Addition Of Amines Research Articles

Development and validation of LC-QTOF-MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine in ticagrelor API.

The foremost objective of the present study was to develop and validate a new LC-QTOF-MS/MS method for the identification and quantitative determination of 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (DPP) genotoxic impurity through the derivatization process in ticagrelor active pharmaceutical ingredient (API). Owing to the low response of DPP at the specification level, DPP was converted to 4,6-dibenzylamino-5-nitro-2-(propylthio)pyrimidine (DPP derivative) by addition of benzyl amine, then analyzed using mass spectrometry with a time-of-flight analyzer, and good separation was accomplished under the experimental conditions described. The effective separation of DPP derivative was achieved using an Acquity UPLC BEH C18 reverse-phase column (100 × 4.6mm × 1.7μm) with an isocratic program with mobile phase A as 0.1% formic acid in milli Q water and mobile phase B as acetonitrile in the ratio of 20:80 v/v. The flow rate was maintained as 0.4ml/min, the injection volume was 2μl, the autosampler temperature was 5°C, the column oven temperature was ambient and the run time was 6.0min. The diluent used was 0.2% benzyl amine in water and acetonitrile in the ratio of 30:70 v/v. The retention time of the DPP derivative was 2.87 min. The limit of detection and limit of quantification were 0.03 and 0.08 ppm, respectively. The DPP derivative was linear from 1.68 to 12.78 ppm with R2 of 0.9958. Thus, the developed method is valid for the identification and quantitative determination of DPP derivative in ticagrelor API.

Dioxygen-promoted cobalt-catalyzed oxidative hydroamination using unactivated alkenes and free amines

Catalytic Markovnikov-selective hydroamination of unactivated alkenes, in particular by using secondary amines as nucleophiles and/or in an intermolecular setting, remains a challenge. Here we address this problem by developing a cobalt-hydride-catalyzed hydroamination reaction based on a bimetallic redox-triggered oxidative amination pathway. This system enables the use of dioxygen as a sustainable oxidant that is compatible with free amines, while suppressing the facile radical oxygenation that leads to classical Drago-Mukaiyama oxidation. We demonstrate intra- and intermolecular formal addition of secondary amines across unactivated alkenes as well as vinylarenes at ambient temperature. The scope of this method also encompasses alternative nitrogen nucleophiles, such as sulfonamides, amides, and carbamates. Stoichiometric reactions of well-defined organocobalt complexes provide direct evidence for the proposed key amination process.

Ethylamine Iodide Additive Enables Solid-to-Solid Transformed Highly Oriented Perovskite for Excellent Photodetectors.

Perovskite has been widely applied in the optoelectronic field due to its strong light absorption and high carrier mobility. Maintaining high crystallization is critical to fabricate high-performance perovskite devices, where many methods have been reported, such as the use of additives in precursor solutions. However, there are few reports for the working mechanism of these additives. Herein, a new method to obtain highly crystalline formamidinium-lead triiodide (FAPbI3 ) perovskite films by introducing ethylamine iodide (EAI) into perovskite precursors is reported and a novel working mechanism for such alkyl amine additives in the crystallization process of perovskites is proposed. Unlike traditional liquid-to-solid (L-S) crystallization theory, the research results indicate that EAI affects the solid-to-solid (S-S) transition process from the intermediate yellow phase to the final black phase, and this mechanism is further verified to be universal using other common alkyl amines. A self-powered photodetector based on an as-fabricated FAPbI3 film is fabricated with an external quantum efficiency of over 90%. This work provides a deeper understanding of the perovskite crystallization process.

Effect of temperature and chain length of added primary amines on the sphere to rod transition of aqueous ionic micelles

The importance of micelles as templates for nanomaterials is growing day by day. This resulted in an increasing interest for micelles in different sizes and shapes. Addition of n-amines to micellar solutions was found to bring change in the shape of the micelles from sphere to rod in aqueous ionic micellar solutions. The change in shape is qualitatively obtained from sudden change in the slope of pH versus amine concentration plots because the degree or protonation of n-alkylamines depends on the shape of micelles. In the present investigation, pH is measured at different temperatures to elucidate the influence of addition of n-amines on sphere-to-rod transition in aqueous micellar solutions. The surfactants employed in the present investigation are cetyltrimethyl ammonium bromide (CTAB), cetylpyridinium chloride (CPC), and sodium dodecyl sulphate (SDS).As the amine concentration is increased, the pH increases linearly at certain amine concentration and the slope of the resulting straight line changes on further addition of amine. It is noticed that increasing temperature requires more amine for structural transition of aqueous ionic micelles. It is also observed that the effectiveness of added amines leading to shape transition from sphere to rod is in the order of C8NH2>C7NH2> C6NH2.

Amine additives for improved in-ESI H/D exchange.

In-ESI H/D exchange is a convenient technique for analyzing small-molecular complex mixtures. However, such experiments do not yield sufficient levels of exchange or require an elevated temperature of the ion transfer capillary. Increased temperature may result in unexpected additional exchanges of -CH groups that may complicate the interpretation of the H/D exchange data used for identification. Gas-phase H/D exchange depends on the gas-phase basicity of the deuterating agent. In-ESI exchange involves both droplet-phase and gas-phase mechanisms, depending on a particular ion source setup and the deuterating agent used. Therefore, the addition of strong bases to the reaction mixture should facilitate in-ESI exchange. This work aimed to investigate the capabilities of different amines to improve in-ESI H/D exchange compared with pure D2O and to choose an amine modifier to increase the extent of H/D exchange. It was shown that such additives substantially enhanced the extent of H/D exchange in small molecules, peptides, and proteins even without heating the capillary. It was found that the extent of exchange increases in the following order: tertiary amines < secondary amines < primary amines. Therefore, we suggest that amines act as deuterating agents after being exchanged with D2O. These findings may improve H/D exchange applications, especially in small molecule analysis. The observation of improved H/D exchange with amine additives in peptides and proteins may become a subject of future research.

Reaction of Tandem Addition of Aliphatic Amines to Alkenylnitriles Catalyzed by Tris(o-dimethylaminobenzyl)yttrium

Reaction of Tandem Addition of Aliphatic Amines to Alkenylnitriles Catalyzed by Tris(<i>o</i>-dimethylaminobenzyl)yttrium

Synthesis and Characterization of Bis(Β-Diketiminato) Rare-Earth Amido Complexes, Their Activity for Catalytic Addition of Amines to Carbodiimides and Mechanism Study

Synthesis and Characterization of Bis(Β-Diketiminato) Rare-Earth Amido Complexes, Their Activity for Catalytic Addition of Amines to Carbodiimides and Mechanism Study

Sapindus mukorossi seed shell extract mediated green synthesis of CuO nanostructures: an efficient catalyst for C–N bond-forming reactions

An effective biogenic approach is proposed to synthesize size-tunable CuO nanostructures using seed shell extract of Sapindus mukorossi plant to use as efficient catalysts for conjugate addition of amines to acrylonitrile under ambient conditions.

A Mechanistic Study for Aziridination of Nitroalkenes Mediated by N-Chlorosuccinimide.

Direct aziridination of a nitrostyrene is achieved upon treatment with an alkylamine and N-chlorosuccinimide. The reaction is initiated by the Michael addition of amine to nitroalkene. Subsequent N-chlorination and nucleophilic substitution at the nitrogen atom afford 1-alkyl-2-nitroaziridine diastereoselectively. This reaction mechanism was clarified by NMR studies.

Lanthanide-Catalyzed Tandem Addition of Amines to Cyanoalkenes: Synthesis of Cyclic Amidines.

A tandem insertion of aliphatic nitriles and unactivated alkenes to the N-H bond of secondary aliphatic amines catalyzed by simple trialkyl rare-earth metal complexes was disclosed. This reaction provides a highly atom-economic and stereoselective way to a range of cyclic amidines under mild reaction conditions.

Effect of amine and glycol-based grinding aids utilization rate on grinding efficiency and rheological properties of cementitious systems

In this study, it is aimed to give a new viewpoint of choosing utilization rates and type of grinding aids (GA), taking into account cement-polycathoxylate ether-based water-reducing admixture (PCE) compatibility. For this purpose, the effects of amine and glycol-based GA utilization rate on clinker grinding efficiency and the physical properties of cement were investigated. The setting time, fresh state, rheological properties, and compressive strength of the mixtures prepared with the produced cements were examined. In addition to the control cement containing no GA, two series of cement were produced by the addition of amine- and glycol-based GA to the clinker in four different contents. GA were added to the clinker at the rate of 0.025-0.050-0.075–0.1% of the total clinker and gypsum weight. Triisopropanolamine (TIPA) and Diethanol Isopropanolamine (DEIPA) were used as amine-based and Diethylene Glycol (DEG) and Ethylene Glycol (EG) as glycol-based. Thus, a total of 17 different types of cement having similar Blaine fineness were produced. According to the results, the GA utilization caused the production of cement with narrower particle size distribution. Besides, the GA utilization contributed significantly in terms of grinding efficiency and 28-day strength, and this positive effect increased gradually until a certain GA dosage. It was remarked that the TIPA showed high performance in terms of grinding efficiency and compressive strength, however, the reverse of this behavior was observed in the fresh state rheological properties. In terms of rheological properties, glycol-based GA performed better than amine-based. Irrespective of the GA type, 0.025% and 0.05% were obtained the optimum GA utilization rate in terms of cement-PCE compatibility and compressive strength, respectively.

Primary Amine Nucleophilic Addition to Nitrilium Closo-Dodecaborate [B12H11NCCH3]-: A Simple and Effective Route to the New BNCT Drug Design.

In the present work, a convenient and straightforward approach to the preparation of borylated amidines based on the closo-dodecaborate anion [B12H11NCCH3NHR]−, R=H, Alk, Ar was developed. This method has two stages. A nitrile derivative of the general form [B12H11NCCH3]− was obtained, using a modified technique, in the first stage. On the second stage the resulting molecular system interacted with primary amines to form the target amidine products. This approach is characterised by a simple chemical apparatus, mild conditions and high yields of the final products. The mechanism of the addition of amine to the nitrile derivative of the closo-dodecaborate anion was studied, using quantum-chemical methods. The interaction between NH3 and [B12H11NCCH3]− ammonia was chosen as an example. It was found that the structure of the transition state determines the stereo-selectivity of the process. A study of the biological properties of borylated amidine sodium salts indicated that the substances had low toxicity and could accumulate in cancer cells in significant amounts.

PH-Dependent Selective Colorimetric Detection of Proline and Hydroxyproline with Meldrum’s Acid-Furfural Conjugate

Activated 2-furfural gives intense color formation when reacted with amines, due to a ring opening reaction cascade that furnishes a conjugated molecular system. Unique colorimetric characteristic of this reaction makes it an interesting candidate for developing chemosensors operating in visible range. Among many activated 2-furfural derivatives, Meldrum’s acid furfural conjugate (MAFC) recently gained significant interest as colorimetric chemosensor. MAFC has been explored as selective chemosensor for detecting amines in solution, secondary amines on polymer surfaces and even nitrogen rich amino acids (AA) in aqueous solution. In this work, the pH dependency of MAFC-AA reaction is explored. It was found that proline gives an exceptionally fast colored reaction at pH 11, whereas at other pHs, no naked eye color product formation was observed. The reaction sequence including ring opening reaction upon nucleophilic addition of cyclic amine of proline resulting in a conjugated triene was confirmed by NMR titrations. The highly pH dependent reaction can e.g., potentially be used to detect proline presence in biological samples. An even more intense color formation takes place in the reaction of natural proline derivative 4-hydroxyproline. The detection limit of proline and 4-hydroxyproline with MAFC solution was found to be 11 µM and 6 µM respectively.

Aromatic tetra-glycidyl ether versus tetra-glycidyl amine epoxy networks: Influence of monomer structure and epoxide conversion

In this work, two epoxy resins, bis(2,7 glycidyl ether naphthalenediol) methane (NNE), tetraglycidyl diaminodiphenylmethane (TGDDM) and a miscible blend of the two are cured with 4,4′-diaminodiphenylsulfone (DDS) to investigate the differences between glycidyl ether and glycidyl amine crosslinked networks. This work explores in depth, and directly compares for the first time, the structure/property relationships of a highly aromatic and thermally stable glycidyl ether epoxy network with a well-known highly aromatic and thermally stable glycidyl amine epoxy network. The highly aromatic naphthalene motif of NNE imparts improved thermal stability and a significantly higher glass transition temperature, above 340 °C depending on the measurement technique. However, it also produces comparatively lower epoxide conversion, higher moisture ingress and lower flexural properties. These properties are attributed to the NNE having higher free volume and glassy state mobility as suggested by the sub-ambient β relaxations. The glycidyl ether groups react primarily via epoxide amino addition displaying only very minor evidence of homopolymerisation or other side reactions even at 240 °C. This contrasts with the glycidyl amine groups of TGDDM which exhibit a much higher degree of non-epoxy amine addition. Increasing cure conversion also increases the glass transition temperature, fracture toughness and reduced coefficient of thermal expansion. Overall, the results show that despite some reduced mechanical and thermal properties the NNE epoxy resin system is a very thermally stable high temperature epoxy resin based upon glycidyl ether functional groups suitable for a wide range of new applications.

Size and Quality Enhancement of 2D Semiconducting Metal-Organic Chalcogenolates by Amine Addition.

The use of two-dimensional (2D) materials in next-generation technologies is often limited by small lateral size and/or crystal defects. Here, we introduce a simple chemical strategy to improve the size and overall quality of 2D metal-organic chalcogenolates (MOCs), a new class of hybrid organic-inorganic 2D semiconductors that can exhibit in-plane anisotropy and blue luminescence. By inducing the formation of silver-amine complexes during a solution growth method, we increase the average size of silver phenylselenolate (AgSePh) microcrystals from <5 μm to >1 mm, while simultaneously extending the photoluminescence lifetime and suppressing mid-gap emission. Mechanistic studies using 77Se NMR suggest dual roles for the amine in promoting the formation of a key reactive intermediate and slowing down the final conversion to AgSePh. Finally, we show that amine addition is generalizable to the synthesis of other 2D MOCs, as demonstrated by the growth of single crystals of silver 4-methylphenylselenolate (AgSePhMe), a novel member of the 2D MOC family.

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide).

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N+≡C–R triple bond of the propionitrilium derivative [8-EtC≡N-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]. The reactions with primary amines result in the formation of mixtures of E and Z isomers of amidines, whereas the reactions with secondary amines lead selectively to the E-isomers. The crystal molecular structures of E-[8-EtC(NMe2)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)], E-[8-EtC(NEt2)=HN-3,3′-Co(1,2- C2B9H10)(1′,2′-C2B9H11)] and E-[8-EtC(NC5H10)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] were determined by single crystal X-ray diffraction.

Aqueous Solutions of Peptides and Trialkylamines Lead to Unexpected Peptide Modification.

When trialkylamines are added to buffered solutions of peptides, unexpected adducts can be formed. These adducts correspond to Schiff base products. The source of the reaction is the unexpected presence of aldehydes in amines. The aldehydes can be detected in a few ways. Most importantly, they can lead to unanticipated results in proteomics experiments. Their undesirable effects can be minimized through the addition of other amines.

A review of the syntheses of (thio)flavones, 4‐quinolones, (thio)aurones, and azaaurones from 2′‐substituted alkynones

AbstractFlavones have been prepared by the 6‐endo cyclization of o‐alkynoylphenols, cyclization/deprotection of 2′‐protected alkynones, or carbonylative coupling of 2‐halophenols with arylacetylenes and subsequent cyclization. (Z)‐Aurones have been prepared by the 5‐exo cyclization of o‐alkynoylphenols or oxidation of (Z)‐benzylidenebenzofuran‐3‐ols with MnO2. Thioflavones have been prepared by deprotection/6‐endo cyclization of S‐protected alkynones or by the addition of sulfur to 2′‐halo(methoxy)alkynones and subsequent cyclization. Deprotection and 5‐exo cyclization of S‐benzylated alkynones using HCOOH afforded (Z)‐thioaurones. 2‐Phenyl‐4‐quinolones have been prepared by the 6‐endo cyclization of 2′‐aminoalkynones or by the addition of amines to 2′‐haloalkynones and subsequent cyclization. Furthermore, the treatment of 2′‐aminoalkynones with triphenylphosphine afforded (Z)‐azaaurones by 5‐exo cyclization.

Understanding water mediated proton migration in conversion of π-bond in olefinic carbon atoms into C–N bond to form β-amino adducts

The aza-Michael reactions with a variety of substrates were conducted in water affording the quantitative yields without any external catalyst, which is contrary to that published in literature. A more rational approach to analyze this problem was by conducting this conspicuous reaction with a variety of substrates in water and the results were analyzed using advanced theoretical calculations. Our investigation on the role of water in the reaction proposed a mechanism wherein water plays dual role both as medium as well as catalyst to facilitate the C–N bond formation using powerful tool in its armory, the “H-bonding”. Reactions were conducted in the absence of an external catalyst or co-solvents and, hence, are a greener approach in organic synthesis. The reactions of 15 examples were conducted with a variety of substrates to afford the addition products in the range of 70–95% yield. Theoretical studies on the transition state analysis suggested that it was the assistance of water, through H-bonding, that facilitated the conjugate addition of amine and proton transfer from ammonium ion, which could happen through two equally possible pathways.

Thiolactone-Functional Pullulan for In Situ Forming Biogels.

Gelation in the presence of cells with minimum cytotoxicity is highly desirable for materials with applications in tissue engineering. Herein, the naturally occurring polysaccharide pullulan is functionalized with thiolactones that undergo ring-opening addition of amines. As a result, the modified pullulan can be cross-linked with diamines and/or amine-containing biological substrates enhancing the system's versatility (e.g., gelatin and cell-binding ligands GHK/GRGDS). Thiolactone degrees of substitution of 2.5 or 5.0 mol % are achieved, and respective hydrogels exhibit mesh sizes of 27.8 to 49.1 nm. Cell proliferation studies on chosen gels (G' ≅ 500 Pa, over 14 days) demonstrate that for normal human dermal fibroblasts (NHDFs), both gelatin and GRGDS equally support cell proliferation, while in the case of hepatocytes (HepG2), the presence of GRGDS and GHK improve cell proliferation 10-fold compared to gelatin. Cells remain viable and in one instance were successfully encapsulated by in situ gelation, altogether confirming the mild and biocompatible nature of this strategy to produce biogels using biologically active substrates as cross-linkers.