Formation Of Heterocycles Research Articles

Unsaturated organosilanes: synthesis, transformations and applications

The urgency of improving the efficiency of known methods and developing new ones for the synthesis of unsaturated silanes is caused by the need to obtain useful compounds, including biologically active ones, on their basis. This review considers methods for the preparation of unsaturated silanes, their transformations and prospects for their use as precursors in organic and organoelement synthesis. A large number of substituted organosilicon products are given, including those capable of further functionalization and the formation of heterocycles, including silaheterocycles. <br> The bibliography includes 205 references.

Woollins’ Reagent: A Graphical Review of Its Main Synthetic Uses

AbstractWoollins’ reagent (W.R.) was initially used for the selenation of carbonyl compounds. However, various synthetic applications utilizing this reagent have since been discovered, making it increasingly useful. Examples include the formation of heterocycles, the stereospecific reduction of olefins, and the synthesis of selenoic acids, among others. Consequently, synthetic studies of W.R. derivatives have become increasingly relevant due to the growing demand for selenated compounds in various applications. Two notable examples are the agricultural sector, with the development of pesticides, and the pharmaceutical sector, with the development of antivirals, antioxidants, and neuroprotectors, among others. Hence, this graphical review aims to address the synthetic diversity that W.R. can provide, presenting examples of its main synthetic uses.

Combined analysis of transcriptome and metabolome reveals the effects of novel aroma-producing Naumovozyma castellii on Feng-flavor Baijiu

Feng-flavor Baijiu has an elegant and pleasant aroma and is one of the four traditional famous liquors in China. A strain of Naumovozyma castellii XF0241 with excellent fermentation performance and rich aroma compounds was isolated and screened from the Feng-flavor fermented grains. Metabolomic analysis showed that the main flavor compounds of XF0241 are esters, terpenes, and heterocyclic compounds, which are important aroma and flavor compounds in Feng-flavor Baijiu. Compared with the model strain N. castellii CBS4309, the yeast's ester, terpenes and heterocyclic compounds were up-regulated by 168.99±45.31 %, 103.54±28.45% and 108.46±36.78% respectively. After adding additional XF0241 to the Feng-flavor fermented grains, the flavor compounds became more abundant, among which the ester showed the highest increase, followed by terpenoids and heterocyclic compounds. Transcriptomic analysis showed that 1134 genes were differentially expressed. The combined analysis of transcriptome and metabolome revealed that 10 enzymes related to ester production and 3 enzymes related to terpenoid biosynthesis, and 1 enzyme related to heterocyclic formation were significantly upregulated. We believe that XF0241 is one of the core yeasts of Feng-flavor Baijiu. Its production of rich aroma compounds plays an important role in the formation of the special aroma of liquor.

Recent Advances in the Application of 2-Aminobenzothiazole to the Multicomponent Synthesis of Heterocycles.

Heterocycles are a vital class of compounds in numerous fields, including drug discovery, agriculture, and materials science. Efficient methods for the synthesis of heterocycles remain critical for meeting the demands of these industries. Recent advances in multicomponent reactions (MCRs) utilizing 2-aminobenzothiazole (ABT) have shown promising results for the formation of heterocycles. The versatility of 2-aminobenzothiazole in this context has enabled the rapid and efficient construction of diverse heterocyclic structures. Various synthetic methodologies and reactions involving 2-aminobenzothiazole are discussed, highlighting its importance as a valuable building block in the synthesis of complex heterocycles. The potential applications of these heterocycles in drug discovery and material science are also explored. Overall, this review provides a comprehensive overview of the current state of research in the field and offers insights into the future directions of this promising area of study. We highlight the potential of ABT as a versatile and sustainable starting material in heterocyclic synthesis via MCRs, with significant implications for the chemical industry.

Synthesis of various dihydro‐thiazole and selenazole heterocycles

We prepared numerous thiazole derivatives from push‐pull alkenes such as nitroenamines, enaminoester, and enaminonitrils in a two‐step reaction with thiocyanate ion. The first step was the formation of the thiocyanate‐substituted push‐pull alkene from an iodine‐containing intermediary. We demonstrated this sequence through the preparation and identification of the iodine‐substituted enamines. In the second step, thiazole ring closure took place in methanol, at room temperature. The imino group of the condensed thiazole ring systems was successfully acylated. The same reaction sequence with potassium selenocyanate resulted in two selenocyanate and a selenazole heterocyclic derivatives. The mechanism of the reaction with thiocyanate ion and the heterocycle formation was investigated by computational methods. We performed quantum chemical calculations, involving both the thermodynamic and the kinetic aspects of the ring closure reaction.

Synthesis of organotin(IV) heterocycles containing a xanthenyl group by a Barbier approach via ultrasound activation: synthesis, crystal structure and Hirshfeld surface analysis.

A series of organotin heterocycles of general formula [{Me2C(C6H3CH2)2O}SnR2] [R= methyl (Me, 4), n-butyl (n-Bu, 5), benzyl (Bn, 6) and phenyl (Ph, 7)] was easily synthesized by a Barbier-type reaction assisted by the sonochemical activation of metallic magnesium. The 119Sn{1H} NMR data for all four compounds confirm the presence of a central Sn atom in a four-coordinated environment in solution. Single-crystal X-ray diffraction studies for 17,17-dimethyl-7,7-diphenyl-15-oxa-7-stannatetracyclo[11.3.1.05,16.09,14]heptadeca-1,3,5(16),9(14),10,12-hexaene, [Sn(C6H5)2(C17H16O)], 7, at 100 and 295 K confirmed the formation of a mononuclear eight-membered heterocycle, with a conformation depicted as boat-chair, resulting in a weak Sn...O interaction. The Sn and O atoms are surrounded by hydrophobic C-H bonds. A Hirshfeld surface analysis of 7 showed that the eight-membered heterocycles are linked by weak C-H...π, π-π and H...H noncovalent interactions. The pairwise interaction energies showed that the cohesion between the heterocycles are mainly due to dispersion forces.

Practical Synthesis of 7-Bromo-4-chloro-1H-indazol-3-amine: An Important Intermediate to Lenacapavir.

7-Bromo-4-chloro-1H-indazol-3-amine is a heterocyclic fragment used in the synthesis of Lenacapavir, a potent capsid inhibitor for the treatment of HIV-1 infections. In this manuscript, we describe a new approach to synthesizing 7-bromo-4-chloro-1H-indazol-3-amine from inexpensive 2,6-dichlorobenzonitrile. This synthetic method utilizes a two-step sequence including regioselective bromination and heterocycle formation with hydrazine to give the desired product in an overall isolated yield of 38-45%. The new protocol has been successfully demonstrated on hundred-gram scales without the need for column chromatography purification. This new synthesis provides a potential economical route to the large-scale production of this heterocyclic fragment of Lenacapavir.

Advances in the Synthesis of Heterocycles with Two and Three Heteroatoms using Hydrazonoyl Halides

AbstractThe review covers the results of studies published in the literature on the use of hydrazonoyl halides in the synthesis of five‐ (pyrazoles, thiazoles, triazoles, oxa‐ and thiadiazoles), six‐ (oxa‐ and thiadiazines, indazoles, pyridazines, pyrazines, tetrazines) or seven‐membered (benzotriazepine) heterocycles. In the formation of these heterocycles, the main intermediate stage of the reaction is the in situ generation of nitrilimine, which enters into a cycloaddition reaction with substituted acetylenes (including in situ generated benzynes, naphthynes), allenes, activated olefins, anthranilic acid derivatives, organosulfur compounds (mercaptoaldehydes, mercaptocarboxylic acids) or with fused heterocycles. Examples are given of the formation of heterocycles by replacing the halogen atom from a hydrazonoyl halide molecule with a nucleophilic group, followed by exhaustive intramolecular cyclization into the target compound. There are discussions of reactions in which the cycloaddition of the nitrilimine to the in situ synthesized Knoevenagel condensation product (from CH‐acid compounds, such as di‐ and monocarbonyl compounds, dinitrile malonic acid) occurs, leading to spiro‐linked or conventional pyrazoles. Some syntheses of biologically active representatives are shown.

A deconstruction-reconstruction strategy for pyrimidine diversification.

Structure-activity relationship (SAR) studies are fundamental to drug and agrochemical development, yet only a few synthetic strategies apply to the nitrogen heteroaromatics frequently encountered in small molecule candidates1-3. Here we present an alternative approach in which we convert pyrimidine-containing compounds into various other nitrogen heteroaromatics. Transforming pyrimidines into their correspondingN-arylpyrimidinium salts enables cleavage into a three-carbon iminoenamine building block, used for various heterocycle-forming reactions. This deconstruction-reconstruction sequence diversifies the initial pyrimidine core and enables access to various heterocycles, such as azoles4. In effect, this approach allows heterocycle formation on complex molecules, resulting in analogues that would be challenging to obtain by other methods. We anticipate that this deconstruction-reconstruction strategy will extend to other heterocycle classes.

A new chapter in the never ending story of cycloadditions: The puzzling case of SO2 and acetylene.

A comprehensive study of the different classes of cycloaddition reactions ([3+2], [2+2], and [2+1]) of SO2 to acetylene and ethylene has been performed using density functional theory (DFT) and composite wavefunction methods. The [3+2] cycloaddition reaction, that was previously explored in the context of the cycloaddition of thioformaldehyde S-methylide (TSM) to ethylene and acetylene, proceeds in a concerted way to the formation of stable heterocycles. In this paper, we extend our study to the [2+2] and [2+1] cycloadditions of SO2 to acetylene, which would produce 1,1-oxathiete-2-oxide and thiirene-1,1-dioxide, respectively. One of the main conclusions is that cyclic 1,1-oxathiete-2-oxide can open through a relatively easy breaking of the SO single bond and rearrange toward sulfinyl acetaldehyde (SA). The SA molecule can easily undergo several internal rearrangements, which eventually lead to sulfenic acid and sulfoxide derivatives of ethenone, 1,2,3-dioxathiole, and CO plus sulfinylmethane. The most probable path, however, produces 2-thioxoacetic acid, whose derivatives (or those of the corresponding acetate) are usually obtained by Willgerodt-Kindler-type sulfuration of acetates. This product can in turn decompose, leading to the final products CO2 and H2CS. Comparison of this decomposition path with that of 2-amino-2-thioxoacetic acid shows that the process occurs through different H-transfer processes.

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts.

N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense, this new method creates two C-N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste.

Medicinal-Chemistry-Driven Approach to 2-Substituted Benzoxazole-Estradiol Chimeras: Synthesis, Anticancer Activity, and Early ADME Profile.

The efficient synthesis of novel estradiol-based A-ring-fused oxazole derivatives, which can be considered as benzoxazole-steroid domain-integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2-aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection-based t-distributed stochastic neighbor embedding (t-SNE), the novel molecules were proved to represent a new chemical space among steroid drugs. They were characterized based on critical physicochemical parameters using in silico and experimental data. The performance of the compounds to inhibit cell proliferation was tested on four human cancer cell lines and non-cancerous cells. Further examinations were performed to reveal IC50 and lipophilic ligand efficiency (LLE) values, cancer cell selectivity, and apoptosis-triggering features. Pharmacological tests and LLE metric revealed that some derivatives, especially the 2-(4-ethylpiperazin-1-yl)oxazole derivative exhibit strong anticancer activity and trigger the apoptosis of cancer cells with relatively low promiscuity risk similarly to the structurally most closely-related and intensively studied anticancer agent, 2-methoxy-estradiol.

A Review on Synthesis, Lanthanide Complexes and Biological Activites of Hydrazone Derivatives of Hydrazinecarbothioamides

Hydrazinecarbothioamides are important intermediates with biological activities in organic chemistry synthesis, especially in the synthesis of biologically active heterocyclic scaffolds and compounds. The uniqueness in of synthesis and a wild range of pharmaceutical, medicinal biological potentials and properties, their preferred application as building brick in and the synthesis of heterocyclic and other important organic compounds and nonlinear optical (NLO) materials have made them attractive derivatives of thiosemicarbazides in the recent years. In this review, a detailed account in terms of synthesis and applications of their hydrazone derivatives and their lanthanide complexes are presented .Further, the biological and analytical applications of newly reported ligands and their complexes are reported. The wide investigation of the lanthanide (III) coordination complexes with organic ligands are mainly due to their structures and strong potential biological and pharmacological properties of hydrazones as derivatives of hydrazinecarbothioamides possess sites that play important roles in the formation of heterocyclics and other biologically active scaffolds.

Atroposelective PIII/PV=O Redox Catalysis for the Isoquinoline-Forming Staudinger-aza-Wittig Reaction.

Herein, we describe the feasibility of atroposelective PIII/PV=O redox organocatalysis by the Staudinger-aza-Wittig reaction. The formation of the isoquinoline heterocycle thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98:2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provide access to a multitude of aromatic heterocycles with precise control over their configuration.

Atroposelective PIII/PV=O Redox Catalysis for the Isoquinoline‐Forming Staudinger–aza‐Wittig Reaction

AbstractHerein, we describe the feasibility of atroposelective PIII/PV=O redox organocatalysis by the Staudinger–aza‐Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co‐catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N‐oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.

From heat to flavor: Unlocking new chemical signatures to discriminate Wuyi rock tea under light and moderate roasting

Roasting is crucial for the distinct flavor of Wuyi rock tea (WRT). This study applied untargeted metabolomics to investigate the effects of roasting on 139 WRT samples roasted at light fire (LF) or moderate fire (MF) intensities. Compared to LF, MF roasting led to a decrease in the cis/trans flavanol ratio by 56% and theanine by 85%, while increasing the levels of N-ethyl-2-pyrrolidione-substituted flavanols (EPSFs), flavonol aglycones and flavone C-glycosides. Two new roast markers, 3-p-coumaroyl 1,5-lactone and 4-p-coumaroyl 1,5-lactone, were identified in WRT and their formation increased with roasting temperature. MF roasting facilitated the formation of diverse heterocycles (e.g., pyrazines) and aldehydes (e.g., (Z)-4-heptenal and (E,E)-2.4-decadienal) that contributed to the augmented roasted and fatty odors in WRT. Additionally, the Maillard product furfuryl methyl ether was solely detected in MF samples. These findings provide novel insights into roast markers in WRT with implications for improving quality control measures during tea roasting.

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of Axially Chiral α-Carbolinones via Heterocycle Formation.

An NHC-catalyzed atroposelective synthesis of axially chiral α-carbolinones from α,β-unsaturated iminoindole derivatives and α-chloroaldehydes was developed. The reaction proceeds through a cascade process including [4 + 2] annulation and then oxidative dehydrogenation with concomitant central-to-axial chirality conversion under mild conditions. The developed method opens a new avenue to efficiently access axially chiral α-carbolinones in moderate to good enantioselectivities.

Crystalline Neutral Aluminum Selenide/Telluride: Isoelectronic Aluminum Analogues of Carbonyls.

Neutral aluminum chalcogenides (R-Al(L)═Ch; L = ligand, Ch = chalcogen), stabilized by a Lewis base ligand, represent isoelectronic counterparts to carbonyl compounds and have long been pursued for isolation. Herein, we present the synthesis of an aluminum selenide, [N]-Al(iPr2-bimy)═Se, and an aluminum telluride, [N]-Al(iPr2-bimy)═Te, under ambient conditions ([N] = 1,8-bis(3,5-di-tert-butylphenyl)-3,6-di-tert-butylcarbazolyl; iPr2-bimy = 1,3-diisoproplylbenzimidazole-2-ylidene). These compounds arise from the oxidation reaction of [N]-Al(iPr2-bimy) with Se and (nBu)3P═Te, respectively. One notable characteristic of the Al and Ch interaction is the presence of an Al-Ch σ bond, strengthened by the electrostatic attraction between the Al+ and Ch- centers as well as the donation of lone pairs from Ch into vacant orbitals at Al. This results in an Al-Ch multiple bond with an ambiphilic nature. Preliminary investigations into their reactivity unveil their remarkable propensity for facile (cyclo)addition reactions with diverse substrates, including PhCCH, PhCN, AdN3, MeI, PhSiH3, and C6F6, leading to the formation of unprecedented main group heterocycles and alumachalcogenides.

Oxime Esters: Flexible Building Blocks for Heterocycle Formation.

Oxime esters as the applicable building blocks, internal oxidizing agents, and directing groups in the synthesis of -, S-, and O-containing heterocycle scaffolds have gained great attention in the last decade. This review provides an overview of recent advances in the cyclization of oxime esters with various functional group reagents under transition metal and transition metal-free catalyzed conditions. Moreover, the mechanistic aspects of these protocols are explained in detail.

3 + 2] Cycloaddition reaction of disubstituted-3-benzylidene succinimide with C, N-disubstituted nitrile imines for synthesizing spiro-heterocycles: A computational study

The relevance of spiro heterocycles in the biomedical sector is enormous. This computational work extensively investigates the stereo-, regio-, chemo-, and site- selectivities of the [3 + 2] cycloaddition reaction of disubstituted-3-benzylidene succinimide (3-BS) with C, N-disubstituted nitrile imines derivatives for the formation of spiro heterocycles. This study employs the B3LYP, B3LYP-D3, M06, M06-2X, and MPWB1K hybrid density functional calculations with the 6-311G(d, p) basis sets. Various computations show that the attachment of the nitrile imine across the olefinic functionality of the disubstituted-3-BS has relatively lower barriers compared to the carbonyl functionalities present. Generally, electron-releasing groups on disubstituted-3-BS increase the activation barriers, whereas electron-withdrawing groups significantly reduce the activation barrier. The GEDT values predicts a low polar character for the [3 + 2] Cycloaddition reaction. Results from local and global parr functions calculations are in accordance with the selectivities and energetic trends observed.