Secondary Aliphatic Amines Research Articles

Synthesis and physical-chemical properties of 8-aminoderivatives of 7-m-bromobenzyl-3-methylxanthine

The current stage of scientific and technological progress in pharmaceutical science is associated with the development of the targeted synthesis of biologically active compounds and the creation of new highly effective and low-toxic drugs on their basis that could compete with expensive imported drugs. A wide range of biological activity of natural xanthines stimulated the search for biologically active compounds among their synthetic analogs, which led to the creation of a row of drugs (Aminophylline, Diprophyllinum, Pentoxiphyllinum, Complamin, etc.) that are used successfully to nowadays. It is known that derivatives of 1- and 7-benzylxanthines exhibit versatile pharmacological effects. It should be noted that 8-bromoxanthines containing benzyl substituents at positions 1 or 7 are convenient synthons for further structural modification of the xanthine molecule. The aim of this work is to study the reaction conditions of 8-bromo-7-m-bromobenzyl-3-methylxanthine with primary and secondary aliphatic amines and to study their physical-chemical properties. Materials and methods . The melting point has been determined with the open capillary method using the PTP-M device. Elemental analysis has been performed with the Elementar Vario L cube, NMR-spectra has been taken on a spectrometer Bruker SF-400 (operating frequency – 400 MHz, solvent – DMSO, internal standard – TMS). Results. The reaction of 7-m-bromobenzyl-8-bromo-3-methylxanthine with amines was carried out in a steel autoclave in methanol at 170 °C. It should be noted that despite the excess of the primary or secondary amine, only the Bromine atom in position 8 of the xanthine molecule was replaced with the formation corresponding 8-amino-7-m-bromobenzyl-3-methylxanthines. The obtained 8-aminoxanthines were white crystalline compounds with high melting points in virtue of their existence in the form of associates due to hydrogen bonds. The structure of the synthesized compounds was unambiguously proved by the method of NMR-spectroscopy. Conclusions. Simply implemented methods for the synthesis of 8-amino-7-m-bromobenzyl-3-methylxanthines were developed. NMR-spectroscopic study of the obtained compounds, which clearly confirms their structure, was conducted. The prospective of the synthesized compounds for subsequent modification of their structure was demonstrated.

Amine-Mediated Bond Cleavage in Oxidized Lignin Models.

Introducing amines/ammonia into lignin cracking will allow novel bond cleavage pathways. Herein, a method of amines/ammonia-mediated bond cleavage in oxidized lignin β-O-4 models was studied using a copper catalyst at room temperature, demonstrating the effect of the amine source on the selectivity of products. For primary and secondary aliphatic amines, lignin ketone models underwent oxidative Cα -Cβ bond cleavage and Cα -N bond formation to generate aromatic amides. For ammonia, the competition between oxygen and ammonia determined the selectivity between Cα -N and Cβ -N bond formation, generating amides and α-keto amides, respectively. For tertiary amines, the lignin models underwent oxidative Cα -Cβ bond cleavage to benzoic acids. Control experiments indicated that amines act as nucleophiles attacking at the Cα or Cβ position of the oxidized β-O-4 linkage to be cleaved. This study represents a novel example that the breakage of oxidized lignin model can be regulated by amines with a copper catalyst.

Organophotoredox-Catalyzed Direct C-H Amination of 2H-Indazoles with Amines.

A general and practical method for the direct C-H amination of 2H-indazoles with a series of amines including aliphatic primary amines, secondary amines, azoles, and sulfoximines via organophotoredox-catalyzed oxidative coupling has been disclosed at room temperature under ambient air conditions. Additionally, this protocol is used for free aminated 2H-indazole synthesis. A mechanistic study revealed that a single electron transfer (SET) pathway might be involved in this reaction.

Osmium-Promoted Transformation of Alkyl Nitriles to Secondary Aliphatic Amines: Scope and Mechanism

The transformation of alkyl nitriles to symmetrical and asymmetrical secondary aliphatic amines promoted by the hexahydride complex OsH6(PiPr3)2 (1) is described, and the mechanisms of the reactions involved are established. Complex 1 catalyzes the aforementioned transformations of aryl-, pyridyl-, and alkoxy-functionalized alkyl nitriles with linear or branched chains. The formation of the secondary amines involves primary imines, primary amines, and secondary imines as organic intermediates. The reactions take place under mild conditions (toluene, 100 °C, and 4 bar of H2). Stoichiometric reactions of 1 with pivalonitrile and 2-methoxyacetonitrile have allowed us to isolate the trihydride azavinylidene derivatives OsH3{═N═CHR}(PiPr3)2 (R = tBu (3), CH2OMe (4)). Their formation involves the insertion of the N–C triple bond of the substrates into an Os–H bond of the unsaturated tetrahydride OsH4(PiPr3)2 (A), which is generated by reductive elimination of H2 from the hexahydride precursor. The reaction of these trihydride azavinylidene species with H2 is the key step for the reduction of the N–C triple bond of the nitriles. In the absence of H2, the attack of A to the azavinylidene ligand produces the rupture of its C(sp2)–C(sp3) bond. As a consequence of this attack and the presence of primary imines and amines in the reaction media, the binuclear complexes (PiPr3)2H4Os(μ-CN)OsH3{κ1-N-(NH═CHCH2OMe)}(PiPr3)2 (5) and (PiPr3)2H4Os(μ-CN)OsH3{κ1-N-(NH2CH2CH2OMe)}(PiPr3)2 (6) have been isolated and characterized by X-ray diffraction analysis, for 2-methoxyacetonitrile. DFT calculations reveal noticeable similarities between the hydrogenations of nitriles to primary imines and those of primary imines to primary amines.

Atomic Pt-Catalyzed Heterogeneous Anti-Markovnikov C-N Formation: Pt10 Activating N-H for Pt1δ+-Activated C═C Attack.

C-N formation is of great significance to synthetic chemistry, as N-containing products are widely used in chemistry, medicine, and biology. Addition of an amine to an unsaturated carbon-carbon bond is a simple yet effective route to produce new C-N bonds. But how to effectively conduct an anti-Markovnikov addition with high selectivity has been a great challenge. Here, we proposed a strategy for highly regioselective C-N addition via hydroamination by using supported Pt. It has been identified that atomic-scale Pt is the active site for C-N addition with Pt12+ for Markovnikov C-N formation and atomic Pt (Pt1δ+ and Pt10) contributing to anti-Markovnikov C-N formation. A selectivity of up to 92% to the anti-Markovnikov product has been achieved with atomic Pt in the addition of styrene and pyrrolidine. A cooperating catalysis for the anti-Markovnikov C-N formation between Pt1δ+ and Pt10 has been revealed. The reaction mechanism has been studied by EPR spectra and in situ FT-IR spectra of adsorption/desorption of styrene and/or pyrrolidine. It has been demonstrated that Pt10 activates amine to be electrophilic, while Pt1δ+ activates C═C by π-bonding to make β-C nucleophilic. The attack of nucleophilic β-C to electrophilic amine affords the anti-Markovnikov addition. This strategy proves highly effective to a variety of substrates in anti-Markovnikov C-N formation, including aromatic/aliphatic amines reacting with aromatic olefins, aromatic/aliphatic olefins with aromatic amines, and linear aliphatic olefins with secondary aliphatic amines. It is believed that the results provide evidence for the function of varied chemical states in monatomic catalysis.

Synthesis of a new class of corrosion inhibitors derived from natural fatty acid: 13‐Docosenoic acid amide derivatives for oil and gas industry

As corrosion inhibitors, a series of new amide derivatives of 13‐docosenoic acid was synthesized in yields of above 90% by reacting 13-docosenoic acid with primary and secondary aliphatic and aromatic amines. The inhibition efficiencies (%IEs) of these compounds at various concentrations for the suppression of corrosion of mild steel in 1.00 M HCl exposed for 96 h (4 days) at temperatures in the range 298–333 K were measured via gravimetric corrosion measurements. At 100 ppm, all compounds yielded satisfactory corrosion %IE in 1.00 M HCl; compounds 2 and 7 exhibited remarkable %IE of 70.0 and 74.7%, respectively. The results of gravimetric measurements further revealed that compound 7 performed excellently at 60 °C, with %IE = 96.8 at 500 ppm. Quantum chemical density functional theory (DFT) calculations helped predict that compound 7 should have more aromatic character, enabling it to serve as a donor-center for the empty d-orbital of the metal atoms, leading to higher corrosion IE. The adsorption of the inhibitor molecules on the surface of mild steel followed the Langmuir adsorption model, and the free energy of adsorption (ΔGads) value indicated that the inhibitors are adsorbed through a combined physisorption and chemisorption mechanism to provide effective surface coverage.

Aminomethoxy derivatives of norbornenylmethanol as biocorrosion inhibitors

Norbornenylmethanol was synthesized by the reaction of cyclopentadiene and allyl alcohol, on the basis of which aminomethoxy derivatives of norbornenylmethanol were synthesized in the presence of formaldehyde and secondary amines by Mannich condensation. The yield of the target products was 43-71%. On the basis of 5-morpholinomethoxymethylbicyclo[2.2.1]-hept-2-ene and hexylbromide (1:1) in the presence of isopropyl alcohol, its complex was obtained. The physic-chemical properties of the synthesized compounds and the resulting complex were determined, their 1% solutions in isopropyl alcohol and 5% solution of 5-morpholinomethoxymethylbicyclo[2.2.1]-hept-2-ene were prepared. Their influence on the vital activity of sulfate-reducing bacteria of the type «Desulfovibrio desulfuricans» in three concentrations (5; 50; 100 mg/L) was studied. Bactericide inhibitors used in industry – AMDOR IK-7 and AMDOR IК-10 were taken as standards. It was determined that all the synthesized compounds and the resulting complex showed high bactericidal properties, moreover, compounds obtained on the basis of cyclic secondary amines showed a higher bactericidal effect against sulfate-reducing bacteria, unlike compounds obtained on the basis of aliphatic secondary amines. Considering that these aminomethoxy derivatives of norbornenylmethanol affect bacteria at very low concentrations, they can be proposed as effective inhibitors against sulfate-reducing bacteria.

Preventing Pd–NHC bond cleavage and switching from nano-scale to molecular catalytic systems: amines and temperature as catalyst activators

Heating Pd/NHC complexes with aliphatic amines induces Pd–NHC bond cleavage, while treating the complexes with primary or secondary aliphatic amines in the presence of strong bases promotes the activation of molecular Pd/NHC catalysis.

CHARACTERISTIC OF COMPLEX COMPOUNDS OF CUPRUM (II) NITRATE WITH ALIPHATIC AMINES PYRIDINE AND ITS DERIVATIVES IN CRYSTAL STATE

Complex compounds of CuCl 2 і Cu(NO 3 ) 2 with aliphatic amines in a crystalline state from alcohol solutions were obtained. The composition of the obtained compounds was determined by the method of equilibrium shift, molar ratios and intersection of the curves. Their electronic and IR spectra were studied, and a wide asymmetric absorption band was detected in the near region with a maximum of 870 - 900 nm. This band is characteristic of compounds of a tetrigonally curved octahedral configuration. The formation of complex compounds Cuprum (II) with amines of 1:1, 1:2 composition was established. Measured vibrational spectra in the region of 500 to 200 см -1 . IR-spectra of samples of complex compounds Cuprum (II) with the aliphatic amines, pyridine and its derivatives was measured as a suspension in vaseline oil. The measurements were carried out on an IKS-228 spectrophotometer. The frequency of stretching vibrations Me-N characterizes the coordination bond. The stretching vibrations of Me-N should manifest themselves in the low-frequency region as a result of a significant mass of the metal atom and the relatively low strength of the coordination bond. The IR spectra indicate Me-N stretching vibrations, which characterize the coordination bond. For aliphatic amines, absorption bands were identified in the region of 440–420 см -1 , which are assigned to V(Cu–N) vibrations. The bands in this region indicate coordination through the base nitrogen atom. The absorption bands of the ligands in the region of 210-220 см -1 disappear in the complex compounds. Most of the frequencies in complex compounds are explained by the dual nature of the σ- and π- dative interactions. In coordination compounds of Cu(NO 3 ) 2 with pyridine and its derivatives, an increase in vibration frequencies is observed with an increase in the stability of complex compounds, which is explained by the double nature of the bond (σ,-and π-dative interaction). Complex compounds were studied by differential thermal analysis. As a result, it was concluded that the nature of the decay of the complexes is affected by the nature of the ligand, complexing agent, electronegativity and polarizing properties of the ligand, steric effects and the nature of cations. The process of breaking the coordination bond for primary and secondary aliphatic amines occurs stepwise, and for tertiary amines in one step. At the first stage, one ligand molecule is cleaved, and at the second, the second molecule. Secondary amines have small cleavage. With an increase in the spatial factors of amines, the thermal stability of the complexes decreases.

Direct Use of Unprotected Aliphatic Amines to Generate N-Heterocycles via β-C-H Malonylation with Iodonium Ylide.

An unprecedented method that enables the direct transformation of unprotected secondary aliphatic amines into functionalized N-heterocycles in the absence of transition metals was developed. The activation of these NH-free amines by the iodonium ylide induces a site-selective β-C-H malonylation process, allowing the construction of three σ-bonds and one π-bond in a simple operation.

N‐Arylation of Nitrogen‐Containing Heterocycles with Cu(II) Complex of 4‐(2,2′:6′,2“‐Terpyridin‐4′‐yl)toluene as a Versatile and Efficient Catalyst

AbstractCopper(II) complex of 4‐(2,2′:6′,2“‐terpyridin‐4′‐yl)toluene(ttpy) was found to be a profitable catalyst for the N‐arylation of a variety of nitrogen‐containing heterocycles, such as some kinds of azoles and a secondary aliphatic amine, with aryl halides (iodides, bromides, and chlorides) under moderate conditions. A variety of functionalized aryl halides were tolerated in good to excellent yields by this air stable and low cost Cu(II)‐based catalytic system. Phenyl boronic acid was also used as an alternative to aryl halides to supply aryl moiety.

Reshaping Ullmann Amine Synthesis in Deep Eutectic Solvents: A Mild Approach for Cu-Catalyzed C-N Coupling Reactions With No Additional Ligands.

The CuI-catalyzed Ullmann amine cross-coupling between (hetero)aryl halides (Br, I) and aromatic and aliphatic amines has been accomplished in deep eutectic solvents as environmentally benign and recycling reaction media. Under optimized conditions, the reaction proceeds smoothly under mild conditions (60–100°C) in air, in the absence of ligands, with a catalyst (CuI) loading of 10 mol% and K2CO3 (aliphatic primary and secondary amines) or t-BuOK (aromatic amines) as the base. A variety of amines have been synthesized in yields up to 98% with a broad substrate scope.

Hydrogen-Bond-Promoted Metal-Free Hydroamination of Alkynes

An original metal-free regio- and stereoselective intermolecular hydroamination of alkynes is described. Various (E)-enamines were obtained from arylacetylenes and aliphatic secondary amines in the presence of ethylene glycol as a solvent. The latter is assumed to play a major role in the mechanism through hydrogen bonding and proton exchange.

Synthesis and Properties of Aminomethoxy Derivatives of 1-Phenoxy-3-(propylsulfanyl)propane

The condensation of 1-phenoxy-3-(propylsulfanyl)propan-2-ol with formaldehyde and secondary aliphatic and heterocyclic amines afforded new aminomethoxy derivatives of 1-phenoxy-3-(propylsulfanyl)- propane in 69–77% yields. The product structure was confirmed by elemental analyses and IR and 1H and 13C NMR spectra. The synthesized compounds were assayed as antiseptics against bacteria and fungi and were shown to be more efficient antimicrobial agents than those currently used in medicine.

Ni-Catalyzed Enantioselective Intermolecular Hydroamination of Branched 1,3-Dienes Using Primary Aliphatic Amines.

A Ni-catalyzed intermolecular enantioselective hydroamination of branched 1,3-dienes is reported. The method is broadly applicable, highly regio-, chemo-, and enantioselective, and provides direct access to valuable chiral allylic amines starting from linear or α-branched aliphatic primary amines or secondary amines. Mechanistic studies have been conducted using 31P NMR spectroscopy for reaction progress monitoring, isotopic labeling experiments (2H), and kinetic analysis. The resting state of the catalyst is a Ni-π-allyl complex, and the outer-sphere nucleophilic attack of H-bonded amine aggregates is proposed to be the rate-determining step. This hypothesis guided the identification of an improved set of reaction conditions for the enantioselective hydroamination of branched 1,3-dienes.

Indolylglycines Backbones in the Synthesis of Enantiopure 3,3‐Spiroindolenines, Indolyl Tetracyclic Hemiaminals, and 3‐Indolyl‐maleimides Frameworks

This paper describes the synthesis of novel N‐substituted 3‐indolylglycines (3IGs), in high yields and optical purity via three‐component Mannich reaction (3CR) of indole and free glyoxylic acid in the presence of primary and secondary aliphatic amines. By using this efficient approach, a series of racemic 3‐indolylglycines (3IGs) as well as the optically pure (S)‐3‐indolylglycine ((S)‐3IG) in multigram synthesis using (R‐1‐phenylethylamine ((R)‐α‐PEA) as chiral pool were synthetized. In parallel investigations, 3IGs were used as the starting material for the highly stereoselective synthesis of spiroindolenines bearing three controlled contiguous stereogenic centers. Despite our expectations, the N‐chloroacetyl esters of 3IGs did not provide the expected spiroindolenine derivatives but led us to the discovery of a new methodology for the preparation of 3‐indolylmaleimides (3IMs); compounds known for their broad range of important biological and fluorescence activities.

Preparation of Ag2S Nanoparticles and using as Catalyst for the A3-coupling (Aldehyde-Amine-Alkyne) Reaction

Microwave assisted facile one-step approach was adopted to prepare mono-dispersed silver sulfide nanoparticles. The structures of the synthesized Ag2S nanoparticles were confirmed by Fourier-transform infrared spectroscopy (FT-IR), diffuse reflectance UV-vis spectroscopy (DRS), X-ray diffractometer (XRD), energy dispersive X-ray analysis (EDX) and transmission electron microscope (TEM). The prepared Ag2S nanoparticles (NPs) were successfully used as a heterogeneous catalyst in the one-pot three-component coupling reaction of aldehydes, amines and alkynes (A3-coupling) toward propargylamines. In this protocol, both aromatic and aliphatic aldehydes and secondary amines were reacted with terminal alkynes in the presence of Ag2S NPs at low catalytic loading (0.5 mol %) that led to the rapid and efficient formation of propargylamines with good to excellent yields. The A3-coupling reaction occurred effectively at 80 oC under solvent-free conditions. The catalyst is easy to prepare and is perfectly stable under the reaction conditions. Also, the Ag2S NPs catalyst can be easily recovered and reused several times and exhibited higher catalytic activity than other some commercially catalysts.

Oxone-sodium nitrite mediated N-nitrosamines formation under mild conditions from secondary amines

Herein, we report an efficient synthesis of N-nitrosamines from cyclic, aliphatic, benzylic, and aromatic secondary amines via a novel straightforward, efficient, and mild chemical process using sodium nitrite and Oxone in methanol as a solvent at 0–5 °C. The demonstrated methodology accounts well for the parameters like cost-effective, short reaction time, clean and safe handling along with good to excellent yields.

New 1,2-dithioether based 2D copper(I) coordination polymer: from synthesis to catalytic application in A3-coupling reaction

A new 2D copper(I) coordination polymeric complex has been synthesized from CuI and 1-(1-{4-chlorophenylthio}propan-2-ylthio)-4-chlorobenzene ([(CuI)2{ArSCH2CH(CH3)SAr}2]n, Ar = 4-ClC6H4) and characterized by high resolution mass spectrometry (HRMS) and single crystal X-ray diffraction techniques. The complex has been employed as a suitable catalyst for a solvent-free, one-pot, three-component A3-coupling reaction. A variety of aromatic and aliphatic aldehydes, terminal alkynes and aliphatic cyclic secondary amines have been used to prepare a library of propargylamines using the 2D-Cu complex at significantly low concentration (0.2 mol%).

Electrochemical synthesis and amidation of benzoin: benzamides from benzaldehydes

Abstract The benzoin condensation starting from benzaldehyde and the subsequent benzoin amidation to benzamide can be efficiently carried out under very mild conditions in an electrolysis cell. Among the advantages of using electrochemistry to generate our active reagents, the use of the easily dosed and non pollutant electron, instead of stoichiometric amounts of redox reagents or bases, usually renders the electrochemical methodology “greener” than classical organic reactions. Benzoin is obtained in good yield (85 %) carrying out the reaction in the room temperature ionic liquid BMIm-BF4. In this electrochemical reaction this liquid salt assumes the double role of solvent-supporting electrolyte system and precatalyst, yielding the corresponding N-heterocyclic carbene. The subsequent benzoin amidation is carried out by electrochemically generated superoxide anion, in the presence of an aliphatic primary or secondary amine. In this case the system superoxide/molecular oxygen acts as base and oxidant, yielding very good yields of benzamides (up to 89 %).