Alkylamines Research Articles

The Preparation of Zr-containing Coordination Polymer as an Efficient Catalyst for Alkylation of Amines and Alcohols

Abstract: A coordination polymer Zr-CIA was developed and employed as a stable and effective catalyst for the alkylation of amines with alcohols or benzyl amines. The Zr-CIA as a new coordination polymer was prepared from 1-(carboxymethyl)-1H-indole-3-carboxylic acid and ZrCl4 through a simple and effective solvothermal method and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), fourier transform infrared (FT-IR), nitrogen adsorption-desorption and X-ray photoelectronic spectroscopy (XPS). The polymer exhibited not only high catalytic activity for the alkylation reaction, but also good reusability in more than five cycles. Meanwhile, mechanistic investigations were carried out to study these reactions.

Narcissus pseudonarcissus L. (Amaryllidaceae) bulb metabolite profiling and biological activities

Various metabolomics approaches have greatly contributed to the study of natural products from medicinal plants. Among thousands of plant species, Narcissus pseudonarcissus L. (Amaryllidaceae) is reputed for its ornamental, industrial, and medicinal applications. This plant is also used traditionally for microbial infections, inflammations, skin complaints, and cancers. Long ago, N. pseudonarcissus has gained considerable research interest thanks to its diverse alkaloids that have been widely studied. However, the non-alkaloidal principles and different bioactivities of this plant were poorly deliberated in previous works. Therefore, this work evaluates the biological potential of N. pseudonarcissus bulbs′ total ethanol extract (TEE) and its derived fractions (I‒IV), along with exploring the overlooked non-alkaloidal metabolites of this amaryllid. Overall, GC‒MS-based analysis of the bulbs led to the identification of varied metabolites, e.g., long-chain alkyl amines, alkylbenzenes, long-chain hydrocarbons, fatty acid derivatives, and phenylpropanoids. Most of these phytochemicals are first characterized herein in either the genus Narcissus or the family Amaryllidaceae. Additionally, the acidic EtOAc fraction (II) exhibited the highest scavenging potential of the 2,2′-diphenyl-1-picrylhydrazyl radical and the greatest ferric reducing power, possibly due to its relatively higher contents of phenolics and flavonoids that were also estimated herein. On the other hand, the basic EtOAc fraction (III) exerted the maximum anti-proliferative actions against Caco-2 (colon) and Mcf-7 (breast) tumor cells, while all of the tested fractions were inactive against HepG-2 (liver) cancer cells. Finally, different N. pseudonarcissus fractions demonstrated varied inhibitory activities against a group of pathogenic bacteria and fungi. Among them, fractions II and III were further observed as good synergists with some standard antimicrobial agents, even against some resistant microbial strains. These data could support the reported use of N. pseudonarcissus in traditional medical systems and help widen its future phytochemical and biological prospection.

Postpolymerization Modification by Nucleophilic Addition to Styrenic Carbodiimides.

Carbodiimides are electrophilic functional groups that react with select nucleophiles under mild conditions. However, their potential as platforms for postpolymerization modification has been relatively underexplored. We describe the synthesis and radical polymerization of a styrenic carbodiimide which undergoes rapid nucleophilic addition with primary and secondary alkyl amines under ambient conditions, even in the presence of other protic nucleophiles. The monomer is amenable to both free and controlled radical (co)polymerization, and we further demonstrate the utility of this approach by preparing covalent adaptable networks through guanylation of the styrenic carbodiimide with difunctional amines. These materials exhibit a variation in relaxation times according to both the guanidine structure and concentration, providing a facile means for tuning dynamic behavior.

Detection of acetone in the human breath as diabetes biomarker based on PPy/WO3 nanocomposite sensor by FFT continuous cyclic voltammetry method

AbstractThis research represents a novel detection method of acetone level in the exhaled breath samples (RH=88 %) based on polypyrrole/tungsten oxide (PPy/WO3) nanocomposite sensor. The PPy/WO3 sensor was fabricated by the deposition of nanocomposite on/between interdigitated electrodes (IDEs) through electrospray coating and was then characterized by FE‐SEM imaging. In this detection method, the coulometric signal of the sensor was calculated using Fast Fourier Continuous Cyclic Voltammetry (FFTCCV), where cyclic voltammetry (CV) was applied to the sensor in the defined potential rang and then charge changes of the sensor was obtained by integration of the current in all scanned potential ranges. FFTCCV method enhances the sensitivity of the sensor when exposed to the gas mixtures containing acetone. In addition to its fast coulometric response time (≤5 s) in the two linear ranges of 0.7–2.8 ppm and 2.8–28.2 ppm (R2=0.99), FFTCCV method provides the low detection limit of 70 ppb, and high sensitivity toward acetone at the optimum values of the parameters. The fabricated sensor showed great selectivity toward acetone when exposed to humid air and some exhaled gas like carbon dioxide, ammonia, methanol, ethanol and alkyl amines. The results were very satisfying as the sensor was capable to detect different acetone levels in human exhaled breath as non‐invasive diagnosis of diabetes with a good correlation (R2≃0.9) to the routine blood sugar test taken by different commercial glucometers results.

Direct Alkylative Amination using 1-Allylsilatrane.

Homoallylic amines prepared via addition of allylsilanes often require preformed imine substrates, metal catalysts, fluoride activators, or use of protected amines. In this metal-free, air- and water-tolerant procedure, aromatic aldehyde and aniline substrates undergo direct alkylative amination using easily accessible 1-allylsilatrane.

Synthesis of 1,2‐Dialkylaminoethers via Photoredox Catalyzed Hydroamination of Vinylethers

AbstractHerein, a general applicable method for the atom‐economic catalytic construction of a broad range of 1,2‐dialkylaminoethers is presented. By taking advantage of an elaborated protocol for the photocatalyzed anti‐Markovnikov selective hydroamination of nonactivated alkenes, a series of 1,2‐dialkylaminoethers was accessed by reacting readily available vinyl ethers with secondary alkyl amines. It was demonstrated that the reaction can be performed at low catalyst loadings while the commonly employed triisopropylbenzene thiol Hydrogen Atom Transfer (HAT)‐catalyst was replaced by an easier accessible mesityl thiol. Furthermore, the inexpensive and readily available diphenyl disulfide was proven as suitable HAT‐catalyst alternative for the efficient hydroamination of simple vinyl ethers.

Photochemically Driven Nickel-Catalyzed Carboxylative C-N Coupling: Scope and Mechanism.

Herein we disclosed an unprecedented photochemically driven nickel-catalyzed carboxylative Buchwald-Hartwig amination to access a wide range of aryl carbamate derivatives. This reaction is performed under mild condition of temperature and atmospheric pressure of CO2 starting from commercially available (hetero)aryl iodides/bromides derivatives and alkyl amines preventing the formation of hazardous and/or toxic waste. Moreover, preliminary mechanistic investigations including stochiometric experiments as well as DFT calculations allow us to shed light on the reaction mechanism.

Photoinduced Deaminative Alkylation of Quinoxalin‐2(1H)‐ones via an Electron Donor‐Acceptor Complex

AbstractFormation of C−C bonds by cleavage of the C(sp3)−N bonds of readily available alkyl amines is a valuable transformation. Herein, we report a method for oxidant‐ and metal‐free photoinduced deaminative alkylation of quinoxalin‐2(1H)‐ones with Katritzky salts as alkyl radical sources. Various alkyl radicals could easily be generated by single‐electron reduction of electron donor–acceptor complexes between the Katritzky salts and sodium acetate. This green, sustainable, operationally simple method has a broad substrate scope, and can be used for gram‐scale synthesis, and late‐stage modification of pharmaceutically relevant molecules.

Migration of Dihydroxy Alkylamines and Their Possible Impurities from Packaging into Foods and Food Simulants: Analysis and Safety Evaluation.

Alkyl diethanolamines are a group of compounds commonly used as antistatic agents in plastic food packaging materials. These additives and their possible impurities have the ability to transfer into the food; hence, the consumer may be exposed to these chemicals. Recently, scientific evidence of unknown adverse effects associated with these compounds was reported. N,N-bis(2-hydroxyethyl)alkyl (C8-C18) amines as well as other related compounds and their possible impurities were analyzed in different plastic packaging materials and coffee capsules using target and non-target LC-MS methods. N,N-bis(2-hydroxyethyl)alkyl amines, precisely, C12, C13, C14, C15, C16, C17 and C18, 2-(octadecylamino)ethanol and octadecylamine, among others, were identified in most of the analyzed samples. It should be emphasized that the latter compounds are not listed in the European Regulation 10/2011 and 2-(octadecylamino)ethanol was classified as high toxicity according to Cramer rules. Migration tests were carried out in foods and in the food simulants Tenax and 20% ethanol (v/v). The results showed that stearyldiethanolamine migrated into the tomato, salty biscuits, salad and Tenax. Lastly, as a crucial step in the risk assessment process, the dietary exposure to stearyldiethanolamine transferred from the food packaging into the food was determined. The estimated values ranged from 0.0005 to 0.0026 µg/kg bw/day.

A Simple Protocol for the C−N Cross‐Coupling of Aryl Chlorides with Amines Applying Ni/NHC Catalysis

AbstractAn efficient protocol for the C−N cross‐coupling of aryl chlorides with (hetero)aryl‐ and alkyl amines under nickel catalysis has been developed. The main advantage of the protocol is the use of a self‐activated Ni/NHC catalytic system generated in situ from readily available bench‐stable air‐tolerant precursors: NiCl2Py2, IPr ⋅ HCl, and sodium tert‐butoxide. A mass spectrometry mechanistic study of the reaction system revealed the dynamics of competitive processes of Ni/NHC active species formation and degradation involving NHC reductive elimination reactions and tert‐butoxide base. Optimization of the NiCl2Py2/IPr ⋅ HCl/tBuONa ratio and the reaction temperature allowed efficient catalysis to be achieved. The developed simple protocol represents an alternative for methods relying on the use of air‐sensitive and unstable Ni(cod)2 or expensive well‐defined Ni/NHC precatalysts.

Total Synthesis of Neuroprotective Agents, (+)-Lycibarbarine A and (-)-Lycibarbarine B.

We describe the convergent total syntheses of lycibarbarines A and B which are potent neuroprotective agents recently isolated from the fruits of Lycium barbarum. The synthesis highlights the construction of a unique spiro oxazine heterocyclic motif imbedded in these natural products. The synthesis is accomplished from the commercially available 8-hydroxyquinaline and 2-deoxy-d-ribose as key starting materials. The synthesis features a Reimer-Tiemann reaction, selective amine alkylation with a keto tosylate derivative, and spiroketalization to form an oxazine core.

Ruthenium Complexes of Bidentate N,N‐Ligand as Catalyst for Selective N‐Alkylation of Amines with Alcohols

AbstractThis report describes the synthesis of a new N‐(4‐(benzo[d]thiazole‐2‐yl)phenyl)‐1‐(pyridine‐2‐yl)methanimine ligand (L1) by the reaction of 2‐(4‐aminophenyl)benzothiazole with pyridine‐2‐carboxaldehyde. The three new ruthenium(II) arene complexes were synthesized by the reaction of L1 with [RuCl2(p‐cymene)]2 (C1), [RuCl2(benzene)]2 (C2), and [RuCl2(hmb)]2 [hmb=hexamethylbenzene] (C3). The new ligand and complexes were characterized with the help of standard analytical techniques like 1H and 13C{1H} Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FTIR), Ultraviolet‐visible (UV‐Visible), High‐Resolution Mass Spectrometry (HRMS), cyclic voltammetry, and elemental analysis techniques. The structure of ruthenium complex (C1) and its bonding mode with the ligand were authenticated with the help of single crystal X‐ray diffraction. The complex showed a pseudo‐octahedral half‐sandwich “piano‐stool” type geometry around the Ru center. The ruthenium arene complexes (C1–C3) were used to catalyze the N‐alkylation of aniline derivatives using aliphatic alcohols (EtOH, PrOH, MeOH). Among all three catalysts, C1 showed the highest yield of alkylated derivatives (up to 95%) with 1.0 mol% catalyst loading. The order of alkylation toward alcohol derivatives was EtOH = PrOH > MeOH. The alkylation reaction with ruthenium arene precursors showed poor yields (30–33%), demonstrating ligand design‘s potential in catalysis reactions. The proton NMR of the reaction mixture after 2 h shows the formation of Ru−H intermediate, which gave the desired alkylated products. Overall, these complexes are promising catalyst candidates for organic transformation.

Gelation Mechanism Revealed in Organometallic Gels: Prevalence of van der Waals Interactions on Oligomerization by Coordination Chemistry.

Shaping of nanomaterials is a necessary step for their inclusion in electronic devices and batteries. For this purpose, the formulation of a moldable material including these nanomaterials is desirable. Organomineral gels are a very interesting option, since the components of the nanomaterial itself form a gel without the help of a binder. As a consequence, the properties of the nanomaterial are not diluted by the binder. In this article we studied organometallic gels based on a [ZnCy2 ] organometallic precursor and a primary alkyl amine which together forms spontaneously gels after few hours. We identified the main parameters controlling the gel properties monitored by rheology and NMR measurements The experiments demonstrate that the gelation time depends on the length of the alkyl chain of the amine and that the gelation mechanism derived firstly from the rigidification of the aliphatic chains of the amine, which takes precedence over the oligomerization of the inorganic backbone. This result highlights that the control of the rheological properties of organometallic gels remains mainly governed by the choice of the amine.

Synthesis and In Vitro Anticancer Evaluation of Chrysin Containing Hybrids and Other Chrysin Derivatives

Chrysin, a well-known naturally occurring flavonoid having several biological effects including antiproliferative activity, was coupled with different pharmacophore structures. Coupling was carried out with spacers of different lengths and types. Structures selected for hybrid formation were amines, cyclic amino acid esters, and (hetero)aromatic compounds. In addition, vindoline, which is a Vinca alkaloid containing an indole skeleton, was also used. The alkylation of amines in the presence of carbonate base resulted in an interesting carbamate side product formation beside the expected amine. We also present the detailed structure elucidation of the carbamates. The in vitro anticancer activities of the synthesized derivatives were examined against 60 human tumor cell lines in National Cancer Institute (NCI, USA).

Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3-sp2 Carbon-Carbon Bonds.

Amines and carboxylic acids are abundant synthetic building blocks that are classically united to form an amide bond. To access new pockets of chemical space, we are interested in the development of amine-acid coupling reactions that complement the amide coupling. In particular, the formation of carbon-carbon bonds by formal deamination and decarboxylation would be an impactful addition to the synthesis toolbox. Here, we report a formal cross-coupling of alkyl amines and aryl carboxylic acids to form C(sp3)-C(sp2) bonds following preactivation of the amine-acid building blocks as a pyridinium salt and N-acyl-glutarimide, respectively. Under nickel-catalyzed reductive cross-coupling conditions, a diversity of simple and complex substrates are united in good to excellent yield, and numerous pharmaceuticals are successfully diversified. High-throughput experimentation was leveraged in the development of the reaction and the discovery of performance-enhancing additives such as phthalimide, RuCl3, and GaCl3. Mechanistic investigations suggest phthalimide may play a role in stabilizing productive Ni complexes rather than being involved in oxidative addition of the N-acyl-imide and that RuCl3 supports the decarbonylation event, thereby improving reaction selectivity.

Supported Ionic Liquid Phase (SILP) Allylic Alkylation of Amines in Continuous Flow.

We present the use of Pd-complex-containing supported ionic liquid phases (SILPs) as a novel approach for continuous-flow allylic alkylation of N-nucleophiles. This immobilization strategy gave simple access to air-tolerating catalyst frameworks, providing rapid and convenient access to various achiral and chiral N-allylation products. Under optimized conditions, the flow-reaction could be maintained for 3.5 hours with constant product output; meanwhile, only a marginal 0.7 wt % of ionic liquid leaching and no detectable palladium-complex leaching could be observed.

Green Synthesis of 2‐Thioxo‐4‐quinazolinone Derivatives in Water

AbstractA series of biologically important 3‐substituted‐2‐thixo‐4‐quinazolinones have been synthesized starting from methyl 2‐isothicyanatobenzoate and amines without the use of additives under mild reaction conditions in water. This transformation tolerates a wide range of amines, which include anilines, alkyl amines, and hydrazines, to afford 60 diverse 3‐substituted‐2‐thixo‐4‐quinazolinones including 34 new compounds at 60 °C for 30 min in good yields. This method avoids the use of organic solvent and the generation of toxic waste to demonstrate a cost efficient, green and sustainable method for the synthesis of 2‐thixo‐4‐quinazolinone derivatives as valuable heterocycles for biological and materials studies.

Development of Silicon Nanowire Array–Metal Hybrid Catalysts for Batch and Flow Organic Reactions

AbstractThe development of highly efficient and reusable supported metal catalysts is important for academic and industrial synthetic organic chemistry; however, their widespread application remains a challenge because supported Pd, Rh, and Pt catalysts are expensive. To overcome these problems, we have developed novel, highly stable, reusable, and selective heterogeneous catalysts consisting of silicon nanowire arrays (SiNAs) and metal nanoparticle composites. Metal nanoparticles on SiNA have been applied as heterogeneous catalysts in the Mizoroki–Heck reaction, C–H arylation, hydrosilylation, hydrogenation, reductive alkylation of amines, and hydrogenative decarboxylation of fatty acids. The catalysts used in this study showed high catalytic activity in batch and microflow conditions. Their structural investigation using X-ray Photoelectron Spectroscopy (XPS) suggests that strong metallic bonding (alloy/agglomeration) between the metal and silicon (metal silicide bond formation) is key to the high catalyst stability.1 Introduction2 Development of Silicon Nanowire Array (SiNA) Hybrid Catalysts and Silicon Nanostructure (SiNS) Hybrid Catalysts3 Application of SiNA-Pd to Organic Synthesis4 SINA-Supported Mono- and Bimetallic Nanoparticles for Hydrogenation Reactions5 Application of SiNA-Pd to Microflow Reductive Alkylation Reactions6 Application of SiNA-Rh to Hydrogenative Decarboxylation Reactions using Microwave Irradiation7 Conclusions

N-Alkylation of Amines by C1-C10 Aliphatic Alcohols Using A Well-Defined Ru(II)-Catalyst. A Metal-Ligand Cooperative Approach.

A Ru(II)-catalyzed efficient and selective N-alkylation of amines by C1-C10 aliphatic alcohols is reported. The catalyst [Ru(L1a)(PPh3)Cl2] (1a) bearing a tridentate redox-active azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline (L1a) is air-stable, easy to prepare, and showed wide functional group tolerance requiring only 1.0 mol % (for N-methylation and N-ethylation) and 0.1 mol % of catalyst loading for N-alkylation with C3-C10 alcohols. A wide array of N-methylated, N-ethylated, and N-alkylated amines were prepared in moderate to good yields via direct coupling of amines and alcohols. 1a efficiently catalyzes the N-alkylation of diamines selectively. It is even suitable for synthesizing N-alkylated diamines using (aliphatic) diols producing the tumor-active drug molecule MSX-122 in moderate yield. 1a showed excellent chemo-selectivity during the N-alkylation using oleyl alcohol and monoterpenoid β-citronellol. Control experiments and mechanistic investigations revealed that the 1a-catalyzed N-alkylation reactions proceed via a borrowing hydrogen transfer pathway where the hydrogen removed from the alcohol during the dehydrogenation step is stored in the ligand backbone of 1a, which in the subsequent steps transferred to the in situ formed imine intermediate to produce the N-alkylated amines.

Optical and scintillation properties of organic–inorganic perovskite-type compounds with various hydroxyl alkyl amines or alkyl ether amines

We evaluated photoluminescence and radiation response properties of organic–inorganic perovskite-type compounds with various hydroxyl alkyl amines or alkyl ether amines (HOCnH2nNH3)2PbCl4 (n = 2: C2–OH, n = 3: C3–OH, n = 4: C4–OH), (CH3CH2OCnH2nNH3)2PbCl4 (n = 2: 2-Ethoxy, n = 3: 3-Ethoxy), and (CH3C2H4OC3H6NH3)2PbCl4 (3-Butoxy). A clear broadband emission peak attributed to self-trapped excitons (STEs) was detected from the C2–OH, C3–OH, and 2-Ethoxy crystals under 310 nm excitation light. Additionally, they showed a fast decay time of 3.5 ns (C2–OH), 5.5 ns (C3–OH), and 3.0 ns (2-Ethoxy), which was ascribed to the recombination of STEs. In the scintillation spectra, the C2–OH, C3–OH, and 2-Ethoxy crystals exhibited a broad emission originating from the recombination to STEs. Furthermore, they exhibited a fast scintillation decay time of 2.2 ns (C2–OH), 3.5 ns (C3–OH), and 1.1 ns (2-Ethoxy) due to the recombination of STEs. Moreover, the light yield of the C3–OH crystal under alpha-ray was the highest, and the yield was estimated to be 1100 photons/5.5 MeV-α, which was higher than that of a ZnO single crystal.