Cyclization Of Nitriles Research Articles

Nickel-catalyzed cyclization of alkynyl nitriles with isocyanide: An expedient way to the synthesis of polysubstituted pyrroles

We herein describe a nickel-catalyzed cascade cyclization of alkynyl nitriles with tert-butylisocyanide under simple reaction conditions. A couple of polysubstituted pyrroles were obtained in moderate yields and with excellent regioselectivity in some cases. The products from this protocol are synthetically useful since the parent pyrrole ring bears one free amino and two cyano groups which enable diverse late-stage transformations.

Coacervate Phase Evolution and Membrane Formation in Natural Seawater.

Marine organisms produce biological materials through the complex self-assembly of protein condensates in seawater, but our understanding of the mechanisms of microstructure evolution and maturation remains incomplete. Here, we show that critical processing attributes of mussel holdfast proteins can be captured by the design of an amphiphilic, fluorescent polymer (PECHIA) consisting of a polyepichlorohydrin backbone grafted with 1-imidazolium acetonitrile. Aqueous solutions of PECHIA were extruded into seawater, wherein the charge repulsion of PECHIA is screened by high salinity, facilitating interfacial condensation via enhanced "cation-dipole" interactions. Diffusion of seawater into the PECHIA solution caused droplets to form immiscibly within the PECHIA phase (i.e., inverse coacervation). Simultaneously, weakly alkaline seawater catalyzes nitrile cyclization and time-dependent solidification of the PECHIA phase, leading to hierarchically porous membranes analogous to porous architectures in mussel plaques. In contrast to conventional polymer processing technologies, processing of this biomimetic polymer required neither organic solvents nor heating and enabled the template-free production of hollow spheres and fibers over a wide range of salinities.

Anionic aza 8π-electrocyclization as an unprecedented pathway versus 7-endo-dig: DFT study on the mechanism of base-catalyzed benzofuroazepine synthesis via cyclization of (2-alkynylbenzyl)oxy nitriles.

DFT calculations are used to disclose the mechanism of Brønsted base-mediated cyclization of (2-alkynylbenzyl)oxy nitriles for the synthesis of benzofuroazepines. In 2015, the synthesis of substituted benzofuroazepines was reported by Zeni et al. via a stepwise mechanism known as 7-endo-dig. However, DFT calculations revealed that the anionic aza 8π-electrocyclization is more favorable than the proposed 7-endo-dig mechanism.

Microwave-assisted rapid synthesis of chiral oxazolines.

Chiral oxazoline compounds play an extremely important role in asymmetric synthesis and drug discovery. Herein a simpler, greener and more efficient microwave-assisted protocol to rapidly access chiral oxazolines is developed using aryl nitriles or cyano-containing compounds and chiral β-amino alcohols as starting materials. The reaction proceeds smoothly in the presence of a recoverable heterogeneous catalyst in either concentrated solution or under solvent-free conditions. The advantages of this method include rapidness, convenience, environmental protection, high atom economy, and excellent yields. The protocol should find wider application in the community in the future.

Synthetic Studies on Cyclocitrinol: Construction of the ABC Ring System Based on Epoxy–Nitrile Cyclization

AbstractThe stereoselective synthesis of a model compound containing the ABC ring system of cyclocitrinol was accomplished. After connecting a C ring allyltitanium segment with an A ring bi­cyclo[4.1.0]heptanone segment, the seven-membered B ring moiety was constructed by an intramolecular cyclization reaction of an epoxy nitrile. The enone moiety was introduced through an oxidative decyanation reaction, and the bicyclo[4.4.1]undecane skeleton with the highly strained olefin moiety was formed through a ring-opening reaction of the bicyclo[4.1.0]heptane substructure.

Total Syntheses of (−)‐Conidiogenone B, (−)‐Conidiogenone, and (−)‐Conidiogenol

AbstractCyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6–8 consecutive stereocenters. The concise total syntheses of (−)‐conidiogenone B, (−)‐conidiogenone, and (−)‐conidiogenol have been accomplished in 14–17 steps. The present work features a HAT‐mediated alkene–nitrile cyclization to access the cis‐biquinane, a Nicholas/Pauson–Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton.

Rapid access to 3-aminoindazoles from nitriles with hydrazines: a strategy to overcome the basicity barrier imparted by hydrazines.

A practical and efficient base mediated synthesis of free 3-aminoindazoles has been developed from the reaction of nitriles with hydrazines, which successfully overcomes the difficulty of using aromatic hydrazines as substrates and allows for the synthesis of a wide range of N-aryl substituted free 3-aminoindazoles in moderate to excellent yields under mild conditions in one-pot. This finding provides a rapid and useful strategy for the synthesis of various functionalized 3-aminoindazole derivatives.

Heterogeneous Copper(I)-Catalyzed Cascade Addition–Oxidative Cyclization of Nitriles with 2-Aminopyridines or Amidines: Efficient and Practical Synthesis of 1,2,4-Triazoles

The heterogeneous cascade addition-oxidative cyclization of nitriles with 2-aminopyridines or amidines was achieved in 1,2-dichlorobenzene or DMSO at 120–130 °C by using a 1,10-phenanthroline-functionalized MCM-41-supported copper(I) complex [Phen-MCM-41-CuBr] as the catalyst and air as the oxidant. The approach was used to generate a wide variety of 1,2,4-triazole derivatives in mostly high yields. This heterogeneous copper(I) catalyst could be easily prepared in a two-step procedure from commercially or readily available and inexpensive reagents and it exhibited higher catalytic activity than the CuBr/1,10-Phen system. Phen-MCM-41-CuBr was also easy to recover and was recyclable up to eight times with almost consistent activity.

Intermolecular coupling and intramolecular cyclization of aryl nitriles on Au(111).

The on-surface dimerization reaction of an organic nitrile on Au(111) is reported. The formation of the product, which contains five newly formed σ-bonds and a diazapyrene core structure, was investigated and characterized by scanning tunneling microscopy. Experimental and computational studies of reference compounds support our findings.

Structural transformation, thermal endurance, and identification of evolved gases during heat treatment processes of carbon fiber polymer precursors focusing on the stereoregularity

Structural transformations of polyacrylonitrile microstructure with varying degrees of stereoregularity during the thermal-oxidative degradation and pyrolysis reactions were investigated employing coupled thermal techniques namely pyrolysis–gas chromatography–mass spectrometry, evolved gas analysis–mass spectrometry, and thermal gravimetric analyzer-FT infrared spectrometry (TG-FTIR) in the temperature range of 200–600 °C. More number of intense peaks with large ionic abundances in the thermal curves and pyrograms indicate that atactic-rich polyacrylonitrile copolymers undergo thermal cleavage, fragmentation and cyclization reactions more readily than isotactic polyacrylonitrile. The mass loss accompanying the thermal reactions was accounted for the evolution of hydrogen cyanide, ammonia, and homologous of alkyl nitrile having molar mass between 47 and 224 m/z; their most probable structures were identified. Thermal analysis results confirm that nitrile cyclization reactions proceed preferentially at isotactic triads leading to a steady and stable thermal-oxidative degradation reactions as compared to atactic-rich polyacrylonitrile. The simultaneous TG-FTIR results of evolved gas analysis also validate the pyrolysis experiments.

A synthesis of novel expanded porphyrinoids: NiII-induced nitrile cyclization of dicyanovinylene-bis(meso-aryl)dipyrrin

NiII-Metallation of dicyanovinylene-bis(meso-aryl)dipyrrin 1 under refluxed toulene conditions resulted in the formation of a bicyclic pyrrolizine ring to afford two isomeric bisNiII expanded porphyrinoid complexes 2a and 2b. Furthermore, acyclic NiII dipyrrin complex 3 was also isolated. The respective structures for 2a, 2b, and 3 were elucidated by X-ray diffraction analysis. Macrocycles 2a and 2b exhibited typical features of aromatic porphyrinoids showing their longest wavelength absorption bands in the near infrared region ranging from 1100 to 1600 nm.

ChemInform Abstract: Copper‐Catalyzed Intermolecular Cyclization of Nitriles and 2‐Aminobenzylamine for 3,4‐Dihydroquinazolines and Quinazolines Synthesis via Cascade Coupling and Aerobic Oxidation.

A copper-catalyzed cascade coupling and aerobic oxidation of aromatic nitriles and 2-aminobenzylamine for the synthesis of 3,4-dihydroquinazolines and quinazolineshas been achieved. The catalytic system, characterized by not adding additives and using molecular oxygen as the sole oxidant, exhibited exquisite substrate specificity and operated under mild conditions through inherently “green” processes.

ChemInform Abstract: Ruthenium‐Catalyzed Aerobic Oxidative Cyclization of Aromatic and Heteroaromatic Nitriles with Alkynes: A New Route to Isoquinolones.

AbstractUnsymmetrically substituted alkynes (XIII) are found to regioselectively react in a fashion where the less hindered C‐H bond of the aromatic nitrile is preferably attacked by the alkyl substituted site of the alkyne.

Ruthenium-catalyzed aerobic oxidative cyclization of aromatic and heteroaromatic nitriles with alkynes: a new route to isoquinolones

The oxidative cyclization of aromatic and heteroaromatic nitriles with alkynes in the presence of a catalytic amount of [{RuCl2(p-cymene)}2], Cu(OAc)2·H2O and KPF6 in acetic acid under air gave isoquinolones in good to excellent yields.

Application of a Raney-Cobalt-Mediated Tandem Reductive Cyclization Protocol to Total Syntheses of the Aspidosperma Alkaloids (±)-Limaspermidine and (±)-1-Acetylaspidoalbidine

The racemic modification of the Aspidosperma alkaloid limaspermidine (1) has been prepared in ten steps including one involving a Raney-cobalt-mediated tandem reductive cyclization of nitrile 8 to give the tetracyclic system 9b. Compound (±)-1 has been converted over two steps into (±)-1-acetylaspidoalbidine [(±)-13].

Synthesis of rumphellaone A via epoxy nitrile cyclization

The first enantioselective total synthesis of rumphellaone A, a cytotoxic 4,5-seco-caryophyllane isolated from the gorgonian coral Rumphella antipathies, has been achieved from a known olefinic alcohol by a 16-step sequence involving Stork's epoxy nitrile cyclization as the key step to concomitantly install a cyclobutane ring and three contiguous stereogenic centers contained in the molecule.

Effect of functional groups of carbon nanotubes on the cyclization mechanism of polyacrylonitrile (PAN)

The cyclization mechanism of polyacrylonitrile (PAN) in PAN/functionalized carbon nanotube (CNT) composites was examined. The surface functionalization of CNTs was carried out by using diazonium reagents with 4-substituted aniline. The results strongly suggest that the type of functional groups on the CNTs strongly influences the cyclization mechanism of PAN during the stabilization process. The nitrile of PAN in F–Ph–CNT/PAN composite was cyclized through the free radical reaction during thermal stabilization whereas nitrile of PAN in COOH–Ph–CNT/PAN composite underwent cyclization via the ionic reaction due to the acid groups on the surfaces of the CNTs. The fluoro functional groups on the CNTs can act as effective external initiators for nitrile cyclization in homo PAN, in contrast to acid functional groups. Consequently, a lower cyclization temperature (265 °C) and enthalpy value (688 J/g) of F–Ph–CNT were shown compared to those of homo PAN.

ChemInform Abstract: Grignard Reagent‐Promoted 6‐endo‐dig Cyclization: Instantaneous Synthesis of Original Dipyrido[1,2‐a:3′,4′‐d]imidazole.

Abstract Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.

Enantioselective synthesis of rumphellaone A via epoxy nitrile cyclization

The first enantioselective synthesis of rumphellaone A, a cytotoxic 4,5- seco-caryophyllane derivative incorporating a γ-lactone ring as its structural feature, has been achieved by using base-induced intramolecular cyclization of an epoxy nitrile intermediate to install its cyclobutane skeleton as well as three contiguous stereocenters as the key transformation.

Grignard reagent-promoted 6- endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2- a:3′,4′- d]imidazole

Dipyrido[1,2- a:3′,4′- d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2- a]pyridines via an efficient Grignard reagent-promoted 6- endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2- a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.