Synthesis Of Nitrogen-containing Heterocycles Research Articles

Regio-, Site- and Stereo-Selective Aziridination of Conjugated Dienes Enabled by Palladium/Copper/Iodide/Oxygen Cooperation.

Vinylaziridines are important building blocks in organic chemistry, especially in the synthesis of nitrogen-containing heterocycles. The direct and efficient transfer of an appropriate nitrogen source to readily accessible conjugated dienes is a notable methodology. The Pd-catalyzed oxidative 1,2-difunctionalization of conjugated dienes through a π-allyl-palladium species should be an ideal method for the selective synthesis of vinylaziridines. However, this method faces the challenge of regioselectivity, often resulting in 1,4-difunctionalization instead. In this study, we developed a Pd-catalyzed aerobic 1,2-difunctionalization of conjugated dienes via a π-allyl-palladium species to achieve regio-, site- and stereo-selective aziridination under the synergistic effects of Pd(II), Cu(I), I-, and O2. The π-allyl palladium species formed in the system undergoes an unusual iodination process, leading to the formation of an allyl iodide intermediate. Subsequently, the vinylaziridine is obtained through intramolecular SN2' substitution of the allyl iodide.

Cp*Ir(III) complexes catalyzed solvent-free synthesis of quinolines, pyrroles and pyridines via an ADC strategy.

A trio of Ir(III) complexes that are held together by a picolinamidato moiety were created. In our earlier research, we demonstrated the catalytic activity of the complexes for producing alpha-alkylated ketones from a ketone or secondary alcohol with a primary alcohol in the presence of a catalytic amount of a Cp*Ir(III) catalyst and tBuOK in toluene at 110 °C using the hydrogen-borrowing technique. Earlier many research groups had synthesized quinoline, pyrrole, and pyridine derivatives using 2-amino alcohol and ketone or secondary alcohol derivatives as starting materials, but in all those cases the reaction conditions are not suitable in terms of green synthesis like more catalyst loading, base loading, long reaction time, and high temperature. In addition, most of the reactions contain phosphine a hazardous by-product, along with the catalyst. Keeping in mind these shortcomings, we tried to expand the use of our catalysts after achieving an excellent result in our previous work, and we were successful in producing quinoline, pyrrole, and pyridine derivatives through acceptor-less dehydrogenative coupling (ADC) procedures at 90-110 °C under neat/solvent-free conditions and achieved good to exceptional yields of those nitrogen-containing heterocycles. This methodology is attractive because it is environmentally benign and allows for the "green" synthesis of nitrogen-containing heterocycles. All that is required is a modest quantity of catalyst and base, and the by-products are merely H2O and H2.

Catalytic synthesis of N-substituted allylarylamines

Some N-substituted allylarylamines, for example, N-(1-methyl-2-butenyl) aniline (N-MBA) form, upon isomerization, not only ortho-, but also para- and 2,6-disubstituted derivatives, which does not fit into generally accepted theory. The amino-Claisen rearrangement (ACR) of N-MBA is catalyzed by Lewis acids, cationites, and arylamine hydrochlorides. This work presents the results of studies of ACR N-MBA in solutions of mineral acids. It was found that the reaction must be carried out in dilute solutions. At H2SO4 concentrations of 0.5 mol/L and below, three parallel reactions are observed with the formation of aniline, 2-(1-methyl-2-butenyl) aniline (2-MBA) and 4-(1-methyl-2-butenyl) aniline (4-MBA). The main product in all cases is 2-MBA, the content of which in the reaction mixture exceeds the amount of 4-MBA and aniline by 7 times, which are formed in approximately equal amounts. Prolonged refluxing of 2-MBA under the reaction conditions does not lead to its isomerization to 4-MBA, i.e., the para-isomer is formed directly from N-MBA. The formation of 2,6-di-(1-methyl-2-butenyl) aniline (DMBA) was not observed. In the presence of palladium catalysts, 2-MBA cyclizes to 2,4-methyl quinoline, which indicates the ortho-arrangement of its substituents; 4-MBA does not cyclize under these conditions. The obtained compounds are of interest in the synthesis of nitrogen-containing heterocycles and other polyfunctional organic compounds.

Methylene blue as an additive for acid-acid-catalyzed tandem reactions targeting on the synthesis of nitrogen-containing heterocycles

Methylene blue (MB) was proven to be an effective and amine-compatible additive for helping the establishment of some acid-acid-catalyzed tandem reactions. Addition of MB to acid-catalyzed reaction system not only allowed the use of some basic amines as substrates, which are generally incompatible with the acid conditions, but also enabled the successful synthesis of many important nitrogen-containing heterocycles, such as β-carbolines, pyridines, and quinazolines, in a straightforward manner.

A decade update on the application of β-oxodithioesters in heterocyclic synthesis.

The diverse synthesis of heterocyclic compounds has always been one of the popular subjects of organic chemistry. To this end, great efforts have been devoted to developing new reagents and establishing new strategies and methods concerning efficiency, selectivity and sustainability. β-Oxodithioesters and their enol tautomers (i.e., α-enolic dithioesters), as a class of simple and readily accessible sulfur-containing synthons, have been widely applied in the construction of various five- and six-membered heterocycles (e.g., thiophenes, thiopyrans, thiazoles, pyridines and quinolines) and other useful open-chain frameworks. Due to their unique chemical structures, β-oxodithioesters bear multiple reaction sites, which enable them to participate in two-component or multicomponent reactions to construct various heterocyclic compounds. In the past decade, the application of β-oxodithioesters in the synthesis of heterocycles has made remarkable progress. Herein, an update on the recent advances in the application of β-oxodithioesters in the synthesis of heterocycles during the period from 2013 to 2023/06 is provided. According to the different types of rings concerning heteroatoms in products, this review is divided into five sections under discussion including (i) synthesis of sulfur-containing heterocycles, (ii) synthesis of sulfur and nitrogen-containing heterocycles, (iii) synthesis of nitrogen-containing heterocycles, (iv) synthesis of nitrogen and oxygen-containing heterocycles, and (v) modification to other open-chain frameworks.

Synthesis of Nitrogen-Containing Heterocycles from Estragole

Synthesis of Nitrogen-Containing Heterocycles from Estragole

Recent developments in the synthesis of nitrogen-containing heterocycles from β-aminovinyl esters/ketones as CC-N donors.

Nitrogen-containing heterocycles are ubiquitous fragments of numerous natural products, pharmaceuticals, designed bioactive drug candidates and agrochemicals. During the past few decades, these compounds have received considerable attention from the synthetic chemistry community, and great efforts have been focused on the development of concise and efficient methods for the synthesis of these heterocyclic skeletons. In this review, we summarize a diverse range of synthetic methods employing β-aminovinyl esters(ketones) as key CC-N-synthons to furnish useful bioactive heterocyclic frameworks, such as quinolines, pyridines, pyrazines, pyrroles, indoles, oxazoles, imidazoles, thiazoles, isothiazoles, pyrazoles, triazoles, and azepines, thus offering new opportunities and expanding the toolbox of synthetic chemistry reactions.

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.

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles.

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

Synthesis of Nitrogen-Containing Heterocycles through Catalytic Dehydrative Cyclization Reactions.

Re2O7 in hexafluoroisopropyl alcohol provides access to cationic intermediates from alcohols through the intermediacy of perrhenate esters. This manuscript describes the application of the system to the formation of a number of weakly basic heterocyclic systems through dehydration reactions and intramolecular nucleophilic addition. The influence of the substrate structure on the reaction rates and stereocontrol is discussed with respect to intermediate ion pairs.

Tandem Catalysis: Synthesis of Nitrogen-Containing Heterocycles

In this Review, we consider all the publications since the beginning of the century that describe tandem reactions resulting in the formation of five-membered aromatic nitrogen heterocycles (thiazole, imidazole, indole, tetrazole, triazole, and isoxazole). The contents of this review are organized by taxonomy and type of tandem catalysis. It covers orthogonal, auto-, and assisted tandem catalysis, providing an overview of tandem reactions applied tonitrogen heterocycles reported in the literature up to March 2020. We believe that this compilation of data will provide a necessary starting reference to developthe applications of tandem catalysis in medicinal chemistry.

Trienamines for the Organocatalytic Synthesis of Nitrogen-Containing Heterocycles

Nitrogen-containing heterocycles (NCH), constitute an important group of molecules, which are widely extended in whole chemical space. These compounds are of great interest due to their diverse biological activities. Currently, many compounds derived from NCH are used as powerful drugs for the treatment of diseases ranging from bactericides to anticancer agents. During last decade, the enantioselective synthesis of numerous heterocyclic compounds has been achieved through the use of chiral organocatalysts. The present contribution explores the application of the aminocatalysis towards the synthesis of NCH, particularly through the trienamine catalysis.

4-(4-Acethylphenyl)-3-hydroxycoumarin in the Synthesis of Nitrogen-containing Heterocycles with a Neoflavonoid Moiety

4-(4-Acetylphenyl)-3-hydroxy-2H-chromen-2-one has been prepared by the reaction of (4-acetylbenzene)diazonium chloride with 3-hydroxy-2H-chromen-2-one under Meerwein reaction conditions. The reactions of 4-(4-bromoacetylphenyl)-3-hydroxy-2H-chromen-2-one with pyridine, 4-methylpyridine, quinolone, and benzo[f]quinoline gave quaternary salts, and the reactions of the same bromo derivative with thioacetamide, thiourea, pyridine-2-amine, pyrimidin-2-amine, and thiazol-2-amine provided corresponding thiazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole derivatives. The reactions of 4-(4-bromoacetylphenyl)-3-hydroxy-2H-chromen-2-one with thiosemicarbazide and aromatic aldehydes involve thiazole ring formation, leading finally to corresponding hydrazones. It was established that 4-(4-acetylphenyl)- and 4-[4-(2-bromoacetyl)phenyl]-3-hydroxy-2H-chromen-2-ones can be used in three-component reactions to form a thiazole ring.

Cu-Catalyzed Cascade Annulation of Diaryliodonium Salts and Nitriles: Synthesis of Nitrogen-Containing Heterocycles

Developing versatile methodologies to construct various nitrogen­-containing heterocycles is a crucially significant part of contemporary organic chemistry. This review summarizes recent developments on the formation of nitrogen-containing heterocycles triggered by diaryliodonium salts. Diaryliodonium salts, as electrophilic arylating agents in the presence of catalytic copper salts, can react with nitriles to give N-arylnitrilium cations, which are highly reactive species. These species can efficiently react with nucleophiles, including C-, N- and O-nucleophiles, to give the corresponding products. This strategy is not only efficient and convenient, but also enables the synthesis of diverse nitrogen-containing heterocycles such as quinolines, quinazolines, and phenanthridines.1 Introduction2 Strategies and Mechanisms3 Cascade Annulations3.1 Cascade Annulation of Diaryliodoniums, Nitriles and C-Nucleo­philes3.2 Cascade Annulation of Diaryliodoniums, Nitriles and N-Nucleo­philes3.3 Cascade Annulation of Diaryliodoniums, Nitriles and O-Nucleo­philes4 Summary and Outlook

Mechanistic Study of SmI2/H2O and SmI2/Amine/H2O-Promoted Chemoselective Reduction of Aromatic Amides (Primary, Secondary, Tertiary) to Alcohols via Aminoketyl Radicals.

Samarium(II) iodide-water and samarium(II) iodide-water-amine complexes have been recognized as valuable reagents for the selective generation of aminoketyl radicals from amides and derivatives. The resulting aminoketyl radicals can undergo reduction or reductive cyclization pathways, providing a powerful method for (i) direct synthesis of alcohols from amides by the challenging N-C bond scission and (ii) synthesis of nitrogen-containing heterocycles via polarity reversal of the amide bond. This report describes mechanistic investigation into samarium(II) iodide-water and samarium(II) iodide-water-amine-mediated generation of benzylic aminoketyl radicals from aromatic primary, secondary, and tertiary amides (benzamides). The mechanistic experiments suggest that the rate and selectivity of the reduction is closely dependent on the water concentration and the type of amide undergoing the reduction. The data also suggest that benzylic aminoketyl radicals generated in the reduction of benzamides are significantly more dependent on the electronic effects of α-substitution than the corresponding aminoketyl radicals generated by single-electron transfer to unactivated aliphatic amides; however, little variation in terms of steric influence of N-substituents is observed. These observations will have implications for the design of reductive processes involving Sm(II)-mediated reduction of amides and reductive umpolung cyclizations via aminoketyl radicals as a key step.

Synthesis of nitrogen-containing heterocycles on the basis of 3-(4-acetylphenyl)-1-methylquinolin-2(1H)-one

The Meerwein reaction of 1-methylquinolin-2(1H)-one with 4-acetylbenzenediazonium chloride gave 3-(4-acetylphenyl)-1-methylquinolin-2(1H)-one which was brominated to 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one. The latter reacted with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine to afford the corresponding quaternary salts, and its reactions with thioacetamide, thiourea, 2-aminopyridine, and 2-aminopyrimidine led to the corresponding thiazole, imidazo[1,2-a]pyridine, and imidazo[1,2-a]pyrimidine derivatives containing a 2-oxoquinoline fragment. 3-(4-{2-[2-(Arylmethylidene)-hydrazinyl]-1,3-thiazol-4-yl}phenyl)-1-methylquinolin-2(1H)-ones were obtained by condensation of 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one with thiosemicarbazide and aromatic aldehydes.

Application of Ugi/De-Boc/Cyclization Strategy in the Synthesis of Nitrogen-Containing Heterocycles

Ugi/de-Boc/cyclization (UDC) strategy represents a "three-step, one-pot procedure", employing the Ugi multi- component reaction utilizing one bi-functional group substrates with N-Boc-protected amino, followed by Boc-deprotection and cyclization to synthesize nitrogen-containing heterocycles. This strategy has the characteristics of rapid, efficiency, econ- omy and structural diversity, which can be used to build libraries of complex nitrogen-containing heterocycles and has drawn much attention recently. In this paper, the research progress of UDC strategy in the synthesis of five-, six- and seven-mem- bered heterocycles and natural products were summarized.

Syntheses of Nitrogen-Containing Heterocycles via Palladium-Catalyzed Intramolecular Dehydrogenative C–H Amination

This article traces the development of catalytic, intramolecular dehydrogenative C–H amination (IDCA) reactions. Over the last 10 years, effective syntheses of carbazoles, indolines and oxindoles via palladium-catalyzed sp2 intramolecular dehydrogenative C–H amination reactions have been realized. While the corresponding amination reactions of sp3 C–H bonds are more challenging, syntheses of pyrrolidines, azetidines, β-lactams and even aziridines via this manifold have been reported. 1 Introduction 2 Intramolecular Aminations of C(sp2)–H Bonds 3 Intramolecular Aminations of C(sp3)–H Bonds 4 Conclusion

ChemInform Abstract: Synthesis of Nitrogen‐Containing Heterocycles from Nitroarenes

AbstractReview: 31 refs.

Synthesis of Nitrogen-Containing Heterocycles from Nitroarenes (Minireview)

This review considers the details of nitroarene interaction with arylacetonitrile, the possibilities for modifying the obtained heterocyclic products, as well as the condensation reactions of nitrobenzoic and nitrophthalic acids with hydrazine and oxalyldihydrazide in oleum. The results were obtained by the authors of this review and were published between 1994 and 2013.