Alkyl Amides Research Articles

Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines

Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines. Our method leverages triflic anhydride-mediated semi-reduction of amides to imines, followed by a photochemical radical alkylation step. This approach broadens the synthetic utility of amides, facilitating late-stage modifications of drug-like molecules and the synthesis of saturated N-substituted heterocycles. The pivotal role of flow technology in developing a scalable and robust process underscores the practicality of this method, significantly expanding the organic chemist’s toolbox for complex amine synthesis.

CoII-organic 'soft' metallo-supramolecular polymer nanofibers for efficient photoreduction of CO2.

Coordination-driven metallo-supramolecular polymers hold significant potential as highly efficient catalysts for photocatalytic CO2 reduction, owing to the covalent integration of the light harvesting unit, catalytic center and intrinsic hierarchical nanostructures. In this study, we present the synthesis, characterization, and gelation behaviour of a novel low molecular weight gelator (LMWG) integrating a benzo[1,2-b:4,5-b']dithiophene core with terpyridine (TPY) units via alkyl amide chains (TPY-BDT). The two TPY ends of the TPY-BDT unit efficiently chelate with metal ions, enabling the formation of a metallo-supramolecular polymer that brings together the catalytic center and a photosensitizer in close proximity, maximizing catalytic efficiency for CO2 reduction. The self-assembly of TPY-BDT with CoII ions yields a Co-TPY-BDT coordination polymer gel (CPG) with a 3D interconnected fibrous morphology, facilitating rapid electron transfer and efficient substrate diffusion. The Co-TPY-BDT CPG achieves an outstanding CO2 to CO conversion, producing 33.74 mmol g-1 of CO in 18 hours with ∼99% selectivity under visible light irradiation, using triethylamine (TEA) as a sacrificial electron donor. Remarkably, the Co-TPY-BDT CPG demonstrates significant catalytic activity even under low-concentration CO2 atmospheres (5% CO2, 95% Ar), producing 1.9 mmol g-1 of CO in 10 hours with a selectivity of 94.6%. Moreover, In situ diffuse reflectance Fourier transform (DRIFT) study, femtosecond transient absorption spectroscopy, and DFT calculations were employed to elucidate the CO2 to CO reaction mechanism.

Selective Synthesis of Z-Michael Acceptors via Hydroalkylation of Conjugated Alkynes.

Hydroalkylation of terminal alkynes is a powerful approach to the synthesis of disubstituted alkenes. However, its application is largely unexplored in the synthesis of α,β-unsaturated carbonyls, which are common among synthetic intermediates and biologically active molecules. The thermodynamically less stable Z-isomers of activated alkenes have been particularly challenging to access because of their propensity for isomerization and the paucity of reliable Z-selective hydroalkylation methods. We developed a highly Z-selective silver-catalyzed hydroalkylation of terminal conjugated alkynes using alkyl boranes as coupling partners. The reaction allows access to (Z)-α,β-unsaturated esters, secondary and tertiary alkyl amides, aryl amides, and alkyl and aryl ketones and tolerates a wide range of functional groups. The reaction can be performed successfully in the presence of alkyl and aryl halides, esters, protected alcohols, and amines. The hydroalkylation involves the formation of an alkynylboronate complex followed by a 1,2-metalate shift. This sequence of steps mechanistically constrains the stereochemical outcome, which, together with mild reaction conditions, ensures high Z-selectivity.

TMSN3 Initiated Electrochemical Mono-Dealkylation of Tertiary Amides.

N-Dealkylation of amides is a general process in living organisms and organic synthetic chemistry, but an efficient chemical approach for this transformation has not been explored. Herein, we report an electrochemical method for the monodealkylation of a wide range of tertiary amides, including benzamides, alkyl amides, lactams, and sulfonamides. The reaction proceeds smoothly under mild conditions using TMSN3 as the initiator and is not limited to deethylation or demethylation. This protocol enables the large synthesis, providing a valuable tool for synthetic organic chemistry.

Safety Assessment of Alkyl Amide MIPA Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 14 alkyl amide MIPA ingredients as used in cosmetics. All of these ingredients are reported to function in cosmetics as a surfactant - foam booster and/or viscosity increasing agent. The Panel considered the available data, as well as data on read-across sources, and concluded these ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis for the Alkylation of Amides

Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis for the Alkylation of Amides

In-situ halloysite functionalization of anionic hybrid gels possessing easily implemented site-specific (alkyl)amide and carboxyl groups

Design of functional materials with tunable properties based on anionically-modified copolymer network of poly (N-isopropyl acrylamide-co-methacrylic acid) P(NIPA-co-MA) containing linear polyacrylamide and various amounts of Halloysite nanotubes (Hal) was presented using a facile route of solution casting. The organic/inorganic nanostructures based on thermo-responsive PNIPA were constructed to create hybrid materials via in situ polymerization with different Hal-loading and then used for the removal of cationic methylene blue (MB) dye from aqueous solutions. To achieve the desired mechanical property, the optimum composition of hybrids was determined following a simple and cost-effective synthesis procedure. In situ one-pot polymerization was promoted by semi-IPN formation, following a much simpler route than traditional preparation approaches for stable cross-linked hybrid formation. The swelling of hybrids decreased by 2.9-fold with loading of 5.40 % Hal, confirming the hydrogen bonding interactions between Hal and PAAm/P(NIPA-co-MA) network. The mechanical properties of Hal-doped hybrid gels showed an increase–decrease tendency with increase of Hal-content from 0.80 to 5.40 % (w/v) due to the high aspect ratio of Hal and strong secondary interactions between Hal and PAAm/P(NIPA-co-MA) chains. The effective cross-link density for Hal-doped hybrids was expressed by a cubic polynomial as a function of Hal concentration. Temperature-sensitive swelling results showed that the advantage of sustained release property of Hal can be combined with excellent controllability of PNIPA-based network. Adsorption results of MB onto Hal-doped hybrids bearing methacrylic acid moieties demonstrated their potential as efficient adsorbents for the removal of cationic dyes. A new route offered by the proposed procedure for design of hybrids containing “green” one-dimensional nanofillers creates an innovative perspective on robust hybrid structures for practical applications.

Sustainable lignin-based powder coatings doped with ZnO displayed excellent UV resistance properties

Lignin with increased polyhydroxyl content (LOH) was prepared via a one-pot synthesis using enzymatically hydrolyzed lignin (EHL) as the raw material. The modified structure and hydroxyl content of LOH were analyzed using FT-IR, 1H NMR, and 31P NMR. LOH was blended with zinc oxide (ZnO), polyester resin and hydroxyl alkyl amide (HAA) to prepare polyester powder coatings. The anti-UV properties of the coating were significantly enhanced by the addition of LOH and ZnO. The coating exhibits exceptional adhesion, rating at level 0, and achieves a pencil hardness of 7H. The gel time for the coating is 195 s, and it has a 5-degree Celsius increase in melting temperature, which greatly enhances its storage stability. Considering a range of factors, the formula LOH7.5 % has been identified as the optimal composition. The results of this study demonstrate an easy approach to developing sustainable lignin-based powder coatings with excellent properties.

A Radical Strategy for the Alkylation of Amides with Alkyl Halides by Merging Boryl Radical-Mediated Halogen-Atom Transfer and Copper Catalysis.

Amide alkylation is a fundamental process in organic chemistry. However, the low nucleophilicity of amides means that divergent coupling with alkyl electrophiles is often not achievable. To circumvent this reactivity challenge, individual amine synthesis followed by amidation with standard coupling agents is generally required. Herein, we demonstrate a radical solution to this challenge by using an amine-borane complex and copper catalysis under oxidative conditions. While borohydride reagents are generally used as reducing agents in ionic chemistry, their conversion into amine-ligated boryl radicals diverts their reactivity toward halogen-atom transfer. This enables the conversion of alkyl halides into the corresponding alkyl radicals for amide functionalization via copper catalysis. The process is applicable to the N-alkylation of primary amides employing unactivated alkyl iodides and bromides, and it was also showcased in the late-state functionalization of both complex amide- and halide-containing drugs.

Gas channeling control with CO2-responsive gel system in fractured low-permeability reservoirs: Enhancing oil recovery during CO2 flooding

During the CO2 flooding process in fractured low-permeability oil reservoirs, the injected CO2 is prone to channeling along fractures due to severe reservoir heterogeneity, resulting in poor development effect. The CO2-responsive gel system shows dual advantages in achieving CO2 capture and plugging gas channeling to enhance oil recovery. This paper constructed a system with good CO2 sensitivity based on long-chain alkyl amide propyl dimethyl tertiary amine first. Subsequently, the properties of the system before and after the response were evaluated through rheological test, and its microstructure was characterized by Cryo-TEM. The system exhibited good CO2 responsiveness, transitioning from low-viscosity solution system to high-viscosity CO2-responsive gel system upon contact with CO2, with its viscosity increasing by nearly five orders of magnitude. The CO2-responsive gel demonstrated excellent shear resistance, viscoelasticity and shear self-repairing ability. The change of microstructure further verified the mechanism of molecules self-assembly in the system under the action of CO2. Then, a series of core physical simulation experiments were carried out to comprehensively evaluate the effects of different factors on the injection capacity, plugging characteristics, dynamic filtration damage performance and EOR effect of CO2-responsive gel. The gel maintained injectability while achieving an exceptional deep plugging effect, and the plugging rate reached 98.77%. It showed good characteristics of low filtration and permeability damage in low permeability reservoirs, effectively ensuring the fracture plugging effect. After the fracture was plugged by gel, the sweep range of CO2 to the matrix significantly expanded, and the gas flooding recovery increased by 18.19–21.7%. Finally, the matrix-fracture dual-media chip model was used to conduct microfluidic experiment, the oil displacement characteristics in different displacement stages were visually clarified, and the synergistic plugging and oil displacement mechanism between the CO2-responsive gel and CO2 was summarized. The research results can provide important insights for the green and efficient application of CO2-responsive gel in fractured low-permeability reservoirs.

The discovery of indazapyroxamet: a novel 3-pyridinyl insecticide targeting piercing/sucking insectsa.

In recent years, the registrations for a number of commercial insecticides utilized for piercing/sucking insects have been cancelled or restricted. To meet this growing need for new hemipteran controlling agrochemicals, we discovered a 2-(pyridin-3-yl)-thiazole compound, with limited insecticidal activity against cotton/melon aphid (Aphis gossypii). The 2-(pyridin-3-yl)-thiazole moiety offered us a basis to pursue the bicyclic 2-(pyridin-3-yl)-2H-indazole carboxamides. Evaluation of such 2-(pyridin-3-yl)-2H-indazole carboxamides revealed that even analogs containing only simple alkyl amides attached at the 4 or 5 positions possess promising insecticidal activity. Extensive optimization of this novel class of 2-(pyridin-3-yl)-2H-indazole carboxamides led to identifying indazapyroxamet for commercial development. © 2024 Society of Chemical Industry.

Unveiling the Molecular Characteristics, Origins, and Formation Mechanism of Reduced Nitrogen Organic Compounds in the Urban Atmosphere of Shanghai Using a Versatile Aerosol Concentration Enrichment System.

Reduced nitrogen-containing organic compounds (NOCs) in aerosols play a crucial role in altering their light-absorption properties, thereby impacting regional haze and climate. Due to the low concentration levels of individual NOCs in the air, the utilization of accurate detection and quantification technologies becomes essential. For the first time, this study investigated the diurnal variation, chemical characteristics, and potential formation pathways of NOCs in urban ambient aerosols in Shanghai using a versatile aerosol concentration enrichment system (VACES) coupled with HPLC-Q-TOF-MS. The results showed that NOCs accounted over 60% of identified components of urban organic aerosols, with O/N < 3 compounds being the major contributors (>70%). The predominance of the positive ionization mode suggested the prevalence of reduced NOCs. Higher relative intensities and number fractions of NOCs were observed during nighttime, while CHO compounds showed an opposite trend. Notably, a positive correlation between the intensity of NOCs and ammonium during the nighttime was observed, suggesting that the reaction of ammonium to form imines may be a potential pathway for the formation of reduced NOCs during the nighttime. Seven prevalent types of reduced NOCs in autumn and winter were identified and characterized by an enrichment of CH2 long-chain homologues. These NOCs included alkyl, cyclic, and aromatic amides in CHON compounds, as well as heterocyclic or cyclic amines and aniline homologue series in CHN compounds, which were associated with anthropogenic activities and may be capable of forming light-absorbing chromophores or posing harm to human health. The findings highlight the significant contributions of both primary emissions and ammonium chemistry, particularly amination processes, to the pollution of reduced NOCs in Shanghai's atmosphere.

Deoxygenative Nucleophilic Phosphonation and Electrophilic Alkylation of Secondary Amides: A Facile Access to Quaternary α-Aminophosphonates.

The widespread occurrence and synthetic accessibility of amides render them valuable precursors for the synthesis of diverse nitrogen-containing compounds. Herein, we present a metal-free and streamlined synthetic strategy for the synthesis of quaternary α-aminophosphonates. This approach involves sequential deoxygenative nucleophilic phosphonation and versatile electrophilic alkylation of secondary amides in a one-pot fashion. Notably, this method enables the direct bis-functionalization of secondary amides with both nucleophiles and electrophiles for the first time, with simple derivatization leading to valuable free α-aminophosphonates by hydrolysis. The protocol has the advantages of operational simplicity, broad functional-group compatibility, environmental friendliness, and scalability to multigram quantities.

Cobalt nanoparticle-catalysed N-alkylation of amides with alcohols.

A protocol for efficient N-alkylation of benzamides with alcohols in the presence of cobalt-nanocatalysts is described. Key to the success of this general methodology is the use of highly dispersed cobalt nanoparticles supported on carbon, which are obtained from the pyrolysis of cobalt(ii) acetate and o-phenylenediamine as a ligand at suitable temperatures. The catalytic material shows a broad substrate scope and good tolerance to functional groups. Apart from the synthesis of a variety of secondary amides (>45 products), the catalyst allows for the conversion of more challenging aliphatic alcohols and amides, including biobased and macromolecular amides. The practical applicability of the catalyst is underlined by the successful recycling and reusability.

Upcycling of Poly(lactic acid) Waste: A Valuable Strategy to Obtain Ionic Liquids.

With the aim to investigate new strategies for upcycling of plastic waste, we performed aminolysis of poly(lactic acid) (PLA), using N,N-dimethylethylenediamine (DMEDA), N,N-dimethylpropylenediamine (DMPDA), and 3-aminopropylimidazole (API) as nucleophiles. The N-substituted lactamides obtained were alkylated by using alkyl halides differing in alkyl chain length, obtaining organic salts that in most cases behaved as ionic liquids (ILs). Both aminolysis of PLA and alkylation of amides were carried out taking into consideration the basic principles of the holistic approach to green chemistry, applied at a laboratory scale, and carefully selecting the nature of the reaction solvent, temperature range, and amount of reagents. Organic salts obtained from the alkylation of N-substituted lactamides were investigated to determine their glass or solid-liquid transitions and their thermal stability. Furthermore, cytotoxicity toward normal lung fibroblasts was also assessed. Data collected show that the proposed strategy represents a valuable protocol to upcycle plastic waste, using it as starting material to obtain alternative solvents of potential industrial relevance.

Pd(II)-Catalyzed C(sp3)–H Activation/Spirocyclization of Alkyl Amides

Pd(II)-Catalyzed C(sp3)–H Activation/Spirocyclization of Alkyl Amides

Anionic-nonionic and nonionic mixed surfactant systems for oil displacement: Impact of ethoxylate chain lengths on the synergistic effect

Compound surfactant system has been extensively studied in enhanced oil recovery (EOR) as the synergistic effect of mixed surfactants can increase the density of surfactants distributed at the oil/water interface, enhancing the interfacial activity and decreasing the interfacial tension. The system can further increase the capillary number and enhance oil recovery for oil-wet reservoirs. Studying the interactions between surfactant molecules is of great significance to the enhancement of practical application performances. In this study, N, N-dihydroxyethyl alkyl amide (CDEA), and Alkylphenol polyoxyethylene carboxylate (APEC) with different EO numbers were mixed to prepare a binary compound oil displacement system. The influence of the EO number on the synergistic effect of the CDEA/APEC system and the EOR potential was measured by interfacial tension, nanomechanical tests and oil-displacement experiments. The results indicate a synergistic effect between CDEA and APEC due to the formation of hydrogen bonds between the hydroxyl groups of CDEA and the EO chains of APEC. An optimal synergistic effect in the system was obtained when the EO number was four. The CDEA/APEC-4 system exhibited an oil/water interfacial tension decrease to 10−2 mN/m at 75 °C and the oil recovery was 57.14 %, which was increased by 19.2 % compared to primary water flooding. However, a longer EO chain length weakened the interaction forces between CDEA and APEC, which diminished the synergistic effect of the system, leading to an increase of the interfacial tension. Due to the flexibility of the EO chain, the increase in the EO number leads to the bending of APEC molecules. The longer EO chain length weakened the interaction forces between CDEA and APEC, which diminished the synergistic effect of the system, leading to an increase of the interfacial tension. The oil-displacement experiment revealed that the EO chains changed the oil recovery and injection pressure by affecting the interfacial tension of the mixed system. This study has significant implications for the formulation design and optimization of agents for oilfield development.

Novel System for the Production of the Bioactive N-alkylamide ‘Spilanthol’ Through Somatic Embryogenesis in Acmella ciliata Kunth (Cass.)

Acmella ciliata Kunth (Cass.), a medicinally important plant in the family Asteraceae, has high commercial value because of its traditional phytomedicinal uses. The plant contains many phytochemicals like alkyl amides, alkaloids, tannins, saponins and flavonoids accountable for most of its pharmacological applications. The study presented here reports the callus culture and somatic embryogenesis of this plant thereby raising a novel system for the subsequent production of the N-alkyl amide ‘spilanthol’, the valuable secondary metabolite presents in it. Murashige and Skoog (MS) medium supplemented with auxins either alone or in combination with cytokinins were used for the induction and maturation of somatic embryos. MS medium supplemented with 2,4-D (0.5, 1.0 and 2.0 mg.L-1) produced black friable callus whereas, 1.0 mg.L-1 NAA in combination with 0.5 mg.L-1 BA induced white, slightly purple coloured friable callus which on further subculture to fresh medium induced somatic embryos that germinated into plantlets upon transfer to MS basal medium. The mode of regeneration via somatic embryogenesis was confirmed by histological analysis through free-hand sectioning and stereomicroscopic observation. The plantlets raised through somatic embryogenesis after a short hardening period, were found to acclimatise in the field at 83.33% efficiency and exhibited genetic uniformity with 96.6% similarity in the ISSR analysis. HPLC analysis of in vitro raised embryogenic callus showed 239.512 µg.g-1 spilanthol content which was comparatively higher than the mother plants (92.19 µg.g-1). The bioproduction of the N-alkylamide ‘spilanthol’ through embryogenic callus can be extended for the scale-up production of this bioactive compound using bioreactor technology for the formulation of phytodrugs.

Palladium-Catalyzed Aerobic Oxidative Spirocyclization of Alkyl Amides with Maleimides via β-C(sp3)-H Activation.

An efficient method for the synthesis of bicyclic spirodiamine molecules via β-C(sp3)-H bond activation of aliphatic amides, followed by cyclization with maleimides, has been developed. The reaction proceeds through an amide-directed β-C(sp3)-H bond activation of alkyl amides and subsequent cyclization with maleimides. The methodology is highly compatible with a wide variety of maleimides. Amides derived from biologically active aliphatic and fatty acids were also found to be highly compatible with the protocol. A palladacycle was synthesized and found to be the active intermediate in this reaction. A plausible reaction mechanism was also proposed to account for this spirocyclization.

Inhomogeneous HfO2 layer growth at atomic layer deposition

Abstract Thin HfO2 films atomic layer deposited from hafnium alkyl amide and oxygen plasma were analysed using spectroscopic ellipsometry and X-ray reflectivity. Low refractive index of the material for samples with less than 30 nm thickness marks the index inhomogeneity at the first stage of growth. The transition from rising density to a more stable growth takes place at about 10 to 25 nm film thickness. HfO2 films used for resistive switching experiments demonstrate either clockwise or counterclockwise behaviour depending on the film thickness. The reason for this may be the disruption of the conductive filament at different metal-insulator interfaces, which could be favoured by several mechanisms.