The first report of [2+2] ketene–imine cycloaddition reactions (Staudinger) on carbon nanotubes

Several new carbon nanotube-functionalized β-lactams have been synthesized from chiral imines derived from β-d-glucopyranosylamine and a ketene from carbon nanotube-based oxyacetic acid via a [2+2] cycloaddition reaction. The cycloadducts were characterized by thermogravimetric analysis, Raman spectrometry, IR, and N₂ adsorption processes.     

An efficacious synthesis of N-1–, C-3–substituted indole derivatives and their antimicrobial studies

A novel series of 11 C-3– and N-1–substituted oxoacetamide indole derivatives were synthesized by reacting with various aromatic amines and alkyl halides. These compounds were characterized by using various spectral techniques, ie, ¹HNMR, ¹HNMR-D₂O, ¹³CNMR, UV, elemental analysis, IR, and mass spectrometery. In vitro, antimicrobial studies of resultant compounds were carried out against two bacterial strains, Pseudomonas aeruginosa and Pseudomonas oryzihabitans using disc plate method. All the tested compounds showed vital efficiency as antimicrobial agents against both the bacterial strains. The results revealed that synthesized indole derivative 2-(1-(3-bromopropyl)-1H-indol-3-yl)-N-(2-nitrophenyl)-2-oxoacetamide displayed the best antimicrobial activity as compared with all other synthesized compounds.     

Formal [4+2] cycloaddition of cyclobutanones bearing alkyne–cobalt complex at their 3-positions

Cyclobutanones bearing an alkyne–cobalt complex at their 3-positions reacted with aldehydes to give formal [4+2] cycloadducts by using tin(IV) chloride as a Lewis acid. Highly substituted tetrahydropyrone derivatives were stereoselectively prepared by this method.     

Nano CuO–Ag-catalyzed synthesis of some novel pyrano[2,3-d] pyrimidine derivatives and evaluation of their bioactivity

A simple, highly efficient, and green method is developed for the synthesis of pyrano[2,3-d] pyrimidine derivatives via Knoevenagel and Michael addition in the presence of nano CuO–Ag as a catalyst. The structures of synthesized target compounds 5a–l were confirmed by spectral and elemental analysis and were screened for their antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH), H₂O₂, and NO methods. Their antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, against Gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus, and antifungal activity against Candida albicans and Candida glabrata was also evaluated. The compounds showed higher bacterial activity than the standard used. Compounds 5b , 5d , 5g , 5h , and 5i exhibited higher free radical scavenging activity than the standard butylated hydroxy toluene (BHT). Compounds 5b , 5d , and 5h showed higher activity on Gram-positive bacteria, and compounds 5b , 5d , 5h , and 5i showed higher activity on Gram-negative bacteria than that of standard tetracycline. Compounds 5b , 5j , and 5l showed much higher antifungal activity against Candida globrata and C. albicans than that of standard Griseofulvin.     

An one-pot approach to the synthesis of triazolobenzothiadiazepine 1,1-dioxide derivatives by basic alumina-supported azide–alkyne [3+2] cycloaddition

An efficient one-pot strategy for the synthesis of triazolobenzothiadiazepine 1,1-dioxide derivatives has been developed by the reaction of 2-azido-N-substituted benzenesulfonamides and propargyl bromide in basic alumina under microwave condition via [3+2] azide–alkyne cycloaddition reaction. This protocol has synthetic advantages in terms of low environmental impact and short reaction time.     

Intramolecular Huisgen [3+2] cycloaddition in water: synthesis of fused pyrrolidine–triazoles

The intramolecular alkyne–azide Huisgen [3+2] cycloaddition reaction as a ‘click-chemistry’ reaction without a metal catalyst has been studied under aerobic conditions. The synthesis of various pyrrolidine–triazole hybrid compounds has also been achieved by using this intramolecular cycloaddition reaction in water with complete 1,5-regioselectivity.     

Study of three-component reaction of α-ketoesters and active methylenes with OH-acids to synthesize new 2-amino-4H-pyran derivatives and evaluation of their antibacterial and antioxidant activities

Research on Chemical Intermediates - Synthesis of new derivatives of 2-amino-4H-pyrans is reported via three-component reaction of α-ketoesters, active methylenes, and OH-acids in the presence...     

Theoretical studies on formal hetero [3+3] cycloaddition reaction between vinylogous amide and α,β-unsaturated imine cation

Density functional theory (DFT) calculations at B3LYP/6-31G** level have been carried out to study the mechanism of title reaction. The whole picture for the possible mechanism has been explored and verified both in gas phase and C₆H₅CH₃ solvent. The calculated results show that this reaction proceeds via the following several steps: (1) addition of two reactant molecules; (2) removing of H⁺ and succedent elimination of NH₃ from intermediates; (3) isomerization and final cyclization of intermediates, in which the elimination step of NH₃ is the rate-controlling one in the whole reaction process. The final product has two competitive parallel paths, in which the 6π-electron electrocyclic ring closure is not reversible.     

Asymmetric [4+2] cycloaddition of azlactones with dipolar copper–allenylidene intermediates for chiral 3,4-dhydroquinolin-2-one derivatives

In this paper, a pybox-copper catalyzed enantioselective decarboxylative [4+2] cycloaddition reaction of ethynyl benzoxazinanones with azlactones has been developed, which provides optically active 3,4-dihydroquinolin-2-ones in high yields with good enantioselectivities and diastereoselectivities. In this transformation, the chiral dipolar copper–allenylidene intermediates are kinetically generated via decarboxylative ethynyl benzoxazinanones, followed by the attack of the enolate azlactones to form enantiomerically enriched 3,4-dihydroquinolin-2-one structures.     

Electrochemical C–H/N–H cross-coupling of 2-phenylindolizines with phenothiazines to synthesize novel N-aryl phenothiazine derivatives

A facile and elegant method for synthesis of novel N–aryl phenothiazine derivatives from 2-phenylindolizines and phenothiazines through direct electrochemical oxidation has been developed. This approach was performed smoothly at room temperature without external oxidant and catalyst. Cyclic voltammetry and in situ FTIR techniques were applied to analyze the cross-coupling process of phenothiazines and 2-phenylindolizines, which helped to select the appropriate reaction potential. Under the optimized conditions, a broad range of substrates were well tolerated, affording the desired products in moderate to excellent isolated yields (up to 91%) with high regioselectivity. Meanwhile, a plausible mechanism involving a radical pathway has been proposed.     

One-pot four-component domino strategy for the synthesis of novel spirooxindole–pyrrolidine/pyrrolizidine-linked 1,2,3-triazole conjugates via stereo- and regioselective [3+2] cycloaddition reactions: In vitro antibacterial and antifungal studies

In this study, a series of highly diversified novel functionalized spirooxindolopyrrolidine and spirooxindolopyrrolizidine-linked 1,2,3-triazole conjugates have been synthesized by a one-pot, four-component condensation of (E)-2-(1-propargyl-2-oxoindoline-3-ylidene)acetophenones as bifunctional dipolarophiles, acenaphthenequinone, α-amino acids with substituted aryl azides using coinage metal catalysts. It was found that CuSO₄/Na ascorbate as a catalyst was more performant than Ag₂CO₃ or CuI. The single-crystal X-ray analysis of one of the cycloadducts proves the structure and the regiochemistry of this reaction. The compounds have been screened for their in vitro antibacterial and antifungal activities using the agar dilution method and display good activities.     

Design and synthesis of [1,2,4]-triazolo isoquinoline derivatives via 1, 3-dipolar [3 + 2] cycloaddition: Reaction of azomethine imine with ethyl cyanoformate as unknown protocol

A series of novel 1, 2, 4-triazolo isoquinoline derivatives (8a-8p) were synthesized starting from 2-phenylethan-1-ol derivative (1) in a 7 step synthetic sequence. The key step in the scheme involves 1, 3-dipolar [3?+?2] cycloaddition of azomethine imine and ethyl cyanoformate as unknown reaction protocol. We have demonstrated the hydrolysis of both ester and benzoyl group in a single step and the corresponding carboxylic acid derivatives were coupled with various amines to generate unknown 1, 2, 4-triazolo isoquinoline derivatives The structures of the compounds (8a-8p) were characterized by ¹H NMR, ¹³C NMR and HRMS analysis.     

β-Cyclodextrin as a supramolecular catalyst for the synthesis of 2Hindazolo[2,1-b]phthalazine-trione derivatives in water and their antimicrobial activities

An efficient and green method has been developed for the synthesis of 2H-indazolo[2,1-b]phthalazinetriones derivatives by employing 15 mol%β-cyclodextrinvia a one-pot multicomponent reaction of aldehyde,dimedone,hydrazine hydrate with succinic anhydride/phthalic anhydride in water at 80 ℃ for first time.The catalyst could be recovered and reused for four consecutive cycles without appreciable loss in catalytic activity and evaluated for in vitro antimicrobial activity against different Gram-positive and Gram-negative bacterial strains.The outcome of the screening study showed that compound 6d,6f and7 n exhibited excellent activity against E.coil.Whereas,compound 6f and 6h exhibited excellent activity against P.aeurginosa,and compound 6c,and 6e displayed again excellent activity against Staphylococcus aureus whereas compound 7o shows excellent activity against S.aureus and B.subtilis when compared with Ampicillin(standard control).The results indicated that maximum compounds are moderately effective against bacterial growth and their effectiveness is highest against standard drugs.     

A novel α,β-unsaturated nitrone-aryne [3+2] cycloaddition and its application in the synthesis of the cortistatin core

We describe here a novel α,β-unsaturated nitrone-aryne [3+2] cycloaddition. The resulting benzoisoxazolines underwent N-O bond reduction-elimination-electrocyclization sequence to furnish a variety of polysubstituted 2H or 2-alkylated-1-benzo-pyrans. The application of this methodology was further demonstrated in the synthesis of the oxa[3.2.1]octene moiety of cortistatin A.     

Iridium-catalyzed [2 + 2 + 2] cycloaddition of α,ω-diynes with nitriles

[Ir(cod)Cl](2)/DPPF or BINAP efficiently catalyzed the cycloaddition of α,ω-diynes with nitriles to give pyridines. The reaction can accommodate a very wide range of nitriles. Both aliphatic and aromatic nitriles smoothly reacted with α,ω-diynes to give pyridines. Ten equivalents of unactivated aliphatic nitrile were enough to give the product in high yield. Aliphatic nitriles bearing an acetal or amino moiety could be used for the reaction. The highly regioselective cycloaddition of unsymmetrical diyne bearing two different internal alkyne moieties was achieved. The observed regioselectivity could be reasonably explained by considering the different reactivities of the α-position in iridacyclopentadiene. Regioselective cycloaddition was successfully applied to the synthesis of terpyridine and quinquepyridine. This chemistry was extended to a new and efficient synthesis of oligoheteroarenes. Five aromatic or heteroaromatic rings were connected in a single operation. [Ir(cod)Cl](2)/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic secondary benzyl nitrile catalyzed by [Ir(cod)Cl](2)/SEGPHOS gave a central carbon chiral pyridine in 80% ee. The mechanism was analyzed on the basis of the B3LYP level of density functional calculations.     

Iridium-catalyzed [2+2+2] cycloaddition of α,ω-diynes with isocyanates

[Ir(cod)Cl](2)/BINAP was found to be an efficient catalyst for the [2+2+2] cycloaddition of α,ω-diynes with isocyanates to give 2-pyridones. A wide range of isocyanates can be used for this reaction. Both aliphatic and aromatic isocyanates smoothly reacted with α,ω-diynes to give 2-pyridones in high yields. Aliphatic isocyanates were more reactive than aromatic isocyanates. For aromatic isocyanates, the electronic properties of the substituents affected the reactivity: electron-donating substituents enhanced the reaction. The reaction of unsymmetrical α,ω-diynes possessing two different internal alkyne moieties with isocyanates was regiospecific and gave a single product. This regioselectivity could be explained by the reaction of iridacyclopentadiene with a nitrogen-carbon double bond. The regioselectivity of the reaction of malonate-derived diyne was controlled by a steric effect, while that of the reaction of ester-tethered diyne was controlled by an electronic effect. [Ir(cod)Cl](2)/chiral diphosphine catalyst could be used for the enantioselective synthesis of C-N axially chiral 2-pyridone. The reaction of diyne 1a with o-methoxyphenyl isocyanate (7a) gave C-N axially chiral 2-pyridone (R)-8aa in 78% yield with 94% ee.     

A tactical approach for the synthesis of novel β-lactam-substituted,polycyclic-fused isoxazolidine derivatives via an intramolecular [3+2] cycloaddition reaction

The synthesis of functionalized β-lactam-substituted, tricyclic chromenoisoxazolidine and tetracyclic naphthopyranoisoxazolidine derivatives by intramolecular nitrone cycloaddition reaction is described. The O-allyl hydroxyaldehyde derivatives, obtained from Baylis–Hillman adducts (BHA) derived from β-lactam aldehyde underwent intramolecular cycloaddition reaction to give β-lactam-substituted, polycyclic isoxazolidine derivatives in good yield. All the products were confirmed by spectral analysis. The products with a β-lactam substituent may find good applications in biological chemistry.