N-arylation Research Articles

9,10-Bis(5H-dibenzo[b,f]azepino)anthracene

The title compound with a donor–π–donor (D–π–D) type triad structure was synthesized by Buchwald–Hartwig amination using 9,10-dibromoanthracene and 5H-dibenzo[b,f]azepine, and characterized by 1H, 13C{1H} NMR, HRMS, and X-ray diffraction analysis. The azepine–anthracene–azepine units are nearly orthogonal to each other, with a torsion angle of 88°. A broad and weak absorption band around 410–480 nm and the low emission character (ΦF = 0.01) suggest the weak intramolecular charge transfer from the azepine to the anthracene unit due to the twisted structure.

Polytriphenylamine Conjugated Microporous Polymers as Versatile Platforms for Tunable Hydrogen Storage.

Hydrogen (H2) as a fuel source presents a promising route toward decarbonization, though challenges in its storage remain significant. This study explores the synthesis and characterization of polytriphenylamine (PTPA)conjugated microporous polymers (CMPs) for H2 storage. Utilizing a combination of Buchwald-Hartwig (BH) coupling, the Bristol-Xi'an Jiaotong (BXJ) approach, and variations in monomer reactive site stoichiometry, a polymer with specific surface areas in excess of 1150 m2g-1 and micropore volume of 0.47cm3g-1 is developed. H2 storage capacities are measured, achieving excess gravimetric uptakes of 1.65 wt.% at 1bar and 2.51wt.% at 50bar and 77 K, with total capacities reaching 4.40 wt.% at 100bar and 77 K. Net adsorption isotherms reveal advantages to H2 storage using PTPA adsorbents over traditional compression up to pressures of 10bar at 77 K. High mass transfer coefficients of 4.95min-1 indicate a strong material affinity for H2. This study highlights the impact of monomer ratio adjustments on the porosity and excess, total, and net H2 adsorption capacities of PTPA-based CMPs, offering insights into the importance of a non-stoichiometric monomer concentration when developing efficient CMP-based H2 storage materials.

Nitrogen-Bridged Fused-Ring Nonacyclic and Heptacyclic A-D-A Acceptors for Organic Photovoltaics.

In this work, we designed two nitrogen-bridged fluorene-based heptacyclic FNT and nonacyclic FNTT ladder-type structures, which were constructed by one-pot palladium-catalyzed Buchwald-Hartwig amination. FNT and FNTT were further end-capped by FIC acceptors to form two FNT-FIC and FNTT-FIC non-fullerene acceptors (NFAs), respectively. The two NFAs exhibit more red-shifted absorption and higher crystallinity compared to those of the corresponding carbon-bridged FCT-FIC and FCTT-FIC counterparts. Grazing incidence wide-angle X-ray scattering (GIWAXS) measurements reveal that the 2-butyloctyl groups on the nitrogen in the convex region of FNT-FIC interdigitate with the dioctyl groups on the fluorene in the concave region of another FNT-FIC, resulting in a lamellar packing structure with a d spacing of 13.27 Å. As a consequence, the PM6:FNT-FIC (1:1 wt %) device achieved a power conversion efficiency (PCE) of only 6.60%, primarily due to the highly crystalline nature of FNT-FIC, which induced significant phase separation between PM6 and FNT-FIC in the blended film. However, FNTT-FIC, featuring 2-butyloctyl groups positioned on the nitrogen within the concave region of its curved skeleton, exhibits improved donor-acceptor miscibility, thereby promoting a more favorable morphology. As a result, the PM6:FNTT-FIC (1:1.2 wt %) device exhibited a higher PCE of 12.15% with an exceptional Voc of 0.96 V. This research demonstrates that placing alkylamino moieties within the concave region of curved A-D-A NFAs leads to a better molecular design.

Synthetic Routes to 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amines: Cross-Coupling and Challenges in SEM-Deprotection

7-Azaindoles are compounds of considerable medicinal interest. During development of the structure–activity relationship for inhibitors of the colony stimulated factor 1 receptor tyrosine kinase (CSF1R), a specific 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amine was needed. Two different synthetic strategies were evaluated, in which the order of the key C-C and C-N cross-coupling steps differed. The best route relied on a chemoselective Suzuki–Miyaura cross-coupling at C-2 on a 2-iodo-4-chloropyrrolopyridine intermediate, and subsequently a Buchwald–Hartwig amination with a secondary amine at C-4. Masking of hydroxyl and pyrroles proved essential to succeed with the latter transformation. The final trimethylsilylethoxymethyl (SEM) deprotection step was challenging, as release of formaldehyde gave rise to different side products, most interestingly a tricyclic eight-membered 7-azaindole. The target 2-aryl-1H-pyrrolo[2,3-b]pyridin-4-amine (compound 3c) proved to be 20-fold less potent than the reference inhibitor, confirming the importance of the N-3 in the pyrrolopyrimidine parent compound for efficient CSF1R inhibition.

Air-stable, well-defined palladium–BIAN–NHC chloro dimer: Highly efficient N-Heterocyclic carbene (NHC) catalyst platform for Buchwald–Hartwig C–N cross-coupling reactions

Buchwald-Hartwig amination has become the fundamental method for constructing molecular architectures throughout chemical research, including the synthesis of pharmaceutical agents, natural products, fine chemicals, and advanced materials. Herein, we report air-stable, well-defined palladium–BIAN–NHC chloro dimer, [Pd(BIAN–NHC)(μ-Cl)Cl]2, for Buchwald-Hartwig C–N cross-coupling reactions of aryl halides. This rapidly activating catalyst framework merges the reactive properties of palladium chloro dimers, [Pd(NHC)(μ-Cl)Cl]2, with the structural features of acenaphthoimidazol-2-ylidenes. [Pd(BIAN–NHC)(μ-Cl)Cl]2 is the most reactive Pd(II)–NHC precatalyst to date, undergoing fast activation under both inert atmosphere and aerobic conditions. The catalyst shows an excellent reactivity in Buchwald-Hartwig amination of aryl halides (59 examples), including challenging substrates, diamination and direct functionalization of pharmaceuticals. The steric protection enables high reactivity under both inert atmosphere and aerobic conditions. [Pd(BIAN–IPr)(μ-Cl)Cl]2 should be routinely utilized for the synthesis of C–N bonds to make valuable amines, where it replaces the most commonly deployed at present IPr (IPr = 1,3-bis(2,6-isopropyl)imidazol-2-ylidene).

Investigating the Origin of Epimerization Attenuation during Pd-Catalyzed Cross-Coupling Reactions.

Palladium-catalyzed cross-couplings remain among the most robust methodologies to form carbon-carbon and carbon-heteroatom bonds. In particular, carbon-nitrogen (C-N) couplings (Buchwald-Hartwig aminations) find widespread use in fine chemicals industries. The use of base in these reactions is critical for catalyst activation and proton sequestration. Base selection also plays an important role in process design, as strongly basic conditions can impact sensitive stereocenters and result in erosion of stereochemical purity. Herein we investigate the role of a Pd catalyst in suppressing base-mediated epimerization of a sultam stereocenter during a C-N cross-coupling reaction to access the RORγ inhibitor GDC-0022. Online high-performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to acquire reaction time course profiles and to delineate epimerization behavior, identify decomposition pathways, and monitor Pd-containing species. Our ability to monitor organopalladium complexes in real time by HPLC-MS provided strong evidence that the degree of epimerization was correlated to the Pd speciation in solution. Specifically, Pd(II) complexes were associated with mitigating epimerization of six-membered sultams. Additional studies showed that the suppression of epimerization in the presence of Pd(II) can impact Pd-catalyzed reactions of other substrates such as enolizable ketones, thus providing practical insight on the execution and optimization of such processes.

Enhanced Photorefractive Performance by Controlling Ion‐Assisted Charge Injection and Accumulation with Random Biphenyl Co‐Polymerized Poly(Carbazolyl‐Amine)

AbstractIn this study, the synthesis of poly(carbazolyl‐amine)s with a random co‐polymerized biphenyl group through the Buchwald–Hartwig amination to enhance ion‐assisted space‐charge‐limited current (SCLC) and achieve efficient performance in photorefractive (PR) polymers, is reported. By modulating the polymer crystallinity, the efficient accumulation of ions near an electrode is achieved and enhanced ion‐assisted SCLC is realized, which results in a magnified electric field inside the polymers. The internal electric field is increased by the stacked charges injected from the electrode, and it is further enhanced by the washing out of ions. The polymer, blended with the electro–optical chromophore and sensitizer, exhibits a high PR sensitivity of 16.7 cm3 kJ−1 and a device stability of up to E = 80 V µm−1 at a wavelength of 633 nm, which is comparable to that of the inorganic crystals Bi12SiO20 and Sn2P2S6.

Synthesis of copper complexes for potential use in the diagnosis of Alzheimer's disease

Background: Since there is currently no cure for Alzheimer's disease (AD), it is important to develop methods that could contribute to its diagnosis and propose new therapeutic approaches for its treatment. Positron emission tomography (PET) is a medical imaging technique that can be used to diagnose Alzheimer's disease, as some radiotracers have been developed to detect amyloid plaques, one of the hallmarks of the disease. However, the radiotracers already used for the diagnosis of AD have a low half-life, which limits their use over the time and requires the presence of a cyclotron close to the examination site. The use of copper complexes could be a good alternative for the development of new radiotracers, since they can be used in PET imaging and have a longer half-life than the other radiotracers already used for AD diagnosis. Aim of the study: Design and synthesize copper complexes that could be used as PET radiotracers able to cross the blood brain barrier and detecting amyloid plaques.Material and methods: The first objective was to design a series of new copper complexes with the capacity to target amyloid plaques inside the brain and contribute to the rational synthesis of such complexes. To this end, theoretical models were used to predict the ability of the complex to cross the blood-brain barrier (BBB) which separates brain from de blood and is main gatekeeper for drugs entering the brain. The models employed consider the physicochemical properties of the molecules. Based on these models, one of the molecules was synthesized in ten steps. The key step in the synthetic strategy was the coupling of a monopicolinate-N-alkylated cyclam-based ligand with a moiety capable of recognizing Aβ plaques via a Buchwald-Hartwig coupling reaction. Potentiometric, spectrophotometric and electron paramagnetic resonance spectroscopic studies were performed to determine the structure and thermodynamic stability of the complex. In addition, the ability to target amyloid plaques was evaluated using brain sections from Alzheimer's disease patients and the cytotoxicity was evaluated using human neuronal cells.Results: A first complex has been designed and synthesized. The physicochemical studies performed indicate that this complex seem to be thermodynamically stable. In addition, cytotoxicity tests on human neuronal cells indicate low toxicity and labeling tests on brain sections from Alzheimer's patients suggest that the complex is capable of recognizing amyloid plaques. Conclusion: We have developed a novel copper complex that is able to detect recognize amyloid plaques. In the future this molecule could be used in PET and contribute to the diagnosis of Alzheimer's disease. From these results, we also propose to develop a new copper complex for tau PET imaging.

Nitrogen-Containing Flavonoids-Preparation and Biological Activity.

In this work, we report the application of Buchwald-Hartwig amination for the preparation of new derivatives of quercetin and luteolin. Our investigation delves into the impact of aniline moiety on antioxidant, and anti-inflammatory activity, cytotoxicity, and the ability of flavonoids to modulate drug-resistance mechanisms in bacteria. The anti-inflammatory activity disappeared after the introduction of aniline into the flavonoids and the cytotoxicity remained low. Although the ability of quercetin and luteolin to modulate bacterial resistance to antibiotics has already been published, this is the first report on the molecular mechanism of this process. Both flavonoids attenuate erythromycin resistance by suppressing the ribosomal methyltransferase encoded by the ermA gene in Staphylococcus aureus. Notably, 4-(trifluoromethyl)anilino quercetin emerged as a potent ErmA inhibitor, likely by interacting with the RNA-binding pocket of ErmA. Additionally, both 4-fluoroanilino derivatives effectively impended the staphylococcal efflux system. All the prepared derivatives exhibited superior activity in modulating gentamicin resistance in S. aureus compared to the parent compounds. Overall, the incorporation of substituted anilines into the flavonoid core significantly enhanced its ability to combat multidrug resistance in bacteria.

Recent synthetic strategies for N-arylation of pyrrolidines: a potential template for biologically active molecules.

The chemistry of nitrogen-containing heterocyclic compounds has been a multifaceted area of research for an extended period due to their varied therapeutic and biological significance. N-Aryl pyrrolidine formed by condensation of aryl group with nitrogen atom of pyrrolidine is present in a wide array of compounds. Various significant activities shown by N-arylated pyrrolidine include anti-Alzheimer, antihypoxic, anticancer, plant activator, analgesic effect, and hepatitis C inhibitor. This review summarizes different synthetic approaches, e.g., transition-metal catalyzed and transition-metal-free synthesis, decarboxylation reaction, reductive amination, nucleophilic cyclization, Ullmann-Goldberg amidation, Buchwald-Hartwig reaction, Chan-Evans-Lam coupling, addition to benzyne, multistep reaction, green synthesis, rearrangement reaction, and multicomponent reaction, to afford the derivatives of N-aryl pyrrolidine. It encompasses synthetic strategies documented from 2015 to 2023.

Latest Developments on Palladium- and Nickel-Catalyzed Cross-Couplings Using Aryl Chlorides: Suzuki–Miyaura and Buchwald–Hartwig Reactions

AbstractPalladium- and nickel-catalyzed cross-couplings are powerful methods for constructing C–C and C–N bonds, particularly through Suzuki–Miyaura and Buchwald–Hartwig reactions. Although aryl iodides, bromides, and triflates are the most commonly used substrates, aryl chlorides are less frequently utilized due to their lower reactivity. However, they are appealing because they are readily available and inexpensive. This short review highlights recent developments on the Suzuki–Miyaura and Buchwald–Hartwig cross-couplings of aryl chlorides, using both homogeneous and heterogeneous catalysis with palladium and nickel.1 Introduction2 Suzuki–Miyaura Cross-Couplings2.1 Homogeneous Palladium Catalysis2.2 Heterogeneous Palladium Catalysis2.3 Homogeneous Nickel Catalysis2.4 Heterogeneous Nickel Catalysis3 Buchwald–Hartwig Amination Reactions3.1 Homogeneous Palladium Catalysis3.2 Heterogeneous Palladium Catalysis3.3 Homogeneous Nickel Catalysis3.4 Heterogeneous Nickel Catalysis4 Conclusion

1,2-Difunctionalization of Aryne with Sulfenamide and Organohalide: Mild and Metal-Free Access to S-(o-Halo)aryl Sulfilimine.

A mild and metal-free approach has been developed for 1,2-difunctionalization of aryne using sulfenamides as a nucleophile and a halogen source (CX4) as an electrophile to synthesize S-(o-halo)aryl sulfilimines. The late-stage functionalizations of halide handles via Suzuki-Miyaura and Buchwald-Hartwig reactions exhibit the synthetic utilities of the products. The chemoselectivity, regioselectivity, rapidity, and use of economical CCl4 are the advantages of this protocol.

Effects of donor substituents on the conformational heterogeneity, photophysical, mechanochromic and electroluminescent properties of the donor-substituted fluorine-containing triphenylpyrimidines

Three derivatives of fluorinated triphenylpyrimidine with the attached carbazole, phenothiazine, or acridan donor moieties are synthesized by Buchwald-Hartwig reactions. The impact of the donor units on emissive and other properties of the compounds is reported. The compounds exhibit excellent thermal stability, competitive photophysical phenomena such as room temperature phosphorescence (RTP) appearing when compounds are molecularly dispersed in the rigid polymer matrix and thermally activated delayed fluorescence (TADF). The compounds with carbazole and phenothiazine donor moieties show the manifestation of triplet–triplet annihilation in the electroluminescence when used as emitters in organic light-emitting diodes (OLEDs). The phenothiazine-containing compound exhibit dual photoluminescence with the blue-shifted peak corresponding to the quasi-axial conformer and a red-shifted peak to the quasi-equatorial conformer. This derivative shows reversible shifts of emission spectra exceeding 100 nm due to the stable (at least 4 cycles) mechanochromic luminescence under the application of external stimuli. After grinding the emission intensity maximum is observed at 555 nm, after fuming at. ca 448 nm and after melting at 555 nm. The photoluminescence shifts and ON/OFF delayed fluorescence of the phenothiazine-based emitter occur due to the alteration between the crystalline and amorphous states. Optimization of the device structure allows to control the charge balance resulting in external quantum efficiency of up to 5.7 % observed for the OLED based on the phenothiazine-based emitter. This compound also shows the biggest response to the presence of oxygen acting as the quencher of triplet excited energy. The film of the compound doped in rigid Zeonex shows an 8.4-fold increase in emission intensity after evacuation. The optical sensor fabricated using the derivative of fluorinated triphenylpyrimidine and phenothiazine is characterized by the Stern-Volmer constant 1.37 × 10-4 ppm−1.

Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

Synthesis of Au–Pd@CeO2 nanocomposite as a potential catalyst for the Buchwald–Hartwig cross-coupling and amination of benzyl alcohol reactions

Synthesis of Au–Pd@CeO2 nanocomposite as a potential catalyst for the Buchwald–Hartwig cross-coupling and amination of benzyl alcohol reactions

Synthesis of 5-(Aryl)amino-1,2,3-triazole-containing 2,1,3-Benzothiadiazoles via Azide-Nitrile Cycloaddition Followed by Buchwald-Hartwig Reaction.

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide-nitrile cycloaddition followed by Buchwald-Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot diarylative Pd-catalyzed heterocyclization opens the straightforward route to triazole-linked carbazole-benzothiadiazole D-A systems. The optical and electrochemical properties of the compound obtained were investigated to estimate their potential application as emissive layers in OLED devises. The quantum yield of photoluminescence (PLQY) of the synthesized D-A derivatives depends to a large extent on electron-donating strengths of donor (D) component, reaching in some cases the values closed to 100%. Based on the most photoactive derivative and wide bandgap host material mCP, a light-emitting layer of OLED was made. The device showed a maximum brightness of 8000 cd/m2 at an applied voltage of 18 V. The maximum current efficiency of the device reaches a value of 3.29 cd/A.

Palladium-catalyzed selective Buchwald–Hartwig C–N coupling of chloroaryl triflates with amines

The chemoselective Buchwald–Hartwig amination developed here showed that the reactivity of the Ar–Cl bond is higher than that of the Ar–OTf bond. Catalyzed by PdCl2/P(t-Bu)3, the reaction selectively aminated the Ar–Cl bond in an aryl system containing both Ar–Cl and Ar–OTf with moderate yield and excellent chemoselectivity, and the significant effect of additives was also found. With the aid of this methodology, we also efficiently synthesized a bicarbazole scaffold that can serve as a valuable precursor for alkaloids such as murrastifoline A&B.

Phenylazo-BODIPYs: Direct Access via Pd-Catalysis

AbstractA new type of functionalized BODIPY dyes is described. Utilizing an established procedure for Buchwald–Hartwig reactions, we have been able to convert α-chloro BODIPYs to α-azo-BODIPYs using phenylhydrazines. Optimization of the reaction conditions and variation of the BODIPY core and the phenylhydrazine were conducted. Absorption and emission spectra were recorded.

Palladium Complexes Derived from Waste as Catalysts for C-H Functionalisation and C-N Bond Formation

Three-way catalysts (TWCs) are widely used in vehicles to convert the exhaust emissions from internal combustion engines into less toxic pollutants. After around 8–10 years of use, the declining catalytic activity of TWCs causes them to need replacing, leading to the generation of substantial amounts of spent TWC material containing precious metals, including palladium. It has previously been reported that [NnBu4]2[Pd2I6] is obtained in high yield and purity from model TWC material using a simple, inexpensive and mild reaction based on tetrabutylammonium iodide in the presence of iodine. In this contribution, it is shown that, through a simple ligand exchange reaction, this dimeric recovery complex can be converted into PdI2(dppf) (dppf = 1,1′-bis(diphenylphosphino)ferrocene), which is a direct analogue of a commonly used catalyst, PdCl2(dppf). [NnBu4]2[Pd2I6] displayed high catalytic activity in the oxidative functionalisation of benzo[h]quinoline to 10-alkoxybenzo[h]quinoline and 8-methylquinoline to 8-(methoxymethyl)quinoline in the presence of an oxidant, PhI(OAc)2. Near-quantitative conversions to the desired product were obtained using a catalyst recovered from waste under milder conditions (50 °C, 1–2 mol% Pd loading) and shorter reaction times (2 h) than those typically used in the literature. The [NnBu4]2[Pd2I6] catalyst could also be recovered and re-used multiple times after the reaction, providing additional sustainability benefits. Both [NnBu4]2[Pd2I6] and PdI2(dppf) were also found to be active in Buchwald–Hartwig amination reactions, and their performance was optimised through a Design of Experiments (DoE) study. The optimised conditions for this waste-derived palladium catalyst (1–2 mol% Pd loading, 3–6 mol% of dppf) in a bioderived solvent, cyclopentyl methyl ether (CPME), offer a more sustainable approach to C-N bond formation than comparable amination protocols.

Efficient solar-driven interfacial evaporation using conjugated microporous polymer networks synthesized from Buchwald–Hartwig coupling

Solar-driven interfacial evaporation (SDIE) has been considered as an effective and sustainable technology to purify water. To optimize heat localization and regulate water-existing forms via developing excellent photothermal materials is a key strategy to enhance SDIE performance. Herein, three novel conjugated microporous polymer networks (namely PBPs) were readily synthesized via Buchwald-Hartwig coupling between aryl bromides and p-phenylenediamine. Under 1 sun irradiation, the pure PBP-He without any additives delivered an excellent water evaporation of 1.18 and 0.96 kg · m−2 · h−1 using pure water, nature seawater as water source, respectively, and the corresponding energy conversion efficiency was up to 81.1 % and 65.7 %. An ever-enhanced SDIE performance was found in the PBPs networks with increased amine-linked sites density. The study provided a promising CMPs-based photothermal conversion platform for water purification, photothermal therapy, and photothermal sterilization, etc.