Condensation Of Amines Research Articles

Synthesis of Anilines by Ruthenium/η5-Phenoxo-Catalyzed Condensation of Phenols and Amines

Synthesis of Anilines by Ruthenium/η5-Phenoxo-Catalyzed Condensation of Phenols and Amines

Iron‐Promoted Redox Access to 2‐Aminobenzoxazoles from Amines, Carbon Disulfide and 2‐Nitrophenols

AbstractA method to assemble 2‐aminobenzoxazoles via iron‐catalyzed redox condensation of amines, carbon disulfide and 2‐nitrophenols is reported. The reaction features advantages of environmentally friendly iron catalyzed conditions, readily available starting materials, and excellent atom‐, step‐ and redox‐ economy compared to known protocols. Experimental investigation suggests a mechanism encompassing iron‐catalyzed reduction of the nitro group of 2‐nitrophenols by the dithiocarbamate group from amine‐CS2 adduct.

Discovery of a Hybrid Molecule with Phytotoxic Activity by Genome Mining, Heterologous Expression, and OSMAC Strategy.

Genome mining in association with the OSMAC (one strain, many compounds) approach provides a feasible strategy to extend the chemical diversity and novelty of natural products. In this study, we identified the biosynthetic gene cluster (BGC) of restricticin, a promising antifungal agent featuring a reactive primary amine, from the fungus Aspergillus sclerotiorum LZDX-33-4 by genome mining. Combining heterologous expression and the OSMAC strategy resulted in the production of a new hybrid product (1), along with N-acetyl-restricticin (2) and restricticinol (3). The structure of 1 was determined by spectroscopic data, including optical rotation and electronic circular dichroism (ECD) calculations, for configurational assignment. Compound 1 represents a fusion of restricticin and phytotoxic cichorin. The biosynthetic pathway of 1 was proposed, in which the condensation of a primary amine of restricticin with a precursor of cichorine was postulated. Compound 1 at 5 mM concentration inhibited the growth of the shoots and roots of Lolium perenne, Festuca arundinacea, and Lactuca sativa with inhibitory rates of 71.3 and 88.7% for L. perenne, 79.4 and 73.0% for F. arundinacea, and 58.2 and 52.9% for L. sativa. In addition, compound 1 at 25 μg/mL showed moderate antifungal activity against Fusarium fujikuroi and Trichoderma harzianum with inhibition rates of 22.6 and 31.6%, respectively. These results suggest that heterologous expression in conjunction with the OSMAC approach provides a promising strategy to extend the metabolite novelty due to the incorporation of endogenous metabolites from the host strain with exogenous compounds, leading to the production of more complex compounds and the acquisition of new physiological functions.

Enhanced Co-Adsorption of Alcohols and Amines for Visible Light Driven Oxidative Condensation Using Iron-Based MOF.

Imines are essential intermediates in organic transformations, and is generally produced by dehydrogenative condensation of alcohols and amines with the assist of specialized catalysts and additives. Heterogeneous photocatalysis provides a sustainable platform for such process without the using of toxic oxidants, yet a functionalized photocatalyst with optimized co-adsorption of reactants needs to be developed to promote the stoichiometric oxidative condensation under ambient conditions. Here, we show that benzyl alcohol and aniline adsorb non-interferingly on the Fe node and the linker sites of the MIL-53(Fe) metal organic frameworks (MOFs), respectively. The co-adsorption of both reactants barely influences the reduction of molecular oxygen to generate oxygen radicals, resulting in efficient formation of benzaldehyde under visible light. Additionally, the weak adsorption of water together with surface acidity of the MIL-53(Fe) promote a rapid condensation of benzaldehyde with aniline and the depletion of generated water, achieving an efficient C-N bond creation for a wide range of substrates.

The synthesis of N,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism.

1,4-Diazepane-6-amine (DAZA) can be alkylated with three 2-hydroxybenzyl pendant arms, resulting in hexadentate chelators suitable for coordination of radiometals like 68Ga. These chelators, N,1,4-tri(alkoxy-2-hydroxybenzyl)-DAZA, can be produced via a one-pot synthesis, with the first step being a carbonyl amine condensation of DAZA with two respective 4-alkoxy-2-hydroxybenzaldehydes, followed by reductive amination with sodium borohydride. While the first step of this reaction is predictable, the subsequent reductive amination can result in either mono-, di- or tri(alkoxy-hydroxybenzyl)-DAZA compounds. Seeking to identify dependencies that might allow a specific reaction control towards the formation of either of the three possible products, and particularly towards the favoured trialkylated DAZA compounds, a variety of synthesis trials were performed. Additionally, computational methods were employed to evaluate the underlying reaction mechanism. Synthesis trials verified that the trialkylated DAZA compounds are formed via direct reductive amination of the dialkylated DAZA compounds. Subsequently, a synthetic method was established, leading to an increase in the percentage of the trialkylated DAZA compounds, which allowed the successful isolation of those hexadentate chelators. Additionally, an alternative pathway proceeding via aminal C-N bond insertion of an attacking third carbonyl moiety was evaluated by means of quantum chemical calculations but so far remains entirely hypothetical.

Progress on the Synthesis and Applications of Aminals: Scaffolds for Molecular Diversity

AbstractAminals, characterized by a central carbon linking two nitrogen atoms, are versatile building blocks in modern chemistry. This review addresses a literature gap by exploring the synthesis and applications of aminals, with a focus on drug discovery and molecular diversity. Beyond medicinal chemistry, aminals find applications as key components in bioactive compounds and as versatile tools in materials chemistry. The review covers fundamental characteristics, synthetic methodologies, stability, and applications, emphasizing alternative synthetic methods to the well-established aldehyde–amine condensation. This inclusive exploration provides insights into diverse synthetic pathways that expand the versatility of the aminal scaffold.1 Introduction2 The Aminal Group3 Aminal Synthesis3.1 Metal-Free Approaches3.2 Metal-Catalyzed Approaches3.3 Photoredox Methodologies3.4 Via Rearrangements3.5 Via Decarboxylative Coupling4 Aminals as Synthetic Tools5 Synthesis of Aminal-Containing Natural Products6 Aminal-Based Materials7 Conclusions

β-Triketones as Reactive Handles for Polymer Diversification via Dynamic Catalyst-Free Diketoenamine Click Chemistry.

The spontaneous condensation of amines with β-triketones (TK), forming β,β'-diketoenamines (DKE) and releasing water as the sole byproduct, exhibits many of the hallmarks of "click" reactions. Such characteristics render TKs as a highly advantageous platform for efficient polymer diversification, even in biological contexts. Leveraging reversible addition-fragmentation chain transfer (RAFT) and photoiniferter polymerization of novel TK-containing vinylic monomers, we synthesized polymers containing pendent TKs with excellent control of molecular weights, even in excess of 106 g mol-1. Under mild, catalyst-free conditions, poly(β-triketone methacrylate) could be modified with a diverse scope of amines containing a plethora of functional groups. The high efficiency of this functionalization approach was further emphasized when grafting-to with poly(ethylene glycol)-amine resulting in bottlebrushes with molecular weights reaching 2.0 × 107 g mol-1. Critically, while the formed DKE linkages are stable under ambient conditions, they undergo catalyst-free, dynamic transamination at elevated temperatures, paving the way for associative covalent adaptable networks. Overall, we introduce pendent triketone moieties into methacrylate and acrylamide polymers, establishing a novel postpolymerization modification technique that facilitates catalyst-free ligation of amines under highly permissible conditions.

Micro-helical Ni3Fe chain encapsulated in ultralight MXene/C aerogel to realize multi-functionality: Radar stealth, thermal insulation, fire resistance, and mechanical properties

Magnetic carbon aerogels with high porosity, ultralow density, and excellent impedance matching are considered to be a promising microwave absorption (MA) material. In this study, ethylene glycol polymerization is used to assemble Ni3Fe particles into a micro-helical chain, which is further wrapped by MXene and then encapsulated in poly-Schiff-base aerogels through the carbonyl–amine condensation reaction. Finally, ultralight TiO2/Ni3Fe/MXene/C (NFMC) aerogels are synthesized through calcination treatment. Benefiting from the electromagnetic synergistic effect of multi-dimensional and multi-component materials, the NFMC-7 aerogel exhibits excellent MA performance with a minimum reflection loss of −61.6 dB at 3.0-mm thickness and an effective absorption bandwidth of 8.16 GHz at 2.77-mm thickness under a low filler loading of 7.6 wt%. Commercial computer simulation technology is used to verify the strong magnetic and dielectric loss characteristics of Ni3Fe chains. At the same time, the NFMC-7 aerogel exhibits excellent radar stealth, heat insulation, compression resistance, and fire resistance performance, which verifies its practical applicability. Overall, this work establishes an effective strategy to fabricate multi-functional magnetic aerogels, which can serve as lightweight, thin, and strong microwave absorbers with broad absorption bandwidth.

Modular Approach to Highly Substituted 3-Methylpyridones.

A method has been developed for the rapid synthesis of highly substituted 3-methylpyridones via the condensation of Baylis-Hillman amines and ketones under benzoic acid catalysis. The process features readily available starting materials, broad substrate scope, high functional group tolerance, excellent regioselectivity, and gram-scale synthesis. We envision that this on-demand construction of 3-methylpyridones will provide exciting opportunities in biological research, therapeutics, and material sciences.

Recent Advances on the Antimicrobial Activities of Schiff Bases and their Metal Complexes: An Updated Overview.

Schiff bases represent a valuable class of organic compounds, synthesized via condensation of primary amines with ketones or aldehydes. They are renowned for possessing innumerable applications in agricultural chemistry, organic synthesis, chemical and biological sensing, coating, polymer and resin industries, catalysis, coordination chemistry, and drug designing. Schiff bases contain imine or azomethine (-C=N-) functional groups which are important pharmacophores for the design and synthesis of lead bioactive compounds. In medicinal chemistry, Schiff bases have attracted immense attention due to their diverse biological activities. This review aims to encompass the recent developments on the antimicrobial activities of Schiff bases. The article summarizes the antibacterial, antifungal, antiviral, antimalarial, and antileishmanial activities of Schiff bases reported since 2011.

Synthesis and Application of Salicylhydrazone Probes with High Selectivity for Rapid Detection of Cu2.

Using the aldehyde amine condensation procedure and the triphenylamine group as the skeleton structure, the new triphenylamine-aromatic aldehyde-succinylhydrazone probe molecule DHBYMH was created. A newly created acylhydrazone probe was structurally characterized by mass spectrometry (MS), NMR, and infrared spectroscopy (FTIR). Fluorescence and UV spectroscopy were used to examine DHBYMH's sensing capabilities for metal ions. Notably, DHBYMH achieved a detection limit of 1.62 × 10-7 M by demonstrating exceptional selectivity and sensitivity towards Cu2+ ions in an optimum sample solvent system (DMSO/H2O, (v/v = 7/3); pH = 7.0; cysteine (Cys) concentration: 1 × 10-4 M). NMR titration, high-resolution mass spectrometry analysis, and DFT computation were used to clarify the response mechanism. Ultimately, predicated on DHBYMH's reversible identification of Cu2+ ions in the presence of EDTA, a molecular logic gate was successfully designed.

Antileakage performance of Schiff base-reinforced thermal energy storage wood for indoor temperature control

Thermal energy storage wood has been rapidly developed as a green and renewable energy-saving building material. In this study, bio-based Schiff bases (VF) were prepared from vanillin and furfurylamine via aldehyde–amine condensation and used as a small molecule fixative. Subsequently, VF and dodecylamine were mixed uniformly and impregnated into rubberwood under pressure, affording thermal energy storage wood (TESW-x%VF). The results revealed that TESW-x%VF exhibited adjustable enthalpy (41.67–88.23 J g−1) and room-temperature phase transition (25°C–27°C). Moreover, the addition of VF improved the antileakage performance of TESW. According to density functional theory calculations, this is because the adsorption energy between VF and dodecylamine molecules has increased by 3–8 times compared to dodecylamine molecules. The above results provide a solution for the leakage issue associated with organic phase-change materials and aid in the future development of energy-saving wood building materials, which also improves the high-value utilization of chemical components in agricultural and forestry crops.

Doxorubicin-based ENO1 targeted drug delivery strategy enhances therapeutic efficacy against colorectal cancer

Alpha-enolase (ENO1), a multifunctional protein with carcinogenic properties, has emerged as a promising cancer biomarker because of its differential expression in cancer and normal cells. On the basis of this characteristic, we designed a cell-targeting peptide that specifically targets ENO1 and connected it with the drug doxorubicin (DOX) by aldehyde–amine condensation. A surface plasmon resonance (SPR) assay showed that the affinity for ENO1 was stronger (KD = 2.5 µM) for the resulting cell-targeting drug, DOX-P, than for DOX. Moreover, DOX-P exhibited acid-responsive capabilities, enabling precise release at the tumor site under the guidance of the homing peptide and alleviating DOX-induced cardiotoxicity. An efficacy experiment confirmed that, the targeting ability of DOX-P toward ENO1 demonstrated superior antitumor activity against colorectal cancer than that of DOX, while reducing its toxicity to cardiomyocytes. Furthermore, in vivo metabolic distribution results indicated low accumulation of DOX-P in nontumor sites, further validating its targeting ability. These results showed that the ENO1-targeted DOX-P peptide has great potential for application in targeted drug-delivery systems for colorectal cancer therapy.

Condensation of Amines with S-Methyl Thiouronium Salts: Another Entry for the Synthesis of Amidines

AbstractWe present a condensation of primary aryl or alkyl amines with S-methyl thiouronium salts to obtain N,N,N′-trisubstituted amidines. High yields, short reaction times, and a fair substrate scope are the noteworthy features of this protocol. Surprisingly, the reaction of a thiouronium salt with 4-aminopyridine gave 1-(4-methoxybenzoyl)piperidine.

Two novel chiral AIEgens as coordination precursors: synthesis, structures and photophysical study

Two novel chiral molecules, (4S)-5,5-dimethyl-2-(4-oxo-4H-chromen-3-yl)thiazolidine-4-carboxylic acid (OCCA) and (4S)-5,5-dimethyl-2-(4-(1,2,2-triphenylvinyl)phenyl)thiazolidine-4-carboxylic acid (TPCA), were successfully synthesized by aldehyde amine condensation reaction, and their structures were characterized by 1H NMR and single crystal X-ray diffraction. The intensities of photoluminescence changed with the aggregation, exhibiting that OCCA and TPCA are aggregation-induced emission luminogens (AIEgens). After complete aggregation, OCCA emitted the purple-blue light at the peak of 388 nm and TPCA emitted the cyan light at the peak of 488 nm. The aggregation-induced emission (AIE) effects for OCCA and TPCA resulted from local state to twisted intermolecular charge transfer (TICT) and restriction of intramolecular motion (RIM), respectively. Other spectra including UV–vis, IR, and Raman spectra were also discussed in detail.

From propenolysis to enyne metathesis: tools for expedited assembly of 4a,8a-azaboranaphthalene and extended polycycles with embedded BN.

The synthesis of BN-containing molecules, which have an interesting isosteric relationship to their parent all-C cores, has drawn a great deal of attention as an avenue to alter and tune molecular function. Nevertheless, many cores with embedded BN are still hard to synthesize, and thus, further effort is required in this direction. Herein, we present an integrated approach to BN-containing polycycles rooted in an exceptionally clean B-N condensation of amines with a tri-allylborane. Having released propene as the only byproduct, the resulting BN precursors are seamlessly telescoped into BN-containing polycyclic cores via a set of additional methodologies, either developed here ad-hoc or applied for the first time for the synthesis of BN-cycles. As the "sharpening stone" of the process, BN-embedded naphthalene, which has previously only been obtained in low yield, can now be synthesized efficiently through propenolysis, ring-closing metathesis and a new high-yielding aromatization. As a more advanced application, an analogously obtained BN-containing bis-enyne is readily converted to BN-containing non-aromatic tetra-, penta- and hexacyclic structures via ring-closing enyne metathesis, followed by the Diels-Alder cycloaddition. The resulting air-sensitive structures are easily handled by preventive hydration (quaternization) of their B-N bridge; reverting this hydration restores the original Bsp2-Nsp2 structure. In the future, these structures may pave the way to BN-anthracenes and other π-extended BN-arenes.

Cobalt-Catalyzed Chemodivergent Synthesis of Cyclic Amines and Lactams from Ketoacids and Anilines Using Hydrosilylation.

Here, commercially available Co2(CO)8 was utilized as an efficient catalyst for chemodivergent synthesis of pyrrolidines and pyrrolidones from levulinic acid and aromatic amines under slightly different hydrosilylation conditions. 1.5 and 3 equiv of phenylsilane selectively yielded pyrrolidone and pyrrolidine, respectively. Various ketoacids and amines were successfully tested. Plausible mechanism involves the condensation of levulinic acid and amine to form an imine, which cyclizes to 3-pyrrolidin-2-one followed by reduction to pyrrolidone. The final reduction of pyrrolidone gave pyrrolidine.

Preparation and p-phenylenediamine detection mechanism of a dialdehyde cellulose and a 7-amino-4-methylcoumarin-based fluorescent probe

A novel fluorescent probe, fluorescent dialdehyde cellulose (FDAC), was prepared to detect p-phenylenediamine (PPD) in water samples conveniently and quickly. This was achieved by grafting 7-amino-4-methylcoumarin (AMC) onto dialdehyde cellulose (DAC) via an aldol–amine condensation reaction. This method is greener, more economical, and simpler than existing methods for preparing fluorescent probes. The probe was found to be more effective for PPD detection in polar solvents, with less interference from pH and other compounds present in the sample matrix. The photoluminescence of FDAC at λex/λem = 340/430 nm was statically quenched by PPD, allowing for accurate detection within the range of 10–100 μmol/L under optimal conditions, with a detection limit of 3.2 μmol/L (3 σ/s). Meanwhile, the Schiff base (–C=N– group) generated by the condensation of DAC and AMC increased the reaction activity of the fluorescent moiety and changed the AMC conjugated structure, making FDAC more susceptible to aminolysis with PPD than AMC. This study presents a promising solution for fluorescence detection of aniline compounds, with significant potential for application in fields such as environmental analysis.

Developing a fast and catalyst-free protocol to form C=N double bond with high functional group tolerance.

The carbon-nitrogen double bond (C=N) is a fundamentally important functional group in organic chemistry. This is largely due to the fact that C=N acts as electrophilic synthon to give nitrogen-containing compounds. Here, we report the condensation of primary amine or hydrazine with very electron-deficient aldehyde to form C=N bond in the absence of any catalysts (metals and acids). The protocol performs at room temperature and applies water as co-solvent. Two hundred examples are presented here. With its intrinsic advantages of wide substrate scopes, excellent efficiency (high yields and short reaction time), operational simplicity, mild condition (room temperature as reaction temperature, no catalysts, no additions, water as co-solvent and opening to air) and available starting materials, the protocol can be compatible with various drugs, prodrugs, dyes and pharmacophores containing primary amino group. In addition, we also successfully apply this protocol to rapidly synthesize the core scaffolds of bioactive molecules.

Synthesis of Thioureas, Thioamides, and Aza-Heterocycles via Dimethyl-Sulfoxide-Promoted Oxidative Condensation of Sulfur, Malonic Acids, and Amines.

Malonic acid and derivatives have been well-known to undergo monodecarboxylation under relatively mild conditions and have been exclusively used as a C2 synthon. We report herein their new application as a C1 synthon via double decarboxylation promoted by sulfur and dimethyl sulfoxide. In the presence of amines as nucleophiles, a wide range of thioureas and thioamides as well as N-heterocycles were obtained in good to excellent yields under mild heating conditions.