Secondary Arylamines Research Articles

Catalyst Free Synthesis of 4‐Aryl/Alkylamino‐1,2‐Naphthoquinones: Applications in Fluorescence Microscopy

AbstractAn efficient one‐step reagent‐free synthesis of 4‐Aryl/alkylamino‐1,2‐naphthoquinones in water and iPrOH (1 : 1) mixture was carried out at room temperature (RT) using 4‐amino‐3‐hydroxynaphthalene‐1‐sulfonic acid and various primary and secondary aryl and alkyl amines. The reaction did not proceed in the absence of air or oxygen. In all cases, good yields (isolated yield: ≥65 %) were observed. The compounds exhibited fluorescence emission bands (400–470 nm) in the visible region upon excitation at their respective λmax values (330–350 nm). We evaluated in vitro cytotoxicity of some of the derivatives against two human breast cancer cell lines (MCF‐7, and MDA‐MB‐231) using the WST‐1 assay. The naphthoquinone derivatives did not show any cytotoxic effects at concentration levels relevant to cellular fluorescence imaging. The imaging experiments revealed that a few of the derivatives hold the potential to be used as cellular fluorescent imaging probes.

Para-selective nitrobenzene amination lead by C(sp2)-H/N-H oxidative cross-coupling through aminyl radical

Arylamines, serving as crucial building blocks in natural products and finding applications in multifunctional materials, are synthesized on a large scale via an electrophilic nitration/reduction sequence. However, the current methods for aromatic C–H amination have not yet attained the same level of versatility as electrophilic nitration. Here we show an extensively investigated transition metal-free and regioselective strategy for the amination of nitrobenzenes, enabling the synthesis of 4-nitro-N-arylamines through C(sp2)-H/N-H cross-coupling between electron-deficient nitroarenes and amines. Mechanistic studies have elucidated that the crucial aspects of these reactions encompass the generation of nitrogen radicals and recombination of nitrobenzene complex radicals. The C(sp2)-N bond formation is demonstrated to be highly effective for primary and secondary arylamines as well as aliphatic amines under mild conditions, exhibiting exceptional tolerance towards diverse functional groups in both nitroarenes and amines (>100 examples with yields up to 96%). Notably, this C(sp2)-H/N-H cross-coupling exhibits exclusive para-selectivity.

High-Pressure Promoted Nazarov-like Electrocyclization Enables Access to trans-4,5-Diamino-cyclopent-2-enones Bearing Electron-Poor Anilines.

Unlike secondary alkyl amines and electron-rich anilines, secondary electron-poor anilines are challenging amine sources to explore the chemical space of Lewis acid-catalyzed condensation-based transformations with furfural. In this work, we report the efficient synthesis of trans-4,5-diamino cyclopentenones (DCP) using a high-pressure promoted Nazarov-like electrocyclization of Stenhouse salts arising from the Sc(III)-catalyzed condensation of furfural with secondary electron-poor anilines. The reaction enables access to otherwise difficult-to-access DCP and compatibility with a large scope of alkyl and aryl secondary amines. A 2- to 18-fold increase in yields for electron-poor anilines was highlighted using this approach in the synthesis of a pharmacologically active compound.

Amino-λ3 -iodane-Enabled Electrophilic Amination of Arylboronic Acid Derivatives.

In this report, we describe the use of amino-λ3 -iodanes in the electrophilic amination of arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one with an NH2 group, were synthesized and used in the amination, allowing the synthesis of a wide range of primary and secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that the reaction proceeds through an electrophilic amination process from a tetravalent borate complex with a B-N dative bond.

Amino‐λ3‐iodane‐Enabled Electrophilic Amination of Arylboronic Acid Derivatives

AbstractIn this report, we describe the use of amino‐λ3‐iodanes in the electrophilic amination of arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one with an NH2 group, were synthesized and used in the amination, allowing the synthesis of a wide range of primary and secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that the reaction proceeds through an electrophilic amination process from a tetravalent borate complex with a B−N dative bond.

Photoredox-catalysed hydroaminoalkylation of on-DNA N-arylamines.

An efficient approach to the photoredox-catalysed hydroaminoalkylation between on-DNA secondary N-substituted (hetero)arylamines and vinylarenes has been developed and explored. The methodology was examined with a broad scope of vinylarenes and secondary arylamines to establish a preferred building block profile for the process. Compatible substrates furnished the desired derivitised amine products in modest to excellent conversions and with minimal or no detectable by-products.

Near-infrared piezochromism of AIE-active luminophore in hybridized local and charge-transfer excited state—the effect of shortened donor-acceptor distance

A close-bonded D-A-D′ luminophore BOTPA was designed via direct coupling of secondary arylamine derivatives (D, D′) with benzothiadiazole cyanostilbene group (A). Both near-infrared (NIR) aggregation-induced emission (AIE) and hybridized local and charge-transfer (HLCT) effects, which endow it with highly efficient NIR piezochromic performance, are observed owing to its especially short D-A distance and twisted conformation. The luminophore shows bright fluorescence at 740 nm with an absolute photoluminescence quantum yield (PLQY) as large as 13.2%. Remarkable piezochromism with high sensitivity (11.0 nm•Gpa−1) completely in the NIR region (700–840 nm) could be observed from BOTPA crystals, which is rarely found in piezochromic materials (PCMs). The effects of the shortened D-A distance towards the highly efficient NIR piezochromism are confirmed via single-crystal analysis, in-situ FTIR and theoretical calculations. This work provides a new strategy for the development of high-efficiency NIR PCMs which possess strong penetrating capacity.

Ureate Titanium Catalysts for Hydroaminoalkylation: Using Ligand Design to Increase Reactivity and Utility

Hydroaminoalkylation describes the atom-economical catalytic synthesis of amines by forming new Csp3–Csp3 bonds using readily available amine and alkene feedstocks. Herein, we describe an earth-abundant and cost-efficient titanium catalyst generated in situ using commercially available Ti(NMe2)4 and a simple to synthesize urea proligand. This system demonstrates high TOFs for hydroaminoalkylation with unactivated substrates and features easy to use commercially available titanium amido precursors. Additionally, a high catalytic activity, scope of reactivity, and regioselectivity are all demonstrated in the transformation of unactivated terminal olefins with various alkyl and aryl secondary amines. Finally, syntheses of useful amine-containing monomers suitable for the generation of amine-containing materials, as well as amine-containing building blocks for medicinal chemistry, are disclosed. These preparative methods avoid the necessity of glovebox techniques and are modified to be useful to all synthetic chemists.

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines.

The first Ni(OTf)2-catalyzed hydroamination of ynamides 2 was developed by reacting with secondary amines (1 and 4). This protocol features excellent regioselectivity, a broad substrate scope of secondary aryl amines, and good functional group tolerance for ynamides. Using this method, a variety of substituted ethene-1,1-diamine compounds were prepared in moderate to excellent yields with high regioselectivities.

Cobalt nanoclusters coated with N-doped carbon for chemoselective nitroarene hydrogenation and tandem reactions in water

Subnanometric cobalt nanoclusters covered by N-doped carbon layers (Co@NC-800) catalyze the chemoselective reduction of nitroarenes and the one-pot synthesis of secondary aryl amines and isoindolinones in aquo media under mild reaction conditions.

Single and bi-excitonic characteristics of ligand-modified silicon nanoparticles as demonstrated via single particle photon statistics and plasmonic effects.

Silicon nanoparticles (Si NPs) are of great interest to researchers due to their fluorescence properties, low toxicity, and the low cost of the Si precursor. Recent studies have shown that Si NPs surface-modified with secondary aryl amine ligands emit light at wavelengths ranging from cyan to yellow and with quantum yields of up to 90%. The predominant emitting state in these species has been assigned to a charge-transfer (CT) transition from the ligand to the Si particle as the emission wavelength is determined by the dipolar properties of the ligand rather than the size of the Si core. This contribution focuses on the single-molecule emission properties of Si NPs functionalized with a 1,2,3,4-tetrahydrocarbazole-4-one ligand (Te-On) which have a peak emission wavelength of 550 nm and a quantum yield of 90%. In single-particle dispersed emission spectra, a weak long-wavelength sideband is seen in addition to the dominant yellow emission derived from the CT state. The photon statistical behavior of single Si NPs in the red emission region is consistent with that of a state having collective or bi-excitonic character. In contrast, the yellow emission exhibits predominantly CT character. Deposition of the sample onto a thin gold film causes the CT emission to be quenched whereas that attributed to a bi-exciton state of the Si core is enhanced. These results provide new insights into the mechanism of single-molecule intensity fluctuation in these surface-modified silicon nanoparticles that will benefit proposed applications in biological labeling and as single-photon sources.

A Novel Modified Cross-Coupling of Phenols and Amines Using Dichloroimidazolidinedione (DCID)

Phenols are considered as an ideal alternative to aryl halides as coupling partners in cross-coupling reactions. In the present work a copper-catalyzed cross-coupling of phenols with various aromatic and aliphatic amines for the synthesis of secondary aryl amines using dichloroimidazolidinedione (DCID) as a new and efficient activating agent has been developed. Substituted phenols were compatible with the standard reaction conditions. The two proposed mechanisms, which are based on the oxidation addition of copper with Ar-OMCID (MCID: Monochloroimidazolidinedione), are also discussed.

Palladium Complexes Based on Ylide-Functionalized Phosphines (YPhos): Broadly Applicable High-Performance Precatalysts for the Amination of Aryl Halides at Room Temperature.

Palladium allyl, cinnamyl, and indenyl complexes with the ylide‐substituted phosphines Cy3P+−C−(R)PCy2 (with R=Me (L1) or Ph (L2)) and Cy3P+−C−(Me)PtBu2 (L3) were prepared and applied as defined precatalysts in C−N coupling reactions. The complexes are highly active in the amination of 4‐chlorotoluene with a series of different amines. Higher yields were observed with the precatalysts in comparison to the in situ generated catalysts. Changes in the ligand structures allowed for improved selectivities by shutting down β‐hydride elimination or diarylation reactions. Particularly, the complexes based on L2 (joYPhos) revealed to be universal precatalysts for various amines and aryl halides. Full conversions to the desired products are reached mostly within 1 h reaction time at room temperature, thus making L2 to one of the most efficient ligands in C−N coupling reactions. The applicability of the catalysts was demonstrated for aryl chlorides, bromides and iodides together with primary and secondary aryl and alkyl amines, including gram‐scale applications also with low catalyst loadings of down to 0.05 mol %. Kinetic studies further demonstrated the outstanding activity of the precatalysts with TOF over 10.000 h−1.

Photodriven Photocatalyst/Metal-Free Direct C-C/C-N Bond Formation: Synthesis of Indoles via EDA Complexes.

The photodriven direct C-C/C-N bond formation initiated by electron donor-acceptor (EDA) complexes for the synthesis of indoles has been accomplished via [3+2] annulations of secondary arylamines with alkynes using IC4F9 as oxidants in the absence of any photocatalysts and metals. This green transformation exhibits the advantages of operational simplicity, good functional tolerances, and mild reaction conditions. The in situ generated EDA complexes derived from arylamines with alkynes were characterized by UV-vis absorption spectrometry and NMR titration experiments.

Synthesis of secondary arylamine copolymers with Iron(II) clathrochelate units and their functionalization into tertiary Polyarylamines via Buchwald-Hartwig cross-coupling reaction

We report the synthesis of three secondary arylamine copolymers bearing iron(II) clathrochelate units (CLP1-3). Three of the latter copolymers were post-modified into their tertiary arylamine moieties (PCLP1-3) using a mild palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. Interestingly, the functionalization of the secondary arylamine groups has resulted in the formation of highly soluble target compounds PCLP1-3, which allowed for their simple isolation and full analysis via various techniques. It is noteworthy that a prototypical secondary arylamine iron(II) clathrochelate monomer CLM1 was synthesized and post-modified into its tertiary arylamine target compound CLM2. The current study discloses the first examples on making secondary arylamine copolymers with clathrochelate constituents, and proves the possible post-modification of the latter compounds into tertiary arylamine, which proves the modularity of iron(II) clathrochelate unit to make functional polymers. Formation of the monomers and copolymers was confirmed by 1H- and 13C- nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS), Thermogravimetric Analysis (TGA), scanning electron microscopy (SEM), and UV–Vis absorption spectroscopy.

Взаимодействие пиперилена и его хлорпроизводных с ароматическими аминами

The article considers the possibility of introducing a pentenyl radical into the structure of aromatic amines by the interaction of the latter with piperylene and its chlorine derivatives, 4-chloro-2-pentene and 3,4-dichloro-2-pentene. Direct alkenylation of aniline with piperylene in the presence of Lewis acids leads to C-alkenyl arylamines. The most effective catalyst is AlCl3. Along with the expected 2- and 4-(1-methyl-2-butenyl) anilines, the formation of 2,4-di- and 2,4,6-tri-(1-methyl-2-butenyl) anilines is observed, the latter being virtiually the only product in the reaction with a 5-fold excess of piperylene. In addition to Lewis acids, H3PO4 deposited on kieselguhr or silica gel, as well as polyphosphoric acid, were used to catalyze this reaction. Under the action of these catalysts, ortho- and para-alkenylated anilines are mainly formed, and the yield of the ortho-isomer, reaching 34%, always exceeds the yield of the para-product. It is possible that, under these conditions, N-alkenylation occurs simultaneously with direct C-alkenylation followed by an amino rearrangement. The yield of the 2,4-dialkenyl product does not exceed 8%, and trialkenylated aniline is completely absent. The optimal reaction temperature is in the range of 180-200 °C, at higher temperatures the yield of the target products decreases due to the polymerization of piperylene. Various aniline derivatives are also involved in the reaction with piperylene. When one of the ortho positions in the arylamine molecule is occupied, as in ortho-toluidine or in 2-chloroaniline, a mixture of the three products is formed in comparable amounts. The reaction of meta-toluidine with piperylene also leads to the mixture of three products, and the substitution does not affect the 2-position between the amino and methyl groups. If both ortho-positions are occupied, as in 2-methyl-6-ethylaniline, the reaction is quite successfully under way in the para-position (yield is 61%). To increase the selectivity of the process, the alkylation of aromatic amines is best carried out not by piperylene, but by its chlorine derivatives. The reaction of aniline with 4-chloro-2-pentene takes place in the environment of triethylamine and leads to N-(1-methyl-2-butenyl) aniline with a yield of 80%. Other primary and secondary arylamines react in the same way. The reaction with 3,4-dichloro-2-pentene proceeds under more severe conditions. If the reaction of aromatic amines with 4-chloro-2-pentene is carried out not in triethylamine medium, but in an excess of arylamine itself as a solvent, then not N- but C-substituted products are formed. The reaction proceeds as a consequitive-simultameous process. In the first stage, N-alkenylation occurs with the formation of N-(1-methyl-2-butenyl) arylamine followed by an amino rearrangement of Claisen under the catalytic action of evolved HCl. Alongside with the obvious predominance of ortho-substituted arylamine (64-82%), para-isomers and, in some cases 5-12% of 2,4- or 2,6-disubstituted compounds were found in the reaction products. The amino rearrangement in the interaction of arylamines with 3,4-dichloro-2-pentene proceeds with exceptional ortho-selectivity. Alkyl groups at nitrogen and ortho positions accelerate, and ortho-chloro, para-methyl, 2,4-dimethyl substituents slow down the process, while the meta-methyl group has no significant effect. The same dependence was observed in the case of 4-chloro-2-pentene. Thus, pentenyl fragment can be introduced in various ways into the structure of aromatic amines: by direct interaction with piperylene in the presence of catalysts, N-alkenylation of 4-chloro-2-pentene and 3,4-dichloro-2-pentene in triethylamine medium and reaction of arylamines with chlorine derivatives of piperylene, accompanied by an amino rearrangement of Claisen.

Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines.

The ability to use soluble organic amine bases in Pd-catalyzed C-N cross-coupling reactions has provided a long-awaited solution to the many issues associated with employing traditional, heterogeneous reaction conditions. However, little is known about the precise function of these bases in the catalytic cycle and about the effect of variations in base structure on catalyst reactivity. We used 19F NMR to analyze the kinetic behavior of C-N coupling reactions facilitated by different organic bases. In the case of aniline coupling reactions employing DBU, the resting state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction was found to be inhibited by base. In general, however, depending on the binding properties of the chosen organic base, increased concentration of the base can have a positive or negative influence on the reaction rate. Furthermore, the electronic nature of the aryl triflate employed in the reaction directly affects the reaction rate. The fastest reaction rates were observed with electronically neutral aryl triflates, while the slowest were observed with highly electron-rich and -deficient substrates. We propose a model in which the turnover-limiting step of the catalytic cycle depends on the relative nucleophilicity of the base compared to that of the amine. This hypothesis guided the discovery of new reaction conditions for the coupling of weakly binding amines, including secondary aryl amines, which were unreactive nucleophiles in our original protocol.

Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines.

The air- and water-stable π-allyliridium C,O-benzoate modified by ( S)-tol-BINAP, ( S)-Ir-II, catalyzes highly regio- and enantioselective Tsuji-Trost-type aminations of racemic branched alkyl-substituted allylic acetates using primary or secondary (hetero)aromatic amines. Specifically, in the presence of ( S)-Ir-II (5 mol%) in DME solvent at 60-70 °C, α-methyl allyl acetate 1a (100 mol%) reacts with primary (hetero)aromatic amines 2a-2l (200 mol%) or secondary (hetero)aromatic amines 3a-3l (200 mol%) to form the branched products of allylic amination 4a-4l and 5a-5l, respectively, as single regioisomers in good to excellent yield with uniformly high levels of enantioselectivity. As illustrated by the conversion of heteroaromatic amine 3m to adducts 6a-6g, excellent levels of regio- and enantioselectivity are retained across diverse branched allylic acetates bearing normal alkyl or secondary alkyl substituents. For reactants 3n-3p, which incorporate both primary and secondary aryl amine moieties, regio- and enantioselective amination occurs with complete site-selectivity to furnish adducts 7a-7c. Mechanistic studies involving amination of the enantiomerically enriched, deuterium-labeled acetate 1h corroborate C-N bond formation via outer-sphere addition.

Enantioselective Copper-Catalyzed Hydroamination of Vinylarenes with Anthranils.

Copper hydride-catalyzed asymmetric hydroamination of olefins with anthranils has been realized in high efficiency and high enantioselectivity, affording enantioenriched secondary arylamines tethered to a benzylic alcohol. The bifunctionality of the product has been employed in diverse derivatization reactions.

Mechanism of Boron-Catalyzed N-Alkylation of Primary and Secondary Arylamines with Ketones Using Silanes under “Wet” Conditions

Density functional theory (DFT) calculations have been carried out to study the mechanism of N-alkylation of primary and secondary arylamines with aldehydes and ketones under the catalysis of the Lewis acid B(C6F5)3 using silanes. The B(C6F5)3-mediated reduction of organic substrates is usually reported under anhydrous conditions. It is noteworthy that Ingleson and co-workers have established that B(C6F5)3 could act as a water tolerant catalyst in N-alkylation of arylamines with aldehydes/ketones. Our DFT calculation results revealed that both Lewis acid B(C6F5)3 and water play important roles in the condensation of amine and aldehyde to generate an imine intermediate and in the subsequent reduction of imine to yield an amine product. In the condensation reaction, Bronsted acid B(C6F5)3-H2O acts as the effective catalyst to promote the proton transfer process. The activation free energy barrier is calculated to be 21.1 kcal/mol, which is 23.0 kcal/mol lower than that of the water-assisted condensation pat...