Primary Aliphatic Amines Research Articles

A Novel Ring-Opening/Ring-Closing Cascade Reaction Selectively Induced by Aliphatic Primary Amine Using Phenolic Hydroxyl as a Traceless Directing Group

AbstractAn interesting ring-closing/ring-opening cascade reaction selectively induced by aliphatic primary amine for the synthesis of functionalized aminomaleimides is described. This work features phenolic hydroxyl as a traceless directing group that forms a critical six-membered intermediate and then a lactone ammonolysis/intramolecular amidation sequence. This two-step, one-pot practical protocol has broad substrate scope (39 examples) and delivers structurally diverse aminomaleimides in good to excellent yields.

Development of a new force field for the family of primary aliphatic amines using the three steps systematic parameterization procedure

The applicability of the three steps systematic parametrization procedure (3SSPP) to develop a force field for primary amines was evaluated in the present work. Previous simulations of primary amines show that current force fields (FF) can underestimate some experimental values under room conditions. Therefore, we propose a new set of parameters, for an united atom (UA) model, that can be used for short and long amines which predict correctly thermodynamic and dynamical properties. Following the 3SSPP methodology, the partial charges are chosen to match the experimental dielectric constant whereas the Lennard-Jones (LJ) parameters, ε and σ, are fitted to reproduce the surface tension at the vapor-liquid interface and the liquid density, respectively. Simulations were initially conducted for the propylamine molecule by introducing three different types of carbon atoms, Cα and Cβ, with electric charges, and Cn, without charge. Then, modifying the charges of the carbons and using the transferable LJ parameters, the new set of constants for long amines were found. The results show good agreement for the experimental dielectric constant and mass density with a percentage error less than 1% surface tension the error is up to 4% ethylamine, the new charges were obtained from a fitting function calculated from the long amines results. For these molecules, the values of the dielectric constant and the surface tension present errors of the order of 10% with the experimental data. Miscibility of the amines was also tested with the new parameters and the results show reasonable agreement with experiments.

Diastereospecific arylation and cascade deconstructive amidation/thioesterification of readily available lactam-fused bromolactones.

An intrinsic goal when designing synthetic methodology is to identify approaches whereby readily accessible precursors are converted into an array of products, which efficiently tap into new 3D-chemical space. In these studies, readily available bicyclic lactam-bromolactones have been interrogated in several fragment growth protocols by utilizing the halogen and lactone motifs as versatile linchpins for strategic construction of C-C, C-N, C-O, and C-S bonds. Diastereospecific C(sp3)-C(sp2) Kumada coupling of sterically imposing [5,5]-bicyclic lactam-bromolactones with several aryl Grignard reagents, under palladium catalysis, furnishes diarylmethane-tethered lactam-lactones in synthetically attractive yields, stereoinvertive fashion, and with a tolerance for many functional groups. When [5,6]-bicyclic lactam-bromolactones, which are prone to β-hydride elimination are employed, efficient arylation is observed only under Co(acac)3-catalyzed conditions. Importantly, these [5,6]-bicyclic lactam-bromolactones undergo retentive arylation, independent of the transition metal catalyst. A base-mediated cascade deconstructive amidation of the [5,6]-bicyclic lactam-bromolactones with primary aliphatic amines proceeds efficiently to afford epoxide-tethered lactam carboxamides, which bear four contiguous stereocenters. Furthermore, an unusual route to homoallylic thioesters has been uncovered through deconstructive contra-thermodynamic thioesterification of the lactam-fused bromolactone precursors.

Catalyst‐ and Solvent‐Free Thioamidation of Aromatic Aldehydes through a Willgerodt‐Kindler Reaction

AbstractA simple, straightforward, and highly efficient approach has been developed to synthesize thioamide derivatives under catalyst‐ and solvent‐free conditions at 100 °C/room temperature. Total 51 thioamides were synthesized via a one‐pot multicomponent Willgerodt‐Kindler reaction between substituted aromatic aldehydes, elemental sulfur powder and amines with 70–98 % yield within 20–70 min using cyclic secondary amines and 1.5–24 h using aliphatic primary and secondary amines. The cyclic secondary amines react faster than aliphatic amines. Twenty‐one newer compounds were prepared and characterized by 1H NMR, 13C NMR, HRMS. Mild reaction conditions, good yields, and a wide range of reactions demonstrate the excellent synthetic utility of this method. The developed protocol showed that there is no need to collect, purify, recycle, and remove the solvent after the reaction is complete. Reaction rates are generally high due to the high availability of reactants, i. e., shortens the reaction time, is environmentally friendly, and which makes the overall process more sustainable and economical.

Niobium Bis‐ and Mono(Pentafulvene) Complexes: E−H Bond Cleavage and Insertion Reactions (E=C, N, O)

AbstractBis(η5:η1‐(di‐para‐tolyl)pentafulvene)niobium chloride (1) reacts with methyl lithium via salt metathesis to the methylated bis(pentafulvene)niobium complex 2, and with lithium 2,6‐diisopropylanilide addition and subsequent N−H bond activation to the imido mono(pentafulvene)niobium complex 3. Avoiding the competing protonation of the chloride, bis(pentafulvene)niobium complex 2 reacts with primary aromatic and aliphatic amines to form terminal niobocene imido complexes, and with water to form the analog terminal oxo complex. Secondary methyl amines undergo a simultaneous N−H and C−H activation to form niobaaziridines under mild conditions. In contrast to other reported examples, 3 can be employed to investigate the uncontested reactivity of mono(pentafulvene)niobium complexes. Reaction with 4‐tert‐butylphenol selectively yields a niobocene phenolate complex. Unprecedented for mono(pentafulvene)niobium complexes, treating 3 with multiple‐bond‐containing substrates (nitriles, isocyanates) smoothly results the insertion into the Nb‐Cexo σ‐bond, forming the corresponding alkylidene amido and imidato complexes.

A Photoinduced, Nickel-Catalyzed Reaction for the Stereoselective Assembly of C-Linked Glycosides and Glycopeptides.

C-Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C-C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox-active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et3 N) under blue LED illumination to deliver C-alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross-coupling. Through this manifold, innate CO2 H and NH2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late-stage glycosylation.

A Photoinduced, Nickel‐Catalyzed Reaction for the Stereoselective Assembly of C‐Linked Glycosides and Glycopeptides

AbstractC‐Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C−C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox‐active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et3N) under blue LED illumination to deliver C‐alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross‐coupling. Through this manifold, innate CO2H and NH2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late‐stage glycosylation.

Bio-based polybenzoxazines coatings for efficient marine antifouling

It is a subject of great practical significance and challenge to endow marine coatings with both excellent bacterial killing and antifouling properties. In this work, a series of bio-based organic coatings demonstrating high antibacterial rate, strong algae-killing ability and satisfied real-sea fouling resistance were reported. The main-chain type benzoxazine (MCBZ) resins were prepared from the renewable daidzein and furfurylamine, together with polyetheramine, long aliphatic chain primary amines, and paraformaldehyde. By adjusting the amines, the overall performance of synthesized MCBZs could be manipulated. Results indicated that the low surface energy of obtained MCBZ could prevent fouling adhesion, and the synergistic effect of long alkyl chains and daidzein led to the efficient anti-fouling. Notably, besides the low curing temperature of 200 °C, excellent processing property and good substrate adhesion (5.02 MPa), poly (12-fu-MCBZ) also possessed 94.5 % antibacterial rate, 100 % algae-killing ability and excellent real-sea antifouling performance. This work provides us a new strategy to solve the marine biological pollution using renewable raw materials.

Pickering Emulsions Synergistically Stabilized by Aliphatic Primary Amines and Silica Nanoparticles.

Innovation in emulsion compositions is necessary to enrich emulsion formulations and applications. Herein, Pickering emulsions were prepared using silica nanoparticles and aliphatic primary amines with an oil-water ratio of 1:1 (v/v). Contact angle experiments revealed that the in situ hydrophobization of nanoparticles was caused by the surface adsorption of amine molecules. Notably, the interactions between amine compounds and the surface of silica nanoparticles were electrostatic attractions and mutual hydrogen bonding. The existence of hydrogen bonds was further confirmed by demulsification experiments using a chaotropic agent DMF and increasing temperatures. The hydrophobicity of silica nanoparticles can be effectively improved using most commercially available aliphatic primary amines such as n-hexylamine, n-octylamine, n-decylamine, dodecylamine, and tetradecylamine. The minimum concentrations of the aforementioned amines necessary for stabilizing the emulsions with 0.3 wt % silica nanoparticles are 3, 0.6, 0.3, 0.06, and 0.03 mM, respectively, decreasing significantly with increasing alkyl chain length. With the increase of the amine concentrations, the hydrophobicity of silica particles monotonically increased and finally resulted in the inversion of emulsions. The amine concentrations for emulsion phase inversion were 150, 40, 30, 20, and 20 mM, respectively, in the presence of 0.3 wt % silica nanoparticles. In this work, silica nanoparticles were hydrophobized using aliphatic primary amines. The composite stabilizers developed are useful for developing novel stimuli-responsive Pickering emulsions, while the synergistic effects introduced herein are also helpful in expanding the hydrophobization methods available for nanoparticles.

Acrylonitrile Adducts: An Efficient Adsorbent Media for Removal of Iron from Water

Highly efficacious one-pot microwave-assisted acrylonitrile adducts acts as efficient adsorbent for Fe2+ ion removal from aqueous media. It followed Langmuir adsorption isotherm with maximum % removal of 95.31 % for Fe2+ ions.

Nutritional Quality, Chemical, and Functional Characteristics of Hemp (Cannabis sativa ssp. sativa) Protein Isolate.

(1) Background: Hemp seeds are a source of plant-based protein, making them an appropriate supplement to a plant-based diet. The current work was focused on the preparation of the protein isolate from the hemp seeds with eco-friendly and cheap technology. Moreover, it evaluated the physicochemical and functional properties of hemp protein isolate for its potential application in food manufacturing. (2) Methods: The protein content of hemp seeds has been isolated through two main steps: (1) extraction of the protein content of an alkaline pH (10-12); (2) precipitation of the extracted protein on an acidic pH as an isoelectric point (pH = 4.5). (3) Results: The edastin protein is the most predominant protein in the protein profile with a molecular weight of 58.1 KDa beside albumin with a molecular weight of 31.5 KDa. The FTIR spectrum detected the absorption peaks of the amide I at 1750 and 1600 cm-1, which pointed to C=O stretching while N-H stretching at 1650-1580 cm-1. The peak at 3250 is found to be related to N-H stretching of the aliphatic primary amine (3400-3300 cm-1) and the N-H stretching for the secondary (II) amine appeared at 3350-3310 cm-1. The Hemp protein isolate (HPI) showed a high content of arginine (15.52 g/100 g), phenylalanine + tyrosine (9.63 g/100 g), methionine + cysteine (5.49 g/100 g), leucine + isoleucine (5.21 g/100 g), and valine (4.53 g/100 g). It contains a moderate level of threonine (3.29 g/100 g) and lysine (2.50 g/100 g) with tryptophan as the limiting amino acid (0.22 g/100 g). The HPI showed an appropriate water-and-oil holding capacity (4.5 ± 2.95 and 2.33 ± 1.88 mL/g, respectively). The foaming capacity of the HPI was increased with increasing the pH values to reach the maximum value at pH 11 (67.23 ± 3.20%). The highest emulsion ability index of the HPI was noted at pH 9 (91.3 ± 2.57 m2/g) with low stability (19.15 ± 2.03). (4) Conclusions: A strong positive correlation (r = 0.623) was shown between protein concentration and solubility. The current easy-to-use, cheap, and eco-friendly technology provides the industrial sector with a cheap protein isolate for manufacturing protein-rich diet and beverages. The HPI showed a good nutritional quality and functional properties that might be helpful in utilizing it in different food products such as beverages and bakery products.

Zn catalyzed a simple and convenient method for thiourea synthesis

A straightforward and convenient synthesis of symmetrical and unsymmetrical thiourea derivatives by the reaction of primary amines and carbon disulfide in the presence of a Zn catalyst is presented. Under modest reaction conditions, a range of biologically relevant thiourea derivatives can be produced in good to outstanding yields without a lengthy work-up. A variety of primary aliphatic and aromatic amines with various substituted functional groups were transformed into thiourea derivatives. Zn-mediated symmetric thiourea creation occurs at room temperature for aliphatic amines, whereas for aromatic amines it occurs at 60°C. However, unsymmetrical thiourea for aliphatic amines occurs at 0°C. Benefits of this method include environment-friendly reaction conditions, sustainability, and enumerating tolerance of functional groups such as hydroxyl and halides. Experimental observations were rationalized by DFT calculations based on transition structures and zwitterionic intermediate stabilities.

YfeX - A New Platform for Carbene Transferase Development with High Intrinsic Reactivity.

Carbene transfer biocatalysis has evolved from basic science to an area with vast potential for the development of new industrial processes. In this study, we show that YfeX, naturally a peroxidase, has great potential for the development of new carbene transferases, due to its high intrinsic reactivity, especially for the N-H insertion reaction of aromatic and aliphatic primary and secondary amines. YfeX shows high stability against organic solvents (methanol and DMSO), greatly improving turnover of hydrophobic substrates. Interestingly, in styrene cyclopropanation, WT YfeX naturally shows high enantioselectivity, generating the trans product with 87 % selectivity for the (R,R) enantiomer. WT YfeX also catalyzes the Si-H insertion efficiently. Steric effects in the active site were further explored using the R232A variant. Quantum Mechanics/Molecular Mechanics (QM/MM) calculations reveal details on the mechanism of Si-H insertion. YfeX, and potentially other peroxidases, are exciting new targets for the development of improved carbene transferases.

Synthesis of Unsymmetrical Vicinal Diamines via Directed Hydroamination.

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.

Synthesis and characterization of Bis(β‐diketiminato) rare‐earth amido complexes, their activity for catalytic addition of amines to carbodiimides

Reactions of anhydrous RECl3 (RE = Sm, Nd) with 2 equiv. of NaL2-Me (L2-Me = [N(2-MeC6H4)C(Me)]2CH−) afforded the dimeric chlorides [Sm(L2-Me)2(μ-Cl)]2 (1) and [Nd(L2-Me)2(μ-Cl)]2 (2). Salt metathesis reactions between chloride complexes and NaN(SiMe3)2 in THF yielded a series of bis(β-diketiminato) rare-earth amido complexes RE(L2-Me)2[N(SiMe3)2] (RE = Sm (3), Nd (4), Yb (5), Y (6), Pr (7)). Complexes 1−7 were fully characterized including X-ray single crystal structure analyses. Complexes 3−7 can serve as efficient pre-catalysts for catalytic addition of amines to carbodiimides to afford multi-substituted guanidines. Catalytic activity was influenced by the rare-earth metals with an active sequence of Y (6) ∼ Yb (5) < Pr (7) < Nd (4) < Sm (3). The present catalytic addition reaction using complex 3 showed a wide scope of substrates including primary and secondary aromatic amines and aliphatic cyclic amines. The mechanism investigation by the isolation and characterization of the intermediates of the amido complexes RE(L2-Me)2(NHPh)(THF) (RE = Sm (8), Nd (9), Yb (10)) and guanidinate complexes Sm(L2-Me)2[(C6H5NH)C(NCy)2] (11) and Nd(L2-Me)2[(C6H5N)C(NHCy)(NCy)] (12). Their reactivity revealed that the present catalytic addition proceeded through amine-exchange reaction between the pre-catalyst amido complex and an amine to a novel amido complex, nucleophilic addition of the formed amido species to a carbodiimide to yield a guanidinate species, and protonation reaction of the guanidinate species by an amine to regenerate amido species and release the final product.

Chiral Amines via Enantioselective π-Allyliridium-C,O-Benzoate-Catalyzed Allylic Alkylation: Student Training via Industrial-Academic Collaboration.

Cyclometalated π-allyliridium-C,O-benzoate complexes discovered in the Krische laboratory display unique amphiphilic properties, catalyzing both nucleophilic carbonyl allylation and electrophilic allylation of diverse amines as well as nitronates. Given the importance of chiral amines in FDA-approved small-molecule drugs, a collaboration with medicinal chemists at Genentech that included on-site graduate student internships was undertaken to explore and expand the scope of π-allyliridium-C,O-benzoate-catalyzed allylic amination and related processes. As described in this Account, our collective experimental studies have unlocked asymmetric allylic aminations of exceptionally broad utility and scope. Specifically, using racemic branched alkyl-substituted allylic acetate proelectrophiles, primary and secondary aliphatic or aromatic amines, including indoles, engage in highly regio- and enantioselective allylic amination. Additionally, unactivated nitronates were found to be competent nucleophilic partners for regio- and enantioselective allylic alkylation, enabling entry to β-stereogenic α-quaternary primary amines. Notably, these π-allyliridium-C,O-benzoate-catalyzed allylic substitutions, which display complete branched regioselectivity in reactions of alkyl-substituted allyl electrophiles, complement the scope of corresponding iridium phosphoramidite-catalyzed allylic aminations, which require aryl-substituted allyl electrophiles to promote high levels of branched regioselectivity. Computational, kinetic, ESI-CID-MS, and isotopic labeling studies were undertaken to understand the mechanism of these processes, including the origins of regio- and enantioselectivity. Isotopic labeling studies suggest that C-N bond formation occurs through outer-sphere addition to the π-allyl. DFT calculations corroborate C-N bond formation via outer-sphere addition and suggest that early transition states and distinct trans effects of diastereomeric chiral-at-iridium π-allyl complexes render the reaction less sensitive to steric effects, accounting for complete levels of branched regioselectivity in reactions of hindered amine and nitronate nucleophiles. Reaction progress kinetic analysis (RPKA) reveals a zero-order dependence on allyl acetate, a first-order dependence on the catalyst, and a fractional-order dependence on the amine. As corroborated by ESI-CID-MS analysis, the 0.4 kinetic order dependence on the amine may reflect the intervention of cesium-bridged amine dimers, which dissociate to form monomeric cesium amide nucleophiles. Hence, the requirement of cesium carbonate (vs lower alkali metal carbonates) in these processes may reside in cesium's capacity for Lewis acid-enhanced Brønsted acidification of the amine pronucleophile. Beyond the development of catalytic processes for the synthesis of novel chiral amines, the present research was conducted by graduate students who benefited from career development experiences associated with training in both academic and industrial laboratories.

Fluorescence turn on amine detection in a cationic covalent organic framework

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and have shown great potential for various applications. When functionalized with suitable emission sites, guest uptake via the ionic moieties of iCOFs can cause a significant change in luminescence, making them excellent candidates for chemosensors. In here, we present a luminescence sensor in the form of an ionic covalent organic framework (TGH+•PD) composed of guanidinium and phenanthroline moieties for the detection of ammonia and primary aliphatic amines. TGH+•PD exhibits strong emission enhancement in the presence of selective primary amines due to the suppression of intramolecular charge transfer (ICT) with an ultra-low detection limit of 1.2 × 10‒7 M for ammonia. The presence of ionic moieties makes TGH+•PD highly dispersible in water, while deprotonation of the guanidinium moiety by amines restricts its ICT process and signals their presence by enhanced fluorescence emission. The presence of ordered pore walls introduces size selectivity among analyte molecules, and the iCOF has been successfully used to monitor meat products that release biogenic amine vapors upon decomposition due to improper storage.

FTIR screening of phytocompounds in plant Spermacoce hispida L. of Vallimalai Hills at Vellore district

The objective of this study is to detect the FTIR fingerprints of phytocompounds in the plant Spermacoce hispida L. The FTIR analysis of methanol leaf extract of plant Spermacoce hispida L. revealed the presence of 19 bioactive phytocompounds such as aliphatic primary amine, alkene, alkanes, amine salt, aldehydes, aromatic compound, α, β-unsaturated ester, conjugated alkene, nitro compound, sulfonyl chloride, phenol, aromatic amine, alkyl aryl ether, vinyl ether, ester, tertiary alcohol, primary alcohol, carboxylic acids and halo compound.

Formylation Reaction of Amines Using &lt;i&gt;N&lt;/i&gt;-Formylcarbazole

Formamides are useful starting materials for pharmaceutical syntheses. Although various synthetic methods have been documented in this regard, the use of N-formylcarbazole as a formylation reagent for amines has not yet been reported. We report here the first examples of the use of N-formylcarbazole for the formylation of amines. The characteristic reactivity of N-formylcarbazole enables the selective formylation of sterically less hindered aliphatic primary and secondary amines. In contrast, sterically bulkier amines and weakly nucleophilic amines such as anilines are less reactive under the reaction conditions.

One-pot multistep Henry-Michael reaction with notable upshots using reduced graphene oxide supported bifunctional catalysts

We concocted peculiar and exceedingly sound bifunctional MNPs/AA-rGO (MNPs = Fe and/or Nb2O5 nanoparticles; AA = aromatic and/or aliphatic primary amine derivatives such as benzene-1,4-diamine (BD) or ethylenediamine (ED); rGO = reduced graphene oxide) catalysts with an acid-base twofold activation mechanism bestowing base characteristics by the amine scaffold and Lewis acidic sites triggered by MNPs doped on the peripheral of rGO. Surprisingly, Nb2O5/BD-rGO demonstrated excellent performance for one-pot Henry-Michael reaction via acid-base supportive effect with 90.6 and 88.9% conversions of benzaldehyde and β-nitrostyrene, respectively, and an admirable product selectivity (i.e., 93.2%) of 2-(2-nitro-phenylethyl)malononitrile.