Tertiary Alkylamines Research Articles

B(C6F5)3-catalyzed β-C(sp3)-H alkylation of tertiary amines with 2-aryl-3H-indol-3-ones.

The β-C-H functionalization of amines is one of the most powerful tools for the synthesis of saturated nitrogen-containing heterocycles in organic synthesis. However, the β-C-H functionalization of amines via redox-neutral addition with cyclic-ketimines is still unprecedented. Herein, the β-C-H functionalization of tertiary amines is described, providing the corresponding 1,3-diamines containing the indolin-3-one moiety in high yields via the B(C6F5)3-catalyzed borrowing hydrogen strategy. According to the experimental results, a possible catalytic cycle has been proposed to rationalize the process of this reaction. Notably, the β-C-H alkylation of amines is external oxidant- and transition-metal-free, which makes a significant contribution to promoting economical chemical synthesis.

Transition-metal free C–N bond formation from alkyl iodides and diazonium salts via halogen-atom transfer

Construction of C-N bond continues to be one part of the most significant goals in organic chemistry because of the universal applications of amines in pharmaceuticals, materials and agrochemicals. However, E2 elimination through classic SN2 substitution of alkyl halides lead to generation of alkenes as major side-products. Thus, formation of a challenging C(sp3)-N bond especially on tertiary carbon center remains highly desirable. Herein, we present a practical alternative to prepare primary, secondary and tertiary alkyl amines with high efficiency between alkyl iodides and easily accessible diazonium salts. This robust transformation only employs Cs2CO3 promoting halogen-atom transfer (XAT) process under transition-metal-free reaction conditions, thus providing a rapid method to assemble diverse C(sp3)-N bonds. Moreover, diazonium salts served as alkyl radical initiator and amination reagent in the reaction. Mechanism studies suggest this reaction undergo through halogen-atom transfer process to generate active alkyl radical which couples with diazonium cations to furnish final products.

Construction of N-loaded conjugated polymer for highly effective removal of iodine in organic solution

Efficient capture of radioiodine is critical during nuclear fuel reprocessing and nuclear accidents. The development of material with excellent adsorption properties of radioiodine has always been a significant challenge. Three kinds of N-loaded conjugated polymers were prepared using the solvothermal method by changing the N-group in pyrrole. The effect of nitrogen type on the structure of conjugated polymers was investigated by SEM, BET, FT-IR, XPS, and EPR. Despite their low specific surface area, their mesoporous structure is conducive to transporting iodine molecules. The results showed that in the conjugated system, the adsorption capacity of alkyl tertiary amines for iodine was better than that of aminoethyl tertiary amines and secondary amines, and the maximum adsorption capacity could reach 737.4 mg/g. The adsorption mechanism of iodine on N-loaded conjugated polymer is mainly the interaction of charge transfer between iodine and N-aromatic in the organic solution.

Deaminative Cyclization of Tertiary Amines for the Synthesis of 2-Arylquinoline Derivatives with a Nonsubstituted Vinylene Fragment

With triethylamine as a vinylene source, a convenient protocol for the regioselective synthesis of β,γ-nonsubstituted 2-arylquinolines from aldehydes and arylamines has been accomplished. The deaminative cyclization is also extended to long-chain tertiary alkylamines, enabling diverse alkyl groups to be concurrently installed into the pyridine rings. This process demonstrates a new conversion pathway for the simultaneous dual C(sp3)-H bond functionalization of tertiary amines, wherein the transient acyclic enamines generated in situ undergo the Povarov reaction.

Copper hydride catalysis enables facile access to fluorinated α-chiral tertiary trialkylamines

In the September issue of Chem Catalysis , the Xiong and Zhang groups leveraged the power of density functional theory (DFT) to unveil new mechanistic insight into the regiochemically reversed, enantioselective copper-catalyzed hydroamination reaction. Their findings enabled the development of a new method to access fluorine-containing α-chiral tertiary alkylamines. In the September issue of Chem Catalysis , the Xiong and Zhang groups leveraged the power of density functional theory (DFT) to unveil new mechanistic insight into the regiochemically reversed, enantioselective copper-catalyzed hydroamination reaction. Their findings enabled the development of a new method to access fluorine-containing α-chiral tertiary alkylamines.

Radical cross-coupling access to α-chiral tertiary alkylamines by a Cu(I) catalyst

The radical cross-coupling reaction is important in recent chemistry. In the September issue of Chem Catalysis , Guan, Xiong, Zhang, and co-workers reported regio- and enantioselective synthesis of α-chiral tertiary-alkylamines through Cu(I)-catalyzed radical cross-coupling. Density functional theory (DFT) computations predicted this reaction and elucidated mechanistic details. Tetrahydrofuran (THF) solvent plays crucial roles in increasing regioselectivity and yield. The radical cross-coupling reaction is important in recent chemistry. In the September issue of Chem Catalysis , Guan, Xiong, Zhang, and co-workers reported regio- and enantioselective synthesis of α-chiral tertiary-alkylamines through Cu(I)-catalyzed radical cross-coupling. Density functional theory (DFT) computations predicted this reaction and elucidated mechanistic details. Tetrahydrofuran (THF) solvent plays crucial roles in increasing regioselectivity and yield.

Dislodging Dichromate in Mine Slops Applying Flat Supplying Membrane Equipment Containing Carrier N235/7301.

A novel flat supplying membrane equipment (FSME) with a sodium hydroxide solution and a mixture of N235/7301 and petroleum has been studied for dislodging dichromate (which can be expressed as Cr (VI) or Cr2O72−) from simulated mine slops. The FSME contained three parts: as a feeding cell, a reacting cell, and a supplying cell. The flat Kynoar membrane was inlaid in the middle of the reacting cell, using the mixed solutions of petroleum and sodium hydroxide, with Tri (octyl decyl) alkyl tertiary amine (N235/7301) as the carrier in the supplying cell and the mine slops with Cr (VI) as the feeding section. The impact parameters of pH and the other ion density in the feeding solutions, the voluminal ratio of petroleum to sodium hydroxide solution and N235/7301 concentration in the supplying solutions were investigated for the obtaining of the optimal technique parameters. It was found that the dislodging rate of Cr (VI) could reach 93.3% in 215 min when the concentration of carrier (N235/7301) was 0.20 mol/L, the voluminal ratio of petroleum and sodium hydroxide in the supplying cell was 1:1, the pH of the feeding section was 4.00, and the Cr (VI) cinit was 3.00 × 10−4 mol/L. The practicability and steadiness of FSME were gained through the exploration of Cr (VI) adsorption on the membrane surface.

Copper-catalyzed hydroamination of polyfluoroalkyl substituted alkenes via asymmetric radical cross-coupling access to α-chiral tertiary alkylamines

α-Chiral tertiary alkylamines are quintessential scaffolds in pharmaceuticals, bioactive molecules, and organic materials. Although there has been substantial advancement in the synthesis of chiral amides or sulfonamides through open-shell pathway in recent years, it remains problematic to efficiently obtain optically active aliphatic amines, especially α -chiral tertiary alkylamines. Herein, we have demonstrated, by means of density functional theory calculations jointly with experimental studies, that the chiral C–N bond can be forged through a mechanically unprecedented radical cross-coupling of a Cu(I)-bounded dialkyl amine radical species with a carbon-based radical species. Consequently, by virtue of this protocol, a diversity of important optically active β -polyfluoroalkyl substituted α -chiral tertiary alkylamines have been efficiently constructed with high enantioselectivity. • CuH-catalyzed asymmetric reversal hydroamination • Cu-catalyzed enantioselective radical cross-coupling • Efficient construction of β-polyfluoroalkyl-substituted α-chiral tertiary alkylamines • Theoretical mechanistic insight and experimental synthesis A Cu-catalyzed radical cross-coupling of in-situ -generated Cu(I)-bounded dialkyl amine radical species with a carbon-based radical species to create a chiral C–N bond has been disclosed for the first time to our knowledge. By virtue of this approach, asymmetric radical hydroamination of β-aryl substituted polyfluoroalkyl alkenes with hydroxylamine derivatives have been successfully implemented to access an array of important β-polyfluoroalkyl substituted α-chiral tertiary alkylamines in an excellent regio-and enantioselective manner. A Cu-catalyzed radical cross-coupling of in-situ -generated Cu(I)-bounded dialkyl amine radical species with a carbon-based radical species to create a chiral C–N bond has been disclosed for the first time to our knowledge. By virtue of this approach, asymmetric radical hydroamination of β-aryl substituted polyfluoroalkyl alkenes with hydroxylamine derivatives has been successfully implemented to access an array of important β-polyfluoroalkyl substituted α-chiral tertiary alkylamines in an excellent regio- and enantioselective manner.

Molecular logic with ferrocene-rylene conjugates: A comparison of naphthalenediimide, naphthalimide and perylenediimide Pourbaix sensor designs

Four molecules designed as Pourbaix sensors with rylene dyes (naphthalenediimide, 4-amino-1,8-naphthalimide, perylenediimide) are compared. Each molecule is constructed modularly according to an electron-donor–spacer–fluorophore–spacer–receptor format based on photoinduced electron transfer (PET). The modules consist of ferrocene as the electron donor, a tertiary alkyl amine as the proton receptor, and a rylene dye as the fluorophore connected by a methylene and ethylene spacer, respectively. The proton and oxidant-induced fluorescent spectral changes of the 4-amino-1,8-naphthalimide models include internal charge transfer (ICT) character. Two of the discussed logic gates switch on emitting fluorescence in the presence of acid (H+) and oxidant (Fe3+) according to two-input AND logic, while two of the logic gates remain off according to two-input PASS 0 logic.

Efficient synthesis of β-substituted amines via combining deoxygenation of amides with photochemical organocatalysis

Catalytic deoxygenative conversion of amides to substituted amines is an efficient pathway for amine synthesis. α-Substituted amines are generally obtained by classic nucleophilic addition of nucleophiles to active electrophilic intermediates formed from amides. Here, we develop a deoxygenative reaction of amides that combines iridium catalysis and photochemical organocatalysis, giving structurally diverse β-substituted tertiary alkylamines with moderate to excellent yields (up to 93%) with broad substrate scope (57 examples). Mechanistic studies suggest that the combination of iridium (Ir)-catalyzed partial reduction of amides and photochemical organocatalysis of α-bromoketones under visible light plays a crucial role in cross-coupling of these two readily accessible feedstocks. The active electrophilic radicals from photochemical organocatalysis act as functionalization partners with the in-situ -formed enamine intermediates from the Ir-catalyzed reduction of amides instead of traditional nucleophilic addition to iminium ions, leading to formation of β-substituted amines. • Combination of Ir-catalyzed reduction of amide and photochemical organocatalysis • Coupling of active electrophilic radicals with enamine intermediates • Tandem catalysis: Ir catalysis, photochemical organocatalysis, Ir catalysis • Deoxygenative functionalization of amides to β-substituted amines Deoxygenative functionalization of ubiquitous amides to synthetically important amines is of great significance. Jiang et al. develop deoxygenative cross-coupling of amides with electrophilic radicals by rational combination of Ir-catalyzed reduction of amides with photochemical organocatalysis, leading to a suite of functionally and structurally diverse β-substituted amines.

Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Cyclopropanes and Cyclobutanes Guided by Tertiary Alkylamines.

Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp3)–H arylation of aminomethyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C–H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Central to the success of this strategy is the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes γ-C–H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C–H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymmetrization of N-isobutyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of functionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.

Styrene hydroaminoalkylation with primary alkylamines

Hydroaminoalkylation (HAA) of alkenes is one of the most appealing methods for the construction of α-alkylated amines, and impressive advances in intermolecular HAA of non-electrophilic alkenes have been made for secondary and tertiary alkylamine substrates. We recently developed a general catalytic solution for HAA with unprotected primary alkylamines using a combination of organophotoredox catalysis and hydrogen atom transfer (HAT) catalysis.

Multi-Ion Bridged Pathway of N-Oxides to 1,3-Dipole Dilithium Oxide Complexes.

Roussi's landmark work on the generation of 1,3-dipoles from tertiary amine N-oxides has not reached its full potential since its underlying mechanism is neither well explored nor understood. Two competing mechanisms were previously proposed to explain the transformation involving either an iminium ion or a diradical intermediate. Our investigation has revealed an alternative mechanistic pathway that explains experimental results and provides significant insights to guide the creation of new N-oxide reagents beyond tertiary alkylamines for direct synthetic transformations. Truhlar's M06-2x functional and Møller-Plesset second-order perturbation theory with Dunning's [jul,aug]-cc-pv[D,T]z basis sets and discrete-continuum solvation models were employed to determine activation enthalpies and structures. During these mechanistic explorations, we discovered a unique multi-ion bridged pathway resulting from the rate-determining step, which was energetically more favorable than other alternate mechanisms. This newly proposed mechanism contains no electrophilic intermediates, strengthening the reaction potential by broadening the reagent scope and limiting the possible side reactions. This thoroughly defined general mechanism supports a more direct route for improving the use of N-oxides in generating azomethine ylide-dilithium oxide complexes with expanded functional group tolerance and breadth of chemistry.

Rhodium catalyzed 2‐alkyl‐benzimidazoles synthesis from benzene‐1,2‐diamines and tertiary alkylamines as alkylating agents

Substituted 2‐alkyl‐benzimidazoles were synthesized from benzene‐1,2‐diamine and tertiary amines as alkylating agent under polystyrene supported rhodium (Rh@PS) nanoparticles (NPs) catalyzed conditions. The heterogeneous rhodium catalyst was applied first time for the synthesis of 2‐alkyl‐benzimidazoles. The reaction followed through oxidation of alkylamines, transamination, and oxidative cyclisation with benzene‐1,2‐diamines for the corresponding products synthesis with good yields. The process is applicable for vast substrate scope, several functional groups are tolerable, and the Rh@PS catalyst is recyclable up to four cycles without significant loss in catalytic activity.

Inhibitory effect of alkyl groups on N-nitrosamine formation from secondary and tertiary alkylamines with monochloramine

N -nitrosamines are contaminants of emerging concern, and controlling these chemicals in potable water and recycled water for potable reuse has become important for protecting public health. This study aimed to evaluate the influence of the alkyl chain lengths of N -nitrosamine precursors (secondary and tertiary amines) on the formation of N -nitrosamines via chloramination. The molar conversion efficiency from dimethylamine, an N -nitrosodimethylamine (NDMA) precursor, to NDMA (0.67%) was greater than that from diethylamine, an N -nitrosodiethylamine (NDEA) precursor, to NDEA (0.38%). Similarly, the molar conversion efficiency from trimethylamine to NDMA (0.92%) was greater than from triethylamine to NDEA (0.33%). Interestingly, a considerable difference in molar conversion efficiencies were observed for tertiary amines with the N , N -dialkyl- α -arylamine structure: the molar conversion efficiencies from N , N -dimethylbenzylamine and N , N -diethylbenzylamine to NDMA and NDEA were 50.2% and 1.7%, respectively. These results indicate that amines with ethyl groups have lower potentials for producing the corresponding N -nitrosamines than those with methyl groups. These differences in yields between amines with methyl and ethyl groups can be explained by the difference in electron density in the nitrogen atom of the amine, which influences the protonation of the amine and stabilization of intermediate species. These findings could be useful for enhancing source control of water and wastewater by regulating runoff or industrial wastewater containing high concentrations of specific N -nitrosamine precursors. • Formation of four N -nitrosamines from the secondary and tertiary amines were tested. • The molar conversion of amines having ethyl group were lower than those of methyl group. • Benzylamines had higher molar conversion values in comparison with simple alkylamines. • Longer alkyl chains in amines suppressed N -nitrosamine formation reactions.

Titanium-Catalyzed Intermolecular Hydroaminoalkylation of Alkenes with Tertiary Amines.

The first cationic titanium catalyst system for the intermolecular hydroaminoalkylation of alkenes with various tertiary alkylamines is presented. Corresponding reactions which involve the addition of the α‐C−H bond of a tertiary amine across the C−C double bond of an alkene take place at temperatures close to room temperature with excellent regioselectivity to deliver the branched products exclusively. Interestingly, for selected amines, α‐C−H bond activation occurs not only at N‐methyl but also at N‐methylene groups.

Titanium‐Catalyzed Intermolecular Hydroaminoalkylation of Alkenes with Tertiary Amines

AbstractThe first cationic titanium catalyst system for the intermolecular hydroaminoalkylation of alkenes with various tertiary alkylamines is presented. Corresponding reactions which involve the addition of the α‐C−H bond of a tertiary amine across the C−C double bond of an alkene take place at temperatures close to room temperature with excellent regioselectivity to deliver the branched products exclusively. Interestingly, for selected amines, α‐C−H bond activation occurs not only at N‐methyl but also at N‐methylene groups.

Debenzylative Sulfonylation of Tertiary Benzylamines Promoted by Visible Light

AbstractAn efficient, general, inexpensive, and environmentally friendly photosynthesis of sulfonamides via visible light promoted debenzylative sulfonylation of tertiary benzylamines is described. Compared to the traditional S−N coupling reactions, which are promoted by oxidative C−N bond cleavage of symmetrical tertiary alkylamines, this strategy provides a selective C−N bond cleavage protocol and avoids the use of transition‐metal, explosive oxidants, and ligands.

Visible-light triggered photochemical reaction for the synthesis of dumbbell-like bis aminomethyl-1, 2 dihydrofullerene dimers via addition of α-amino radicals

Single electron transfer-mediated photochemical reaction of C60 fullerene with simple bis-α-silyl tertiary alkyl/benzyl amines has been developed for the straightforward and valuable construction of dumbbell-like single-bonded bis aminomethyl-1, 2-dihydrofullerenes under milder condition. In these studies of photoinduced SET reactions, α-amino radicals serve as the reactive key intermediate, which was selectively obtained by using the bis-α-silyl tertiary alkyl amines as starting materials. The present strategy was compatible with various 2, 2′-oxybis (ethane-2, 1-diyl) bis (2-(alkyl/benzyl-substituted ((trimethylsilyl) methyl) amino) acetate) for the synthesis of bis aminomethyl-1, 2-dihydrofullerenes under a photocatalyst-free condition.

Chiral Near-Infrared Fluorophores by Self-Promoted Oxidative Coupling of Cationic Helicenes with Amines/Enamines.

In one pot, tertiary alkyl amines are oxidized to enamines by cationic dioxa[6]helicene, which further reacts as electrophile and oxidant to form mono or bis donor-π-acceptor coupling products. This original and convergent synthetic approach provides a strong extension of conjugation yielding chromophores that absorb intensively in far-red or NIR domains (λmax up to 791 nm) and fluoresce in the NIR as well (λmax up to 887 nm). Intense ECD properties around 790 nm with a |Δϵ| value up to 60 M-1 cm-1 are observed.