Buchwald-Hartwig Amination Reaction Research Articles

Intelligent predicting reaction performance in multi-dimensional chemical space using quantile regression forest

Buchwald-Hartwig amination reaction is widely applied in synthetic organic chemistry, which faces tedious and complex experimental process. In 2018, an interesting yield prediction technique is proposed via machine learning (random forest) in Science. However, the method is based on point prediction with many feature descriptors. For tackling these problems, complements and improvements have been made from the perspectives of machine learning and statistics, including feature dimensionality reduction, distributed prediction and visualization, so as to provide accurate and reliable decision information.

Controlling Regioselectivity in Palladium-Catalyzed C-H Activation/Aryl-Aryl Coupling of 4-Phenylamino[2.2]paracyclophane.

Selective activation/functionalization of C−H bonds has emerged as an atom‐ and step‐economical process at the forefront of modern synthetic chemistry. This work reports palladium‐catalyzed exclusively para‐selective C−H activation/aryl–aryl bond formation with a preference over N‐arylation under the Buchwald–Hartwig amination reaction of 4‐phenylamino[2.2]paracyclophane. This innovative synthetic strategy allows a facile preparation of [2.2]paracyclophane derivatives featuring disparate para‐substitutions at C‐4 and C‐7 positions in a highly selective manner, gives access to a series of potential candidates for [2.2]paracyclophane‐derived new planar chiral ligands. The unprecedented behavior in reactivity and preferential selectivity of C−C coupling over C−N bond formation via C−H activation is unique to the [2.2]paracyclophane scaffold compared to the non‐cyclophane analogue under the same reaction conditions. Selective C−H activation/aryl–aryl bond formation and sequential C−N coupling product formation is evidenced unambiguously by X‐ray crystallography.

Facile access to conjugated polymers under aerobic conditions via Pd-Catalyzed direct arylation and aryl amination polycondensation

Facile polymerization reaction conditions were developed for synthesizing conjugated polymers via direct arylation and the Buchwald-Hartwig aryl amination reactions under aerobic conditions. Refluxing the reaction solvent and using XPhos Pd G2 as a precatalyst proved to be a tolerant polymerization protocol for direct arylation polycondensation, which eliminates the need for an inert gas atmosphere and can successfully proceed using commercially available, reagent-grade N,N-dimethylformamide (DMF) as the solvent. This strategy was also successfully applied to the Buchwald-Hartwig aryl amination polycondensation in toluene, which provided poly(triarylamine)s in air.

Ligand Effects of BrettPhos and RuPhos on Rate-Limiting Steps in Buchwald-Hartwig Amination Reaction Due to the Modulation of Steric Hindrance and Electronic Structure.

The differences in catalytic activity between two catalyst ligands of Buchwald–Hartwig amination reaction, BrettPhos versus RuPhos, were investigated using density functional theory (DFT) calculations. The reaction process consists of three consecutive steps: (1) oxidative addition, (2) deprotonation, and (3) reductive elimination. Among them, the rate-limiting step of Pd-BrettPhos catalytic system is oxidative addition but that of Pd-RuPhos catalytic system is reductive elimination due to their differences in steric hindrance and electronic structure. It was also revealed that amines with large-size substituents or halides with electron-withdrawing groups would reduce the activation energy barriers of the reactions. The insights gained from the calculations of the Buchwald–Hartwig amination reaction would be helpful for the rational designing of new catalysts and reactions.

An efficient phenylaminecarbazole-based three-dimensional hole-transporting materials for high-stability perovskite solar cells

Hole-transport materials (HTMs) are the key material for preparing high-performing perovskite solar cells (PSCs). Herein, we present a novel and efficient hole-transporting material, 9,9-dioctyl fluorenyl phenylamine carbazole linked methoxy triphenylamines (CzPAF-OMeTAD), which was synthesized via Buchwald–Hartwig amination reactions from very cheap raw materials such as phenylcarbazole with 9,9-dioctyl fluorene bridge and arylamine terminals. It is demonstrated the synthesized CzPAF-OMeTAD with 9,9-dioctyl fluorene as bridge shows a higher hydrophobic and further induce a higher water contact angle of 91° relative to that (79°) for commonly Spiro-OMeTAD with spirofluorene linked methoxy triphenylamines. Further, CzPAF-OMeTAD also exhibits a deeper highest occupied molecular orbital (HOMO) energy level of −5.30 eV and a higher hole mobility of 3.83 × 10−5 cm2V-1S−1, indicating a potential hole-transport material for high-performance perovskite solar cells. Thus, PSCs were fabricated by using the CzPAF-OMeTAD as HTMs, and the resulting cell demonstrates a high power conversion efficiency (PCE) of 15.35% and very high stability. For example, after 20 days of aging with relative humidity of 60%, the PCE still exhibit retention more than 87% of their initial values for corresponding cell. These are ascribed to the improved film-forming ability by sufficient amount of alkyl chains in CzPAF-OMeTAD and a higher hole-mobility for CzPAF-OMeTAD. These results implied our current research provides huge potential direction in the development of highly efficient and stable PSCs with further optimizing HTMs in the future.

Synthesis and nonlinear optical properties of novel conjugated small molecules based on coumarin donor

Novel electronic donor with polycyclic structure based on coumarin was designed and prepared. Pyrrolidine acting as an isolated group was introduced to the donor by the Buchwald-Hartwig amination reaction. Such a novel electronic donor demonstrated great electron-donating capability and an excellent isolation effect. Both chromophores exhibited a D-π-A-π-A molecular structure. Such a structure has great advantages in energy matching, dipole interaction, and electron transfer, compared to the single D-π-A structure. The chemical structures of novel chromophores based on this donor were characterized by 1H nuclear magnetic resonance spectroscopy, 13C nuclear magnetic resonance spectroscopy, and mass spectrometry. The largest electro-optic coefficients are approximately 31.2 and 42.6 pm/V for chromophores NLO-C and NLO-P, respectively, at 1310 nm; otherwise, both chromophores NLO-C and NLO-P exhibit high thermal decomposition temperatures, i.e., 276 and 237 °C, respectively.

Palladium Catalyst with Task-Specific Ionic Liquid Ligands: Intracellular Reactions and Mitochondrial Imaging with Benzothiadiazole Derivatives.

A water-soluble and charge-tagged palladium complex (PdMAI) was found to function inside breast cancer live cells of the MCF-7 lineage as an efficient catalyst for cross-coupling reaction. PdMAI, bearing two ionophilic task-specific ionic liquids as ligands, efficiently catalyzed both in cellulo Suzuki and Buchwald-Hartwig amination reactions. For the first time, therefore, the Buchwald-Hartwig amination is described to occur inside the highly complex cellular environment. The 2,1,3-benzothiadiazole (BTD) core was used as the base for the syntheses, and two π-extended fluorescent derivatives (BTD-2APy) and (BTD-1AN), which were found to emit in the green and red channels, had impressive mitochondrial affinity. These chromophores allowed for selective mitochondrial imaging and tracking.

Step-by-step real time monitoring of a catalytic amination reaction

The multiple reaction monitoring mode of a triple quadrupole mass spectrometer is used to examine the Buchwald-Hartwig amination reaction at 0.1% catalyst loading in real-time using sequential addition of reagents to probe the individual steps in the cycle. This is a powerful new method for probing reactions under realistic conditions.

Buchwald-Hartwig amination of the chloro substituted benzobicyclo[3.2.1]octadiene skeleton using primary benzylic amines

Promising test results on biological activity of our previously described benzobicyclo[3.2.1]octadienes, obtained by intramolecular photochemical cycloaddition of o-vinylphenyl substituted butadienes, prompted us to continue with the further functionalization of this basic skeleton. Synthesis was extended to amino substituted benzobicyclo[3.2.1] octadienes starting from the chloro derivative. Novel benzobicyclo[3.2.1]octadiene benzylamines were prepared for the first time by Buchwald-Hartwig amination from the photoproduct obtained by highly efficient continuous flow-photochemistry setup. The novel amino substituted benzobicyclo[3.2.1]octadienes are especially interesting because of their methano-bridged junction of the three aromatic units at defined geometries as this gives them potential as molecular clips with very promising ADME properties due to the amino functional group. This is the first example of the Buchwald-Hartwig amination reaction on a rigid non-planar system.

Synergistic Ligand Effect between N-Heterocyclic Carbene (NHC) and Bicyclic Phosphoramidite (Briphos) Ligands in Pd-Catalyzed Amination

A synergistic ligand effect between NHC and phosphorus ligands in Pd-catalyzed Buchwald–Hartwig amination reactions was demonstrated with tunable π-acceptor bicyclic bridgehead phosphoramidite (briphos) ligands. The catalytic activity of NHC-Pd-L (L = phosphorus ligand) precatalysts depends on the electronic properties of L. A NHC-Pd-L catalyst with an N-cyclohexyl-substituted briphos ligand was found to be highly efficient. A series of C–N bond coupling reactions between primary or secondary amines and aryl chlorides were performed with high yields under mild reaction conditions.

Design, Synthesis, Opto–Electrochemical and Theoretical Investigation of Novel Indolo[2, 3‐b]naphtho[2, 3‐f]quinoxaline Derivatives for n–Type Materials in Organic Electronics

AbstractA series of seven new donor–acceptor compounds based on indolo[2, 3‐b]naphtho[2, 3–f] quinoxaline were synthesized by using Buchwald–Hartwig amination reaction between 12–bromo–9–heptyl–5H–indolo[2, 3–b]naphtho[2, 3–f]quinoxaline‐5,15‐(9H)–dione (1) and diaryl/cyclic amine (2–5) and by Suzuki–Miyaura coupling reaction of 1 with aryl boronic acid (6–8). The synthesized molecules were studied to determine their absorption, emission, electrochemical, thermal properties. Theoretical properties were also studied by time dependent density functional theory (TD‐DFT). The HOMO and LUMO energy levels of 2–8 are in the range of −6.51 to −6.84 eV and –3.00 to –3.30 eV respectively. Low−lying LUMO energy levels of 2–8 are very similar to well−known n−type materials. On the basis of experimental and theoretical studies synthesized compounds could act as n−type materials in organic electronics.

Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

Synthesis and optoelectronic investigation of triarylamines based on imidazoanthraquinone as donor–acceptors for n-type materials

A series of five new donor–acceptor molecules based on imidazo-anthraquinone-amines have been synthesized and characterized. The structure-property relationship in these molecules is systematically examined by absorption-emission spectroscopy, cyclic voltammetry and theoretical studies. Optical properties of these molecules have been studied in solvents of varying polarity as well as in neat solid film and found to be affected by the nature of triarylamine substituent with broad absorption windows, strong charge transfer transitions (425–502 nm), high molar extinction coefficients and emission in green light (500–568 nm). Electrochemical data indicated that the dyes possess relatively low-lying LUMO values ( $$-3.18$$ to $$-3.42$$ eV) while TGA studies revealed good thermal stability. The donor-acceptor architecture and HOMO–LUMO energies were further rationalized using DFT calculations. Experimental studies along with theoretical calculations suggest that these compounds have potential to be used as n-type materials in optoelectronic devices. Imidazoanthraquinone–amine derivatives with donor–acceptor molecular architecture were synthesized using Buchwald–Hartwig amination reaction featuring ICT absorption and low lying LUMO energy level ( $$-3.18$$ to $$-3.42$$ eV). These are comparable with well-known n-type materials for their applications in organic electronics.

An Efficient Microwave-Assisted Synthesis of Novel 2-{4-[(3-Aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones and Their Antimicrobial Activity

The Buchwald–Hartwig amination reaction between 2-chloro-3-aryl-1,8-naphthyridines and 2-(4-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione in the presence of the catalytic system Pd(PPh3)4 and the base KO-t-Bu in toluene was studied. The reaction was initiated by microwave irradiation. Highly efficient synthesis has been developed for 2-{4-[(3-aryl-1,8-naphthyridin-2-yl)amino]phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones. Structures of the synthesized compounds were evaluated by IR, 1H and 13C NMR spectroscopy. All products were tested for antimicrobial activity against Escheria coli, Bacillus subtilis, Klebsiella pneumoniae, and Staphylococcus aureus.

Blue organic light-emitting diodes based on spiro[fluorene-indeno]pyridine derivatives

ABSTRACTWe designed and synthesized two blue fluorescent materials based on spiro[9H-fluorene-9, 5′-[5H] indeno[1, 2-b] pyridine via Buchwald-Hartwig amination and Suzuki coupling reaction. To characterize their electroluminescent properties, multilayered organic light emitting diodes (OLEDs) were fabricated with the following device structures: ITO(180 nm)/2-TNATA(60 nm)/NPB(20 nm)/α,β-ADN: 3, 5, or 10 wt% blue dopants (30 nm)/Bphen(30 nm)/Liq(2 nm)/Al(100 nm). All the devices showed blue emissions with high electroluminescent efficiencies. Particularly, a device using 7′-((4-(N,N-diphenyl)-styryl)-4-phenyl)-spiro[9H-fluorene-9, 5′-[5H] indeno[1, 2-b] pyridine] as a dopant material with 10 wt% doping concentration exhibited highly efficient blue emission with an external quantum efficiency of 4.46% at 20 mA/cm2 and the CIE coordinates of (0.18, 0.30) at 1000 cd/m2. In this device, the twisted structural feature of emitter originated from spiro-type core prevented self-quenching and lead to the improved efficiencies even at high doping concentration in the device.

Transmissive-to-Black Electrochromic Devices Based on Cross-Linkable Tetraphenylethene-Diphenylamine Derivatives

Transmissive-to-black switching organic electrochromic device based on a cross-linkable, symmetric diphenylamine derivative with a tetraphenylethene core is reported. The tetraphenylethene-diphenylamine derivative, TPOSt with thermally cross-linkable styrene end groups and the model derivative, TPOMe were synthesized as a mixture of cis- and trans- isomers by Buchwald-Hartwig amination reactions. Cross-linked films of TPOSt on ITO showed a reversible, two-electron redox peak at 0.69 V vs Ag/AgCl corresponding to the formation of TPOSt dications which exhibited an absorption spectra spanning the entire visible region and extending up to 1100 nm. Further, the electrochromic switching between a highly transmissive, light yellow colored neutral state (L*= 97, a*= -5, b*= 16) and a black coloured oxidized state (L*= 41, a*= 2, b*= 8) with high optical contrasts (up to 50%ΔT) and reasonably low switching times (<10 s) were demonstrated over 1500 cycles using a simple electrochromic device design [FTO/EC layer/ ...

Fluorinated Unsymmetrical N,N'-Diaryl Imidazolium Salts-New Functionalized NHC-Ligand Precursors.

An efficient and scaled-up synthesis of the imidazol-2-ylidene-based unsymmetrical NHC precursors bearing the sterically demanding hexafluoroisopropylalkoxy group [(CF3 )2 (OR)C-] at the ortho position of the N-aryl substituent was developed. The key step of the method involved the transformation of a Mes-substituted oxazolinium tetrafluoroborate salt through the reaction with the corresponding binucleophilic fluoroalkyl-substituted aniline. The subsequent post-modification of the resulting hydroxyl-containing salt through a simple one-step O-alkylation protocol provided access to a new family of unsymmetrical fluorinated NHC precursors. These compounds were successfully utilized for the preparation of several novel metal complexes. The molecular structures of some NHC precursors and their metal complexes have been unambiguously characterized by single-crystal X-ray diffraction analysis. A preliminary evaluation of the catalytic activity of the palladium complexes was performed on a Buchwald-Hartwig amination reaction. As a result, two PEPPSI-type (PEPPSI=pyridine-enhanced pre-catalyst preparation stabilization and initiation) Pd complexes have demonstrated promising activity in alkane solvents.

An efficient palladium-catalyzed synthesis of 1-heteroaryl-4-aminopiperidine derivatives from heteroaryl chlorides

An efficient protocol for the synthesis of 1-heteroaryl-4-(N-methyl)aminopiperidines starting from heteroaryl chloride derivatives is described. A broad range of 1-heteroaryl-4-(N-Boc-N-methyl)aminopiperidine derivatives were obtained in good to excellent yields using DavePhos as optimal ligand for Pd-catalyzed Buchwald-Hartwig amination reaction. After a mild and efficient acidolysis the amination products could be obtained successfully.

A novel route for C-N coupling reaction: Alternative synthesis of 2-N-benzylaminoquinoline-3-carbonitrile in aqueous media

The present work relates to a process for C-N Coupling which can be used in a variety of chemical reactions. Work provides a process for C-N coupling between aryl halide and aliphatic amines also a low-cost process for C-N Coupling. It is to develop a process for C-N coupling that explores Buchwald-Hartwig amination reaction. Process may use for making N-alkylaminoquinoline which has industrial applications as a ligand.

Synthesis and properties of benzothiadiazole-pyridine system: The modulation of optical feature

In this work, two new benzothiadiazole (BTD)-based compounds 1 and 2 were elaborately designed and synthesized, to explore the modulation on the interesting optical properties. Briefly, bipyridine-substituted compound 1 was synthesized via a modified Buchwald-Hartwig amination reaction with relatively high yield, and then derivative 2 was prepared by a following dehydrogenation reaction. The result in steady-state spectroscopic analysis and DFT/TDDFT calculation suggest the readily polarized nature of 1. In contrast, the readily polarized nature was declined in π-conjugated molecule 2, indicating the blue-shifted absorption and emission. Interestingly, negative cubic nonlinear refraction behavior in 1 is greater than that in π-conjugated system 2. Furthermore, in case 1 or 2, the photophycal property was considerably influenced by the external transition metal ion (M = Ag+, Cu2+ or Fe3+). Especially, because of the existence of external Fe3+ in case 1, initially negative nonlinear refraction signal became a positive one. Such exciting result is quietly useful for the design and synthesis of new functional BTD-based dye material.