Nitrogen Substituents Research Articles

Enantioselective Synthesis of β-Fluoro-β-aryl-α-aminopentenamides by Organocatalytic [2,3]-Sigmatropic Rearrangement.

The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.

Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity.

The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2-4 mg L-1 .

Practical Preparation of Octa- and Tetrabromoperylene Diimides and Derivatives Thereof

A mild synthesis of fully brominated perylene dianhydride and diimides in one step from easily available unsubstituted precursors is presented. The partial reduction of ortho-bromo substituents with hydrazine hydrate allowed for a gram-scale synthesis of a valuable intermediate, 1,6,7,12-tetrabromoperylene diimide. Several new twisted fully core-substituted perylene diimide derivatives having sulfur, nitrogen, or oxygen substituents were synthesized using regioselective nucleophilic substitution reactions.

Synthesis and characterization of dual-colored electrochromic materials based on 4′-(4-alkyl ester)-4,2′:6′,4″-terpyridinium derivatives

This study aims to achieve dual-color properties for pyridinium-salt-based electrochromic materials. A novel series of 4′-(4-alkyl ester)-4,2′:6′,4″-terpyridinium derivatives were designed and synthesized through the introduction of an ester group onto the benzene ring of 2,4-di(4-pyridyl)-4-benzylpyridinium derivatives. Dual-electrochromic devices based on these compounds were fabricated. Multiple shades of green and yellowish green colors were obtained by changing the type of carboxylic acids and the nitrogen substituents. The type of carboxylic acids and the nitrogen substituents significantly influenced their electrochromic properties. 4′-(4-Alkyl ester)-4,2′:6′,4″-terpyridinium derivatives show good electrochromic properties such as high coloration efficiency, reasonable contrast, satisfactory optical memories, and redox stability. The dual-electrochromic materials are promising candidates for applications in electrochromic display systems.

Exploration of tertiary aminosquaramide bifunctional organocatalyst in controlled/living ring-opening polymerization of l-lactide

A series of tertiary aminosquaramides as bifunctional organocatalysts in the ring-opening polymerization (ROP) of l-lactide (l-LA) were developed, allowing the activation of both the l-LA monomer and the alcohol group of the initiator/propagating species. Further, the impact of tertiary nitrogen substituents on catalytic activity in ROP of l-LA was explored. The tertiary aminosquaramide— an air-stable and moisture-stable catalyst—exhibited superior activity in contest with thiourea counterpart when both were equipped with a similar tertiary amine group. Kinetic and chain-extension experiments indicated that the formed poly(l-LA) is featured with narrow polydispersity and high end-group fidelity, hallmarks of a living polymerization process. The initiator efficiency was further executed at ease by preparation of an ABA triblock copolymer poly (l-LA)-b-poly (ethylene glycol)-b-poly (l-LA) in the presence of a dual-headed PEG macroinitiator. 1H NMR titration experiments suggested a bifunctional catalytic mechanism, wherein both the l-LA monomer and the propagating hydroxyl group were activated en route to polymerization. The 1H NMR, SEC, and MALDI-TOF MS measurements validated the quantitative incorporation of the initiator in the polymeric chains and enchainment over competitive trans-esterification reaction. Overall, the structure-activity relationships were surveyed to uncover aminosquaramide as a new bifunctional dual hydrogen-bond donor catalyst for living ROP of l-LA. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017

Efficient stereochemical communication in phosphine-amine palladium-complexes: Exploration of N-substituent effects in coordination chemistry and catalysis

Six-membered chelate complexes of type [Pd(1a-e)Cl2] (2a-e) and [Pd(1a-e)(η3-PhCHCHCHPh)]BF4 (3a-e) of a series of systematically varied chiral phosphine-amine ligands (S,S)-Ph2PCH(CH3)CH2CH(CH3)NHR 1a-e (R = benzyl 1a, R = ethyl 1b, R = (S)-α-phenylethyl 1c, R = isopropyl 1d, R = methyl 1e) have been studied. The complexes 2a-e were characterized by X-ray crystallography, DFT analysis and in solution by 1D and 2D NMR spectroscopy. A very good correlation has been observed between the steric demand of the N-substituent and the distortion of the chelate. Furthermore, it has been proved that sterically more demanding N-substituents are capable of distorting the chelate to a larger extent along one single, well defined conformational pathway. The careful variation of the N-substituent thus allows a precise stereochemical fine tuning of the metal's coordination sphere. As a substantiation of this concept, the investigation of complexes 3a-e revealed that the exo/endo ratio as well as the twisting of the allyl moiety around the Pd-allyl axis can easily be modified by the proper choice of the nitrogen substituent. Furthermore, Pd-catalysts with ligands 1a-e provided high enantioselectivities (up to 96%) in asymmetric allylic alkylation reactions.

Backbone-Substituted β-Ketoimines and Ketoiminate Clusters: Transoid Li2O2 Squares and D2-Symmetric Li4O4 Cubanes. Synthesis, Crystallography and DFT Calculations

The preparation and crystal structures of four β-ketoimines with bulky aryl nitrogen substituents (2,6-diisopropylphenyl and 2,4,6-trimethylphenyl) and varying degrees of backbone methyl substitution are reported. Backbone substitution “pinches” the chelate ring. Deprotonation with n-butyllithium leads to dimeric Li2O2 clusters, as primary laddered units, with an open transoid geometry as shown by crystal structures of three examples. The coordination sphere of each lithium is completed by one tetrahydrofuran ligand. NMR spectra undertaken in either C6D6 or 1:1 C6D6/d8-THF show free THF in solution and the chemical shifts of ligand methyl groups experience significant ring-shielding which can only occur from aryl rings on adjacent ligands. Both features point to conversion to higher-order aggregates when the THF concentration is reduced. Recrystallization of the materials from hydrocarbon solutions results in secondary laddering as tetrameric Li4O4 clusters with a cuboidal core, three examples of which have been crystallographically characterised. These clusters are relatively insoluble and melt up to 250 °C; a consideration of the solid-state structures indicates that the clusters with 2,6-diisopropylphenyl substituents form very uniform ball-like molecular structures that will only be weakly solvated.

Hydrosilylation of Olefins Catalyzed by Iron Complexes Bearing Ketimine-Type Iminobipyridine Ligands

A series of NNN-pincer iron complexes bearing ketimine-type iminobipyridene (BPI) ligands were prepared. These iron complexes were effective catalysts for the hydrosilylation of olefins using primary, secondary, and tertiary silanes. The effect of the substituents on the imino carbon on the catalytic activity was examined, and it was found that an appropriate combination of the imino carbon and imino nitrogen substituents led to complexes with quite high catalytic activity: the turnover number achieved was up to 42000. These iron catalytic systems provide a low-cost and promising alternative to currently employed precious metal systems for the hydrosilylation of olefins.

Synthesis of Electron‐Deficient Tetrahydro‐ and Dihydroimidazo[1,2‐f]phenanthridines by Microwave‐Mediated IMDAF Reactions

N‐Substituted tetrahydroimidazo[1,2‐f]phenanthridines (TIPs) and dihydroimidazo[1,2‐f]phenanthridines (DIPs) have a variety of interesting properties, but structural variations of these compounds have, until now, included nitrogen substituents. Herein, TIPs and DIPs that have electron‐withdrawing groups on the phenanthridine moiety have been synthesized. A microwave‐mediated one‐pot intramolecular Diels–Alder reaction of furan (IMDAF) and subsequent aromatization were employed as the key steps. The electron‐deficient dihydrophenanthridines constructed by an IMDAF were oxidized in situ by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), and the salts generated were treated with benzylamine to give N‐benzyl TIP compounds. These TIPs were remarkably stable towards air‐mediated oxidation relative to those TIPs that do not contain electron‐withdrawing substituents and were isolated in high yields. Electron‐deficient TIPs were easily oxidized to give the corresponding DIPs by treatment with N‐bromosuccinimide.

Carboranes as Aryl Mimetics in Catalysis: A Highly Active Zwitterionic NHC-Precatalyst.

Modern catalysis takes advantage of aryl-based interactions to tune and control reactions. In the design of N-heterocyclic-carbene catalysts, both the electronic and steric nature of the nitrogen substituents play a crucial role. Although hydrocarbon-based systems and especially aryl residues have contributed considerably to overcome multifaceted catalytic challenges, the unique properties of carborane moieties, including delocalized charge, potential planar chirality, and well-known thermodynamic stability, offer unprecedented opportunities to develop new catalysts while being employed as aryl mimetics. We report a straightforward synthetic route to a novel zwitterionic triazolium-based N-heterocyclic carbene (NHC) precatalyst bearing a 7,8-dicarba-nido-undecaboranyl substituent. The catalyst's excellent activity and its broad applicability are demonstrated in a wide range of organocatalytic transformations. Comparison of the performance with known N-aryl NHC catalysts offers preliminary insights into the stereoelectronic nature of this nido-carboranyl substituent.

The Advantages of Cyclic Over Acyclic Carbenes To Access Isolable Capto-Dative C-Centered Radicals.

A cyclic and an acyclic di(amino)carbene as well as a cyclic and an acyclic (alkyl)(amino)carbene cleanly react with benzoyl chloride to give the corresponding adducts 1+cyc , 1+acy , 2+cyc , and 2+acy , respectively. The reduction of 1+cyc and 2+cyc derived from cyclic carbenes affords the corresponding radicals 1cyc and 2cyc that are stable at room temperature. In contrast, radicals 1acy and 2acy , derived from acyclic carbenes, cannot be isolated. It is shown that 1acy is as thermodynamically stabilized as its cyclic counterpart 1cyc , but its instability is the result of β-hydrogens of the nitrogen substituent, along with the enhanced flexibility around C-N bonds, which allow for a H. -migration-elimination process. Radical 2acy is thermodynamically unstable, and undergoes disproportionation into the corresponding iminium 2+acy and enolate 2-acy . This is due to the excessive steric hindrance, which prevents electron-delocalization on the NCCO fragment, and thus, the capto-dative stabilization. This work suggests general guidelines for the design of highly persistent (amino)(carboxy)radicals, especially by emphasizing the key advantage of cyclic patterns.

In situ electrochemical synthesis of Ni(I) complexes with aminomethylphosphines as intermediates for hydrogen evolution

Nickel (I) complexes of 1,5-diaza-3,7-diphosphacyclooctane PPh2NR2 ligands were obtained from precursor Ni(II) by exhaustive electrolysis of [Ni(PPh2NR2)2]2+ precursors at the Ni(II/I) couple potential and characterized by several techniques. Paramagnetic Ni(I) complexes were investigated by cyclic voltammetry, spectroelectrochemistry UV/Vis and ESR methods at room temperature and in a frozen solution. Catalytic behavior of Ni(I) complex in different ligand environment for hydrogen evolution from acid depends from the ligand nature. The two possible catalytic cycles were proposed depending on the nitrogen substituents in 1,5-diaza-3,7-diphosphacyclooctane.

ANTIPROLIFERATIVE ACTIVITY OF NEW 6-BROMINE DERIVATIVES OF 7-ANILINO-1-ARYLISOQUINOLINEQUINONES

A variety of 6-bromine-containing 7-anilino-1-arylisoquinolinequinones 2a-g were synthesized to evaluate their half-wave potentials and in vitro antiproliferative activity on gastric and leukemia cancer cell lines. The new compounds displayed significant IC50 values in the range: 1.31 to 11.04 μM. The structure activity relationship analysis of the new series suggest that the antiproliferative activity is dependent, in part, on the push-pull electronic effects of the nitrogen and bromine substituents inserted into the redox fragment of the 1-arylisoquinolinequinone scaffold. Linear regression analysis provided satisfactory relationships between the log IC50 and ClogP values for the AGS gastric cancer cell line.

A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compounds

Summary Direct catalytic methods for the stereoselective introduction of various non-protected amines at the carbon atom adjacent to a carbonyl group remain elusive in synthetic chemistry, even though they offer the most straightforward entry to chiral α-aminocarbonyl compounds. Here, we demonstrate that the in situ activation of hydroxylamines with trichloroacetonitrile enables direct transfer of their amine moieties to the C-3 position of oxindoles with rigorous enantiocontrol under the catalysis of chiral 1,2,3-triazolium salts. This protocol provides a powerful and practical means of accessing optically active 3-aminooxindoles with a wide array of alkyl and aryl substituents on nitrogen. Other carbonyl compounds, such as β-ketoesters and α-cyanoesters, can also be directly transformed into the corresponding α-aminocarbonyls with high enantioselectivity.

Zwitterionic Ring-Opening Polymerization of N-Substituted Eight-Membered Cyclic Carbonates to Generate Cyclic Poly(carbonate)s.

The zwitterionic ring-opening polymerization of N-functionalized eight-membered cyclic carbonates with N-heterocyclic carbenes (NHC) in the absence of alcohol initiators generates cyclic polycarbonates of Mn ∼ 30-100 kDa. The polymerization behavior of these eight-membered cyclic azacarbonates depends sensitively on the nature of the nitrogen substituent. The N-benzyl-substituted eight-membered cyclic carbonate (8CCBn) polymerizes readily with 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene to generate cyclic polycarbonates with molecular weights of Mn = 14 000 to 96 000 Da. In contrast, the N-phenyl-substituted cyclic carbonate (8CCPh) catalytically dimerizes in the presence of the NHC to afford the crystalline cyclic dimer. The zwitterionic ring-opening copolymerization of δ-valerolactone (VL) and the cyclic carbonates afford gradient cyclic copolymers. The cyclic topology of both the homopolymers and copolymers was supported by MALDI-TOF MS and intrinsic viscosity measurements. 13C NMR and differential scanning calorimetry of the cyclic copolymers are indicative of a gradient sequence distribution as a consequence of the more rapid enchainment of the cyclic carbonates relative to valerolactone.

Synthesis and characterization of Zwitterionic Zn(II) and Cu(II) coordination compounds with ring-substituted 2,2′-biimidazole derivatives

Zwitterionic coordination compounds with strongly asymmetrical charge distribution were synthesized and characterized. Ring-substituted biimidazoles were used as the primary ligands for Zn and Cu compounds. Formation of Zwitterionic coordination compound was found to be strongly dependent on the pH of the reaction medium as well as on the ring and nitrogen substituents of the ligand. Reaction of the Df-R2biim (Df-R2biim=2,2′-bi-1R-imidazole-5,5′-dicarboxaldehyde, R=Me, Et or Pr) with ZnCl2 in neutral conditions led to binuclear compounds [Zn2Cl4(Df-R2biim)2] with two bridging ligands (1a–c). Reaction with CuCl2·2H2O gave neutral mononuclear compound [CuCl2(Df-Me2biim)] (1d) with chelating biimidazole ligand. In acidic conditions (pH=3–4) the imidazole nitrogens were either fully or partially protonated, which prevented the bidentate coordination of the ligands. Furthermore, aldehyde substituents of Df-R2biim ligands were involved in acetal formation with methanol solvent. Under acidic conditions the primary products were either ion pairs [MCl4][C14H24N4O4]·(M=Zn 3a, M=Cu 3b) with fully protonated H2L2+ counter cation or desired Zwitterionic coordination compounds [ZnCl3(C16H27N4O4)] (2a), [ZnCl3(C18H31N4O4)] (2b), [CuCl3(C16H27N4O4)] (2c), or [CuCl3(C18H31N4O4)] (2d) with partially protonated monodentate HL+ ligand. Zwitterions were obtained only with ligands having both aldehyde groups as ring-substituents and longer alkyl chains (ethyl or propyl) as N-substituents. In other cases ion pairs were formed as final products. Zwitterions were found to decompose in alcoholic solutions. In methanol solution, Zwitterionic compounds released neutral ligand and HZnCl3. All main products were characterized by NMR, elemental analysis and single-crystal X-ray diffraction.

Nitrogen Modified Carbon Nano-Materials as Stable Catalysts for Phosgene Synthesis

The carbon-catalyzed reaction of Cl2 and CO constitutes the most important industrial route to phosgene. Although defects in carbon lead to surface chemical reactions, direct polarization of C-heteroatom bonds induces a more successful Cl2 catalytic activation, the rate-determining step in the overall catalytic cycle. The interplay between the electron-donating and -withdrawing ability of the incorporated nitrogen substituents on the formation and stabilization of active sites was examined by X-ray photoelectron and Raman spectroscopy. Mechanistic studies indicate that the polarized Cl2 induced by the direct interaction of Cl2 with a strongly electron-deficient carbon site in close proximity to a nitrogen substituent is essential for phosgene production. Nitrogen substitution into ordered carbon materials led to very active and stable carbon catalysts for COCl2 synthesis.

ChemInform Abstract: Octa‐1,7‐diene‐4,5‐diamine Derivatives: Useful Intermediates for the Stereoselective Synthesis of Nitrogen Heterocycles and Ligands for Asymmetric Catalysis

AbstractReview: [65 refs.

Factors Controlling the Reactivity and Selectivity of the Diels-Alder Reactions Involving 1,2-Azaborines.

The factors controlling the reactivity and endo/exo selectivity of the Diels-Alder reactions involving 1,2-azaborines have been computationally explored within the density functional theory framework. It is found that the AlCl3-catalyzed [4 + 2]-cycloaddition reaction between these dienes and N-methylmaleimide proceeds concertedly and leads almost exclusively to the corresponding endo cycloadduct, which is in good agreement with previous experimental observations. In addition, the effect of the substituent directly attached to the boron atom of the 1,2-azaborine on the process is also analyzed in detail. To this end, the combination of the activation strain model of reactivity and the energy decomposition analysis methods has been applied to gain a quantitative understanding into the origins of the endo selectivity of the process as well as the influence of the boron and nitrogen substituent on the barrier heights of the transformations.

Synthesis and Evaluation of [(18) F]-Ammonium BODIPY Dyes as Potential Positron Emission Tomography Agents for Myocardial Perfusion Imaging.

Recently, we demonstrated the potential of a [(18) F]-trimethylammonium BODIPY dye for cardiac imaging. This is the first example of the use of the [(18) F]-ammonium BODIPY dye for positron emission tomography (PET) myocardial perfusion imaging (MPI). In this report, we extend our study to other ammonium BODIPY dyes with different nitrogen substituents. These novel ammonium BODIPY dyes were successfully prepared and radiolabeled by the SnCl4 -assisted (18) F-(19) F isotopic exchange method. The microPET results and the biodistribution data reveal that nitrogen substituent changes have a significant effect on the in vivo and pharmacological properties of the tracers. Of the novel [(18) F]-ammonium BODIPY dyes prepared in this work, the [(18) F]-dimethylethylammonium BODIPY is superior in terms of myocardium uptake and PET imaging contrast. These results support our hypothesis that the ammonium BODIPY dyes have a great potential for use as PET/optical dual-modality MPI probes.