Basic Amine Research Articles

One-pot silyl imidate formation-N-alkylation reactions of amides with propargyl propionates

The combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and i-Pr2NEt promotes the N-alkylation of primary and secondary amides with propargyl propionates. The amide substrates are believed to undergo conversion to nucleophilic silyl imidates in the presence of TMSOTf and the amine base, conditions which also promote propargyl cation formation in the same flask through the loss of trimethylsilyl propionate, leading to N-propargylation of the amide. A range of amides and propargyl propionates react efficiently in this reliable one-pot process with yields ranging from 19 to 99%.

The role of mixed ligand approach in enhancing catalytic activity of copper-based MOFs in knoevenagel condensation

The stability and catalytic activity of the amino-functionalized metal-organic frameworks based on Cu were tested in an organic reaction, Knoevenagel condensation. By utilizing different ratios of benzene-1,4-dicarboxylic acid (H2BDC) and 2-amino-benzene-1,4-dicarboxylic acid (NH2-BDC), the amine content was modulated for the synthesis. The amino-based MOFs synthesized with the 1 to 2, 2 to 1, and 1 to 1 ratio of BDC and NH2-BDC that NH2(33%)-Cu-MOF showed the best catalytic performance. The optimum balance between the amount of pore size and the basic amine sites of the framework was provided by this ratio. Also, the activity of catalysts was tested for various substrates' electron-withdrawing and electron-donating groups. Further analyses proved the stability of the NH2(33%)-Cu-MOF. After the catalysis process, the catalyst remained crystalline, and the stability of the framework was proved by PXRD patterns, proving it readily regenerated for the next cycle. Also, the catalytic mechanism has been checked.

Cooperative Carbon Dioxide Capture in Diamine-Appended Magnesium-Olsalazine Frameworks.

Diamine-appended Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks have emerged as promising candidates for carbon capture owing to their exceptional CO2 selectivities, high separation capacities, and step-shaped adsorption profiles, which arise from a unique cooperative adsorption mechanism resulting in the formation of ammonium carbamate chains. Materials appended with primary,secondary-diamines featuring bulky substituents, in particular, exhibit excellent stabilities and CO2 adsorption properties. However, these frameworks display double-step adsorption behavior arising from steric repulsion between ammonium carbamates, which ultimately results in increased regeneration energies. Herein, we report frameworks of the type diamine-Mg2(olz) (olz4- = (E)-5,5'-(diazene-1,2-diyl)bis(2-oxidobenzoate)) that feature diverse diamines with bulky substituents and display desirable single-step CO2 adsorption across a wide range of pressures and temperatures. Analysis of CO2 adsorption data reveals that the basicity of the pore-dwelling amine─in addition to its steric bulk─is an important factor influencing adsorption step pressure; furthermore, the amine steric bulk is found to be inversely correlated with the degree of cooperativity in CO2 uptake. One material, ee-2-Mg2(olz) (ee-2 = N,N-diethylethylenediamine), adsorbs >90% of the CO2 from a simulated coal flue stream and exhibits exceptional thermal and oxidative stability over the course of extensive adsorption/desorption cycling, placing it among top-performing adsorbents to date for CO2 capture from a coal flue gas. Spectroscopic characterization and van der Waals-corrected density functional theory calculations indicate that diamine-Mg2(olz) materials capture CO2 via the formation of ammonium carbamate chains. These results point more broadly to the opportunity for fundamentally advancing materials in this class through judicious design.

Copper MOFs performance in the cycloaddition reaction of CO2 and epoxides

The research in advanced materials for effective CO2 capture and conversion is an imperative duty for the next years. In this sense MOF materials are being intensively tested for this purpose. Herein, seven different copper-based MOF materials with different functional organic groups in their linkers have been assessed to comprehend some structural features that influence the CO2 transformation via cycloaddition reaction with epoxides: Cu-URJC-1 (tetrazole group), Cu-URJC-8 (primary amine group), Cu-MOF-74 (hydroxyl group), JUC-62 (azo group), PCN-16 (triple bond group), HNUST-1 (amide group) and HKUST-1. When epichlorohydrin was used as a substrate, Cu-URJC-8 produced the best epoxide conversion (90%) and selectivity to cyclic carbonate (>99%), despite showing a modest surface area. This result can be explained by the higher basicity of primary amines than other basic functional organic groups of the MOFs. However, when styrene oxide was used as substrate, Cu-URJC-1 led to the best reaction results with a conversion and selectivity toward cyclic carbonate of 60 and 86%, respectively. This result was achieved because this material presents the synergic effect of having in its flexible structure 12 Å channels, that favors the styrene oxide diffusion, and a great number of basic nitrogen atoms, which can increase the reactivity of carbon dioxide. In summary, the presence of nitrogen atoms in the organic linker increases the CO2 conversion by promoting the reactivity of this molecule.

Biocompatible Lysine Protecting Groups for the Chemoenzymatic Synthesis of K48/K63 Heterotypic and Branched Ubiquitin Chains.

The elucidation of emerging biological functions of heterotypic and branched ubiquitin (Ub) chains requires new strategies for their preparation with defined lengths and connectivity. While in vitro enzymatic assembly using expressed E1-activating and E2-conjugating enzymes can deliver homotypic chains, the synthesis of branched chains typically requires extensive mutations of lysines or other sequence modifications. The combination of K48- and K63-biased E2-conjugating enzymes and two new carbamate protecting groups-pyridoxal 5'-phosphate (PLP)-cleavable aminobutanamide carbamate (Abac group) and periodate-cleavable aminobutanol carbamate (Aboc group)-provides a strategy for the synthesis of heterotypic and branched Ub trimers, tetramers, and pentamers. The Abac- and Aboc-protected lysines are readily prepared and incorporated into synthetic ubiquitin monomers. As these masking groups contain a basic amine, they preserve the overall charge and properties of the Ub structure, facilitating folding and enzymatic conjugations. These protecting groups can be chemoselectively removed from folded Ub chains and monomers by buffered solutions of PLP or NaIO4. Through the incorporation of a cleavable C-terminal His-tag on the Ub acceptor, the entire process of chain building, iterative Abac deprotections, and global Aboc cleavage can be conducted on a resin support, obviating the need for handling and purification of the intermediate oligomers. Simple modulation of the Ub monomers affords various K48/K63 branched chains, including tetramers and pentamers not previously accessible by synthetic or biochemical methods.

Recyclable dual-curing thiol-isocyanate-epoxy vitrimers with sequential relaxation profiles

Two series of poly(thiourethane)s-poly(thiol-epoxy) hybrids were prepared from dual-curing, stoichiometric thiol:isocyanate:epoxy mixtures. 1-methylimidazole (MI) was used as initiator for the thiol-isocyanate and thiol-epoxy curing reactions. A salt of tetraphenylborate derived from highly basic amine 1,5,7 triazabicyclo [4,4,0]dec-5-ene (TBD) was used as catalyst for the activation of bond exchange reactions. The curing kinetics and the glass transition temperature (Tg) of the samples were studied by differential scanning calorimetry (DSC). Thermal stability was characterized by thermogravimetric analysis (TGA). Stress relaxation dynamics related to the bond exchange reactions were studied by dynamic mechanical analysis (DMA). Recyclability of the fully cured samples according to the DMA results was carried out by hot-pressing at elevated temperatures. The results show that the curing process takes place in a controlled and sequential way: the thiol-isocyanate reaction takes place first, at moderate temperatures, followed by the thiol-epoxy reaction, which is completed at higher temperatures. The analysis of stress relaxation evidences a complex two-step relaxation behavior depending on the contribution of isocyanate and epoxy groups to the mixture. Isocyanate-rich materials show a simple relaxation process corresponding to the trans-thiocarbamoylation exchange reactions. Epoxy-rich materials show, in contrast, a two-step relaxation processes evidencing that trans-thiocarbamoylation alone may not be sufficient to relax the stress completely, due to an apparently permanent network structure. However, complete stress relaxation is possible for epoxy-rich materials through additional bond exchange reactions such as transesterification or dynamic thiol-Michael, but at a slower rate. Depending on the composition and the temperature, full recycling of the material can be achieved at moderate temperatures in a timescale of minutes to hours.

A Route to Potent, Selective, and Biased Salvinorin Chemical Space.

The salvinorins serve as templates for next generation analgesics, antipruritics, and dissociative hallucinogens via selective and potent agonism of the kappa-opioid receptor (KOR). In contrast to most opioids, the salvinorins lack basic amines and bind with high affinity and selectivity via complex polyoxygenated scaffolds that have frustrated deep-seated modification by synthesis. Here we describe a short asymmetric synthesis that relies on a sterically confined organocatalyst to dissociate acidity from reactivity and effect Robinson annulation of an unactivated nucleophile/unstable electrophile pair. Combined with a cobalt-catalyzed polarized diene-alkyne cycloaddition, the route allows divergent access to a focused library of salvinorins. We appraise the synthesis by its generation of multiple analogs that exceed the potency, selectivity, stability, and functional bias of salvinorin A itself.

Nonacid Carbon Materials as Catalysts for Monoethanolamine Energy-Efficient Regeneration.

In the CO2 capture process, solid acid catalysts have been widely adopted to decrease energy consumption in the amine regeneration process owing to abundant acid sites. However, acid sites unavoidably degenerate in the basic amine solution. To address the challenge, nonacid carbon materials including carbon molecular sieves, porous carbon, carbon nanotubes, and graphene are first proposed to catalyze amine regeneration. It is found that carbon materials can significantly increase the CO2 desorption amount by 47.1-72.3% and reduce energy consumption by 32-42%. In 20 stability experiments, CO2 loading was stable with the max difference value of 0.01 mol CO2/mol monoethanolamine (MEA), and no obvious increase in the relative heat duty (the maximum difference is 4%) occurred. The stability of carbon materials is superior to excellent solid acid catalysts, and the desorption performance is comparable. According to the results of theoretical calculation and experimental characterization, the electron-transfer mechanism of nonacid carbon materials is proposed, which is not only beneficial for MEA regeneration but also the probable reason for the stable catalytic activity. Owing to the excellent catalytic performance of carbon nanotube (CNT) in the HCO3- decomposition, nonacid carbon materials are quite promising to enhance the desorption performance of novel blend amines, which will further reduce the cost of carbon capture in the industry. This study provides a new strategy to develop stable catalysts used for amine energy-efficient regeneration.

Discovery of a Series of Indane-Containing NBTIs with Activity against Multidrug-Resistant Gram-Negative Pathogens.

The rise of multidrug-resistant (MDR) Gram-negative bacteria is a major global health problem necessitating the discovery of new classes of antibiotics. Novel bacterial topoisomerase inhibitors (NBTIs) target the clinically validated bacterial type II topoisomerases with a distinct binding site and mechanism of action to fluoroquinolone antibiotics, thus avoiding cross-resistance to this drug class. Here we report the discovery of a series of NBTIs incorporating a novel indane DNA binding moiety. X-ray cocrystal structures of compounds 2 and 17a bound to Staphylococcus aureus DNA gyrase-DNA were determined, revealing specific interactions with the enzyme binding pocket at the GyrA dimer interface and a long-range electrostatic interaction between the basic amine in the linker and the carboxylate of Asp83. Exploration of the structure-activity relationship within the series led to the identification of lead compound 18c, which showed potent broad-spectrum activity against a panel of MDR Gram-negative bacteria.

Methylene blue as an additive for acid-acid-catalyzed tandem reactions targeting on the synthesis of nitrogen-containing heterocycles

Methylene blue (MB) was proven to be an effective and amine-compatible additive for helping the establishment of some acid-acid-catalyzed tandem reactions. Addition of MB to acid-catalyzed reaction system not only allowed the use of some basic amines as substrates, which are generally incompatible with the acid conditions, but also enabled the successful synthesis of many important nitrogen-containing heterocycles, such as β-carbolines, pyridines, and quinazolines, in a straightforward manner.

General cross-coupling reactions with adaptive dynamic homogeneous catalysis.

Cross-coupling reactions are among the most important transformations in modern organic synthesis1-3. Although the range of reported (het)aryl halides and nucleophile coupling partners is very large considering various protocols, the reaction conditions vary considerably between compound classes, necessitating renewed case-by-case optimization of the reaction conditions4. Here we introduce adaptive dynamic homogeneous catalysis (AD-HoC) with nickel under visible-light-driven redox reaction conditions for general C(sp2)-(hetero)atom coupling reactions. The self-adjustive nature of the catalytic system allowed the simple classification of dozens of various classes of nucleophiles in cross-coupling reactions. This is synthetically demonstrated in nine different bond-forming reactions (in this case, C(sp2)-S, Se, N, P, B, O, C(sp3, sp2, sp), Si, Cl) with hundreds of synthetic examples under predictable reaction conditions. The catalytic reaction centre(s) and conditions differ from one another by the added nucleophile, or if required, a commercially available inexpensive amine base.

Coupling coloration of meta‐aramid fabric utilising diazonium salts from weakly basic aromatic amines

AbstractMeta‐aramid fibre exhibits poor dyeing performance when treated using conventional dyeing methods. In this study, coloration of meta‐aramid fabrics was performed at room temperature utilising diazonium salts from weakly basic aromatic amines and was achieved via in situ construction of azo chromophores on the meta‐phenylenediamine moiety. To promote diazonium‐salt penetration into the meta‐aramid fibre, the pretreatment of meta‐aramid fabrics with dimethyl sulfoxide at 55°C for 30 min and the utilisation of methanol were involved during the coloration process. As a result, the fabrics could be coloured with deep, levelled and firm shades of brown series. The azo chromophore is derived from the skeleton of the polyamide chain. Therefore, the coloured fabrics exhibit good resistance to organic solvents as well as good to excellent colour fastness to soaping, rubbing and sublimation. A study of the coloration mechanism revealed that the terminal and middle meta‐phenylenediamine moieties serve as the main coupling reaction sites. When treated with a diazonium salt, the highly reactive terminal meta‐phenylenediamine moiety reacted first and generated chromophores with an absorption peak in the long‐wavelength region. However, such chromophores only contributed a limited colour depth owing to the limited number of the terminals. If excess diazonium salts were used, the main hue can be attributed to the azo chromophores based on the massive middle meta‐phenylenediamine moieties, although these moieties are less reactive than the terminal meta‐phenylenediamine moieties.

Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs

Phosphorus Fluoride Exchange (PFEx) represents a cutting-edge advancement in catalytic click-reaction technology. Drawing inspiration from Nature's phosphate connectors, PFEx facilitates the reliable coupling of P(V)-F loaded hubs with aryl alcohols, alkyl alcohols, and amines to produce stable, multidimensional P(V)-O and P(V)-N linked products. The rate of P-F exchange is significantly enhanced by Lewis amine base catalysis, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). PFEx substrates containing multiple P-F bonds are capable of selective, serial exchange reactions via judicious catalyst selection. In fewer than four synthetic steps, controlled projections can be deliberately incorporated along three of the four tetrahedral axes departing from the P(V) central hub, thus taking full advantage of the potential for generating three-dimensional diversity. Furthermore, late-stage functionalization of drugs and drug fragments can be achieved with the polyvalent PFEx hub, hexafluorocyclotriphosphazene (HFP), as has been demonstrated in prior research.

Monitoring food quality ‐ effect of curcumin in the development of polyethylene/thermoplastic starch based smart packaging

AbstractSmart packaging relies on the one‐to‐one interaction of food with its packaging or its environment to monitor food quality and safety. Colorimetric pH indicators (synthetic, natural) working in a smart food packaging system are particularly striking when used with fresh foodstuffs such as fish and meat that perish quickly and require real‐time freshness monitoring. In this study, curcumin (Cur) was used as a natural pH indicator to produce sustainable smart packaging material. Towards this objective, low‐density polyethylene (LDPE) and thermoplastic starch (TPS) blend‐based films containing Cur were prepared using a twin screw extrusion and hot‐pressing processes. Besides, two different compositions of LDPE/TPS mixture (50/50 and 70/30) were used as the matrix. Thermal, mechanical, morphological properties, an affinity for water, and color change properties of LDPE/TPS/Cur films were investigated. They showed a significant color change from yellow to brown at pH: 10 at the end of the seventh day, especially in the 50 LDPE/50 TPS mixture. 50 LDPE/50 TPS mixture with 7% curcumin content gave the highest tensile strength of 8.03 Mpa. When the same mixture was used to monitor chicken meat spoilage at 25°C, meat samples have shown color changes from light yellow to light brown due to the increased content of total volatile basic amines. As a result, it has been suggested that 50 LDPE/50 TPS mixture containing 7% Cur can be used as a smart packaging material.

Lysosomal trapping of 4-dimethylamino-1-{3-(1-methyl-1H-imidazole-2-yl)propanoyl}piperidine, a hydrophilic and weakly basic amine, in human aortic vascular smooth muscle cells

Some weakly basic compounds lead to cell death accompanied by cellular vacuolation. The novel analgesic agent, 4-dimethylamino-1-{3-(1-methyl-1H-imidazole-2-yl)propanoyl}piperidine (DMIP), is a hydrophilic and weakly basic compound that induces vacuolation in the vascular smooth muscle cells in dogs. Here, we investigated the vacuolation mechanism and the potential cytotoxicity of DMIP using human aortic vascular smooth muscle cells. When cells were treated with DMIP (0.1, 0.3, and 1 mM) for 6, 24, and 48 h, clear cytoplasmic vacuolation was observed at 1 mM after 24 and 48 h, along with an increase in the intracellular DMIP concentration. The vacuolation and intracellular DMIP were markedly reduced by bafilomycin A1, a vacuolar H+-ATPase inhibitor. The late endosome marker Rab7 and lysosome marker LAMP-2 were highly expressed but the early endosome marker Rab5 and autophagosome marker LC3 were not expressed specifically on the vacuolar membranes. These results suggested that the most vacuoles were enlarged late endosomes/lysosomes, resulting from the accumulation of DMIP by ion trapping. Moreover, DMIP did not affect lysosomal membrane integrity and was less cytotoxic than chloroquine, an inducer of phospholipidosis. The current study provides further insight into the mechanisms of vacuolation and lysosomal trapping induced by the hydrophilic and weakly basic amine DMIP.

How Chemical Nature of Fixed Groups of Anion-Exchange Membranes Affects the Performance of Electrodialysis of Phosphate-Containing Solutions?

Innovative ion exchange membranes have become commercially available in recent years. However, information about their structural and transport characteristics is often extremely insufficient. To address this issue, homogeneous anion exchange membranes with the trade names ASE, CJMA-3 and CJMA-6 have been investigated in NaxH(3-x)PO4 solutions with pH 4.4 ± 0.1, 6.6 and 10.0 ± 0.2, as well as NaCl solutions with pH 5.5 ± 0.1. Using IR spectroscopy and processing the concentration dependences of the electrical conductivity of these membranes in NaCl solutions, it was shown that ASE has a highly cross-linked aromatic matrix and mainly contains quaternary ammonium groups. Other membranes have a less cross-linked aliphatic matrix based on polyvinylidene fluoride (CJMA-3) or polyolefin (CJMA-6) and contain quaternary amines (CJMA-3) or a mixture of strongly basic (quaternary) and weakly basic (secondary) amines (CJMA-6). As expected, in dilute solutions of NaCl, the conductivity of membranes increases with an increase in their ion-exchange capacity: CJMA-6 < CJMA-3 << ASE. Weakly basic amines appear to form bound species with proton-containing phosphoric acid anions. This phenomenon causes a decrease in the electrical conductivity of CJMA-6 membranes compared to other studied membranes in phosphate-containing solutions. In addition, the formation of the neutral and negatively charged bound species suppresses the generation of protons by the "acid dissociation" mechanism. Moreover, when the membrane is operated in overlimiting current modes and/or in alkaline solutions, a bipolar junction is formed at the CJMA- 6/depleted solution interface. The CJMA-6 current-voltage curve becomes similar to the well-known curves for bipolar membranes, and water splitting intensifies in underlimiting and overlimiting modes. As a result, energy consumption for electrodialysis recovery of phosphates from aqueous solutions almost doubles when using the CJMA-6 membrane compared to the CJMA-3 membrane.

Intermolecular Acid–Base‐Pairs Containing Poly (p‐Terphenyl‐co‐Isatin Piperidinium) for High Temperature Proton Exchange Membrane Fuel Cells

How to optimize and regulate the distribution of phosphoric acid in matrix, and pursuing the improved electrochemical performance and service lifetime of high temperature proton exchange membrane (HT‐PEMs) fuel cell are significant challenges. Herein, bifunctional poly (p‐terphenyl‐co‐isatin piperidinium) copolymer with tethered phosphonic acid (t‐PA) and intrinsic tertiary amine base groups are firstly prepared and investigated as HT‐PEMs. The distinctive architecture of the copolymer provides a well‐designed platform for rapid proton transport. Protons not only transports through the hydrogen bond network formed by the adsorbed free phosphoric acid (f‐PA) anchored by the tertiary amine base groups, but also rely upon the proton channel constructed by the ionic cluster formed by the t‐PA aggregation. Thorough the design of the structure, the bifunctional copolymers with lower PA uptake level (&lt;100%) display prominent proton conductivities and peak power densities (99 mS cm−1, 812 mW cm−2 at 160 °C), along with lower PA leaching and higher voltage stability, which is a top leading result in disclosed literature. The results demonstrate that the design of intermolecular acid–base‐pairs can improve the proton conductivity without sacrificing the intrinsic chemical stability or mechanical property of the thin membrane, realizing win‐win demands between the mechanical robustness and electrochemical properties of HT‐PEMs.

Light-Promoted Ni-Catalyzed Cross-Coupling of Aryl Chlorides with Hydrazides: Application to the Synthesis of Rizatriptan.

A general and highly efficient photochemical C-N coupling reaction of challenging (hetero)aryl chlorides with hydrazides is reported. Catalyzed by a Ni(II)-bipyridine complex, this reaction provides an efficient tool for the synthesis of arylhydrazines in the presence of a soluble organic amine base without an external photosensitizer. The reaction features a wide substrate range (54 examples) and excellent functional group tolerance. The method has also been successfully applied to the three-step concise synthesis of rizatriptan, an effective drug for migraine and cluster headaches.

Discovery of blood–brain barrier permeant amine-functionalized aurones as inhibitors of activated microglia

Sulfuretin, a naturally occurring aurone is reported to inhibit macrophage and microglia activation. A series of aurones incorporating basic amines and lipophilic functionalities at ring A and/or ring B were synthesized to improve upon present sulfuretin activity towards targeting brain microglia while overcoming the blood–brain barrier (BBB). Evaluation of the ability of the aurones to inhibit lipopolysaccharide (LPS)-stimulated nitric oxide (NO) secretion by murine BV-2 microglia has identified several inhibitors showing significant NO reduction at 1 to 10 µM. Potent inhibitors were represented by aurones with bulky, planar moieties at ring A (3f) or at ring B (1e and 1f) and having a pendant piperidine at ring B (1a, 2a, 2b, and 3f). The active aurones inhibited the BV-2 microglia polarizing towards the M1 state as indicated by attenuation of IL-1β and TNF-α secretions in LPS-activated microglia but did not induce the microglia towards the M2 state. The aurones 2a, 2b, and 1f showed high passive BBB permeability in the parallel artificial membrane permeability assay (PAMPA) owing to their optimal lipophilicities. 2a, being non-cell toxic, BBB permeant and potent, represents a new lead for the development of aurones as inhibitors of activated microglia.

Stimuli Response of Eu3+-Based Metallo-Supramolecular Polymers toward Pharmaceutical Amines.

Metallo-supramolecular polymers offer a highly controllable platform for sensing. Their modular characteristics obtained by the ability of varying both building blocks, the metal ion and the organic ligand, provide tunability of their optical and chemical properties. Specifically, polymers based on lanthanide ions and conjugated aromatic ligands exhibit enhanced luminescence properties that can be altered by external stimulation. Herein, using europium-based polymers, we demonstrate the ability to detect different pharmaceutical amines, including in complex biological media, based on their luminescence quenching efficiency as a result of their polymer dissociation capacity. A combination of absorption, luminescence, and NMR measurements reveals combined static and dynamic quenching mechanisms that enable selective sensing of strong basic amines with high pKa values.