N-arylation Research Articles

Reactions’ Descriptors Selection and Yield Estimation Using Metaheuristic Algorithms and Voting Ensemble

Bioactive compounds in plants, which can be synthesized using N-arylation methods such as the Buchwald-Hartwig reaction, are essential in drug discovery for their pharmacological effects. Important descriptors are necessary for the estimation of yields in these reactions. This study explores ten metaheuristic algorithms for descriptor selection and model a voting ensemble for evaluation. The algorithms were evaluated based on computational time and the number of selected descriptors. Analyses show that robust performance is obtained with more descriptors, compared to cases where fewer descriptors are selected. The essential descriptor was deduced based on the frequency of occurrence within the 50 extracted data subsets, and better performance was achieved with the voting ensemble than other algorithms with RMSE of 6.4270 and R2 of 0.9423. The results and deductions from this study can be readily applied in the decision-making process of chemical synthesis by saving the computational cost associated with initial descriptor selection for yield estimation. The ensemble model has also shown robust performance in its yield estimation ability and efficiency.

Effect of arylamino-carbazole containing hole transport materials on the device performance and lifetime of OLED

We synthesized four hyper-conjugated aromatic hole transporting materials with different molecular geometry and energy levels by attaching arylamino moiety attached to the carbazole core. A brominated carbazole moiety reacted with an arylamino moiety using a Buchwald-Hartwig reaction. The characteristics of these hole transporting materials were investigated using TGA, DSC, UV–Vis and luminescence spectroscopy. The energy levels of all materials used in this study were estimated from cyclic voltammograms and absorption spectra. The hole transporting properties of the synthesized molecules were measured using single-carrier devices. All four hole transporting materials showed similar hole mobility. The effectiveness of hole transporting materials was compared by fabricating green-emitting organic light emitting diode (OLED) devices. It turned out that the device performances were critically dependent on the relative energy levels of the hole transporting layer and emission layer. However, the molecular geometry greatly influenced the device lifetime, determining thermally induced crystallization by the heat produced during device operation. • Hole transporting materials with different molecular symmetry were synthesized. • Hole transporting materials profoundly affect device performances and lifetime. • Device performances were affected by the energy level relative to the emission layer. • Device lifetime is affected by the molecular geometry of hole transporting materials.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

A General Catalyst for Buchwald-Hartwig Amination to Prepare Secondary Five-Membered Heteroaryl Amines with Breaking the Base Barrier

A General Catalyst for Buchwald-Hartwig Amination to Prepare Secondary Five-Membered Heteroaryl Amines with Breaking the Base Barrier

An efficient Buchwald–Hartwig amination protocol enables the synthesis of new branched and polymeric hole transport materials for perovskite solar cells

Efficient and sustainable Buchwald-Hartwig amination enables the synthesis of new branched and polymeric HTL materials for perovskite solar cells with performances comparable with those of Spiro-OMeTAD.

Thioarylation of anilines using dual catalysis: two-step synthesis of phenothiazines.

A two-step synthesis of phenothiazines has been developed using a dual-catalytic ortho-thioarylation reaction of anilines as the key step. Activation of N-(2-bromophenylthio)succinimide was achieved using the super Lewis acid, iron(III) triflimide and the Lewis base, diphenyl selenide, resulting in an accelerated and efficient ortho-thioarylation reaction of various protected aniline derivatives and less reactive, unprotected analogues. The thioarylated adducts were then cyclised to the desired phenothiazines using either an Ullmann-Goldberg or Buchwald-Hartwig coupling reaction. The dual catalytic thioarylation and copper(I)-catalysed cyclisation approach was used for the four-step synthesis of methopromazine, a neuroleptic agent with antipsychotic activity.

Deep Forest-Based Intelligent Yield Predicting of Buchwald-Hartwig Coupling Reaction

Buchwald-Hartwig coupling reaction is widely used in organic chemical synthesis, yield prediction is particularly important. In 2018, Science reported a yield prediction method based on random forest, but this method lacks feature learning. Therefore, an intelligent prediction and analysis method of coupling reaction yield based on deep forest is proposed. Combined with the advantages of deep learning and ensemble learning, the new deep model in the form of non-neural network is explored, which has good characterization learning ability and low difficulty in adjusting parameters, realizes the efficient prediction of chemical reaction, and analyzes the factors that have a significant impact on the prediction of reaction yield.

Acridine Based Small Molecular Hole Transport Type Materials for Phosphorescent OLED Application.

Two small molecular hole-transporting type materials, namely 4-(9,9-dimethylacridin-10(9H)-yl)-N-(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-N-phenylaniline (TPA-2ACR) and 10,10′-(9-phenyl-9H-carbazole-3,6-diyl)bis(9,9-dimethyl-9,10-dihydroacridine) (PhCAR-2ACR), were designed and synthesized using a single-step Buchwald–Hartwig amination between the dimethyl acridine and triphenylamine or carbazole moieties. Both materials showed high thermal decomposition temperatures of 402 and 422 °C at 5% weight reduction for PhCAR-2ACR and TPA-2ACR, respectively. TPA-2ACR as hole-transporting material exhibited excellent current, power, and external quantum efficiencies of 55.74 cd/A, 29.28 lm/W and 21.59%, respectively. The achieved device efficiencies are much better than that of the referenced similar, 1,1-Bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC)-based device (32.53 cd/A, 18.58 lm/W and 10.6%). Moreover, phenyl carbazole-based PhCAR-2ACR showed good device characteristics when applied for host material in phosphorescent OLEDs.

A Simple Synthetic Route to Well‐Defined [Pd(NHC)Cl(1‐tBu‐indenyl)] Pre‐catalysts for Cross‐Coupling Reactions

AbstractThe development of robust, more efficient, general, easily accessible Pd(II)–NHC pre‐catalysts remains a key issue in cross‐coupling applications. A selection of well‐defined, air and moisture stable [Pd(NHC)Cl(1‐tBu‐indenyl)] (NHC=IPr, IPrCl, IMes, SIMes, IPr*) pre‐catalysts have been synthesized in good to excellent yields by reacting [Pd(1‐tBu‐indenyl)(μ‐Cl)]2 and various NHC⋅HCl precursors in the presence of the weak base K2CO3 in green acetone. The synthesized Pd(II)‐NHC derivatives displayed excellent catalytic activity in classical Suzuki‐Miyaura and Buchwald–Hartwig reactions, especially when IPrCl is employed as ancillary ligand. Additionally, in the challenging Suzuki‐Miyaura reaction between esters and arylboronic acids, the [Pd(IPr*)Cl(1‐tBu‐indenyl)] complex exhibited the optimum catalytic activity under very mild reaction conditions.

New Unsymmetrically Substituted Benzothiadiazole-Based Luminophores: Synthesis, Optical, Electrochemical Studies, Charge Transport, and Electroluminescent Characteristics.

Three new benzothiadiazole (BTD)-containing luminophores with different configurations of aryl linkers have been prepared via Pd-catalyzed cross-coupling Suzuki and Buchwald–Hartwig reactions. Photophysical and electroluminescent properties of the compounds were investigated to estimate their potential for optoelectronic applications. All synthesized structures have sufficiently high quantum yields in film. The BTD with aryl bridged carbazole unit demonstrated the highest electrons and holes mobility in a series. OLED with light-emitting layer (EML) based on this compound exhibited the highest brightness, as well as current and luminous efficiency. The synthesized compounds are not only luminophores with a high photoluminescence quantum yield, but also active transport centers for charge carriers in EML of OLED devices.

2,2,5,5-Tetramethyloxolane (TMO) as a Solvent for Buchwald–Hartwig Aminations

2,2,5,5-Tetramethyloxolane (TMO) as a Solvent for Buchwald–Hartwig Aminations

Stable Diarylamine-Substituted Tris(2,4,6-trichlorophenyl)methyl Radicals: One-Step Synthesis, Near-Infrared Emission, and Redox Chemistry

Stable Diarylamine-Substituted Tris(2,4,6-trichlorophenyl)methyl Radicals: One-Step Synthesis, Near-Infrared Emission, and Redox Chemistry

Synthesis and characterization of an isopropylBippyPhos precatalyst

A review of our high throughput reaction screening data revealed that BippyPhos was frequently associated with successful outcomes in Buchwald – Hartwig amination reactions. A barrier to the wider use of this ligand, particularly among those performing smaller scale work, may be the lack of a readily available precatalyst. We describe the multi-gram synthesis and characterization of isopropylBippyPhos, and its conversion to isopropylBippyPhos Pd G2, a biaryl phosphine precatalyst. We demonstrate the competency of isopropylBippyPhos Pd G2 in palladium catalyzed Buchwald – Hartwig amination reactions and in Suzuki – Miyaura cross coupling reactions.

XGBoost-based intelligence yield prediction and reaction factors analysis of amination reaction.

Buchwald-Hartwig amination reaction catalyzed by palladium plays an important role in drug synthesis. In the last few years, machine learning-assisted strategies emerged and quickly gained attention. In this article, an importance and relevance-based integrated feature screening method is proposed to effectively filter high-dimensional feature descriptor data. Then, a regularized machine learning boosting tree model, eXtreme Gradient Boosting, is introduced to intelligently predict reaction performance in multidimensional chemistry space. Furthermore, convergence, interpretability, generalization, and the internal association between reaction conditions and yields are excavated, which provides intelligent assistance for the optimal design of coupling reaction system and evaluating the reaction conditions. Compared with recently published results, the proposed method requires fewer feature descriptors, takes less time, and achieves more accurate prediction accuracy.

Buchwald-Hartwig Amination of Aryl Halides with Heterocyclic Amines in the Synthesis of Highly Fluorescent Benzodifuran-Based Star-Shaped Organic Semiconductors.

The study of palladium-catalyzed amination of bromobenzene with aromatic and heterocyclic amines, widely used in the synthesis of organic semiconductors, was performed. The best conditions for the coupling of aryl bromides with carbazole, diphenylamine, phenoxazine, phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, and their derivatives have been developed. Based on the results, nine new star-shaped organic semiconductors, exhibiting up to 100% fluorescent quantum yield in the 400–550 nm range, have been synthesized in good yields. The TDDFT calculations of the absorption spectra revealed a good correlation with experimental results and slight solvatochromic effects with a change in the polarity of the solvent.

Buchwald-Hartwig Amination of Coordinating Heterocycles Enabled by Large-but-Flexible Pd-BIAN-NHC Catalysts.

A new class of large-but-flexible Pd-BIAN-NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N-heterocyclic carbene) has been rationally designed to enable the challenging Buchwald-Hartwig amination of coordinating heterocycles. This robust class of BIAN-NHC catalysts permits cross-coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron-deficient heterocycles containing multiple heteroatoms with BIAN-INon (N,N'-bis(2,6-di(4-heptyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-8-ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN-NHC scaffold.

Micellar Buchwald-Hartwig Coupling of Aryl and Heteroarylamines for the Synthesis of DNA-Encoded Libraries.

DNA-encoded libraries are a very efficient means of identifying ligands for protein targets in high throughput. To fully maximize their use, it is essential to be able to carry out efficient reactions on DNA-conjugated substrates. Arylamines are privileged motifs in druglike molecules, and methods for their incorporation into DNA-encoded libraries are highly desirable. One of the preferred methods for their preparation, the Buchwald-Hartwig coupling, does not perform well on DNA conjugates using current approaches. We report the application of our recently developed micellar technology for on-DNA chemistry to the Buchwald-Hartwig reaction. Optimization of conditions led to a robust, high-yielding method for the synthesis of DNA-conjugated aryl and heteroarylamines, which is broad in substrate scope for both the arylamine and the DNA-conjugated aryl halide and is fully compatible with DNA-encoding and decoding procedures. This method will enable the preparation of diverse, high-fidelity libraries of biarylamines.

D−A−D based pyrido-pyrazino[2,3-b]indole amines as blue-red fluorescent dyes: Photophysical, aggregation-induced emission, electrochemical and theoretical studies

Herein donor−acceptor−donor (D−A−D) structured, pyridopyrazino[2,3-b]indole amines 2–6 were designed and synthesized via C–N coupled Buchwald-Hartwig amination reaction and characterized by spectroscopic methods. C–N coupling in molecules offers intramolecular charge transfer (ICT) transitions at longer wavelengths (λmax = 400–459 nm) in absorption spectra reminiscent D−A assembly. Dyes covers broad range of emission and emit in blue to red region with emission maxima 433–600 nm in solvent and solid film. Dyes 2, 5 and 6 explore the aggregation-induced emission (AIE) characteristics. Further C–N blending of various donor with pyridopyrazino[2,3-b]indole acceptor results in suppressed band gap (1.99–2.43 eV) and comparable HOMO (−5.17 to −5.71 eV) and LUMO (−3.18 to −3.28 eV) energies with reported small organic ambipolar materials. DFT and TDDFT calculations agree with the experimental opto-electrochemical data. Moreover, computed small singlet and triplet excitation energy difference (ΔEST (0.01–0.14 eV)) suggest thermally activated delayed fluorescent (TADF) emitting properties of dyes. Thus pyridopyrazino[2,3−b]indole amine dyes propose their potential application in optoelectronic devices.

Kernel Methods for Predicting Yields of Chemical Reactions.

The use of machine learning methods for the prediction of reaction yield is an emerging area. We demonstrate the applicability of support vector regression (SVR) for predicting reaction yields, using combinatorial data. Molecular descriptors used in regression tasks related to chemical reactivity have often been based on time-consuming, computationally demanding quantum chemical calculations, usually density functional theory. Structure-based descriptors (molecular fingerprints and molecular graphs) are quicker and easier to calculate and are applicable to any molecule. In this study, SVR models built on structure-based descriptors were compared to models built on quantum chemical descriptors. The models were evaluated along the dimension of each reaction component in a set of Buchwald-Hartwig amination reactions. The structure-based SVR models outperformed the quantum chemical SVR models, along the dimension of each reaction component. The applicability of the models was assessed with respect to similarity to training. Prospective predictions of unseen Buchwald-Hartwig reactions are presented for synthetic assessment, to validate the generalizability of the models, with particular interest along the aryl halide dimension.

Improved Buchwald–Hartwig Amination by the Use of Lipids and Lipid Impurities

The development of green Buchwald–Hartwig aminations has long been considered challenging, due to the high sensitivity of the reaction to the environment. Here we show that food-grade and waste vegetable oils, triglycerides originating from animals, and natural waxes can serve as excellent green solvents for Buchwald–Hartwig amination. We further demonstrate that amphiphiles and trace ingredients present in triglycerides as additives have a decisive effect on the yields of Buchwald–Hartwig aminations.