Domino synthesis of fused hexacyclic imidazoquinolinoacridinones catalyzed by CuI/l-proline

A three-component reaction of 2-halogenated aromatic aldehydes, 1H-benzo[d]imidazol-5-amine and cyclohexane-1,3-diones is described, and gives imidazoquinolinoacridinone derivatives in good yields catalyzed by CuI/l-proline. This Domino reaction constructs a fused hexacyclic skeleton in one-pot containing two new rings, six new bonds and an Ullmann-type C–N bond coupling reaction.     

An alternative approach for the synthesis of aryl-alkyl tellurides: reaction of aryl iodides with metal alkyltellurolates promoted by CuI

Aryl iodides react with metal organotellurolates in tetrahydrofuran/dimethylformamide in the presence of CuI (5 mol %) or CuI (5 mol %) and 1,10-phenanthroline (10 mol %) to afford the corresponding aryl-alkyl tellurides in good yields.     

4-Quinolone fused heterocyclic ring systems by intramolecular reactions of 4-quinolone-2-carboxamides

A versatile synthetic route to new 4-quinolone-based polycyclic systems is described. TFA-catalyzed intramolecular reaction of N-unsubstituted quinolone-2-carboxylic acid amides gives structurally diverse compounds, depending on the length of the chain. Acid treatment of β-oxoamides furnishes 3H-pyrazino[1,2-a]quinoline-4,6-diones, due to the nucleophilic attack of N-1 to the carbonyl group, whereas TFA treatment of δ- and ε-oxoamides leads to the formation of tetracyclic compounds by a tandem heteroannulation reaction.     

Pseudo five-component process for the synthesis of functionalized tricarboxamides using CuI nanoparticles as reusable catalyst

An efficient and multicomponent method has been developed for the synthesis of functionalized tricarboxamides at room temperature using CuI nanoparticles as catalyst. This method involved fivecomponent coupling reactions of Meldrum's acid, isocyanides with aromatic aldehydes and amines at room temperature. Atom economy, wide range of products, excellent yields in short time and mild reaction conditions are some of the important features of this protocol. Notably, this catalyst could be recycled and reused for several times without significantly decreasing the catalytic activity.     

碘化亚铜/乙二胺催化氮杂环化合物的N-芳基化反应

以碘化亚铜/乙二胺为催化体系,研究了卤代芳烃和氮杂环化合物的Ullmann反应。 结果表明,氮杂环化合物的pKa越小,芳基化反应越容易进行,p-π共轭形成的富电子卤代芳烃有利于反应,非p-π共轭的富电子卤代芳烃使反应变难。     

Divergent synthesis of fused Benzo-xanthene and oxazine derivatives via Cu-catalyst

Cu-Cu₂O combination showed synergic effects in catalyzing intramolecular Ullmann coupling reaction for halo-Betti bases to afford fused benzo-xanthenes from both electron-rich and electron-deficient aromatic systems in good yield under mild reaction conditions. The sterically hindered halo-Betti bases also provided products in excellent yield. Under optimized condition, a gram scale reaction was also performed to afford the product in excellent yield. However, without ortho-halo substituted Betti-bases failed to afford fused benzo-xanthene derivatives. Exploring the reaction optimization without Cu metal, serendipitously it was produced 1,3-oxazine derivatives in excellent yield via intramolecular cross-dehydrogenative coupling (CDC) reaction. Similarly, electron-rich, electron-deficient and sterically hindered Betti-bases provided the products in good to excellent yield under mild condition.     

Synthesis of heterocyclic compounds IV1 pyrazol-1′-ylpyridines2

2-Pyrazol-1-ylpyridines were synthesized by condensation of pyridylhydrazines with 1,3-dicarbonyl compounds or by theUllmann arylation of pyrazoles with halopyridines.Taken in part from the Master's thesis ofA. A. A. Pinto, Instituto Militar de Engenharia, Rio de Janeiro, 1978.     

(CuI)P4Se4: An Adduct of Polymeric P4Se4 with CuI

Pure yellow (CuI)P₄Se₄ was prepared by reaction of stoichiometric amounts of CuI, red P, and gray Se in evacuated silica ampoules. The crystal structure was determined from single crystals at room temperature. (CuI)P₄Se₄ crystallizes in the orthorhombic system, space group Cmca with a = 14.770 (1) Å, b = 12.029 (1) Å, c = 12.449 (1) Å, V = 2211.9(6) ų, and Z = 8. The structure refinement converged to R = 0.0190 (wR = 0.0272) for 1020 independent reflections and 51 parameters. A prominent feature of the crystal structure are neutral polymeric P₄Se₄ strands which are connected by copper iodide. These strands consist of norbornane analogous P₄Se₃ cages which are linked by selenium bridges. The polymers are achiral since a mirror plane exists perpendicular to the strands. The single polymers are connected by [Cu₂I₂] units to form layers. These layers are stacked along the b axis and are connected by van der Waals-interactions only. Raman spectra of (CuI)P₄Se₄ differ significantly from Raman spectra of (CuI)₃P₄Se₄ and catena-(P₄Se₄)_x.     

Novel rearrangements of fused zwitterionic heterocyclic systems

(E)-2-Chlorodimethylstannyl-3-diethylboryl-2-pentene (1) reacts with the C-lithiated azoles 2 (derived from thiazole (2a), 4-methylthiazole (2b), 1,4-dimethylimidazole (2c), benzoxazole (2d) and benzthiazole (2e)) to eliminate LiCl, giving first mixtures containing compounds with either a coordinative N--- bond (3) or the zwitterionic isomer with an Sn---N bond (4), or both, and in some cases a rearranged product (5) with a 1,2,5-azastannaborole unit is also present. The zwitterionic compounds 4 tend to rearrange into the heterocycles 5 in which the heteroaromatic system is no longer present and two new C---C bonds, a new B---C and a new B---N bond are formed. The reactions were monitored by multinuclear NMR (¹H, ¹¹B, ¹³C, ¹⁴N and ¹¹⁹Sn NMR) which also served for the characterization of the final products. In the case of 5e, the molecular structure was determined by single-crystal X-ray analysis (monoclinic; space group P2₁/n; A=11.691(2), B=12.396(2), C=13.149(2) Å; β=93.41(2)°).     

Three-component synthesis of novel trifluoromethyl-containing tetrahydropyran derivatives

l-Proline-catalyzed reaction of ethyl 4,4,4-trifluoroacetoacetate, cinnamaldehyde and anilines provide a novel method for preparation of ethyl-6-(arylamino)-2-hydroxy-4-phenyl-2-(trifluoromethyl)tetrahydro-2H-pyran-3-carboxylate derivatives in good yields. The reaction was conducted by initial Michael addition, followed by intra-molecular cyclization under mild conditions. The structure of a typical ethyl-2-hydroxy-4-phenyl-6-(m-tolylamino)-2-(trifluoromethyl)tetrahydro-2H-pyran-3-carboxylate (4h) was confirmed by XRD analysis. A plausible mechanism is presented.     

Selectfluor mediated one pot synthesis of cyclohexanone ring fused isoxazole derivatives

A Selectfluor and base mediated protocol for the synthesis of cyclohexanone ring fused isoxazole derivatives from isoxazoline N-oxides has been successfully developed. This rapid, one-pot, two-step transformation is achieved in acetonitrile, through nitroso intermediate followed by hydration, defluorination and N–O coupling in the presence of triethylamine. The scope and mechanism of the protocol have been demonstrated.     

A convenient new synthesis of fused 1,2,4-triazoles: the oxidation of heterocyclic hydrazones using copper dichloride

A series of 1,2,4-triazoles have been prepared by oxidative intramolecular cyclization of heterocyclic hydrazones with copper dichloride. General applicability of this simple transformation was confirmed by the synthesis of moderate to high yields of 1,2,4-triazolo[4,3-a]pyridines, 1,2,4-triazolo[4,3-a]pyrimidines, 1,2,4-triazolo[4,3-b]pyridazines, 1,2,4-triazolo[4,3-a]phthalazines, and 1,2,4-triazolo[4,3-a]quinoxalines. A 1,2,4-triazolo[4,3-e]purine-6,8(7H)-dione was obtained in a lower yield.     

An efficient BINAM-copper(II) catalyzed Ullmann-type synthesis of diaryl ethers

A wide range of diaryl ethers are synthesized from the corresponding aryl iodides and phenols through Ullmann type coupling reactions in the presence of a catalytic amount of easily available BINAM-Cu(OTf)₂ complex under mild reaction conditions. Less reactive aryl bromides have also been shown to react with phenols under identical reaction conditions to give good yields of the diaryl ethers without increasing the reaction temperature and time.     

Efficient copper-catalyzed C-S cross-coupling of heterocyclic thiols with aryl iodides

A copper-catalyzed cross-coupling of heterocyclic thiols with aryl iodides is reported. The reaction was carried out in the presence of CuI (5 mol %), 1,10-phenanthroline (10 mol %) and K₂CO₃ (1.3 equiv) in DMF at 120 °C. A variety of heterocyclic sulfides were prepared in high selectivities and yields.     

Energetic heterocyclic N-oxides: synthesis and performance

Novel synthetic strategies toward construction and functionalization of nitrogen-rich energetic compounds bearing at least one heterocyclic N-oxide scaffold are briefly overviewed. The present focus review summarizes main recent advances (published in the period 2017–2022) in the chemistry of five- and six-membered heterocyclic N-oxides as well as their linear combinations and fused bi-, tri- and tetraheterocyclic frameworks which are of paramount importance for the development of next-generation energetic materials. Physicochemical properties along with detonation performance and mechanical sensitivities of the reported high-energy substances are discussed and their application potential is especially emphasized.     

Regioselective synthesis of fused ring heterocyclic derivatives of ketene aminals and their biological activities

A regioselective and convenient methodology was developed to synthesize heterocyclic derivatives, bearing imidazole, piperidines, and azepines rings. The N-arylnitrones derived from 3-formylchromones were selected to react with heterocyclic ketene aminal to furnish the structurally attractive and pharmacologically important fused ring heterocycles. The N-arylnitrone moiety of 3-formylchromone was used to activate the formyl group for regioselective fused ring heterocycles synthesis, whereas, the effect of substituents at aryl functionality of nitrones were studied to improve the yield of target fused ring heterocyclic products. The synthesized compounds (10-12) were evaluated for their in vitro cytotoxic and antifungal influences. In cytotoxic (brine shrimp lethality) assay, compound 11e was found to be active with LD₅₀ = 4.1 × 10⁻⁶ μg/mL.     

SmI2 mediated synthesis of 2,3-disubstituted indole derivatives

A novel preparation of 2,3-disubstituted indole derivatives was achieved through SmI₂ induced intramolecular reductive coupling reactions of acylamido carbonyl compounds.     

Synthesis of novel heterocyclic fused 1,3-diazabuta-1,3-dienes and accompanying rearrangements in their cycloaddition reactions with ketenes: synthesis of heterocyclic fused pyrimidinone derivatives

The reactions of 1,3-diazabuta-1,3-dienes 1 with 2-aminothiophenol have been shown to result in excellent yields of N-benzothiazol-2-yl-N′-aryl benzamidines 2. Their regioselective [4+2] cycloadditions with various ketenes are shown to yield novel benzothiazolo pyrimidinones 4. A similar and convenient protocol for the synthesis of bisthiosubstituted 1,3-diazabuta-1,3-dienes 8 and 9 and interesting rearrangements accompanying their [4+2] cycloadditions with a number of ketenes are described.     

Synthesis of substituted benzene derivatives by homo- and hetero-coupling of 2-bromobenzaldehyde and bromovinylaldehydes followed by McMurry coupling

A convenient synthetic approach to substituted benzene derivatives by modified Ullmann cross-coupling of 2-bromobenzaldehyde and bromovinylaldehydes followed by intramolecular McMurry coupling has been developed.     

Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

3-(Benzo[d][1,3]dioxol-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one reacted with each of thiourea and 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one to give the corresponding pyrimidine-2(1H)-thiones. Then, these compounds reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to afford the corresponding [1,2,4]triazolo[4,3-a]pyrimidines and their related fused pyridines. Moreover, chalcone was cyclocondensed with 2-cyanothioacetamide to give pyridine-2(1H)-thione and taken as a key synthon to novel 2-(methylthio)pyridothienopyrimidin-4(3H)-one derivative. The above derivative reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to yield the corresponding pyridothieno[3,2-d][1,2,4]triazolo[4,3-a]pyrimidines. Study of the in vitro antimicrobial activities of the newly pyrimidines were performed. Pyridothienopyrimidine 24a showed the highest inhibitory activity against all bacteria with MIC values of 3.9, 7.81, 7.81, and 15.62 μg/mL, respectively, against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, respectively, as compared to reference drugs. Molecular docking was studied to predict of the optimized conformation of pyrimidines as active ligands against the Escherichia coli alkaline phosphatase. The structures of the hybrid molecules were elucidated by IR, Mass, ¹H NMR, and ¹³C NMR spectra as well as elemental analyses.