Synthesis Of Various Heterocyclic Compounds Research Articles

NHC-Catalyzed Enantioselective Transformations Involving α-Bromoenals.

α-Haloenals, especially, α-bromoenals considered as one of the important building blocks in organic synthesis. They can participate in various (3+2)-, (3+3)-, (3+4)-, and (2+4)-annulation reactions with other organic molecules in the presence of an NHC catalyst to produce enantioenriched carbo-, and heterocyclic compounds. Herein, we have described NHC-catalyzed enantioselective transformations of α-bromoenals in the synthesis of various heterocycles, and carbocycles, as well as acyclic organic compounds.

A Comprehensive Examination of Heterocyclic Scaffold Chemistry for Antitubercular Activity.

Tuberculosis is a communicable disease which affects humans particularly the lungs and is transmitted mainly through air. Despite two decades of intensive research aimed at understanding and combating tuberculosis, persistent biological uncertainties continue to hinder progress. Nowadays, heterocyclic compounds have proven themselves in effective treatment of tuberculosis because of their wide range of biological and pharmacological activities. Antituberculosis or antimycobacterial agents encompass a broad array of compounds utilized singly or in conjunction to combat Mycobacterium infections, spanning from tuberculosis to leprosy. Here, we summarize the synthesis of various heterocyclic compounds which includes the greener synthetic route as well as use of nano compounds as catalyst along with their anti TB activities.

Visible-Light-Mediated Divergent and Regioselective Vicinal Difunctionalization of Styrenes with Arylazo Sulfones.

Activated by visible light, arylazo sulfones can serve as multifaceted reactants and are employed in diazenylation, sulfonylation, and arylation reactions under (photo)catalyst-free conditions. Such versatile reactivity enabled us to develop an operationally simple, regioselective, and tunable difunctionalization of styrenes with arylazo sulfones to produce α-sulfonyl arylhydrazones and 1,2-alkoxyarylated products in moderate to excellent yields. Furthermore, such difunctionalized products have been exploited as key building blocks for the synthesis of various heterocycles.

The Molecular Diversity Scope of Meldrum's Acid in Multicomponent Reactions

AbstractMulticomponent reactions (MCRs) have gained significant attention in the field of organic synthesis due to their ability to efficiently construct complex molecular structures in a single step. Among the reagents employed in MCRs, Meldrum's acid has emerged as a highly versatile and valuable starting material, offering a wide range of molecular diversity. This comprehensive review explores the molecular diversity scope of Meldrum's acid in various MCRs, focusing on its unique attributes and the greener aspects of its application. Meldrum's acid possesses several remarkable features that contribute to its suitability as a key component in MCRs. Its high acidity enables effective participation in a variety of chemical reactions, while its rigid structure provides stability and allows for precise control of the reaction pathways. Furthermore, the ability of Meldrum's acid to undergo both nucleophilic and electrophilic attacks makes it highly versatile in the construction of diverse molecular frameworks. Its low steric hindrance further enhances its reactivity, facilitating efficient bond formation. By surveying the literature from the last five years (2018–2022), we delve into the broad range of applications of Meldrum's acid in MCRs. The review encompasses the synthesis of various heterocyclic compounds, highlighting the significance of Meldrum's acid in achieving molecular diversity. Moreover, particular emphasis is placed on the greener aspects of utilizing Meldrum's acid, considering the growing demand for environmentally friendly synthetic approaches. This includes exploring greener solvents, milder reaction conditions, and reduced waste generation.

An Overview of Palladium-Catalyzed Fabrication of Some Heterocyclic Frameworks

Abstract: Heterocycles are the largest family of organic compounds due to their wide applications as therapeutic agents, synthetic intermediates, scaffolds, building blocks or fine chemicals. Heterocyclic compounds are continuously used in material science, biotechnology, pharmaceutical and agrochemical industries. In the past few years, the use of transition metal complexes especially palladium as a heterogeneous catalyst has become a trend for the synthesis of various organic compounds. Pd-catalyzed reactions have proven to be effective ways for synthesising a variety of heterocyclic compounds, which are a popular class of molecules in chemical study. Hence, in this review we have discussed the palladium catalyzed synthesis of various heterocyclic compounds i,e. furan, indole, quinoline, coumarin and some other heterocycle derivatives.

Photocatalytic Charge-Transfer Complex Enables Hydroarylation of Alkenes for Heterocycle Synthesis

Here, we report a photocatalytic charge-transfer complex (CTC) strategy for one electron reduction of alkenes using thiolate as a catalytic electron donor. This catalytic CTC system could engage hydroarylation of both activated and unactivated alkenes for the synthesis of various heterocycles. The reactions do not require any photocatalysts or acids and are easy to perform. Mechanistic studies revealed the formation of a CTC between catalytic thiolate and alkene.

New Developments of Chiral Palladium‐Aqua Complexes as Cooperative Brønsted Acid‐Base Catalysts in Organic Synthesis

AbstractBased upon their exceptional reactivity as cooperative Brønsted acid‐base catalysts chiral diphosphane Pd‐aqua complexes have successfully been utilized in a broad range of asymmetric transformations. Originally discovered by Sodeoka 25 years ago, they readily form reactive chiral Pd enolates upon deprotonation of β‐dicarbonyl compounds and simultaneously, a Brønsted acid liberated from the catalyst activates the electrophile. After the initial report and some ensuing papers had been published in the early 2000s, the field lay dormant for more than a decade. In recent years, however, new developments towards the enantioselective synthesis of various heterocycles and other useful compounds have evolved which take advantage of the unique properties of chiral Pd‐aqua complexes.

New Aspects of the Reaction of Thioacetamide and N-Substituted Maleimides.

N-Arylmaleimides are universal substrates for the synthesis of various heterocyclic compounds with a wide spectrum of biological activity. However, their reactions with thioacetamides have not been comprehensively studied. We studied the reactions of thioacetamide with N-arylmaleimides under various conditions. We established for the first time that three types of products: epithiopyrrolo[3,4-c]pyridines, pyrrolo[3,4-c]pyridines and 3,3'-thiobis(1-arylpyrrolidine-2,5-diones) can be obtained in different conditions. In all cases, two maleimide molecules are involved in the reaction. 3,3'-Thiobis(1-arylpyrrolidine-2,5-diones) are the major products when the reaction is conducted at boiling in acetic acid. When thioacetamide and N-arylmaleimide are kept in dioxane at 50 °C, epithiopyrrolo[3,4-c]pyridines can be isolated, which, when heated in dioxane, in acetic acid or in methanol in the presence of catalytic amounts of sodium methoxide, are converted into pyrrolo[3,4-c]pyridines by eliminating hydrogen sulfide. The reaction of thioacetamide and N-arylmaleimide in dioxane at boiling temperature with the portioned addition of N-arylmaleimide leads predominantly to the formation of pyrrolo[3,4-c]pyridines. The reaction of thioacetamide with N-alkylmaleimides under all the above conditions leads predominantly to the formation of the corresponding sulfides. The structure of the compounds obtained was characterized by a set of spectral analysis methods and X-ray diffraction (XRD) data.

Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures

AbstractDialkyl acetylenedicarboxylates (DAAD) are the class of acetylenic compounds that are broadly used in organic synthesis in a noticeable quantity. Their wide application has made them an important moiety in heterocyclic compounds and drug discovery programs. Dialkyl acetylenedicarboxylate is a di‐ester in which the ester groups are conjugated with a carbon‐carbon triple bond. As such, the molecule is very electrophilic, and is broadly used as a dienophile in various cycloaddition reactions, for example the Diels‐Alder reaction. In addition, it is a strong Michael acceptor. Due the importance of dialkyl acetylenedicarboxylate in organic synthesis, we are trying to show the applications of this compound in the synthesis of different heterocycles using multicomponent reactions. In this review, we show recent advances (2016–2022) for the synthesis of various heterocycles that have different ring sizes (five, six and seven membered, Spiro and fused heterocycles), using DAAD via multicomponent reactions.

Arylidenemalononitriles as Versatile Synthons in Heterocyclic Synthesis.

Arylidenemalononitriles are valuable synthons for the construction of a variety of novel complex heterocyclic motifs, fused heterocycle derivatives, and spirocyclic compounds. They are versatile chemical intermediates and have increasing applications in industry, agriculture, medicine, and biological science. The aim of this review is to highlight the preparation methods and reactions of arylidenemalononitriles in the synthesis of various heterocyclic compounds. In this review, we have presented the application of arylidenemalononitriles to construct a variety of heterocycles. Various catalysts for the preparation of arylidnemalononitriles have been described.

Azides in the Synthesis of Various Heterocycles.

In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal, catalyzed, or noncatalyzed reaction conditions. The aforementioned reactions in the aim to prepare basic five-, six-, organometallic heterocyclic-membered systems and/or their fused analogs. This review article also provides a report on the developed methods describing the synthesis of various heterocycles from organic azides, especially those reported in recent papers (till 2020). At the outset, this review groups the synthetic methods of organic azides into different categories. Secondly, the review deals with the functionality of the azido group in chemical reactions. This is followed by a major section on the following: (1) the synthetic tools of various heterocycles from the corresponding organic azides by one-pot domino reaction; (2) the utility of the chosen catalysts in the chemoselectivity favoring C−H and C-N bonds; (3) one-pot procedures (i.e., Ugi four-component reaction); (4) nucleophilic addition, such as Aza-Michael addition; (5) cycloaddition reactions, such as [3+2] cycloaddition; (6) mixed addition/cyclization/oxygen; and (7) insertion reaction of C-H amination. The review also includes the synthetic procedures of fused heterocycles, such as quinazoline derivatives and organometal heterocycles (i.e., phosphorus-, boron- and aluminum-containing heterocycles). Due to many references that have dealt with the reactions of azides in heterocyclic synthesis (currently more than 32,000), we selected according to generality and timeliness. This is considered a recent review that focuses on selected interesting examples of various heterocycles from the mechanistic aspects of organic azides.

Oxa-Michael Addition Reactions of 3-hydroxy-2-azetidinones: Synthesis of 1, 3, 4-Trisubstituted-2-Azetidinones

Abstract:The manuscript describes a facile and an efficient methodology for the synthesis of 1, 3, 4 trisubstituted-β-lactams by base mediated oxa-Michael addition reactions of 3-hydroxy-2- azetidinones with acetylenic esters under different reaction conditions. These functionalized 1, 3, 4-trisubstituted-azetidin-2-ones are useful organic synthons for the synthesis of various heterocyclic compounds having diverse pharmacological applications.

Efficient Synthetic Access to Novel Indolo[2,3-b]Quinoxaline-based Heterocycles.

This paper showed the synthetic capability of the indolo[2,3-b]quinoxaline nucleus to be provided as an excellent precursor for the synthesis of various heterocyclic compounds. These synthetic routes proceed via the formation of 3-(6H-indolo[2,3-b]quinoxalin-6-yl) propane hydrazide (2). The carbohydrazide 2 and its reactions with different reagents give five and six-membered rings, such as 1,3,4-thiadiazole, 1,3,4- oxadiazole, 1,2,4-triazole, and 1,2,4-triazine. All chemicals used in the current study were of analytical grade. Melting points were determined using an APP Digital ST 15 melting point apparatus and were uncorrected. FT-IR spectra were recorded on a Pye- Unicam SP3-100 and Shimadzu-408 spectrophotometers in KBr pellets and given in (cm-1) KBr. The NMR spectra were detected by a Bruker AV-400 spectrometer (400 MHz for 1H, 100 MHz for 1C and 40.55 MHz for 15N), Institute of Organic Chemistry, Karlsruhe, Germany. Chemical shifts were expressed as δ (ppm) with TMS as an internal reference. Mass spectrometry was provided on a Varian MAT 312 instrument in EI mode (70 eV). The target compounds were obtained, and their structures were completely elucidated by various spectral and elemental analyses (Ft-IR, 1H-NMR, 13;C-NMR, and mass spectrometry). The current work showed a view of the reactivity of the carbohydrazide group. The carbohydrazide 2 was obtained from the hydrazinolysis of carboethoxy compound 1 and exploited as a key intermediate to synthesize heterocyclic compounds with different rings.

Reusable Iron/Iron Oxide-based Nanoparticles Catalyzed Organic Reactions

ABSTRACT:The last decade has witnessed a remarkable progress in the field of nanoscience and nanotechnology. Nanoparticles have been extensively used in diverse areas, including medicine, sensor, and catalysis. The easy accessibility of nanoparticles (NPs) with different shapes, sizes and compositions has inspired researchers to investigate their applications in catalysis. Recently, magnetic nanoparticles, such as iron-based nanoparticles, have attracted much consideration due to their unique properties, such as superparamagnetism, greater surface area, surface-to-volume ratio, and easy separation methodology. They increase the competence of organic reactions in terms of activity, selectivity, yield, simplicity, and sustainability. In this review, we focus on the developments of iron/iron oxide-based nanoparticles-catalyzed organic reactions and some examples of magnetic iron oxide nanoparticles as carriers/support for the main catalyst in organic reactions. Owing to magnetic properties, these nanocatalysts can be easily recovered from the reaction mixture by an external magnet and reused for several runs without loss of catalytic activity. Iron-based nanoparticles are used in a wide range of catalytic processes and applications. Notable focus has been on the hydrogenation of alkenes and alkynes, and also the hydrogenation of nitroarenes to aniline. Other catalyzed organic reactions, such as hydroboration of aldehydes and ketones, oxidative dehydrogenation of N-heterocycles, azide-alkyne cycloaddition reactions, synthesis of various heterocyclic compounds, multicomponent reactions, and crosscoupling reactions for C–C and C–heteroatom bond formation have been covered.

Annulation of 2‐Alkynylanilines: The Versatile Chemical Compounds

Abstract2‐Alkynylanilines as versatile building blocks have been widely applied for the construction of nitrogen atom‐containing heterocycles in organic synthesis. The focus of this review is on the application of 2‐alkynylaniline and its derivatives in the metal‐catalyzed or metal‐free synthesis of various heterocycles including indoles, oxindoles, indazoles, benzisoxazoles, quinolines, benzoxazines, benzothiazines, quinazolines, cinnolines, and seven‐ and eight‐membered heterocycles.

Benzils: A Review on their Synthesis

AbstractThis review segregates and outlines all the aspects of the synthesis of Benzil for almost two centuries. Here, state of the art review includes the early synthesis in 1836 to the advancement made over the past years in the knowledge of the preparation of benzil derivatives till the present. Benzil is one of the important and highly underrated organic compounds in which two adjacent carbonyl groups are flanked by two phenyl rings. Apart from its diverse functionality, the reactivity of benzils proclaims its prospects as a reagent for the synthesis of various heterocycles. On recasting benzil, it is possible to obtain a wide variety of utilities in pharmaceuticals, polymer, and material chemistry. This contemplation of the review gives a general perspective of reaction routes, mechanisms and highlights the conversions due to oxidation, and accentuates benzil as an emerging putative target.

Synthesis of Deuterated Heterocycles with Me2NCD(OMe)2 and Evaluation of the Products for Metabolism by Aldehyde Oxidase.

The metabolic oxidation of drug-like small molecules by aldehyde oxidase (AO) has commonly been mitigated through the incorporation of deuterium at the oxidation site. We report that dimethylformamide dimethyl acetal and related compounds undergo rapid CH to CD isotopic exchange upon exposure to methanol-d and similar deuterated alcohols. This isotopic exchange process can be used to synthesize Me2NCD(OMe)2 and has significant implications for the use of Me2NCD(OMe)2 in the synthesis of specifically deuterium-labeled compounds. The application of Me2NCD(OMe)2 to the synthesis of various heterocycles that have been associated with AO metabolism is described, and we report the impact of deuteration on the rate of in vitro AO-mediated metabolism.

Friedel-Crafts alkylation reaction efficiently catalyzed by a di-amide functionalized Zr(IV) metal-organic framework

In this work, a di-amide functionalized Zr(IV) metal-organic framework (MOF, 1) was synthesized and characterized with powder XRD, FT-IR, FE-SEM and elemental analysis. Furthermore, thermogravimetric analysis (TGA) of 1 showed thermal stability up to 275 °C. High chemical stability of the MOF was noticed in different organic solvents, under acidic and basic conditions. The BET surface area of this porous framework was 632 m2/g and pore volume was 0.35 cm3/g at p/po = 0.5. Activated MOF material (1′) displayed noticeable catalytic performance in the Friedel-Crafts alkylation between indole (IND) and β-nitrostyrene (NS). The desired product was obtained in quantitative yield using 1′ as a solid catalyst in ethanol at 40 °C. Catalyst stability was proved by leaching and reusability tests. This catalyst also exhibited broad substrate scope for the synthesis of various heterocyclic compounds. Comparison of the present catalytic results with reported data clearly indicates that this solid is able to promote the reaction effectively to attain higher yields by appropriate design of linker with amide functionality.

An Efficient Access to 3,5‐Disubstituted Isoxazoles with Anthranilate Ester Moiety: Alkaloid Lappaconitine – Aryl Conjugates with an Isoxazole Linker

AbstractAlkynones have gained great attention as useful building blocks in organic synthesis. They have been emerged as key intermediates in the synthesis of various heterocycles. In the present study, the alkynylketones derived from antranylic acids esters or alkaloid lappaconitine were employed as a platform for late‐stage derivatisation. The synthesis of regioisomeric 3,5‐diarylisoxazoles was achieved starting from ethyl N‐acetyl‐5‐iodoanthranilate. A range of 3,5‐disubstituted isoxazoles, containing the plant alkaloid lappaconitine moiety at the C‐3 position were convenience synthesized by a consecutive three‐component alkynylation‐cyclocondensation sequence starting from of 5′‐ethynyllappaconitine, aroyl chlorides, and hydroxylamine hydrochloride. Notably, several 5‐hydroxy‐4,5‐dihydroisoxazoles were obtained in good yields as main products in this three component reaction by using Et3N as the base and i‐PrOH as the solvent in cyclocondensation step.

Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

As part of natural products or biologically active compounds, the synthesis of nitrogen-containing heterocycles is becoming incredibly valuable. Palladium is a transition metal that is widely utilized as a catalyst to facilitate carbon-carbon and carbon-heteroatom coupling; it is used in the synthesis of various heterocycles. This review includes the twelve years of successful indole synthesis using various palladium catalysts to establish carbon-carbon or carbon-nitrogen coupling, as well as the conditions that have been optimized.