Attack Of Amine Research Articles

Iron(II) Phthalocyanine-Catalyzed Homodimerization and Tandem Diamination of Diazo Compounds with Primary Amines: Access to Construct Substituted 2,3-Diaminosuccinonitriles in One-Pot.

We herein first report the homodimerization and tandem diamination of diazo compounds with primary amines catalyzed by the iron(II) phthalocyanine (PcFe(II)), which can construct one C-C bond and two C-N bonds within 20 min in one-pot. Compared to the traditional metal-catalyzed N-H insertion reaction between amines with diazo reagents, the developed reaction almost does not generate the N-H insertion product, but the homodimerization/tandem diamination product. The proposed mechanism studies indicate that primary amines play a crucial role in the homocoupling of diazo compounds via dimerization of iron(III)-acetonitrile radical generated from the reaction between diazoacetonitrile with PcFe(II) coordinated by bis(amines); the β-hydride elimination is involved, and then, the attack of primary amines toward the carbon atoms on the formed C-C bond is followed. Moreover, this novel reaction can be used to effectively prepare substituted 2,3-diaminosuccinonitriles with high yields and even up to >99:1 d.r., encouragingly these products contain both 1,2-diamines and succinonitrile motifs, which are two classes of important organic compounds with significant applications in many yields. This reaction is also suitable for the gram-scale preparation of 2,3-bis(phenylamino)succinonitrile (2a) with a yield of 84%. Therefore, the developed reaction represents a new type of transformation.

An Efficient One-Pot, Three-Component Synthesis of Tetrasubstituted Pyrroles under Catalyst- and Solvent-Free Conditions

AbstractAn environmentally benign, catalyst- and solvent-free, three-component synthesis of tetrasubstituted pyrroles was established. The reaction proceeds via a nucleophilic attack of primary amine on dialkyl acetylenedicarboxylate followed by Michael addition with β-nitrostyrene and successive intramolecular cyclization and aromatization to yield 1,2,3,4-tetrasubstituted pyrroles in good to excellent yields. A wide range of primary amines including aromatic amines and benzylamines were coupled with differently substituted β-nitrostyrenes and dialkyl acetylenedicarboxylate. Furthermore, compared to previous reported methods, the present study is highly atom economical and environmentally benign and can be scaled up.

Tin-Free Synthesis of 2,2′-Biphenyl Gold(III) Complexes Using Dibenzosilol

Gold(III) complexes with dianionic 2,2′-biphenyl ligands stand out for their oxophilic Lewis acid character in combination with a stable and well-defined square planar geometry. They have been demonstrated to be unique and efficient chiral (pre)catalysts. Furthermore, their chemical and physical properties make them interesting for stoichiometric studies as well as organic electronics. These complexes are commonly prepared by transmetallating the bph ligand from undesirable and potentially toxic organotin compounds onto gold salts, making their synthesis problematic for health and the environment. Here, we present a tin-free synthesis using stable and nontoxic dibenzosilol as a transmetallating agent, accessing the same range of gold complexes as the dibenzostannanol-based synthesis. Furthermore, we confirm that corresponding isonitrile gold(III) complexes can be transformed into carbene gold(III) complexes by the nucleophilic attack of amines, opening up the route to new gold(III) catalyst design strategies.

Structure and Additive-free Transamidation of Planar N-Cyano Amides

Although transamidation of amides generally requires metals, additives, or harsh conditions, we present here a facile transamidation of N-cyano amides with various amines at ambient temperature without any additive. N-cyano amides preferred the trans conformation and have a reduced double bond character revealed by crystal analysis. The DFT study indicates that the transamidation reaction proceeds through the direct attack of amine on the amide carbonyl since the LUMO (or LUMO+1) is located at the carbonyl moiety.

Divergent Approach for Regioselective Synthesis of Linearly and Angularly Fused Benzoimidazoquinazolinones from Isatoic Anhydrides.

Ph3P-I2-mediated condensation reactions of isatoic anhydrides and o-phenylenediamines have been developed for the regioselective syntheses of a wide range of linearly and angularly fused benzoimidazoquinazolinones. The selectivity of the products relies on the generation of either highly electrophilic oxyphosphonium or less reactive imidate intermediates. A direct amine attack at the C-2 position of the oxyphosphonium intermediate presumably drives the reaction toward the linearly fused products, whereas an attack of the diamine at the C-4 position of the in situ generated cyclic imidate leads to the angularly fused derivatives. This strategy serves as a practical handle for the efficient synthesis of other related heterocycles.

Photocatalytic Oxo-Amination of Aryl Cyclopropanes through an Unusual SN2-Like Ring-Opening Pathway: Won >99% ee.

One-pot oxo-amination of unactivated cyclopropanes with safe, green dioxygen as an oxidant and low-cost amines as nitrogen sources has generated interest since this can directly result in uniform β-located difunctional units. Formation of the three-electron cation radical followed by the nucleophilic attack of amines to open the strained ring of cyclopropanes catalyzed by classic noble-complex photocatalysts was a promising strategy. However, this ring-opening pathway could not maintain the entire second-order nucleophilic substitution (SN2) conversion, which generally led to unsatisfactory enantioselectivity (enantiomeric excess (ee) value ∼60%). Here, we demonstrate that for such a one-step oxo-amination of cyclopropanes with benign dioxygen and pyrazoles, a highly uniform inversion of configuration could be first accomplished through a TiO2 photocatalyst. This strategy features low-cost, semiheterogeneous photocatalysis and environmentally friendly reaction conditions, without using any sacrificial reagent or additive. Importantly, our protocol not only provides a relatively broad substrate scope tolerant to a certain range of substituted cyclopropanes and pyrazoles, resulting in various β-amino ketone products (∼50 examples) with excellent conversions and yields, but also retains excellent enantioselectivity (ee value ∼99%). A concerted SN2 ring opening raised from an oxetane cation intermediate rather than a conventional three-electron cation radical prior to attaching to dioxygen was proposed.

Chemical reactivity of morpholine with cis and trans-(+)-4R limonene oxide using density functional theory (DFT)

The regioselectivity and the type of predominant interaction between secondary amine and 1:1 mixture of cis and trans limonene oxide, was investigated. Density functional theory (DFT B3LYP/6-31G (d,p) was employed to explain theoretically the regioselectivity of reaction associated by using a variety of approaching methods including the frontier molecular orbitals theory. The calculations were compared with the reported experimental results of this reactions. It was found that the results are not in agreement with the experiments results, where the attack of the secondary amine will occur on trans limonene oxide, which means that the regioselectivity and the reaction mechanism observed are under steric control.

Effect of N-Methylation on Dopamine Surface Chemistry.

Dopamine (DA) surface chemistry has received significant attention because of its applicability in a wide range of research fields and the ability to graft functional molecules onto numerous solid surfaces. Various DA derivatives have been newly synthesized to identify key factors affecting the coating efficiency and to advance the coating system development. The oxidation of catechol into quinone followed by internal cyclization via the nucleophilic attack of primary amine is crucial for DA-based surface coating. Thus, it is expected that the amine group's nucleophilicity control directly affects the coating efficiency. However, it has not been systematically investigated, and most studies have been conducted with the focus on the transformation of amines into amides, despite such approaches decreasing the coating efficiency; the nitrogen in amides is less nucleophilic than that in free amines. In this study, we investigated the effect of N-alkylation on dopamine surface chemistry. N,N-Dimethyldopamine (DMDA) was newly synthesized, and the coating efficiency was systematically compared with DA and N-methyldopamine (MDA). DA N-monomethylation improved the coating rate by increasing the nitrogen nucleophilicity, whereas N,N-dimethylation dramatically decreased the DA surface coating property. In addition, MDA remained capable of universal surface coating and secondary reactions using the surface catechols. This study provides opportunities for developing coating materials with advanced functions and an improved coating rate.

Synthesis of (Hyper)Branched Monohydroxyl Alkoxysilane Oligomers toward Silanized Urethane Prepolymers.

The aim of this work was the synthesis of (hyper)branched oligomers based on trialkoxysilane in various conditions and further application of them in order to modify the urethane prepolymers. Hydroxyl-terminated trialkoxysilane was used as a monomer for homo-condensation. It was obtained by reaction of 3-aminopropyl trialkoxysilane (APTES) with ethylene carbonate (EC). The reaction was based on the attack of amine at the carbonyl carbon atom followed by ring opening of the carbonate to give a urethane (carbamate) product. The next step was the condensation via substitution of ethoxy groups on silicon atom with the terminal hydroxyalkyl groups present in the primary product with the evolution of ethanol. Accordingly, the impact of temperature and type of catalyst on process efficiency was investigated. A quantitative analysis of reaction progress and products of the conversion of EC together with ethanol evolution was conducted by means of gas chromatography, which allowed us to determine the formation of monomeric product and, indirectly, of oligomeric products. It was found that at room temperature after 24 h, the majority of the monomeric product was isolated, whereas at elevated temperature in the presence of Ti-based catalyst, further condensation of the monomer into branched oligomers was preferred, and, moreover, the application of vacuum intensified that process. The obtained products were structurally characterized by 1H and 29Si NMR, MALDI-ToF and Gel Permeation Chromatography. Finally, two different alkoxysilane products, monomeric and oligomeric, were applied for modification of urethane prepolymer, forming silanized one (SPUR). The influence of the silanizing agent on the mechanical and thermal properties of the moisture-cured products was shown before and after additional conditioning in water.

Lewis Acid Zn(OTf)2 Catalyzed Synthesis ofImidazo[1,2‐a]pyridines by [3+2] Annulation of 2‐Amino Pyridines and Propargylic Alcohols

AbstractA novel synthetic protocol for functionalized imidazo[1,2‐a]pyridines were accomplished in one pot by reacting 2‐amino pyridines and propargylic alcohols promoted by lewis acid catalyst. The protocol presented herein, proceeds via Meyer‐Schuster type of rearrangement leading to in situ generation of electron deficient allene and subsequent nucleophilic attack of amines followed by intramolecular cyclization in [3+2] cycloaddition fashion leading to title compounds. Simple reaction conditions, excellent yields and high compatibility are the advantages of this protocol.

Copper-Catalyzed [5 + 1] Cyclization of o-Pyrrolo Anilines and Heterocyclic N-Tosylhydrazones for Access to Spiro-dihydropyrrolo[1,2-a]quinoxaline Derivatives.

An inexpensive copper-catalyzed sequential reaction process, proceeding via a nucleophilic attack of amine to Cu-carbene generated in situ from heterocyclic N-tosylhydrazone precursors followed by a 1,2-H shift/oxidative cyclization cascade of N-ylides, has been described, smoothly generating the corresponding structurally various spiro-dihydropyrrolo[1,2-a]quinoxaline derivatives. Furthermore, the significance of this protocol can be also highlighted by its diverse conversions of the synthetic compounds to the potentially bioactive molecules such as the 2-substituted pyrrolo[1,2-a]quinoxalins.

Synthesis of Benzenesulfonamide Derivatives via Ring Opening of Aziridines in the Presence of Magnetically Retrievable Graphene Based (CoFe@rGO) Nanohybrid

Graphene based magnetic nanohybrids have engrossed considerable research curiosity because of their exceptional properties and diverse applications associated with green chemistry. In this regard, a practical, facile and regioselective preparation of 1,2-diamines from N-tosylaziridine/(S)-(+)-2-Benzyl-1-(p-tolylsulfonyl)aziridine and aryl amines in the presence of magnetically separable graphene based nanohybrid (CoFe@rGO) has been proposed under mild and solvent free conditions. The FT-IR, FE-SEM, XPS, XRD and TEM spectroscopic analysis confirmed the formation of the CoFe@rGO nanohybrids. For unsymmetrical aziridine, nucleophilic attack of aryl amines was observed to take place selectively at the more substituted carbon atom of aziridine ring. Environmentally benign, efficient, shorter reaction time, solvent-free conditions, low catalyst loading, excellent reaction yields and reusability of the catalyst for six consecutive runs without significant loss in its activity are the key advantages of this protocol.Graphical Abstract

Photoimageable Organic Coating Bearing Cyclic Dithiocarbonate for a Multifunctional Surface.

We report the fabrication of photocross-linkable and surface-functionalizable polymeric thin films using reactive cyclic dithiocarbonate (DTC)-containing copolymers. The chemical functionalities of these material surfaces were precisely defined with light illumination. The DTC copolymers, namely, poly(dithiocarbonate methylene methacrylate-random-alkyl methacrylate)s, were synthesized via reversible addition-fragmentation chain transfer polymerization, and the reaction kinetics was thoroughly analyzed. The copolymers were cross-linked into a coating using a bifunctional urethane cross-linker that contains a photolabile o-nitrobenzyl group and releases aniline upon exposure to light. The nucleophilic attack of the aromatic amine opens the DTC group, forming a carbamothioate bond and generating a reactive thiol group in the process. The surface concentrations of the unreacted DTC and thiol were effectively controlled by varying the amounts of the copolymer and the cross-linker. The use of methacrylate comonomers led to additional reactive surface functionality such as carboxylic acid via acid hydrolysis. The successful transformations of the resulting DTC, thiol, and carboxylic acid groups to different functionalities via sequential nucleophilic ring opening, thiol-ene, and carbodiimide coupling reactions under ambient conditions were confirmed quantitatively using X-ray photoelectron spectroscopy. The presented chemistries were readily adapted to the immobilization of complex molecules such as a fluorophore and a protein in lithographically defined regions, highlighting their potential in creating organic coatings that can have multiple functional groups under ambient conditions.

Ring opening of N-hydroxyphthalimide to construct phenylurea derivatives

Arylurea and their analogues have been one of the most ubiquitous backbone during the past century, and extensive studies have been conducted to establish practical synthetic methods for their derivatives. In particular, it is an effective pathway to synthesize arylureas by using commercially available phthalimide compounds. Reported herein is a triethoxyphosphine promoted ring-opening of the N-hydroxyphthalimide (NHPI) by the nucleophilic attack of amines. This transformation shows a wide range of functional-group tolerance under mild reaction conditions.

Highly Efficient Production of Tailored Monascus Pigments by Using a Biocompatible Chemical Reaction Interfacing with Microbial Metabolism

A biocompatible reaction interfacing with microbial metabolism is an efficient approach for production of desired chemicals. Monascus pigments are a traditional natural food colorant from a microbial source. The major color components are red Monascus pigments (RMPs) with various primary amine resides as well as some minor components of yellow ones (YMPs) and orange ones (OMPs). Herein, we elucidate the pathway of OMP degradation involving nucleophilic attack of water on OMPs for the first time. On the basis of OMP degradation and the conversion of OMPs into RMPs sharing a similar reaction mechanism, i.e., nucleophilic attack of water or primary amine on the activated OMPs, we design cascade reactions including biosynthesis of OMPs and biocompatible chemical conversion of OMPs into the stable RMPs with a single glycine residue using a flexible combining chemocatalyst (phosphate ion) and micellar catalyst (Triton X-100). The cascade reactions ensure that OMPs maintain a very low concentration during microbial fermentation by rapid chemical conversion of OMPs into the stable RMPs. In this way, the metabolite profile of microbial fermentation is tailored to RMPs with a single glycine residue as the major color components while free of OMPs and YMPs. Meanwhile, the possible OMP degradation as well as feedback inhibition is eliminated, and a high concentration of RMPs 3.2 mM (1.4 g/L) is also achieved. Designing cascade reactions also has potential for the efficient microbial fermentation of other azaphilone alkaloids.

Inorganic-polymerization crosslinked tissue-siloxane hybrid as potential biomaterial for bioprosthetic heart valves.

Bioprosthetic heart valve (BHV) replacement is increasingly used for treating valve-related diseases worldwide but the current commercially used BHVs treated with glutaraldehyde (Glut) often failed within 12-15 years due to degradation, thrombosis, inferior biocompatibility, and calcification. Herein, 3-glycidyloxypropyl trimethoxysilane (GPTMS) was used to crosslink porcine pericardium (PP) at the concentration (vol/vol) of 0.25%, 1%, 2%, and 4% and their performance for potential application in BHVs was evaluated. The crosslinking mechanism mainly involved the ring-opening of epoxide by amine attack and silanol poly-condensation. The stability of collagen in higher concentration (1%, 2%, and 4%) GPTMS crosslinked PPs (GPTMS-PPs) was clearly increased. GPTMS-PPs showed no cytotoxicity and supported the growth of endothelial cells while Glut-PP did not. GPTMS-PPs were less prothrombotic than Glut-PP. GPTMS-PP crosslinked at 1% concentration showed comparable mechanical properties to Glut-PP while had better anti-tearing performance. The subcutaneous implantation in rat for 30 days showed that GPTMS crosslinking was able to effectively inhibit the calcification of BHV.

5-(4H)-Oxazolones and Their Benzamides as Potential Bioactive Small Molecules.

The five membered heterocyclic oxazole group plays an important role in drug discovery. Oxazolones present a wide range of biological activities. In this article the synthesis of 4-substituted-2-phenyloxazol-5(4H)-ones from the appropriate substituted aldehydes via an Erlenmeyer–Plochl reaction is reported. Subsequently, the corresponding benzamides were produced via a nucleophilic attack of a secondary amine on the oxazolone ring applying microwave irradiation. The compounds are obtained in good yields up to 94% and their structures were confirmed using IR, 1H-NMR, 13C-NMR and LC/MS data. The in vitro anti-lipid peroxidation activity and inhibitory activity against lipoxygenase and trypsin induced proteolysis of the novel derivatives were studied. Inhibition of carrageenin-induced paw edema (CPE) and nociception was also determined for compounds 4a and 4c. Oxazolones 2a and 2c strongly inhibit lipid peroxidation, followed by oxazolones 2b and 2d with an average inhibition of 86.5%. The most potent lipoxygenase inhibitor was the bisbenzamide derivative 4c, with IC50 41 μM. The benzamides 3c, 4a–4e and 5c were strong inhibitors of proteolysis. The replacement of the thienyl moiety by a phenyl group does not favor the protection. Compound 4c inhibited nociception higher than 4a. The replacement of thienyl groups by phenyl ring led to reduced biological activity. Docking studies of the most potent LOX inhibitor highlight interactions through allosteric mechanism. All the potent derivatives present good oral bioavailability.

Synthesis, structure and anticancer activity of new geldanamycin amine analogs containing C(17)- or C(20)- flexible and rigid arms as well as closed or open ansa-bridges

The nucleophilic attack of amines at C(17) or C(17)/C(20) positions of geldanamycin’s (GDM) benzoquinone, via initial 1,4-Michael conjugate addition mechanism, yield new analogs with closed or open ansa-bridges (1–31), respectively. X-ray structures of analogs 22 and 24 reveals an unexpected arrangement of the ansa-bridge in solid (conformer B), that is located between those of conformers A, prevailing in solution (trans-lactam), and C, crucial at binding to Hsp90 (cis-lactam). The structure of a new-type conformer B allows to better understand the molecular recognition mechanism between the GDM analogs and the target Hsp90. Combined analysis of: anticancer test results (SKBR-3, SKOV-3, PC-3, U-87, A-549) and those performed in normal cells (HDF), KD values and docking modes at Hsp90 as well as clogP parameters, reveals that the rigid C(17)-arm (piperidyl, cyclohexyl) with a H-bond acceptor as carbonyl group together with a lipophilicity clogP∼3 favor high potency of analogs, even up to IC50 ∼0.08 μM, at improved selectivity (SIHDF > 30), when compared to GDM. The most active 25 show higher anticancer potency than 17-AAG (in SKOV-3 and A-549) as well as reblastatin (in SKBR-3 and SKOV-3). Opening of the ansa-bridge within GDM analogs, at the best case, decreases activity (IC50∼2 μM) and toxicity in HDF cells (SIHDF∼2–3), relative to GDM.

Photo-oxidation of lysozyme triggered by riboflavin is O2-dependent, occurs via mixed type 1 and type 2 pathways, and results in inactivation, site-specific damage and intra- and inter-molecular crosslinks

Photosensitized protein oxidation is a promising tool for medical procedures such as photochemical tissue bonding (PTB). We have recently reported that the binding of rose Bengal, a sensitizer employed in PTB, to lysozyme modulates the photooxidation and crosslinking of this protein. In this work we examined the photooxidation and crosslinking of lysozyme mediated by riboflavin (RF) an endogenous sensitizer also employed in PTB. We hypothesized that since RF does not bind strongly to proteins, the mechanism(s) and extent of enzymatic inactivation, amino acid modification and protein crosslinking would be dependent on the presence of O2, and differ to that induced by rose Bengal. This hypothesis was tested using UV–visible spectrophotometry, isothermal titration calorimetry (ITC), SDS-PAGE gels, quantification of amino acid consumption, and LC-MS analysis of sites of modification and crosslinks. Under N2, limited damage was detected arising from type 1 (radical) chemistry with formation of specific intra- (Tyr20-Tyr23) and inter- (Tyr23-Trp108) molecular crosslinks. In contrast, the presence of O2 triggered extensive protein damage through mixed type 1 and type 2 (1O2) mechanisms leading to Trp, Met, Tyr and His oxidation, loss of enzymatic activity and protein dimerization. LC-MS analysis provided evidence for crosslinking via radical-radical recombination reactions (Trp28-Tyr53), and secondary reactions involving nucleophilic attack of the side-chain amine of Lys116 on carbonyl groups. Overall, this behavior is in marked contrast to that detected with rose Bengal indicating that the mechanisms and sites of photo-oxidative damage, and consequences for protein function, can be modulated by the choice of sensitizing dye.

Asymmetric Three‐Component Heck Arylation/Amination of Nonconjugated Cyclodienes

AbstractSubstituted cyclohexylamines are becoming increasingly important in drug discovery. Asymmetric Heck insertion/amination of nonconjugated cyclodienes proceeds to give 5‐aryl cyclohexenylamines with good enantioselectivity and exclusive trans configurations. Primary and secondary anilines, indoline, and benzylamines are suitable amines. The weakly donating diphosphite Kelliphite forms a deep unsymmetrical pocket, which is essential for stereoselective anti attack of amines.