N-alkylation Of Amines Research Articles

ChemInform Abstract: From Regioselective Condensation to Regioselective N‐Alkylation: A Novel and Environmentally Benign Strategy for the Synthesis of N,N′‐Alkyl Aryl Ureas and N,N′‐Dialkyl Ureas.

A protocol for the synthesis of N,N′-alkyl aryl ureas and N,N′-dialkyl ureas by transition metal-catalyzed regioselective N3-alkylation of the N-monosubstituted ureas with alcohols was proposed and accomplished. In the presence of an iridium/base system, the desired N,N′-alkyl aryl ureas and N,N′-dialkyl ureas were obtained with 70–93 % yields, and no isomeric N1-alkylated and N3-dialkylated products were formed in all cases. From both synthetic and environmental point of views, the reaction is highly attractive because of easily available starting materials, high atom efficiency and the formation of water as the only side product. Apparently, the research opens up the design of regioselective N-alkylation of amines with alcohols based on the regioselective condensation of amines with aldehydes, facilitating the progress of the “hydrogen autotransfer” (or “hydrogen-borrowing”) process.

N-alkylation of amines by homogeneous ruthenium complexes in the presence of free diphosphines

Chemoselective N-alkylation of amines by ruthenium complexes in the presence of free diphosphine ligands under mild conditions is described. Octyl amine and aniline were chosen as aliphatic and aromatic amines to investigate the effect of different phosphines, reaction times, and temperature on conversion, as well as selectivity towards related secondary and tertiary amines. After optimization of the reaction conditions, this catalytic system was used for N-alkylation of other amines and has shown moderate to very good yields. The reaction products were monitored by GC–MS. The crystal structure of [Ru(NO3)2CO(PPh3)2] with a monodentate and a bidentate nitrate was determined by X-ray crystallographic analysis.

Ag nanoparticles on mixed Al2O3–Ga2O3 supports as catalysts for the N-alkylation of amines with alcohols

The combination of AgNO3 with NaH results in Ag nanoparticles that can selectively perform alcohol aminations under mild reaction conditions (110°C). NaH not only serves as a reducing agent for the Ag salt, but also activates the alcohol for dehydrogenation to the corresponding ketone/aldehyde. The stability of the particles can be improved by immobilizing them onto mixed Al2O3–Ga2O3 supports; the combination of Ga and Al provides materials with stronger Lewis acidic sites compared to pure alumina or gallium oxide supports. This leads to catalysts with enhanced activities, without the necessity of adding external Lewis acids. Detailed TEM characterization also reveals a close interaction between the Ag NPs and the gallium oxide phase. The obtained catalysts are recyclable and show activity for the alcohol amination using a variety of aliphatic and aromatic amines under mild conditions.

One pot catalytic NO2 reduction, ring hydrogenation, and N-alkylation from nitroarenes to generate alicyclic amines using Ru/C-NaNO2

A report to produce alicyclic amines and subsequent N-alkylation with alcohols using Ru/C-NaNO2 catalyzed facile transformation of nitrobenzene was investigated. Effects of solvent, temperature, pressure, reaction time, and molar-ratio of substrate/catalyst on product composition were also studied. These mechanistic studies explain that nitrobenzene undergoes hydrogenation reaction in the following order; –NO2 reduction to –NH2, aromatic ring-hydrogenation to alicyclic, and from the reaction of alcohol to give N-alkylated amines. This investigation shed lights on possible application to polyurethane chemistry since these amines are used as important precursors for diisocyanates.

A Polymeric Boron-Iridium Bimetallic Catalyst for the N-Alkylation of Amines

A Polymeric Boron-Iridium Bimetallic Catalyst for the N-Alkylation of Amines

Metal-Free, Mild, Nonepimerizing, Chemo- and Enantio- or Diastereoselective N-Alkylation of Amines by Alcohols via Oxidation/Imine–Iminium Formation/Reductive Amination: A Pragmatic Synthesis of Octahydropyrazinopyridoindoles and Higher Ring Analogues

A mild step and atom-economical nonepimerizing chemo- and enantioselective N-alkylating procedure has been developed via oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Brønsted acid catalysis in DMPU as solvent and a stoichiometric amount of amine. The optimized conditions were further extended for the nonenzymatic kinetic resolution of the chiral amine thus formed under nonenzymatic in situ hydrogen-transfer conditions using VAPOL-derived phosphoric acid (VAPOL-PA) as the Brønsted acid catalyst. The enantioselective cascade of the presented reaction was successfully utilized in the synthesis of octahydropyrazinopyridoindole and its higher ring analogues.

ChemInform Abstract: Development of a General Non‐noble Metal Catalyst for the Benign Amination of Alcohols with Amines and Ammonia.

The N-alkylation of amines or ammonia with alcohols is a valuable route for the synthesis of N-alkyl amines. However, as a potentially clean and economic choice for N-alkyl amine synthesis, non-noble metal catalysts with high activity and good selectivity are rarely reported. Normally, they are severely limited due to low activity and poor generality. Herein, a simple NiCuFeOx catalyst was designed and prepared for the N-alkylation of ammonia or amines with alcohol or primary amines. N-alkyl amines with various structures were successfully synthesized in moderate to excellent yields in the absence of organic ligands and bases. Typically, primary amines could be efficiently transformed into secondary amines and N-heterocyclic compounds, and secondary amines could be N-alkylated to synthesize tertiary amines. Note that primary and secondary amines could be produced through a one-pot reaction of ammonia and alcohols. In addition to excellent catalytic performance, the catalyst itself possesses outstanding superiority, that is, it is air and moisture stable. Moreover, the magnetic property of this catalyst makes it easily separable from the reaction mixture and it could be recovered and reused for several runs without obvious deactivation.

Tandem Synthesis of N‐Alkylated Amides from Aldoximes and Alcohols by Using a Ru/Ir Dual‐Catalyst System

In the same boat: Tandem rearrangement/N-alkylation reactions in the presence of a Ru/Ir dual-catalyst system affords the desired N-alkylated amines in good-to-excellent yields with no intermediate amides or over-alkylated N,N-dialkylated amides. This environmentally friendly tandem reaction employs readily available starting materials, affords excellent selectivities for the N-alkylated amides, and shows high atom efficiency.

Heterogeneous Ni Catalysts for N-Alkylation of Amines with Alcohols

Nickel nanoparticles loaded onto various supports (Ni/MOx) have been prepared and studied for the N-alkylation of amines with alcohols. Among the catalysts, Ni/θ-Al2O3 prepared by in situ H2-reduction of NiO/θ-Al2O3 shows the highest activity, and it acts as reusable heterogeneous catalyst for the alkylation of anilines and aliphatic amines with various alcohols (benzyl and aliphatic alcohols) under additive free conditions. Primary amines are converted into secondary amines and secondary amines into tertiary amines. For the reaction of aniline with an aliphatic alcohol the catalyst shows higher turnover number (TON) than precious metal-based state-of-the-art catalysts. Mechanistic studies suggest that the reaction proceeds through a hydrogen-borrowing mechanism. The activity of Ni catalysts depends on the nature of support materials; acid–base bifunctional supports give higher activity than basic or acidic supports, indicating that acid–base sites on supports are necessary. The presence of basic (pyridin...

Development of a General Non‐Noble Metal Catalyst for the Benign Amination of Alcohols with Amines and Ammonia

The N-alkylation of amines or ammonia with alcohols is a valuable route for the synthesis of N-alkyl amines. However, as a potentially clean and economic choice for N-alkyl amine synthesis, non-noble metal catalysts with high activity and good selectivity are rarely reported. Normally, they are severely limited due to low activity and poor generality. Herein, a simple NiCuFeOx catalyst was designed and prepared for the N-alkylation of ammonia or amines with alcohol or primary amines. N-alkyl amines with various structures were successfully synthesized in moderate to excellent yields in the absence of organic ligands and bases. Typically, primary amines could be efficiently transformed into secondary amines and N-heterocyclic compounds, and secondary amines could be N-alkylated to synthesize tertiary amines. Note that primary and secondary amines could be produced through a one-pot reaction of ammonia and alcohols. In addition to excellent catalytic performance, the catalyst itself possesses outstanding superiority, that is, it is air and moisture stable. Moreover, the magnetic property of this catalyst makes it easily separable from the reaction mixture and it could be recovered and reused for several runs without obvious deactivation.

Bifunctional iridium-(2-aminoterephthalate)–Zr-MOF chemoselective catalyst for the synthesis of secondary amines by one-pot three-step cascade reaction

A simple and efficient method for the synthesis of N-alkyl amines via a cascade reaction (hydrogenation + reductive amination) using a new recyclable hybrid catalyst that combines the catalytic power of transition metal complexes with the architecture of metal organic frameworks (MOFs).

Heterogeneous Bimetallic Pt-Sn/γ-Al<SUB>2</SUB>O<SUB>3</SUB> Catalyzed N-Alkylation of Amines: Ef-ficient Synthesis of Secondary and Tertiary Amines

N-alkylation of amines with alcohols through a borrowing hydrogen strategy is a green route to amines. heterogeneous bimetallic pt-sn/gamma-al2o3 catalyzed the reactions of primary (secondary) amines with alcohols in the absence of external hydrogen source, efficiently affording secondary (tertiary) amines with water and a small amount of imines as the by-products. various functional groups in the substrates were tolerated in the catalytic system. the pt-sn/gamma-al2o3 catalyst was easily recycled, suggesting its potential application in the production of secondary and tertiary amines.

N-Alkylation of amines with alcohols over nanosized zeolite beta

Direct N-alkylation of amines with alcohols was successfully performed by using nanosized zeolite beta, which showed the highest catalytic activity among other conventional zeolites. This method has several advantages, such as eco-friendliness, moderate to high yields, and simple work-up procedure. The catalyst was successfully recovered and reused without significant loss of activity and only water is produced as co-product. In addition, imines were also efficiently prepared from the tandem reactions of amines with 2-, 3- and 4-nitrobenzyl alcohols using nanosized zeolite beta.

Cyclometalated metal–organic frameworks as stable and reusable heterogeneous catalysts for allylic N-alkylation of amines

Metal-organic frameworks (MOFs) functionalized via Ir(I) cyclometalation are shown to be effective as heterogeneous catalysts for the allylic N-alkylation of various amines. The MOF catalysts are one of the first and most effective MOF-based heterogeneous organometallic catalysts for the direct formation of C-N bonds. In addition, these MOFs represent a rare, stable and reusable, class of reactive Ir catalysts.

Magnetite (Fe3O4) silica based organic–inorganic hybrid copper(ii) nanocatalyst: a platform for aerobic N-alkylation of amines

A magnetically recoverable, efficient and selective copper based nanocatalyst has been synthesised via covalent grafting of 2-acetylthiophene on a silica coated magnetic nanosupport followed by metallation with copper acetate. The obtained organic–inorganic hybrid nanomaterial has been characterized by electron microscopy techniques (SEM and TEM with EDS), XRD, VSM, FT-IR and AAS. The catalytic performance of the novel nano-catalyst is evaluated in the active transformation of various aromatic amines to industrially-important alkylated amines. The nanocomposites afford high turnover frequency and high selectivity for amines under aerobic conditions. Furthermore, the heterogeneous nature of the catalyst allows easy magnetic recovery and regeneration, which makes the present protocol highly beneficial to address the industrial needs and environmental concerns.

Microwave assisted N-alkylation of amine functionalized crystal-like mesoporous phenylene-silica

N-alkylation reaction of amine functionalized phenylene moieties in crystal-like mesoporous silica is successfully achieved with about 87% of conversion in two reaction cycles. A potassium iodide catalyzed method commonly used for the selective N-monoalkylation of aniline is adapted and optimized to the N-monoalkylation reactions of the amine functionalized periodic mesoporous phenylene-silica (NH2-PMO) under microwave irradiation with preservation of the ordered mesostructure and of the crystal-like molecular scale periodicity of the material. This functionalization opens an avenue for the preparation of new materials with different amino-alkyl groups specially designed for a desired application, namely on the adsorption or catalytic fields.

Ruthenium(II) carbonyl complexes containing pyridine carboxamide ligands and PPh3/AsPh3/Py coligands: Synthesis, spectral characterization, catalytic and antioxidant studies

New ruthenium(II) carbonyl complexes bearing pyridine carboxamide and triphenylphosphine/triphenylarsine/pyridine have been prepared by direct reaction of ruthenium(II) precursors with some pyridine carboxamide ligands, N,N-bis(2-pyridinecarboxamide)-1,2-ethane (H2L1), N,N-bis(2-pyridinecarboxamide)-1,2-benzene (H2L2) and N,N-bis(2-pyridinecarboxamide)-trans-1,2-cyclohexane (H2L3). The organic ligands offering two Namide and two Npyridine donor sites to the metal centre. They have been characterized by elemental analyses, FT-IR, UV–Visible, NMR (1H, 13C and 31P) and ESI-MS techniques. Based on the above data, an octahedral structure has been assigned for all the complexes. The catalytic efficiency of the complexes in transfer hydrogenation of ketones in the presence of iPrOH/KOH and N-alkylation of amine in the presence of tBuOK was examined. Furthermore, the antioxidant activity of the ligands and its ruthenium(II) complexes were determined by DPPH radical, nitric oxide radical, hydroxyl radical and hydrogen peroxide scavenging methods, which indicates that the ruthenium(II) complexes exhibit more effective antioxidant activity than the ligands alone.

A new approach to isoindolinone derivatives by sequential palladium iodide-catalyzed oxidative aminocarbonylation–heterocyclization of 2-ethynylbenzamides

A novel approach to functionalized isoindolinone derivatives 3 is presented. It is based on a cascade process, consisting of PdI2/KI-catalyzed oxidative monoaminocarbonylation of secondary 2-ethynylbenzamides 1 with nucleophilic secondary amines 2, followed by intramolecular conjugate addition of the arylamido group to the alkynylamido group of the intermediate alkynylamides. Products have been obtained in high to excellent yields starting from different N-alkyl 2-ethynylbenzamides and amines, under relatively mild conditions (100°C under 40atm of a 4:1 mixture of CO–air), working in a MeCN–amine mixture (2:1, v/v) for 5–15h.

Ruthenium(II) Picolyl-NHC Complexes: Synthesis, Characterization, and Catalytic Activity in Amine N-alkylation and Transfer Hydrogenation Reactions

Ruthenium(II) p-cymene complexes with picolyl-functionalized N-heterocyclic carbenes [(η6-p-cymene)Ru(L)(Cl)][PF6] (L = 3-methyl-1-(2-picolyl)imidazol-2-ylidene (1a), 3-isopropyl-1-(2-picolyl)imidazol-2-ylidene (1b), 3,4,5-trimethyl-1-(2-picolyl)imidazol-2-ylidene (1c), 3-mesityl-1-(2-picolyl)imidazol-2-ylidene (1d), 3-methyl-1-(2-picolyl)benzoimidazol-2-ylidene (1e), 3-methyl-1-(2-picolyl)-4,5-dichloroimidazol-2-ylidene (1f), 3-phenyl-1-(2-picolyl)imidazol-2-ylidene (1g)) have been synthesized and characterized. Compounds 1a–g were recrystallized, and X-ray crystal structures are reported for 1a,f. Furthermore, compounds 1a–f show catalytic activity in transfer hydrogenation of ketones and N-alkylation of amines. Notably, complexes 1a,c,f were found to be very efficient and versatile catalysts toward transfer hydrogenation of a wide range of ketones and imines in addition to N-alkylation of several amines.

Carbon, Hydrogen, and Nitrogen Isotope Fractionation Associated with Oxidative Transformation of Substituted Aromatic N-Alkyl Amines

We investigated the mechanisms and isotope effects associated with the N-dealkylation and N-atom oxidation of substituted N-methyl- and N,N-dimethylanilines to identify isotope fractionation trends for the assessment of oxidations of aromatic N-alkyl moieties by compound-specific isotope analysis (CSIA). In laboratory batch model systems, we determined the C, H, and N isotope enrichment factors for the oxidation by MnO(2) and horseradish peroxidase (HRP), derived apparent (13)C-, (2)H-, and (15)N-kinetic isotope effects (AKIEs), and characterized reaction products. The N-atom oxidation pathway leading to radical coupling products typically exhibited inverse (15)N-AKIEs (up to 0.991) and only minor (13)C- and (2)H-AKIEs. Oxidative N-dealkylation, in contrast, was subject to large normal (13)C- and (2)H-AKIEs (up to 1.019 and 3.1, respectively) and small (15)N-AKIEs. Subtle changes of the compound's electronic properties due to different types of aromatic and/or N-alkyl substituents resulted in changes of reaction mechanisms, rate-limiting step(s), and thus isotope fractionation trends. The complex sequence of electron and proton transfers during the oxidative transformation of substituted aromatic N-alkyl amines suggests highly compound- and mechanism-dependent isotope effects precluding extrapolations to other organic micropollutants reacting along the same degradation pathways.