Reaction Of Secondary Amines Research Articles

A singular chromatographic column breakthrough: Achieving full polarity range separations with the epoxy propanol molecular cage bonded silica stationary phase

The epoxy propanol molecular cage bonded silica stationary phase, RCC3-GLD@silica, synthesized through the ring-opening reaction of secondary amine with epoxy propanol using RCC3-R as the scaffold unit, was successfully prepared as confirmed by infrared spectroscopy, thermogravimetric analysis, and nitrogen adsorption-desorption characterization. This stationary phase demonstrated excellent separation performance in both reversed-phase and hydrophilic chromatography modes, effectively separating a wide variety of compounds including alkylbenzenes, polycyclic aromatic hydrocarbons, phenols, anilines, sulfonamides, nucleosides, amino acids, sugars, and acids. The development of RCC3-GLD@silica benefits from the synergistic effects of its hydrophobic and hydrophilic actions, as evidenced by the U-shaped characteristic of the retention factor for nucleoside compounds with changes in the aqueous content of the mobile phase, further confirming the simultaneous presence of reversed-phase and hydrophilic chromatography mechanisms. Not only did this stationary phase successfully separate 33 compounds in reversed-phase chromatography mode, but it also separated 54 compounds in hydrophilic interaction chromatography mode, showcasing its broad separation capability from weakly polar to strongly polar compounds on a single chromatographic column. This indicates a wide application prospect in the field of chromatographic analysis.

Probing the limits of tetraalkylthiuram disulfide synthesis by direct reaction of secondary amines with CS2: The structures of Cy2NC(S)SSC(S)NCy2 and Cy2NC(S)SSSSC(S)NCy2

Reaction of Cy2NH with CS2 in NaOH/H2O, followed by oxidation with I2, yields a complex mixture that includes the tetracyclohexylthiuram disulfide, Cy2NC(S)SSC(S)NCy2, in mixture with S8 and the tetrasulfide Cy2NC(S)SSSSC(S)NCy2. Direct reaction of 2 eq of Cy2NH with CS2 in EtOH, followed by I2 oxidation, does not yield isolable Cy2NC(S)SSC(S)NCy2, even though other tetraalkylthiuram disulfides are effectively produced by this protocol. Deprotonation of Cy2NH with t BuLi, followed by treatment with CS2 and then oxidative coupling with I2 yields Cy2NC(S)SSC(S)NCy2 in ∼74% yield, suggesting secondary amines that are branched at the α carbon may generally require this lattermost approach to the corresponding tetraalkylthiuram disulfide. Evaporation of an Et2O solution of the crude product mixture obtained from the CS2/NaOH/H2O reaction yielded a triclinic form of Cy2NC(S)SSC(S)NCy2, which contained two independent molecules in its asymmetric unit with opposite C 2 handedness. This same product mixture contained Cy2NC(S)SSSSC(S)NCy2, which was identified crystallographically in monoclinic C2/c and is the first such tetrasulfide to be characterized by X-ray diffraction. A second polymorph of Cy2NC(S)SSC(S)NCy2, obtained by evaporation of an acetone solution, is disordered across a mirror plane in monoclinic P21/m. This monoclinic polymorph of Cy2NC(S)SSC(S)NCy2 is the only tetraalkylthiuram disulfide found to crystallize on a mirror plane.

Role of Carbonyl Compounds for N-Nitrosamine Formation during Nitrosation: Kinetics and Mechanisms.

N-Nitrosamines are potential human carcinogens frequently detected in natural and engineered aquatic systems. This study sheds light on the role of carbonyl compounds in the formation of N-nitrosamines by nitrosation of five secondary amines via different pathways. The results showed that compared to a control system, the presence of formaldehyde enhances the formation of N-nitrosamines by a factor of 5-152 at pH 7, depending on the structure of the secondary amines. Acetaldehyde showed a slight enhancement effect on N-nitrosamine formation, while acetone and benzaldehyde did not promote nitrosation reactions. For neutral and basic conditions, the iminium ion was the dominant intermediate for N-nitrosamine formation, while carbinolamine became the major contributor under acidic conditions. Negative free energy changes (<-19 kcal mol-1) and relatively low activation energies (<18 kcal mol-1) of the reactions of secondary amines with N2O3, iminium ions with nitrite and carbinolamines with N2O3 from quantum chemical computations further support the proposed reaction pathways. This highlights the roles of the iminium ion and carbinolamine in the formation of N-nitrosamines during nitrosation in the presence of carbonyl compounds, especially in the context of industrial wastewater.

N-Heterocyclic carbene: thiazolylidene–Cu(I) complexes: microwave-assisted synthesis and use as catalyst in A3 reaction

A simple method involving microwave-assisted reaction of 3-benzylthiazolium/benzothiazolium bromides with cuprous oxide has been developed for the synthesis of four new N-heterocyclic carbene (NHC): thiazolylidene/benzothiazolylidene–Cu(I) complexes. Structures of the complexes could be established on the basis of the IR, 1H, and 13C NMR studies and elemental analysis. A representative NHC:benzothiazolylidene–Cu(I) complex was used as catalyst for the microwave-assisted A3 reaction of phenylacetylene with a secondary amine and aldehyde to obtain new substituted propargylamines in excellent yields. A theoretical investigation of the model A3 reaction at the DFT level reveals initial coordination of the alkyne with the NHC–Cu(I) complex followed by its attack on the iminium ion generated from the reaction of secondary amine with aldehyde. In the presence of the catalyst, the activation free energy barrier (ΔG#) is lowered by ca. 3 kcal mol−1.

Copper-Catalyzed Multicomponent Reactions of Intramolecular and Intermolecular Thiotrifluoromethylation of Alkenes: Access to CF3-Containing 2-Iminothiazolidines and Isothioureas.

A copper-catalyzed multicomponent reaction of secondary amines bearing allyl substitution, isothiocyanates, and Togni reagent II has been developed under Cs2CO3 in DCE at 75 °C. An intermolecular multicomponent reaction of thioureas, activated and unactivated alkenes, and Togni reagent II has also been developed under DMAP in acetonitrile at room temperature. These two alkene difunctionalization reactions provide CF3-containing 2-iminothiazolindines and isothioureas in moderate to excellent yields with broad substrate scope and good functional group tolerance, respectively.

Photoredox-Catalyzed Carbonyl Alkylative Amination with Diazo Compounds: A Three-Component Reaction for the Construction of γ-Amino Acid Derivatives.

A photoredox-catalyzed reaction of secondary amines, aldehydes, diazo compounds, and Hantzsch ester is reported, affording biologically active γ-amino acid derivatives in high yields. This one-pot process tolerates a broad range of functional groups and various drug molecules and biologically active compounds. Remarkably, a gram-scale reaction and diverse transformations of γ-amino acid derivatives were successfully performed, and the utility of the products is demonstrated in the synthesis of therapeutic agent pregabalin.

Limitations of Simon test in new psychoactive substances analysis

New psychoactive substances (NPS) are nowadays a prevalent group of illicit drugs, one of which are synthetic cathinones. The widespread usage of NPS requires fast, reliable, selective and sensitive analytical methods for their identification as well as differentiation. Colorimetric tests are among the most frequently used methods for screening analysis of NPS in forensic sciences because they are fast, cheap and simple they found application in roadside, borders and airport controls, as well as are used for employees control at workplaces. In this paper we present limitations of colorimetric tests based on the example of one of the Simon test’s variant which was used to analyze synthetic cathinones samples. 163 seized drugs samples were analyzed. Used variant of the Simon test comprises reaction of secondary amines with sodium nitroprusside, sodium carbonate and acetaldehyde resulting in deep blue coloration. Our study indicated that the test gives a very low positive results percentage (3%), as well as many false negative results (88%). No pattern in color changes could be observed regarding samples belonging to one group of compounds in order to identify it even when lacking the expected observation. Another important aspects regarding colorimetric test is the fact that observations are very subjective. although this method is fast and easy to perform, it does not provide unambiguous results and thus, they always should be confirmed with the use of other analytical techniques such as LC-MS/MS or GC-MS/MS.

Development of new graphene/epoxy nanocomposites and study of cure kinetics, thermal and mechanical properties

New graphene/polymer nanocomposites were prepared using graphene nanoplatelets (GNPs) and the epoxy system Epilok 60–566/Curamine 32–494. The GNPs were first dispersed into the curamine hardener using bath ultrasonication, followed by the addition of the epoxy resin. The cure kinetics were studied by DSC under non-isothermal and under isothermal conditions. The kinetic parameters of the curing process were determined using the non-isothermal Kissinger and Ozawa-Flynn-Wall models. The degree of curing increased with the addition of GNPs, while the activation energy decreased by 13.7 % for the primary amine reaction and by 6.6 % for the secondary amine reaction with epoxy groups as obtained from Kissinger. An increase in thermal stability by the addition of GNPs was identified in the range of 360–580 ℃ using TGA. In terms of mechanical properties, addition of an optimum amount of 0.5 %wt of GNPs in the hardener improved the Young’s Modulus by 37 %. Nanoindentation measurements showed 9.4 % improvement in hardness at 0.7 %wt.

The study of the curing mechanism, kinetic and mechanical performance of polyurethane/epoxy composites using aliphatic and aromatic amines as curing agents

The cure kinetics of thermosetting polyurethane/epoxy composites based on oligomeric diglycidyl ether of bisphenol A and branched oligomeric diphenylmetane diisocyanate and polymeric aliphatic amine or mixture of low molecular weight aromatic amines as hardener was studied. It was shown that curing process comprises three stages: at first, a polyurethane network is formed, after that amine hardener react with epoxy oxirane rings with formation linear oligomers, and at the final stage of curing, the network is formed by reaction of secondary amines obtained on the second stage with epoxy oxirane rings. The isoconversional methods of Flynn–Wall–Ozawa and Kissinger-Akahira-Sunose were employed to investigate activation energy as a function of curing degree. The correlation between Ea and α determined by these methods indicated that there were autocatalytic effects in curing systems under study. Interestingly, the mixture of low molecular weight aromatic amines curing compositions exhibited the highest tensile strength and elongation among all materials studied. It means that slow curing with separated stage of composite formation leads to composite with more regular structure which improved their mechanical performance.

Rhodium-catalyzed formation of silylcarbamates from the reaction of secondary amines with CO2 and hydrosilanes

The reaction of (4-methyl-pyridine-2-iloxy)dimethylsilane (NSiMe–H, 1) with [RhCl(coe)2]2 gives the rhodium(III) complex [Rh(Cl)(κ2-NSiMe)2] (2), which reacts with a stoichiometric amount of AgCF3CO2 to afford [Rh(κ2-CF3CO2)(κ2-NSiMe)2] (3). Complexes 2 and 3 have been fully characterized by elemental analysis and NMR spectroscopy. The solid-state structure of 3 has been confirmed by X-ray diffraction analysis. Moreover, the activity of complex 3 as catalyst for the reaction of secondary amines with CO2 (3 bar) and hydrosilanes has been studied. The outcomes of these catalytic studies show that under these conditions complex 3 promotes the selective formation of silylcarbamates.

Convenient fabrication of BiOBr ultrathin nanosheets with rich oxygen vacancies for photocatalytic selective oxidation of secondary amines

Photocatalytic oxidation has been widely employed in organic synthesis, by virtue of the green, mild and simple reaction conditions as well as high selectivity. Introducing oxygen vacancies (OVs) with proper concentrations into the photocatalysts has been proven as an effective strategy to boost the catalytic performances. However, the currently used treatment method under high temperature at reducing atmosphere inevitably introduces a large number of OVs at the interior of the catalyst and serving as the recombination centers of carriers. To address this issue, here we develop a facile solvothermal process to prepare ultrathin BiOBr nanosheets with rich surface OVs. This method effectively decreases the bulk of the material and the ratio of interior OVs, rendering most of the OVs exposed on the surfaces which act as exposed catalytic sites and enhance the separation of carriers, therefore significantly elevates the photocatalytic performances. For the photo-oxidation reaction of secondary amines, under the conditions of visible light, ambient temperature and atmosphere, the BiOBr nanosheets featuring rich surface OVs deliver a doubled conversion compared to those with low OV concentrations, and a high selectivity of 99%, a high stability as the performance shows no reduction after 5 times of circular reaction.

Synthesis, Characterization, and Heterogeneous Catalytic Activity of Sulfamic Acid Functionalized Magnetic IRMOF‐3

In this work, post‐synthesis modification of Fe3O4/IRMOF‐3 nanocomposite with chlorosulfonic acid groups afforded sulfamic acid‐functionalized magnetic metal‐organic frameworks (Fe3O4/IRMOF‐3/SO3H). Functionalization was followed through FT‐IR, XRD, TGA, BET, FESEM/EDS and elemental analysis. The catalytic efficiency of the as‐prepared nanocomposite was evaluated through one‐pot pseudo four‐component reaction of secondary amines, malononitrile, and salicylaldehyde in EtOH under mild conditions. The magnetic tendency of the functionalized IRMOF‐3 enabled simple decantation from the reaction mixture with use of an external magnetic field, with subsequent catalyst reuse for at least five times without significant loss of catalytic efficiency.

Iodine-mediated oxidative N-N coupling of secondary amines to hydrazines.

An I2-mediated N-N coupling reaction has been established for oxidative dimerization of N-aryl aminopyridines to a variety of novel hydrazine derivatives under mild conditions. This synthetic method does not require use of transition metals and can be conveniently carried out on a gram scale. It is also applicable to diphenylamine and N-alkyl aniline substrates.

Copper‐Catalyzed Highly Efficient Acetylene‐Mannich Reaction of Secondary Amines, Paraformaldehyde and Terminal Alkynes

AbstractA Cu(0)‐catalyzed multicomponent reaction of tetrahydroisoquinolines (THIQ), paraformaldehyde and terminal alkynes to form propargylamines is developed. This protocol worked well for other secondary amines too. Acetylene‐Mannich products were obtained in high yields (up to 98% yields). This acetylene‐Mannich reaction is operationally simple, scalable and exhibits high functional‐group tolerance.

DDQ-Mediated Cross-Dehydrogenative-Coupling Reaction of Secondary Amines with Dialkyl Phosphonates

This work reports a DDQ-mediated cross-dehydrogenative-coupling reaction of secondary amines with dialkyl phosphonates under mild conditions. This reaction proceeds efficiently without involving visible light or transition-metal catalysis. This new approach provides efficient access to biologically important α-aminophosphonates.

Differentiation between enamines and tautomerizable imines in the oxidation reaction with TEMPO

Enamine and imine represent two of the most common reaction intermediates in syntheses, and the imine intermediates containing α-hydrogen often exhibit the similar reactivity to enamines due to their rapid tautomerization to enamine tautomers. Herein, we report that the minor structural difference between the enamine and the enamine tautomer derived from imine tautomerization results in the different chemo- and regioselectivity in the reaction of cyclohexanones, amines and TEMPO: the reaction of primary amines furnishes the formal oxygen 1,2-migration product, α-amino-enones, while the reaction of secondary amines under similar conditions generates exclusively arylamines via consecutive dehydrogenation on the cyclohexyl rings. The 18O-labeling experiment for α-amino-enone formation revealed that TEMPO served as oxygen transfer reagent. Experimental and computational studies of reaction mechanisms revealed that the difference in chemo- and regioselectivity could be ascribed to the flexible imine-enamine tautomerization of the imine intermediate containing an α-hydrogen.

Reactions of Secondary Amines with Dichlorocarbene Generated in Aqueous–Alkaline Medium in the Presence of N-Methylmorpholine N-Oxide

Dichlorocarbene generated from chloroform in aqueous–alkaline medium in the presence of N-methylmorpholine N-oxide is converted to phosgene which reacts in situ with secondary amines to afford tetrasubstituted ureas.

Oxidative Rearrangement of Secondary Amines Using Hypervalent Iodine(III) Reagent.

A hypervalent iodine(III) reagent mediated oxidative skeletal rearrangement reaction of secondary amines is reported. The transformation, which uses PhI(OAc)2 in CF3CH2OH, was found to be highly efficient at inducing the direct 1,2-C-to-N migration of secondary amines. This method offers facile and divergent access to polycyclic and macrocyclic indole-fused compounds. The synthetic potential of the method is also demonstrated through its application to several substrates, including secondary as well as primary amines.

Formation and inhibition of N-nitrosodiethanolamine in cosmetics under pH, temperature, and fluorescent, ultraviolet, and visual light

ABSTRACTN-nitrosodiethanolamine (NDELA), a type of nitrosamine, is a possible human carcinogen that may form in cosmetic products. The aim of this study was to examine the formation and inhibition of NDELA through chemical reactions of secondary amines including mono-ethanolamine, di-ethanolamine (DEA), and tri-ethanolamine (TEA), and sodium nitrite (SN) under varying conditions such as pH, temperature, and fluorescent, ultraviolet (UV), and visual light (VIS) using liquid chromatography-mass spectroscopy. In a mixture of TEA and SN under acidic conditions pH 2, residual NDELA concentrations rose significantly under various storage conditions in the following order: 50°C > 40°C > UV (2 W/m2) > VIS (4000 lux) > fluorescent light > 25°C > 10°C. In a mixture of DEA and SN under the same acidic pH 2 conditions, NDELA formation was significantly elevated in the following order: UV (2 W/m2) > VIS (4000 lux) > 50°C > 40°C > fluorescent light > 25°C > 10°C. Inhibition of NDELA formation by d-mannitol, vitamin C (Vit C), or vitamin E (Vit E) was determined under varying conditions of pH, temperature, and fluorescent, UV, and VIS. At high concentrations of 100 or 1000 µg/ml, Vit E significantly decreased residual NDELA compared with control levels under acidic pH 2, but not under basic pH 6. Among various antioxidants, Vit E reacted more effectively with many nitrosating agents such as nitrate and nitrite found in cosmetic products. Therefore, to reduce NDELA, it is recommended that cosmetics be stored under cool/amber conditions and that Vit E or Vit C inhibitors of nitrosation be optimally added to cosmetic formulations at concentrations between 100 and 1000 µg/ml.

Efficient Method for the Synthesis of Propargylamines Using a Biomaterial Containing Copper Nanoparticles as Impressive and Reusable Nanocatalyst

Preparation and catalytic performance of nanosized copper particles supported on expanded corn starch (ECS) was investigated. The catalyst was characterized by inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray powder diffraction (XRD), N2-sorption analysis, thermogravimetric analysis (TGA), energy dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). The copper nanoparticles supported on expanded corn starch (CuNPs@ECS) were found to be a very efficient and durable catalyst for the preparation of propargylamines by three component reaction of secondary amines, aldehydes and alkynes. The catalyst can be successfully recycled and reused without significant loss of efficiency in 4 reaction runs. The procedure described here offers an easy and practical method accompanied by higher yields, and environmentally benign system. Keywords: Aldehyde, amine, copper, expanded-starch, nanosized, propargylamine.