Primary Arylamines Research Articles

One‐Pot Generation of Benzynes from Phenols: Formation of Primary Anilines by the Deoxyamination of Phenols

Benzynes were selectively generated in-situ from phenols and trapped regioselectively by potassium hexamethyldisilazide to form primary anilines following acidic workup. The direct conversion of a phenolic hydroxyl group to a free amino group is a useful method for the preparation of primary aryl amines that are hard to synthesize using coupling reactions involving phenol derivatives with ammonia. While reactions of ortho - and meta -substituted phenols produced meta-substituted anilines exclusively, those of para -substituted phenols provided ortho -silylanilines.

Regioselective synthesis of carboxylic and fluoromethyl tetrazoles enabled by silver-catalyzed cycloaddition of diazoacetates and aryl diazonium salts

Here we present a dipolar [3 + 2] cycloaddition transformation of diazoacetates with arenediazonium salts under silver catalysis, thus offering a straightforward approach for the regioselective construction of carboxylic tetrazoles. Several merits are accompanied with this reaction including readily available starting reagents, broad coupling scope, high yields, and friendly reaction conditions. The synthetic value is further showcased by one-pot conversion of commercially available primary arylamines to tetrazoles and successful transformations of the cycloadducts into valuable 5-fluoromethyltetrazoles and an analogue of P2X3 receptor antagonist.

A new ligand for copper-catalyzed amination of aryl halides to primary(hetero)aryl amines

N,N′-Bis(3,5-dimethoxyphenyl)cyclopentane-1,1-dicarboxamide was found as a new ligand for copper-catalyzed amination of aryl iodides, bromides and chlorides to afford various primary (hetero)aryl amines. These reactions proceeded efficiently under mild conditions when inexpensive aqueous ammonia (28% NH3 in H2O) was used as the amino source.

Fluorescent recognition and selective detection of nitrite ions with carbon quantum dots

The nitrite ion (NO2-) is a vital inorganic species that occurs both in natural ecological systems and human bodies. The high concentration of NO2- can be harmful for animal and human health. It is important to develop a simple, sensitive, reliable, and economic methodology to precisely monitor NO2- in various environmental and biological fields. Thus, a novel nitrite biosensor based on carbon quantum dots (PA-CDs) has been constructed and prepared via a high-efficiency, one-pot hydrothermal route using primary arylamines (PA) such as m-phenylenediamine. The device exhibits bright green fluorescence and a high quantum yield of 20.1% in water. In addition, the PA-CDs also possess two broad linear ranges: 0.05-1.0μM and 1.0-50μM with a low detection limit of 7.1nM. The classical diazo reaction is firstly integrated into the PA-CD system by primary arylamines, which endows the system with high sensitivity and specific selectivity towards nitrite. Importantly, the nanosensor can detect NO2- in environmental water and serum samples with high fluorescence recoveries, demonstrating its feasibility in practical applications. This work broadens a new method to fabricate novel nanosensors and provides a prospective application for fluorescent carbon quantum dots (CDs). Graphical abstract.

Aerobic oxidation of primary benzylic amines to amides and nitriles catalyzed by ruthenium carbonyl clusters carrying N,O-bidentate ligands.

Four trinuclear ruthenium carbonyl clusters, (6-BrPyCHRO)2Ru3(CO)8 (R = 4-OCH3C6H4, 1a; R = 4-BrC6H4, 1b) and (2-OC6H4-HC[double bond, length as m-dash]N-C6H4R)2Ru3(CO)8 (R = 4-OCH3, 2a; R = 4-Br, 2b), were synthesized from the reactions of Ru3(CO)12 with the corresponding N,O-bidentate ligands (two pyridyl alcohols and two Schiff bases) respectively in a ratio of 1 : 2. Three new complexes 1b, 2a and 2b have been fully characterized by elemental analysis, FT-IR, NMR and X-ray crystallography. The catalytic activity of these ruthenium complexes for the aerobic oxidation of primary benzylic amines to amides and nitriles in the presence of t-BuOK was investigated, of which the Schiff base complex 2a was found to exhibit the highest activity.

Mechanistic Study of Hydroamination of Alkyne through Tantalum-Based Silica-Supported Surface Species

Selective hydroamination of terminal alkynes with primary aryl amines is catalyzed by an unprecedented well-defined silica-supported tantalum complex [(≡Si–O−)Ta(η1σ-NEtMe)2(=NtBu)]. A molecular-level characterization of the surface organometallic Ta species was done with the help of characterization techniques including in situ infrared, 1H and 13C solid-state NMR (including double and triple quanta sequencing), and X-ray absorption spectroscopies. These were complemented by the state-of-the-art DNP-SENS 15N characterization. Several catalytic intermediates have been isolated, in particular the 4-membered metallacycle ring intermediate resulting from the anti-Markovnikov addition of the alkyne to the surface tantalum imido. A mechanism is proposed that is on the isolation of all intermediates. A density functional theory (DFT) calculation has confirmed all the elementary steps and intermediates that were fully characterized.

Asymmetric Ring-Opening of Donor–Acceptor Cyclopropanes with Primary Arylamines Catalyzed by a Chiral Heterobimetallic Catalyst

An efficient catalytic asymmetric ring-opening reaction of donor–acceptor cyclopropanes with primary arylamines was developed. The reaction was achieved through the utilization of a chiral heterobi...

ACCESSIBILITY OF ZWITTERIONIC COMPOUNDS FROM PRIMARY AMINES AND 2,5-DIHYDROXY-1,4-BENZOQUINONE

Following the discovery of an unprecedented transamination reaction between primary alkylamines and a quinonoid molecule of the type C 6 H 2 (NHCH 2 R) 2 (=O)2 (I), obtained from commercially available diaminoresorcinol.2HCl, we have extended this method to the use of primary arylamines and found that, in contrast, secondary amines led to a different outcome. Whereas functionalized molecules of type I , which are best described as 6π +6π zwitterions, were obtained with aniline or 4-methoxyaniline, no transamination was observed with tBuNH 2 in ethanol. However, a reaction which afforded salt 2-methylpropan-2-aminium 4-(methylamino)-3,6-dioxocyclohexa-1,4-dien-1-olate ( 2b) took place in water and resulted from hydrolysis of the imine group and deprotonation of 5-hydroxy-2-(methylamino)-4-(methylimino)-cyclohexa-2,5-dienone ( 1a) . Under similar conditions, secondary amines led to comparable results. The cations associated with the anionic quinonoid are readily exchanged in the presence of a primary amine. Whereas for the transamination reaction, basic amines react under mild conditions, slightly harsher conditions are needed for less basic amines such as piperidine, diisopropylamine, or diethylamine. Transamination reactions were also performed with 5-hydroxy-2-(methylamino)-4-(methylimino)-cyclohexa-2,5-dienone ( 1a) , which is more soluble in organic solvents than 2-amino-5-hydroxy-4-iminocyclohexa-2,5-dienone (compound I ) This led to the first examples of quinonoidal zwitterions functionalized with different alkyl groups on the nitrogen atoms. A number of compounds were characterized by X-ray diffraction, which allowed a better understanding of their electronic situation, and in many cases, the presence of multiple hydrogen-bond donors and acceptors results in crystal packings dominated by these interactions.

Sm-Catalyzed Synthesis and Biological Activity of Acyclic and Cyclic Azadiperoxides

Acyclic diaminodiperoxides and cyclic azadiperoxides are synthesized by the reaction of 1,1-bis-(hydroperoxy)cycloalkanes with formaldehyde and primary arylamines in the presence of Sm-containing catalysts [SmCl3·6H2O, Sm(NO3)3·6H2O, SmCl3/γ-Al2O3, and Sm(NO3)3/γ-Al2O3]. The chemoselectivity of this three-component reaction depends on the position of the substituent (F,Cl) in the phenyl ring of the primary arylamines. Signals of the cyclic aminoperoxides were assigned considering the conformation dynamics of the tetraoxazocane cycle with two rigid peroxide bonds. The structure of the acyclic diaminodiperoxides was reliably determined by X-ray diffraction analysis. The synthesized acyclic diaminodiperoxides were found to exhibit anticancer activity.

Взаимодействие пиперилена и его хлорпроизводных с ароматическими аминами

The article considers the possibility of introducing a pentenyl radical into the structure of aromatic amines by the interaction of the latter with piperylene and its chlorine derivatives, 4-chloro-2-pentene and 3,4-dichloro-2-pentene. Direct alkenylation of aniline with piperylene in the presence of Lewis acids leads to C-alkenyl arylamines. The most effective catalyst is AlCl3. Along with the expected 2- and 4-(1-methyl-2-butenyl) anilines, the formation of 2,4-di- and 2,4,6-tri-(1-methyl-2-butenyl) anilines is observed, the latter being virtiually the only product in the reaction with a 5-fold excess of piperylene. In addition to Lewis acids, H3PO4 deposited on kieselguhr or silica gel, as well as polyphosphoric acid, were used to catalyze this reaction. Under the action of these catalysts, ortho- and para-alkenylated anilines are mainly formed, and the yield of the ortho-isomer, reaching 34%, always exceeds the yield of the para-product. It is possible that, under these conditions, N-alkenylation occurs simultaneously with direct C-alkenylation followed by an amino rearrangement. The yield of the 2,4-dialkenyl product does not exceed 8%, and trialkenylated aniline is completely absent. The optimal reaction temperature is in the range of 180-200 °C, at higher temperatures the yield of the target products decreases due to the polymerization of piperylene. Various aniline derivatives are also involved in the reaction with piperylene. When one of the ortho positions in the arylamine molecule is occupied, as in ortho-toluidine or in 2-chloroaniline, a mixture of the three products is formed in comparable amounts. The reaction of meta-toluidine with piperylene also leads to the mixture of three products, and the substitution does not affect the 2-position between the amino and methyl groups. If both ortho-positions are occupied, as in 2-methyl-6-ethylaniline, the reaction is quite successfully under way in the para-position (yield is 61%). To increase the selectivity of the process, the alkylation of aromatic amines is best carried out not by piperylene, but by its chlorine derivatives. The reaction of aniline with 4-chloro-2-pentene takes place in the environment of triethylamine and leads to N-(1-methyl-2-butenyl) aniline with a yield of 80%. Other primary and secondary arylamines react in the same way. The reaction with 3,4-dichloro-2-pentene proceeds under more severe conditions. If the reaction of aromatic amines with 4-chloro-2-pentene is carried out not in triethylamine medium, but in an excess of arylamine itself as a solvent, then not N- but C-substituted products are formed. The reaction proceeds as a consequitive-simultameous process. In the first stage, N-alkenylation occurs with the formation of N-(1-methyl-2-butenyl) arylamine followed by an amino rearrangement of Claisen under the catalytic action of evolved HCl. Alongside with the obvious predominance of ortho-substituted arylamine (64-82%), para-isomers and, in some cases 5-12% of 2,4- or 2,6-disubstituted compounds were found in the reaction products. The amino rearrangement in the interaction of arylamines with 3,4-dichloro-2-pentene proceeds with exceptional ortho-selectivity. Alkyl groups at nitrogen and ortho positions accelerate, and ortho-chloro, para-methyl, 2,4-dimethyl substituents slow down the process, while the meta-methyl group has no significant effect. The same dependence was observed in the case of 4-chloro-2-pentene. Thus, pentenyl fragment can be introduced in various ways into the structure of aromatic amines: by direct interaction with piperylene in the presence of catalysts, N-alkenylation of 4-chloro-2-pentene and 3,4-dichloro-2-pentene in triethylamine medium and reaction of arylamines with chlorine derivatives of piperylene, accompanied by an amino rearrangement of Claisen.

Copper(II) complexes with barbiturate derivatives: Synthesis, characterization and catalytic applications

Barbiturate derivatives were prepared by the reaction of 5-formylbarbiturates and primary aryl amines. The corresponding copper(II) complexes were synthesized by treatment of copper(II) acetate monohydrate with the prepared barbiturate derivatives. All the novel compounds were characterized by elemental analysis and spectroscopic methods. The structures of 3b and 3j were determined with X-ray crystallography. The X-ray crystallographic studies revealed that complexes 3b and 3j are 2-D coordination polymers. Also, the catalytic activities of the copper(II) complexes were examined for the peroxidative oxidation of cyclohexane under mild conditions. The results showed that the yields of the oxidation products were in the range 11.3–22.1%, depending upon the complex used and the promoter.

The mechanism and structure-activity relationship of amide bond formation by silane derivatives: a computational study.

The condensation of carboxylic acids and amines mediated by silane derivatives provided a straightforward and sustainable method for amide bond formation with minimal waste. However, the detailed mechanism and structure-activity relationship of substrates, the topics that are of interest for both academic and industrial applications, were not clear. Herein, a systematic computational study was conducted to solve the two questions. We found that the two previously proposed mechanisms involving intramolecular acyl transfer or silanolate were less likely because the associated silanone intermediate and zwitterion adducts were too unstable with higher overall energy barriers. By comparison, the mechanism involving deprotonation of carboxylic acids, addition of carboxylates on silane reagents, dihydrogen formation to afford an acyloxysilane intermediate, carboxylic-acid-assisted addition of amines, and concerted proton transfer/amide formation, was found to be more favorable with overall energy barriers varying between 24 and 28 kcal mol-1 for the different calculated cases. Meanwhile, the dihydrogen formation and amide formation processes are both potential rate-determining steps. Energy composition, atomic charge, and distortion-interaction analyses indicated that the steric effect of silane reagents was more important than the electronic effect, making less bulky silane reagents more reactive. On the other hand, the dihydrogen formation process was mainly controlled by the electronic effect of the substituents of carboxylic acids and amines while the amide formation process was mainly influenced by their steric effect. As a result, less bulky, less acidic alkyl carboxylic acids are more reactive than unsaturated carboxylic acids, and less bulky, medium basic primary alkyl amines are more reactive than secondary alkyl amines and primary aryl amines. The related results provided deeper mechanistic insights into the amide bond formation mediated by silane derivatives and can act as a reference for further experimental design.

New synthesis of tetraoxaspirododecane-diamines and tetraoxazaspirobicycloalkanes.

An efficient method for the synthesis of new spiro-tetraoxadodecanediamines and tetraoxazaspirobicycloalkanes has been developed by reactions of primary arylamines with gem-dihydroperoxides and α,ω-dialdehydes (glyoxal, pentanedial) catalyzed by lanthanide catalysts. A potential pathway for formation of tetraoxaspirododecane-diamines and tetraoxazospirobicycloalkanes has been proposed that involves generation of intermediate tetraoxaspiroalkanediols under the reaction conditions. The structures of the crystalline products have been confirmed by XRD. It was shown that the synthesized tetraoxazaspirobicycloalkanes exhibit high cytotoxic activity against Jurkat, K562, and U937 tumor cultures and Fibroblasts.

Palladium(II) Complexes with N-Phosphanyl-N-heterocyclic Carbenes as Catalysts for Intermolecular Alkyne Hydroaminations.

The catalytic potential of palladium(II) complexes with chelating N-phosphanyl-N-heterocyclic carbenes featuring a saturated imidazolin-2-ylidene or tetrahydropyrimid-2-ylidene ring has been investigated in intermolecular alkyne hydroamination reactions. The complexes were found to be among the most active Pd-based catalysts for these processes and to enable the use of low reaction temperatures (40 °C) and of solventless conditions. The Pd complexes require activation by 2 equiv of a silver salt to remove chlorido ligands from the metal coordination sphere; they can however also be presynthesized in active form, which allows their use under silver-free conditions. The hydroamination reaction was found to efficiently proceed with terminal alkynes and different ring-substituted, primary arylamine substrates.

Divergent Late-Stage (Hetero)aryl C-H Amination by the Pyridinium Radical Cation.

(Hetero)arylamines constitute some of the most prevalent functional molecules, especially as pharmaceuticals. However, structurally complex aromatics currently cannot be converted into arylamines, so instead, each product isomer must be assembled through a multistep synthesis from simpler building blocks. Herein, we describe a late-stage aryl C-H amination reaction for the synthesis of complex primary arylamines that other reactions cannot access directly. We show and rationalize through a mechanistic analysis the reasons for the wide substrate scope and the constitutional diversity of the reaction, which gives access to molecules that would not have been readily available otherwise.

Divergent Late‐Stage (Hetero)aryl C−H Amination by the Pyridinium Radical Cation

Abstract(Hetero)arylamines constitute some of the most prevalent functional molecules, especially as pharmaceuticals. However, structurally complex aromatics currently cannot be converted into arylamines, so instead, each product isomer must be assembled through a multistep synthesis from simpler building blocks. Herein, we describe a late‐stage aryl C−H amination reaction for the synthesis of complex primary arylamines that other reactions cannot access directly. We show and rationalize through a mechanistic analysis the reasons for the wide substrate scope and the constitutional diversity of the reaction, which gives access to molecules that would not have been readily available otherwise.

Mechanism of Boron-Catalyzed N-Alkylation of Primary and Secondary Arylamines with Ketones Using Silanes under “Wet” Conditions

Density functional theory (DFT) calculations have been carried out to study the mechanism of N-alkylation of primary and secondary arylamines with aldehydes and ketones under the catalysis of the Lewis acid B(C6F5)3 using silanes. The B(C6F5)3-mediated reduction of organic substrates is usually reported under anhydrous conditions. It is noteworthy that Ingleson and co-workers have established that B(C6F5)3 could act as a water tolerant catalyst in N-alkylation of arylamines with aldehydes/ketones. Our DFT calculation results revealed that both Lewis acid B(C6F5)3 and water play important roles in the condensation of amine and aldehyde to generate an imine intermediate and in the subsequent reduction of imine to yield an amine product. In the condensation reaction, Bronsted acid B(C6F5)3-H2O acts as the effective catalyst to promote the proton transfer process. The activation free energy barrier is calculated to be 21.1 kcal/mol, which is 23.0 kcal/mol lower than that of the water-assisted condensation pat...

Probing the Influence of PAd-DalPhos Ancillary Ligand Structure on Nickel-Catalyzed Ammonia Cross-Coupling

We report herein on the results of our combined experimental/computational study regarding the catalytic performance of PAd-DalPhos (L1) in nickel-catalyzed ammonia arylation for primary aniline synthesis. Primary arylamine C–N reductive eliminations occurring from arylnickel(II) parent amido complexes of the type (L)Ni(Ph)(NH2) were modeled by use of density-functional theory (DFT) methods, for a series of L1 derivatives. The dual aims were to assess the effect of structural modifications to L1 on potentially rate-limiting C–N reductive elimination and to identify promising candidates for experimental inquiry. Increasing the steric demand of the Paryl groups from o-tolyl (in L1) to mesityl (in L16) resulted in a significant lowering of the barrier to C–N reductive elimination (ΔG⧧RE), which can be attributed in part to interactions between the ligand Paryl groups and the nickel-bound amido ligand, as observed in noncovalent interaction (NCI) plots of the reductive elimination transition-state structures....

Cyclic (Alkyl)amino Carbene Complex of Aluminum(III) in Catalytic Guanylation Reaction of Carbodiimides

Herein we report the synthesis of a cyclic (alkyl)amino carbene (cAAC) complex of AlMe3. This complex was used as an efficient catalyst for the guanylation reaction of carbodiimides with primary arylamines and secondary amines to deliver guanidine derivatives in good to excellent yields. This catalytic protocol can tolerate a wide range of functional groups. Furthermore, the longevity of the catalyst was tested in successive catalytic cycles, which indicated a sustained catalytic activity over a multiple cycles. The mechanistic pathway was well understood with the help of stoichiometric reaction and DFT study.

Pd-catalyzed C-N coupling of primary (het)arylamines with 5-substituted 3-chloro-4H-1,2,6-thiadiazin-4-ones

The Buchwald-Hartwig Pd-catalyzed C-N coupling reaction of 5-substituted 3-chloro-4H-1,2,6-thiadiazin-4-ones with primary (het)arylamines is described, affording twenty new 3,5-disubstituted 4H-1,2,6-thiadiazin-4-ones in 56–99% yield. The protocol enables the mild preparation of difficult to access 3,5-dianilino-1,2,6-4H-thiadiazin-4-ones. The reaction scope and limitations are discussed.