Basic Amine Research Articles

The reaction of thionyl chloride with β amino alcohols: A computational investigation to delineate the mechanisms of the well-established synthesis that forms the 1-chloro-(2-alkylamino)ethanes and the 1,2,3 alkyloxathiazolidine-2-oxide compounds

The substitution reaction mechanism of β-amino alcohols and thionyl chloride to form the 1-chloro-(2-alkylamino)ethane and the 1,2,3-alkyloxathiazolidine-2-oxide products was investigated using computational methods. The reactions that result in these compounds are very similar, they both use the N-(2-alkyl/arylamino)ethanols and thionyl chloride, however the synthesis of 1,2,3-alkyl/aryloxathiazolidine-2-oxide requires the use of an amine base, which quite commonly results in a purer product, not a different compound as is the case here. The mechanism of the formation of 1-chloro-(2-alkylamino)ethanes, involves the formation of a quaternary nitrogen species as one of the first steps. This step has a low relative energy barrier and occurs readily. It occurred in the reaction of all substituents tested except for the methyl and phenyl substituents. Based on this work it was demonstrated that the amine base is not actually needed to form the 1,2,3-alkyl/aryloxathiazolidine-2-oxide. Experimental reactions to produce the 1-chloro-(2-alkylamino)ethanes were performed and the products were characterized by 1H and 13C-NMR and GC-MS. The GC-MS experimental results supported the computational results, in that trace amounts of the 1,2,3-oxathiazolidine-2-oxides were found in the residue of this reaction. This demonstrated that the 1,2,3-oxathiazolidine -2-oxides can be formed in trace amounts without a base. The base would be required to make the 1,2,3-alkyloxathiazolidine-2-oxides in higher yields. The computational chemistry results demonstrate that the amine base suppresses the quaternization of the nitrogen by reacting preferentially with the acidic protons, which is the normal mode of action of the amine base in thionyl chloride reactions.

Photoinduced Catalytic Alkylation of Active Methine Compounds with Nonactivated Alkenes Using Yttrium Triflate as a Lewis Acid Catalyst

Photoinduced catalytic alkylation reactions of active methine compounds with nonactivated alkenes have been developed using an organophotocatalyst, a metal Lewis acid, an arylthiol, and an amine base catalyst system. The alkylation reactions proceeded smoothly under ambient conditions with blue light irradiation, affording the desired products bearing quaternary carbon centers in high yields. Furthermore, enantioselective alkylation with an nonactivated alkene was achieved using a chiral Lewis acid.

A General Platform for Copper-Catalyzed Atom Transfer Radical Addition with Electron-Deficient Olefins.

We disclose a broad platform for copper-catalyzed atom transfer radical addition (ATRA) of electron-deficient olefins. Catalytic Cu(dtbbpy)2(OTf)2 enables radical addition of electron-deficient alkyl halides to acrylates, acrylamides, and vinyl sulfones in fair to excellent yields. The resultant ATRA products can be used in a variety of telescoped reactions, including substitution with basic amine nucleophiles to afford α-amino esters. The synthetic utility of the products is further demonstrated through derivatization to give substituted cyclopropanes and a γ,δ-unsaturated ester.

Supramolecular pre‐organisation rhodium and iridium metal complexes within M12L24 self‐assembled nanospheres for the confined synthesis Rh/Ir alloyed nanoparticles

Controlling the size and composition of metal nanoparticles is of considerable interest, as these are essential to their catalytic properties. We report the controlled synthesis Rh nanoparticles by preorganisation of metal complexes inside Pt12L24 nanospheres based on complementary hydrogen bonds before the reduction step that leads to nanoparticle formation. The encapsulated RhI complexes (Rh‐s @ G‐sphere) led to reasonable size control (2.8 ± 0.9 nm). We also report the formation of Rh‐Ir alloyed nanoparticles with varying Rh/Ir compositions. These heterometallic particles were evaluated in the hydrogenation of cinnamaldehyde (7) as a probe reaction. Besides a high activity in this probe reaction, the Rh particles also catalyzed the conversion of the solvent (CH3CN). The formed basic amine leads to follow‐up reactions of the product and compatibility issues with the hosting nanosphere. The solvent hydrogenation was effectively suppressed by using the Rh:Ir alloyed nanoparticles, provided that they contain >66% Ir. The Rh:Ir alloyed nanoparticles displayed high catalytic activity, reaching optimal selectivity and activity at an 8:16 ‐ Rh:Ir ratio. The combined catalytic results illustrate that pre‐organisation of the metal complexes in the nanosphere before the reduction with hydrogen effectively facilitates the formation of Rh:Ir alloyed nanoparticles.

Discovery of a novel, selective CK2 inhibitor class with an unusual basic scaffold

CK2 is a Ser/Thr-protein kinase playing a crucial role in promoting cell growth and survival, hence it is considered a promising target for anti-cancer drugs. However, many previously reported CK2 inhibitors lack selectivity. In search of novel scaffolds for selective CK2 inhibition, we identified a dihydropyrido-thieno[2,3-d]pyrimidine derivative displaying submicromolar inhibitory activity against CK2α. This scaffold captured our interest because of the basic secondary amine, a rather unusual motif for CK2 inhibitors. Our optimization strategy comprised the incorporation of a 4-piperazinyl moiety as a linker group and introduction of varying substituents on the pendant phenyl ring. All resulting compounds exhibited potent CK2α inhibition, with IC50 values in the nanomolar range. Compound 10b demonstrated the most balanced activity profile with a cell-free IC50 value of 36.7 nM and a notable cellular activity with a GI50 of 7.3 μM and 7.5 μM against 786-O renal cell carcinoma and U937 lymphoma cells, respectively. 10b displayed excellent selectivity when screened against a challenging kinase selectivity profiling panel. Moreover, 10b inhibited CK2 in the cells, albeit less potently than CX-4945, but induced cell death more strongly than CX-4945. Altogether, we have identified a novel CK2 inhibitory scaffold with drug-like physicochemical properties in a favorable basic pKa range.

Design, synthesis, and evaluation of antitumor activity of quinazoline derivatives containing different terminal segments of basic amine groups

Design, synthesis, and evaluation of antitumor activity of quinazoline derivatives containing different terminal segments of basic amine groups

Molybdenum Complex-Catalyzed N-Alkylation of Bulky Primary and Secondary Amines.

Aliphatic allylic amines are present in a large number of complex and pharmaceutically relevant molecules. The direct amination of allylic electrophiles serves as the most common method toward the preparation of these motifs. However, the use of feedstock reaction components (allyl alcohol and aliphatic amine) in these transformations remains a great challenge. Such a challenge primarily stems from the high Lewis basicity and large steric hindrance of aliphatic amines, in addition to the low reactivity of allylic alcohols. Herein, we report a general solution to these challenges. The developed protocol allows an efficient allylic amination of allyl alcohols with sterically bulky aliphatic amines in the presence of an inexpensive earth-abundant molybdenum complex. This simple and economic protocol also enables regioselective branched amination; the practicality of the reaction was shown in an efficient, scaled-up synthesis of several drugs.

Hydroaminoalkylation for Amine Functionalization of Vinyl‐Terminated Polyethylene Enables Direct Access to Responsive Functional Materials

AbstractWhile functionalized polyethylenes (PEs) exhibit valuable characteristics, the constraints of existing synthetic approaches limit the variety of readily incorporated functionality. New methods to generate functionalized PEs are required to afford new applications of this common material. We report 100 % atom economic tantalum‐catalyzed hydroaminoalkylation of vinyl‐terminated polyethylene (VTPE) as a method to produce amine‐terminated PE. VTPEs with molecular weights between 2200–16800 g/mol are successfully aminated using solvent‐free conditions. Our catalytic system is efficient for the installation of both aromatic and aliphatic amines, and can be carried out on multigram scale. The associating amine functional groups afford modified material properties, as measured by water contact angle, differential scanning calorimetry (DSC) and polymer rheology. The basic amine functionality offers the opportunity to convert inert PE into stimuli‐responsive materials, such that the protonation of aminated PE affords the generation of functional antibacterial PE films.

Hydroaminoalkylation for Amine Functionalization of Vinyl-Terminated Polyethylene Enables Direct Access to Responsive Functional Materials.

While functionalized polyethylenes (PEs) exhibit valuable characteristics, the constraints of existing synthetic approaches limit the variety of readily incorporated functionality. New methods to generate functionalized PEs are required to afford new applications of this common material. We report 100 % atom economic tantalum-catalyzed hydroaminoalkylation of vinyl-terminated polyethylene (VTPE) as a method to produce amine-terminated PE. VTPEs with molecular weights between 2200-16800 g/mol are successfully aminated using solvent-free conditions. Our catalytic system is efficient for the installation of both aromatic and aliphatic amines, and can be carried out on multigram scale. The associating amine functional groups afford modified material properties, as measured by water contact angle, differential scanning calorimetry (DSC) and polymer rheology. The basic amine functionality offers the opportunity to convert inert PE into stimuli-responsive materials, such that the protonation of aminated PE affords the generation of functional antibacterial PE films.

Overcoming strong retention barriers of A- and V-series nerve agents on silica sorbents

The present study explores the potential of silica solid phase extraction for gas chromatography mass spectrometric analyses of A- and V-series nerve agents. Owing to the presence of basic amidine and amine moieties, these analyte undergo strong ionic interactions with inherently acidic silica surfaces, producing poor recoveries. Subtle optimizations in the elution composition empowered the analytes to overcome the retention barriers from sorbent surfaces. Acetone containing 10 % (v/v) NH4OH effectively minimized strong analyte-sorbent interactions allowing good to excellent recoveries. Recoveries for A-series agents ranged from 88 to 96 %. VX, which is reported to be poorly recoverable from such sorbent matrices offered best data so far, reaching up to 74 % under optimized conditions. The method detection limits for the selected analytes in mass spectrometric analysis ranged from 47 to 171 ng/ml. Strong affinities of analytes towards silica sorbent were further exploited to expand the scope of analysis and establish the method's efficacy for a wide range of organic matrices. The applicability of the method to the real world applications was also validated in blind spiking exercises in diverse organic liquid samples received in 48th, 50th and 52nd proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW).

Mechanism and Origins of Nucleophile‐Controlled Regioselectivity of Palladium‐Catalyzed Allylic C−H Amination of 1,4‐Dienes: A Computational Study

AbstractDensity functional theory calculations have been conducted to investigate the palladium‐catalyzed allylic C−H amination of 1,4‐dienes with commonly available amines. The computations indicate that the reaction begins with the allylic C−H bond cleavage through the concerted proton and two‐electron transfer process to forge the η3‐allyl Pd(II) species. The ensuing C−N bond formation was found to be highly dependent on the basicity of the nucleophile, enabling the regioselectivity switch upon change of the nucleophile. With the weakly basic aromatic amine, the reaction occurs through the hydrogen‐bonding enabled inner‐sphere nucleophilic attack pathway. The distance between the reacting carbon atom and the terminal carbon atom is responsible for the Z/E‐selectivity. The regioselectivity is primarily due to steric repulsion between the allyl group and the ligand. On the other hand, the outer‐sphere nucleophilic attack pathway is favored for the reaction with the more basic aliphatic cyclic amine. The change of the coordinating mode of the allylic moiety was found to play a crucial role in determining the regioselectivity.

RETRACTION: Aggregation‐Induced Emission‐Active Donor‐Substituted Aroyl‐S,N‐Ketene Acetals via Nucleophilic Amine Base Attack

AbstractRetraction: L. Biesen, T.J.J. Müller, “Aggregation‐Induced Emission‐Active Donor‐Substituted Aroyl‐S,N‐Ketene Acetals via Nucleophilic Amine Base Attack”, ChemPhotoChem 2023, 7, e202300111, https://doi.org/10.1002/cptc.202300111.The above article, published online on 25 August 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor‐in‐Chief, Deanne Nolan; Chemistry Europe; and Wiley‐VCH GmbH. The retraction has been agreed at the request of the authors, who informed the editor of significant errors in the structural assignment of compounds 3a, 3c and 3e, in addition to instrumental error affecting solid state and aggregate quantum yield measurements. As a result, the conclusions reported in the article are not considered reliable.

Hydride Shuttle Catalysis: From Conventional to Inverse Mode.

Hydride shuttle catalysis has emerged as a powerful synthetic platform, enabling the selective formation of C-C bonds to yield sp3-rich structures. By virtue of the compelling reactivity of sterically encumbered Lewis acids from the frustrated Lewis pair regime, hydride shuttle catalysis enables the regioselective functionalization of alkyl amines at either the α- or β-position. In contrast to classical Lewis acid reactivity, the increased steric hindrance prevents interaction with the Lewis basic amine itself, instead leading to reversible abstraction of a hydride from the amine α-carbon. The created positive charge facilitates the occurrence of transformations before hydride rebound or a similar capture event happen. In this Perspective, we outline a broad selection of transformations featuring hydride shuttle catalysis, as well as the recently developed approach of inverse hydride shuttle catalysis. Both strategies give rise to a wide array of functionalized amines and offer elegant approaches to otherwise elusive bond formations.

Quantitative recovery and regeneration of basic deep eutectic solvent for biomass treatment with industrialized membrane-based strategy

As a new type of ionic liquids, basic deep eutectic solvents have been reported as emerging medium for biorefinery, extraction, catalysis and so on. Quantitative recovery with recycling of basic DES was important for the scale utilization of biomass and the environmental conservation. An electrodialysis-based method was designed for divisionally regenerating basic DES choline chloride-monoethanol amine (ChCl-MEA) after pretreatment of wheat straw. Influence of primary process parameters on recovery of ChCl-MEA was studied and recovery economy of ChCl-MEA was analyzed. Recovery ratio of ChCl and MEA varied within 89.2 %-96.0 % and 93.3 %-97.9 %. Energy consumption of ChCl-MEA recovery changed within 4.2–29.4 kW·h/kg. Transport rate of basic DES ChCl-MEA altered in the range of 12.2–464.7 mmol/(m2·min). Process economy analysis proved that recovery cost of basic DES ChCl-MEA was less than 7 % (0.81–7.07 $/kg) of DES purchase cost. Insight brought by this study indicated a technically feasible and economical approach for basic DES recycling after biomass pretreatment.

Sulfur-Promoted Access to 3-Arylquinoxalin-2-ones by Oxidative Coupling of o-Phenylenediamines with Arylacetates.

We disclose the synthesis of 3-arylquinoxalin-2-ones from o-phenylenediamines and readily available arylacetates. The method harnesses the selective oxidative property of elemental sulfur in the presence of amine base catalyst and DMSO. The reactions are operationally simple and tolerate a wide range of functional groups.

Repellency, toxicity, and physiological actions of low molecular weight basic amines in mosquitoes.

This study investigated the behavioral responses and toxicity of three basic amines: 1-methylpiperazine, 1-methylpyrrolidine, and triethylamine (TEA), compounds suggested previously to be anosmic in vapor exposures to caged mosquitoes. These compounds showed repellency of Aedes aegypti mosquitoes, followed by flightlessness, knockdown, and paralysis, all increasing with exposure time and dosage. Electrophysiological experiments showed a blocking effect on nerve discharge of the Drosophila melanogaster larval central nervous system (CNS) with little evidence of hyperexcitation. Blockage of voltage-gated (Kv2) potassium channel currents under patch clamp occurred at similar concentrations. Involvement of K+ channels in the action of basic amines was supported by behavior and CNS recordings of a Shaker Kv1 mutant exposed to TEA, where instead of blockage, a hyperexcitation of nerve firing was observed. Experiments on cockroach leg mechanoreceptors demonstrated neuronal excitation and on mosquito antennae strong electroantennogram (EAG) signals with an augmentation of blank air responses after a single puff of basic amine. The neurophysiological effects of basic amines are consistent with K+ channel block, whereas the antennal EAG response was not obviously associated with anosmia. The low-dose effects of basic amines appear to be repellency and bradykinesia. Overall, the findings provide key insights into the mechanisms underlying the biological activity of basic amines. © 2024 Society of Chemical Industry.

Characterization of Germanium Nanoparticles from Arylgermanium Trihydrides.

Germanium is a promising basis for nanomaterials due to its low toxicity and valuable optical and electronic properties. However, germanium nanomaterials have seen little research compared to other group 14 elements due to unpredictable chemical behavior and high costs. Here, we report the dehydrocoupling of o-tolylgermanium trihydride to amorphous nanoparticles. The reaction is facilitated through reflux at 162 °C and can be accelerated with an amine base catalyst. Through cleavage of both H2 and toluene, new Ge-Ge bonds form. This results in nanoparticles consisting of crosslinked germanium with o-tolyl termination. The particles are 2-6 nm in size and have masses above approximately 3500 Da. The organic substituents are promising for further functionalization. Combined with strong absorption up to 600 nm and moderate solubility and air stability, there are numerous possibilities for future applications.

Reactivity of diethyl benzylidenemalonates with secondary cyclic amine dimers in acetonitrile: Structure-reactivity relationships and mechanism

We report on a kinetic study for the nucleophilic addition reactions of diethyl 4-X-substituted benzylidenemalonates 1a-c (X = N(CH3)2, OCH3 and CH3) with N-nucleophiles, such as morpholine 2a, piperidine 2b and pyrrolidine 2c by UV–vis spectroscopy in acetonitrile solution at 20 °C. The Hammett plots demonstrate much better linear correlations with σp+ constants than with σp constants. These results are best interpreted in terms of ground state stabilization through resonance interactions between the electron-donating substituent and the CO2Et group. The effect of amine basicity on the reaction rate was examined quantitatively, leading to linear correlations with high βnuc values in the 0.82–0.93 range. The origin of the abnormally high βnuc values was interpreted in terms of dimer mechanism. Finally, with the help of our new proposed linear free energy relationship log k1K (20 °C) = sN (E + N) + log K, the stability of the dimer amines (K) have been evaluated from the measured apparent second-order rate constant (k1K) and the previously reported E, N and sN parameters of the employed electrophiles 1a-c and nucleophiles 2a-c. Additionally, a complementary theoretical study utilizing Density Functional Theory (DFT) with the B3LYP/6-311g(d,p) method was conducted in acetonitrile. An attempt is made to establish the correlation between equilibrium constant and stabilization energy the studied systems.

Retraction Note: Metal free cross-dehydrogenative N-N coupling of primary amides with Lewis basic amines

Retraction Note: Metal free cross-dehydrogenative N-N coupling of primary amides with Lewis basic amines

Comparative Assessment of Amine-Based Absorption and Calcium Looping Techniques for Optimizing Energy Efficiency in Post-Combustion Carbon Capture

<p>The escalating levels of atmospheric CO2 have underscored the necessity for developing effective carbon capture and storage (CCS) technologies. This study investigates the advancements in post-combustion CO2 capture technologies, specifically examining the efficiency of amine-based absorption and calcium looping methods. Amine absorbents were synthesized using three amino acids—Lysine, Alanine, and Arginine—supplemented with and without NaOH/KOH additives. Absorption trials were conducted in a bench-scale column across a range of temperatures. The calcium looping process involved repeated carbonation and calcination cycles using CaO to capture and release CO2. A statistical analysis employing ANOVA, was utilized to determine the influence of variables such as amine concentration, base concentration, and temperature on the efficiency of CO2 absorption. The study found that Lysine-based absorbents, adding NaOH, achieved a CO2 capture rate of up to 75% at a temperature of 30°C. Additionally, the calcium looping method exhibited consistent cyclic capacities for over 25 cycles, with a regeneration energy requirement estimated at 3.5 GJ/ton of CO2. While the amine-based systems demonstrated higher capture rates, they also required significant energy for solvent regeneration. The statistical analysis confirmed that amine concentration, base concentration, and temperature are critical factors influencing the efficiency of CO2 absorption. The findings of this study underscore the potential of optimized amine solutions and calcium looping as viable strategies for post-combustion CO2 capture, contributing valuable insights that promote sustainable practices in climate change mitigation.</p>