Cycloaddition Of Nitrilimines Research Articles

ChemInform Abstract: [3 + 3]‐Cycloaddition of Donor—Acceptor Cyclopropanes with Nitrile Imines Generated in situ: Access to Tetrahydropyridazines.

Donor–acceptor cyclopropanes are reacted under the influence of a Lewis acid with hydrazonyl chlorides to afford tetrahydropyridazines. Formally, this transformation can be regarded as a [3 + 3]-cycloaddition of three-membered rings and nitrile imines generated in situ. This efficient method provides fast access to a variety of structurally diverse pyridazine derivatives. The structure of a typical product was confirmed by X-ray crystallography.

Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines

In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,β-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a “side chain” characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15–60 μM for exposure time of 24–72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.

Kinetics and mechanism of the 1,3-dipolar cycloaddition of nitrilimine with thione-containing dipolarophile: a detailed DFT study

The 1,3-dipolar cycloadditions are extensively used for the preparation of five-membered heterocycles. A mechanism consisting of two pathways was proposed for production of two regioisomers of the 1,3-dipolar cycloaddition of the nitrilimine and a thione-containing dipolarophile. Here, we have investigated the kinetics and mechanism of this reaction using density functional theory. Two possible mechanisms of A and B have been investigated in which Cl− is present in the structure of the nitrilimine reactant in the case of mechanism A, while it is absent in the case of mechanism B. Mechanism A, involving Cl−, has higher barrier energy than mechanism B, and so is rejected. Mechanism B involves two pathways, I and II, which lead to two regioisomers with different percentages in the products. Both of the pathways are one-step. Pathway II involves the attack of the nitrogen atom of the nitrilimine on the carbon atom of the C=S group of the dipolarophile. The product of pathway II is kinetically and thermodynamically a more favorable product than its regioisomer produced in the other pathway. The obtained results are in agreement with the experimental results.

3 + 3]-Cycloaddition of Donor-Acceptor Cyclopropanes with Nitrile Imines Generated in Situ: Access to Tetrahydropyridazines.

Donor-acceptor cyclopropanes are reacted under the influence of a Lewis acid with hydrazonyl chlorides to afford tetrahydropyridazines. Formally, this transformation can be regarded as a [3 + 3]-cycloaddition of three-membered rings and nitrile imines generated in situ. This efficient method provides fast access to a variety of structurally diverse pyridazine derivatives. The structure of a typical product was confirmed by X-ray crystallography.

Modulation of the exfoliated graphene work function through cycloaddition of nitrile imines.

After the feasibility of the 1,3-dipolar cycloaddition reaction between nitrile imines and exfoliated graphene by density functional theory calculations was proved, very few-layer graphene was effectively functionalized using this procedure. Hydrazones with different electronic properties were used as precursors for the 1,3-dipoles, and microwave irradiation as an energy source enabled the reaction to be performed in a few minutes. The anchoring of organic addends on the graphene surface was confirmed by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis. Ultraviolet photoelectron spectroscopy (UPS) was used to measure the work function and band gap of these new hybrids. Our results demonstrate that it is possible to modulate these important electronic valence band parameters by tailoring the electron richness of the organic addends and/or the degree of functionalization.

Stoichiometry-controlled cycloaddition of nitrilimines with unsymmetrical exocyclic dienones: microwave-assisted synthesis of novel mono- and dispiropyrazoline derivatives

The Microwave-assisted 1,3-dipolar cycloaddition of (E,E)-1,3-bisarylidenetetral-2-ones with nitrilimines affords a series of mono- and dispiropyrazolines in good to excellent yields.

Synthesis and anti-inflammatory activity of 1,4-[bis(3-arylmethane sulfonylvinyl)]benzenes, 1,4-[bis(3-arylmethanesulfonylpyrazolyl and isoxazolyl)]benzenes

The title compounds were prepared by cycloaddition of nitrile imines and nitrile oxides to the 1,4-bis(E)-2-((arylmethanesulfonyl)vinyl)benzene and studied their anti-inflammatory activity. Among the tested compounds, 6c, 6d, 7c and 7d exhibited promising anti-inflammatory activity.

Cycloaddition of Nitrile Imines to Graphene. a Theoretical and Experimental Approach

Graphene is a unique material with outstanding mechanical and electronic properties.1 The modulation of the electronic properties of graphene by chemical functionalization as well as the control over the opening of its band gap are of great interest, because of the potential of this material for a wide range of applications.2 Due to the lower reactivity of graphene, compared to other carbon nanostructures, the range of reactions available for functionalization of this material is smaller than in the case of other carbon nanostructures as fullerene or carbon nanotubes. Although most of the studies involving graphene functionalization has been performed by amidation of the carboxylic groups at the edges or by using diazonium salts,3 examples of 1,3-dipolar cycloaddition of azomethine ylide have been also described,4 but there are not examples in the literature of cycloaddition of other less reactive dipoles as nitrile imines or nitrile oxides. In most cycloaddition reactions to [60]fullerene, the LUMO of the fullerene cage is shifted to higher values by 0.15 eV. Nevertheless, we have previously demonstrated that, in the cycloaddition of nitrile imines to fullerenes, affording pyrazolinofullerenes, the LUMO of C60 is not shifted to higher values due to the electron-acceptor character of the pyrazoline ring.5,6 So, cycloaddition of nitrile imines to graphene, if the reaction works, can be useful to modulate the band-gap in a different way than other cycloaddition reactions. We present here the theoretical and experimental studies on the 1,3-dipolar cycloaddition of nitrile imines to graphene.

English

A new series of 1,2,4-triazole derivatives (4a-j, 6a-j) have been synthesized by the 1,3-dipolar cycloaddition of a suitable nitrilimines 2 to pyruvaldehyde (2-oxopropanal) hydrazones having (COPh, COOMe, COOEt, Me/Me and Me/Ph) 3 and 5. Both analytical and spectroscopical data of all the synthesized compounds are in full agreement with the proposed structures. The microbial features of the synthesized compounds were studied by a known method.

ChemInform Abstract: Synthesis of Substituted 2,4,5,6‐Tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6‐Tetrahydropyrrolo[3,4‐c]pyrazoles by Intramolecular Nitrilimine Cycloaddition.

AbstractTreatment of sensitive hydrazonyl chlorides with triethylamine results in the formation of nitrilimine intermediates.

Synthesis of Amido‐linked Oxazolyl/Thiazolyl/Imidazolyl Pyrazoles and Isoxazoles

The amido‐linked oxazolyl/thiazolyl/imidazolyl pyrazoles and isoxazoles were prepared from the synthetic intermediates oxazolyl/thiazolyl/imidazolyl acrylamides adpoting1,3‐dipolar cycloaddition of nitrile imines and nitrile oxides.

ChemInform Abstract: 1,3‐Dipolar Cycloaddition Reactions: Synthesis of 5‐Benzyl‐1‐(2′,4′‐dibromophenyl)‐3‐(4′′‐substituted phenyl)‐3a,4,6,6a‐tetrahydro‐1H,5H‐pyrrolo[3,4‐c]pyrazole‐4,6‐dione Derivatives.

Abstract1,3‐Dipolar cycloaddition of nitrilimines, generated in situ from hydrazonoyl bromides (I), with N‐benzylmaleimide provides stereoselectively the cis‐fused pyrrolopyrazole derivatives (III) (9 examples) in good yield.

Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Both substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles have been synthesized by the 3+2 intramolecular dipolar cycloaddition of nitrilimines to alkynes. This cyclization has been extended to more versatile 3-bromo derivatives by the use of alkynylbromides as dipolarophiles.

Synthesis and antimicrobial activity of (1,4-phenylene)bis(arylsulfonylpyrazoles and isoxazoles)

A new class of (1,4-phenylene)bis(arylsufonylpyrazoles and isoxazoles) were synthesized by 1,3-dipolar cycloaddition of nitrile imines and nitrile oxides to the 1,4-bis((E)-2-(arylsulfonyl)vinyl)benzenes in the presence of chloramine-T. Compound 7f exhibited pronounced antimicrobial activity.

1, 3-Dipolar cycloaddition reactions: Synthesis of 5-benzyl-1-(2′,4′-dibromophenyl)-3-(4″-substituted phenyl)-3a,4,6,6a-tetrahydro-1H, 5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives

1,3-Dipolar cycloaddition of nitrilimines 3 with N-benzyl maleimide 4 has provided 5-benzyl-1-(2′,4′-dibromophenyl)-3-(4″-substituted phenyl)-3a,4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives 5 in excellent yield as the only isomer through a concerted pathway.

An Effective Nitrilimine Cycloaddition for the Synthesis of 1,3,5-Trisubsti- tuted 1,2,4-Triazoles from Oximes with Hydrazonoyl Hydrochlorides

An effective 1,3-dipolar cycloaddition for the synthesis of 1,3,5-trisubstituted 1,2,4-triazole derivatives was developed by reacting oximes with hydrazonoyl hydrochlorides using triethylamine as a base. The desired 1,3,5-trisubstituted 1,2,4-triazoles were obtained in good yields and the reaction was applicable to aliphatic, cyclic aliphatic, aromatic and heterocyclic oxime substrates.

Isomeric Cyclopropenes Exhibit Unique Bioorthogonal Reactivities

Bioorthogonal chemistries have provided tremendous insight into biomolecule structure and function. However, many popular bioorthogonal transformations are incompatible with one another, limiting their utility for studies of multiple biomolecules in tandem. We identified two reactions that can be used concurrently to tag biomolecules in complex environments: the inverse electron-demand Diels-Alder reaction of tetrazines with 1,3-disubstituted cyclopropenes, and the 1,3-dipolar cycloaddition of nitrile imines with 3,3-disubstituted cyclopropenes. Remarkably, the cyclopropenes used in these transformations differ by the placement of a single methyl group. Such orthogonally reactive scaffolds will bolster efforts to monitor multicomponent processes in cells and organisms.

Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones

Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones are reported. The spiro[pyrazolin-3,3'-oxindole] products are formed in good yields (up to 98%) and high enantioselectivity (up to 99% ee).

Asymmetric Catalytic 1,3-Dipolar Cycloaddition Reaction of Nitrile Imines for the Synthesis of Chiral Spiro-Pyrazoline-Oxindoles

A new 1,3-dipolar cycloaddition of nitrile imines with 3-alkenyl-oxindoles was catalyzed by a new chiral Mg(ClO(4))(2) complex of an N,N'-dioxide ligand. The reaction is so far the sole catalytic synthesis of spiro-pyrazoline-oxindole derivatives. A wide variety of substrates were explored to obtain good yields (up to 98%) and excellent enantioselectivities (up to 99%). This cycloaddition expands the scope of propargyl anion type 1,3-dipole in the construction of 2-pyrazoline subunit.

Mg–Al hydrotalcite as an efficient catalyst for microwave assisted regioselective 1,3-dipolar cycloaddition of nitrilimines with the enaminone derivatives: A green protocol

Microwave assisted generation of in situ nitrilimines and their regioselective 1,3-dipolar cycloaddition reaction with enaminones to produce pyrazole derivatives by Mg–Al hydrotalcite (Mg–Al HT) catalyst is introduced. Short reaction times with high yields (90–94%), the absence of an organic solvent and reuse of the catalyst for at least five times without loss of activity could regard as cost effective, environmentally friendly and greener process. The fresh and used catalysts were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Raman spectroscopy, N2 physisorption and temperature programmed desorption by CO2 (CO2-TPD) to understand the role of hydrotalcite in the reaction mechanism and the robust nature of the catalyst. It appears that better microwave absorptivity of the catalyst with Mg–Al HT structure might be responsible for shorter reaction times with high yields. A plausible mechanism for 1,3-dipolar cycloaddition over the Mg–Al HT is proposed.