Covalent Organic Frameworks Based Photoenzymatic Nano-reactor for Asymmetric Dynamic Kinetic Resolution of Secondary Amines.

Bio-catalysis represents a highly efficient and stereoselective method for the synthesis of valuable chiral compounds, however, the poor stability and limited reaction types of free enzymes restrict their wide application in industrial production. In this work, to overcome these problems, a multifunctional photoenzymatic nanoreactor CALB@COF-Ir was developed through the encapsulation of Candida antarctica lipase B (CALB) in a photosensitive covalent organic framework COF-Ir. This bio-nanocluster serves as efficient catalysts in asymmetric dynamic kinetic resolution (DKR) of secondary amines to give a series of chiral amines in high yields (up to 99 %) and enantioselectivities (up to 99 % ee). The well-designed COF-Ir not only acts as safety cover to prevent CALB from deactivation but promotes racemization of secondary amines via photo-induced hydrogen atom transfer (HAT) process. Photoelectric characterization and TDDFT calculation revealed that (ppy)2Ir units in COF-Ir play crucial role in this photocatalytic system which enhance its photo-redox properties through facilitating the separation between photoelectrons (e-) and holes (h+). Furthermore, the heterogeneous photoenzymatic nanoreactor could be recycled for five rounds with slight decline of catalytic reactivity.

Synthesis of aminomethyl linked (+)-usnic acid derivatives via the Mannich reaction and evaluation of their biological activities.

(+)-Usnic acid (UA), a natural dibenzofuran derivative, abundantly produced by lichens and possess wide number of biomedical applications including antibacterial, anti-inflammatory, anti-oxidant and anticancer activities. In the present study, as series of usnic acid derivatives (3a-3i) were synthesised using Mannich reaction assessed for their antioxidant, α-glucosidase, and anticancer activities. The in vitro antioxidant activity showed that compound 3d displayed potent antioxidant activity by scavenging the activities of DPPH and ABTS+. The compounds 3d and 3e showed potent cytotoxic activity against HepG2 cancer cells by arresting the cell cycle at S phase and regulating the Bax/BcL2 expression and subsequently induce the apoptosis. Overall, the results clearly indicated that (+)-usnic acid derivatives bearing secondary amines are useful scaffolds for the development of drug candidates for treatment of oxidative stress mediated cancer and metabolic disorders.

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant, Antibiotic, and Antifungal Activities.

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH4 , the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by 1 H-NMR, 13 C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC50 values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC50 values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol (4 d) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol (7 d) were determined to be 18.1 µg and 35.1 µg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.

Cobalt-Catalyzed Enantioselective Hydroamination of Arylalkenes with Secondary Amines.

Catalytic asymmetric hydroamination of alkenes with Lewis basic amines is of great interest but remains a challenge in synthetic chemistry. Here, we developed a Co-catalyzed asymmetric hydroamination of arylalkenes directly using commercially accessible secondary amines. This process enables the efficient access to valuable α-chiral tertiary amines in good to excellent yields and enantioselectivities. Mechanistic studies suggest that the reaction includes a CoH-mediated hydrogen atom transfer (MHAT) with arylalkenes, followed by a pivotal catalyst controlled SN 2-like pathway between in situ generated electrophilic cationic alkylcobalt(IV) species and free amines. This radical-polar crossover strategy not only provides a straightforward and alternative approach for the synthesis of enantioenriched α-tertiary amines, but also underpins the substantial opportunities in developing asymmetric radical functionalization of alkenes with various free nucleophiles in oxidative MHAT catalysis.

Arabinogalactan propargyl ethers in the A3-coupling reaction with aldehydes and secondary cyclic amines.

A family of novel pharmacologically prospective carbohydrate polymer aminomethylpropargyl derivatives has been synthesized by CuI-catalyzed A3-coupling reaction of arabinogalactan propargyl ethers with aldehydes and secondary amines in DMSO at 23-65 °Ð¡. The arabinogalactan derivatives bearing phenyl, pyridinе, and furan moieties in combination with piperidyne, pyrrolidyne, morpholine fragments are prepared in up to 95 % yield and 0.3-2.0 degree of substitution. Conversion of the propargyl groups of the starting arabinogalactan ethers reaches in most cases 80-100 %. The non-catalyzed aminoalkylation (96-100 °Ð¡, degree of substitution up to 1.1) of propargylated AG proceeds both at the ethynyl and hydroxy centers to afford mainly the products of C-substitution. Some of the synthesized compounds and their hydrochlorination products show the pronounced bacteriostatic activity with respect to Gram-negative microorganism.

Detection of seven Alternaria toxins in edible and medicinal herbs using ultra-high performance liquid chromatography-tandem mass spectrometry.

Alternaria mycotoxins are ubiquitous mycotoxins that contaminate food and animal feed. Here, an UPLC-MS/MS was developed and used for the detection of seven Alternaria mycotoxins in 19 different edible and medicinal herbs. Extensive optimization resulted in a simple and convenient sample preparation procedure with satisfactory extraction and a lower matrix effect. LOQs ranged from 0.01 to 2.0 ng/mL. Recoveries varied between 71.44% and 112.65%, with RSD less than 12%. The method was successfully applied for use in the mycotoxin analysis of 260 samples. A high percentage (28.46%) of samples were contaminated by 1-5 mycotoxins. Alternariol mono methylether was the predominant mycotoxin with high percentage of positive samples (37.5%), followed by alternariol (22.5%), alternariol (17.5%), tentoxin (10.83%), altertoxin Ⅰ (7.5%), and altenusin (4.17%). Collectively, the natural incidence data obtained from this study will help with better, validated risk assessments and efforts towards more comprehensive, future regulation.

Distribution and Fate of Ultraviolet Absorbents and Industrial Antioxidants in the St. Lawrence River, Quebec, Canada.

Ultraviolet absorbents (UVAs) and industrial antioxidants (IAs) are contaminants of emerging concern. In this study, we investigated the distribution and partitioning of these contaminants in surface water, suspended particulate matter (SPM), sediment, and various tissues of lake sturgeon (Acipenser fulvescens) and northern pike (Esox lucius) from the St. Lawrence River (SLR), Quebec, Canada. Results indicated that 2,6-di-tert-butyl-1,4-benzoquinone (BHTQ) was the dominant contaminant in the dissolved phase of the surface water, with median concentrations of 43, 15, and 123 ng/L for three sampling sites, respectively. Surface water collected downstream of a major city showed higher levels of various UVAs, BHTQ, and diphenylamine compared to the upstream, suggesting the influence of the urban activities on the contamination of these emerging contaminants in the SLR. SPM showed greater sorption capacities of most target contaminants compared to those of the sediment. Different contamination profiles were found in lake sturgeon and northern pike, implying that the accumulation of UVAs and IAs in fish depends on their feeding behavior. The field-based tissue-specific bioaccumulation factors (BAFs) for frequently detected contaminants (log BAF 1.5-4.2) were generally comparable to or lower than the Estimation Program Interface modeling results (1.4-5.0), indicating that some of these contaminants may be less bioaccumulative than previously expected.

Construction of a sandwich-like UiO-66-NH2@Pt@mSiO2 catalyst for one-pot cascade reductive amination of nitrobenzene with benzaldehyde.

Heterogeneous noble metal-based catalysts with stable, precise structures and high catalytic performance are of great research interest for sustainable catalysis. Herein, we designed the novel sandwich-like metal-organic-framework composite nanocatalyst UiO-66-NH2@Pt@mSiO2 using UiO-66-NH2@Pt as the core, and mesoporous SiO2 as the shell. The obtained UiO-66-NH2@Pt@mSiO2 catalyst shows a well-defined structure and interface, and the protection of the mSiO2 shell can efficiently prevent Pt NPs from aggregating and leaching in the reaction process. In the one-pot cascade reaction of nitroarenes and aromatic aldehydes to secondary amines, UiO-66-NH2@Pt@mSiO2 shows excellent catalytic performance due to acid catalytic sites provided by UiO-66-NH2 and Pt hydrogenation catalytic sites. Furthermore, the porous structure of the UiO-66-NH2@Pt@mSiO2 catalyst also enhances reactant diffusion and improves the reaction efficiency. This work provides a new avenue to meticulously design well-defined nanocatalysts with superior catalytic performance and stability for challenging reactions.

NH Stretching Frequencies of Intramolecularly Hydrogen-Bonded Systems: An Experimental and Theoretical Study.

The vibrational NH stretching transitions in secondary amines with intramolecular NH···O hydrogen bonds were investigated by experimental and theoretical methods, considering a large number of compounds and covering a wide range of stretching wavenumbers. The assignment of the NH stretching transitions in the experimental IR spectra was, in several instances, supported by measurement of the corresponding ND wavenumbers and by correlation with the observed NH proton chemical shifts. The observed wavenumbers were correlated with theoretical wavenumbers predicted with B3LYP density functional theory, using the basis sets 6-311++G(d,p) and 6-31G(d) and considering the harmonic as well as the anharmonic VPT2 approximation. Excellent correlations were established between observed wavenumbers and calculated harmonic values. However, the correlations were non-linear, in contrast to the results of previous investigations of the corresponding OH···O systems. The anharmonic VPT2 wavenumbers were found to be linearly related to the corresponding harmonic values. The results provide correlation equations for the prediction of NH stretching bands on the basis of standard B3LYP/6-311++G(d,p) and B3LYP/6-31G(d) harmonic analyses, with standard deviations close to 38 cm-1. This is significant because the full anharmonic VPT2 analysis tends to be impractical for large molecules, requiring orders of magnitude more computing time than the harmonic analysis.

Catalytic Reductive Amination of Aldehydes and Ketones With Nitro Compounds: New Light on an Old Reaction.

Reductive amination of carbonyl compounds with primary amines is a well-established synthetic methodology for the selective production of unsymmetrically substituted secondary and tertiary amines. From the industrial and green chemistry perspective, it is attractive to combine reductive amination with the synthesis of primary amines in a single one-pot catalytic process. In this regard, nitro compounds, which are readily available and inexpensive feedstocks, received much attention as convenient precursors to primary amines in such processes. Although the direct reductive coupling of nitro compounds with aldehydes/ketones to give secondary and tertiary amines has been known since the 1940's, due to the development of highly efficient and selective non-noble metal-based catalysts a breakthrough in this area was made in the last decade. In this short overview, recent progress in the methodology of the reductive amination with nitro compounds is summarized together with applications to the synthesis of bioactive amines and heterocycles. Remaining challenges in this field are also analyzed.

Carbon-Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium-Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines.

We report a hydroaminative cyclization of enynes using phosphine-quinolinolato rhodium catalysts. The hydroaminative cyclization of 2-vinylphenylacetylene derivatives with secondary amines gives 2-aminoindenes in good yields. The reaction is considered to proceed through carbon-carbon bond formation on a catalytically generated aminocarbene ligand.

Beyond the Simple Copper(II) Coordination Chemistry with Quinaldinate and Secondary Amines.

Copper(II) acetate has reacted in methanol with quinaldinic acid (quinoline-2-carboxylic acid) to form [Cu(quin)2(CH3OH)]∙CH3OH (1) (quin- = an anionic form of the acid) with quinaldinates bound in a bidentate chelating manner. In the air, complex 1 gives off methanol and binds water. The conversion was monitored by IR spectroscopy. The aqua complex has shown a facile substitution chemistry with alicyclic secondary amines, pyrrolidine (pyro), and morpholine (morph). trans-[Cu(quin)2(pyro)2] (2) and trans-[Cu(quin)2(morph)2] (4) were obtained in good yields. The morpholine system has produced a by-product, trans-[Cu(en)2(H2O)2](morphCOO)2 (5) (morphCOO- = morphylcarbamate), a result of the copper(II) quinaldinate reaction with ethylenediamine (en), an inherent impurity in morpholine, and the amine reaction with carbon dioxide. (pyroH)[Cu(quin)2Cl] (3) forms on the recrystallization of [Cu(quin)2(pyro)2] from dichloromethane, confirming a reaction between amine and the solvent. Similarly, a homologous amine, piperidine (pipe), and dichloromethane produced (pipeH)[Cu(quin)2Cl] (11). The piperidine system has afforded both mono- and bis-amine complexes, [Cu(quin)2(pipe)] (6) and trans-[Cu(quin)2(pipe)2] (7). The latter also exists in solvated forms, [Cu(quin)2(pipe)2]∙CH3CN (8) and [Cu(quin)2(pipe)2]∙CH3CH2CN (9). Interestingly, only the piperidine system has experienced a reduction of copper(II). The involvement of amine in the reduction was undoubtedly confirmed by identification of a polycyclic piperidine compound 10, 6,13-di(piperidin-1-yl)dodecahydro-2H,6H-7,14-methanodipyrido[1,2-a:1',2'-e][1,5]diazocine.

Iron-Mediated Electrophilic Amination of Organozinc Halides using Organic Azides.

A wide range of alkyl-, aryl- and heteroarylzinc halides were aminated with highly functionalized alkyl, aryl, and heterocyclic azides. The reaction proceeds smoothly at 50 °C within 1 h in the presence of FeCl3 (0.5 equiv) to furnish the corresponding secondary amines in good yields. This method was extended to peptidic azides and provided the arylated substrates with full retention of configuration. To demonstrate the utility of this reaction, we prepared two amine derivatives of pharmaceutical relevance using this iron-mediated electrophilic amination as the key step.

Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of α,ß-Unsaturated Aldehydes.

Chirality is one of the most important attributes for its presence in a vast majority of bioactive natural products and pharmaceuticals. Asymmetric organocatalysis methods have emerged as a powerful methodology for the construction of highly enantioenriched structural skeletons of the target molecules. Due to their extensive application of organocatalysis in the total synthesis of bioactive molecules and some of them have been used in the industrial synthesis of drugs have attracted increasing interests from chemists. Among the chiral organocatalysts, chiral secondary amines (MacMillan's catalyst and Jorgensen's catalyst) have been especially considered attractive strategies because of their impressive efficiency. Herein, we outline advances in the asymmetric total synthesis of natural products and relevant drugs by using the strategy of chiral secondary amine catalyzed reactions of α,ß-unsaturated aldehydes in the last eighteen years.

Emerging aromatic secondary amine contaminants and related derivatives in various dust matrices in China.

Aromatic secondary amines (Ar-SAs), constituted of several analogues with varied substitutions in molecular structure, are among the most frequently used anthropogenic antioxidants. Despite the reported toxicity effects, little information is available on their environmental contamination, except for few particular congeners such as diphenylamine. In this study, the occurrence of two kinds of Ar-SAs, substituted diphenylamines (S-DPAs) and novel substituted p-phenylenediamines (S-PPDs), was investigated in dust samples collected from outdoor rubber playgrounds and residential houses. Seven S-DPAs (GM: 102 ng/g) and two S-PPDs (GM: 20.9 ng/g) were detected in indoor dust. Significantly higher concentrations of S-DPAs (GM: 422 ng/g) and S-PPDs (GM: 31.6 ng/g) were observed in playground dust (p < 0.05). Different dominant Ar-SA congeners were found for indoor dust (low molecular weight Ar-SAs) and playground dust (high molecular weight Ar-SAs), indicating varied sources of Ar-SAs for different dust matrices. Apart from these parent chemicals, three diphenylamine derivatives, including N-nitrosodiphenylamine, 2-nitrodiphenylamine, and 4-nitrodiphenylamine, were also confirmed in indoor dust (GM: 35.7 ng/g) and playground dust (GM: 7.88 ng/g). A preliminary estimated daily intake calculation via dust ingestion indicated no immediate health risk to Chinese population. To our knowledge, this is the first report on the occurrence of a wide range of Ar-SAs and related derivates in dust matrices.

Shape-Pure, Nearly Monodispersed CsPbBr3 Nanocubes Prepared Using Secondary Aliphatic Amines.

Fully inorganic cesium lead halide perovskite (CsPbX3) nanocrystals (NCs) have been extensively studied due to their excellent optical properties, especially their high photoluminescence quantum yield (PLQY) and the ease with which the PL can be tuned across the visible spectrum. So far, most strategies for synthesizing CsPbX3 NCs are highly sensitive to the processing conditions and ligand combinations. For example, in the synthesis of nanocubes of different sizes, it is not uncommon to have samples that contain various other shapes, such as nanoplatelets and nanosheets. Here, we report a new colloidal synthesis method for preparing shape-pure and nearly monodispersed CsPbBr3 nanocubes using secondary amines. Regardless of the length of the alkyl chains, the oleic acid concentration, and the reaction temperature, only cube-shaped NCs were obtained. The shape purity and narrow size distribution of the nanocubes are evident from their sharp excitonic features and their ease of self-assembly in superlattices, reaching lateral dimensions of up to 50 µm. We attribute this excellent shape and phase purity to the inability of secondary amines to find the right steric conditions at the surface of the NCs, which consequently limits the formation of low-dimensional structures. Furthermore, no contamination from other phases was observed, not even from Cs4PbBr6, presumably due to the poor ability of secondary aliphatic amines to coordinate to PbBr2 and, hence, to provide a reaction environment that is depleted in Pb.

Lanthanide-Catalyzed Tandem Insertion of Secondary Amines with 2-Alkynylbenzonitriles: Synthesis of Aminoisoindoles.

A lanthanide-catalyzed intermolecular hydroamination of 2-alkynylbenzonitriles with secondary amines has been disclosed, providing a streamlined access to a range of aminoisoindoles in moderate to excellent yields. The salient features of this reaction include high bond-formation efficiency, mild reaction conditions, 100 % atomic efficiency and good functional group tolerance. This methodology has also been successfully applied to the construction of other nitrogen-containing compounds, such as 5 H-imidazo[2,1-a]isoindoles and isoquinolines. A plausible mechanism for the formation of aminoisoindoles involving initial N-H activation by a lanthanide complex followed by C≡N insertion into a Ln-N bond to form an amidinate lanthanide intermediate, which undergoes the cyclization is proposed.

Biphenyl sulfonic acid ligands for catalytic C-N cross coupling of aryl halides with anilines and secondary amines.

The use of two biphenyl sulfonic acid ligands for the catalytic C-N cross coupling of aryl halides with anilines, 3-aminopyridine, and secondary amines is reported. Our results represent a significant improvement compared to state of the art methods especially with regards to the removal of palladium.

A series of (E)-5-(arylideneamino)-1-tert-butyl-1H-pyrrole-3-carbonitriles and their reduction products to secondary amines: syntheses and X-ray structural studies.

An efficent access to a series of N-(pyrrol-2-yl)amines, namely (E)-1-tert-butyl-5-[(4-chlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H16ClN3, (7a), (E)-1-tert-butyl-5-[(2,4-dichlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H15Cl2N3, (7b), (E)-1-tert-butyl-5-[(pyridin-4-ylmethylene)amino]-1H-pyrrole-3-carbonitrile, C15H16N4, (7c), 1-tert-butyl-5-[(4-chlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H18ClN3, (8a), and 1-tert-butyl-5-[(2,4-dichlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H17Cl2N3, (8b), by a two-step synthesis sequence (solvent-free condensation and reduction) starting from 5-amino-1-tert-butyl-1H-pyrrole-3-carbonitrile is described. The syntheses proceed via isolated N-(pyrrol-2-yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P-1 from compound (7a) to (8a) and P21/c to P-1 from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)-H...N hydrogen bonds. However, in the case of (7a)-(7c), C-H...Cl interactions are strong enough to help in the three-dimensional architecture, as observed in Hirshfeld surface maps.

One-pot Reductive Amination of carbonyl Compounds with Nitro Compounds by Transfer Hydrogenation over Co-Nx as catalyst.

A new method was developed for the synthesis of secondary amines through the one-pot reductive amination of carbonyl compounds with nitro compounds using formic acid as the hydrogen donor over a heterogeneous non-noble-metal catalyst (Co-Nx /C-800-AT, generated by the pyrolysis of the cobalt phthalocyanine/silica composite at 800°C under a N2 atmosphere and subsequent etching by HF). Both nitrogen and cobalt were of considerable importance in the transfer hydrogenation reactions with formic acid.