N-alkyl Anilines Research Articles

Atomic-Level Asymmetric Tuning of the Co1-N3P1 Catalyst for Highly Efficient N-Alkylation of Amines with Alcohols.

Despite the extensive development of non-noble metals for the N-alkylation of amines with alcohols, the exploitation of catalysts with high selectivity, activity, and stability still faces challenges. The controllable modification of single-atom sites through asymmetric coordination with a second heteroatom offers new opportunities for enhancing the intrinsic activity of transition metal single-atom catalysts. Here, we prepared the asymmetric N/P hybrid coordination of single-atom Co1-N3P1 by absorbing the Co-P complex on ZIF-8 using a concise impregnation-pyrolysis process. The catalyst exhibits ultrahigh activity and selectivity in the N-alkylation of aniline and benzyl alcohol, achieving a turnover number (TON) value of 3480 and a turnover frequency (TOF) value of 174-h. The TON value is 1 order of magnitude higher than the reported catalysts and even 37-fold higher than that of the homogeneous catalyst CoCl2(PPh3)2. Furthermore, the catalyst maintains its high activity and selectivity even after 6 cycles of usage. Controlling experiments and isotope labeling experiments confirm that in the asymmetric Co1-N3P1 system, the N-alkylation of aniline with benzyl alcohol proceeds via a transfer hydrogenation mechanism involving the monohydride route. Theoretical calculations prove that the superior activity of asymmetric Co1-N3P1 is attributed to the higher d-band energy level of Co sites, which leads to a more stable four-membered ring transition state and a lower reaction energy barrier compared to symmetrical Co1-N4.

N-Alkylation of Anilines with Primary Alcohols by MOF-Derived CoNx Nanoparticles on N-Doped Carbon

N-Alkylation of Anilines with Primary Alcohols by MOF-Derived CoNx Nanoparticles on N-Doped Carbon

Visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one.

The synthesis of amines through N-alkylation is particularly attractive. Herein, a strategy for visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one was developed in the presence of NH4Br, which avoid the use of metals, bases and ligands. In addition, gram-scale experiments proved that the system has the potential to be scaled.

Visible-Light-Induced Selective α-Fluoroarylation of Secondary N-Alkyl Anilines with Polyfluoroarenes via Direct C-H/C-F Coupling.

Direct and selective fluoroarylations of nucleophilic secondary alkylanilines with polyfluoroarenes were first realized through visible-light-induced C-H/C-F couplings with the assistance of bases. Varieties of α-polyfluoroarylanilines were selectively produced with this protocol from polyfluoroarenes and N-alkylanilines, including natural products and pharmaceutical molecule derivatives. Mechanistic studies illustrated base-promoted photochemical C-H cleavage of the α-C-H bonds of alkylanilines to produce the N-α-carbon radical and then radical addition to polyfluoroarenes.

Catalytic activity of Cu-BTC metal organic framework for borrowing hydrogen and tandem reactions of an alcohol under solvent and base free condition

The Cu-BTC (copper(II)-benzene-1,3,5-tricarboxylate) metal–organic framework was found to be a potential, stable and reusable catalyst for the solvent- and base-free borrowing hydrogen and tandem reactions of an alcohol. The Cu-BTC exhibited borrowing hydrogen activity in N-alkylation of aniline with benzyl alcohol, a model reaction of borrowing hydrogen, giving the saturated product (N-alkylated aniline). However, the formation of unsaturated product (chalcone) in the reaction of acetophenone with benzyl alcohol for α-C-alkylation, another model reaction of borrowing hydrogen, showed potential of Cu-BTC for the catalysis of tandem reactions to synthesize unsaturated products utilizing alcohols as a reagent. The study shows that the Cu-O pair sites of Cu-BTC are involved in the catalysis of borrowing hydrogen and tandem reactions.

Methanol as a Potential Hydrogen Source for Reduction Reactions Enabled by a Commercial Pt/C Catalyst

Catalytic reduction reactions using methanol as a transfer hydrogenating agent is gaining significant attention because this simple alcohol is inexpensive and produced on a bulk scale. Herein, we report the catalytic utilization of methanol as a hydrogen source for the reduction of different functional organic compounds such as nitroarenes, olefins, and carbonyl compounds. The key to the success of this transformation is the use of a commercially available Pt/C catalyst, which enabled the transfer hydrogenation of a series of simple and functionalized nitroarenes-to-anilines, alkenes-to-alkanes, and aldehydes-to-alcohols using methanol as both the solvent and hydrogen donor. The practicability of this Pt-based protocol is showcased by demonstrating catalyst recycling and reusability as well as reaction upscaling. In addition, the Pt/C catalytic system was also adaptable for the N-methylation and N-alkylation of anilines via the borrowing hydrogen process. This work provides a simple and flexible approach to prepare a variety of value-added products from readily available methanol, Pt/C, and other starting materials.

Electron transfer catalysis mediated by 3d complexes of redox non-innocent ligands possessing an azo function: a perspective.

It was first reported almost two decades ago that ligands with azo functions are capable of accepting electron(s) upon coordination to produce azo-anion radical complexes, thereby exhibiting redox non-innocence. Over the past two decades, there have been numerous reports of such complexes along with their structures and diverse characteristics. The ability of a coordinated azo function to accept one or more electron(s), thereby acting as an electron reservoir, is currently employed to carry out electron transfer catalysis since they can undergo redox transformation at mild potentials due to the presence of energetically accessible energy levels. The cooperative involvement of redox non-innocent ligand(s) containing an azo group and the coordinated metal centre can adjust and modulate the Lewis acidity of the latter through selective ligand-centred redox events, thereby manipulating the capacity of the metal centre to bind to the substrate. We have summarized the list of first row transition metal complexes of iron, cobalt, nickel, copper and zinc with redox non-innocent ligands incorporating an azo function that have been exploited as electron transfer catalysts to effectuate sustainable synthesis of a wide variety of useful chemicals. These include ketazines, pyrimidines, benzothiazole, benzoxazoles, N-acyl hydrazones, quinazoline-4(3)H-ones, C-3 alkylated indoles, N-alkylated anilines and N-alkylated heteroamines. The reaction pathways, as demonstrated by catalytic loops, reveal that the azo function of a coordinated ligand can act as an electron sink in the initial steps to bring about alcohol oxidation and thereafter, they serve as an electron pool to produce the final products either via HAT or PCET processes.

A one-step base-free synthesis of N-arylamides via modified pivaloyl mixed anhydride mediated amide coupling.

Pivalic anhydride is shown to be an effective reagent for direct amidation of carboxylic acids with N-alkyl anilines. The only by-product of this reaction is nontoxic pivalic acid, which can be easily removed by aqueous workup. The reactions are conducted under mild conditions and found to be compatible with a range of carboxylic acids, including aromatic, heterocyclic, acrylic, and aliphatic carboxylic acids and amino acids generating the desired amides in short reaction times.

Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(μ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines.

Nickel-catalyzed mild synthesis of functional γ-amino butyric acid esters via direct α-C(sp3)-H allylation of N-alkyl anilines with allyl sulfones.

Herein, by employing a readily available Ni(OAc)2·4H2O/TBHP catalyst system, we present a new method for mild synthesis of α-methylene-γ-amino butyric acid esters via direct α-C(sp3)-H allylation of N-alkyl anilines with allyl sulfones under oxidative nickel catalysis. The synthetic protocol proceeds with good substrate and functional group compatibility, operational simplicity, the use of base metal catalysts and easily accessible feedstocks, and no need for pre-functionalization of the α-site of N-alkyl anilines. In addition, the obtained products are applicable for further elaboration of functional molecules.

Development of a Graphene Oxide-Supported N-Heterocyclic Carbene Copper(I) Complex as a Heterogeneous Catalyst for the Selective N-Monoalkylation of Amines

A new N-heterocyclic carbene (NHC) copper(I) complex supported on graphene oxide (GO-NHC-Cu) was synthesised and thoroughly characterised by various instrumental techniques such as FT-IR, FT-Raman, PXRD, XPS, FESEM, EDX, HRTEM, TGA and ICP-OES. The catalytic activity of the supported complex was explored in the N-alkylation of anilines with alcohols under solvent-free and aerobic conditions to afford monoalkylated products in good to excellent yields (20 products, 83–96%). All products were isolated and characterised by 1H and 13C{1H} NMR spectroscopy. The catalyst was recuperated from the reaction mixture by simple filtration and reused for up to five successive cycles with insignificant loss in the catalytic activity. The control experiments showed that the reaction proceeded in aerobic conditions. The green chemistry metrics for the reaction were found to be fairly close to the ideal values: carbon efficiency (95.9%), E-factor (0.15), atom economy (92.14%), process mass intensity (1.15) and reaction mass efficiency (86.80%). The air stability, selectivity, recyclability of the catalyst, and the high yields of the products under solvent-free conditions are some of the salient features of the reported methodology.

Efficient thiocyanation of aromatic compounds using NH4SCN, DMSO and H2SO4

A simple, efficient, and smooth thiocyanation of indoles, phenols and aniline derivatives using NH4SCN, DMSO and H2SO4 in DMF is introduced. Using this procedure, diverse indoles and N-alkyl indoles are selectively thiocyanated at the C-3 position. para-free anilines, N-alkyl anilines and phenols undergo thiocyanation at the para position selectively.

Photocatalytic Synthesis of Quinolines via Povarov Reaction under Oxidant-Free Conditions

We describe here an approach for synthesizing quinolines either from N-alkyl anilines or from anilines and aldehydes. A dual-catalyst system consisting of a photocatalyst and a proton reduction cocatalyst is employed. Without the use of any sacrificial oxidant and under extremely mild conditions, the reactions afford quinolines in excellent yields and produce H2 as a byproduct.

Directed Evolution of Artificial Metalloenzymes in Whole Cells.

Artificial metalloenzymes (ArMs), created by introducing synthetic cofactors into protein scaffolds, are an emerging class of catalyst for non-natural reactions. Although many classes of ArMs are known, in vitro reconstitution of cofactors and proteins has been a limiting step in the high-throughput screening and directed evolution of ArMs because purification of individual host proteins is time-consuming. We describe the application of a platform to combine mutants of the P450 enzyme CYP119 and the cofactor Ir(Me)MPIX in vivo, by coexpression of the CYP119 mutants with the heme transporter encoded by the hug operon, to the directed evolution of ArMs containing Ir(Me)MPIX in whole cells. We applied this platform to the development an ArMs catalyzing the insertion of the acyclic carbene from α-diazopropanoate esters (Me-EDA) into the N-H bonds of N-alkyl anilines, a combination of carbene and amine classes for which mutant enzymes of natural hemoproteins previously reacted with low enantioselectivity. The mutants of the artificial metalloenzyme Ir(Me)CYP119 identified by an evolution campaign involving more than 4000 mutants are shown to catalyze the reaction of Me-EDA with N-methyl anilines to form chiral chiral amino esters with high TON and good enantioselectivity, thereby demonstrating that the directed evolution of ArMs can rival that of natural enzymes in vivo.

Investigation of molecular interactions by volumetric, transport, spectral and DFT studies in some liquid binaries of N-methyl-2-pyrrolidone with N-alkyl anilines in the temperature range 303.15–318.15 K

• Mixtures of NMP & N-alkyl anilines are studied at 303.15–318.15 K. • NMP + N-alkyl aniline system has hydrogen bonding interactions operated. • Viscosity values are used to check validity of several empirical relations. • IR studies suggest specific interaction and support thermodynamic findings. • SPARTON modeling & DFT studies are performed to calculate the interaction energies.

Synthesis of N-Alkyl Anilines from Arenes via Iron-Promoted Aromatic C-H Amination.

We report both an intermolecular C-H amination of arenes to access N-methylanilines and an intramolecular variant for the synthesis of tetrahydroquinolines. A newly developed, highly electrophilic aminating reagent was key for the direct synthesis of unprotected N-methylanilines from simple arenes. The reactions display a broad functional group tolerance and employ catalytic amounts of a benign iron salt under mild reaction conditions.

Diastereoselective and Reversed Regioselective Annulations of N-Alkyl Anilines to Julolidines and Lilolidines.

A three-component annulation reaction of N-alkyl anilines, cyclic 1,3-dicarbonyl compounds, and aryl aldehydes to julolidines and lilolidines is reported. The 6π-electrocyclization enabled the annulation to proceed with reversed regioselectivity as compared with the annulation that occurs in the Povarov reaction. Both cyclic and acyclic N-alkyl anilines participated in the reaction to provide a wide range of julolidines and lilolidines as the single regio- and diastereoisomers in good to excellent yields.

Visible-light-promoted radical cross-coupling of para-quinone methides with N-substituted anilines: an efficient approach to 2,2-diarylethylamines.

An efficient protocol to access 2,2-diarylethylamines via visible-light-promoted radical reactions of para-quinone methides (p-QMs) with N-alkyl anilines has been disclosed. These reactions feature metal-free, redox-neutral, and mild reaction conditions with wide functional group compatibility.

Partial Molar Volumes and Spectral Studies on Binary Mixtures of p-Chloroacetophenone with Aniline and N-Alkyl Anilines

Ultrasonic velocities (u), viscosities (η) and densities (ρ) were measured for the binary mixtures of p-chloroacetophenone with aniline, N-methylaniline and N,N-dimethylaniline over the whole range of composition at different temperatures (303.15 K to 318.15 K) and at atmospheric pressure 0.1 MPa. Excess molar volume (VE), deviation in viscosity (Δη) and deviation in isentropic compressibility (Δks) have been calculated and fitted to Redlich-Kister polynomial equation to obtain their coefficients and standard deviations. The analyzed viscosity data of binary liquid mixtures were used to test the Grunberg-Nissan, Katti-Chaudari and Hind semi-empirical equations. The FTIR spectral study supports the experimental data to explain the molecular interactions between unlike molecules. Partial molar volumes of binary mixtures were evaluated for better understanding of intermolecular interactions of the above binary mixtures.

Ag/GO nanocatalysts for N-alkylation

Here we report, for the first time, the catalytic activity towards N-alkylation reactions of an Ag/GO nanocatalyst. The nanocatalyst was obtained through a “green” approach and directly used in N-alkylation of aniline, showing high conversion and selectivity in short times and mild conditions. The reusability of Ag/GO nanohybrid was also checked, showing a very small loss of activity after six consecutive cycles. The efficiency of Ag/GO nanohybrid was ascribed not only to the high availability of Ag exposed on the GO carpet, but also to the combination of silver and GO enhancing the Ag catalytic activity.