Formamide Research Articles

A Copper-Catalyzed Synthesis of Pyridoquinazolinones via C(sp2)-H Functionalization and Annulation of Benzoic Acids with 2-Aminopyridines.

A facile synthesis of pyridoquinazolinones has been accomplished via C(sp2)-H functionalization and annulation of benzoic acids with 2-aminopyridines using Cu(OAc)2 as catalyst in DMSO. The reaction involves the formation of amides which on ortho amination followed by trans-amidation afford a wide array of products under ligand/base-free conditions.

Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted 177Lu-Labeled Cancer Theranostics.

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp(NMe)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer's tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, para-aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.

Achieving Uniform Deposition of Zn with Amide Additives for Metal Anodes Stabilization.

The practical applications of aqueous zinc-ion batteries (AZIBs) are hindered by detrimental effects such as dendrites formation at the Zn metal anode interface and parasitic side reactions induced by H2O. Hence, we propose adding amide additives to the Zn sulfate electrolyte (ZSO) to regulate the composition and properties of the electrolytes, thereby stabilizing the Zn anode interface. Different amide molecules containing formamide (FA), acetamide (AA), or trifluoroacetamide (TFA) are discussed. The polar C═O group shared by amide molecules can interact with Zn2+, forming their solvation shells. The molecules can also facilitate the transport of Zn2+ and increase the conductivity of the electrolytes. Additionally, amide molecules can interact with H2O through hydrogen bonds to limit the erosion of active H2O on the Zn anode. The unique -H, -CH3, and -CF3 groups of the molecules result in different polarities and varying numbers of interaction sites with H2O and Zn2+, leading to some differences in the protective effects of the Zn anode. The stability and lifespan of Zn||Zn batteries assembled with amide electrolytes have significantly improved, especially those with TFA. Moreover, the Zn||NH4V4O10 full cells demonstrate remarkable capacity retention, and the overall performance of the batteries has also been enhanced.

Diastereoselective Synthesis of N-Heterocycle Substituted Cyclobutanes via Michael Addition onto Cyclobutenes.

Herein, we present a method for the diastereoselective synthesis of N-heterocycle-substituted cyclobutanes from commercially available bromocyclobutanes. This method enables the efficient formation of various heterocyclic aminocyclobutane esters and amides using simple reagents. Notably, N-nucleophiles such as imidazoles, azoles, and nucleobase derivatives were successfully incorporated, enhancing the chemical diversity of small ring building blocks for medicinal chemistry applications.

Strong and Environmental-Friendly Adhesive Glass Based on Chitin Nanoparticles

Chitin is a biopolymer that can be used as a candidate material for a strong and environmentally friendly glass adhesive. In the form of nanoparticles with needle-like morphology and attractive functional groups in the form of amide and hydroxyl, Chitin Nanoparticle (ChNP) shows a strong Van der Walls adhesive force against glass. In the study, ChNP was successfully isolated from crab shells from the sea of Lombok. The isolated ChNP has a characteristic size around 351 nm with -chitin conformation and needle-shaped morphology. Based on the results of shear strength testing, 0.42 mg of ChNP can withstand a load of 21 kg and the addition of Gum Arabic (GA) and Hen Egg White lysozyme (HEWL) in a ratio of 1: 1 to ChNP succeeded in increasing adhesion by 72%.

Copper‐Catalyzed Tandem Cyclization of 2‐(Alkynylaryl)Acetonitriles and Amines: Access to 3‐Hydroxyisoindolinones

AbstractHerein, we describe an approach to the synthesis of 3‐hydroxyisoindolinone derivatives via copper‐catalyzed tandem cyclization of 2‐(alkynylaryl)acetonitriles and amines. This reaction is compatible with 2‐(alkynylaryl)acetonitriles and primary alkyl amines containing various functional groups, providing the corresponding 3‐hydroxyindolinone derivatives with yields ranging from 44%–82%. Preliminary mechanistic studies suggest that the reaction involves oxidation of the benzylic carbon, amide formation, hydration of the alkyne and intramolecular cyclization to produce various 3‐hydroxyisoindolinones. The practicality of the strategy was further demonstrated by gram‐scale synthesis, late‐stage functionalizations, and the post modification of natural products.

Formation and Stability of Benzylic Amide [2]- and [3]Rotaxanes: An Intercomponent Interactions Study.

One of the most recent focuses in supramolecular chemistry is developing molecules designed to exhibit programmable properties at the molecular level. Rotaxanes, which function as molecular machines with movements controlled by external stimuli, are prime candidates for this purpose. However, the controlled synthesis of rotaxanes, especially amide-benzylic rotaxanes with more than two components, remains an area ripe for exploration. In this study, we aim to elucidate the formation of amide-benzylic [3]rotaxanes using a thread that includes a conventional succinamide station and an innovative triazole-carbonyl station. Including the triazole-carbonyl station introduces new perspectives into the chemistry of rotaxanes, influencing their conformation and dynamics. The synthesis of two-station rotaxanes with varying stoppers demonstrated that the macrocycle consistently occupies the succinamide station, providing greater stability as evidenced by NMR and SC-XRD analyses. The presence of a triazole-carbonyl station facilitated the formation of a second macrocycle exclusively when a secondary amide was employed as the stopper group, presumably due to decreased steric hindrance. Moreover, the second macrocycle directly forms at the triazole-carbonyl station. This investigation reveals that slight modifications in the thread structure can dramatically impact the formation, stability, and interactions between components of rotaxanes.

Reactions of an Anionic Gallylene with Azobenzene or Azide Compounds Through C(sp2)-H and C(sp3)-H Activation.

The activation of inert C-H bonds remains a challenge in current chemistry. Here, we report the excellent reactivity of the anionic gallylene species [LGa:][Na(THF)3] (L = [(2,6-iPr2C6H3)NC(CH3)]22-, 1) that allows the selective activation one ortho sp2 C-H bond of several azobenzene and azide derivatives at ambient temperature, with the transfer of the hydrogen atom to one of the nitrogen atoms. The process leads to the formation of the aryl amido products [LGa-κ2N,C-PhNN(H)(p-R-C6H3)][Na(solvent)3] (2, R = H solvent = DME (1,2-Dimethoxyethane); 3, R = -OMe, solvent = DME; 4, R = -NMe2 solvent = THF), [LGa-κ2N,C-(m-CH3-C6H4)NN(H)(m-CH3-C6H3)][Na(15-C-5)2] (5) with new Ga-C and Ga-N bonds. Moreover, 1 is also effective for the C-H activation of two azides RN3 (R = 2,4,6-Me3C6H2 or 2,6-iPr2C6H3), resulting in the formation of gallium amides [LGa(NH-2-(CH2)-4,6-Me2C6H2)][Na(15-C-5)2] (6) and [LGa(NH-2,6-iPr2C6H3)2][Na(THF)5] (7) through intra- or intermolecular sp3 C-H amination. Significantly, these reactions occur for the highly challenging activation of inert C(sp2)-H and C(sp3)-H bonds, thus demonstrating the excellent reactivity of the Ga(I) species 1. The products 2-7 were characterized by X-ray crystallography, 1H and 13C NMR, UV-vis spectroscopy, and density functional theory (DFT) calculations.

Visible-Light-Driven Method for the Selective Synthesis of Amides and N-Acylureas from Carboxylic Acids and Thioureas.

In this work, we developed a visible-light-driven method for the selective synthesis of amides and N-acylureas from carboxylic acids and thioureas. This protocol was featured as avoidance of additional oxidants and transition metal catalysts, simple manipulations, low cost, broad substrate scope, and good functional group tolerance. As only oxygen serves as the oxidation reagent, this method provides a promising synthesis candidate for the formation of N-aryl amides and N-acylureas, including late-stage functionalization of complex pharmaceutical molecules and biologically active molecules.

An Optical Au3+ Sensor Based on layer-by-layer PEI/PAA-Rho thin Films on ITO.

This study presents the development of a sensitive and selective gold ion (Au3+) sensor utilizing layer-by-layer (LbL) assembled thin films composed of polyethylenimine (PEI) and poly (acrylic acid) (PAA) conjugated with rhodamine (Rho). The first study revealed that the polymeric sensors (PAA-Rho) demonstrated significant selectivity and sensitivity in their colorimetric and fluorescence responses to Au3+ compared to other metal ions. In their spirolactam form, the polymeric sensors were non-fluorescent but could selectively transform into the fluorescent ring-opened amide form upon interaction with Au3+ ions, resulting in fluorescence enhancement and observable color changes. Common co-existing metal ions showed negligible interference in the detection of Au3+. The LbL sensor exhibited a linear increase in absorbance with the addition of bilayers, confirming successful film deposition. Surface morphology analysis using SEM, along with structural confirmation via ATR-FTIR and XRD, further validated the sensor's capability to detect cation. Results demonstrated that the LbL sensor exhibited selectivity for Au3+ ions within the range 1 × 10-6 to 1 × 10-3 M. This approach offers an easily understandable and intrinsically sensitive means for detecting Au3+ ions in both environmental and biological applications.

Earth-abundant catalyst for modification of wheat straw to enhance ammonia mitigation from fertilized alkaline soil

In this study, inexpensive earth-abundant catalyst of Co/TiO2 is coupled with a low-temperature modification approach to enhance NH3 adsorption capacity on wheat straw (WS). The highest NH3 uptake achieved is 111.9 mg/g, with 80.8 % retention even after 3 h of desorption. Mechanistic investigation indicates that the enhanced adsorption capacity stems from Co/TiO2, which facilitates generation of reactive oxygen species, leading improved ultra-micropore structure that enhances the interaction between NH3 and oxygen-containing functional groups through a trapping effect. The robust stability of adsorbed NH3 is attributed to the formation of amides or amines. Incorporation of only 1 wt% WS-Co to urea-fertilized alkaline soil reduced NH3 volatilization by 83.1 %. The significant effect is primarily attributed to the excellent adsorption capacity of WS-Co, rather than alterations in the relative abundance of the microbial community. These findings present a novel approach for development of effective fertiliser additive to mitigate NH3 volatilization from alkaline soil.

Pyrrolidine derivatives as α-amylase and α-glucosidase inhibitors: Design, synthesis, structure-activity relationship (SAR), docking studies and HSA binding

In our pursuit of developing effective inhibitors for the enzymes α-amylase and α-glucosidase, which play a crucial role in carbohydrate metabolism related to type-2 diabetes, we synthesized compounds featuring a pyrrolidine ring. The synthesis involved coupling N-Boc-proline with various aromatic amines, resulting in the formation of distinct N-Boc proline amides. To investigate the influence of the Boc group on enzyme inhibition, the Boc group was subsequently removed. In vitro, testing against α-amylase and α-glucosidase, with metformin and acarbose as reference standards, revealed that the 4-methoxy analogue 3g showed noteworthy inhibitory activity, with IC50 values of 26.24 and 18.04 μg/mL, respectively. Compounds 3a with an IC50 value of 36.32 μg/mL and 3f with an IC50 value of 27.51 μg/mL displayed significant inhibitory activity against α-amylase and α-glucosidase, respectively. The results of molecular docking studies of the most potent pyrrolidine derivatives 3a and 3g with α-amylase and 3f and 3g with α-glucosidase showed good agreement with experimental data. Moreover, compound 3g showed strong binding interactions with HSA having binding constant values of 7.08 × 105 M−1 and 4.77 × 105 M−1 using UV–visible and fluorescence spectrophotometry, respectively.

β-Silyl alkynoates: Versatile reagents for biocompatible and selective amide bond formation.

The study introduces a previously unidentified method for amide bond formation that addresses several limitations of conventional approaches. It uses the β-silyl alkynoate molecule, where the alkynyl group activates the ester for efficient amide formation, while the bulky TIPS (triisopropylsilane) group prevents unwanted 1,4-addition reactions. This approach exhibits high chemoselectivity for amines, making the method compatible with a wide range of substrates, including secondary amines, and targets the specific ε-amino group of lysine among the native amino ester's derivatives. It maintains stereochemistry during amide bond formation and TIPS group removal, allowing a versatile platform for postsynthesis modifications such as click reactions and peptide-drug conjugations. These advancements hold substantial promise for pharmaceutical development and peptide engineering, opening avenues for research applications.

Crosslinking reactions of a model aminated lignin compound as a platform for building thermosetting polymers for lignin-based bio adhesives

As millions of tons of kraft lignin are being wasted, a potential application is to use its crosslinking reactions to build thermosetting bio adhesives. However, the crosslinking reactions between lignin molecules are not fully understood. The present study aims to elucidate the crosslinking reactions of the model lignin compound guaiacylglycerol-β-guaiacyl ether (GGE) via one-step hydroxymethylation/ amination with formaldehyde and diethylenetriamine (DETAM), or one-step glyoxylation/ amination with glyoxal and DETAM via liquid NMR techniques such as 1H NMR, 13C NMR, 2D 1H–13C, and 1H–15N HSQC NMR. Specifically, the 2D 1H–13C HSQC NMR spectra confirm the presence of –CH2–NH– with a chemical shift of 1H 2.6–3.6/13C 40–60 ppm, and the formation of methylene linkages via the crosslinking reaction. Also, the 2D 1H–15N HSQC NMR spectra clearly detect the formation of amide and imine bonds at 1H 7.8/15N 110 and 1H 8.07/15N 121.5 ppm from the crosslinked GGE.

Single‐Pot Synthesis and Optimization of CCF@GO Nanocatalyst for Efficient Direct Oxidative Amidation of Carboxylic Acids and N,N‐Dialkylformamides

ABSTRACTIn this study, an efficient catalytic protocol using CuCoFe2O4@GO (CCF@GO) for the synthesis of amide bond (−CONH−) via direct coupling of carboxylic acids and N,N‐dialkylformamides is presented. The CCF@GO nanocatalyst has been synthesized via a single‐pot solvothermal method, by changing the proportions of copper and cobalt (1:1, 1:3, and 3:1). Catalyst screening, employing a model reaction with benzoic acid and dimethylformamide (DMF), revealed that the 1:1 proportion of CCF@GO catalyst exhibited excellent efficiency, achieving a high conversion (98%) towards amide formation. The enhanced catalytic efficiency observed in CCF@GO catalysts can be ascribed to the uniform distribution of active copper and cobalt species on the graphene oxide support, which possesses a high surface area. Optimization of the reaction was conducted by varying parameters such as temperature, solvent, catalyst loading, and oxidant. The prepared catalyst was characterized using various analytical techniques including XRD, FTIR, XPS, SEM, EDX mapping, and TEM. Furthermore, this heterogeneous nanocatalyst demonstrated recoverability using an external magnet and reused up to five times with just a modest loss of catalytic performance.

New Analogues of the Nicotinamide Phosphoribosyltransferase Inhibitor FK866 as Potential Anti-Pancreatic Cancer Agents.

During the past two decades, many nicotinamide phosphoribosyltransferase (NAMPT) inhibitors were prepared and tested because this enzyme is overexpressed in pancreatic cancer. Although FK866 is a well-known, strong NAMPT inhibitor, it suffers severe drawbacks. Our work aimed to synthesize efficient NAMPT inhibitors featuring better pharmacokinetic properties than the pyridine-containing FK866. To this aim, the new anticancer agents were based on benzene, pyridazine, or benzothiazole moieties as a cap group instead of the pyridine unit found in FK866 and other NAMPT inhibitors. The new compounds, prepared exploiting standard heterocycle chemistry and coupling reactions (e.g., formation of amides, ureas, and cyanoguanidines, copper-mediated azide-alkyne cycloaddition), have been fully characterized using NMR and HRMS analyses. Their activity has been evaluated using cytotoxicity and intracellular NAD depletion assays in the human pancreatic cancer cell line MiaPaCa-2. Among the 14 products obtained, compound 28, bearing a pyridazine unit as the cap group and a thiophene moiety as the tail group, showed 6.7 nanomolar inhibition activity in the intracellular NAD depletion assay and 43 nanomolar inhibition in the MiaPaCa-2 cells cytotoxicity assay, comparable to that observed for FK866. The positive results observed for some newly synthesized molecules, particularly those carrying a thiophene unit as a tail group, indicate that they could act as in vivo anti-pancreatic cancer agents.

Synthesis of Simplified 2-Desmethyl Sanctolide A Analogs.

A one-pot, sequential phosphate tether-mediated method for the synthesis of simplified 2-desmethyl sanctolide A analogs is reported. Western side-chain diversification was achieved using a pot-efficient, sequential cross metathesis (CM)/ring-closing metathesis (RCM)/H2/dephosphorylation procedure. Further diversification was achieved by Me3Al-mediated amide formation, Yamaguchi esterification, and RCM macrocyclization to access five C11/C12 Z-configured, 2-des-methyl sanctolide A analogs with improved stability.

Ortho-quinone methide driven synthesis of kynurenic acid lactams.

Lactam formation of different KYNA amides and Mannich bases mediated by ortho-quinone methide has been investigated. The efficiency of the two routes of the cyclization process was revealed and the influence of diverse amide side chains was explored. In this regard compounds bearing a tertiary amine function in the amide side chain resulted in the formation of the lactam product, while the formation of dimer derivatives was observed in the case of other KYNA amides. Furthermore, derivatives bearing different substituents on the KYNA B ring were synthesized and their effects on the ring-closure reaction were investigated.

Amorphous MoS2/MoO3 Nanosheets as High‐Efficient Polysulfide Barrier in Li−S Batteries

AbstractLithium‐sulfur batteries (LSBs) are seriously impeded by poor reaction kinetics and the polysulfides shuttling, leading to low utilization of sulfur and poor cycling performance. Herein, amorphous MoS2/MoO3 nanosheets are prepared by a one‐step formamide (FA)‐assisted strategy. Due to the merits of high adsorption capability and good catalytic activity of MoS2, relatively high electronic conductivity and strong polarity of MoO3, and abundant active sites of amorphous nanosheet structure, the LSBs based on amorphous MoS2/MoO3‐2 nanosheets coated separator exhibit an outstanding specific capacity (1420.2 mA h g−1 at 0.1 C), excellent rate capacity (505.4 mA h g−1 at 5 C), and long cycle life (a negligible decay rate of 0.063 % per cycle at 0.5 C). This work provides an idea for designing efficient amorphous catalytic materials in LSBs.

First-Order Derivative Spectrophotometry for Simultaneous Determination of Vitamin C and Nicotinamide: Application in Quantitative Analysis of Cocrystals.

Vitamin C (l-ascorbic acid, ASC) and the amide form of vitamin B3 nicotinamide (NIC) can form cocrystals through hydrogen bonding. Currently, there is a lack of fast and reliable alternatives for precisely quantifying cocrystal components and their purity. Spectrophotometric analysis for quantifying such vitamin preparations is challenging due to overlapping absorbance bands in a narrow wavelength range in the ultraviolet (UV) region. Moreover, ASC undergoes progressive degradation if not diluted in a proper medium, requiring stability during quantitative analysis. This study adopted a fast, simple, and reliable two-component spectrophotometric assay for simultaneously determining ASC and NIC based on the first-order derivative spectrophotometry (FODS) method using sodium oxalate as a stabilizer for vitamin C. The FODS method showed linearity between 2 and 24 μg·mL-1 and good precision. The standard addition method was employed to validate FODS, with high recovery percentages (96.5 to 102.4% for ASC and 95.3 to 101.9% for NIC). The FODS method was successfully applied to quantify ASC and NIC in bulk powder produced by the gas antisolvent method. The proposed method could estimate cocrystal purity through mass balance regarding the expected 1:1 stoichiometry, confirmed by PXRD and DSC. Cocrystal purity determined by the FODS method (58-100%) aligned well with results from LC-MS (62-100%), with an accuracy exceeding 97%. The FODS method is as sensitive and accurate as high-performance liquid chromatography for simultaneously determining vitamin concentrations deriving from cocrystals. However, it is less costly, more efficient, and a suitable alternative to classical solid-state methods for estimating cocrystal purity.