible Light and Its Application for the CH-Peroxidation of Barbituric Acids

TiO2 is one of the most promising heterogeneous photoredox catalysts employed in oxidative pollutant destruction, CO2 reduction, water splitting, disinfection, solar cell design and organic synthesis. Due to the wide bandgap of TiO2, visible light energy is not sufficient for its activation, and electron/hole pairs generated upon UV irradiation demonstrate limited selectivity for application in organic synthesis. Thus, the development of TiO2-based catalytic systems activated by visible light is highly attractive. In the present work we demonstrate the generation of t-BuOO• radicals from tert-butylhydroperoxide catalyzed using commercially available unmodified TiO2 under visible light. This finding was used for the highly selective CH-peroxidation of barbituric acids, which contrasts with the behavior of the known TiO2/H2O2/UV photocatalytic system used for deep oxidation of organic pollutants.

Nickel-Imidazolium Low Transition Temperature Mixtures with Lewis-Acidic Character.

Low transition temperature mixtures (LTTMs) are a new generation of solvents that have found extensive application in organic synthesis. The interactions between the components often generate highly activated, catalytically active species, thus opening the possibility of using LTTMs as catalysts, rather than solvents. In this work, we introduce a nickel-based imidazolium LTTM, study its thermal behavior and explore its catalytic activity in the solvent-free allylation of heterocycles with allylic alcohols. This system is effective in this reaction, affording the corresponding products in excellent yield without the need for additional purifications, thus resulting in a very environmentally friendly protocol.

Advances in Transition‐Metal‐Catalyzed Hydrogermylation of Alkenes and Alkynes†

Comprehensive SummaryHydrogermylation of alkenes and alkynes provides a straightforward synthetic route to organogermanium compounds that have been found applications in organic synthesis, medicinal chemistry, and material science. This paper reviews the advances in transition‐metal‐catalyzed hydrogermylation of unsaturated carbon‐carbon bonds, including alkenes, alkynes, dienes, and allenes, with the objective of providing readers with the status of the field. Progress, problems, and perspectives in this field are discussed.

Phenothiazine-linked covalent triazine frameworks for enhanced photocatalytic aerobic oxidation reactions

The novel phenothiazine-linked covalent triazine framework (CTF, named as TPDH-PTBA), as well as the benzene- or triazine-linked counterparts (named as TPDH-TFPB and TPDH-TAPT, respectively), have been synthesized via direct polycondensation of terephthalimidamide and trisformyl precursors in DMF. Characterization of these three CTFs indicated the formation of macrocycle rings that were formed via covalently linked phenothiazine (or benzene) and triazine units. Among the CTFs, TPDH-PTBA with phenothiazine units exhibited a relatively broad band gap of ∼2.08 eV and excellent photocatalytic activity towards aerobic oxidation reactions. Specifically, the conversion rates of photocatalytic benzylamine coupling and anisothioether oxidation reactions by TPDH-PTBA were almost 100%, significantly higher than those of TPDH-TFPB and TPDH-TAPT. We proposed a photocatalytic pathway of these CTFs based on the experimental and theoretical evidences. Our findings highlight the potential of structural design at the molecular level to improve the intrinsic properties and photocatalytic performance of CTFs. These resulting porous organic polymers offer promise for green and sustainable application in organic synthesis and pollutant degradation.

Organic Synthesis Using Nitroxides.

Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure R1R2N-O•. The spin distribution over the nitroxide N and O atoms contributes to the thermodynamic stability of these radicals. The presence of bulky N-substituents R1 and R2 prevents nitroxide radical dimerization, ensuring their kinetic stability. Despite their reactivity toward various transient C radicals, some nitroxides can be easily stored under air at room temperature. Furthermore, nitroxides can be oxidized to oxoammonium salts (R1R2N═O+) or reduced to anions (R1R2N-O-), enabling them to act as valuable oxidants or reductants depending on their oxidation state. Therefore, they exhibit interesting reactivity across all three oxidation states. Due to these fascinating properties, nitroxides find extensive applications in diverse fields such as biochemistry, medicinal chemistry, materials science, and organic synthesis. This review focuses on the versatile applications of nitroxides in organic synthesis. For their use in other important fields, we will refer to several review articles. The introductory part provides a brief overview of the history of nitroxide chemistry. Subsequently, the key methods for preparing nitroxides are discussed, followed by an examination of their structural diversity and physical properties. The main portion of this review is dedicated to oxidation reactions, wherein parent nitroxides or their corresponding oxoammonium salts serve as active species. It will be demonstrated that various functional groups (such as alcohols, amines, enolates, and alkanes among others) can be efficiently oxidized. These oxidations can be carried out using nitroxides as catalysts in combination with various stoichiometric terminal oxidants. By reducing nitroxides to their corresponding anions, they become effective reducing reagents with intriguing applications in organic synthesis. Nitroxides possess the ability to selectively react with transient radicals, making them useful for terminating radical cascade reactions by forming alkoxyamines. Depending on their structure, alkoxyamines exhibit weak C-O bonds, allowing for the thermal generation of C radicals through reversible C-O bond cleavage. Such thermally generated C radicals can participate in various radical transformations, as discussed toward the end of this review. Furthermore, the application of this strategy in natural product synthesis will be presented.

Organoselenium compounds. Chemistry and applications in organic synthesis.

Selenium, originally described as a toxin, turns out to be a crucial trace element for life that appears as selenocysteine and its dimer, selenocystine. From the point of view of drug developments, selenium-containing drugs are isosteres of sulfur and oxygen with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. In this article we have focused on the relevant features of the selenium atom, above all, the corresponding synthetic approaches to access a variety of organoselenium molecules along with the proposed reaction mechanisms. The preparation and biological properties of selenosugars, including selenoglycosides, selenonucleosides, selenopeptides, and other selenium-containing compounds will be treated. We have attempted to condense the most important aspects and interesting examples of the chemistry of selenium into a single article.

Photochemical Benzylation of White Phosphorus.

Organophosphorus compounds (OPCs) have wide application in organic synthesis, material sciences, and drug discovery. Generally, the vast majority of phosphorus atoms in OPCs are derived from white phosphorus (P4). However, the large-scale preparation of OPCs mainly proceeds through the multistep and environmentally toxic chlorine route from P4. Herein, we report the direct benzylation of P4 promoted by visible light. The cheap and readily available benzyl bromide was used as a benzylation reagent, and tetrabenzylphosphonium bromide was directly synthesized from P4. In addition, the metallaphotoredox catalysis strategy was applied to functionalize P4 for the first time, which significantly improved the application range of the substituted benzyl bromide.

Arylacetonitrilases: Potential Biocatalysts for Green Chemistry.

Nitrilases are the enzymes that catalyze the hydrolysis of nitriles to corresponding carboxylic acid and ammonia. They are broadly categorized into aromatic, aliphatic, and arylacetonitrilases based on their substrate specificity. Most of the studies pertaining to these enzymes in the literature have focused on aromatic and aliphatic nitrilases. However, arylacetonitrilases have attracted the attention of academia and industry in the last several years due to their aryl specificity and enantioselectivity. They have emerged as interesting biocatalytic tools in green chemistry to synthesize useful aryl acids such as mandelic acid and derivatives of phenylacetic acid. The aim of the present review is to collate information on the arylacetonitrilases and their catalytic properties including enantioselectivity and potential applications in organic synthesis.

Visible‐Light‐Induced Synthesis of Thioethers through Three‐Component Reactions of α‐Diazoesters, Thiols, and Cyclic Ethers

AbstractThioethers are important sulfur‐containing compounds that have widespread application in organic synthesis, medicinal chemistry and materials science. Herein, a visible‐light‐mediated three‐component reaction of α‐diazoester, thiol, and cyclic ether leading to thioether has been developed at room temperature. Through this methodology, a variety of three‐component coupling products with the introduction of the ring‐opening of ether could be efficiently assembled under photocatalyst‐ and additive‐free conditions.

Organopotassium-Catalyzed Silylation of Benzylic C(sp3 )-H Bonds.

Benzylsilanes have found increasing applications in organic synthesis as bench-stable synthetic intermediates, yet are mostly produced by stoichiometric procedures. Catalytic alternatives based on the atom-economical silylation of benzylic C(sp3 )-H bonds remain scarcely available as specialized directing groups and catalytic systems are needed to outcompete the kinetically-favored silylation of C(sp2 )-H bonds. Herein, we describe the first general and catalytic-in-metal undirected silylation of benzylic C(sp3 )-H bonds under ambient, transition metal-free conditions using stable tert-butyl-substituted silyldiazenes (tBu-N=N-SiR3 ) as silicon source. The high activity and selectivity of the catalytic system, exemplified by the preparation of various mono- or gem-bis benzyl(di)silanes, originates from the facile generation of organopotassium reagents, including tert-butylpotassium.

Organopotassium‐Catalyzed Silylation of Benzylic C(sp3)−H Bonds

AbstractBenzylsilanes have found increasing applications in organic synthesis as bench‐stable synthetic intermediates, yet are mostly produced by stoichiometric procedures. Catalytic alternatives based on the atom‐economical silylation of benzylic C(sp3)−H bonds remain scarcely available as specialized directing groups and catalytic systems are needed to outcompete the kinetically‐favored silylation of C(sp2)−H bonds. Herein, we describe the first general and catalytic‐in‐metal undirected silylation of benzylic C(sp3)−H bonds under ambient, transition metal‐free conditions using stable tert‐butyl‐substituted silyldiazenes (tBu−N=N−SiR3) as silicon source. The high activity and selectivity of the catalytic system, exemplified by the preparation of various mono‐ or gem‐bis benzyl(di)silanes, originates from the facile generation of organopotassium reagents, including tert‐butylpotassium.

EFFECT OF MICROWAVE IRRADIATION TIME TO DEACETYLATION PROCESS OF CHITIN FROM SHRIMP SHELLS

Microwaves have been used in various organic synthesis applications. The use of microwaves provides many advantages, including relatively short start-up and heating times, energy efficiency and process costs, easy and precise process control, selective heating, better final product quality, and improved dry material quality. Microwaves were used in this study to convert chitin into chitosan and to determine the effect of deacetylation time on the degree of deacetylation of chitosan, which was in accordance with the Indonesian National Standard (SNI 7949:2013). The chitin deacetylation process was carried out by varying the heating time to 5, 7, 11, and 15 minutes with a power of 350 W. Two grams of chitin were mixed with 40 mL of 70% NaOH solution in a beaker. The mixture was put in a microwave at a constant temperature of 70 °C. Chitosan was washed until neutral and then dried in an oven. The degree of deacetylation (DD) was analyzed using Fourier Transform Infrared (FTIR) spectroscopy. The results showed that A deacetylation degree of 79.96% was achieved at a reaction time of 15 min. The water content of chitosan was determined to be 9.15%.