Secondary Aliphatic Amines Research Articles

Base-promoted amide synthesis from aliphatic amines and ynones as acylation agents through C-C bond cleavage.

A new protocol for the synthesis of amides via base-promoted cleavage of the C(sp)-C(CO) bond of ynones with aliphatic primary and secondary amines under transition-metal-, ligand-, and oxidant-free conditions has been developed. This method exhibits a wide substrate scope, high functional group tolerance and exclusive chemoselectivity, as well as mild reaction conditions.

Copper-catalyzed amination of an α-C(sp3)-H bond in inactivated ethers to synthesize α-aminonitriles.

A copper-catalyzed functionalization of inert cyclic ethers was developed to provide α-aminonitriles via a cascade oxidation/amination/ring-opening/cyanation reaction. A series of highly versatile α-aminonitriles were obtained from primary or secondary anilines, and heterocyclic and aliphatic amines with high yields. This process features excellent functional group tolerance, a broad substrate scope, and high activity under ambient conditions.

Formation of N-nitrosamines by micelle-catalysed nitrosation of aliphatic secondary amines.

N-Nitrosamines are an important class of potent human carcinogens and mutagens that can be present in water and wastewater. For instance, N-nitrosamines can be formed by reaction of nitrosating agents such as NO+ or N2O3 formed from nitrite under acidic conditions with secondary amine precursors by an acid-catalysed nitrosation pathway. This study investigates the catalytic effect of cationic and anionic micelles on the nitrosation of secondary aliphatic amines in the presence of nitrite at different pH values. The results of this study demonstrate that the nitrosation of hydrophobic secondary amines (e.g., dipropylamine and dibutylamine) by nitrite was significantly enhanced in the presence of micelles of the cationic surfactant cetyltrimethylammonium chloride whereas anionic micelles formed by sodium dodecylsulfate did not significantly enhance the formation of N-nitrosamines. Rate enhancements of up to 100-fold were observed for the formation of N-nitrosodibutylamine in the presence of cetyltrimethylammonium chloride. The magnitude of the catalytic effect of cationic micelles on the nitrosation reaction depended mainly of the hydrophobicity of the amine precursors (i.e., alkyl chain length), the stability and the charge of the micelles and pH. One important enhancement factor is the lowering of the pKa of the precursor alkylammonium ion due to the electrical potential at the micelle-water interface by up to ∼2.5 pH units. These results suggest that cationic micelle-forming surfactants might play a role in the formation of N-nitrosamines in wastewater, consumer products and in industrial processes using high concentrations of cationic surfactants.

Diastereoselective C-H carbonylative annulation of aliphatic amines: a rapid route to functionalized γ-lactams.

A palladium(ii)-catalysed C(sp3)-H carbonylation of free(NH) secondary aliphatic amines to 2-pyrrolidinones is described. A correlation between the nature of the carboxylate ligand and the diastereoselectivity and yield of the process was observed. As such, under these optimal conditions a range of aliphatic amines were converted to the corresponding trans-4,5-disubstituted 2-pyrrolidines with good d.r. and yield.

Determination of secondary aliphatic amines in surface and tap waters as benzenesulfonamide derivatives using GC-MS

Determination of secondary aliphatic amines in surface and tap waters as benzenesulfonamide derivatives using GC-MS

Formation of α-Monosubstituted Propargylamines from Terminal Alkynes and Secondary Amines Using a (PNO)Rh/Cu Tandem Catalyst System

A novel (PNO)Rh/CuBr (PNO: phosphine-quinolinolate) tandem catalyst system was developed for facile synthesis of α-monosubstituted propargylamines from aliphatic terminal alkynes and secondary amines. Various terminal alkynes and amines were applicable to this reaction and the corresponding propargylamines were obtained in good yields.

Selective Palladium(II)‐Catalyzed Carbonylation of Methylene β‐C−H Bonds in Aliphatic Amines

AbstractPalladium(II)‐catalyzed C−H carbonylation reactions of methylene C−H bonds in secondary aliphatic amines lead to the formation of trans‐disubstituted β‐lactams in excellent yields and selectivities. The generality of the C−H carbonylation process is aided by the action of xantphos‐based ligands and is important in securing good yields for the β‐lactam products.

Selective Palladium(II)-Catalyzed Carbonylation of Methylene β-C-H Bonds in Aliphatic Amines.

Palladium(II)-catalyzed C-H carbonylation reactions of methylene C-H bonds in secondary aliphatic amines lead to the formation of trans-disubstituted β-lactams in excellent yields and selectivities. The generality of the C-H carbonylation process is aided by the action of xantphos-based ligands and is important in securing good yields for the β-lactam products.

Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing.

The reductive aminase from Aspergillus oryzae (AspRedAm) was combined with a single alcohol dehydrogenase (either metagenomic ADH-150, an ADH from Sphingobium yanoikuyae (SyADH), or a variant of the ADH from Thermoanaerobacter ethanolicus (TeSADH W110A)) in a redox-neutral cascade for the biocatalytic alkylation of amines using primary and secondary alcohols. Aliphatic and aromatic secondary amines were obtained in up to 99 % conversion, as well as chiral amines directly from the racemic alcohol precursors in up to >97 % ee, releasing water as the only byproduct.

Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing

AbstractThe reductive aminase from Aspergillus oryzae (AspRedAm) was combined with a single alcohol dehydrogenase (either metagenomic ADH‐150, an ADH from Sphingobium yanoikuyae (SyADH), or a variant of the ADH from Thermoanaerobacter ethanolicus (TeSADH W110A)) in a redox‐neutral cascade for the biocatalytic alkylation of amines using primary and secondary alcohols. Aliphatic and aromatic secondary amines were obtained in up to 99 % conversion, as well as chiral amines directly from the racemic alcohol precursors in up to >97 % ee, releasing water as the only byproduct.

Cavity-containing rhenium metallacycle treated evanescent wave infrared chemical sensors for the selective determination of odorous amines in the atmosphere

An evanescent wave infrared chemical sensor was developed for the selective detection of odorous amino compounds in the atmosphere. To achieve this goal, cavity-containing rhenium metallacycles with multi-recognition sites were prepared and used as host molecules to modify the surface of an evanescent wave infrared (EWIR) sensing element. The unique cavity structure with hydrophobic properties of the Re metallacycle permits the selective trapping of suitably sized compounds with proper functionalities. To explore the scope of the process, two different Re metallacycles were synthesized and used to trap a series of volatile organic compounds (VOCs) with different functionalities. Based on the results, Re metallacycles are selective to detect amino compounds as evidenced by the peak shifts for CO absorption after the amino compounds had been adsorbed. The hydrophobic pocket and hydroxyl groups in the Re metallacycles were also verified to provide extra forces to stabilize the attraction of amino compounds. The efficiency of the Re metallacycles in detecting amino compounds follows the order of amine with phenyl ring > aliphatic primary amine∼cyclo-amine > aliphatic secondary amine > aliphatic tertiary amine. This sensor was applied to detect benzyl amine and a linear range up to 1mg/L could be obtained with a detection limit close to 4μg/L.

Synthesis and acetylcholinesterase inhibitory activity of polymethoxyflavone Mannich base derivatives

A series of novel polymethoxyflavone Mannich base derivatives 1―8 was synthesized by Mannich reaction of 5-hydroxy-3,7,3′,4′-tetramethoxyflavone 9 with various secondary aliphatic amines and formaldehyde. Their acetylcholinesterase(AChE) inhibitory activities were evaluated. The results showed that most of them exhibited AChE inhibitory activity and especially piperidin-1-yl methyl substituent derivative 5(IC50=0.238 μmol/L) demonstrated stronger activity comparable with the positive control, neoeserinemethyl sulfate(IC50=1.39 μmol/L), which is worthy of further development as an agent for Alzheimer’s disease treatment.

Lithium‐Catalyzed anti‐Markovnikov Intermolecular Hydroamination Reactions of Vinylarenes and Simple Secondary Amines

AbstractVarious β‐arylethylamine derivatives were straightforwardly obtained by the lithium‐catalyzed anti‐Markovnikov selective intermolecular hydroamination reaction of secondary aliphatic amines with vinylarenes. The use of only 1.5 mol % LiCH2TMS as a solid base in THF proved to be efficient to deliver the target products at room temperature with up to complete conversions. Both reaction partners were, moreover, used in equivalent amounts; thus, this protocol best respects the concepts of sustainable chemistry for the easy preparation of lead structures for pharmaceutically active compounds.

Nature Inspires an Aerobic Coupling of Phenol and Amine

In this issue of Chem , Lumb and colleagues report on an effective and simple catalytic system of copper and diamine ligands for the bio-inspired and unified synthesis of 1,2-aminophenols through direct aerobic phenol-amine coupling. Using this method, they prepared a structurally diverse family of 1,2-aminophenols and their derived heterocycles, including immunosuppressive benzoxazoles and the indole alkaloid cephalandole A.

Direct access to the optically active VAChT inhibitor vesamicol and its analogues via the asymmetric aminolysis of meso-epoxides with secondary aliphatic amines.

First highly enantioselective synthesis of biologically important vesamicol, benzovesamicol, and their derivatives was achieved via the desymmetrization of meso-epoxides with secondary aliphatic amines (4-phenylpiperidine derivatives) using a chiral [salenCo(iii)-BF4] catalyst at room temperature. All products were obtained in good yield and with excellent optical induction.

Electrosynthesis of Arylsulfonamides from Amines and Sodium Sulfinates Using H2O‐NaI as the Electrolyte Solution at Room Temperature

AbstractWith H2O as the solvent and NaI as the supporting electrolyte, a green and efficient electrochemical route has been developed to synthesize arylsulfonamides via I2 electrogenerated in situ at a graphite anode to promote the reaction of sodium sulfinates with aromatic or aliphatic primary and secondary amines. The target products could be obtained in good to excellent yields at room temperature.

Elegant way to build β-lactams

The strained cyclic amides known as β-lactams have shown up in the skeletons of many medicinally important molecules, including the antibiotic penicillin and the cardiac drug Zetia (ezetimibe). Chemists at the University of Cambridge have developed a new way (shown) to make this structural motif by using a palladium catalyst to join aliphatic secondary amines and carbon monoxide gas in a process that involves C–H activation followed by carbonylation (Science 2016, DOI: 10.1126/science.aaf9621). The reaction tolerates a broad range of functional groups and can be used on a molecule that’s fairly complex, says Matthew J. Gaunt, who led the research effort. “Amines occur in most drugs, so there’s the potential chemists could use this methodology to perform late-stage C–H functionalization on an already complex molecule,” he says. “I think that could be very powerful for drug discovery.” Mechanistic studies suggest that the reaction proceeds by a distinct reaction pathway, wherein

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

AbstractA mild and metal‐free approach to C−N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso‐substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal‐free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal‐free C−N coupling reactions.

Metal-free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution.

A mild and metal-free approach to C-N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal-free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal-free C-N coupling reactions.

Cobalt-Catalyzed Synthesis of Aromatic, Aliphatic, and Cyclic Secondary Amines via a “Hydrogen-Borrowing” Strategy

The replacement of precious metals with inexpensive, less toxic, and earth-abundant elements in typical noble-metal-mediated organic transformations is a major goal in current synthetic chemistry and industries. The metal-catalyzed N-alkylation of amines with other amines through a “hydrogen-borrowing” principle represents a green and atom-economical reaction for the synthesis of secondary amines. However, catalysts developed thus far that are effective for this process remain quite scarce and are only limited to a few ruthenium and iridium complexes. In this work, we present a cobalt-catalyzed selective alkylation of amines with amines to synthesize a large variety of secondary amines. A range of amine substrates have been converted to the corresponding products through hetero- or homocoupling between amines. Cyclic sec-amines are also achieved from diamine precursors as rare examples.