Basic Amine Research Articles

4-(3-Aminoazetidin-1-yl)pyrimidin-2-amines as High-Affinity Non-imidazole Histamine H3 Receptor Agonists with in Vivo Central Nervous System Activity.

Despite the high diversity of histamine H3 receptor (H3R) antagonist/inverse agonist structures, partial or full H3R agonists have typically been imidazole derivatives. An in-house screening campaign intriguingly afforded the non-imidazole 4-(3-azetidin-1-yl)pyrimidin-2-amine 11b as a partial H3R agonist. Here, the design, synthesis, and structure–activity relationships of 11b analogues are described. This series yields several non-imidazole full agonists with potencies varying with the alkyl substitution pattern on the basic amine following the in vitro evaluation of H3R agonism using a cyclic adenosine monophosphate response element-luciferase reporter gene assay. The key compound VUF16839 (14d) combines nanomolar on-target activity (pKi = 8.5, pEC50 = 9.5) with weak activity on cytochrome P450 enzymes and good metabolic stability. The proposed H3R binding mode of 14d indicates key interactions similar to those attained by histamine. In vivo evaluation of 14d in a social recognition test in mice revealed an amnesic effect at 5 mg/kg intraperitoneally. The excellent in vitro and in vivo pharmacological profiles and the non-imidazole structure of 14d make it a promising tool compound in H3R research.

Modulation of Pharmacologically Relevant Properties of Piperidine Derivatives by Functional Groups in an Equatorial or Axial β-Position to the Amino Group.

Thirteen epimeric pairs of 5-substituted N-piperonyl-3-phenylpiperidine derivatives were synthesized in order to explore the stereospecific modulation of basicity, lipophilicity, aqueous solubility, and membrane permeation by functional groups in equatorial or axial positions beta to the amine unit. While this comprehensive data set provides enhanced insight into multiple factors that affect basicity and lipophilicity, it fills an important knowledge gap, providing a frame of reference for the property-based design of bioactive compounds. Impacts on amine basicity are very pronounced for the β-equatorial functional groups and parallel basicity-lowering effects known for acyclic amine derivatives. For β-axial functional groups, the basicity-lowering effects are generally decreased, with the nitrile group as the only exception. Basicity and lipophilicity modulations observed for β-axial functional groups are quite diverse and rationalized in terms of intramolecular hydrogen bonding, dipolar interactions, and special solvation effects. Aqueous solubility and (artificial) membrane permeability are discussed with reference to lipophilicity.

Controlled release of hydrogen isotope compounds and tunneling effect in the heterogeneously-catalyzed formic acid dehydrogenation

The hydrogen isotope deuterium is widely used in the synthesis of isotopically-labeled compounds and in the fabrication of semiconductors and optical fibers. However, the facile production of deuterium gas (D2) and hydrogen deuteride (HD) in a controlled manner is a challenging task, and rational heterogeneously-catalyzed protocols are still lacking. Herein, we demonstrate the selective production of hydrogen isotope compounds from a combination of formic acid and D2O, through cooperative action by a PdAg nanocatalyst on a silica substrate whose surface is modified with amine groups. In this process, D2 is predominantly evolved by the assist of weakly basic amine moieties, while nanocatalyst particles in the vicinity of strongly basic amine groups promote the preferential formation of HD. Kinetic data and calculations based on semi-classically corrected transition state theory coupled with density functional theory suggest that quantum tunneling dominates the hydrogen/deuterium exchange reaction over the metallic PdAg surfaces.

Synthesis, structural characterization and antimicrobial activities of triorganotin(IV)azo-carboxylates derived from ortho/para-amino benzoic acids and β-naphthol

Triorganotin (IV) complexes 1–3 were synthesized by the reaction of azo-carboxylic acid viz. 2/4-(2-hydroxynaphthylazo)benzoic acids with appropriate triorganotin(IV) chlorides [R = Me (compounds 1 and 2) and Bu (compound 3)] in presence of triethyl amine base. The complexes were characterized by elemental analysis, IR and multinuclear (1H and 13C- and 119Sn)-NMR spectroscopy. The structures and mode of coordination around tin ions in the complexes were determined by single crystal X-ray crystallography. The complexes exhibit trigonal bipyramidal geometry around tin atoms where the base of the equatorial plane is being occupied by the three alkyl groups [Me or Bu] while the axial positions are occupied by carboxylate oxygen atoms in 2 and in case of 1 and 3, by carboxylate and phenoxide oxygen atoms, respectively. It has been found that, the crystal structure of 1 or 3 is a cyclic dimeric, whereas 2 exhibits a polymeric structure. The 119Sn NMR studies show that all complexes have four-coordinate structures indicating dissociation of these complexes in solution state. The complexes were also screened for their antimicrobial activity and the compound 3 was found to exhibit effective antimicrobial activity.

Steam-Stable Basic Immobilized Amine Sorbent Pellets for CO2 Capture Under Practical Conditions.

Pelletization of basic immobilized amine sorbent (BIAS) particles is required to improve their mechanical strength and facilitate their practical CO2 capture application under fixed or dynamic reactor conditions. Herein, we utilized two methods to prepare amine-functionalized BIAS pellets. Method (ii-a) involved combining latex polychloroprene (PC)/polyamine solutions with fly ash (FA)/BIAS powder to form sorbent pellets. Alternatively, method (ii-b) entailed shaping and drying wet pastes of binder solution plus FA/SiO2 powder into pellet supports. These supports were then functionalized with leach-resistant polyethylenimine MW = 800 (PEI800)/N-N-diglycidyl-4-glycidyloxyaniline (tri-epoxide cross-linker, E3) or ethylenamine E100/E3 mixtures. All pellets were screened for CO2 capture by thermogravimetric analysis (dry 14% CO2/N2, 55-75 °C), H2O stability by accelerated water washing, and mechanical strength by crush and ball-mill attrition testing. The mechanism of superior method (ii-b) pellet formation was uncovered by N2 physisorption measurements, diffuse reflectance infrared Fourier transform spectroscopy, and scanning electron microscopy. Extended fixed bed testing of optimum E3/PEI800-0.13/1 pellets under practical conditions revealed complete CO2 capture stability of 1.5 mmol CO2/g after 48 h of continuous steam exposure (7.2% H2O/He, 105 °C) and minimal 14.6% loss in capacity after 75 hours of combined CO2 capture cycling and steam treating (48 h). This slight oxidative degradation could be alleviated by incorporating a K2CO3 antioxidant into the pellet formulation. Overall, the robust physiochemical properties of the polyamine/cross-linker method (ii-b) pellets confirm their suitability for pilot-scale testing.

Cooperative Tertiary Amine/Chiral Iridium Complex Catalyzed Asymmetric [4+3] and [3+3] Annulation Reactions

Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis. Nevertheless, the accomplishment of stereoselective annulations combining two types of dipole species, independently generated from the activations of organocatalysts and metal complexes, still remains as a challenging task. Now, Morita-Baylis-Hillman carbonates from isatins and carbamate-functionalized allyl carbonates could be chemoselectively activated by achiral Lewis basic tertiary amines and chiral iridium complexes. The zwitterionic allylic ylides and 1,4-π-allyliridium dipoles formed in situ are assembled in a highly stereoselective [4+3] annulation pattern. Similar cooperative catalytic strategy could be applied for the reactions of Morita-Baylis-Hillman carbonates and vinyl aziridines, furnishing an asymmetric [3+3] annulation reaction also with excellent stereocontrol.

Integrated CO2 Capture and Conversion to Formate and Methanol: Connecting Two Threads.

The capture of CO2 from concentrated emission sources as well as from air represents a process of paramount importance in view of the increasing CO2 concentration in the atmosphere and its associated negative consequences on the biosphere. Once captured using various technologies, CO2 is desorbed and compressed for either storage (carbon capture and storage (CCS)) or production of value-added products (carbon capture and utilization (CCU)). Among various products that can be synthesized from CO2, methanol and formic acid are of high interest because they can be used directly as fuels or to generate H2 on demand at low temperatures (<100 °C), making them attractive hydrogen carriers (12.6 and 4.4 wt % H2 in methanol and formic acid, respectively). Methanol is already produced in huge quantities worldwide (100 billion liters annually) and is also a raw material for many chemicals and products, including formaldehyde, dimethyl ether, light olefins, and gasoline. The production of methanol through chemical recycling of captured CO2 is at the heart of the so-called "methanol economy" that we have proposed with the late Prof. George Olah at our Institute. Recently, there has been significant progress in the low-temperature synthesis of formic acid (or formate salts) and methanol from CO2 and H2 using homogeneous catalysts. Importantly, several studies have combined CO2 capture and hydrogenation, where captured CO2 (including from air) was directly utilized to produce formate and CH3OH without requiring energy intensive desorption and compression steps. This Account centers on that topic. A key feature in the combined CO2 capture and conversion studies reported to date for the synthesis of formic acid and methanol is the use of an amine or alkali-metal hydroxide base for capturing CO2, which can assist the homogeneous catalysts in the hydrogenation step. We start this Account by examining the combined processes where CO2 is captured in amine solutions and converted to alkylammonium formate salts. The effect of amine basicity on the reaction rate is discussed along with catalyst recycling schemes. Next, methanol synthesis by this combined process, with amines as capturing agents, is explored. We also examine the system developments for effective catalyst and amine recycling in this process. We next go through the effect of catalyst molecular structure on methanol production while elucidating the main deactivating pathway involving carbonylation of the metal center. The recent advances in first-row transition metal catalysts for this process are also mentioned. Subsequently, we discuss the capture of CO2 using hydroxide bases and conversion to formate salts. The regeneration of the hydroxide base (NaOH or KOH) at low temperatures (80 °C) in cation-conducting direct formate fuel cells is presented. Finally, we review the challenges in the yet unreported integrated CO2 capture by hydroxide bases and conversion to methanol process.

SYNTHESIS OF 2- (2I – ACYLOXY-ETHOXY) ETHYL CHLORIDE AND THEIR INTERACTION WITH AMIDES AND ALKALI METAL RHODANIDES

This work is aimed at studying the reaction of nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with amines and a rhodanide ion and developing methods of synthesizing a 2-(2'-acyloxy-ethoxy) ethylchlorides, rhodanides, and their derivatives previously unknown in specialized literature. In the chlorohydrin molecule of diethylene glycol, there are two reaction centers that allow carrying out nucleophilic substitution reactions, as well as reactions that promote them with electrophilic reagents. The authors carried out several experiments for acylating diethylene glycol chlorohydrine with carbonic acids, reactions of nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with various amines as well as synthesized the chloracetoxyethyl ether of rhodane acetic acid. While studying the nucleophilic substitution of 2-(2'-acyloxy-ethoxy) ethylchlorides with the rhodanide ion, it was discovered that only the chlorine atom was replaced. The possibility of the nucleophilic substitution of the ethylene chlorohydrine was shown by the example of N-methyl and N-ethylanilines. It was discovered that the hydroxyl group of diethylene glycol could react with carbonic acids in the presences of catalysts and, therefore, encourage esterification. It has been found out that the nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with the rhodanide ion goes smoothly in the presence of potassium iodide acting as an activator and that the acyloxy group is unaffected. It has been discovered that the primary role in the nucleophilic substitution of alcoxyalkylhalides is played by the basicity of amines and the essence and position of substituents relative to the alcoxyl group of the haloid atom.

Synthesis and Characterization of Strong Cyclometalated Iridium Photoreductants for Application in Photocatalytic Aryl Bromide Hydrodebromination

A series of potent bis-cyclometalated iridium photoreductants with electron-rich β-diketiminate (NacNac) ancillary ligands is described. Structure–property analysis reveals that substituent modification of the NacNac ligands has a large effect on the ground-state IrIV/IrIII potential, which shifts cathodically as the NacNac is made more electron-rich. In addition, the excited-state IrIV/*IrIII potentials are ca. 300–500 mV more negative than that of fac-Ir(ppy)3 (ppy = 2-phenylpyridine), indicating that these compounds have much more reducing excited states. Rate constants for excited-state electron transfer between these photosensitizers and benzophenone are ∼2–3 times faster than fac-Ir(ppy)3, demonstrating that these complexes are both kinetically and thermodynamically more potent for excited-state electron transfer. We use these photosensitizers to optimize a simple reaction procedure for photocatalytic debromination of aryl bromide substrates, which requires only the photosensitizer, blue light, and an amine base, without silanes or other additives that are used in previously reported methods.

Bis(imidazolidine)pyridine‐CoCl2: A Novel, Catalytically Active Neutral Complex for Asymmetric Michael Reaction of 1,3‐Carbonyl Compounds with Nitroalkenes

AbstractA neutral bis(imidazolidine)pyridine (PyBidine)‐CoCl2 complex showed catalytic activity for the Michael reaction of malonates with nitroalkenes. The results indicated that a weak amine base aided enolate formation from the neutral complex, in which the N−H proton of the imidazolidine ligand played a significant role.magnified image

ACCESSIBILITY OF ZWITTERIONIC COMPOUNDS FROM PRIMARY AMINES AND 2,5-DIHYDROXY-1,4-BENZOQUINONE

Following the discovery of an unprecedented transamination reaction between primary alkylamines and a quinonoid molecule of the type C 6 H 2 (NHCH 2 R) 2 (=O)2 (I), obtained from commercially available diaminoresorcinol.2HCl, we have extended this method to the use of primary arylamines and found that, in contrast, secondary amines led to a different outcome. Whereas functionalized molecules of type I , which are best described as 6π +6π zwitterions, were obtained with aniline or 4-methoxyaniline, no transamination was observed with tBuNH 2 in ethanol. However, a reaction which afforded salt 2-methylpropan-2-aminium 4-(methylamino)-3,6-dioxocyclohexa-1,4-dien-1-olate ( 2b) took place in water and resulted from hydrolysis of the imine group and deprotonation of 5-hydroxy-2-(methylamino)-4-(methylimino)-cyclohexa-2,5-dienone ( 1a) . Under similar conditions, secondary amines led to comparable results. The cations associated with the anionic quinonoid are readily exchanged in the presence of a primary amine. Whereas for the transamination reaction, basic amines react under mild conditions, slightly harsher conditions are needed for less basic amines such as piperidine, diisopropylamine, or diethylamine. Transamination reactions were also performed with 5-hydroxy-2-(methylamino)-4-(methylimino)-cyclohexa-2,5-dienone ( 1a) , which is more soluble in organic solvents than 2-amino-5-hydroxy-4-iminocyclohexa-2,5-dienone (compound I ) This led to the first examples of quinonoidal zwitterions functionalized with different alkyl groups on the nitrogen atoms. A number of compounds were characterized by X-ray diffraction, which allowed a better understanding of their electronic situation, and in many cases, the presence of multiple hydrogen-bond donors and acceptors results in crystal packings dominated by these interactions.

Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma.

CDK4 and CDK6 are kinases with similar sequences that regulate cell cycle progression and are validated targets in the treatment of cancer. Glioblastoma is characterized by a high frequency of CDKN2A/CCND2/CDK4/CDK6 pathway dysregulation, making dual inhibition of CDK4 and CDK6 an attractive therapeutic approach for this disease. Abemaciclib, ribociclib, and palbociclib are approved CDK4/6 inhibitors for the treatment of HR+/HER2- breast cancer, but these drugs are not expected to show strong activity in brain tumors due to poor blood brain barrier penetration. Herein, we report the identification of a brain-penetrant CDK4/6 inhibitor derived from a literature molecule with low molecular weight and topological polar surface area (MW = 285 and TPSA = 66 Å2), but lacking the CDK2/1 selectivity profile due to the absence of a basic amine. Removal of a hydrogen bond donor via cyclization of the pyrazole allowed for the introduction of basic and semi-basic amines, while maintaining in many cases efflux ratios reasonable for a CNS program. Ultimately, a basic spiroazetidine (cpKa = 8.8) was identified that afforded acceptable selectivity over anti-target CDK1 while maintaining brain-penetration in vivo (mouse Kp,uu = 0.20-0.59). To probe the potency and selectivity, our lead compound was evaluated in a panel of glioblastoma cell lines. Potency comparable to abemaciclib was observed in Rb-wild type lines U87MG, DBTRG-05MG, A172, and T98G, while Rb-deficient cell lines SF539 and M059J exhibited a lack of sensitivity.

Microgel/silica hybrid colloids: Bioinspired synthesis and controlled release application

In the present work, we demonstrate that polymer based functional microgels can be used as autocatalytic template for the bioinspired deposition of silica nanoparticles inside the microgel network under ambient conditions. Temperature responsive poly(N-vinyl caprolactam) based microgels were synthesized by precipitation polymerization using glycidyl methacrylate as a comonomer. These microgels were further reacted with aminoethanthiol to develop amine functional groups inside the microgels. A water soluble silica precursor (PEGPEOS) was developed by modification of hyperbranched polyethoxysiloxane with polyethylene glycol monomethyl ether. Microgel/silica hybrid colloids were prepared by simultaneous PEGPEOS conversion and silica deposition in the microgels. TEM studies showed that silica nanoparticles of approximately 10 nm in size were deposited inside the microgel network owing to the strong acidbase interaction between the acidic silica and basic amine groups. DLS results indicated that the incorporation of silica nanoparticles reduced the thermal sensitivity of microgels. Molecular dynamics simulations were performed to investigate the interaction between silica precursor and microgels based on radial distribution function and interaction energy. The developed hybrid microgels were further explored for controlled release of aspirin used as a model drug. The preliminary results indicated that the presence of silica rich domains in the microgel network remarkably retarded aspirin release.

COtab: Expedient and Safe Setup for Pd-Catalyzed Carbonylation Chemistry.

Bench-stable tablets (COtabs) have been developed for the rapid and safe production of carbon monoxide. The tablets can be made in less than 5 min without the use of a glovebox and only require a stock solution of an amine base to liberate a specific quantity of CO in a two-chamber system. The COtabs were tested in five different carbonylation reactions and provided similar yields compared to literature procedures. Finally, a gram-scale reaction was conducted, as well as 13C-isotope labeling of the anticancer drug, olaparib.

Tetrahydro-3-benzazepines with fluorinated side chains as NMDA and σ1 receptor antagonists: Synthesis, receptor affinity, selectivity and antiallodynic activity

The class of tetrahydro-1H-3-benzazepines was systematically modified in 1-, 3- and 7-position. In particular, a F-atom was introduced in β- or γ-position of the 4-phenylbutyl side chain in 3-position. Ligands with the F-atom in γ-position possess higher GluN2B affinity than analogs bearing the F-atom in β-position. This effect was attributed to the reduced basicity of β-fluoro amines. 3-Benzazepines with a benzylic OH moiety show moderate GluN2B affinity, but considerable selectivity over the σ2 receptor. However, removal of the benzylic OH moiety led to increased GluN2B affinity, but reduced GluN2B/σ2 selectivity. With respect to GluN2B affinity the phenol 17b with a γ-fluorophenylbutyl moiety in 3-position represents the most interesting fluorinated ligand (Ki(GluN2B) = 16 nM). Most of the synthesized ligands reveal either similar GluN2B and σ1 affinity or higher σ1 affinity than GluN2B affinity. The methyl ether 16b shows high σ1 affinity (Ki(σ1) = 6.6 nM) and high selectivity over a broad panel of receptors and transporters. The high antiallodynic activity in the mouse capsaicin assay proved the σ1 antagonistic activity of 16b.

1,5‐Diaza‐3,7‐Diphosphacyclooctane Bis‐Ligand Nickel(II) Complexes as Oxygen Reduction Catalysts for Proton‐Exchange Membrane Fuel Cells

Membrane electrode assemblies (MEAs) with 1,5‐diaza‐3,7‐diphosphacyclootane organometallic bis‐ligand nickel(II) complexes [Ni(PPh2NPh2)2]2+2.[BF4]− [1(Ph‐Ph)] and [Ni(PPh2NBn2)2]2+2.[BF4]− [2(Ph‐Bn)] as a part of oxygen reduction reaction (ORR) catalysts for proton‐exchange membrane fuel cells (PEMFCs) are built and tested. The complexes are characterized by atomic force microscopy (AFM), electron spin resonance (ESR), cyclic voltammetry (CV), and differential scanning calorimetry‐thermogravimetric analysis (DSC‐TGA). Electrochemical activity toward ORR and catalytic stability of compounds is tested by chronoamperometry (CA). The electrochemical activity of catalysts and ORR mechanisms is studied by rotating disk electrode (RDE). A performance analysis of the PEMFC is carried out. A peak power density of about 11.84 mW cm−2 and a current density of 80 mA cm−2 are measured for 2(Ph‐Bn)/C cathode and Pt/C anode catalysts, respectively. Chronoamperometric tests in 0.5 m H2SO4 for 3 h show an excellent stability for the compound 2(Ph‐Bn). The performance of 1(Ph‐Ph)/C catalyst and the chronoamperometric stability of 1(Ph‐Ph) are worse. A possible relationship between the catalysts’ performance and basicity of pendant amines on the base of the proposed ORR mechanism with two metal centers is discussed.

Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I

HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PRTri) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PRTri mutant range from 17 to 40 nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PRTri mutant in complex with inhibitor 1 at 1.5 Å resolution shows minor changes in interactions with inhibitor compared with the corresponding wild type PR complex. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. Hence, inhibition is influenced by small coordinated changes in hydrophobic interactions.

Design, synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents

Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, 1H NMR, 13C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00–0.39 µg/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1–21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC50 value of <1.23 μg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.

Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated.

The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, we found Tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. We synthesized Tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homology models indicated that a hydrogen bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, our data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the Tubastatin A scaffold.

DABCOnium: An Efficient and High-Voltage Stable Singlet Oxygen Quencher for Metal-O2 Cells.

Singlet oxygen (1O2) causes a major fraction of the parasitic chemistry during the cycling of non‐aqueous alkali metal‐O2 batteries and also contributes to interfacial reactivity of transition‐metal oxide intercalation compounds. We introduce DABCOnium, the mono alkylated form of 1,4‐diazabicyclo[2.2.2]octane (DABCO), as an efficient 1O2 quencher with an unusually high oxidative stability of ca. 4.2 V vs. Li/Li+. Previous quenchers are strongly Lewis basic amines with too low oxidative stability. DABCOnium is an ionic liquid, non‐volatile, highly soluble in the electrolyte, stable against superoxide and peroxide, and compatible with lithium metal. The electrochemical stability covers the required range for metal–O2 batteries and greatly reduces 1O2 related parasitic chemistry as demonstrated for the Li–O2 cell.