Acylation Of Amines Research Articles

Phototriggered Generation of Ynol Ethers and Their Rearrangement to Ketenes.

This study developed reactions for the phototriggered generation of reactive ynol ethers using alkoxycyclopropenones. The resulting ynol ethers underwent rearrangement to ketenes, which subsequently participated in cycloaddition with alkynes and the acylation of amines. The alkoxy groups in the ynol ethers significantly influenced on the reactivity toward their rearrangement to ketenes. Reasonable transition state structures for the rearrangement reaction were found through density functional theory calculations, and the reactivity of the ynol ethers could be predicted by these calculations.

Novel 1,2,4-triazole-maleamic acid derivatives: synthesis and evaluation as anticancer agents with carbonic anhydrase inhibitory activity

Hybrid compounds with 1,2,4-triazole ring and a hydrazone moiety were designed and synthesized by amine acylation of uncommon triaminogunidine derivatives using maleic anhydride. Synthesized compounds were characterized by various spectral techniques, including FTIR, 1H NMR, 13C NMR, and HRMS. Furthermore, the proposed structure of TM-2 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their anticancer activity in vitro against the colon cancer cell line HCT116 and the ovarian cancer cell line A2780. Among them, some compounds, TM-3, TM-4, and TM-14, exhibited remarkable antiproliferative activity in the cell line A2780, with IC50 values of 6.11, 5.15, and 5.93 µM, respectively. Further investigation revealed that these compounds could inhibit cancerous cell growth by inducing an increase in caspase-3 activity. In addition, antioxidant capabilities, interaction with plasmid pBR322 DNA, and inhibitory effects against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms, namely hCA I and hCA II, of the synthesized compounds were also assessed. Finally, computational studies, such as DFT calculation, molecular docking, and in silico predictions of ADME/T analysis, were conducted to gain an understanding of the specific reactive sites of the compounds, the binding modes in the active sites, and the pharmacokinetic parameters of the newly synthesized hybrid compounds, which were calculated to establish their drug-likeness properties.

Gold‐Zinc Co‐Catalyzed Alkynoate Hydrocarboxylation with N‐Protected Amino Acids for Preparation of Storable Acylating Reagents and Racemization‐Free Peptide Synthesis

AbstractHydrocarboxylation of methyl 2‐octynoate, a chemical commercially available at a low cost, with N‐protected amino acids was developed with a gold‐zinc cooperative catalyst constructed with a 5‐[(2,2′‐bipyridin)‐5‐yl]imidazo[1,5‐a]pyridin‐3‐ylidene to prepare α‐methoxycarbonyl enol esters as acylating reagents. The α‐methoxycarbonyl enol esters were isolable through silica‐gel column chromatography and storable without precautions regarding moisture. Acylation of free amines with the α‐methoxycarbonyl enol esters proceeded without epimerization of the stereogenic center derived from the enol esters, affording analytically pure dipeptide compounds through filtration and hexane‐washing.

Expedient method for acylation of amines, alcohols and thiol using trimethylsilyl acetate

Expedient method for acylation of amines, alcohols and thiol using trimethylsilyl acetate

Highly Practical Aqueous Phase Acylation of Phenols, Amines and Alcohols Employing New Green Acylation Reagents Derived From DBU

AbstractTwo new Lewis base adducts (LBAs) of DBU were prepared, isolated in grams scale and are employed as Green reagents for base free benzoylation and pivaloylation in water. The structures of these reagents are unambiguously confirmed and the practicality of these LBAs (transient species) in organic synthesis as operationally simple protecting reagents of various phenols, amines, and alcohols in water at ambient temperature is explored. The products are furnished in very good yields (up to 95 %) and are purified just by filtration followed by recrystallization thus avoiding column chromatography. The Lewis base, DBU is recycled and reused for the preparation of LBAs. The methodology is an environmentally benign due to aqueous phase, base free reaction, chromatography free purificatios, ambient temperature reactions and recycling DBU.

Efficient iron-catalyzed direct acylation of amines with carboxylic acids and esters under oxygenated conditions

A new use for dioxygen at atmospheric pressure as an inducer of a highly efficient iron-catalyzed direct amidation between amines and carboxylic acids or esters in a biodegradable greener solvent such as diethyl carbonate has been discovered.

Photocatalytic α-Trifluoromethylthiolation of N-Acyl Amines

Photocatalytic α-Trifluoromethylthiolation of <i>N</i>-Acyl Amines

Quaternization-spiro design of chlorine-resistant and high-permeance lithium separation membranes

Current polyamide lithium extraction nanofiltration membranes are susceptible to chlorine degradation and/or low permeance, two problems that are hard to reconcile. Here we simultaneously circumvented these problems by designing a quaternized-spiro piperazine monomer and translating its beneficial properties into large-area membranes (1 × 2 m2) via interfacial polymerization with trimesoyl chloride. The quaternary ammonium and spiral conformation of the monomer confer more positive charge and free volume to the membrane, leading to one of the highest permeance (~22 L m−2 h−1 bar−1) compared to the state-of-the-art Mg2+/Li+ nanofiltration membranes. Meanwhile, membrane structures are chlorine resistant as the amine–acyl bonding contains no sensitive N-H group. Thus the high performance of membrane is stable versus 400-h immersion in sodium hypochlorite, while control membranes degraded readily. Molecular simulations show that the high permeance and chlorine resistance, which were reproducible at the membrane module level, arise from the spiral conformation and secondary amine structures of the monomer.

Kinetics and Mechanism of Azole n-π*-Catalyzed Amine Acylation.

Azole anions are highly competent in the activation of weak acyl donors, but, unlike neutral (aprotic) Lewis bases, are not yet widely applied as acylation catalysts. Using a combination of in situ and stopped-flow 1H/19F NMR spectroscopy, kinetics, isotopic labeling, 1H DOSY, and electronic structure calculations, we have investigated azole-catalyzed aminolysis of p-fluorophenyl acetate. The global kinetics have been elucidated under four sets of conditions, and the key elementary steps underpinning catalysis deconvoluted using a range of intermediates and transition state probes. While all evidence points to an overarching mechanism involving n-π* catalysis via N-acylated azole intermediates, a diverse array of kinetic regimes emerges from this framework. Even seemingly minor changes to the solvent, auxiliary base, or azole catalyst can elicit profound changes in the temporal evolution, thermal sensitivity, and progressive inhibition of catalysis. These observations can only be rationalized by taking a holistic view of the mechanism and a set of limiting regimes for the kinetics. Overall, the analysis of 18 azole catalysts spanning nearly 10 orders of magnitude in acidity highlights the pitfall of pursuing ever more nucleophilic catalysts without regard for catalyst speciation.

Iron containing di-cationic ionic liquid [DIL]2+[2FeCl4]2− as a highly efficient catalyst for the acylation of alcohols, phenols and amines

In this study, we describe the synthesis of an efficient catalyst for the acylation of alcohols, phenols, and amines in the presence of 3,3′-(ethane-1,2-diyl)bis(1-methyl-1H-imidazol-3-ium) tetrachloroferrate [DIL]2+[2FeCl4]2− and acetyl chloride (acylating reagent). Remarkably, when exposed to 7 mol% of catalyst [DIL]2+[2FeCl4]2− in a solvent-free environment, acetyl chloride demonstrated excellent acylation activity in a shorter period of time. As a result, a generic approach for the acylation of alcohols, phenols, and amines has been developed. As an ionic liquid, [DIL]2+[2FeCl4]2− can be easily recovered and reused up to five times in a row with little loss of catalytic activity. TGA and DSC analyses were also performed to determine the thermal robustness of [DIL]2+[2FeCl4]2−. We were able to illustrate the several advantages of this acylation approach. It provides better yields in less time and opens up the possibility of a safe, environmentally friendly remedy for acylation reaction.

A strategy for the treatment of lung carcinoma by in situ immobilization of Ag nanoparticles on the surface of Fe3O4 nanoparticles that modified by lignin

This work describes an eco-friendly approach for in situ immobilization of Ag nanoparticles on the surface of Fe3O4 nanoparticles that modified by lignin, without using any toxic reducing and capping agents. The structure, morphology, and physicochemical properties were characterized by various analytical techniques such as Fourier transformed infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), inductively coupled plasma (ICP) and vibrating sample magnetometer (VSM). The Fe3O4/Lignin/Ag NPs was proven to be highly efficient nanocatalyst for the acylation of various amines by utilizing acetic anhydride as a reagent in solvent-free conditions with good yields of acetamide products. The nanocatalyst was easily magnetically recovered and recycled 10 times without any significant loss of catalytic activity. The nanocomposite was also explored biologically in the anticancer assays. Exposure of the Fe3O4/Lignin/Ag NPs samples to lung (NCI-H661, NCI-H1563, CALU 1 and ChaGo-K-1) cancer cells resulted in cell death, which was mostly due to necrosis but slightly due to late apoptosis. The green-synthesized Fe3O4/Lignin/Ag NPs induced cell death, suggesting anticancer prospects that may offer new insight into the development of an anticancer nanomedicine.

Synthesis of dichloroacetamides and study of their anti-tumor activity

Dichloroacetic acid and its derivatives exhibit the properties of metabolic cytoprotectors and apoptosis inducers. Nowadays evaluation of these derivatives is being conducted regarding the induction of immunogenic cell death. Therefore, the search for new derivatives of dichloroacetic acid as potential antitumor agents has a certain perspective and may be successful for the molecular design of «drug-like» structures.&#x0D; The aim of the work was the development of synthetic approaches to the obtaining of dichloroacetic acid amides and the primary screening of the antitumor activity of the synthesized compounds.&#x0D; Synthetic studies were conducted using reagents from the companies «Merck» (Darmstadt, Germany) and «Sigma-Aldrich» (Missouri, USA). 1H NMR spectra were measured on a Varian VXR-400 instrument, and LC-MS spectra on an Agilent 1100 Series LCMS instrument. The anticancer activity of the synthesized compounds was studied according to the international scientific program of the US National Cancer Institute – DTP (Developmental Therapeutic Program).&#x0D; Amides were synthesized based on acylation reactions of the corresponding substituted ethylamines and aminobenzoic acids with methyldichloroacetate and dichloroacetyl chloride. The use of two methods of acylation of amines allows obtaining the target compounds with sufficient purity and satisfactory yields (44–98%). The structure and purity of the synthesized compounds were confirmed by the methods of elemental analysis, LCMS spectrometry and 1H NMR spectroscopy.&#x0D; It was shown that dichloroacetyl chloride and methyl dichloroacetate are effective acylating agents, which was confirmed by the synthesis of a series of amides based on substituted ethylamines and aromatic amino acids. Moderate antitumor activity of dichloroacetamides was established on some melanoma, leukemia, and renal cancer cell lines. The highest activity was observed for 4-(2,2-dichloroacetylamino)-2-hydroxybenzoic acid, against which the mitotic activity of the LOX IMV melanoma line was 45.83%. Preliminary data on the antitumor activity indicate certain prospects for the search for anticancer agents in the group of dichloroarylacetamides in comparison with alkyl amides.

N-Formylsaccharin: A Sweet(able) Formylating Agent in Mechanochemistry.

The acylation of amines has always attracted a deep interest as a synthetic route due to its high versatility in organic chemistry and biochemical processes. The purpose of this article is to present a mechanochemical acylation procedure based on the use of acyl-saccharin derivatives, namely N-formylsaccharin, N-acetylsaccharin, and N-propionylsaccharin. This protocol furnishes a valuable solvent-free alternative to the existing processes and aims to be highly beneficial in multi-step procedures due to its rapid and user-friendly workup.

A photo- and redox actives mesoporous 3D covalent organic framework enables highly efficient metal-free photoredox catalysis

Visible-light photoredox catalysis has been emerged as prominent methodology for efficient chemical synthesis. However, the relying use of soluble noble-metal photoredox catalysts suffer from long-term supply, inefficient separation, and could pos serious threats to the environment. Development of recyclable metal-free photoredox catalyst is thus highly significance. Herein, suitable molecular chromophore and redox units are condensed into photo- and redox active mesoporous 3D COF (3D TAPPy-TFPA) that enable highly efficient photoredox catalysis. The 3D COF displayed high crystallinity, mesoporous channel, and excellent structural stability. Optical and electrochemical studies revealed the excellent light harvesting, redox activity and effective generation of reactive radical species to induce photoredox catalysis. As proof-of-concept, 3D TAPPy-TFPA efficiently catalyzed the visible-light induced photoredox thiol-ene cross coupling and thiol radical mediated acylation of amines with activities surpassing most of the reported soluble photoredox catalysts. Beside recoverable, 3D TAPPy-TFPA showcased the previously inaccessible diacylation of amine into di-amide with high selectivity. This report shows robust design of outstanding and low-cost photoredox catalyst and paves the development of functional 3D COFs.

Novel Cobalt‐Supported Silica‐Coated Ferrite Nanoparticles Applicable for Acylation of Amine, Phenol, and Thiols Derivatives under Solvent‐Free Condition

AbstractThe straightforward co‐precipitation approach was used to effectively manufacture novel silica‐coated magnetic nanoparticles doped with cobalt (Co3O4). These nanoparticles were characterized using Field Emission Scanning Electron Microscopy (FE‐SEM), Energy‐Dispersive X‐ray Spectroscopy (EDS), Wavelength‐Dispersive Spectroscopy (WDX), Powder X‐ray Diffraction Spectroscopy (PXRD), Fourier transform infrared spectroscopy (FT‐IR), Thermo‐gravimetric Analysis (TGA), Inductive coupled plasma‐optical emission spectrometry (ICP‐OES), and Transmission Electron Microscopy (TEM), etc. Intriguingly, the catalytic performance of these nanocrystals for the amines, phenols, alcohols, and thiols acylation processes was examined in solvent‐free conditions, with outstanding yields. These nanoparticles were recycled at least 12 times without losing their catalytic activity.

Dual Activation of Carboxylic Acid Functionality by Protic Ionic Liquid: Solvent and Metal Free Strategy for Selective Esterification of Alcohols and Acylation of Aromatic Amines

AbstractHighly efficient and chemoselective esterification of alcohols and acylation of aromatic amines with carboxylic acids using imidazolium based protic ionic liquid, 1‐butyl‐imidazolium trifluoroacetate ([HBIm]TFA) as activator has been realized under organic volatile solvent free condition. The protic ionic liquid played dual role for activation of carboxylic acid which was proved by NMR study. A very interesting aspect of the present protocol is the acylation of less basic aromatic amines than the more reactive aliphatic amines as the later one forms salt with carboxylic acid. Our methodology offers several advantages like high yield, fast, efficient, chemo‐selectivity, metal and other coupling agent free procedure, recyclability of ionic liquid used and formation of water as the only by‐product.

CO2 -Promoted Direct Acylation of Amines and Phenols by the Activation of Inert Thioacid Salts.

Herein a carbon dioxide-promoted synthetic approach for the direct amidation between unactivated thioacid salts and amines under mild conditions was developed for a wide range of substrates. The method afforded amides in good to excellent yields under transition-metal-free and activation-reagent-free conditions, in sharp contrast to early methodologies on amide synthesis based on transition-metal catalysis. The method offered a greener and transition metal-free protocol applicable to pharmaceuticals preparations. Phenolic compounds were also found to be suitable acylation substrates with potassium thiosulfide KHS as the only byproduct. Moreover, this approach was applied to amide synthesis of valuable bio-active molecules such as moclobemide, melatonin, and a fungicide. Insights into the reaction mechanism involving carbon dioxide were provided through NMR spectroscopy and computational calculations. A plausible mechanism was proposed that involves weak interactions between carbon dioxide and potassium thioacetate in a dynamic equilibrium state formation of a six-membered ring.

Facile Synthesis of Amides through Transamidation with Iodine under Neat Conditions

AbstractIodine and NH2OH.HCl mediated transamidation of unactivated amides with a variety of amines under thermal/microwave irradiations. The current strategy is effective for a wide variety of primary, secondary, and tertiary amides and allows formylation, acylation, and benzoylation of various amines. The primary advantages of the current protocol are simple, rapid, absence of metal catalyst, low‐cost starting material as a solvent, and low environmental impact during the synthesis process.

Synthesis and Antiproliferative Activity of Triphenylphosphonium Derivatives of Natural Allylpolyalkoxybenzenes.

Derivatives of natural allylpolyalkoxybenzenes conjugated to triphenylphosphonium (TPP) cations by aliphatic linkers of three, six, seven, and eight atoms were synthesized to examine the role of the polyalkoxybenzene pharmacophore, TPP fragment, and linker length in antiproliferative activities. The key synthetic procedures included (i) hydroboration–oxidation of apiol, dillapiol, myristicin, and allyltetramethoxybenzene; (ii) acylation of polyalkoxybenzyl alcohols or amines; and (iii) condensation of polyalkoxybenzaldehydes followed by hydrogenation and cyclopropyl–homoallyl rearrangement. The targeted TPP conjugates as well as the starting allylbenzenes, the corresponding alkylpolyalkoxybenzenes, and the respective alkyl-TPP salts were evaluated for cytotoxicity in a panel of human cancer cell lines using MTT and Click-iT-EdU assays and in a sea urchin embryo model. The linker of three carbon atoms was identified as favorable for selective cancer cell growth inhibition. Although the propyl-TPP salt was cytotoxic at low micromolar concentrations, the introduction of a polyalkoxybenzene moiety significantly potentiated inhibition of both cell growth and de novo DNA synthesis in several human cancer cell lines, HST-116 colon cancer, A375 melanoma, PC-3 prostate cancer, and T-47D breast carcinoma cells, while it failed to produce any developmental abnormalities in the sea urchin embryos.

Plasma flow chemistry for direct N-acylation of amines by esters.

The direct N-acylation of amines by esters in a microreactor is described using argon plasma, thereby producing amides in good to excellent yields.