Tertiary Aromatic Amines Research Articles

Structure-Activity Relationship of Benzophenazine Derivatives for Homogeneous and Heterogenized Photooxygenation Catalysis.

Singlet oxygen is a powerful oxidant used in various applications, such as organic synthesis, medicine, and environmental remediation. Organic and inorganic photosensitizers are commonly used to generate this reactive species through energy transfer with the triplet ground state of oxygen. We describe here a series of novel benzophenazine derivatives as a promising class of photosensitizers for singlet oxygen photosensitization. In this study, we investigated the structure-activity relationship of these benzophenazine derivatives. Akin to a molecular compass, the southern fragment was first functionalized with either aromatic tertiary amines, alkyl tertiary amines, aromatic sulfur groups, alkyl sulfur groups, or cyclic ethers. Enhanced photophysical properties (in terms of triplet excited-state lifetime, absorption wavelength, triplet state energy, and O2 quenching capabilities) were obtained with cyclic ether and sulfur groups. Conversely, the presence of an amine moiety was detrimental to the photocatalysts. The western and northern fragments were also investigated and slightly undesirable to negligible changes in photophysical properties were observed. The most promising candidate was then immobilized on silica nanoparticles and its photoactivity was evaluated in the citronellol photooxidation reaction. A high NMR yield of 97 % in desired product was obtained, with only a slight decrease over several recycling runs (85 % in the fourth run). These results provide insights into the design of efficient photosensitizers for singlet oxygen generation and the development of heterogeneous systems.

Thioxanthrone-based ionic liquid as efficient and recyclable photocatalyst for α-cyanidation reaction of aromatic tertiary amines

A stabile and recyclable photocatalyst IL-TX was designed and synthesized by introducing the dye photocatalyst thioxanthenone into ionic liquids and its excellent photocatalytic performance was demonstrated by photophysical and electronic performance tests. The IL-TX was applied as a recyclable photocatalyst for α-cyanidation reaction of aromatic tertiary amines in MeOH at room temperature under blue light irradiation, and a range of cyanide products were obtained in good to excellent yields. Furthermore, the practicality of this protocol was further demonstrated through the optimization of the synthesis of the drug praziquantel and the natural product 8-oxopseudopalmatine. This study provides a greener and sustainable solution for photocatalytic cyanation reaction.

Chemometric modeling of pharmaceuticals for partitioning between sludge and aqueous phase during the wastewater treatment process.

Computational techniques, such as quantitative structure-property relationships (QSPRs), can play a significant role in exploring the important chemical features essential for the degree of sorption or sludge/water partition coefficient (Kd) towards sewage sludge of wastewater treatment process to evaluate the environmental consequence and risk of pharmaceuticals. The current research work aims to construct a predictive QSPR model for the sorption of 148 diverse active pharmaceutical ingredients (APIs) in sewage sludge during wastewater treatment. For the development of the model, we employed easily computable 2D descriptors as independent variables. The model has been developed following the Organization for Economic Cooperation and Development's (OECD) guidelines. It has undergone internal and external validation using a variety of methodologies, as well as been tested for its applicability domain. A measure of hydrophobicity, i.e., MLOGP2, showed the most promising contribution in modeling the sorption coefficient of APIs. Among other parameters, the number of tertiary aromatic amines, the presence of electronegative atoms like N, O, and Cl, the size of a molecule, the number of aromatic hydroxyl groups, the presence of substituted aromatic nitrogen atoms and alkyl-substituted tertiary carbon atoms were also found to be influential for the regulation of solid water partition coefficient of APIs during the wastewater treatment process. The statistical validity tests performed on the developed partial least squares (PLS) model showed that it is statistically evident, robust, and predictive (R2Train = 0.750, Q2LOO = 0.683, Q2F1 = 0.655, Q2F2 (or R2Test) = 0.651). In addition, the predictivity of the constructed model was further inspected by using the "prediction reliability indicator" tool for 14 external APIs.

Novel chromatic reaction based on the redox reaction between tertiary aromatic amines and gold(Ⅲ) or cerium(Ⅳ)

Abstract Herein, a novel chromatic reaction based on the oxidative self-coupling of tertiary aromatic amines and driven by a redox reaction with gold(III) or cerium(IV) is developed. The dimers resulting from the oxidation of tertiary aromatic amines with gold(III) or cerium(IV) show colors depending on their chemical structures. Substituting a hydrogen atom on the aromatic ring with a methyl or methoxy group induces a bathochromic shift in the color developed via oxidation. This redox reaction is highly selective for gold(III) and cerium(IV) because of their high redox potentials and complexation abilities with tertiary aromatic amines, thus suggesting the development of a selective analytical method for gold(III) and cerium(IV). Cyclic voltammograms and ultraviolet–visible light absorption spectra confirm that the oxidative coupling of tertiary aromatic amines develops color. The addition of reductants, such as l-ascorbic acid, degrades the color of the resultant colored species, thus indicating that the quinoid structure of the colored species caused color development. Thus, the developed redox reaction of tertiary aromatic amines with gold(III) or cerium(IV) provides a new chromogenic platform for determining gold(III), cerium(IV), and ascorbic acid.

Isocyanides as Catalytic Electron Acceptors in the Visible Light Promoted Oxidative Formation of Benzyl and Acyl Radicals.

The recent disclosure of the ability of aromatic isocyanides to harvest visible light and act as single electron acceptors when reacting with tertiary aromatic amines has triggered a renewed interest in their application to the development of green photoredox catalytic methodologies. Accordingly, the present work explores their ability to promote the generation of both alkyl and acyl radicals starting from radical precursors such as Hantzsch esters, potassium alkyltrifluoroborates, and α-oxoacids. Mechanistic studies involving UV-visible absorption and fluorescence experiments, electrochemical measurements of the ground-state redox potentials along with computational calculations of both the ground- and the excited-state redox potentials of a set of nine different aromatic isocyanides provided key insights to promote a rationale design of a new generation of isocyanide-based organic photoredox catalysts. Importantly, the green potential of the investigated chemistry has been herein demonstrated by a direct and easy access to deuterium labeled compounds.

Palladium-catalyzed and norbornene-mediated C-H amination and C-O alkenylation of aryl triflates.

The C-H amination and C-O alkenylation of aryl triflates was achieved through Pd/norbornene (NBE) cooperative catalysis. By this strategy, various ortho-alkenyl tertiary anilines including those bearing functional groups were produced in good to excellent yields. This reaction represents a new conversion model for phenoxides. It expands the scope of Catellani-type reactions and the application of phenoxides in organic synthesis.

Design, synthesis, and biological evaluation of aromatic tertiary amine derivatives as selective butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease

Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17–1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE < 20 nM, eeAChE > 10 μM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Aβ1−42 induced damage. It also demonstrated that 17c and 19c were able to restore cognitive impairment in vivo test. These data suggest that 17c and 19c represent promising candidate for follow-up in the drug-discovery process against AD.

Decarboxylative tandem C-N coupling with nitroarenes via SH2 mechanism

Aromatic tertiary amines are one of the most important classes of organic compounds in organic chemistry and drug discovery. It is difficult to efficiently construct tertiary amines from primary amines via classical nucleophilic substitution due to consecutive overalkylation. In this paper, we have developed a radical tandem C-N coupling strategy to efficiently construct aromatic tertiary amines from commercially available carboxylic acids and nitroarenes. A variety of aromatic tertiary amines can be furnished in good yields (up to 98%) with excellent functional group compatibility under mild reaction conditions. The use of two different carboxylic acids also allows for the concise synthesis of nonsymmetric aromatic tertiary amines in satisfactory yields. Mechanistic studies suggest the intermediacy of the arylamine–(TPP)Fe(III) species and might provide a possible evidence for an SH2 (bimolecular homolytic substitution) pathway in the critical C-N bond formation step.

Visible-light photocatalytic metal-free multicomponent Ugi-like chemistry

The direct photoexcitation of isocyanides is able to trigger a collection of Ugi-like multicomponent reactions under metal-free conditions and in the absence of any additives starting from both linear and cyclic tertiary aromatic amines.

Copper‐Catalyzed Cascade N‐Dealkylation/N‐Methyl Oxidation of Aromatic Amines by Using TEMPO and Oxygen as Oxidants

AbstractA novel tandem N‐dealkylation and N‐methyl aerobic oxidation of tertiary aromatic amines to N‐arylformamides using copper and TEMPO has been developed. This methodology suggested an alternative synthetic route from N‐methylarylamines to N‐arylformamides.

The Dark Side of Isocyanides: Visible-Light Photocatalytic Activity in the Oxidative Functionalization of C(sp3)-H Bonds.

The possibility to harness aromatic isocyanides as visible-light photocatalysts in the α-amino C(sp3)–H functionalization is herein presented. Actually, the three-component cross-dehydrogenative coupling of aromatic tertiary amines with isocyanides and water leads to amide products under very mild conditions in high yields and with a good substrate scope. While the reaction with aromatic isocyanides proceeds upon direct photoexcitation, aliphatic isocyanides are able to form a photoactive electron–donor–acceptor complex with aromatic amines. Moreover, the use of a catalytic loading of an aromatic isocyanide promotes the oxidative coupling of N-phenyl-1,2,3,4-tetrahydroisoquinoline with an array of different (pro)nucleophiles in good to excellent yields, thus providing the proof-of-concept for the development of a new highly tunable class of organic visible-light photocatalysts.

Nickel-Catalyzed Oxidative Transamidation of Tertiary Aromatic Amines with N-Acylsaccharins

AbstractThe use of tertiary amines as surrogates for secondary amines has prominent advantages in terms of stabilization and ease of handling. A Ni-catalyzed transamidation of N-acylsaccharins with tertiary aromatic amines is reported. By using tert-butyl hydroperoxide as the terminal oxidant, this reaction permits selective cleavage of the C(sp3)–N bonds of unsymmetrical tertiary aromatic amines depending on the sizes of the alkyl substituents.

α‐Cyanation of Aromatic Tertiary Amines using Malononitrile as a Low‐Toxic Cyanide Source under the Catalysis of NiGa Layered Double Oxide

AbstractNiGa layered double oxide (Ni3Ga‐LDO) has been found to be an efficient heterogeneous catalyst for the α‐cyanation of aromatic tertiary amines using malononitrile as a low‐toxic cyanide source. Various aniline and aryltetrahydroisoquinoline derivatives were found to be tolerated by the catalytic system, and good to excellent yields for the corresponding products could be obtained. The results indicated that CN− might be produced via a oxidation‐decomposition path, and the reaction probably proceeded via a cross‐dehydrogenative coupling process. In addition, good stability and recyclability were observed for Ni3Ga‐LDO catalyst in the reaction.

One-Pot Synthesis of α-Halo β-Amino Acid Derivatives via the Difunctional Coupling of Ethyl α-Diazoacetate with Silyl Halides and N,O-Acetals or Aromatic Tertiary Amines

The difunctionalization of ethyl α-diazoacetate (EDA) using silyl halides as a nucleophile and N,O-acetals as an electrophile under metal-free conditions is described. This process undergoes a novel three-component coupling (3-CC) reaction using EDA, which leads to a one-pot preparation of α-halo β-amino acid esters. Also, this protocol could be adapted to accept an electrophile composed of aromatic tertiary amines. In both 3-CC reactions, the key reaction intermediate is an iminium intermediate that can be easily and effectively generated either from N,O-acetals or from aromatic tertiary amines.

Chemometric modeling of power conversion efficiency of organic dyes in dye sensitized solar cells for the future renewable energy

The present study reports chemometric modeling of power conversion efficiency (PCE) of dye sensitized solar cells (DSSCs) using the biggest available data set till date which comprises around 1200 dyes covering 7 chemical classes. To extract the best structural features required for higher PCE, we have developed multiple partial least squares (PLS) quantitative structure-property relationship (QSPR) models for the Triphenylamine, Phenothiazine, Indoline, Porphyrin, Coumarin, Carbazole and Diphenylamine chemical classes using descriptors derived from the best subset selection method followed by selection of best five models in each dataset based on the Mean Absolute Error (MAE) values. The models were validated both internally and externally followed by the consensus predictions employing “Intelligent Consensus Predictor” tool to examine whether the quality of predictions can be improved with the “intelligent” selection of multiple PLS models. The quality of predictions for the respective external sets showed that the consensus models (CM) are better than the individual models (IM) in most of the cases. From the insights of the developed models, we concluded that attributes like a packed structure toward higher conductivity of electrons, auxiliary donor fragment of aromatic tertiary amines, number of thiophenes inducing the bathochromic shift and augmenting the absorption, presence of additional electron donors, enhancement of electron-donating abilities, number of non-aromatic conjugated C(sp2) which helps as conjugation extension units to broaden the absorption and highly conjugated π-systems exert positive contributions to the PCE. On the contrary, features negatively contributing to PCE are the followings: fragments which lower the tendency of localized π–π* transition, fragments related to larger volume and surface area of dyes along with hydrophobicity resulting in poor adhesion, fragment RC = N causing dye hydrolysis, steric hindrance for π electronic mobility, fragments enhancing polarity, etc. The identified features from the best QSPR model of the coumarin dataset was employed in designing of ten more efficient coumarin dyes (predicted %PCE ranging from 8.93 to 10.62) than the existing ones.

Electronic properties’ modulation of D–A–A via fluorination of 2-cyano-2-pyran-4-ylidene-acetic acid acceptor unit for efficient DSSCs: DFT-TDDFT approach

Considerable attentions have been drawn towards modulation of organic dyes with the goal of realizing effectual dye-sensitized solar cells using density functional theory (DFT). In this respect, a series of D–A1–A2 dyes containing 2-vinyl-5-(5-vinyl-2-thienyl) thiophene bridged with C=S group (A1), 2-Cyano-2-pyran-4-ylidene-acetic acid (A2) and tertiary aromatic amines as donor (D) were designed and theoretically investigated for dye-sensitized solar cells (DSSCs). These dyes were simulated using DFT and time-dependent density functional theory to calculate their electronic and optical properties, molecular reactivity indices, natural population analysis, maximum open circuit voltage (VOC) and light harvesting efficiency (LHE). The results showed that the position as well as number of fluorine atoms on Cyano-2-pyran-4-ylidene-acetic acid unit have effect on the electronic properties without necessary change the band gap energy of the dyes; therefore tuned/modulated molecular properties of the dyes. Also, dyes with donor unit containing N,N-diphenylaniline (DA-7) presented lowest band gap than those containing N-(2-pyridyl)pyridin-2-amine (DA-8) and carbazole (DA-9); thus N-phenyl-aniline unit is a better electron donor.

Computational modelling and characterisation of phosphole adopted in triphenyl amine photosensitisers for solar cell applications

Considerable attention has been drawn towards modulation of organic dyes with the goal of realizing effective dye sensitized solar cell (DSSC) using theoretical methods. In this respect, five D-π -A dyes containing organophosphole compounds as π-bridge, and tertiary aromatic amine as donor (D) were designed and theoretically investigated for dye-sensitized solar cells (DSSCs). These molecular dyes were simulated using Density Functional Theory (DFT) and Time–Dependent Density Functional Theory (TDFT) to estimate their optical and electronic properties, molecular reactivity indices, natural population analysis and Light Harvesting Efficiency (LHE). The results showed that the position of the organophosphole molecules, as well as their nature, affects the electronic and light harvesting properties making modeled compounds more proficient solar cell sensitisers.

Transition‐Metal‐Free Three‐Component Synthesis of Tertiary Aryl Amines from Nitro Compounds, Boronic Acids, and Trialkyl Phosphites

AbstractThe synthesis of aromatic amines is of continuous interest in chemistry. An exceptionally versatile three‐component reaction that directly transforms inexpensive nitro compounds, boronic acids, and trialkyl phosphites into tertiary aromatic amines has been realized. The reaction tolerates alkyl and aryl substituents on the nitro and boronic acid moieties, as well as functionalized phosphites. No transition‐metal catalysis is required. The method is orthogonal to other classical metal‐catalyzed syntheses since it tolerates the presence of halogens, and also permits the synthesis of functionalized compounds such as α‐amino ester derivatives.magnified image

Well-Designed N-Heterocyclic Carbene Ligands for Palladium-Catalyzed Denitrative C–N Coupling of Nitroarenes with Amines

The C–N bond formation is one of the fundamental reactions in organic chemistry, because of the widespread presence of amine moieties in pharmaceuticals and biologically active compounds. Palladium-catalyzed C–N coupling of haloarenes represents one of the most efficient approaches to aromatic amines. Nitroarenes are ideal alternative electrophilic coupling partners, since they are inexpensive and readily available. The denitration and cross-coupling using nitroarenes as the electrophilic partners is challenging, because of the low reactivity of the Ar–NO2 bond toward oxidative addition. We report here the C–N coupling of nitroarenes and amines using palladium/5-(2,4,6-triisopropylphenyl)imidazolylidene[1,5-a]pyridines as the catalyst. The ligands are readily available from commercial chemicals. The reaction shows broad substrate scope and functional group tolerance. The method is applicable to both aromatic and aliphatic amines, and many secondary and tertiary aromatic amines bearing various functional g...

Analysis of the Possibility and Conditions of Application of Methylene Blue to Determine the Activity of Radicals in Model System with Preaccelerated Cross-Linking of Polyester Resins.

Unsaturated polyester resins are usually processed using a curing system consisting of initiator and accelerator introduced into the resin. Actually, the producers apply built-in amine accelerators which can be named as preaccelerators. Commonly used preaccelerators for unsaturated resins are tertiary aromatic amines of which incorporation into resin structure may bring better stability. It also causes shorter gelation time of resins because of formation of active RO• radicals that initiate polymerization. Investigated radical reactions are too fast and there is no possibility of freezing it (in unsaturated polyester) to measure with Electron Paramagnetic Resonance (EPR). The analytical methodology on radicals activity measurement in model of preaccelerated unsaturated polyester resin reaction with methylene blue as indicator was presented. Using methylene blue as indicator allows us to determine the activity of forming radicals in three-component system (cobalt salt, amine preaccelerator, peroxide, or hydroperoxide) during the reaction of radicals generating. Changes in radicals activity using methylene blue as interceptor can be observed by changes of transmittance in the UV-Vis spectrum in the range 400-950 nm.