Synthesis Of Various Heterocyclic Compounds Research Articles

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.

Ceric Ammonium Nitrate supported on Hy-Zeolite Catalyzed Oxidative Condensation Reaction and its Docking Studies

The chemistry of chalcone has been recognized as a significant field of study. Chalcone serve as to prepare starting materials for the synthesis of various heterocyclic compounds. From the backbone of reported literature, we have developed an alternative heterogeneous and simple catalytic system for the synthesis of chalcones via the oxidative condensation of benzyl alcohol with substituted acetophenone using metal nitrate supported HY-Zeolite as a catalyst. 30 mol% CAN supported HY-zeolite has been efficiently used as a catalyst for the oxidative condensation reaction of benzyl alcohol with substituted acetophenones in the presence of hydrogen peroxide as an oxidant in toluene to afford the corresponding chalcones in good to moderate yields. Docking studies were carried out for the synthesized compounds towards the protein Lysine aminotransferase using the software.

Synthesis of N,N'-Diacylhydrazines and their Use in Various Synthetic Transformations

Background: N,N'-Diacylhydrazines are involved in many synthetic transformations. The current work reviews the synthesis of N,N'-diacylhydrazines and their use in various synthetic transformations. Results: Three synthetic routes are commonly used to produce N,N'-diacylhydrazines. They are produced through the coupling of acyl chlorides and carbohydrazides, the reaction of hydrazine hydrate and carboxylic acids or isocyanates, and the dimerization of carbohydrazides. They can be oxidized to produce the corresponding esters and act as precursors in the synthesis of various heterocycles such as 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles, pyrazoles, tetrazines, and crown ethers. Conclusions: Various synthetic procedures have been reported for the production of N,N'- diacylhydrazines. N,N'-Diacylhydrazines are involved in the synthesis of various heterocycles.

Cyclodesulfurization: An Enabling Protocol for Synthesis of Various Heterocycles

AbstractHeterocycles closely intertwine chemistry with biology reflecting the presence of nitrogen‐based heterocyclic ring structure in nearly 75 % of small‐molecule drugs. The number of reported strategies for the synthesis of several “privileged scaffolds” has expanded, amongst which, cyclodesulfurization of thioureas offers a quick access to highly substituted heterocycles, thereby playing a role of an excellent tool in organic syntheses of natural products and pharmaceutically active compounds. This comprehensive review emphasizes the applications of cyclodesulfurization as an integral synthetic step in the synthesis of nitrogen, oxygen and sulfur‐containing heterocycles. Furthermore, a survey of cyclodesulfurizing agents reported since 2000 is comprehensively reviewed and summarized.

Microwave and Conventional Study of Coumarin-Oxadiazole Adducts and their Anti-Microbial Evaluation.

Nowadays, researchers are progressively concentrated to generate economical, affordable and also greener synthesis approach for the synthesis of various heterocycles. On look at the beauty of coumarin molecules and oxazoles, it seems to be lead molecules in the anti-microbial area. With the target to identify efficient molecules, we studied 2-oxo-2H-chromen-4-yl-2-((5-substituted aryl-1,3,4-oxadiazol-2-yl) thio)acetate derivatives using two synthetic protocol/methods, i.e. conventional synthesis and microwave-based synthesis. Two simultaneous methods, i.e. conventional and microwave synthesis have been used for the synthe-sis of 2-oxo-2H-chromen-4-yl-2-((5-substituted aryl-1,3,4-oxadiazol-2-yl)thio)acetate (6a-l) derivatives. The desired molecules were synthesized by conventional and microwave synthesis and a comparative study was carried out to identify an easy route for industrial applications. The confirmations of the compounds were carried out by spectroscopic techniques such as IR, 1H NMR, 13C NMR, mass spectra and elemental analysis. All synthesized compounds were evaluated for their in-vitro antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Staphylococcus pyogenes), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and antifungal activity (Candida albicans, Aspergillus niger). All conventional synthesis of final coumarin derivatives were completed within 4-6 h. While that of microwave-based reaction took comparatively more reaction time. Surprisingly, the compounds 6f and 6g could not be synthesized by microwave radiation even after 32 minutes of irradiation. As to the medicinal application part, microbial evaluation of synthesized analogues showed that the compounds 6b, 6e, 6d, and 6j were found more potent in comparison to the reference drug.

Alkynoates as Versatile and Powerful Chemical Tools for the Rapid Assembly of Diverse Heterocycles under Transition-Metal Catalysis: Recent Developments and Challenges.

Heterocycles, heteroaromatics and spirocyclic entities are ubiquitous components of a wide plethora of synthetic drugs, biologically active natural products, marketed pharmaceuticals and agrochemical targets. Recognizing their high proportion in drugs and rich pharmacological potential, these invaluable structural motifs have garnered significant interest, thus enabling the development of efficient catalytic methodologies providing access to architecturally complex and diverse molecules with high atom-economy and low cost. These chemical processes not only allow the formation of diverse heterocycles but also utilize a range of flexible and easily accessible building units in a single operation to discover diversity-oriented synthetic approaches. Alkynoates are significantly important, diverse and powerful building blocks in organic chemistry due to their unique and inherent properties such as the electronic bias on carbon-carbon triple bonds posed by electron-withdrawing groups or the metallic coordination site provided by carbonyl groups. The present review highlights the comprehensive picture of the utility of alkynoates (2007-2019) for the synthesis of various heterocycles (> 50 types) using transition-metal catalysts (Ru, Rh, Pd, Ir, Ag, Au, Pt, Cu, Mn, Fe) in various forms. The valuable function of versatile alkynoates (bearing multifunctional groups) as simple and useful starting materials is explored, thus cyclizing with an array of coupling partners to deliver a broad range of oxygen-, nitrogen-, sulfur-containing heterocycles alongside fused-, and spiro-heterocyclic compounds. In addition, these examples will also focus the scope and reaction limitations, as well as mechanistic investigations into the synthesis of these heterocycles. The biological significance will also be discussed, citing relevant examples of drug molecules highlighting each class of heterocycles. This review summarizes the recent developments in the synthetic methods for the synthesis of various heterocycles using alkynoates as readily available starting materials under transition-metal catalysis.

2-Acetylbenzimidazole: a Valuable Synthon for the Synthesis of Biologically Active Molecules

Benzimidazole is an important moiety from a medicinal chemistry perspective due to its various biological activities such as antimicrobial, anti-cancer, anti-diabetic, anti-Alzheimers, and anti-inflammatory, etc. 2-acetylbenzimidazole is exploited to obtain various heterocyclic compounds of pharmacological interest. This review's main motive is to present the literature on 2-acetylbenzimidazole chemistry and provide valuable and up-to-date information for its applications. The present review is carried out by compiling literature from 1964 to 2020 concerning the synthesis and biological aspects of various heterocyclic compounds derived from 2-acetylbenzimidazole. Literature was collected from various online search engines viz. Google Scholar, PubMed, Science Direct, Core, and Semantic scholar. 2-acetylbenzimidazole has been successfully employed as a synthon to obtain heterocyclic system viz. oxirane, pyrazoline, thiazole, pyrazole, isoxazoline, isoxazole, pyridine, pyrimidine, thiazine, diazepine, and other miscellaneous rings. 2-acetylbenzimidazole has shown promise for the convenient synthesis of various heterocyclic compounds. The reactions can be carried out on various reactive sites of 2-acetylbenzimidazole, which are the carbonyl group and the amino group. This review will help to explore various heterocyclic compounds and particularly in the synthesis of biologically useful compounds.

Advances in polymer electrode materials for alkali metals (lithium, sodium and potassium)-ion rechargeable batteries

Organic polymer materials gain much attentions due to its high nature abundance, tuneable property with respect to functional groups, easy processing, low-cost alternate to their inorganic counter-part. The conversion of one functional group to others, building cyclic skeleton, synthesis of various heterocycles, protection of one sensitive functional group during the conversion of another one in a substituted molecule, low temperature and high pressure reactions, etc. are the part of synthetic chemistry. Especially, care is needed to synthesis electrochemically active compounds for energy storage applications. Almost, all secondary batteries decorated with the organic polymer materials as part/full of the electrodes design. This review summarizes the synthesis of electrochemically active organic redox polymers such as carbonyl, organosulfur, conducting polymers and its application in various alkali metal-ion rechargeable batteries as electrode components.

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

AbstractThe trifluoromethyl (CF3) group is an advantageous structural motif in various biologically active molecules as well as materials, which is depicted by steadily increasing demand from the industries involved in drug discovery, agrochemicals and material development. β‐trifluoromethyl α,β‐unsaturated carbonyl compounds constitute a very efficient building blocks as starting material in the synthesis of fluorinated molecules. Their usage for the synthesis of various heterocycles and organic molecules bearing stereogenic carbon containing CF3 motif has received significant attention during the recent times. This review provides the existing methods for the synthesis of β‐substituted trifluoromethyl‐α,β‐unsaturated ketones and the efforts made by researchers for the synthetic development through various reactions by employing them as synthetic building blocks for trifluoromethylated organic scaffolds.magnified image

A novel organic reaction leading to new 2-N-substituted benzoic acid ion-pair. A combination of physicochemical and theoretical calculations approaches

The 2-aminobenzimidazole (ABZ)-2-N-propanoyl benzoic acid 1 which is an intermediate of synthesis of various heterocyclic compounds was synthesized. The structure of 1 was confirmed by FT-IR, NMR (1D and 2D) spectra and XRD. The molecular structure of compound 1 was characterized by single-crystal X-ray structure determination and theoretical calculations based on DFT, HF and MP2 methods. The NBO analysis was used mainly in order to study the influence of electronic delocalization on the mechanism. Experimental, DFT, HF and MP2/6-31G(d) optimized bond lengths, bond angles and hydrogen bonding for the structure are studied also.The structure analysis shows that the 3D-supramolecular architecture of 1 is stabilized by means six-(S6) intramolecular and eight-(R22(8)) membered intermolecular hydrogen bonds, together with extensive C—H…O and C—H…π interactions between the carboxylate anion and the 2-aminobenzimidazolium cation. Furthermore, parameters derived from density functional theory in a local sense, in particular the softness and Fukui function were used to interpret and predict the mechanism of the reaction.

Synthesis of Heterocycles through Denitrogenative Cyclization of Triazoles and Benzotriazoles.

During the past few decades, there has been considerable growth in the development of denitrogenative reactions of triazole skeletons to construct valuable cyclic compounds, particularly heterocycles. Despite the inherent difficulty of the ring-opening of triazole derivatives, many novel and efficient approaches have arisen in this area mainly with the use of transition metal (such as rhodium, palladium, silver, copper) catalysis, photolysis, or free radical mediated reactions. Generally, these procedures begin with the ring-opening of 1,2,3-triazoles or benzotriazoles followed by N2 extrusion and subsequent diverse transformations, which enable the rapid synthesis of various heterocycles in a single step. To avoid overlap with other related reviews, this minireview covers the recent advances in the denitrogenative cyclization of 1,2,3-triazoles since 2016 and the denitrogenative cyclization of benzotriazoles since 2012.

Synthesis and optical characterization of new ketocyanine dyes with extended polymethine chaines

AbstractNew symmetrical and unsymmetrical near‐infrared absorbing ketocyanine‐type dyes are synthesized and their optical characterization is done. The relationships between their structure and optical properties are discussed. The synthesized ketocyanine dyes show a positive solvatochromism and are poorly fluorescent. A new procedure for the preparation of N,N,N′,N′‐tetramethylvinamidinium perchlorate, which was a very useful reagent for the synthesis of various heterocyclic compounds as well as for the preparation of cyanine dyes is developed.

RЕACTION OF O-ARYL(METHYL)SULFONATES OF 1,4-QUINONE MONOOXIMES WITH HYDRAZINES

Aroylhydrazones contain the active pharmacophore group >C=N–NH–CO–. These compounds show antimicrobial, antibacterial, and even anticancer activity. In addition, aroylhydrazones are synthons in the synthesis of various heterocyclic compounds. The purpose of this work is to define the features of the reaction of aryl(benzoyl)hydrazines with O-sulfonates of 1,4-quinone monooxime and to synthesize the benzoquinone hydrazones based on them. In the result of reaction of 1,4-quinone monoxime O-sulfonates with phenylhydrazine the p-tolyl(methyl)sulfates of the corresponding aminophenols were obtained. Subsequent treatment of these sulfates with water and acidification led to sulfate destruction and formation of a mixture of the corresponding aminophenol and p-tolyl(methyl)sulfate acid. We did not obtain 1,4-benzoquinone hydrazones. Thus, in the reaction of 1,4-quinone monoxime O-sulfonates with phenylhydrazine, the first stage is the N–O bond break with reduction of quinoid ring, and this redox process is due to the high basicity of aryl hydrazines. The aroylhydrazones of 1,4-benzoquinone were obtained only in the reaction of aroylhydrazines with 1,4-quinone monoxime O-sulfonates, containing two alkyl substituents in the both orthopositions to the carbonyl group of the quinoid ring. The first step of this reaction is also the =N–O– bond breaking of the starting sulfonates and formation of corresponding quinone imines. 2,6-Disubstituted quinone monoimines have less redox potential, and aroylhydrazines are less basic than arylhydrazines, therefore, the formation of corresponding aroylhydrazones of 1,4-benzoquinone is possible. The variation of the substituent attached to the oxygen atom of the starting 1,4-quinone monooxime O-sulfonates (MeSO2 or Ts) does not affect the reaction route.

A facile approach to hybrid compounds containing a tricyclic diterpenoid and fluorine-substituted heterocycles

2,3-Butadienes have become valuable building blocks in the synthesis of various heterocyclic compounds. The Pd-catalyzed cross-coupling and cyclization reaction of N-(2,3-butadienyl)carboxamide of isopimaric acid with fluorine-substituted 2-iodophenols proceeds with the formation of optically active fluorinated benzofuran and benzopyrane derivatives of isopimaric acid. This transformation opens a potential route to the synthesis of hybrid compounds containing a tricyclic diterpenoid moiety and several fluorinated benzoannelated heterocycles.

Green synthetic strategies toward thiazoles: a sustainable approach

In current era of environmental crisis, green chemistry has regained a significant role in overcoming the harmful consequences of conventional chemistry in every aspect. Green chemistry approaches like use of green solvents, green catalysts, green reagents, phasetransfer catalysts, solid support synthesis, and microwave irradiation-based synthesis provide an environmentally friendly and safe platform for the pilot and bulk synthesis of various heterocyclic compounds. Many pharmaceutical companies and researchers have showed their interest toward greener approaches for the development of medicinal products, as they minimize the production of waste and costs of the synthetic process. Accordingly, researchers continuously make attempts to incorporate these strategies for the synthesis of sulfur-containing heterocyclic compounds such as thiazoles, thiazolidines, and benzothiazoles, etc. The present review compiles various green synthetic approaches including use of green solvents, catalysts, solid support synthesis, microwave irradiation- and ultrasonication-mediated processes, for the synthesis of thiazoles and their derivatives.

Aromatic Heterocycles as Productive Dienophiles in the Inverse Electron-Demand Diels-Alder Reactions of 1,3,5-Triazines.

Heterocycles are often found as the structural nucleus in natural products and biological active compounds. Consequently, research toward the discovery and development of novel and efficient synthetic methodologies is of constant interest to organic chemists. Diels-Alder reactions are powerful at forming multiple bonds simultaneously, often with stereoselectivity, and thus are one of the most widely used synthetic methodologies in organic syntheses. Inverse electron-demand Diels-Alder (IEDDA) reactions, a subclass of Diels-Alder reactions, have been developed for the efficient synthesis of various heterocycles, with 1,3,5-triazines used as azadienes. The initial 1,3,5-triazine IEDDA reactions mostly included nonaromatic, electron-rich species such as vinyl ethers, enamines, ynamines, and amidines as dienophiles, producing in high yields pyrimidine derivatives with excellent regioselectivity. We hypothesized that some electron-rich aromatic heterocycles could be studied as potential dienophiles for 1,3,5-triazine IEDDA reactions; 5-aminopyrazoles proved to be productive dienophiles leading to high yields of pyrazolopyrimidines. Subsequently, many studies were reported to investigate the mechanism and scope of this new type of IEDDA reaction. Mechanistically, this new type of IEDDA reaction is quite interesting since it entails two aromatic compounds proceeding through a perceived high energy nonaromatic transition state, leading to a new aromatic compound, a counterintuitive process. Both theoretical and experimental studies provide key insights to this reaction mechanism, with learnings from these studies possibly stimulating unconventional thinking in other areas. Theoretical calculations of these cascade reactions of amino-substituted heterocycles with 1,3,5-triazines indicate that the reactions occur in a stepwise fashion via a highly polar zwitterionic intermediate; elimination of ammonia from IEDDA adducts and subsequent retro Diels-Alder reaction drive the reaction toward the fully aromatized IEDDA products. This amino substituent is critical in determining the regioselectivity and driving the cascade reactions to completion. With regard to reaction scope, many amino-heterocycles such as pyrroles, imidazoles, furans, thiophenes, and indoles all proved to be productive dienophiles for this new IEDDA reaction, leading to various fused-pyrimidines in a single step with moderate to high yields and high regioselectivity. Application of this new IEDDA reaction with 1,3,5-triazines was reported to lead to interesting heterocyclic compounds such as nucleoside natural product nebularine and analogues, as well as fluorine-containing fused pyrimidines with potential for biological activities.Herein, the scope of various aromatic heterocycles as dienophiles in the 1,3,5-triazine IEDDA reaction is reviewed. Moreover, both experimental and theoretical studies of the mechanisms for this interesting cascade IEDDA reaction are discussed. Finally, applications of this new type (aromatic heterocycles as dienophiles with 1,3,5-triazines as azadienes) of IEDDA reaction are also covered.

Synthesis of heterocyclic compounds through nucleophilic phosphine catalysis

Nucleophilic phosphine catalysis is a practical and powerful tool for the synthesis of various heterocyclic compounds with the advantages of environmentally friendly, metal-free, and mild reaction conditions. The present report summarizes the construction of four to eight-membered heterocyclic compounds containing nitrogen, oxygen and sulphur atoms through phosphine-catalyzed intramolecular annulations and intermolecular [2+2], [3+2], [4+1], [3+1+1], [5+1], [4+2], [2+2+2], [3+3], [4+3] and [3+2+3] annulations of electron-deficient alkenes, allenes, alkynes and Morita-Baylis-Hillman carbonates.

Arylglyoxals as Versatile Synthons for Heterocycles Through Multi-Component Reactions

Arylglyoxals are important synthons that have been used in the construction of a diverse spectrum of compounds. The use of multicomponent approaches in organic synthesis due to its environmentally friendly nature is a step forward towards sustainability. This review will offer the reader insightful perspectives on the use of arylglyoxals for the synthesis of various heterocyclic compounds like pyrroles, pyrazoles, furans, imidazoles, indoles, oxazoles, pyridines, quinazolines, pyrans, etc using multicomponent approach.

Recent advances in the application of acetophenone in heterocyclic compounds synthesis

Acetophenone is an interesting synthon in the most organic reactions. Acetophenone has been utilized in the synthesis of many heterocyclic compounds. Acetophenone and most of its derivatives are commercially available or readily accessible and hence are ideal synthon for multicomponent reactions including the three- and four-component reactions. Also, the biological activities of some compounds were studied. Herein, we want to review the application of the acetophenone as starting material in the synthesis of various heterocyclic compounds including fused and five-, six-, seven-membered rings via multicomponent reactions.

N'-(1-([1,1'-biphenyl]-4-yl)ethylidene)-2-cyanoacetohydrazide as scaffold for the synthesis of diverse heterocyclic compounds as prospective antitumor and antimicrobial activities

In this article, the main target was to study the antitumor and antimicrobial efficacy of new heterocycles conjugated with biphenyl moiety in-vitro. This was implemented by utilizing N'-(1-([1,1'-biphenyl]-4-yl)ethylidene)-2-cyanoacetohydrazide 3 as a material for the synthesis of various heterocyclic compounds. Among of them, some compounds were selected and assayed against two antitumor cell lines as (HepG2) and (HCT-116). Conspicuously, the achieved results showed that compounds 6, 13, and 23 possess significant potency against both cancer cell lines. Particularly, compound 13 exhibited a remarkable efficacy, similar to the standard anticancer drug (doxorubicin), against both cancer cell lines. Noteworthy, compound 13 may serve as a potential anticancer therapeutic drug in the future. On the other hand, In-vitro antifungal and antibacterial activities of selected compounds were assayed and the results indicated that the compound 6 exhibited significant potency against Candida albicans, while compounds 6 and 8 displayed spectacular results for the antibacterial study.