Aryl Amides Research Articles

ChemInform Abstract: Copper(I) Catalyzed C(sp2)—N Bond Formation: Synthesis of Pyrrolo[3,2‐c]quinolinone Derivatives.

AbstractA novel route towards pyrroloquinolinones via direct intramolecular amide arylation is developed.

ChemInform Abstract: Palladium‐Catalyzed Synthesis of Aryl Amides Through Silanoate‐Mediated Hydrolysis of Nitriles.

AbstractThe starting amide salts are prepared by reaction of appropriate nitriles with Tms—OK according to a known procedure.

Polymorphic Crystalline Structure and Crystal Morphology of Enantiomeric Poly(lactic acid) Blends Tailored by a Self-Assemblable Aryl Amide Nucleator

Stereocomplex (SC) crystallization has been an effective method to improve the heat resistance of poly(lactic acid) (PLA). However, the preparation of SC-type PLA material is still a challenge because SC crystallization is much less prevailing than homocrystallization in the high-molecular-weight (HMW) poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic blends. In this study, we have successfully promoted SC formation and controlled crystal morphology of a HMW PLLA/PDLA blend by using a self-assemblable aryl amide nucleator, N,N′,N″-tricyclohexyl-1,3,5-benzenetricarboxylamide (BTCA). Crystallization kinetics, polymorphic crystalline structure, crystal morphology and superstructure of BTCA-nucleated PLLA/PDLA blends were investigated. During the nonisothermal melt crystallization and isothermal crystallization at different temperatures (80–170 °C), the crystallization rate of PLLA/PDLA blend is significantly promoted and the fraction of SCs is enhanced with incorporating small amount of BTCA. SCs a...

ChemInform Abstract: A Simple Method for the Synthesis of Furfuryl Ketones and Furylacetic Acid Derivatives.

AbstractA simple method for the synthesis of aryl furfuryl ketones (III), amides (V), and furylacetic acid esters (VII) based on the radical alkylation of furan derivatives (II) with corresponding xanthogenates is developed.

Nickel-Catalyzed Negishi Cross-Coupling of Bromodifluoroacetamides.

A nickel-catalyzed Negishi coupling of bromodifluoroacetamides with arylzinc reagents has been developed. This reaction allows access to difluoromethylated aromatic compounds containing a variety of aryl groups and amide moieties. Furthermore, highly effective transformation of the functionalized difluoromethyl group (-CF2CONR(1)R(2)) was realized via microwave-assisted reduction under mild conditions. The notable features of this strategy are its generality and its use of a low-cost nickel catalyst and ligand; thus, this reaction provides a facile method for applications in drug discovery and development.

ChemInform Abstract: [4 + 3] Cycloadditions with Bromo‐Substituted Morita—Baylis—Hillman Adducts of Isatins and N‐(ortho‐Chloromethyl)aryl Amides

Abstractto give challenging aza‐spirocycloheptane oxindole scaffolds

Non-isothermal crystallization kinetics of wood-flour/polypropylene composites in the presence of β-nucleating agent

The influence of aryl amide compounds (TMB) as β-nucleating agents, on the non-isothermal crystallization of a wood-flour/polypropylene composite (WF/PP) prepared by compression molding was investigated by wide-angle X-ray diffraction and differential scanning calorimetry. TMB was proved to be an effective β-crystalline nucleating agent for WF/PP. The DSC data showed that the crystallization peak temperature (Tp) increased and the half-time (t1/2) decreased with the addition of TMB. Three theoretical models were used to analyze the non-isothermal crystallization process. The modified Avrami method and Mo method successfully explained the non-isothermal crystallization behavior of PP and its composites. Their activation energies for non-isothermal crystallization were determined basing on the Kissinger method.

IBX-mediated synthesis of indazolone via oxidative N-N bond formation and unexpected formation of quinazolin-4-one: in situ generation of formaldehyde from dimethoxyethane.

Synthesis of indazolone derivatives, which exhibit diverse biological and pharmaceutical activities, were achieved by hypervalent λ(5) iodine reagents, such as iodoxybenzoic acid (IBX),-mediated oxidative N-N bond forming cyclization. In this study, the equivalence of IBX was optimized to promote the formation of N-N bond by oxidatively generated acylnitrenium ion. Dimethoxyethane and dichloroethane were discovered as alternative solvents and the reaction could be conducted in more concentrated condition. Some unprecedented substrates successfully afforded the corresponding indazolone in new condition discovered in this study. When the reactions were conducted in DME solvent, substrates with no electron-rich phenyl substituted amides afforded the unanticipated quinazolin-4-ones in moderate yields, which were not formed in DCE solvent. The formation of quinazolin-4-ones was attributed to the in situ generation of formaldehyde from DME. Therefore, the reaction might undergo different pathway in DME when the substrate aryl amides have phenyl rings without electron donating substituents.

Neutral cholic acid–coumarin conjugate exhibit excellent anion binding properties by cooperative aryl CH and amide NH segments

A neutral cholic acid–coumarin conjugate was developed for anion recognition. It is revealed by the experimental and theoretical results that the coumarin group can provide CH segments as hydrogen bond donors by cooperation with the adjoining amide NH segments. With excellent biocompatibility, this receptor with coumarin as fluorescence sensors also have the potential to be used as an efficient and non-destructive probe for anion detection in living cells. This work displays a new insight into the importance of coumarin group as anion recognition group, which is not well presented so far.

A palladium–bisoxazoline supported catalyst for selective synthesis of aryl esters and aryl amides via carbonylative coupling reactions

The catalytic synthesis of aryl esters and amides has been successfully achieved in the presence of the efficient palladium–bisoxazoline supported on Merrifield's resin (Pd–BOX-M).

Base-catalyzed synthesis of aryl amides from aryl azides and aldehydes.

Aryl amides have been used as important compounds in pharmaceuticals, materials and in molecular catalysis. The methods reported to prepare aryl amides generally require very specific reagents, and the most popular carboxyl-amine coupling reactions demand stoichiometric activators. Herein, we report that aryl azides react with aldehydes under base-catalyzed conditions to yield aryl amides efficiently. Mechanistic investigations support the formation of triazoline intermediates via azide-enolate cycloaddition, which subsequently undergo rearrangement to give amides by either thermal decomposition (20-140 °C) or aqueous acid work-up at room temperature. The strategy does not require nucleophilic anilines and is especially efficient for highly electron-deficient aryl amides, including perfluoroaryl amides, which are otherwise challenging to synthesize.

ChemInform Abstract: Synthesis and Cytotoxic Activity of N,N′‐(Arylmethylene)bisamides.

AbstractThirty three title products are prepared upon the reaction of cinnamamide or acrylamides with a broad range of aryl amides.

Effect of an aryl amide derivative on the crystallization behaviour and impact toughness of poly(ethylene terephthalate)

Poly(ethylene terephthalate) (PET) and aryl amide derivative (TMB-5) blends were prepared by melt blending. It was found that TMB-5 shows a significant nucleation effect on PET and especially the non-isothermal nucleation efficiency reached up to 80.7% at a very low content of 0.6 wt% TMB-5. The effects of TMB-5 on the crystallization behavior and mechanical properties of PET were systematically investigated. DSC results show that crystallization temperature of PET apparently increased by nearly 20 °C with the addition of 0.6 wt% TMB-5 during the cooling process. A remarkable acceleration in the crystallization rate of PET was achieved as analyzed using the Avrami equation. Wide angle X-ray diffraction (WAXD) and polarized optical microscopy (POM) results show that the addition of TMB-5 remarkably increases the crystallinity and nuclei density of PET. Small angle X-ray scattering (SAXS) measurements reveal that the long period of PET decreased and lamellar thickness increased with an increase in TMB-5 content. The impact strength of PET was greatly enhanced by the addition of TMB-5, and a toughening mechanism was proposed.

Amide-functionalized pillar[5]arenes as a novel class of macrocyclic receptors for the sensing of H2PO4- anion.

A novel class of amide-functionalized pillar[5]arenes, that is, alkyl and aryl amide derivatives, has been synthesized. Highly selective binding of the dihydrogen phosphate anion over a range of anions by the new synthetic receptors is reported. First, the "binding strength-selectivity" relationship has been decided for the pillar[5]arene/anion systems.

K2CO3-promoted formation of aryl esters from primary aryl amides by the acyl-acyl exchange process.

A new acyl-acyl exchange reaction has been developed for the formation of aryl esters from primary aryl amides. The reaction could occur under mild reaction conditions with catalytic quantities of K2CO3, and could afford moderate to good yields of the desired products.

Pentamethylcyclopentadienyltitanium aryl(pyridyl)amide complexes: Synthesis, characterization and catalytic performance for olefin polymerization

A series of new half-sandwich pentamethylcyclopentadienyl titanium (IV) aryl(pyridyl)amide complexes, Cp*TiCl2[N(Ar)(2-Py)] [Ar = 2,6-iPr2Ph (1), 2,6-Et2Ph (2), 2,6-Me2Ph (3), 4-MePh (4)], have been synthesized from the reactions of Cp*TiCl3 with the lithium salts of the corresponding aryl(pyridyl)amido ligands in toluene. A byproduct with two aryl(pyridyl)amido ligands, Cp*TiCl[N(4-MePh)(2-Py)]2 (5) was also obtained from the synthetic reaction of complex 4 in a small amount. The new titanium complexes 1–4 were characterized by 1H and 13C NMR and elemental analyses. The molecular structures of complexes 1, 2, 4 and 5 were determined by single-crystal X-ray diffraction analysis. X-ray crystallographic analysis on complexes 1, 2, 4 demonstrates that these complexes possess a relatively crowded hepta-coordinating environment surrounding the central titanium atom. Upon activation with AliBu3 and Ph3CB(C6F5)4, complexes 1–4 exhibited moderate to high catalytic activity for ethylene and propylene polymerization, producing high molecular weight linear polyethylene and atactic polypropylene. It was found that complex 1 shows the highest catalytic activity for ethylene polymerization while complex 4 shows the highest catalytic activity for propylene polymerization among these complexes under similar conditions.

A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.

CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme-unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non-Arrhenius, suggesting a two-step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non-metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging.

Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity.

Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4Rα bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.

Palladium-Catalyzed Synthesis of Aryl Amides through Silanoate-Mediated Hydrolysis of Nitriles

A procedure for the formation of aryl amides through the palladium-catalyzed coupling of nitriles and aryl bromides, via the formation of intermediary silanoate derived imidate species is reported. Optimization was undertaken and examples of the process are described that furnish the products in up to 86% isolated yield.

Palladium supported on triphenylphosphine-functionalized porous organic polymer: an efficient heterogeneous catalyst for aminocarbonylation

An efficient route for the catalytic synthesis of aryl amides via the aminocarbonylation of aryl iodides with amines is described using palladium supported on triphenylphosphine-functionalized porous organic polymer (Pd@KAPs(Ph-PPh3)) as the catalyst. Under low carbon monoxide pressure, the catalyst exhibited remarkable activity, and only 0.5 mol% palladium loading was required to achieve moderate to excellent yields (70–97 %) of aryl amides. The catalyst can be easily separated by a simple filtration process and recycled up to seven times with only minor loss of activity. The salient features of this protocol are the simplicity in handling of catalyst, low CO pressure, good functional group tolerance, high catalytic activity, negligible palladium leaching and effective catalyst recyclability.