Synthesis Of Amides Research Articles

Electron-Donor-Mediated Divergent Transformation of Br-RF via EDA Complex for the Synthesis of Fluorine-Containing Oxindoles and Amides.

We have developed an unprecedented electron-donor-controlled divergent reaction between N-alkylsulfonylated acrylamides and Br-RF, facilitated by an electron donor-acceptor (EDA) complex, for the synthesis of fluorine-containing oxindoles and amides. Key to this divergent transformation is the EDA complex generation by altering electron donors. This approach has several advantages, such as broad substrate scope, being metal-catalyst- and photocatalyst-free, and having good functional group tolerance.

Ortho Arylation of N-Aryl Amides and the Construction of Diagonal Tetraarylbenzenediamines and N-Doped Fulminenes via BBr3-Derived Dibromoboracycles.

The synthesis of biaryl amides, which are prevalent motifs in bioactive molecules, often necessitates lengthy and inefficient procedures. To address these limitations, catalytic C-H activation protocols have emerged, enabling the direct ortho-arylation of aryl amides. However, these protocols often suffer from issues such as lack of selectivity, reliance on stoichiometric oxidants, and the requirement for excess reagents and harsh reaction conditions. To overcome these challenges, we present a novel and highly selective protocol for the ortho-arylation of N-aryl amides and ureas. The high selectivity originates from the directed installation of BBr3 to form a boracycle, which then undergoes cross-coupling with an aryl halide. Our method offers significant advantages, including mild reaction conditions, excellent site-specificity, and scalability. The protocol demonstrates broad compatibility with a diverse range of readily accessible functionalized anilides and aryl iodides, as evidenced by 55 successful examples yielding products in the 30-95% range. Furthermore, our methodology surpasses conventional approaches by facilitating the one-pot selective diagonal diarylation of dianilides. This capability unlocks the construction of previously unattainable diagonal aryl systems, which serve as valuable precursors for the synthesis of diagonal tetraarylbenzenediamines and N-doped fulminene, two crucial compound classes in materials science.

Synthesis of α-Quaternary Amides via Cp*Co(III)-Catalyzed Sequential C-H Bond Addition to 1,3-Dienes and Isocyanates.

The synthesis of sterically congested amides was accomplished via Cp*Co(III)-catalyzed sequential C-H bond addition to 1,3-dienes followed by aminocarbonylation with isocyanates, a coupling partner that had never been utilized in sequential C-H bond addition reactions. A variety of C-H bond reactants, internally substituted dienes, and aromatic isocyanates provided secondary amide products incorporating α-all-carbon quaternary centers. The conversion of the amide products to other useful compound classes was also demonstrated.

Redox-Neutral Umpolung Synthesis of α-Functionalized Amides

Redox-Neutral Umpolung Synthesis of α-Functionalized Amides

Direct Synthesis of Benzothiazoles and Benzoxazoles from Carboxylic Acids Utilizing (o-CF3PhO)3P as a Coupling Reagent.

A general and efficient method for the direct synthesis of benzothiazoles and benzoxazoles from carboxylic acids with 2-aminobenzenethiols or 2-aminophenols using (o-CF3PhO)3P as a simple coupling reagent has been developed. Diverse benzothiazoles and benzoxazoles were synthesized in moderate to excellent yields. And the gram-scale preparation of benzothiazole and benzoxazole also proceeded smoothly under the mild conditions. Moreover, a plausible reaction mechanism was discussed, with (o-CF3PhO)3P and its hydrolysis product (o-CF3PhO)2P(O)H contributing to the formation of the target products as an amide synthesis coupling agent and a cyclization reaction promoter, respectively.

Synthesis and Anti-Inflammatory Activity of New Nicotinoyl Amides

The article presents the results of a study of the amination reaction of nicotinic acid chlorohydride with amines morpholine, cytisine, and 1-aminoadamantane, which are often used in the search and creation of drugs for respiratory and circulatory stimulants. The study was conducted to search for new biologically active compounds with anti-inflammatory activity. The synthesis of new aminoamides was carried out by the interaction of nicotinic acid with molecules of morpholine, cytisine, and adamantane in anhydrous ethanol. As a result of the conducted studies, new amides of nicotinic acid with high yields (90.7–93.1%) were obtained. The structures of the new compounds were determined using NMR 1H and 13C spectroscopy methods, as well as data from two-dimensional spectra of COSY (1H-1H), HMQC (1H-13C), HMBC (1H-13C) and mass spectrometry. The results of an experimental study of the anti-inflammatory activity of synthesized new amides are presented. The anti-inflammatory effect of nicotinic acid N-adamantylamide was established, other new amides were ineffective compared with ibuprofen (p2 < 0.05).

Cholesterol-Supported Liquid-Phase Synthesis of Betaines and Organic Cations without Chromatography.

Cholesterol was explored as a support for liquid-phase synthesis. Without the need for chromatography, the cholesterol-supported liquid-phase approach gave access to diverse betaines possessing chiral ammonium, phosphonium, and sulfonium ions. The cholesterol-supported method was further demonstrated by the synthesis of cationic amides and hydrazides.

Amide Synthesis from Decarboxylative Coupling of Isocyanates and Carboxylic Acids.

Isocyanates are versatile electrophiles that can react with a wide range of nucleophiles to afford important organic structures. Although the reactions between isocyanates and alcohols, amines and organometallic reagents have been well established, the synthesis of amides through the decarboxylative condensation of carboxylic acids and isocyanates is less appreciated. In this review, the synthesis of isocyanates and its application on amide synthesis through the condensation with carboxylic acids are summarized and discussed. It is our hope that this review will attract more attention to this less mentioned transformation and inspire new developments in the fields of organic synthesis, polymer synthesis and chemical biology.

Visible-Light-Driven Method for the Selective Synthesis of Amides and N-Acylureas from Carboxylic Acids and Thioureas.

In this work, we developed a visible-light-driven method for the selective synthesis of amides and N-acylureas from carboxylic acids and thioureas. This protocol was featured as avoidance of additional oxidants and transition metal catalysts, simple manipulations, low cost, broad substrate scope, and good functional group tolerance. As only oxygen serves as the oxidation reagent, this method provides a promising synthesis candidate for the formation of N-aryl amides and N-acylureas, including late-stage functionalization of complex pharmaceutical molecules and biologically active molecules.

Synthesis and characterization of 3,5-bis((2-hydroxybenzylidene)amino)-N-(2-hydroxyphenyl)benzamide and Zn(II) complex: Investigation of chromic, fluorescence and DPPH radical scavenging behaviours

Novel amido-Schiff base 3,5-bis((2-hydroxybenzylidene)amino)-N-(2-hydroxyphenyl)benzamide (2a) has been obtained by the reaction of Schiff base 1a with 2-hydroxyaniline in the presence of coupling agent N,N′-dicyclohexylcarbodiimide. Schiff base (1a) which serves as the starting compound in amide synthesis was produced from the condensation of 3,5-diaminobenzoic acid with salicylaldehyde in a 1:2 mol ratio. Tetrahedral geometry with 1:1 [M:L] stoichiometry Zn(II) complex (3a) was newly synthesized by the complexation reaction of ligand 2a with zinc(II) nitrate. 1a and 2a displayed a broad emission band at λem = 456 and 472 nm with a blue fluorescent in pure DMSO, while 3a emitted a strong greenish-blue fluorescent with the λem = 485 nm (λexc = 365 nm). The fluorescence efficiency of 1a was poor compared to the others. The λem in aqueous DMSO solution (v/v, 1:1) had ∼8–33 nm red-shift with respect to that of pure solution. The λem gave ∼1–15 nm red-shift with very low emission efficiency in acidic DMSO media. The results suggested that the aggregation caused quenching properties of 1a–3a in pure, aqueous, and acidic DMSO system with a 50 % water fraction. The fluorescence of the compounds appeared to be visibly very bright in basic DMSO media. All the compounds were also screened for antioxidant activity using UV–Vis spectroscopy. They were found to be not effective DPPH radical scavengers in DMSO.

Nickel-Catalyzed Cross-Coupling of Aziridines with Thioesters toward Atom-Economic Synthesis of β-Sulfanyl Amides.

Thioesters have been recognized as a class of powerful bifunctional reagents, namely, great donors of acyl and sulfide moieties. However, such application in value-added synthesis is still very limited to date. Herein, a nickel-catalyzed cross-coupling reaction system of aziridines with thioesters was developed under redox-neutral and mild conditions. This catalytic method provides an atom-economic route for the synthesis of diverse β-sulfanyl amide derivatives with wide substrate scope (43 examples), good functional group tolerance, and regioselectivity.

Synthesis of N-heterocyclic amides from imidazoheterocycles through convergent paired electrolysis.

An efficient ring opening of imidazoheterocycles induced by a direct C-H azidation resulting in an unusual formation of N-heterocyclic amides has been successfully developed through convergent paired electrolysis. A broad scope of pyridylbenzamides could be obtained in moderate to excellent yields under exogenous-oxidant, electrolyte- and metal-free electrochemical conditions. The methodology was transferred to continuous flow conditions resulting in notable improvements particularly in terms of cost-efficiency over traditional batch versions.

Deciphering the acidophilia and acid resistance in Acetilactobacillus jinshanensis dominating baijiu fermentation through multi-omics analysis

Lactic acid bacteria (LAB) are pivotal in constructing the intricate bio-catalytic networks underlying traditional fermented foods such as Baijiu. However, LAB and their metabolic mechanisms are partially understood in Moutai flavor Baijiu fermentation. Here, we found that Acetilactobacillus jinshanensis became the· dominant species with relative abundance reaching 92%, where the acid accumulated rapidly and peaked at almost 30 g/kg in Moutai flavor Baijiu. After separation, purification, and cultivation, A. jinshanensis exhibited pronounced acidophilia and higher acid resistance compared to other LAB. Further integrated multi-omics analysis revealed that fatty acid synthesis, cell membrane integrity, pHi and redox homeostasis maintenance, protein and amide syntheses were possibly crucial acid-resistant mechanisms in A. jinshanensis. Structural proteomics indicated that the surfaces of A. jinshanensis proteases contained more positively charged amino acid residues to maintain protein stability in acidic environments. The genes HSP20 and acpP were identified as acid-resistant genes for A. jinshanensis by heterologous expression analysis. These findings not only enhance our understanding of LAB in Baijiu, providing a scientific basis for acid regulation for production process, but also offer valuable insights for studying core species in other fermentation systems.

Metal and Photocatalyst-Free Amide Synthesis via Decarbonylative Condensation of Alkynes and Photoexcited Nitroarenes.

Depending on the intrinsic photoactivity of nitroarenes, we herein developed a practical Brønsted acid-catalyzed decarbonylative amide synthesis from alkynes and photoexcited nitroarenes without any metal or photocatalyst. This method exhibited compatibility with water and air, broad substrate applicability, marvelous functional group tolerance, and wide applications in scale-up synthesis, late-stage functionalization, and total synthesis. Mechanism studies and DFT calculations supported that a 1,3,2-dioxazole intermediate was involved, and gaseous carbon monoxide was the only byproduct during amide construction.

Organoboron catalysis for direct amide/peptide bond formation.

Amides and peptides are ubiquitous functional groups found in several natural and artificial materials, and they are essential for the advancement of life and material sciences. In particular, their relevance in clinical medicine and drug discovery has increased in recent years. Dehydrative condensation of readily available carboxylic acids with amines is the most "direct" method for amide synthesis; however, this methodology generally requires a stoichiometric amount of condensation agent (coupling reagent). Catalytic direct dehydrative amidation has become an "ideal" methodology for synthesizing amides from the perspective of green chemistry, with water as the only byproduct in principle, high atom efficiency, environmentally friendly, energy saving, and safety. Conversely, organoboron compounds, such as boronic acids, which are widely used in various industries as coupling reagents for Suzuki-Miyaura cross-coupling reactions or pharmaceutical structures, are environmentally friendly molecules that have low toxicity and are easy to handle. Based on the chemical properties of organoboron compounds, they have potential Lewis acidity and the ability to form reversible covalent bonds with dehydration, making them attractive as catalysts. This review explores studies on the development of direct dehydrative amide/peptide bond formation reactions from carboxylic acids using organoboron catalysis, classifying them based on chemical bonding and catalysis over approximately 25 years, from the early developmental days to 2023.

Amide and peptide synthesis via nickel-catalyzed cross-electrophile coupling

Amide and peptide synthesis via nickel-catalyzed cross-electrophile coupling

Amide synthesis from DDQ-mediated electrochemical Beckmann rearrangement

Beckmann rearrangement, a classical reaction of introducing nitrogen to carbon skeleton compounds for amide synthesis, is widely used in academia and industry. Herein, an electrochemical Beckmann rearrangement is reported, utilizing 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a mediator to prevent the over-electro-oxidation of products, which could afford amide in excellent yield.

200 Years of The Haloform Reaction: Methods and Applications.

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive a-halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavouring. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used.

Desulfonation-associated direct amide bond formation between N-sulfonyl-1,2,3-triazoles with carboxylic acids

We have developed a highly N2-regioselective method for direct construction of amide bond from N-sulfonyl-1,2,3-triazoles and carboxylic acids in the presence of bases at 60 °C in air. The developed reaction provides the corresponding products with high yields (up to 90 %) and a broad substrate compatibility including aryl acids, heterocyclic acids, and alkyl acids. Mechanistic studies show that the reaction proceeds through a direct nucleophilic attack of N-sulfonyl-1,2,3-triazoles to carboxylate anions via a base- and water-involved synergistic desulfonation process. This work presents an unusual water-involved example for direct synthesis of amides utilizing readily available starting materials under mild conditions.

Nickel‐Catalyzed Reductive Amidation of Aryl Sulfonium Salts with Isocyanates for Amide Synthesis via C−S Bond Activation

AbstractA nickel‐catalyzed reductive amidation of aryl sulfonium salts with isocyanates for amide synthesis via C−S bond cleavage was developed. The reactions proceeded smoothly at ambient temperature in the presence of nickel catalyst and manganese metal in DMF to give a variety of amides in moderate to good yields with wide functional group tolerance.